WorldWideScience

Sample records for lethal metastatic pancreatic

  1. Icotinib plus gemcitabine for metastatic pancreatic cancer: a case report.

    Science.gov (United States)

    Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

    2015-03-21

    A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative.

  2. Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

    Directory of Open Access Journals (Sweden)

    Anoopa A. Koshy MD

    2013-01-01

    Full Text Available A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment.

  3. Rad51 expression levels predict synthetic lethality and metastatic potential in high grade breast cancers

    International Nuclear Information System (INIS)

    Wiegmans, A.P.; Al-Ejeh, F.; Khanna, K.K.

    2012-01-01

    Among women with breast cancer, 30-40% will develop metastatic disease and only achieve an overall survival of less than 5 years. Despite new-targeted therapy, breast tumors that harbour similar histology or molecular phenotype differ in their response to treatment. To uncover potential new therapeutic targets and improve outcome, we performed data mining of cancer micro array databases. We found that high expression of the homologous recombination protein, RAD51, was significantly associated with high-grade breast cancer, aggressive subtypes and increased risk of metastasis. We confirmed using immunohistochemistry that RAD5 1 was highly expressed in metastatic tumours and high-grade triple negative, HER2+ and luminal-B tumours. This provided a rationale for targeting RAD5 1 in high-grade, therapy-resistant breast cancers. Here, we report for the first time preclinical evaluation of RAD5 1 as a therapeutic target. We found that, in-vitro high RAD5 expressing cell lines were resistant to PARP inhibitor while knockdown reversed this resistance. In-vivo, knockdown of RAD5 1 inhibited metastatic progression using a syngeneic breast cancer model and the seeding of human xenografts to distant sites, including brain and lung. Concurrent PARP inhibition reduced primary tumor growth and delayed metastasis supporting synthetic lethality in-vivo. Together these insights provide pre-clinical data demonstrating RAD5 1 as a new biomarker and potential therapeutic target against aggressive metastatic breast cancer. (author)

  4. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-01-01

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  5. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  6. Thyroid and pancreatic hormones in lethally irradiated rats

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Praslicka, M.

    1985-01-01

    The concentrations of thyroxine, triiodothyronine and reverse triiodothyronine, glucagon and insulin in the serum or plasma were determined by radioimmunoassay in male rats of the Wistar strain 1, 6, 24, 48 and 72 hours after irradiation with 14.35 Gy (1500R) of X-rays. The irradiated and sham-irradiated rats were starved till examination. The concentrations of thyroxine and triiodothyronine dropped 6 hours after irradiation as compared with controls, the concentration of thyroxine also dropped after 72 hours. The level of reverse triiodothyronine in irradiated rats increased in the terminal period. The level of insulin dropped 24 hours after irradiation, at 72 hours it was higher than that in controls. The concentration of glucagon in irradiated rats increased in the terminal phase of radiation disease. The results document the diverse reaction of hormones in lethally irradiated rats and contribute to a deeper recognition of metabolic imbalance in the course of radiation disease. (author)

  7. ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.

    Science.gov (United States)

    Drosos, Yiannis; Escobar, David; Chiang, Ming-Yi; Roys, Kathryn; Valentine, Virginia; Valentine, Marc B; Rehg, Jerold E; Sahai, Vaibhav; Begley, Lesa A; Ye, Jianming; Paul, Leena; McKinnon, Peter J; Sosa-Pineda, Beatriz

    2017-09-11

    Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras G12D ). We show that partial or total ATM deficiency cooperates with Kras G12D to promote highly metastatic pancreatic cancer. We also reveal that ATM is activated in pancreatic precancerous lesions in the context of DNA damage and cell proliferation, and demonstrate that ATM deficiency leads to persistent DNA damage in both precancerous lesions and primary tumors. Using low passage cultures from primary tumors and liver metastases we show that ATM loss accelerates Kras-induced carcinogenesis without conferring a specific phenotype to pancreatic tumors or changing the status of the tumor suppressors p53, p16 Ink4a and p19 Arf . However, ATM deficiency markedly increases the proportion of chromosomal alterations in pancreatic primary tumors and liver metastases. More importantly, ATM deficiency also renders murine pancreatic tumors highly sensitive to radiation. These and other findings in our study conclusively establish that ATM activity poses a major barrier to oncogenic transformation in the pancreas via maintaining genomic stability.

  8. Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice

    Directory of Open Access Journals (Sweden)

    Liao Dezhong J

    2008-01-01

    Full Text Available Abstract Background Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Results Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT and liver metastatic lesions (LM compared to normal pancreas (NP. In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1 and Serine proteinase inhibitor A1 (Serpina1, and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. Conclusion We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

  9. Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.

    Science.gov (United States)

    Thakur, Archana; Bollig, Aliccia; Wu, Jiusheng; Liao, Dezhong J

    2008-01-24

    Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

  10. Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan

    Directory of Open Access Journals (Sweden)

    Ko AH

    2016-03-01

    Full Text Available Andrew H KoDivision of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA Abstract: Nanoliposomal irinotecan (nal-IRI was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in

  11. Metastatic tonsillar squamous cell carcinoma masquerading as a pancreatic cystic tumor and diagnosed by EUS-guided FNA.

    Science.gov (United States)

    Glass, Ryan; Andrawes, Sherif A; Hamele-Bena, Diane; Tong, Guo-Xia

    2017-11-01

    Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound-guided fine needle aspiration biopsy (EUS-FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS-FNA during evaluation of pancreatic cystic lesion. © 2017 Wiley Periodicals, Inc.

  12. [Management of localized, locally advanced and metastatic pancreatic adenocarcinoma].

    Science.gov (United States)

    Delpero, Jean-Robert; Turrini, Olivier; Raoul, Jean-Luc

    2015-03-01

    Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

  13. Suppression of AKT phosphorylation restores rapamycin-based synthetic lethality in SMAD4-defective pancreatic cancer cells.

    Science.gov (United States)

    Le Gendre, Onica; Sookdeo, Ayisha; Duliepre, Stephie-Anne; Utter, Matthew; Frias, Maria; Foster, David A

    2013-05-01

    mTOR has been implicated in survival signals for many human cancers. Rapamycin and TGF-β synergistically induce G1 cell-cycle arrest in several cell lines with intact TGF-β signaling pathway, which protects cells from the apoptotic effects of rapamycin during S-phase of the cell cycle. Thus, rapamycin is cytostatic in the presence of serum/TGF-β and cytotoxic in the absence of serum. However, if TGF-β signaling is defective, rapamycin induced apoptosis in both the presence and absence of serum/TGF-β in colon and breast cancer cell lines. Because genetic dysregulation of TGF-β signaling is commonly observed in pancreatic cancers-with defects in the Smad4 gene being most prevalent, we hypothesized that pancreatic cancers would display a synthetic lethality to rapamycin in the presence of serum/TGF-β. We report here that Smad4-deficient pancreatic cancer cells are killed by rapamycin in the absence of serum; however, in the presence of serum, we did not observe the predicted synthetic lethality with rapamycin. Rapamycin also induced elevated phosphorylation of the survival kinase Akt at Ser473. Suppression of rapamycin-induced Akt phosphorylation restored rapamycin sensitivity in Smad4-null, but not Smad4 wild-type pancreatic cancer cells. This study shows that the synthetic lethality to rapamycin in pancreatic cancers with defective TGF-β signaling is masked by rapamycin-induced increases in Akt phosphorylation. The implication is that a combination of approaches that suppress both Akt phosphorylation and mTOR could be effective in targeting pancreatic cancers with defective TGF-β signaling. ©2013 AACR.

  14. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ma Yue

    2011-03-01

    Full Text Available Abstract Background The objectives of the present study are to investigate the efficacy and safety profile of gemcitabine-based combinations in the treatment of locally advanced and metastatic pancreatic adenocarcinoma (LA/MPC. Methods We performed a computerized search using combinations of the following keywords: "chemotherapy", "gemcitabine", "trial", and "pancreatic cancer". Results Thirty-five trials were included in the present analysis, with a total of 9,979 patients accrued. The analysis showed that the gemcitabine-based combination therapy was associated with significantly better overall survival (OS (ORs, 1.15; p = 0.011, progression-free survival (PFS (ORs, 1.27; p Conclusions Gemcitabine in combination with capecitabine or oxaliplatin was associated with enhanced OS and ORR as compared with gemcitabine in monotherapy, which are likely to become the preferred standard first-line treatment of LA/MPC.

  15. Cervical Spine pain as a presenting complaint in metastatic pancreatic cancer: a case report.

    Science.gov (United States)

    Rosenberg, Emily; Buchtel, Lindsey

    2016-01-01

    A 48 year-old female presented to her primary care physician with a two-month history of neck pain with negative cervical spine x-rays. During that office visit, the patient was noted to be tachycardic with EKG revealing ST depressions, which led to hospital admission. Acute coronary syndrome was ruled out, however, persistent neck pain warranted inpatient MRI of the cervical spine, which revealed a cervical spine lesion. Extensive investigation and biopsy ultimately confirmed stage IV pancreatic adenocarcinoma with metastases to the bone, liver, and likely lung. In the literature, the findings of a primary metastatic site being bone is rare with only a few case reports showing vertebral or sternal metastasis as the first clinical manifestation of pancreatic cancer. The uniqueness of this case lies in the only presenting complaint being cervical spine pain in the setting of extensive metastases to the liver, bone, and likely lung.

  16. Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study.

    Science.gov (United States)

    Imaoka, Hiroshi; Mizuno, Nobumasa; Hara, Kazuo; Hijioka, Susumu; Tajika, Masahiro; Tanaka, Tsutomu; Ishihara, Makoto; Hirayama, Yutaka; Hieda, Nobuhiro; Yoshida, Tsukasa; Okuno, Nozomi; Shimizu, Yasuhiro; Niwa, Yasumasa; Yamao, Kenji

    2016-01-01

    Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30-60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC. We conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed. Median overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45-2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71-1.40). The present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  17. Treatment of Leptomeningeal Carcinomatosis in a Patient with Metastatic Pancreatic Cancer: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    William Rainey Johnson

    2018-05-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related death with a median survival of 3–11 months when metastatic. We present a patient with metastatic pancreatic cancer and an exceptional response to initial systemic chemotherapy with FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin. Despite evidence of disease control on body imaging, he developed symptomatic leptomeningeal disease and brain metastases 29 months into treatment. He received aggressive treatment with capecitabine and irinotecan, intrathecal topotecan, and eventually bevacizumab. He did well for 36 weeks on this regimen until developing sepsis. This patient significantly outlived his expected survival and, moreover, did so with very good quality of life. This case demonstrates the natural history of pancreatic cancer progressing to involve the central nervous system when systemic disease is otherwise responsive to chemotherapy. It is the first case to demonstrate the potential effectiveness of intrathecal topotecan in combination with systemic chemotherapy for the treatment of leptomeningeal metastases of pancreatic cancer.

  18. Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer: Report From the 2015 Coffey-Holden Prostate Cancer Academy Meeting

    Science.gov (United States)

    Miyahira, Andrea K.; Lang, Joshua M.; Den, Robert B.; Garraway, Isla P.; Lotan, Tamara L.; Ross, Ashley E.; Stoyanova, Tanya; Cho, Steve Y.; Simons, Jonathan W.; Pienta, Kenneth J.; Soule, Howard R.

    2018-01-01

    BACKGROUND The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: “Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer,” was held in La Jolla, California from June 25 to 28, 2015. METHODS The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. RESULTS The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. DISCUSSION This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients. PMID:26477609

  19. Nab-Paclitaxel plus gemcitabine in patients with metastatic pancreatic adenocarcinoma: experience of use

    Directory of Open Access Journals (Sweden)

    Elena Ferris Villanueva

    2015-02-01

    Full Text Available Objective: To evaluate the results obtained with the combined use of nab-paclitaxel and gemcitabine in the treatment of patients with metastatic pancreatic adenocarcinoma. Materials and methods: Retrospective observational study. Patients treated with nab-paclitaxel and gemcitabine between January of 2013 and January of 2014 were selected. Demographical and clinical data were gathered. Results: 15 patients (mean age 59,4 ± 10,3 years were included. All patients received the combination of nab-paclitaxel and gemcitabine in first-line metastatic disease. Nine received adjuvant treatment before the disease was metastatic. The median progression-free survival rate with combined nab-paclitaxel and gemcitabine was 5,6 months (95% CI: 4,44 - 8,03. In two patients the treatment was stopped due to toxicity. Conclusions: The treatment with nab-paclitaxel and gemcitabine in our patients resulted in progression-free survival rates similar to those published in clinical trials with good treatment tolerability

  20. Nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreatic cancer: utility and experience from the clinic

    Directory of Open Access Journals (Sweden)

    Kundranda MN

    2016-01-01

    Full Text Available Madappa N Kundranda, Tomislav Dragovich Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA Abstract: Pancreatic ductal adenocarcinoma remains one of the deadliest epithelial cancers, primarily due to late diagnosis, early metastasis and the lack of effective treatments. With recent advances in systemic therapies, the median survival for metastatic disease has essentially doubled to approximately 1 year, and a significant number of patients are receiving multiple lines of therapy. One such first-line therapy is the combination of gemcitabine with nab-paclitaxel, which was approved by the US Food and Drug Administration in 2013. This standard option is now serving as a backbone to other novel combinations. In this review, we focus on the development of this combination, its clinical utility, and real-life experiences of managing patients with metastatic pancreatic ductal adenocarcinoma receiving gemcitabine and nab-paclitaxel. Keywords: pancreatic ductal adenocarcinoma, nab-paclitaxel, MPACT trial, PRODIGE 4/ACCORD 11 trial

  1. Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Nina V Chaika

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways in primary tumor and metastases of patients with pancreatic adenocarcinoma.We analyzed the metabolic gene (those involved in glycolysis, tri-carboxylic acid pathway, pentose-phosphate pathway and fatty acid metabolism expression profiles of primary and metastatic lesions from pancreatic cancer patients by gene expression arrays. We observed two principal results: genes that were upregulated in primary and most of the metastatic lesions; and genes that were upregulated only in specific metastatic lesions in a site-specific manner. Immunohistochemical (IHC analyses of several metabolic gene products confirmed the gene expression patterns at the protein level. The IHC analyses also revealed differential tumor and stromal expression patterns of metabolic enzymes that were correlated with the metastasis sites.Here, we present the first comprehensive studies that establish differential metabolic status of tumor and stromal components and elevation of aerobic glycolysis gene expression in pancreatic cancer.

  2. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs). Recent insights and advances

    International Nuclear Information System (INIS)

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, R.T.

    2012-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. (author)

  3. Deformation-driven, lethal damage to cancer cells. Its contribution to metastatic inefficiency.

    Science.gov (United States)

    Weiss, L

    1991-04-01

    Direct and indirect, in vivo and in vitro observations are in accord with the hypothesis that as a consequence of their deformation within capillaries, cancer cells undergo sphere-to-cylinder shape-transformations that create a demand for increased surface area. When this demand cannot be met by apparent increases in surface area accomplished by nonlethal, surface "unfolding," the cell surface membrane is stretched; if expansion results in more than a 4% increase in true surface area, the membrane ruptures, resulting in cancer cell death. It is suggested that this deformation-driven process is an important factor in accounting for the rapid death of circulating cancer cells that have been trapped in the microvasculature. Therefore, this mechanism is thought to make a significant contribution to metastatic inefficiency by acting as a potent rate-regulator for hematogenous metastasis.

  4. Nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreatic cancer: utility and experience from the clinic

    OpenAIRE

    Dragovich, Tomislav; Kundranda,Madappa

    2016-01-01

    Madappa N Kundranda, Tomislav Dragovich Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA Abstract: Pancreatic ductal adenocarcinoma remains one of the deadliest epithelial cancers, primarily due to late diagnosis, early metastasis and the lack of effective treatments. With recent advances in systemic therapies, the median survival for metastatic disease has essentially doubled to approximately 1 year, and a significant number of patients are receiving m...

  5. The value of positron emission tomography/computed tomography for evaluating metastatic disease in patients with pancreatic cancer.

    Science.gov (United States)

    Kim, Mi-Jin; Lee, Kwang Hyuck; Lee, Kyu Taek; Lee, Jong Kyun; Ku, Bon-Ho; Oh, Cho-Rong; Heo, Jin Seok; Choi, Seong-Ho; Choi, Dong Wook

    2012-08-01

    Routine application of positron emission tomography/computed tomography (PET/CT) for pancreatic cancer staging remains a controversial approach. The purpose of this study was to reassess the clinical impact of PET/CT for the detection of distant metastasis of pancreatic cancer. From January 2006 to June 2009, 125 patients with histologically proven pancreatic cancer that had undergone PET/CT at our hospital were retrospectively reviewed. To evaluate the clinical efficacy of PET/CT on the management plan, the post-PET/CT management plans were compared with the pre-PET/CT management plans. After the conventional staging workup, we determined that 76 patients (60.8%) had resectable lesions, whereas 48 patients had unresectable lesions. One patient underwent explorative laparotomy due to equivocal resectability. Positron emission tomography/computed tomography diagnosed distant metastasis in only 2 (2.6%) of the 76 patients with resectable lesions, and these patients did not undergo unnecessary surgical treatment. Complete resection was not performed in 8 of the 74 operative patients because they had distant metastasis detected during the operative procedure. Positron emission tomography/computed tomography diagnosed distant metastasis in 32 of the 44 patients with metastatic lesions that were histologically shown to have sensitivity of 72.7%. Positron emission tomography/computed tomography has a limited role in the evaluation of metastatic disease from pancreatic cancer.

  6. Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

    Science.gov (United States)

    Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

    2018-03-01

    Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

  7. Potentials of plasma NGAL and MIC-1 as biomarker(s in the diagnosis of lethal pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Sukhwinder Kaur

    Full Text Available Pancreatic cancer (PC is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1 are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91 and compared it with those in healthy control (HC individuals (n = 24 and patients with chronic pancreatitis (CP, n = 23. The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2, 219.2 U/mL (7.8 and 4.5 ng/mL (4.1, respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81% but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively. For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively. CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2 pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml. Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029. Overall, MIC-1 in combination with CA19-9 improved the diagnostic

  8. Immunotherapy for pancreatic cancer: present and future.

    Science.gov (United States)

    Aroldi, Francesca; Zaniboni, Alberto

    2017-06-01

    Despite the identification of some efficient drugs for the treatment of metastatic pancreatic cancer, this tumor remains one of the most lethal cancers and is characterized by a strong resistance to therapies. Pancreatic cancer has some unique features including the presence of a microenvironment filled with immunosuppressive mediators and a dense stroma, which is both a physical barrier to drug penetration and a dynamic entity involved in immune system control. Therefore, the immune system has been hypothesized to play an important role in pancreatic cancer. Thus, therapies acting on innate or adaptive immunity are being investigated. Here, we review the literature, report the most interesting results and hypothesize future treatment directions.

  9. Cetuximab plus gemcitabine/oxaliplatin (GEMOXCET) in first-line metastatic pancreatic cancer: a multicentre phase II study

    Science.gov (United States)

    Kullmann, F; Hollerbach, S; Dollinger, M M; Harder, J; Fuchs, M; Messmann, H; Trojan, J; Gäbele, E; Hinke, A; Hollerbach, C; Endlicher, E

    2009-01-01

    Targeting the epidermal growth factor receptor pathway in pancreatic cancer seems to be an attractive therapeutic approach. This study assessed the efficacy of cetuximab plus the combination of gemcitabine/oxaliplatin in metastatic pancreatic cancer. Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma. The primary end point was response according to RECIST. Patients received cetuximab 400 mg m−2 at first infusion followed by weekly 250 mg m−2 combined with gemcitabine 1000 mg m−2 as a 100 min infusion on day 1 and oxaliplatin 100 mg m−2 as a 2-h infusion on day 2 every 2 weeks. Between January 2005 and August 2006, a total of 64 patients (22 women (34%), 42 men (66%); median age 64 years (range 31–78)) were enrolled at seven study centres. On October 2007, a total of 17 patients were alive. Sixty-two patients were evaluable for baseline and 61 for assessment of response to treatment in an intention-to-treat analysis. Six patients had an incomplete drug combination within the first cycle of the treatment plan (n=4 hypersensitivity reactions to the first cetuximab infusion, n=2 refused to continue therapy). Reported grade 3/4 toxicities (% of patients) were leukopaenia 15%, anaemia 8%, thrombocytopaenia 10%, diarrhoea 7%, nausea 18%, infection 18% and allergy 7%. Cetuximab-attributable skin reactions occurred as follows: grade 0: 20%, grade 1: 41%, grade 2: 30% and grade 3: 10%. The intention-to-treat analysis of 61 evaluable patients showed an overall response rate of 33%, including 1 (2%) complete and 19 (31%) partial remissions. There were 31% patients with stable and 36% with progressive disease or discontinuation of the therapy before re-staging. The presence of a grade 2 or higher skin rash was associated with a higher likelihood of achieving objective response. Median time to progression was 118 days, with a median overall survival of 213 days. A clinical benefit response was noted in

  10. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Daniel A Monti

    Full Text Available Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week, using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier. There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.Clinicaltrials.gov NCT00954525.

  11. Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer.

    Science.gov (United States)

    Zhao, Shanshan; Geybels, Milan S; Leonardson, Amy; Rubicz, Rohina; Kolb, Suzanne; Yan, Qingxiang; Klotzle, Brandy; Bibikova, Marina; Hurtado-Coll, Antonio; Troyer, Dean; Lance, Raymond; Lin, Daniel W; Wright, Jonathan L; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2017-01-01

    Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential. Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum. Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Dose escalation to rash for erlotinib plus gemcitabine for metastatic pancreatic cancer: the phase II RACHEL study.

    Science.gov (United States)

    Van Cutsem, E; Li, C-P; Nowara, E; Aprile, G; Moore, M; Federowicz, I; Van Laethem, J-L; Hsu, C; Tham, C K; Stemmer, S M; Lipp, R; Zeaiter, A; Fittipaldo, A; Csutor, Z; Klughammer, B; Meng, X; Ciuleanu, T

    2014-11-25

    This phase II, open-label, randomised study evaluated whether patients with metastatic pancreatic cancer receiving erlotinib/gemcitabine derived survival benefits from increasing the erlotinib dose. After a 4-week run-in period (gemcitabine 1000 mg m(-2) once weekly plus erlotinib 100 mg per day), patients with metastatic pancreatic cancer who developed grade 0/1 rash were randomised to receive gemcitabine plus erlotinib dose escalation (150 mg, increasing by 50 mg every 2 weeks (maximum 250 mg); n=71) or gemcitabine plus standard-dose erlotinib (100 mg per day; n=75). The primary end point was to determine whether overall survival (OS) was improved by increasing the erlotinib dose. Secondary end points included progression-free survival (PFS), incidence of grade ⩾2 rash, and safety. Erlotinib dose escalation induced grade ⩾2 rash in 29 out of 71 (41.4%) patients compared with 7 out of 75 (9.3%) patients on standard dose. Efficacy was not significantly different in the dose-escalation arm compared with the standard-dose arm (OS: median 7.0 vs 8.4 months, respectively, hazard ratio (HR), 1.26, 95% confidence interval (CI): 0.88-1.80; P=0.2026; PFS: median 3.5 vs 4.5 months, respectively, HR, 1.09, 95% CI: 0.77-1.54; P=0.6298). Incidence of adverse events was comparable between randomised arms. The erlotinib dose-escalation strategy induced rash in some patients; there was no evidence that the higher dose translated into increased benefit.

  13. The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients

    Directory of Open Access Journals (Sweden)

    Matteo Piciucchi

    2017-03-01

    Full Text Available Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR, the Odonera Prognostic Nutritional Index (PNI, the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis. In a single center cohort study, inflammatory-based scores were assessed at diagnosis and their prognostic relevance as well as that of clinic-pathological variables were evaluated through multiple logistic regression and survival probability analysis. In 206 patients, age, male sex, tumor size, presence of distant metastasis, access to chemotherapy, and an NLR > 5 but not other scores were associated with overall survival (OS at multivariate analysis. Patients with an NLR < 5 had a median survival of 12 months compared to 4 months in those with an NLR > 5. In the 81 patients with distant metastasis at diagnosis, an NLR > 5 resulted in the only variable significantly associated with survival. Among patients with metastatic disease who received chemotherapy, the median survival was 3 months in patients with an NLR > 5 and 7 months in those with an NLR < 5. The NLR might drive therapeutic options in PDAC patients, especially in the setting of metastatic disease.

  14. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  15. Vascular Targeting in Pancreatic Cancer: The Novel Tubulin-Binding Agent ZD6126 Reveals Antitumor Activity in Primary and Metastatic Tumor Models

    Directory of Open Access Journals (Sweden)

    Axel Kleespies

    2005-10-01

    Full Text Available ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic disease, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic disease could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.

  16. Patterns of Chemotherapy Use in a U.S.-Based Cohort of Patients with Metastatic Pancreatic Cancer.

    Science.gov (United States)

    Abrams, Thomas A; Meyer, Gary; Meyerhardt, Jeffrey A; Wolpin, Brian M; Schrag, Deborah; Fuchs, Charles S

    2017-08-01

    Few population studies have examined patterns of systemic therapy administration in metastatic pancreatic cancer (MPC) or the predictors associated with specific treatment choices. We assessed 4,011 consecutive MPC patients who received chemotherapy between January 2005 and December 2015 at academic, private, and community-based oncology practices subscribing to a U.S.-wide chemotherapy order entry system capturing disease, patient, provider, and treatment data. Multivariate analyses of these prospectively recorded characteristics identified significant predictors of specific therapeutic choices. Overall, 100 different regimens were used in first-line treatment of MPC. First-line gemcitabine monotherapy usage fell steadily from 72% in 2006 to 16% in 2015. This steep decline mirrored increases in first-line usage of both 5 fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine + nab-paclitaxel. Younger male patients were more likely to receive FOLFIRINOX as first-line treatment, whereas patients treated at community practices and by oncologists with lower MPC patient volume were more likely to receive gemcitabine plus nab-paclitaxel (all p  ≤ .05). Among all patients receiving first-line chemotherapy for MPC, 49% went on to receive second-line therapy and 19% received third-line therapy; administration of second- and third-line therapies increased steadily over the time course of follow-up. Younger patients and those treated by oncologists with higher MPC patient volume were more likely to receive second- and third-line therapies. This population-based study provides insight into treatment patterns of MPC in the U.S. Usage patterns varied greatly according to patient and provider characteristics. This study examined real world metastatic pancreatic cancer treatment patterns in the United States with the goals of understanding changes in chemotherapy treatment frequencies over time and determining the individual predictors that

  17. Near-lethal respiratory failure after recombinant human thyroid-stimulating hormone use in a patient with metastatic thyroid carcinoma.

    Science.gov (United States)

    Goffman, Thomas; Ioffe, Vladimir; Tuttle, Michael; Bowers, John T; Mason, M Elizabeth

    2003-08-01

    A patient with widely metastatic differentiated thyroid cancer who had been heavily pretreated with (131)I was given recombinant human thyroid stimulating hormone (rhTSH) prior to (131)I treatment. Clinical and physical data from both this case and the literature suggest that the recombinant hormone, not the (131)I, may have caused a significant portion of the tumor swelling, which in turn was the most likely cause of the patient's symptoms. The potential effect of (131)I-induced tumor swelling and direct radiation effect on the lung is also analyzed. We review the potential hazards associated with rhTSH in patients with metastasis and propose means of minimizing this risk.

  18. A Phase 2 Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI#6366)

    Science.gov (United States)

    Carvajal, Richard D.; Tse, Archie; Shah, Manish A.; Lefkowitz, Robert A.; Gonen, Mithat; Gilman-Rosen, Lisa; Kortmansky, Jeremy; Kelsen, David P.; Schwartz, Gary K.; O'Reilly, Eileen M.

    2014-01-01

    Background/Aims Pancreatic adenocarcinoma (PC) harbors frequent alterations of p16, resulting in cell cycle dysregulation. A phase I study of docetaxel and flavopiridol, a pan-cyclin dependent kinase inhibitor, demonstrated encouraging clinical activity in PC. This phase II study was designed to further define the efficacy and toxicity of this regimen in patients with previously treated PC. Methods Patients with gemcitabine-refractory, metastatic PC were treated with docetaxel 35 mg/m2 followed by flavopiridol 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Tumor measurements were performed every two cycles. A Simon two-stage design was used to evaluate the primary endpoint of response. Results Ten patients were enrolled; nine were evaluable for response. No objective responses were observed; however, three patients (33%) achieved transient stable disease, with one of these patients achieving a 20% reduction in tumor size. Median survival was 4.2 months, with no patients alive at the time of analysis. Adverse events were significant, with seven patients (78%) requiring ≥1 dose reduction for transaminitis (11%), grade 4 neutropenia (33%), grade 3 fatigue (44%), and grade 3 diarrhea (22%) Conclusions The combination of flavopiridol and docetaxel has minimal activity and significant toxicity in this patient population. These results reflect the challenges of treating patients with PC in a second-line setting where the risk/benefit equation is tightly balanced. PMID:19451750

  19. Oxaliplatin-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Pancreatic Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Takatsugu Ogata

    2017-10-01

    Full Text Available Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancreatic adenocarcinoma with peritoneal dissemination. GEMOX consists of gemcitabine (1,000 mg/m2 and oxaliplatin (100 mg/m2 on day 1, repeated every 2 weeks. The second cycle of GEMOX was administered as planned. However, he appeared to have difficulties with daily activities. Two days later, he visited the emergency room complaining of drowsiness. On examination, the patient had a Glasgow Coma Scale (GCS score of 14 (E4V4M6, and asterixis was not present. Blood examination revealed a serum ammonia level of 202 µg/dL. The levels of serum hepatic enzymes were only mildly elevated, and the hemoglobin level was typical for this patient. Computed tomography, magnetic resonance imaging, lumbar puncture test, and blood culture showed no abnormality. Based on these results, he was diagnosed with oxaliplatin-induced hyperammonemia. One day after hospitalization, GCS score had significantly decreased to 6 (E1V1M4. His consciousness disorder improved after administration of a nutritional supplement containing a high concentration of branched-chain amino acids for 5 days, and the level of serum ammonia improved to 79 µg/dL. He stated that he could not remember the episode. The findings of this case suggest the importance of examining serum ammonia levels in patients receiving an oxaliplatin-containing regimen who develop disordered consciousness.

  20. Eligibility of Metastatic Pancreatic Cancer Patients for First-Line Palliative Intent nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX.

    Science.gov (United States)

    Peixoto, Renata D; Ho, Maria; Renouf, Daniel J; Lim, Howard J; Gill, Sharlene; Ruan, Jenny Y; Cheung, Winson Y

    2017-10-01

    The PRODIGE and MPACT trials showed superiority of FOLFIRINOX and nab-paclitaxel plus gemcitabine (NG) over gemcitabine alone, respectively. However, both had strict inclusion criteria. We sought to determine the characteristics of patients with metastatic pancreatic cancer (MPC) which inform the appropriateness of first-line chemotherapy FOLFIRINOX and NG in routine practice. Patients with MPC who initiated palliative chemotherapy with gemcitabine from 2000 to 2011 at the British Columbia Cancer Agency were identified. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. Eligibility criteria for each regimen were in accordance with the respective pivotal phase III trials. A total of 473 patients were included: 25% of the patients were eligible for FOLFIRINOX versus 45% for NG. Main reasons for FOLFIRINOX ineligibility were Eastern Cooperative Oncology Group (ECOG) performance status (PS)≥2 (56.5%), age older than 75 years (19.0%), and bilirubin>1.5× upper limit of normal (18.6%), whereas those for NG ineligibility were bilirubin > upper limit of normal (24.5%), ECOG PS≥3 (14.6%), and cardiac dysfunction (13.8%). Univariate analyses revealed that FOLFIRINOX and NG-eligible patients had longer median overall survival than their respective ineligible group (8.6 vs. 4.7 mo, Paccounting for ECOG PS in the multivariate model, however, eligibility for either FOLFIRINOX or NG no longer predicted for better overall survival. The majority of patients with MPC are not candidates to either NG or FOLFIRINOX due to restrictive eligibility requirements. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

  1. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial

    Directory of Open Access Journals (Sweden)

    Tabernero J

    2017-02-01

    Full Text Available Josep Tabernero,1 Volker Kunzmann,2 Werner Scheithauer,3 Michele Reni,4 Jack Shiansong Li,5 Stefano Ferrara,6 Kamel Djazouli7 1Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain; 2Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany; 3Medizinische Universität Wien, Wien, Austria; 4San Raffaele Scientific Institute, Milan, Italy; 5Celgene Corporation, Summit, NJ, USA; 6Celgene Corporation, Boudry, Switzerland; 7Celgene Corporation, Paris, France Purpose: The global Phase III MPACT trial demonstrated superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone as first-line treatment for metastatic pancreatic cancer. Region was a randomization stratification factor in the MPACT trial. This subgroup analysis of MPACT examined efficacy and safety of patients treated in Western Europe.Patients and methods: Patients received nab-paclitaxel plus gemcitabine or gemcitabine alone as first-line treatment for metastatic pancreatic cancer as previously described. A total of 76 patients were included in this analysis (n=38 for each arm.Results: Differences between the overall Western European cohort and the intention-to-treat population included lower percentages of male patients (46% and 58%, respectively and patients with biliary stents (8% and 17%, and higher percentages of patients with Karnofsky performance status of 90–100 (78% and 60% and primary tumors in the body of the pancreas (48% and 31%. The median overall survival was 10.7 months with nab-paclitaxel plus gemcitabine vs 6.9 months with gemcitabine alone (hazard ratio [HR]: 0.82 [95% confidence interval (CI: 0.48–1.40]; P=0.471. Median progression-free survival was 5.3 vs 3.7 months, respectively (HR: 0.70 [95% CI: 0.37–1.33]; P=0.277. The independently assessed overall response rate was 18% vs 5% (response rate ratio, 3.50 [95% CI: 0.78–15.78]; P=0.076. The most common grade ≥3 adverse events with nab

  2. 3'-Deoxy-3'-18F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    Challapalli, Amarnath; Barwick, Tara; Merchant, Shairoz; Pearson, Rachel A.; Howell, Elizabeth C.; Maxwell, Ross J.; Mauri, Francesco; Sumpter, Katherine; Aboagye, Eric O.; Sharma, Rohini

    2015-01-01

    3'-Deoxy-3'- 18 F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CT KSF ) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PET KSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35 %). Maximum standardised uptake value at 60 min post-injection (SUV 60,max ) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV 60,max increase of ≥ 12 % resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100 %, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV 60,max were not predictive of survival. FLT PET/CT detected changes in proliferation, with early increase in SUV 60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer. (orig.)

  3. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Science.gov (United States)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  4. Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

    Directory of Open Access Journals (Sweden)

    Christopher Williams

    2005-01-01

    Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

  5. Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed.

    Science.gov (United States)

    Hurwitz, Herbert I; Uppal, Nikhil; Wagner, Stephanie A; Bendell, Johanna C; Beck, J Thaddeus; Wade, Seaborn M; Nemunaitis, John J; Stella, Philip J; Pipas, J Marc; Wainberg, Zev A; Manges, Robert; Garrett, William M; Hunter, Deborah S; Clark, Jason; Leopold, Lance; Sandor, Victor; Levy, Richard S

    2015-12-01

    Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer. In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m(2) twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation. In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation-based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%). Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation. © 2015 by American Society of Clinical Oncology.

  6. Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

    Directory of Open Access Journals (Sweden)

    Golden Daniel W

    2012-09-01

    Full Text Available Abstract Background Unresectable pancreatic cancer (UPC has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT as definitive treatment for UPC and the CA 19–9 response to therapy have an impact on overall survival (OS. Methods From 1997–2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy. All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other and 24 received adjuvant chemotherapy. Results 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy. Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19–9 post-CRT Conclusions CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19–9

  7. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

    International Nuclear Information System (INIS)

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

    2012-01-01

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3′ untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible

  8. Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung

    International Nuclear Information System (INIS)

    Kalinina, Tatyana; Simon, Ronald; Otto, Benjamin; Dierlamm, Judith; Schwarzenbach, Heidi; Effenberger, Katharina E; Bockhorn, Maximilian; Izbicki, Jakob R; Yekebas, Emre F; Güngör, Cenap; Thieltges, Sabrina; Möller-Krull, Maren; Murga Penas, Eva Maria; Wicklein, Daniel; Streichert, Thomas; Schumacher, Udo; Kalinin, Viacheslav

    2010-01-01

    Pancreatic cancer is still associated with devastating prognosis. Real progress in treatment options has still not been achieved. Therefore new models are urgently needed to investigate this deadly disease. As a part of this process we have established and characterized a new human pancreatic cancer cell line. The newly established pancreatic cancer cell line PaCa 5061 was characterized for its morphology, growth rate, chromosomal analysis and mutational analysis of the K-ras, EGFR and p53 genes. Gene-amplification and RNA expression profiles were obtained using an Affymetrix microarray, and overexpression was validated by IHC analysis. Tumorigenicity and spontaneous metastasis formation of PaCa 5061 cells were analyzed in pfp -/- /rag2 -/- mice. Sensitivity towards chemotherapy was analysed by MTT assay. PaCa 5061 cells grew as an adhering monolayer with a doubling time ranging from 30 to 48 hours. M-FISH analyses showed a hypertriploid complex karyotype with multiple numerical and unbalanced structural aberrations. Numerous genes were overexpressed, some of which have previously been implicated in pancreatic adenocarcinoma (GATA6, IGFBP3, IGFBP6), while others were detected for the first time (MEMO1, RIOK3). Specifically highly overexpressed genes (fold change > 10) were identified as EGFR, MUC4, CEACAM1, CEACAM5 and CEACAM6. Subcutaneous transplantation of PaCa 5061 into pfp -/- /rag2 -/- mice resulted in formation of primary tumors and spontaneous lung metastasis. The established PaCa 5061 cell line and its injection into pfp -/- /rag2 -/- mice can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease

  9. Comparison of treatment patterns and economic outcomes among metastatic pancreatic cancer patients initiated on nab-paclitaxel plus gemcitabine versus FOLFIRINOX.

    Science.gov (United States)

    McBride, Ali; Bonafede, Machaon; Cai, Qian; Princic, Nicole; Tran, Oth; Pelletier, Corey; Parisi, Monika; Patel, Manish

    2017-10-01

    The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P + G) and FOLFIRINOX. The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P + G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment. Duration of therapy, per patient per month (PPPM) costs of total healthcare, mPC-related treatment, and supportive care were measured during first-line therapy. 550 mPC patients met selection criteria (nab-P + G, n = 294; FOLFIRINOX, n = 256). There was no difference in duration of therapy (p = 0.60) between nab-P + G and FOLFIRINOX. Compared with FOLFIRINOX, patients with nab-P + G had higher chemotherapy drug costs but lower treatment administration costs and supportive care costs (all p < 0.01). Patients treated with nab-P + G (vs FOLFIRINOX) had similar treatment duration but lower costs of outpatient prescriptions, treatment administration and supportive care. Lower supportive care costs in the nab-P + G cohort were mainly driven by lower utilization of pegfilgrastim and anti-emetics.

  10. Response gene to complement-32 enhances metastatic phenotype by mediating transforming growth factor beta-induced epithelial-mesenchymal transition in human pancreatic cancer cell line BxPC-3

    Directory of Open Access Journals (Sweden)

    Zhu Liang

    2012-03-01

    RNA silencing and gene overexpression, we further demonstrated that RGC-32 mediated TGF-β-induced EMT and migration in BxPC-3 cells. Conclusions The results above indicated that RGC-32 might be a novel metastasis promoting gene in pancreatic cancer and it enhances metastatic phenotype by mediating TGF-β-induced EMT in human pancreatic cancer cell line BxPC-3.

  11. Serum levels of LDH, CEA, and CA19-9 have prognostic roles on survival in patients with metastatic pancreatic cancer receiving gemcitabine-based chemotherapy.

    Science.gov (United States)

    Tas, Faruk; Karabulut, Senem; Ciftci, Rumeysa; Sen, Fatma; Sakar, Burak; Disci, Rian; Duranyildiz, Derya

    2014-06-01

    Serum LDH, CEA, and CA19-9 levels are important tumor markers in pancreatic cancer. The purpose of this study was to evaluate the clinical significance of serum LDH, CEA, and CA19-9 levels in metastatic pancreatic cancer (MPC) receiving gemcitabine-based chemotherapy. In this retrospective study, we analyzed the outcome of 196 MPC patients who are treated with gemcitabine-based chemotherapy in our clinic. Positivity rates of serum LDH, CEA, and CA19-9 were 22, 40, and 83 %, respectively. Likewise, the rates of very high serum levels of tumor markers were correlated with these positivity rates (9 % for LDH, 30 % for CEA, and 55 % for CA19-9). The serum LDH levels were significantly higher in older patients (p = 0.05) and also in the patients with large tumors (p = 0.05), hepatic metastasis (p = 0.01), hypoalbuminemia (p = 0.01), and unresponsive to chemotherapy (p = 0.04). However, no correlation was found between both serum CEA and CA19-9 levels and possible prognostic factors (p > 0.05). The significant relationships were found between the serum levels of CEA and CA19-9 (r s = 0.24, p = 0.004), and serum LDH and CEA (r(s) = 0.193, p = 0.02). But, there was no correlation between serum LDH and CA19-9 levels (p = 0.39). One-year overall survival rate was 12.8 % (95 % CI 8-18). Increased serum levels of all the tumor markers significantly had adverse affect on survival (p = 0.001 for LDH, p = 0.002 for CEA, and p = 0.007 for CA19-9). However, no difference was observed in between high levels and very high levels of serum markers for all tumor markers (p > 0.05). Patients with normal serum levels of all three tumor markers had better outcome than others (p = 0.002) and those with normal serum LDH and CEA levels (whatever CA19-9) levels had associated with better survival compared with other possible alternatives (p CEA, and CA19-9 had significant affect on survival in MPC patients.

  12. Long-term outcomes of {sup 131}Iodine mIBG therapy in metastatic gastrointestinal pancreatic neuroendocrine tumours: single administration predicts non-responders

    Energy Technology Data Exchange (ETDEWEB)

    Mulholland, Nicola; Chakravartty, Riddhika; Devlin, Lindsey; Kalogianni, Eleni; Corcoran, Ben; Vivian, Gillian [King' s College Hospital, Department of Nuclear Medicine, London (United Kingdom)

    2015-12-15

    {sup 131}Iodine (I131)-metaiodobenzylguanidine (mIBG) is a radionuclide-based treatment option for metastatic gastrointestinal-pancreatic neuroendocrine tumours (GEP NET). This study aimed at identifying prognostic indicators of long-term outcome based on initial evaluation following a first mIBG treatment (7400 MBq) in a patient cohort with such tumours, with a secondary aim of evaluating progression-free survival (PFS) and overall survival (OS) following mIBG therapy. Retrospective review of the hospital records was performed to identify a cohort of 38 adult patients who underwent {sup 131}Iodine-mIBG therapy over a 9-year period for metastatic GEP NETs and neuroendocrine tumours with an unknown primary. Treatment response was evaluated based on radiological criteria (RECIST1.1), biochemical markers [serum Chromogranin A (CgA)/urinary 5HIAA] and symptomatic response at clinical follow-up, all evaluated at 3-6 months from first mIBG treatment. Progression-free survival (PFS) and overall survival (OS) from the first mIBG treatment were recorded. At 3-6 months following a single mIBG therapy, 75 %, 67 %, and 63 % of patients showed either a partial response (PR) or stable disease (SD) on radiological, biochemical, and symptomatic criteria, respectively. Complete response (CR) was not seen in any patient. OS from the date of diagnosis and from the first therapy was 8 years +/-1.1 (95 % CI 5.7 to 10.2 years) and 4 years+/-0.69 (95 % CI 2.6-5.3 years), respectively. Twenty-nine percent of patients were alive at 10 years. Significant survival advantage was seen in patients with SD/PR as compared to those who had progressive disease (PD) for each of these three criteria. Biochemical, radiological (RECIST 1.1) and symptomatic assessment of disease status at 3 to 6 months after first I131-mIBG therapy stratifies patients with a poor prognosis. This can be used to identify patients who may benefit from alternative strategies of treatment. (orig.)

  13. A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

    Science.gov (United States)

    Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

    2016-01-01

    Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

  14. Prediction of overall survival for metastatic pancreatic cancer: Development and validation of a prognostic nomogram with data from open clinical trial and real-world study.

    Science.gov (United States)

    Hang, Junjie; Wu, Lixia; Zhu, Lina; Sun, Zhiqiang; Wang, Ge; Pan, Jingjing; Zheng, Suhua; Xu, Kequn; Du, Jiadi; Jiang, Hua

    2018-06-01

    It is necessary to develop prognostic tools of metastatic pancreatic cancer (MPC) for optimizing therapeutic strategies. Thus, we tried to develop and validate a prognostic nomogram of MPC. Data from 3 clinical trials (NCT00844649, NCT01124786, and NCT00574275) and 133 Chinese MPC patients were used for analysis. The former 2 trials were taken as the training cohort while NCT00574275 was used as the validation cohort. In addition, 133 MPC patients treated in China were taken as the testing cohort. Cox regression model was used to investigate prognostic factors in the training cohort. With these factors, we established a nomogram and verified it by Harrell's concordance index (C-index) and calibration plots. Furthermore, the nomogram was externally validated in the validation cohort and testing cohort. In the training cohort (n = 445), performance status, liver metastasis, Carbohydrate antigen 19-9 (CA19-9) log-value, absolute neutrophil count (ANC), and albumin were independent prognostic factors for overall survival (OS). A nomogram was established with these factors to predict OS and survival probabilities. The nomogram showed an acceptable discrimination ability (C-index: .683) and good calibration, and was further externally validated in the validation cohort (n = 273, C-index: .699) and testing cohort (n = 133, C-index: .653).The nomogram total points (NTP) had the potential to stratify patients into 3-risk groups with median OS of 11.7, 7.0 and 3.7 months (P < .001), respectively. In conclusion, the prognostic nomogram with NTP can predict OS for patients with MPC with considerable accuracy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    Science.gov (United States)

    2017-04-18

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  16. Phase 2, multicenter, open-label study of tigatuzumab (CS-1008), a humanized monoclonal antibody targeting death receptor 5, in combination with gemcitabine in chemotherapy-naive patients with unresectable or metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    Forero-Torres, Andres; Infante, Jeffrey R; Waterhouse, David; Wong, Lucas; Vickers, Selwyn; Arrowsmith, Edward; He, Aiwu Ruth; Hart, Lowell; Trent, David; Wade, James; Jin, Xiaoping; Wang, Qiang; Austin, TaShara; Rosen, Michael; Beckman, Robert; Roemeling, Reinhard von; Greenberg, Jonathan; Saleh, Mansoor

    2013-01-01

    Tigatuzumab is the humanized version of the agonistic murine monoclonal antibody TRA-8 that binds to the death receptor 5 and induces apoptosis of human cancer cell lines via the caspase cascade. The combination of tigatuzumab and gemcitabine inhibits tumor growth in murine pancreatic xenografts. This phase 2 trial evaluated the efficacy of tigatuzumab combined with gemcitabine in 62 chemotherapy-naive patients with histologically or cytologically confirmed unresectable or metastatic pancreatic cancer. Patients received intravenous tigatuzumab (8 mg/kg loading dose followed by 3 mg/kg weekly) and gemcitabine (1000 mg/m 2 once weekly for 3 weeks followed by 1 week of rest) until progressive disease (PD) or unacceptable toxicity occurred. The primary end point was progression-free survival (PFS) at 16 weeks. Secondary end points included objective response rate (ORR) (complete responses plus partial responses), duration of response, and overall survival (OS). Safety of the combination was also evaluated. Mean duration of treatment was 18.48 weeks for tigatuzumab and 17.73 weeks for gemcitabine. The PFS rate at 16 weeks was 52.5% (95% confidence interval [CI], 39.3–64.1%). The ORR was 13.1%; 28 (45.9%) patients had stable disease and 14 (23%) patients had PD. Median PFS was 3.9 months (95% CI, 2.2–5.4 months). Median OS was 8.2 months (95% CI, 5.1–9.6 months). The most common adverse events related to tigatuzumab were nausea (35.5%), fatigue (32.3%), and peripheral edema (19.4%). Tigatuzumab combined with gemcitabine was well tolerated and may be clinically active for the treatment of chemotherapy-naive patients with unresectable or metastatic pancreatic cancer

  17. Targeting Insulin-Like Growth Factor 1 Receptor Inhibits Pancreatic Cancer Growth and Metastasis

    Science.gov (United States)

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Arumugam, Arunkumar; Nandy, Sushmita; Boopalan, Thiyagarajan; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor β. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer. PMID:24809702

  18. Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    Konski, Andre; Meyer, Joshua E.; Joiner, Michael; Hall, Michael J.; Philip, Philip; Shields, Anthony; McSpadden, Erin; Choi, Minsig; Adaire, Beth; Duncan, Gail; Meropol, Neal J.; Cescon, Terrence P.; Cohen, Steven J.

    2014-01-01

    Purpose: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0–1 who had received 0–1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 and 8, E once PO QD, and twice daily RT fractions separated by at least 4 h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. Conclusion: This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients

  19. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  20. FDA Approves Irinotecan Liposome to Treat Pancreatic Cancer

    Science.gov (United States)

    Patients with metastatic pancreatic cancer that has progressed after receiving gemcitabine-based chemotherapy now have a new treatment option: irinotecan liposome in combination with fluorouracil and leucovorin.

  1. Therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Takeda, Yutaka; Kitagawa, Toru; Nakamori, Shoji

    2009-01-01

    Pancreatic cancer remains one of the most difficult diseases to cure. Japan pancreas society guidelines for management of pancreatic cancer indicate therapeutic algorithm according to the clinical stage. For locally limited pancreatic cancer (cStage I, II, III in Japanese classification system), surgical resection is recommended, however prognosis is still poor. Major randomized controlled trials of resected pancreatic cancer indicates that adjuvant chemotherapy is superior to observation and gemcitabine is superior to 5-fluorouracil (FU). For locally advanced resectable pancreatic cancer (cStage IVa in Japanese classification system (JCS)), we perform neoadjuvant chemoradiotherapy. Phase I study established a recommended dose of 800 mg gemcitabine and radiation dose of 36 Gy. For locally advanced nonresectable pancreatic cancer (cStage IVa in JCS), chemoradiotherapy followed by chemotherapy is recommended. Although pancreatic cancer is chemotherapy resistant tumor, systemic chemotherapy is recommended for metastatic pancreatic cancer (cStage IVb in JCS). Single-agent gemcitabine is the standard first line agent for the treatment of advanced pancreatic cancer. Meta-analysis of chemotherapy showed possibility of survival benefit of gemcitabine combination chemotherapy over gemcitabine alone. We hope gemcitabine combination chemotherapy or molecular targeted therapy will improve prognosis of pancreatic cancer in the future. (author)

  2. Lethal Epistaxis.

    Science.gov (United States)

    Byard, Roger W

    2016-09-01

    Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. © 2016 American Academy of Forensic Sciences.

  3. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

    2010-12-16

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  4. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    International Nuclear Information System (INIS)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L.

    2010-01-01

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis

  5. 3'-Deoxy-3'-{sup 18}F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Challapalli, Amarnath; Barwick, Tara; Merchant, Shairoz [Imperial College London (ICL), Department of Surgery and Cancer, London (United Kingdom); Pearson, Rachel A.; Howell, Elizabeth C.; Maxwell, Ross J. [Newcastle University, Northern Institute for Cancer Research, Newcastle (United Kingdom); Mauri, Francesco [Imperial College Healthcare NHS Trust, Department of Pathology, London (United Kingdom); Sumpter, Katherine [Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals NHS Foundation Trust, London (United Kingdom); Aboagye, Eric O. [Imperial College London (ICL), Department of Surgery and Cancer, London (United Kingdom); ICL, Hammersmith Hospital, Department of Surgery and Cancer, London (United Kingdom); Sharma, Rohini [ICL, Department of Investigative Medicine, London (United Kingdom)

    2015-05-01

    3'-Deoxy-3'-{sup 18}F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CT{sub KSF}) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PET{sub KSF} images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35 %). Maximum standardised uptake value at 60 min post-injection (SUV{sub 60,max}) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV{sub 60,max} increase of ≥ 12 % resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100 %, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV{sub 60,max} were not predictive of survival. FLT PET/CT detected changes in proliferation, with early increase in SUV{sub 60,max} predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer. (orig.)

  6. Pancreatitis - discharge

    Science.gov (United States)

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... You were in the hospital because you have pancreatitis. This is a swelling of the pancreas. You ...

  7. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  8. Fluorescent humanized anti-CEA antibody specifically labels metastatic pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model

    Science.gov (United States)

    Lwin, Thinzar M.; Miyake, Kentaro; Murakami, Takashi; DeLong, Jonathan C.; Yazaki, Paul J.; Shivley, John E.; Clary, Bryan; Hoffman, Robert M.; Bouvet, Michael

    2018-03-01

    Specific tumor targeting can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively target and label pancreatic cancer and its metastases in a clinically relevant patient derived xenograft mouse model.

  9. A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial.

    Science.gov (United States)

    Bachet, Jean-Baptiste; Chibaudel, Benoist; Bonnetain, Franck; Validire, Pierre; Hammel, Pascal; André, Thierry; Louvet, Christophe

    2015-10-06

    Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC. AFUGEM is a two-stage, open-label, randomized, multicenter, phase II trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed. The AFUGEM trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC. AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.

  10. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  11. Chronic Pancreatitis.

    Science.gov (United States)

    Stram, Michelle; Liu, Shu; Singhi, Aatur D

    2016-12-01

    Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Interventional radiological treatment in complications of pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Memis, Ahmet E-mail: ahmemis@yahoo.com; Parildar, Mustafa

    2002-09-01

    Percutaneous interventional therapy plays an important role in treating complications of acute and chronic pancreatitis. With the development of cross-sectional imaging and advanced interventional techniques, percutaneous drainage has become the preferred treatment for pancreatic fluid collections such as acute collections, pseudocysts and abscesses. Abscess and pancreatic hemorrhage are the most life threatening complications of pancreatitis. Massive hemorrhage is rare but frequently lethal. As a rule, bleeding complications of pancreatitis require prompt diagnosis and an aggressive surgical approach. In unstable patients with a severely bleeding pseudoaneurysm, hemostasis can be obtained by occlusion with mechanical devices.

  13. Interventional radiological treatment in complications of pancreatitis

    International Nuclear Information System (INIS)

    Memis, Ahmet; Parildar, Mustafa

    2002-01-01

    Percutaneous interventional therapy plays an important role in treating complications of acute and chronic pancreatitis. With the development of cross-sectional imaging and advanced interventional techniques, percutaneous drainage has become the preferred treatment for pancreatic fluid collections such as acute collections, pseudocysts and abscesses. Abscess and pancreatic hemorrhage are the most life threatening complications of pancreatitis. Massive hemorrhage is rare but frequently lethal. As a rule, bleeding complications of pancreatitis require prompt diagnosis and an aggressive surgical approach. In unstable patients with a severely bleeding pseudoaneurysm, hemostasis can be obtained by occlusion with mechanical devices

  14. Pancreatic Carcinoma With Hepatic Metastasis And Early Signs Of ...

    African Journals Online (AJOL)

    Pancreatic carcinoma is one of the lethal neoplasms. Involvement of pancreatic body and tail are uncommon compared to that of the head and neck. Sinistral portal hypertension is a rare complication of pancreatic tumor which results from obstruction of portal vein tributaries. Imaging may be the only clue to diagnosis.

  15. Prevention and Intervention Strategies in Acute Pancreatitis

    NARCIS (Netherlands)

    Besselink, M.G.H.

    2008-01-01

    Acute pancreatitis is a common, costly, potentially lethal, and poorly understood disease, mostly caused by gallstones. In the past decade the incidence of acute pancreatitis in the Netherlands increased by 50% to over 3400 admissions in 2006, most likely due to an increase of gallstone disease.

  16. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  17. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  18. Pancreatic Cysts

    Science.gov (United States)

    ... enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the ... alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. ...

  19. Metastatic Cancer

    Science.gov (United States)

    Metastatic cancer is cancer that spreads from its site of origin to another part of the body. Learn how cancer spreads, possible symptoms, common sites where cancer spreads, and how to find out about treatment options.

  20. Whole genomes redefine the mutational landscape of pancreatic cancer

    OpenAIRE

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (...

  1. [Treatments for Pancreatic Cancer with Oligometastasis].

    Science.gov (United States)

    Furuse, Junji

    2017-10-01

    Pancreatic cancer, adenocarcinoma, generally rapidly progresses, and if a metastatic lesion is detected, chemotherapy is applied even in solitary metastasis. However, surgical resection for solitary metastasis have been reported to achieve long survival in some pancreatic cancer patients. In a prospective study of surgery for hepatic and lymph node oligometastasis of pancreatic cancer, long survival of 5 years or more was reported around 10%. Furthermore, longer survival and fewer rerecurrence were achieved with surgery in lung metastasis than in liver metastasis and loco-regional recurrence. Although there has been no establishment of concept or no consensus of treatment strategy for oligometastasis in pancreatic cancer, some patients with pancreatic cancer have long disease-free survival by surgery for oligometastasis. A population of pancreatic cancer patients who have benefits of surgery for oligometastasis should be identified, and it is necessary to establish treatments for oligometastasis as standard treatments in pancreatic cancer.

  2. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  3. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  4. Ultrasonographic diagnosis of pancreatic and peripancreatic cancer

    International Nuclear Information System (INIS)

    Park, Churl Min; Kim, Ho Kyun; Yoon, Yup; Lee, Sun Wha; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Seventeen cases of cancers in and adjacent to the pancreas were studied by high resolution and wide field real time ultrasonographic scanner with 3.5 MHz linear array electronically focusing transducer. The result were as follows: 1. In a total of 17 cases, 7 cases were pancreatic cancers and the rests were 3 cases of ampulla of Vaster cancer, 3 cases of distal CBD cancers, and 4 cases of metastatic cancers, respectively. 2. Pancreatic cancers were located mainly in head portion, and metastatic cancers were noted in head, tail, and retropancreatic areas. 3. The sizes of all distal CBD cancer were less than 1.8 cm, usually smaller than other tumors, and the size of metastatic cancers were variable (1-6 cm). 4. The shape, margin, contour and echogenicity of the tumors were variable. 5. Pancreatic duct showed marked dilatation in one of pancreatic cancer, and mild dilatation in one of ampulla of Vater cancer. 6. The caliber of extrahepatic duct were moderately or markedly dilated in nearly all cases except 2 cases of pancreatic body cancer. 7. The pancreatic margin is partially obliterated in pancreatic and ampulla of Vater cancers but not in distal CBD cancer. 8. Gallbladder enlargement is secondary change due to the obstruction of extrahepatic bile duct. 9. Effects on the vessels are due to not only direct mass effect but direct invasion resulting in obliteration. The most commonly involved vessels are spleno-portal junction, splenic vein and portal vein. In case of pancreatic cancer in uncinate process, the superior mesenteric vessels are displaced anteriorly. 10. Surrounding metastatic lesions were suspected in pancreatic and ampulla of Vater cancer, but not seen in distal CBD cancer. 11. Ascites were seen in only two cases of metastasis

  5. Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients.

    Directory of Open Access Journals (Sweden)

    Jayasree Chakraborty

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize that heterogeneity reflects underlying differences at the histologic or genetic level and will therefore correlate with patient outcome. We quantify heterogeneity of PDAC with texture analysis to predict 2-year survival. Using fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes classifier, the proposed features achieve an area under receiver operating characteristic curve (AUC of 0.90 and accuracy (Ac of 82.86% with the leave-one-image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross-validation. We conclude that texture analysis can be used to quantify heterogeneity in CT images to accurately predict 2-year survival in patients with pancreatic cancer. From these data, we infer differences in the biological evolution of pancreatic cancer subtypes measurable in imaging and identify opportunities for optimized patient selection for therapy.

  6. Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients.

    Science.gov (United States)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Cunanan, Kristen M; Escalon, Joanna G; Allen, Peter J; Lowery, Maeve A; O'Reilly, Eileen M; Gönen, Mithat; Do, Richard G; Simpson, Amber L

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize that heterogeneity reflects underlying differences at the histologic or genetic level and will therefore correlate with patient outcome. We quantify heterogeneity of PDAC with texture analysis to predict 2-year survival. Using fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes classifier, the proposed features achieve an area under receiver operating characteristic curve (AUC) of 0.90 and accuracy (Ac) of 82.86% with the leave-one-image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross-validation. We conclude that texture analysis can be used to quantify heterogeneity in CT images to accurately predict 2-year survival in patients with pancreatic cancer. From these data, we infer differences in the biological evolution of pancreatic cancer subtypes measurable in imaging and identify opportunities for optimized patient selection for therapy.

  7. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ayesha Salahuddin

    2014-01-01

    Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.

  8. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  9. Pancreatic cancer stromal biology and therapy

    Science.gov (United States)

    Xie, Dacheng; Xie, Keping

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

  10. Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

    Science.gov (United States)

    2017-07-15

    Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

  11. Pancreatic trauma.

    Science.gov (United States)

    Lahiri, R; Bhattacharya, S

    2013-05-01

    Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases

  12. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  13. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-12-01

    deprivation therapy (ADT) or androgen receptor (AR) pathway inhibition (ARPI) but eventually develops into lethal castration resistance prostate cancer ...AWARD NUMBER: W81XWH-14-1-0553 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Gleave...Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0553 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Martin Gleave 5d

  14. Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer.

    Science.gov (United States)

    Shaib, Walid L; Ip, Andrew; Cardona, Kenneth; Alese, Olatunji B; Maithel, Shishir K; Kooby, David; Landry, Jerome; El-Rayes, Bassel F

    2016-02-01

    Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC. Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized. ©AlphaMed Press.

  15. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Surlin Valeriu

    2012-09-01

    Full Text Available Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performed for other diagnostic reasons. Intraoperative discovery is even rarer and poses problems of differential diagnosis with other pancreatic tumors. Association with chronic pancreatitis is rare and usually due to pancreatic duct obstruction by the tumor. We describe the case of a patient with a small non-functioning neuroendocrine tumor in the pancreatic tail accidentally discovered during surgery for delayed traumatic splenic rupture associated with chronic alcoholic pancreatitis. The tumor of 1.5cm size was well differentiated and confined to the pancreas, and was resected by a distal splenopancreatectomy. Conclusions Surgeons should be well aware of the rare possibility of a non-functional neuroendocrine tumor in the pancreas, associated with chronic pancreatitis, surgical resection being the optimal treatment for cure. Histopathology is of utmost importance to establish the correct diagnosis, grade of differentiation, malignancy and prognosis. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2114470176676003.

  16. TRAUMATIC PANCREATITIS

    Science.gov (United States)

    Berne, Clarence J.; Walters, Robert L.

    1953-01-01

    Traumatic pancreatitis should be considered as a diagnostic possibility when trauma to the epigastrium is followed by phenomena suggestive of intra-abdominal injury. The presence or absence of hyperamylasemia should be established immediately. Even when traumatic pancreatitis is believed to exist, any suggestion of injury to other viscera should indicate laparotomy. Retroperitoneal rupture of the duodenum may simulate traumatic pancreatitis in all respects, including hyperamylasemia. X-ray studies may be of value in differentiation. Non-complicated traumatic pancreatitis is best treated conservatively. Gunshot and knife wounds of the pancreas should be drained. PMID:13094537

  17. Acute pancreatitis.

    Science.gov (United States)

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

  18. Pancreatitis in Children.

    Science.gov (United States)

    Sathiyasekaran, Malathi; Biradar, Vishnu; Ramaswamy, Ganesh; Srinivas, S; Ashish, B; Sumathi, B; Nirmala, D; Geetha, M

    2016-11-01

    Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].

  19. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    Science.gov (United States)

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

  20. Metastatic tumor of the pancreas: helical CT findings

    International Nuclear Information System (INIS)

    Lee, Soon Jin; Lee, Won Jae; Lim, Hyo Keun; Kim, Seung Hoon; Kim, Kyeong Ah; Choi, Sang Hee; Jang, Hyun Jung; Lee, Ji Yeon

    2000-01-01

    To analyze the helical computed tomographic (CT) findings of distant metastatic tumors to the pancreas and to determine the differential points between these and primary pamcreatic carcinomas. We sruveyed 22 patients with metastatic tumor of the pancreas, proven on the basis of clinical and pathological findings. Seventeen patients were men, and five were women, and their ages ranged between 36 and 83 years. Their primary conditions were lung cancer (n=3D15), rectal cancer (n=3D2), melanoma of the foot, chondrosarcoma of the sacrum, cervical cancer, leiomyosarcoma of the uterus, and extragonadal choriocarcinoma of the mediastinum. We retrospectively reviewed the abdominal helical CT findings, analysing the number, location, size and attenuation of masses, as well as secondary change, which included dilatation of the pancreatic and biliary ducts and invasion of peripancreatic tissue or vessels. We also evaluated the differential findings of primary pancreatic cancer. Sixteen patients had a solitary focal mass, while in five, two masses were present. Among the 22 patients, low-density nodular masses were present in 21; in the other, in whom multiple metastasis from chondrosarcoma had occurred, there was dense calcification. The size of metastatic masses varied, ranging from 0.6 to 6 cm in diameter. The pancreatic duct proximal to the mass was dilated in ten cases, while the bile duct was dilated in six. The metastatic masses masses demonstrated no peripancreatic or vascular invasion, though they showed a discrete margin and contour bulging. Single metastasis to the pancreas was most common, and metastatic masses had a discrete margin, with contour bulging. There was no peripancreatic or vascular invasion. If the metastasis involved a single low-attenuated mass, however, with pancreatic or biliary dilatation, it was difficult to differentiate this from primary pancreatic cancer. (author)

  1. Chronic pancreatitis.

    Science.gov (United States)

    Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

    2017-09-07

    Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

  2. Nutrition Following Pancreatic Surgery

    Science.gov (United States)

    ... BACK Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Nutrition Following Pancreatic Surgery Home Facing Pancreatic Cancer Living with Pancreatic Cancer Diet and Nutrition Nutrition Following Pancreatic Surgery Ver esta página en ...

  3. Acute Pancreatitis in Children

    Science.gov (United States)

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... Acute Pancreatitis in Children Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and ...

  4. miR-1271 inhibits migration, invasion and epithelial-mesenchymal transition by targeting ZEB1 and TWIST1 in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Liu, Huaize; Wang, Han; Liu, Xiaoxiao; Yu, Tingting

    2016-01-01

    Pancreatic cancer (PC) remains one of the most lethal types of cancer in adults. The purpose of this study was to determine the role of miR-1271 in regulation of epithelial mesenchymal transition (EMT) and metastasis of pancreatic cancer cells. miR-1271 was identified to be significantly down-regulated in PC tissues by miRNA array. Also, an increase of EMT-regulators ZEB1 and TWIST1 expression level is accompanied by a decrease of miR-1271. We showed that expression of miR-1271 was significantly down-regulated in PC tissues as compared with that in normal tissues. In addition, our results showed that miR-1271 expression levels were decreased while ZEB1 and TWIST1 expression levels were increased in detected PC cell lines. Moreover, ectopic expression of miR-1271 suppressed and antagomiR-1271 promoted proliferation, migration, and invasion in SW1990 and PANC-1 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-1271 inhibited expression of ZEB1 and TWIST1, which are master regulators of tumor metastasis. Our study first indicates that miR-1271 functions as a suppressor in regulating of pancreatic cancer EMT by targeting ZEB1 and TWIST1, and it promise as a therapeutic target and prognostic marker for metastatic pancreatic cancer. - Highlights: • miR-1271 is downregulated in pancreatic cancer tissues and cell lines. • miR-1271 regulates cell metastasis ability and EMT marker expression. . • miR-1271 directly targets ZEB1 and TWIST1. • ZEB1 and TWIST1 are functionally related to the effects of miR-1271.

  5. miR-1271 inhibits migration, invasion and epithelial-mesenchymal transition by targeting ZEB1 and TWIST1 in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Huaize [Department of Developmental Genetics, Nanjing Medical University, Nanjing 210029 (China); Wang, Han [The First Clinical Medical College of Nanjing Medical University, Nanjing 210029 (China); Liu, Xiaoxiao [Department of Biotechnology, Nanjing Medical University, Nanjing 210029 (China); Yu, Tingting, E-mail: tingting@njmu.edu.cn [Department of Developmental Genetics, Nanjing Medical University, Nanjing 210029 (China)

    2016-04-01

    Pancreatic cancer (PC) remains one of the most lethal types of cancer in adults. The purpose of this study was to determine the role of miR-1271 in regulation of epithelial mesenchymal transition (EMT) and metastasis of pancreatic cancer cells. miR-1271 was identified to be significantly down-regulated in PC tissues by miRNA array. Also, an increase of EMT-regulators ZEB1 and TWIST1 expression level is accompanied by a decrease of miR-1271. We showed that expression of miR-1271 was significantly down-regulated in PC tissues as compared with that in normal tissues. In addition, our results showed that miR-1271 expression levels were decreased while ZEB1 and TWIST1 expression levels were increased in detected PC cell lines. Moreover, ectopic expression of miR-1271 suppressed and antagomiR-1271 promoted proliferation, migration, and invasion in SW1990 and PANC-1 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-1271 inhibited expression of ZEB1 and TWIST1, which are master regulators of tumor metastasis. Our study first indicates that miR-1271 functions as a suppressor in regulating of pancreatic cancer EMT by targeting ZEB1 and TWIST1, and it promise as a therapeutic target and prognostic marker for metastatic pancreatic cancer. - Highlights: • miR-1271 is downregulated in pancreatic cancer tissues and cell lines. • miR-1271 regulates cell metastasis ability and EMT marker expression. . • miR-1271 directly targets ZEB1 and TWIST1. • ZEB1 and TWIST1 are functionally related to the effects of miR-1271.

  6. A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

    Directory of Open Access Journals (Sweden)

    F. de Clerck

    2015-01-01

    Full Text Available Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.

  7. [Pancreatic trauma].

    Science.gov (United States)

    Arvieux, C; Guillon, F; Létoublon, Ch; Oughriss, M

    2003-10-01

    Early diagnosis of pancreatic trauma has always been challenging because of the lack of correlation between the initial clinical symptomatology, radiologic and laboratory findings, and the severity of the injury. Thanks to the improved performance of spiral CT scanning and magnetic resonance pancreatography, it is now often possible to make an early diagnosis of pancreatic contusion, to localize the site of the injury, and (most importantly) to identify injury to the main pancreatic duct which has major implications for the management of the case. When the trauma victim is unstable, radiologic work-up may be impossible and urgent laparotomy is required. Control of hemorrhage is the primary concern here and a damage control approach with packing may be appropriate; if the pancreatic head has been destroyed, a pancreaticoduodenectomy with delayed reconstruction may be required. If the trauma victim is stable, the treatment strategy will be governed by a variety of parameters--age, clinical condition, associated local anatomic findings (pancreatitis, injury to the duodenum or biliary tract), involvement of the pancreatic duct, and localization of the injury within the gland (to right or left of the mesenteric vessels).

  8. Combined treatment of unresectable pancreatic carcinoma

    International Nuclear Information System (INIS)

    Ohashi, Kazuhiko; Yamao, Kenji; Watanabe, Yoshihiro; Morimoto, Takeshi

    1999-01-01

    For patients with unresectable pancreatic carcinoma, a few kind of treatment including chemoradiation, intraoperative radiation and intra-arterial chemotherapy was done. Chemoradiation using 5FU, CDDP, ADM and radiation to the lesion and liver was performed in 16 patients, showing a response rate of 10%. One-year survivals rate and mean a survival period of this group was 11.7% and 6.6 months respectively. Postmortem autopsy in 6 cases revealed insufficient therapeutic effects in both primary and metastatic site. Because of above-mentioned reasons, chemoradiation therapy to the pancreatic carcinoma, which we did, was estimated as ineffective. (author)

  9. Out-FOXing Pancreatic Cancer | Center for Cancer Research

    Science.gov (United States)

    Pancreatic cancer is one of the most lethal cancer types worldwide with increasing incidence and mortality rates in the United States. Consequently, it is projected to become the second leading cause of cancer death by 2020. Poor patient outcomes are due to a combination of diagnosis at an advanced stage and a lack of effective treatments. However, a better understanding of the molecular pathways at work in pancreatic cancers may lead to the identification of novel therapeutic targets.

  10. Role of epithelial mesenchymal transition (EMT in pancreatic ductal adenocarcinoma (PDAC: is tumor budding the missing link?

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou

    2013-09-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC ranks as the fourth commonest cause of cancer death while its incidence is increasing worldwide. For all stages, survival at 5 years is <5%. The lethal nature of pancreatic cancer is attributed to its high metastatic potential to the lymphatic system and distant organs. Lack of effective therapeutic options contributes to the high mortality rates of PDAC. Recent evidence suggests that epithelial-mesenchymal transition (EMT plays an important role to the disease progression and development of drug resistance in PDAC. Tumor budding is thought to reflect the process of epithelial-mesenchymal transition (EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals. In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated and an association between high-grade budding and aggressive clinicopathological features of the tumors as well as worse outcome of the patients was found. The identification of EMT phenotypic targets may help identifying new molecules so that future therapeutic strategies directed specifically against them could potentially have an impact on drug resistance and invasiveness and hence improve the prognosis of PDAC patients. The aim of this short review is to present an insight on the morphological and molecular aspects of EMT and on the factors that are involved in the induction of EMT in PDAC.

  11. Surgical management of acute necrotizing pancreatitis: a 13-year experience and a systematic review

    NARCIS (Netherlands)

    Nieuwenhuijs, V. B.; Besselink, M. G. H.; van Minnen, L. P.; Gooszen, H. G.

    2003-01-01

    BACKGROUND: The course of acute pancreatitis (AP) is unpredictable and can vary from mild to lethal. Mortality varies from low ( <2%) in mild cases to high (20%-70%) in the case of infected pancreatic necrosis. Surgical management has not been investigated in well-designed trials. Based on

  12. [Pancreatic ultrasonography].

    Science.gov (United States)

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  13. Epithelial-to-Mesenchymal Transition in Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Carla Cano

    2010-01-01

    Full Text Available Epithelial to mesenchymal transition (EMT is a physiologic process that allows morphological and genetic changes of carcinoma cells from an epithelial to a mesenchymal phenotype, which is the basis of the high metastatic potential of pancreatic cancer cells. EMT is triggered by various tumor microenvironmental factors, including cytokines, growth factors, and chemotherapeutic agents. This review summarizes the state-of-the-art knowledge on the molecular mechanisms that support pancreatic cancer EMT and the evidences that support its involvement in invasiveness/aggressiveness, and the drug resistance of pancreatic cancer cells.

  14. Acute Pancreatitis

    DEFF Research Database (Denmark)

    Bertilsson, Sara; Håkansson, Anders; Kalaitzakis, Evangelos

    2017-01-01

    Aims: We aimed to evaluate the potential relation between the incidence of (alcoholic and non-alcoholic) acute pancreatitis (AP) and alcohol consumption in the general population, and whether the occurrence of AP shows any seasonal variation, particularly in relation to periods with expected...... consumption in the general population do not appear to be related to changes in the incidence of AP and there are no significant seasonal differences in the occurrence of AP in Sweden. Short summary: The incidence of acute pancreatitis (AP) is increasing, and alcohol is still recognized as one of the most...

  15. Histopathological effects of lethal and sub-lethal concentrations of ...

    African Journals Online (AJOL)

    The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

  16. Endosonography of groove pancreatitis

    NARCIS (Netherlands)

    Tio, T. L.; Luiken, G. J.; Tytgat, G. N.

    1991-01-01

    Groove pancreatitis is a rare form of chronic pancreatitis. Distinction between pancreatitis and pancreatic carcinoma is often difficult. Two cases of groove pancreatitis diagnosed by endosonography are described. A hypoechoic pattern between the duodenal wall and pancreas was clearly imaged in both

  17. Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis.

    Directory of Open Access Journals (Sweden)

    Hiromitsu Ito

    Full Text Available Patients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs, but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs. In the present study, we found that CSCs were highly metastatic and dominantly localized at the invading tumor margins in a liver metastasis model. Microarray and siRNA screening assays showed that doublecortin-like kinase 1 (DCLK1 was predominantly expressed with histone modification in pancreatic CSCs with invasive and metastatic potential. Overexpression of DCLK1 led to amoeboid morphology, which promotes the migration of pancreatic cancer cells. Knockdown of DCLK1 profoundly suppressed in vivo liver metastasis of pancreatic CSCs. Clinically, DCLK1 was overexpressed in the metastatic tumors in patients with pancreatic cancer. Our studies revealed that DCLK1 is essential for the invasive and metastatic properties of CSCs and may be a promising epigenetic and therapeutic target in human pancreatic cancer.

  18. Autoimmune Pancreatitis.

    Science.gov (United States)

    Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T

    2017-07-01

    Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.

  19. Chronic Pancreatitis

    International Nuclear Information System (INIS)

    Betancur, Jorge

    2002-01-01

    It is presented a case of a man with alcoholic chronic pancreatitis, whose marked dilatation of the ducts reasoned the issue. The severe untreatable pain was the surgery indication, which was practiced without complications either during or after the surgery. By the way, a shallow revision of the literature is made, by mentioning classification, physiopatholoy, clinical square, medical, surgical and endoscopic treatment

  20. Chronic Pancreatitis

    International Nuclear Information System (INIS)

    Vavrecka, A.; Bilicky, J.

    2011-01-01

    Chronic pancreatitis is an ongoing inflammatory process that may over time lead to mal digestion, malabsorption and diabetic syndrome. Identification of risk (etiological) factors based on classifications TIGAR-O or later M-ANNHEIM. These factors (environmental and / or genetic) leads to failure of the stability of the digestive and lysosomal enzymes in the acinar cells, resulting in premature activation of digestive enzymes in the pancreas, and repeated nekroinflamation and fibrosis. The incidence has of the upward trend. Clinically the disease manifests itself in most cases with pain and possibly with nonspecific dyspeptic troubles. Decisive role in the diagnosis playing imaging methods, trans abdominal ultrasonography, computed tomography, magnetic resonance imaging, magnetic cholangiopancretography and foremost endoscopic ultrasonography, which has the highest sensitivity and specificity. Endoscopic retrograde cholangiopancreatography is currently regarded as a method for therapy, not for diagnosis. Less importance is now attached to a functional test. Symptomatic treatment is usually conservative. Abstinence is necessary, easily digestible, but calorie-rich diet with reduced fat. Most patients needed treatment with analgesics. In case of insufficient effect of analgesics is necessary to consider endoscopic therapy or surgery. If the external secretory insufficiency is present are served pancreatic extracts. Diabetic syndrome requires insulin delivery. Generally, chronic pancreatitis is a disease treatable but incurable. Proportion of patients are also dying of pancreatic cancer. (author)

  1. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    Directory of Open Access Journals (Sweden)

    P. V. Novokhatny

    2014-02-01

    Full Text Available Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis. Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE. Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by

  2. Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege–Potter syndrome

    Directory of Open Access Journals (Sweden)

    Andrew J. Degnan, MD, MPhil

    2017-03-01

    Full Text Available We report a rare case of metastatic malignant solitary fibrous tumor (SFT that presented with hypoglycemia because of insulin growth factor-2 production. Initial workup included computed tomography imaging that revealed a large, partially necrotic liver mass, a hypervascular pancreatic head lesion, and 2 renal lesions. Following hepatic resection, pancreatic head resection and nephrectomy, all these lesions demonstrated pathological findings that were consistent with SFT. The patient also had a history of an intracranial mass that had been previously resected and treated with gamma knife therapy at an outside institution, which was found to also be SFT. Six months after initial pancreatic head resection, the patient developed a new lesion involving the pancreatic tail that was found to represent recurrent metastatic SFT. This case emphasizes the highly aggressive nature of extrapleural SFT, while rare, and the role of imaging in follow-up for disease recurrence.

  3. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2017-09-26

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  4. Ny klassifikation af pancreatitis acuta

    DEFF Research Database (Denmark)

    Hansen, Benny Østerbye; Schmidt, Palle Nordblad

    2011-01-01

    The course of acute pancreatitis is in the initial phase dominated by a systemic inflammatory response, later by local complications. A new classification defines three specific types of pancreatitis: 1) interstitial oedematous pancreatitis and 2) necrotizing pancreatitis with pancreatic...

  5. Suicide Lethality: A Concept Analysis.

    Science.gov (United States)

    DeBastiani, Summer; De Santis, Joseph P

    2018-02-01

    Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

  6. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... E-News Sign-Up Home Patient Information Children/Pediatric Chronic Pancreatitis in Children Chronic Pancreatitis in Children What symptoms would my child have? Frequent or chronic abdominal pain is the most common symptom of pancreatitis. The ...

  7. PANCREATIC CANCER

    Directory of Open Access Journals (Sweden)

    Alojz Pleskovič

    2003-12-01

    Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

  8. Pancreatic Metastasis in a Child Suffering with Treated Stage 4 Neuroblastoma

    International Nuclear Information System (INIS)

    Kim, Eun Young; Yoo, So Young; Kim, Ji Hye; Sung, Ki Woong

    2008-01-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and its metastasis to distant organs such as bone, bone marrow and liver is well documented. However, pancreatic metastasis of neuroblastoma has not yet been reported in the medical literature. We report here on a 4-year old boy who had a metastatic relapse in his pancreas, combined with pancreatitis, after remission of stage 4 neuroblastoma. In conclusion, we present here a very rare case of neuroblastoma that metastasized to the pancreas in a 4- year-old boy. Pancreatic metastasis should be taken into consideration for those patients who are found to have pancreatic nodules concurrent with neuroblastoma

  9. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    Science.gov (United States)

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract : Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  10. Autoimmune pancreatitis can develop into chronic pancreatitis

    Science.gov (United States)

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  11. Autoimmune pancreatitis can develop into chronic pancreatitis.

    Science.gov (United States)

    Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki

    2014-05-21

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

  12. The epidemiology of pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B

    2013-06-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. The Epidemiology of Pancreatitis and Pancreatic Cancer

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B.

    2013-01-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

  14. Pre-metastatic niches

    DEFF Research Database (Denmark)

    Peinado, Héctor; Zhang, Haiying; Matei, Irina R.

    2017-01-01

    It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour......-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche....

  15. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

    2011-02-24

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  16. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Bournet, Barbara; Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome; Buscail, Louis; Cordelier, Pierre

    2011-01-01

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer

  17. A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Jeran K Stratford

    2010-07-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease.We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7-10.0. Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group.Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary.

  18. Tumor clone dynamics in lethal prostate cancer.

    Science.gov (United States)

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; S de Bono, Johann; Demichelis, Francesca; Attard, Gerhardt

    2014-09-17

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers. Copyright © 2014, American Association for the Advancement of Science.

  19. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  20. Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection.

    Science.gov (United States)

    Tejero, Héctor; Montero, Francisco; Nuño, Juan Carlos

    2016-01-01

    RNA viruses get extinct in a process called lethal mutagenesis when subjected to an increase in their mutation rate, for instance, by the action of mutagenic drugs. Several approaches have been proposed to understand this phenomenon. The extinction of RNA viruses by increased mutational pressure was inspired by the concept of the error threshold. The now classic quasispecies model predicts the existence of a limit to the mutation rate beyond which the genetic information of the wild type could not be efficiently transmitted to the next generation. This limit was called the error threshold, and for mutation rates larger than this threshold, the quasispecies was said to enter into error catastrophe. This transition has been assumed to foster the extinction of the whole population. Alternative explanations of lethal mutagenesis have been proposed recently. In the first place, a distinction is made between the error threshold and the extinction threshold, the mutation rate beyond which a population gets extinct. Extinction is explained from the effect the mutation rate has, throughout the mutational load, on the reproductive ability of the whole population. Secondly, lethal defection takes also into account the effect of interactions within mutant spectra, which have been shown to be determinant for the understanding the extinction of RNA virus due to an augmented mutational pressure. Nonetheless, some relevant issues concerning lethal mutagenesis are not completely understood yet, as so survival of the flattest, i.e. the development of resistance to lethal mutagenesis by evolving towards mutationally more robust regions of sequence space, or sublethal mutagenesis, i.e., the increase of the mutation rate below the extinction threshold which may boost the adaptability of RNA virus, increasing their ability to develop resistance to drugs (including mutagens). A better design of antiviral therapies will still require an improvement of our knowledge about lethal

  1. Consistent expression of guanylyl cyclase-C in primary and metastatic gastrointestinal cancers.

    Directory of Open Access Journals (Sweden)

    Hadi Danaee

    Full Text Available The transmembrane receptor guanylate cyclase-C (GCC has been found to be expressed in colorectal cancers. However, limited data are available on GCC protein expression in non-colorectal gastrointestinal tumors and few studies have reported whether GCC protein expression was consistently preserved in synchronous primary and metastatic cancer tissues.GCC protein status was assessed by immunohistochemistry in tumor specimens from individuals (n = 627 with gastrointestinal tumors, including esophageal (n = 130, gastric (n = 276, pancreatic (n = 136, and colorectal (n = 85 primary and metastatic tumors. Tissue specimens consisted of tissue microarrays containing esophageal, gastric, pancreatic tumors, and whole-slide tissue sections from colorectal cancer patients with matching primary and metastatic tumors.Among the evaluated esophageal, gastric, and pancreatic tumors, the frequency of GCC positivity at the protein level ranged from 59% to 68%. GCC was consistently expressed in primary and matched/synchronous metastatic lesions of colorectal cancer tissues derived from the same patients.This observational study demonstrated the protein expression of GCC across various gastrointestinal malignancies. In all cancer histotypes, GCC protein localization was observed predominantly in the cytoplasm compared to the membrane region of tumor cells. Consistent immunohistochemistry detection of GCC protein expression in primary colorectal cancers and in their matched liver metastases suggests that the expression of GCC is maintained throughout the process of tumor progression and formation of metastatic disease.

  2. [External pancreatic fistulas management].

    Science.gov (United States)

    Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

    The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

  3. Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jiangang Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

  4. Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Yusuf Gunay

    2012-01-01

    Full Text Available Introduction. Reports of epithelial ovarian carcinomas metastatic to the pancreas are very rare. We herein present a metastasis of high grade papillary serous ovarian cancer to mid portion of pancreas. Case. A 42-year-old patient was admitted with a non-specified malignant cystic lesion in midportion of pancreas. She had a history of surgical treatment for papillary serous ovarian adenocarcinoma. A cystic lesion was revealed by an abdominal computerized tomography (CT performed in her follow up . It was considered as primary mid portion of pancreatic cancer and a distal pancreatectomy was performed. The final pathology showed high-grade papillary serous adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. Discussion. Metastatic pancreatic cancers should be considered in patients who present with a solitary pancreatic mass and had a previous non-pancreatic malignancy. Differential diagnosis of primary pancreatic neoplasm from metastatic malignancy may be very difficult. A biopsy for tissue confirmation is required to differentiate primary and secondary pancreatic tumors. Although, the value of surgical resection is poorly documented, resection may be considered in selected patients. Conclusion. Pancreatic metastasis of ovarian papillary serous adenocarcinoma has to be kept in mind when a patient with pancreatic mass has a history of ovarian malignancy.

  5. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla

    2016-01-01

    Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

  6. Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function

    Science.gov (United States)

    Osterman, Carlos J. Diaz; Lynch, James C.; Leaf, Patrick; Gonda, Amber; Ferguson Bennit, Heather R.; Griffiths, Duncan; Wall, Nathan R.

    2015-01-01

    Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through

  7. CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ishan Roy

    Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

  8. Isolated pancreatic metastases from a bronchogenic small cell carcinoma.

    LENUS (Irish Health Repository)

    Walshe, T

    2012-01-31

    We describe the case of a 60 year old female smoker who presented with a three month history of weight loss (14 Kg), generalized abdominal discomfort and malaise. Chest radiography demonstrated a mass projected inferior to the hilum of the right lung. Computed Tomography of thorax confirmed a lobulated lesion in the right infrahilar region and subsequent staging abdominal CT demonstrated a low density lesion in the neck of the pancreas. Percutaneous Ultrasound guided pancreatic biopsy was performed, histology of which demonstrated pancreatic tissue containing a highly necrotic small cell undifferentiated carcinoma consistent with metastatic small cell carcinoma of the bronchus.

  9. Surgery for oligometastasis of pancreatic cancer.

    Science.gov (United States)

    Lu, Fengchun; Poruk, Katherine E; Weiss, Matthew J

    2015-08-01

    The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.

  10. Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary tumor and pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Kim, Yong-il; Kim, Seok-ki; Paeng, Jin Chul; Lee, Ho-Young

    2014-01-01

    Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT

  11. Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer in vitro

    Directory of Open Access Journals (Sweden)

    Liermann Jakob

    2017-11-01

    Full Text Available Chemoradiation of locally advanced non-metastatic pancreatic cancer can lead to secondary operability by tumor mass reduction. Here, we analyzed radiomodulating effects of oridonin and ponicidin in pancreatic cancer in vitro. Both agents are ent-kaurane diterpenoids, extracted from Isodon rubescens, a plant that is well known in Traditional Chinese Medicine. Cytotoxic effects have recently been shown in different tumor entities for both agents.

  12. Non-Lethal Weapons Program

    Science.gov (United States)

    Sheets Frequently Asked Questions Non-Lethal Weapons FAQs Active Denial System FAQs Human Electro -Muscular Incapacitation FAQs Related Links Business Opportunities Contact JNLWD Congressional Engagement , Wednesday, Sept 20, 2017. The Active Denial System, blunt-impact munitions, dazzling lasers, LRAD 100X

  13. Cutaneous metastatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Joshi Arun

    2001-01-01

    Full Text Available A 5.5-year-old male presented with asymptomatic nodules and plaques on his scalp and pubic region of 2 months′ duration. He was having productive cough, haemoptysis, chest pain, anorexia and weight loss and receiving antitubercular treatment for these symptoms for last 3 months. Clinical diagnosis of cutaneous metastatic disease was made. Chest x-ray revealed multiple coin shaped shadows on both sides with pleural effusion. Routine investigations were normal except for anemia and hyperuricemia. Biopsy of skin nodules showed features of metastatic adenocarcinoma. Features and significance of cutaneous metastases are discussed.

  14. Intracardiac Metastatic Rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Tae Ho Kim

    2015-12-01

    Full Text Available A 70-year-old man who visited Samsung Medical Center reported experiencing palpitation for 2 weeks. He had undergone excision of a mass in the right buttock due to rhabdomyosarcoma 7 years prior to this visit. Transesophageal echocardiography showed a pedunculated mass in the left ventricle, which was thought to be a vegetation of infective endocarditis, metastasis of the primary tumor, or thrombus. He underwent removal of the cardiac tumor, and the pathologic report was metastatic rhabdomyosarcoma. Thus, here, we report a rare case of metastatic rhabdomyosarcoma in the left ventricle.

  15. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

    Science.gov (United States)

    Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

    2016-02-01

    Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

  16. Survivin as a radioresistance factor in pancreatic cancer

    International Nuclear Information System (INIS)

    Asanuma, Koichi; Moriai, Ryosuke; Yajima, Tomomi; Yagihashi, Atsuhito; Yamada, Mikako; Kobayashi, Daisuke; Watanabe, Naoki

    2000-01-01

    We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy. (author)

  17. Pancreatitis-imaging approach

    Science.gov (United States)

    Busireddy, Kiran K; AlObaidy, Mamdoh; Ramalho, Miguel; Kalubowila, Janaka; Baodong, Liu; Santagostino, Ilaria; Semelka, Richard C

    2014-01-01

    Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI. PMID:25133027

  18. Pathogenic mechanisms of pancreatitis

    Science.gov (United States)

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  19. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO

    OpenAIRE

    Ramadani, Naser; Dedushi, Kreshnike; Mu?aj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-01-01

    The aim: The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. Materials and methodology: This retrospective research s...

  20. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance

    OpenAIRE

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-01

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resis...

  1. Metastatic melanoma of mesentery

    International Nuclear Information System (INIS)

    Shamim, M. S.; Ali, S.A.; Shirazi, B.; Shamim, M.

    2004-01-01

    A case of malignant melanoma metastatic to small bowel mesentery in an old female is reported. Her primary malignant melanoma of nasal mucosa was already treated. She presented with intestinal obstruction, underwent surgical excision of the tumour and was tumour-free postoperatively. (author)

  2. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Miroslav Vujasinovic

    2017-02-01

    Full Text Available Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  3. Paratesticular adenocarcinoma. Unusual presentation of metastasis of pancreatic cancer

    International Nuclear Information System (INIS)

    Ocvirk, J.; Seruga, B.

    2007-01-01

    Metastatic paratesticular adenocarcinoma from the pancreatic cancer is very rare. To our knowledge, there are less than 20 cases published in the literature. We experienced a case of paratesticular adenocarcinoma from the primary pancreatic cancer. A 42-year-old man was presented with locoregionally advanced carcinoma of the tail of the pancreas with intraoperatively found liver metastases and with a tumour in the right hemi-scrotum. Ultrasound of the scrotum revealed a paratesticular tumour. A fine needle aspiration biopsy (FNAB) confirmed a poorly differentiated adenocarcinoma and it was in concordance with the diagnosis of the primary tumour. The patient started treatment with chemotherapy with gemcitabine. Unfortunately, he progressed one month later and the treatment was discontinued. Outcome in the adenocarcinoma of the pancreas is dismal. The only possible treatment option for metastatic disease is systemic therapy but the results are disappointing, as in the present case. (author)

  4. Lethal mechanisms in gastric volvulus.

    Science.gov (United States)

    Omond, Kimberley J; Byard, Roger W

    2017-01-01

    A 55-year-old wheelchair-bound woman with severe cerebral palsy was found at autopsy to have marked distention of the stomach due to a volvulus. The stomach was viable, and filled with air and fluid and had pushed the left dome of the diaphragm upwards causing marked compression of the left lung with a mediastinal shift to the right (including the heart). There was no evidence of gastric perforation, ischaemic necrosis or peritonitis. Removal of the organ block revealed marked kyphoscoliosis. Histology confirmed the viability of the stomach and biochemistry showed no dehydration. Death in cases of acute gastric volvulus usually occurs because of compromise of the gastric blood supply resulting in ischaemic necrosis with distention from swallowed air and fluid resulting in perforation with lethal peritonitis. Hypovolaemic shock may also occur. However, the current case demonstrates an alternative lethal mechanism, that of respiratory compromise due to marked thoracic organ compression.

  5. Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

    Science.gov (United States)

    Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M

    2016-06-01

    Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.

  6. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

    NARCIS (Netherlands)

    T.C. Tran; G. van 't Hof; G. Kazemier (Geert); W.C.J. Hop (Wim); C.J. Pek (Chulja); A.W. van Toorenenbergen (Albert); H. van Dekken (Herman); C.H.J. van Eijck (Casper)

    2008-01-01

    textabstractBackground: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and

  7. Imaging of pancreatic diseases

    International Nuclear Information System (INIS)

    Akisada, Masayoshi; Hiramatsu, Yoshihiro; Ishikawa, Nobuyoshi; Tatezawa, Akira; Matsumoto, Kunihiko

    1982-01-01

    There has been no definite examining technique for the early diagnosis of pancreatic diseases, especially small cancers of the pancreas less than 3 cm. Plain abdominal X-rays do not produce reliable roentgenological signs of acute pancreatitis, but the advent of CT has elucidated the condition to some extent. Upper gastrointestinal series are alleged to demonstrate abnormal findings in 80% of cases of pancreatic cancer or cyst. Pancreatic RI scintigraphy expresses the function and anatomy, and the sensitivity with 75 Se is 88%, similar to 87% by US and 80% by CT. Although endoscopic retrograde cholangiopancreatography visualizes extrapancreatic secretory function, as well as the morphology of pancreas, differentiation is not easy in many cases. The greatest indication for US was cysts. The detection rate of pancreatic cancers is similar between plain and contrast CTs, and pancreatic angiography is not specific for pancreatic cancers. (Chiba, N.)

  8. Endocrine pancreatic function changes after acute pancreatitis.

    Science.gov (United States)

    Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

    2011-10-01

    This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

  9. Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Pancreatic Adenocarcinoma.

    Science.gov (United States)

    2015-10-01

    The SCAN pancreatic cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Cancer Comprehensive Network (2014), the European Society of Medical Oncology (2012), Cancer Care Ontario (2013), the Japan Pancreas Society (2013) and the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, and the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (2005). Recommendations on the management of resected, borderline resectable, locally advanced and metastatic pancreatic adenocarcinoma were developed. These adapted guidelines form the SCAN Guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore.

  10. Traumatic Pancreatitis: A Rare Complication of Cardiopulmonary Resuscitation.

    Science.gov (United States)

    Aziz, Muhammad

    2017-08-17

    An elderly gentleman was successfully revived after undergoing cardiopulmonary resuscitation (CPR) for cardiac arrest. Post CPR, the patient developed acute pancreatitis which was likely complication of inappropriately delivered chest compressions which caused further complications and resulted in the death of the patient. This case underlines the importance of quality chest compressions that includes correct placement of hands by the operator giving chest compressions to avoid lethal injuries to the receiver.

  11. [Non surgical treatment of pancreatic cancers].

    Science.gov (United States)

    Bleiberg, H; Gerard, B; Hendlisz, A; Jagodzinski, R

    1997-09-01

    Pancreatic cancer is a disease difficult to treat. Diagnosis is late, cancer remaining clinically unapparent even if locally advanced or metastatic. Few patients can be submitted to curative surgery. Even if resection is possible, 5-year survival varies from 0% to 18% according to series. Some data suggest that chemotherapy with or without radiotherapy could influence disease free survival but a benefit on overall survival has not been demonstrated. For locally advanced disease, the results of a trial published in 1968, showed that a combination of radiotherapy and 5-Fluorouracil (5FU) improved median survival as compared to radiotherapy alone (5.5 versus 10 months). Since then, no progress has been achieved. At the present time, survival of patients with metastatic pancreatic cancer cannot be improved. Very recently, a new agent, gemcitabine, has been compared to 5FU. Criteria for activity were based on clinical improvement analgesia consumption, performance status and weight gain. Twenty-four percent of the patients treated with gemcitabine had a clinical benefit as compared to 5% for those treated with 5FU. Other studies comparing chemotherapy to best supportive care show a significant decrease of depression and anxiety as well as an improvement in quality of life for patients being treated.

  12. Curable Metastatic Colorectal Cancer

    OpenAIRE

    Hochster, Howard S.

    2010-01-01

    Colon cancer, though already metastatic, may still be curable through multi-modality approaches, which require combined planning between medical and surgical oncologists. Retrospective surgical series have historically shown 5-year survival or “cures” for 30% to 50% of patients with solitary or a few resectable liver metastases. The role of adjuvant chemotherapy in this setting has been poorly defined. A recent European Organization for Research and Treatment of Cancer (EORTC) study randomize...

  13. Challenges of drug resistance in the management of pancreatic cancer.

    LENUS (Irish Health Repository)

    Sheikh, Rizwan

    2012-02-01

    The current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and\\/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.

  14. Intraoperative radiotherapy in pancreatic cancer: A systematic review

    International Nuclear Information System (INIS)

    Ruano-Ravina, Alberto; Almazan Ortega, Raquel; Guedea, Ferrran

    2008-01-01

    Background and purpose: Intraoperative radiotherapy (IORT) has been considered for treatment of pancreas cancer since local recurrence rates are very high. This study assesses the efficacy and safety of IORT in pancreatic cancer. Materials and methods: We conducted a systematic review of scientific literature from January 1995 to February 2007, including Medline, Embase, ISI Web of Science and HTA (Health Technology Assessment). By applying a series of inclusion criteria, two independent reviewers selected those studies in which a minimum of 30 patients received IORT and which furnished survival results based on a minimum 3-month follow-up. Results: Fourteen papers were included, one was an IORT assessment report, 5 were cohort studies, and the remaining 8 were case series studies, 2 of which belonged to the same series. In general, these studies showed that IORT could slightly increase survival among patients with pancreatic cancer in localized stages. However, the results were not conclusively in favor of IORT in the case of pancreatic cancer in locally advanced and metastatic stages. There were no published studies that assessed quality of life. Conclusions: There is no clear evidence to indicate that IORT is more effective than other therapies in treating pancreatic cancer in locally advanced and metastatic stages

  15. Laparoscopic pancreatic cystogastrostomy.

    Science.gov (United States)

    Obermeyer, Robert J; Fisher, William E; Salameh, Jihad R; Jeyapalan, Manjula; Sweeney, John F; Brunicardi, F Charles

    2003-08-01

    The purpose of the review was to evaluate the feasibility and outcome of laparoscopic pancreatic cystogastrostomy for operative drainage of symptomatic pancreatic pseudocysts. A retrospective review of all patients who underwent laparoscopic pancreatic cystogastrostomy between June 1997 and July 2001 was performed. Data regarding etiology of pancreatitis, size of pseudocyst, operative time, complications, and pseudocyst recurrence were collected and reported as median values with ranges. Laparoscopic pancreatic cystogastrostomy was attempted in 6 patients. Pseudocyst etiology included gallstone pancreatitis (3), alcohol-induced pancreatitis (2), and post-ERCP pancreatitis (1). The cystogastrostomy was successfully performed laparoscopically in 5 of 6 patients. However, the procedure was converted to open after creation of the cystgastrostomy in 1 of these patients. There were no complications in the cases completed laparoscopically and no deaths in the entire group. No pseudocyst recurrences were observed with a median followup of 44 months (range 4-59 months). Laparoscopic pancreatic cystgastrostomy is a feasible surgical treatment of pancreatic pseudocysts with a resultant low pseudocyst recurrence rate, length of stay, and low morbidity and mortality.

  16. Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors

    International Nuclear Information System (INIS)

    Okamoto, Yuko; Kawamoto, Hirofumi; Takaki, Akinobu; Ishida, Etsuji; Ogawa, Tsuneyoshi; Kuwaki, Kenji; Kobayashi, Yoshiyuki; Sakaguchi, Kohsaku; Shiratori, Yasushi

    2007-01-01

    Objective: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors. Materials and methods: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography. Results: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (κ coefficient = 0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p = 0.063). Conclusion: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors

  17. Successful Control of Liver Metastases From Pancreatic Solid-Pseudopapillary Neoplasm (SPN) Using Hepatic Arterial Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Violari, Elena G., E-mail: eviolari@live.com; Brody, Lynn A.; Covey, Anne M.; Erinjeri, Joseph P.; Getrajdman, George I.; Sofocleous, Constantinos T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States); Reidy, Diane L. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, Gastrointestinal Oncology Service (United States); Jarnagin, William R. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Service (United States); Brown, Karen T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States)

    2015-04-15

    No systemic agents that are known to be effective for the treatment of solid-pseudopapillary neoplasm (SPN) are available. We report the prolonged and sustained control of metastatic pancreatic SPN to the liver using hepatic arterial embolization (HAE), where a total of 13 HAE sessions were performed over a 6-year period.

  18. Genetics Home Reference: hereditary pancreatitis

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Hereditary pancreatitis Hereditary pancreatitis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Hereditary pancreatitis is a genetic condition characterized by recurrent episodes ...

  19. Imaging of Spinal Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Lubdha M. Shah

    2011-01-01

    Full Text Available Metastases to the spine can involve the bone, epidural space, leptomeninges, and spinal cord. The spine is the third most common site for metastatic disease, following the lung and the liver. Approximately 60–70% of patients with systemic cancer will have spinal metastasis. Materials/Methods. This is a review of the imaging techniques and typical imaging appearances of spinal metastatic disease. Conclusions. Awareness of the different manifestations of spinal metastatic disease is essential as the spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT best delineates osseous integrity, while MRI is better at assessing soft tissue involvement. Physiologic properties, particularly in treated disease, can be evaluated with other imaging modalities such as FDG PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease.

  20. Role of endoscopic ultrasonography in evaluation of metastatic lesions to the pancreas: a tertiary cancer center experience.

    Science.gov (United States)

    Atiq, Muslim; Bhutani, Manoop S; Ross, William A; Raju, Gottumukkala S; Gong, Yun; Tamm, Eric P; Javle, Milind; Wang, Xuemei; Lee, Jeffrey H

    2013-04-01

    Metastatic lesions to the pancreas pose diagnostic challenges with regards to their differentiation from primary pancreatic cancer. Data on the yield of endoscopic ultrasonography (EUS)-guided fine-needle aspiration in detection of these lesions are limited. This is a retrospective review of 23 patients referred to a tertiary referral center for further evaluation of suspected pancreatic metastases. Main outcome measures were diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration in evaluation of metastatic lesions to the pancreas. Of 644 patients, 23 (3.6%) undergoing EUS of the pancreas were diagnosed to have metastatic disease to the pancreas based on clinical, radiological, and cytological results. Mean (SD) age was 64.3 (11.7) years. Of the 23 patients, 18 (78.3%) were asymptomatic. Mean (SD) size of lesion on EUS was 39.1 (19.9) mm. A diagnosis of malignant lesion was made in 21 of 23 cases, with a diagnostic accuracy of 91.3%. Metastatic lesions to the pancreas present as incidental, solitary mass lesions on staging or surveillance imaging. Endoscopic ultrasonography-guided fine-needle aspiration is an important tool in the characterization and further differentiation of metastatic lesions to the pancreas from primary pancreatic cancer.

  1. Complete Remission of Pancreatic Pseudoaneurysm Rupture with Arterial Embolization in a Patient with Poor Risk for Surgery: A Case Report

    Directory of Open Access Journals (Sweden)

    Kuang-En Chu

    2012-05-01

    Full Text Available Pancreatic pseudoaneurysm is a rare vascular complication of chronic pancreatitis resulting from erosion of the pancreatic or peripancreatic artery into a pseudocyst that is identified as a pulsating vascular malformation which may lead to lethal complications if left untreated. Many publications in the literature consider angiography as the first step in the management of pancreatic pseudoaneurysm to stabilize the patient’s critical condition; it should be followed by surgical intervention as the definite treatment. We report a rare case of pancreatic pseudoaneurysm rupture with hemodynamic embarrassment in a critical patient with multiple comorbid conditions and poor risk for surgery who responded dramatically to angiographic management as a single therapeutic modality without further surgical intervention. The results observed in our patient suggest that pancreatic pseudoaneurysm may be successfully managed with angiography only and that not all cases require surgical intervention. This is particularly relevant in critically ill patients in whom surgical intervention would be unfeasible.

  2. Pancreatic cancer risk in hereditary pancreatitis

    OpenAIRE

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

  3. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    OpenAIRE

    P. V. Novokhatny

    2014-01-01

    Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study...

  4. Prevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Stefan Kuroczycki-Saniutycz

    2017-02-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDA accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

  5. Pancreatic Exocrine Function Testing

    OpenAIRE

    Berk, J. Edward

    1982-01-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and par...

  6. Electroshock weapons can be lethal!

    Science.gov (United States)

    Lundquist, Marjorie

    2008-03-01

    Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

  7. IMMUNOMODULATION AND TREATMENT OF ACUTE DESTRUCTIVE PANCREATITIS IN A MULTIDISCIPLINARY SURGICAL HOSPITAL.

    Science.gov (United States)

    Vinokurov, M M; Saveliev, V V; Gogolev, N M; Yalynskya, T V

    2015-01-01

    This work is based on the analysis of complex treatment of 497 patients with pancreatic necrosis treated at the surgical department of the Republican Hospital No2-Center for Emergency the Republic of Sakha (Yakutia) in the period from 2010 to 2015. The study was able to adapt and improve the two-tier immunocorretion in pancreatic necrosis in a multidisciplinary surgical hospital that along with the other constituents of intensive therapy has allowed a whole to reduce the amount of intra-abdominal and extraabdominal complications--sterile pancreatic necrosis phase--from 23.6% to 14.6 and 31 6% to 15.0% respectively, total lethality--from 17.6% to 7.2% lethality in patients with non-operated group--from 15.6% to 2.2% lethality in the group of patients operated--18.4% to 10.9%. In the phase of infectious complications of pancreatic necrosis lethality rate decreased from 45.8% to 37.7%.

  8. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Allen, Barry J.; Abbas Rizvi, Syed M.; Qu, Chang F.; Smith, Ross C.

    2011-01-01

    Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213 Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro-metastatic

  9. Hereditary pancreatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Raphael KL

    2016-07-01

    Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: Hereditary pancreatitis (HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

  10. Hereditary chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Mössner Joachim

    2007-01-01

    Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

  11. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

    Science.gov (United States)

    Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

    2008-01-01

    Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

  12. [Chronic pancreatitis diagnosed after the first attack of acute pancreatitis].

    Science.gov (United States)

    Bojková, Martina; Dítě, Petr; Uvírová, Magdalena; Dvořáčková, Nina; Kianička, Bohuslav; Kupka, Tomáš; Svoboda, Pavel; Klvaňa, Pavel; Martínek, Arnošt

    2016-02-01

    One of the diseases involving a potential risk of developing chronic pancreatitis is acute pancreatitis. Of the overall number of 231 individuals followed with a diagnosis of chronic pancreatitis, 56 patients were initially treated for acute pancreatitis (24.2 %). Within an interval of 12- 24 months from the first attack of acute pancreatitis, their condition gradually progressed to reached the picture of chronic pancreatitis. The individuals included in the study abstained (from alcohol) following the first attack of acute pancreatitis and no relapse of acute pancreatitis was proven during the period of their monitoring. The etiology of acute pancreatitis identified alcohol as the predominant cause (55.3 %), biliary etiology was proven in 35.7 %. According to the revised Atlanta classification, severe pancreatitis was established in 69.6 % of the patients, the others met the criterion for intermediate form, those with the light form were not included. Significant risk factors present among the patients were smoking, obesity and 18 %, resp. 25.8 % had pancreatogenous diabetes mellitus identified. 88.1 % of the patients with acute pancreatitis were smokers. The majority of individuals with chronic pancreatitis following an attack of acute pancreatitis were of a productive age from 25 to 50 years. It is not only acute alcoholic pancreatitis which evolves into chronic pancreatitis, we have also identified this transition for pancreatitis of biliary etiology.

  13. Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Nilgun Gurbuz

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

  14. Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Nilgun Gurbuz

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D- mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

  15. Stages of Pancreatic Cancer

    Science.gov (United States)

    ... overweight. Having a personal history of diabetes or chronic pancreatitis . Having a family history of pancreatic cancer or ... have not started treatment. Five types of standard treatment are used: Surgery ... Whipple procedure : A surgical procedure in which the head of the pancreas , ...

  16. Pancreatic Islet Cell Transplantation

    Science.gov (United States)

    Warnock, Garth L.; Rajotte, Ray V.

    1992-01-01

    Transplantation of insulin-producing tissue offers a physiologic approach to restoration of glycemic control. Whereas transplantation of vascularized pancreatic grafts has recently achieved encouraging results, pancreatic islet cell transplantation holds the promise of low morbidity and reduced requirements for agressive immunosuppression for recipients. Islet cell transplantation was recently demonstrated to induce euglycemia with insulin independence. Imagesp1656-a PMID:21221366

  17. Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

    1995-01-01

    To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

  18. Imaging of pancreatitis

    International Nuclear Information System (INIS)

    Prassopoulos, P.

    2012-01-01

    Full text: Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable involvement of peripancreatic tissues or remote organ systems. Mild AP accounts for 75-80% of the cases and it is characterized by interstitial oedema, absent or minimal organ dysfunction, lack of complications and, usually, uneventful recovery. Severe AP is characterized by pancreatic necrosis, protracted clinical course, high incidence of complications, and high mortality rate. The diagnosis of acute pancreatitis (AP) is generally based on clinical and laboratory findings. The role of imaging is to confirm diagnosis, to assess disease severity - especially by detecting pancreatic necrosis-, to reveal complications of the disease and to guide interventions). Contrast- enhanced multidetector CT is the current 'gold standard' imaging modality in the evaluation of patients with AP. The spectrum of findings seen on CT ranges from a normal appearance to diffuse pancreatic enlargement with poorly defined pancreatic contour and heterogeneous attenuation. Stranding of the fat surrounding the pancreas and fluid collections in the anterior pararenal space, the peritoneal cavity or elsewhere, acquiring the form of the anatomic space where they are developed, may also be disclosed. Lack of pancreatic parenchyma enhancement is indicative of the presence of pancreatic necrosis. CT may reveal biliary tract calculi, calcifications in patients with AP combined with chronic pancreatitis- and air in an inflamed pancreas. Pancreatic abscess is usually seen on CT as a focal low attenuation area with a thick wall that may exhibit enhancement following i.v. contrast media administration. Haemorrhage, pseudoaneurysms, renal and splenic parenchyma complications can also be demonstrated by CT. Balthazar et.al have developed CT classification and severity scores based on the presence of fluid collections and pancreatic necrosis. These scores correlate with the incidence of morbidity and

  19. Effect of lethal and sub-lethal concentrations of tobacco (Nicotiana ...

    African Journals Online (AJOL)

    Lethal and sub-lethal bioassays on Clarias gariepinus were conducted to evaluate the toxicity of tobacco (Nicotiana tobaccum) leaf dust on weight gain and haematological indices of Clarias gariepinus (mean weight 10.5±0.70g) in glass aquaria with aeration system. The concentrations used during the lethal exposure are: ...

  20. miR-146a Suppresses Invasion of Pancreatic Cancer Cells

    Science.gov (United States)

    Li, Yiwei; VandenBoom, Timothy G.; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan; Philip, Philip A.; Sarkar, Fazlul H.

    2010-01-01

    The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-κB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-κB regulatory kinase interleukin 1 receptor–associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IκBα, NF-κB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3′-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-κB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents. PMID:20124483

  1. Pancreatic Carcinoma: the Disease that Kills.

    Science.gov (United States)

    Kabashi, Serbeze; Dedushi, Kreshnike; Ramadani, Naser; Mucaj, Sefedin; Hoxhaj, Asrtrit; Jerliu, Naim

    2016-02-01

    The purpose of this case report is to demonstrate the clinical symptoms and laboratory changes that have occurred very late and were very few in number even the imaging studies performed at that time showed an intensive local tumor growth associated with the wide infiltration of the both adjacent and distant upper abdominal structures. A 71-year-old male patient who was a chronic alcohol abuser and ex smoker (quit smoking 8 years earlier) presented with symptoms of mild pain on epigastric region that irradiated toward the back and significant weight loss. The initial ultrasonography (US) examination was performed, followed by the lab tests and multidetector computed tomography (MDCT) examination. The diagnostic studies confirmed the presence of the pancreatic's body mass. The ordered laparoscopic evaluation established definitive diagnosis. Initial US examination showed heterogeneous pseudo-cystic changes and slight edema of the pancreatic parenchyma associated with the multiple oval hyperechogenic lesions of liver - the signs highly suggestive of secondary metastatic deposits. The other imaging findings that were obtained with the use of the MDCT confirmed the presence of an expansive primary process of the body of the pancreas associated with the secondary metastatic changes in liver. In addition, the consecutive lymphadenopathy was revealed along hepatoduodenal ligament, retropancreatic region and intraperitoneal compartment. Tumor markers resulted with the high values of the AFP of 2.3, CA19-9 of 423.0 U/mL, and CEA of 219.0 ng/mL. The specimen of the tumor tissue taken during laparoscopic biopsy was sent for histologic examination and the final result was "metastatic adenocarcinoma of pancreas". Pancreatic body carcinoma has always been associated with poor prognosis because diagnosis is made at the advanced stage of the disease. Therefore, poor prognosis might be improved if early diagnosis could be made. Recent researches confirmed genetic predisposition for

  2. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  3. Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors.

    Science.gov (United States)

    Dralle, Henning; Krohn, Sabine L; Karges, Wolfram; Boehm, Bernhard O; Brauckhoff, Michael; Gimm, Oliver

    2004-12-01

    Nonfunctioning neuroendocrine pancreatic tumors (NFNEPTs) comprise about one-third of pancreatic endocrine tumors. Based on immunohistochemistry, nonfunctioning tumors are difficult to distinguish from functioning ones; therefore the final diagnosis is basically the result of a synopsis of pathology and clinical data. Owing to their incapacity to produce hormone-dependent symptoms, NFNEPTs are detected incidentally or because of uncharacteristic symptoms resulting from local or distant growth. About two-thirds of NFNEPTs are located in the pancreatic head, so jaundice may be a late symptom of this tumor. Modern diagnostic procedures are best applied by a stepwise approach: first endoscopic ultrasonography and computed tomography/magnetic resonance imaging followed by somatostatin receptor scintigraphy or positron emission tomography (or both). Due to significant false-positive and false-negative findings, for decision-making the latter should be confirmed by a second imaging modality. Regarding indications for surgery and the surgical approach to the pancreas, three pancreatic manifestations of NFNEPTs can be distinguished: (1) solitary benign non-multiple endocrine neoplasia type 1 (non-MEN-1); (2) multiple benign MEN-1; and (3) malignant NFNEPTs. Reviewing the literature and including our experience with 18 NFNEPTs (8 benign, 10 malignant) reported here, the following conclusions can be drawn: (1) Solitary benign non-MEN-1 NFNEPTs can be removed by enucleation or by pancreas-, spleen-, and duodenum-preserving techniques in most cases. The choice of surgical technique depends on the location and site of the tumor and its anatomic relation to the pancreatic duct. (2) With multiple benign MEN-1 NFNEPTs, because of the characteristics of the underlying disease a preferred, more conservative concept (removal of only macrolesions) competes with a more radical procedure (left pancreatic resection with enucleation of head macrolesions). Further studies are necessary to

  4. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance.

    Science.gov (United States)

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-30

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future.

  5. Fatal hemorrhagic–necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus

    Directory of Open Access Journals (Sweden)

    Bongiovanni Laura

    2014-05-01

    Full Text Available Asian palm civets (Paradoxurus hermaphroditus, or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.

  6. Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus).

    Science.gov (United States)

    Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

    2014-05-01

    Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.

  7. Metastatic Merkel Cell Carcinoma (MCC) of Pancreas.

    Science.gov (United States)

    Kartal, K; Hamaloğlu, E

    2015-01-01

    Merkel cell carcinoma (MCC) is a rare, agressive, neurocutaneous malignancy with a high potential to metastasize. We present a 59 year-old woman referred to general surgery department with a complaint of epigastric pain. The abdominal computed tomography (CT) performed and revealed amass of 3 cm in the head of the pancreas. The significant debate in the patient's medical history was that she had a MCC in size of 5 cm removed from the left gluteal region 7 months ago. Following preoperative preparation a pancreatic oduodenectomy with Whipple procedure was performed fort hepancreatic head mass. As the tumor showed morphologically similar properties with the patient's primary neoplasm, it was accepted as a metastatic MCC. Following the operation the patient received adjuvant chemotherapy and at a 30 months follow-up it was observed that the patient is disease free and has no complications related to the disease progression or recurrence. Although MCC is an aggresive and poor prognostic tumor, good results can be obtained with correct diagnosis and proper surgical treatment. Celsius.

  8. Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

    International Nuclear Information System (INIS)

    Akita, Shingo; Kubota, Koji; Kobayashi, Akira; Misawa, Ryosuke; Shimizu, Akira; Nakata, Takenari; Yokoyama, Takahide; Takahashi, Masafumi; Miyagawa, Shinichi

    2012-01-01

    Highlights: ► BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. ► BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. ► BMC-derived activated PSCs can produce PDGF and TGF β1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin (αSMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) β1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 ± 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGFβ1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

  9. Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

    Energy Technology Data Exchange (ETDEWEB)

    Akita, Shingo; Kubota, Koji [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Kobayashi, Akira, E-mail: kbys@shinshu-u.ac.jp [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Misawa, Ryosuke; Shimizu, Akira; Nakata, Takenari; Yokoyama, Takahide [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Takahashi, Masafumi [Center for Molecular Medicine Division of Bioimaging Sciences, Jichi Medical University, 3311-1 Yakushiji, Shimono, Tochigi 329-0498 (Japan); Miyagawa, Shinichi [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. Black-Right-Pointing-Pointer BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. Black-Right-Pointing-Pointer BMC-derived activated PSCs can produce PDGF and TGF {beta}1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin ({alpha}SMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) {beta}1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 {+-} 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGF{beta}1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

  10. Group B streptococcal metastatic endophthalmitis.

    Science.gov (United States)

    Nagelberg, H P; Petashnick, D E; To, K W; Woodcome, H A

    1994-04-15

    Reports of invasive Group B Streptococcus infection in adults with underlying medical conditions have been increasing. Ocular infection with this organism is unusual. Metastatic endophthalmitis in adults caused by this organism has been reported rarely and has only been associated with endocarditis. We encountered two cases of Group B streptococcal metastatic endophthalmitis in adults who did not have endocarditis. These cases reflect the increasing incidence of invasive Group B Streptococcus infection with its varying manifestations. Additionally, they emphasize the importance of considering this pathogen as a cause of metastatic endophthalmitis in adults with predisposing illnesses.

  11. Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

    Directory of Open Access Journals (Sweden)

    Wenyan Hu

    Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

  12. The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers.

    Science.gov (United States)

    Jin, H; Wu, Y; Tan, X

    2017-08-01

    Pancreatic cancer is one of the most deadly cancers, with dismal prognosis due to its poor early detection rate and high metastatic rate. Thus, elucidation of the molecular mechanisms accounting for its metastasis and discovery of competent biomarkers is required. Exosomes are multivesicular body-derived small extracellular vesicles released by various cell types that serve as important message carriers during intercellular communication. They are also known to play critical roles during cancer-genesis, cancer-related immune reactions, and metastasis. They also possess promising potential as novel biomarkers for cancer early detection. Therefore, extensive studies on pancreatic cancer-derived exosomes are currently being performed because they hold the promising potential of elevating the overall survival rate of patients with pancreatic cancer. In the present review, we focus on the role of exosomes in pancreatic cancer-related immune reactions, metastasis, and complications, and on their potential application as pancreatic cancer biomarkers.

  13. PKD signaling and pancreatitis

    Science.gov (United States)

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

    Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

  14. Pancreatitis in scrub typhus

    Directory of Open Access Journals (Sweden)

    Alok Bhatt

    2014-01-01

    Full Text Available Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.

  15. Successful neoadjuvant peptide receptor radionuclide therapy for an inoperable pancreatic neuroendocrine tumour

    Directory of Open Access Journals (Sweden)

    Tiago Nunes da Silva

    2018-04-01

    Full Text Available Non-functional pancreatic neuroendocrine tumours (NETs can present with advanced local or distant (metastatic disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET.

  16. Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

    2014-02-26

    The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

  17. Factors influencing circadian rhythms in acetaminophen lethality.

    Science.gov (United States)

    Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

    1984-01-01

    Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

  18. Sorafenib for Metastatic Thyroid Cancer

    Science.gov (United States)

    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  19. TGF-β in pancreatic cancer initiation and progression: two sides of the same coin.

    Science.gov (United States)

    Shen, Wei; Tao, Guo-Qing; Zhang, Yu; Cai, Bing; Sun, Jian; Tian, Zhi-Qiang

    2017-01-01

    Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-β (TGF-β) signaling plays a dual role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-β signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-β signaling in the preclinical and clinical setting. In this review, we highlight the dual roles of TGF-β and touch upon the perspectives on therapeutic target of TGF-β signaling in pancreatic cancer.

  20. Surgical Approaches to Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel Hartmann

    2015-01-01

    Full Text Available Chronic pancreatitis is a progressive inflammatory disease resulting in permanent structural damage of the pancreas. It is mainly characterized by recurring epigastric pain and pancreatic insufficiency. In addition, progression of the disease might lead to additional complications, such as pseudocyst formation or development of pancreatic cancer. The medical and surgical treatment of chronic pancreatitis has changed significantly in the past decades. With regard to surgical management, pancreatic head resection has been shown to be a mainstay in the treatment of severe chronic pancreatitis because the pancreatic head mass is known to trigger the chronic inflammatory process. Over the years, organ-preserving procedures, such as the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple, have become the surgical standard and have led to major improvements in pain relief, preservation of pancreatic function, and quality of life of patients.

  1. Sonic hedgehog signaling inhibition provides opportunities for targeted therapy by sulforaphane in regulating pancreatic cancer stem cell self-renewal.

    Directory of Open Access Journals (Sweden)

    Mariana Rodova

    Full Text Available Dysregulation of the sonic hedgehog (Shh signaling pathway has been associated with cancer stem cells (CSC and implicated in the initiation of pancreatic cancer. Pancreatic CSCs are rare tumor cells characterized by their ability to self-renew, and are responsible for tumor recurrence accompanied by resistance to current therapies. The lethality of these incurable, aggressive and invasive pancreatic tumors remains a daunting clinical challenge. Thus, the objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables, inhibits self-renewal capacity of human pancreatic CSCs. Interestingly, we demonstrate here that Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Given the requirement for Hedgehog in pancreatic cancer, we investigated whether hedgehog blockade by SFN could target the stem cell population in pancreatic cancer. In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN, suggesting the clonogenic depletion of the CSCs. Interestingly, SFN inhibited the components of Shh pathway and Gli transcriptional activity. Interference of Shh-Gli signaling significantly blocked SFN-induced inhibitory effects demonstrating the requirement of an active pathway for the growth of pancreatic CSCs. SFN also inhibited downstream targets of Gli transcription by suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4 as well as PDGFRα and Cyclin D1. Furthermore, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases. Our data reveal the essential role of Shh-Gli signaling in controlling the characteristics of pancreatic CSCs. We propose that pancreatic cancer preventative effects of SFN may result from inhibition of the Shh pathway

  2. “Stealth dissemination” of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Circulating tumor cells (CTCs) appear to be involved in early dissemination of many cancers, although which characteristics are important in metastatic spread are not clear. Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal a...

  3. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Perspectives in Pancreatic Pain

    Directory of Open Access Journals (Sweden)

    A. S. Salim

    1997-01-01

    Full Text Available This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described.

  5. Pancreatic exocrine function testing

    International Nuclear Information System (INIS)

    Goff, J.S.

    1981-01-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each

  6. Familial Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Stephen J. Lanspa

    2010-11-01

    Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.

  7. CT diagnosis of pancreatic carcinoma and chronic pancreatitis

    International Nuclear Information System (INIS)

    Luan Baoqing; Jin Erhu; Zhang Lizhen; Jiang Haibin

    1997-01-01

    To improve the diagnostic accuracy of pancreatic carcinoma and chronic pancreatitis. The CT findings of 154 cases with pancreatic carcinoma, chronic pancreatitis and mis-diagnosed other pancreatic diseases proven clinically and pathologically were analysed. Slice thickness of 8 mm and slice interval of 8 mm were used and thin-section scan and enhancement study were performed in some cases. The main signs in degassing and differential diagnosis between pancreatic carcinoma and chronic pancreatitis included: (1) focal or diffuse enlargement and density abnormality of pancreas; (2) dilated common bile duct was suddenly obstructed, peripancreatic blood vessels were invaded and cancerous thrombus was revealed, enlargement of abdominal lymph nodes and metastasis in the liver were discovered; (3) calcium deposit in the pancreatic duct area and dilated pancreatic duct which passed through the lesion or not; (4) presence and location of pancreatic cyst and its relationship to pancreatic contour. CT is the imaging modality of choice in the diagnosis of pancreatic carcinoma and chronic pancreatitis at present. The diagnostic accuracy of CT was over 90% in this series

  8. Hypermutation in pancreatic cancer

    OpenAIRE

    Humphris, Jeremy L.; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J.; Johns, Amber L.; McKay, Skye; Chang, David K.; Miller, David K.; Pajic, Marina; Kassahn, Karin S.; Quinn, Michael C.J.; Bruxner, Timothy J.C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechan...

  9. Management of pancreatic trauma.

    Science.gov (United States)

    Girard, E; Abba, J; Arvieux, C; Trilling, B; Sage, P Y; Mougin, N; Perou, S; Lavagne, P; Létoublon, C

    2016-08-01

    Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated. Retrospective study of PT treated in the University Hospital of Grenoble over a 22-year span. The decision for initial laparotomy depended on hemodynamic status as well as on associated lesions. Main pancreatic duct lesions were always searched for. PT lesions were graded according to the AAST classification. Of a total of 46 PT, 34 were grades II or I. Hemodynamic instability led to immediate laparotomy in 18 patients, for whom treatment was always drainage of the pancreatic bed; morbidity was 30%. Eight patients had grade III injuries, six of whom underwent immediate operation: three underwent splenopancreatectomy without any major complications while the other three who had simple drainage required re-operation for peritonitis, with one death related to pancreatic complications. Four patients had grades IV or V PT: two pancreatoduodenectomies were performed, with no major complication, while one patient underwent duodenal reconstruction with pancreatic drainage, complicated by pancreatic and duodenal fistula requiring a hospital stay of two months. The post-trauma course was complicated for all patients with main pancreatic duct involvement. Our outcomes were similar to those found in the literature. In patients with distal PT and main pancreatic duct involvement, simple drainage is associated with high morbidity and mortality. For proximal PT, the therapeutic options of drainage versus pancreatoduodenectomy must be weighed; pancreatoduodenectomy may be unavoidable when the duodenum is injured as well. Two-stage (resection first, reconstruction later) could be an effective alternative in the emergency setting when there are other associated traumatic lesions. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Transporting Patients with Lethal Contagious Infections

    National Research Council Canada - National Science Library

    Swartz, Colleen

    2002-01-01

    .... The AIT is a unique military medical team capable of worldwide air evacuation and management of a limited number of patients who are potentially exposed to known and unknown lethal communicable...

  11. Tissue Transglutaminase (TG2)-Induced Inflammation in Initiation, Progression, and Pathogenesis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Kapil, E-mail: kmehta@mdanderson.org; Han, Amy [Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (United States); Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030 (United States)

    2011-02-25

    Pancreatic cancer (PC) is among the deadliest cancers, with a median survival of six months. It is generally believed that infiltrating PC arises through the progression of early grade pancreatic intraepithelial lesions (PanINs). In one model of the disease, the K-ras mutation is an early molecular event during progression of pancreatic cancer; it is followed by the accumulation of additional genetic abnormalities. This model has been supported by animal studies in which activated K-ras and p53 mutations produced metastatic pancreatic ductal adenocarcinoma in mice. According to this model, oncogenic K-ras induces PanIN formation but fails to promote the invasive stage. However, when these mice are subjected to caerulein treatment, which induces a chronic pancreatitis-like state and inflammatory response, PanINs rapidly progress to invasive carcinoma. These results are consistent with epidemiologic studies showing that patients with chronic pancreatitis have a much higher risk of developing PC. In line with these observations, recent studies have revealed elevated expression of the pro-inflammatory protein tissue transglutaminase (TG2) in early PanINs, and its expression increases even more as the disease progresses. In this review we discuss the implications of increased TG2 expression in initiation, progression, and pathogenesis of pancreatic cancer.

  12. Experiences in therapy for lethal midline granuloma

    International Nuclear Information System (INIS)

    Tosaka, Kaoru; Ishikawa, Takeru

    1982-01-01

    Four cases of the lethal midline granuloma or malignant granuloma of the nose were treated by irradiation and chemotherapy, which are generally prescribed for malignant lymphomas. Clinical, histological and laboratory examination indicated that they were the lethal midline granuloma and clearly differentiated from Wegener's granulomatosis or malignant lymphoma. All of the cases exhibited primary remission. The four cases were observed up to 38, 22, 14, and 10 months since the beginning of the therapy, showing no local or general recurrence. (author)

  13. Pathobiological implications of MUC16 expression in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Dhanya Haridas

    Full Text Available MUC16 (CA125 belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC, the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

  14. Results of intraoperative radiotherapy for pancreatic cancers

    International Nuclear Information System (INIS)

    Okazaki, Atsushi; Shinozaki, Jun; Noda, Masanobu

    1991-01-01

    Reported are the results and observations of the authors who, from July 1986 through December 1989, have used electron beam intraoperative radiotherapy (IORT) on 20 patients with locally advanced pancreatic cancers, said number including 3 patients given a resection. In 14 of the 17 unresected patients, a chief symptom was pain, and 8 patients were given a celiac plexus block at the same time. The results and observations are given below. Life-threatening complications occurred in two patients, i.e., an insufficient pancreatojejunostomy, and a perforative peritonitis. In 12 of 13 evaluable patients, pain control was achieved for a mean period of 5 months, indicating that an IORT with celiac plexus block may be useful for palliation. In the resected patients, the mean survival time was 6 months, whereas in the unresected patients, the mean survival time was 7 months. The common cause of death in the unresected patients was a metastatic dissemination. Finally, in 3 of the 5 unresected patients, marked effects such as massive fibrosis were seen in the pancreatic tumor on autopsy. (author)

  15. Management of unresectable, locally advanced pancreatic adenocarcinoma.

    Science.gov (United States)

    Salgado, M; Arévalo, S; Hernando, O; Martínez, A; Yaya, R; Hidalgo, M

    2018-02-01

    The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

  16. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    International Nuclear Information System (INIS)

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-01-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  17. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  18. Type 1 autoimmune pancreatitis.

    Science.gov (United States)

    Zen, Yoh; Bogdanos, Dimitrios P; Kawa, Shigeyuki

    2011-12-07

    Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed

  19. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh

    2011-12-01

    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  20. Ablation of phosphoinositide 3-kinase-gamma reduces the severity of acute pancreatitis.

    Science.gov (United States)

    Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

    2004-12-01

    In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-gamma (PI3K gamma) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3K gamma, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3K gamma significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3K gamma-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3K gamma, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3K gamma. Our results thus suggest that inhibition of PI3K gamma may be of therapeutic value in acute pancreatitis.

  1. Ablation of Phosphoinositide 3-Kinase-γ Reduces the Severity of Acute Pancreatitis

    Science.gov (United States)

    Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P.; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

    2004-01-01

    In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-γ (PI3Kγ) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3Kγ, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3Kγ significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3Kγ-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3Kγ, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3Kγ. Our results thus suggest that inhibition of PI3Kγ may be of therapeutic value in acute pancreatitis. PMID:15579443

  2. Altered central pain processing after pancreatic surgery for chronic pancreatitis

    NARCIS (Netherlands)

    Bouwense, S. A.; Ahmed Ali, U.; ten Broek, R. P.; Issa, Y.; van Eijck, C. H.; Wilder-Smith, O. H.; van Goor, H.

    2013-01-01

    Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. Patients with CP

  3. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model

    International Nuclear Information System (INIS)

    Marques, Ines J; Bagowski, Christoph P; Weiss, Frank Ulrich; Vlecken, Danielle H; Nitsche, Claudia; Bakkers, Jeroen; Lagendijk, Anne K; Partecke, Lars Ivo; Heidecke, Claus-Dieter; Lerch, Markus M

    2009-01-01

    Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For primary human tumours we establish here a simple, fast, sensitive and cost-effective in vivo model to analyse tumour invasion and metastatic behaviour. We fluorescently labelled small explants from gastrointestinal human tumours and investigated their metastatic behaviour after transplantation into zebrafish embryos and larvae. The transparency of the zebrafish embryos allows to follow invasion, migration and micrometastasis formation in real-time. High resolution imaging was achieved through laser scanning confocal microscopy of live zebrafish. In the transparent zebrafish embryos invasion, circulation of tumour cells in blood vessels, migration and micrometastasis formation can be followed in real-time. Xenografts of primary human tumours showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumour tissue was implanted. Furthermore, primary human tumour cells, when organotopically implanted in the zebrafish liver, demonstrated invasiveness and metastatic behaviour, whereas primary control cells remained in the liver. Pancreatic tumour cells showed no metastatic behaviour when injected into cloche mutant embryos, which lack a functional vasculature. Our results show that the zebrafish is a useful in vivo animal model for rapid analysis of invasion and metastatic behaviour of primary human tumour specimen

  4. Metabolic pancreatitis: Etiopathogenesis and management

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2013-01-01

    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  5. Road Accident due to a Pancreatic Insulinoma

    Science.gov (United States)

    Parisi, Amilcare; Desiderio, Jacopo; Cirocchi, Roberto; Grassi, Veronica; Trastulli, Stefano; Barberini, Francesco; Corsi, Alessia; Cacurri, Alban; Renzi, Claudio; Anastasio, Fabio; Battista, Francesca; Pucci, Giacomo; Noya, Giuseppe; Schillaci, Giuseppe

    2015-01-01

    Abstract Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays. PMID:25816027

  6. CT of pancreatitis

    International Nuclear Information System (INIS)

    Fukuda, Toshio

    1990-01-01

    One hundred and two cases of acute and chronic pancreatitis were studied by computed tomography. Fluid collection was detected by CT in 45 cases, and the common extrapancreatic sites of involvement included the lesser sac (13 cases), anterior pararenal space (9 cases), transverse mesocolon (7 cases) and posterior pararenal space (5 cases). Ten cases of spontaneous resolution of pancreatic pseudocysts were encountered. Cystojejunostomy was done on 6 patients. A 4-to-6-weeks time interval has been currently accepted as necessary for pseudocyst wall maturation. However, the surgery was not possible in two patients in this series since the cyst wall was too thin. It is considered that the time over 3 months is required for surgical anastomosis of the cyst to the gastrointestinal tract. Pancreatic abscess has become the most common cause of death from pancreatitis. In this series pancreatic abscess occurred in 8 patients. Gas collection in the pancreas was observed in only one patient. In the other patients, pseudocysts had become infected and converted to abscesses. The CT number of 4 infected pseudocysts was less than 15 HU. Thus, it was not possible to distinguish infected from noninfected pseudocysts by CT. The author studied 9 patients with focal inflammatory mass of the pancreas with histologically proved severe fibrosis. All masses were small. Angiography showed occlusion or marked stenosis of the splenic vein in 3 cases. The postcontract CT (after intravenous bolus injection) in 7 cases of focal inflammatory mass demonstrated almost equal enhanced effect of the mass as compared with the adjacent normal pancreatic parenchyma. This finding is considered to be useful in distinguishing inflammatory mass from pancreatic carcinoma. (author)

  7. Road accident due to a pancreatic insulinoma: a case report.

    Science.gov (United States)

    Parisi, Amilcare; Desiderio, Jacopo; Cirocchi, Roberto; Grassi, Veronica; Trastulli, Stefano; Barberini, Francesco; Corsi, Alessia; Cacurri, Alban; Renzi, Claudio; Anastasio, Fabio; Battista, Francesca; Pucci, Giacomo; Noya, Giuseppe; Schillaci, Giuseppe

    2015-03-01

    Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays.

  8. Acute pancreatitis: staging with CT

    International Nuclear Information System (INIS)

    Gialeli, E.; Petrocheilou, G.; Georgaki, S.; Tzemailas, I.; Adraktas, A.; Charilas, G.; Patsiogiannis, V.

    2012-01-01

    Full text: Introduction: Computed Tomography (CT) is the imaging modality of choice for the diagnosis and staging of acute pancreatitis and its complications. Objectives and tasks: The purpose of this presentation is to demonstrate the findings in CT images which are useful for staging acute pancreatitis according to Balthazar, their significance and restrictions. Materials and methods: CT images from patients who were referred to our Department for an abdominal CT scan for the diagnosis or/and staging of acute pancreatitis were retrospectively studied. Results: In acute pancreatitis, CT helps to stage the severity of inflammatory process, to detect pancreatic necrosis and to depict local complications. CT severity index (CTSI), which was proposed by Balthazar et al, combines the grade of pancreatitis with the extent of pancreatic necrosis assigning points to the patients in order to find the severity index which scales from 0-10. More points are given for a higher grade of pancreatitis and for more extensive necrosis. Types of pancreatitis according to CTSI are: interstitial (Balthazar grade A-C), exudative (Balthazar grade D or E), necrotising (Balthazar grade E, CTSI:10) and central gland necrotising. Patients with pancreatitis but no collections or necrosis have an interstitial (mild) pancreatitis. In exudative pancreatitis there is normal enhancement of the entire pancreas associated with extensive peripancreatic collections. Necrotizing (severe) pancreatitis is characterized by protacted clinical course, high incidence of local complications and high mortality rate. Central gland necrosis is a subtype of necrotizing pancreatitis. Conclusions: The combination of CT imaging and clinical and laboratory evaluation allows the early diagnosis of acute pancreatitis. Acute pancreatitis may vary from a mild uneventful disease to a severe life-threatening illness with multisystemic organ failure. Thus, it is crucial to identify patients who are at high risk of severe

  9. Hereditary pancreatitis for the endoscopist

    OpenAIRE

    Patel, Milan R.; Eppolito, Amanda L.; Willingham, Field F.

    2013-01-01

    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68–81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis trans...

  10. Pharmacological challenges in chronic pancreatitis

    OpenAIRE

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal ...

  11. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  12. Whole genomes redefine the mutational landscape of pancreatic cancer.

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K; Kassahn, Karin S; Bailey, Peter; Johns, Amber L; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C J; Robertson, Alan J; Fadlullah, Muhammad Z H; Bruxner, Tim J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen H; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Lee, Hong C; Jones, Marc D; Nagrial, Adnan M; Humphris, Jeremy; Chantrill, Lorraine A; Chin, Venessa; Steinmann, Angela M; Mawson, Amanda; Humphrey, Emily S; Colvin, Emily K; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Pettitt, Jessica A; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; Graham, Janet S; Niclou, Simone P; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A; Gill, Anthony J; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Pearson, John V; Biankin, Andrew V; Grimmond, Sean M

    2015-02-26

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

  13. Whole genomes redefine the mutational landscape of pancreatic cancer

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J.; Fink, J. Lynn; Holmes, Oliver; Kazakoff, Stephen H.; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Lee, Hong C.; Jones, Marc D.; Nagrial, Adnan M.; Humphris, Jeremy; Chantrill, Lorraine A.; Chin, Venessa; Steinmann, Angela M.; Mawson, Amanda; Humphrey, Emily S.; Colvin, Emily K.; Chou, Angela; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S.; Kench, James G.; Pettitt, Jessica A.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B.; Graham, Janet S.; Niclou, Simone P.; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A.; Gill, Anthony J.; Eshleman, James R.; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A.; Pearson, John V.; Biankin, Andrew V.; Grimmond, Sean M.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. PMID:25719666

  14. Pancreatic Carcinoma: the Disease that Kills

    Science.gov (United States)

    Kabashi, Serbeze; Dedushi, Kreshnike; Ramadani, Naser; Mucaj, Sefedin; Hoxhaj, Asrtrit; Jerliu, Naim

    2016-01-01

    The purpose of this case report is to demonstrate the clinical symptoms and laboratory changes that have occurred very late and were very few in number even the imaging studies performed at that time showed an intensive local tumor growth associated with the wide infiltration of the both adjacent and distant upper abdominal structures. A 71-year-old male patient who was a chronic alcohol abuser and ex smoker (quit smoking 8 years earlier) presented with symptoms of mild pain on epigastric region that irradiated toward the back and significant weight loss. The initial ultrasonography (US) examination was performed, followed by the lab tests and multidetector computed tomography (MDCT) examination. The diagnostic studies confirmed the presence of the pancreatic’s body mass. The ordered laparoscopic evaluation established definitive diagnosis. Initial US examination showed heterogeneous pseudo-cystic changes and slight edema of the pancreatic parenchyma associated with the multiple oval hyperechogenic lesions of liver - the signs highly suggestive of secondary metastatic deposits. The other imaging findings that were obtained with the use of the MDCT confirmed the presence of an expansive primary process of the body of the pancreas associated with the secondary metastatic changes in liver. In addition, the consecutive lymphadenopathy was revealed along hepatoduodenal ligament, retropancreatic region and intraperitoneal compartment. Tumor markers resulted with the high values of the AFP of 2.3, CA19-9 of 423.0 U/mL, and CEA of 219.0 ng/mL. The specimen of the tumor tissue taken during laparoscopic biopsy was sent for histologic examination and the final result was “metastatic adenocarcinoma of pancreas”. Pancreatic body carcinoma has always been associated with poor prognosis because diagnosis is made at the advanced stage of the disease. Therefore, poor prognosis might be improved if early diagnosis could be made. Recent researches confirmed genetic

  15. Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Thilo Welsch

    Full Text Available BACKGROUND: Erythropoietin (Epo administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC. METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150, serum Epo (sEpo, n = 87 and tissue expression of Epo/Epo receptor (EpoR, n = 104 was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05 and PDAC (p<0.001, reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46, 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99 but not in PDAC (O/P = 0.85. Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml were not significantly different in M0 (20% and M1 (30% groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05. The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold

  16. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland (Ingo)

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are

  17. Genetic basis of chronic pancreatitis

    NARCIS (Netherlands)

    Jansen, JBMJ; Morsche, RT; van Goor, Harry; Drenth, JPH

    2002-01-01

    Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was

  18. Multidisciplinaire behandeling van chronische pancreatitis

    NARCIS (Netherlands)

    Kempeneers, M. A.; Besselink, M. G.; Issa, Y.; van Hooft, J. E.; van Goor, H.; Bruno, M. J.; van Santvoort, H. C.; Boermeester, M. A.

    2017-01-01

    - Chronic pancreatitis is a progressive inflammatory disease, which leads to a severe decrease in quality of life and reduced life expectancy.- 85-90% of patients with chronic pancreatitis consult the doctor because of pain.- Pain in chronic pancreatitis has a multifactorial aetiology, with

  19. Pancreatic Cancer—Patient Version

    Science.gov (United States)

    Pancreatic cancer can form in exocrine cells and neuroendocrine cells. The exocrine type is more common and is usually found at an advanced stage. Pancreatic neuroendocrine tumors are less common but have a better prognosis. Start here to find information on pancreatic cancer treatment, research, and statistics.

  20. Robotic transgastric cystgastrostomy and pancreatic debridement in the management of pancreatic fluid collections following acute pancreatitis.

    Science.gov (United States)

    Kirks, Russell C; Sola, Richard; Iannitti, David A; Martinie, John B; Vrochides, Dionisios

    2016-01-01

    Pancreatic and peripancreatic fluid collections may develop after severe acute pancreatitis. Organized fluid collections such as pancreatic pseudocyst and walled-off pancreatic necrosis (WOPN) that mature over time may require intervention to treat obstructive or constitutional symptoms related to the size and location of the collection as well as possible infection. Endoscopic, open surgical and minimally invasive techniques are described to treat post-inflammatory pancreatic fluid collections. Surgical intervention may be required to treat collections containing necrotic pancreatic parenchyma or in locations not immediately apposed to the stomach or duodenum. Comprising a blend of the surgical approach and the clinical benefits of minimally invasive surgery, the robot-assisted technique of pancreatic cystgastrostomy with pancreatic debridement is described.

  1. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T

    1985-01-01

    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reti......In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane......, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found...... in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support...

  2. The Hemostasis Apparatus in Pancreatic Cancer and Its Importance beyond Thrombosis

    International Nuclear Information System (INIS)

    Echrish, Hussein; Madden, Leigh A.; Greenman, John; Maraveyas, Anthony

    2011-01-01

    Laboratory evidence of aberrant coagulation is found in the majority of patients with advanced pancreatic cancer and a clinical consequence of this is the high incidence and prevalence of vascular thromboembolic events. Other sequelae are hypothesized to be the facilitation and acceleration of mechanisms that define the malignant phenotype, such as invasion, trafficking and anchoring, establishing the metastatic niche and inducing angiogenesis. We review the in vitro and preclinical evidence that supports the role of the coagulation apparatus in the metastatic process of pancreatic cancer, with a particular emphasis on interaction of this pathway with clinically-targeted growth factor receptor pathways. Links between hemostasis, angiogenesis and epidermal growth factor pathways and their significance as therapeutic targets are considered

  3. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer.

    Science.gov (United States)

    Riva, Francesca; Dronov, Oleksii I; Khomenko, Dmytro I; Huguet, Florence; Louvet, Christophe; Mariani, Pascale; Stern, Marc-Henri; Lantz, Olivier; Proudhon, Charlotte; Pierga, Jean-Yves; Bidard, Francois-Clement

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. An Extremely Rapid Case of Pneumonitis with the Use of Nivolumab for Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Rubens Barros Costa

    2018-01-01

    Full Text Available Pancreatic cancer is the fourth most common cancer death in the United States despite comprising a small percentage of the total number of cancer cases. The estimated 5-year overall survival (OS for patients with distant metastatic disease is approximately 3%. New treatment options are an unmet need and remain an area of active investigation. A 53-year-old male with metastatic pancreatic cancer presented to the hospital with acute-on-chronic respiratory failure approximately 24 hours after receiving a novel therapeutic combination. Chest imaging showed marked changes as concerning for pneumonitis. Infectious workup was negative. The patient had initial clinical improvement after receiving initial intravenous steroids and oxygen support but eventually deteriorated later opting for supportive measures only. With infection ruled out, drug-induced pneumonitis was felt to be the likely cause of the radiologic and clinical changes. The rapidity of onset of symptoms is the aspect being highlighted in this case.

  5. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0390 TITLE: Theranostics Targeting Metastatic Breast Cancer PRINCIPAL INVESTIGATOR: Zheng Li CONTRACTING ORGANIZATION...Breast Cancer 5b. GRANT NUMBER W81XWH-15-1-0390 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Zheng Li 5e. TASK NUMBER 5f. WORK UNIT...14 Theranostics Targeting Metastatic Breast  Cancer   A. Introduction (1paragraph) The overall goal of this proposal is to prepare TrkC

  6. Immunotherapy of distant metastatic disease

    DEFF Research Database (Denmark)

    Schadendorf, D; Algarra, S M; Bastholt, L

    2009-01-01

    Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated with signif......Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated...

  7. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.; Bakker, Olaf J.; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W. Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.; Boermeester, Marja A.

    2016-01-01

    Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch

  8. an extended pancreatic normal subjects and ~in pancreatItIs In ...

    African Journals Online (AJOL)

    function . . patIents. N. H. GILlNSKY, A. S. MEE, I. N. MARKS. Summary. Exocrine pancreatic response was evaluated in patients with varying degrees of pancreatic damage and in control subjects by ... hormones, the Lundh meal and an oral pancreatic function test .... is any different from that of the cells in me normal gland.

  9. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis

    NARCIS (Netherlands)

    Cahen, Djuna L.; Gouma, Dirk J.; Nio, Yung; Rauws, Erik A. J.; Boermeester, Marja A.; Busch, Olivier R.; Stoker, Jaap; Lameris, Johan S.; Dijkgraaf, Marcel G. W.; Huibregtse, Kees; Bruno, Marco J.

    2007-01-01

    BACKGROUND: For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS: All symptomatic patients with chronic pancreatitis and a distal

  10. Drug-induced pancreatitis.

    Science.gov (United States)

    Nitsche, Claudia; Maertin, Sandrina; Scheiber, Jonas; Ritter, Christoph A; Lerch, Markus M; Mayerle, Julia

    2012-04-01

    Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs.

  11. Imaging in pancreatic transplants

    International Nuclear Information System (INIS)

    Heller, Matthew T; Bhargava, Puneet

    2014-01-01

    Pancreatic transplantation, performed alone or in conjunction with kidney transplantation, is an effective treatment for advanced type I diabetes mellitus and select patients with type II diabetes mellitus. Following advancements in surgical technique, postoperative management, and immunosuppression, pancreatic transplantation has significantly improved the length and quality of life for patients suffering from pancreatic dysfunction. While computed tomography (CT) and magnetic resonance imaging (MRI) have more limited utility, ultrasound is the preferred initial imaging modality to evaluate the transplanted pancreas; gray-scale assesses the parenchyma and fluid collections, while Doppler interrogation assesses vascular flow and viability. Ultrasound is also useful to guide percutaneous interventions for the transplanted pancreas. With knowledge of the surgical anatomy and common complications, the abdominal radiologist plays a central role in the perioperative and postoperative evaluation of the transplanted pancreas

  12. Lethality Index 2008-2014: Less shootings, same lethality, more opacity

    Directory of Open Access Journals (Sweden)

    Carlos Silva Forné

    2017-11-01

    Full Text Available This article evaluates the use of lethal force by Mexican federal security forces during shootings with presumed members of organized crime from 2008-2014. The authors use official data and press reports on deaths and wounded in shootings to construct indicators such as the number of dead civilians over the number of dead officials from the federal security forces and the number of dead civilians over the number of wounded civilians. In a context where certain factors that contribute to an excessive use of force become more common, the results of the study show a growing use of lethal force. This raises questions over the possible excessive use of lethal force as a normal or systematic practice. The study also shows a growing context of opacity in the information available to evaluate the use of lethal force and the general lack of a legal framework to regulate the use of lethal force in Mexico.

  13. Cystic pancreatic lymphangioma

    Directory of Open Access Journals (Sweden)

    Alihan Gurkan

    2012-04-01

    Full Text Available Lymphangioma of the pancreas is a rare benign tumor of lymphatic origin. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas. Herein, we report a case of cystic pancreatic lymphangioma diagnosed in 34 year-old female patient who was hospitalized for a slight pain in the epigastrium and vomiting. Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum. During the laparoscopic surgery, a well circumscribed polycystic tumor was completely excised preserving the pancreatic duct. The patient made a complete recovery and is disease-free 12 months postoperatively.

  14. Necrotizing pancreatitis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Bendersky VA

    2016-10-01

    Full Text Available Victoria A Bendersky,1 Mohan K Mallipeddi,2 Alexander Perez,2 Theodore N Pappas,2 1School of Medicine, 2Department of Surgery, Duke University, Durham, NC, USA Abstract: Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications. Keywords: necrotizing pancreatitis, pancreatic necrosectomy, VARD, pancreatic debridement, pancreatic collections

  15. [Pancreatic serous cystadenoma associated with pancreatic heterotopia].

    Science.gov (United States)

    Mohamed, Hedfi; Dorra, Belghachem; Hela, Bouhafa; Cherif, Abdelhedi; Azza, Sridi; Karim, Sassi; Khadija, Bellil; Adnen, Chouchene

    2016-01-01

    Pancreatic heterotopias (HP) are rare. They can occur at any age with a slight male predominance. These lesions are usually asymptomatic and they are often found incidentally during upper or lower GI endoscopy or during the anatomo-pathological examination of an organ which was resected for other reasons; they can be isolated or associated with a digestive pathology. We report, through observation, the association of HP with serous cystadenoma of the pancreas discovered during examinations to identify the etiology of isolated abdominal pain. The aim of this study is to analyse clinical and histological features of this rare pathology.

  16. Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

    Science.gov (United States)

    Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

    2014-01-10

    The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

  17. Metastatic skeletal leiomyomatosis (leiomyomatosis ossea)

    International Nuclear Information System (INIS)

    Pimentel, Jose Raimundo; De Almeida, Ana Luzia Brito; Aymore, Ierece Lins; Pinto, Edna Pottes; Osthoff, Laura; Smith, Julius

    2002-01-01

    We present a unique case of metastatic leiomyomatosis to the skeleton. The very extensive involvement of the axial and peripheral skeleton with ''ring'' lesions and associated cyclical premenstrual pain eventually led to the correct diagnosis and total relief with hormonal therapy. (orig.)

  18. Metastatic skeletal leiomyomatosis (leiomyomatosis ossea)

    Energy Technology Data Exchange (ETDEWEB)

    Pimentel, Jose Raimundo [Radiologic Clinic Felippe Mattoso, Rio de Janeiro (Brazil); De Almeida, Ana Luzia Brito; Aymore, Ierece Lins [Claudio Lemos Surgical Pathology Laboratory, Rio de Janeiro (Brazil); Pinto, Edna Pottes [Edna Pottes Pinto Clinic, Rio de Janeiro (Brazil); Osthoff, Laura [Basilio Clinic, Rio de Janeiro (Brazil); Smith, Julius [National Cancer Institute (INCA), Rio de Janeiro (Brazil)

    2002-01-01

    We present a unique case of metastatic leiomyomatosis to the skeleton. The very extensive involvement of the axial and peripheral skeleton with ''ring'' lesions and associated cyclical premenstrual pain eventually led to the correct diagnosis and total relief with hormonal therapy. (orig.)

  19. KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Keisuke Taniuchi

    2014-12-01

    Full Text Available Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.

  20. Tetrofosmin in metastatic breast cancer

    International Nuclear Information System (INIS)

    Berghammer, P.; Obwegeser, R.; Ulm, M.; Wiltschke, C.; Kubista, E.; Sinzinger, H.; Zielinski, C.

    1997-01-01

    Tetrofosmin (1,2-bis[bis(2-ethoxyethyl)phosphino]ethan) is currently under investigation for its tumor seeking properties, encouraged by the incidental finding of a malignant breast-lesion on myocardial scintigraphy in 1995 (Rambaldi et al, Clin Nucl Med 1995) using tetrofosmin. Recent reports have confirmed tetrofosmins role in detecting primary tumors in breast cancer. To investigate whether tetrofosmin significantly helps detect metastatic lesions in such patients we performed tetrofosmin scintigraphy in 21 patients with metastatic breast cancer. Patients and methods: Median age of patients was 61 years. In one patient the primary site was unknown. All patients had at least one distant metastasis. 550 MBq of 99m-Tc-tetrofosmin was administered ten minutes before imaging was begun. After obtaining a planar image, a single photon emission computed tomography (SPECT) was done of every suspected distant lesion. CT-scans or MRI were used to confirm positive correlation with tetrofosmin scintigraphy. Results: Tetrofosmin scintigraphy correctly diagnosed metastatic disease in 71 % of patients with no false negative and two false positive results. In each of the two patients a mediastinal hot spot suggestive of malignancy was found, but none of those lesions could be proven using CT scans. Excluding patients with liver metastasis from the present analysis, 91 % of all metastasis would have been correctly diagnosed. The first patient in our department had a large metastasis in the upper mediastinum which could not be seen on regular chest films. In the patient in whom the primary site of cancer was unknown, tetrofosmin scintigraphy showed three consecutive nodules in the left mammary, gland in a coronary fashion. Magnetic resonance imaging then confirmed two single nodules of 0.8 cm in diameter. Conclusions: Evaluating 21 patients, the present study was performed to investigate tetrofosmins properties of detecting metastatic lesions in patients with breast cancer. A 91

  1. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. Copyright © 2011 S. Karger AG, Basel.

  2. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  3. Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells

    OpenAIRE

    SOMASAGARA, RANGANATHA R.; DEEP, GAGAN; SHROTRIYA, SANGEETA; PATEL, MANISHA; AGARWAL, CHAPLA; AGARWAL, RAJESH

    2015-01-01

    Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcita...

  4. pH-sensitive K+ channel TREK-1 is a novel target in pancreatic cancer

    DEFF Research Database (Denmark)

    Sauter, Daniel Rafael Peter; Sørensen, Christiane Elisabeth; Rapedius, Markus

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and new therapeutic targets are urgently needed. One of the hallmarks of cancer is changed pH-homeostasis and potentially pH-sensors may play an important role in cancer cell behavior. Two-pore potassium channels (K2P) are p...... proliferation and migration indicating that hyperpolarization of Vm attenuates cancer cell behavior. TREK-1 may therefore be a promising novel target for PDAC therapy....

  5. Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress.

    Science.gov (United States)

    Yu, Tao; Wang, Yong-Tao; Chen, Pan; Li, Yu-Hua; Chen, Yi-Xin; Zeng, Hang; Yu, Ai-Ming; Huang, Min; Bi, Hui-Chang

    2015-01-01

    Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. © 2015 S. Karger AG, Basel.

  6. Effects of Nicotinamide N-Methyltransferase on PANC-1 Cells Proliferation, Metastatic Potential and Survival Under Metabolic Stress

    Directory of Open Access Journals (Sweden)

    Tao Yu

    2015-01-01

    Full Text Available Background: Aberrant expression of Nicotinamide N-methyltransferase (NNMT has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Methods: Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. Results: NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. Conclusions: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.

  7. Metronidazole-Induced Pancreatitis

    Directory of Open Access Journals (Sweden)

    E. O'Halloran

    2010-01-01

    Conclusion. This case provides the eighth report of Metronidazole induced pancreatitis. All of the cases were reported in females and ran a benign course.Early diagnosis, discontinuation of the drug and supportive care will lead to a successful recovery in the majority of cases.

  8. Pancreatic Islet Transplantation

    Science.gov (United States)

    ... auto-transplantation is performed following total pancreatectomy—the surgical removal of the whole pancreas—in patients with severe and chronic, or long lasting, pancreatitis that cannot be managed by other treatments. This procedure is not considered experimental. Patients with ...

  9. Radioimmunoassay of pancreatic glucagon

    International Nuclear Information System (INIS)

    Nooijen, W.J.

    1979-01-01

    The author presents some of the problems and concepts related to the development of a radioimmunoassay of pancreatic glucagon. A specific derivatization of glucagon for raising specific anti-glucagon antisera is introduced, and special procedures for diminishing the non-specific effect are outlined. (G.T.H.)

  10. Pancreatitis del surco

    Directory of Open Access Journals (Sweden)

    Susana Araújo-Fernández

    2014-03-01

    It is a rare disease, but we must keep it in mind when we make the differential diagnosis of patients with abdominal pain of unknown origin. It is very important to distinguish this pathology from a pancreatic head carcinoma, as both treatments and prognosis differ greatly, so we believe important communication of a new case.

  11. Nanoparticle Albumin-Bound-Paclitaxel in the Treatment of Metastatic Urethral Adenocarcinoma: The Significance of Molecular Profiling and Targeted Therapy

    Directory of Open Access Journals (Sweden)

    Yasmin M. Abaza

    2014-01-01

    Full Text Available Primary urethral cancer is rare and accounts for only 0.003% of all malignancies arising from the female genitourinary tract. Due to the rarity of this disease, no consensus exists regarding the optimal therapeutic approach. Nanoparticle albumin-bound-paclitaxel has been shown to be effective in the treatment of a number of malignancies including metastatic breast, pancreatic, and bladder cancer. We present a 67-year-old woman with advanced metastatic urethral adenocarcinoma resistant to two lines of chemotherapy (ifosfamide/paclitaxel/cisplatin and irinotecan/5-fluorouracil/leucovorin that showed a dramatic response to nanoparticle albumin-bound-paclitaxel. This is the first case report to document the use and efficacy of nanoparticle albumin-bound-paclitaxel in the treatment of unresectable metastatic urethral cancer.

  12. In vitro cytotoxicity of alpha conjugates for human pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Qu, C.; Li, Y.; Rizvi, M.A.; Allen, B.; Samra, J.; Smith, R.

    2003-01-01

    Targeted Alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The aim of this study is to demonstrate the cytotoxicity of different alpha conjugates in vitro to human metastatic pancreatic cancer cell lines (CAPAN-1, CFPAN-1 and PANC-1). We are labeling the C595 and J591 (non-specific controls) monoclonal antibodies (Mabs) with 213 Bi were performed according to the standard methods in our laboratory. 213 Bi-C595 is specifically cytotoxic to CAPAN-1, CFPAN-1 and PANC-1cell lines in a concentration-dependent fashion. While non-specific alpha conjugates only killed very small fractions of pancreatic cancer cells. These alpha conjugates might be useful agents for the treatment of micro-metastases in pancreatic cancer patients with over-expression of the targeted receptors

  13. Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    2013-06-01

    Full Text Available We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.

  14. Genetics Home Reference: Amish lethal microcephaly

    Science.gov (United States)

    ... 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population. Related Information What information about a genetic condition can statistics provide? Why are some genetic ... gene cause Amish lethal microcephaly . The SLC25A19 gene provides instructions for ...

  15. The evolution of lethal intergroup violence

    OpenAIRE

    Kelly, Raymond C.

    2005-01-01

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

  16. The evolution of lethal intergroup violence.

    Science.gov (United States)

    Kelly, Raymond C

    2005-10-25

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

  17. A new lethal sclerosing bone dysplasia

    International Nuclear Information System (INIS)

    Kingston, H.M.; Freeman, J.S.; Hall, C.M.

    1991-01-01

    A neonate is described with a lethal sclerosing bone dysplasia associated with prenatal fractures and craniofacial abnormalities including microcephaly, exophthalmos, hypoplastic nose and mid-face, small jaw and nodular hyperplasia of the gums. Parental consanguinity suggests that an autosomal recessive mutation is the likely aetiology. (orig.)

  18. Surgical Treatment of Acute Pancreatitis.

    Science.gov (United States)

    Werner, Jens; Uhl, Waldemar; Büchler, Markus W.

    2003-10-01

    Patients with predicted severe necrotizing pancreatitis as diagnosed by C-reactive protein (>150 mg/L) and/or contrast-enhanced computed tomography should be managed in the intensive care unit. Prophylactic broad-spectrum antibiotics reduce infection rates and survival in severe necrotizing pancreatitis. Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy is a causative therapy for gallstone pancreatitis with impacted stones, biliary sepsis, or obstructive jaundice. Fine needle aspiration for bacteriology should be performed to differentiate between sterile and infected pancreatic necrosis in patients with sepsis syndrome. Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for surgery. Patients with sterile pancreatic necrosis should be managed conservatively. Surgery in patients with sterile necrosis may be indicated in cases of persistent necrotizing pancreatitis and in the rare cases of "fulminant acute pancreatitis." Early surgery, within 14 days after onset of the disease, is not recommended in patients with necrotizing pancreatitis. The surgical approach should be organ-preserving (debridement/necrosectomy) and combined with a postoperative management concept that maximizes postoperative evacuation of retroperitoneal debris and exudate. Minimally invasive surgical procedures have to be regarded as an experimental approach and should be restricted to controlled trials. Cholecystectomy should be performed to avoid recurrence of gallstone-associated acute pancreatitis.

  19. Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Juan; Xin, Beibei; Wang, Hui; He, Xiaodan [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China); Wei, Wei; Zhang, Ti [Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Tianjin 300060 (China); Shen, Xiaohong, E-mail: zebal2014@163.com [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China)

    2016-08-01

    Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. - Highlights: • Gastrin induces ABCG2 expression mediated by NF-κB activation. • Gastrin regulates NF-κB's function that binds to the ABCG2 promoter in BxPC-3 cells. • Gastrin promotes the SP proportion in BxPC-3 cells by modulating ABCG2 expression via activation of NF-κB molecule. • Gastrin induces an increase in migration and invasion potential in pancreatic cancer cell by regulating NF-κB/ABCG2 signaling.

  20. Eosinophilic Pancreatitis: A Rare Cause of Recurrent Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Jennifer Reppucci

    2017-03-01

    Full Text Available Eosinophilic pancreatitis is a rare form of recurrent acute pancreatitis that demonstrates distinct histologic features, including diffuse, periductal, acinar, and septal inflammatory infiltrates comprised of a pure or predominant population of eosinophils, eosinophilic phlebitis and arteritis, and localized eosinophilic infiltrates with pseudocyst formation. It is associated with elevated serum immunoglobulin E levels, an elevated eosinophil count with systemic manifestations, and eosinophilic infiltrates in other organs of the gastrointestinal tract. We present a case of eosinophilic pancreatitis in a 44-year-old man who was diagnosed after pancreatic resection for recurrent bouts of acute pancreatitis. While the gross and histologic evaluations matched other reported cases of eosinophilic pancreatitis, our patient had only minimal peripheral eosinophilia, no reported history of symptoms related to elevated eosinophilia or immunoglobulin E, and only mild eosinophilic infiltrates in his gallbladder.

  1. Legumain is activated in macrophages during pancreatitis

    NARCIS (Netherlands)

    Edgington-Mitchell, L.E.; Wartmann, T.; Fleming, A.K.; Gocheva, V.; Linden, W.A. van der; Withana, N.P.; Verdoes, M.; Aurelio, L.; Edgington-Mitchell, D.; Lieu, T.; Parker, B.S.; Graham, B.; Reinheckel, T.; Furness, J.B.; Joyce, J.A.; Storz, P.; Halangk, W.; Bogyo, M.; Bunnett, N.W.

    2016-01-01

    Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked

  2. Acute pancreatitis: clinical vs. CT findings

    International Nuclear Information System (INIS)

    Hill, M.C.; Barkin, J.; Isikoff, M.B.; Silver stein, W.; Kalser, M.

    1982-01-01

    In a prospective study of 91 patients with acute pancreatitis, computed tomographic (CT) findings were correlated with the clinical type of acute pancreatitis. In acute edematous pancreatitis (63 patients; 16 with repeat CT), CT was normal (28%) or showed inflammation limited to the pancreas (61%). Phlegmonous changes were present in 11%, including one patient with focal pancreatic hemorrhage, indicating that clinically unsuspected hemorrhagic pancreatitis can occur. In acute necrotizing (hemorrhagic, suppurative) pancreatitis (nine patients; eight with repeat CT), no patient had a normal CT scan and 89% had phlegmonous changes. One patient had hemorrhagic pancreatitis and three had abscesses. In acute exacerbation of chronic pancreatitis (10 patients; three with repeat CT), there were pancreatic calcifications (70%), a focal mass (40%), and pancreatic ductal dilation (30%). On follow-up CT, the findings of acute pancreatitis did not always disappear with resolution of the clinical symptons. This was especialy true of phlegmonous pancreatitis, where the CT findings could persist for months

  3. Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis

    Science.gov (United States)

    Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George

    2011-01-01

    Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. Conclusions DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress. PMID:21801698

  4. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    Directory of Open Access Journals (Sweden)

    Alison Gartland

    2016-09-01

    Full Text Available Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

  5. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... were compared with preoperative endoscopic retrograde cholangiopancreatography (ERCP) morphology. The preoperatively elevated pressure decreased in all patients but one, to normal or slightly elevated values. The median pressure decrease was 50% (range, 0-90%; p = 0.01). The drainage anastomosis (a...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  6. Gangliocytic paraganglioma of duodenum metastatic to lymph nodes and liver and extending into the retropancreatic space

    DEFF Research Database (Denmark)

    Amin, S M; Albrechtsen, N Wewer; Forster, J

    2013-01-01

    Gangliocytic paraganglioma (GP) is a rare benign neuroendocrine tumour found most often in the duodenum. To our knowledge, only a dozen cases of possibly malignant duodenal GP with local lymph node metastasis and only one case with liver metastasis have previously been published. Herein, we report...... an unusual case of GP of the duodenum spreading to the retropancreatic space and metastatic to the liver and lymph nodes. Additionally, the present tumour secreted pancreatic polypeptide (PP) which was detected in the serum during the follow-up period. We suggest that serum PP could be a valuable marker...

  7. Management strategies for autoimmune pancreatitis.

    Science.gov (United States)

    Kamisawa, Terumi; Takuma, Kensuke; Hara, Seiichi; Tabata, Taku; Kuruma, Sawako; Inaba, Yoshihiko; Gopalakrishna, Rajesh; Egawa, Naoto; Itokawa, Fumihide; Itoi, Takao

    2011-10-01

    Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.

  8. [Robot-assisted pancreatic resection].

    Science.gov (United States)

    Müssle, B; Distler, M; Weitz, J; Welsch, T

    2017-06-01

    Although robot-assisted pancreatic surgery has been considered critically in the past, it is nowadays an established standard technique in some centers, for distal pancreatectomy and pancreatic head resection. Compared with the laparoscopic approach, the use of robot-assisted surgery seems to be advantageous for acquiring the skills for pancreatic, bile duct and vascular anastomoses during pancreatic head resection and total pancreatectomy. On the other hand, the use of the robot is associated with increased costs and only highly effective and professional robotic programs in centers for pancreatic surgery will achieve top surgical and oncological quality, acceptable operation times and a reduction in duration of hospital stay. Moreover, new technologies, such as intraoperative fluorescence guidance and augmented reality will define additional indications for robot-assisted pancreatic surgery.

  9. Diagnostic Management of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dabizzi, Emanuele [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States); Assef, Mauricio Saab [Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Dr. Cesário Motta Jr. #61 Cep: 01221-020, São Paulo (Brazil); Raimondo, Massimo, E-mail: raimondo.massimo@mayo.edu [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States)

    2011-01-31

    Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used.

  10. Diagnostic Management of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Dabizzi, Emanuele; Assef, Mauricio Saab; Raimondo, Massimo

    2011-01-01

    Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used

  11. Current knowledge on pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Juan eIovanna

    2012-01-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3-5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes and the deregulation of many signalling pathways. Therefore, the strategies targeting these molecules as well as their downstream signalling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical and therapeutic aspects of pancreatic cancer.

  12. Current Knowledge on Pancreatic Cancer

    International Nuclear Information System (INIS)

    Iovanna, Juan; Mallmann, Maria Cecilia; Gonçalves, Anthony; Turrini, Olivier; Dagorn, Jean-Charles

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  13. Current Knowledge on Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iovanna, Juan [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France); Mallmann, Maria Cecilia [Centre d’Investigation Clinique de Marseille, Marseille (France); Gonçalves, Anthony [Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille (France); Turrini, Olivier [Département de Chirurgie Oncologique, Institut Paoli-Calmettes, Marseille (France); Dagorn, Jean-Charles, E-mail: juan.iovanna@inserm.fr [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France)

    2012-01-31

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  14. CT findings of pancreatic disease

    International Nuclear Information System (INIS)

    Lee, Mi Sook; Park, In Sook; Jeon, Doo Sung; Kim, Hong Soo; Rhee, Hak Song; Won, Jong Jin

    1988-01-01

    CT was found to be a reliable, often specific, and noninvasive method for detecting pancreatic diseases. In a study of pancreatic lesions, 37 cases having satisfactory operative and histological proofs were analyzed by CT at PMC from Jan. 1986 to Oct. 1987. The results were as following: 1. Male:female is 26:11. 2. The incidence of pancreatic disease were as follows: 1) Pancreatic cancer:21 cases (56%) a.Head:12 cases b.Body:4 cases c.Tail:1 case d.Body and tail:1 case e.Uncinate process:2 cases f.Entire pancreas: 1 case 2) Acute pancreatitis: 6 cases (16%) 3) Chronic pancreatitis:5 cases (14%) 3. The characteristic CT findings: 1) 100% of pancreatic head cancer showed focal mass or alteration of pancreatic head contour and biliary tree dilatation, and 33% (7/12) fat line obliteration. 2) All of other pancreatic cancer except head appeared as focal mass or contour alteration and fat line obliteration. 3) Total 6 cases of acute pancreatitis showed that 5 cases diffuse enlargement of pancreas, 3 fluid collection (2 cases:left anterior pararenal and posterior pararenal space and lesser sac, 1 case:only pancreas body) and 1 case abscess formation. 4) Total 5 cases of chronic pancreatitis revealed diffuse enlargement 2 cases and atrophy 1 case, pancreatic ductal dilatation 3 cases, calcification 2 cases, and biliary tree dilatation with CBD tapering appearance 1 case. 5) All cases of pseudocysts were well marginated cystic lesions that located at head in 3 cases and tail 3 cases, and 4 cases were well defined pure cystic masses but 1 case was well capsulated cyst with multiple internal septation

  15. Pancreatic scintiphotography in diabetes mellitus

    International Nuclear Information System (INIS)

    Nishimoto, Norimasa; Sowa, Etsuji; Fujii, Satoru; Seki, Junichi; Wada, Masahisa

    1975-01-01

    Pancreatic scintiphotography was performed in 108 cases of patients with diabetes mellitus. Scintiphotos were taken at 30 min. after intravenous injection of approximately 200μCi of 75 Se-selenomethionine using a Toshiba gamma camera. The relationship between the degree of pancreatic uptake of 75 Se-selenomethionine and the types and duration of diabetes, vascular complications and the average range of fasting blood sugar levels were studied. In some cases, pancreatic scintiphotos were taken at 10, 30 and 50 min. after injection of 75 Se-selenomethionine, and the degrees of the pancreatic uptake were compared on each time course. Only two out of 24 cases of insulin-dependent diabetics showed normal pancreatic scintiphotos. On the other hand, two out of 47 cases of mild diabetics treated with diet alone showed no uptake in pancreatic scintiphotos. There was a tendency toward abnormal pancreatic scintiphotos in chronic diabetics. Especially, of the 15 cases who had diabetes for more than eleven years, only one case showed a normal pancreatic scintiphoto. Abnormal pancreatic scintiphotos were found more frequently in the group of poorly controlled diabetics than in the group of well controlled diabetics. In cases showing normal pancreatic scintiphotos, diabetic retinopathy was less frequently found. Out of 36 cases which had sequential pancreatic scintiphotos, hypertension and/or arteriosclerosis were found more frequently in the 20 cases which showed a delay in reaching a plateau of the activity. However, the uptake in sequential pancreatic scintiphotos showed no definite correlation between diabetic retinopathy and other diabetic conditions. (auth.)

  16. Pancreatic scintiphotography in diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Nishimoto, N; Sowa, E; Fujii, S; Seki, J; Wada, M [Osaka City Univ. (Japan). Faculty of Medicine

    1975-09-01

    Pancreatic scintiphotography was performed in 108 cases of patients with diabetes mellitus. Scintiphotos were taken at 30 min. after intravenous injection of approximately 200..mu..Ci of /sup 75/Se-selenomethionine using a Toshiba gamma camera. The relationship between the degree of pancreatic uptake of /sup 75/Se-selenomethionine and the types and duration of diabetes, vascular complications and the average range of fasting blood sugar levels were studied. In some cases, pancreatic scintiphotos were taken at 10, 30 and 50 min. after injection of /sup 75/Se-selenomethionine, and the degrees of the pancreatic uptake were compared on each time course. Only two out of 24 cases of insulin-dependent diabetics showed normal pancreatic scintiphotos. On the other hand, two out of 47 cases of mild diabetics treated with diet alone showed no uptake in pancreatic scintiphotos. There was a tendency toward abnormal pancreatic scintiphotos in chronic diabetics. Especially, of the 15 cases who had diabetes for more than eleven years, only one case showed a normal pancreatic scintiphoto. Abnormal pancreatic scintiphotos were found more frequently in the group of poorly controlled diabetics than in the group of well controlled diabetics. In cases showing normal pancreatic scintiphotos, diabetic retinopathy was less frequently found. Out of 36 cases which had sequential pancreatic scintiphotos, hypertension and/or arterioscl-erosis were found more frequently in the 20 cases which showed a delay in reaching a plateau of the activity. However, the uptake in sequential pancreatic scintiphotos showed no definite correlation between diabetic retinopathy and other diabetic conditions.

  17. Management of advanced pancreatic cancer in daily clinical practice.

    Science.gov (United States)

    Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

    2016-01-01

    The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

  18. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

    OpenAIRE

    S. CHAHAL, MANPREET; TERESA KU, H.; ZHANG, ZHIHONG; M. LEGASPI, CHRISTIAN; LUO, ANGELA; M. HOPKINS, MANDI; E. MEIER, KATHRYN

    2016-01-01

    Background: Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Materials and Methods: Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Results: Many differences were observed between non-metastatic and meta...

  19. Metastatic hidradenocarcinoma: Surgery and chemotherapy.

    Science.gov (United States)

    Amel, Trabelsi; Olfa, Gharbi; Faten, Hammedi; Makrem, Hochlef; Slim, Ben Ahmed; Moncef, Mokni

    2009-12-01

    Hidradenocarcinoma is a rare carcinoma of high malignant potential. It most metastasizes to regional lymph nodes and distant viscera. We report a case of 52-year-old woman who presented with an invasive hidradenocarcinoma of the finger, treated with surgical excision. The patient presented with skin and lymph node metastases four years after, treated by chemotherapy. Hidradenocarcinoma is an aggressive tumor. It seems important to use adjuvant therapies particularly for recurrent and metastatic forms.

  20. Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

    OpenAIRE

    Elie Aoun; Adam Slivka; Dionysios J Papachristou; David C Whitcomb; Ferga C Gleeson; Georgios I Papachristou

    2007-01-01

    Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

  1. Food-Induced Acute Pancreatitis.

    Science.gov (United States)

    Manohar, Murli; Verma, Alok K; Upparahalli Venkateshaiah, Sathisha; Goyal, Hemant; Mishra, Anil

    2017-12-01

    Food allergy, a commonly increasing problem worldwide, defined as an adverse immune response to food. A variety of immune-related effector cells such as mast cells, eosinophils, neutrophils, and T cells are involved in food-related allergic responses categorized as IgE mediated, non-IgE mediated, and mixed (IgE and non-IgE) depending upon underlying immunological mechanisms. The dietary antigens mainly target the gastrointestinal tract including pancreas that gets inflamed due to food allergy and leads acute pancreatitis. Reports indicate several food proteins induce pancreatitis; however, detailed underlying mechanism of food-induced pancreatitis is unexplored. The aim of the review is to understand and update the current scenario of food-induced pancreatitis. A comprehensive literature search of relevant research articles has been performed through PubMed, and articles were chosen based on their relevance to food allergen-mediated pancreatitis. Several cases in the literature indicate that acute pancreatitis has been provoked after the consumption of mustard, milk, egg, banana, fish, and kiwi fruits. Food-induced pancreatitis is an ignored and unexplored area of research. The review highlights the significance of food in the development of pancreatitis and draws the attention of physicians and scientists to consider food allergies as a possible cause for initiation of pancreatitis pathogenesis.

  2. Conservative treatment of chronic pancreatitis.

    Science.gov (United States)

    Löhr, J-Matthias; Haas, Stephen L; Lindgren, Fredrik; Enochsson, Lars; Hedström, Aleksandra; Swahn, Fredrik; Segersvärd, Ralf; Arnelo, Urban

    2013-01-01

    Chronic pancreatitis is a progressive inflammatory disease giving rise to several complications that need to be treated accordingly. Because pancreatic surgery has significant morbidity and mortality, less invasive therapy seems to be an attractive option. This paper reviews current state-of-the-art strategies to treat chronic pancreatitis without surgery and the current guidelines for the medical therapy of chronic pancreatitis. Endoscopic therapy of complications of chronic pancreatitis such as pain, main pancreatic duct strictures and stones as well as pseudocysts is technically feasible and safe. The long-term outcome, however, is inferior to definitive surgical procedures such as resection or drainage. On the other hand, the medical therapy of pancreatic endocrine and exocrine insufficiency is well established and evidence based. Endoscopic therapy may be an option to bridge for surgery and in children/young adolescents and those unfit for surgery. Pain in chronic pancreatitis as well as treatment of pancreatic exocrine insufficiency follows established guidelines. Copyright © 2013 S. Karger AG, Basel.

  3. [Acute pancreatitis associated with hypercalcaemia].

    Science.gov (United States)

    Tun-Abraham, Mauro Enrique; Obregón-Guerrero, Gabriela; Romero-Espinoza, Larry; Valencia-Jiménez, Javier

    2015-01-01

    Hypercalcaemia due to primary hyperparathyroidism is a rare cause of acute pancreatitis, with a reported prevalence of 1.5 to 8%. There is no clear pathophysiological basis, but elevated parathyroid hormone and high serum calcium levels could be responsible for calcium deposit in the pancreatic ducts and activation of pancreatic enzymes, which may be the main risk factor for developing acute pancreatitis. The aim of this report is to describe four cases. Four cases are reported of severe pancreatitis associated with hypercalcaemia secondary to primary hyperparathyroidism; three of them with complications (two pseudocysts and one pancreatic necrosis). Cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, studies showed the parathyroid adenoma. Surgical resection was the definitive treatment in all four cases. None of the patients had recurrent acute pancreatitis events during follow-up. Acute pancreatitis secondary to hypercalcaemia of primary hyperparathyroidism is rare; however, when it occurs it is associated with severe pancreatitis. It is suspected in patients with elevated serum calcium and high parathyroid hormone levels. Imaging techniques such as cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, should be performed, to confirm clinical suspicion. Surgical resection is the definitive treatment with excellent results. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  4. Pancreatic adenocarcinoma and diabetes mellitus

    International Nuclear Information System (INIS)

    Novotna, T.

    2015-01-01

    Impaired glucose tolerance or frank diabetes mellitus is known to occur more frequently in patients with pancreatic cancer than in the general population. At the time of the diagnosis of pancreatic cancer, more than 70% of patients taking the glucose tolerance test show diabetes or impaired glucose tolerance (1). Relationship among diabetes mellitus and pancreatic cancer is vague but sure, although neither the nature nor the sequence of the possible cause – effect relationship has been established. The reason for the high frequency of glucose intolerance in patients with pancreatic cancer remains controversial. (author)

  5. Systemic therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Andrezalova Vochyanova, I.; Salek, T.

    2012-01-01

    Pancreatic cancer is the fourth comment cause of cancer-related death in men. Most patients with pancreatic cancer are diagnosed at advanced, non-resectable stage. Late detection, early metastases, difficult surgical approached, cancer resistant to systemic chemo and radiotherapy - all contribute to its in faust prognosis. Only about 5 % of patients will live 5 years after diagnosis. Gemcitabine - based combination treatments is the standard for advanced pancreatic cancer. The combination of fluorouracil, folinic acid, irinotecan and oxaliplatin led to median survival of 11 months. No standard second-line treatment exists for pancreatic cancer. (author)

  6. Diagnosis of pancreatic disease

    International Nuclear Information System (INIS)

    Bautz, W.; Skalej, M.; Kalender, W.

    1990-01-01

    This paper reports on CT scanners with continuously rotating measurement systems enable volume scanning of a body section when used with continuous patient transport (spiral CT). Because of its relatively small volume, the complete pancreas can be scanned in a single breathhold. For pancreatic examinations, 1 continuous, 1- second scans with a table feed of 10 mm/sec were obtained on a Siemens SOMATOM Plus. Contrast material (50 mL) was power injected immediately before the start of measurements. CT images were reconstructed from the volume data set at 2-mm intervals. Fifty-six patients with pancreatitis, carcinoma or metastases of the pancreas; endocrine-active tumors; or Echinococcus were examined with both conventional and spiral CT

  7. Imaging of pancreatic tumors

    International Nuclear Information System (INIS)

    Brambs, Hans-Juergen; Juchems, Markus

    2010-01-01

    Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

  8. Danish Pancreatic Cancer Database

    DEFF Research Database (Denmark)

    Fristrup, Claus; Detlefsen, Sönke; Palnæs Hansen, Carsten

    2016-01-01

    : Death is monitored using data from the Danish Civil Registry. This registry monitors the survival status of the Danish population, and the registration is virtually complete. All data in the database are audited by all participating institutions, with respect to baseline characteristics, key indicators......AIM OF DATABASE: The Danish Pancreatic Cancer Database aims to prospectively register the epidemiology, diagnostic workup, diagnosis, treatment, and outcome of patients with pancreatic cancer in Denmark at an institutional and national level. STUDY POPULATION: Since May 1, 2011, all patients...... with microscopically verified ductal adenocarcinoma of the pancreas have been registered in the database. As of June 30, 2014, the total number of patients registered was 2,217. All data are cross-referenced with the Danish Pathology Registry and the Danish Patient Registry to ensure the completeness of registrations...

  9. Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

    Science.gov (United States)

    Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

    2011-01-01

    Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

  10. Significant prolongation of segmental pancreatic allograft survival in two species

    Energy Technology Data Exchange (ETDEWEB)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-06-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

  11. Significant prolongation of segmental pancreatic allograft survival in two species

    International Nuclear Information System (INIS)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-01-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival

  12. Lethal neonatal short-limbed dwarfism

    International Nuclear Information System (INIS)

    Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee

    1986-01-01

    We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

  13. Lethal neonatal short-limbed dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee [Catholic Medical College, Seoul (Korea, Republic of)

    1986-02-15

    We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

  14. Mining of lethal recessive genetic variation in Danish cattle

    DEFF Research Database (Denmark)

    Das, Ashutosh

    2015-01-01

    in fertility. The primary objective of this PhD projekt was to identify recessive lethal gentic variants in the main Danish dairy cattle breed. Holstein-Friesian utilzing next generation sequencing (NGS) data. This study shows a potential for the use of the NGS-based reverse genetic approach in identifying...... lethal or semi-lethal recessive gentic variation...

  15. Rare incidence of tumor lysis syndrome in metastatic prostate cancer following treatment with docetaxel.

    Science.gov (United States)

    Bhardwaj, Sharonlin; Varma, Seema

    2018-03-01

    Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors. In this report, the authors describe a specific case of tumor lysis syndrome in a patient with metastatic prostate cancer following treatment with docetaxel.

  16. Pancreatic enzyme replacement therapy.

    Science.gov (United States)

    Layer, P; Keller, J; Lankisch, P G

    2001-04-01

    Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

  17. Transplantable pancreatic acinar carcinoma

    International Nuclear Information System (INIS)

    Warren, J.R.; Reddy, J.K.

    1981-01-01

    Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with [3H]-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with [3H]-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed

  18. Lethal midline granuloma syndrome: a diagnostic dilemma

    International Nuclear Information System (INIS)

    Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle; Oliveira, Ana Luiza Vianna Sobral de Magalhaes; Marchon Junior, Joao Luiz

    2012-01-01

    The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

  19. Lethal Interpersonal Violence in the Middle Pleistocene

    OpenAIRE

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-P?rez, Ana; Pablos, Adri?n; Mart?nez, Ignacio; Quam, Rolf M.; G?mez-Olivencia, Asier; Berm?dez de Castro, Jos? Mar?a; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force ...

  20. Lethal midline granuloma syndrome: a diagnostic dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle [Radiology, Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (HUCFF-UFRJ), Rio de Janeiro, RJ (Brazil); Oliveira, Ana Luiza Vianna Sobral de Magalhaes [Resident of Medical Practice, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil); Marchon Junior, Joao Luiz [Unit of Computed Tomography, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil)

    2012-11-15

    The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

  1. Lethal interpersonal violence in the Middle Pleistocene.

    Directory of Open Access Journals (Sweden)

    Nohemi Sala

    Full Text Available Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  2. Lethal interpersonal violence in the Middle Pleistocene.

    Science.gov (United States)

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  3. Sequential changes from minimal pancreatic inflammation to advanced alcoholic pancreatitis.

    Science.gov (United States)

    Noronha, M; Dreiling, D A; Bordalo, O

    1983-11-01

    A correlation of several clinical parameters and pancreatitis morphological alterations observed in chronic alcoholics with and without pancreatic is presented. Three groups of patients were studied: asymptomatic chronic alcoholics (24); non-alcoholic controls (10); and cases with advanced chronic pancreatitis (6). Clinical, biochemical and functional studies were performed. Morphological studies were made on surgical biopsy specimens in light and electron microscopy. The results of this study showed: 1) fat accumulates within pancreatic acinar cells in alcoholics drinking more than 80 g of ethanol per day; 2) ultrastructural changes found in acinar cells of the alcoholics are similar to those described for liver cells; 3) the alterations found in alcoholics without pancreatitis are also observed in those with advanced chronic pancreatitis. An attempt to correlate the sequential changes in the histopathology of alcoholic pancreatic disease with the clinical picture and secretory patterns was made. According to these observations, admitting the ultrastructural similarities between the liver and the pancreas and the recently demonstrated abnormalities of lipid metabolism in pancreatic cells in experimental animal research, the authors postulate a toxic-metabolic mechanism as a likely hypothesis for the pathogenesis of chronic alcoholic inflammation of the pancreas.

  4. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

    Science.gov (United States)

    Gilliland, Taylor M; Villafane-Ferriol, Nicole; Shah, Kevin P; Shah, Rohan M; Tran Cao, Hop S; Massarweh, Nader N; Silberfein, Eric J; Choi, Eugene A; Hsu, Cary; McElhany, Amy L; Barakat, Omar; Fisher, William; Van Buren, George

    2017-03-07

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

  5. Differential diagnosis of focal pancreatitis and pancreatic cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

    1999-01-01

    The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

  6. Computed tomography scans of metastatic hepatic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Kazumasa; Fukuda, Haruyuki; Nemoto, Yutaka [Osaka City Univ. (Japan). Faculty of Medicine

    1984-01-01

    Computed tomography scans of 114 metastatic hepatic tumors were reviewed. Central low density was found in 82 cases (71.9%) and seems to be characteristic to metastatic hepatic tumors. Dynamic CT was performed on 34 cases, and 21 (61.8%) of these had ring enhancement at the arterial phase. Most of metastatic hepatic tumors could be differentiated from hepatocellular carcinoma. However, metastatic hepatic tumors from renal cell carcinoma, renal rhabdomyosarcoma, malignant melanoma and leiomyosarcoma could not be differentiated from hepatocellular carcinoma, even with use of dynamic study.

  7. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  8. General Information about Pancreatic Cancer

    Science.gov (United States)

    ... overweight. Having a personal history of diabetes or chronic pancreatitis . Having a family history of pancreatic cancer or ... have not started treatment. Five types of standard treatment are used: Surgery ... Whipple procedure : A surgical procedure in which the head of the pancreas , ...

  9. [Identifying the severe acute pancreatitis].

    Science.gov (United States)

    Acevedo Tizón, Anais; Targarona Modena, Javier; Málaga Rodríguez, Germán; Barreda Cevasco, Luis

    2011-01-01

    To compare patients with acute necrotizing pancreatitis without any additional complications during their hospital stay (Group A) versus patients with Acute Necrotizing Pancreatitis with additional complications during their hospital stay (Group B). Data obtained from a pre-existing base from hospitalized patients with diagnosis of acute necrotizing pancreatitis in the specialized unit of "Unidad de Pancreatitis Aguda Grave del Hospital Nacional Edgardo Rebagliati Martins" between 2000 and 2010. Data included patients with diagnosis of acute necrotizing pancreatitis, of ages 18 and over. Data from 215 patients with acute necrotizing pancreatitis was included. Patients from Group A represented 32% (68) and from Group B 68% (147). Group A had a average of 39 hospitalized days and Group B had an average of 56 days (p=0.01). From Group A 22% had more than 50% of necrosis while 43% of Group B had this extension of necrosis (p pancreatitis, based on the presence of necrosis, behave likewise. It is an extended necrosis, described as more than 50% of pancreatic necrosis, and not the presence itself which will determine additional complications during the course of disease and a greater mortality.

  10. Surgical Management of Chronic Pancreatitis.

    Science.gov (United States)

    Parekh, Dilip; Natarajan, Sathima

    2015-10-01

    Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

  11. Acute necrotizing pancreatitis in rats

    NARCIS (Netherlands)

    B. van Ooijen (Baan)

    1988-01-01

    textabstractThe specific aim of the present study was to investigate whether eicosanoids play a role in acute necrotizing pancreatitis. Because of the limited number of patients with acute pancreatitis admitted to the hospital each year, as well as the practical difficulties encountered in

  12. Splanchnic venous thrombosis and pancreatitis.

    Science.gov (United States)

    Nadkarni, Nikhil A; Khanna, Sahil; Vege, Santhi Swaroop

    2013-08-01

    Pancreatitis is an inflammatory process with local and systemic manifestations. One such local manifestation is thrombosis in splanchnic venous circulation, predominantly of the splenic vein. The literature on this important complication is very sparse. This review offers an overview of mechanism of thrombosis, its pathophysiology, diagnosis, and management in the setting of acute as well as chronic pancreatitis.

  13. Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

    Science.gov (United States)

    2018-04-27

    Extrahepatic Bile Duct Adenocarcinoma, Biliary Type; Gallbladder Adenocarcinoma, Biliary Type; Metastatic Pancreatic Adenocarcinoma; Recurrent Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Gallbladder Cancer AJCC V7; Stage III Hepatocellular Carcinoma AJCC v7; Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Carcinoma

  14. Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives.

    Science.gov (United States)

    Hosseini, Mina; Hassanian, Seyed Mahdi; Mohammadzadeh, Elham; ShahidSales, Soodabeh; Maftouh, Mina; Fayazbakhsh, Hasan; Khazaei, Majid; Avan, Amir

    2017-07-01

    Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted. The antitumor activity of curcumin in several tumors, including prostate, breast and colorectal cancers have investigated. A recent phase II trial explored the effects of curcumin in advanced pancreatic cancer patient. They found that oral curcumin was well tolerated. Another trial showed the activity of 8,000 mg of curcumin in combination with gemcitabine in patients with advanced pancreatic cancer. This review summarizes the current knowledge about possible molecular mechanisms of curcumin in PDAC with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. J. Cell. Biochem. 118: 1634-1638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Aberrant glycogen synthase kinase 3β in the development of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Takeo Shimasaki

    2012-01-01

    Full Text Available Development and progression of pancreatic cancer involves general metabolic disorder, local chronic inflammation, and multistep activation of distinct oncogenic molecular pathways. These pathologic processes result in a highly invasive and metastatic tumor phenotype that is a major obstacle to curative surgical intervention, infusional gemcitabine-based chemotherapy, and radiation therapy. Many clinical trials with chemical compounds and therapeutic antibodies targeting growth factors, angiogenic factors, and matrix metalloproteinases have failed to demonstrate definitive therapeutic benefits to refractory pancreatic cancer patients. Glycogen synthase kinase 3β (GSK3β, a serine/threonine protein kinase, has emerged as a therapeutic target in common chronic and progressive diseases, including cancer. Here we review accumulating evidence for a pathologic role of GSK3β in promoting tumor cell survival, proliferation, invasion, and resistance to chemotherapy and radiation in pancreatic cancer. We also discuss the putative involvement of GSK3β in mediating metabolic disorder, local inflammation, and molecular alteration leading to pancreatic cancer development. Taken together, we highlight potential therapeutic as well as preventive effects of GSK3β inhibition in pancreatic cancer.

  16. Cancer Stem Cells, EMT, and Developmental Pathway Activation in Pancreatic Tumors

    International Nuclear Information System (INIS)

    Hindriksen, Sanne; Bijlsma, Maarten F.

    2012-01-01

    Pancreatic cancer is a disease with remarkably poor patient survival rates. The frequent presence of metastases and profound chemoresistance pose a severe problem for the treatment of these tumors. Moreover, cross-talk between the tumor and the local micro-environment contributes to tumorigenicity, metastasis and chemoresistance. Compared to bulk tumor cells, cancer stem cells (CSC) have reduced sensitivity to chemotherapy. CSC are tumor cells with stem-like features that possess the ability to self-renew, but can also give rise to more differentiated progeny. CSC can be identified based on increased in vitro spheroid- or colony formation, enhanced in vivo tumor initiating potential, or expression of cell surface markers. Since CSC are thought to be required for the maintenance of a tumor cell population, these cells could possibly serve as a therapeutic target. There appears to be a causal relationship between CSC and epithelial-to-mesenchymal transition (EMT) in pancreatic tumors. The occurrence of EMT in pancreatic cancer cells is often accompanied by re-activation of developmental pathways, such as the Hedgehog, WNT, NOTCH, and Nodal/Activin pathways. Therapeutics based on CSC markers, EMT, developmental pathways, or tumor micro-environment could potentially be used to target pancreatic CSC. This may lead to a reduction of tumor growth, metastatic events, and chemoresistance in pancreatic cancer

  17. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

    Science.gov (United States)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C; Bakker, Olaf J; van Goor, Harry; Nieuwenhuijs, Vincent B; Bollen, Thomas L; van Ramshorst, Bert; Witteman, Ben J; Brink, Menno A; Schaapherder, Alexander F; Dejong, Cornelis H; Spanier, B W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H; Besselink, Marc G; Gooszen, Hein G; van Santvoort, Hjalmar C; Boermeester, Marja A

    2016-05-01

    Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch hospitals from December 2003 through March 2007. We collected information on disease course, outpatient visits, and hospital readmissions, as well as results from imaging, laboratory, and histology studies. Standardized follow-up questionnaires were sent to all available patients to collect information on hospitalizations and interventions for pancreatic disease, abdominal pain, steatorrhea, diabetes mellitus, medications, and alcohol and tobacco use. Patients were followed up for a median time period of 57 months. Primary end points were recurrent pancreatitis and CP. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis. Recurrent pancreatitis developed in 117 patients (17%), and CP occurred in 51 patients (7.6%). Recurrent pancreatitis developed in 12% of patients with biliary disease, 24% of patients with alcoholic etiology, and 25% of patients with disease of idiopathic or other etiologies; CP occurred in 3%, 16%, and 10% of these patients, respectively. Etiology, smoking, and necrotizing pancreatitis were independent risk factors for recurrent pancreatitis and CP. Acute Physiology and Chronic Health Evaluation II scores at admission also were associated independently with recurrent pancreatitis. The cumulative risk for recurrent pancreatitis over 5 years was highest among smokers at 40% (compared with 13% for nonsmokers). For alcohol abusers and current smokers, the cumulative risks for CP were similar-approximately 18%. In contrast, the cumulative risk of CP increased to 30% in patients who smoked and abused alcohol. Based on a retrospective analysis of patients admitted to Dutch hospitals, a first

  18. Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer

    Directory of Open Access Journals (Sweden)

    Riihimäki Matias

    2013-01-01

    Full Text Available Abstract Background Cancer of unknown primary site (CUP is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. Methods 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. Results Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66–0.72]. The exceptions were cancer of the pancreas (1.71 [1.54–1.90], liver (1.58 [1.36–1.85], and stomach (1.16 [1.02–1.31]. For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06–1.46]. The median survival time of CUP patients was three months. Conclusions Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the

  19. Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry

    Directory of Open Access Journals (Sweden)

    Dilip K Das

    2011-01-01

    Full Text Available Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.

  20. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases...

  1. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion...

  2. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic

  3. Acute Pancreatitis: Etiology, Pathology, Diagnosis, and Treatment.

    Science.gov (United States)

    Majidi, Shirin; Golembioski, Adam; Wilson, Stephen L; Thompson, Errington C

    2017-11-01

    Acute pancreatitis is a fascinating disease. In the United States, the two most common etiologies of acute pancreatitis are gallstones and excessive alcohol consumption. The diagnosis of acute pancreatitis is made with a combination of history, physical examination, computed tomography scan, and laboratory evaluation. Differentiating patients who will have a benign course of their pancreatitis from patients who will have severe pancreatitis is challenging to the clinician. C-reactive protein, pro-calcitonin, and the Bedside Index for Severity of Acute Pancreatitis appeared to be the best tools for the early and accurate diagnosis of severe pancreatitis. Early laparoscopic cholecystectomy is indicated for patients with mild gallstone pancreatitis. For patients who are going to have a prolonged hospitalization, enteral nutrition is preferred. Total parenteral nutrition should be reserved for patients who cannot tolerate enteral nutrition. Prophylactic antibiotics are not indicated for patients with pancreatic necrosis. Surgical intervention for infected pancreatic necrosis should be delayed as long as possible to improve patient outcomes.

  4. Management of acute pancreatitis in children.

    Science.gov (United States)

    Abu-El-Haija, Maisam; Lin, Tom K; Nathan, Jaimie D

    2017-10-01

    Pediatric acute pancreatitis has been on the rise in the last decades, with an incidence close to adult pancreatitis. In the majority of cases acute pancreatitis resolves spontaneously, but in a subset of children the disease progresses to severe acute pancreatitis with attendant morbidity and mortality. Pediatric acute pancreatitis in this era is recognized as a separate entity from adult acute pancreatitis given that the causes and disease outcomes are different. There are slow but important advances made in understanding the best management for acute pancreatitis in children from medical, interventional, and surgical aspects. Supportive care with fluids, pain medications, and nutrition remain the mainstay for acute pancreatitis management. For complicated or severe pancreatitis, specialized interventions may be required with endoscopic or drainage procedures. Surgery has an important but limited role in pediatric acute pancreatitis.

  5. Chronic pancreatitis. Some important historical aspects.

    Science.gov (United States)

    Navarro, Salvador

    2018-06-08

    Since ancient times the increase of size and hardness sometimes presented by the abdominal structure known as the pancreas has attracted attention. Portal was the first to describe the clinical signs of chronic pancreatitis in 1803. In 1815, Fleischman speculated about the potential role of excessive alcohol consumption. Comfort coined the term "chronic relapsing pancreatitis" in 1946 and described hereditary pancreatitis 6 years later. Zuidema defined tropical pancreatitis in 1959 and 2 years later Sarles described another form of pancreatitis to which Yoshida gave the name autoimmune pancreatitis in 1995. Groove pancreatitis was described by Potet in 1970. Obstructive pancreatitis was defined in 1984 and Ammann identified idiopathic pancreatitis 3 years later. This article gives a historical account of the pioneers who developed the knowledge of how to assess the characteristics that allowed the different forms of chronic pancreatitis to be defined. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  6. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.; Bakker, Olaf J.; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.; Boermeester, Marja A.

    2016-01-01

    Background & Aims: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. Methods: We performed a cross-sectional study of 669 patients with a first episode of acute

  7. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ali, U.A.; Issa, Y.; Hagenaars, J.C.; Bakker, O.J.; Goor, H. van; Nieuwenhuijs, V.B.; Bollen, T.L.; Ramshorst, B. van; Witteman, B.J.; Brink, M.A.; Schaapherder, A.F.; Dejong, C.H.; Spanier, B.W.; Heisterkamp, J.; Harst, E. van der; Eijck, C.H. van; Besselink, M.G.; Gooszen, H.G.; Santvoort, H.C. van; Boermeester, M.A.

    2016-01-01

    BACKGROUND & AIMS: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. METHODS: We performed a cross-sectional study of 669 patients with a first episode of acute

  8. Galectin-4 Reduces Migration and Metastasis Formation of Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ana I Belo

    Full Text Available Galectin-4 (Gal-4 is a member of the galectin family of glycan binding proteins that shows a significantly higher expression in cystic tumors of the human pancreas and in pancreatic adenocarcinomas compared to normal pancreas. However, the putative function of Gal-4 in tumor progression of pancreatic cancer is still incompletely understood. In this study the role of Gal-4 in cancer progression was investigated, using a set of defined pancreatic cancer cell lines, Pa-Tu-8988S (PaTu-S and Pa-Tu-8988T (PaTu-T, as a model. These two cell lines are derived from the same liver metastasis of a human primary pancreatic adenocarcinoma, but differ in their growth characteristics and metastatic capacity. We demonstrated that Gal-4 expression is high in PaTu-S, which shows poor migratory properties, whereas much lower Gal-4 levels are observed in the highly metastatic cell line PaTu-T. In PaTu-S, Gal-4 is found in the cytoplasm, but it is also secreted and accumulates at the membrane at sites of contact with neighboring cells. Moreover, we show that Gal-4 inhibits metastasis formation by delaying migration of pancreatic cancer cells in vitro using a scratch assay, and in vivo using zebrafish (Danio rerio as an experimental model. Our data suggest that Gal-4 may act at the cell-surface of PaTu-S as an adhesion molecule to prevent release of the tumor cells, but has in addition a cytosolic function by inhibiting migration via a yet unknown mechanism.

  9. Evaluation of pancreatic scintigram in the diagnosis of pancreatic diseases

    International Nuclear Information System (INIS)

    Takai, Yukihiro; Ueda, Noriyuki; Takasago, Noritsugu; Minemoto, Hiromasa; Namiki, Masayoshi

    1981-01-01

    The classification of accumulative patterns with the pancreatic scintigram findings of chronic pancreatitis and carcinoma of the pancreas were compared with endoscopic retrograde pancreatography (ERP) findings and Pancreozymin-Secretin test (P-S test). I) The frequency of pancreatic cancer was 93%, whilst, the chronic pancreatitis was 88% in the abnormal pancreatic scintigram. II) In the scintigram the type II (localyzed defect shadows) of pancreatic cancer was comparatively high and it is proportional to evidence. derived from ERP. Localized diagnostic certainty is helpful, although the two tests are related. The P-S test is only restricted to the carcinoma of head, whilst, scintigram is more useful to detect the carcinoma of the body and tail of the pancreas. III) As for the chronic pancreatitis, there are various accumulative patterns. This is resemblance to that of ERP findings, but in the P-S normal test, it showed discrepancy in part of the result. Particularly, in the type I (slightly generalized low uptake with density silhouette) and type II. Therefore in order to obtain an accurate diagnosis, it is essential to have both the P-S test and scintigram. (author)

  10. Pancreatic islet transplantation

    Directory of Open Access Journals (Sweden)

    Corrêa-Giannella Maria

    2009-09-01

    Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

  11. Metronidazole-induced pancreatitis.

    LENUS (Irish Health Repository)

    O'Halloran, E

    2010-01-01

    A 25-year-old caucasian lady presented to the Accident & Emergency department complaining of acute onset severe epigastric pain radiating through to the back with associated nausea and vomiting. A diagnosis of acute pancreatitis was made. Symptoms commenced after the third dose of Metronidazole therapy prescribed for a recurrent periodontal abscess. The patient described a similar episode 10 months previously. On neither occasion were any other medications being taken, there was no history of alcohol abuse and no other gastro-intestinal aetiology could be identified on imaging. Symptoms resolved quickly upon discontinuation of the antibiotic agent. We conclude therefore that Metronidazole can reasonably be identified as the only potential causative agent.

  12. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  13. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  14. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  15. REPORT OF SEVEN CASES OF METASTATIC TUMOURS

    African Journals Online (AJOL)

    Major Adebayo

    Metastatic lesions may mimic odontogenic infections and other disease conditions in the oral cavity in presentation leading to late diagnosis by the unwary clinician. In Nigeria, reports on jaw tumours from metastasis elsewhere are quite scarce. This report presents a series of histologically verified metastatic tumours to the ...

  16. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, R.L.; Braasch, J.W.; O' Bryan, E.M.; Watkins, E. Jr.

    1983-03-01

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.

  17. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  18. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  19. Comparison of regional pancreatic tissue fluid pressure and endoscopic retrograde pancreatographic morphology in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation. The predrain......The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation...

  20. Redox signaling in acute pancreatitis

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-01-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

  1. Redox signaling in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Salvador Pérez

    2015-08-01

    Full Text Available Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  2. Molecular biology of pancreatic cancer.

    Science.gov (United States)

    Zavoral, Miroslav; Minarikova, Petra; Zavada, Filip; Salek, Cyril; Minarik, Marek

    2011-06-28

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  3. Pharmacological challenges in chronic pancreatitis.

    Science.gov (United States)

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-11-14

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids are often prescribed as pain treatment. Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time. Furthermore, the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug. As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis. The factors may not have clinical relevance, but may explain inter-individual variations in responses to a given drug, in patients with chronic pancreatitis.

  4. Investigation of treatment strategy for advanced cancer according to treatment of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    XU Kecheng

    2013-10-01

    Full Text Available The majority of pancreatic cancer diagnoses are made at the advanced stage and when metastasis has already occurred, and the 1- and 5-year survival rates are extremely low. Cemcitabine remains the most frequently applied treatment option, yet the most effective chemotherapeutic agents and combinations with multiple agents and/or radiotherapy only marginally improve patient survival and may even establish an environment conducive to cancer cells with stem cell-like characteristics. An alternative treatment modality, cryoablation, is available and has been applied at our institute to patients with unresectable pancreatic cancer since 2001. In this article, we present our collective experience with patient outcome using cryoablation, alone or combined with other treatment modalities such as brachytherapy (125iodine seed implantation. The overall outcomes have been encouraging, suggesting that comprehensive therapy including cryoablation may prolong the survival of patients with advanced or metastatic pancreatic cancer, and we are achieving particular success with a novel combination of percutaneous cryoablation, cancer microvascular intervention with 125iodine seed implantation, and combined immunotherapy (3C applied using an individualized patient strategy (P. The 1- through 10-year survival rates of 145 patients treated with the so-called “3C+P model” are presented in support of this new strategy as a promising new treatment for advanced and metastatic cancer

  5. Obstructive jaundice secondary to pancreatic head adenocarcinoma in a young teenage boy: a case report

    Directory of Open Access Journals (Sweden)

    Khattab Mohammed

    2011-09-01

    Full Text Available Abstract Introduction Pancreatic adenocarcinoma is extremely rare in childhood. We report a case of metastatic pancreatic adenocarcinoma in a 13-year-old boy, revealed by jaundice. Case presentation A 13-year-old Moroccan boy was admitted with obstructive jaundice to the children's Hospital of Rabat, Department of Pediatric Oncology. Laboratory study results showed a high level of total and conjugated bilirubin. Computerized tomography of the abdomen showed a dilatation of the intra-hepatic and extra-hepatic bile ducts with a tissular heterogeneous tumor of the head of the pancreas and five hepatic lesions. Biopsy of a liver lesion was performed, and a histopathological examination of the sample confirmed the diagnosis of metastatic ductal adenocarcinoma of the pancreas. Our patient underwent a palliative biliary derivation. After that, chemotherapy was administered (5-fluorouracil and epirubicin, however no significant response to treatment was noted and our patient died six months after diagnosis. Conclusion Malignant pancreatic tumors, especially ductal carcinomas, are exceedingly rare in the pediatric age group and their clinical features and treatment usually go unappreciated by most pediatric oncologists and surgeons.

  6. Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma

    Science.gov (United States)

    Rohloff, J; Zinke, J; Schoppmeyer, K; Tannapfel, A; Witzigmann, H; Mössner, J; Wittekind, C; Caca, K

    2002-01-01

    Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients. British Journal of Cancer (2002) 86, 1270–1275. DOI: 10.1038/sj/bjc/6600232 www.bjcancer.com © 2002 Cancer Research UK PMID:11953884

  7. Pathophysiology of chronic pancreatitis.

    Science.gov (United States)

    Brock, Christina; Nielsen, Lecia Møller; Lelic, Dina; Drewes, Asbjørn Mohr

    2013-11-14

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful.

  8. Pathophysiology of chronic pancreatitis

    Science.gov (United States)

    Brock, Christina; Nielsen, Lecia Møller; Lelic, Dina; Drewes, Asbjørn Mohr

    2013-01-01

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful. PMID:24259953

  9. Solitary main pancreatic ductal calculus of possible biliary origin causing acute pancreatitis.

    Science.gov (United States)

    Chaparala, Ramakrishna Prasad Chowdary; Patel, Rafiuddin; Guthrie, James Ahsley; Davies, Mervyn Huw; Guillou, Pierre J; Menon, Krishna V

    2005-09-10

    Pancreatic ductal calculi are most often associated with chronic pancreatitis. Radiological features of chronic pancreatitis are readily evident in the presence of these calculi. However, acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. A 59-year-old man presented with a first episode of acute pancreatitis. Contrast enhanced computerized tomography (CT) scan and endoscopic retrograde cholangiopancreatography (ERCP) revealed a calculus in the main pancreatic duct in the head of the pancreas causing acute pancreatitis. There were no features suggestive of chronic pancreatitis on CT scanning. The episode acute pancreatitis was managed conservatively. ERCP extraction of the calculus failed as the stone was impacted in the main pancreatic duct resulting in severe acute pancreatitis. Once this resolved, a transduodenal exploration and extraction of the pancreatic ductal calculus was performed successfully. Crystallographic analysis revealed the composition of the calculus was different to that seen in chronic pancreatitis, but more in keeping with a calculus of biliary origin. This could be explained by migration of the biliary calculus via the common channel into the main pancreatic duct. Following the operation the patient made an uneventful recovery and was well at two-year follow up. Acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. Failing endoscopic extraction, transduodenal exploration and extraction is a safe option after resolution of acute pancreatitis.

  10. Pancreatic panniculitis associated with acute pancreatitis and hemorrhagic pseudocysts: A case report

    International Nuclear Information System (INIS)

    Jang, Yong Suk; Kim, Mi Sung; Park, Chan Sub; Park, Ji Yeon; Park, Noh Hyuck

    2012-01-01

    Pancreatic panniculitis is an inflammation and necrosis of fat at distant foci in patients with pancreatic disorders, most frequently, pancreatitis and pancreatic carcinoma. Clinically, pancreatic panniculitis is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk. The usual sites are the distal parts of the lower extremities. To the best of our knowledge, there have not been many reports for the radiologic findings of pancreatic panniculitis. In this article, we report a case of pancreatic panniculitis, including radiologic findings of CT and ultrasonography. The patient was presented with painful subcutaneous nodules on the trunk, and had underlying acute pancreatitis and hemorrhagic pseudocysts

  11. Pancreatic panniculitis associated with acute pancreatitis and hemorrhagic pseudocysts: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Yong Suk; Kim, Mi Sung; Park, Chan Sub; Park, Ji Yeon; Park, Noh Hyuck [Kwandong Univ., Myongji Hospital, Goyang (Korea, Republic of)

    2012-10-15

    Pancreatic panniculitis is an inflammation and necrosis of fat at distant foci in patients with pancreatic disorders, most frequently, pancreatitis and pancreatic carcinoma. Clinically, pancreatic panniculitis is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk. The usual sites are the distal parts of the lower extremities. To the best of our knowledge, there have not been many reports for the radiologic findings of pancreatic panniculitis. In this article, we report a case of pancreatic panniculitis, including radiologic findings of CT and ultrasonography. The patient was presented with painful subcutaneous nodules on the trunk, and had underlying acute pancreatitis and hemorrhagic pseudocysts.

  12. Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.

    Science.gov (United States)

    Pakkasjärvi, Niklas; Ritvanen, Annukka; Herva, Riitta; Peltonen, Leena; Kestilä, Marjo; Ignatius, Jaakko

    2006-09-01

    Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.

  13. Suicide Intent and Accurate Expectations of Lethality: Predictors of Medical Lethality of Suicide Attempts

    Science.gov (United States)

    Brown, Gregory K.; Henriques, Gregg R.; Sosdjan, Daniella; Beck, Aaron T.

    2004-01-01

    The degree of intent to commit suicide and the severity of self-injury were examined in individuals (N = 180) who had recently attempted suicide. Although a minimal association was found between the degree of suicide intent and the degree of lethality of the attempt, the accuracy of expectations about the likelihood of dying was found to moderate…

  14. Potentially lethal damage and its repair

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1989-01-01

    Two forms termed fast-and slow-potentially lethal lethal damage (PLD) are introduced and discussed. The effect on the survival of x-irradiated Chinese hamster cells (V79) of two different post-treatments is examined in plateau- and in log-phases of growth. The postirradiation treatments used : a) incubation in hypertonic solution, and b) incubation in conditioned medium obtained from plateau-phase. Similar reduction in survival was caused by postirradiation treatment with hypertonic phosphate buffered saline, and similar increased in survival was effected by treatment in conditioned medium in plateau- and in log-phases cells. However, repair of PLD sensitive to hypertonic treatment was faster (half time, 5-10 min)(f-PLD repair) and independent from the repair of PLD (half time, 1-2 hour)(s-PLD repair) observed in conditioned medium. The results indicate the induction of two forms of PLD by radiation. Induction of both PLD was found to decrease with increasing LET of the radiation used. Identification of the molecular processes underlying repair and fixation of PLD is a task of particular interest, since it may allow replacement of a phenomenological definition with a molecular definition. Evidence is reviewed indicating the DNA double strand breaks (directly or indirectly induced) may be the DNA lesions underlying PLD. (author)

  15. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  16. Severe Acute Pancreatitis in Pregnancy

    Directory of Open Access Journals (Sweden)

    Bahiyah Abdullah

    2015-01-01

    Full Text Available This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes.

  17. Necrotizing pancreatitis: challenges and solutions.

    Science.gov (United States)

    Bendersky, Victoria A; Mallipeddi, Mohan K; Perez, Alexander; Pappas, Theodore N

    2016-01-01

    Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications.

  18. Vitamin D and pancreatic cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.

    2008-01-01

    Sun exposure has been associated with lower death rates for pancreatic cancer in ecological studies. Skin exposure to solar ultra-violet B radiation induces cutaneous production of precursors to 25-hydroxy (OH) vitamin D (D) and is considered the primary contributor to vitamin D status in most populations. Pancreatic islet and duct cells express 25-(OH) D3-1α-hydroxylase that generates the biologically active 1,25-dihydroxy(OH)2 D form. Thus, 25(OH)D concentrations could affect pancreatic fun...

  19. Recent Progress in Pancreatic Cancer

    Science.gov (United States)

    Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

    2013-01-01

    Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

  20. Lethal domestic violence in eastern North Carolina.

    Science.gov (United States)

    Gilliland, M G; Spence, P R; Spence, R L

    2000-01-01

    Strategies for preventing domestic violence can be tailored to a particular geographic or socioeconomic area if the patterns of domestic violence in the area are known. National statistics, although widely available, may not be applicable to a specific region. We reviewed homicide deaths in Eastern North Carolina between 1978 and 1999 to identify patterns in this rural area. Approximately 20% of the homicide deaths in eastern North Carolina are caused by intimate partners. Women accounted for 53% of the victims in 1976, similar to national figures but not rising to 72% as seen nationally in 1998. Latinos are an increasing presence in the area, but had only one recorded episode of lethal violence against an intimate partner. Gunshots accounted for most of the deaths (59% in men, 72% in women). Knowledge of such patterns can assist in selecting prevention strategies for this particular area. Over the last 25 years increasing attention has been devoted to domestic violence (DV), initially defined as abuse committed against a spouse, former spouse, fiancée, boy- or girlfriend, or cohabitant. As time has passed, the definition has been broadened to include other family members--elders, children, and siblings. The Centers for Disease Control and Prevention (CDC) now uses the term "intimate partner violence" for intentional emotional or physical abuse inflicted by a spouse, ex-spouse, a present or former boy- or girlfriend, or date. For the purposes of this paper, we consider DV interchangeable with intimate partner violence. There has been a national concern that abusive events are under-reported. The National Crime Victimization Survey, an anonymous household survey, indicated nearly 1 million incidents of non-lethal intimate partner violence per year between 1992 and 1996. The number decreased from 1.1 million in 1993 to 840,000 in 1996. Attempts to validate such data for a given geographic area often require subjects to violate anonymity--this may account for lower

  1. Pancreatic tissue fluid pressure and pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N

    1992-01-01

    A casual relation between pancreatic pressure and pain has been searched for decades but lack of appropriate methods for pressure measurements has hindered progress. During the 1980's the needle method has been used for direct intraoperative pancreatic tissue fluid pressure measurements and later...... for percutaneous sonographically-guided pressure measurements. Clinical and experimental evaluation of the method showed comparable results at intraoperative and percutaneous measurements and little week-to-week variation. Furthermore, comparable pressures in duct and adjacent pancreatic tissue were found, i.......e. the needle pressure mirrors the intraductal pressure. Comparisons of pain registrations, morphological and functional parameters with pancreatic tissue fluid pressure measurements have revealed a relation between pressure and pain which probably is causal. In patients with pain the high pressures previously...

  2. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  3. Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis.

    Science.gov (United States)

    Ueda, Junji; Tanaka, Masao; Ohtsuka, Takao; Tokunaga, Shoji; Shimosegawa, Tooru

    2013-03-01

    Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13-22.73; P = .03). This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis. Copyright © 2013 Mosby, Inc. All rights reserved.

  4. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Taylor M. Gilliland

    2017-03-01

    Full Text Available Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL. The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016 addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC. We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1 patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2 patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3 enteral nutrition (EN should be preferred as a nutritional intervention over total parenteral nutrition (TPN postoperatively; and, (4 a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of

  5. Inhibition of SIRT1 combined with gemcitabine therapy for pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Gong DJ

    2013-07-01

    Full Text Available Dao-Jun Gong,1 Jia-Min Zhang,1 Min Yu,1 Bo Zhuang,1 Qing-Qu Guo21Department of Hepatobiliary-Pancreatic Surgery, Jinhua Hospital of Zhejiang University, Jinhua, People's Republic of China; 2Department of Surgery, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of ChinaBackground: Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods.Methods: Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo.Results: The cleaved poly ADP ribose polymerase (PARP-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05 and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05.Conclusion: Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single

  6. Magnetic resonance imaging of pancreatitis: An update

    Science.gov (United States)

    Manikkavasakar, Sriluxayini; AlObaidy, Mamdoh; Busireddy, Kiran K; Ramalho, Miguel; Nilmini, Viragi; Alagiyawanna, Madhavi; Semelka, Richard C

    2014-01-01

    Magnetic resonance (MR) imaging plays an important role in the diagnosis and staging of acute and chronic pancreatitis and may represent the best imaging technique in the setting of pancreatitis due to its unmatched soft tissue contrast resolution as well as non-ionizing nature and higher safety profile of intravascular contrast media, making it particularly valuable in radiosensitive populations such as pregnant patients, and patients with recurrent pancreatitis requiring multiple follow-up examinations. Additional advantages include the ability to detect early forms of chronic pancreatitis and to better differentiate adenocarcinoma from focal chronic pancreatitis. This review addresses new trends in clinical pancreatic MR imaging emphasizing its role in imaging all types of acute and chronic pancreatitis, pancreatitis complications and other important differential diagnoses that mimic pancreatitis. PMID:25356038

  7. Groove Pancreatitis – A Mimic of Pancreatic and Periampullary Tumors

    Directory of Open Access Journals (Sweden)

    Sivakami R Pradheepkumar

    2017-10-01

    Full Text Available Groove Pancreatitis (GP is a rare form of focal chronic pancreatitis involving the pancreatico-duodenal groove (PDG. GP was first described by Becker in 1973. Though, GP has been described so many years ago, it is still unfamiliar among most physicians because of lack of sufficient case studies and clinical similarity of GP to conventional pancreatitis. Imaging based differentiation of GP from other lesions, like pancreatic and periampullary adenocarcinoma is also not possible in all the cases, unless there are typical findings favoring GP. Since, the line of treatment and outcome is totally different in these two conditions, appreciation of the fine differences between these two entities is very significant. Groove pancreatitis is symptomatically treated with medicines and only for patients with continuous and severe symptoms which are not amenable to medical treatment surgical management is considered. Radiological differentiation of GP from pancreatic and periampullary malignancies will help to avoid unnecessary surgery in the initial stages. We report two cases of GP, one of pure and other of segmental form where we found typical imaging features which pointed to the diagnosis of GP with a small discussion about the Computed tomography (CT and Magnetic Resonance Imaging (MRI appearance of this entity as well as its differential diagnosis.

  8. [Pancreatic anastomosis in operative treatment of chronic pancreatitis].

    Science.gov (United States)

    Bellon, E; Izbicki, J R; Bockhorn, M

    2017-01-01

    Chronic pancreatitis (CP) is an irreversible, inflammatory process, which is characterized by progressive fibrosis of the pancreas and leads to abdominal pain, endocrine and exocrine insufficiency. Surgical therapy is indicated by the absence of pain relief and local complications. The target of the surgical approach is to relieve the pancreatic and bile ducts and resection of the fibrotic and calcified parenchyma. Drainage procedures, such as the Partington-Rochelle method, are used in patients with isolated congestion of the pancreatic duct without further organ complications, such as inflammatory processes of the pancreatic head; however, patients with CP often have an inflammatory swelling of the pancreatic head. In this case classical pancreatoduodenectomy (PD) or organ-sparing duodenum-preserving pancreatic head resection (DPPHR) with its various techniques (e.g. Beger, Frey, Bern and V‑shape) can be applied. Due to similar long-term results PD should be carried out in cases of suspicion or detection of malignancies and DPPHR for treatment of CP.

  9. Pancreatic duct stones in patients with chronic pancreatitis: surgical outcomes.

    Science.gov (United States)

    Liu, Bo-Nan; Zhang, Tai-Ping; Zhao, Yu-Pei; Liao, Quan; Dai, Meng-Hua; Zhan, Han-Xiang

    2010-08-01

    Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.

  10. Pancreatic Cancer Diagnostics and Treatment – Current State

    Directory of Open Access Journals (Sweden)

    Zdeněk Krška

    2015-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60–80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5. In contrast R0 resection shows the survival 18–27 months. Laboratory and imaging screening methods are not indicated on large scale. Risk factors are smoking, alcohol abuse, chronic pancreatitis, diabetes mellitus. Genetic background in most PDAC has not been detected yet. Some genes connected with high risk of PDAC (e.g. BRCA2, PALB2 have been identified as significant and highly penetrative, but link between PDAC and these genes can be seen only in 10–20%. This article surveys perspective oncogenes, tumour suppressor genes, microRNA. Albeit CT is still favoured over other imaging methods, involvement of NMR rises. Surgery prefers the “vessel first” approach, which proves to be justified especially in R0 resection. According to EBM immunotherapy same as radiotherapy are not significant in PDAC treatment. Chemotherapy shows limited importance in conversion treatment of locally advanced or borderline tumours or in case of metastatic spread. Unified procedures cannot be defined due to inhomogenous arrays. Surgical resection is the only chance for curative treatment of PDAC and depends mainly on timely indication for surgery and quality of multidisciplinary team in a high-volume centre.

  11. Autoimmune pancreatitis. An update

    International Nuclear Information System (INIS)

    Helmberger, T.

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also

  12. Pancreatic scintigraphy in diabetes mellitus

    International Nuclear Information System (INIS)

    Shio, Hiroshi; Ueki, Jyuichi; Nomura, Kozi; Nakamura, Yoshifumi

    1983-01-01

    Pancreatic scintigraphy was performed on 67 diabetic patients (42 males and 25 females) in order to study exocrine pancreatic functions in primary diabetes. Relationships between visualization and the onset age, sex, morbid period, presence or absence of retinitis, good or poor control of blood glucose control and the therapeutic modality of diabetes were examined. Abnormality was detected in 34 cases (50.7%), being frequent among male patients in their 50s. The more serious the diabetes, i.e., with a longer morbid period, poorer blood glucose control and worse retinitis, the higher was the frequency of abnormality in pancreatic visualization. The frequency of abnormality was high in association with insulin treatment, oral tablets and single dietary treatment in that order. The more severe the hypoinsulinism, the higher was the frequency of abnormality. This technique can be used as a screening means for exocrine pancreatic function tests on diabetics. (Chiba, N.)

  13. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  14. Valsartan-induced acute pancreatitis.

    Science.gov (United States)

    Can, Burak; Sali, Mursel; Batman, Adnan; Yilmaz, Hasan; Korkmaz, Ugur; Celebi, Altay; Senturk, Omer; Hulagu, Sadettin

    2014-01-01

    Gastrointestinal toxicity is uncommon among patients treated with angiotensin II receptor antagonists. A 58-year-old man presented with nausea, vomiting and constant pain in the epigastrium that radiated to the flanks. He received treatment with valsartan (160 mg daily) for hypertension. The clinical, biochemical and radiological findings were compatible with a diagnosis of acute pancreatitis. After the patient achieved a clinical and biochemical recovery, the valsartan therapy was started again. Six weeks later, he returned to the hospital with an attack of pancreatitis. Subsequently, he returned with repeated attacks of pancreatitis twice, and the valsartan was discontinued. Ten months after the treatment, the patient had no complaints. When severe abdominal symptoms occur for no apparent reason during treatment with valsartan, a diagnosis of pancreatitis should be considered.

  15. Clinical pancreatic islet transplantation.

    Science.gov (United States)

    Shapiro, A M James; Pokrywczynska, Marta; Ricordi, Camillo

    2017-05-01

    Clinical pancreatic islet transplantation can be considered one of the safest and least invasive transplant procedures. Remarkable progress has occurred in both the technical aspects of islet cell processing and the outcomes of clinical islet transplantation. With >1,500 patients treated since 2000, this therapeutic strategy has moved from a curiosity to a realistic treatment option for selected patients with type 1 diabetes mellitus (that is, those with hypoglycaemia unawareness, severe hypoglycaemic episodes and glycaemic lability). This Review outlines the techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation, and discusses indications, optimization of recipient immunosuppression and management of adjunctive immunomodulatory and anti-inflammatory strategies. The potential risks, long-term outcomes and advances in treatment after the transplant are also discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.

  16. Computed tomography of lethal medline granuloma

    International Nuclear Information System (INIS)

    Lee, Ho Suk; Kim, Tae Ho; Suh, Kyung Jin; Kim, Tae Hun; Kim, Yong Joo; Kang, Duk Sik

    1991-01-01

    In order to clarify the CT findings of lethal midline granuloma (LMG) diagnosed clinically or histopathologically, the authors retrospectively analyzed 12 patients who were seen at Kyungpook National University Hospital from February 1985 to August 1989. CT showed nasal mucosal thickening and / or soft tissue mass (9 case), spreading of the lesions along the facial subcutaneous fat plane (8 cases), invasion into the paranasal sinuses (5 cases), bone destruction (5 cases), nasopharyngeal mass lesion (2 cases), and extension of the lesion into the infratemporal fossa (1 case). In spite of the fact that CT does not make definitive diagnosis of LMG, it permits evaluation of the extent of the lesion, detection of the combined lesion, differential diagnