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Sample records for advanced intrahepatic cholangiocarcinoma

  1. Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy

    OpenAIRE

    Dreyer, Chantal; Sablin, Marie-Paule; Bouattour, Mohamed; Neuzillet, Cindy; Ronot, Maxime; Dokmak, Safi; Belghiti, Jacques; Guedj, Nathalie; Paradis, Valérie; Raymond, Eric; Faivre, Sandrine

    2015-01-01

    Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50...

  2. A case of advanced intrahepatic cholangiocarcinoma successfully treated with chemosensitivity test-guided systemic chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Kazumichi Abe; Takeru Wakatsuki; Fumiko Katsushima; Kyoko Monoe; Yukiko Kanno; Atsushi Takahashi; Junko Yokokawa; Hiromasa Ohira

    2009-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment Ⅷ of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion.After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

  3. Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for advanced-stage unresectable intrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    A standard treatment for unresectable advanced-stage intrahepatic cholangiocarcinoma (IHCC) has not yet been established. Although neoadjuvant concurrent chemoradiotherapy (CCRT) and liver transplantation are associated with long-term survival in select patients, the outcomes of CCRT for advanced-stage unresectable IHCC remain unclear. The aim of our study was to evaluate the outcomes of CCRT in patients with unresectable advanced-stage IHCC. We retrospectively reviewed the records of all patients with unresectable advanced stage (stage IVa or IVb) IHCC who were pathologically diagnosed and treated at National Cancer Center, Korea, from June 2001 to March 2012. Of the total of 92 patients, 25 (27.1%) received capecitabine plus cisplatin (XP) chemotherapy with external radiotherapy (RT) (XP-CCRT group) and 67 (72.8%) received XP chemotherapy alone (XP group). The clinical characteristics and outcomes of the 2 groups were compared. The 92 patients comprised 72 male and 20 female patients, with a median age of 58 years (range 26–78 years). The baseline clinical characteristics of the 2 groups were similar. Patients in the XP-CCRT group received a mean 44.7 Gy of RT and a mean 5.6 cycles of XP chemotherapy, whereas patients in the XP group received a mean 4.0 cycles. The disease control rate was higher in the XP-CCRT group than in the XP group, but the difference was not statistically significant (56.0% vs. 41.5%, p = 0.217). Although neutropenia was significantly more frequent in the XP-CCRT than in the XP group (48% vs. 9%, p < 0.001), the rates of other toxicities and > grade 3 toxicities did not differ. At a median follow-up of 5.3 months, PFS (4.3 vs. 1.9 months, p = 0.001) and OS (9.3 vs. 6.2 months, p = 0.048) were significantly longer in the XP-CCRT than in the XP group. XP-CCRT was well tolerated and was associated with longer PFS and OS than XP chemotherapy alone in patients with unresectable advanced IHCC. Controlled randomized trials are required to

  4. Serum Markers of Intrahepatic Cholangiocarcinoma

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    Giulia Malaguarnera

    2013-01-01

    Full Text Available Cholangiocarcinoma (CCA is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9, Carcinogenic Embryonic antigen (CEA, and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1 Mucins, Tumour Markers2- pyruvate-Kinase (TuM2- PK and metalloproteinase-7 (MMP-7 have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value.

  5. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...... underlying the diversity of growth patterns of this malignancy remain a clinical concern. It is crucial to advance our present understanding of the molecular pathogenesis of CCA to improve current clinical strategies and patient outcome. This will facilitate the delineation of patient subsets...

  6. Current status of intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian Yang; Lu-Nan Yan

    2008-01-01

    Intrahepatlc cholangiocarcinoma (ICC) is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.

  7. Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

    OpenAIRE

    Borad, Mitesh J.; Champion, Mia D.; Egan, Jan B.; Liang, Winnie S.; Rafael Fonseca; Bryce, Alan H.; Ann E McCullough; Barrett, Michael T.; Katherine Hunt; Maitray D Patel; Young, Scott W.; Collins, Joseph M.; Silva, Alvin C; Condjella, Rachel M.; Matthew Block

    2014-01-01

    Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among...

  8. Intrahepatic cholangiocarcinoma presenting as liver abscess: report of two cases

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    Kim, Kwon Hyoung; Cho, On Koo; Kim, Yong Soo; Rhim, Hyun Chul; Koh, Byung Hee [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-10-01

    Intrahepatic cholangiocarcinoma is the second most common primary malignant hepatic neoplasm. We describe two cases of intrahepatic cholangiocarcinoma which initially presented as liver abscess both clinically and radiologically. Mucin-hypersecretion from the tumor cells and extensive necrosis or secondary bacterial infection was responsible for the radiologic appearance of a liver abscess.=20.

  9. Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Høgdall, Dan; O'Rourke, Colm J; Taranta, Andrzej;

    2016-01-01

    Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic...

  10. AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a significant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.

  11. Intrahepatic cholangiocarcinoma: Epidemiology, risk factors, diagnosis and surgical management.

    Science.gov (United States)

    Zhang, Han; Yang, Tian; Wu, Mengchao; Shen, Feng

    2016-09-01

    Intrahepatic cholangiocarcinoma (ICC), the least common form of cholangiocarcinomas, is a rare hepatobiliary malignancy that arises from the epithelial cells of the intrahepatic bile ducts. The incidence of ICC has been rising in the global scale over the last twenty years, which may reflect both a true increase and the trend of earlier detection of the disease. Other than some well recognized causative risk factors, the association between viral and metabolic factors and ICC pathogenesis has been increasingly identified recently. Surgical resection is currently the only feasible modality with a curative ability, but the resectability and curability remain low. The high invasiveness of ICC predisposes the tumors to multifocality, node metastasis and vascular invasions, leading to poor long-term survival after resection. The role of liver transplantation is controversial, while locoregional treatments and systematic therapies may provide survival benefits, especially in patients with unresectable and advanced tumors. The present review discussed the epidemiology, risk factors, surgical and multimodal management of ICCs, which mainly focused on the outcomes and factors associated with surgical treatment. PMID:26409434

  12. Clinicopathological and prognostic significance of epithelial mesenchymal transition-related protein expression in intrahepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Yao X

    2012-10-01

    Full Text Available Xing Yao,1,* Xiang Wang,1,* Zishu Wang,2,* Licheng Dai,1 Guolei Zhang,1 Qiang Yan,1 Weimin Zhou11Huzhou Central Hospital, Zhejiang Huzhou, 2Department of Medical Oncology, First Affiliated Hospital, Bengbu Medical College, Anhui, People’s Republic of China *These authors contributed equally to this workBackground: The aim of this study was to examine the patterns of expression of epithelial-mesenchymal transition (EMT-related proteins in intrahepatic cholangiocarcinoma. The clinicopathological and prognostic value of these markers was also evaluated.Methods: We detected the expression status of three EMT-related proteins, ie, E-cadherin, vimentin, and N-cadherin, by immunohistochemistry in consecutive intrahepatic cholangiocarcinoma specimens from 96 patients.Results: The frequency of loss of the epithelial marker E-cadherin, and acquisition of mesenchymal markers, vimentin and N-cadherin, in intrahepatic cholangiocarcinoma was 43.8%, 37.5% and 57.3%, respectively. Altered expression of EMT markers was associated with aggressive tumor behavior, including lymph node metastasis, undifferentiated-type histology, advanced tumor stage, venous invasion, and shorter overall survival. Moreover, loss of E-cadherin was retained as an independent prognostic factor for patients with intrahepatic cholangiocarcinoma in multivariate analysis.Conclusion: Our results suggest that the EMT process is associated with tumor progression and a poor outcome in patients with intrahepatic cholangiocarcinoma, and inhibition of EMT might offer novel promising molecular targets for the treatment of affected patients.Keywords: intrahepatic cholangiocarcinoma, epithelial-mesenchymal transition, expression, prognosis, immunohistochemistry

  13. Clinicopathologic significance of slug expression in human intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To explore the expression and function of slug,a transcriptional repressor,in human intrahepatic cholangiocarcinoma(IHCC)and identify its role in IHCC progression.METHODS:Expression of slug was detected in 36 cases of IHCC and 12 cases of normal intrahepatic bile ducts and liver parenchyma by immunohistochemistry.The patients were divided into low slug expression group(< 20%of carcinoma cells stained)and high slug expression group(≥20%of carcinoma cells stained).Slug expression was correlated with clini...

  14. Unusual Images of Mass-Forming Intrahepatic Cholangiocarcinoma

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    Kazuki Takakura

    2013-09-01

    Full Text Available We experienced a case of mass-forming intrahepatic cholangiocarcinoma which could not been diagnosed accurately without pathologic findings. A 78-year-old Japanese woman with no particular symptoms was admitted for changes in liver function tests. Ultrasonography revealed a solid liver tumor. When there are no typical imaging features, no pathognomonic clinical findings and no obvious risk factors for any specific hepatic tumor, it may be difficult to make an accurate diagnosis before surgical resection. The lesion was resected on the basis of a high degree of suspicion for malignancy and submitted for pathologic evaluation. Microscopically, the neoplasm was a moderately differentiated adenocarcinoma with abundant fibrous stroma, consistent with a mass-forming cholangiocarcinoma. This case exemplifies the importance of considering the various tumorous and non-tumorous diseases in the differential diagnosis of a liver mass with atypical features, especially when malignancy cannot be excluded.

  15. Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma

    Science.gov (United States)

    Andrici, Juliana; Goeppert, Benjamin; Sioson, Loretta; Clarkson, Adele; Renner, Marcus; Stenzinger, Albrecht; Tayao, Michael; Watson, Nicole; Farzin, Mahtab; Toon, Christopher W.; Smith, Ross C.; Mittal, Anubhav; Samra, Jaswinder S.; Hugh, Thomas J.; Chou, Angela; Lawlor, Rita T.; Weichert, Wilko; Schirmacher, Peter; Sperandio, Nicola; Ruzzenente, Andrea; Scarpa, Aldo; Gill, Anthony J.

    2016-01-01

    Abstract BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that functions as a tumor suppressor gene. Double hit BAP1 inactivation has been reported in a range of tumor types, including intrahepatic cholangiocarcinoma (ICC), sometimes in association with germline mutation. We performed immunohistochemistry for BAP1 on a well-characterized cohort of 211 ICC patients undergoing surgical resection with curative intent at 3 institutions based in 3 different countries. The median age at diagnosis was 65 years (range, 36.5–86) and 108 (51%) were men. Negative staining for BAP1 (defined as completely absent nuclear staining in the presence of positive internal controls in nonneoplastic cells) occurred in 55 ICCs (26%). BAP1 loss predicted a strong trend toward improved median survival of 40.80 months (95% CI, 28.14–53.46) versus 24.87 months (95% CI, 18.73–31.01), P = 0.059). In a multivariate model including age, sex, BAP1 status, tumor stage, tumor grade, lymphovascular invasion, and tumor size, female sex was associated with improved survival (hazard ratio [HR] 0.54; 95% CI, 0.34–0.85), while advanced tumor stage and lymphovascular invasion (HR 1.89; 95% CI, 1.09–3.28) correlated with decreased survival. In a multivariate analysis, high grade tumors were associated with BAP1 loss (odds ratio [OR] 3.32; 95% CI, 1.29–8.55), while lymphatic invasion was inversely associated with BAP1 loss (OR 0.36; 95% CI, 0.13–0.99). In conclusion, we observed a trend toward improved prognosis in ICC associated with absent expression of BAP1 and an association of BAP1 loss with higher histological grade and absent lymphatic invasion. Female sex was associated with improved survival while advanced tumor stage and lymphatic invasion were associated with decreased survival. PMID:26765459

  16. Distant skeletal muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome

    Institute of Scientific and Technical Information of China (English)

    Oh Sung Kwon; Young Sook Park; Jong Eun Joo; Dae Won Jun; Sang Heum Kim; Mee Yeon Chung; Nam In Kim; Moon Hee Song; Han Hyo Lee; Seung Hwan Kim; Yoon Ju Jo

    2007-01-01

    Intrahepatic cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium, which frequently invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenals, and brain. However, distant skeletal muscle metastasis of cholangiocarcinoma has never been described before to the best of our knowledge and, furthermore, Budd-Chiari syndrome secondary to intrahepatic cholangiocarcinoma is also extremely rare. Here we present the first case overall of distant muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome. A 44-year-old man admitted to the hospital with complaints of abdominal distension, edema of both legs, back pain and anorexia of 30 o" duration. Computed tomography and ultrasonography-guided percutaneous muscle biopsy established intrahepatic cholangiocarcinoma with disseminated thrombosis from inferior vena cava to bilateral iliac and femoral veins, and multiple skeletal muscle metastases in bilateral buttock and erector spinal muscle.

  17. Review to better understand the macroscopic subtypes and histogenesis of intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuichi; Sanada; Yujo; Kawashita; Satomi; Okada; Takashi; Azuma; Shigetoshi; Matsuo

    2014-01-01

    Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma(ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy.

  18. Multiple cellular origins and molecular evolution of intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Wei, Miaoyan; Lü, Lisheng; Lin, Peiyi; Chen, Zhisheng; Quan, Zhiwei; Tang, Zhaohui

    2016-09-01

    Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy associated with unfavorable prognosis and for which no effective treatments are available. Its molecular pathogenesis is poorly understood. Genome-wide sequencing and high-throughput technologies have provided critical insights into the molecular basis of ICC while sparking a heated debate on the cellular origin. Cancer exhibits variabilities in origin, progression and cell biology. Recent evidence suggests that ICC has multiple cellular origins, including differentiated hepatocytes; intrahepatic biliary epithelial cells (IBECs)/cholangiocytes; pluripotent stem cells, such as hepatic stem/progenitor cells (HPCs) and biliary tree stem/progenitor cells (BTSCs); and peribiliary gland (PBG). However, both somatic mutagenesis and epigenomic features are highly cell type-specific. Multiple cellular origins may have profoundly different genomic landscapes and key signaling pathways, driving phenotypic variation and thereby posing significant challenges to personalized medicine in terms of achieving the optimal drug response and patient outcome. Considering this information, we have summarized the latest experimental evidence and relevant literature to provide an up-to-date view of the cellular origin of ICC, which will contribute to establishment of a hierarchical model of carcinogenesis and allow for improvement of the anatomical-based classification of ICC. These new insights have important implications for both the diagnosis and treatment of ICC patients. PMID:26940139

  19. MUC1 and MUC5AC mucin expression in liver fluke-associated intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Chanchai Boonla; Banchob Sripa; Peti Thuwajit; Ubon Cha-On; Anucha Puapairoj; Masanao Miwa; Sopit Wongkham

    2005-01-01

    AIM: To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma (ICC). Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined.METHODS: The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated.RESULTS: Fifty-two patients (60%) exhibited both MUC1 and MUC5AC expressions, whereas 31% expressed either MUC1or MUC5AC, and 9% expressed neither. High MUC1immunoreactivity displayed a significant correlation with tumor progression as reflected by vascular invasion (P<0.001),whereas high expression of MUC5AC significantly correlated with neural invasion (P = 0.022) and advanced ICC stage (P = 0.008). Patients with high expression of MUC1 had a significantly shorter survival (P = 0.0002). According to multivariate analyses, MUC1 reactivity (P = 0.026),histological grading and stage of tumor represented the least probability of survival.CONCLUSION: MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.

  20. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

    Science.gov (United States)

    Selaru, Florin M; Streppel, Mirte M; Lucas, Donald J; Niknafs, Noushin; Guthrie, Violeta Beleva; Maitra, Anirban; Argani, Pedram; Offerhaus, G Johan A; Roa, Juan Carlos; Roberts, Lewis R; Gores, Gregory J; Popescu, Irinel; Alexandrescu, Sorin T; Dima, Simona; Fassan, Matteo; Simbolo, Michele; Mafficini, Andrea; Capelli, Paola; Lawlor, Rita T; Ruzzenente, Andrea; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, Filippo; Scarpa, Aldo; Jarnagin, William; Klimstra, David; Karchin, Rachel; Velculescu, Victor E; Hruban, Ralph H; Vogelstein, Bert; Kinzler, Kenneth W; Papadopoulos, Nickolas; Wood, Laura D

    2014-01-01

    Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas. PMID:24185509

  1. Liver involvement of multiple myeloma mimicking intrahepatic cholangiocarcinoma: a case report

    International Nuclear Information System (INIS)

    Nodular hepatic involvement of multiple myeloma is very rare. We report here on a case of nodular hepatic involvement of multiple myeloma that mimicked intrahepatic cholangiocarcinoma. In patients with multiple myeloma, hepatic involvement of the multiple myeloma might be included in the differential diagnosis of hepatic mass

  2. Adjuvant Transarterial Chemoembolization Following Liver Resection for Intrahepatic Cholangiocarcinoma Based on Survival Risk Stratification

    OpenAIRE

    Jun LI; WANG, QING; Lei, Zhengqing; Wu, Dong; Si, Anfeng; Wang, Kui; Wan, Xuying; Wang, Yizhou; Yan, Zhenlin; Xia, Yong; LAU, WAN YEE; Wu, Mengchao; Shen, Feng

    2015-01-01

    The accurate predictive performance of the established prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) following liver resection was reconfirmed in an independent cohort with 553 patients. Based on the survival risk stratification using the nomogram, adjuvant transarterial chemoembolization following liver resection might be suitable only for ICC patients with high scores from the nomogram.

  3. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Mitesh J Borad

    2014-02-01

    Full Text Available Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM. In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.

  4. Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2, interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.

  5. Intrahepatic and hilar mass-forming cholangiocarcinoma: Qualitative and quantitative evaluation with diffusion-weighted MR imaging

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    Fattach, Hassan El, E-mail: hassangreenmed@gmail.com [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Dohan, Anthony, E-mail: anthony.dohan@lrb.aphp.fr [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris-Diderot, Sorbonne Paris Cité, 10 Avenue de Verdun, 75010 Paris (France); UMR INSERM 965-Paris 7 “Angiogenèse et recherche translationnelle”, 2 rue Amboise Paré, 75010 Paris (France); Guerrache, Youcef, E-mail: docyoucef05@yahoo.fr [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Dautry, Raphael, E-mail: raphael.dautry@lrb.aphp.fr [Department of Abdominal Imaging, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris-Diderot, Sorbonne Paris Cité, 10 Avenue de Verdun, 75010 Paris (France); and others

    2015-08-15

    Highlights: • DW-MR imaging helps depicts all intrahepatic or hilar mass-forming cholangiocarcinomas. • DW-MRI provides best conspicuity of intrahepatic or hilar mass-forming cholangiocarcinomas than the other MRI sequences (P < 0.001). • The use of normalized ADC using the liver as reference organ results in the most restricted distribution of ADC values of intrahepatic or hilar mass-forming cholangiocarcinomas (variation coefficient = 16.6%). - Abstract: Objective: To qualitatively and quantitatively analyze the presentation of intrahepatic and hilar mass-forming cholangiocarcinoma with diffusion-weighted magnetic resonance imaging (DW-MRI). Materials and methods: Twenty-eight patients with histopathologically proven mass-forming cholangiocarcinoma (hilar, n = 17; intrahepatic, n = 11) underwent hepatic DW-MRI at 1.5-T using free-breathing acquisition and three b-values (0,400,800 s/mm{sup 2}). Cholangiocarcinomas were evaluated qualitatively using visual analysis of DW-MR images and quantitatively with conventional ADC and normalized ADC measurements using liver and spleen as reference organs. Results: All cholangiocarcinomas (28/28; 100%) were visible on DW-MR images. DW-MRI yielded best conspicuity of cholangiocarcinomas than the other MRI sequences (P < 0.001). Seven cholangiocarcinomas (7/11; 64%) showed hypointense central area on DW-MR images. Conventional ADC value of cholangiocarcinomas (1.042 × 10{sup −3} mm{sup 2}/s ± 0.221 × 10{sup −3} mm{sup 2}/s; range: 0.616 × 10{sup −3} mm{sup 2}/s to 2.050 × 10{sup −3} mm{sup 2}/s) was significantly lower than that of apparently normal hepatic parenchyma (1.362 × 10{sup −3} mm{sup 2}/s ± 0.187 × 10{sup −3} mm{sup 2}/s) (P < 0.0001), although substantial overlap was found. No significant differences in ADC and normalized ADC values were found between intrahepatic and hilar cholangiocarcinomas. The use of normalized ADC using the liver as reference organ resulted in the most restricted

  6. Trousseau's Syndrome Caused by Intrahepatic Cholangiocarcinoma: An Autopsy Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Takashi Yuri

    2014-05-01

    Full Text Available An autopsy case report of Trousseau's syndrome caused by intrahepatic cholangiocarcinoma is presented, and seven previously reported cases are reviewed. A 73-year-old woman experiencing light-headedness and dementia of unknown cause for 6 months developed severe hypotonia. A hypointense lesion compatible with acute cerebral infarction was detected by magnetic resonance imaging. Abdominal computed tomography revealed an ill-defined large liver mass in the right lobe. The mass was not further investigated because of the patient's poor condition. She died of multiple organ failure, and an autopsy was conducted. Postmortem examination revealed intrahepatic cholangiocarcinoma, fibrous vegetations on the mitral valves and multiple thromboemboli in the cerebrum, spleen and rectum. Trousseau's syndrome is defined as an idiopathic thromboembolism in patients with undiagnosed or concomitantly diagnosed malignancy. This syndrome is encountered frequently in patients with mucin-producing carcinomas, while the incidence in patients with intrahepatic cholangiocarcinoma is uncommon. We found that tissue factor and mucin tumor marker (CA19-9, CA15-3 and CA-125 expression in cancer cells may be involved in the pathogenesis of thromboembolism. A patient with unexplained thromboembolism may have occult visceral malignancy; thus, mucin tumor markers may indicate the origin of a mucin-producing carcinoma, and postmortem examination may play an important role in revealing the hidden malignancy.

  7. Two classes of intrahepatic cholangiocarcinoma defined by relative abundance of mutations and copy number alterations.

    Science.gov (United States)

    Kim, Young-Ho; Hong, Eun-Kyung; Kong, Sun-Young; Han, Sung-Sik; Kim, Seoung-Hoon; Rhee, Je-Keun; Hwang, Soo-Kyung; Park, Sang-Jae; Kim, Tae-Min

    2016-04-26

    Intrahepatic cholangiocarcinoma (ICC) is a biliary tree-origin epithelial malignancy in liver with unfavorable clinical outcomes. Systematic genome analyses may advance our understanding of ICC pathogenesis also improving current diagnostic and therapeutic modalities. In this study, we analyzed 17 ICC tumor-vs-matched normal pairs using either whole-exome (n = 7), transcriptome sequencing (n = 7) or both platforms (n = 3). For somatic mutations, we identified recurrent mutations of previously reported genes such as KRAS, TP53, APC as well as epigenetic regulators and those of TGFβ signaling pathway. According to the abundance of somatic mutations and DNA copy number alterations (CNA), ten ICC exome cases were distinguished into two classes as those primarily driven by either somatic mutations (M class) or CNAs (C class). Compared to M class ICCs (92-147 somatic mutations; n = 5) with a relative deficit of CNAs, C class ICCs (54-84 mutations; n = 5) harbor recurrent focal CNAs including deletions involving CDKN2A, ROBO1, ROBO2, RUNX3, and SMAD4. We also show that transcriptome sequencing can be used for expression-based ICC categorization but the somatic mutation calling from the transcriptome can be heavily influenced by the gene expression level and potentially, by posttranscriptional modification such as nonsense mediated decay. Along with a substantial level of mutational heterogeneity of ICC genomes, our study reveals previously unrecognized two ICC classes defined by relative abundance of somatic mutations over CNAs or vice versa, which should be considered in the selection of genotyping platforms and sensitive screening of targets for ICC therapeutics.

  8. Two classes of intrahepatic cholangiocarcinoma defined by relative abundance of mutations and copy number alterations

    Science.gov (United States)

    Kim, Young-Ho; Hong, Eun-Kyung; Kong, Sun-Young; Han, Sung-Sik; Kim, Seoung-Hoon; Rhee, Je-Keun; Hwang, Soo-Kyung; Park, Sang-Jae; Kim, Tae-Min

    2016-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a biliary tree-origin epithelial malignancy in liver with unfavorable clinical outcomes. Systematic genome analyses may advance our understanding of ICC pathogenesis also improving current diagnostic and therapeutic modalities. In this study, we analyzed 17 ICC tumor-vs-matched normal pairs using either whole-exome (n = 7), transcriptome sequencing (n = 7) or both platforms (n = 3). For somatic mutations, we identified recurrent mutations of previously reported genes such as KRAS, TP53, APC as well as epigenetic regulators and those of TGFβ signaling pathway. According to the abundance of somatic mutations and DNA copy number alterations (CNA), ten ICC exome cases were distinguished into two classes as those primarily driven by either somatic mutations (M class) or CNAs (C class). Compared to M class ICCs (92–147 somatic mutations; n = 5) with a relative deficit of CNAs, C class ICCs (54–84 mutations; n = 5) harbor recurrent focal CNAs including deletions involving CDKN2A, ROBO1, ROBO2, RUNX3, and SMAD4. We also show that transcriptome sequencing can be used for expression-based ICC categorization but the somatic mutation calling from the transcriptome can be heavily influenced by the gene expression level and potentially, by posttranscriptional modification such as nonsense mediated decay. Along with a substantial level of mutational heterogeneity of ICC genomes, our study reveals previously unrecognized two ICC classes defined by relative abundance of somatic mutations over CNAs or vice versa, which should be considered in the selection of genotyping platforms and sensitive screening of targets for ICC therapeutics. PMID:27009864

  9. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas.

    Science.gov (United States)

    Wang, P; Dong, Q; Zhang, C; Kuan, P-F; Liu, Y; Jeck, W R; Andersen, J B; Jiang, W; Savich, G L; Tan, T-X; Auman, J T; Hoskins, J M; Misher, A D; Moser, C D; Yourstone, S M; Kim, J W; Cibulskis, K; Getz, G; Hunt, H V; Thorgeirsson, S S; Roberts, L R; Ye, D; Guan, K-L; Xiong, Y; Qin, L-X; Chiang, D Y

    2013-06-20

    Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79). Mutations in IDH1 or IDH2 were associated with longer overall survival (P=0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (P=0.021). IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors. PMID:22824796

  10. Decrease of deleted in malignant brain tumour-1 (DMBT-1) expression is a crucial late event in intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Sasaki, M; Huang, S-F; Chen, M-F;

    2003-01-01

    AIMS: To investigate the participation of DMBT-1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN-L) arising in hepatolithiasis. DMBT-1 plays a role in mucosal immune defence. METHODS AND RESULTS: The e...

  11. DIFFERENCE IN BIOLOGICAL CHARACTERISTICS AND SENSITIVITY TO CHEMOTHERAPY AND RADIOTHERAPY BETWEEN INTRAHEPATIC AND EXTRAHEPATIC CHOLANGIOCARCINOMA CELLS IN VITRO

    Institute of Scientific and Technical Information of China (English)

    Xiao-ran He; Xiao-peng Wu

    2008-01-01

    Objective To investigate and compare the biological characteristics and sensitivity to chemotherapy and radiother-apy of intrahepatic and extrahepatie cholangiocarcinoma cells in vitro.Methods The intrahepatic and extrahepatie eholangiocarcinoma cell lines were established, and cells with steady passage were chosen to study the biological characteristics including morphology, growth dynamics, chromosome, and levels of cancer antigen (CA)125, CA 19-9, alpha-fetoprotein (AFP), and carcino-embryonic antigen (CEA).M.eanwhile, MTT assay was used to determine the sensitivity of both kinds of cells to 6 chemotherapeutic drugs, inclu-ding cisplatin, paclitaxel, harringtonine, 5-fluorouracil, vincristine, and aelacimomycin, and the inhibitory rate of ceils under the irradiation of 10 Gy ray was also measured.Reanlts The intrahepatic cholangiocarcinoma cells were mostly fusiform in shape, and extrahepatic eholangiocar-cinoma cells were mostly round or polygon in shape. Their doubling time was 26. 3 hours and 23.1 hours, respectively.Their average number of chromosomes was 59 (range, 38-84) and 67 (range, 49-103 ), respectively. The chromo-some karyotypes of most intrahepatlc ebolangiocarcinoma cells were hyperdiploid and hypotriploid, while hypertriploid was predominant in extrahepatic cholangioearcinoma cells. The level of CA 125 in supernatant of extrahepatic cholangio-carcinoma cells increased obviously, while levels of other determined tumor markers in both kinds of cells were all with-in normal range. The intrahepatic cholangiocarcinoma cells were low sensitive to cisplatin and paclitaxel, but not sensi-tive to the other 4 chemotherapeutic drugs. The extrahepatic cholangiocarcinoma cells were high sensitive to eisplatin,but not sensitive to the other 5 drugs. Both kinds of cells had poor sensitivity to radiotherapy.Conelusions Intrahepatic and extrahepatie cbolangiocareinoma cells show differences in shape, doubling time,chromosome karyotype, tumor marker level, and

  12. Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion

    Institute of Scientific and Technical Information of China (English)

    Somchai Pinlaor; Mariko Murata; Reiji Semba; Shosuke Kawanishi; Banchob Sripa; Ning Ma; Yusuke Hiraku; Puangrat Yongvanit; Sopit Wongkham; Chawalit Pairojkul; Vajarabhongsa Bhudhisawasdi; Shinji Oikawa

    2005-01-01

    AIM: Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodG) formation has been implicated in initiation and/or promotion of inflammation-mediated carcinogenesis.The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma.METHODS: We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α (HIF-1α) with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma.RESULTS: Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors.HIF-1α expression was correlated with inducible nitric oxide synthase (iNOS) expression (r= 0.369 and P = 0.025)and 8-oxodG formation (r = 0.398 and P = 0.015).Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion (r = 0.386 and P= 0.018). Moreover, 8-nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion (P = 0.042and P = 0.026, respectively). These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis.CONCLUSION: The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.

  13. Intrahepatic cholangiocarcinoma in a patient with Wilson's disease: a case report.

    Science.gov (United States)

    Mukai, Yosuke; Wada, Hiroshi; Eguchi, Hidetoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Kawamoto, Koichi; Gotoh, Kunihito; Takeda, Yutaka; Tanemura, Masahiro; Umeshita, Koji; Hori, Yumiko; Morii, Eiichi; Doki, Yuichiro; Mori, Masaki

    2016-12-01

    The incidence of hepatobiliary malignancies, and especially intrahepatic cholangiocarcinoma (ICC), for patients with Wilson's disease (WD), is very low, even for cirrhotic patients. A 44-year-old male was admitted to our department for treatment of a liver tumor. He was diagnosed with WD at the age of 15. According to radiological findings, his liver tumor was a suspected hepatocellular carcinoma (HCC) or a combined hepatocellular and cholangiocellular carcinoma. A partial resection of liver segments 8 (S8) and 5 (S5) was subsequently performed due to the intraoperative suspicion of intrahepatic metastasis at the surface of S5. Postoperative histology revealed that the resected portion of S8 contained an ICC; the removed S5 portion comprised a regenerative nodule with hemosiderosis. To date, the patient has survived without tumor recurrence for more than 44 months following surgery. A survey of the literature, inclusive of case reports, would suggest that surgical resection is the primary course of action for a WD patient with ICC, if liver function can be preserved and curative resection performed. PMID:27005296

  14. Intrahepatic cholangiocarcinoma in a patient with Wilson's disease: a case report.

    Science.gov (United States)

    Mukai, Yosuke; Wada, Hiroshi; Eguchi, Hidetoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Kawamoto, Koichi; Gotoh, Kunihito; Takeda, Yutaka; Tanemura, Masahiro; Umeshita, Koji; Hori, Yumiko; Morii, Eiichi; Doki, Yuichiro; Mori, Masaki

    2016-12-01

    The incidence of hepatobiliary malignancies, and especially intrahepatic cholangiocarcinoma (ICC), for patients with Wilson's disease (WD), is very low, even for cirrhotic patients. A 44-year-old male was admitted to our department for treatment of a liver tumor. He was diagnosed with WD at the age of 15. According to radiological findings, his liver tumor was a suspected hepatocellular carcinoma (HCC) or a combined hepatocellular and cholangiocellular carcinoma. A partial resection of liver segments 8 (S8) and 5 (S5) was subsequently performed due to the intraoperative suspicion of intrahepatic metastasis at the surface of S5. Postoperative histology revealed that the resected portion of S8 contained an ICC; the removed S5 portion comprised a regenerative nodule with hemosiderosis. To date, the patient has survived without tumor recurrence for more than 44 months following surgery. A survey of the literature, inclusive of case reports, would suggest that surgical resection is the primary course of action for a WD patient with ICC, if liver function can be preserved and curative resection performed.

  15. Difference of hepatocellular carcinoma from intrahepatic cholangiocarcinoma as the cause of biliary obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Cho, June Sik; Kim, Dae Hong; Shin, Kyung Sook; Kwak, Jin Keun [Chungnam University Hospital, Taejon (Korea, Republic of)

    1998-04-01

    The purpose of this study is to evaluate the usefulness of dynamic CT during the hepatic arterial phase with rapid IV injection of contrast material in distinguishing hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICAC) as the cause of biliary obstruction. We retrospectively reviewed two-phase dynamic incremental CT or helical CT findings in 22 patients with intrahepatic duct obstruction secondary to pathologically proven HCCs (n=12) or ICACs (n=10). Two-phase CT scans were obtained 20 - 45 seconds (hepatic arterial phase) or 2 minutes (equilibrium phase) after the initiation of a bolus injection of contrast material (5 mL/sec, 150 mL). The enhancement patterns of tumors, as seen on two-phase images, were classified as hypo-, iso-, or hyperattenuated, relative to surrounding liver parenchyma. Two-phase images were compared and correlated with pathologic findings. Our results suggest that dynamic CT during the hepatic arterial phase, with rapid IV injection of contrast material, is useful for the differentiation of HCC from ICAC as the cause of biliary obstruction. (author). 20 refs., 1 tab., 4 figs.

  16. Sarcopenia as a prognostic factor in hepatolithiasis-associated intrahepatic cholangiocarcinoma patients following hepatectomy: a retrospective study

    OpenAIRE

    Zhou, Gongting; Bao, Haili; Zeng, Qiqiang; Hu, Weijian; Zhang, Qiyu

    2015-01-01

    Background: Sarcopenia is closely associated with poor performance status and high mortality in cancer patients. The present study is to determine the correlation between sarcopenia and prognosis of hepatectomy for hepatolithiasis-associated intrahepatic cholangiocarcinoma (IHHCC). Methods: Sixty-seven eligible IHHCC patients who underwent hepatectomy, between January 2000 and August 2014 were retrospectively evaluated. Sarcopenia was determined from skeletal muscle index (SMI), assessed by s...

  17. Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ubol Chuensumran; Sopit Wongkham; Chawalit Pairojkul; Siri Chauin; Songsak Petmitr

    2007-01-01

    AIM: To characterize and evaluate DNA alterations among intrahepatic cholangiocarcinoma (ICC) patients.METHODS: DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that alters most frequently in ICC was cloned, sequenced, and identified by comparison with known nucleotide sequences in the genome database (www.ncbi.nlm.nih.gov). The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by x2-test.The Kaplan-Meier method was used to analyze survival rates.RESULTS: From 33 primers, an altered DNA fragment (518 bp) amplified from BC17 random primer was found frequently in the tumors analyzed and mapped to chromosome 17p13.2. Sixteen of 52 (31%) cases showed DNA amplification, while 7 (13%) showed allelic loss. Interestingly, DNA amplification on chromosome 17p13.2 was associated with a good prognosis, median survival time (wk) of amp vs no amp was 44.14 vs 24.14,P = 0.002; whereas allelic loss of this DNA sequence corresponded with a poor prognosis, median survival time (wk) of loss vs no loss was 18.00 vs 28.71, P =0.019). Moreover, Kaplan-Meier curves comparing the DNA alterations with survival depicted highly significant separation that the median survival time equal to DNA amplification, allelic loss, and normal was 44.14 wk,18.00 wk, and 24.29 wk, respectively (P = 0.005).CONCLUSION: Alterations in the DNA sequence on chromosome 17p13.2 may be involved in cholangiocarcinogenesis, and could be used as a prognostic marker in the treatment of ICC patients.

  18. Claudin-7-positive synchronous spontaneous intrahepatic cholangiocarcinoma, adenocarcinoma and adenomas of the gallbladder in a Bearded dragon (Pogona vitticeps).

    Science.gov (United States)

    Jakab, Csaba; Rusvai, Miklós; Szabó, Zoltán; Gálfi, Péter; Marosán, Miklós; Kulka, Janina; Gál, János

    2011-03-01

    In this study, synchronous spontaneous, independent liver and gallbladder tumours were detected in a Bearded dragon (Pogona vitticeps). The multiple tumours consisted of intrahepatic cholangiocarcinoma as well as in situ adenocarcinoma and two adenomas of the gallbladder. The biliary epithelial cells and the cholangiocarcinoma showed membranous cross-immunoreactivity for claudin-7. The gallbladder epithelial cells, its adenoma and adenocarcinoma showed basolateral cross-reactivity for claudin-7. We think that the humanised anti-claudin-7 antibody is a good marker for the detection of different primary cholangiocellular and gallbladder tumours in Bearded dragons. The cholangiocytes, the cholangiocarcinoma, the endothelial cells of the liver and the epithelial cells and gallbladder tumours all showed claudin-5 cross-reactivity. The humanised anti-cytokeratin AE1-AE3 antibody showed cross-reactivity in the biliary epithelial cells, cholangiocarcinoma cells, epithelial cells and tumour cells of the gallbladder. It seems that this humanised antibody is a useful epithelial marker for the different neoplastic lesions of epithelial cells in reptiles. The humanised anti-α-smooth muscle actin (α-SMA) antibody showed intense cross-reactivity in the smooth muscle cells of the hepatic vessels and in the muscle layer of the gallbladder. The portal myofibroblasts, the endothelial cells of the sinusoids and the stromal cells of the cholangiocarcinoma and gallbladder tumours were positive for α-SMA. The antibovine anti-vimentin and humanised anti-Ki-67 antibodies did not show crossreactivity in the different samples from the Bearded dragon. PMID:21354945

  19. Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    YAN Xue-qiang; ZHANG Wei; ZHANG Bi-xiang; LIANG Hui-fang; ZHANG Wan-guang; CHEN Xiao-ping

    2013-01-01

    Background Smad4 is found mutated in many cancers.It acts as a tumor suppressor in the regulation of TGF-β signaling pathway.The objective of this work was to study the expression of Smad4 in intrahepatic cholangiocarcinoma (ICC) and its relationship with the biological behavior and prognosis of the disease.Methods Forty-nine paraffin-embedded ICC specimens and nine normal liver tissues were analyzed by immunohistochemical methods using Smad4 monoclonal antibodies.The expression of Smad4 was compared with the clinical pathological characteristics of the patients.Results The expression of Smad4 was 100% positive in normal liver tissues,which was higher than that in the ICC (44.9%).Negative labeling of the Smad4 protein was found in 26.1% (6/23) of well-differentiated ICCs and 61.5%(16/26) of poorly to moderately differentiated ICCs,and 34.3% (12/35) and 71.4% (10/14) showed negative Smad4 labeling (P=0.018) of ICC at pathological Tumor Node Metastasis (pTNM) stage Ⅰ-Ⅱ and pTNM stage Ⅲ-Ⅳ separately.Furthermore,72% (8/11) of lymph node metastatic ICCs and 73.3% (11/15) of intrahepatic metastatic ICCs showed negative labeling of the Smad4 protein.The loss of Smad4 expression in those metastatic ICCs was significantly more severe compared with non-metastatic ICCs (P=0.000).Conclusions The expression of Smad4 was associated with the histological grade,clinical stage,and metastasis of ICC (P <0.05).The detection of Smad4 may be helpful in determining the degree of malignancy and prognosis of ICC.

  20. Intrahepatic mass-forming cholangiocarcinoma: prognostic value of preoperative gadoxetic acid-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Jieun; Chung, Yong Eun; Kim, Myeong-Jin; Choi, Jin-Young [Yonsei University, College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Nahm, Ji Hae; Park, Young Nyun [Yonsei University, College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Kim, Ha Yan [Yonsei University, College of Medicine, Biostatistics Collaboration Unit, Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung-Sik [Yonsei University, College of Medicine, Department of General Surgery, Seoul (Korea, Republic of)

    2016-02-15

    To assess whether gadoxetic acid-enhanced MRI could be used as a prognostic factor for intrahepatic mass-forming cholangiocarcinomas (IMCCs). Forty-one patients with pathologically proven IMCCs who underwent preoperative gadoxetic acid-enhanced MRI were included. The signal intensity of the IMCCs on hepatobiliary phase (HBP) MRI was qualitatively analyzed by two radiologists, and categorized into intermediate or hypointense groups. Analysis of clinicopathological prognostic factors and correlations of imaging and histology were also performed. Survival time and time to recurrence (TTR) were analyzed. Of the 41 IMCCs, 23 were in the intermediate group and 18 were in the hypointense group on HBP MRI. IMCCs in the intermediate group were associated with shorter survival time (P = 0.048) and TTR (P = 0.002) than the IMCCs of the hypointense group. Only the intermediate group on HBP MRI had a significantly shorter TTR on multivariate analysis (P = 0.012). The IMCCs of the intermediate group showed a tendency for more abundant tumour fibrous stroma than those of the hypointense group (P = 0.027). The enhancement of IMCCs on HBP gadoxetic acid-enhanced MRI appears to correlate with tumour aggressiveness and outcomes due to the tumour fibrous stromal component. Thus, HBP images could be a useful prognostic factor for IMCCs after surgery. (orig.)

  1. MiR-145 functions as a tumor suppressor targeting NUAK1 in human intrahepatic cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Xinkui; Sun, Daoyi; Chai, Hao; Shan, Wengang [Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province (China); Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China); Yu, Yue [Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China); Pu, Liyong [Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province (China); Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China); Cheng, Feng, E-mail: docchengfeng@njmu.edu.cn [Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province (China); Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province (China)

    2015-09-18

    The dysregulation of micro (mi)RNAs is associated with cancer development. The miRNA miR-145 is downregulated in intrahepatic cholangiocarcinoma (ICC); however, its precise role in tumor progression has not yet been elucidated. Novel (nua) kinase family (NUAK)1 functions as an oncogene in various cancers and is a putative target of miR-145 regulation. In this study, we investigated the regulation of NUAK1 by miR-145 in ICC. We found that miR-145 level was significantly decreased in ICC tissue and cell lines, which corresponded with an increase in NUAK1 expression. NUAK1 was found to be a direct target of miR-145 regulation. The overexpression of miR-145 in ICC cell lines inhibited proliferation, growth, and invasion by suppressing NUAK1 expression, which was associated with a decrease in Akt signaling and matrix metalloproteinase protein expression. Similar results were observed by inhibiting NUAK1 expression. These results demonstrate that miR-145 can prevent ICC progression by targeting NUAK1 and its downstream effectors, and can therefore be useful for clinical diagnosis and targeted therapy of ICC. - Highlights: • MiR-145 suppresses ICC proliferation and invasion abilities. • We demonstrated that miR-145 directly targets NUAK1 in ICC. • MiR-145 expression in ICC was associated with Akt signaling and MMPs expression.

  2. Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: evidence from a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhou Yanming

    2012-07-01

    Full Text Available Abstract Background Studies investigating the association between Hepatitis B virus (HBV and hepatitis C virus (HCV infections and intrahepatic cholangiocarcinoma (ICC have reported inconsistent findings. We conducted a meta-analysis of epidemiological studies to explore this relationship. Methods A comprehensive search was conducted to identify the eligible studies of hepatitis infections and ICC risk up to September 2011. Summary odds ratios (OR with their 95% confidence intervals (95% CI were calculated with random-effects models using Review Manager version 5.0. Results Thirteen case–control studies and 3 cohort studies were included in the final analysis. The combined risk estimate of all studies showed statistically significant increased risk of ICC incidence with HBV and HCV infection (OR = 3.17, 95% CI, 1.88-5.34, and OR = 3.42, 95% CI, 1.96-5.99, respectively. For case–control studies alone, the combined OR of infection with HBV and HCV were 2.86 (95% CI, 1.60-5.11 and 3.63 (95% CI, 1.86-7.05, respectively, and for cohort studies alone, the OR of HBV and HCV infection were 5.39 (95% CI, 2.34-12.44 and 2.60 (95% CI, 1.36-4.97, respectively. Conclusions This study suggests that both HBV and HCV infection are associated with an increased risk of ICC.

  3. TAZ regulates cell proliferation and sensitivity to vitamin D3 in intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Xiao, Heng; Tong, Rongliang; Yang, Beng; Lv, Zhen; Du, Chengli; Peng, Chuanhui; Ding, Chaofeng; Cheng, Shaobing; Zhou, Lin; Xie, Haiyang; Wu, Jian; Zheng, Shusen

    2016-10-28

    The transcriptional coactivator with PDZ binding motif (TAZ) is reported as one of the nuclear effectors of Hippo-related pathways. TAZ is found overexpressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in Intrahepatic Cholangiocarcinoma (ICC). In this study, we found that TAZ is expressed more in ICC tissues than in peritumoral tissue, and a robust expression of TAZ is correlated with a lower overall survival rate of ICC patients after hepatectomy. TAZ knockdown results in an increase in cell apoptosis, a promotion of cell-cycle arrest and a decrease in tumor size and weight in vivo through an increased expression of p53. Vitamin D3 can also inhibit cell proliferation by promoting p53 expression in ICC cells. A reduction in TAZ can also enhance the sensitivity of tumor cells to vitamin D by regulating the p53/CYP24A1 pathway. In conclusion, TAZ is associated with the proliferation and drug-resistance of ICC cells, and could be a novel therapeutic target for the treatment of ICC.

  4. Risk factors for intrahepatic cholangiocarcinoma: A case- control study in China

    Institute of Scientific and Technical Information of China (English)

    Yan-Ming Zhou; Zheng-Feng Yin; Jia-Mei Yang; Bin Li; Wen-Yu Shao; Feng Xu; Yu-Lan Wang; Dian-Qi Li

    2008-01-01

    AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China.METHODS: A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus, hypertention, hepatolithiasis, primary sclerosing cholangitis, liver fluke infection (Clonorchis sinensis), was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression.RESULTS: Compared with controls, ICC patients had a higher prevalence of HBsAg seropositivity (48.4% vs 9.6%, P < 0.000), and hepatolithiasis (5.4% vs 1.1%, P = 0.001). By multivariate analysis, the significant risk factors for development of ICC were HBsAg seropositivity (adjusted OR, 8.876, 95% CI, 5.973-13.192), and hepatolithiasis (adjusted OR, 5.765, 95% CI, 1.972-16.851). The prevalence of anti-HCV seropositivity, diabetes mellitus, hypertention, cigarette smoking, and alcohol consumption were not significantly different between cases and controls.CONCLUSION: These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.

  5. Risk factors of intrahepatic cholangiocarcinoma in patients with hepatolithiasis:a case-control study

    Institute of Scientific and Technical Information of China (English)

    Zhen-YuLiu; Yan-MingZhou; Le-HuaShi; Zheng-FengYin

    2011-01-01

    BACKGROUND: Why 3.3% to 10% of all patients with hepatolithiasis develop intrahepatic cholangiocarcinoma (ICC) remains unknown. We carried out a hospital-based case-control study to identify risk factors for the development of ICC in patients with hepatolithiasis in China. METHODS: Eighty-sevenpatientswithpathologicallydiagnosed hepatolithiasis associated with ICC and 228 with hepatolithiasis alone matched by sex, age (±2 years), hospital admittance and place of residence were interviewed during the period of 2000-2008. Odds ratios (OR) and 95% confidence intervals (CI) were calculatedforeachriskfactor. RESULTS: Among the patients with hepatolithiasis associated with ICC, the mean age was 57.7 years and 61.0% were female. Univariate analysis showed that the significant risk factors for ICC development in hepatolithiasis were smoking, family history of cancer, appendectomy during childhood (under age 20), and duration of symptoms >10 years. In multivariate stepwise logistic regression analysis, smoking (OR=1.931, 95%CI: 1.000-3.731), family history of cancer (OR=5.175, 95% CI:1.216-22.022), and duration of symptoms >10 years (OR=2.348, 95% CI: 1.394-3.952) were independent factors. CONCLUSION: Smoking, family history of cancer and duration of symptoms >10 years may be risk factors for ICC in patients with hepatolithiasis.

  6. GNAS1 T393C Polymorphism Is Associated with Clinical Course in Patients with Intrahepatic Cholangiocarcinoma

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    Klaus J. Schmitz

    2007-02-01

    Full Text Available BACKGROUND/AIMS: The GNAS1 locus encodes the Gas protein, which stimulates the formation of cycloadenosinemonophosphate (cAMP. The cAMP pathway mediates pleiotropic effects, including the regulation of apoptosis and proliferation. We have recently shown that TT genotypes of the single-nucleotide polymorphism T393C in the gene GNAS1 predict the clinical outcome of patients with various carcinomas. METHODS: Eighty-seven patients with intrahepatic cholangiocarcinoma (ICC were retrospectively genotyped to elucidate a potential association between T393C genotypes and clinical outcome. RESULTS: ICCs of patients with homozygous TT genotypes revealed a higher proliferation rate and a lower apoptotic rate. Homozygous TT patients were at highest risk for cancer-related deaths (hazard ratio = 2.74; 95% confidence interval = 1.03-7.28 compared with C-allele carriers. Kaplan-Meier curves for disease-specific overall and local recurrence-free survival in a subgroup with Ro-resected ICC showed a significant association of T393 homozygosity with outcome, which was confirmed in multivariate Cox regression analysis. CONCLUSIONS: GNAS1 T393C is a novel independent host factor for disease progression in patients with ICC. Our finding that TT homozygosity (and not CC homozygosity was associated with unfavorable clinical outcome points to the complex and differing functional effects induced by GNAS1 T393C polymorphism in various human carcinomas.

  7. BSEP and MDR3: Useful Immunohistochemical Markers to Discriminate Hepatocellular Carcinomas From Intrahepatic Cholangiocarcinomas and Hepatoid Carcinomas.

    Science.gov (United States)

    Fujikura, Kohei; Yamasaki, Takashi; Otani, Kyoko; Kanzawa, Maki; Fukumoto, Takumi; Ku, Yonson; Hirose, Takanori; Itoh, Tomoo; Zen, Yoh

    2016-05-01

    We herein examined the immunohistochemical expression of 2 hepatocyte-specific transporters (bile salt export pump [BSEP] and multidrug-resistance protein 3 [MDR3]) in hepatocellular carcinomas (HCCs, n=54), intrahepatic cholangiocarcinomas (n=34), combined hepatocellular and cholangiocarcinomas (n=23), and hepatoid carcinomas originated from extrahepatic organs (n=27) to compare their diagnostic values with those of arginase-1 (ARG1) and hepatocyte paraffin-1 (HepPar-1). BSEP was expressed in 91% of HCCs and MDR3 in 83%. Although their sensitivities were slightly lower than those of ARG1 (96%) and HepPar-1 (93%), the 2 transporters appeared to be more specific for HCCs. ARG1 and HepPar-1 were expressed in intrahepatic cholangiocarcinomas (9% and 6%) and hepatoid carcinomas (22% and 44%, respectively), whereas BSEP and MDR3 were entirely negative in these neoplasms, except for 1 case of BSEP-positive hepatoid carcinoma of the esophagus. The highly specific expression of BSEP and MDR3 in hepatocytes was recapitulated in additional examinations of combined hepatocellular and cholangiocarcinomas, in which the expression of the transporters was restricted to morphologically hepatocellular areas. In contrast, ARG1 and HepPar-1 were also variably positive in areas of biliary or indeterminate differentiation. We also applied BSEP and MDR3 immunohistochemistry to 8 biopsy cases of poorly differentiated primary liver cancer, in which the original diagnosis was not conclusive. The diagnosis of HCC was retrospectively suggested in 2 cases expressing both BSEP and MDR3. In conclusion, given the highly specific expression of BSEP and MDR3 in HCCs, immunohistochemistry for these transporters will be useful not only for determining hepatocellular differentiation in primary liver cancers but also for discriminating HCCs from hepatoid carcinomas. PMID:26735860

  8. Mutations in Isocitrate Dehydrogenase 1 and 2 Occur Frequently in Intrahepatic Cholangiocarcinomas and Share Hypermethylation Targets with Glioblastomas

    OpenAIRE

    Wang, Pu; Dong, Qiongzhu; Zhang, Chong; Kuan, Pei-Fen; Liu, Yufeng; Jeck, William R.; Andersen, Jesper B.; JIANG, Wenqing; Savich, Gleb L.; Tan, Ting-Xu; Auman, J. Todd; Hoskins, Janelle M; Misher, Anne D.; Moser, Catherine D.; Yourstone, Scott M

    2012-01-01

    Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas, and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine (5hmC) and higher 5-methylcytosine (5mC) levels, as well as increased dimethylation of histone H3K79. Mutations in IDH1 or IDH2 were associated with longer overall survival (p...

  9. Hepatitis B virus infection: A favorable prognostic factor for intrahepatic cholangiocarcinoma after resection

    Institute of Scientific and Technical Information of China (English)

    Hua-Bang Zhou; Meng-Chao Wu; He-Ping Hu; Hui Wang; Yu-Qiong Li; Shuang-Xi Li; Hao Wang; Dong-Xun Zhou; Qian-Qian Tu; Qing Wang; Shan-Shan Zou

    2011-01-01

    AIM: To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. METHODS: A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or in liver tissue. Clinicopathological characteristics and survival rate of the patients were evaluated. RESULTS: All patients underwent anatomical resection. Their 1- and 3-year survival rates were 60.6% and 32.1%, respectively. Multivariate analyses revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were the independent prognostic factors for the survival rate of ICC patients. The median disease-free survival time of the patients was 5.0 mo. The number of tumors, microscopic satellite lesion, and vascular invasion were the independent prognostic factors for the disease-free survival rate of the patients. The prognostic factors affecting the survival rate of ICC patients with HBV infection and those without HBV infection were not completely consistent. Alkaline phosphatase > 119 U/L, microscopic satellite lesion, vascular invasion, and lymphatic metastasis were the independent factors for the patients with HBV infection, while r-glutamyltransferase > 64 U/L, microscopic satellite lesion, and poor tumor differentiation were the independent factors for the patients without HBV infection. CONCLUSION: HBV infection is a valuable clinical factor for predicting tumor invasiveness and clinical outcome of ICC patients. ICC patients with HBV infection should be distinguished from those without HBV infection because they have different clinicopathological characteristics, prognostic factors and outcomes after surgical

  10. Differentiating mass-forming intrahepatic cholangiocarcinoma from atypical hepatocellular carcinoma using gadoxetic acid-enhanced MRI

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    Chong, Y.S. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Y.K., E-mail: jmyr@dreamwiz.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, M.W.; Kim, S.H.; Lee, W.J.; Rhim, H.C.; Lee, S.J. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-08-15

    Aim: To examine the differential features of mass-forming intrahepatic cholangiocarcinoma (ICC) from atypical hypovascular hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). Materials and methods: The institutional review board approved this retrospective study and waived informed patient consent. Seventy patients with pathologically proven ICCs (35) and hypovascular atypical HCCs (35) who had undergone preoperative gadoxetic acid-enhanced MRI were enrolled in this study. Images were analysed for the shape of the lesions and presence of hyperintensity on the T1-weighted image (T1WI) and hypo- or hyperintense areas on the T2-weighted image (T2WI). In addition, images were analysed for the presence of linear hyperintensity or multifocal, tiny, hyperintense foci on T2WI and the presence of rim enhancement during early dynamic phases and a central enhancement with a hypointense rim (target appearance) on the 10 and 20 min hepatobiliary phase images. The significance of these findings was determined by the X{sup 2} test. Results: Univariate analysis revealed that the following significant parameters favour ICC or hypovascular HCC; the presence of T2 hypo- and hyperintense areas and target appearance on the 10 min hepatobiliary phase images favour ICC, and the presence of T2 linear hyperintensity and T2 multifocal hyperintense foci favour hypovascular HCC (p < 0.05). Multivariate analysis revealed that only target appearance on the 10 min hepatobiliary phase was predictive of ICC (p = 0.002) as 30 ICCs (85.7%) showed this feature. However, the target appearance was also observed in all six scirrhous HCCs. Conclusion: A target appearance on the 10 min hepatobiliary phase images is the best predictor for identifying mass-forming ICC at gadoxetic acid-enhanced MRI.

  11. Distinct Clinicopathologic and Genetic Features of 2 Histologic Subtypes of Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Hayashi, Akimasa; Misumi, Kento; Shibahara, Junji; Arita, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro; Fukayama, Masashi

    2016-08-01

    Previous studies have identified 2 clinically significant morphologic subtypes of intrahepatic cholangiocarcinoma (ICC) on the basis of anatomic location and/or histologic appearances. Recognizing that these classification schemes are not always applicable practically, this study aimed to establish a novel classification system based on mucin productivity and immunophenotype and to determine the rationale of this classification by examining the clinicopathologic and genetic characteristics of the 2 subtypes defined by this method. We retrospectively investigated 102 consecutive ICC cases and classified them on the basis of mucin productivity and immunophenotype (S100P, N-cadherin, and NCAM). We found that 42 and 56 cases were classified as type 1 and type 2 ICCs, respectively, and only 4 cases were of indeterminate type. Type 1 ICC, generally characterized by mucin production and diffuse immunoreactivity to S100P, arose less frequently in chronic liver diseases and showed higher levels of serum CEA and CA 19-9 than did type 2 ICC, which generally showed little mucin production and exhibited immunoreactivity to N-cadherin and/or NCAM. Type 1 ICC was characterized by several pathologic features, including higher frequencies of perineural invasion and lymph node metastasis. Although the log-rank test demonstrated that type 1 ICC had significantly worse survival, the multivariate Cox regression analysis showed no prognostic significance of this histologic subtype. Genetic analyses revealed that KRAS mutation was significantly more frequent in type 1 ICC, whereas IDH mutation and FGFR2 translocation were restricted to type 2 ICC. In conclusion, the present classification of ICC based on mucin productivity and immunophenotype identified 2 subtypes with clinicopathologic significance.

  12. Knockdown of Sall4 inhibits intrahepatic cholangiocarcinoma cell migration and invasion in ICC-9810 cells.

    Science.gov (United States)

    Zhu, Lei; Huang, Feizhou; Deng, Gang; Nie, Wanpin; Huang, Wei; Xu, Hongbo; Zheng, Shaopeng; Yi, Zhongjie; Wan, Tao

    2016-01-01

    In spite of improvements in surgical technology, the resectability and curability of intrahepatic cholangiocarcinoma (ICC) are still low. Our previous study showed that the strong Sal-like protein 4 (Sall4)-positive cases had shorter overall survival compared to Sall4-negative cases, indicating an oncogenic role of Sall4 in ICC. In this study, we aimed to explore the precise mechanism of Sall4 on ICC cell invasion and metastasis. We evaluated the expression of Sall4, PTEN, and Bmi-1 in 28 cases of adjacent tissues and 175 cases of ICC tissues by using immunohistochemical staining. We found that the expression of Sall4 and Bmi-1 was significantly increased in ICC tissues compared with the adjacent tissues, while PTEN expression was reduced in ICC tissues compared with the adjacent tissues, and there was a reverse relationship between Sall4 and PTEN in ICC, whereas there was a positive correlation in Sall4 and Bmi-1 expression in ICC. In addition, overall survival analysis showed that ICC patients with low PTEN exhibited a worse prognosis than ICC patients with high PTEN, and lower Bmi-1 expression showed a better prognosis than ICC patients with high Bmi-1. By a battery of experiments in vitro, we demonstrated that Sall4 promotes ICC cell proliferation, and progression of ICC might be through PTEN/PI3K/Akt and Bmi-1/Wnt/β-catenin signaling and enhancing epithelial-mesenchymal transition process. Thus, Sall4 may be a potential target for the treatment of ICC metastasis.

  13. Influence of surgical margins on overall survival after resection of intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Tang, Haowen; Lu, Wenping; Li, Bingmin; Meng, Xuan; Dong, Jiahong

    2016-01-01

    Abstract Background: Surgical resection is shown to present the best chance of cure in the treatment of intrahepatic cholangiocarcinoma (ICC). However, the appropriate length of the negative margin remains unclear. The aim of the present meta-analysis was to investigate whether a clear margin of 10 mm or more (≥10 mm) conferred any survival benefit over a margin of less than 10 mm (Web of Science, EMBASE, and the Cochrane Library were systematically searched to identify eligible studies published in English from the initiation of the databases to February 2016. Overall survival rates were pooled by using the hazard ratio and the corresponding 95% confidence interval (CI). Random-effect models were utilized because of between-study heterogeneity. Results: Six studies (eight cohorts) reporting on 712 patients were analyzed: 269 (37.80%) were in the 10 mm or more negative margin group, and 443 (62.20%) were in the less than 10 mm negative margin group. The pooled hazard ratio for the less than 10 mm group was found to be 1.59 (95% CI: 1.09–2.32) when this group was compared with the 10 mm or more group (reference), with moderate between-study heterogeneity (I2 = 45.30%, P = 0.07). Commensurate results were identified by sensitivity analysis. Conclusion: The result of this meta-analysis suggests a long-term survival (overall survival) advantage for negative margins of 10 mm or more in comparison with negative margins less than 10 mm for patients undergoing surgical resection of ICC. PMID:27583880

  14. Effect of transforming growth factor-β1 on human intrahepatic cholangiocarcinoma cell growth

    Institute of Scientific and Technical Information of China (English)

    Tetsuya Shimizu; Takashi Tajiri; Shigeki Yokomuro; Yoshiaki Mizuguchi; Yutaka Kawahigashi; Yasuo Arima; Nobuhiko Taniai; Yasuhiro Mamada; Hiroshi Yoshida; Koho Akimaru

    2006-01-01

    AIM: To elucidate the biological effects of transforming growth factor-β1 (TGF-β1) on intrahepatic cholangiocarcinoma (ICC).METHODS: We investigated the effects of TGF-β1 on human ICC cell lines (HuCCT1, MEC, and HuH-28) by monitoring the influence of TGF-β1 on tumor growth and interleukin-6 (IL-6) expression in ICC cells.RESULTS: All three human ICC cell lines produced TGF-β1 and demonstrated accelerated growth in the presence of TGF-β1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-β1-induced stimulation of the expression of TGF-β1, as well as a decrease in TGF-β1 mRNA expression induced by neutralizing anti-TGF-β1 antibody. These results indicate that TGF-β1 stimulates the production and function of TGF-β1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-β1 antibody. Experiments using HuCCT1 revealed a TGF-β1-induced acceleration of IL-6 protein expression and mRNA levels. These findings demonstrate a functional interaction between TGF-β1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-β1 induced no growth effect in HuCCT1 in the presence of small interfering RNA against a specific cell surface receptor of IL-6 and signal transducer and activator of transcription-3.CONCLUSION: ICC cells produce TGF-β1 and confer a TGF-β1-induced growth effect in an autocrine fashion.TGF-β1 activates IL-6 production, and the functional interaction between TGF-β1 and IL-6 contributes to ICC cell growth by TGF-β1.

  15. Yttrium-90 Radioembolization for Unresectable Standard-chemorefractory Intrahepatic Cholangiocarcinoma: Survival, Efficacy, and Safety Study

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    Rafi, Shoaib; Piduru, Sarat M. [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States); El-Rayes, Bassel; Kauh, John S. [Emory University School of Medicine, Department of Hematology and Medical Oncology (United States); Kooby, David A.; Sarmiento, Juan M. [Emory University School of Medicine, Department of Surgical Oncology in Surgery (United States); Kim, Hyun S., E-mail: kevin.kim@emory.edu [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States)

    2013-04-15

    To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 {+-} 193 [95 % confidence interval (CI) 374-1130] and 345 {+-} 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 {+-} 190 (95 % CI 78-822) and 345 {+-} 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 {+-} 309 (95 % CI 0-1010) days versus 345 {+-} 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. Y90 radioembolization is effective for unresectable standard-chemorefractory ICC.

  16. Change in total lesion glycolysis and clinical outcome after 90Y radioembolization in intrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Introduction: Our aim was to assess the prognostic value of post-treatment decrease in total lesion glycolysis (ΔTLG) assessed by 2-[18 F]-fluorodeoxyglucose ([18 F] FDG) PET-CT performed 6 weeks after 90Y radioembolization (90Y RE) in patients affected by intrahepatic cholangiocarcinoma (ICC). Methods: A total of 18 patients were accepted into our department for 90Y RE. Before the procedure, all patients underwent [18 F] FDG PET-CT, and total lesion glycolysis was calculated. Six weeks after 90Y administration, PET scan was performed, and ΔTLG was determined. Patients underwent follow up by imaging and laboratory at quarterly intervals until death or for at least 24 months from 90Y RE. Furthermore, subjects were divided in 2 groups (group 1: 6 weeks ΔTLG > 50%, group 2: ΔTLG < 50%). Kaplan–Meier method was used to achieve time to progression (TTP) and overall survival (OS) curves for each group. TTP and OS curves were compared to demonstrate eventual relevant differences between the 2 groups. Results: Seventeen patients underwent 90Y RE, and one subject was considered ineligible. According to PET Response Criteria in Solid Tumors, partial response was found in 14 patients (82.4%), stable disease in 3 (17.6%). No patient showed complete metabolic response. The mean OS for all patients was 64.5 ± 5.0 weeks. Subjects with a ΔTLG > 50% and ΔTLG < 50% had a mean OS of 79.6 ± 3.6 and 43.1 ± 2.0 weeks, respectively (p < 0.001). TTP resulted of 28.9 ± 3.8 weeks for the whole cohort. Patients with ΔTLG > 50% had a significantly longer TTP (mean 36.9 ± 3.6 weeks) than those with ΔTLG < 50% (mean 13.7 ± 1.7 weeks, p = 0.001). Conclusion: Our results indicate that 90Y RE can be an effective and safe therapy for ICC. ΔTLG calculated on post-treatment [18 F] FDG PET-CT agrees with patients' final outcome

  17. Delayed-Phase Cone-Beam CT Improves Detectability of Intrahepatic Cholangiocarcinoma During Conventional Transarterial Chemoembolization

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    Schernthaner, Ruediger Egbert [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology (United States); Lin, MingDe [Philips Research North America, Ultrasound and Interventions (United States); Duran, Rafael; Chapiro, Julius; Wang, Zhijun; Geschwind, Jean-François, E-mail: jfg@jhmi.edu [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology (United States)

    2015-08-15

    PurposeTo evaluate the detectability of intrahepatic cholangiocarcinoma (ICC) on dual-phase cone-beam CT (DPCBCT) during conventional transarterial chemoembolization (cTACE) compared to that of digital subtraction angiography (DSA) with respect to pre-procedure contrast-enhanced magnetic resonance imaging (CE-MRI) of the liver.MethodsThis retrospective study included 17 consecutive patients (10 male, mean age 64) with ICC who underwent pre-procedure CE-MRI of the liver, and DSA and DPCBCT (early-arterial phase (EAP) and delayed-arterial phase (DAP)) just before cTACE. The visibility of each ICC lesion was graded by two radiologists on a three-rank scale (complete, partial, and none) on DPCBCT and DSA images, and then compared to pre-procedure CE-MRI.ResultsOf 61 ICC lesions, only 45.9 % were depicted by DSA, whereas EAP- and DAP-CBCT yielded a significantly higher detectability rate of 73.8 % and 93.4 %, respectively (p < 0.01). Out of the 33 lesions missed on DSA, 18 (54.5 %) and 30 (90.9 %) were revealed on EAP- and DAP-CBCT images, respectively. DSA depicted only one lesion that was missed by DPCBCT due to streak artifacts caused by a prosthetic mitral valve. DAP-CBCT identified significantly more lesions than EAP-CBCT (p < 0.01). Conversely, EAP-CBCT did not detect lesions missed by DAP-CBCT. For complete lesion visibility, DAP-CBCT yielded significantly higher detectability (78.7 %) compared to EAP (31.1 %) and DSA (21.3 %) (p < 0.01).ConclusionDPCBCT, and especially the DAP-CBCT, significantly improved the detectability of ICC lesions during cTACE compared to DSA. We recommend the routine use of DAP-CBCT in patients with ICC for per-procedure detectability and treatment planning in the setting of TACE.

  18. Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Nisana Tepsiri; Liengchai Chaturat; Banchob Sripa; Wises Namwat; Sopit Wongkham; Vajarabhongsa Bhudhisawasdi; Wichittra Tassaneeyakul

    2005-01-01

    AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase P1 (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined.METHODS: Five human CCA cell lines (KKU-100, KKU M055, KKU-M156, KKU-M214 and KKU-OCA17) weretreated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC50 values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC50 values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC50 values (<5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC50 values of etoposide, doxorubicin and pirarubicin (r = 0.86-0.98, ,P<0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug

  19. Dynamic enhancement patterns of intrahepatic cholangiocarcinoma in cirrhosis on contrast-enhanced computed tomography: risk of misdiagnosis as hepatocellular carcinoma.

    Science.gov (United States)

    Li, Rui; Cai, Ping; Ma, Kuan-Sheng; Ding, Shi-Yi; Guo, De-Yu; Yan, Xiao-Chu

    2016-01-01

    This study aimed to assess the features of intrahepatic cholangiocarcinoma (ICC) at computerized tomography (CT) and verify the risk of misdiagnosis of ICC as hepatocellular carcinoma (HCC) in cirrhosis. CT appearances of 98 histologically confirmed ICC nodules from 84 cirrhotic patients were retrospectively reviewed, taking into consideration the pattern and dynamic contrast uptake during the arterial, portal venous and delayed phases. During the arterial phase, 53 nodules (54.1%) showed peripheral rim-like enhancement, 35 (35.7%) hyperenhancement, 9 (9.2%) hypoenhancement and 1 (1.0%) isoenhancement. The ICC nodules showed heterogeneous dynamic contrast patterns, being progressive enhancement in 35 nodules (35.7%), stable enhancement in 28 nodules (28.6%), wash-in and wash-out pattern in 15 nodules (15.3%) and all other enhancement patterns in 20 nodules (20.4%). There were no significant differences in the dynamic vascular patterns of ICC according to nodule size (p > 0.05). ICC in cirrhosis has varied enhancement patterns at contrast-enhanced multiphase multidetector CT. Though the majority of ICC did not display typical radiological hallmarks of HCC, if dynamic CT scan was used as the sole modality for the non-invasive diagnosis of nodules in cirrhosis, the risk of misdiagnosis of ICC for HCC is not negligible.

  20. Ring finger protein 43 expression is associated with genetic alteration status and poor prognosis among patients with intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Talabnin, Chutima; Janthavon, Patcharee; Thongsom, Sunisa; Suginta, Wipa; Talabnin, Krajang; Wongkham, Sopit

    2016-06-01

    Ring finger E3 ligases have roles in processes central to maintenance of genomic integrity and cellular homeostasis. Many ring finger E3 ligases are implicated in malignancy. Ring finger protein 43 (RNF43) is a ring finger E3 ligase that negatively regulates the Wnt/β-catenin signaling pathway. RNF43 is frequently mutated in several types of malignancy, including intrahepatic cholangiocarcinoma (ICC). The significance of its expression in ICC has not, however, been reported. We determined RNF43 expression and identified RNF43 polymorphisms in ICC tissues. We also investigated the correlation between RNF43 expression and RNF43 mutation status, RNF43 polymorphisms, clinicopathological features, and prognosis of ICC patients. RNF43 reduced expression in ICC, and the reduction of RNF43 messenger RNA expression was significantly correlated with the presence of rs2257205 and RNF43 somatic mutations, confirming that all RNF43 somatic mutations in ICC are inactivating. Overall survival was worst in patients with down-regulation of RNF43. Univariate and multivariate analyses revealed that RNF43 expression was an independent prognostic factor. There was no statistically significant association between RNF43 messenger RNA and protein expression nor any clinicopathological features or RNF43 polymorphisms. The results imply that RNF43 is down-regulated in ICC and may play a crucial role during development of ICC.

  1. Coffee consumption and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma by sex: The Liver Cancer Pooling Project

    Science.gov (United States)

    Petrick, Jessica L.; Freedman, Neal D.; Graubard, Barry I.; Sahasrabuddhe, Vikrant V.; Lai, Gabriel Y.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Boggs, Deborah A.; Buring, Julie E.; Chan, Andrew T.; Chong, Dawn Q.; Fuchs, Charles S.; Gapstur, Susan M.; Gaziano, John Michael; Giovannucci, Edward L.; Hollenbeck, Albert R.; King, Lindsay Y.; Koshiol, Jill; Lee, I-Min; Linet, Martha S.; Palmer, Julie R.; Poynter, Jenny N.; Purdue, Mark P.; Robien, Kim; Schairer, Catherine; Sesso, Howard D.; Sigurdson, Alice J.; Zeleniuch-Jacquotte, Anne; Wactawski-Wende, Jean; Campbell, Peter T.; McGlynn, Katherine A.

    2015-01-01

    Background Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Methods In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC n=860, ICC n=260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Results Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; ptrend cups/day=3 cups/day vs. non-drinker, 0.71, 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no relationship between coffee consumption and ICC. Conclusions These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. Impact Further research into specific coffee compounds and mechanisms that may account for these associations is needed. PMID:26126626

  2. Contrast-Enhanced Ultrasound in the Diagnosis of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Controversy over the ASSLD Guideline

    Directory of Open Access Journals (Sweden)

    Le-Hang Guo

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC and intrahepatic cholangiocarcinoma (ICC are both regarded as primary liver cancers, having different biological behaviors and prognoses. Correct differentiation between them is essential for surgical planning and prognosis assessment. In 2005, the American Association for the Study of Liver Diseases (AASLD recommended that noninvasive diagnosis of HCC is achievable by a single dynamic technique (including contrast-enhanced ultrasound (CEUS showing intense arterial uptake followed by washout of contrast in the venous-delayed phases. However, CEUS has been dropped from the diagnostic techniques in the latest AASLD guideline according to the opinion of some authors from Europe that CEUS may offer false positive HCC diagnosis in patients with ICC. Since the update of AASLD guideline has been released, increased attention has been paid to this interesting topic. Remarkable controversy over this issue is present and this removal was not well received in Europe and Asia. This commentary summarized the opinions for the role of CUES in differentiation between HCC and ICC in recent years. It is concluded that prospective studies with strict design and large case series are mandatory to solve the controversies and stratification of ICC in terms of tumor size and liver background is also essential.

  3. Differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma on gadoxetic acid-enhanced liver MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rihyeon; Shin, Cheong-Il; Yoon, Jeong Hee; Joo, Ijin; Kim, Seong Ho; Hwang, Inpyeong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Lee, Jeong Min; Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Seoul (Korea, Republic of); Lee, Eun Sun; Choi, Byung Ihn [Chung-Ang University Hospital, Department of Radiology, Seoul (Korea, Republic of)

    2016-06-15

    To determine the different imaging features of intrahepatic mass-forming cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). This retrospective study was institutional review board approved and the requirement for informed consent was waived. Patients who underwent gadoxetic acid-enhanced MRI with histologically confirmed IMCCs (n = 46) or HCCs (n = 58) were included. Imaging features of IMCCs and HCCs on gadoxetic acid-enhanced MRI including T2- and T1-weighted, diffusion weighted images, dynamic study and hepatobiliary phase (HBP) images were analyzed. Univariate and multivariate logistic regression analyses were performed to identify relevant differentiating features between IMCCs and HCCs. Multivariate analysis revealed heterogeneous T2 signal intensity and a hypointense rim on the HBP as suggestive findings of IMCCs and the wash-in and ''portal wash-out'' enhancement pattern as well as focal T1 high signal intensity foci as indicative of HCCs (all, p < 0.05). When we combined any three of the above four imaging features, we were able to diagnose IMCCs with 94 % (43/46) sensitivity and 86 % (50/58) specificity. Combined interpretation of enhancement characteristics including HBP images, morphologic features, and strict application of the ''portal wash-out'' pattern helped more accurate discrimination of IMCCs from HCCs. (orig.)

  4. Intrahepatic cholangiocarcinoma diagnosed via endoscopic retrograde cholangiopancreatography with a short double-balloon enteroscope

    OpenAIRE

    Ikeura, Tsukasa; Shimatani, Masaaki; Takaoka, Makoto; Matsushita, Mitsunobu; Miyoshi, Hideaki; Kurishima, Akiko; Sumimoto, Kimi; Miyamoto, Sachi; Okazaki, Kazuichi

    2013-01-01

    Endoscopic retrograde cholangiopancreatography (ERCP) using a double-balloon enteroscope (DBE) in patients with bowel reconstruction due to a previous abdominal surgery is now widely accepted. In particular, a short DBE, which has a 2.8-mm working channel and 152-cm working length, is useful for ERCP because of its good rotational and straightening ability and the availability of various conventional ERCP accessories through the working channel. Herein we report a case of intrahepatic cholang...

  5. Taurolithocholic acid promotes intrahepatic cholangiocarcinoma cell growth via muscarinic acetylcholine receptor and EGFR/ERK1/2 signaling pathway.

    Science.gov (United States)

    Amonyingcharoen, Sumet; Suriyo, Tawit; Thiantanawat, Apinya; Watcharasit, Piyajit; Satayavivad, Jutamaad

    2015-01-01

    Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract and its occurrence is associated with chronic cholestasis which causes an elevation of bile acids in the liver and bile duct. The present study aimed to investigate the role and mechanistic effect of bile acids on the CCA cell growth. Intrahepatic CCA cell lines, RMCCA-1 and HuCCA-1, were treated with bile acids and their metabolites to determine the growth promoting effect. Cell viability, cell cycle analysis, EdU incorporation assays were conducted. Intracellular signaling proteins were detected by western immunoblotting. Among eleven forms of bile acids and their metabolites, only taurolithocholic acid (TLCA) concentration dependently (1-40 µM) increased the cell viability of RMCCA-1, but not HuCCA-1 cells. The cell cycle analysis showed induction of cells in the S phase and the EdU incorporation assay revealed induction of DNA synthesis in the TLCA-treated RMCCA-1 cells. Moreover, TLCA increased the phosphorylation of EGFR, ERK 1/2 and also increased the expression of cyclin D1 in RMCCA-1 cells. Furthermore, TLCA-induced RMCCA-1 cell growth could be inhibited by atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, AG 1478, a specific EGFR inhibitor, or U 0126, a specific MEK 1/2 inhibitor. These results suggest that TLCA induces CCA cell growth via mAChR and EGFR/EKR1/2 signaling pathway. Moreover, the functional presence of cholinergic system plays a certain role in TLCA-induced CCA cell growth.

  6. Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009

    Institute of Scientific and Technical Information of China (English)

    Murad Aljiffry; Mark J Walsh; Michele Molinari

    2009-01-01

    Several advances in diagnosis, treatment and palliation of cholangiocarcinoma (CC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. CC is a relatively rare tumor and the main risk factors are: chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree. While the incidence of intra-hepatic CC is increasing, the incidence of extra-hepatic CC is trending down. The only curative treatment for CC is surgical resection with negative margins. Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy. Magnetic resonance imaging/ magnetic resonance cholangiopancreatography, positron emission tomography scan, endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging. Adjuvant therapy, palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC. For most of these patients biliary stenting provides effective palliation. Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief, improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization, hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.

  7. Selecting molecular therapeutic drug targets based on the expression profiles of intrahepatic cholangiocarcinomas and miRNA-mRNA regulatory networks.

    Science.gov (United States)

    Sun, Boshi; Xie, Changming; Zheng, Tongsen; Yin, Dalong; Wang, Jiabei; Liang, Yingjian; Li, Yuejin; Yang, Guangchao; Shi, Huawen; Pei, Tiemin; Han, Jihua; Liu, Lianxin

    2016-01-01

    The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing yearly, making it the second most common carcinoma after hepatocellular carcinoma among primary malignant liver tumors. Integrated miRNA and mRNA analysis is becoming more frequently used in antitumor ICC treatment. However, this approach generates vast amounts of data, which leads to difficulties performing comprehensive analyses to identify specific therapeutic drug targets. In this study, we provide an in-depth analysis of ICC function, identifying potential highly potent antitumor drugs for antitumor therapy. Two sets of whole genome expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Using modular bioinformatic analysis, six core functional modules were identified for ICC. Based on a Fisher's test of the Cmap small molecule drug database, 65 drug components were identified that regulated the genes of these six core modules. Literature mining was then used to identify 15 new potential antitumor drugs. PMID:26498995

  8. Recurrent Amplification at 13q34 Targets at CUL4A, IRS2, and TFDP1 As an Independent Adverse Prognosticator in Intrahepatic Cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Ting-Ting Liu

    Full Text Available Amplification of genes at 13q34 has been reported to be associated with tumor proliferation and progression in diverse types of cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA has yet to be explored. We examined two iCCA cell lines and 86 cases of intrahepatic cholangiocarcinoma to analyze copy number of three target genes, including cullin 4A (CUL4A, insulin receptor substrate 2 (IRS2, and transcription factor Dp-1 (TFDP1 at 13q34 by quantitative real-time polymerase chain reaction. The cell lines and all tumor samples were used to test the relationship between copy number (CN alterations and protein expression by western blotting and immunohistochemical assays, respectively. IRS2 was introduced, and each target gene was silenced in cell lines. The mobility potential of cells was compared in the basal condition and after manipulation using cell migration and invasion assays. CN alterations correlated with protein expression levels. The SNU1079 cell line containing deletions of the target genes demonstrated decreased protein expression levels and significantly lower numbers of migratory and invasive cells, as opposed to the RBE cell line, which does not contain CN alterations. Overexpression of IRS2 by introducing IRS2 in SUN1079 cells increased the mobility potential. In contrast, silencing each target gene showed a trend or statistical significance toward inhibition of migratory and invasive capacities in RBE cells. In tumor samples, the amplification of each of these genes was associated with poor disease-free survival. Twelve cases (13.9% demonstrated copy numbers > 4 for all three genes tested (CUL4A, IRS2, and TFDP1, and showed a significant difference in disease-free survival by both univariate and multivariate survival analyses (hazard ratio, 2.69; 95% confidence interval, 1.23 to 5.88; P = 0.013. Our data demonstrate that amplification of genes at 13q34 plays an oncogenic role in iCCA featuring adverse disease

  9. Cholangiocarcinoma and malignant bile duct obstruction: Areview of last decades advances in therapeutic endoscopy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In the last decades many advances have been achievedin endoscopy, in the diagnosis and therapy ofcholangiocarcinoma,however blood test, magneticresonance imaging, computed tomography scan mayfail to detect neoplastic disease at early stage, thus thediagnosis of cholangiocarcinoma is achieved usuallyat unresectable stage. In the last decades the roleof endoscopy has moved from a diagnostic role toan invaluable therapeutic tool for patients affectedby malignant bile duct obstruction. One of the majorissues for cholangiocarcinoma is bile ducts occlusion,leading to jaundice, cholangitis and hepatic failure.Currently, endoscopy has a key role in the work upof cholangiocarcinoma, both in patients amenable tosurgical intervention as well as in those unfit for surgeryor not amenable to immediate surgical curative resectionowing to locally advanced or advanced disease, withpalliative intention. Endoscopy allows successful biliarydrainage and stenting in more than 90% of patientswith malignant bile duct obstruction, and allows rapidreduction of jaundice decreasing the risk of biliary sepsis.When biliary drainage and stenting cannot be achievedwith endoscopy alone, endoscopic ultrasound-guidedbiliary drainage represents an effective alternativemethod affording successful biliary drainage in morethan 80% of cases. The purpose of this review is tofocus on the currently available endoscopic managementoptions in patients with cholangiocarcinoma.

  10. Irinotecan drug eluting beads used as a treatment of advanced intra hepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Jean Amede Roch

    2008-10-01

    Full Text Available

    This report describes a 74-year-old male with unresectable intrahepatic cholangiocarcinoma (ICC. However surgical procedure is the only curative treatment, it often seems to be ineffective because of the aggressive behaviour of the disease. The role of systemic chemotherapy in the ICC is undefined with a median survival between 6.43 to 12.17 months obtained by using the combination chemotherapy of gemcitabine with cisplatin. In the present case, we performed a targeted treatment using drug eluting beads (DEB with irinotecan (IRI administered as transarterial-chemoembolization (TACE. After one session, the tumour vascularity decreased significantly at the one month evaluation on computed tomography (CT scan of the liver.  This case report suggested that minimally invasive transcatheter DEB embolization could be a promising, safe and effective treatment for selective patients with unresectable ICC.

  11. Cholelithiasis and the risk of intrahepatic cholangiocarcinoma: a Meta-analysis%胆道结石并发肝内胆管癌风险的Meta分析

    Institute of Scientific and Technical Information of China (English)

    朱征海; 蔡浩; 顾盐炎; 赵万文; 胡伟东; 陈超波

    2015-01-01

    目的 明确肝外胆管结石及胆囊结石并发肝内胆管癌(Intrahepatic cholangiocarcinoma,ICC)风险,为胆道结石的临床治疗提供参考.方法 计算机检索PubMed、EmBase以及CBM等数据库,查找胆道结石以及胆囊结石并发ICC风险的队列研究或者病例对照研究.应用STATA软件对所获得研究数据行Meta分析,根据研究间异质性选择固定效应模型或者随机效应模型.采用Egger检验评估发表偏倚.结果 共有6篇病例对照研究纳入分析,包括123 713例患者,其中ICC 4 753例,无瘤对照118 960例.Meta分析结果显示,胆管结石为ICC发病的高危因素(OR:17.64,95% CI:11.14 ~27.95),除外肝内胆管结石,肝外胆管结石导致的ICC发病风险仍较高(OR:11.79,95% CI:4.17~ 33.35).此外,胆囊结石也是ICC发病危险因素(OR:2.07,95% CI:1.17 ~3.67).结论 肝外胆管结石与胆囊结石均为ICC发病的重要危险因素.%Objective To clarify the association of pre-existing choledocholithiasis or cholecystolithiasis and the development of intrahepatic cholangiocarcinoma(ICC).Methods A computerized literature search was performed in Pubmed,EmBase and CBM.Cohort and case control studies on the risk of choledocholithiasis or cholecystolithiasis developing ICC was included.Meta-analysis was performed using STATA version 12.0.Either a fix or random effect model was used according to heterogeneity among studies.Egger's test was performed to assess publication bias.Results A total of 6 case control studies fulfilled our inclusion criteria including 123,713 patients,4,753 for ICC and 118,960 for tumor free controls.Bile duct stone contributed to the development of ICC (OR:15.64,95% CI 9.33-26.23).Apart from hepatolithiasis,there was still a high risk of ICC development for choledocholithiasis (OR:11.05,95 % CI:4.02 ~ 30.37).Cholecystolithiasis is also a risk factor for ICC (OR:2.35,95 % CI:1.28 ~ 4.31).Conclusion Both choledocholithiasis and

  12. Immunohistochemical expression of mismatch repair genes: A screening tool for predicting mutator phenotype in liver fluke infection-associated intrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Upama Liengswangwong; Anant Karalak; Yukio Morishita; Masayuki Noguchi; Thiravud Khuhaprema; Petcharin Srivatanakul; Masanao Miwa

    2006-01-01

    AIM: To clarify possible contributions of DNA mismatch repair (MMR) system in carcinogenesis of liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) by using immunohistochemical assay.METHODS: A total of 29 ICC samples, which had been assessed for genomic instability by a PCR-based method, were used for study. They were examined immunohistochemically to demonstrate protein expression of two MMR genes, hMSH2 and hMLH1.Results obtained were compared with their mutator phenotype assessed previously.RESULTS: Either hMSH2or hMLH1 protein was obviously expressed in 28 of 29 (96.6%) ICC samples.Positive nuclear localization of hMSH2 or hMLH1 protein was observed in 86.2% (25/29) or 93.1% (27/29) ICC cases, respectively, while their negative nuclear reactivity was only detected in 13.8% (4/29) or 6.9% (2/29) ICC cases analyzed, respectively.CONCLUSION: Our study, probably for the first time,showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associated cholangiocarcinogenesis. These results confirm previous findings on mutational status of these genes assessed through a PCR-based method. The immunohistochemical analysis has proven to be an effective and sensitive approach for screening MMR deficiency regardless of somatic inactivation or promoter hypermethylation of hMSH2 and/or hMLH1 gene. Furthermore,immunohistochemistry is more advantageous compared to mutator phenotyping assay in terms of simplicity,less time consuming and cost effectiveness for screening possible involvements of target MMR genes in tumorigenesis.

  13. Effects of WWOX on metastasis of intrahepatic cholangiocarcinoma%WWOX对肝内胆管细胞癌转移的影响

    Institute of Scientific and Technical Information of China (English)

    方雯; 徐三荣; 李相成; 张海

    2014-01-01

    目的:检测包含WW域的氧化还原酶(WW domain containing oxidoreductase,WWOX)在肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)组织及细胞的表达情况,分析其表达水平与ICC临床特征的相关性,并探索其对ICC细胞迁移、侵袭能力的影响.方法:采用半定量/定量PCR测定ICC组织及细胞中WWOX的表达水平;转染重组质粒pcDNA3.1B-WWOX-Flag,过表达ICC细胞内的WWOX水平;采用细胞划痕及侵袭实验,观察过表达WWOX对ICC迁移、侵袭能力的影响;蛋白免疫印迹检测迁移、侵袭通路相关分子.结果:WWOX在ICC组织及细胞中表达下调,其下调与ICC的转移明显相关(P<0.05);转染pcDNA3.1B-WWOX-Flag质粒可上调ICC细胞WWOX蛋白的表达;过表达WWOX抑制ICC细胞迁移、侵袭能力(P< 0.001);过表达WWOX可激活细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)磷酸化,进而下调基质金属蛋白酶9的活性,最终抑制ICC的转移过程.结论:WWOX在ICC中表达下调,体外实验证实过表达WWOX抑制ICC的迁移、侵袭能力.

  14. Metabolic characteristics distinguishing intrahepatic cholangiocarcinoma: a negative pilot study of (18)F-fluorocholine PET/CT clarified by transcriptomic analysis.

    Science.gov (United States)

    Kwee, Sandi A; Okimoto, Gordon S; Chan, Owen Tm; Tiirikainen, Maarit; Wong, Linda L

    2016-01-01

    PET using fluorine-18 fluorocholine ((18)F-fluorocholine) may detect malignancies that involve altered choline metabolism. While (18)F-fluorocholine PET/CT has shown greater sensitivity for detecting hepatocellular carcinoma (HCC) than (18)F-fluoro-D-deoxyglucose (FDG) PET/CT, it is not known whether it can also detect intrahepatic cholangiocarcinoma (ICC), a less common form of primary liver cancer. Clinical, radiographic, and histopathologic data from 5 patients with ICC and 23 patients with HCC from a diagnostic trial of liver (18)F-fluorocholine PET/CT imaging were analyzed to preliminarily evaluate (18)F-fluorocholine PET/CT for ICC. Imaging was correlated with whole-genome expression profiling to identify molecular pathways associated with tumor phenotypes. On PET/CT, all ICC tumors demonstrated low (18)F-fluorocholine uptake with a significantly lower tumor to mean background uptake ratio than HCC tumors (0.69 vs. 1.64, p ICC and HCC patients (8.0 vs. 7.7, p = 0.74). Two ICC patients demonstrated increased tumor metabolism on FDG PET/CT, while immunohistochemical analysis of ICC tumors revealed overexpression of glucose transporter 1 (GLUT-1) and hexokinase indicating a hyper-glycolytic phenotype. Gene expression analysis revealed down-regulation of farnesoid-X-receptor and other lipid pathways in ICC relative to HCC, and up-regulation of glycolytic pathways and GLUT-1 by HIF1α. These results imply limited utility of (18)F-fluorocholine in ICC, however, significant metabolic differences between ICC, HCC, and parenchymal liver tissue may still provide clues about the underlying liver pathology. Gene and protein expression analysis support hyperglycolysis as a more dominant metabolic trait of ICC.

  15. Proposal of a new staging system for intrahepatic cholangiocarcinoma: Analysis of surgical patients from a nationwide survey of the Liver Cancer Study Group of Japan

    Science.gov (United States)

    Sakamoto, Yoshihiro; Matsuyama, Yutaka; Sakamoto, Michiie; Izumi, Namiki; Kadoya, Masumi; Kaneko, Shuichi; Ku, Yonson; Kudo, Masatoshi; Takayama, Tadatoshi; Nakashima, Osamu

    2016-01-01

    BACKGROUND In the current American Joint Committee on Cancer/International Union Against Cancer staging system (seventh edition) for intrahepatic cholangiocarcinoma (ICC), tumor size was excluded, and periductal invasion was added as a new tumor classification‐defining factor. The objective of the current report was to propose a new staging system for ICC that would be better for stratifying the survival of patients based on data from the nationwide Liver Cancer Study Group of Japan database. METHODS Of 756 patients who underwent surgical resection for ICC between 2000 and 2005, multivariate analyses of the clinicopathologic factors of 419 patients who had complete data sets were performed to elucidate relevant factors for inclusion in a new tumor classification and staging system. RESULTS Overall survival data were best stratified using a cutoff value of 2 cm using a minimal P value approach to discriminate patient survival. The 5‐year survival rate of 15 patients who had ICC measuring ≤2 cm in greatest dimension without lymph node metastasis or vascular invasion was 100%, and this cohort was defined as T1. Multivariate analysis of prognostic factors for 267 patients with lymph node‐negative and metastasis‐negative (N0M0) disease indicated that the number of tumors, the presence arterial invasion, and the presence major biliary invasion were independent and significant prognostic factors. The proposed new system, which included tumor number, tumor size, arterial invasion, and major biliary invasion for tumor classification, provided good stratification of overall patient survival according to disease stage. Macroscopic periductal invasion was associated with major biliary invasion and an inferior prognosis. CONCLUSIONS The proposed new staging system, which includes a tumor cutoff size of 2 cm and major biliary invasion, may be useful for assigning patients to surgery. Cancer 2016;122:61–70. © 2015 The Authors. Cancer published by Wiley

  16. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Jensen, Lars Henrik; Sorensen, Morten;

    2011-01-01

    Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (C......), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC)....

  17. Intrahepatic cholestasis without jaundice

    Institute of Scientific and Technical Information of China (English)

    Thomas Namdar; Andreas Raffel; Stefan Andreas Topp; Jan Schulte am Esch; Günther Fürst; Wolfram Trudo Knoefel; Claus Ferdinand Eisenberger

    2009-01-01

    BACKGROUND: Cholangiocarcinoma (CC), the most common biliary tract malignancy, is frequently seen in advanced unresectable stages and is typically localized extrahepatically. Early diagnosis is unusual because of nonspeciifc symptoms. Painless jaundice is usually the ifrst sign of tumor. METHOD: We present a patient with a CC (Klatskin tumor) with a complete biliary drainage by an aberrant bile duct without jaundice. RESULTS: A 67-year-old woman presented with persisting elevation of liver parameters. Diagnostic tests showed a Klatskin tumor typeⅡ. A curative right hepatic trisegmentectomy was performed after liver volume augmentation by preoperative vein embolization. CONCLUSIONS: A direct drainage of the right posterior bile duct into the common bile duct as an aberrant hepatic duct is a rare variation and is present in less than 5% of the population. In case of persistently perturbed liver function tests, an aberrant bile duct can cover up severe intrahepatic cholestasis and even obscure the diagnosis of a Klatskin tumor. Up to now it has not been described in the literature.

  18. Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma:Detection by oligonucleotide microarray and real-time PCR analysis

    Institute of Scientific and Technical Information of China (English)

    Holger G Hass; Oliver Nehls; Juergen Jobst; Andrea Frilling; Ulrich Vogel; Stephan Kaiser

    2008-01-01

    AIM: To investigate the molecular pathways involved in human cholangiocarcinogenesis by gene expression profiling.METHODS: Oligonucleotide arrays (Affymetr/x U133A)were used to establish a specific gene expression profile of intrahepatic CCC in comparison to corresponding nonmalignant liver tissue.To validate the expression values of the most overexpressed genes, RT-PCR experiments were performed.RESULTS: Five hundred and fifty-two statistically differentially expressed genes/ESTs (221 probes significantly up-regulated, 331 probes down-regulated;P2;≥70%) were identified.Using these data and two-dimensional cluster analysis,a specific gene expression profile was obtained allowing fast and reproducible differentiation of CCC, which was confirmed by supervised neuronal network modelling.The most consistently overexpressed gene (median fold change 33.5, significantly overexpressed in 100%)encoded osteopontin.Furthermore, an association of various genes with the histopathological grading could be demonstrated.CONCLUSION: A highly specific gone expression profile for intrahepatic CCC was identified, allowing for its fast and reproducible discrimination against nonmalignant liver tissue and other liver masses.The most overexpressed gene in intrahepatic CCC was the gene encoding osteopontin.These data may lead to a better understanding of human cholangiocarcinogenesis.

  19. Perihilar cholangiocarcinoma: Current therapy

    Institute of Scientific and Technical Information of China (English)

    Wei; Zhang; Lu-Nan; Yan

    2014-01-01

    Perihilar cholangiocarcinoma, which is a rare primary malignancy, originates from the epithelial cells of the bile duct. Usually invading the periductal tissues and the lymph nodes, perihilar cholangiocarcinoma is commonly diagnosed in the advanced stage of the disease and has a dismal prognosis. Currently, complete hepatectomy is the primary therapy for curing this disease. Perioperative assessment and available surgical procedures can be considered for achieving a negative margin resection, which is associated with long-term survival and better quality of life. For patients with unresectable cholangiocarcinoma, several palliative treatments have been demonstrated to produce a better outcome; and liver transplantation for selected patients with perihilar cholangiocarcinoma is promising and desirable. However, the role of palliative treatments and liver transplantation was controversial and requires more evidence and substantial validity from multiple institutions. In this article, we summarize the data from multiple institutions and discuss the resectability, mortality, morbidity and outcome with different approaches.

  20. Diagnosis and treatment for advanced hilar cholangiocarcinoma: experience of 24 cases

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this paper is to evaluate the efficacy of the surgical treatment for advanced hilar cholangiocarcinoma(CCA)in order to improve the resection rate and curative effect.A retrospective analysis was performed on the data of 24 patients who had undergone surgical treatment for advanced hilar CCA.According to the Bismuth classification,there were four cases of type IIIa,six cases of type IIIb,and 14 cases of type Ⅳ.Based on the treatment approaches,these resection group:There were five cases(one type Ⅲa,three type Ⅲb,and one type Ⅳ).The tumor visible to the naked eyes was resected thoroughly and the cut margin was free of tumor by microscopic examination.Then,Roux-en-Y hepatico-jejunal anastomosis was pergroup:There were 11 cases.The bile flow was restored by Roux-en-Y hepatico-jejunal anastomosis directly in five cases(two type Ⅲa,three type Ⅲb)and by internal drainage through a hepatico-jejunal bridge in the other biliary drainage group:There were eight cases of type Ⅳ,including three cases with the internal drainage through hepatico-jejunal bridge by laparotomy,three cases with endoscopic retrograde biliary drainage(ERBD),two cases with percutaneous transhepatic biliary drainage(PTBD).The rate of radical resection was 20.8% and the overall resection rate was 66.7%.All of the 24 patients were followed-up.The cumulative surviving rates were significantly different among these three groups(Log-rank X2=17.56,P=0.0002).For advanced hilar CCA,the best choice of treatment is radical resection.If radical resection is impractical,palliative resection combined with partial hepatectomy can significantly prolong the survival time.Internal drainage through a hepatico-jejunal bridge can enhance the surgical resection rate and decrease the occurrence rate of postoperative biliary leakage.

  1. Diagnosis and initial management of cholangiocarcinoma with obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    Takashi Tajiri; Hiroshi Yoshida; Yasuhiro Mamada; Nobuhiko Taniai; Shigeki Yokomuro; Yoshiaki Mizuguchi

    2008-01-01

    Cholangiocarcinoma is the second most common primary hepatic cancer. Despite advances in diagnostic techniques during the past decade, cholangiocarcinoma is usually encountered at an advanced stage. In this review,we describe the classification, diagnosis, and initial management of cholangiocarcinoma with obstructive jaundice.

  2. 腹腔淋巴结清扫对肝内胆管细胞癌预后影响的系统评价%Effect of abdominal lymphadenectomy on prognosis of intrahepatic cholangiocarcinoma: a systematic review and Meta analysis

    Institute of Scientific and Technical Information of China (English)

    曾永毅; 黎蕴通; 张翔

    2016-01-01

    Objective To systematically review the prognostic factors of intrahepatic cholangiocarcinoma (ICC) and clinical significance of abdominal lymphadenectomy.Methods PubMed was queried with the terms of "intrahepatic cholangiocarcinoma,survival,surgery,lymph or vascular invasion" to find all studies published from January 2005 to December 2015.Authors were contacted by letters for the publications that were initially ineligible due to insufficient information for data extraction,responses were received,so these publications were included.Data were analyzed and evaluated by 2 independent researchers.Prognostic factors of ICC (vascular invasion,bile duct invasion,lymphatic vessel invasion,lymph node metastasis and peripheral nerve invasion) and related-factors of surgical method (R0 resection and lymph node dissected) were analyzed.The 3-,5-year survival rate,tumor-free survival rate and effect of lymph node dissected for prognosis of patients were extracted.Heterogeneity was analyzed by the chi-squared test and I2 test.The hazard ratio (HR) and 95% confidence interval (CI) were transformed to Log (HR) and standard errors (SE) Log (HR).HR and 95% CI of clinical factors associated with outcomes were done using univariate COX regression models.Publication bias was evaluated by the Egger's method,visualizing with funnel plot.Results A total of 48 publications including 7 868 patients with ICC were eligible to be included in this analysis,12 of 48 publications were included in the Mata analysis.Of 7 868 patients with ICC,vascular invasion,bile duct invasion,lymphatic vessel invasion,lymph node metastasis,peripheral nerve invasion,R0 resection and lymph node dissected were detected in 30% (5%-98%),40% (11%-59%),45% (35%-65%),28% (9%-100%),25% (7%-55%),79% (35%-100%) and 64% (9%-100%),respectively.The 3-,5-year survival rate and 3-,5-year tumor-free survival rate were 39% (16%-65%),29%(5%-60%) and 34% (3%-60%),23

  3. Co‑expression of the carbamoyl‑phosphate synthase 1 gene and its long non‑coding RNA correlates with poor prognosis of patients with intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Ma, Sen-Lin; Li, Ai-Jun; Hu, Zhao-Yang; Shang, Fu-Sheng; Wu, Meng-Chao

    2015-12-01

    The mechanisms leading to high rates of malignancy and recurrence of human intrahepatic cholangiocarcinoma (ICC) remain unclear. It is difficult to diagnose and assess the prognosis of patients with ICC in the clinic due to the lack of specific biomarkers. In addition, long non‑coding RNAs (lncRNAs) have been reported to serve important roles in certain types of tumorigenesis however a role in ICC remains to be reported. The aim of the current study was to screen for genes and lncRNAs that are abnormally expressed in ICC and to investigate their biological and clinicopathological significance in ICC. The global gene and lncRNA expression profiles in ICC were measured using bioinformatics analysis. Carbamoyl‑phosphate synthase 1 (CPS1) and its lncRNA CPS1 intronic transcript 1 (CPS1‑IT1) were observed to be upregulated in ICC. The expression of CPS1 and CPS1‑IT1 was measured in 31 tissue samples from patients with ICC and a number of cell lines. The effects of CPS1 and CPS1‑IT1 on the proliferation and apoptosis of the ICC‑9810 cell line were measured. In addition, the clinicopathological features and survival rates of patients with ICC with respect to the gene and lncRNA expression status were analyzed. CPS1 and CPS1‑IT1 were co‑upregulated in ICC tissues compared with non‑cancerous tissues. Knockdown of CPS1 andor CPS1‑IT1 reduced the proliferation and increased the apoptosis of ICC‑9810 cells. Additionally, clinical analysis indicated that CPS1 and CPS1‑IT1 were associated with poor liver function and reduced survival rates when the relative expression values were greater than 4 in cancer tissues. The comparisons between the high CPS1 expression group and the low expression group indicated significant differences in international normalized ratio (P=0.048), total protein (P=0.049), indirect bilirubin (P=0.025), alkaline phosphatase (P=0.003) and disease‑free survival (P=0.034). In addition, there were differential trends in CA19‑9

  4. INTRAHEPATIC CHOLELITHIASIS

    Directory of Open Access Journals (Sweden)

    M. MEHDI HAFIZI

    1987-05-01

    Full Text Available A case o f Intrahepatic stone and its t r eat ment i s present e d . The t ype s o f i ntrahepatic s tones , t h e etiological f act o r , t he ways of di agno s is and t reatment a re b eing discussed. The disease is common in far Eastern c ountri es a nd Asian Are a, with c lonorchi s s i nens is inf estation, but s peci ally in Iran when the s tones i s a lone in Intrahepatic ducts without extrahepatic duc t stone,as this case repor t , i s very rare.

  5. Mucins and NCAM (CD56 in intrahepatic cholangiocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Anna Beatriz Telles Esperança

    2014-06-01

    Full Text Available Introduction: Cholangiocarcinoma is the second most common malignant neoplasm of the hepatobiliary system. During cholangiocarcinogenesis phenotypic changes occur in the ductal epithelium, including the expression of mucins (MUC. However, the evaluating studies of the expression of mucins in the different stages of cholangiocarcinogenesis are scarce. CD56 has also contributed in differentiating benign ductal proliferation and cholangiocarcinoma; however, its expression has not been evaluated in dysplastic epithelium of the bile duct yet. Objective: To assess immunohistochemical profile of (MUC 1, 2, 5, 6, and CD56 in cholangiocarcinoma, pre-neoplastic and reactive lesions in the epithelium of intrahepatic bile ducts. Material and methods: Immunohistochemical expression of MUC 1, 2, 5, 6, and CD56 were studied for 11 cases of cholangiocarcinoma and 83 intrahepatic bile ducts (67 reactive and 16 dysplastic. Variables were considered significant when p < 0.05. Results: The expression of MUC1 occurred in about 90% of the cholangiocarcinomas, contrasting with the low frequency of positive cases in reactive and dysplastic bile ducts (p < 0.001. However, there was no statistically significant difference in the expression of MUC5, MUC6 and CD56 between the reactive or dysplastic lesions and cholangiocarcinoma. The anti-MUC2 antibody was negative in all cases. Conclusions: MUC1 contributed for the differential diagnosis between cholangiocarcinoma and pre-neoplastic and reactive/regenerative lesions of intrahepatic bile ducts, and it should compose the antibodies panel aiming at improvement of these differential diagnoses. In contrast, MUC2, MUC5, MUC6 and CD56 were not promising in differentiating all the phases of cholangiocarcinogenesis.

  6. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Jensen, Lars Henrik; Sorensen, Morten;

    2011-01-01

    INTRODUCTION: Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O......) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC). METHODS: In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours and no other treatments...... or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC. RESULTS: Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1 and 15, and C 1 000 mg/m(2...

  7. Cholangiocarcinoma, gone without the Wnt?

    Science.gov (United States)

    Noll, Anne Tr; Cramer, Thorsten; Olde Damink, Steven Wm; Schaap, Frank G

    2016-09-18

    Cholangiocarcinoma (CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7B and Wnt10A were found to be highly overexpressed in human CCA tissue. Wnt7B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68(+) macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA. Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10a increased during the (pre-cancerous) regenerative phase, while Wnt7b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion, eliminating a major source of Wnt7b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover, specific inhibitors of the canonical Wnt pathway (ICG-001 and C-59) caused reduction of tumor area and number, in xenograft and

  8. 动态增强CT和MRI扫描在诊断肝内周围性肿块型胆管细胞癌中的应用分析%Application of dynamic enhanced CT and MRI scan in diagnosis of intrahepatic peripheral cystic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    孙冰

    2015-01-01

    Objective: To analyze the application of dynamic enhanced CT and MRI scan in diagnosis of intrahepatic pe-ripheral cystic cholangiocarcinoma.Methods:In February 2013 to February to the hospital diagnosised as intrahepatic cholan-giocarcinoma patients with peripheral mass type 52 cases as the object of study. All patients underwent dynamic enhanced CT and MRI scanning, of two different diagnostic methods of clinical results were analyzed.Results: CT plain scan all the lesions showed slightly low density, MRI t1w1 showed slightly low signal, T2W2 showed slightly higher signal; dynamic enhanced scan, 52 cases of CT scan in patients with 20 cases of delayed enhancement after were obvious characteristics. MRI scanning in 16 cases in arterial phase and portal venous phase lesions around a line like enhancement, edge enhancement in 8 cases after delayed scan-ning showed obvious porphyritic strengthening; the accurate rate of CT diagnosis was 98.08%, the accuracy of MRI diagnosis of 96.15%, the difference was not significant (P>0.05).Conclusion:The diagnostic accuracy of CT and MRI scan in diagnosis of intrahepatic peripheral cystic carcinoma is high, and the image is clear, which provides theoretical basis for clinical treatment.%目的:分析动态增强CT和MRI扫描在诊断肝内周围性肿块型胆管细胞癌中的应用价值。方法选取于2013年2月至2014年2月来院经诊断确诊为肝内周围性肿块型胆管细胞癌患者52例作为研究对象,均行动态增强CT和MRI扫描,对两种不同诊断方法的临床结果进行分析。结果 CT平扫所有肿块均呈稍低密度,MRI平扫T1W1呈稍低信号, T2W2呈稍高信号;动态增强扫描时,52例CT扫描患者中20例延迟强化后均后特征明显,MRI扫描中16例患者动脉期、门静脉期病灶周围呈线状样强化,边缘强化8例延迟扫描后呈明显的斑状强化;CT诊断的准确率为98.08%,MRI诊断的准确率为96.15%,差异不显著(P>0.05)。

  9. Radiofrequency ablation of recurrent cholangiocarcinoma after orthotopic liver transplantation - a case report

    Institute of Scientific and Technical Information of China (English)

    Rakesh Rai; Derek Manas; John Rose

    2005-01-01

    AIM: To report the use of radiofrequency ablation in the treatment of recurrenct cholangiocarcinoma in the transplanted liver.METHODS: A lady who underwent orthotopic liver transplantation (OLT) for intrahepatic cholangiocarcinoma recurrence of tumour 13 mo after tralsplantation inspite of adjuvant chemotherapy. Her recurrent tumour was treated with radiofrequency ablation.RESULTS: She survived for 18 mo following the recurrence of her tumour.CONCLUSION: Radiofrequency ablation can be used safely in the transplanted liver to treat recurrent tumour.

  10. Pathological and Molecular Biological Fundament of CT Features of Intrahepatic Cholangiocarcinoma%肝内胆管癌CT表现的病理学和分子生物学基础

    Institute of Scientific and Technical Information of China (English)

    乔慧洁; 王滨

    2004-01-01

    肝内胆管癌(intrahepatic cholangiocarcinoma。ICC)又称胆管细胞癌或外周型胆管癌,是肝脏第二高发的原发恶性肿瘤,仅次于肝细胞癌(hepatocellular carcinoma,HCC)。ICC发生率较低,占原发性肝癌的3.25%,研究人员临床观察结果显示,近年来ICC的发病率呈上升趋势。ICC具有发生隐匿、发展迅速、

  11. Cancer review: Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Yezaz Ahmed Ghouri

    2015-01-01

    Full Text Available Cholangiocarcinoma (CCA is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the last decades, CCA incidence rates had significantly increased. In addition to known established risk factors, novel possible risk factors (i.e. obesity, hepatitis C virus have been identified that are of high importance in developed countries where CCA prevalence rates have been low. CCA tends to develop on the background of inflammation and cholestasis. In recent years, our understanding of the molecular mechanisms of cholangiocarcinogenesis has increased, thereby, providing the basis for molecularly targeted therapies. In its diagnostic evaluation, imaging techniques have improved, and the role of complementary techniques has been defined. There is a need for improved CCA biomarkers as currently used ones are suboptimal. Multiple staging systems have been developed, but none of these is optimal. The prognosis of CCA is considered dismal. However, treatment options have improved throughout the last two decades for carefully selected subgroups of CCA patients. Perihilar CCA can now be treated with orthotopic liver transplantation with neoadjuvant chemoradiation achieving 5-year survival rates of 68%. Classically considered chemotherapy-resistant, the ABC-02 trial has shown the therapeutic benefit of combination therapy with gemcitabine and cisplatin. The benefits of adjuvant treatments for resectable CCA, local ablative therapies and molecularly targeted therapies still need to be defined. In this article, we will provide the reader with an overview over CCA, and discuss the latest developments and controversies.

  12. Progressive familial intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Tomohide Hori; Justin H. Nguyen; Shinji Uemoto

    2010-01-01

    BACKGROUND: Three types of progressive familial intrahepatic cholestasis (PFIC) have been identiifed, but their etiologies include unknown mechanisms. DATA SOURCES: A PubMed search on "progressive familial intrahepatic cholestasis" and "PFIC" was performed on the topic, and the relevant articles were reviewed. RESULTS: The etiologies of the three PFIC types still include unknown mechanisms. Especially in PFIC type 1, enterohepatic circulation of bile acid should be considered. Ursodeoxycholic acid, partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS: Since the etiologies and disease mechanisms of PFIC are still unclear, detailed studies are urgently required. Strategies for more advanced therapies are also needed. These developments in the future are indispensable, especially for PFIC type 1 patients.

  13. Clinical and biological significance of precursor lesions ofintrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Cholangiocarcinoma (CC) is primarily a malignant tumorof older adults most prevalent in Southeast Asia, whereliver fluke infestation is high. However the etiology inwestern countries is unknown. Although the incidence ofextrahepatic cholangiocarcinoma has remained constant,incidence of intrahepatic CC (ICC) which differs inmorphology, pathogenesis, risk factors, treatment andprognosis is increasing. While this increase is associatedwith hepatitis C virus infection, chronic nonalcoholicliver disease, obesity, and smoking, the pathogenesisof ICC and molecular alterations underlying the carcinogenesisare not completely elucidated. Benignbiliary lesions such as biliary intraepithelial neoplasia,intraductal papillary neoplasm of the bile duct, vonMeyenburg complex or bile duct hamartoma, and bileduct adenoma have been associated with ICC. For eachof these entities, evidence suggests or supports a roleas premalignant lesions. This article summarized theimportant biological significance of the precursor lesionsof ICC and the molecular mechanisms that may beinvolved in intrahepatic cholangiocarcinogenesis.

  14. Prognostic factors in patients with advanced cholangiocarcinoma:Role of surgery,chemotherapy and body mass index

    Institute of Scientific and Technical Information of China (English)

    Mirna H Farhat; Ali I Shamseddine; Ayman N Tawil; Ghina Berjawi; Charif Sidani; Wael Shamseddeen; Kassem A Barada

    2008-01-01

    AIM:To study the factors that may affect survival of cholangiocarcinoma in Lebanon.METHODS:A retrospective review of the medical records of 55 patients diagnosed with cholangiocarcinoma at the American University of Beirut between 1990 and 2005 was conducted.Univariate and multivariate analyses were performed to determine the impact of surgery,chemotherapy,body mass index,bilirubin level and other factors on survival.RESULTS:The median survival of all patients was 8.57 mo (0.03-105.2).Univariate analysis showed that low bilirubin level (<10 mg/dL),radical surgery and chemotherapy administration were significantly associated with better survival (P = 0.012,0.038 and 0.038,respectively).In subgroup analysis on patients who had no surgery,chemotherapy administration prolonged median survival significantly (17.0 mo vs 3.5 too,P = 0.001).Multivariate analysis identified only low bilirubin level < 10 mg/dL and chemotherapy administration as independent predictors associated with better survival (P < 0.05).CONCLUSION:Our data show that palliative and postoperative chemotherapy as well as a bilirubin level < 10 mg/dL are independent predictors of a significant increase in survival in patients with cholangiocarcinoma.

  15. Cholangiocarcinoma: A compact review of the literature

    Institute of Scientific and Technical Information of China (English)

    Yucel Ustundag; Yusuf Bayraktar

    2008-01-01

    Cholangiocarcinoma (CC) is a devastating cancer aris-ing from biliary epithelia. Unfortunately, the incidence of this disease is increasing in Western countries. These tumors progress insidiously, and liver failure, biliary sepsis, malnutrition and cancer cachexia are general modes of death associated with this disease. To dale, no established therapy for advanced dis-ease has been established or validated. However, our knowledge in tumor biology is increasing dramatically and new drugs are under investigation for treatment of this notorious tumor. In clinical practice, there are better diagnostic tools in use to facilitate an earlier diagnosis of CC, at least in those patients with known risk factors. CC is resectable for cure in only a small percentage of patients. Preoperative staging for vas-cular and biliary extension of CC is very important in this tumor. Laparoscopy and recently endosonography seem to protect against unnecessary laparotomies in these patients. During the last 15 years, aggressive surgical approaches, including combined liver resec-tions and vascular reconstructive surgical expertise, have improved survival in patients with CC. Surgery is contraindicated in CC cases having primary sclerosing cholangitis (PSC). Although CC was previously consid-ered a contraindication to liver transplantation, new cautious protocols, including neo-adjuvant chemora-diation therapies and staging procedures before the transplantation, have made it possible to achieve long-term survival after liver transplantation in this disease. New ablative therapies with photodynamic therapy, intraductal high-intensity ultrasonography and chemo- therapy-impregnated plastic biliary endoprosthesis are important steps in the palliative management of extra-hepatic CCs. Radiofrequency and chemo-embolization methods are also applicable for intra-hepatic CCs as palliative modes of treatment. We need more prospec-tive randomized controlled trials to evaluate the role of the new

  16. Survival analysis of cholangiocarcinoma: A 10-year experience in Malaysia

    Institute of Scientific and Technical Information of China (English)

    Ahmad Ramzi Yusoff; Mohd Muzammil Abdul Razak; Yoong Boon Koon; R Vijeyasingam; Siti Zuraidah Mahmud

    2012-01-01

    AIM: To investigate the clinical features and survival of patients treated for cholangiocarcinoma in our institution and to analyze the factors affecting their survival. METHODS: This retrospective cohort study assessed patients diagnosed with cholangiocarcinoma between January 1997 and December 2007 at the University Malaya Medical Centre in Malaysia. The clinical data and associated outcomes were collected using a structured proforma. RESULTS: Of the 69 patients diagnosed with cholangiocarcinoma, 38 (55%) were male; mean patient age was 61 years. Twelve patients(17%) had intrahepatic, 38 (55%) had perihilar and 19 (28%) had distal tumors. Only 12 patients underwent curative surgery, including seven R0 resections. Only one patient died within 30 d after surgery. The overall median survival was 4 mo, whereas the median survival of R0 resected patients was 16 mo. The overall 1-, 2- and 3-year cumulative survival rates were 67%, 17% and 17%, respectively. Survival rates were significantly associated with curative resection (P= 0.002), intrahepatic tumor (P = 0.003), negative margin status (P = 0.013), early tumor stage (P = 0.016), higher tumor differentiation (P = 0.032) and absence of jaundice (P = 0.038). Multivariate analysis showed that tumor location was a significant independent predictor of patient survival. CONCLUSION: Curative, margin-negative resection of early stage, well-differentiated intrahepatic tumors is associated with improved patient survival.

  17. Cholangiocarcinoma: A 7-year experience at a single center in Greece

    Institute of Scientific and Technical Information of China (English)

    Alexandra Alexopoulou; Aspasia Soultati; Spyros P Douralds; Larissa Vasilieva; Athanasios J Archimandritis

    2008-01-01

    AIM: To evaluate survival rate and clinical outcome of cholangiocarcinoma. METHODS: The medical records of 34 patients with cholangiocarcinoma, seen at a single hospital between the years 1999-2006, were retrospectively reviewed. RESULTS: Thirty-four patients with a median age of 75 years were included. Seventeen (50%) had painless jaundice at presentation. Sixteen (47.1%) were perihilar, 15 (44.1%) extrahepatic and three (8.8%) intrahepatic. Endoscopic retrograde cholangiography (ERCP) and/or magnetic resonance cholangiography (MRCP) were used for the diagnosis. Pathologic confirmation was obtained in seven and positive cytological examination in three. Thirteen patients had co-morbidities (38.2%). Four cases were managed with complete surgical resection. All the rest of the cases (30) were characterized as non-resectable due to advanced stage of the disease. Palliative biliary drainage was performed in 26/30 (86.6%). The mean follow-up was 32 mo (95% CI, 20-43 mo). Overall median survival was 8.7 mo (95% CI, 2-16 mo). The probability of 1-year, 2-year and 3-year survival was 46%, 20% and 7%, respectively. The survival was slightly longer in patients who underwent resection compared to those who did not, but this difference failed to reach statistical significance. Patients who underwent biliary drainage had an advantage in survival compared to those who did not (probability of survival 53% vs 0% at 1 year, respectively, P = 0.038). CONCLUSION: Patients with cholangiocarcinoma were usually elderly with co-morbidities and/or advanced disease at presentation. Even though a slight amelioration in survival with palliative biliary drainage was observed, patients had dismal outcome without resection of the tumor.

  18. Liver transplantation for cholangiocarcinoma:Current status and new insights

    Institute of Scientific and Technical Information of China (English)

    Gonzalo; Sapisochín; Elena; Fernández; de; Sevilla; Juan; Echeverri; Ramón; Charco

    2015-01-01

    Cholangiocarcinoma is a malignant tumor of the biliary system that can be classified into intrahepatic(i CCA),perihiliar(ph CCA) and distal. Initial experiences with orthotopic liver transplantation(OLT) for patientswith i CCA and ph CCA had very poor results and this treatment strategy was abandoned. In the last decade,thanks to a strict selection process and a neoadjuvant chemoradiation protocol,the results of OLT for patients with non-resectable phC CA have been shown to be excellent and this strategy has been extended worldwide in selected transplant centers. Intrahepatic cholangiocarcinoma is a growing disease in most countries and can be diagnosed both in cirrhotic and in non-cirrhotic livers. Even though OLT is contraindicated in most centers,recent investigations analyzing patients that were transplanted with a misdiagnosis of HCC and were found to have an iC CA have shown encouraging results. There is some information suggesting that patients with early stages of the disease could benefit from OLT. In this review we analyze the current stateof-the-art of OLT for cholangiocarcinoma as well as the new insights and future perspectives.

  19. Expression of RECK Gene and MMP-9 in Hilar Cholangiocarcinoma and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In order to study the expression of transformation suppressor gene RECK and MMP-9 in hilar cholangiocarcinomas and its clinical significance, and explore the roles of RECK gene in metastasis and invasion of hilar cholangiocarcinoma, the expression levels of RECK, and MMP-9 mRNA were detected by using reverse transcription-polymerase reaction in 42 paraffin-embedded samples of hilar cholangiocarcinomas and 10 samples of benign bile duct diseases. The results showed that in hilar cholangiocarcinoma tissues, the expression of RECK gene was 0. 235± 0. 062, significantly lower than in normal bile duct tissues (0. 533±0. 024, P<0.05). In hilar cholangiocarcinoma tissues, the expression of MMP-9 (0. 528±0. 039) was significantly higher than in the normal tissues (0. 311±0. 032, P<0.05). The expression of RECK gene was closely related to the intrahepatic and surrounding organs invasion (P<0.05). It was concluded that RECK gene could inhibit the expression of MMP-9 in hilar cholangiocarcinomas and closely correlated with the biological behaviors. The abnormal expression of RECK gene might be one of the molecular mechanisms of hilar cholangiocarcinoma metastasis.

  20. Identification of CXCL5/ENA-78 as a factor involved in the interaction between cholangiocarcinoma cells and cancer-associated fibroblasts.

    Science.gov (United States)

    Okabe, Hirohisa; Beppu, Toru; Ueda, Mitsuharu; Hayashi, Hiromitsu; Ishiko, Takatoshi; Masuda, Toshiro; Otao, Ryu; Horlad, Hasita; Mima, Kosuke; Miyake, Keisuke; Iwatsuki, Masaaki; Baba, Yoshifumi; Takamori, Hiroshi; Jono, Hirofumi; Shinriki, Satoru; Ando, Yukio; Baba, Hideo

    2012-11-15

    Knowledge of tumor-stromal interactions is essential for understanding tumor development. We focused on the interaction between cholangiocarcinoma and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma and reported their positive interaction in vitro and in vivo. The aim of this study is to identify the key protein involved in the interaction between cholangiocarcinoma cells and CAFs and its role on cholangiocarcinoma progression. Using the conditioning medium from cholangiocarcinoma cells, hepatic stellate cells and coculture of them, Protein-Chip analysis with SELDI-TOF-MS showed that the peak of an 8,360-Da protein remarkably increased in the coculture medium. This protein was identified as CXCL5/ENA78, epithelial cell-derived neutrophil-activating peptide-78, by q-TOF/MS/MS analysis. Two cholangiocarcinoma cell lines, HuCCT1 and RBE, produced CXCL5 that promoted their invasion and migration in an autocrine fashion. These effects of CXCL5 significantly decreased by inhibition of CXC-receptor 2, which is the receptor for CXCL5. In addition, IL-1β produced by hepatic stellate cells induced the expression of CXCL5 in cholangiocarcinoma cells. In human tissue samples, a significant correlation was observed between CAFs and CXCL5 produced by cholangiocarcinoma cells in intrahepatic cholangiocarcinoma (p = 0.0044). Furthermore, the high-CXCL5-expression group exhibited poor overall survival after curative hepatic resection (p = 0.027). The presence of tumor-infiltrating neutrophils expressing CD66b was associated with CXCL5 expression in tumor cells (p < 0.0001). These data suggest that CXCL5 is important for the interaction between cholangiocarcinoma and CAFs, and inhibition of tumor-stromal interactions may be a useful therapeutic approach for cholangiocarcinoma.

  1. Endoscopic drainage in patients with inoperable hilar cholangiocarcinoma

    OpenAIRE

    Park, Ye Jin; Kang, Dae Hwan

    2012-01-01

    Hilar cholangiocarcinoma has an extremely poor prognosis and is usually diagnosed at an advanced stage. Palliative management plays an important role in the treatment of patients with inoperable hilar cholangiocarcinoma. Surgical, percutaneous, and endoscopic biliary drainage are three modalities available to resolve obstructive jaundice. Plastic stents were widely used in the past; however, self-expanding metal stents (SEMS) have become popular recently due to their long patency and reduced ...

  2. Palliation:Hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Mahesh; Kr; Goenka; Usha; Goenka

    2014-01-01

    Hilar cholangiocarcinomas are common tumors of the bile duct that are often unresectable at presentation. Palliation, therefore, remains the goal in the majority of these patients. Palliative treatment is particularly indicated in the presence of cholangitis and pruritus but is often also offered for high-grade jaundice and abdominal pain. Endoscopic drainage by placing stents at endoscopic retrograde cholangio-pancreatography(ERCP) is usually the preferred modality of palliation. However, for advanced disease, percutaneous stenting has been shown to be superior to endoscopic stenting. Endosonography-guided biliary drainage is emerging as an alternative technique, particularly when ERCP is not possible or fails. Metal stents are usually preferred over plastic stents, both for ERCP and for percutaneous bili-ary drainage. There is no consensus as to whether it is necessary to place multiple stents within advanced hi-lar blocks or whether unilateral stenting would suffice. However, recent data have suggested that, contrary to previous belief, it is useful to drain more than 50% of the liver volume for favorable long-term results. In the presence of cholangitis, it is beneficial to drain all of the obstructed biliary segments. Surgical bypass plays a limited role in palliation and is offered primarily as asegment Ⅲ bypass if, during a laparotomy for resec-tion, the tumor is found to be unresectable. Photody-namic therapy and, more recently, radiofrequency abla-tion have been used as adjuvant therapies to improve the results of biliary stenting. The exact technique to be used for palliation is guided by the extent of the bili-ary involvement(Bismuth class) and the availability of local expertise.

  3. 细胞外基质蛋白1与原发性肝内胆管细胞癌及淋巴结转移的相关性分析%Correlation of extracellular matrix protein 1 with primary intrahepatic cholangiocarcinoma and ;lymph node metastasis

    Institute of Scientific and Technical Information of China (English)

    何坤; 胡泽民; 阮嘉后; 储兵; 周载平; 黄锐钦

    2015-01-01

    Objective To investigate the application value of extracellular matrix protein 1 (ECM1) in primary intrahepatic cholangiocarcinoma (PICC) and lymph node metastasis (LNM). Method There were 3 groups in the study,including PICC without metastasis(n=9), PICC with LNM metastasis(n=21),and normal bile duct tissue specimens(n=10). Immunohistochemical(IHC)staining and evaluation,and RT⁃PCR of mRNA were used in the study. Results IHC staining showed that no expression of ECM1 was found in normal bile duct tissue specimens,whereas expression of ECM1 was found in both PICC specimens with and without LNM metastasis. The expression level of ECM1 mRNA in normal bile duct tissue specimens was low,but abnormally increased in non⁃metastatic PICC patients and further increased in PICC with LNM metastasis(all P<0.001). The correlation coefficient between ECM1 mRNA and PICC without metastasis was 0.979(P=0.000). The correlation coefficient between ECM1 mRNA and PICC with LNM was 0.871 (P=0.000). Logistic regression analysis showed that ECM1 was an independent predictor of PICC,based on the formula:total score=7.992 log(ECM1+0.001)-5.200. The cut⁃off point was 0.00. The score above 0.00 would be indicative of malignancy. Conclusion ECM1 shows good correlation with the occurrence of PICC and LNM metastasis.%目的:研究细胞外基质蛋白1(ECM1)在原发性肝内胆管细胞癌(PICC)发生及淋巴结转移(LNM)中的应用价值。方法 PICC无转移组9例、PICC有LNM组21例,正常胆管组织标本10例。行免疫组织化学(IHC)染色和评估、RT⁃PCR mRNA实验。结果 IHC染色显示:ECM1在正常胆管组织标本不表达,PICC中以及LNM标本中均有表达。ECM1 mRNA在正常胆管组织标本中很少,在PICC中异常升高,LNM的患者中升高更多,差异有统计学意义(均为P<0.001)。ECM1 mRNA与PICC未转移的相关系数r=0.979,P=0.000。ECM1 mRNA与PICC有LNM的相关系数r=0.871,P=0.000

  4. An unusual case of intrahepatic portosystemic venous shunt

    Directory of Open Access Journals (Sweden)

    Pumersha Naidoo

    2013-06-01

    Full Text Available Intrahepatic portosystemic venous shunts are rare vascular anomalies that may be detected in asymptomatic patients, given the recent advances in radiological imaging techniques. Accurate shunt evaluation and classification can be performed with ultrasound and multi-detector computed tomography. We report an unusual case of an intrahepatic portosystemic venous shunt with an incidental finding of neurofibroma.

  5. Endoscopic tissue diagnosis of cholangiocarcinoma.

    LENUS (Irish Health Repository)

    Harewood, Gavin C

    2008-09-01

    The extremely poor outcome in patients with cholangiocarcinoma, in large part, reflects the late presentation of these tumors and the challenging nature of establishing a tissue diagnosis. Establishing a diagnosis of cholangiocarcinoma requires obtaining evidence of malignancy from sampling of the epithelium of the biliary tract, which has proven to be challenging. Although endoscopic ultrasound-guided fine needle aspiration performs slightly better than endoscopic retrograde cholangiopancreatography in diagnosing cholangiocarcinoma, both endoscopic approaches demonstrate disappointing performance characteristics.

  6. Current research in perineural invasion of cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Deng Xi-Yun

    2010-03-01

    Full Text Available Abstract Background Perineural invasion is a common path for cholangiocarcinoma (CCA metastasis, and it is highly correlated with postoperative recurrence and poor prognosis. It is often an early event in a disease that is commonly diagnosed in advanced stages, and thus it could offer a timely therapeutic and diagnostic target if better understood. This article systematically reviews the progress of CCA neural invasion-related molecules. Methods Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to December 2009, using the keywords "cholangiocarcinoma," "perineural invasion," "nerve growth factor"(NGF, "neural cell adhesion molecule" (NCAM, "matrix metalloproteinase"(MMP, "neurotransmitter," "acetylcholine" (Ach, and "transforming growth factor" (TGF." Additional papers and book chapters were identified by a manual search of references from the key articles. Results From above we found that the molecules NGF, NCAM, MMP, Ach and TGF may have prognostic significance in, and offer clues to the mechanism of CCA neural invasion. Conclusions Cholangiocarcinoma's increasing worldwide incidence is especially poignant in view of both the lacking effective therapies, and the fact that it is commonly diagnosed in advanced stages. As CCA neural invasion often appears early, more complete characterization of its molecular pathology could lead to the identification of targets for the diagnosis and therapy of this devastating malignancy.

  7. Diagnostic approaches for cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Cholangiocarcinomas arise from the epithelial cells of the bile ducts and are associated with poor prognosis. Despite new diagnostic approaches, the definite diagnosis of this malignancy continues to be challenging. Cholangiocarcinomas often grow longitudinally along the bile duct rather than in a radial direction. Thus, large tumor masses are frequently absent and imaging techniques, including ultrasound, CT, and MRI have only limited sensitivity. Tissue collection during endoscopic (ERCP) and/or percutaneous transhepatic (PTC) procedures are usually used to confirm a definitive diagnosis of cholangiocarcinoma. However, forceps biopsy and brush cytology provide positive results for malignancy in about only 50% of patients. Percutaneous and peroral cholangioscopy using fiber-optic techniques were therefore developed for direct visualization of the biliary tree, yielding additional information about endoscopic appearance and tumor extension, as well as a guided biopsy acquistion. Finally, endoscopic ultrasonography (EUS) complements endoscopic and percutaneous approaches and may provide a tissue diagnosis of tumors in the biliary region through fine- needle aspiration. In the future, new techniques allowing for early detection, including molecular markers, should be developed to improve the diagnostic sensitivity in this increasing tumor entity.

  8. BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype

    Science.gov (United States)

    Al-Shamsi, Humaid O.; Anand, Deepa; Shroff, Rachna T.; Jain, Apurva; Zuo, Mingxin; Conrad, Claudius; Vauthey, Jean-Nicolas

    2016-01-01

    Background BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. Methods The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. Results Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. Conclusions BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1-targeted therapies need to be investigated. PMID:27563445

  9. MR diagnosis of hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Li; LU Jian-ping; TIAN Jian-ming; WANG Fei; LIU Qi

    2001-01-01

    To evaluate the role of MRI and MRCP in the classifying and staging of hilar cholangiocarcinoma. Methods: MRI and MRCP imaging of 23 hilar cholangiocarcinoma were analyzed retrospectively and were compared with surgical and pathological findings. Results: The classifying configuration: infiltrating type (n=11),mass type (n=12); The classifying Bismuth: type Ⅰ (n=2), type Ⅱ (n=15), type Ⅲ (n=6), tumor invading blood vessels (n=9), no metastasis to lymph node, liver parenchyma and abdomen. Conclusion: MR is effective in classifying hilar cholangiocarcinoma, evaluating tumor size and the involvement of bile duct. However, the involvement of blood vessel tends is insufficient.

  10. Benefits of Metformin Use for Cholangiocarcinoma.

    Science.gov (United States)

    Kaewpitoon, Soraya J; Loyd, Ryan A; Rujirakul, Ratana; Panpimanmas, Sukij; Matrakool, Likit; Tongtawee, Taweesak; Kootanavanichpong, Nusorn; Kompor, Ponthip; Chavengkun, Wasugree; Kujapun, Jirawoot; Norkaew, Jun; Ponphimai, Sukanya; Padchasuwan, Natnapa; Pholsripradit, Poowadol; Eksanti, Thawatchai; Phatisena, Tanida; Kaewpitoon, Natthawut

    2015-01-01

    Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention. PMID:26745042

  11. Staging of extrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Preoperative staging of extrahepatic cholangiocarcinoma is important in determining the best treatment plan. Several classification systems have been suggested to determine the operability and extent of surgery. Longitudinal tumor extent is especially important in extrahepatic cholangiocarcinoma because operative methods differ depending on the tumor extent. The Bismuth-Corlette classification system provides useful information when planning for surgery. However, this classification system is not adequate for selecting surgical candidates. Anatomic variation of the bile duct and gross morphology of the tumor must be considered simultaneously. Lateral spread of the tumor can be evaluated based on the TNM staging provided by American Joint Committee on Cancer (AJCC). However, there is a potential for ambiguity in the distinction of T1 and T2 cancer from one another. In addition, T stage does not necessarily mean invasiveness. Blumgart T staging is helpful for the assessment of resectability with the consideration of nodal status and distant metastasis as suggested by the AJCC cancer staging system. Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary tools used in the assessment of longitudinal and lateral spread of a tumor when determining respectability. Diagnostic laparoscopy and positron emission tomography (PET) may play additional roles in this regard. (orig.)

  12. Current update on combined hepatocellular-cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Suresh Maximin

    2014-01-01

    Combined hepatocellular cholangiocarcinoma tends to present with an more aggressive behavior and a poorer prognosis than either hepatocellular carcinoma or cholangiocarcinoma. An accurate preoperative diagnosis and aggressive treatment planning can play crucial roles in appropriate patient management.

  13. Progressive familial intrahepatic cholestasis

    OpenAIRE

    Baussan Christiane; Gonzales Emmanuel; Davit-Spraul Anne; Jacquemin Emmanuel

    2009-01-01

    Abstract Progressive familial intrahepatic cholestasis (PFIC) refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appea...

  14. Peribiliary hepatic cysts presenting as hilar cholangiocarcinoma in a patient with end-stage liver disease

    Science.gov (United States)

    Lim, Jane; Nissen, Nicholas N.; McPhaul, Christopher; Annamalai, Alagappan; Klein, Andrew S.; Sundaram, Vinay

    2016-01-01

    Peribiliary cysts are cystic dilatations of peribiliary glands in the liver. They are present in ~50% of cirrhotic patients, but are underrecognized because they are usually asymptomatic and rarely present as obstructive jaundice. A 63-year-old male with hepatitis C cirrhosis, awaiting liver transplantation, had a new finding of intrahepatic dilatation on magnetic resonance imaging. This was initially concerning for cholangiocarcinoma, but was ultimately diagnosed as peribiliary cysts. Peribiliary cysts can imitate cholangiocarcinoma on imaging. Therefore, awareness of this condition is essential because misdiagnosis may lead to inappropriate delay or denial for liver transplantation. The ideal imaging modalities to identify peribiliary cysts are magnetic resonance cholangiography and drip infusion cholangiographic computed tomography, though hepatic dysfunction may limit the usefulness of the latter. Peribiliary cysts should be considered in cirrhotic patients with cholestasis, biliary dilatations and negative biopsy of the biliary system for malignancy. PMID:27511912

  15. Intrahepatic cholestasis of pregnancy

    Directory of Open Access Journals (Sweden)

    Beuers Ulrich

    2007-05-01

    Full Text Available Abstract Intrahepatic cholestasis of pregnancy (ICP is a cholestatic disorder characterized by (i pruritus with onset in the second or third trimester of pregnancy, (ii elevated serum aminotransferases and bile acid levels, and (iii spontaneous relief of signs and symptoms within two to three weeks after delivery. ICP is observed in 0.4–1% of pregnancies in most areas of Central and Western Europe and North America, while in Chile and Bolivia as well as Scandinavia and the Baltic states roughly 5–15% and 1–2%, respectively, of pregnancies are associated with ICP. Genetic and hormonal factors, but also environmental factors may contribute to the pathogenesis of ICP. Intrahepatic cholestasis of pregnancy increases the risk of preterm delivery (19–60%, meconium staining of amniotic fluid (27%, fetal bradycardia (14%, fetal distress (22–41%, and fetal loss (0.4–4.1%, particularly when associated with fasting serum bile acid levels > 40 μmol/L. The hydrophilic bile acid ursodeoxycholic acid (10–20 mg/kg/d is today regarded as the first line treatment for intrahepatic cholestasis of pregnancy. Delivery has been recommended in the 38th week when lung maturity has been established.

  16. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups

    Science.gov (United States)

    Mafficini, Andrea; Wood, Laura D.; Corbo, Vincenzo; Melisi, Davide; Malleo, Giuseppe; Vicentini, Caterina; Malpeli, Giorgio; Antonello, Davide; Sperandio, Nicola; Capelli, Paola; Tomezzoli, Anna; Iacono, Calogero; Lawlor, Rita T.; Bassi, Claudio; Hruban, Ralph H.; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, Filippo; Scarpa, Aldo

    2014-01-01

    One-hundred-fifty-three biliary cancers, including 70 intrahepatic cholangiocarcinomas (ICC), 57 extrahepatic cholangiocarcinomas (ECC) and 26 gallbladder carcinomas (GBC) were assessed for mutations in 56 genes using multigene next-generation sequencing. Expression of EGFR and mTOR pathway genes was investigated by immunohistochemistry. At least one mutated gene was observed in 118/153 (77%) cancers. The genes most frequently involved were KRAS (28%), TP53 (18%), ARID1A (12%), IDH1/2 (9%), PBRM1 (9%), BAP1 (7%), and PIK3CA (7%). IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC. Multivariate analysis identified tumour stage and TP53 mutations as independent predictors of survival. Alterations in chromatin remodeling genes (ARID1A, BAP1, PBRM1, SMARCB1) were seen in 31% of cases. Potentially actionable mutations were seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of cancers; ii) mTOR pathway activation was documented by immunohistochemistry in 51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF-ß/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine kinase receptors were found in 9% cases. Our study identified molecular subgroups of cholangiocarcinomas that can be explored for specific drug targeting in clinical trials. PMID:24867389

  17. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

    Medline Plus

    Full Text Available ... What are the limitations of TIPS? What is a Transjugular Intrahepatic Portosystemic Shunt (TIPS)? A transjugular intrahepatic ... encourage linking to this site. × Recommend RadiologyInfo to a friend Send to (friend's e-mail address): From ( ...

  18. Intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Victoria Geenes; Catherine Williamson

    2009-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.

  19. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

    Medline Plus

    Full Text Available ... anti-inflammatory drugs (NSAIDs) or blood thinners several days prior to your procedure and instructed to not ... overnight at the hospital for one or more days. What is Transjugular Intrahepatic Portosystemic Shunt (TIPS)? What ...

  20. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

    Medline Plus

    Full Text Available ... bear denotes child-specific content. Related Articles and Media Radiation Dose in X-Ray and CT Exams Contrast Materials Venography Images related to Transjugular Intrahepatic Portosystemic Shunt (TIPS) About ...

  1. Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience

    Energy Technology Data Exchange (ETDEWEB)

    Kose, Fatih, E-mail: fatihkose@gmail.com [Baskent University Faculty of Medicine, Department of Medical Oncology, Adana (Turkey); Oguzkurt, Levent [Department of Interventional Radiology, Adana (Turkey); Besen, Ayberk; Sumbul, Taner; Sezer, Ahmet; Karadeniz, Cemile; Disel, Umut; Mertsoylu, Huseyin; Ozyilkan, Ozgur [Baskent University Faculty of Medicine, Department of Medical Oncology, Adana (Turkey)

    2012-08-15

    Purpose: Patients with advanced cholangiocarcinoma present with high rate of local complications. The primary aim of this study is to report clinical course of advanced cholangiocarcinoma patients those who were presented with biliary obstruction and treated with percutaneous biliary stenting. Material and methods: Patients with unresectable locally advanced or metastatic cholangiocarcinoma followed by our center for a period of 4 years were analyzed. For statistical analysis demographic and clinical characteristics of patients, primary biliary drainage method, metal stent occlusion rate, time to stent occlusion, and overall survival rates were recorded. Results: A total of 34 eligible patients were analyzed. 27 patients had metal stent placement. These 27 patients formed the basis of this study. Median overall survival (OS) was 6.0 months. After metal stent deployment bilurubin levels were normalized within a mean of 10 days. During the follow-up period, 13 patients were experienced metal stent occlusion. Median TtSO was 10 weeks. Cytotoxic chemotherapy was administered to 14 (52%) patients. Patients without stent dysfunction had significantly higher rate of chemotherapy exposure rate (p = 0.021). Statistical analysis, however, failed to exhibit significant effect of stent dysfunction on OS. Conclusion: In advanced cholangiocarcinoma, relief of bile duct obstruction is an important part of the initial patient management. This study therefore described the clinical value of percutaneous metal stent in cholangiocarcinoma patients and raises the question about patency of metal stent in cholangiocarcinoma whether we can expect success similar to the success achieved in pancreas carcinoma.

  2. Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience

    International Nuclear Information System (INIS)

    Purpose: Patients with advanced cholangiocarcinoma present with high rate of local complications. The primary aim of this study is to report clinical course of advanced cholangiocarcinoma patients those who were presented with biliary obstruction and treated with percutaneous biliary stenting. Material and methods: Patients with unresectable locally advanced or metastatic cholangiocarcinoma followed by our center for a period of 4 years were analyzed. For statistical analysis demographic and clinical characteristics of patients, primary biliary drainage method, metal stent occlusion rate, time to stent occlusion, and overall survival rates were recorded. Results: A total of 34 eligible patients were analyzed. 27 patients had metal stent placement. These 27 patients formed the basis of this study. Median overall survival (OS) was 6.0 months. After metal stent deployment bilurubin levels were normalized within a mean of 10 days. During the follow-up period, 13 patients were experienced metal stent occlusion. Median TtSO was 10 weeks. Cytotoxic chemotherapy was administered to 14 (52%) patients. Patients without stent dysfunction had significantly higher rate of chemotherapy exposure rate (p = 0.021). Statistical analysis, however, failed to exhibit significant effect of stent dysfunction on OS. Conclusion: In advanced cholangiocarcinoma, relief of bile duct obstruction is an important part of the initial patient management. This study therefore described the clinical value of percutaneous metal stent in cholangiocarcinoma patients and raises the question about patency of metal stent in cholangiocarcinoma whether we can expect success similar to the success achieved in pancreas carcinoma.

  3. Genetics Home Reference: progressive familial intrahepatic cholestasis

    Science.gov (United States)

    ... a protein called the bile salt export pump (BSEP). This protein is found in the liver, and ... ABCB11-related intrahepatic cholestasis ATP8B1-related intrahepatic cholestasis BSEP deficiency Byler disease Byler syndrome FIC1 deficiency low ...

  4. Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yun-Fei [Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University (China); Yang, Xiao-Qing [Department of Pathology, Shandong University (China); Lu, Xiao-Fei [Department of Gastrointestinal Surgery, Jinan Central Hospital (China); Guo, Sen; Liu, Yi; Iqbal, Mohammad; Ning, Shang-Lei; Yang, Hui [Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University (China); Suo, Ning [Department of Anatomy, Shandong University (China); Chen, Yu-Xin, E-mail: yxu8@bidmc.harvard.edu [Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University (China)

    2014-03-28

    Highlights: • FGFR4 is significantly related with N stage in IHCC, with T stage and TNM stage in PHCC. • FGFR4 is an independent prognostic factor in IHCC and PHCC. • FGFR4 promotes proliferation, invasion and EMT in cholangiocarinoma cell lines. • Inhibitor AP24354 can decrease proliferation, invasion and induce apoptosis of CCA. - Abstract: Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of several cancers, but the correlation between FGFR4 expression and cholangiocarcinoma (CCA) has not been well elucidated. We investigated the expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with clinicopathologic parameters and survival rate. The rate of FGFR4 higher expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41) in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC (P = 0.002) and PHCC (P = 0.019) with univariate analysis, and also identified as an independent prognostic factor in IHCC (P = 0.045) and PHCC (P = 0.049) with multivariate analysis. Additionally, with functional assays in vitro, we found FGFR4 can induce proliferation, invasion and epithelial–mesenchymal transition (EMT) of CCA cell lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354 can suppress proliferation, invasion and induce apoptosis of CCA cells. In conclusion, FGFR4 expression can be identified as a significant independent prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may act as a potential therapeutic target.

  5. Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma

    International Nuclear Information System (INIS)

    Highlights: • FGFR4 is significantly related with N stage in IHCC, with T stage and TNM stage in PHCC. • FGFR4 is an independent prognostic factor in IHCC and PHCC. • FGFR4 promotes proliferation, invasion and EMT in cholangiocarinoma cell lines. • Inhibitor AP24354 can decrease proliferation, invasion and induce apoptosis of CCA. - Abstract: Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of several cancers, but the correlation between FGFR4 expression and cholangiocarcinoma (CCA) has not been well elucidated. We investigated the expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with clinicopathologic parameters and survival rate. The rate of FGFR4 higher expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41) in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC (P = 0.002) and PHCC (P = 0.019) with univariate analysis, and also identified as an independent prognostic factor in IHCC (P = 0.045) and PHCC (P = 0.049) with multivariate analysis. Additionally, with functional assays in vitro, we found FGFR4 can induce proliferation, invasion and epithelial–mesenchymal transition (EMT) of CCA cell lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354 can suppress proliferation, invasion and induce apoptosis of CCA cells. In conclusion, FGFR4 expression can be identified as a significant independent prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may act as a potential therapeutic target

  6. Transjugular intrahepatic portosystemic shunt.

    Science.gov (United States)

    Ochs, Andreas

    2005-01-01

    The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional treatment resulting in decompression of the portal system by creation of a side-to-side portosystemic anastomosis. Since its introduction 16 years ago, more than 1,000 publications have appeared demonstrating broad acceptance and increasing clinical use. This review summarizes our present knowledge about technical aspects and complications, follow-up of patients and indications. A technical success rate near 100% and a low occurrence of complications clearly depend on the skills of the operator. The follow-up of the TIPS patient has to assess shunt patency, liver function, hepatic encephalopathy and the possible development of hepatocellular carcinoma. Shunt patency can best be monitored by duplex sonography and can avoid routine radiological revision. Short-term patency may be improved by anticoagulation, while such a treatment does not influence long-term patency. Stent grafts covered with expanded polytetrafluoroethylene show promising long-term patency comparable with that of surgical shunts. With respect to the indications of TIPS, much is known about treatment of variceal bleeding and refractory ascites. The thirteen randomized studies that are available to date show that survival is comparable in patients receiving TIPS or endoscopic treatment for acute or recurrent variceal bleeding. Another group comprises patients with refractory ascites and related complications, such as hepatorenal syndrome and hepatic hydrothorax. It has been demonstrated that TIPS improves these complications. Five randomized studies comparing TIPS with paracentesis and one study comparing TIPS with the peritoneo-venous shunt showed good response of ascites but controversial results on survival. In addition, TIPS has been successfully applied to patients with Budd-Chiari syndrome, portal vein thrombosis, before liver transplantation, and for the treatment of ectopic variceal bleeding. PMID:15920326

  7. [The rational diagnostic of cholangiocarcinoma].

    Science.gov (United States)

    Rydlo, Martin; Dvořáčková, Jana; Kupka, Tomáš; Klvaňa, Pavel; Havelka, Jaroslav; Uvírová, Magdalena; Geryk, Edvard; Czerný, Daniel; Jonszta, Tomáš; Bojková, Martina; Hrabovský, Vladimír; Jelínková, Veronika; Martínek, Arnošt; Dítě, Petr

    2016-02-01

    Cholangiocarcinoma (CC) is a rare malignant tumour arising from cholangiocytes, and its prognosis is usually unfavourable, mostly as a result of late diagnosis of the tumour. The current incidence of cholangiocarcinoma in the Czech Republic is 1.4/100,000 inhabitants per year; in less than 30 % of patients with CC, one of the known risk factors can be identified, most frequently, primary sclerosing cholangitis. Only patients with early diagnosed and surgically amenable cholangiocarcinoma are likely to have a longer survival time; in their case, survival for more than five years has been achieved in 20 % to 40 %. From the perspective of the need for early diagnosis of CC, a significant part is played by imaging and histopathologic evaluation; the early diagnostic significance of oncomarkers is limited. The rational early diagnosis of CC consists in effective use of differentiated advantages of different imaging modalities - MRI with DSA appears to be the optimal method, endosonography is a sensitive method for the identification of malignancy in the hepatic hilum or distal common bile duct, MRCP (magnetic resonance cholangiopancreatography) is used to display pathological changes in the biliary tree, ERCP (endoscopic retrograde cholangiopancreatography) allows material removal for histopathological examination. Other new approaches are also beneficial, such as IDUS - intraductal ultrasonography of biliary tract or SPY-GLASS, enabling examination of the bile ducts by direct view with the possibility of taking targeted biopsies. Sensitivity and specificity of histology and cytology can be increased by using the molecular cytogenetic FISH method, i.e. fluorescence in situ by hybridization, with a specificity of 97 %. PMID:27172439

  8. Progressive familial intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Baussan Christiane

    2009-01-01

    Full Text Available Abstract Progressive familial intrahepatic cholestasis (PFIC refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP. Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3, impair biliary phospholipid secretion resulting in PFIC3. Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis can be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation

  9. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

    Medline Plus

    Full Text Available ... overnight at the hospital for one or more days. What is Transjugular Intrahepatic Portosystemic Shunt (TIPS)? What are some common uses of the procedure? How should I prepare? What does the equipment look like? How does the procedure work? How is the procedure performed? What will I ...

  10. Pulmonary vasculitis associated with cholangiocarcinoma of liver.

    OpenAIRE

    Ong, E L; Evans, S; Hanley, S. P.

    1989-01-01

    A 62 year old woman presented with an acute pulmonary vasculitis which responded to treatment with oral steroids. Investigations over one year revealed a cholangiocarcinoma of the liver. The association of vasculitis with neoplastic diseases remains a diagnostic challenge.

  11. Mandibular metastasis of cholangiocarcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    You, Tae Min [Dept. of Advanced General Dentistry, Dankook University, Cheonan (Korea, Republic of); Kim, Kee Dong; Jeong, Ho Gui; Park, Won Se [Advanced General Dentistry, Dankook University, Cheonan (Korea, Republic of)

    2015-12-15

    Tumors metastasizing from distant regions to the oral and maxillofacial region are uncommon, comprising only 1%-2% of all malignancies. Cholangiocarcinoma is a malignancy that arises from cholangiocytes, which are epithelial cells that line the bile ducts. These cancers are difficult to diagnose and have a poor prognosis. In this paper, we report a rare case of mandibular metastasis of cholangiocarcinoma diagnosed at the primary site and discuss the radiographic findings observed in this case.

  12. Different {sup 18}F-FDG Uptake According to Tumor Location and Morphology of Cholangiocarcinoma and Its Clinical Implication

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Seok; Lee, Yoon Jae; Lim, Seok Tae; Sohn, Myung Hee; Lee, Seung Ok [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2009-08-15

    {sup 18}F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. However, pattern of FDG uptake in biliary malignancies and its clinical significance have not been studied well. The purpose of this study was to assess the additional value of {sup 18}F-FDG PET in differential diagnosis and prognosis of cholangiocarcinoma (CC) according to the tumor location and tumor morphology. From April 2005 to May 2008, eighty two patients (M:F=55:27, age 66.2{+-}9.6 yrs) with CC underwent {sup 18}F-FDG PET. For semiquantitative analysis, the maximum standardized uptake value (SUV{sub max}) was obtained from the primary tumor. The difference of SUV{sub max} according to the tumor location and tumor growth pattern, such as scirrhous type, nodular type, polypoid type were compared. Overall sensitivity of PET scan was 81.7% in CC. SUV{sub max} on PET scan in intrahepatic CC was significantly higher compared to extrahepatic CC. In extrahepatic CC, polypoid type showed significantly higher SUV{sub max} compared to scirrhous type. {sup 18}F-FDG PET may have a significant impact on clinical decision-making and on the management of Intrahepatic cholangiocarcinoma. And it is related to the shape of the tumor and the sensitivity of detection is higher in the mass-forming type than in the scirrhous type.

  13. Splenosis simulating an intrahepatic mass

    Institute of Scientific and Technical Information of China (English)

    晁明; 徐宏伟

    2004-01-01

    Splenosis is the autotransplantation of splenic tissue that usually follows traumatic rupture of the spleen. Splenic implants may be seeded within or beyond the peritoneal cavity.1 The most frequent locations of splenosis in the descending order are the serosal surface of the small intestine, the greater omentum, parietal peritoneum, surface of the large intestine, mesentery, undersurface of the diaphragm and the thorax.1,2 However, intrahepatic splenosis is very rare. We recently encountered a patient in whom results of ultrasonography (US) and computed tomography (CT) revealed an intrahepatic mass that consisted of ectopic splenic tissue. To our knowledge, this is the fifth report of ectopic splenic tissue in the liver in the English-language literature. We present the imaging findings of the splenic implants in the liver and discuss the diagnosis and its practical significance.

  14. Current therapy of hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Stephanie HiuYan Lau; WanYee Lau

    2012-01-01

    BACKGROUND: Hilar cholangiocarcinoma (HC) is an adeno-carcinoma of the extrahepatic biliary tree arising from the main left or right hepatic ducts or their confluence. This tumor is still considered to be difficult to treat or to cure. DATA SOURCES: We reviewed the medical literature on HC. Relevant and updated information on this tumor was analyzed in a concise and easy-to-read manner. The article is not intended to be a systematic review, but an extensive search was conducted on PubMed and MEDLINE using the keywords "hilar cholangiocarcinoma" and "Klatskin tumor" until July 2011. RESULTS: The selection and the timing of management options for patients with HC are determined by the degree of certainty of the diagnosis, the general condition of the patients, the underlying liver function and the stage of the disease. Current treatment of HC can be divided into curative and palliative treatment. For the curative treatment, local excision should only be used on small tumors which are confined to the bile duct wall and Bismuth I papillary carcinoma. Partial hepatectomy should be combined with caudate lobe resection and porta-hepatis lymph node dissection. The results of these major resections can be improved with portal vein embolization, and staging laparoscopy and laparoscopic ultrasound. The role of preoperative biliary drainage is controversial. Autotransplantation for HC gave disappointing results while the Mayo Protocol of chemoradiation for selecting patients with unresectable HC for orthotopic liver transplantation has been widely accepted. Palliative treatment included bypass surgery, endoscopic or percutaneous stenting, photodynamic therapy, intraluminal brachytherapy, and external radiation and systemic therapy. CONCLUSIONS: Adequate surgery with R0 resection should be the main goal of treatment. For patients with unresectable HC, treatment aims to improve the quality and quantity of their survival.

  15. Intrahepatic splenosis: a case report

    International Nuclear Information System (INIS)

    Splenosis is heterotopic autotransplantation and seeding of splenic tissue. In the literature, only a few cases of splenosis involving the liver and the radiologic characteristics of these lesions have been reported. We report a case of intrahepatic splenosis diagnosed by ultrasound, computed tomography, magnetic resonance imaging and scintigraphic features. To our knowledge, our patient is the first case diagnosed only by radiologic and radionuclide examination without any intervention. (orig.)

  16. Clinical analysis of biliary stent placement combined with gamma-knife for the treatment of complex hilar cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhi-qiang FENG

    2011-05-01

    Full Text Available Objective To evaluate the therapeutic effect of biliary stent placement combined with gamma-knife for the treatment of complex hilar cholangiocarcinoma.Methods Five patients with type IV hilar cholangiocarcinoma,according to Bismuth classification,combined with stenosis of distant common bile duct were treated with biliary stent placement and gamma-knife.The left intrahepatic bile duct was catheterized under the guidance of ultrasound,followed by catheterization of right intrahepatic bile duct aided by percutaneous transhepatic cholangiography for drainage(PTCD.Three biliary stents were inserted to relieve obstruction.Patients then underwent gamma-knife treatment after subsidence of jaundice,and bilirubin,followed by determination of transaminase and observation of the condition of the tumor.Results Total bilrubin,direct bilrubin and alanine transaminase of patients were 289.38±101.43μmol/L,180.42±72.50μmol/L and 148.80±82.65 U/L respectively before PTCD,and 94.2±20.43μmol/L,62.37±30.41μmol/L and 109.27±45.52 U/L,respectively,7 days after PTCD,and they declined to 27.20±14.60μmol/L,20.58±9.33μmol/L and 59.80±35.18 U/L,respectively,one month after PTCD.Five patients survived for 10,13,14,17 and 24 months,respectively.The median survival time was 15 months.Conclusion The combination of insertion of metallic stents and gamma-knife therapy is a safe and effective treatment for complex hilar cholangiocarcinoma,and this therapeutic strategy may improve survival rate and control the rate of grouth of carcinoma.

  17. Schisandrin B inhibits cell proliferation and induces apoptosis in human cholangiocarcinoma cells.

    Science.gov (United States)

    Yang, Xiaohui; Wang, Shuai; Mu, Yunchuan; Zheng, Yixiong

    2016-10-01

    Cholangiocarcinoma (CCA) is the second most common hepatic cancer with high resistance to current chemotherapies and extremely poor prognosis. The present study aimed to examine the effects of schisandrin B (Sch B) on CCA cells both in vitro and in vivo and to examine its underlying mechanism. We found that Sch B inhibited the viability and proliferation of CCA cells in a dose- and time-dependent manner as assessed by MTT and colony formation assays. The flow cytometric assay revealed G0/G1 phase arrest in the Sch B-treated HCCC-9810 and RBE cells. In addition, Sch B induced intrahepatic cholangiocarcinoma apoptosis as shown by the results of Annexin V/PI double staining. Rhodamine 123 staining revealed that Sch B decreased the mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanistically, western blot analysis indicated that Sch B induced apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9 and cleaved PARP, and by downregulating cyclin D1, Bcl-2 and CDK-4. Moreover, Sch B significantly inhibited HCCC-9810 xenograft growth in athymic nude mice. In summary, these findings suggest that Sch B exhibited potent antitumor activities via the induction of CCA apoptosis and that Sch B may be a promising drug for the treatment of CCA. PMID:27499090

  18. Pancreatic cancer risk variant ABO rs505922 in patients with cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Marcin Krawczyk; Florentina Mihalache; Aksana H(o)blinger; Monica Acalovschi; Frank Lammert; Vincent Zimmer

    2011-01-01

    The aim of this study was to investigate an association between the development of cholangiocarcinoma (CCA) and the ABO variant rs505922 (known to increase pancreatic cancer risk) in a large cohort of European individuals with CCA. In total, 180 individuals with CCA and 350 CCA-free controls were included. The ABO variant rs505922 was genotyped using a polymerase chain reaction-based assay. Association between this single nucleotide polymorphism (SNP) and CCA was tested in contingency tables. Neither allele distributions nor association tests and regression analysis provided evidence for an increased risk of CCA among carriers of the ABO variant (all P > 0.05). Nevertheless, we documented a deviation from Hardy-Weinberg equilibrium in the entire CCA cohort (P = 0.028) and for patients with intrahepatic (P = 0.037) but not extrahepatic tumor localization (P > 0.05). The association tests did not provide evidence for a prominent role of the investigated SNP in the genetic risk of CCA. However, Hardy-Weinberg disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants future studies investigating a potential CCA risk modulation by individual blood groups.

  19. Molecular mechanism of cholangiocarcinoma carcinogenesis.

    Science.gov (United States)

    Maemura, Kosei; Natsugoe, Shoji; Takao, Sonshin

    2014-10-01

    Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with a poor prognosis, which often arises from conditions causing long-term inflammation, injury, and reparative biliary epithelial cell proliferation. Several conditions are known to be major risk factors for cancer in the biliary tract or gallbladder, including primary sclerosing cholangitis, liver fluke infection, pancreaticobiliary maljunction, and chemical exposure in proof-printing workers. Abnormalities in various signaling cascades, molecules, and genetic mutations are involved in the pathogenesis of CCA. CCA is characterized by a series of highly recurrent mutations in genes, including KRAS, BRF, TP53, Smad, and p16(INK4a) . Cytokines that are affected by inflammatory environmental conditions, such as interleukin-6 (IL-6), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and platelet-derived growth factor (PDGF), play an important role in cancer pathogenesis. Prominent signaling pathways important in carcinogenesis include TGF-β/Smad, IL-6/STAT-3, PI3K/AKT, Wnt, RAF/MEK/MAPK, and Notch. Additionally, some microRNAs regulate targets in critical pathways of CCA development and progression. This review article provides the understanding of the genetic and epigenetic mechanism(s) of carcinogenesis in CCA, which leads to the development of new therapeutic targets for the prevention and treatment of this devastating cancer. PMID:24895231

  20. Heterotopic Pancreas Mimicking Cholangiocarcinoma. Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Atindriya Biswas

    2007-01-01

    Full Text Available Context Majority of the patients developing obstructive jaundice have an underlying malignancy. Identification of a benign pathology like heterotopic pancreas as an aetiology is uncommon and usually occurs only subsequent to a major operation. Case report We report a case of heterotopic pancreas adjacent to the ampulla of Vater mimicking distal cholangiocarcinoma. A 47- year-old patient presented with abdominal pain and obstructive jaundice. ERCP demonstrated a distal common bile duct stricture suspicious of cholangiocarcinoma. He underwent a pylorus-preserving pancreaticoduodenectomy. Histology showed a nodule of heterotopic pancreatic tissue adjacent to the ampulla. Conclusion We have reviewed the literature on heterotopic pancreas of the periampullary region presenting with biliary obstruction. This is a rare entity and remains difficult to diagnose, despite advances in radiological and endoscopic imaging techniques. For symptomatic patients with an established diagnosis of periampullary heterotopic pancreas, local excision may be sufficient. However, in the absence of unequivocal imaging or histological confirmation of benign pathology, and when there is a suspicion of underlying malignancy, pancreaticoduodenectomy may be the only treatment option, as in this case.

  1. Partial Hepatectomy with Skeletonization of the Hepatoduodenal Ligament for Hilar Cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    JIANGXiaoqing; ZHANGBaihe; 等

    2002-01-01

    Objective To summarize the surgical experience of partial hepatectomy with skeletonization of the hepatoduodenal ligament in the treatment of hilar cholangiocarcinoma.Methods Between Jan.1999 and Dec,2001,67 consecutive patients with hilar cholangiocarcinoma underwent surgical exploration at the Second Military Medical University,Eastern Hepatobiliary Surgery Hospital.The clinical data of these patients were reviewed.Results Of the 67 patients,65(97%) underwent surgical resection.Fourty-nine patients(73%) received curative resection:22 skeletonization resection(SR) and 27 SR combined with partial hepatectomy.In 16 patients(9%) with curative resection the tumor margin was histologically postive and the resection was therefore considered palliative.The tumors were classified according to Bismuth with SR was type Ⅱ(17cases),various types of partial hepatectomy with SR was type Ⅲ and type IV.Right lobectomy with right caudate lobectomy was indicated in type Ⅲ(6cases),left lobectomy with complete caudate lobectomy in type Ⅲb(15cases),right loobectomy with complete caudate lobectomy(3 cases),left lobectomy with complete caudate lobectomy(9 cases) and quadrate lobectomy(2 cases)in type IV.SR and left lobectomy with complete caudate lobectomy was successfully performed in 2 patients(3%) who had undergone palliative biliary resection and cholangiojejunostomy before.Eight patients(12%) had local resecton of the tumor with Roux-en-Y hepaticojejunostomy reconstruction using intrahepatic stents.Two patients(3%) had palliative biliary drainage.Combined portal vein resection was performed in 13 patients(20%) and hepatic artery resection in 27 patients(40%) .Twenty-four atients(36%) had no postoperative complication,23 patients(34%) had minor complications only ,and the remaining 20 patients(30%) had major complications.Of the 20 patients with major complications,14 recovered,the remaining 6 patients died from hepatorenal failure with other organ failures,from myocardial

  2. Multiple intrahepatic pseudocysts in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    David Casado; Luis Sabater; Julio Calvete; Empar Mayordomo; Luis Aparisi; Juan Sastre; Salvador Lledo

    2007-01-01

    Liver pseudocysts are a very rare complication in acute pancreatitis with only a few cases previously described. The lack of experience and literature on this condition leads to difficulties in the differential diagnosis and management. We report herein a case of acute pancreatitis who developed multiple intrahepatic pseudocysts. After complete imaging evaluation, the diagnosis was still unclear and the patient was operated on. The presence of liver lesions in patients with acute pancreatitis should raise the possibility of intrahepatic pseudocysts.

  3. Ultrasonographic findings of intrahepatic bile duct stone

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Suk; Na, Hae Kyung; Yoon, Chong Hyun [National Medical Center, Seoul (Korea, Republic of)

    1989-10-15

    The intrahepatic duct stones are prevalent in East Asia and pose serious health problem because of the frequent recurrence and often associated suppurative cholangitis. Accurate diagnosis and localization of intrahepatic duct stones are essential to good prognosis and selection of adequate therapeutic method. We studied 112 cases of intrahepatic duct stones diagnosed with ultrasound and confirmed by operation or other radiologic studies for recent 3 years from May 1986 to May 1989 at Department Of Radiology, National Medical Center, and analysed ultrasonographic findings. The results were as follows: 1. Among 112 cases, 73 (65%) were female, 39 (35%) were male with predominancy in 5th decade. 2. The most common location of intrahepatic duct stones was left intrahepatic duct in 48 cases (43%), followed by right intrahepatic duct in 42 cases (37.5%) and both intrahepatic ducts in 22 cases (19.5%). In respect of segmental distribution, left lateral segment is the most common location (53 cases, 34%), followed by right posterior segment (43 cases, 27%). 3. Ultrasonographic findings were as follows: Nodular pattern is the most common (59 cases, 53%), followed by tubular or linear impacted pattern (23 cases, 20%), irregular heterogenous conglomerated mass (13 cases, 12%), smooth homogenous single mass (10 cases, 9%) and mixed (7 cases, 6%) in orders. Ductal dilatations were classified by diffuse dilatation (16 cases, 14%), localized dilatation (50 case, 45%) and no dilatation (46 cases, 41%). Many of the tubular impacted stones showed no ductal dilatation and single mass showed ductal dilatations in all cases. 4. In 53 cases (47%), combined extrahepatic duct stones were present. 5. As associated findings, liver cirrhosis in 11 cases (10%), cholangitis in 9 cases (8%), cholecystitis in 7 cases (6%), hepatic and pericholangitic abscess in 3 cases(3%) and CBD cancer, GB cancer, acute pancreatitis in 2 cases (2%) respectively.

  4. The interventional treatment of intrahepatic bilomas

    International Nuclear Information System (INIS)

    Objective: To explore the interventional treatment and the etiologic causes of intrahepatic bilomas. Methods: During the period of 2005-2010, a total of 15 patients with intrahepatic bilomas were treated with interventional therapy. The causes of bilomas included TACE procedure (n=11), trauma (n=1) and surgery (n=3). Under ultrasound guidance, puncturing together with catheter insertion was accomplished, then continuous drainage was carried out in all patients. Washing of the biloma cavity with antibiotics was performed in all cases. The changes in draining amount and the imaging findings were observed to judge the healing condition of the intrahepatic bilomas. Results: After the drainage treatment the bilomas were closed within 30 days (n=8), or within 30 to 60 days (n=2) or after 60 days (n=3), and the drainage tubes were then removed. In the remaining two cases, liver transplantation was adopted in one and death to tumor deterioration occurred in another. Conclusion: Intrahepatic biloma is a kind of complication caused by surgical operation, trauma, TACE, etc. The interventional therapy is minimally-invasive, safe and effective for the treatment of intrahepatic bilomas. (authors)

  5. Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters

    Institute of Scientific and Technical Information of China (English)

    Bo Zhai; He-Xin Yan; Shu-Qin Liu; Lei Chen; Meng-Chao Wu; Hong-Yang Wang

    2008-01-01

    AIM: To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma (ICC).METHODS: An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit.RESULTS: The expression of E-cadherin and P120 was reduced in 27 cases (64.3%) and 31 cases (73.8%), respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade (X2=9.333, P=009 and X2=11.71, P=0.003), TNM stage (X2=8.627, P=0.035 and X2=13.123, P=0.004), intrahepatic metastasis (X2=7.292, P=0.007 and X2=4.657, P=0.041, respectively) and patients' survival (X2=6.351, P=0.002 and X2=4.023, P=0.000, respectively). In addition, the expression of P120 was in concordance with that of E-cadherin (X2=13.797, P=0.000), indicating that the expression of P120 may be dependent on that of E-cadherin. Finally, only P120 expression was found to be an independent prognostic factor in Cox regression model (r=0.088, P=0.049).CONCLUSION: Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markers for predicting tumor invasion, metastasis and patients' survival, but only P120 is an independent prognostic factor for ICC.

  6. Percutaneous transhepatic biliary drainage for hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of PTBD in treating malignant biliary obstruction caused by hilar cholangiocarcinoma. Methods: We retrospectively analyzed the data of 103 patients(M:62,F:41)with malignant obstructive jaundice caused by hilar cholangiocarcinoma. After taking percutaneous transhepatic cholangiography, metallic stent or plastic external catheter or external-internal catheter for drainage was deployed and then followed up was undertaken with clinical and radiographic evaluation and laboratory. examination. Results: All patients went though PTBD successfully (100%). According to Bismuth classification, all 103 cases consisted of I type(N=30), II type (N=30), III type (N=26) and IV type (N=17). Thirty-nine cases were placed with 47 stents and 64 eases with drainage tubes. 4 cases installed two stems for bilateral drainage, 2 cases installed two stents because of long segmental strictures with stent in stent, 1 case was placed with three stents, and 3 cases installed stent and plastic catheter together. Sixty-four cases received plastic catheters in this series, 35 cases installed two or more catheters for bilateral drainage, 28 cases installed external and internal drainage catheters, 12 eases installed external drainage catheters, and 24 eases installed both of them. There were 17 patients involving incorporative infection before procedure, 13 cases cured after procedure, and 15 new patients got inflammation after procedure. 13 cases showed increase of amylase (from May, 2004), 8 eases had bloody bile drainage and 1 case with pyloric obstruction. Total serum bilirubin reduced from (386 ± 162) μmol/L to (161 ± 117) μmol/L, (P<0.01) short term curative effect was related with the type of hilar cholangiocarcinoma. The survival time was 186 days(median), and 1, 3, 6, 12 month survival rate were 89.9%, 75.3%, 59.6%, 16.9%, respectively. Conclusion: Percutaneous transhepatic bile drainage is a safe and effective palliative therapy of malignant

  7. Unusual causes of intrahepatic cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    Elias E Mazokopakis; John A Papadakis; Diamantis P Kofteridis

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis,including consumption of Teucrium polium (family Lamiaceae) in the form of tea,Stauffer's syndrome,treatment with tamoxifen citrate for breast cancer,infection with Coxiella Burnetii (acute Q fever),and infection with Brucella melitensis (acute brucellosis).

  8. Unusual causes of intrahepatic cholestatic liver disease

    OpenAIRE

    Mazokopakis, Elias E.; Papadakis, John A; Kofteridis, Diamantis P.

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis, including consumption of Teucrium polium (family Lamiaceae) in the form of tea, Stauffer’s syndrome, treatment with tamoxifen citrate for breast cancer, infection with Coxiella Burnetii (acute Q fever), and infection with Brucella melitensis (acute brucellosis).

  9. Metallic stent and stereotactic conformal radiotherapy for hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of metallic stent combined with stereotactic conformal radiotherapy (SCRT) for hilar cholangiocarcinoma. Methods: Fifty-four patients with hilar cholangiocarcinoma were analyzed, including 31 treated with stent plus stereotactic conformal radiotherapy (combined group) and 23 with metallic stent alone (control group). Results: The mean survival time of combined group was 11.1 ± 4.6 months, compared with 5.1 ± 2.8 months of the control group, giving a significant difference between the two groups (P<0.01). Conclusion: The combination of metallic stent and stereotactic conformal radiotherapy is more effective than metallic stent alone for unresectable hilar cholangiocarcinoma. (authors)

  10. C-11 Choline and FDG PET/CT Imaging of Primary Cholangiocarcinoma – a Comparative Analysis

    Directory of Open Access Journals (Sweden)

    Chanisa Chotipanich

    2015-01-01

    Full Text Available Objective(s: This study aimed to compare the diagnostic values of 11C-choline and 18F-fluorodeoxyglucose (18F-FDG positron emission tomography/computed tomography (PET/CT in patients with cholangiocarcinoma (CCA. Methods: This prospective study was conducted on 10 patients (6 males and 4 females, aged 42-69 years, suspected of having CCA based on CT or magnetic resonance imaging (MRI results. 11C-choline and 18F-FDG PET/CT studies were performed in all patients over 1 week. PET/CT results were visually analyzed by 2 independent nuclear medicine physicians and quantitatively by calculating the tumor-to-background ratio (T/B. Results: No 11C-choline PET/CT uptake was observed in primary extrahepatic or intrahepatic CCA cases. Intense 18F-FDG avidity was detected in the tumors of 8 patients (%80. Two patients, who were 18F-FDG negative, had primary extrahepatic CCA. Ki-67 measurements were positive in all patients (range; 14.2%-39.9%. The average T/B values of 11C-choline and 18F-FDG were 0.4±0.2 and 2.0±1.0 in all cases of primary CCA, respectively; these values were significantly lower for 11C-choline (P

  11. FDG-positron emission tomography/computed tomography and standardized uptake value in the primary diagnosis and staging of hilar cholangiocarcinoma

    NARCIS (Netherlands)

    A.T. Ruys; R.J. Bennink; H.L. van Westreenen; M.R. Engelbrecht; O.R. Busch; D.J. Gouma; T.M. van Gulik

    2011-01-01

    Background: The diagnosis and staging of hilar cholangiocarcinoma (HCCA) remain challenging despite recent advances in imaging. Little is known about the use of positron emission tomography/computed tomography (PET/CT) in HCCA. Objectives: This study aimed to evaluate the additional value of FDG-PET

  12. Cholangiocarcinoma accompanied by desmoid-type fibromatosis

    Institute of Scientific and Technical Information of China (English)

    Nan Xu; Zhe-Yu Chen; Lu-NanYan; Jia-YingYang; Wen-TaoWang; Shu-Guang Jing

    2011-01-01

    BACKGROUND: Cholangiocarcinoma complicated by intra-abdominal desmoid-type fibromatosis (DTF) is uncommon. There are no reports on patients with this type of fibromatosis, in which the pre-operative treatment (including diagnosis), surgical approach, post-operative pathologic reports, and prognosis are discussed. METHOD: The clinicopathological features of a 49-year-old man were retrospectively analyzed. RESULTS: Cholangiocarcinoma located in the inferior segment of the bile duct was considered pre-operatively on the basis of clinical findings. At the time of pancreaticoduodenectomy, the mesojejunum was stiff without nodules or a mass at a distance of approximately 80 cm from the ligament of Treitz. Complete excision of the entire lesion of the intestinal mesenteric contracture and its subsidiary was performed. Post-operative pathologic findings confirmed an adenocarcinoma located at the extremity of the common bile duct and infiltrating the full thickness of the common bile duct as well as the deep muscular layer of the duodenum. The contracted jejunal mesentery was shown to have DTF. The patient was alive with no evidence of recurrence after a follow-up of 6 months. CONCLUSIONS: The patient had a rare hereditary disease with intra-abdominal DTF, which manifests the characteristics of an aggressive growth pattern and a high rate of local recurrence;conservative therapy is recommended. Complete excision of the fibromatous lesion during pancreaticoduodenectomy may maximally decrease the risk of local recurrence.

  13. [Appropriate Biliary Drainage Methods for Unresectable Cholangiocarcinomas].

    Science.gov (United States)

    Oishi, Tatsurou; Kanemoto, Yoshiaki; Yoshioka, Yuuta; Sawada, Ryuuichirou; Sekine, Sachi; Miyanaga, Hiroto; Sakahira, Hideki; Takahashi, Hironori; Miyamoto, Katsufumi; Koyama, Takashi

    2015-11-01

    We investigated the efficacy of different biliary drainage methods for the treatment of unresectable cholangiocarcinomas. We performed a retrospective study of 28 patients with unresectable cholangiocarcinomas who underwent biliary drainage at our hospital between January 2008 and June 2014 to compare the incidence of post-drainage stent dysfunction (SD) and reintervention (RI) for SD according to primary drainage method, lesion site, and complication status (the presence or absence of cholangitis). The duration of stent patency was compared between the different stent types. No significant differences in the incidence of SD and RI were found according to primary drainage methods, lesion site, or the presence or absence of cholangitis. The mean durations of stent patency for plastic and metal stents were 2.7 months and 7.4 months, respectively, suggesting that metal stents should be selected when the estimated prognosis is ≥2 months. Furthermore, metal stent placement, rather than the additional placement of plastic stents, should be considered a feasible option in cases of SD. PMID:26805093

  14. Transjugular Intrahepatic Portosystemic Shunt (TIPS)

    Medline Plus

    Full Text Available ... the current generation of GORE-TEX-lined stents Serious complications, reported in fewer than five percent of ... limitations of TIPS? Patients with more advanced liver disease are at greater risk for worsening liver failure ...

  15. Heterogeneity of the intrahepatic biliary epithelium

    Institute of Scientific and Technical Information of China (English)

    Shannon Glaser; Heather Francis; Sharon DeMorrow; Gene LeSage; Giammarco Fava; Marco Marzioni; Julie Venter; Gianfranco Alpini

    2006-01-01

    The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids,carbon tetrachloride (CCl4) or α-naphthylisothiocyanate (ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium.These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts.Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies.

  16. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

    Directory of Open Access Journals (Sweden)

    Chantragan Srisomsap

    2010-01-01

    Full Text Available Cholangiocarcinoma (CCA and hepatocellular carcinoma (HCC occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1 and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2, laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma.

  17. Cystic micropapillary neoplasm of peribiliary glands with concomitant perihilar cholangiocarcinoma.

    Science.gov (United States)

    Uchida, Tsuneyuki; Yamamoto, Yusuke; Ito, Takaaki; Okamura, Yukiyasu; Sugiura, Teiichi; Uesaka, Katsuhiko; Nakanuma, Yasuni

    2016-02-21

    We report a case of a 75-year-old man with cystic micropapillary neoplasm of peribiliary glands detected preoperatively by radiologic examination. Enhanced computed tomography showed a low-density mass 2.2 cm in diameter in the right hepatic hilum and a cystic lesion around the common hepatic duct. Under a diagnosis of perihilar cholangiocarcinoma, right hepatectomy with caudate lobectomy and bile duct resection were performed. Pathological examination revealed perihilar cholangiocarcinoma mainly involving the right hepatic duct. The cystic lesion was multilocular and covered by columnar lining epithelia exhibiting increased proliferative activity and p53 nuclear expression; it also contained foci of micropapillary and glandular proliferation. Therefore, the lesion was diagnosed as a cystic micropapillary neoplasm of peribiliary glands and resembled flat branch-type intraductal papillary mucinous neoplasm of the pancreas. Histological examination showed the lesion was discontinuous with the perihilar cholangiocarcinoma. Immunohistochemistry showed the cystic neoplasm was strongly positive for MUC6 and that the cholangiocarcinoma was strongly positive for MUC5AC and S100P. These results suggest these two lesions have different origins. This case warrants further study on whether this type of neoplasm is associated with concomitant cholangiocarcinoma as observed in pancreatic intraductal papillary mucinous neoplasm with concomitant pancreatic duct adenocarcinoma. PMID:26900302

  18. Imaging and interventions in hilar cholangiocarcinoma: A review

    Institute of Scientific and Technical Information of China (English)

    Kumble; Seetharama; Madhusudhan; Shivanand; Gamanagatti; Arun; Kumar; Gupta

    2015-01-01

    Hilar cholangiocarcinoma is a common malignant tumor of the biliary tree. It has poor prognosis with very low 5-year survival rates. Various imaging modalities are available for detection and staging of the hilar cholangiocarcinoma. Although ultrasonography is the initial investigation of choice, imaging with contrast enhanced computed tomography scan or magnetic resonance imaging is needed prior to management. Surgery is curative wherever possible. Radiological interventions play a role in operable patients in theform of biliary drainage and/or portal vein embolization. In inoperable cases, palliative interventions include biliary drainage, biliary stenting and intra-biliary palliative treatment techniques. Complete knowledge of application of various imaging modalities available and about the possible radiological interventions is important for a radiologist to play a critical role in appropriate management of such patients.We review the various imaging techniques and appearances of hilar cholangiocarcinoma and the possible radiological interventions.

  19. The role of liver transplantation for hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Durgatosh Pandey; Kang-Hoe Lee; Kai-Chah Tan

    2007-01-01

    BACKGROUND:Hilar cholangiocarcinoma is a devastating disease. Surgery is the only potentially curative modality. However, the results of surgical resection for hilar cholangiocarcinomas are disappointing. The introduction of liver transplantation for this condition has brought new hope for the management of this disease. The aim of this review is to discuss the role of liver transplantation in this disease. DATA SOURCES:A MEDLINE search was conducted for the articles on liver transplantation for hilar cholangiocarcinoma. Their results have been compiled and compared with the existing literature on resection for this disease. RESULTS:The earlier series on liver transplantation for hilar cholangiocarcinoma were not encouraging because of poor patient selection. The Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver transplantation has shown remarkable success (survival at 1-, 3-, and 5-year post-transplantation being 92%, 82%, and 82%, respectively). With better patient selection and integration of neoadjuvant chemoradiation, the long-term survival is superior to that of the patients who undergo resection, as shown by the published literature on resection. The limitations of organ availability can be overcome by the living donor liver transplantation programme. This review article discusses the rationale, pros and cons of liver transplantation vis-à-vis resection for hilar cholangiocarcinoma. CONCLUSIONS:Liver transplantation, especially living donor liver transplantation, is a new and exciting alternative to resection for hilar cholangiocarcinoma. Integration of neoadjuvant chemoradiation has the potential to further improve the curative potential of liver transplantation. The strategy of combining neoadjuvant chemoradiation and liver transplantation brings new hope for the treatment of this dififcult disease.

  20. CHOLANGIOCARCINOMA: STRATEGY OF DIAGNOSTIC AND TREATMENT

    Directory of Open Access Journals (Sweden)

    C. Gouillat

    2005-10-01

    Full Text Available Cancers of the biliary tree located within the hilum of the liver, are classified according to the pattern of right and left hepatic ductal involvement (Bismuth classification. For this kind of cancers (Klatskin tumors the treatment is controversy. The diagnosis and tumor stage are established by some explorations: ultrasound exam, computed tomography (CT, helical CT, MRI (magnetic resonance imagery, ERCP (endoscopic retrograde cholangiopancreatography. The laparoscopic assessment is useful (with intraoperative ultrasonography and had an accuracy of 53% in some papers. There are two therapeutic strategies: the "aggressive" attitude (surgical resection and palliative treatment. Surgical resections are indicated in elective patients; these techniques include hepatectomies, resection of the main biliary duct, cholecystectomy and sometimes, hepato-duodeno-pancreatectomy. The most optimistic statistics show a postoperative mortality of 10%, a morbidity of 60% and a R0 resection rate of 60%. The mean survival rate was 30-40 month. Palliative treatment includes: the trans-tumoral endo-prothesis (inserted by surgery or, better, by minimally invasive techniques - ERCP, interventional radiology and percutaneous external biliary drainage. Conclusions: A correct assessment of the Klatskin tumors is necessary for therapeutic strategy. The aggressive surgical treatment is indicated only in elective patients and with a multidisciplinary team. Surgeons are playing a key role in the management of cholangiocarcinoma.

  1. Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Kwak TW

    2015-04-01

    Full Text Available Tae Won Kwak,1,* Hee Jae Shin,2,* Young-Il Jeong,1 Myoung-Eun Han,3 Sae-Ock Oh,3 Hyun-Jung Kim,4 Do Hyung Kim,5 Dae Hwan Kang1 1Biomedical Research Institute, Pusan National University Hospital, Busan, 2Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 3Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, 4Genewel Co Ltd. Gyeonggi-do, 5School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea *These authors contributed equally to this work Background: The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. Methods: The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. Results: Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight

  2. Combining biological agents and chemotherapy in the treatment of cholangiocarcinoma

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Jakobsen, Anders

    2011-01-01

    is not always possible. Chemotherapy is effective and the combination of cisplatin and gemcitabine is considered a standard treatment of inoperable cholangiocarcinoma. Biological targeted treatment to date has minor effect when given as monotherapy, but some of the drugs hold promise as an adjunct...... to chemotherapy. It should, however, be noted that most of the trials are based on few patients, and thus far the literature does not allow for a conclusion as to the role of biological treatment on cholangiocarcinoma. This situation calls for well-designed randomized trials, and international cooperation as well...

  3. Poorly Differentiated Gastric Adenocarcinoma Can Mimic Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Urasaki, Tetsuya; Kodaira, Makoto; Hibino, Masaki; Yamagata, Shingo; Watanabe, Yukihiro; Terazawa, Yasuyuki; Sano, Munetaka; Kuriki, Ken

    2016-01-01

    This report describes two cases with obstructive jaundice caused by poorly differentiated gastric adenocarcinoma. Computed tomography scans showed circumferential stenosis in the hilar bile ducts. Endoscopic retrograde cholangiopancreatography showed dilatation of the bilateral hepatic ducts and stenosis of the common hepatic ducts from the bifurcation of the bilateral hepatic ducts. The first diagnoses were hilar cholangiocarcinoma and biliary drainage decreased serum bilirubin; however, both patients died of cancer within a short period of time. Autopsies revealed lymphatic vessel invasion and possible subepithelial invasion by gastric adenocarcinoma into the hilar bile ducts. A differential diagnosis should thus be required in suspected cases of hilar cholangiocarcinoma. PMID:27301505

  4. Medical risk factors associated with cholangiocarcinoma in Taiwan: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Chang

    Full Text Available BACKGROUND: Cholangiocarcinoma, including intra- and extrahepatic cholangiocarcinoma, is a rare but highly lethal cancer. Despite effort in finding the risk factors of cholangiocarcinoma, the causes of most cholangiocarcinoma remain unknown. This study utilized a population-based case-control design using data from the National Health Insurance Research Database (NHIRD of Taiwan to assess the medical conditions associated with cholangiocarcinoma. METHODS: 5,157 incident cases of cholangiocarcinoma diagnosed during 2004 to 2008 and 20,628 controls matched to the cases on sex, age, and time of diagnosis (reference date for the controls were identified from the NHIRD. Medical risk factors were ascertained from the NHIRD for each individual. Conditional logistic regression was performed to evaluate the association between cholangiocarcinoma and each medical risk factor. RESULTS: The results showed that factors associated with an increased risk of cholangiocarcinoma included cholangitis, cholelithiasis, cholecystitis, cirrhosis of liver, alcoholic liver disease, chronic non-alcoholic liver disease, hepatitis B, hepatitis C, diabetes, chronic pancreatitis, inflammatory bowel disease, and peptic ulcer. In addition, sex and age differences were observed. CONCLUSIONS: This study confirms the association between cholangiocarcinoma and several less established risk factors, including diabetes, inflammatory bowel disease, hepatitis B, hepatitis C, and peptic ulcer (proxy for the presence of Helicobacter Pylori. Future studies should focus on finding additional environmental and genetic causes of cholangiocarcinoma.

  5. Cholangiocarcinomas: New Insights from the Discovery of Stem Cell Niches in Peribiliary Glands of the Biliary Tree

    Directory of Open Access Journals (Sweden)

    Vincenzo Cardinale

    2014-01-01

    Full Text Available Peribiliary glands (PBGs are located in the large intrahepatic and extrahepatic bile ducts. Although they were described many years ago, their functions have been elucidated only in the last couple of years when our group demonstrated that PBGs are niches of multipotent stem/progenitor cells of endodermal origin. These cells express genes of multipotency and can be rapidly differentiated in vitro into hepatocytes, cholangiocytes, and endocrine pancreatic cells. PBGs share common features, in terms of stem/progenitor cell niches, with pancreatic duct glands and colon crypts, glandular structures representing in the adult life the endodermal remnants of fetal life. PBG stem/progenitor cells participate in the renewal of surface biliary epithelium and are active players in chronic pathologies of the biliary tree as well as in cholangiocarcinomas (CCA. Specifically, a large amount of recent evidence indicates that the pure mucin-CCA originates from PBGs; this could explain the similarities with pancreatic ductal adenocarcinoma and colorectal cancer, which also originate from transformed gland cells. In this paper, we summarized our recent findings concerning structure and functions of PBGs with the implications for liver pathophysiology and, specifically, for cancers of the biliary tree.

  6. Neoadjuvant Down-Sizing of Hilar Cholangiocarcinoma with Photodynamic Therapy—Long-Term Outcome of a Phase II Pilot Study

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    Andrej Wagner

    2015-11-01

    Full Text Available Hilar cholangiocarcinoma (CC is non-resectable in the majority of patients often due to intrahepatic extension along bile duct branches/segments, and even after complete resection (R0 recurrence can be as high as 70%. Photodynamic therapy (PDT is an established palliative local tumor ablative treatment for non-resectable hilar CC. We report the long-term outcome of curative resection (R0 performed after neoadjuvant PDT for downsizing of tumor margins in seven patients (median age 59 years with initially non-resectable hilar CC. Photofrin® was injected intravenously 24–48 h before laser light irradiation of the tumor stenoses and the adjacent bile duct segments. Major resective surgery was done with curative intention six weeks after PDT. All seven patients had been curatively (R0 resected and there were no undue early or late complications for the neoadjuvant PDT and surgery. Six of seven patients died from tumor recurrence at a median of 3.2 years after resection, the five-year survival rate was 43%. These results are comparable with published data for patients resected R0 without pre-treatment, indicating that neoadjuvant PDT is feasible and could improve overall survival of patients considered non-curatively resectable because of initial tumor extension in bile duct branches/segments—however, this concept needs to be validated in a larger trial.

  7. Improved outcome of resection of hilar cholangiocarcinoma (Klatskin tumor)

    NARCIS (Netherlands)

    S. Dinant; M.F. Gerhards; E.A.J. Rauws; O.R.C. Busch; D.J. Gouma; T.M. van Gulik

    2006-01-01

    Background: Treatment of hilar cholangiocarcinoma (Klatskin tumors) has changed in many aspects. A more extensive surgical approach, as proposed by Japanese surgeons, has been applied in our center over the last 5 years; it combines hilar resection with partial hepatectomy for most tumors. The aim o

  8. Cholestasis and Pruritus: Progressive Familial Intrahepatic Cholestasis?

    Directory of Open Access Journals (Sweden)

    Gökhan Tümgör

    2016-08-01

    Full Text Available Progressive familial intrahepatic cholestasis (PFIC has a significant place among the childhood cholestasis. It is the second most frequent liver transplant indication met in some liver transplant institutions. It constitutes approximately 10-15% of all cases of cholestasis and liver transplant. PFIC is an autosomal recessively inherited disorder and causes hepatocellular-originated cholestasis. In the period from infancy to adulthood it may cause death due to liver failure. PFIC has three types and the most frequently observed clinical symptoms of all three types are; pruritus, hepatitis, growth retardation, hepatomegaly, and splenomegaly. The prognosis of these three types of PFIC is different. The complications of PFIC are; portal hypertension, liver failure, cirrhosis, hepatocellular carcinoma, and extrahepatic symptoms. Although medical and surgical treatments are applied in order to improve the patients’ life quality, most of the cases require liver transplantation in the early stage.

  9. Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy

    OpenAIRE

    Savander, M; Ropponen, A; Avela, K.; Weerasekera, N; Cormand, B; Hirvioja, M-L; Riikonen, S.; Ylikorkala, O; Lehesjoki, A-E; C. Williamson; Aittomäki, K.

    2003-01-01

    Background and aims: The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes (BSEP, FIC1, and MDR3) on the development of this disease.

  10. Intrahepatic localization of pancreatic pseudocyst: a case report.

    Science.gov (United States)

    Baydar, Behlül; Cantürk, Fatih; Alper, Emrah; Aslan, Fatih; Akpınar, Zehra; Cengız, Onur; Kandemır, Altay; Ünsal, Belkıs

    2013-01-01

    The location of a pseudocyst in the liver is an exceptional event. We report here a case developing right and left intrahepatic pseudocyst following acute biliary pancreatitis. Ultrasound and computed tomography scan revealed a 13-cm right and two 4-cm left intrahepatic collections. Percutaneous puncture permitted us to detect a high level of amylase in the collection, confirming the diagnosis of intrahepatic pseudocyst. Percutaneous drainage resulted in 3000 mL of fluid discharge. The mechanism involved in this patient was rupture of the pancreatic pseudocyst in the retroperitoneal cavity and erosion reaching the right hepatic parenchyma retroperitoneally posterior to the hepatoduodenal ligament and the left hepatic parenchyma via the hepatogastric ligament. Besides, endoscopic sphincterotomy was performed with endoscopic retrograde cholangiopancreatography for cholangitis. After performing endoscopic sphincterotomy, the cysts in the left lobe resolved dramatically. Intrahepatic pseudocyst should be kept in mind when an intrahepatic collection is found in a patients with chronic or recent episode of acute pancreatitis. Computed tomography and high level of amylase in the collection plays an important role for diagnosing this complication. In case of abdominal pain and large intrahepatic pseudocyst, percutaneous drainage can be performed.

  11. Long-term survival after intraluminal brachytherapy for inoperable hilar cholangiocarcinoma: A case report

    Institute of Scientific and Technical Information of China (English)

    Siu-Yin Chan; Ronnie T. Poon; Kelvin K. Ng; Chi-Leung Liu; Raymond T. Chan; Sheung-Tat Fan

    2005-01-01

    Surgical resection with a tumor-free margin is the onlycurative treatment for hilar cholangiocarcinoma (Klatskin tumor). However, over half of the patients present late with unresectable tumors. Radiotherapy using external beamirradiation or intraluminal brachytherapy (ILBT) has been used to treat unresectable hilar cholangiocarcinoma with satisfactory outcome. We reported a patient with unresectable hilar cholangiocarcinoma surviving more than 6 years after combined external beam irradiation and ILBT.

  12. Review of endoscopic techniques in the diagnosis and management of cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Katherine Nguyen; James T Sing Jr

    2008-01-01

    Cholangiocarcinoma is a rare malignancy of the biliary tract. Key factors in determining therapeutic options include knowledge of tumor extent, anatomy and obtaining tissue diagnosis. Endoscopically, there are three modalities available to make the diagnosis of cholangiocarcinoma. These include endoscopic retrograde cholangiopancreatography, endoscopic ultrasound with fine needle aspiration and cholangioscopy. Management of cholangiocarcinoma endoscopically is typically confined to stent placement for palliative purposes or as a bridge to surgery. In this article, we will review the endoscopic techniques available for the diagnosis and management of cholangiocarcinoma.

  13. Percutaneous intraductal radiofrequency ablation combined with metal stent implantation for the treatment of advanced hilar cholangiocarcinoma%经皮肝穿胆道射频消融联合金属支架植入治疗晚期肝门部胆管癌的临床价值

    Institute of Scientific and Technical Information of China (English)

    方兆山; 向飞; 刘星星; 黄海

    2016-01-01

    目的 探讨经皮肝穿刺(PTC)胆道内射频消融(RFA)联合金属支架(SEMs)植入术治疗晚期肝门部胆管癌(HCCA)的安全性和疗效.方法 回顾性分析32例晚期HCCA胆道内RFA联合SEMs植入术治疗的患者资料.分析术后30 d并发症和支架通畅时间、生存时间和死亡率等.结果 手术技术成功率100.0%,术后30 d无严重并发症发生,轻微并发症发生率25.0%,其中胆道感染发生率12.5%,疼痛发生率12.5%;中位支架通畅时间为196 d(95%可信区间173~218 d);中位生存时间229 d(95%可信区间211~246d);RFA术后1月、3月死亡率为0,6月死亡率21.9%.结论 经皮肝穿刺胆道内射频消融联合金属支架植入术治疗无法手术切除的肝门部胆管癌是安全可行的,短期可获得一定临床疗效.%Objective To evaluate the safety and short-term efficacy of percutaneous intraductal radiofrequency ablation(RFA) combined with metal stent implantation in the treatment of advanced hilar cholangiocarcinoma(HCCA).Methods The data 32 patients with unresectable HCCA,treated with percutaneous intraductal radiofrequency ablation and self-expanding metal stent (SEMs)implantation,were retrospectively analyzed.The incidence of complications 30 days after operation,stent patency time,survival time,and mortality were analyzed.Results The surgery successful rate was 100.0%.30 days after surgery,no one occurred severe complications and 8 patients (25.0%) got mild complications;among which,4 (12.5%) got cholangitis and 4(12.5%) abdominal pain.The median stent patency time after RFA was 196 d (95% CI 173-218 d).The median survival time was 229 d (95% CI 211-246 d) from the time of the first RFA in each patient.The first RFA procedure of each patient was defined as starting point.1,3,and 6 months after RFA,the mortalities were 0.0%,0.0%,and 21.9%,respectively.Conclusions Percutaneous intraductal RFA combined with SEMs implantation is a technically feasible

  14. Operation treatment method of Bismuth-Corlette Ⅲ, Ⅳ hilar cholangiocarcinoma%Bismuth-Corlette Ⅲ、Ⅳ型肝门部胆管癌的手术治疗方式

    Institute of Scientific and Technical Information of China (English)

    鲁正; 王冬冬

    2016-01-01

    肝门部胆管癌亦称胆管上段癌、围肝门部胆管癌、Klatskin瘤等.Bismuth-CorletteⅢ型肝门部胆管癌指肿瘤侵犯右肝管(Ⅲa)或左肝管(Ⅲb),Bismuth-CorletteⅣ型肝门部胆管癌指左右肝内胆管均已受侵犯.在严格把握手术指征的前提下,经过充分的术前管理,Bismuth-CorletteⅢ、Ⅳ型肝门部胆管癌扩大肝切除是一种安全可行的手术方式.在进行扩大肝切除同时,应视情况积极选择右半肝切除和联合尾状叶切除.同时应常规施行肝十二指肠韧带淋巴结骨骼化清扫,并视情况扩大至腹腔干、主动脉旁及胰头后方.在能够根治性切除的前提下,应切除受侵犯血管,并视情况对所切除血管积极进行重建.%Hilar cholangiocarcinoma (HCCA) is also known as cancer at the upper part of bile duct,perihilar cholangiocarcinoma or Klatskin tumor,etc.Bismuth-Corlette type Ⅲ hilar cholangiocarcinoma refers to tumor invading right hepatic duct (Ⅲa) or left hepatic duct (Ⅲb).While Bismuth-Corlette type Ⅳ hilar cholangiocarcinoma refers to both left and right intrahepatic bile ducts being invaded.Under the premise of strictly grasping the indications of surgery,if preoperative management is conducted carefully,extended hepatic resection is a safe and feasible surgery to remove Bismuth-Corlette type Ⅲ and type Ⅳ hilar cholangiocarcinoma.When conducting extended hepatic resection,right hepatectomy and combined caudate lobectomy should be conducted depending on the circumstances.Routine skeletization lymph node dissection of the hepatoduodenal ligament is performed,which could be expanded into celiac trunk,para-aortic area and the rear of pancreatic head.In the premise of radical resection,invaded vessels should be removed and then reconstructed depending on circumstances.

  15. Orthotopic liver transplantation with hepatopancreatoduodenectomy for hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    HE Xiao-shun; ZHANG Shao; ZHU Xiao-feng; WANG Dong-ping; MA Yi; WANG Guo-dong; JU Wei-qiang; WU Lin-wei; HUANG Jie-fu

    2007-01-01

    @@ Although the surgical treatment for hilar cholangiocarcinoma represents the only potentially curative option, local excision and major hepatectomy1 have failed to produce a favorable survival figure over the last decade. This is partly due to local tumor recurrences within the resection margin, perineural sheaths infiltration,and the regional lymph nodes metastasis after the surgery.Recently, an extended bile duct resection combined with total hepatectomy, pancreatoduodenectomy, and

  16. Metal stents: a bridge to surgery in hilar cholangiocarcinoma

    OpenAIRE

    Grünhagen, Dirk J.; Dunne, Declan FJ; Sturgess, Richard P; Stern, Nick; Hood, Stephen; Fenwick, Stephen W; Poston, Graeme J; Malik, Hassan Z

    2012-01-01

    Background Obstructive jaundice in patients with hilar cholangiocarcinoma is a known risk factor for hepatic failure after liver resection. Plastic stents are most widely used for preoperative drainage. However, plastic stents are known to have limited patency time and therefore, in palliative settings, the self-expanding metal stent (SEMS) is used. This type of stent has been shown to be superior because it allows for rapid biliary decompression and a reduced complication rate after insertio...

  17. Heterotopic Pancreas Mimicking Cholangiocarcinoma. Case Report and Literature Review

    OpenAIRE

    Atindriya Biswas; Ehab A. Husain; Roger M Feakins; Abraham, Ajit T

    2007-01-01

    Context Majority of the patients developing obstructive jaundice have an underlying malignancy. Identification of a benign pathology like heterotopic pancreas as an aetiology is uncommon and usually occurs only subsequent to a major operation. Case report We report a case of heterotopic pancreas adjacent to the ampulla of Vater mimicking distal cholangiocarcinoma. A 47- year-old patient presented with abdominal pain and obstructive jaundice. ERCP demonstrated a distal common bile duct strictu...

  18. Plasma Lipidomics as a Tool for Diagnosis of Extrahepatic Cholangiocarcinoma in Biliary Strictures: a Pilot Study.

    Science.gov (United States)

    Prachayakul, Varayu; Thearavathanasingha, Phataraphong; Thuwajit, Chanitra; Roytrakul, Sittiruk; Jaresitthikunchai, Janthima; Thuwajit, Peti

    2016-01-01

    Biliary obstruction is a common clinical manifestation of various conditions, including extrahepatic cholangiocarcinoma. However, a screening test for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction is not yet available. According to the rationale that the biliary system plays a major role in lipid metabolism, biliary obstruction may interfere with lipid profiles in the body. Therefore, plasma lipidomics may help indicate the presence or status of disease in biliary obstruction suspected extrahepatic cholangiocarcinoma. This study aimed to use plasma lipidomics for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction. Plasma from healthy volunteers, patients with benign biliary obstruction extrahepatic cholangiocarcinoma, and other related cancers were used in this study. Plasma lipids were extracted and lipidomic analysis was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Lipid profiles from extrahepatic cholangiocarcinoma patients showed significant differences from both normal and benign biliary obstruction conditions, with no distinction between the latter two. Relative intensity of the selected lipid mass was able to successfully differentiate all extrahepatic cholangiocarcinoma samples from patient samples taken from healthy volunteers, patients with benign biliary obstruction, and patients with other related cancers. In conclusion, lipidomics is a non-invasive method with high sensitivity and specificity for identification of extrahepatic cholangiocarcinoma in patients with biliary obstruction. PMID:27644677

  19. Orotate phosphoribosyl transferase mRNA expression and the response of cholangiocarcinoma to 5-fluorouracil

    Institute of Scientific and Technical Information of China (English)

    Chariya Hahnvajanawong; Jariya Chaiyagool; Wunchana Seubwai; Vajarabhongsa Bhudhisawasdi; Nisana Namwat; Narong Khuntikeo; Banchob Sripa

    2012-01-01

    AIM:To determine whether expression of certain enzymes related to 5-fluorouracil (5-FU) metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma (CCA).METHODS:The histoculture drug response assay (HDRA) was performed using surgically resected CCA tissues.Tumor cell viability was determined morphologically with hematoxylin and eosin-and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues.The mRNA expression of thymidine phosphorylase (TP),orotate phosphoribosyl transferase (OPRT),thymidylate synthase (TS),and dihydropyrimidine dehydrogenase (DPD) was determined with realtime reverse transcriptase-polymerase chain reaction.The levels of gene expression and the sensitivity to 5-FU were evaluated.RESULTS:Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital,Khon Kaen University from 2007 to 2009.HDRA was used to determine the response of these CCA tissues to 5-FU.Based on the dose-response curve,200 μg/mL 5-FU was selected as the test concentration.The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU.When the relationship between TP,OPRT,TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined,only OPRT mRNA expression was significantly correlated with the response to 5-FU.The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group (0.41 ± 0.25 vs 0.22 ± 0.12,P < 0.05).CONCLUSION:OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA.Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.

  20. Intrahepatic haematoma in a patient on long-term haemodialysis.

    Science.gov (United States)

    Lai, K N; Disney, A P; Mathew, T H

    Spontaneous intrahepatic haematoma is an uncommon potentially fatal complication in uraemic patients receiving long-term haemodialysis, particularly in those taking anticoagulant and antiplatelet drugs. Prompt diagnosis, withdrawal of anticoagulant and antiplatelet therapy, cautious transfusion, and careful dialysis with regional heparinisation are essential in the management and may help to avoid surgical intervention in the presence of a tendency to bleed. Noninvasive organ imaging such as ultrasonography and computerised axial tomography are helpful in diagnosis and monitoring of progress. A case of intrahepatic haematoma in a 37-year-old man who had been receiving long-term haemodialysis since 1976 is described.

  1. Primary amyloidosis presenting intrahepatic cholestasis and fulminant hepatic failure

    OpenAIRE

    Ozturk Ates; Kemal Kosemehmetoglu; Gunes Guner; Yusuf Bayraktar

    2015-01-01

    A 69-year-old man noticed abdominal pain located on right upper quadrant. Physical examination showed hepatosplenomegaly and icteric discoloration of sclera. On evaluation, patient was diagnosed to have hepatic amyloidosis related monoclonal gammopathy of undetermined significance (MGUS) and sinusoidal obstruction syndrome with intrahepatic cholestasis. In this case report we emphasize fulminant hepatic failure due to primer amyloidosis in diagnosed with MGUS patient.

  2. Novel target genes and a valid biomarker panel identified for cholangiocarcinoma

    Science.gov (United States)

    Andresen, Kim; Boberg, Kirsten Muri; Vedeld, Hege Marie; Honne, Hilde; Hektoen, Merete; Wadsworth, Chrisopher A.; Clausen, Ole Petter; Karlsen, Tom Hemming; Foss, Aksel; Mathisen, Øystein; Schrumpf, Erik; Lothe, Ragnhild A.; Lind, Guro E.

    2012-01-01

    Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate is high due to late clinical presentation. CpG island promoter methylation is frequently seen in cancer development. In the present study, we aimed at identifying novel epigenetic biomarkers with the potential to improve the diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated counterparts were compared with previously published gene expression profiles of primary tumors and with non-malignant controls. Genes responding to the epigenetic treatment that were simultaneously downregulated in primary cholangiocarcinoma compared with controls (n = 43) were investigated for their promoter methylation status in cancer cell lines from the gastrointestinal tract. Genes commonly methylated in cholangiocarcinoma cell lines were subjected to quantitative methylation-specific polymerase chain reaction in a total of 93 clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1, SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and were unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel methylation-based biomarker panel showed high sensitivity and specificity for cholangiocarcinoma. The potential of these markers in early diagnosis of this cancer type should be further explored. PMID:22983262

  3. Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hyun Ah Yoon; Myung Hwan Noh; Byung Geun Kim; Ji Sun Han; Jin Seok Jang; Seok Ryeol Choi; Jin Sook Jeong; Jin Ho Chun

    2011-01-01

    AIM: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.RESULTS: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T

  4. PTEN and PDCD4 are Bona Fide Targets of microRNA-21 in Human Cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Chang-zheng Liu; Wei Liu; Yi Zheng; Jin-mei Su; Jing-jing Li; Lan Yu; Xiao-dong He; Song-sen Chen

    2012-01-01

    Objective To investigate the expression profile of microRNA-21 in human cholangiocarcinoma tissues and to validate its bona fide targets in human cholangiocarcinoma cells.Methods The expression profile ofmicroRNA-21 in human cholangiocarcinoma tissues and cholangiocarcinoma cell line,QBC939,was evaluated by using real-time PCR analysis.The bona fide targets of microRNA-21 were analyzed and confirmed by dual luciferase reporter gene assay and western blot,respectively.The expressional correlation of microRNA-21 and its targets was probed in human cholangiocarcinoma tissues by using real-time PCR,locked nucleic acid in situ hybridization (LNA-ISH),and immunohistochemistry analysis.Results Real-time PCR analysis revealed that microRNA-21 expression depicted a significant up-regulation in human cholangiocarcinoma tissues about 5.6-fold as compared to the matched normal bile duct tissues (P<0.05).The dual luciferase reporter gene assay revealed endogenous microRNA-21 in cholangiocarcinoma cell line,QBC939,inhibited the luciferase reporter activities of wild-type PTEN (P<0.01) and PDCD4 (P<0.05) and had no this effect on mutated PTEN and PDCD4.Moreover,loss of microRNA-21 function led to a significant increase of PTEN and PDCD4 protein levels in QBC939 cells.Elevated microRNA-21 levels were accompanied by marked reductions of PTEN and PDCD4 expression in the same cholangiocarcinoma tissue.Conclusion microRNA-21 expression is up-regulated in human cholangiocarcinoma and PTEN,PDCD4 are direct effectors of microRNA-21.

  5. Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes

    Science.gov (United States)

    Mimaki, Sachiyo; Totsuka, Yukari; Suzuki, Yutaka; Nakai, Chikako; Goto, Masanori; Kojima, Motohiro; Arakawa, Hirofumi; Takemura, Shigekazu; Tanaka, Shogo; Marubashi, Shigeru; Kinoshita, Masahiko; Matsuda, Tomonari; Shibata, Tatsuhiro; Nakagama, Hitoshi; Ochiai, Atsushi; Kubo, Shoji; Nakamori, Shoji; Esumi, Hiroyasu; Tsuchihara, Katsuya

    2016-01-01

    Cholangiocarcinoma is a relatively rare cancer, but its incidence is increasing worldwide. Although several risk factors have been suggested, the etiology and pathogenesis of the majority of cholangiocarcinomas remain unclear. Recently, a high incidence of early-onset cholangiocarcinoma was reported among the workers of a printing company in Osaka, Japan. These workers underwent high exposure to organic solvents, mainly haloalkanes such as 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. We performed whole-exome analysis on four cases of cholangiocarcinoma among the printing workers. An average of 44.8 somatic mutations was detected per Mb in the genome of the printing workers’ cholangiocarcinoma tissues, approximately 30-fold higher than that found in control common cholangiocarcinoma tissues. Furthermore, C:G-to-T:A transitions with substantial strand bias as well as unique trinucleotide mutational changes of GpCpY to GpTpY and NpCpY to NpTpY or NpApY were predominant in all of the printing workers’ cholangiocarcinoma genomes. These results were consistent with the epidemiological observation that they had been exposed to high concentrations of chemical compounds. Whole-genome analysis of Salmonella typhimurium strain TA100 exposed to 1,2-DCP revealed a partial recapitulation of the mutational signature in the printing workers’ cholangiocarcinoma. Although our results provide mutational signatures unique to occupational cholangiocarcinoma, the underlying mechanisms of the disease should be further investigated by using appropriate model systems and by comparison with genomic data from other cancers. PMID:27267998

  6. Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Hiroyuki Isayama; Takeshi Tsujino; Yousuke Nakai; Takashi Sasaki; Keiichi Nakagawa; Hideomi Yamashita; Taku Aoki; Kazuhiko Koike

    2012-01-01

    AIM:To determine the efficacy of external beam radiotherapy (EBRT),with or without intraluminal brachytherapy (ILBT),in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS:We analyzed 64 patients with locally advanced hilar cholangiocarcinoma,including 25 who underwent resection (17 curative and 8 non-curative),28 treated with radiotherapy,and 11 who received best supportive care (BSC).The radiotherapy group received EBRT (50 Gy,30 fractions),with 11 receiving an additional 24 Gy (4 fractions) ILBT by iridium-192 with remote after loading.ILBT was performed using percutaneous transhepatic biliary drainage (PTBD) route.Uncovered metallic stents (UMS) were inserted into nonresected patients with obstructive jaundice,with the exception of four patients who received percutaneous transhepatic biliary drainage only.UMS were placed endoscopically or percutaneously,depending on the initial drainage procedure.The primary endpoints were patient death or stent occlusion.Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups.Stent patency was compared in the radiotherapy and BSC groups.RESULTS:No statistically significant differences in patient characteristics were found among the resection,radiotherapy,and BSC groups.Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone;cholangitis occurred after endoscopic stenting,and patients were treated with PTBD.A total of 16 patients were administered additional systemic chemotherapy (5-fluorouracil-based regimen in 9,S-1 in 6,and gemcitabine in 1).Overall survival varied significantly among groups,with median survival times of 48.7 mo in the surgery group,22.1 mo in the radiotherapy group,and 5.7 mo in the BSC group.Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery (P =0.0076).Cumulative survival in the

  7. Hilar Cholangiocarcinoma Diagnosed and Treated Early, in Prejaundice Phase

    Directory of Open Access Journals (Sweden)

    Denes M.

    2014-08-01

    Full Text Available Hilar cholangiocarcinoma, Klatskin tumor or proximal bile duct cancer, is a tumor growing in the right hepatic duct, left hepatic duct or at their confluence. It is a relatively rare but devastating disease. The tight stricture of the biliary ducts and the development of obstructive jaundice are the main characteristics of the disease. In the early phase, symptoms are nonspecific and jaundice is not present, leading to delayed diagnosis and denying the possibility of curative treatment. We present the case of a 74 years old woman who was referred to us with ambiguous symptomatology and without jaundice. The ultrasound and CT scan showed dilation of the left biliary tree, without increase of the cholestatic enzymes. Magnetic resonance cholangiography depicted a tumor in the left hepatic duct (3X3 cm. with enlargement of the bile ducts above. The surgical treatment consisted of left hepatectomy and hilar lymph nodes dissection. The pathology findings showed a cholangiocarcinoma with a few hilar nodes involvement. Our approach was potentially curative. Unfortunately these situations are seldom because in the majority of cases the patients have obstructive jaundice at presentation and the tumors are unresectable. We consider that a magnetic resonance cholangiography made when we suspect a bile duct tumor, leads us to an early diagnosis and gives us the possibility of a potential curative surgical treatment.

  8. Hepatic por tal cholangiocarcinoma:a clinical analysis of 70 cases

    Institute of Scientific and Technical Information of China (English)

    Hong-Yi Zhang; Zhi-Qiang Feng; Ya-Lin Kong; Hong-Yi Zhang; Xiao-Jun He; Hui Zhang; Cheng-Li Liu; Gang Zhao; Mei Xiao; Xi-Dong Zhang

    2008-01-01

    BACKGROUND: The incidence of hepatic portal cholangiocarcinoma is increasing and it is always associated with poor survival. This study analyzed an effective therapeutic method. METHODS: A retrospective analysis was made on 70 patients with hepatic portal cholangiocarcinoma admitted between January 2004 and February 2007 to the General Hospital of Air Force PLA. RESULTS: Forty-seven patients had hepatic duct-jejunum anastomosis after resection of hepatic portal cholangiocarcinoma. Internal or external biliary drainage and canals for internal radiation were performed in those patients unift for operation. Among the 70 patients, 5 died within 15 months, 27 survived more than 24 months, and the others survived 4-18 months. CONCLUSION: Surgery is the primary therapeutic method for hepatic portal cholangiocarcinoma. Internal or external biliary drainage can prolong the life-span.

  9. Impact of bile acids on the growth of human cholangiocarcinoma via FXR

    OpenAIRE

    Zhang Yinxin; Dong Ying; Shi Yihui; Wang Hongxia; Dai Jiaqi; Wang Jian

    2011-01-01

    Abstract Background The objective of the study was to investigate the effect of different types of bile acids on proliferation of cholangiocarcinoma and the potential molecular mechanisms. Methods PCR assay and Western blot were performed to detect the expression of farnesoid × receptor (FXR) in mRNA and protein level. Immunohistochemical analysis was carried out to monitor the expression of FXR in cholangiocarcinoma tissues from 26 patients and 10 normal controls. The effects on in vivo tumo...

  10. Developmental intrahepatic shunts of childhood: radiological features and management

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the role of radiological techniques in the diagnosis and management of developmental intrahepatic shunts. Hepatic vascular fistulae are recognised sequelae of liver trauma and intrahepatic tumours. However, there are rare developmental malformations which may present in childhood or later life and which may carry life-threatening complications. Retrospective analysis of clinical and radiological data was carried out in 24 patients. Anomalies evaluated were: (a) direct communication between hepatic artery and hepatic veins; (b) congenital hepatoportal arteriovenous malformations; and (c) congenital portocaval anastomosis with persistent flow through the ductus venosus. Although rare, the prompt recognition of these vascular anomalies allows early surgical or radiological intervention and reversal of the haemodynamic complications. (orig.)

  11. Normal anatomical variation of the intrahepatic portal vein in Korean

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jae Cheon; Seo, Heung Suk; Kim, Yong Soo; Rhim, Hyun Chul; Koh, Byung Hee; Cho, On Koo; Moon, Won Jin; Lee, Tae Hee [Hanyang Univ., Seoul (Korea, Republic of). Coll. of Medicine

    1997-12-01

    The purpose of this study is to determine the prevalence of variations in the intrahepatic portions of portal veins, as visualized by arterial portograms, and to examine the surgical implications of these findings in Koreans. Five hundred and nineteen arterial portograms of 519 patients with no evidence of vascular tumor invasion or distortion were retrospectively reviewed. In all patients, the main, right, right anterior, right posterior and left portal vein were visualized. On arterial portogram, variations in the intrahepatic portions of the portal veins are frequently seen. The recognition of such variations is important in the preoperative evaluation of patients with hepatic tumors, since the variations may have implications for tumor resection, for the localization of tumor thrombi and in interventional radiologic procedures involving the portal vein. (author).13 refs., 1 tab., 4 figs.

  12. Intrahepatic Duct Stones Harboring Ascariasis Ova: A Case Report.

    Science.gov (United States)

    Lee, Chen-Fang; Lee, Wei-Chen; Wu, Ren-Chin; Chen, Tse-Ching

    2016-03-01

    Ascariasis lumbricoides is one of the most common helminthic infestations in humans. Despite the fact that the prevalence of ascariasis in developed countries has been decreasing, biliary ascariasis can cause serious complications, such as acute cholangitis, pancreatitis, and liver abscess. Here we presented a rare ascariasis-related complication-hepatolithiasis.A 60-year-old female patient had symptoms of recurrent cholangitis. Abdominal computed tomography scan revealed left intrahepatic duct stones with left liver lobe atrophy. Endoscopic retrograde cholangiopancreatography was performed, but the stones could not be removed due to left main intrahepatic duct stenosis. The patient was treated with left hemi-hepatectomy. Unexpectedly, Ascaris ova were found on the histopathological examination. She received antihelminthic therapy orally and was on regular follow-up without any complications.Our study indicates that clinicians should be aware of biliary ascariasis in patients with hepatolithiasis, though not living in endemic areas. PMID:27015193

  13. Congenital hepatoportal arteriovenous fistula associated with intrahepatic portal vein aneurysm and portohepatic venous shunt: case report

    International Nuclear Information System (INIS)

    A congenital hepatoportal arteriovenous fistula associated with an intrahepatic portal vein aneurysm is a rare type of arteriovenous malformation. Only 14 pediatric cases have been reported to the best of the authors' knowledge. An intrahepatic shunt between the portal and systemic veins is also relatively rare. We report a case of a congenital hepatoportal arteriovenous fistula associated with an intrahepatic portal vein aneurysm and a portohepatic venous shunt in a neonate who presented with tachypnea and melena

  14. Strong expression of CD133 is associated with increased cholangiocarcinoma progression

    Institute of Scientific and Technical Information of China (English)

    Kawin Leelawat; Taweesak Thongtawee; Siriluck Narong; Somboon Subwongcharoen; Sa-ad Treepongkaruna

    2011-01-01

    AIM: To determine the role of CD133 in cholangiocar-cinoma progression.METHODS: CD133 protein expression was evaluated by immunohistochemistry in 34 cholangiocarcinoma specimens. In addition, proliferation, chemoresistance and invasive properties of CD133-enriched (CD133+) and CD133-depleted (CD133-) RMCCA1 cholangiocarci-noma cells were studied and compared.RESULTS: Strong CD133 expression was observed in 67.6% (23/34) of the cholangiocarcinoma specimens. Strong expression of CD133 was significantly associat-ed with nodal metastasis (P = 0.009) and positive sur-gical margin status (P = 0.011). In the in vitro study, both the CD133+ and CD133- cells had similar prolifera-tion abilities and resistance to chemotherapeutic drugs. However, the CD133+ cells had a higher invasive ability compared with CD133- cells.CONCLUSION: CD133+ cells play an important role in the invasiveness of cholangiocarcinoma. Targeting of the CD133+ cells may be a useful approach to improve treatment against cholangiocarcinoma.

  15. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Zhongqi [Department of Hepatobiliary & Pancreas Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021 (China); Yu, Huimei [Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021 (China); Cui, Ni [Bethune Medical College, Jilin University, Changchun, Jilin 130021 (China); Kong, Xianggui; Liu, Xiaomin; Chang, Yulei [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun, Jilin 130033 (China); Wu, Yao [Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021 (China); Sun, Liankun, E-mail: sunlk@jlu.edu.cn [Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021 (China); Wang, Guangyi, E-mail: wgymd@sina.com [Department of Hepatobiliary & Pancreas Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021 (China)

    2015-07-01

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy.

  16. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    International Nuclear Information System (INIS)

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy

  17. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA).

    Science.gov (United States)

    Banales, Jesus M; Cardinale, Vincenzo; Carpino, Guido; Marzioni, Marco; Andersen, Jesper B; Invernizzi, Pietro; Lind, Guro E; Folseraas, Trine; Forbes, Stuart J; Fouassier, Laura; Geier, Andreas; Calvisi, Diego F; Mertens, Joachim C; Trauner, Michael; Benedetti, Antonio; Maroni, Luca; Vaquero, Javier; Macias, Rocio I R; Raggi, Chiara; Perugorria, Maria J; Gaudio, Eugenio; Boberg, Kirsten M; Marin, Jose J G; Alvaro, Domenico

    2016-05-01

    Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.

  18. Transjugular Intrahepatic Portosystemic Shunts in Patients with Hepatic Malignancy

    OpenAIRE

    Wallace, Michael J.; Madoff, David C.

    2005-01-01

    Since its first clinical application in 1988, the transjugular intrahepatic portosystemic shunt (TIPS) has emerged as a safe and effective means of managing patients with morbid portal hypertension. Despite the considerable body of literature on TIPS, portal decompression in patients with malignancy has not been sufficiently examined. These patients typically experience sequelae of portal hypertension that requires palliation. The purpose of this article is to review the reported experience w...

  19. Primary amyloidosis presenting intrahepatic cholestasis and fulminant hepatic failure

    Directory of Open Access Journals (Sweden)

    Ozturk Ates

    2015-06-01

    Full Text Available A 69-year-old man noticed abdominal pain located on right upper quadrant. Physical examination showed hepatosplenomegaly and icteric discoloration of sclera. On evaluation, patient was diagnosed to have hepatic amyloidosis related monoclonal gammopathy of undetermined significance (MGUS and sinusoidal obstruction syndrome with intrahepatic cholestasis. In this case report we emphasize fulminant hepatic failure due to primer amyloidosis in diagnosed with MGUS patient.

  20. Cholangiocarcinoma in Magnetic Resonance Cholangiopancreatography and Fascioliasis in Endoscopic Ultrasonography

    Directory of Open Access Journals (Sweden)

    Amir Houshang Mohammad Alizadeh

    2011-10-01

    Full Text Available Fascioliasis is a worldwide zoonotic infection with Fasciola hepatica and Fasciola gigantica. The zoonoses are particularly endemic in sheep-raising countries and are also endemic in Iran. Typical symptoms that may be associated with fascioliasis can be divided by phases of the disease, including the acute or liver phase, the chronic or biliary phase, and ectopic or pharyngeal fascioliasis. Cholestatic symptoms may be absent, and in some cases diagnosis and treatment may be preceded by a long period of abdominal pain, eosinophilia and vague gastrointestinal symptoms. We report a case with epigastric and upper quadrant abdominal pain for the last 4 years, with imaging suggesting cholangiocarcinoma. Considering a new concept of endoscopic ultrasonography, at last F. hepatica was extracted with endoscopic retrograde cholangiography.

  1. Tumor markers as a diagnostic key for hilar Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Juntermanns B

    2010-08-01

    Full Text Available Abstract Objective Hilar cholangiocarcinoma is the fourth most common gastrointestinal malignancy. CA19-9 and CEA are helpful devices in the management of gastrointestinal malignancies and belong to clinical routine in surgical oncology. But the validity of these parameters in terms of tumor extension and prognosis of bile duct malignancies still remains unclear. Methods From 1998 to 2008, we obtained preoperative CA19-9 and CEA serum levels in 136 patients with hilar cholangiocarcinoma. We correlated tumor stage, resectability rate and survival with preoperative CA 19-9 and CEA serum levels. Results CA19-9 (UICC I: 253 ± 561 U/ml; UICC II: 742 ± 1572 U/ml; UICC III: 906 ± 1708 U/ml; UICC IV: 1707 ± 3053 U/ml and CEA levels (UICC I: 2.9 ± 3.8 U/ml; UICC II: 4.6 ± 6.5 U/ml; UICC III: 18.1 ± 29.6 U/ml; UICC IV: 22.7 ± 53.9 U/ml increase significantly with rising tumor stage. Patients with pre operative serum levels of CA19-9 (> 1000 U/ml and CEA (> 14.4 ng/ml showed a significant poorer resectability rate and survival than patients with lower CA19-9 and CEA serum levels respectively. Conclusion CA19-9 and CEA serum levels are associated with the tumor stage. If preoperatively obtained CA19-9 and CEA serum levels are highly elevated patients have an even worse survival and the frequency of irresectability is significantly higher.

  2. Untangling the Complexity of Liver Fluke Infection and Cholangiocarcinoma in NE Thailand Through Transdisciplinary Learning.

    Science.gov (United States)

    Ziegler, A D; Echaubard, P; Lee, Y T; Chuah, C J; Wilcox, B A; Grundy-Warr, C; Sithithaworn, P; Petney, T N; Laithevewat, L; Ong, X; Andrews, R H; Ismail, T; Sripa, B; Khuntikeo, N; Poonpon, K; Tungtang, P; Tuamsuk, K

    2016-06-01

    This study demonstrates how a transdisciplinary learning approach provided new insights for explaining persistent Opisthorchis viverrini infection in northern Thailand, as well as elucidating problems of focusing solely on the parasite as a means of addressing high prevalence of cholangiocarcinoma. Researchers from diverse backgrounds collaborated to design an investigative homestay program for 72 Singaporean and Thai university students in five northeast Thai villages. The students explored how liver fluke infection and potential cholangiocarcinoma development are influenced by local landscape dynamics, aquatic ecology, livelihoods, food culture and health education. Qualitative fieldwork was guided daily by the researchers in a collaborative, co-learning process that led to viewing this health issue as a complex system, influenced by interlinked multidimensional factors. Our transdisciplinary experience has led us to believe that an incomplete understanding of these linkages may reduce the efficacy of interventions. Further, viewing liver fluke infection and cholangiocarcinoma as the same issue is inadvisable. Although O. viverrini infection is an established risk factor for the development of cholangiocarcinoma, multiple factors are known to influence the likelihood of acquiring either. Understanding the importance of the current livelihood transition, landscape modification and the resulting mismatch between local cultures and new socio-ecological settings on cholangiocarcinoma initiation and liver fluke transmission is of critical importance as it may help readjust our view of the respective role of O. viverrini and other socioeconomic risk factors in cholangiocarcinoma etiology and refine intervention strategies. As demonstrated in this study, transdisciplinary approaches have the potential to yield more nuanced perspectives to complex diseases than research that focuses on specific aspects of their epidemiology. They may therefore be valuable when designing

  3. Intrahepatic Pseudoaneurysms Complicating Transjugular Liver Biopsy in Liver Transplantation Patients: Three Case Reports

    International Nuclear Information System (INIS)

    An intrahepatic pseudoaneurysm is a rare complication following transjugular liver biopsy. Transarterial embolization is considered a safe and effective treatment for treating pseudoaneurysms. Herein we report three cases of intrahepatic pseudoaneurysms following transjugular liver biopsies. The three pseudoaneurysms were managed by the following methods: transarterial embolization, percutaneous transhepatic embolization, and close observation

  4. Intrahepatic Pseudoaneurysms Complicating Transjugular Liver Biopsy in Liver Transplantation Patients: Three Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Seung Won; Ko, Gi Young; Yoon, Hyun Ki; Gwon, Dong Il; Sung, Kyu Bo [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2010-04-15

    An intrahepatic pseudoaneurysm is a rare complication following transjugular liver biopsy. Transarterial embolization is considered a safe and effective treatment for treating pseudoaneurysms. Herein we report three cases of intrahepatic pseudoaneurysms following transjugular liver biopsies. The three pseudoaneurysms were managed by the following methods: transarterial embolization, percutaneous transhepatic embolization, and close observation

  5. Intrahepatic splenosis mimicking hepatocellular carcinoma in a cirrhotic liver

    International Nuclear Information System (INIS)

    We report a patient who has a cirrhotic liver secondary to hepatitis C virus infection with a liver lesion incidentally found on routine liver ultrasound. The patient had a history of splenectomy 30 years earlier. The magnetic resonance imaging (MRI) characteristics suggested the diagnosis of intrahepatic splenosis, which is confirmed by core needle biopsy. Knowledge of these imaging findings makes this entity important to be considered in the differential diagnosis of a hepatic tumor in the presence of a history of splenic trauma or surgery. (author)

  6. Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA.

    Science.gov (United States)

    Kolykhalov, A A; Agapov, E V; Blight, K J; Mihalik, K; Feinstone, S M; Rice, C M

    1997-07-25

    More than 1% of the world's population is chronically infected with hepatitis C virus (HCV). HCV infection can result in acute hepatitis, chronic hepatitis, and cirrhosis, which is strongly associated with development of hepatocellular carcinoma. Genetic studies of HCV replication have been hampered by lack of a bona fide infectious molecular clone. Full-length functional clones of HCV complementary DNA were constructed. RNA transcripts from the clones were found to be infectious and to cause disease in chimpanzees after direct intrahepatic inoculation. This work defines the structure of a functional HCV genome RNA and proves that HCV alone is sufficient to cause disease. PMID:9228008

  7. Appropriate choice of surgical strategies in managing hilar cholangiocarcinoma%肝门部胆管癌手术方式的正确选择

    Institute of Scientific and Technical Information of China (English)

    彭承宏; 程坤

    2012-01-01

    Hilar cholangiocarcinoma is a rare tumor with a poor prognosis.Due to advances in preoperative imaging and enhanced comprehension of tumor biological behavior,surgical management of hilar cholangiocarcinoma has evolved since its original description.Currently,it has been accepted that complete surgical resection provides the only possibility for cure or long-term survival,however,the surgical management of hilar cholangiocarcinoma is extremely challenging because of its anatomical location and vascular proximity.In order to achieve complete resection, several surgical approaches have been investigated and evaluated regarding major hepatic resection,lymph node dissection,vascular resection,extended resection and liver transplantation,however,there are still many disputations. Furthermore,many surgical technical difficulties exist in biliary reconstruction after resection owing to anatomical problems.Focusing on the disputes and problems mentioned above,we herein review and discuss surgical strategies in managing hilar cholangiocarcinoma.%肝门部胆管癌由Klatskin在1965年首次描述,是指发生在左肝管、右肝管、左右肝管分叉部和肝总管上段的胆管黏膜上皮恶性肿瘤[1].其发病率近30年来有增加趋势,占胆道肿瘤的67%,多数患者预后差,术后5年的生存率<30%,根治性R0切除是目前惟一可能获得治愈或提高长期生存率的方法[2].由于肝门部胆管癌解剖的复杂性以及肿瘤本身具有肝转移、淋巴结转移、周围血管侵犯及神经浸润的生物学特性,其手术治疗仍然颇为棘手.如何提高R0切除率是目前肝胆外科医师面临的挑战.

  8. Effects of ursodeoxycholic acid on intrahepatic cholestasis in rats

    Institute of Scientific and Technical Information of China (English)

    李兰娟; 徐小微; 吕芳芳; 赵年丰

    2003-01-01

    Objective To investigate the effects of treatment with ursodeoxycholic acid (UDCA) on intrahepatic cholestasis in rats, and to explore its mechanism.Method Rats suffering from intrahepatic cholestasis were treated with UDCA. Their serum alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), γ-glutamyl transpeptidase (γ-GT), total cholesterol (TCH), bile flow, total bile acid excretion, total Na+ and TCH of bile were measured before and after treatment. In addition, the changes of liver tissue under microscrope were observed and recorded.Results Compared with the control group, serum ALT, ALP, TBIL, DBIL, γ-GT and TCH of rats in the treatment group decreased, while bile flow, total bile acid excretion, total Na+ and TCH decreased significantly. Degeneration of hepatocytes, infiltration of inflamed cells and proliferation of small bile ducts in the treatment group were improved under microscope.Conclusion UDCA may have therapeutic effects on cholestatic hepatitis. The mechanism may involve in its hydrophilicity, choleretic effect and immune modulation.

  9. Detection of Primary Malignancy and Metastases with FDG PET/CT in Patients with Cholangiocarcinomas: Lesion-based Comparison with Contrast Enhanced CT.

    Science.gov (United States)

    Elias, Youssef; Mariano, Aladin T; Lu, Yang

    2016-09-01

    The current National Comprehensive Cancer Network (NCCN) Guidelines consider the role of 2-deoxy-2-(18)F-fluoro-d-glucose positron emission tomography/computer tomography (FDG PET/CT) in the evaluation of cholangiocarcinoma (CCA) as "uncertain," and have recommended contrast enhanced computed tomography (CECT) but not FDG PET/CT as a routine imaging test for CCA workup. We set out to compare the diagnostic performance of FDG PET/CT and CECT in patients with CCA. The retrospective study included patients with CCA who underwent FDG PET/CT and CECT within 2-month interval between 2011 and 2013 in our hospital. Lesion-based comparison was conducted. Final diagnoses were made based on the composite clinical and imaging data with minimal 6-month follow-up. A total of 18 patients with 28-paired tests were included. There is a total of 142 true malignant lesions as revealed by the 6-paired pre-treatment and 22-paired post-treatment tests. On a lesion-based analysis, the sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and accuracies of PET/CT and CECT for detection of CCA were 96.5%, 55.5%, 97.2%, 50.0%, 94.1% and 62.2%, 66.7%, 96.7%, 10.0%, 62.5%, respectively. FDG PET/CT detected more intrahepatic malignant and extrahepatic metastases; and had significant higher sensitivity, NPV, and accuracy than CECT, while similar in specificity and PPV. No true positive lesion detected on CECT that was missed on PET/CT, and none of the false negative lesions on PET/CT were detected on CECT. Six patients had paired pretreatment tests, and FDG PET/CT results changed planned management in three patients. Our data suggest that FDG PET/CT detect more primary and metastatic lesions and lead to considerable changes in treatment plan in comparison with CECT. PMID:27651736

  10. An inguinal hernia sac tumor of extrahepatic cholangiocarcinoma origin

    Directory of Open Access Journals (Sweden)

    Yamazaki Hidehiro

    2006-03-01

    Full Text Available Abstract Background Metastatic hernia sac tumor from biliary malignancy is extremely rare with only one such case previously reported. We herein report an additional case of extrahepatic cholangiocarcinoma presenting as a hernia sac tumor. Case presentation A 78-year-old man presented with an irreducible right inguinal hernia associated with a firm tumor, 2.0 cm in diameter. A computed tomography scan demonstrated a soft tissue density mass with heterogeneous enhancement within the right inguinal canal. The patient underwent a hernia repair and the hernia sac tumor was resected. Histological examination of the tumor revealed a metastatic adenocarcinoma suggesting the tumor was of pancreato-biliary origin. Further investigation using imaging studies disclosed a primary tumor in the upper bile duct. The patient died of the disease nine months after the resection. Conclusion Hernia sac tumors should be considered when an irreducible, growing mass appears within an inguinal hernia. Computed tomography may be useful for the early detection of hernia sac tumors from undiagnosed intra-abdominal malignancies.

  11. INTRAOPERATIVE ULTRASOUND EXAMINATION OF HILAR CHOLANGIOCARCINOMA /TUMOR OF KLATSKIN /

    Directory of Open Access Journals (Sweden)

    Daniel V. Kostov

    2012-07-01

    Full Text Available Purpose: To compare the opportunities of the intraoperative ultrasound examination of the liver with the preoperative imaging methods – Computer tomography (CT, Ultrasound examination (US in detecting hepatic lesions in patients with tumor of Klatskin (hilar cholangiocarcinoma.Patients and methods: This is a prospective study of 7 patients, which had undergone open operative intervention for tumor of Klatskin. The affecting of the liver by the tumor process was examined preoperatively with Ultrasound examination and Computer tomography with contrast amplification, and by inspection and palpation and intra operative ultrasound during the operative intervention.Results: The maximum numbers of malignant lesions are found by IOUS - totally 21. Preoperative ultrasound found 5 lesions or 23,80% of the maximum number and preoperative CT – 9 or 33,33%. The information from IOUS changed the operative plan in 2/7 of the patients (28,57%. A biliary stent was placed under the control of IOUS in one patient with a heavy hyperbilirubinemia – 791,6 µmol/l.Conclusions: IOUS is significantly helpful in surgery of tumor of Klatskin. Besides the precise localization and staging of the tumor the information of IOUS changes the surgical strategy in some patients.

  12. Genetic and epigenetic changes associated with cholangiocarcinoma: From DNA methylation to microRNAs

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Cholangiocarcinomas are malignant epithelial liver tumors arising from the intra- and extra-hepatic bile ducts. Little is known about the molecular development of this disease, and very few effective treatment options are available. Thus, prognosis is poor. Genetic and epigenetic changes play an integral role in the neoplastic transformation of human cells to their malignant counterparts. This review summarizes some of the more prevalent genetic alterations (by microRNA expression)and epigenetic changes (hypermethylation of specific gene promoters) that are thought to contribute to the carcinogenic process in cholangiocarcinoma.

  13. Induction of biliary cholangiocarcinoma cell apoptosis by 103Pd cholangial radioactive stent γ-rays

    Institute of Scientific and Technical Information of China (English)

    HE Gui-jin; DAI Chao-liu; SUN Dan-dan; JI Da-wei; SUI Dong-ming; YU Fa-qiang; GAO Qin-yi; DAI Xian-wei; GAO Hong; JIANG Tao

    2008-01-01

    Background In recent years, interventional tumor therapy, involving implantation of intra-cholangial metal stents through percutaneous trans-hepatic punctures, has provided a new method for treating cholangiocarcinoma, 103Pd cholangial radioactive stents can concentrate high radioactive dosages into the malignant tumors and kill tumor cells effectively, in order to prevent re-stenosis of the lumen caused by a relapsed tumor. The aim of the present study was to investigate the efficacy of y-rays released by the 103Pd biliary duct radioactive stent in treating cholangiocarcinoma via induction of biliary cholangiocarcinoma cell apoptosis.Methods A group of biliary duct cancer cells was collectively treated with a dose of y-rays. Cells were then examined by the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl terazolium-bromide (MTT) technique for determining the inhibition rate of the biliary duct cancer cells, as well as with other methods including electron microscopy, DNA agarose gel electrophoresis, and flow cytometry were applied for the evaluation of their morphological and biochemical characteristics. The growth curve and the growth inhibition rate of the cells were determined, and the changes in the ultrastructure of the cholangiocarcinoma cells and the DNA electrophoresis bands were examined under a UV-lamp.Results The y-ray released by 103Pd inhibited cholangiocarcinoma cell growth, as demonstrated when the growth rate of the cells was stunned by a γ-ray with a dosage larger than 197.321 MBq. Typical features of cholangiocarcinoma cell apoptosis were observed in the 197.321 MBq dosage group, while cell necrosis was observed when irradiated by a dosage above 245.865 MBq. DNA agarose gel electrophoresis results were different between the 197.321 MBq irradiation dosage group, the 245.865 MBq irradiation dosage group, and the control group.Conclusions 103Pd radioactive stents which provide a radioactive dosage of 197.321 MBq are effective in the treatment of

  14. Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Jongkonnee; Thanasai; Temduang; Limpaiboon; Patcharee; Jearanaikoon; Banchob; Sripa; Chawalit; Pairojkul; Srisurang; Tantimavanich; Masanao; Miwa

    2010-01-01

    AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, resp...

  15. Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Tae Yoon Lee; Young Koog Cheon; Chan Sup Shim; Young Deok Cho

    2012-01-01

    To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC).METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December,1999 to January,2011.Out of 232 patients,thirty-three patients with unresectable hilar CC were treated.Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT.Fifteen patients in the control group were treated with metal stents alone.Porfimer sodium (2 mg/kg)was administered intravenously to PDT patients.Fortyeight hours later,PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography.After performance of PDT,uncovered metal stents were inserted to ensure adequate decompression and bile drainage.Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test.RESULTS:The PDT and control patients were comparable with respect to age,gender,health status,pretreatment bilirubin,and hilar CC stage.When compared to control,the PDT group was associated with significantly prolonged stent patency (median 244 ±66 and 177 ± 45 d,respectively,P =0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d,respectively,P =0.006).Early complication rates were similar between the groups (PDT group 17%,control group 13%) and all patients were treated conservatively.Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%).Of these 26patients,twenty-two were treated endoscopically and four were treated with external drainage.CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates.The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.

  16. Biloma following repeated transcatheter arterial embolization and complicated by intrahepatic duct stones: A case report

    Institute of Scientific and Technical Information of China (English)

    Ming-Jen Chen; Ching-Chung Lin; Wen-Hsiung Chang; Fei-Shih Yang

    2005-01-01

    Biloma is an encapsulated bile collection outside the biliary tree due to a bile leak. It is occasionally found following traumatic liver injury or iatrogenic injury to the biliary tract, induced either during an endoscopic or surgical procedure. It is a rare complication of transcatheter arterial embolization (TAE). Although biloma can be shrunk by appropriate aspiration or drainage in majority of cases,we report a case of intrahepatic biloma following repeated TAE for hepatocellular carcinoma (HCC) and complicated by infection and intrahepatic stones. This particular constellation of problems has not been reported before and the intrahepatic stones need to be removed by percutaneous procedure.

  17. Intrahepatic cholestasis of pregnancy-current achievements and unsolved problems

    Institute of Scientific and Technical Information of China (English)

    Jurate Kondrackiene; Limes Kupcinskas

    2008-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder. Maternal effects of ICP are mild; however, there is a clear association between ICP and higher frequency of fetal distress, preterm delivery, and sudden intrauterine fetal death. The cause of ICP remains elusive, but there is evidence that mutations in genes encoding hepatobiliary transport proteins can predispose for the development of ICP. Recent data suggest that ursodeoxycholic acid is currently the most effective pharmacologic treatment, whereas obstetric management is still debated. Clinical trials are required to identify the most suitable monitoring modalities that can specifically predict poor perinatal outcome. This article aims to review current achievements and unsolved problems of ICP.

  18. Bile peritonitis due to intra-hepatic bile duct rupture

    Institute of Scientific and Technical Information of China (English)

    R Lochan; BV Joypaul

    2005-01-01

    Generalized biliary peritonitis is a serious intra-abdominal emergency. Most of them occur due to duodenal ulcer perforation and rapidly evolve into bacterial peritonitis due to contamination by gut organisms and food. In this situation, recognition of the pathology and its treatment is straightforward and is usually associated with a good outcome. There are a few unusual causes of biliary peritonitis, of which rupture of the biliary tree is one.We describe a rare case of biliary peritonitis due to rupture of an intra-hepatic biliary radical. Unusual causes of peritonitis do interrupt our daily routine emergency surgical experience. Rapid recognition of the presence of peritonitis, adequate resuscitation, recognition of operative findings, establishment of biliary anatomy, and performance of a meticulous surgical procedure resulted in a good outcome.

  19. Intrahepatic cholestasis of pregnancy: When should you look further?

    Institute of Scientific and Technical Information of China (English)

    Winita Hardikar; Shivani Kansal; Ronald P J Oude Elferink; Peter Angus

    2009-01-01

    Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy (ICP), a condition associated with significant fetal complications. Although the etiology of ICP is unclear in many cases, certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect,which may not only affect subsequent pregnancies,but may be an indicator of more serious subsequent liver disease. We report a kindred of Anglo-Celtic descent, among whom many members present with ICP, gallstones or cholestasis related to use of oral contraception. Genetic studies revealed a novel mutation in the ABCB4 gene, which codes for a phospholipid transport protein. The clinical significance of this mutation and the importance of identifying such patients are discussed.

  20. Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand

    Institute of Scientific and Technical Information of China (English)

    Masanao; Miwa; Satoshi; Honjo; Gyokukou; You; Masakazu; Tanaka; Kazuhiko; Uchida; Petcharin; Srivatanakul; Thiravud; Khuhaprema; Watcharin; Loilome; Anchalee; Techasen; Chaisiri; Wongkham; Temduang; Limpaiboon; Puangrat; Yongvanit; Sopit; Wongkham

    2014-01-01

    Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients’ lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.

  1. Non-Surgical Therapy for Unresectable Hilar Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Manuel Liberato

    2013-12-01

    Full Text Available Hilar cholangiocarcinoma (HCCA is characterised by late clinical symptoms. As a consequence, most patients will not undergo surgery, and palliation is the main goal of therapy. For the few patients that undergo potentially curative surgery, the need for preoperative biliary drainage (PBD continues to be debated and remains controversial, as there are many reports with conflicting results. For the palliation of unresectable HCCA, endoscopic or percutaneous transhepatic drainage (PTD is typically preferred over surgical palliative resection. PTD can be useful in patients with altered anatomy, as a guide to endoscopic procedures (rendezvous technique, after failure of endotherapy or as a rescue therapy for the drainage of segments that have been opacified by endoscopy. Endoscopic palliative bile duct drainage can be performed with plastic stents (PSs or self-expandable metal stents (SEMSs. Several studies have compared PSs and SEMSs for the palliation of HCCA, and all have been in favor of SEMS placement, which is associated with a lower number of reinterventions, superior cumulative stent patency and even improved survival. The optimal technique for endoscopic palliative metal stent placement and the benefits of bilateral versus unilateral stenting remain controversial and highly debated. Drainage of only 25-30% of the liver volume may be sufficient to ameliorate jaundice in most cases of HCCA. However, reports of bilateral drainage are associated with longer stent patency, lower reintervention rates and, perhaps, a better quality of life for patients. Furthermore, newly available stents may be associated with higher rates of technical success and increasing successful reintervention rates in bilateral stenting.

  2. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    Science.gov (United States)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  3. Berberine inhibits growth and induces G1 arrest and apoptosis in human cholangiocarcinoma QBC939 cells.

    Science.gov (United States)

    He, Wei; Wang, Bin; Zhuang, Yun; Shao, Dong; Sun, Kewen; Chen, Jianping

    2012-01-01

    The chemotherapeutic approach using non-toxic natural products may be one of the strategies for the management of the cholangiocarcinoma. Here we report that in vitro treatment of human cholangiocarcinoma QBC939 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability and induced cell death in a dose-dependent manner, which was associated with an increase in G1 arrest. Our western blot analysis showed that berberine-induced G1 cell cycle arrest was mediated through the increased expression of cyclin-dependent kinase inhibitors (Cdki) proteins (Cip1/p21 and Kip1/p27); a simultaneous decrease in Cdk2 and Cdk4 and cyclins D1, and reduced activity of the Cyclins-Cdk complex. In additional studies, treatment of QBC939 cells with different concentrations (10, 40, 80 μM) of berberine for 48 h resulted in a significant dose-dependent increase in apoptosis compared to the non-berberine-treated control, which was associated with an increased expression of pro-apoptotic protein Bax and decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Together, this study for the first time identified berberine as a chemotherapeutic agent against human cholangiocarcinoma cells QBC939 cells in vitro. Further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the management of cholangiocarcinoma.

  4. Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Sakata; Yoshio Shirai; Toshifumi Wakai; Tatsuya Nomura; Eiko Sakata; Katsuyoshi Hatakeyama

    2005-01-01

    AIM: To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage (PTBD) for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature.METHODS: A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 mo. The English language literature (PubMed, National Library of Medicine, Bethesda, MD, USA), from January 1966through December 2004, was reviewed.RESULTS: Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau (6%)at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma (including our three patients), two survived for more than 5 years after the excision of isolated catheter tract metastases.CONCLUSION: Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.

  5. Survival and an overview of decision-making in patients with cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Håvard Mjørud Forsmo; Arild Horn; Asgaut Viste; Dag Hoem; Kjell Øvrebø

    2008-01-01

    BACKGROUND: Cholangiocarcinoma is rare, accounting for approximately 3%of all gastrointestinal cancers. This study aimed to identify the survival rate among surgically treated and palliated patients, and secondly to identify parameters that could predict a curative resection. METHODS: A total of 121 patients, 55 men and 66 women, median age 70 years (range 31-91), who had been treated for cholangiocarcinoma in the period of 1990-2005 were evaluated retrospectively. RESULTS: Curative resection was performed in 40 patients (33%), whereas 81 received palliative treatment (67%). 16%(19 of 121) of the patients had an explorative laparotomy without tumour resection. Age above 65 years (OR 3.4;95%CI 1.4-8.4;P=0.008), weight loss (OR 8.5;95%CI 1.5-46;P=0.01) or tumour location (The resection rate of hilar cholangiocarcinoma was lower than that of intrapancreatic cancer.) (OR 2.7; 95% CI 1.7-4.5; P=0.001) predicted palliative treatment. The adjusted 5-year survival rate of patients who received tumour resection and palliative treatment was 30%and 1.2%, respectively (P CONCLUSIONS: In few patients with a resectable cholangiocarcinoma, an explorative laparotomy is often necessary to evaluate resectability. However, long-term survival is signiifcantly better in patients who received radical surgical resection.

  6. Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis

    NARCIS (Netherlands)

    Lankisch, Tim O; Metzger, Jochen; Negm, Ahmed A; Vosskuhl, Katja; Schiffer, Eric; Siwy, Justyna; Weismüller, Tobias J; Schneider, Andrea S; Thedieck, Kathrin; Baumeister, Ralf; Zürbig, Petra; Weissinger, Eva M; Manns, Michael P; Mischak, Harald; Wedemeyer, Jochen

    2011-01-01

    UNLABELLED: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes C

  7. Reversal of Jaundice in Two Patients with Inoperable Cholangiocarcinoma Treated with Cisplatin and Gemcitabine Combination

    Directory of Open Access Journals (Sweden)

    Maarten Criel

    2012-01-01

    Full Text Available Two patients are presented with severe jaundice, due to inoperable cholangiocarcinoma. The chemotherapeutic approach in patients with severe jaundice is discussed. Many schedules of chemotherapy were developed in this tumor type with normal serum bilirubin. We report here the first successful use of cisplatin and gemcitabine combination chemotherapy in these patients. Tolerability was good and liver function tests gradually improved.

  8. Brachytherapy and percutaneous stenting in the treatment of cholangiocarcinoma: A prospective randomised study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the effect of radiation therapy including intraluminal brachyterapy with iridium-192 on survival of patients with malignant biliary strictures (cholangiocarcinoma, histologically improved) treated with metallic stent in a prospective randomised study. Method and materials: In the prospective randomised study, 21 patients with cholangiocarcinoma were treated with implantation of percutaneous stents followed with intraluminal Ir-192 brachytherapy (mean dose 30 Gy) and external radiotherapy (mean dose 50 Gy) and 21 patients were treated only with stents insertion. We did not find any statistically significant differences in age and tumor localization between these two groups of patients. Results: All the patients died. In the group of patients treated with brachytherapy and with stent implantation, the mean survival time was 387.9 days. In the group of patients treated only with stent insertion the mean survival was 298 days. In effort to eliminate possible effect of external radiotherapy we treated the control group of eight patients with cholangiocarcinoma by stent insertion and brachyterapy only. Conclusion: Our results show that combined radiation therapy could extend the survival in the patients with cholangiocarcinoma obstruction

  9. Analysis of the placement of multiple metallic stents in the treatment of hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical efficacy of multiple stents placement in the management of hilar cholangiocarcinoma, especially in the complex cases of which the hepatic ducts are invaded. Methods: Forty-five consecutive patients with hilar cholangiocarcinoma were treated with percutaneous transhepatic placement of two or three self-expandable metallic endoprostheses. The cause of hilar obstructions in these patients were all cholangiocarcinoma, including Bismuth classification type II (n 12), IIIa (n 17), IIIb (n 10), and IV (n 6). Two or 3 stents were placed in the configuration of T, Y or X over the strictures. Results: Stent placement with 2 or 3 endoprostheses was successful in all patients. All patients showed significant decrease in serum bilirubin level. The mortality rate within 30 days of stent placement was 2.2% (1/45). The mean survival and stent patency times were 215.3 d (26- 516 d) and 181.5 d (26-473 d), respectively. Conclusion: Deploying of multiple metallic stents is an effective method to treat complex hilar cholangiocarcinoma, especially for the cases of which hepatic ducts are invaded; the hepatic ducts should be drained as much as possible. (authors)

  10. Prognostic analysis of surgical treatment of peripheral cholangiocarcinoma: Two decades of experience at Chang Gung Memorial Hospital

    Institute of Scientific and Technical Information of China (English)

    Yi-Yin Jan; Chun-Nan Yeh; Ta-Sen Yeh; Tse-Ching Chen

    2005-01-01

    AIM: To analyze the prognostic factors influencing the overall survival of peripheral cholangiocarcinoma (PCC)patients undergoing surgical treatment during 25 years at a single institution.METHODS: This study retrospectively reviewed prospectively collecting data about 373 patients with histologically proven PCC who underwent surgical treatment between 1977 and 2001.RESULTS: Three hundred and seventy-three PCC patients (159 men and 214 women) underwent surgical treatment from 1977 to 2001. Among them, 187 PCC patients underwent hepatectomy and 135 had curative resection (curative resectability rate: 36.2%). The follow-up duration ranged from 1.05 to 167.6 mo (mean/median = 14.1/7.2 mo).Overall cumulative survival rates at 1, 3, and 5 years were 32.5%, 9.2%, and 4.1%, respectively. Univariate log-rank analysis identified the following as adverse influences on overall survival: presence of symptoms, absence of mucobilia, elevated CEA and CA 19-9 levels, non-papillary tumor type, receiving non-hepatectomy, advanced tumor staging, lack of post-operative chemotherapy, and radiotherapy. Meanwhile, multivariate Cox's proportional hazard analysis demonstrated that absence of mucobilia,non-papillary tumor type, advanced tumor staging, nonhepatectomy, and lack of post-operative chemotherapy were the five independent prognostic factors that adversely affected overall survival.CONCLUSION: Favorable overall survival of PCC patients undergoing surgical treatment depends on early tumor stage, presence of mucobilia, papillary tumor type, hepatic resection, and post-operative chemotherapy.

  11. Clinicopathological Characteristics and Prognostic Factors of Intrahepatic Biliary Cystadenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming-Yue Xu; Xian-Jie Shi; Tao Wan; Yu-Rong gang; Hong-Guang Wang; Wen-Zhi Zhang; Lei He

    2015-01-01

    Background:Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma (IBCA) or suspected IBCAs,but controversy exists regarding the prognosis for IBCAs.This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures.Methods:Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included.The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma (IBC);factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models.Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test.Results:IBCAs had a strong female predominance,and the most common presenting symptoms were abdominal pain or discomfort.Compared with IBCs,IBCAs occurred in older patients,in more male patients,and were associated statistically significant abnormal increase in alanine aminotransferase (P =0.01) and total bilirubin (P =0.04).Mural nodules were more frequently seen with IBCAs and may associate with malignancy.It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings.Although complete resection is recommended,enucleation with negative margins also achieved good outcomes.Median overall patient survival was 76.2 months;survival at 1,3,and 5 years was 88.0%,68.7%,and 45.8%,respectively.Radical resection and noninvasive tumor type were independent prognostic factors for overall survival.Conclusions:It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings.Complete resection is recommended for curative treatment,and patients should be closely followed

  12. Clinicopathological Characteristics and Prognostic Factors of Intrahepatic Biliary Cystadenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ming-Yue Xu

    2015-01-01

    Full Text Available Background: Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma (IBCA or suspected IBCAs, but controversy exists regarding the prognosis for IBCAs. This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures. Methods: Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included. The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma (IBC; factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Results: IBCAs had a strong female predominance, and the most common presenting symptoms were abdominal pain or discomfort. Compared with IBCs, IBCAs occurred in older patients, in more male patients, and were associated statistically significant abnormal increase in alanine aminotransferase (P = 0.01 and total bilirubin (P = 0.04. Mural nodules were more frequently seen with IBCAs and may associate with malignancy. It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings. Although complete resection is recommended, enucleation with negative margins also achieved good outcomes. Median overall patient survival was 76.2 months; survival at 1, 3, and 5 years was 88.0%, 68.7%, and 45.8%, respectively. Radical resection and noninvasive tumor type were independent prognostic factors for overall survival. Conclusions: It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings. Complete resection is recommended for curative treatment

  13. Intrahepatic biliary injuries associated with radiofrequency ablation of hepatic malignancies

    Institute of Scientific and Technical Information of China (English)

    FU Ying; YANG Wei; WU Jin-yu; YAN Kun; WU Wei; XING Bao-cai; CHEN Min-hua

    2011-01-01

    Background Biliary injury after radiofrequency ablation can cause serious consequences including death. However, there are limited data regarding bile duct changes with or without complications associated with radiofrequency ablation of hepatic malignancies. This study aimed to assess the incidence, prognosis and risk factors of intrahepatic biliary injury associated with radiofrequency ablation.Methods Between June 2001 and January 2009, 638 patients with hepatic malignancies (405 with hepatocellular carcinoma, and 233 with liver metastasis) who had 955 treatment sessions were enrolled in this study. Imaging and laboratory data, the course of treatment, and patient outcomes were reviewed retrospectively. The risk factors of biliary injury and the impact on overall survival of patients were analyzed. The chi-square test, Fisher's exact test, Kaplan-Meier curves and stepwise Logistic regression model were used for statistical analysis where appropriate.Results Biliary injury was observed in 17 patients after 17 ablation sessions based on imaging findings. The overall incidence of biliary injury was 1.8% (17/955) with an average onset time of 12 weeks (2-36 weeks). Mild, moderate and severe complications of biliary injury were identified in 9, 6 and 2 cases, respectively. The median survival time after detection of biliary injury was 40 months. There seemed no notable difference in overall survival between patients with and those without biliary injuries. By multivariate analysis, vessel infiltration (P=0.034) and treatment session ≥4 times (P=0.025) were independent risk factors for biliary injury of hepatocellular carcinoma; while tumor located centrally was the only independent risk factor in the metastasis group (P=0.043).Conclusions The incidence of biliary injury was not frequent (1.8%). Through appropriate treatment, intrahepatic bile duct injuries seemed not affect the patients' long-term survival. Additionally, risk factors may be helpful for selecting

  14. Intrahepatic biliary cystadenocarcinoma:clinical analysis of 4 cases

    Institute of Scientific and Technical Information of China (English)

    Qiang Yu; Tao Chen; Yun-Le Wan; Jun Min; Yu Cheng; Hua Guo

    2009-01-01

    BACKGROUND: Intrahepatic biliary cystadenocarcinoma (IBC) is a low-incidence disease which is often mis-diagnosed because of insufifcient recognition. This study aimed to investigate the clinical features, diagnosis and treatment of the disease. METHOD: The clinical data of 4 IBC patients treated in the Second Afifliated Hospital of Sun Yat-Sen University were retrospectively analyzed. RESULTS: The 4 patients complained of right upper abdominal pain and mass or masses. One patient presented with moderate fever and chills, and two had moderately impaired liver function. The levels of carbohydrate antigens (CA125 and CA19-9) were signiifcantly elevated and the level of carcinoembryonic antigen was slightly elevated in 3 patients. The level of serum transaminase was elevated in 2 patients, and the level of serum total bilirubin elevated in 2. Intrahepatic cystic masses ranging from 5.0 to 20.5 cm in diameter were found in all patients by ultrasound and CT/MR scan. Three of the 4 patients were misdiagnosed on admission as having hepatic cyst and one as having hepatic abscess. Radical removal of masses was performed in three patients after pathological diagnosis. One patient died from tumor recurrence 7 years after operation, 2 were followed up for 12 and 17 months without evidence of recurrence. The high risk patients who received palliative therapy were closely followed up. CONCLUSIONS: The diagnosis of IBC without speciifc clinical features mainly depends on imaging and pathological examination. Increased levels of serum CA125 and CA19-9 might contribute to the diagnosis and prognosis of some IBC patients. Radical excision is the only effective treatment.

  15. Huge hepatocellular carcinoma with multiple intrahepatic metastases: An aggressive multimodal treatment

    Directory of Open Access Journals (Sweden)

    Satoshi Yasuda

    2015-01-01

    Conclusion: Multimodal treatment involving hepatectomy and TACE might be a good treatment strategy for patients with huge HCC with multiple intrahepatic metastases if the tumors are localized in the liver without distant or peritoneal metastasis.

  16. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis

    NARCIS (Netherlands)

    Jansen, PLM; Strautnieks, SS; Jacquemin, E; Hadchouel, M; Sokal, EM; Hooiveld, GJEJ; Koning, JH; De Jager-Krikken, A; Kuipers, F; Stellaard, F; Bijleveld, CMA; Gouw, A; Van Goor, H; Thompson, RJ; Muller, M

    1999-01-01

    Background & Aims: Progressive familiar intrahepatic cholestasis (PFIC), an inherited liver disease of childhood, is characterized by cholestasis and either normal or increased serum gamma-glutamyltransferase activity. Patients with normal gamma-glutamyltransferase activity have mutations of the FIC

  17. Cardiac and renal effects of a transjugular intrahepatic portosystemic shunt in cirrhosis

    DEFF Research Database (Denmark)

    Busk, Troels M; Bendtsen, Flemming; Møller, Søren

    2013-01-01

    Refractory ascites and recurrent variceal bleeding are among the serious complications of portal hypertension and cirrhosis for which a transjugular intrahepatic portosystemic shunt (TIPS) can be used. Cirrhotic patients have varying degrees of haemodynamic derangement, mainly characterized...

  18. Adenocarcinoma arising from intrahepatic heterotopic pancreas: A case report and literature review

    OpenAIRE

    Yan, Mao-Lin; Wang, Yao-Dong; Tian, Yi-Feng; Lin, Ying

    2012-01-01

    Heterotopic pancreas is mostly found incidentally, and adenocarcinoma arising from heterotopic pancreas appears to be extremely rare. A case of a 46-year-old woman with adenocarcinoma arising from intrahepatic heterotopic pancreas is reported herein. Computed tomography demonstrated a mass located in the bile duct of the left hepatic lobe. Pathological examination revealed a moderately differentiated adenocarcinoma arising from intrahepatic heterotopic pancreas with nerve infiltration. This m...

  19. Impact of bile acids on the growth of human cholangiocarcinoma via FXR

    Directory of Open Access Journals (Sweden)

    Zhang Yinxin

    2011-10-01

    Full Text Available Abstract Background The objective of the study was to investigate the effect of different types of bile acids on proliferation of cholangiocarcinoma and the potential molecular mechanisms. Methods PCR assay and Western blot were performed to detect the expression of farnesoid × receptor (FXR in mRNA and protein level. Immunohistochemical analysis was carried out to monitor the expression of FXR in cholangiocarcinoma tissues from 26 patients and 10 normal controls. The effects on in vivo tumor growth were also studied in nude mouse model. Results Free bile acids induced an increased expression of FXR; on the contrary, the conjugated bile acids decreased the expression of FXR. The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. More specifically, when the use of free bile acids combined with FXR agonist GW4064, the tumor cell inhibitory effect was even more pronounced. But adding FXR antagonist GS into the treatment attenuated the tumor inhibitory effect caused by free bile acids. Combined treatment of GS and CDCA could reverse the regulating effect of CDCA on the expression of FXR. Administration of CDCA and GW 4064 resulted in a significant inhibition of tumor growth. The inhibitory effect in combination group (CDCA plus GW 4064 was even more pronounced. Again, the conjugated bile acid-GDCA promoted the growth of tumor. We also found that FXR agonist GW4064 effectively blocked the stimulatory effect of GDCA on tumor growth. And the characteristic and difference of FXR expressions were in agreement with previous experimental results in mouse cholangiocarcinoma tissues. There was also significant difference in FXR expression between normal and tumor tissues from patients with cholangiocarcinoma. Conclusions The imbalance of ratio of free and conjugated bile acids may play an important role in tumorigenesis of cholangiocarcinoma. FXR, a member of the nuclear receptor superfamily, may mediate the

  20. Inlfuences of Resveratrol on the Proliferation of Cholangiocarcinoma Cells and Expression of p21 and p27 Proteins

    Institute of Scientific and Technical Information of China (English)

    Liu Yong; Qian Huaxiang; Zhuo Ma; Xu Jianzhong

    2013-01-01

    Objective:To explore the effects of resveratrol on the proliferation of cholangiocarcinoma cells and expression of p21 and p27 proteins. Methods:The influences of resveratrol on the proliferation of cholangiocarcinoma cells and expression of p21 and p27 proteins were detected by methyl thiazolyl tetrazolium (MTT) method and Western blotting method, respectively. Results:Resveratrol had a conspicuous inhibitory effect on the proliferation of cholangiocarcinoma QBC939 cells, and was concentration-and time-dependant (P Conclusion:Resveratrol can signiifcantly inhibit the proliferation of cholangiocarcinoma QBC939 cells, which may be related to regulation of p21 and p27 expression and negative regulation to cell cycles.

  1. Multidetector row CT study of percutaneous transhepatic intrahepatic portosystemic shunt

    International Nuclear Information System (INIS)

    Objective: To investigate imaging features of the liver, portal vein and hepatic vein or transhepatic inferior vena cava in patients with severe liver cirrhosis in multidetector row computed tomography (MDCT), and assess the feasibility, safety and clinical significance of percutaneous transhepatic intrahepatic portosystemic, shunt (PTIPS). Methods: Fifty patients with severe liver cirrhosis confirmed by clinical data and imaging examination were enrolled in this study. Simulation of intrahepatic portosystemic shunt by percutaneous transhepatic, approach is as follows. The right midaxillary line (the eighth oi ninth intercostal space) was selected as puncture point A the right branch of portal vein was puncture point B, transhepatic inferior vena cava was puncture point C, and the distal part of right portal vein was D. A-B-C connection is simulated as percutaneous transhepatic puncture tract, C-B-D connection is simulated as portosystemic shunt tract. After tri-phase contrast-enhanced CT scanning, postprocessing images through multiple planner reconstruction (MPR) were obtained. The data were indicated statistically by x-bar±s. And 9.5% confidence interval for mean was calculated. Anatomic relationship among the right portal vein, transhepatic inferior vena cava, hepatic artery and bile duct were analyzed for all patients. Results: The length of the needle (A-B-C) is (145.7±14.8) mm. The curvature of the needle (the angle of A-B line and B-C line) is (145.0±9.9) . The length of transhepatic shunt tract (B-C) is (42.7±7.2) mm. The length of the shunt tract (C-B-D) is (117.7±11.6) mm; The angle of the shunt tract (the angle of B-C line and B-D line) is (108.5±5.9)°. In 24/50 patients, transhepatic inferior vena cava locate in the dorsal of the right portal vein, in 26/50 patients they are in the same plane. In all patients, the right branches of hepatic artery and bile duct locate in the ventral of the right portal vein. Conclusion: The procedure of PTIPS is

  2. Duration of Inflammatory Bowel Disease Is Associated With Increased Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis and IBD

    Science.gov (United States)

    Gulamhusein, Aliya F.; Eaton, John E.; Tabibian, James H.; Atkinson, Elizabeth J.; Juran, Brian D.; Lazaridis, Konstantinos N.

    2016-01-01

    OBJECTIVES Primary sclerosing cholangitis (PSC) often coexists with inflammatory bowel disease (IBD) and can be complicated by cholangiocarcinoma (CCA), a lethal malignancy for which reliable predictors remain unknown. We aimed to characterize the influence of colectomy and IBD duration on risk of CCA in patients with PSC-IBD. METHODS A retrospective review of patients with PSC-IBD seen at the Mayo Clinic, Rochester, between January 2005 and May 2013 was performed. The primary outcome was time to development of CCA and our goal was to determine whether the risk differed between patients with and without colectomy. Risk factors were assessed using univariable and multivariable Cox proportional hazard models where colectomy, IBD disease duration, and development of advanced liver disease were treated as time-dependent covariates. RESULTS A total of 399 patients with PSC-IBD were included in the study, of whom 137 had a colectomy and 123 patients developed CCA. Age-adjusted univariate Cox proportional hazard models demonstrated that colectomy (hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.05–2.22, P =0.02) and duration of IBD (HR 1.37, 95% CI 1.15–1.63, P PSC-IBD, and colectomy itself does not modify this risk. These findings identify a subset of patients who are at high risk of this lethal complication and in need of close surveillance. PMID:27002801

  3. microRNA与胆管癌关系的研究进展%MicroRNAs in cholangiocarcinoma: recent progress

    Institute of Scientific and Technical Information of China (English)

    周璐璐

    2013-01-01

    microRNA(miRNA)是一组内源性的非编码RNA,其通过转录后水平调节靶基因的表达,在细胞增殖、分化、凋亡及肿瘤的发生、发展中起重要作用.笔者就近年来microRNA在胆管癌研究领域的最新进展进行综述,主要介绍miR-21,miR-370,let-7家族,miR-373,miR-200家族,miR-29b,miR-204,miR-320等与胆管癌的关系.%MicroRNAs (miRNAs) are tiny, endogenously expressed noncoding RNAs that act as the posttranscriptional regulators of gene expression, and play very important roles in cell proliferation, differentiation and apoptosis as well as in cancer occurrence and development. In this paper, the authors overview the recent advances of miRNAs involvement in cholangiocarcinoma, focusing on miR-21, miR-370, let-7 family, miR-373, miR-200 family, miR-29b, miR-204 and miR-320.

  4. Intra-hepatic cholestasis of pregnancy: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Sangita Ghosh

    2013-01-01

    Full Text Available Intra-hepatic cholestasis of pregnancy is a cholestatic disorder characterized by i pruritus, with onset in the third trimester of pregnancy, without any primary skin lesions, ii elevated fasting serum bile acids > 10 μmol / L (and elevated serum transaminases, iii spontaneous relief of signs and symptoms within two to three weeks after delivery, and iv absence of other disease that cause pruritus and jaundice. It is believed to be a multi-factorial disease with interplay between genetic, environmental and hormonal factors. Incidence is between 0.02% to 2.4% of all pregnancies; with wide geographical variations. Maternal prognosis is usually good but can result in adverse fetal outcomes like meconium staining of amniotic fluid, fetal bradycardia and even fetal loss. Response to anti-histaminic is poor. Of all the medical therapies that have been described for the treatment for IHCP, ursodeoxycholic acid has the best response in relieving pruritus in mother, and probably has a role in preventing even the perinatal complications. Timely diagnosis and treatment is urged in order to prevent fetal complications and an early delivery between 37 to 38 weeks should be contemplated in severe cases, especially once fetal lung maturity is attained.

  5. Hepatopancreatoduodenectomy for anastomotic recurrence from residual cholangiocarcinoma: report of a case.

    Science.gov (United States)

    Natsume, Seiji; Ebata, Tomoki; Yokoyama, Yukihiro; Igami, Tsuyoshi; Sugawara, Gen; Takahashi, Yu; Nagino, Masato

    2014-05-01

    Resection of cholangiocarcinoma often results in a positive ductal margin, from carcinoma in situ (CIS) near the main tumor; however, the biological behavior of the residual CIS after surgical resection remains equivocal. We report a case of late local recurrence of CIS, defined as long-term tumor progression from CIS residue at the ductal stump. The patient, a 73-year-old man, had undergone bile duct resection for distal cholangiocarcinoma, leaving positive ductal margins with CIS. A biliary stricture was found 10 years later at the site of anastomosis, and right hepatectomy with pancreatoduodenectomy was performed. Based on histological analogy and the evidence of remnant CIS, a final diagnosis of late local recurrence from the CIS foci was made. This uncommon mode of recurrence should be considered in patients with early-stage disease with expected favorable survival because salvage surgery is feasible for selected patients.

  6. Endopancreatic Bile Duct Cholangiocarcinoma in a Patient with Peutz-Jeghers Syndrome

    Directory of Open Access Journals (Sweden)

    Alexandros K. Charalabopoulos

    2011-01-01

    Full Text Available Peutz-Jeghers syndrome is a rare autosomal dominant inherited disease characterized by a special type of hamartomatous gastrointestinal polyps combined with mucocutaneous melanin pigmentations. Patients with the syndrome have a high risk of developing neoplasia, with colon, small bowel, and stomach being the most common gastrointestinal sites. Herein, we present the occurrence of a rare tumor in patients with Peutz-Jeghers syndrome; a cholangiocarcinoma of the endopancreatic bile duct. A minireview is also presented. It can be concluded that cholangiocarcinoma remains a possible diagnosis in PJS patients, as in others that present with biliary obstruction. PJS patients may be at higher risk than others in view of their propensity for malignancy.

  7. Hemobilia as the initial manifestation of cholangiocarcinoma in a hemophilia B patient

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Hemobilia is a rare manifestation of hemophilia and is usually iatrogenic following liver biopsy. There are only few reports of spontaneous hemobilia in hemophilia patients. Cholangiocarcinoma is a well- established cause of hemobilia. We describe a case of a 70-year-old male, with known haemophilia B and a past history of papillotomy, who presented with classical symptoms of hemobilia. The initial diagnostic work-up failed to demonstrate a potential cause of bleeding other than the coagulopathy. Three months later, he was readmitted to our hospital with a second episode of hemobilia. During the second work-up, a cholangiocarcinoma was diagnosed both by imaging studies and by a significant elevation of cancer antigen 19-9. Although hemobilia could be attributed to hemophilia, especially in a patient with previous papillotomy, an underlying malignancy of the biliary tree should be suspected.

  8. Alopecia: a common paraneoplastic manifestation of cholangiocarcinoma in humans and animals

    OpenAIRE

    Antoniou, Efstathios; Paraskeva, Panorea; Smyrnis, Anastasios; Konstantopoulos, Kostas

    2012-01-01

    The coincidence of alopecia and a tumour may indicate the paraneoplastic nature of alopecia. Paraneoplastic alopecia is not uncommon in animals, feline paraneoplastic alopecia being the best example known. We present a case of alopecia coinciding with the presentation of a cholangiocarcinoma in a woman. Following surgical resection of the tumour, alopecia resolved spontaneously and it reappeared on local recurrence, 2 years later. As far as pathogenesis is concerned, the coincidence of alopec...

  9. A single nucleotide polymorphism in EZH2 predicts overall survival rate in patients with cholangiocarcinoma

    OpenAIRE

    Paolicchi, Elisa; PACETTI, PAOLA; Giovannetti, Elisa; MAMBRINI, ANDREA; ORLANDI, MASSIMO; Crea, Francesco; Romani, Antonello A.; TARTARINI, ROBERTA; DANESI, ROMANO; Peters, Godefridus J; Cantore, Maurizio

    2013-01-01

    Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance. The aim of the current study was to evaluate the correlation between EZH2 SNPs and clinical outcome. Using PROMO3.0, GeneCard and MicroSNiper, 4 EZH2 SNPs with functional...

  10. Radiological Imaging for Assessing the Respectability of Hilar Cholangiocarcinoma: A Systematic Review and Meta-Analysis

    OpenAIRE

    Hongchen Zhang; Jian Zhu; Fayong Ke; Mingzhe Weng; Xiangsong Wu; Maolan Li; Zhiwei Quan; Yingbin Liu; Yong Zhang; Wei Gong1*

    2015-01-01

    Hilar cholangiocarcinoma (HCC) remains one of the most difficult tumors to stage and treat. The aim of the study was to assess the diagnostic efficiency of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computer tomography (PET/CT) in evaluating the resectability of HCC. A systematic search was performed of the PubMed, EMBASE, and Cochrane databases. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and di...

  11. Role of diffusion-weighted magnetic resonance imaging in the diagnosis of extrahepatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To determine the clinical value of diffusion-weight- ed imaging (DWI) for the diagnosis of extrahepatic cholangiocarcinoma (EHCC) by comparing the diagnostic sensitivity of DWI and magnetic resonance cholan-giopancreatography (MRCP). METHODS: Magnetic resonance imaging examination was performed in 56 patients with suspected EHCC. T1- weighted imaging, T2-weighted imaging, MRCP and DWI sequence, DWI using single-shot spin-echo echoplanar imaging sequence with different b values (100, 300, 500, 800 and 1...

  12. Hepatic mucormycosis mimicking hilar cholangiocarcinoma:A case report and literature review

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Mucormycosis is a rare but invasive opportunistic fungal infection associated with a high mortality rate,and normally occurs in immunocompromised patients. In this report,we describe an immunocompetent patient suffering from hepatic mucormycosis secondary to adrenal mucormycosis,which masquerades as hilar cholangiocarcinoma. After surgical procedure and treatment with amphotericin B and itraconazole,the patient recovered well and had a 2-year infection-free survival. To our knowledge,this special clinical m...

  13. Portal vein occlusion after biliary metal stent placement in hilar cholangiocarcinoma.

    Science.gov (United States)

    Woo, Kyung Hee; Kim, Jin Bae; Chang, Yoon Jung; Kim, Hyo Jung; Baek, Il Hyun; Ko, Jin Seok; Woo, Ji Young; Kim, Hong Dae; Lee, Myung Seok

    2008-06-01

    Acute symptomatic portal vein obstruction related to biliary stenting is an extremely rare but life-threatening complication. This usually occurs in patients with either tumor invasion into the portal vein or pre-existing portal vein thrombus. Therefore, the portal vein should be carefully evaluated before placing a biliary metallic stent in such patients. We describe a case of acute portal vein obstruction after placing metallic biliary stents in a patient with a periductal-infiltrating type of hilar cholangiocarcinoma. PMID:20485610

  14. Association between praziquantel treatment and cholangiocarcinoma: a hospital-based matched case–control study

    OpenAIRE

    Kamsa-ard, Supot; Luvira, Vor; Pugkhem, Ake; Luvira, Varisara; Thinkhamrop, Bandit; Suwanrungruang, Krittika; Bhudhisawasdi, Vajarabhongsa

    2015-01-01

    Background Infection by the liver fluke, Opisthorchis viverrini, remains an important public health problem in Thailand and has resulted in the highest prevalence of infection and incidence of subsequent cholangiocarcinoma (CCA) in the world. Praziquantel (PZQ) is the antihelminthic drug of choice for treatment. Previous studies in hamsters showed that repeated infection and PZQ treatment could increase the risk of CCA. However, the few available epidemiology studies in humans have shown uncl...

  15. Establishment and characterization of a cholangiocarcinoma cell line (RMCCA-1) from a Thai patient

    Institute of Scientific and Technical Information of China (English)

    Panthip Rattanasinganchan; Kawin Leelawat; Sa-ard Treepongkaruna; Chintana Tocharoentanaphol; Somboon Subwongcharoen; Tuangporn Suthiphongchai; Rutaiwan Tohtong

    2006-01-01

    AIM: To establish and characterize a new cell line derived from peripheral cholangiocarcinoma of a Thai patient.METHODS: The peripheral cholangiocarcinoma specimen surgically obtained from the patient was aseptically processed by washing and mincing before culturing in Ham's F12 medium containing 10% fetal bovine serum. After 3 mo, when the cell line has become homogeneous and stabilized, several features were investigated, including growth characteristics,immunofluorescence staining for cytokeratins, expression of tumor markers, chromosomal analysis by G-banding and multicolour fluorescence in situ hybridization (mFISH), in vitro migration and invasion characteristics.RESULTS: The RMCCA-1 cell line has been established.These cells proliferated as a monolayer with a population doubling time of 48 h. Immunofluorescence staining showed positive staining for human cytokeratin 7 and 19 verifying the biliary epithelial origin. RMCCA-1secreted carbohydrate antigen 19-9 (CA19-9), but insignificant levels of carcinoembryonic antigen (CEA)and α-fetoprotein (AFP). Chromosome analysis identified aneuploidy karyotypes with a modal chromosome number of 59. RMCCA-1 exhibited a low level of in vitro invasiveness, but a high degree of motility. The cell line exhibited a significant number of chromosomal aberrations as shown by mFISH and G-banding methods.CONCLUSION: A new cell line derived from peripheral cholangiocarcinoma of a Thai patient has been established. This cell line shows a low level of in vitro invasiveness, but a high degree of motility. It will serve as a valuable tool for further studies on tumor biology,molecular pathogenesis, metastatic mechanism and response to therapeutic drugs of cholangiocarcinoma.

  16. Prospective study of MMP7 serum levels in the diagnosis of cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Kawin; Leelawat; Siriluck; Narong; Jerasak; Wannaprasert; Thawee; Ratanashu-ek

    2010-01-01

    AIM: To determine whether the serum level of matrix metalloproteinase-7 (MMP7) has the potential to diagnosis cholangiocarcinoma from benign biliary tract diseases. METHODS: This study was performed according to the PRoBE (a prospective-specimen-collection, retrospectiveblinded-evaluation) design. A total of 187 patients with obstructive jaundice were consecutively enrolled. After the diagnostic status of these patients was ascertained, their levels of serum MMP7 were assayed and compared with serum carbohy...

  17. Peroral cholangioscopy for non-invasive papillary cholangiocarcinoma with extensive superficial ductal spread

    Institute of Scientific and Technical Information of China (English)

    Toshifumi Wakai; Yoshio Shirai; Katsuyoshi Hatakeyama

    2005-01-01

    Papillary carcinoma arising from the extrahepatic bile duct often shows superficial ductal spread. We report herein the case of a patient with extensive superficial spread of non-invasive papillary cholangiocarcinoma,which was depicted with peroral cholangioscopy. A 65-year-old woman presented with the sudden-onset of severe epigastric pain. Ultrasonography revealed acute acalculous cholecystitis. Endoscopic retrograde cholangiography found small protruding lesions around the confluence of the cystic duct, suggestive of a cholangiocarcinoma. As the contour of the middle and upper bile ducts it was slightly irregular on the cholangiogram, the presence of superficial ductal spread was suspected. Peroral cholangioscopy revealed small papillary lesions around the confluence of the cystic duct and fine granular mucosal lesions in the middle and upper bile ducts and the right hepatic duct, suggesting a superficially spreading tumor. A right hepatectomy with bile duct resection was performed and no residual tumor was found. Histological examination revealed a non-invasive papillary carcinoma arising from the cystic duct with extensive superficial spread. Our experience of this case and a review of the literature suggest that a fine granular or fine papillary appearance of the ductal mucosae on cholangioscopy indicates superficial spread of papillary cholangiocarcinoma, for which peroral cholangioscopy is an efficient diagnostic option.

  18. Treatment of hepatic portal cholangiocarcinoma with combination of metallic stent and local therapy

    International Nuclear Information System (INIS)

    Purpose: To improve the therapeutic effectiveness of hilar cholangiocarcinoma and prolong the survival period by stenting and local therapy. Materials and methods: Twenty-four patients (men 8, women 16) with hilar cholangiocarcinoma were treated by percutaneous transhepatic cholangiography and drainage (PTCD), 18 of them were treated by local therapy and placement of stents, then PTCD tubes were pulled out one week later. Another 6 patients were treated only by PTCD. Results: Among 24 patients receiving PTCD, total bilirubin value was decreased in 22 patients, and no change occurred in 2 patients, who died within 1 month. For the 18 patients receiving combined treatment of local therapy and placement of metallic stents after PTCD, the mean survival period was 10 months and the longest survival period was 24 months, while the mean survival period with tube-free was 5.5 months, and the longest survival period with tube-free was 17 months. Another 6 patients were treated only by PTCD, with mean survival period of 2 months and the longest survival period of 6 months. conclusion: (1) The survival time for patients receiving local therapy and placement of metallic stent was much longer than those receiving PTCD alone. (2) Unfavorable prognosis occurred when BIL level had no change or even an increase after PTCD. (3) The combination of placement of metallic stents and local therapy after PTCD offered an effective nonoperative method in the treatment of hilar cholangiocarcinoma

  19. Effects of targeting magnetic drug nanopar ticles on human cholangiocarcinoma xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    Tao Tang; Jian-Wei Zheng; Bo Chen; Hong Li; Xi Li; Ke-Ying Xue; Xing Ai; Sheng-Quan Zou

    2007-01-01

    BACKGROUND: Targeting is a new therapeutic tool for malignant tumor as a result of combining nanotechnology with chemotherapeutics. The aim of our study was to investigate the effects of magnetic nanoparticles enveloping a chemotherapeutic drug on human cholangiocarcinoma xenografts in nude mice. METHODS:The human cholangiocarcinoma xenograft model was established in nude mice with the QBC939 cell line. The nude mice were randomly assigned to 7 groups. 0.9% saline or magnetic nanoparticles, including high (group 2), medium (group 4) and low (group 5) dosages, were given to nude mice through the tail vein 20 days after the QBC939 cell line was implanted. Calculations were made 35 days after treatment in order to compare the volumes, inhibition ratios and growth curves of the tumors in each group. Mice in each group were sacriifced randomly to collect tumor tissues and other organs for electron microscopy and pathological examination. RESULTS:The high and medium dosage groups were signiifcantly different from the control group (P CONCLUSION: Magnetic nanoparticles can inhibit the growth of human cholangiocarcinoma xenografts in nude mice.

  20. Correlation of p53 gene mutation and expression of P53 protein in cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Fang Liu; Hao Zhang; Shi-Guang Zhu; Xian-Ting Zhou; Hai-Long Su; Zheng Xu; Shao-Jun Li

    2006-01-01

    AIM: To characterize the tumor suppressor gene p53 mutations and study the correlation of p53 gene mutation and the expression of P53 protein in cholangiocarcinoma.METHODS: A total of 36 unselected, frozen samples of cholangiocarcinoma were collected. p53 gene status(exon 5-8) and P53 protein were examined by automated sequencing and immunohistochemical staining, combined with the clinical parameters of patients.RESULTS: p53 gene mutations were found in 22 of 36 (61.1%) patients. Nineteen of 36 (52.8%) patients were positive for P53 protein expression. There were significant differences in extent of differentiation and invasion between the positive and negative expression of P53 protein. However, there were no significant differences in pathologic parameters between the mutations and non-mutations.CONCLUSION: The alterations of the p53 gene evaluated by DNA sequence analysis is relatively accurate. Expression of P53 protein could not act as an independent index to estimate the prognosis of cholangiocarcinoma.

  1. Cholangiocarcinoma presenting as a solitary epididymal metastasis: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Bailey David M

    2007-08-01

    Full Text Available Abstract Background Solid tumor metastasis to the epididymis is a rare occurrence and is mostly discovered incidentally at autopsy or after therapeutic orchidectomy for prostate cancer. Other primary carcinomas that have been demonstrated to metastasize to the paratesticular region include those originating in the stomach, kidney, ileum, and colon. Case presentation A 72-year-old gentleman presented with a firm and tender mass involving the right epididymis. On examination, he was jaundiced. Computed tomography of the abdomen demonstrated an obstructive stricture of the extra-hepatic bile ducts, in keeping with a cholangiocarcinoma, through which a metal stent was endoscopically inserted for symptomatic relief. Subsequent right radical orchidectomy yielded a diffusely infiltrative adenocarcinoma obliterating the epididymis, extending into the rete testis, vas deferens and spermatic cord and showing widespread vascular and perineural invasion. Residual epididymal, rete, and testicular tubules showed no in situ neoplasia. Morphologically and immunohistochemically the features were in keeping with a metastasis from a primary cholangiocarcinoma. Conclusion Only two cases of bile duct carcinoma metastasising to the male genital tract have previously been reported in the literature, the testis being the main site of metastasis in both cases. To our knowledge, this is the first described case of cholangiocarcinoma metastasising primarily to the epididymis, and presenting as a solitary epididymal metastasis in the absence of disseminated disease. It serves to highlight the importance of performing a thorough examination of the male external genitalia both clinically, in the follow up of cancer patients, and at autopsy.

  2. Experience with gemcitabine and cisplatin in the therapy of inoperable and metastatic cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Chaiyut Charoentum; Sumitra Thongprasert; Busyamas Chewaskulyong; Sutthirak Munprakan

    2007-01-01

    AIM:To study the activity of gemcitabine and cisplatin in a cohort of patients with inoperable or metastatic cholangiocarcinoma.METHODS: Chemotherapy-naive patients with pathologically proven cholangiocarcinoma, receiving treatment that consisted of gemcitabine at 1250 mg/m2in a 30-min infusion on d 1 and 8, and cisplatin at 75 mg/m2 at every 21-d cycle, were retrospectively analyzed.RESULTS: From June 2003 to December 2005, 42patients were evaluated. Twelve patients (28%) had unresectable disease and 30 (72%) had metastatic disease. There were 28 males and 14 females with a median age of 51 years (range 33-67) and median ECOG PS of 1 (range 0-2). A total of 171 cycles were given with a median number of cycles of 4 (range 1-6).There were 0 CR, 9 PR, 11 SD and 13 PD (response rate 21%). Grade 3-4 hematologic toxicities were: anemia in 33%, neutropenia in 22% and thrombocytopenia in 5%.Non-hematologic toxicity was generally mild. No cases of febrile neutropenia or treatment-related death were noted. The median survival was 10.8 mo (range 8.4-13mo) and progression free survival was 8.5 mo. One-year survival rate was 40%.CONCLUSION: Our results indicate that the combination of gemcitabine and cisplatin had consistent efficacy in patients with unresectable or metastatic cholangiocarcinoma.

  3. Effect of intra-hepatic arterial infusion chemotherapy for patients with liver metastasis from breast cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy of intra-hepatic arterial infusion chemotherapy for patients with liver metastasis from breast cancer. Methods: 1993-1998 years, Thirty four patients with liver metastasis from breast cancer had received epi-adriamycin, cisplatin, mitomycin and 5-fluorouracil by intrahepatic arterial infusion chemotherapy. Twelve patients had received embolization. Results: Six patients (17.65%) had a complete response, 12 patients (35.29%) had a partial response. The overall response rate was 52.94%. Cumulative survival rates at 1, 2, 3 and 4 years were 56.90%, 25.00%, 5.00% and 5.00% respectively (Kaplan-Meier method). The median overall survival time was 11.5 months. Conclusion: Intra-hepatic arterial infusion chemotherapy is safe and effective for liver metastasis from breast cancer and should be the first choice of treatment for these patients

  4. Clinical results of the transjugular intrahepatic portosystemic shunt

    International Nuclear Information System (INIS)

    To evaluate the clinical results of transjugular intrahepatic portosystemic shunt(TIPS) for the control of variceal bleeding. TIPS creation was attempted in 23 patients with endoscopically confirmed variceal bleeding. Most patients had multiple episodes of bleeding in the past and have been treated with multiple endoscopic sclerotherapies. Pre-and post-procedural hepatic and portal vein pressures were measured. After creation of TIPS patients were followed up at regular intervals. TIPS has been successfully accomplished in 22 of 23 patients using Wallstent(n = 21) and Strecker stent(n = 1). Immediate bleeding control was achieved in all patients with shunt creation. No procedure-related complication was noted. Portal vein pressure was reduced from 30.7 ± 5.8 mmHg to 20.8 ± 4.7 mmHg. The mean pressure gradient of portosystemic shunt dropped from 22.8 ± 6.0 prior to TIPS to 12.2 ± 4.1 immediately after. During the follow-up period (6-556 days, mean; 10 months), seven patients died; progressive hepatic failure (n 4), variceal rebleeding (n = 2), and respiratory failure(n = 1). Hepatic encephalopathy after TIPS was noted in 7 patients(31.8%). Variceal rebleeding occurred in 3 patients(13.6%). The remaining 15 patients have survived an average of 11 months. This results suggest that TIPS is a safe and effective method for lowering portal pressure and controlling variceal bleeding. Furthermore if these initial results are encouraged by further long-term observation, TIPS could replace endoscopic and risky surgical intervention

  5. Preoperative assessment of hilar cholangiocarcinoma:combination of cholangiographyandCTangiography

    Institute of Scientific and Technical Information of China (English)

    Shi-An Yu; Cheng Zhang; Jia-Min Zhang; Gen-Jun Mao; Long-Tang Xu; Xiao-Kang Wu; Jin-Er Shu; Guang-Hong Lv; Zhang-Dong Zheng

    2010-01-01

    BACKGROUND: Hilar cholangiocarcinoma is one of the most dififcult carcinomas to manage because of the location of the main tumor at the hepatic hilus and the complex anatomy of the biliary, arterial, and portal systems. To plan an operation, it is important to acquire accurate information about the relationship between hilar cholangiocarcinoma and adjacent vessels. This study aimed to evaluate the clinical value of cholangiography combined with spiral CT three-dimensional (3D) angiography for a preoperative assessment of hilar cholangiocarcinoma. METHODS: From March 2007 to August 2009, cholangiography was performed in 13 patients with hilar cholangiocarcinoma. Meanwhile, contrast-enhanced abdominal scanning was performed using 16-slice spiral CT, and the 3D images of the hepatic artery and portal vein were acquired. The level and range of invasion of the hepatic artery, the portal vein, and the bile duct, the preoperative Bismuth classiifcation, and T-staging were recorded and compared with those after surgical exploration. RESULTS: The hepatic artery and portal vein were recon-structed successfully in all these patients. Percutaneous transhepatic cholangiography was performed in 9 patients, endoscopic retrograde cholangiopancreatography in 1, and magnetic resonance cholangiopancreatography in 3. The CT angiography records of invasion of the hepatic artery were consistent with the results of explorations in these patients. The data from 5 of the 13 patients were consistent with those on invasion of the portal vein. The results of the Bismuth classiifcation and the T-staging system were consistent with those of surgical exploration in 12 of the 13 patients. Seven of 8 patients who were estimated to be suitable for operation based on images were curatively treated and 5 who were judged to be unsuitable for curative operation by cholangiography and CT angiography were conifrmed intraoperatively and underwent palliative procedures. CONCLUSIONS

  6. The diagnostic value of joint detection of serum CA19-9, CA125 and CA242 for cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Cui Da-Peng; Han Lei; Liu Zhen-Xian; Yang He; Zhang Ying-Chun

    2016-01-01

    Objective:To study the diagnostic value of joint detection of serum CA19-9, CA125 and CA242 for cholangiocarcinoma.Methods:A total of 35 patients with cholangiocarcinoma who received surgical resection in our hospital were selected as malignant group, 30 patients with cholelithiasis who received surgical resection in our hospital during the same period were selected as benign group, serum samples were collected before surgery to determine CA19-9, CA125 and CA242 content, and cholangiocarcinoma tissue and normal bile duct tissue were collected after surgery to determine the content of proliferation and invasion molecules. Results:Serum CA19-9, CA125 and CA242 levels of malignant group were significantly higher than those of control group; PROX-1, Ki-67, Bcl-2, Bad, Gab1, LOXL2, TRPM7 and CXCL12 levels in cholangiocarcinoma tissue were higher than those in benign bile duct tissue, and E-cadherin level was lower than that in benign bile duct tissue; serum CA19-9, CA125 and CA242 levels were positively correlated with PROX-1, Ki-67, Bcl-2, Bad, Gab1, LOXL2, TRPM7 and CXCL12 levels, and negatively correlated with E-cadherin level.Conclusion:Joint detection of serum CA19-9, CA125 and CA242 can not only provide reference for the diagnosis of cholangiocarcinoma, but can also provide basis for the evaluation of proliferation, invasion and other malignant biological behaviors.

  7. Does bilioenteric anastomosis impair results of liver resection in primary intrahepatic lithiasis?

    Institute of Scientific and Technical Information of China (English)

    Paulo; Herman; Marcos; V; Perini; Vincenzo; Pugliese; Julio; Cesar; Pereira; Marcel; Autran; C; Machado; William; A; Saad; Luiz; AC; D; Albuquerque; Ivan; Cecconello

    2010-01-01

    AIM:To evaluate the long-term results of liver resection for the treatment of primary intrahepatic lithiasis.Prognostic factors,especially the impact of bilioenteric anastomosis on recurrence of symptoms were assessed.METHODS:Forty one patients with intrahepatic stones and parenchyma fibrosis/atrophy and/or biliary stenosis were submitted to liver resection.Resection was associated with a Roux-en-Y hepaticojejunostomy in all patients with bilateral stones and in those with unilateral disease and dilation of...

  8. The interventional treatment for biliary recurrent obstruction after palliative T tube drainage in patients with obstruction due to cholangiocarcinoma

    International Nuclear Information System (INIS)

    Objective: To explore the interventional method to treat biliary recurrent jaundice after T tube drainage in patients with malignant obstructive jaundice due to cholangiocarcinoma. Methods: 7 biliary metallic stents were placed in 7 patients with recurrent jaundice after T-tube drainage in cholangiocarcinoma cases. Results: Stent placement was once successful in all 7 cases with successful rate of 100%. For all cases, TBIL, ALT, GTP and AKP values 7 days postoperatively were significantly lower than that of preoperation together with subsidence of jaundice satisfactorily for 100% after the treatment. Conclusions: Percutaneous placement of biliary metallic stents was effective economic, minimal invasive and safe for palliation of biliary recurrent jaundice after T tube drainage in cholangiocarcinoma-induced obstructive jaundice

  9. Intrahepatic HBV DNA as a predictor of antivirus treatment efficacy in HBeAg-positive chronic hepatitis B patients

    Institute of Scientific and Technical Information of China (English)

    Hai-Ying Lu; Zhong-Hou Han; Yong Chen; Li-Wei Zhuang; Yan-Yan Yu; Hadad Ivan; Chong-Wen Si; Zheng Zeng; Jun Li; Dong-Ming Hou; Xin-Yue Chen

    2007-01-01

    AIM:To evaluate the effect of antiviral agents on intrahepatic HBV DNA in HBeAg-positive chronic hepatitis B patients.METHODS: Seventy-one patients received treatment with lamivudine, interferon alpha (IFN-α2b) or sequential therapy with lamivudine-IFN-α2b for 48 wk. All subjects were followed up for 24 wk. Serum and intrahepatic HBV DNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP.RESULTS: At the end of treatment, the intrahepatic HBV DNA level in 71 patients decreased from a mean of (6.1 ± 1.0) log10 to (4.9 ± 1.4) log10. Further, a larger decrease was seen in the intrahepatic HBV DNA level in patients with HBeAg seroconversion. Intrahepatic HBV DNA level (before and after treatment) was not significantly affected by the patients'HBV genotype, or by the probability of virological flare after treatment.CONCLUSION: Intrahepatic HBV DNA can be effectively lowered by antiviral agents and is a significant marker for monitoring antivirus treatment. Low intrahepatic HBV DNA level may achieve better efficacy of antivirus treatment.

  10. Radiation Exposure in Transjugular Intrahepatic Portosystemic Shunt Creation

    Energy Technology Data Exchange (ETDEWEB)

    Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Maruzzelli, Luigi, E-mail: lmaruzzelli@ismett.edu; Cortis, Kelvin, E-mail: kelvincortis@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); D’Amico, Mario, E-mail: mdamico@ismett.edu [University of Palermo, Department of Radiology (Italy); Floridia, Gaetano, E-mail: gfloridia@ismett.edu; Gallo, Giuseppe, E-mail: ggallo@ismett.edu; Tafaro, Corrado, E-mail: ctafaro@ismett.edu; Luca, Angelo, E-mail: aluca@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy)

    2016-02-15

    PurposeTransjugular intrahepatic portosystemic shunt (TIPS) creation is considered as being one of the most complex procedures in abdominal interventional radiology. Our aim was twofold: quantification of TIPS-related patient radiation exposure in our center and identification of factors leading to reduced radiation exposure.Materials and methodsThree hundred and forty seven consecutive patients underwent TIPS in our center between 2007 and 2014. Three main procedure categories were identified: Group I (n = 88)—fluoroscopic-guided portal vein targeting, procedure done in an image intensifier-based angiographic system (IIDS); Group II (n = 48)—ultrasound-guided portal vein puncture, procedure done in an IIDS; and Group III (n = 211)—ultrasound-guided portal vein puncture, procedure done in a flat panel detector-based system (FPDS). Radiation exposure (dose-area product [DAP], in Gy cm{sup 2} and fluoroscopy time [FT] in minutes) was retrospectively analyzed.ResultsDAP was significantly higher in Group I (mean ± SD 360 ± 298; median 287; 75th percentile 389 Gy cm{sup 2}) as compared to Group II (217 ± 130; 178; 276 Gy cm{sup 2}; p = 0.002) and Group III (129 ± 117; 70; 150 Gy cm{sup 2}p < 0.001). The difference in DAP between Groups II and III was also significant (p < 0.001). Group I had significantly longer FT (25.78 ± 13.52 min) as compared to Group II (20.45 ± 10.87 min; p = 0.02) and Group III (19.76 ± 13.34; p < 0.001). FT was not significantly different between Groups II and III (p = 0.73).ConclusionsReal-time ultrasound-guided targeting of the portal venous system during TIPS creation results in a significantly lower radiation exposure and reduced FT. Further reduction in radiation exposure can be achieved through the use of modern angiographic units with FPDS.

  11. Endoscopic transcystic stent placement for an intrahepatic abscess due to gallbladder perforation

    Institute of Scientific and Technical Information of China (English)

    Myung Soo Kang; Do Hyun Park; Ki Du Kwon; Jeong Hoon Park; Suck-Ho Lee; Hong-Soo Kim; Sang-Heum Park; Sun-Joo Kim

    2007-01-01

    Perforation of the gallbladder with cholecystohepatic communication is a rare cause of liver abscess. Because it is a rare entity, the treatment modality has not been fully established. We report for the first time a patient with an intrahepatic abscess due to gallbladder perforation successfully treated by endoscopic stent placement into the gallbladder who had a poor response to continuous percutaneous drainage.

  12. Complications of percutaneous transhepatic biliary drainage in patients with dilated and nondilated intrahepatic bile ducts

    International Nuclear Information System (INIS)

    Percutaneous transhepatic biliary drainage (PTBD) have been described as an effective technique to obtain biliary access. Between January 1996 and December 2006, a total of 419 consecutive patients with endoscopically inaccessible bile ducts underwent PTBD. The current retrospective study evaluated success and complication rates of this invasive technique. PTBD was successful in 410/419 patients (97%). The success rate was equal in patients with dilated and nondilated bile ducts (p = 0.820). In 39/419 patients (9%) procedure related complications could be observed. Major complications occurred in 17/419 patients (4%). Patients with nondilated intrahepatic bile ducts had significantly higher complication rates compared to patients with dilated intrahepatic bile ducts (14.5% vs. 6.9%, respectively [p = 0.022]). Procedure related deaths were observed in 3 patients (0.7%). In conclusion, percutaneous transhepatic biliary drainage is an effective procedure in patients with dilated and nondilated intrahepatic bile ducts. However, patients with nondilated intrahepatic bile ducts showed a higher risk for procedure related complications.

  13. Association between biliary complications and technique of hilar division (extrahepatic vs. intrahepatic in major liver resections

    Directory of Open Access Journals (Sweden)

    Gamaletsos Evangelos

    2006-08-01

    Full Text Available Abstract Background Division of major vascular and biliary structures during major hepatectomies can be carried out either extrahepatically at the porta hepatic or intrahepatically during the parenchymal transection. In this retrospective study we test the hypothesis that the intrahepatic technique is associated with less early biliary complications. Methods 150 patients who underwent major hepatectomies were retrospectively allocated into an intrahepatic group (n = 100 and an extrahepatic group (n = 50 based on the technique of hilar division. The two groups were operated by two different surgical teams, each one favoring one of the two approaches for hilar dissection. Operative data (warm ischemic time, operative time, blood loss, biliary complications, morbidity and mortality rates were analyzed. Results In extrahepatic patients, operative time was longer (245 ± 50 vs 214 ± 38 min, p Conclusion Intrahepatic hilar division is as safe as extrahepatic hilar division in terms of intraoperative blood requirements, morbidity and mortality. The extrahepatic technique is associated with more severe bile leaks and biliary injuries.

  14. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats.

    Science.gov (United States)

    Margolis, Lee M; Rivas, Donato A; Ezzyat, Yassine; Gaffney-Stomberg, Erin; Young, Andrew J; McClung, James P; Fielding, Roger A; Pasiakos, Stefan M

    2016-01-01

    The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g(-1) lower (p protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p health benefits associated with CR-specifically reduction in intrahepatic triglyceride content-may be enhanced by consuming a higher-protein/lower-carbohydrate diet. PMID:27649241

  15. Genetics and Molecular Modeling of New Mutations of Familial Intrahepatic Cholestasis in a Single Italian Center.

    Directory of Open Access Journals (Sweden)

    Isabella Giovannoni

    Full Text Available Familial intrahepatic cholestases (FICs are a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Three distinct forms are described: FIC1 and FIC2, associated with low/normal GGT level in serum, which are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and defects in ABCB11 encoding bile salt export pump protein, respectively; FIC3, linked to high GGT level, involves impaired biliary phospholipid secretion due to defects in ABCB4, encoding multidrug resistance 3 protein. Different mutations in these genes may cause either a progressive familial intrahepatic cholestasis (PFIC or a benign recurrent intrahepatic cholestasis (BRIC. For the purposes of the present study we genotyped 27 children with intrahepatic cholestasis, diagnosed on either a clinical or histological basis. Two BRIC, 23 PFIC and 2 BRIC/PFIC were identified. Thirty-four different mutations were found of which 11 were novel. One was a 2Mb deletion (5'UTR- exon 18 in ATP8B1. In another case microsatellite analysis of chromosome 2, including ABCB11, showed uniparental disomy. Two cases were compound heterozygous for BRIC/PFIC2 mutations. Our results highlight the importance of the pathogenic role of novel mutations in the three genes and unusual modes of their transmission.

  16. Genetic Determinants of Drug-induced Cholestasis and Intrahepatic Cholestasis of Pregnancy

    NARCIS (Netherlands)

    C. Pauli-Magnus; P.J. Meier; B. Stieger

    2010-01-01

    Intrahepatic cholestasis of pregnancy and drug-induced cholestasis are two clinically important forms of acquired cholestatic liver disease. The understanding of the underlying mechanisms of acquired cholestasis has recently made considerable progress by the identification of canalicular ATP-binding

  17. Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver

    DEFF Research Database (Denmark)

    Vestentoft, Peter S; Jelnes, Peter; Hopkinson, Branden M;

    2011-01-01

    BACKGROUND: During liver development, intrahepatic bile ducts are thought to arise by a unique asymmetric mode of cholangiocyte tubulogenesis characterized by a series of remodeling stages. Moreover, in liver diseases, cells lining the Canals of Hering can proliferate and generate new hepatic...

  18. Genetics and Molecular Modeling of New Mutations of Familial Intrahepatic Cholestasis in a Single Italian Center

    Science.gov (United States)

    Giovannoni, Isabella; Callea, Francesco; Bellacchio, Emanuele; Torre, Giuliano; De Ville De Goyet, Jean; Francalanci, Paola

    2015-01-01

    Familial intrahepatic cholestases (FICs) are a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Three distinct forms are described: FIC1 and FIC2, associated with low/normal GGT level in serum, which are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and defects in ABCB11 encoding bile salt export pump protein, respectively; FIC3, linked to high GGT level, involves impaired biliary phospholipid secretion due to defects in ABCB4, encoding multidrug resistance 3 protein. Different mutations in these genes may cause either a progressive familial intrahepatic cholestasis (PFIC) or a benign recurrent intrahepatic cholestasis (BRIC). For the purposes of the present study we genotyped 27 children with intrahepatic cholestasis, diagnosed on either a clinical or histological basis. Two BRIC, 23 PFIC and 2 BRIC/PFIC were identified. Thirty-four different mutations were found of which 11 were novel. One was a 2Mb deletion (5’UTR- exon 18) in ATP8B1. In another case microsatellite analysis of chromosome 2, including ABCB11, showed uniparental disomy. Two cases were compound heterozygous for BRIC/PFIC2 mutations. Our results highlight the importance of the pathogenic role of novel mutations in the three genes and unusual modes of their transmission. PMID:26678486

  19. Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation.

    Science.gov (United States)

    Prytz, Hanne; Keiding, Susanne; Björnsson, Einar; Broomé, Ulrika; Almer, Sven; Castedal, Maria; Munk, Ole Lajord

    2006-12-01

    Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5-year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC; however, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG-PET results with histology of explanted livers. Dynamic FDG-PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high-grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver. In conclusion, dynamic FDG-PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG-PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC.

  20. Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan.

    Science.gov (United States)

    Sato, Yasunori; Kubo, Shoji; Takemura, Shigekazu; Sugawara, Yasuhiko; Tanaka, Shogo; Fujikawa, Masahiro; Arimoto, Akira; Harada, Kenichi; Sasaki, Motoko; Nakanuma, Yasuni

    2014-01-01

    Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of γ-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development.

  1. Percutaneous Irreversible Electroporation of Unresectable Hilar Cholangiocarcinoma (Klatskin Tumor): A Case Report

    International Nuclear Information System (INIS)

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant tumors located near large vessels or bile ducts. The presence of metal objects in the ablation zone, such as Wallstents, is generally considered a contraindication for IRE, because tissue heating due to power conduction may lead to thermal complications. This report describes a 66-year-old female with a Bismuth–Corlette stage IV unresectable cholangiocarcinoma with a metallic Wallstent in the common bile duct, who was safely treated with percutaneous IRE with no signs for relapse 1 year after the procedure

  2. Percutaneous Irreversible Electroporation of Unresectable Hilar Cholangiocarcinoma (Klatskin Tumor): A Case Report.

    Science.gov (United States)

    Melenhorst, Marleen C A M; Scheffer, Hester J; Vroomen, Laurien G P H; Kazemier, Geert; van den Tol, M Petrousjka; Meijerink, Martijn R

    2016-01-01

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant tumors located near large vessels or bile ducts. The presence of metal objects in the ablation zone, such as Wallstents, is generally considered a contraindication for IRE, because tissue heating due to power conduction may lead to thermal complications. This report describes a 66-year-old female with a Bismuth-Corlette stage IV unresectable cholangiocarcinoma with a metallic Wallstent in the common bile duct, who was safely treated with percutaneous IRE with no signs for relapse 1 year after the procedure. PMID:25994516

  3. Effect of mutated IκBα transfection on multidrug resistance in hilar cholangiocarcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Ru-Fu Chen; Zhi-Hua Li; Xian-He Kong; Ji-Sheng Chen

    2005-01-01

    AIM: To explore the expression effect of mutated IκBαtransfection on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells by inhibiting the activity of nuclear transcription factor-κB (NF-κB).METHODS: We used the mutated IκBα plasmid to transfect QBC939HCVC+ cells and QBC939 cells, and electrophoretic gel mobility shift assay (EMSA) to detect the binding activity of NF-κB DNA and the effect of the transfrecting mutated IκBα plasmid on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells and its expression protein (P-GP).RFSULTS: Plasmid DNA was digested by restriction enzymes Xbal and Hand Ⅲ, and its product after electrophoresis showed two bands with a big difference in molecular weight,with a size of 4.9 kb and 1.55 kb respectively, which indicated that the carrier was successfully constructed and digested with enzymes. The radioactivity accumulation of QBC939HCVC+and QBC939 cells transfected with mutated IκBα plasmid was significantly lower than that of the control group not transfected with mutated IκBα plasmid. Double densimeter scanning showed that the relative signal density between the tansfection group and non-transfection group was significantly different, which proved that the mutated IκBα plasmid could inhibit the binding activity of NF-κB DNA in hilar cholangiocarcinoma cells. Compared to control group not transfected with m IκBα plasmid, the expression level of MDR-1mRNA in the QBC939 and QBC939HCVC+ cells transfected with mutated IκBα plasmid was lower. The expression intensity of P-GP protein in QBC939 and QBC939HCVC+ cells transfected with mutated IκBα was significantly lower than that of the control group not transfected with mutated IκBα plasmid.CONCLUSION: The mutated IκBα plasmid transfection can markedly reverse the multidrug resistance of hilar cholangiocarcinoma cells. Interruption of NF-κB activity may become a new target in gene therapy for hilar cholangiocarcinogenesic carcinoma.

  4. Apoptosis of human cholangiocarcinoma cells induced by ESC-3 from Crocodylus siamensis bile

    Institute of Scientific and Technical Information of China (English)

    Wei Song; Dong-Yan Shen; Jin-He Kang; Shan-Shan Li; Hui-Wang Zhan; Yan Shi; You-Xiong Xiong; Ge Liang; Qing-xi Chen

    2012-01-01

    AIM:To investigate the effects of ESC-3 isolated from crocodile bile on the growth and apoptosis induction of human cholangiocarcinoma cells.METHODS:ESC-3 was isolated from crocodile bile by Sephadex LH-20 and RP-18 reversed-phase column.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was conducted to determine the effects of ESC-3 on the proliferation of human cholangiocarcinoma cell lines (QBC939,Sk-ChA-1 and MZ-ChA-1).Giemsa staining,Hoechst 33258 and acridine orange/ethidium bromide staining showed the morphological changes of Mz-ChA-1 cells exposed to ESC-3 at different concentrations.Flow cytometry with regular propidium iodide (PI) staining was performed to analyze the cell cycle distribution of Mz-ChA-1 cells and to assess apoptosis by annexin v-fiuorescein isothiocyanate (VFITC)/PI staining.Rh123 staining was used to detect the alteration of mitochondrial membrane potential (△Ψm).The protein levels of Bax,Bcl-2,Cdk2,cytochrome c and caspase-3 were further confirmed by Western blotting.RESULTS:ESC-3 significantly inhibited the growth of three human cholangiocarcinoma cell lines and arrested Mz-ChA-1 cell cycle at G0/G1 phase.Mz-ChA-1 cells showed typical apoptotic morphological changes after treated with ESC-3 (10 μg/mL) for 48 h.Cell death assay indicated that Mz-ChA-1 cells underwent apoptosis in a dose-dependent manner induced by ESC-3.In addition,ESC-3 treatment could downregulate the protein level of Bcl-2 and upregulate the Bax,leading to the increase in the ratio of Bax to Bcl-2 in Mz-ChA-1 cells.Meanwhile,cytochrome c was released from the mitochondria into the cytosol,which subsequently initiated the activation of caspase-3.All these events were associated with the collapse of the mitochondrial membrane potential.CONCLUSION:ESC-3,the active ingredient of crocodile bile,induced apoptosis in Mz-ChA-1 cells through the mitochondria-dependent pathway and may be a potential chemotherapeutic drug for the treatment of

  5. Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Kim DH

    2013-04-01

    Full Text Available Do Hyung Kim,1,2,* Young-Il Jeong,1,* Chung-Wook Chung,1 Cy Hyun Kim,1,2 Tae Won Kwak,1 Hye Myeong Lee,1 Dae Hwan Kang1,21National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, 2School of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, South Korea *These authors equally contributed to this work. Background: Cholangiocarcinoma is a malignant tumor arising from the epithelium of the bile ducts. In this study, we prepared sorafenib-loaded biliary stents for potential application as drug-delivery systems for localized treatment of extrahepatic cholangiocarcinoma. Methods: A sorafenib-coated metal stent was prepared using an electrospray system with the aid of poly(ε-caprolactone (PCL, and then its anticancer activity was investigated using human cholangiocellular carcinoma (HuCC-T1 cells in vitro and a mouse tumor xenograft model in vivo. Anticancer activity of sorafenib against HuCC-T1 cells was evaluated by the proliferation test, matrix metalloproteinase (MMP activity, cancer cell invasion, and angiogenesis assay in vitro and in vivo. Results: The drug-release study showed that the increased drug content on the PCL film induced a faster drug-release rate. The growth of cancer cells on the sorafenib-loaded PCL film surfaces decreased in a dose-dependent manner. MMP-2 expression of HuCC-T1 cells gradually decreased according to sorafenib concentration. Furthermore, cancer cell invasion and tube formation of human umbilical vein endothelial cells significantly decreased at sorafenib concentrations higher than 10 mM. In the mouse tumor xenograft model with HuCC-T1 cells, sorafenib-eluting PCL films significantly inhibited the growth of tumor mass and induced apoptosis of tumor cells. Various molecular signals, such as B-cell lymphoma (Bcl-2, Bcl-2-associated death promoter, Bcl-x, caspase-3, cleaved caspase-3, Fas, signal transducer and activator of transcription 5

  6. Apoptotic activity of caged xanthones from Garcinia hanburyi in cholangiocarcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Chariya; Hahnvajanawong; Wongwarut; Boonyanugomol; Tapanawan; Nasomyon; Watcharin; Loilome; Nisana; Namwat; Natthinee; Anantachoke; Wichittra; Tassaneeyakul; Banchob; Sripa; Wises; Namwat; Vichai; Reutrakul

    2010-01-01

    AIM:To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma(CCA) KKU-100 and KKU-M156 cells.METHODS:Four caged xanthones,selected on the basis of their anticancer potency and chemical structure diversities(i.e.isomorellin,isomorellinol,forbesione and gambogic acid) were used in this study.Growth inhibition of these caged xanthones was determined using the sulforhodamine B assay.Induction of apoptosis was assessed by observing cell morphology,ethidi...

  7. Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro

    Directory of Open Access Journals (Sweden)

    Itharat Arunporn

    2010-09-01

    Full Text Available Abstract Background Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6, human laryngeal (Hep-2, and human hepatocarcinoma (HepG2 cell lines in vitro. Methods Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC50 (concentration that inhibits cell growth by 50% and the selectivity index (SI were calculated. Results The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi and one folklore recipe (Pra-Sa-Prao-Yhai exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhai recipe showed potent cytotoxic activity with mean IC50 values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC50 ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC50 ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC50 = 9.67 μg/ml. The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC50 = 757 micromolar. The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC50 = 24.09 μg/ml, SI = 8.6. Conclusions The

  8. Potential diagnostic and prognostic biomarkers for cholangiocarcinoma in serum and bile.

    Science.gov (United States)

    Wang, Bin; Chen, Liang; Chang, Hao-Teng

    2016-06-01

    Cholangiocarcinoma (CCA) is a devastating malignancy that is difficult to treat because of its insensitivity to conventional therapies and the inability to detect early tumor formation. Novel molecular techniques have enabled the use of serum and bile markers for CCA diagnosis and prognosis. Herein, we summarize the principal characteristics of serum and bile markers of CCA. Biomarkers such as interleukin-6, matrix metalloproteinases, serotonin (5-hydroxytryptamine) and bile acids have shown promise for improving CCA diagnosis. Several markers such as CYFRA 21-1, MK-1 and C-reactive protein were recently shown to be effective for CCA prognosis. PMID:27232281

  9. Percutaneous Irreversible Electroporation of Unresectable Hilar Cholangiocarcinoma (Klatskin Tumor): A Case Report.

    Science.gov (United States)

    Melenhorst, Marleen C A M; Scheffer, Hester J; Vroomen, Laurien G P H; Kazemier, Geert; van den Tol, M Petrousjka; Meijerink, Martijn R

    2016-01-01

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant tumors located near large vessels or bile ducts. The presence of metal objects in the ablation zone, such as Wallstents, is generally considered a contraindication for IRE, because tissue heating due to power conduction may lead to thermal complications. This report describes a 66-year-old female with a Bismuth-Corlette stage IV unresectable cholangiocarcinoma with a metallic Wallstent in the common bile duct, who was safely treated with percutaneous IRE with no signs for relapse 1 year after the procedure.

  10. Percutaneous Irreversible Electroporation of Unresectable Hilar Cholangiocarcinoma (Klatskin Tumor): A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Melenhorst, Marleen C. A. M., E-mail: m.melenhorst@vumc.nl; Scheffer, Hester J., E-mail: hj.scheffer@vumc.nl; Vroomen, Laurien G. P. H., E-mail: la.vroomen@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands); Kazemier, Geert, E-mail: g.kazemier@vumc.nl; Tol, M. Petrousjka van den, E-mail: mp.vandentol@vumc.nl [VU University Medical Center, Department of Surgery (Netherlands); Meijerink, Martijn R., E-mail: mr.meijerink@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands)

    2016-01-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant tumors located near large vessels or bile ducts. The presence of metal objects in the ablation zone, such as Wallstents, is generally considered a contraindication for IRE, because tissue heating due to power conduction may lead to thermal complications. This report describes a 66-year-old female with a Bismuth–Corlette stage IV unresectable cholangiocarcinoma with a metallic Wallstent in the common bile duct, who was safely treated with percutaneous IRE with no signs for relapse 1 year after the procedure.

  11. Dicoumarol enhances gemcitabine-induced cytotoxicity in high NQO1-expressing cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Benjaporn; Buranrat; Auemduan; Prawan; Upa; Kukongviriyapan; Sarinya; Kong-petch; Veerapol; Kukongviriyapan

    2010-01-01

    AIM: To investigate whether dicoumarol, a potent inhibitor of NAD(P)H quinone oxidoreductase-1 (NQO1), potentiates gemcitabine to induce cytotoxicity in chol-angiocarcinoma cells (CCA) and the role of reactive oxygen generation in sensitizing the cells. METHODS: Four human cell lines with different NQO1 activity were used; the human CCA cell lines, KKU-100, KKU-OCA17, KKU-M214, and Chang liver cells. NQO1 activity and mRNA expression were determined. The cells were pretreated with dicoumarol at relevant con...

  12. Determining the effect of transforming growth factor-β1 on cdk4 and p27 in gastric cancer and cholangiocarcinoma

    OpenAIRE

    Lee, Sung Ryol; SHIN, JAE WOOK; Kim, Hyung Ook; Son, Byung Ho; Yoo, Chang Hak; Shin, Jun Ho

    2012-01-01

    Gastric cancer and cholangiocarcinoma are problematic throughout the world due to their destructive malignancy. In attempts to treat cholangiocarcinoma and gastric cancer, researchers often explore the effects of transforming growth factor-β1 (TGF-β1). TGF-β1 plays a crucial role in causing cell cycle arrest and fibrosis in cancer cells. The present study aimed to identify whether TGF-β1 is capable of functioning as an antitumor agent in two cancer cell lines; cholangiocarcinoma and gastric c...

  13. Total biliary diversion as a treatment option for patients with progressive familial intrahepatic cholestasis and Alagille syndrome

    NARCIS (Netherlands)

    van der Woerd, Wendy L; Kokke, Freddy T; van der Zee, David C; Houwen, RHJ

    2015-01-01

    BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) with low gamma-glutamyl transpeptidase (GGT) and Alagille syndrome are associated with persistent cholestasis and severe pruritus. Various types of biliary diversion have been used to reduce this pruritus and prevent liver dysfunction.

  14. The BH3 Only Protein Mimetic Obatoclax Sensitizes Cholangiocarcinoma Cells to Apo2L/TRAIL-Induced Apoptosis

    Science.gov (United States)

    Mott, Justin L.; Bronk, Steve F.; Mesa, Ruben A.; Kaufmann, Scott H.; Gores, Gregory J.

    2008-01-01

    Human cholangiocarcinomas evade apoptosis by overexpression of Mcl-1. The drug obatoclax (GX15–070) inhibits anti-apoptotic members of the Bcl-2 family including Mcl-1. Purpose To determine if obatoclax sensitizes human cholangiocarcinoma cells to apoptosis. Experimental Design The human cholangiocarcinoma cell lines, KMCH, KMBC, and TFK, were employed for these studies. Protein expression was assessed by immunoblot, and protein-protein interactions detected by co-precipitation of the polypeptide of interest with S-tagged Mcl-1. Activation of Bak and Bax was observed by immunocytochemistry with conformation specific antisera. Results Obatoclax induced minimal apoptosis alone; however, it increased apoptosis 3- to 13-fold in all three cancer cell lines when combined with Apo2L/TRAIL. Obatoclax did not alter cellular expression of Bid, Bim, Puma, Noxa, Bak, Bax, Mcl-1 or cFLIP. Mcl-1 binding to Bak was readily identified in untreated cells, and this association was disrupted by treating the cells with obatoclax. Additionally, Bim binding to Mcl-1 was markedly decreased by obatoclax treatment. We also identified alterations in Bak and Bax conformation following treatment with obatoclax plus Apo2L/TRAIL, but not with either Apo2L/TRAIL or obatoclax alone. Conclusions In conclusion, obatoclax releases Bak and Bim from Mcl-1 and sensitizes human cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis. Obatoclax is a potentially promising adjunctive agent for the treatment of this cancer. PMID:18723481

  15. Placement of multiple metal stents for malignant intrahepatic biliary obstruction via an endoscopic ultrasound-guided choledochoduodenostomy fistula.

    Science.gov (United States)

    Akiyama, Dai; Hamada, Tsuyoshi; Nakai, Yousuke; Isayama, Hiroyuki; Takagi, Kaoru; Mizuno, Suguru; Koike, Kazuhiko

    2015-01-01

    Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) using a fully-covered self-expandable metal stent (SEMS) is increasingly used as an alternative to failed endoscopic retrograde cholangiopancreatography. An EUS-CDS fistula can provide endoscopists with a new approach route for intrahepatic bile ducts. Here, we present successful placement of multiple SEMS for intrahepatic biliary obstruction via an EUS-CDS fistula. PMID:26462843

  16. Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome

    Institute of Scientific and Technical Information of China (English)

    Graciela Martínez-Pallí; Britt B Drake; Joan-Carles García-Pagán; Joan-Albert Barberà; Miguel R Arguedas; Robert Rodriguez-Roisin; Jaume Bosch; Michael B Fallon

    2005-01-01

    AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of hepatopulmonary syndrome (HPS).METHODS: Seven patients, three of them with advanced HPS, in whom detailed pulmonary function tests were performed before and after TIPS placementat the University of Alabama Hospital and at the Hospital Clinic, Barcelona, were considered.RESULTS: TIPS patency was confirmed by hemodynamic evaluation. No changes in arterial blood gases were observed in the overall subset of patients. Transient arterial oxygenation improvement was observed in only one HPS patient, early after TIPS, but this was not sustained 4 mo later.CONCLUSION: TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS.

  17. Percutaneous Treatment of Malignant Jaundice Due to Extrahepatic Cholangiocarcinoma: Covered Viabil Stent Versus Uncovered Wallstents

    International Nuclear Information System (INIS)

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement.

  18. Percutaneous treatment of malignant jaundice due to extrahepatic cholangiocarcinoma: covered Viabil stent versus uncovered Wallstents.

    Science.gov (United States)

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Bezzi, Mario; Passariello, Roberto; Hatzidakis, Adam

    2010-02-01

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement. PMID:19495871

  19. Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Andreas Weber; Claus van Weyhern; Falko Fend; Jochen Schneider; Bruno Neu; Alexander Meining; Hans Weidenbach; Roland M Schmid; Christian Prinz

    2008-01-01

    AIM:To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS:Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures.Fifty-eight consecutive patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS:Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy.The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients).In 20/58 patients (34.5%),diagnosis were obtained by both positive cytology and positive histology,in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION:Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors.In our eyes,additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.

  20. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

    Science.gov (United States)

    Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

    2016-08-01

    Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments. PMID:27279267

  1. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

    Science.gov (United States)

    Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

    2016-08-01

    Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments.

  2. Successful Outcome of Chronic Intrahepatic Cholestasis in an Adult Patient with Sickle Cell/β+ Thalassemia

    Directory of Open Access Journals (Sweden)

    Efthymia Vlachaki

    2014-01-01

    Full Text Available Sickle cell/β+ thalassemia (Hb S/β+thal is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β+thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β+thal.

  3. Sonographic differentiation of pneumobilia from intrahepatic stone: U.F.O. sign

    International Nuclear Information System (INIS)

    Pneumobilia is one of the most troublesome problem in the sonographic examination of the hepatobiliary system, and the differentiation of air from intrahepatic stone is very important. We have analyzed the sonographic characteristics of 42 cases of pneumobilia dn 56 cases of intrahepatic stones over a period of 4 years. New findings of pneumobilia we observed were U.F.O. sign, wing like artefact, and nonvisualization of the lumen of the bile filled duct. Findings of pneumobilia only were U.F.O. sign, nng down and wing like artefact. Findings of stone only were ecdhogenic foci larger than 1.5cm, heterogeneous echo, wedge, shell, or sandwich like contour, and visible lumen of the bile duct

  4. Congenital, solitary, large, intrahepatic arterioportal fistula in a child: management and review of the literature

    International Nuclear Information System (INIS)

    Congenital intrahepatic arterioportal fistula (APF) is a rare condition. In most cases, the symptoms and complications develop during infancy. We report here the incidental finding of a large and solitary congenital APF in a 13-year-old boy, with subsequent related clinical complications. At angiography, an APF connecting the left hepatic artery and the left branch of the portal vein (PV) was demonstrated with reversed flow in the left and main PV. The fistula was successfully occluded, in a single embolisation session, using an Amplatzer occlusion device. This was associated with immediate restoration of normal hepatopetal flow in the PV and followed by resolution of the clinical signs of portal hypertension. This patient is the oldest child with congenital intrahepatic APF to be reported. We emphasise the interest of using a large device (Amplatzer) to occlude a solitary large APF in a single session and, more importantly, to avoid other possible complications related to embolisation. (orig.)

  5. Novel A TPSB1 mutation in an adult male with progressive familial intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Bao-Cheng Deng; Sa Lv; Wei Cui; Rui Zhao; Xu Lu; Jian Wu; Pei Liu

    2012-01-01

    Progressive familial intrahepatic cholestasis type 1 is a rare disease that is characterized by low serum γ-glutamyltransferase levels due to mutation in ATP8B1.We present a 23-year-old male who experienced persistent marked pruritus for eighteen years and recurrent jaundice for thirteen years,in addition to cholestasis that eventually became fatal.Genetic sequencing studies of the entire coding (exon) sequences of ATP8B1 and ABCB11 uncovered a novel heterozygous missense 3035G>T mutation (S1012I) and a synonymous 696T>C mutation in ATP8B1.The patient's progression was associated with not only impaired familial intrahepatic cholestasis 1 (FIC1) function but also impaired bile salt export pump expression due to the impaired FIC1 function.Our findings show that patients with intermittent cholestasis can develop progressive liver disease even after several decades and require regular follow up.

  6. Intrahepatic Cholestasis of Pregnancy and Serum Bile Acids in HIV-Infected Pregnant Women

    OpenAIRE

    Weinberg, Adriana; Allshouse, Amanda; Kinzie, Kay; Cho, Alice; Davies, Jill K.; Mc Farland, Elizabeth J

    2015-01-01

    Objectives Intra-hepatic cholestasis of pregnancy (ICP) is uncommon, but has severe effects on pregnancy outcomes. ICP is characterized by elevated serum bile acids and liver enzymes and preferentially affects women with liver disorders. We compared bile acids and pregnancy outcomes of HIV-infected pregnant women, who commonly have elevated live enzymes, with uninfected controls. Methods Twenty-four HIV-infected, including 2 co-infected with hepatitis C virus (HCV), and 25 uninfected women we...

  7. Establishment of an animal model of ischemic type intrahepatic biliary lesion in rabbits

    Institute of Scientific and Technical Information of China (English)

    Qin-Song Sheng; Da-Zhi Chen; Ren Lang; Qiang He; Yong-Jiu Yang; Zhao-Wei Qu; De-Fang Zhao; Xiao-Sheng Zhang

    2009-01-01

    AIM: To explore a method to establish an animal model of ischemic type intrahepatic biliary lesion in rabbits. METHODS: Forty Japanese white rabbits of clean grade were divided randomly into four groups (10 rabbits per group) including sham operation (SO) group, and artery-bile obstruction (ABO)-1 h group, ABO-2 h group and ABO-3 h group. All the rabbits in this study underwent the same initial surgical procedure in which the liver was prepared as for graft removal during liver transplantation. Subsequently in the SO group, no additional vascular intervention was performed, while in groups ABO-1 h, ABO-2 h and ABO-3 h, the animals underwent combined clamping of the hepatic artery and common bile duct with microvascular clips for 1, 2 and 3 h, respectively. After the scheduled occlusion time, the clip was removed to recover blood supply. The animals were killed 4 wk after operation. The survival rate, liver function, cholangiography and histopathological manifestation of the rabbits in each group were observed. RESULTS: The survival rate was 100% in groups SO, ABO-1 h and ABO-2 h, while it was 60% in group ABO-3 h. At each observation time, the change degree of the indexes of liver function was proportional to the clamping time (ABO-3 h > ABO-2 h > ABO-1 h > SO, P < 0.05). Cholangiographical and histopathologic manifestations both showed that intrahepatic biliary lesion aggravated proportionally with the increase of the clamping time. CONCLUSION: An animal model of ischemic type intrahepatic biliary lesion in rabbits is successfully established, which may provide a reliable technique for basic and clinical research into the etiology, development and prophylaxis of ischemic type intrahepatic biliary lesion after liver transplantation.

  8. Asymptomatic Intrahepatic Portosystemic Venous Shunt: To Treat or Not To Treat?

    Science.gov (United States)

    Palvanov, Arkadiy; Marder, Ruth Leah; Siegel, David

    2016-09-01

    Intrahepatic portosystemic venous shunts (IPSVSs) are rare vascular malformations. They can be asymptomatic or present with various symptoms including encephalopathy. We present two cases of IPSVS, one involving a patient presenting with altered mental status and the other discovered incidentally. While there is no question that patients presenting with symptomatic IPSVS should undergo definitive treatment, there is no consensus regarding elective therapy for asymptomatic lesions.

  9. Urinary reducing substances in neonatal intrahepatic cholestasis caused by citrin deficiency

    OpenAIRE

    Ajmal Kader; Christina Ong; Veena Logarajah; Kong Boo Phua; Ee Shien Tan

    2014-01-01

    Neonatal cholestasis due to citrin deficiency is an autosomal recessive metabolic disorder caused by mutations in SLC25A13 gene. Mutations in this gene have a relatively high prevalence in East-Asian races compared to European or Afro-Caribbean races. Mutations in both sets of chromosomes often lead to self-limiting early onset cholestasis and growth retardation referred as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). It is associated with a wide range of metabolic d...

  10. Partial Internal Biliary Diversion: A Solution for Intractable Pruritus in Progressive Familial Intrahepatic Cholestasis Type 1

    Science.gov (United States)

    Ganesh, Ramaswamy; Suresh, Natarajan; Sathiyasekeran, Malathi; Ramachandran, Priya

    2011-01-01

    Biliary diversion offers a potential option for intractable pruritus in children with chronic cholestatic disorders. Progressive familial intrahepatic cholestasis (PFIC) is an inherited disorder of impaired bile acid transport and excretion, which presents with jaundice and pruritus in the first few months of life and progresses to cirrhosis by infancy or adolescence. We report a child with PFIC type 1 who underwent internal biliary diversion for intractable pruritus and was relieved of his symptoms. PMID:21546727

  11. Intrahepatic Bile Duct Regeneration in Mice Does Not Require Hnf6 or Notch Signaling through Rbpj

    OpenAIRE

    Walter, Teagan J.; Vanderpool, Charles; Cast, Ashley E.; Huppert, Stacey S.

    2014-01-01

    The potential for intrahepatic bile duct (IHBD) regeneration in patients with bile duct insufficiency diseases is poorly understood. Notch signaling and Hnf6 have each been shown to be important for the morphogenesis of IHBDs in mice. One congenital pediatric liver disease characterized by reduced numbers of IHBDs, Alagille syndrome, is associated with mutations in Notch signaling components. Therefore, we investigated whether liver cell plasticity could contribute to IHBD regeneration in mic...

  12. Role of ABCC2 common variants in intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Silvia Sookoian; Gustavo Castano; Carlos J Pirola

    2008-01-01

    The pathogenesis of intrahepatic cholestasis of pregnancy (ICP), a disorder that adversely affects maternal wellbeing and fetal outcome, is unclear. However, multiple factors probably interact along with a genetic predisposition. We would like to add some comments on a paper recently published concerning the role of ABCB11 and ABCC2 polymorphisms in both ICP and contraceptive-induced cholestasis, especially in the light of our recently published findings about a positive association between ICP and ABCC2 common variants.

  13. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats

    Directory of Open Access Journals (Sweden)

    Lee M. Margolis

    2016-09-01

    Full Text Available The purpose of this investigation was to assess the influence of calorie restriction (CR alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL, and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL or CR (40% restriction, adequate (10%, or high (32% protein (PRO milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g−1 lower (p < 0.05 in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN, stearoyl-CoA destaurase-1 (SCD1 and pyruvate dehydrogenase kinase, isozyme 4 (PDK4 were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05, respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05 in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR—specifically reduction in intrahepatic triglyceride content—may be enhanced by consuming a higher-protein/lower-carbohydrate diet.

  14. Treatment of Portosystemic Shunt Myelopathy with a Stent Graft Deployed through a Transjugular Intrahepatic Route

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Deepak, E-mail: deepakjain02@yahoo.com; Arora, Ankur, E-mail: aroradrankur@yahoo.com [Institute of Liver and Biliary Sciences, Department of Radiology (India); Deka, Pranjal, E-mail: drpranjaldeka@gmail.com [Institute of Liver and Biliary Sciences, Department of Hepatopancreatobiliary Surgery (India); Mukund, Amar, E-mail: dramarmukund@gmail.com; Bhatnagar, Shorav, E-mail: drshorav@yahoo.com [Institute of Liver and Biliary Sciences, Department of Radiology (India); Jindal, Deepti, E-mail: deepijindal@rediffmail.com; Kumar, Niteen, E-mail: drniteenkumar@gmail.com; Pamecha, Viniyendra, E-mail: viniyendra@yahoo.co.uk [Institute of Liver and Biliary Sciences, Department of Hepatopancreatobiliary Surgery (India)

    2013-08-01

    A case of surgically created splenorenal shunt complicated with shunt myelopathy was successfully managed by placement of a stent graft within the splenic vein to close the portosystemic shunt and alleviate myelopathy. To our knowledge, this is the first report of a case of shunt myelopathy in a patient with noncirrhotic portal fibrosis without cirrhosis treated by a novel technique wherein a transjugular intrahepatic route was adopted to deploy the stent graft.

  15. Adiponectin Is Inversely Associated With Intramyocellular and Intrahepatic Lipids in Obese Premenopausal Women

    OpenAIRE

    Bredella, Miriam A.; Torriani, Martin; Ghomi, Reza H.; Thomas, Bijoy J.; Brick, Danielle J.; Gerweck, Anu V.; Harrington, Lindsey M.; Miller, Karen K.

    2010-01-01

    Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noni...

  16. Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1

    OpenAIRE

    Hasegawa, Yasuhiro; Hayashi, Hisamitsu; Naoi, Sotaro; Kondou, Hiroki; Bessho, Kazuhiko; Igarashi, Koji; Hanada, Kentaro; Nakao, Kie; Kimura, Takeshi; Konishi, Akiko; Nagasaka, Hironori; Miyoshi, Yoko; Ozono, Keiichi; Kusuhara, Hiroyuki

    2014-01-01

    Background Progressive familial intrahepatic cholestasis type 1 (PFIC1), an inherited liver disease caused by mutations in ATP8B1, progresses to severe cholestasis with a sustained intractable itch. Currently, no effective therapy has been established for PFIC1. Decreased function of the bile salt export pump (BSEP) in hepatocytes is suggested to be responsible for the severe cholestasis observed in PFIC1. We found a previously unidentified pharmacological effect of 4-phenylbutyrate (4PB) tha...

  17. Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis

    OpenAIRE

    Treepongkaruna, Suporn; Gaensan, Amornphun; Pienvichit, Paneeya; Luksan, Ondrej; Knisely, AS; Sornmayura, Pattana; Jirsa, Milan

    2009-01-01

    Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum γ-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3,...

  18. Morphologic Findings in Progressive Familial Intrahepatic Cholestasis 2 (PFIC2): Correlation With Genetic and Immunohistochemical Studies

    OpenAIRE

    Evason, Kimberley; Bove, Kevin E.; Finegold, Milton J; Knisely, A. S.; Rhee, Sue; Rosenthal, Philip; Miethke, Alexander G.; Karpen, Saul J; Ferrell, Linda D; Kim, Grace E.

    2011-01-01

    Progressive familial intrahepatic cholestasis, type 2 (PFIC2), characterized by cholestasis in infancy that may progress to cirrhosis, is caused by mutation in ABCB11, which encodes bile salt export pump (BSEP). We correlated histopathologic, immunohistochemical, and ultrastructural features in PFIC2 with specific mutations and clinical course. Twelve patients with clinical PFIC2 and ABCB11 mutations were identified, and 22 liver biopsy and explant specimens were assessed. All had hepatocellu...

  19. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy

    OpenAIRE

    Pauli-Magnus, Christiane; Meier, Peter J; Stieger, Bruno

    2010-01-01

    Intrahepatic cholestasis of pregnancy and drug-induced cholestasis are two clinically important forms of acquired cholestatic liver disease. The understanding of the underlying mechanisms of acquired cholestasis has recently made considerable progress by the identification of canalicular ATP-binding cassette (ABC) transporters as likely targets for these forms of cholestasis. Cholestasis of pregnancy is linked to estrogen and progesterone metabolites. These metabolites have been shown to impa...

  20. Irreversible Electroporation of a Hepatocellular Carcinoma Lesion Adjacent to a Transjugular Intrahepatic Portosystemic Shunt Stent Graft

    Energy Technology Data Exchange (ETDEWEB)

    Niessen, Christoph; Jung, Ernst Michael; Wohlgemuth, Walter A. [Department of Radiology, University Medical Center Regensburg, Regensburg D-93053 (Germany); Trabold, Benedikt [Department of Anaesthesia, University Medical Center Regensburg, Regensburg D-93053 (Germany); Haimerl, Michael; Schreyer, Andreas; Stroszczynski, Christian; Wiggermann, Philipp [Department of Radiology, University Medical Center Regensburg, Regensburg D-93053 (Germany)

    2013-07-01

    We report in a 65-year-old man hepatocellular carcinoma adjacent to a transjugular intrahepatic portosystemic shunt stent-graft which was successfully treated with irreversible electroporation (IRE). IRE is a new non-thermal tissue ablation technique which uses electrical pulses to induce cell necrosis by irreversible membrane poration. IRE proved to be more advantageous in the ablation of perivascular tumor with little injury to the surrounding structures.

  1. Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients: Technical Considerations and Review of the Literature

    OpenAIRE

    Patel, Nilesh H.; Patel, Jay; Behrens, George; Savo, Anthony

    2005-01-01

    Transjugular intrahepatic portosystemic shunt (TIPS) is an accepted therapeutic option for the treatment of complications of portal hypertension, such as refractory variceal bleeding, refractory ascites, refractory hepatic hydrothorax and Budd-Chiari syndrome, in cirrhotic livers. However, portal hypertension is uncommon after liver transplantation, and when it occurs, it has been related to hepatic vein outflow obstruction, small liver donor size, rejection, or recurrence of the original dis...

  2. Transjugular Intrahepatic Portosystemic Shunt (TIPS) Migration to the Heart Diagnosed by Emergency Department Ultrasound

    OpenAIRE

    Wendler, Carlan; Shoenberger, Jan Marie; Mailhot, Thomas; Perera, Phillips

    2012-01-01

    A 57-year-old man presented to our emergency department with altered mental status. He had a past medical history significant for cirrhosis and previous placement of a transjugular intrahepatic portosystemic shunt (TIPS). On cardiac auscultation, a new heart murmur and an unexpected degree of cardiac ectopy were noted. On the 12-lead electrocardiogram, the patient was noted to have multiple premature atrial contractions, corroborating the irregular heart rhythm on physicalexam. A focused beds...

  3. Endoscopic stenting for hilar cholangiocarcinoma: efficacy of unilateral and bilateral placement of plastic and metal stents in a retrospective review of 480 patients

    OpenAIRE

    Liberato Manuel José; Canena Jorge Manuel

    2012-01-01

    Abstract Background Endoscopic biliary drainage of hilar cholangiocarcinoma is controversial with respect to the optimal types of stents and the extent of drainage. This study evaluated endoscopic palliation in patients with hilar cholangiocarcinoma using self-expandable metallic stents (SEMS) and plastic stents (PS).We also compared unilateral and bilateral stent placement according to the Bismuth classification. Methods Data on 480 patients receiving endoscopic biliary drainage for hilar ch...

  4. Measurement of serum carcinoembryonic antigen, carbohydrate antigen 19-9, cytokeratin-19 fragment and matrix metalloproteinase-7 for detecting cholangiocarcinoma: a preliminary case-control study.

    Science.gov (United States)

    Lumachi, Franco; Lo Re, Giovanni; Tozzoli, Renato; D'Aurizio, Federica; Facomer, Flavio; Chiara, Giordano B; Basso, Stefano M M

    2014-11-01

    Cholangiocarcinoma is a malignant tumor of the liver arising from the bile duct epithelium, accounting for 10-25% of all primary hepatic cancers. The clinical presentation of this tumor is not specific and the diagnosis of early cholangiocarcinoma is difficult, especially in patients with other biliary diseases. Measurement of serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) are commonly used to monitor response to therapy, but are also useful for confirming the presence of a cholangiocarcinoma. In this setting, other biomarkers have been previously tested, including cytokeratin-19 fragment (CYFRA 21-1) and the matrix metalloproteinase-7 (MMP7). The purpose of this retrospective study was to determine the clinical usefulness of the assay of serum CEA, CA 19-9, CYFRA 21-1 and MMP7, individually and together, as tumor markers for the diagnosis of cholangiocarcinoma. Twenty-four patients (14 men, 10 women, 62.6±8.2 years of age) with histologically-confirmed cholangiocarcinoma (cases) and 25 age- and sex-matched patients with benign liver disease (controls) underwent measurement of these biomarkers. The mean values of all serum markers of patients with cholangiocarcinoma were significantly higher (pCYFRA 21-1: 76%, 79% and 78%; MMP7: 78%, 77% and 80%, respectively. The combination of all serum markers afforded 92.0% sensitivity and 96% specificity in detecting cholangiocarcinoma, showing the highest diagnostic accuracy (94%). In conclusion, our preliminary results suggest that the measurement of all four biomarkers together can help in the early detection of cholangiocarcinoma. PMID:25368272

  5. Intraductal radiofrequency ablation of tumour ingrowth into an uncovered metal stent used for inoperable cholangiocarcinoma.

    Science.gov (United States)

    Lui, K L; Li, K K

    2013-12-01

    A 91-year-old woman diagnosed to have an inoperable cholangiocarcinoma had an uncovered metal stent inserted for palliative drainage. About 1.5 years later, tumour ingrowth into the metal stent caused cholangitis. Intraductal radiofrequency ablation was applied to create local coagulative tumour necrosis and the necrotic tissue was removed via a balloon catheter. A plastic stent was inserted to empirically treat any ensuing potential bile duct injury. The patient was discharged without complication with good palliative drainage. Intraductal radiofrequency ablation is a new technique for the treatment of metal stent occlusion due to tumour ingrowths. This is the first case report of this relatively safe and feasible new technique for the treatment of tumour ingrowth into a metal stent used as palliation for malignant biliary obstruction. PMID:24310661

  6. Duodenoportal fistula caused by peptic ulcer after extended right hepatectomy for hilar cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Uchiyama Kazuhisa

    2006-11-01

    Full Text Available Abstract Background A fistula between the duodenum and the main portal vein near a peptic ulcer is extremely rare, and only two cases of duodenal ulcers have been reported in the past. Case presentation We report a 68-year-old man with a diagnosis of anemia who had a history of extended right hepatectomy for hilar cholangiocarcinoma 20 months previously. The first endoscopic examination revealed a giant peptic ulcer with active bleeding at the posterior wall of the duodenal bulbs, and hemostasis was performed. Endoscopic treatment and transarterial embolization were performed repeatedly because of uncontrollable bleeding from the duodenal ulcer. Nevertheless, he died of sudden massive hematemesis on the 20th hospital day. At autopsy, communication with the main portal vein and duodenal ulcer was observed. Conclusion It should be borne in mind that the main portal vein is exposed at the front of the hepatoduodenal ligament in cases with previous extrahepatic bile duct resection.

  7. Management of hilar cholangiocarcinoma in the North of England: Pathology, treatment, and outcome

    Institute of Scientific and Technical Information of China (English)

    SD Mansfield; O Barakat; RM Charnley; BC Jaques; CB O'Suilleabhain; PJ Atherton; D Manas

    2005-01-01

    AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center.METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed.RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these,36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively.The 5-year survival rate was 4.2% for all patients, 21%for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P<0.05).Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions.CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality.Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.

  8. Triptolide induces apoptotic cell death of human cholangiocarcinoma cells through inhibition of myeloid cell leukemia-1

    International Nuclear Information System (INIS)

    Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant to current chemotherapies. CCA cells frequently overexpress the antiapoptotic protein myeloid cell leukemia-1(Mcl-1), which is responsible for its extraordinary ability to evade cell death. Triptolide, a bioactive ingredient extracted from Chinese medicinal plant, has been shown to inhibit cell proliferation and induce apoptosis in several cancers. CCK-8 assay was performed to detect cell survival rate in vitro. DAPI staining and Flow cytometry were used to analyze apoptosis. Western blot was performed to determine the expression levels of caspase-3, caspase-7, caspase-9, PARP, and Mcl-1. Quantitative real-time PCR and immunofluorescence were used to detect the expression levels of Mcl-1. The nude mice xenograft model was used to evaluate the antitumor effect of triptolide in vivo. Triptolide reduced cell viability in cholangiocarcinoma cell lines in a dose- and time-dependent manner, with IC50 values of 12.6 ± 0.6 nM, 20.5 ± 4.2 nM, and 18.5 ± 0.7 nM at 48 h for HuCCT1, QBC939, and FRH0201 respectively. Triptolide induced apoptosis in CCA cell lines in part through mitochondrial pathway. Using quantitative real-time PCR, western blot and immunofluorescence, we have shown that triptolide downregulates Mcl-1 mRNA and protein levels. Furthermore, triptolide inhibited the CCA growth in vivo. Triptolide has profound antitumor effect on CCA, probably by inducing apoptosis through inhibition of Mcl-1. Triptolide would be a promising therapeutic agent for CCA

  9. A combination of liver fluke infection and traditional northeastern Thai foods associated with cholangiocarcinoma development.

    Science.gov (United States)

    Sriraj, Pranee; Boonmars, Thidarut; Aukkanimart, Ratchadawan; Songsri, Jiraporn; Sripan, Panupan; Ratanasuwan, Panaratana; Boonjaraspinyo, Sirintip; Wongchalee, Nadchanan; Laummaunwai, Porntip

    2016-10-01

    Opisthorchis viverrini infection is one of the risk factors for cholangiocarcinoma (CCA) in northeast Thailand, a region with one of the highest reported incidence rates of CCA. The traditional practice of eating raw fish, repeated exposure to liver flukes, and consumption of nitrosamine-contaminated food are major risk factors for CCA. So far, there have been no reports about which northeastern traditional dishes may be involved in CCA development. The present study, thus, investigated the effects of traditional foods. It focused specifically on the consumption of fermented foods in combination with O. viverrini infection in hamsters. Syrian hamsters were divided into six groups: (i) normal hamsters, (ii) O. viverrini infection only and (iii)-(vi) O. viverrini infection plus fermented foods (pla som-fish fermented for 1 day), som wua-fermented beef, som phag-fermented vegetables, and pla ra-fish fermented for 6 months. Syrian hamster livers were used for analysis of histopathological changes through hematoxylin and eosin; Sirius Red; and immunohistostaining for cytokeratin-19, proliferating cell nuclear antigen, and CA19-9. Hamster sera were used for liver and kidney function tests. Results of all O. viverrini-infected groups and fermented food groups showed that histopathological changes consisted primarily of aggregations of inflammatory cells surrounding the hepatic bile duct, especially at the hilar region. However, there was a difference in virulence. Interestingly, aggregations of inflammatory cells, new bile duct formation, and fibrosis were observed in subcapsular hepatic tissue, which correlated to positive immunohistochemical staining and increased liver function test. The present study suggests that fermented food consumption can exacerbate cholangitis and cholangiofibrosis, which are risk factors for cholangiocarcinoma-associated opisthorchiasis. PMID:27271702

  10. EFFECTS OF CYCLOOXYGENASE-2 ANTISENSE VECTOR ON PROLIFERATION OF HUMAN CHOLANGIOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    Gao-song Wu; Sheng-quan Zou; Xiao-yong Wu; Fa-zu Qiu

    2004-01-01

    Objective To transfect antisense vector of human cyclooxygenase-2 (COX-2) gene into COX-2 highly expressing cholangiocarcinoma cell line QBC939 and explore its biological activities and role in carcinogenesis.Methods QBC939 cells were transfected with antisense vector of human COX-2 gene using LipoVecTM transfecting technique. Transfected cells were selected with G418; COX-2 mRNA was examined using reverse transcription polymerase chain reaction (RT-PCR) and COX-2 protein expression was detected by immunocytochemistry using isozyme selective antibodies. The proliferative status of transfected cells was measured by using methabenzthiazuron (MTT) assay; Cell cycle and apoptosis were analyzed by using flow cytometry.Results RT-PCR showed a lower COX-2 mRNA level in antisense vector transfected cells and immunocytochemistry showed a weaker COX-2 protein expression in antisense vector transfected cells. The antisense vector transfected cells proliferative index decreased significantly (P< 0.01), the percentage of S phase decreased remarkably (P< 0.05) in antisense vector transfected cells (9.27% ± 1.91%) compared with that in QBC939 cells without transfection(16.35% ± 2.87%), and the percentage of G0/G 1 phase increased remarkably (P < 0.05) in antisense vector transfected cells (75.16%±4.13%) compared with that in QBC939 cells without transfection (57.31%± 10.16%). Transfection with antisense vector of human COX-2 gene had no significant influence on the apoptosis in QBC939 cells (P > 0.05).Conclusion Transfection with antisense vector of human COX-2 gene could inhibit the proliferation of human cholangiocarcinoma QBC939 cells.

  11. EGFR, FLT1 and heparanase as markers identifying patients at risk of short survival in cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Andreas-Claudius Hoffmann

    Full Text Available BACKGROUND: Cholangiocarcinoma remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of fms-related tyrosine kinase 1/vascular endothelial growth factor receptor 1 (FLT1/VEGFR1, heparanase (HPSE and epidermal growth factor receptor (EGFR gene expression in patients with resected CCC. METHODS: 47 formalin-fixed paraffin embedded FFPE tumor samples from patients with resected CCC were analyzed. FFPE tissues were dissected using laser-captured microdissection and analyzed for FLT1, FLT4, HPSE, Hif1a, VEGFA/C, HB-EGF, PDGFA, PDGF-RA and EGFR mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels are expressed as ratios between the target gene and internal reference genes (beta-actin, b2mg, rplp2, sdha. RESULTS: EGFR, FLT1 and HPSE expression levels were significantly associated with overall survival (OS. FLT1 showed the strongest significant independent association with overall survival in a multivariate cox regression analysis when compared to the other genes and clinicopathological factors with a nearly 5 times higher relative risk (4.74 of dying earlier when expressed in low levels (p = 0.04. ROC Curve Analysis revealed that measuring EGFR potentially identifies patients at risk of a worsened outcome with a sensitivity of 80% and a specificity of 75% (p = 0.01. CONCLUSIONS: EGFR and FLT1 seem to be potential markers to identify those patients at high risk of dying from cholangiocarcinoma. Therefore these markers may help to identify patient subgroups in need for a more aggressive approach in a disease that is in desperate need for new approaches.

  12. Duration of Inflammatory Bowel Disease Is Associated With Increased Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis and IBD

    Science.gov (United States)

    Gulamhusein, Aliya F.; Eaton, John E.; Tabibian, James H.; Atkinson, Elizabeth J.; Juran, Brian D.; Lazaridis, Konstantinos N.

    2016-01-01

    OBJECTIVES Primary sclerosing cholangitis (PSC) often coexists with inflammatory bowel disease (IBD) and can be complicated by cholangiocarcinoma (CCA), a lethal malignancy for which reliable predictors remain unknown. We aimed to characterize the influence of colectomy and IBD duration on risk of CCA in patients with PSC-IBD. METHODS A retrospective review of patients with PSC-IBD seen at the Mayo Clinic, Rochester, between January 2005 and May 2013 was performed. The primary outcome was time to development of CCA and our goal was to determine whether the risk differed between patients with and without colectomy. Risk factors were assessed using univariable and multivariable Cox proportional hazard models where colectomy, IBD disease duration, and development of advanced liver disease were treated as time-dependent covariates. RESULTS A total of 399 patients with PSC-IBD were included in the study, of whom 137 had a colectomy and 123 patients developed CCA. Age-adjusted univariate Cox proportional hazard models demonstrated that colectomy (hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.05–2.22, P =0.02) and duration of IBD (HR 1.37, 95% CI 1.15–1.63, P <0.01) were associated with an increased risk of CCA, and colonic neoplasia (HR 1.52, 95% CI 0.97–2.37, P =0.06) and colectomy for colonic neoplasia (HR 1.62, 95% CI 1.01–2.61, P =0.05) approached significance. Among patients with a history of colectomy, colonic neoplasia as the indication for surgery was associated with a particularly increased risk of CCA (HR 2.91, 95% CI 1.24–6.84, P =0.01) compared with medically refractory disease. On multivariate analysis, duration of IBD remained significantly associated with CCA (HR 1.33, 95% CI 1.11–1.60, P <0.01). The influence of IBD duration on CCA risk was not modified after colectomy (P =0.69). CONCLUSIONS Prolonged duration of IBD is associated with an increased risk of CCA in patients with PSC-IBD, and colectomy itself does not modify this risk

  13. Sodium Iodide Symporter and Phosphatase and Tensin Homolog Deleted on Chromosome Ten Expression in Cholangiocarcinoma Analysis with Clinicopathological Parameters

    OpenAIRE

    Han, Sang Young; Lee, Sung Wook; Baek, Yang Hyun; Kim, Ha Yoen; Kim, Jong Han; Jeong, Jin Sook; Roh, Young Hoon; Kim, Young Hoon; Park, Byung Ho; Kwon, Hee Jin; Cho, Jin Han; Nam, Kyung Jin

    2012-01-01

    Background/Aims This study was performed to investigate the correlation of sodium iodide symporter (NIS) expression with the functionality and loss of phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression in human cholangiocarcinoma (CCA). Methods Immunohistochemistry for the expression of NIS and PTEN was performed in 60 biopsy specimens of CCA. The clinicopathological parameters were retrospectively identified from medical records. The expression pattern of NIS and loss...

  14. Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Viola Baradari; Michael H(o)pfner; Alexander Huether; Detlef Schuppan; Hans Scherübl

    2007-01-01

    AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin)or the novel anticancer agents sorafenib or bortezomib.METHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes.Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH).Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry.RESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275-induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G1/S checkpoint, which was associated with induction of the cyclin-dependent kinase inhibitor p21Waf/CIP1. Furthermore,additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multikinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects.CONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new,targeted anticancer agents.

  15. Scabraside D Extracted from Holothuria scabra Induces Apoptosis and Inhibits Growth of Human Cholangiocarcinoma Xenografts in Mice.

    Science.gov (United States)

    Assawasuparerk, Kanjana; Vanichviriyakit, Rapeepun; Chotwiwatthanakun, Charoonroj; Nobsathian, Saksit; Rawangchue, Thanakorn; Wittayachumnankul, Boonsirm

    2016-01-01

    Scabraside D, a sulfated triterpene glycoside extract from sea cucumber Holothulia scabra, shows various biological activities, but effects on human cholangiocarcinoma cells have not previously been reported. In the present study, we investigated the activity of scabraside D against human cholangiocarcinoma (HuCCA) both in vitro and for tumor growth inhibition in vivo using a xenograft model in nude mice. Scabraside D (12.5-100 μg/mL) significantly decreased the viability and the migration of the HuCCA cells in a dose-dependent manner, with 50% inhibitory concentration (IC50) of 12.8 ± 0.05 μg/mL at 24 h. It induced signs of apoptotic cells, including shrinkage, pyknosis and karyorrhetic nuclei and DNA fragmentation on agarose gel electrophoresis. Moreover, by quantitative real-time PCR, scabraside D effectively decreased Bcl-2 while increasing Bax and Caspase-3 gene expression levels suggesting that the scabraside D could induce apoptosis in HuCCA cells. In vivo study demonstrated that scabraside D (1 mg/kg/day, i.p. for 21 days) significantly reduced growth of the HuCCA xenografts without adverse effects on the nude mice. Conclusively, scabraside D induced apoptosis in HuCCA cells and reduced the growth of HuCCA xenographs model. Therefore, scabraside D may have potential as a new therapeutic agent for cholangiocarcinoma. PMID:26925636

  16. Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients

    DEFF Research Database (Denmark)

    Grunnet, M; Christensen, I J; Lassen, U;

    2014-01-01

    determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. DESIGN AND METHODS: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n=108). A test set......PAR(I-III)+uPAR(II-III) after 2cycles of chemotherapy was associated with poor survival (HR=1.79, 95% CI:1.08-2.97, p=0.023, n=57). This predictor, however, was not significant in the test set (p=0.21, 26 events in 27 patients). CONCLUSION: The baseline level of uPAR(I-III)+uPAR(II-III) is a predictor of survival in inoperable......BACKGROUND: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to...

  17. Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-sun [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine (Korea, Republic of); Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of); Rhim, Hyunchul [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine (Korea, Republic of) and Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of)]. E-mail: forest@smc.samsung.co.kr; Cho, On Koo [Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of); Koh, Byung Hee [Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of); Kim, Yongsoo [Department of Diagnostic Radiology, Hanyang University College of Medicine (Korea, Republic of)

    2006-09-15

    Purpose: To evaluate the pattern and risks for intrahepatic recurrence after percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC). Materials and methods: We studied 62 patients with 72 HCCs ({<=}4 cm) who were treated with percutaneous RF ablation. The mean follow-up period was 19.1 months (6.0-49.1). We assessed the incidence and cumulative disease-free survival of local tumor progression (LTP) and intrahepatic distant recurrence (IDR). To analyze the risk factors, we examined the following, for the LTP: (1) tumor diameter, (2) contact with vessels, (3) degree of approximation to hepatic hilum, (4) contact with hepatic capsule, (5) presence of ablative safety margin, (6) degree of benign periablational enhancement and (7) serum alpha-fetoprotein; for the IDR: (1) severity of hepatic disease, (2) presence of HBsAg, (3) serum alpha-fetoprotein, (4) whether RF ablation was the initial treatment and (5) multiplicity of tumor for IDR. Results: The incidence of overall recurrence, LTP and IDR was 62.9%, 26.4% and 53.2%, respectively. The cumulative disease-free survival rates were 52%, 82% and 56% at 1 year, 26%, 63% and 30% at 2 years, respectively. Univariate analysis showed that the significant risk factors for LTP were: a tumor with a diameter >3 cm, contact of HCC with a vessel and an insufficient safety margin (p < 0.05). A multivariate stepwise Cox hazard model showed that the measurement of a tumor diameter >3 cm and insufficient safety margin were independent factors. Only the increased serum alpha-fetoprotein was a significant risk factor for IDR (p < 0.05). Conclusion: Intrahepatic recurrence after percutaneous RF ablation is common. Large HCC (>3 cm) with high serum alpha-fetoprotein should be treated more aggressively because of higher risk for recurrence.

  18. Surgical management of intrahepatic vessels in children with stage Ⅲ/Ⅳ hepatoblastoma

    Institute of Scientific and Technical Information of China (English)

    PANG Yan-li; ZHAO Wei; YANG He-ying; LIU Qiu-liang; ZHANG Da; QIN Pan; YUE Ming

    2013-01-01

    Background Hepatoblastoma (HB) is a rare childhood tumor.We investigated the effect of intraoperative management of the intrahepatic major vessels in children with HB.Methods Between April 2005 and August 2012,surgical resection was performed on 50 children with hepatoblastoma.These children were divided into a vessel-ligation group (n=20) and a vessel-repair group (n=30).In the vessel-ligation group,the intrahepatic major vessels were ligated and removed together with the tumor and the affected liver lobe/liver parenchyma.In the vessel-repair group,the affected intrahepatic major vessels were dissected and preserved as much as possible and the normal liver lobe/liver parenchyma and blood supply from these vessels were also preserved.The outcomes were analyzed by postoperative follow-up.Results In the vessel-ligation group,two patients gave up surgery,six patients underwent palliative resection,and 12 patients underwent en b/oc resection; four patients died of liver failure and eight patients fully recovered and were discharged.In the vessel-repair group,all 30 patients underwent en b/oc resection and were discharged after satisfactory healing.After a follow-up time of 5-36 months (median:20 months),two patient in the vessel-ligation group survived and 22 patients in the vessel-repair group survived.Conclusions Patients with HB can be successfully treated by tumor resection with vascular repair.This method prevents postoperative liver failure,ensures Patient safetv during the perioperative period,and allows for early chemotherapy.

  19. Intrahepatic Left to Right Portoportal Venous Collateral Vascular Formation in Patients Undergoing Right Portal Vein Ligation

    Energy Technology Data Exchange (ETDEWEB)

    Lienden, K. P. van, E-mail: k.p.vanlienden@amc.uva.nl [Academic Medical Center, University of Amsterdam, Department of Interventional Radiology (Netherlands); Hoekstra, L. T. [Academic Medical Center, University of Amsterdam, Department of Surgery (Netherlands); Bennink, R. J. [Academic Medical Center, University of Amsterdam, Department of Nuclear Medicine (Netherlands); Gulik, T. M. van [Academic Medical Center, University of Amsterdam, Department of Surgery (Netherlands)

    2013-12-15

    Purpose: We investigated intrahepatic vascular changes in patients undergoing right portal vein ligation (PVL) or portal vein embolization (PVE) in conjunction with the ensuing hypertrophic response and function of the left liver lobe. Methods: Between December 2008 and October 2011, 7 patients underwent right PVL and 14 patients PVE. Computed tomographic (CT) volumetry to assess future remnant liver (FRL) and functional hepatobiliary scintigraphy were performed in all patients before and 3 weeks after portal vein occlusion. In 18 patients an intraoperative portography was performed to assess perfusion through the occluded portal branches. Results: In all patients after initially successful PVL, reperfused portal veins were observed on CT scan 3 weeks after portal occlusion. This was confirmed in all cases during intraoperative portography. Intrahepatic portoportal collaterals were identified in all patients in the PVL group and in one patient in the PVE group. In all other PVE patients, complete occlusion of the embolized portal branches was observed on CT scan and on intraoperative portography. The median increase of FRL volume after PVE was 41.6 % (range 10-305 %), and after PVL was only 8.1 % (range 0-102 %) (p = 0.179). There were no differences in FRL function between both groups. Conclusion: Preoperative PVE and PVL are both methods to induce hypertrophy of the FRL in anticipation of major liver resection. Compared to PVE, PVL seems less efficient in inducing hypertrophy of the nonoccluded left lobe. This could be caused by the formation of intrahepatic portoportal neocollateral vessels, through which the ligated portal branches are reperfused within 3 weeks.

  20. Anabolic Androgen-induced Intrahepatic Cholestasis Presented With Normal AND#947;-Glutamyl-Transpeptidase

    Directory of Open Access Journals (Sweden)

    Savvoula Savvidou

    2014-04-01

    A case report of a young male with remarkable jaundice due to acute anabolic androgen-induced cholestasis is presented. Interestingly, and #947;-glutamyl transpeptidase remained normal throughout the patient's diagnostic workup. Histopathology was indicative of pure, and ldquo;bland and rdquo; intrahepatic cholestasis with minimal inflammation but significant fibrosis. The patient was successfully treated with ursodeoxycholic acid and glucocorticosteroids. The significance of normal and #947;-glutamyl transpeptidase along with the histopathological findings and the possible pathophysiological mechanisms are finally discussed. [J Interdiscipl Histopathol 2014; 2(2.000: 98-103

  1. Liver resection for the treatment of a congenital intrahepatic portosystemic venous shunt

    Institute of Scientific and Technical Information of China (English)

    Michail Papamichail; Amir Ali; Alberto Quaglia; John Karani; Nigel Heaton

    2016-01-01

    Intrahepatic portosystemic shunts (IPSS) are rare congenital anomalies arising from disordered portal vein em-bryogenesis. It has been described in both children and adults and may be asymptomatic or be associated with a variety of neurophysiological and pulmonary complications. When rec-ognized, early intervention to occlude the shunt will reverse the associated complications. Literature review reports of surgical and radiological occlusion of the shunt, but due to its rarity, a standard therapeutic protocol has not been established. A case of a 38-year-old woman with abdominal pain and low grade encephalopathy, diagnosed with an IPSS and treated by right hepatectomy was reported.

  2. Body composition changes after transjugular intrahepatic portosystemic shunt in patients with cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Jonathan; Montomoli; Peter; Holland-Fischer; Giampaolo; Bianchi; Henning; GrФnbk; Hendrik; Vilstrup; Giulio; Marchesini; Marco; Zoli

    2010-01-01

    AIM:To investigate the effect of transjugular intra-hepatic porto-systemic shunt (TIPS) on malnutrition in portal hypertensive cirrhotic patients.METHODS: Twenty-one patients with liver cirrhosis and clinical indications for TIPS insertion were investigated before and 1, 4, 12, 52 wk after TIPS. For each patient we assayed body composition parameters [dry lean mass, fat mass, total body water (TBW)], routine liver and kidney function tests, and free fatty acids (FFA). Glucose and insulin were measured for t...

  3. Pancreaticoportal Fistula and Disseminated Fat Necrosis After Revision of a Transjugular Intrahepatic Portosystemic Shunt

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Seth J., E-mail: kleins@mir.wustl.edu; Saad, Nael [Washington University School of Medicine, Interventional Radiology Section, Mallinckrodt Institute of Radiology (United States); Korenblat, Kevin [Washington University School of Medicine, Division of Gastroenterology, Department of Internal Medicine (United States); Darcy, Michael D. [Washington University School of Medicine, Interventional Radiology Section, Mallinckrodt Institute of Radiology (United States)

    2013-04-15

    A 59-year old man with alcohol related cirrhosis and portal hypertension was referred for transjugular intrahepatic portosystemic shunt (TIPS) to treat his refractory ascites. Ten years later, two sequential TIPS revisions were performed for shunt stenosis and recurrent ascites. After these revisions, he returned with increased serum pancreatic enzyme levels and disseminated superficial fat necrosis; an iatrogenic pancreaticoportal vein fistula caused by disruption of the pancreatic duct was suspected. The bare area of the TIPS was subsequently lined with a covered stent-graft, and serum enzyme levels returned to baseline. In the interval follow-up period, the patient has clinically improved.

  4. Liver resection for the treatment of a congenital intrahepatic portosystemic venous shunt

    Institute of Scientific and Technical Information of China (English)

    Michail Papamichail; Amir Ali; Alberto Quaglia; John Karani; Nigel Heaton

    2015-01-01

    Intrahepatic portosystemic shunts (IPSS) are rare congenital anomalies arising from disordered portal vein em-bryogenesis. It has been described in both children and adults and may be asymptomatic or be associated with a variety of neurophysiological and pulmonary complications. When rec-ognized, early intervention to occlude the shunt will reverse the associated complications. Literature review reports of surgical and radiological occlusion of the shunt, but due to its rarity, a standard therapeutic protocol has not been established. A case of a 38-year-old woman with abdominal pain and low grade encephalopathy, diagnosed with an IPSS and treated by right hepatectomy was reported.

  5. Technical note: Reduction of radiation dose using ultrasound guidance during transjugular intrahepatic portosystemic shunt procedure

    International Nuclear Information System (INIS)

    The transjugular intrahepatic portosystemic shunt (TIPS) procedure for decompression of the portal venous system generally performed under fluoroscopic guidance has undergone continuous technical modifications recently. Due to the length of the procedure, the fluoroscopy times are reasonably high, thus increasing the risk from ionizing radiation. Radiation doses were measured for 19 patients using dose area product (DAP) meter. The average DAP value for the TIPS procedure was 63.86 Gy cm2 (21.12-117.07). Radiation doses to patients can be reduced with the use of USG guidance and intermittent fluoroscopy screening

  6. RE: Endovascular Treatment of Congenital Intrahepatic Portosystemic Shunts with Amplatzer Plugs

    Energy Technology Data Exchange (ETDEWEB)

    Sierre, Sergio; Alonso, Jose; Lipsich, Jose [Hospital Nacional de Pediatria ' JP Garrahan' , Combate de los Pozos, Buenos (Argentina)

    2012-01-15

    In our paper entitled 'Endovascular treatment of congenital portal vein fistulas with the Amplatzer occlusion device' published in the Journal of Vascular and Interventional Radiology in 2004, we already reported the use of the AVP in the treatment of an intrahepatic portosystemic venous shunt. This situation does not undervalue the quality of the reported case, but for didactic purposes, we believe it is important to state that the work of Dr. Lee confirms, as was previously reported, that these devices are useful and safe for these rare situations.

  7. Imaging Findings of Intrahepatic Bile Duct Adenoma (Peribiliary Gland Hamartoma): a Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Kim, You Sung; Rha, Sung Eun; Oh, Soon Nam; Jung, Seung Eun; Shin, Yu Ri; Choi, Byung Gil; Byun, Jae Young; Jung, Eun Sun; Kim, Dong Goo [Catholic University of Korea, Seoul St.Mary' s Hospital, Seoul (Korea, Republic of)

    2010-10-15

    Intrahepatic bile duct adenoma is a rare benign epithelial hepatic tumor derived from bile duct cells. We report the imaging findings of a patient with bile duct adenoma, which appeared as a small heterogeneously enhancing mass with focal small cystic change on CT and MRI. Follow-up images at seven months showed a slight increase in tumor size, which could be partly explained by intratumoral hemorrhage on pathologic examination. Although rare, bile duct adenoma should be considered as a differential diagnosis of a small hypervascular tumor located in the periphery of liver. Focal cystic change and intratumoral hemorrhage may occur

  8. Diffusion weighted MRI in intrahepatic bile duct adenoma arising from the cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    An, Chansik [Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Sumi; Choi, Yoon Jung [National Health Insurance Corporation Ilsan Hospital, Goyang (Korea, Republic of)

    2013-10-15

    A 64-year-old male patient with liver cirrhosis underwent a CT study for hepatocellular carcinoma surveillance, which demonstrated a 1.4-cm hypervascular subcapsular tumor in the liver. On gadoxetic acid-enhanced MRI, the tumor showed brisk arterial enhancement and persistent hyperenhancement in the portal phase, but hypointensity in the hepatobiliary phase. On diffusion-weighted MRI, the tumor showed an apparent diffusion coefficient twofold greater than that of the background liver parenchyma, which suggested that the lesion was benign. The histologic diagnosis was intrahepatic bile duct adenoma with alcoholic liver cirrhosis.

  9. A novel ABCB11 mutation in an Iranian girl with progressive familial intrahepatic cholestasis

    Directory of Open Access Journals (Sweden)

    Sassan Saber

    2013-01-01

    Full Text Available Progressive familial intrahepatic cholestasis is an autosomal recessive liver disorder caused by (biallelic mutations in the ATP8B1 of ABCB11 gene. A nine-year-old girl with cholestasis was referred for genetic counseling. She had a family history of cholestasis in two previous expired siblings. Genetic analysis of the ABCB11 gene led to the identification of a novel homozygous mutation in exon 25. The mutation 3593- A > G lead to a missense mutation at the amino acid level (His1198Arg. This mutation caused PFIC2 due to abnormal function in the bile salt export pump protein (BSEP.

  10. Successful pregnancy after ileal exclusion in progressive familial intrahepatic cholestasis type 2.

    Science.gov (United States)

    Czubkowski, Piotr; Jankowska, Irena; Pawlowska, Joanna

    2015-01-01

    Progressive familial intrahepatic cholestasis type 2 (PFIC 2) results from mutations in ABCB11 gene coding bile salt export pump (BSEP). Medical treatment is usually unsuccessful and surgery intervention is necessary. Partial external biliary diversion (PEBD) is regarded as the first choice of surgical treatment. Ileal exclusion (IE) is an alternative operation if external stoma is not tolerated; however, a favorable outcome is uncertain. In chronic liver diseases pregnancy brings additional risk of deterioration of liver function and generally is not recommended. We present the first case report of successful pregnancy in a genetically confirmed PFIC 2 patient after surgical conversion from PEBD to IE. PMID:26019043

  11. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II

    OpenAIRE

    Wang, Lin; Soroka, Carol J.; Boyer, James L.

    2002-01-01

    PFIC II is a subtype of progressive familial intrahepatic cholestasis (PFIC) that is associated with mutations in the ABCB11 gene encoding the bile salt export pump (BSEP). However it is not known how these mutations cause this disease. To evaluate these mechanisms, we introduced seven PFIC II–associated missense mutations into rat Bsep and assessed their effects on Bsep membrane localization and transport function in MDCK and Sf9 cells, respectively. Five mutations, G238V, E297G, G982R, R115...

  12. Recanalization of an Occluded Intrahepatic Portosystemic Covered Stent via the Percutaneous Transhepatic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Chih Yang; Liang, Po Chin [National Taiwan University Hospital, Taipei (China)

    2010-08-15

    A 41-year-old woman with liver cirrhosis had recurrent portal hypertension and bleeding from esophageal varices due to complete occlusion of a previously inserted transjugular intrahepatic portosystemic shunt stent. Because recanalization of the stent by the transjugular approach was unsuccessful, ultrasound-guided entry to the splenic vein and portal vein was used. After catheter-directed intrathrombus thrombolysis, successful opening of the stent was achieved and a stent was placed. We herein report a rare case in which thrombolysis and recanalization of a TIPS stent were performed via a percutaneous transhepatic approach

  13. Current diagnosis and management of post-transjugular intrahepatic portosystemic shunt refractory hepatic encephalopathy.

    Science.gov (United States)

    Pereira, Keith; Carrion, Andres F; Martin, Paul; Vaheesan, Kirubahara; Salsamendi, Jason; Doshi, Mehul; Yrizarry, Jose M

    2015-12-01

    Transjugular intrahepatic portosystemic shunt has evolved into an important option for management of complications of portal hypertension. The use of polytetrafluoroethylene covered stents enhances shunt patency. Hepatic encephalopathy (HE) remains a significant problem after TIPS placement. The approach to management of patients with refractory hepatic encephalopathy typically requires collaboration between different specialties. Patient selection for TIPS requires careful evaluation of risk factors for HE. TIPS procedure-related technical factors like stent size, attention to portosystemic pressure gradient reduction and use of adjunctive variceal embolization maybe important. Conservative medical therapy in combination with endovascular therapies often results in resolution or substantial reduction of symptoms. Liver transplantation is, however, the ultimate treatment. PMID:26332169

  14. Most common SLC25A13 mutation in 400 Chinese infants with intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To establish the real time fluorescence polymerase chain reaction(RT-PCR) with dual labeled probes for fast detection of SLC25A13 gene mutation 851del4.METHODS:Four hundred infants(< 1 year of age) with unexplained intrahepatic cholestasis from 18 provinces or municipalities in China were enrolled in this study for detecting their SLC25A13 gene mutation 851del4.Suitable primers and fluorescence-labeled probes for detecting SLC25A13 gene mutation 841del4 were designed.Normal and mutant sequences were det...

  15. [Stevens-Johnson syndrome plus intrahepatic cholestasis caused by clindamycin or chlorpheniramine].

    Science.gov (United States)

    Sahagún Flores, J E; Soto Ortiz, J A; Tovar Méndez, C E; Cárdenas Ochoa, E C; Hernández Flores, G

    2009-05-15

    A 48-year-old woman was hospitalized with the diagnosis of hepatitis. She presented with symptoms of jaundice, headache, elevated bilirubin, and elevated hepatic enzymes. She related a recent episode of a bronchial infection that was treated during the previous eight days with paracetamol (500mg, 2 doses only), chlorpheniramine, betamethasone and clindamycin. After an initial clinical and laboratorial improvement, she began to complain of pruritus of the palms and soles. Thereafter, vesicles evolving to blisters developed and a deterioration of her general health ensued. Serologies for hepatitis A, B, and C viruses were negative. Intrahepatic cholestasis and Stevens Johnson Syndrome (SJS) were the final diagnosis. The association of the Stevens Johnson Syndrome and intrahepatic cholestasis simultaneously, related to adverse drug reactions, is very rare. The drugs reportedly involved are mainly antibiotics, such as ampicillin, vancomycin, amoxicillin/clavulinic acid and erythromycin. Other drugs involved are non-steroidal anti-inflamatory drugs, such as mefenamic acid, ibuprofen, and sulindac. The reactions can be minor or severe and can even cause death, an outcome that has been reported in patients of all races and ethnic groups, but appears to be more rare in patients of Latin origin. We present a discussion of this case and review the main characteristics of the Stevens Johnson Syndrome.

  16. Hepatobiliary scintigraphy in chronic intrahepatic cholestasis. Diagnosis of primary sclerosing cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Aburano, Tamio; Takayama, Teruhiko; Shuke, Noriyuki

    1987-05-01

    Primary sclerosing cholangitis (PSC) is a rare disease of unknown origin, leading to chronic intermittent cholestasis. Due to its low incidence, insidious clinical onset and varied clinical picture, the diagnosis is often delayed by years. PSC is sometimes diagnosed falsely as another disease of chronic intermittent cholestasis, primary biliary cirrhosis (PBC). In the present study, the hepatobiliary imaging with Tc-99m diethyl IDA was done in a total of 14 patients with chronic intermittent cholestasis including 3 patients with PSC and 11 patients with PBC, in order to decide its clinical usefulness as a noninvasive method for the differentiation between PSC and PBC. All three patients with PSC showed a typical pattern of radionuclide stasis within the area of intrahepatic and/or extrahepatic ductal system, representing the stenosis on endoscopic retrograde cholangiogram. On the other hand, none of 11 patients with PBC showed any radionuclide stasis within the area of intrahepatic and/or extrahepatic ductal system. This result suggests that the radionuclide hepatobiliary imaging may be a noninvasive method for investigating patients with chronic intermittent cholestasis, leading to earlier differentiation between PSC and PBC.

  17. Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients.

    Science.gov (United States)

    Tazawa, Yusaku; Kobayashi, Keiko; Abukawa, Daiki; Nagata, Ikuo; Maisawa, Shunichi; Sumazaki, Ryo; Iizuka, Toshiyuki; Hosoda, Yoshito; Okamoto, Manabu; Murakami, Jun; Kaji, Shunsaku; Tabata, Ayako; Lu, Yao Bang; Sakamoto, Osamu; Matsui, Akira; Kanzaki, Susumu; Takada, Goro; Saheki, Takeyori; Iinuma, Kazuie; Ohura, Toshihiro

    2004-11-01

    A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.

  18. Intrahepatic biliary cystic neoplasms: Surgical results of 9 patients and literature review

    Institute of Scientific and Technical Information of China (English)

    Ali Emre; Kür(s)at Rahmi Serin; (I)lgin (O)zden; Yaman Tekant; Orhan Bilge; Aydin Alper; Mine Güllüo(g)lu; Koray Güven

    2011-01-01

    AIM: To investigate the eligible management of the cystic neplasms of the liver.METHODS: The charts of 9 patients who underwent surgery for intrahepatic biliary cystic liver neoplasms between 2003 and 2008 were reviewed retrospectively. Informed consent was obtained from the patients and approval was obtained from the designated review board of the institution.RESULTS: All patients were female with a median(range) age of 49 (27-60 years). The most frequent symptom was abdominal pain in 6 of the patients. Four patients had undergone previous laparotomy (with otherdiagnoses) which resulted in incomplete surgery or recurrences. Liver resection (n=6) or enucleation (n=3) was performed. The final diagnosis was intrahepatic biliary cystadenoma in 8 patients and cystadenocarcinoma in 1 patient. All symptoms resolved after surgery.There has been no recurrence during a median (range)31 (7-72) mo of follow up.CONCLUSION: In spite of the improvement in imagingmodalities and increasing recognition of biliary cystadenoma and cystadenocarcinoma, accurate preoperative diagnosis may be difficult. Complete surgical removal(liver resection or enucleation) of these lesions yields satisfying long-term results.

  19. Intrahepatic natural killer T cell populations are increased in human hepatic steatosis

    Institute of Scientific and Technical Information of China (English)

    Michael Adler; Sarah Taylor; Kamalu Okebugwu; Herman Yee; Christine Fielding; George Fielding; Michael Poles

    2011-01-01

    AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease(NAFLD).METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during surgery.The biopsy was assessed for steatosis and immunocyte infiltration. Intrahepatic lymphocytes (IHLs) were isolated from the remainder of the liver biopsy,and peripheral blood mononuclear cells (PBMCs) were isolated from the blood. Expression of surface proteins on both IHLs and PBMCs were quantified using flow cytometry.RESULTS: Twenty-seven subjects participated in this study. Subjects with moderate or severe steatosis had a higher percentage of intrahepatic CD3+/CD56+ NKT cells (38.6%) than did patients with mild steatosis(24.1%, P = 0.05) or those without steatosis (21.5%, P= 0.03). Patients with moderate to severe steatosis alsohad a higher percentage of NKT cells in the blood (12.3%) as compared to patients with mild steatosis (2.5% P =0.02) and those without steatosis (5.1%, P = 0.05).CONCLUSION: NKT cells are significantly increased in the liver and blood of patients with moderate to severe steatosis and support the role of NKT cells in NAFLD.

  20. Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients with Cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keunyoung; Kim, Seongjang; Kim, Injoo; Kim, Dong Uk; Kim, Heeyoung; Kim, Sojung; Ahn, Sang Hyun [Pusan National Univ. Hospital, Busan (Korea, Republic of)

    2014-06-15

    Although diffuse splenic {sup 18}F-fluorodeoxyglucose (F-18 FDG) uptake exceeding hepatic activity, is considered abnormal, its clinical significance is rarely discussed in the literature. The aim of this study was to determine the contributing factors causing diffusely increased splenic FDG uptake in patients with cholangiocarcinoma. From January 2010 to March 2013, 140 patients (84 men, 56 women) were enrolled in this study. All patients had been diagnosed with cholangiocarcinoma and underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) for the pretreatment staging work up. Clinical records were reviewed retrospectively. Various hematological parameters, C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver function tests were conducted within 2 days after the F-18 FDG PET/CT study. Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19 patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP) 7 days before F-18 FDG PET/CT. The CRP level (p <0.001) and white blood cell count (p =0.023) were significantly higher in the group of patients with diffuse splenic FDG uptake. The hemoglobin (p <0.001) and the hematocrit (p <0.001) were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic enzymes, liver function test results, and tumor markers were not significantly different between the patients who did or did not have diffusely increased splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR, 1.211; 95% CI, 1.051-1.871). In conclusion, our study demonstrated that concurrent inflammation could be associated with diffusely increased splenic FDG uptake. We suggest that performing ERCP before F-18 FDG PET

  1. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

    Directory of Open Access Journals (Sweden)

    Plengsuriyakarn Tullayakorn

    2012-03-01

    Full Text Available Abstract Background Chemotherapy of cholangiocarcinoma (CCA, a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR, the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL, fruits of Piper chaba Hunt. (De-Plee: PC, and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively. PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL, analgesic (CUR and

  2. Dermatological Diseases Associated with Pregnancy: Pemphigoid Gestationis, Polymorphic Eruption of Pregnancy, Intrahepatic Cholestasis of Pregnancy, and Atopic Eruption of Pregnancy

    OpenAIRE

    Christine Sävervall; Freja Lærke Sand; Simon Francis Thomsen

    2015-01-01

    Dermatoses unique to pregnancy are important to recognize for the clinician as they carry considerable morbidity for pregnant mothers and in some instances constitute a risk to the fetus. These diseases include pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. This review discusses the pathogenesis, clinical importance, and management of the dermatoses of pregnancy.

  3. Rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases following combined loco-regional therapy

    International Nuclear Information System (INIS)

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  4. Rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases following combined loco-regional therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei [Dept. of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore (Singapore)

    2013-08-15

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  5. Rapid Intra-Hepatic Dissemination of Hepatocellular Carcinoma with Pulmonary Metastases Following Combined Loco-Regional Therapy

    OpenAIRE

    Pua, Uei

    2013-01-01

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  6. A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump

    NARCIS (Netherlands)

    Plass, JRM; Mol, O; Heegsma, J; Geuken, M; Elling, G; Muller, M; Faber, KN; Jansen, PLM

    2004-01-01

    Background Aims: Progressive familial intrahepatic cholestasis type 2 (PFIC-2) patients have a defect in the hepatocanalicular bile salt secretion. The disease is caused by mutations in the bile salt export pump (BSEP). Ten different missense mutations have been described. In this study, we analysed

  7. Endoscopic variceal ligation plus propranolol vs. transjugular intrahepatic portosystemic stent shunt : A long-term randomized trial

    NARCIS (Netherlands)

    Sauer, P; Hansmann, J; Richter, GM; Stremmel, W; Stiehl, A

    2002-01-01

    Background and Study Aims: After a first variceal bleeding episode in patients with cirrhosis of the liver, treatment with transjugular intrahepatic portosystemic stent shunt (TIPS) and endoscopic variceal ligation (EVL) plus propranolol were compared, with regard to prevention of variceal rebleedin

  8. Determining the effect of transforming growth factor-β1 on cdk4 and p27 in gastric cancer and cholangiocarcinoma

    Science.gov (United States)

    LEE, SUNG RYOL; SHIN, JAE WOOK; KIM, HYUNG OOK; SON, BYUNG HO; YOO, CHANG HAK; SHIN, JUN HO

    2013-01-01

    Gastric cancer and cholangiocarcinoma are problematic throughout the world due to their destructive malignancy. In attempts to treat cholangiocarcinoma and gastric cancer, researchers often explore the effects of transforming growth factor-β1 (TGF-β1). TGF-β1 plays a crucial role in causing cell cycle arrest and fibrosis in cancer cells. The present study aimed to identify whether TGF-β1 is capable of functioning as an antitumor agent in two cancer cell lines; cholangiocarcinoma and gastric cancer. The downregulation of cyclin dependent kinase (cdk) 4 and the upregulation of p27 were investigated, in order to identify possible antitumor functions of TGF-β1. A number of different methods were implemented, including cell proliferation assay, bicinchoninic acid (BCA) assay and western blot analysis with TGF-β1, AGS (human gastric cancer cell line) and SUN-1196 (human cholangiocarcinoma cell line). In the AGS study, cdk4 values decreased from 1.000 to 0.670 and then to 0.664, with increasing TGF-β1 concentrations of 0, 0.5 and 5 ng/ml, respectively. By contrast, p27 values increased from 1.000 to 1.391 and then to 1.505, with increasing TGF-β1 concentrations of 0, 0.5 and 5 ng/ml, respectively. In the SUN-1196 study, p27 values increased from 0.548 to 0.807 and then to 0.844 with increasing TGF-β1 concentrations of 5, 25 and 50 ng/ml, respectively. Certain concentrations of TGF-β1 play antitumor roles in gastric cancer through the down-regulation of cdk4 and upregulation of p27. Certain TGF-β1 concentrations also have antitumor roles in cholangiocarcinoma through the upregulation of p27. With these results, we came a step closer to finding a cure for cholangiocarcinoma and gastric cancer. PMID:23420090

  9. Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines.

    Science.gov (United States)

    Müller, Alena; Barat, Samarpita; Chen, Xi; Bui, Khac Cuong; Bozko, Przemyslaw; Malek, Nisar P; Plentz, Ruben R

    2016-05-01

    Cholangiocarcinoma (CC) worldwide is the most common biliary malignancy with poor prognostic value and new systemic treatments are desirable. Plant extracts like bromelain and papain, which are cysteine proteases from the fruit pineapple and papaya, are known to have antitumor activities. Therefore, in this study for the first time we investigated the anticancer effect of bromelain and papain in intra- and extrahepatic human CC cell lines. The effect of bromelain and papain on human CC cell growth, migration, invasion and epithelial plasticity was analyzed using cell proliferation, wound healing, invasion and apoptosis assay, as well as western blotting. Bromelain and papain lead to a decrease in the proliferation, invasion and migration of CC cells. Both plant extracts inhibited NFκB/AMPK signalling as well as their downstream signalling proteins such as p-AKT, p-ERK, p-Stat3. Additionally, MMP9 and other epithelial-mesenchymal-transition markers were partially found to be downregulated. Apoptosis was induced after bromelain and papain treatment. Interestingly, bromelain showed an overall more effective inhibition of CC as compared to papain. siRNA mediated silencing of NFκB on CC cells indicated that bromelain and papain have cytotoxic effects on human CC cell lines and bromelain and partially papain in comparison impair tumor growth by NFκB/AMPK signalling. Especially bromelain can evolve as promising, potential therapeutic option that might open new insights for the treatment of human CC. PMID:26935541

  10. Genetic Abnormalities in Biliary Brush Samples for Distinguishing Cholangiocarcinoma from Benign Strictures in Primary Sclerosing Cholangitis

    Science.gov (United States)

    Timmer, Margriet R.; Lau, Chiu T.; Meijer, Sybren L.; Fockens, Paul; Rauws, Erik A. J.; Ponsioen, Cyriel Y.; Calpe, Silvia; Krishnadath, Kausilia K.

    2016-01-01

    Background. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and is strongly associated with cholangiocarcinoma (CCA). The lack of efficient diagnostic methods for CCA is a major problem. Testing for genetic abnormalities may increase the diagnostic value of cytology. Methods. We assessed genetic abnormalities for CDKN2A, TP53, ERBB2, 20q, MYC, and chromosomes 7 and 17 and measures of genetic clonal diversity in brush samples from 29 PSC patients with benign biliary strictures and 12 patients with sporadic CCA or PSC-associated CCA. Diagnostic performance of cytology alone and in combination with genetic markers was evaluated by sensitivity, specificity, and area under the curve analysis. Results. The presence of MYC gain and CDKN2A loss as well as a higher clonal diversity was significantly associated with malignancy. MYC gain increased the sensitivity of cytology from 50% to 83%. However, the specificity decreased from 97% to 76%. The diagnostic accuracy of the best performing measures of clonal diversity was similar to the combination of cytology and MYC. Adding CDKN2A loss to the panel had no additional benefit. Conclusion. Evaluation of MYC abnormalities and measures of clonal diversity in brush cytology specimens may be of clinical value in distinguishing CCA from benign biliary strictures in PSC. PMID:27127503

  11. Genetic Abnormalities in Biliary Brush Samples for Distinguishing Cholangiocarcinoma from Benign Strictures in Primary Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    Margriet R. Timmer

    2016-01-01

    Full Text Available Background. Primary sclerosing cholangitis (PSC is a chronic inflammatory liver disease and is strongly associated with cholangiocarcinoma (CCA. The lack of efficient diagnostic methods for CCA is a major problem. Testing for genetic abnormalities may increase the diagnostic value of cytology. Methods. We assessed genetic abnormalities for CDKN2A, TP53, ERBB2, 20q, MYC, and chromosomes 7 and 17 and measures of genetic clonal diversity in brush samples from 29 PSC patients with benign biliary strictures and 12 patients with sporadic CCA or PSC-associated CCA. Diagnostic performance of cytology alone and in combination with genetic markers was evaluated by sensitivity, specificity, and area under the curve analysis. Results. The presence of MYC gain and CDKN2A loss as well as a higher clonal diversity was significantly associated with malignancy. MYC gain increased the sensitivity of cytology from 50% to 83%. However, the specificity decreased from 97% to 76%. The diagnostic accuracy of the best performing measures of clonal diversity was similar to the combination of cytology and MYC. Adding CDKN2A loss to the panel had no additional benefit. Conclusion. Evaluation of MYC abnormalities and measures of clonal diversity in brush cytology specimens may be of clinical value in distinguishing CCA from benign biliary strictures in PSC.

  12. Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma

    International Nuclear Information System (INIS)

    Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case-control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log-rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX-2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX-2 has been shown to contribute to cholangiocarcinogenesis, the COX-2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival

  13. Antitumor effect of metformin on cholangiocarcinoma: In vitro and in vivo studies.

    Science.gov (United States)

    Fujimori, Takayuki; Kato, Kiyohito; Fujihara, Shintaro; Iwama, Hisakazu; Yamashita, Takuma; Kobayashi, Kiyoyuki; Kamada, Hideki; Morishita, Asahiro; Kobara, Hideki; Mori, Hirohito; Okano, Keiichi; Suzuki, Yasuyuki; Masaki, Tsutomu

    2015-12-01

    Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC). Treatment with the anti-diabetic drug metformin has been associated with reduced cancer incidence in patients with type 2 diabetes. Thus, the present study evaluated the effects of metformin on human CCA cell proliferation in vitro and in vivo and identified the microRNAs associated with its antitumor effects. Metformin inhibited the proliferation of the CCA cell lines HuCCT-1 and TFK-1 and blocked the G0 to G1 cell cycle transition, accompanied by AMP kinase pathway activation. Metformin treatment also led to marked decreases in cyclin D1 and cyclin-dependent kinase (Cdk) 4 protein levels and retinoblastoma protein phosphorylation. However, this drug did not affect p27kip protein expression. In addition, it reduced the phosphorylation of Axl, EphA10, ALK and PYK, as well as tumor proliferation in athymic nude mice with xenograft tumors. Furthermore, it markedly altered microRNA expression. These findings suggest that metformin may have clinical use in the treatment of CCA. PMID:26398221

  14. Role of serum total sialic acid in differentiating cholangiocarcinoma from hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Prachya Kongtawelert; Pisit Tangkijvanich; Siriwan Ong-Chai; Yong Poovorawan

    2003-01-01

    AIM:This study was designed to evaluate the clinical application of serum total sialic acid (TSA) in the diagnosis of cholangiocarcinoma (CCA).METHODS: Serum TSA was determined by periodateresorcinol microassay in 69 patients with CCA, 59 patients with hepatocellular carcinoma (HCC), 37 patients with cirrhosis, 61 patients with chronic hepatitis and 50 healthy blood donors.RESULTS: The mean serum TSA concentration in CCA (2.41±0.70 mmol/L) was significantly higher than those of HCC, cirrhosis, chronic hepatitis and healthy blood donors (1.41±0.37 mmol/L, 1.13±0.31 mmol/L, 1.16±0.26 mmol/L, and 1.10±0.14 mmol/L, respectively; P<0.001). Based on ROC curve analysis, a cut-off point of 1.75 mmol/L discriminated between CCA and HCC with a sensitivity,specificity and accuracy of 82.6%, 83.1%, and 82.8%,respectively.CONCLUSION: Based on our results, serum TSA would be a useful marker for the differential diagnosis of CCA from HCC.

  15. Inflammatory cytokines suppress arylamine N-acetyltransferase 1 in cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the effect of inflammatory cytokines on arylamine N-acetyltransferase 1 (NAT1), which is a phase-Ⅱ enzyme involved in the biotransformation of aromatic and heterocyclic amines found in food, drugs and the environment.METHODS: Human cholangiocarcinoma KKU-100 cells were treated with a mixture of proinflammatory cytokines (interferon-y, interleukin-1β and tumor necrosis factor-α)for 48 h, and the effect on NAT1 activity was assessed by high performance liquid chromatography, while NAT1 expression was determined by reverse-transcription polymerase chain reaction. The oxidative stress on the cells was examined by the formation of nitric oxide,superoxide anion and glutathione (GSH) levels. The cells were also treated with S-nitroso-glutathione (GSNO), a nitric oxide donor, to see if the responses were similar to those obtained with the inflammatory cytokines.RESULTS: Cytokines suppressed NAT1 activity,reducing the Vmax without affecting the Km. Cytokines also had a significant impact on the induction of nitric oxide production and in reducing the redox ratios of glutathione (GSH) and GSH disulfide. Treatment with GSNO for 2-48 h reduced NAT1 activity without affecting the GSH ratio. Moreover, inflammatory cytokines and GSNO suppressed NAT1 mRNA expression.CONCLUSION: These findings indicate an association between inflammation and suppression of NAT1, which perhaps contributes to chemical-mediated toxicity and carcinogenesis.

  16. A case of Fasciola hepatica infection mimicking cholangiocarcinoma and ITS-1 sequencing of the worm.

    Science.gov (United States)

    Kang, Bong Kyun; Jung, Bong-Kwang; Lee, Yoon Suk; Hwang, In Kyeom; Lim, Hyemi; Cho, Jaeeun; Hwang, Jin-Hyeok; Chai, Jong-Yil

    2014-04-01

    Fascioliasis is a zoonotic infection caused by Fasciola hepatica or Fasciola gigantica. We report an 87-year-old Korean male patient with postprandial abdominal pain and discomfort due to F. hepatica infection who was diagnosed and managed by endoscopic retrograde cholangiopancreatography (ERCP) with extraction of 2 worms. At his first visit to the hospital, a gallbladder stone was suspected. CT and magnetic retrograde cholangiopancreatography (MRCP) showed an intraductal mass in the common bile duct (CBD) without proximal duct dilatation. Based on radiological findings, the presumed diagnosis was intraductal cholangiocarcinoma. However, in ERCP which was performed for biliary decompression and tissue diagnosis, movable materials were detected in the CBD. Using a basket, 2 living leaf-like parasites were removed. The worms were morphologically compatible with F. hepatica. To rule out the possibility of the worms to be another morphologically close species, in particular F. gigantica, 1 specimen was processed for genetic analysis of its ITS-1 region. The results showed that the present worms were genetically identical (100%) with F. hepatica but different from F. gigantica.

  17. Radiological diagnosis and intervention of cholangiocarcinomas (CC); Radiologische Diagnostik und Intervention von Cholangiokarzinomen (CC)

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Zangos, S.; Eichler, K.; Gruber-Rouh, T.; Hammerstingl, R.M.; Weisser, P. [Frankfurt Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Trojan, J. [Frankfurt Univ. (Germany). Medizinische Klinik I: Gastroenterologie, Endokrinologie, Pneumologie/Allergologie

    2012-10-15

    To present current data on diagnosis, indication and different therapy options in patients with cholangiocarcinoma (CC) based on an analysis of the current literature and clinical experience. The diagnostic routine includes laboratory investigations with parameters of cholestasis and also serum tumor markers CA19 - 9 and CEA. After ultrasound for clarifying a tumor and/or dilated bile ducts, contrast-enhanced magnetic resonance imaging (MRI) should be performed with magnetic resonance cholangiography (MRCP). The accuracy (positive predictive value) for diagnosing a CC is 37 - 84 % (depending on the location) for ultrasound, 79 - 94 % for computed tomography (CT), and 95 % for MRI and MRCP. An endoscopic retrograde cholangiography (ERCP) can then be planned, especially if biliary drainage or cytological or histological specimen sampling is intended. A curative approach can be achieved by surgical resection, rarely by liver transplantation. However, many patients are not eligible for surgery. In addition to systemic chemotherapy, locoregional therapies such as transarterial chemoembolization (TACE), hepatic arterial infusion (HAI) - also known as chemoperfusion -, drug eluting beads-therapy (DEB) as well as thermoablative procedures, such as laser-induced thermotherapy (LITT), microwave ablation (MWA) and radiofrequency ablation (RFA) can be provided with a palliative intention.

  18. Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.

    Science.gov (United States)

    Harmancı, Özgür; Ensaroğlu, Fatih; Özçay, Figen; Öcal, Serkan; Korkmaz, Murat; Özdemir, B Handan; Selçuk, Haldun; Moray, Gökhan; Haberal, Mehmet

    2015-11-01

    We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months.

  19. Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.

    Science.gov (United States)

    Harmancı, Özgür; Ensaroğlu, Fatih; Özçay, Figen; Öcal, Serkan; Korkmaz, Murat; Özdemir, B Handan; Selçuk, Haldun; Moray, Gökhan; Haberal, Mehmet

    2015-11-01

    We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months. PMID:26640927

  20. Intrahepatic CD8+ lymphocyte trapping during tolerance induction using mushroom derived formulations: A possible role for liver in tolerance induction

    Institute of Scientific and Technical Information of China (English)

    Mony Shuvy; Tiberiu Hershcovici; Cristina Lull-Noguera; Harry Wichers; Ofer Danay; Dan Levanon; Lidya Zolotarov; Yaron Ilan

    2008-01-01

    AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis.METHODS: Four groups of mice were studied.Colitis was induced by intracolonic instillation of TNBS in groups A and B.Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin.Mice were evaluated for development of macroscopic and microscopic.The immune effects of Shiitakke were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay.RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by significant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively).This beneficial effect was associated with a significant increase in the intrahepatic CD8+ lymphocyte trapping,demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio.These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells.A similar effect was observed when Shiitake was administered to animals without disease induction.CONCLUSION: Shiitake extract affected livermediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis.

  1. Hilar cholangiocarcinoma: preoperative evaluation with a three dimensional volumetric interpolated breath-hold examination magnetic resonance imaging sequence

    Institute of Scientific and Technical Information of China (English)

    YIN Long-lin; SONG Bin; XU Juan; LI Ying-chun

    2007-01-01

    Background Early detection and accurate staging are crucial for planning treatment and improving survival rate of hilar cholangiocarcinomas. This study investigated the diagnostic value of a three dimensional, spoiled gradient echo,T1-weighted magnetic resonance (MR) imaging sequence (3D volumetric interpolated breath-hold examination, 3D-VIBE) in the preoperative evaluation of hilar cholangiocarcinoma.Methods Thirty-one patients with surgically and histologically confirmed hilar cholangiocarcinomas underwent preoperative MR imaging examination. Unenhanced two-dimensional T1- and T2-weighted images, 2D MR cholangiopancreatographs (MRCP), gadolinium enhanced 3D-VIBE images in the early arterial, late arterial and portal venous phases followed by 2D T1-weighted images in the equilibrium phase were acquired. Images from 3D-VIBE, 2D T1-weighted enhanced sequences and 2D MRCP were interpreted by two abdominal radiologists through consensus reading in blind manner, focussing on the assessment of the morphological type, the longitudinal extent of tumor infiltration in the bile ducts and the involvement of neighbouring blood vessels. The accuracy of 3D-VIBE and 2D T1-weighted enhanced sequences in assessing the tumor resectability was compared.Results All the 31 tumors were directly displayed and accurately classified on 3D-VIBE images whereas 8 periductal infiltrating tumors (8/31, 25.8%) were not depicted on 2D T1-weighted enhanced images. Using the Bismuth Corlette classification, 3D-VIBE was closer to MRCP in delineating the intraductal extent of tumor infiltration than 2D T1-weighted enhanced (28/31, 90.3%; 10/31,32.3%; χ2=22.0, P<0.05). Involvement of the hepatic artery, the portal venous trunk and their branches was shown more frequently on 3D VIBE than 2D T1-weighted enhanced images. The positive predictive value and accuracy of 3D-VIBE (84.2%; 90.3%) for assessing tumor resectability were higher than those of 2D T1-weighted enhanced images (64.0%; 71.0%, all P

  2. A large congenital and solitary intrahepatic arterioportal fistula in an old woman

    Institute of Scientific and Technical Information of China (English)

    Zhen-Ya Lu; Jian-Yang Ao; Tian-An Jiang; Zhi-Yi Peng; Zhan-Kun Wang

    2009-01-01

    Arterioportal fistula (APF) is a rare cause of portal hypertension and may lead to death. APF can be congenital, post-traumatic, iatrogenic (transhepatic intervention or biopsy) or related to ruptured hepatic artery aneurysms. Congenital APF is a rare condition even in children. In this case report, we describe a 73-year-old woman diagnosed as APF by ultrasonography, computed tomography, and hepatic artery selective arteriography. The fistula was embolized twice but failed, and she still suffered from alimentary tract hemorrhage. Then, selective arteriography of the hepatic artery was performed again and venae coronaria ventriculi and short gastric vein were embolized. During the 2-year follow-up, the patient remained asymptomatic. We therefore argue that embolization of venae coronaria ventriculi and short gastric vein may be an effective treatment modality for intrahepatic APF with severe upper gastrointestinal bleeding.

  3. Clinical significance of serum glycochlicacid detection in diagnosis of intrahepatic cholestasis of pregnancy

    International Nuclear Information System (INIS)

    Intrahepatic cholestasis of pregnancy (ICP) occurred in the middle and later phase of pregnancy. ICP had considerable effect on the perinatal babies. To further study the effect of serum glycochlicacid in diagnosis of ICP, serum glycochlicacid was measured by radio-immunoassay in normal pregnancy women and ICP pregnant women. The determination of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were taken as contrast. Serum glycochlicacid is significantly higher (P < 0.01) in ICP pregnant women than in normal pregnant women. The positive rate of serum glycochlicacid was 100%, the positive rate of ALT was 80%, the positive rate of ALP was 40%. Serum glycochlicacid is the most sensitive serologic index in diagnosis of ICP

  4. Coil embolization of a congenital intrahepatic arterioportal fistula: increasing experience in management

    International Nuclear Information System (INIS)

    Congenital intrahepatic arterioportal fistula (IAPF) is a rare condition and there is limited experience of transcatheter embolization. We report here the transcatheter coil embolization of an incidentally found, asymptomatic congenital IAPF in a 16-month-old patient. After demonstrating that the IAPF was fed by two branches of a dilated left hepatic artery and drained into an aneurysm of the left portal vein, the feeding arteries were superselectively catheterized and occluded by microcoils in a single session. Follow-up was uneventful for 1 year. With respect to this and previously reported cases, we believe that embolization of feeding arteries is a safe and effective method that should be the primary choice of treatment; however, further cases should be reported to confirm this belief. (orig.)

  5. Transjugular Intrahepatic Portosystemic Shunt for Maintenance of Portal Venous Patency in Liver Transplant Candidates

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    Ron Charles Gaba

    2013-01-01

    Full Text Available Maintenance of portal venous patency is vital to liver transplant candidates, as the presence of portal vein thrombosis (PVT adversely impacts clinical outcomes by increasing surgical complexity and decreasing postoperative survival. By enhancing portal venous blood flow, transjugular intrahepatic portosystemic shunt (TIPS creation may enable clearance of PVT and preservation of portal venous patency in cirrhotic patients. Herein, we describe four cases in which TIPS produced and sustained an open portal venous system in liver transplant candidates with partial PVT. All patients demonstrated rapid and effective flow-enabled clearance of clot and intermediate to long-term preservation of portal venous flow. On this basis, we propose that maintenance of portal venous patency in liver transplant candidates with partial PVT represents a developing indication for TIPS.

  6. Transjugular Intrahepatic Portosystemic Shunt (TIPS Migration to the Heart Diagnosed by Emergency Department Ultrasound

    Directory of Open Access Journals (Sweden)

    Carlan Wendler

    2012-12-01

    Full Text Available A 57-year-old man presented to our emergency department with altered mental status. He had a past medical history significant for cirrhosis and previous placement of a transjugular intrahepatic portosystemic shunt (TIPS. On cardiac auscultation, a new heart murmur and an unexpected degree of cardiac ectopy were noted. On the 12-lead electrocardiogram, the patient was noted to have multiple premature atrial contractions, corroborating the irregular heart rhythm on physical exam. A focused bedside emergency ultrasound of the heart was then performed. This exam revealed an apparent foreign body in the right atrium. It appeared as if the patient’s TIPS had migrated from the heart into the right atrium. This case, as well as the literature describing thisunusual complication of TIPS placement, is reviewed in this case report

  7. [Intrahepatic cholestasis associated with parenteral nutrition: an experimental study in rats].

    Science.gov (United States)

    Salas Martínez, J; Morán Penco, J M; Mahedero Ruiz, G; García Gamito, F; Limón Mora, M; Maciá Botejara, E; Vinagre Velasco, L M

    1989-01-01

    Intrahepatic cholestasis is a condition often observed in patients receiving parenteral nutrition, especially in new born babies who are underweight (taurina. This makes it impossible to achieve a correct conjugation of toxic biliary acids. The access of nutrients to the liver may have an effect on this. An experimental study on rats was performed, administering an oral diet at the expense of lipids (20% Intralipid, 60% of caloric needs) and glucose (40% of caloric needs) in one group, another group received amino acid supplements to this diet (16N) at a proteic rate of 2 gr/kg of weight and day orally, with an identical diet to the above, except that the proteic intake was intraperitoneal. Two control groups were established. We found a microvacuolization in hepatic fat with the help of an electronic microscope in the groups lacking proteins and those with oral or intraperitoneal supplements of amino acids, as well as an increase in plasmatic AST.

  8. Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Suporn Treepongkaruna; Amornphun Gaensan; Paneeya Pienvichit; Ondrej Luksan; AS Knisely; Pattana Sornmayura; Milan Jirsa

    2009-01-01

    Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11 , which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum γ-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11 , a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type 2.

  9. Transjugular Intrahepatic Portosystemic Shunt (TIPS) Migration to the Heart Diagnosed by Emergency Department Ultrasound.

    Science.gov (United States)

    Wendler, Carlan; Shoenberger, Jan Marie; Mailhot, Thomas; Perera, Phillips

    2012-12-01

    A 57-year-old man presented to our emergency department with altered mental status. He had a past medical history significant for cirrhosis and previous placement of a transjugular intrahepatic portosystemic shunt (TIPS). On cardiac auscultation, a new heart murmur and an unexpected degree of cardiac ectopy were noted. On the 12-lead electrocardiogram, the patient was noted to have multiple premature atrial contractions, corroborating the irregular heart rhythm on physical exam. A focused bedside emergency ultrasound of the heart was then performed. This exam revealed an apparent foreign body in the right atrium. It appeared as if the patient's TIPS had migrated from the heart into the right atrium. This case, as well as the literature describing this unusual complication of TIPS placement, is reviewed in this case report. PMID:23358693

  10. Importance of intrahepatic mechanisms to gluconeogenesis from alanine during exercise and recovery

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    Wasserman, D.H.; Williams, P.E.; Lacy, D.B.; Green, D.R.; Cherrington, A.D.

    1988-04-01

    These studies were performed to assess the importance of intrahepatic mechanisms to gluconeogenesis in the dog during 150 min of treadmill exercise and 90 min of recovery. Sampling catheters were implanted in an artery and portal and hepatic veins 16 days before experimentation. Infusions of (U-/sup 14/C)alanine, (3-/sup 3/H)glucose, and indocyanine green were used to assess gluconeogenesis. During exercise, a decline in arterial and portal vein plasma alanine and in hepatic blood flow led to a decrease in hepatic alanine delivery. During recovery, hepatic blood flow was restored to basal, causing an increase in hepatic alanine delivery beyond exercise rates but still below resting rates. Hepatic fractional alanine extraction increased from 0.26 +/- 0.02 at rest to 0.64 +/- 0.03 during exercise and remained elevated during recovery. Net hepatic alanine uptake was 2.5 +/- 0.2 mumol.kg-1.min-1 at rest and remained unchanged during exercise but was increased during recovery. The conversion rate of (/sup 14/C)alanine to glucose had increased by 248 +/- 38% by 150 min of exercise and had increased further during recovery. The efficiency with which alanine was channeled into glucose in the liver was accelerated to a rate of 338 +/- 55% above basal by 150 min of exercise but declined slightly during recovery. In conclusion, 1) gluconeogenesis from alanine is accelerated during exercise, due to an increase in the hepatic fractional extraction of the amino acid and through intrahepatic mechanisms that more efficiently channel it into glucose.

  11. Transjugular Intrahepatic Portosystemic Shunt Dysfunction: Concordance of Clinical Findings, Doppler Ultrasound Examination, and Shunt Venography

    Science.gov (United States)

    Owen, Joshua M; Gaba, Ron Charles

    2016-01-01

    Objectives: The objective of this study was to evaluate the concordance between clinical symptoms, Doppler ultrasound (US), and shunt venography for the detection of stent-graft transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. Materials and Methods: Forty-one patients (M:F 30:11, median age 55 years) who underwent contemporaneous clinical exam, Doppler US, and TIPS venography between 2003 and 2014 were retrospectively studied. Clinical symptoms (recurrent ascites or variceal bleeding) were dichotomously classified as present/absent, and US and TIPS venograms were categorized in a binary fashion as normal/abnormal. US abnormalities included high/low (>190 or 50 cm/s), absent flow, and return of antegrade intra-hepatic portal flow. Venographic abnormalities included shunt stenosis/occlusion and/or pressure gradient elevation. Clinical and imaging concordance rates were calculated. Results: Fifty-two corresponding US examinations and venograms were assessed. The median time between studies was 3 days. Forty of 52 (77%) patients were symptomatic, 33/52 (64%) US examinations were abnormal, and 20/52 (38%) TIPS venograms were abnormal. Concordance between clinical symptoms and TIPS venography was 48% (25/52), while the agreement between US and shunt venography was 65% (34/52). Clinical symptoms and the US concurred in 60% (31/52) of the patients. The sensitivity of clinical symptoms and US for the detection of venographically abnormal shunts was 80% (16/20) and 85% (17/20), respectively. Both clinical symptoms and the US had low specificity (25%, 8/32 and 50%, 16/32) for venographically abnormal shunts. Conclusion: Clinical findings and the US had low concordance rates with TIPS venography, with acceptable sensitivity but poor specificity. These findings suggest the need for improved noninvasive imaging methods for stent-graft TIPS surveillance.

  12. Autoimmune BSEP disease: disease recurrence after liver transplantation for progressive familial intrahepatic cholestasis.

    Science.gov (United States)

    Kubitz, Ralf; Dröge, Carola; Kluge, Stefanie; Stross, Claudia; Walter, Nathalie; Keitel, Verena; Häussinger, Dieter; Stindt, Jan

    2015-06-01

    Severe cholestasis may result in end-stage liver disease with the need of liver transplantation (LTX). In children, about 10 % of LTX are necessary because of cholestatic liver diseases. Apart from bile duct atresia, three types of progressive familial intrahepatic cholestasis (PFIC) are common causes of severe cholestasis in children. The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively. All transporters are localized in the canalicular membrane of hepatocytes and together mediate bile salt and phospholipid transport. In some patients with PFIC-2 disease, recurrence has been observed after LTX, which mimics a PFIC phenotype. It could be shown by several groups that inhibitory anti-BSEP antibodies emerge, which most likely cause disease recurrence. The prevalence of severe BSEP mutations (e.g., splice site and premature stop codon mutations) is very high in this group of patients. These mutations often result in the complete absence of BSEP, which likely accounts for an insufficient auto-tolerance against BSEP. Although many aspects of this "new" disease are not fully elucidated, the possibility of anti-BSEP antibody formation has implications for the pre- and posttransplant management of PFIC-2 patients. This review will summarize the current knowledge including diagnosis, pathomechanisms, and management of "autoimmune BSEP disease." PMID:25342496

  13. Microbiota studies in the bile duct strongly suggest a role for Helicobacter pylori in extrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Avilés-Jiménez, F; Guitron, A; Segura-López, F; Méndez-Tenorio, A; Iwai, S; Hernández-Guerrero, A; Torres, J

    2016-02-01

    Biliary tract cancer or extrahepatic cholangiocarcinoma (ECCA) represents the sixth commonest cause of cancer in the gastrointestinal tract in western countries. We aimed to characterize the microbiota and its predicted associated functions in the biliary tract of ECCA and benign biliary pathology (BBP). Samples were taken from 100 patients with ECCA and 100 patients with BBP by endoscopic cholangio-pancreatography for DNA extraction. Ten patients with ECCA and ten with BBP were selected for microbiota studies using the V4-16S rRNA gene and sequenced in Illumina platform. Microbiota analyses included sample-to-sample distance metrics, ordination/clustering and prediction of functions. Presence of Nesterenkonia sp. and Helicobacter pylori cagA and vacA genes were tested in the 100 ECCA and 100 BBP samples. Phylum Proteobacteria dominated all samples (60.4% average). Ordination multicomponent analyses showed significant microbiota separation between ECCA and BBP (p 0.010). Analyses of 4002 operational taxonomic units with presence variation in at least one category probed a separation of ECCA from BBP. Among these, Nesterenkonia decreased, whereas Methylophilaceae, Fusobacterium, Prevotella, Actinomyces, Novosphingobium and H. pylori increased in ECCA. Predicted associated functions showed increased abundance of H. pylori virulence genes in ECCA. cagA and vacA genes were confirmed by PCR in ECCA and BBP samples. This is the first microbiota report in ECCA and BBP to show significant changes in microbial composition. Bacterial species unusual for human flora were found: Methylophilaceae and Nesterenkonia are reported in hypersaline soils, and Mesorhizobium is a nitrogen-fixing bacterium. Enrichment of virulence genes confirms previous studies suggesting that H. pylori might be associated with ECCA. PMID:26493848

  14. Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Torsten Voigtländer

    Full Text Available BACKGROUND: The diagnosis of cholangiocarcinoma (CC is challenging especially in patients with primary sclerosing cholangitis (PSC and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2 has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis. AIM: To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC. METHODS: Bile and serum Angpt-2 levels were measured in patients with CC (n=45, PSC (n=74, CC complicating PSC (CC/PSC (n=11 and patients with bile duct stones (n=37 in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9. Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2. RESULTS: Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05. Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC analysis resulted in a higher area under the curve (AUC value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI: 0.74-0.93 versus 0.65-0.87, respectively. Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature. CONCLUSIONS: Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.

  15. Greater Biosynthetic Liver Dysfunction in Primary Sclerosing Cholangitis Suggests Co-existent or Impending Cholangiocarcinoma

    Science.gov (United States)

    Trilianos, Panagiotis; Agnihotri, Abhishek; Ucbilek, Enver; Gurakar, Ahmet

    2016-01-01

    Background and Aim: Patients with primary sclerosing cholangitis (PSC) who develop cholangiocarcinoma (CCA) have a median survival of less than 6 months. In half of cases, PSC and CCA will be diagnosed either concurrently or within a year of one another. The aim of the present study is to demonstrate that the degree of biochemical liver dysfunction is associated with concomitant or impending CCA. Methods: We did a chart review of patients diagnosed with PSC and CCA up to 18 months from presentation (“CCA” group) as well as patients with PSC that underwent transplantation with no sign of CCA in their explanted liver (“nCCA” group). Along with demographic data and follow-up length, we recorded their presenting liver function tests, including alanine and aspartate aminotransferases (ALT, AST), total bilirubin (TBil), alkaline phosphatase (ALP), international normalization ratio (INR), and serum Ca 19-9 levels. Differences between mean values of the two groups were analyzed with a student’s t-test. Results: Twenty-four patients were included. The “CCA” group consisted of eight patients, and the “non-CCA” group had 16 patients. There was no significant difference between the two groups in their presenting values of ALT, ALP, or serum Ca 19-9. However, the “CCA” group had significantly higher levels of AST, TBil, and INR. Conclusion: Patients with PSC and concurrent or impending CCA appear to exhibit significantly greater biochemical liver dysfunction than those who do not develop CCA. Therefore, newly-diagnosed PSC patients presenting with these findings may warrant more rigorous evaluation. PMID:27047765

  16. Trefoil factors: Tumor progression markers and mitogens via EGFR/MAPK activation in cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Kanuengnuch Kosriwong; Trevelyan R Menheniott; Andrew S Giraud; Patcharee Jearanaikoon; Banchob Sripa; Temduang Limpaiboon

    2011-01-01

    AIM: To investigate trefoil factor (TFF ) gene copy number, mRNA and protein expression as potential biomarkers in cholangiocarcinoma (CCA). METHODS: TFF mRNA levels, gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction (PCR), quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA, precancerous bile duct dysplasia and from disease-free controls. The functional impact of recombinant human (rh)TFF2 peptide treatment on proliferation and epidermal growth factor receptor (EGFR)/mitogenactivated protein kinase (MAPK) signaling was assessed in the CCA cell line, KMBC, by viable cell counting and immunoblotting, respectively. RESULTS: TFF1 , TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls, and was unrelated to gene copy number. TFF1 immunoreactivity was strongly increased in both dysplasia and CCA, whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls. By contrast, TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA. Kaplan-Meier analysis found no association of TFF mRNA, protein and copy number with age, gender, histological subtype, and patient survival time. Treatment of KMBC cells with rhTFF2 stimulated proliferation, triggered phosphorylation of EGFR and downstream extracellular signal related kinase (ERK), whereas co-incubation with the EGFR tyrosine kinase inhibitor, PD153035, blocked rhTFF2-dependent proliferation and EGFR/ERK responses. CONCLUSION: TFF mRNA/protein expression is indicative of CCA tumor progression, but not predictive for histological sub-type or survival time. TFF2 is mitogenic in CCA via EGFR/MAPK activation.

  17. Ultrasound-guided percutaneous transhepatic cholangiography and drainage in patients with hilar cholangiocarcinoma.

    Science.gov (United States)

    Laméris, J S; Hesselink, E J; Van Leeuwen, P A; Nijs, H G; Meerwaldt, J H; Terpstra, O T

    1990-05-01

    The use of ultrasound-guided PTCD in 49 patients with hilar cholangiocarcinoma was evaluated. In 11 patients PTCD was performed as a preoperative measure either to outline tumor extension or to treat cholangitis. Postoperatively, the catheters were used to stent bilioenteric anastomoses and served to guide iridium wires for radiotherapy in nine patients with nonresectable tumor or tumor residue after resection. In 20 inoperable patients with tumor diameter smaller than 3 cm and in whom at least one catheter could be manipulated through the tumor, PTCD was combined with internal and external radiotherapy. The remaining 18 patients were palliated with PTCD only. In 29 patients (59%) complete drainage of the biliary system was achieved. Twenty-seven of these had complete internal drainage using endoprostheses. Two had a combination of an endoprosthesis and external catheter drainage. Of the 20 patients (41%) with incomplete drainage, 12 had endoprostheses, four had a catheter and an endoprosthesis, and in the remaining four external catheter drainage was the optimum result. PTCD was successful in treating eight of ten patients with cholangitis and 12 of 16 patients with pruritus. Procedure-related complication occurred in 11 patients (22%). With the exception of one, all complications could be classified as minor, requiring only conservative measures. A major complication was seen in a patient with ascitic fluid and severe cholangitis. PTCD caused a bacterial peritonitis, of which the patient died. The median survival of patients treated with PTCD alone only was 4 months. A significant increase in survival was noted in patients treated with PTCD and radiotherapy (median survival 8 months).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma.

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    Yimin Wang

    Full Text Available As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3 plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA; however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20 can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA.

  19. Endoscopic sphincterotomy and risk of cholangiocarcinoma: a population-based cohort study in Finland and Sweden

    Science.gov (United States)

    Strömberg, Cecilia; Böckelman, Camilla; Song, Huan; Ye, Weimin; Pukkala, Eero; Haglund, Caj; Nilsson, Magnus

    2016-01-01

    Background and study aims: Elevated long-term risk of cholangiocarcinoma is reported after endoscopic sphincterotomy (ES), but in a previous study we found a trend towards a decreased risk. The aim of this study was to evaluate the association in a larger cohort with a longer follow-up. Patients and methods: Data concerning all patients having had an inpatient endoscopic retrograde cholangiopancreatography (ERCP) were collected from the hospital discharge registries of Finland and Sweden. Incident cases of malignancy were identified through linkage to the nationwide Cancer Registries. Patients with a diagnosis of malignancy, before or within 2 years of the ERCP, were excluded. The cohorts were followed until a diagnosis of malignancy, death or emigration, or end of follow-up (end of 2010). The relative risk of malignancy was calculated as standardized incidence ratio (SIR) compared with the general population, inherently adjusting for age, gender, and calendar year of follow-up. Results: A total of 69 925 patients undergoing ERCP from 1976 through 2008 were included in the pooled cohort. ES was performed in 40 193 subjects. The risk of malignancy was elevated in the total cohort (SIR = 2.3; 95 % confidence interval [CI] 2.1 – 2.5) irrespective of whether ES was performed or not. The SIRs diminished with duration of follow-up. Conclusions: We found an elevated risk of malignancy both in the bile ducts alone and in the bile ducts, liver or pancreas together, after ERCP. The risk was the same, regardless of whether ES had been performed or not, so ES was unlikely to be the cause, and a common carcinogenic exposure previous to the ERCP procedure, possibly ductal gallstone disease, was more likely.

  20. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    International Nuclear Information System (INIS)

    Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation. CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab

  1. Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma

    Science.gov (United States)

    Andresen, Kim; Boberg, Kirsten Muri; Vedeld, Hege Marie; Honne, Hilde; Jebsen, Peter; Hektoen, Merete; Wadsworth, Christopher A.; Clausen, Ole Petter; Lundin, Knut E.A.; Paulsen, Vemund; Foss, Aksel; Mathisen, Øystein; Aabakken, Lars; Schrumpf, Erik; Lothe, Ragnhild A.

    2015-01-01

    Early detection of the highly aggressive malignancy cholangiocarcinoma (CCA) remains a challenge but has the potential to render the tumor curable by surgical removal. This study evaluates a biomarker panel for the diagnosis of CCA by DNA methylation analyses of biliary brush samples. The methylation status of 13 candidate genes (CDO1, CNRIP1, DCLK1, FBN1, INA, MAL, SEPT9, SFRP1, SNCA, SPG20, TMEFF2, VIM, and ZSCAN18) was investigated in 93 tissue samples (39 CCAs and 54 nonmalignant controls) using quantitative methylation‐specific polymerase chain reaction. The 13 genes were further analyzed in a test series of biliary brush samples (15 CCAs and 20 nonmalignant primary sclerosing cholangitis controls), and the methylation status of the four best performing markers was validated (34 CCAs and 34 primary sclerosing cholangitis controls). Receiver operating characteristic curve analyses were used to evaluate the performance of individual biomarkers and the combination of biomarkers. The 13 candidate genes displayed a methylation frequency of 26%‐82% in tissue samples. The four best‐performing genes (CDO1, CNRIP1, SEPT9, and VIM) displayed individual methylation frequencies of 45%‐77% in biliary brushes from CCA patients. Across the test and validation biliary brush series, this four‐gene biomarker panel achieved a sensitivity of 85% and a specificity of 98%, with an area under the receiver operating characteristic curve of 0.944. Conclusion: We report a straightforward biomarker assay with high sensitivity and specificity for CCA, outperforming standard brush cytology, and suggest that the biomarker panel, potentially in combination with cytological evaluation, may improve CCA detection, particularly among primary sclerosing cholangitis patients. (Hepatology 2015;61:1651–1659) PMID:25644509

  2. Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma

    International Nuclear Information System (INIS)

    The molecular mechanisms of CC (cholangiocarcinoma) oncogenesis and progression are poorly understood. This study aimed to determine the genome-wide expression of genes related to CC oncogenesis and sarcomatous transdifferentiation. Genes that were differentially expressed between CC cell lines or tissues and cultured normal biliary epithelial (NBE) cells were identified using DNA microarray technology. Expressions were validated in human CC tissues and cells. Using unsupervised hierarchical clustering analysis of the cell line and tissue samples, we identified a set of 342 commonly regulated (>2-fold change) genes. Of these, 53, including tumor-related genes, were upregulated, and 289, including tumor suppressor genes, were downregulated (<0.5 fold change). Expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPARγ, KRT17, UCHL1, IGFBP7 and SPARC proteins was immunohistochemically verified in human and hamster CC tissues. Additional unsupervised hierarchical clustering analysis of sarcomatoid CC cells compared to three adenocarcinomatous CC cell lines revealed 292 differentially upregulated genes (>4-fold change), and 267 differentially downregulated genes (<0.25 fold change). The expression of 12 proteins was validated in the CC cell lines by immunoblot analysis and immunohistochemical staining. Of the proteins analyzed, we found upregulation of the expression of the epithelial-mesenchymal transition (EMT)-related proteins VIM and TWIST1, and restoration of the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 during sarcomatoid transdifferentiation of CC. The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis

  3. Endoscopic stenting for hilar cholangiocarcinoma: efficacy of unilateral and bilateral placement of plastic and metal stents in a retrospective review of 480 patients

    Directory of Open Access Journals (Sweden)

    Liberato Manuel José

    2012-08-01

    Full Text Available Abstract Background Endoscopic biliary drainage of hilar cholangiocarcinoma is controversial with respect to the optimal types of stents and the extent of drainage. This study evaluated endoscopic palliation in patients with hilar cholangiocarcinoma using self-expandable metallic stents (SEMS and plastic stents (PS.We also compared unilateral and bilateral stent placement according to the Bismuth classification. Methods Data on 480 patients receiving endoscopic biliary drainage for hilar cholangiocarcinoma between September 1995 and December 2010 were retrospectively reviewed to evaluate the following outcome parameters: technical success (TS, functional success (FS, early and late complications, stent patency and survival. Patients were followed from stent insertion until death or stent occlusion. Patients were divided into 3 groups according to the Bismuth classification (Group 1, type I; Group 2, type II; Group 3, type > III. Results The initial stent insertion was successful in 450 (93.8% patients. TS was achieved in 204 (88.3% patients treated with PS and in 246 (98.8% patients palliated with SEMS (p P P  Conclusions SEMS insertion for the palliation of hilar cholangiocarcinoma offers higher technical and clinical success rates in the ITT analysis as well as lower complication rates and a superior cumulative stent patency when compared with PS placement in all Bismuth classifications. The cumulative patency of bilateral SEMS or PS stents was significantly higher than that of unilateral SEMS or PS stents, with lower occlusion rates in Bismuth II patients.

  4. Hepatitis C virus core upregulates the methylation status of the RASSF1A promoter through regulation of SMYD3 in hilar cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Ning Guo; Rufu Chen; Zhihua Li; Yonggang Liu; Di Cheng; Quanbo Zhou; Jiajia Zhou; Qing Lin

    2011-01-01

    Increasing evidence has been accumulated indicating the important role of epigenetic regulation in tumor genesis.Previously, we observed that the transfection of hepatitis C virus core (HCVc) protein led to malignant transformation in normal biliary cells, and that tumor suppressor gene RASSFIA was downregulated in many hilar cholangiocarcinoma patients by hypermethylation in the promoter region. In the present study, we found SET and MYND domain-containing protein 3 (SMYD3), a novel histone methyltransferase, was overexpressed in cholangiocarcinoma patients especially in those with HCV infection. Transfection of HCVc into hilar cholangiocarcinoma cell lines QBC939 and FRH0201 could upregulate the expression of SMYD3 and promote cell growth, which was consistent with the results of our clinical research.This phenomenon indicated that SMYD3 was related to the epigenetic regulation of cholangiocarcinoma genesis with HCV infection. Overexpression of SMYD3 could inhibit RASSFIA expression, whereas inhibition of SMYD3 by siRNA improved its expression. Methylationspecific polymerase chain reaction (MS-PCR) results showed the methylation status of RASSFIA promoter was regulated by SMYD3. In conclusion, HCVc could upregulate the methylation status of the RASSFIA promoter through regulation of SMYD3, and histone methylation may affect the DNA methylation of downstream gene by an unknown mechanism.

  5. Detection of Cholangiocarcinoma with Magnetic Resonance Spectroscopy of Bile in Patients with and without Primary Sclerosing Cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Albiin, N.; Smith, I.C.P.; Arnelo, U.; Lindberg, B.; Bergquist, A.; Dolenko, B.; Bryksina, N.; Bezabeh, T. (Divs. of Radiology and Surgery, Dept. for Clinical Science, Intervention, Technology, Karolinska Inst., Stockholm (Sweden))

    2008-10-15

    Background: Early detection of cholangiocarcinoma (CC) is very difficult, especially in patients with primary sclerosing cholangitis (PSC) who are at increased risk of developing CC. Purpose: To evaluate 1H magnetic resonance spectroscopy (1H-MRS) of bile as a diagnostic marker for CC in patients with and without PSC. Material and Methods: The institutional review board approved the study, and all patients gave informed consent. Bile from 49 patients was sampled and investigated using 1H-MRS. MR spectra of bile samples from 45 patients (18 female; age range 22-87 years, mean age 57 years) were analyzed both conventionally and using computerized multivariate analysis. Sixteen of the patients had CC, 18 had PSC, and 11 had other benign findings. Results: The spectra of bile from CC patients differed from the benign group in the levels of phosphatidylcholine, bile acids, lipid, and cholesterol. It was possible to distinguish CC from benign conditions in all patients with malignancy. Two benign non-PSC patients were misclassified as malignant. The sensitivity, specificity, and accuracy were 88.9%, 87.1%, and 87.8%, respectively. Conclusion: With 1H-MRS of bile, cholangiocarcinoma could be discriminated from benign biliary conditions with or without PSC

  6. Immune Responses of Dendritic Cells Loaded with Antigens from Apoptotic Cholangiocarcinoma Cells Caused by γ-Irradation

    Institute of Scientific and Technical Information of China (English)

    WUGang; HANBenli; PEIXuetao

    2002-01-01

    Objective:To investigate the induction cytotoxic T cells(CTLs) with antitumor activity and therapeutic efficacy after dendritic cells(DCs) acquired antigen from apoptotic cholangiocarcinoma cells caused by γ-irradiation. Methods:DCs from peripheral blood mononuclear cells (PBMC) that maintain the antigen capturing and processing capacity charateristic of immature cells have been established in vitro, using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). Then, in cholangiocarcinoma cells apoptosis was induced by γ-irradiation. The experimental groups were as follows:(1)coculture of DCs and apoptotic cancer cells and T cells;(2)coculture of DCs and necrotic cancer cells and T cells;(3)coculture of DCs, cultured cancer cell and T cells. They are cocultured for 7 days.DCs and T cells were riched, isolated and their antitumor response was tested. Results:The cells had typical dendritic morphology, expressed high levels of CDla and B7, acquired antigen from apoptotic cells caused by γ-irradiation and induced an increased T cell stimulatory capacity in mixed lymphocyte reactions (MLR). Conclusion:DCs obtained from PBMCs using GM-CSF and IL-4 can efficiently present antigen derived from apoptotic cells caused by γ-irradiation and efficiently induce T cells.This strategy, therefore, may present an effective approach to transduce DCs with antigen.

  7. Induction of MITF expression in human cholangiocarcinoma cells and hepatocellular carcinoma cells by cyclopamine, an inhibitor of the Hedgehog signaling.

    Science.gov (United States)

    Samatiwat, Papavee; Takeda, Kazuhisa; Satarug, Soisungwan; Ohba, Koji; Kukongviriyapan, Veerapol; Shibahara, Shigeki

    2016-01-29

    Microphthalmia-associated transcription factor (MITF) is a key regulator of differentiation of melanocytes and retinal pigment epithelial cells, but it also has functions in non-pigment cells. MITF consists of multiple isoforms, including widely expressed MITF-A and MITF-H. In the present study, we explored the potential role played by the Hedgehog signaling on MITF expression in two common types of primary liver cancer, using human cholangiocarcinoma cell lines, the KKU-100 and HuCCT1, along with the HepG2 human hepatocellular carcinoma cell line. Importantly, cholangiocarcinoma is characterized by the activated Hedgehog signaling. Here we show that MITF-A mRNA is predominantly expressed in all three human liver cancer cell lines examined. Moreover, cyclopamine, an inhibitor of the Hedgehog signalling, increased the expression levels of MITF proteins in HuCCT1 and HepG2 cells, but not in KKU-100 cells, suggesting that MITF expression may be down-regulated in some liver cancer cases. PMID:26773496

  8. Development of a Health Education Modification Program Regarding Liver Flukes and Cholangiocarcinoma in High Risk Areas of Nakhon Ratchasima Province Using Self-Efficacy and Motivation Theory.

    Science.gov (United States)

    Kaewpitoon, Soraya J; Rujirakul, Ratana; Wakkuwattapong, Parichart; Benjaoran, Fuangfa; Norkaew, Jun; Kujapun, Jirawoot; Ponphimai, Sukanya; Chavenkun, Wasugree; Kompor, Porntip; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    A quasi-experimental study was conducted to develop a health education modification program based on self-efficacy and motivation regarding liver flukes and cholangiocarcinoma development in Keang Sanam Nang district, Nakhon Ratchasima province, Thailand. A total of 36 individuals were invited to participate in the program and were screened for population at risk of liver fluke infection and cholangiocarcinoma using SUT-OV-001 and SUT-CCA-001. Development of health education modification program regarding liver fluke and cholangiocarcinoma prevention included 3 steps: (1) preparation, (2) health education program, and (3) follow-up and evaluation. The study was implemented for 10 weeks. Pre-and-post-test knowledge was measured with questionnaires, Kuder-Richardson-20: KR-20 = 0.718,and Cronbach's Alpha Coefficient = 0.724 and 0.716 for perception and outcome expectation questionnaires. Paired and independent t-tests were applied for data analysis. The majority of the participants were female (55.6%), aged between ≤50 and 60 years old (36.1%), married (86.1%), education level of primary school (63.9%), agricultural occupation (80.6%), and income <4,000 Baht (44.4%). The results revealed that after the health education program, the experimental group had a mean score of knowledge, perception, and outcome expectation regarding liver fluke and cholangiocarcinoma prevention significantly higher than before participation and in the control group. In conclusion, this successful health education modification program for liver fluke and cholangiocarcinoma, therefore may useful for further work behavior modification in other epidemic areas. PMID:27356716

  9. Intrahepatic Cholestasis of Pregnancy Levels of Sulfated Progesterone Metabolites Inhibit Farnesoid X Receptor Resulting in a Cholestatic Phenotype

    OpenAIRE

    Abu-Hayyeh, Shadi; Papacleovoulou, Georgia; Lövgren-Sandblom, Anita; Tahir, Mehreen; Oduwole, Olayiwola; Jamaludin, Nurul Akmal; Ravat, Sabiha; Nikolova, Vanya; Chambers, Jenny; Selden, Clare; Rees, Myrddin; Marschall, Hanns-Ulrich; Parker, Malcolm G.; Williamson, Catherine

    2013-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3α-sulfated progesterone metabolites have been shown to be elevated in ICP, leading us to study the impact of sulfated progesterone metabolites on farnesoid X receptor (FXR)-mediated bile acid homeostasis pathways. Here...

  10. Mortality and complications in patients with portal hypertension who underwent transjugular intrahepatic portosystemic shunt (TIPS) - 12 years experience

    OpenAIRE

    Fernanda Ribeiro Funes; Rita de C. M. A. da Silva; Paulo César Arroyo Jr.; William José Duca; Adinaldo Adhemar Menezes da Silva; Renato Ferreira da Silva

    2012-01-01

    CONTEXT: Transjugular intrahepatic portosystemic shunt (TIPS) is the non-surgical treatment option with low level of morbi-mortality and possibility of accomplishment in patients with severe hepatic dysfunction which aims at decompressing the portal system treating or reducing the portal hypertension complications. OBJECTIVE: Outline the profile analyze global and early mortality, and the complications presented by cirrhotic patients who underwent TIPS for treatment of digestive hemorrhage by...

  11. Transcriptional Dynamics of Bile Salt Export Pump during Pregnancy: Mechanisms and Implications in Intrahepatic Cholestasis of Pregnancy

    OpenAIRE

    Song, Xiulong; Vasilenko, Alexander; Chen, Yuan; Valanejad, Leila; Verma, Ruchi; Yan, Bingfang; Deng, Ruitang

    2014-01-01

    Bile salt export pump (BSEP) is responsible for biliary secretion of bile acids, a rate limiting step in the enterohepatic circulation of bile acids and transactivated by nuclear receptor farnesoid x receptor (FXR). Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent disorder among diseases unique to pregnancy and primarily occurs in the third trimester of pregnancy with a hallmark of elevated serum bile acids. Currently, the transcriptional regulation of BSEP during pregnancy a...

  12. Adjuvant Intrahepatic Injection Iodine-131-Lipiodol Improves Prognosis of Patients with Hepatocellular Carcinoma After Resection: a Meta-Analysis.

    Science.gov (United States)

    Hong, Ye; Wu, Lu-Peng; Ye, Feng; Zhou, Yan-Ming

    2015-12-01

    High incidence of intrahepatic recurrence is a major surgical limitation following hepatectomy of hepatocellular carcinoma (HCC). This study was intended to investigate the effects of adjuvant intrahepatic injection of iodine-131-lipiodol on disease recurrence and survival in patients with HCC who underwent resection. A computerized literature search was performed to identify relevant articles. Data synthesis was performed using Review Manager 5.0 software, and results are presented as odds ratio (OR) with 95 % confidence intervals. Two randomized controlled trials and three case-control studies with a total of 334 participants were analyzed. Iodine-131-lipiodol treatment achieved significantly lower rates of intrahepatic recurrence (OR = 0.48, 95 % confidence interval (95 % CI) = 0.30-0.74; P = 0.001) and early recurrence (<2 year) (OR = 0.45, 95 % CI = 0.23-0.89; P = 0.02). Likewise, iodine-131-lipiodol treatment improved both the 5-year disease-free survival and overall survival significantly (OR = 1.85, 95 % CI = 1.13-3.03; P = 0.01; OR = 2.00, 95 % CI = 0.99-4.04; P = 0.05, respectively). Adjuvant intrahepatic injection of iodine-131-lipiodol resulted in a preventive effect on recurrence and improved survival after resection of HCC. Further larger, multi-centred, randomized prospective trial is warranted. PMID:27011542

  13. A small solitary non-parasitic hepatic cyst causing an intra-hepatic bile duct stricture: a case report

    Directory of Open Access Journals (Sweden)

    Hong Taeho

    2010-08-01

    Full Text Available Abstract Introduction We report an unusual presentation of a small hepatic cyst causing cholangitis. Case presentation A 70-year-old Asian man was hospitalized for aggravated chronic pain in the right upper portion of his abdomen. Fever developed after admission. Laboratory tests revealed elevated hepatobiliary enzymes, inflammatory markers and carbohydrate antigen 19-9 without hyperbilirubinemia. Ultrasound and computed tomography demonstrated dilatation of the left intra-hepatic bile ducts. Endoscopic retrograde cholangiopancreatography showed that the right intra-hepatic bile ducts were normally filled with contrast medium, but the left intra-hepatic bile ducts were not seen in the confluence. A left hepatectomy was performed because a hidden malignancy could not be excluded. The surgical findings showed no tumor around the bile duct but rather a 2 cm cyst in segment four of Couinaud's category of the liver around the hilum. The pathology report was a solitary non-parasitic hepatic cyst compressing the bile duct. Conclusion A very small solitary hepatic cyst might cause hepatic duct stricture if it is located near the hepatic hilum, and should be considered in the differential diagnosis of a hepatic duct stricture.

  14. Intraductal neoplasm of the intrahepatic bile duct:Clinicopathological study of 24 cases

    Institute of Scientific and Technical Information of China (English)

    Yoshiki Naito; Hironori Kusano; Osamu Nakashima; Eiji Sadashima; Satoshi Hattori; Tomoki Taira; Akihiko Kawahara

    2012-01-01

    AIM:To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB).METHODS:Clinicopathological features of 24 cases of INihB,which were previously diagnosed as biliary papilIomatosis or intraductal growth of intrahepatic biliary neoplasm,were reviewed.Mucin immunohistochemistry was performed for mucin (MUC)1,MUC2,MUC5AC and MUC6.Ki-67,P53 and β-catenin immunoreactivity were also examined.We categorized each tumor as adenoma (low grade),borderline (intermediate grade),and malignant (carcinoma in situ,high grade including tumors with microinvasion).RESULTS:Among 24 cases of INihB,we identified 24 tumors.Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB).In contrast,the remaining four tumors (17%) showed both tubular and papillary structures.In three of the four tumors (75%),macroscopic mucin secretion was limited but microscopic intracellular mucin was evident.Histologically,16 tumors (67%) were malignant,three (12%) were borderline,and five (21%) were adenoma.Microinvasion was found in four cases (17%).Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P =0.0095).Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2± 15.5 vs 7.5 ± 6.3,P < 0.01).In the 16 malignant cases,expression of MUC5AC showed borderline significant association with high Ki-67 LI (P =0.0622).Nuclear expression of β-catenin was observed in two (8%)of the 24 tumors,and these two tumors also showed MUC1 expression.P53 was negative in all tumors.CONCLUSION:Some cases of INihB have a tubular structure,and are subcategorized as IPNB with tubular structure.MUC1 expression in INihB correlates positively with degree of malignancy.

  15. Establishment and characterization of a novel human cholangiocarcinoma cell line with high metastatic activity.

    Science.gov (United States)

    Uthaisar, Kwuntida; Vaeteewoottacharn, Kulthida; Seubwai, Wunchana; Talabnin, Chutima; Sawanyawisuth, Kanlayanee; Obchoei, Sumalee; Kraiklang, Ratthaphol; Okada, Seiji; Wongkham, Sopit

    2016-09-01

    Cholangiocarcinoma (CCA) is a highly metastatic tumor, and the lung is a common site of metastasis. A greater understanding of the biology of metastases is needed to improve treatment outcomes. Herein, a highly metastatic human CCA subline, KKU-213L5 from an original cell line, KKU-213 that has marginally metastatic ability, was established and characterized. KKU-213L5 was selected in vivo through the fifth serial passage of pulmonary metastasized tissues via tail-vein injection in NOD/scid/Jak3 mice. The metastatic abilities of the KKU-213L5 cells were compared with the parental line in vitro and in vivo. The expression profile of this metastatic cell line was determined using real-time PCR. KKU-213L5 cells were found to possess higher metastatic phenotypes, i.e., growth rates, stem cell surface markers (CD133), migration and invasion characteristics when compared with the parental cells. Compared to the KKU-213 cells, KKU-213L5 cells formed larger tumors in subcutaneous xenografted mice and had a >10-fold increase in lung metastases in the tail-vein injected metastatic mouse model. Mice injected intravenously with KKU-213L5 cells had a significantly shorter survival. Analysis of the expressed genes related to progression of cancer revealed significant upregulation of anterior gradient protein-2 (AGR2) and suppression of KiSS-1 in the KKU-213L5 cells. The association of these two genes with metastasis was affirmed in CCA patient tissues since increased AGR2 expression and decreased KiSS-1 expression were found in higher stage patient tumors. In conclusion, a highly metastatic human CCA cell line was established and characterized. It is plausible that the differential expression between the parental KKU-213 and highly metastatic KKU-213L5 cells may be beneficial to classify novel genes associated with metastasis. The KKU-213L5 cell line should serve as a valued device for discovering the molecular mechanisms of CCA metastasis and enabling the search for an

  16. The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Wang Xin-sheng

    2010-07-01

    Full Text Available Abstract Objectives This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC to identify its role in tumor progression. Methods The expression of Snail and Slug mRNA in 52 human tissue samples of EHC was investigated. The mRNA of Snail and Slug were quantified using reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. We then investigated transfection of Slug cDNA in endogenous E-cadherin-positive human EHC FRH0201 cells, selectively induced the loss of E-cadherin protein expression, and then small interfering RNA (siRNA for inhibition of Slug expression in endogenous Slug-positive human EHC QBC939 cells, selectively induced the loss of Slug protein expression. A Boyden chamber transwell assay was used for invasion. Results Slug mRNA was overexpressed in 18 cases (34.6% of EHC compared with adjacent noncancerous tissue. E-Cadherin protein expression determined in the same 52 cases by immunohistochemistry was significantly down-regulated in those cases with Slug mRNA overexpression (P = 0.0001. The tumor and nontumor ratio of Slug mRNA was correlated with nodal metastasis(p = 0.0102, distant metastasis (p = 0.0001and Survival time(p = 0.0443. However, Snail mRNA correlated with neither E-cadherin expression nor tumor invasiveness. By inhibiting Slug expression by RNA interference, we found that reduced Slug levels upregulated E-cadherin and decreased invasion in QBC939 cell. When the QBC939 cells was infected with Slug cDNA,, significant E-cadherin was downregulated and increased invasion in QBC939 cell. Conclusions The results suggested that Slug expression plays an important role in both the regulation of E-cadherin expression and in the acquisition of invasive potential in human EHC. Slug is possibly a potential target for an antitumor therapy blocking the functions of invasion and metastasis in human EHCs.

  17. Cytotoxicity, toxicity, and anticancer activity of Zingiber officinale Roscoe against cholangiocarcinoma.

    Science.gov (United States)

    Plengsuriyakarn, Tullayakorn; Viyanant, Vithoon; Eursitthichai, Veerachai; Tesana, Smarn; Chaijaroenkul, Wanna; Itharat, Arunporn; Na-Bangchang, Kesara

    2012-01-01

    Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/ DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median IC50 (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and 27.86 μg/ml, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to

  18. Intrahepatic transplantation of hepatic oval cells for fulminant hepatic failure in rats

    Institute of Scientific and Technical Information of China (English)

    Chen-Xuan Wu; Qi Zou; Zheng-Yan Zhu; Ying-Tang Gao; Yi-Jun Wang

    2009-01-01

    AIM:To evaluate the effect of intrahepatic transplantation of hepatic oval cells (HOC) on fulminant hepatic failure (FHF) in rats. METHODS:HOC obtained from rats were labeled wi th green fluocescent protein (GFP) or 5, 6- carboxyfluorescein diacetate succinmidyl ester (CFDASE). Cell fluorescence was observed under fluorescent microscope at 6, 24, 48 and 72 h after labeling. CFDASE labeled HOC (5 × 106 cells each rat) were injected into livers of rats with FHF induced by D-galactosamine. Serum albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were measured at different time points. Liver function of rats was examined on days 3, 7, 14 and 21 after HOC transplantation. RESULTS:The positive rate of GFP and CFDA-SE labeled HOC was 10% and 90%, respectively, with no significant change in cell viabilities. The survival rate was higher in HOC transplantation group than in control group, especially 48 (9/15 vs 6/15) and 72 h (9/15 vs 4/15) after HOC transplantation. The serum ALT, AST and TBil levels were decreased while the serum Alb level was increased after HOC transplantation. Fluorescence became faded and diffused in liver tissues, suggesting that proliferation and differentiation occur in transplanted HOC. CONCLUSION:CFDA-SE is superior to GFP in labeling HOC, although fluorescence intensity is decreased progressively with cell division. HOC transplantation can improve the liver function and increase the survival rate of recipients.

  19. Predictors of premature delivery in patients with intrahepatic cholestasis of pregnancy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the predictive value of clinical symptoms and biochemical parameters for prematurity in intrahepatic cholestasis of pregnancy (ICP).METHODS: Sixty symptomatic patients with ICP were included in this retrospective analysis. Preterm delivery was defined as delivery before 37 wk gestation.Predictors of preterm delivery were disclosed by binary multivariate logistic regression analysis.RESULTS: Mean time of delivery was 38.1 ± 1.7 wk.No stillbirths occurred. Premature delivery was observed in eight (13.3%) patients. Total fasting serum bile acids were higher (47.8 ± 15.2 vs 41.0 ± 10.0 μmol/L, P <0.05), and pruritus tended to start earlier (29.0 ± 3.9 vs 31.6 ± 3.3 wk, P = 0.057) in patients with premature delivery when compared to those with term delivery.Binary multivariate logistic regression analysis revealed that early onset of pruritus (OR 1.70, 95% CI 1.23-2.95,P = 0.038) and serum bile acid (OR 2.13, 95% CI 1.13-3.25, P = 0.013) were independent predictors of preterm delivery.CONCLUSION: Early onset of pruritus and high levels of serum bile acids predict preterm delivery in ICP, and define a subgroup of patients at risk for poor neonatal outcome.

  20. Transjugular Intrahepatic Portosystemic Shunt Placement During Pregnancy: A Case Series of Five Patients

    International Nuclear Information System (INIS)

    Background and AimsComplications of portal hypertension, such as variceal hemorrhage and ascites, are associated with significant increases in both mortality and complications during pregnancy. Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating portal hypertension, but the safety of TIPS during pregnancy is largely unknown. In this series, we review five patients who underwent TIPS placement while pregnant and describe their clinical outcomes.MethodsFive pregnant patients with cirrhosis and portal hypertension underwent elective TIPS for complications of portal hypertension (four for secondary prevention of variceal bleeding and one for refractory ascites). Outcomes measured were recurrent bleeding episodes or need for further paracenteses during pregnancy, estimated radiation dose to the fetus and gestational age at delivery. All patients were followed after delivery to evaluate technical and clinical success of the procedure.ResultsAll five patients survived pregnancy and went on to deliver successfully. When TIPS was performed for secondary prevention of variceal bleeding (n = 4), no patients demonstrated variceal bleeding after TIPS placement. When TIPS was performed for refractory ascites (n = 1), no further paracenteses were required. All patients delivered successfully, albeit prematurely. Average radiation dose estimated to the fetus was 16.3 mGy.ConclusionsThis series suggests that TIPS can be performed in selective pregnant patients with portal hypertension, with little added risk to the mother or fetus

  1. Effects of Three Different Fibrates on Intrahepatic Cholestasis Experimentally Induced in Rats

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    Alaa El-Sisi

    2013-01-01

    Full Text Available Background. Activation of PPARα modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPARα agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE plus chlorpromazine (CPZ in rats. Method. 100 male albino rats (150–200 gm were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four groups received either ursodeoxycholic acid, fenofibrate, bezafibrate, or gemfibrozil for 7 days; 2 days before EE + CPZ, three other groups received one of the three fibrates after GW6471, a selective PPARα antagonist in addition to EE + CPZ. The final group received GW6471 alone. Results. The three fibrates showed marked reduction ( in serum levels of ALP, GGT, ALT, AST, total bile acids, bilirubin, TNFα, and IL-1β and in hepatic malondialdehyde level as well as a significant increase in bile flow rate ( in addition to improvements in histopathological parameters compared to diseased group. In groups which received GW6471, these effects were completely abolished with fenofibrate and partially blocked with bezafibrate and gemfibrozil. Conclusion. Short-term administration of fibrates to EE/CPZ-induced intrahepatic cholestatic rats exerted beneficial effects on hepatocellular damage and apoptosis. Fenofibrate anticholestatic effect was solely PPARα dependent while other mechanisms played part in bezafibrate and gemfibrozil actions.

  2. Urinary reducing substances in neonatal intrahepatic cholestasis caused by citrin deficiency

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    Ajmal Kader

    2014-06-01

    Full Text Available Neonatal cholestasis due to citrin deficiency is an autosomal recessive metabolic disorder caused by mutations in SLC25A13 gene. Mutations in this gene have a relatively high prevalence in East-Asian races compared to European or Afro-Caribbean races. Mutations in both sets of chromosomes often lead to self-limiting early onset cholestasis and growth retardation referred as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD. It is associated with a wide range of metabolic derangements including galactosemia and aminoacidemia, which can be detected on the newborn blood spot screening. Galactose, being a reducing sugar, can also be detected using Clinitest® (Clinitest® Reagent Tablets, Bayer Corporation, Diagnostics Division, Elkhart, IN, USA, a common screening test used in the work up of metabolic and hepatic diseases. In the western population classical galactosemia is often suspected when non glucose reducing substances are detected in the urine of infants with cholestasis. However in East-Asian races the prevalence of classical galactosemia is very low whilst galactosemia due to altered uridine diphosphate-galactose epimerase activity in NICCD is more common. We present a case of NICCD in an East-Asian infant with cholestasis and persistently positive urine reducing substance. Conclusion: NICCD deficiency should be considered as a differential diagnosis in any infant with cholestasis and persistently positive urinary reducing substances.

  3. Malignant potential of intrahepatic biliary papillomatosis: a case report and review of the literature

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    Arkadopoulos Nikolaos

    2006-10-01

    Full Text Available Abstract Background Biliary papillomatosis (BP is a rare disease entity with a strong malignant potential. It is characterized by multiple papillary adenomas involving both the intrahepatic and extrahepatic biliary tree. BP was considered in the past to be a disease with low malignant potential. However, a current review of the English literature revealed a high rate of malignant occurrence of approximately 41% and histological analysis along with the expression pattern of mucin core proteins (MUC and mucin carbohydrate antigens suggests that BP is a borderline or low grade malignant neoplasm with a high malignant potential. Case presentation A 68 year-old male patient was referred to our hospital due to the presence of sudden right upper quadrant abdominal pain, nausea and dark urine. Imaging workup demonstrated dilatation of the left hepatic duct without the presence of a space-occupying lesion. A left hepatectomy and cholecystectomy were carried out and histological analysis revealed a moderately to poorly differentiated carcinoma of the left hepatic duct in the background of biliary papillomatosis. Postoperative course was uneventful. Unfortunately, two years after initial diagnosis the patient rapidly deteriorated and died from multiple pulmonary secondary deposits. Conclusion BP should not be considered to be a benign disease. The clinical behavior, the high recurrence rate and the even higher malignant transformation occurrence, as well as the presence of carcinogenetic indicators (K-ras mutation, overexpression of p53, MUC and Tn antigens strongly support that BP is a low-grade neoplasm with high malignant potential.

  4. Comparison of a new stent and Wallstent for transjugular intrahepatic portosystemic shunt in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Gao Jun Teng; Michael A. Bettmann; P. Jack Hoopes; Li Yang

    2001-01-01

    AIM To evaluate a new balloon-expandablestainless steel stent (Cordis stent ) in atransjugular intrahepatic portosystemic shunt(TIPS) porcine model and compared withWallstent.METHODS TIPS was performed in 26 normaldomestic pigs weighing 20 kg-30 kg using aCordis stent or Wallstent (13 pigs in each stent).All pigs were sacrificed at the 14th day afterTIPS. The stent deployment delivery system,stent patency, and stent recoil after placementwere evaluated. Proliferative response inrepresentative histological sections from thecenter, hepatic and portal regions of the twostent designs were quantified.RESULTS The shunt was widely patent in 4pigs in the Cordis stent group (4/12, prematuredead in 1 pig), and in 5 pigs in the Wallstentgroup (5/13). All remaining stents of bothdesigns were occluded or stenotic. The meanquantified proliferation including thickness ofthe proliferation and the ratio of proliferation:total area in three assayed regions in Cordisstent and Wallstent was 2.18 mm:2.00 mm, and59.18 mm2: 51.66 mm2, respectively (P >0.05).The delivery system and mechanical propertiesof the Cordis stent fuctioned well.CONCLUSION The new Cordis stent isappropriate for TIPS procedure.

  5. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy

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    Ling Yu

    2014-01-01

    Full Text Available Objective. To determine the correlation between maternal bile acid (BA level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A 5.5 mg/kg BA, (B 1.4 mg/kg BA, and (C 1 ml physiological saline. Levels of total bile acid (TBA, ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats.

  6. Urokinase perfusion prevents intrahepatic ischemic-type biliary lesion in donor livers

    Institute of Scientific and Technical Information of China (English)

    Ren Lang; Qiang He; Zhong-Kui Jin; Dong-Dong Han; Da-Zhi Chen

    2009-01-01

    AIM: To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions (IITBLs). METHODS: A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions. The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year. The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year. In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver. The incidence of IITBLs was compared between the two groups. RESULTS: In the control group, the incidence of IITBLs was 5.9% (13/220 cases) after 3-11 mo of transplantation. In the experimental group, two recipients (1.4%) developed IITBLs at 3 and 6 mo after transplantation, respectively. The difference in the incidence between the two groups was statistically significant ( P < 0.05). CONCLUSION: Double perfusion of cadaveric livers from non-heart-beating donors with urokinase may reduce the incidence of IITBLs.

  7. The transjugular intrahepatic portosystemic stentshunt (TIPSS): A new nonoperative, transjugular percutaneous procedure

    International Nuclear Information System (INIS)

    In a 49-year-old male patient suffering from severe symptoms of end-stage portal hypertension and Child's stage C metabolic status, an intrahepatic stent-assisted portosystemic shunt was established for the first time exclusively by means of interventional radiology. Via transjugular access, a modified Brockenbrough needle was used to puncture the right branch of the portal vein via the right liver vein. As a target, a Dormia-basket was used that had previously been exposed in the right main portal branch. After successful puncture and balloon dilation of the artificial tract, two Palmaz stents were implanted to keep the tract permanently open. The portosystemic pressure gradient dropped from 38 to 18 mm Hg. The clinical status of the patient improved substantially during the following days. However, the patient died on day 11 after the procedure because of sudden onset of acute respiratory distress arising from acute nosocomial fungus and cytomegalovirus infection worsened by his primary immunoincompetence. Autopsy demonstrated a totally patent shunt without superficial thrombus. Microscopically, a thin endothelial layer on the inner shunt surface was found to be present. (orig.)

  8. In Search of an Accurate Evaluation of Intrahepatic Cholestasis of Pregnancy

    Directory of Open Access Journals (Sweden)

    Manuela Martinefski

    2012-01-01

    Full Text Available Until now, biochemical parameter for diagnosis of intrahepatic cholestasis of pregnancy (ICP mostly used is the rise of total serum bile acids (TSBA above the upper normal limit of 11 μM. However, differential diagnosis is very difficult since overlapped values calculated on bile acids determinations, are observed in different conditions of pregnancy including the benign condition of pruritus gravidarum. The aim of this work was to determine the better markers in ICP for a precise diagnosis together with parameters associated with severity of symptoms and treatment evaluation. Serum bile acid profiles were evaluated using capillary electrophoresis in 38 healthy pregnant women and 32 ICP patients and it was calculated the sensitivity, specificity, accuracy, predictive values and the relationships of certain individual bile acids in pregnant women in order to replace TSBA determinations. The evaluation of the results shows that LCA and UDCA/LCA ratio provided information for a more complete and accurate diagnosis and evaluation of ICP than calculation of solely TSBA levels in pregnant women.

  9. In vitro proliferation and differentiation of hepatic oval cells and their potential capacity for intrahepatic transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z.; Chen, J. [Liaocheng People' s Hospital, Department of Hepatobiliary Surgery, Liaocheng, Shandong, China, Department of Hepatobiliary Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong (China); Li, L.; Ran, J.H.; Liu, J. [The First People' s Hospital of Kunming, Kunming, Yunnan, China, The First People’s Hospital of Kunming, Kunming, Yunnan (China); Gao, T.X.; Guo, B.Y. [Dongchangfu Hospital of Women and Child Health Care, Liaocheng, Shandong (China); Li, X.H.; Liu, Z.H.; Liu, G.J.; Gao, Y.C.; Zhang, X.L. [Liaocheng People' s Hospital, Department of Hepatobiliary Surgery, Liaocheng, Shandong, China, Department of Hepatobiliary Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong (China)

    2013-07-30

    Hepatic oval cells (HOCs) are recognized as facultative liver progenitor cells that play a role in liver regeneration after acute liver injury. Here, we investigated the in vitro proliferation and differentiation characteristics of HOCs in order to explore their potential capacity for intrahepatic transplantation. Clusters or scattered HOCs were detected in the portal area and interlobular bile duct in the liver of rats subjected to the modified 2-acetylaminofluorene and partial hepatectomy method. Isolated HOCs were positive for c-kit and CD90 staining (99.8% and 88.8%, respectively), and negative for CD34 staining (3.6%) as shown by immunostaining and flow cytometric analysis. In addition, HOCs could be differentiated into hepatocytes and bile duct epithelial cells after leukemia inhibitory factor deprivation. A two-cuff technique was used for orthotopic liver transplantation, and HOCs were subsequently transplanted into recipients. Biochemical indicators of liver function were assessed 4 weeks after transplantation. HOC transplantation significantly prolonged the median survival time and improved the liver function of rats receiving HOCs compared to controls (P=0.003, Student t-test). Administration of HOCs to rats also receiving liver transplantation significantly reduced acute allograft rejection compared to control liver transplant rats 3 weeks following transplantation (rejection activity index score: control=6.3±0.9; HOC=3.5±1.5; P=0.005). These results indicate that HOCs may be useful in therapeutic liver regeneration after orthotopic liver transplantation.

  10. Transjugular Intrahepatic Portosystemic Shunt Placement During Pregnancy: A Case Series of Five Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ingraham, Christopher R., E-mail: cringra@uw.edu; Padia, Siddharth A., E-mail: spadia@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu [University of Washington, Department of Interventional Radiology (United States); Easterling, Thomas R., E-mail: easter@uw.edu [University of Washington, Department of Obstetrics and Gynecology (United States); Liou, Iris W., E-mail: irisl@medicine.washington.edu [University of Washington, Department of Medicine (United States); Kanal, Kalpana M., E-mail: kkanal@uw.edu [University of Washington, Physics Section, Department of Radiology (United States); Valji, Karim, E-mail: kvalji@uw.edu [University of Washington, Department of Interventional Radiology (United States)

    2015-10-15

    Background and AimsComplications of portal hypertension, such as variceal hemorrhage and ascites, are associated with significant increases in both mortality and complications during pregnancy. Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating portal hypertension, but the safety of TIPS during pregnancy is largely unknown. In this series, we review five patients who underwent TIPS placement while pregnant and describe their clinical outcomes.MethodsFive pregnant patients with cirrhosis and portal hypertension underwent elective TIPS for complications of portal hypertension (four for secondary prevention of variceal bleeding and one for refractory ascites). Outcomes measured were recurrent bleeding episodes or need for further paracenteses during pregnancy, estimated radiation dose to the fetus and gestational age at delivery. All patients were followed after delivery to evaluate technical and clinical success of the procedure.ResultsAll five patients survived pregnancy and went on to deliver successfully. When TIPS was performed for secondary prevention of variceal bleeding (n = 4), no patients demonstrated variceal bleeding after TIPS placement. When TIPS was performed for refractory ascites (n = 1), no further paracenteses were required. All patients delivered successfully, albeit prematurely. Average radiation dose estimated to the fetus was 16.3 mGy.ConclusionsThis series suggests that TIPS can be performed in selective pregnant patients with portal hypertension, with little added risk to the mother or fetus.

  11. Cardiac and renal effects of a transjugular intrahepatic portosystemic shunt in cirrhosis.

    Science.gov (United States)

    Busk, Troels M; Bendtsen, Flemming; Møller, Søren

    2013-05-01

    Refractory ascites and recurrent variceal bleeding are among the serious complications of portal hypertension and cirrhosis for which a transjugular intrahepatic portosystemic shunt (TIPS) can be used. Cirrhotic patients have varying degrees of haemodynamic derangement, mainly characterized by peripheral arterial vasodilatation, central underfilling and activation of several vasoactive systems. These changes affect the heart, the lungs and the kidneys in particular. The cardiac effects of TIPS are immediate and are related to the redirection of blood from the splanchnic circulation into the systemic circulation, resulting in worsening of the hyperdynamic circulation with increasing cardiac output and decreasing systemic vascular resistance; further, TIPS may unmask a latent diastolic dysfunction of the heart. However, the renal effects of TIPS seem to be beneficial as renal function tends to improve in patients with the hepatorenal syndrome. The clinical and haemodynamic effects of TIPS have been studied intensively and will be reviewed in the present paper. Considerable knowledge on the effects of TIPS on the pathophysiology of cirrhosis has been gained, but studies on the central haemodynamic effects are warranted to refine the already applied treatments and develop new treatment modalities. PMID:23325273

  12. Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome.

    Science.gov (United States)

    Meissner, Eric G; Wu, David; Osinusi, Anu; Bon, Dimitra; Virtaneva, Kimmo; Sturdevant, Dan; Porcella, Steve; Wang, Honghui; Herrmann, Eva; McHutchison, John; Suffredini, Anthony F; Polis, Michael; Hewitt, Stephen; Prokunina-Olsson, Ludmila; Masur, Henry; Fauci, Anthony S; Kottilil, Shyamasundaran

    2014-08-01

    BACKGROUND. Hepatitis C virus (HCV) infects approximately 170 million people worldwide and may lead to cirrhosis and hepatocellular carcinoma in chronically infected individuals. Treatment is rapidly evolving from IFN-α-based therapies to IFN-α-free regimens that consist of directly acting antiviral agents (DAAs), which demonstrate improved efficacy and tolerability in clinical trials. Virologic relapse after DAA therapy is a common cause of treatment failure; however, it is not clear why relapse occurs or whether certain individuals are more prone to recurrent viremia. METHODS. We conducted a clinical trial using the DAA sofosbuvir plus ribavirin (SOF/RBV) and performed detailed mRNA expression analysis in liver and peripheral blood from patients who achieved either a sustained virologic response (SVR) or relapsed. RESULTS. On-treatment viral clearance was accompanied by rapid downregulation of IFN-stimulated genes (ISGs) in liver and blood, regardless of treatment outcome. Analysis of paired pretreatment and end of treatment (EOT) liver biopsies from SVR patients showed that viral clearance was accompanied by decreased expression of type II and III IFNs, but unexpectedly increased expression of the type I IFN IFNA2. mRNA expression of ISGs was higher in EOT liver biopsies of patients who achieved SVR than in patients who later relapsed. CONCLUSION. These results suggest that restoration of type I intrahepatic IFN signaling by EOT may facilitate HCV eradication and prevention of relapse upon withdrawal of SOF/RBV. TRIAL REGISTRATION. ClinicalTrials.gov NCT01441180.

  13. Molecular hydrogen attenuates hypoxia/reoxygenation injury of intrahepatic cholangiocytes by activating Nrf2 expression.

    Science.gov (United States)

    Yu, Jianhua; Zhang, Weiguang; Zhang, Rongguo; Jiang, Guixing; Tang, Haijun; Ruan, Xinxian; Ren, Peitu; Lu, Baochun

    2015-11-01

    Hypoxia/reoxygenation (H/R) injury of cholangiocytes causes serious biliary complications during hepatobiliary surgeries. Molecular hydrogen (H2) has been shown to be effective in protecting various cells and organs against oxidative stress injury. Human liver cholangiocytes were used to determine the potential protective effects of hydrogen against cholangiocyte H/R injury and explore the underlying mechanisms. We found that H2 ameliorated H/R-induced cholangiocytes apoptosis. Our study revealed that H2 activated NF-E2-related factor 2 (Nrf2) and downstream cytoprotective protein expression. However, the protective function of H2 was abolished when Nrf2 was silenced. Apoptosis in cholangiocytes isolated from a rat model of liver ischemia/reperfusion injury indicated that H2 significantly attenuates ischemia/reperfusion cholangiocyte injury in vivo. In conclusion, our study shows that H2 protects intrahepatic cholangiocytes from hypoxia/reoxygenation-induced apoptosis in vitro or in vivo, and this phenomenon may depend on activating Nrf2 expression.

  14. Scintigraphic evaluation of hepatic blood flow after intrahepatic portosystemic shunt (TIPS).

    Science.gov (United States)

    Menzel, J; Schober, O; Reimer, P; Domschke, W

    1997-06-01

    In patients with liver cirrhosis a transjugularly placed intrahepatic portocaval shunt (TIPS) is a non-surgical portosystemic device which aims to reduce portal venous pressure. In comparison with Doppler sonography, we evaluated in 28 patients the diagnostic impact of liver perfusion scintigraphy (with technetium-99m diethylene triamine penta-acetic acid) in the assessment of changes in the hepatic blood flow after TIPS shunting. The arterial and portal contributions to hepatic flow were calculated from the areas under the biphasic time-activity curve. In the course of TIPS shunting, patency is threatened by reocclusion. Angiography is the gold standard for TIPS shunt reassessment. However, there is a need for a less invasive diagnostic procedure, such as scintigraphy or Doppler sonography, for the early detection of shunt insufficiency. Scintigraphy demonstrated that prior to TIPS shunting the portal venous contribution to hepatic perfusion was reduced to 29.2%, this reduction being due to portal hypertension. After TIPS placement a significant increase in portal venous perfusion was observed (38.2%; Pscintigraphically measured portal venous contribution to hepatic blood flow. Hepatic perfusion scintigraphy appears to be a valuable method to determine the immediate effect of TIPS on hepatic blood flow. Post-TIPS follow-up studies of hepatic haemodynamics by liver perfusion scintigraphy appear able to contribute to the detection of TIPS shunt occlusion before the clinical consequences of this complication have become apparent. PMID:9169570

  15. Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

    Institute of Scientific and Technical Information of China (English)

    Maria Angela Bellomo-Brandao; Paula D Andrade; Sandra CB Costa; Cecilia AF Escanhoela; Jose Vassallo; Gilda Porta; Adriana MA De Tommaso; Gabriel Hessel

    2009-01-01

    AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology,histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods. METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's files and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specific positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%),and PCR, 6/77 (8%). Only one patient had positive immunohistochemical findings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity,88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%.CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.

  16. Duodenal variceal bleeding after balloon-occluded retrograde transverse obliteration: Treatment with transjugular intrahepatic portosystemic shunt

    Institute of Scientific and Technical Information of China (English)

    Min Joung Kim; Byoung Kuk Jang; Woo Jin Chung; Jae Seok Hwang; Young Hwan Kim

    2012-01-01

    We report a case of duodenal varix bleeding as a long term complication of balloon occluded retrograde transvenous obliteration (BRTO),which was successfully treated with a transjugular intrahepatic portosystemic shunt (TIPS).A 57-year-old man was admitted to the emergency room suffering from melena.He had undergone BRTO to treat gastric varix bleeding 5 mo before admission.Endoscopy and a computed tomography (cr) scan showed complete obliteration of the gastric varix,but the nodular varices in the second portion of the duodenum expanded after BRTO,and spurting blood was seen.TIPS was performed for treatment of duodenal variceal bleeding,because attempts at endoscopic varix ligation were unsuccessful.The postoperative course was uneventful and the patient was discharged without complications.A follow up CT scan obtained 21 mo after TIPS revealed a patent TIPS tract and complete obliteration of duodenal varices,but multinodular hepatocellular carcinoma had developed.He died of hepatic failure 28 mo after TIPS.

  17. The interventional treatment for biliary re-stenosis after metallic stents placement in patients with malignant obstruction due to cholangiocarcinoma

    International Nuclear Information System (INIS)

    Objective: To explore the interventional treatment for biliary re-stenosis after metallic stents placement in patients due to cholangiocarcinoma and evaluate its therapeutic effect. Methods: Percutaneous metallic stents placement or combined with continuously infusion arterial chemotherapeutic and chemotherapeutic embolization were performed in 12 patients with biliary re-stenosis using 12 metallic stents. Results: Once stent placement was 100% successful in all 12 cases, TBIL, ALT, GTP and AKP values 7 days postoperatively were significantly lower than that in preoperation. Jaundice was reduced satisfactorily in 12 patients. 3 patients were undergone continuously arterial chemotherapeutics infusion and chemotherapeutic embolization 4 weeks after stents placement. Conclusions: Percutaneous replacement of biliary metallic stents was effective and safe for palliation of malignant biliary re-stenosis and would be much better when combined with continuously arterial chemotherapeutics infusion and chemotherapeutic embolization

  18. Modifying Health Behavior for Liver Fluke and Cholangiocarcinoma Prevention with the Health Belief Model and Social Support Theory.

    Science.gov (United States)

    Padchasuwan, Natnapa; Kaewpitoon, Soraya J; Rujirakul, Ratana; Wakkuwattapong, Parichart; Norkaew, Jun; Kujapun, Jirawoot; Ponphimai, Sukanya; Chavenkun, Wasugree; Kompor, Pontip; Kaewpitoon, Natthawut

    2016-01-01

    The liver fluke Opisthorchis viverrini is a serious health problem in Thailand. Infection is associated with cholangiocarcinoma (CCA), endemic among human populations in northeast and north Thailand where raw fish containing fluke metacercariae are frequently consumed. Recently, Thailand public health authorities have been organized to reduce morbidity and mortality particularly in the northeast through O. viverrini and CCA screening projects. Health modfication is one of activities included in this campaign, but systemic guidelines of modifying and developing health behavior for liver flukes and CCA prevention in communities towards health belief and social support theory are still various and unclear. Here we review the guidelines for modifying and developing health behavior among populations in rural communities to strengthen understanding regarding perceived susceptibility, severity, benefits, and barriers to liver fluke and CCA prevention. This model may be useful for public health of cancers and related organizations to further health behavior change in endemic areas. PMID:27644606

  19. Fulminant phlegmasia cerulea dolens with concurrent cholangiocarcinoma and a lupus anticoagulant: a case report and review of the literature.

    Science.gov (United States)

    Chang, Grace; Yeh, James J

    2014-07-01

    Phlegmasia cerulea dolens (PCD) is an aggressive and life-threatening form of venous thrombosis complicated by ischemic necrosis. Massive thrombosis extends to collateral veins resulting in venous congestion with fluid sequestration in the interstitium causing collapse of arterioles, which progresses to ischemia and, if severe, circulatory collapse and shock. The mortality rate for PCD is as high as 40%, especially when gangrene develops. PCD has been associated with acquired thrombophilias, including malignancy and antiphospholipid syndrome (APS). We present a unique case of a patient with PCD refractory to anticoagulant and thrombolytic therapy, whose fulminant course was attributed to concurrent cholangiocarcinoma and antiphospholipid antibodies identified by a positive lupus anticoagulant assay. This case highlights the importance of uncovering precipitating causes of thromboembolism, which may offer prognostic information and may necessitate therapy beyond anticoagulation and thrombolysis to reduce the morbidity of PCD. The current literature on PCD and APS, along with their associations with malignancy, is reviewed. PMID:24553060

  20. 肝门部胆管癌的手术治疗%Surgical management of hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    冀亮; 孙备; 姜洪池; 陈华; 白雪巍; 李军

    2013-01-01

    Objective To summarize the experience in surgical management of hilar cholangiocarcinoma.Methods The clinical data of 88 patients with hilar cholangiocarcinoma who received surgical treatment at the First Affiliated Hospital of Harbin Medical University from January 2007 to December 2011 were retrospectively analyzed.All the patients were diagnosed by imaging examination.According to the severity of jaundice and predictive remnant liver volume,19 patients received percutaneous transhepatic cholangial drainage (PTCD) and 4 received portal vein embolization.The fundamental operation consisted of hilar cholangiocarcinoma resection,skeletonization of hepatoduodenum ligament and Roux-en-Y cholangiojejunostomy,and the transanastomotic stent was placed for 6 months.The count data were analyzed using the chi-square test; the survival rate was analysed using the Kaplan-Meier method; the survival was analyzed using the Log-rank test.Results Of the 88 patients,58 patients (including 11 patients who received PTCD) received hilar cholangiocarcinoma resection.Of the 58 patients,43 (including 4 patients who received portal vein embolization preoperatively) received R0 resection,and 15 received palliative resection.Thirty patients received internal and (or) external drainage.Commitant partial hepatectomy was performed on 22 patients (including 9 received left hemihepatectomy,2 received extended left hemihepatectomy,7 received left hemihepatectomy + caudate lobectomy,4 received right hemihepatectomy).Commitant pancreatico-duodenectomy was performed on 7 patients,commitant hepatic artery resection on 3 patients,and commitant portal vein resection on 2 patients.According to the modified Bismuth-Corlette classification,there were 17 patients with type Ⅰ,19 with type Ⅱ,21 with type Ⅲa,20 with type Ⅲb,and 11 with type Ⅳ.Of the 58 patients who received hilar cholangiocarcinoma resection,19 had postoperative complications,and 2 patients died within 30 days after operation

  1. Simultaneous Non-Functioning Neuroendocrine Carcinoma of the Pancreas and Extra-Hepatic Cholangiocarcinoma. A Case of Early Diagnosis and Favorable Post-Surgical Outcome

    Directory of Open Access Journals (Sweden)

    Simone Maurea

    2011-05-01

    Full Text Available Context Thanks to the wide use of diagnostic imaging modalities, multiple primary malignancies are being diagnosed more frequently and different associations of malignancies have been reported in this setting. Case report In this paper, we describe the case of a patient with non-functioning well-differentiated neuroendocrine carcinoma of the head of the pancreas associated with extra-hepatic cholangiocarcinoma, in which an early diagnosis using magnetic resonance imaging allowed a good outcome. Conclusion The simultaneous association of neuroendocrine pancreatic tumors and cholangiocarcinoma has not yet been described; however, this association should be considered and, due to the high contrast of magnetic resonance imaging, this technique is recommended in such patient in order to reach an accurate diagnosis.

  2. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience

    Science.gov (United States)

    Landry, Jerome C.

    2016-01-01

    Background Cholangiocarcinoma (CCA) is a bile duct tumor with a grim prognosis. The median survival after radiotherapy of unresectable disease is 9-12 months. The following is a review of our experience with neoadjuvant (NEO) chemoradiation followed by orthotopic liver transplantation (OLT) for CCA. Methods Ten patients with CCAs were selected as candidates for NEO-OLT between 2008-2011. Patients with unresectable CCA above the cystic duct without intra or extrahepatic metastases were eligible. Primary sclerosing cholangitis (PSC) patients were included due to their poor resection response. Patients initially received external-beam radiation [via conventional fields or volumetric-modulated arc therapy (VMAT)] plus capecitabine (XEL) or 5-fluorouracil (5-FU), followed by either Iridium192 (Ir192) brachytherapy high dose rate (HDR) or external boost. 5-FU or XEL was administered until OLT. Patients underwent periodic surveillance computed tomography (CT)/MRIs after OLT. Primary endpoints included actuarial rates (AR)/crude rates (CR) of overall survival (OS), and local control (LC) at 6, 12, and 24 months. Results Five males and five females were identified. Mean age was 58.3 years (range, 38-71 years). Mean composite radiation dose delivered was 59.0 Gy (range, 54-71.4 Gy). Forty percent of patients had an HDR boost. Fifty percent of patients received XEL during NEO. Two patients were excluded from the analysis as they did not go on to OLT due to metastases (n=1) and death due to GI bleed (n=1). Thirty-eight percent of the OLT patients had a pathological complete response (pCR) after NEO, while 25% required a Whipple due to positive margins. Median follow-up for the OLT group was 23 months (range, 6.5-37 months). Six, twelve, and twenty-four months LC AR was 100%. LC CR was 100% at longest interval (30 months). Six, twelve, and twenty-four months OS AR was 100%, 87.5%, and 87.5%, respectively. Mean OS AR was 30.2 months (95% CI: 22.8-37.7). OS CR was 75% at longest

  3. Intrahepatic transneedle inoculation of VX2 particles for obtaining a solitary hepatic tumor in an animal model

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    Cho, Jin Han; Choi, Jong Cheol; Shin, Tae Beom; Park, Byeong Ho [Dong-A University, School of Medicine, Busan (Korea, Republic of)

    2005-07-15

    The purpose of this study was to develop a large animal (rabbit) model which has a proper solitary intrahepatic tumor with lower leakage rates through less traumatic methods. Consequently, we evaluated tumor progression following the intrahepatic inoculation of VX2 cells into New Zealand white rabbits to acquire baseline data on the progression of a VX2 tumor. Twenty New Zealand white rabbits, each weighting 2.5-3 kg, were selected for this study. A 1 mm{sup 3} VX2 tumor fragment was created and then minced to enable the particles to pass through a 21 G needle mounting in a tuberculin syringe with 0.1 ml of normal saline. The minced VX2 tumor particles were injected into the subcapsular parenchyma of the left hepatic lobe. A 21 G needle was used to avoid penetrating large hepatic vessels. In order to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route, a purse-string suture around the puncture site was made using black silk 4-0. The tumor particles were then injected through the center of the suture. While removing the needle, the suture was tightened to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route. Finally, the injection site was covered with a Surgical patch. The inoculated intrahepatic VX2 tumors were then imaged with a 16 channel multidetector CT every week for the duration of the study. The CT images covered from the lung apex to the pelvic floor. Two radiologists evaluated the size, location, and peritoneal seeding of the tumors as well as metastasis of other organs. Three rabbits were sacrificed as random beginning in the second week, and this process continued on a weekly basis for the duration of the study. The CT images and pathologic findings for the sacrificed rabbits were correlated. The inoculated intrahepatic VX2 tumors were not visible in the first week. By the second week 66.7% were visible on CT images and by the third week all tumors were visible. Of the twenty rabbits, three (15

  4. Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin*

    Science.gov (United States)

    Chen, Jiong-huang; Xiang, Jian-yang; Ding, Guo-ping; Cao, Li-ping

    2016-01-01

    Objective: The aim of our study is to observe the impact of cholangiocarcinoma-derived exosomes on the antitumor activities of cytokine-induced killer (CIK) cells and then demonstrate the appropriate mechanism. Methods: Tumor-derived exosomes (TEXs), which are derived from RBE cells (human cholangiocarcinoma line), were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting (FACS) was performed to determine the phenotypes of TEX-CIK and N-CIK (normal CIK) cells. The concentrations of tumor necrosis factor-α (TNF-α) and perforin in the culture medium supernatant were examined by using an enzyme-linked immunosorbent assay (ELISA) kit. A CCK-8 kit was used to evaluate the cytotoxic activity of the CIK cells to the RBE cell line. Results: The concentrations of TNF-α and perforin of the group TEX-CIK were 138.61 pg/ml and 2.41 ng/ml, respectively, lower than those of the group N-CIK 194.08 pg/ml (Pexosomes inhibit the antitumor activity of CIK cells by down-regulating the population of CD3+, CD8+, NK (CD56+), and CD3+CD56+ cells and the secretion of TNF-α and perforin. TEX may play an important role in cholangiocarcinoma immune escape. PMID:27381730

  5. A long survivor with local relapse of hilar cholangiocarcinoma after R1 surgery treated with chemoradiotherapy: a case report and literature review.

    Science.gov (United States)

    Okabe, Hirohisa; Chikamoto, Akira; Maruno, Masataka; Hashimoto, Daisuke; Imai, Katsunori; Taki, Katsunobu; Arima, Kota; Ishiko, Takatoshi; Uchiyama, Hideaki; Ikegami, Toru; Harimoto, Norifumi; Itoh, Shinji; Yoshizumi, Tomoharu; Beppu, Toru; Baba, Hideo; Maehara, Yoshihiko

    2016-12-01

    The treatment outcome of extrahepatic cholangiocarcinoma remains insufficient because it is difficult to obtain accurate diagnosis of tumor spreading and effective treatment agent is quite limited in spite of substantial current efforts, all of which have been unsuccessful except for gemcitabine plus cisplatin. The patient was a 60-year-old female who had developed hilar cholangiocarcinoma and underwent extrahepatic bile duct resection. Although it was conceivable that it would be the R1 resection, the patient wanted to receive limited resection to avoid postoperative complication mainly because she was depressed. In histology, interstitial spreading of tumor was appreciated at the surgical margin of bile duct. The patient did not accept to receive the additional treatment after the surgery and hardly visited the hospital to take the periodical test for monitoring the residual cancer cells. As expected, the local relapse of tumor was appreciated 1 year after the R1 surgery. She chose radiotherapy and agreed with subsequent S-1 treatment for 26 months. Consequently, elevated CA19-9 was decreased, and local relapse has been successfully controlled for more than 7 years after the relapse of tumor. Here, we report quite a rare case in terms of long survivor after chemoradiotherapy on locally relapsed unresectable hilar cholangiocarcinoma. PMID:27376654

  6. Intrahepatic Transcriptional Signature Associated with Response to Interferon-α Treatment in the Woodchuck Model of Chronic Hepatitis B.

    Directory of Open Access Journals (Sweden)

    Simon P Fletcher

    2015-09-01

    Full Text Available Recombinant interferon-alpha (IFN-α is an approved therapy for chronic hepatitis B (CHB, but the molecular basis of treatment response remains to be determined. The woodchuck model of chronic hepatitis B virus (HBV infection displays many characteristics of human disease and has been extensively used to evaluate antiviral therapeutics. In this study, woodchucks with chronic woodchuck hepatitis virus (WHV infection were treated with recombinant woodchuck IFN-α (wIFN-α or placebo (n = 12/group for 15 weeks. Treatment with wIFN-α strongly reduced viral markers in the serum and liver in a subset of animals, with viral rebound typically being observed following cessation of treatment. To define the intrahepatic cellular and molecular characteristics of the antiviral response to wIFN-α, we characterized the transcriptional profiles of liver biopsies taken from animals (n = 8-12/group at various times during the study. Unexpectedly, this revealed that the antiviral response to treatment did not correlate with intrahepatic induction of the majority of IFN-stimulated genes (ISGs by wIFN-α. Instead, treatment response was associated with the induction of an NK/T cell signature in the liver, as well as an intrahepatic IFN-γ transcriptional response and elevation of liver injury biomarkers. Collectively, these data suggest that NK/T cell cytolytic and non-cytolytic mechanisms mediate the antiviral response to wIFN-α treatment. In summary, by studying recombinant IFN-α in a fully immunocompetent animal model of CHB, we determined that the immunomodulatory effects, but not the direct antiviral activity, of this pleiotropic cytokine are most closely correlated with treatment response. This has important implications for the rational design of new therapeutics for the treatment of CHB.

  7. Relationship between the intrahepatic expression of 'e' and 'c' epitopes of the nucleocapsid protein of hepatitis B virus and viraemia.

    Science.gov (United States)

    Ballaré, M; Lavarini, C; Brunetto, M R; Petruzzelli, E; Dovis, M; Molino, G; Bonino, F

    1989-01-01

    The relationship between hepatitis B viraemia and intrahepatic HBV nucleocapsid proteins (HBcAg and HBeAg) was studied in 18 patients with chronic hepatitis B. Monoclonal antibodies (MoABs) were obtained in BALB/c mice primed with recombinant HBV nucleocapsid proteins. Four MoABs reacting with recombinant proteins gave positive results in competitive assays. Two reacted as anti-HBc and two as anti-HBe. One of them showed a strong affinity for the cytoplasmic, membrane-bound antigen (P23e) of infected hepatocytes while the latter showed a higher specificity for serum HBeAg than for the intrahepatic antigen. Anti-HBc MoABs had a staining capacity for liver cell nuclei comparable with that of polyclonal antibodies. Overall the anti-HBc MoABs stained the liver cell nuclei in 86% of cases, while anti-HBe MoABs stained in 58% of cases. The hepatocyte cytoplasm was stained by anti-HBc MoABs and anti-HBe MoABs in 64% and 72% of cases respectively. Not one of 12 control liver biopsies was stained. Viraemia (HBV-DNA) was measured by dot blot hybridization and was correlated with the number of hepatocytes containing the nucleocapsid antigen. The highest levels of HBV-DNA (greater than 10(8) genomes/ml) were detected in patients with prevalent nuclear staining while the lowest ones were observed in those with prevalent cytoplasmic expression of this antigen. The application of anti-HBV-nucleocapsid MoABs in diagnostics requires careful scrutiny since some are specific for the circulating antigen while others show a higher affinity for the intrahepatic antigen. PMID:2467769

  8. Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort.

    Directory of Open Access Journals (Sweden)

    Michelle Rook

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP has important fetal implications. There is increased risk for poor fetal outcomes, including preterm delivery, meconium staining of amniotic fluid, respiratory distress, fetal distress and demise. METHODS: One hundred and one women diagnosed with ICP between January 2005 and March 2009 at San Francisco General Hospital were included in this study. Single predictor logistic regression models were used to assess the associations of maternal clinical and biochemical predictors with fetal complications. Clinical predictors analyzed included age, race/ethnicity, gravidity, parity, history of liver or biliary disease, history of ICP in previous pregnancies, and induction. Biochemical predictors analyzed included serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, albumin, total protein, and total bile acids (TBA. RESULTS: The prevalence of ICP was 1.9%. Most were Latina (90%. Labor was induced in the majority (87% and most were delivered by normal spontaneous vaginal delivery (84%. Fetal complications occurred in 33% of the deliveries, with respiratory distress accounting for the majority of complications. There were no statistically significant clinical or biochemical predictors associated with an increased risk of fetal complications. Elevated TBA had little association with fetal complications until reaching greater than 100 µmoL/L, with 3 out of 5 having reported complications. ICP in previous pregnancies was associated with decreased risk of fetal complications (OR 0.21, p = 0.046. There were no cases of late term fetal demise. CONCLUSIONS: Maternal clinical and laboratory features, including elevated TBA, did not appear to be substantial predictors of fetal complications in ICP.

  9. Three-Dimensional Path Planning Software-Assisted Transjugular Intrahepatic Portosystemic Shunt: A Technical Modification

    International Nuclear Information System (INIS)

    PurposeThis study was designed to report our results with a modified technique of three-dimensional (3D) path planning software assisted transjugular intrahepatic portosystemic shunt (TIPS).Methods3D path planning software was recently developed to facilitate TIPS creation by using two carbon dioxide portograms acquired at least 20° apart to generate a 3D path for overlay needle guidance. However, one shortcoming is that puncturing along the overlay would be technically impossible if the angle of the liver access set and the angle of the 3D path are not the same. To solve this problem, a prototype 3D path planning software was fitted with a utility to calculate the angle of the 3D path. Using this, we modified the angle of the liver access set accordingly during the procedure in ten patients.ResultsFailure for technical reasons occurred in three patients (unsuccessful wedged hepatic venography in two cases, software technical failure in one case). The procedure was successful in the remaining seven patients, and only one needle pass was required to obtain portal vein access in each case. The course of puncture was comparable to the 3D path in all patients. No procedure-related complication occurred following the procedures.ConclusionsAdjusting the angle of the liver access set to match the angle of the 3D path determined by the software appears to be a favorable modification to the technique of 3D path planning software assisted TIPS

  10. Radiofrequency Ablation for the Treatment of Hepatocellular Carcinoma in Patients with Transjugular Intrahepatic Portosystemic Shunts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jonathan K., E-mail: jonathan.park09@gmail.com [David Geffen School of Medicine at UCLA, Department of Radiology (United States); Al-Tariq, Quazi Z., E-mail: qat200@gmail.com [Stanford University School of Medicine, Department of Radiology (United States); Zaw, Taryar M., E-mail: taryar.zaw@gmail.com; Raman, Steven S., E-mail: sraman@mednet.ucla.edu; Lu, David S.K., E-mail: dlu@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Radiology (United States)

    2015-10-15

    PurposeTo assess radiofrequency (RF) ablation efficacy, as well as the patency of transjugular intrahepatic portosystemic shunts (TIPSs), in patients with hepatocellular carcinoma (HCC).Materials and MethodsRetrospective database review of patients with pre-existing TIPS undergoing RF ablation of HCC was conducted over a 159-month period ending in November 2013. TIPS patency pre- and post-RF ablation was assessed by ultrasound, angiography, and/or contrast-enhanced CT or MRI. Patient demographics and immediate post-RF ablation outcomes and complications were also reviewed.Results19 patients with 21 lesions undergoing 25 RF ablation sessions were included. Child-Pugh class A, B, and C scores were seen in 1, 13, and 5 patients, respectively. Eleven patients (58 %) ultimately underwent liver transplantation. Immediate technical success was seen in all ablation sessions without residual tumor enhancement (100 %). No patients (0 %) suffered liver failure within 1 month of ablation. Pre-ablation TIPS patency was demonstrated in 22/25 sessions (88 %). Of 22 cases with patent TIPS prior to ablation, post-ablation patency was demonstrated in 22/22 (100 %) at immediate post-ablation imaging and in 21/22 (95 %) at last follow-up (1 patient was incidentally noted to have occlusion 31 months later). No immediate complications were observed.ConclusionAblation efficacy was similar to the cited literature values for patients without TIPS. Furthermore, TIPS patency was preserved in the majority of cases. Patients with both portal hypertension and HCC are not uncommonly encountered, and a pre-existing TIPS does not appear to be a definite contraindication for RF ablation.

  11. Primum non nocere: how active management became modus operandi for intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Henderson, Cassandra E; Shah, Reena R; Gottimukkala, Sri; Ferreira, Khaldun K; Hamaoui, Abraham; Mercado, Ray

    2014-09-01

    The Royal College of Obstetrics and Gynecology does not endorse routine active management of intrahepatic cholestasis of pregnancy (ICP)-affected pregnancies. In contrast, the American College of Obstetricians and Gynecologists supports active management protocols for ICP. To investigate this controversy, we evaluated the evidence supporting ICP as a medical indication for early term delivery and the evolution of active management protocols for ICP. Sixteen articles published between 1986 and 2011 were identified. We created 2 groups based on whether obstetric care included active management. Group 1 comprised 6 uncontrolled reports without active management that were published between 1967 and 1983 that described high perinatal mortality rates that primarily were related to prematurity sequel. This group became the fundamental 'core' evidence for ICP-associated stillbirths and by extrapolation justification for active management. Group 2 was comprised of 10 reports in which the authors credited empirically adopted active management with the observed low stillbirth rates in ICP-affected pregnancies. Although the group 1 articles routinely are cited as evidence of ICP-associated stillbirth risk, the 1.2% stillbirth rate (4/331) in this group is similar to the background stillbirth rates of 1.1% (11/1000) and 0.6% (6/1000) in 1967 and 2011, respectively (P = .062 and P = .0614, respectively). Likewise, the stillbirth rates for articles in group 2 were similar to their respective national stillbirth rate. Nevertheless, group 2 articles have become the evidence-based support for active management. We found no evidence to support the practice of active management for ICP. PMID:24704063

  12. Three-Dimensional Path Planning Software-Assisted Transjugular Intrahepatic Portosystemic Shunt: A Technical Modification

    Energy Technology Data Exchange (ETDEWEB)

    Tsauo, Jiaywei, E-mail: 80732059@qq.com; Luo, Xuefeng, E-mail: luobo-913@126.com [West China Hospital of Sichuan University, Institute of Interventional Radiology (China); Ye, Linchao, E-mail: linchao.ye@siemens.com [Siemens Ltd, Healthcare Sector (China); Li, Xiao, E-mail: simonlixiao@gmail.com [West China Hospital of Sichuan University, Institute of Interventional Radiology (China)

    2015-06-15

    PurposeThis study was designed to report our results with a modified technique of three-dimensional (3D) path planning software assisted transjugular intrahepatic portosystemic shunt (TIPS).Methods3D path planning software was recently developed to facilitate TIPS creation by using two carbon dioxide portograms acquired at least 20° apart to generate a 3D path for overlay needle guidance. However, one shortcoming is that puncturing along the overlay would be technically impossible if the angle of the liver access set and the angle of the 3D path are not the same. To solve this problem, a prototype 3D path planning software was fitted with a utility to calculate the angle of the 3D path. Using this, we modified the angle of the liver access set accordingly during the procedure in ten patients.ResultsFailure for technical reasons occurred in three patients (unsuccessful wedged hepatic venography in two cases, software technical failure in one case). The procedure was successful in the remaining seven patients, and only one needle pass was required to obtain portal vein access in each case. The course of puncture was comparable to the 3D path in all patients. No procedure-related complication occurred following the procedures.ConclusionsAdjusting the angle of the liver access set to match the angle of the 3D path determined by the software appears to be a favorable modification to the technique of 3D path planning software assisted TIPS.

  13. Tissue signatures influence the activation of intrahepatic CD8+ T cells against malaria sporozoites

    Directory of Open Access Journals (Sweden)

    Alexandre eMorrot

    2014-08-01

    Full Text Available Plasmodium sporozoites and liver stages express antigens that are targeted to the MHC-Class I antigen-processing pathway. After the introduction of Plasmodium sporozoites by Anopheles mosquitoes, bone marrow-derived dendritic cells in skin-draining lymph nodes are the first cells to cross-present parasite antigens and elicit specific CD8+ T cells. One of these antigens is the immunodominant circumsporozoite protein (CSP. The CD8+ T cell-mediated protective immune response against CSP is dependent on the interleukin loop involving IL-4 receptor expression on CD8+ cells and IL-4 secretion by CD4+ T cell helpers. In a few days, these CD8+ T cells re-circulate to secondary lymphoid organs and the liver. In the liver, the hepatic sinusoids are enriched with cells, such as dendritic, sinusoidal endothelial and Kupffer cells, that are able to cross-present MHC class I antigens to intrahepatic CD8+ T cells. Specific CD8+ T cells actively find infected hepatocytes and target intra-cellular parasites through mechanisms that are both Interferon-g-dependent and -independent. Immunity is mediated by CD8+ T effector or effector-memory cells and, when present in high numbers, these cells can provide sterilizing immunity. Human vaccination trials with recombinant formulations or attenuated sporozoites have yet to achieve the high numbers of specific effector T cells that are required for sterilizing immunity. In spite of the limited number of specific CD8+ T cells, attenuated sporozoites provided multiple times by the endovenous route provided a high degree of protective immunity. These observations highlight that CD8+ T cells may be useful for improving antibody-mediated protective immunity to pre-erythrocytic stages of malaria parasites.

  14. Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol

    Institute of Scientific and Technical Information of China (English)

    Tetsuya Shimizu; Takashi Tajiri; Hiroshi Yoshida; Yasuhiro Mamada; Nobuhiko Taniai; Satoshi Matsumoto; Yoshiaki Mizuguchi; Shigeki Yokomuro; Yasuo Arima; Koho Akimaru

    2006-01-01

    We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct.Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct.On d 46 after surgery, a retrograde transhepatic biliary drainage (RTBD) tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative management, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.

  15. Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts

    Energy Technology Data Exchange (ETDEWEB)

    Padia, Siddharth A., E-mail: spadia@uw.edu; Chewning, Rush H., E-mail: rchewnin@uw.edu; Kogut, Matthew J., E-mail: kogutm@uw.edu; Ingraham, Christopher R., E-mail: cringa@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Bhattacharya, Renuka, E-mail: renuka@uw.edu [University of Washington Medical Center, Division of Gastroenterology and Hepatology, Department of Medicine (United States); Kwan, Sharon W., E-mail: shakwan@uw.edu; Monsky, Wayne L., E-mail: wmonsky@uw.edu; Vaidya, Sandeep, E-mail: svaidya@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Hippe, Daniel S., E-mail: dhippe@uw.edu [University of Washington Medical Center, Department of Radiology (United States); Valji, Karim, E-mail: kvalji@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States)

    2015-08-15

    PurposeLocoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC.MethodsThis retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60 %) underwent treatment for HCC, and 19/48 (40 %) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67 % Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients.ResultsAblation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15 %). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100 % of ablation procedures, 67 % of radioembolization procedures, and 50 % of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001).ConclusionsAblation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization.

  16. Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts.

    Directory of Open Access Journals (Sweden)

    Yun-Ping Lim

    Full Text Available The objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD.We used the research database of the Taiwan National Health Insurance Program to conduct a population-based, case-control study. We identified 9944 patients with antiarrhythmic history who were first diagnosed as having MNLIHD between 2005 and 2010. We identified an additional 19,497 patients with antiarrhythmic history in the same period who did not develop MNLIHD and were frequency-matched using age, sex, and index year to form a control group. Five commercially available antiarrhythmic agents, amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed.The adjusted odds ratio (OR of MNLIHD was 1.60 (95% confidence interval [CI], 1.45-1.77 for amiodarone users versus nonamiodarone users. In subgroup analysis, amiodarone use was significantly associated with an increased risk of MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7-20.5 for patients with comorbidities compared to an OR of 2.43 (95% CI, 1.92-3.06 for those without comorbidities. After adjustment for age, sex, statins, anti-diabetes medications, non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with annual mean defined daily doses of ≤ 30, 31-145, and >145, respectively.The results of the present study indicated that amiodarone might be associated with the development of MNLIHD in a dose-dependent manner, particularly among patients with comorbidities.

  17. Scintigraphic evaluation of hepatic blood flow after intrahepatic portosystemic shunt (TIPS)

    Energy Technology Data Exchange (ETDEWEB)

    Menzel, J. [Department of Medicine B, University of Muenster, Muenster (Germany); Schober, O. [Department of Nuclear Medicine, University of Muenster, Muenster (Germany); Reimer, P. [Department of Radiology, University of Muenster, Muenster (Germany); Domschke, W. [Department of Medicine B, University of Muenster, Muenster (Germany)

    1997-06-10

    In patients with liver cirrhosis a transjugularly placed intrahepatic portocaval shunt (TIPS) is a non-surgical portosystemic device which aims to reduce portal venous pressure. In comparison with Doppler sonography, we evaluated in 28 patients the diagnostic impact of liver perfusion scintigraphy (with technetium-99m diethylene triamine penta-acetic acid) in the assessment of changes in the hepatic blood flow after TIPS shunting. The arterial and portal contributions to hepatic flow were calculated from the areas under the biphasic time-activity curve. In the course of TIPS shunting, patency is threatened by reocclusion. Angiography is the gold standard for TIPS shunt reassessment. However, there is a need for a less invasive diagnostic procedure, such as scintigraphy or Doppler sonography, for the early detection of shunt insufficiency. Scintigraphy demonstrated that prior to TIPS shunting the portal venous contribution to hepatic perfusion was reduced to 29.2%, this reduction being due to portal hypertension. After TIPS placement a significant increase in portal venous perfusion was observed (38.2%; P<0.02). TIPS shunt occlusion was identified in patients by a significant reduction in the scintigraphically measured portal venous contribution to hepatic blood flow. Hepatic perfusion scintigraphy appears to be a valuable method to determine the immediate effect of TIPS on hepatic blood flow. Post-TIPS follow-up studies of hepatic haemodynamics by liver perfusion scintigraphy appear able to contribute to the detection of TIPS shunt occlusion before the clinical consequences of this complication have become apparent. (orig.). With 4 figs., 3 tabs.

  18. Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts

    International Nuclear Information System (INIS)

    PurposeLocoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC.MethodsThis retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60 %) underwent treatment for HCC, and 19/48 (40 %) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67 % Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients.ResultsAblation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15 %). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100 % of ablation procedures, 67 % of radioembolization procedures, and 50 % of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001).ConclusionsAblation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization

  19. Experimental study of an endothelial progenitor cell coated stent in transjugular intrahepatic portosystemic shunt

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy of a self-expandable metal stent coated with autologous endothelial progenitor cells (EPCs) for prevention of restenosis in transjugular intrahepatic portosystemic shunt (TIPS) in a swine model. Methods: EPCs were coated on the metal stents using fibrin gel before TIPS procedure. TIPS was performed in 15 young adult pigs, using an autologous EPC-seeded stent (treatment group, n=9) or a conventional bare metal stent (control group, n=6). All pigs were sacrificed at 2 weeks after TIPS procedure. Portography was performed immediately before the euthanasia. Gross and microscopic pathological exams and immunohistochemical exams of the TIPS track specimens were performed. Fisher test and t test were used to analyse the data. Results: TIPS was performed successfully in all the 15 swine. On day 14 of follow-up, direct portography and necropsy demonstrated that 5 shunts remained patent, 2 shunts stenosed, and the remaining 2 shunts occluded in the treatment group (n=9); while 5 shunts were occluded and one shunt was stenotic in the control group (n=6). The patency rate was 56% vs 0 (P=0.03) between the two groups. Histological analyses showed a greater pseudo-intimal hyperplasia in the TIPS track of the control group than that of the treatment group (pseudointimal thickness at hepatic vein, hepatic parenchyma and portal vein site was (1.2±0.4), (1.3±0.5), (1.5±0.4) mm vs (1.0±0.6), (0.9±0.5), (1.0±0.4) mm respectively (P<0.05). Conclusion: The EPC-coated metal stent is feasibly constructed in vitro and improves the patency in TIPS in a porcine model. (authors)

  20. Application study of regular hepatectomy with choledochoscope in treatment of intrahepatic bile duct stones

    Institute of Scientific and Technical Information of China (English)

    LU De-Bin; LI Qiao-Lin

    2016-01-01

    Objective:To study the clinical effect of regular hepatectomy with choledochoscope in treatment of intrahepatic bile duct stones (IBDS);Methods:A total of 76 cases of patients with complex IBDS treated in our hospital from August 2014 to July 2015 were selected and divided into experimental group (n=38) and control group (n=38) according to random number table, and baseline information of two groups was without statistical significance. Experimental group received regular hepatectomy with choledochoscope and control group received multiple hepatolobectomy. Hepatolobectomy as well as TBIL (total bilirubin), ALB (albumin), ALT (alanine aminotransferase), AST (aspartate aminotransferase), APTT (activated partial thromboplastin time), postoperative complications, recurrence, clinical effect and other indexes of two groups 1 d before operation and 7 d after operation were observed;Results:left hemihepatectomy, left lateral lobectomy, right hemihepatectomy, right posterior lobectomy as well as left lateral and right posterior lobectomy rates of experimental group were not statistically different from those of control group. TBIL, ALB, ALT, AST and APTT of experimental group 7d after operation were not statistically different from those of control group. Excellent and good rate of treatment of experimental group (97.37%) was significantly higher than that of control group (76.32%), incidence of postoperative complications (15.79%) was significantly lower than that of control group (44.74%), stone residue rate of experimental group (5.26%) was significantly lower than that of control group (23.68%), and comparison between groups showed statistical significance;Conclusion:Regular hepatectomy with choledochoscope treatment of IBDS has higher excellent and good rate, more stable liver function indexes as well as lower rate of stone residue and incidence of postoperative complications, and it’s worth application in clinical practice.

  1. Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer

    Science.gov (United States)

    Miao, Ruoyu; Wu, Yan; Zhang, Haohai; Zhou, Huandi; Sun, Xiaofeng; Csizmadia, Eva; He, Lian; Zhao, Yi; Jiang, Chengyu; Miksad, Rebecca A.; Ghaziani, Tahereh; Robson, Simon C.; Zhao, Haitao

    2016-01-01

    Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer. PMID:27618777

  2. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Science.gov (United States)

    Berglin, Lena; Bergquist, Annika; Johansson, Helene; Glaumann, Hans; Jorns, Carl; Lunemann, Sebastian; Wedemeyer, Heiner; Ellis, Ewa C; Björkström, Niklas K

    2014-01-01

    Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC), however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17) and controls (n = 17). We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  3. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Directory of Open Access Journals (Sweden)

    Lena Berglin

    Full Text Available Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC, however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17 and controls (n = 17. We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  4. Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer.

    Science.gov (United States)

    Miao, Ruoyu; Wu, Yan; Zhang, Haohai; Zhou, Huandi; Sun, Xiaofeng; Csizmadia, Eva; He, Lian; Zhao, Yi; Jiang, Chengyu; Miksad, Rebecca A; Ghaziani, Tahereh; Robson, Simon C; Zhao, Haitao

    2016-01-01

    Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer. PMID:27618777

  5. Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer.

    Science.gov (United States)

    Miao, Ruoyu; Wu, Yan; Zhang, Haohai; Zhou, Huandi; Sun, Xiaofeng; Csizmadia, Eva; He, Lian; Zhao, Yi; Jiang, Chengyu; Miksad, Rebecca A; Ghaziani, Tahereh; Robson, Simon C; Zhao, Haitao

    2016-09-13

    Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer.

  6. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Chan-on W

    2015-04-01

    Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

  7. Primary liver tumors. Hepatocellular versus intrahepatic cholangiocellular carcinoma; Primaere Lebertumoren. Hepatozellulaeres vs. intrahepatisches cholangiozellulaeres Karzinom

    Energy Technology Data Exchange (ETDEWEB)

    Wengert, G.J.; Bickel, H.; Breitenseher, J.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Allgemeines Krankenhaus, Wien (Austria)

    2015-01-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (ICC) are the most commonly occurring and important primary liver tumors. Originating from one pluripotent liver stem cell both tumor entities can occur in a cirrhotic liver and also in patients without cirrhosis. Several risk factors have been identified as causative for both carcinomas; therefore, tumor screening is advantageous, especially for high-risk patients who could be diagnosed in an early stage to allow curative treatment. Surgical resection, interventional procedures and transplantation are available as curative treatment options when diagnosed in time. Common characteristic features and morphology in cross-sectional imaging by ultrasound (US), multidetector computed tomography (CT) and magnetic resonance imaging (MRI) as well as screening aspects are presented and discussed. Recent findings show a better understanding of the carcinogenesis model of both liver tumors originating from one pluripotent liver stem cell. Further developments of modern cross-sectional imaging modalities, especially MRI in combination with diffusion-weighted imaging and intravenous administration of hepatocyte-specific contrast agents enable early detection, exact differentiation, staging and treatment evaluation of HCC and ICC In this article we discuss modern, multiparametric imaging modalities, which allow a complete and reliable diagnosis of the majority of these tumor entities. Contrast-enhanced MRI, using hepatocyte-specific contrast agents, is currently the most accurate procedure for the noninvasive diagnosis and treatment evaluation of HCC and ICC. (orig.) [German] Das hepatozellulaere Karziom (HCC) sowie das intrahepatische cholangiozellulaere Karzinom (ICC) zaehlen zu den wichtigsten primaeren Lebertumoren. Mit dem Ursprung aus einer pluripotenten Stammzelle koennen beide Tumorentitaeten bei bestehender, aber auch bei nicht bestehender Leberzirrhose auftreten. Im Folgenden werden

  8. Portal hypertensive enteropathy diagnosed by capsule endoscopy and demonstration of the ileal changes after transjugular intrahepatic portosystemic shunt placement: a case report

    Directory of Open Access Journals (Sweden)

    Carella Alessandra

    2011-03-01

    Full Text Available Abstract Introduction Recent data suggest that mucosal abnormalities can occur even in the duodenum, jejunum, and distal ileum of cirrhosis patients. We present a case of portal hypertensive enteropathy in a cirrhosis patient shown by capsule endoscopy and the effect of transjugular intrahepatic portosystemic shunt on the ileal pictures. Case presentation An 83-year-old Caucasian woman was admitted to our hospital for anemia and a positive fecal occult blood test. An upper gastrointestinal endoscopy revealed small varices without bleeding signs and hypertensive gastropathy. Colonoscopy was negative. To rule out any other cause of bleeding, capsule endoscopy was performed; capsule endoscopy revealed severe hyperemia of the jejunum-ileal mucosa with active bleeding. Because of the persistence of anemia and the frequent blood transfusions, not responding to β-blocker drugs or octreotide infusion, a transjugular intrahepatic portosystemic shunt was performed. Anemia improved quickly after the transjugular intrahepatic portosystemic shunt, and no further blood transfusion was necessary in the follow-up. The patient developed portal encephalopathy two months later and was readmitted to our department. We repeated the capsule endoscopy that showed a significant improvement of the gastric and ileal mucosa without any signs of bleeding. Conclusion Hypertensive enteropathy is a rare condition, but it seems more common with the introduction of capsule endoscopy in clinical practice. This case shows that the jejunum can be a source of bleeding in cirrhosis patients, and this is the first demonstration of its resolution after transjugular intrahepatic portosystemic shunt placement.

  9. Cholangiocarcinoma Secondary to Primary Sclerosing Cholangitis in Explanted Livers: A Single-Center Study in the South of Iran

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    Geramizadeh

    2015-12-01

    Full Text Available Background Primary sclerosing cholangitis (PSC is a chronic disease, characterized by chronic inflammation and fibrosis of bile duct epithelial cells. This is a significant contributory factor to the development of malignancy, most commonly cholangiocarcinoma (CCA, which is the second most common malignant liver tumor. Objectives For the first time in Iran, we intend to describe our experience with cases of PSC, with and without CCA, in explanted livers, and compare our results with those found in other areas of the world. Patients and Methods The study population comprised 181 individuals with a diagnosis of PSC who had undergone liver transplantation in the main liver transplant center of Iran, the largest center of hepatobiliary surgery in the south of that country, over a 3-year period between 2012 and 2014. All explanted livers, with and without CCA, were evaluated. Results Of the 181 patients, 16 were found to have CCA, two of whom had been diagnosed after pathologic study of the explanted livers. Therefore it appeared that 8.8% of the patients with PSC in our center had developed CCA before liver transplantation. Conclusions A comparison of our results with those obtained from other centers in both Western and Asian countries (which reported CCA in 3.6% - 36.5% of patients with PSC, shows that the incidence of CCA in the patients we studied is intermediate.

  10. Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth

    Directory of Open Access Journals (Sweden)

    Hiroaki Haga

    2015-01-01

    Full Text Available The contributions of mesenchymal stem cells (MSCs to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs. We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell–derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell–derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell–derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can “educate” MSCs to induce local microenvironmental changes that enhance tumour cell growth.

  11. EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma.

    Science.gov (United States)

    Yin, Da-Long; Liang, Ying-Jian; Zheng, Tong-Sen; Song, Rui-Peng; Wang, Jia-Bei; Sun, Bo-Shi; Pan, Shang-Ha; Qu, Lian-Dong; Liu, Jia-Ren; Jiang, Hong-Chi; Liu, Lian-Xin

    2016-01-01

    A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment. PMID:27571770

  12. Hepatic artery resection and reconstruction in radical resection of hilar cholangiocarcinoma%肝动脉切除重建在肝门部胆管癌根治术中的应用

    Institute of Scientific and Technical Information of China (English)

    邵益; 严盛; 张启逸; 王伟林; 张珉; 沈岩; 郑树森

    2012-01-01

    目的 探讨肝动脉切除显微外科重建在肝门部胆管癌根治术中的治疗经验和应用价值.方法 回顾性分析2008年8月至2012年3月采用左半肝切除+右肝动脉切除重建伴或不伴门静脉切除重建治疗肝门部胆管癌的7例临床资料.结果 左肝动脉与右肝动脉吻合1例,右肝动脉与右肝动脉对端吻合1例,胃十二指肠动脉与右肝动脉吻合1例,肝固有动脉与右肝动脉吻合4例,伴门静脉切除重建2例.术后病理学检查:中-低分化腺癌2例,低分化腺癌3例,乳头状腺癌2例.手术:R0切除6例,R1切除1例.术后无肝功能衰竭、肝坏死、肝脓肿、胆肠吻合口瘘等并发症及围手术期死亡发生.结论 肝动脉切除显微外科重建提高了进展期肝门部胆管癌的根治切除率,有效控制了术后并发症,安全可行.%Objective To evaluate hepatic artery resection and microsurgical reconstruction in radical resection of Klatskin's tumor.Methods We retrospectively reviewed clinical data of 7 patients with advanced hilar cholangiocarcinoma (Klatskin's tumor) who underwent left hemihepatectomy combined with right hepatic artery resection and microsurgical reconstruction with or without portal vein reconstruction from August 2008 to March 2012.Results Right hepatic artery was reconstructed with end-to-end anastomosis,using the reserved left hepatic artery (n =1),the remanent right hepatic artery (n =1),the hepatic artery proper (n =4) and the gastroduodenal artery (n =1),among those 2 patients underwent concomitant portal vein reconstruction.Post-operative pathology showed middle to low differentiated adenocarcinoma in 2 patients,low differentiated adenocarcinoma in 3 and papillary adenocarcinoma in 2.R0 resection was achieved in 6 patients.There was no post-operative liver failure,biliary-enteric anastomotic leakage or perioperative deaths.Conclusions Hepatic artery resection and microsurgical reconstruction increases the radical resection rate

  13. Biological features of intrahepatic CD4+CD25+ T cells in the naturally tolerance of rat liver transplantation

    Institute of Scientific and Technical Information of China (English)

    LU Ling; ZHANG Feng; PU Liyong; YAO Aihua; YU Yue; SUN Beicheng; LI Guoqiang

    2007-01-01

    The biological features of intrahepatic CD4+CD25+ T regulatory cells in the naturally tolerance of rat liver transplantation were explored.Orthotopic liver transplantation was performed in two allogeneic rat strain combinations,one with fatal immunosuppression despite a complete major histocompatibility complex mismatch.The subjects were divided into three groups according to different donors and recipients [Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DAto-DA].The proportion of intrahepatic CD4+CD25+ T cells from three groups was determined by flow cytometry(FCM)in different time.The intrahepaitc CD4+CD25+ T cells were isolated by magnetic activated cell sorting(MACS)method and identified by FCM.The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4+CD25- T effector cells was analyzed by cell proliferation assay in vitro.Beginning immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group.The proportion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tolerance group.Animals in the Tolerance group showed a second increase in the proportion after day 14.Intrahepatic CD4+CD25+T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction.The purity of CD4+CD25+ T cells sorted by MACS was 86%-93%.The CD4+CD25+ T cells could specifically express the Foxp3 gene compared with CD4+CD25- T cells.In vitro,the spleen cells from LEW rats can irritate the proliferation of CD4+CD25+ T cells more obviously than the syngegnic spleen cells.CD4+CD25+ Tr cells could suppress the proliferation of CD4+CD25- T cells,but the inhibition was reversed by exogenous IL-2(200 U/mL).The CD4+CD25+ T regulatory cells specifically express the Foxp3 gene,which may play an

  14. Suppressing Effects of Down-regulating DNMT1 and DNMT3b Expression on the Growth of Human Cholangiocarcinoma Cell Line

    Institute of Scientific and Technical Information of China (English)

    Shi ZUO; Jian LUO; Minfeng LIU; Lining XU; Jingqing DONG; Wei GUO; Shengquan ZOU

    2008-01-01

    Hypermethylation in the promoter region is an important epigenetic mechanism for the transcriptional repression of a number of cancer-associated genes, and over-expression and/or increased activity of DNA methyltransferases are considered to be the main cause of promoter hypermethylation. In order to explore the roles of two methyltransferase members (DNMT1 and DNMT3b) in the cholangiocarcinoma tumorigenesis, antisense eukaryotic expression plasmid of DNMT1 and DNMT3b gene was constructed respectively, and were co-transfected into the human cholangiocarcinoma cell line QBC-939 to observe their biological effects on the cell growth and proliferation ability, apoptosis, cell cycle alteration, and the tumorigenesis ability in the subcutaneous tissue of nude mouse. The results demonstrated that co-transfection with antisense eukaryotic expression plasmid of DNMT1 and DNMT3b gene and single transfection with antisense eukaryotic expression plasmid of DNMT1 gene can suppress the growth and proliferation of QBC-939, block the cell cycle at G1 phase, increase the apoptosis rate, minimize the tumor size in the subcutaneous tissue of nude mouse. The suppressing biological effect of co-transfection is stronger than single transfection with antisense DNMT1. Meanwhile, single transfection with antisense eukaryotic expression plasmid of DNMT3b gene has no effects on the biological characteristics of QBC-939. This study suggests that DNMT1 gene plays a key role in DNA methylation and DNMT3b gene may act as an accessory to support its function in inactivation of tumor suppressor genes. Combination DNMT1 and DNMT3b will inhere their biological effects and have the synergistic effect on suppressing the growth of human cholangiocarcinoma cell line QBC-939.

  15. Dynamic biliary cholecystography with mebrofenin-Tc-99m in a patient with benign recurrent intrahepatic cholestasis

    International Nuclear Information System (INIS)

    A Caucasian boy with a 16-year history of benign recurrent intrahepatic cholestasis (BRIC) presented dissociation between normal hepatic extraction fraction of mebrofenin-Tc-99m (HEF over 90%) and that of intensive delayed liver 'washout' T 1/2 210 m (normal 20-25 m). This is the second case in Macedonia (population 2.3 million) showing the same pattern of bile dynamic with mebrofenin-Tc-99m: normal HEF, prolonged 'washout'. In Rotor's disease and Dubin-Johnson's syndrome HEF is depressed and 'washout' delayed, whereas in Gilbert's syndrome we found both parameters normal. In our patient the episodes of pruritus were intensive and prolonged, hyperbilirubinaemia 50-100 micromol/L. Gallbladder was hypovolemic, ejection fraction reduced (59%, normal with the employed method over 70%). Growth, body weight and bone age were subnormal. Technetium-sulfur-colloid scans showed enlarged liver, splenomegaly and reduced portal contribution to hepatic blood flow (65%, normal over 70%). (Author)

  16. Recurrent thrombotic occlusion of a transjugular intrahepatic portosystemic stent-shunt due to activated protein C resistance

    Institute of Scientific and Technical Information of China (English)

    Elmar Siewert; Jan Salzmann; Edmund Purucker; Karl Schürmann; Siegfried Matern

    2005-01-01

    The transjugular intrahepatic portosystemic stent-shunt (TIPS) has successfully been used in the management of refractory variceal bleeding and ascites in patients with portal hypertension. Major drawbacks are the induction of hepatic encephalopathy and shunt dysfunction. We present a 59-year-old woman with alcoholic liver cirrhosis who received a TIPS because of recurrent bleeding from esophageal varices. Stent occlusion occurred 4 mo after placement of the TIPS. Laboratory testing revealed resistance to activated protein C (APC). Combination therapy with low-dose enoxaparin and clopidogrel could not prevent her recurrent stent occlusion. Finally, therapy with high-dose enoxaparin was sufficient to prevent further shunt complications up to now (follow-up period of 1 year). In conclusion, early occlusion of a TIPS warrants testing for thrombophilia. If risk factors are confirmed,anticoagulation should be intensified. There are currently no evidence-based recommendations regarding the best available anticoagulant therapy and surveillance protocol for patients with TIPS.

  17. Bilhemia after trans-jugular intra-hepatic porto-systemic shunt and its management with biliary decompression

    Institute of Scientific and Technical Information of China (English)

    Ashwani K Singal; Manoj K Kathuria; Advitya Malhotra; Richard W Goodgame; Roger D Soloway

    2009-01-01

    Bilhemia or bile mixing with blood is a rare clinical problem. The clinical presentation is usually transient self-resolving hyperbilirubinemia, progressive and rapidly rising conjugated hyperbilirubinemia, or recurrent cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) plays an important role in diagnosis and management. Biliary decompression with endoscopic sphincterotomy is useful in treating these patients. If not recognized and treated in time, the condition can be fatal in a significant proportion of patients. This usually occurs after blunt or penetrating hepatic trauma due to a fistulous connection between the biliary radicle and portal or hepatic venous radical. Cases have been described due to iatrogenic trauma such as liver biopsy and percutaneous biliary drainage. However, the occurrence after trans-jugular intra-hepatic porto-systemic shunt (TIPS) is very rare. We report a case of bilhemia presenting as rapidly rising bilirubin after TIPS. The patient was managed successfully with ERCP and removal of a blood clot from the common bile duct.

  18. Transjugular Intrahepatic Portosystemic Shunt for Treatment of Cirrhosis-related Chylothorax and Chylous Ascites: Single-institution Retrospective Experience

    Energy Technology Data Exchange (ETDEWEB)

    Kikolski, Steven G., E-mail: skikolski@ucsd.edu; Aryafar, Hamed, E-mail: haryafar@ucsd.edu; Rose, Steven C., E-mail: scrose@ucsd.edu [University of California San Diego Health Sciences, Department of Radiology (United States); Roberts, Anne C., E-mail: acroberts@ucsd.edu [University of California San Diego Health Sciences, Department of Vascular and Interventional Radiology (United States); Kinney, Thomas B., E-mail: tbkinney@ucsd.edu [University of California San Diego Health Sciences, Department of Radiology (United States)

    2013-08-01

    PurposeTo investigate the efficacy and safety of the use of transjugular intrahepatic portosystemic shunt (TIPS) creation to treat cirrhosis-related chylous collections (chylothorax and chylous ascites).MethodsWe retrospectively reviewed data from four patients treated for refractory cirrhosis-related chylous collections with TIPS at our institution over an 8 year period.ResultsOne patient had chylothorax, and three patients had concomitant chylothorax and chylous ascites. There were no major complications, and the only procedure-related complications occurred in two patients who had mild, treatable hepatic encephalopathy. All patients had improvement as defined by decreased need for thoracentesis or paracentesis, with postprocedure follow-up ranging from 19 to 491 days.ConclusionTIPS is a safe procedure that is effective in the treatment of cirrhosis-related chylous collections.

  19. Transsplenic portal vein reconstruction–transjugular intrahepatic portosystemic shunt in a patient with portal and splenic vein thrombosis

    Directory of Open Access Journals (Sweden)

    Jason T. Salsamendi, MD

    2016-09-01

    Full Text Available Portal vein thrombosis (PVT is a potential complication of cirrhosis and can worsen outcomes after liver transplant (LT. Portal vein reconstruction–transjugular intrahepatic portosystemic shunt (PVR-TIPS can restore flow through the portal vein (PV and facilitate LT by avoiding complex vascular conduits. We present a case of transsplenic PVR-TIPS in the setting of complete PVT and splenic vein (SV thrombosis. The patient had a 3-year history of PVT complicated by abdominal pain, ascites, and paraesophageal varices. A SV tributary provided access to the main SV and was punctured percutaneously under ultrasound scan guidance. PV access, PV and SV venoplasty, and TIPS placement were successfully performed without complex techniques. The patient underwent LT with successful end-to-end anastomosis of the PVs. Our case suggests transsplenic PVR-TIPS to be a safe and effective alternative to conventional PVR-TIPS in patients with PVT and SV thrombosis.

  20. Transsplenic portal vein reconstruction-transjugular intrahepatic portosystemic shunt in a patient with portal and splenic vein thrombosis.

    Science.gov (United States)

    Salsamendi, Jason T; Gortes, Francisco J; Shnayder, Michelle; Doshi, Mehul H; Fan, Ji; Narayanan, Govindarajan

    2016-09-01

    Portal vein thrombosis (PVT) is a potential complication of cirrhosis and can worsen outcomes after liver transplant (LT). Portal vein reconstruction-transjugular intrahepatic portosystemic shunt (PVR-TIPS) can restore flow through the portal vein (PV) and facilitate LT by avoiding complex vascular conduits. We present a case of transsplenic PVR-TIPS in the setting of complete PVT and splenic vein (SV) thrombosis. The patient had a 3-year history of PVT complicated by abdominal pain, ascites, and paraesophageal varices. A SV tributary provided access to the main SV and was punctured percutaneously under ultrasound scan guidance. PV access, PV and SV venoplasty, and TIPS placement were successfully performed without complex techniques. The patient underwent LT with successful end-to-end anastomosis of the PVs. Our case suggests transsplenic PVR-TIPS to be a safe and effective alternative to conventional PVR-TIPS in patients with PVT and SV thrombosis.

  1. Management of empyema of gallbladder with percutaneous cholecysto-duodenal stenting in a case of hilar cholangiocarcinoma treated with common bile duct metallic stenting

    Directory of Open Access Journals (Sweden)

    Sheo Kumar

    2011-01-01

    Full Text Available Empyema of the gallbladder develops when the gallbladder neck is obstructed in the presence of infection, preventing pus from draining via the cystic duct. Treatment options include cholecystectomy or, in patients with comorbidities, drainage via percutaneous cholecystostomy, later followed by cholecystectomy. Here, we describe a 59-year-old man who presented with complaints of recurrent hiccups and was found to have cholangiocarcinoma causing obstruction to cystic duct drainage. The patient was managed successfully by percutaneous transhepatic cholecysto-duodenal self-expandable covered metal stent.

  2. Molecular and cytogenetic abnormality on cholangiocarcinoma%肝门胆管癌细胞分子遗传学异常的研究

    Institute of Scientific and Technical Information of China (English)

    高戈; 邹声泉

    2014-01-01

    Objective To study alterations of molecular cytogenetics of cholangiocarcinoma on chromosome and gene,study the possible involvement of chromosome abnormalities and the genetic susceptibility in pathogenesis of cholangiocarcinoma,investigate chromosome instability and expression of fragile sites of cholangiocarcinoma and relationship each other,and find marker chromosome of cholangiocarcinoma.Methods Chromosomal analysis and fluorescence in situ hybridization (FISH) were used with 9th chromosome libraries to investigate the chromosomal aberration,the chromosome instability and expressiom of fragile sites in patients with cholangiocarcinoma.The genetic alteration and expression of p16 gene were analyzed by polymerase chain reaction single strand comformation polymorphism (PCR-SSCP) and immunohistochemistry.Results Chromosomal aberrations were found in 10 case of patients and 1 case of cell line of cholangiocarcinoma.The chromosome model number was 62.3 and predominantly hyperdiploid,with a chromosome number aberration rate of 83.67%,and a structure aberration rate of 62.8%.9p deletion appeared more frequently(50.8%).p16 gene mutation rate was 58.3% (21/36).The expression of p16 gene was not significantly related with sex and age of the patients,and had a relation with Bismuth type,the depth of invasion and lymph node metastasis.The chromosome gaps (8.75 ± 3.30),chromosome breakpoints (7.63 ± 2.76),abnormal cell rate (13.35 ± 4.73) and expression rate of fragile sites of the patients were markedly higher in patients with cholgnagiocarcinoma than those of normal persons (3.17 ±1.82,2.04±1.76,3.65 ±1.97) (P<0.01).Conclusion Chromosomal aberrations and gene mutation may play an important role in the pathogenesis of cholangiocarcinoma.The alteration of p16 gene and abnormal expression of p16 protein are significantly correlated with the biological behaviors and clinical staging of cholangiocarcinorma and may hence be helpful to prognosis.The increase of

  3. Common and Uncommon Anatomical Variants of Intrahepatic Bile Ducts in Magnetic Resonance Cholangiopancreatography and its Clinical Implication

    Science.gov (United States)

    Sarawagi, Radha; Sundar, Shyam; Raghuvanshi, Sameer; Gupta, Sanjeev Kumar; Jayaraman, Gopal

    2016-01-01

    Summary Background Preoperative knowledge of intrahepatic bile duct (IHD) anatomy is critical for planning liver resections, liver transplantations and complex biliary reconstructive surgery. The purpose of our study was to demonstrate the imaging features of various anatomical variants of IHD using magnetic resonance cholangio-pancreatography (MRCP) and their prevalence in our population. Material/Methods This observational clinical evaluation study included 224 patients who were referred for MRCP. MRCP was performed in a 1.5-Tesla magnet (Philips) with SSH MRCP 3DHR and SSHMRCP rad protocol. A senior radiologist assessed the biliary passage for anatomical variations. Results The branching pattern of the right hepatic duct (RHD) was typical in 55.3% of subjects. The most common variant was right posterior sectoral duct (RPSD) draining into the left hepatic duct (LHD) in 27.6% of subjects. Trifurcation pattern was noted in 9.3% of subjects. In 4% of subjects, RPSD was draining into the common hepatic duct (CHD) and in 0.8% of subjects into the cystic duct. Other variants were noted in 2.6% of subjects. In 4.9% of cases there was an accessory duct. The most common type of LHD branching pattern was a common trunk of segment 2 and 3 ducts joining the segment 4 duct in 67.8% of subjects. In 23.2% of subjects, segment 2 duct united with the common trunk of segment 3 and 4 and in 3.4% of subjects segment 2, 3, and 4 ducts united together to form LHD. Other uncommon branching patterns of LHD were seen in 4.9% of subjects. Conclusions Intrahepatic bile duct anatomy is complex with many common and uncommon variations. MRCP is a reliable non-invasive imaging method for demonstration of bile duct morphology, which is useful to plan complex surgeries and to prevent iatrogenic injuries. PMID:27298653

  4. Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

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    Lieke Thorsten

    2012-10-01

    Full Text Available Abstract Background Cholangiocarcinoma (CC is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. Methods To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry. Results By demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration. Conclusion In this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future.

  5. MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma.

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    Torsten Voigtländer

    Full Text Available Patients with primary sclerosing cholangitis (PSC are at high risk for the development of cholangiocarcinoma (CC. Analysis of micro ribonucleic acid (MiRNA patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC.Serum and bile from consecutive patients with PSC (n = 40 (serum, n = 52 (bile, CC (n = 31 (serum, n = 19 (bile and patients with CC complicating PSC (PSC/CC (n = 12 (bile were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12. The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation.Serum analysis revealed significant differences for miR-1281 (p = 0.001, miR-126 (p = 0.001, miR-26a (p = 0.001, miR-30b (p = 0.001 and miR-122 (p = 0.034 between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001, miR-640 (p = 0.001, miR-1537 (p = 0.003 and miR-3189 (p = 0.001 were significantly different between patients with PSC and PSC/CC in bile.Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

  6. Decreased expression of type Ⅱ tumor suppressor gene RARRES3 in tissues of hepatocellular carcinoma and cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Shun-Yuan Jiang; Jung-Mao Chou; Fur-Jiang Leu; Yu-Yen Hsu; Yu-Lung Shih; Jyh-Cherng Yu; Meei-Shyuan Lee; Rong-Yaun Shyu

    2005-01-01

    AIM: To analyze the expression of retinoic acid receptor responder 3 (RARRES3) protein in paraffin-embedded tissues of hepatocellular carcinoma (HCC) and cholangiocarcinoma(CC), and the correlation of RARRES3 production with tumor differentiation.METHODS: Expression of RARRES3 in tissues from 21CC (10 well-, 7 moderately- and 4 poorly-differentiated)and 32 HCC was determined by immunohistochemistry.RESULTS: Among 21 CC tissues, RARRES3 was detected in 8 (80%) of 10 well-differentiated tumors. Only 2 (18.2%)out of 11 tumors with moderate or poor differentiation showed positive RARRES3 expression. RARRES3 expression in well-differentiated CC was significantly higher than that in tumors with moderate or poor differentiation (Fisher exact test, P<0.01). Expression of RARRES3 was not different between early (Ⅰ and Ⅱ) and late (Ⅲ and Ⅳ) stages of CC.Among 30 HCC tissues, 17 (56.7%) weakly expressed RARRES3 in HCC cells, and 25 (83.3%) normal tissues adjacent to HCC expressed the protein. RARRES3 expression was significantly decreased in HCC tissues compared to that in adjacent normal tissues (logistic regression analysis, OR = 0.27, 95% CI (0.11-0.62), P<0.01).CONCLUSION: Expression of RARRES3 is positively correlated to well-differentiated CC, which supports the role of RARRES3 in malignant epithelial differentiation of the tumor. The decrease in RARRES3 expression in tissues of HCC and CC with moderate and poor differentiation suggests that altered RARRES3 expression may play a role in the carcinogenesis of the liver and biliary tract.

  7. Feasibility and safety of long-term photodynamic therapy (PDT in the palliative treatment of patients with hilar cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Höblinger A

    2011-09-01

    Full Text Available Abstract Background and Aim PDT is an important palliative option for patients with unresectable extrahepatic cholangiocarcinoma (CC. However, the results published to date reported on studies with no more than 6 (mostly up to 4 PDT procedures. Furthermore, the clinical experience of PDT in combination with chemotherapy is limited. The purpose of this retrospective analysis was to evaluate the feasibility and safety of multiple (4 to 14 settings of PDT, combined with biliary drainage, and (in some cases with chemotherapy. Methods Ten patients with unresectable extrahepatic CC were treated with biliary stenting and at least 4 PDT procedures in our department between 10/2005 and 08/2010. Results Ten patients (male/female = 5/5, mean age 68.8 years (range, 54 - 81 years who received at least 4 PDT procedures were analyzed. All patients underwent endoscopic biliary drainage. Nine patients received metallic stents and one patient a plastic stent. In 4 patients (40% bilateral metal stenting (JoStent SelfX® was performed. The mean number of PDT sessions was 7.9 ± 3.9 (range: 4 - 14. Eight patients had elevated bilirubin levels with a mean bilirubin at admission of 9.9 ± 11.3 mg/dL, which had decreased to an average minimum of 1.2 ± 0.9 mg/dL after 3 months. No severe toxicity was noted. Two patients received concomitant chemotherapy (GEMCIS as 1st line, GEMOX plus cetuximab as 2nd line. The median overall survival has not been reached, whereas the estimated survival of all patients was 47.6 months, 95% CI 25.9 - 48.1. Conclusion Long-term PDT in patients with extrahepatic CC is feasible and effective and is accompanied - at least in this cohort- by a survival time of more than 2 years.

  8. Upregulation of retinoic acid receptor-β reverses drug resistance in cholangiocarcinoma cells by enhancing susceptibility to apoptosis.

    Science.gov (United States)

    Ren, Hong-Yue; Chen, Bo; Huang, Gui-Li; Liu, Yu; Shen, Dong-Yan

    2016-10-01

    Retinoic acid receptor β (RARβ), a known tumor suppressor gene, is frequently silenced in numerous malignant types of tumor. Recent reports have demonstrated that loss of RARβ expression may be responsible, in part, for the drug resistance observed in clinical trials. However, little is known about the role of RARβ in regulating drug sensitivity in patients with cholangiocarcinoma (CCA) with a high risk of mortality and poor outcomes. In the present study, low RARβ expression was observed in the majority of CCA tissues investigated (28/33, 84.8%). In addition, the CCA cell line QBC939, which exhibits low RARβ expression, was found to be significantly resistant to chemotherapeutic agents compared with SK‑ChA‑1, MZ‑ChA‑1 and Hccc9810 CCA cell lines, which exhibit high RARβ expression. Furthermore, upregulation of RARβ significantly enhanced the sensitivity of QBC939 cells to common chemotherapeutic agents both in vitro and in vivo. Upregulation of RARβ was shown to increase the expression of proapoptotic genes bax, bak and bim, in addition to caspase‑3 activity, and decrease the expression of antiapoptotic genes bcl‑2, bcl‑xL and mcl‑1. As a result, CCA cells were more susceptible to caspase‑dependent apoptosis. Taken together, these data suggest that RARβ upregulation rendered CCA cells more sensitive to chemotherapeutic agents by increasing the susceptibility of cells to caspase-dependent apoptosis. These results support the hypothesis that RARβ may be an ideal chemosensitization target for the treatment of patients with drug-resistant CCA. PMID:27599527

  9. Catalytically impaired hMYH and NEIL1 mutant proteins identified in patients with primary sclerosing cholangitis and cholangiocarcinoma

    Science.gov (United States)

    Forsbring, Monika; Vik, Erik S.; Dalhus, Bjørn; Karlsen, Tom H.; Bergquist, Annika; Schrumpf, Erik; Bjørås, Magnar; Boberg, Kirsten M.; Alseth, Ingrun

    2009-01-01

    The human hMYH and NEIL1 genes encode DNA glycosylases involved in repair of oxidative base damage and mutations in these genes are associated with certain cancers. Primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease characterized by inflammatory destruction of the biliary tree, is often complicated by the development of cholangiocarcinoma (CCA). Here, we aimed to investigate the influence of genetic variations in the hMYH and NEIL1 genes on risk of CCA in PSC patients. The hMYH and NEIL1 gene loci in addition to the DNA repair genes hOGG1, NTHL1 and NUDT1 were analyzed in 66 PSC patients (37 with CCA and 29 without cancer) by complete genomic sequencing of exons and adjacent intronic regions. Several single-nucleotide polymorphisms and mutations were identified and severe impairment of protein function was observed for three non-synonymous variants. The NEIL1 G83D mutant was dysfunctional for the major oxidation products 7,8-dihydro-8-oxoguanine (8oxoG), thymine glycol and dihydrothymine in duplex DNA, and the ability to perform δ-elimination at abasic sites was significantly reduced. The hMYH R260Q mutant had severe defect in adenine DNA glycosylase activity, whereas hMYH H434D could excise adenines from A:8oxoG pairs but not from A:G mispairs. We found no overall associations between the 18 identified variants and susceptibility to CCA in PSC patients; however, the impaired variants may be of significance for carcinogenesis in general. Our findings demonstrate the importance of complete resequencing of selected candidate genes in order to identify rare genetic variants and their possible contribution to individual susceptibility to cancer development. PMID:19443904

  10. Addition of Molecular Adsorbent Recirculating System (MARS® Albumin Dialysis for the Preoperative Management of Jaundiced Patients with Hilar Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Jean-Marc Regimbeau

    2013-09-01

    Full Text Available The preoperative management of hilar cholangiocarcinoma (HC with jaundice focuses on decreasing the total serum bilirubin level (SBL by performing preoperative biliary drainage (PBD. However, it takes about 6-8 weeks for the SBL to fall at a sufficient extent. The objective of this preliminary study was to evaluate the impact of Molecular Adsorbent Recirculating System (MARS® dialysis (in association with PBD on SBL decrease. From January 2010 to January 2011, we prospectively selected all jaundiced patients admitted to our university hospital for resectable HC and requiring PBD prior to major hepatectomy. The PBD was followed by 3 sessions of MARS dialysis over a period of 72 h. A total of 10 patients with HC were screened and two of them were included (Bismuth-Corlette stage IIIa, gender ratio 1, median age 68 years. The initial SBL in the two patients was 328 and 242 μmol/l, respectively. After three MARS dialysis sessions, the SBL had fallen by 30 and 52%, respectively. After the end of each session, there was a SBL rebound of about 10 μmol/l. The MARS decreased the serum creatinine level, the platelet count and the prothrombin index, but did not modify the serum albumin level. Pruritus disappeared after one and two sessions, respectively. MARS-related morbidity included hypotension (n = 1, tachycardia (n = 1, thrombocytopenia (n = 2 and anaemia (n = 1. When combined with PBD, MARS dialysis appears to accelerate the decrease in SBL and thus may enable earlier surgery. This hypothesis must be validated in a larger study.

  11. Plasma autoantibodies against heat shock protein 70, enolase 1 and ribonuclease/angiogenin inhibitor 1 as potential biomarkers for cholangiocarcinoma.

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    Rucksak Rucksaken

    Full Text Available The diagnosis of cholangiocarcinoma (CCA is often challenging, leading to poor prognosis. CCA arises via chronic inflammation which may be associated with autoantibodies production. This study aims to identify IgG antibodies directed at self-proteins and tumor-associated antigens. Proteins derived from immortalized cholangiocyte cell line (MMNK1 and CCA cell lines (M055, M214 and M139 were separated using 2-dimensional electrophoresis and incubated with pooled plasma of patients with CCA and non-neoplastic controls by immunoblotting. Twenty five immunoreactive spots against all cell lines-derived proteins were observed on stained gels and studied by LC-MS/MS. Among these, heat shock protein 70 (HSP70, enolase 1 (ENO1 and ribonuclease/angiogenin inhibitor 1 (RNH1 obtained the highest matching scores and were thus selected for further validation. Western blot revealed immunoreactivity against HSP70 and RNH1 in the majority of CCA cases and weakly in healthy individuals. Further, ELISA showed that plasma HSP70 autoantibody level in CCA was significantly capable to discriminate CCA from healthy individuals with an area under the receiver operating characteristic curve of 0.9158 (cut-off 0.2630, 93.55% sensitivity and 73.91% specificity. Plasma levels of IgG autoantibodies against HSP70 were correlated with progression from healthy individuals to cholangitis to CCA (r = 0.679, P<0.001. In addition, circulating ENO1 and RNH1 autoantibodies levels were also significantly higher in cholangitis and CCA compared to healthy controls (P<0.05. Moreover, the combinations of HSP70, ENO1 or RNH1 autoantibodies positivity rates improved specificity to over 78%. In conclusion, plasma IgG autoantibodies against HSP70, ENO1 and RNH1 may represent new diagnostic markers for CCA.

  12. Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial.

    Science.gov (United States)

    Li, Hao; Zhang, Zheng-Yun; Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-05-01

    Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733).

  13. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial

    DEFF Research Database (Denmark)

    Stein, A.; Arnold, D.; Bridgewater, J.;

    2015-01-01

    Background: Despite complete resection, disease-free survival (DFS) of patients with cholangiocarcinoma (CCA) is less than 65 % after one year and not more than 35 % after three years. For muscle invasive gallbladder carcinoma (GBCA), prognosis is even worse, with an overall survival (OS) of only...

  14. Focal adhesion kinase and Src phosphorylations in HGF-induced proliferation and invasion of human cholangiocarcinoma cell line, HuCCA-1

    Institute of Scientific and Technical Information of China (English)

    Urai Pongchairerk; Jun-Lin Guan; Vijittra Leardkamolkarn

    2005-01-01

    AIM: To study the role of focal adhesion kinase (FAK) and its association with Src in hepatocyte growth factor (HGF)-induced cell signaling in cholangiocarcinoma progression.METHODS: Previously isolated HuCCA-1 cells were re-characterized by immunofluorescent staining and reverse transcriptase-polymerase chain reaction assay for the expression of cytokeratin 19, HGF and c-Met mRNA. Cultured HuCCA-1 cells were treated with HGF and determined for cell proliferation and invasion effects by MTT and invasion assays. Western blotting, immunoprecipitation, and co-immunoprecipitation were also performed to study the phosphorylation and interaction of FAK and Src. A novel Src inhibitor (AZM555130) was applied in cultures to investigate the effects on FAK phosphorylation inhibition and on cell proliferation and invasion.RESULTS: HGF enhanced HuCCA-1 cell proliferation and invasion by mediating FAK and Src phosphorylations.FAK-Src interaction occurred in a time-dependent manner that Src was proved to be an upstream signaling molecule to FAK. The inhibitor to Src decreased FAK phosphorylation level in correlation with the reduction of cell proliferation and invasion.CONCLUSION: FAK plays a significant role in signaling pathway of HGF-responsive cell line derived from cholangiocarcinoma. Autophosphorylated Src, induced by HGF, mediates Src kinase activation, which subsequently phosphorylates its substrate, FAK, and signals to cell proliferation and invasion.

  15. Diagnosis and Treatment On Hilar Cholangiocarcinoma: 40 Cases Report%40例肝门部胆管癌临床诊断与治疗分析

    Institute of Scientific and Technical Information of China (English)

    梁毅; 苗雄鹰

    2011-01-01

    目的 评价肝门部胆管癌的诊治方法 并确定该病的可治愈性.方法 回顾性分析40例肝门部胆管癌患者的资料,其中行根治性切除术18例,非根治性手术22例.结果 肝门部胆管癌早期无特异症状,误诊率高.行根治性切除术者围术期死亡1例.两组各失访2例,根治性切除术15例,中位生存时间为30(7~70)个月;1、3、5年生存率分别为86.7%,54.5%和25.0%;非根治性切除术20例,中位生存时间为16(4~41)个月;1、3、5年生存率分别为45.0%,7.7%,0.结论 术前影像学检查准确的评价可切除性、术中选择适宜的手术方式、合理应用肝切除术是提高疗效的关键问题.根治性切除术是最佳的治疗方式.%Objective To evaluate the diagnosis and treatment of hilar cholangiocarcinoma and to determine the resectability rate for hilar cholangiocarcinoma. Method Forty patients with hilar cholangiocarcinomas were analyzed retrospectively. 18 cases underwent radical surgery and the others did non-radical operations. Results The misdiagnosis rate was high because of no specific symptoms in the early stage. One patient underwent radical surgery died perioperatively, and 2 cases lost follow-up in each group. The median survival time of 15 patients treated by radical resection was 30 months with the 1, 3, 5-year survival rate was 86.7%, 54.5% and 25.0% respectively. While the median survival time of the non-radical 20 patients was 16 months with 1, 3, 5-year survival rate of 45.0%, 7.7% and 0 respectively. Conclusions Exact preoperative imaging evaluation of resectability, choosing a rational surgical procedure and using a rational approach of hepatectomy are important to prolong postoperative survival time of the patients with hilar cholangiocarcinoma. Radical resection is the best choice for hilar cholangiocarcinoma.

  16. Transjugular Intrahepatic Portosystemic Shunt, Mechanical Aspiration Thrombectomy, and Direct Thrombolysis in the Treatment of Acute Portal and Superior Mesenteric Vein Thrombosis

    International Nuclear Information System (INIS)

    A patient was admitted because of severe abdominal pain, anorexia, and intestinal bleeding. Contrast-enhanced multidetector computed tomography demonstrated acute portal and superior mesenteric vein thrombosis (PSMVT). The patient was treated percutaneously with transjugular intrahepatic portosystemic shunt (TIPS), mechanical aspiration thrombectomy, and direct thrombolysis, and 1 week after the procedure, complete patency of the portal and superior mesenteric veins was demonstrated. TIPS, mechanical aspiration thrombectomy, and direct thrombolysis together are promising endovascular techniques for the treatment of symptomatic acute PSMVT

  17. Preoperative Radiologic and Postoperative Pathologic Risk Factors for Early Intra-Hepatic Recurrence in Hepatocellular Carcinoma Patients Who Underwent Curative Resection

    OpenAIRE

    Kim, Honsoul; Park, Mi-Suk; Park, Young Nyun; Kim, Hyunki; Kim, Kyung Sik; Choi, Jin Sub; Ahn, Sang Hoon; Han, Kwang-Hyub; Kim, Myeong-Jin; Kim, Ki Whang

    2009-01-01

    Purpose The risk of hepatocellular carcinoma (HCC) recurrence must be considered ahead of surgery. This study was undertaken to identify pre-operative risk factors for early intrahepatic recurrence of HCC after curative resection in a large-scale. Materials and Methods We retrospectively reviewed the preoperative three-phase multi-detector CT (MDCT) and laboratory data for 240 HCC patients who underwent curative resection; tumor size, number, gross shape, capsule integrity, distinctiveness of...

  18. Cholecysto-appendicostomy as partial internal biliary drainage in Progressive Familial Intrahepatic Cholestasis Type 1: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Yee Ian Yik

    2016-01-01

    Full Text Available Intractable pruritus secondary to bile salts retention in Progressive Familial Intrahepatic Cholestasis (PFIC can be relieved surgically by diverting bile drainage from ileum to reduce bile salts reabsorption into entero-hepatic circulation. We are reporting on the successful biliary diversion in a child with PFIC, with the use of the appendix as a conduit to drain bile from gallbladder to the colon (cholecysto-appendicostomy.

  19. Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients.

    Science.gov (United States)

    Suzuki, Fumitaka; Miyakoshi, Hideo; Kobayashi, Mariko; Kumada, Hiromitsu

    2009-01-01

    Nucleos(t)ide analogues are utilized for the treatment of chronic HBV infection, and HBe seroconversion and HBV DNA levels are commonly used as markers of viral status and as primary treatment endpoints. Recently, a new assay was prepared for the detection of serum HBV core-related antigen (HBcrAg), consisting of HBcAg, HBeAg, and p22cr, which is a precore protein from amino acid -28 to at least amino acid 150, by coding the precore/core region. In this study, we examined the correlation between serum HBcrAg concentration and viral status by the analysis of serum HBeAg, HBsAg, peripheral HBV DNA, and intrahepatic covalently closed circular DNA (cccDNA) in 57 chronic hepatitis B patients. Intrahepatic cccDNA was detected in all 57 patients, 42 patients were HBcrAg-positive, and serum HBcrAg concentration level was closely correlated with cccDNA. Additionally, positive HBcrAg concentration level results were observed in 6 out of 13 HBsAg seroclearance patients and 20 out of 31 HBV DNA-negative patients. Moreover, the correlation between HBcrAg and cccDNA in these 31 HBV DNA-negative patients was statistically significant (r = 0.482, P = 0.006). These data suggest that serum HBcrAg concentration is well correlated with intrahepatic cccDNA level, and that the measurement of serum HBcrAg may be clinically useful for monitoring intrahepatic HBV viral status, especially in patients under treatment with nucleos(t)ide analogues.

  20. Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholest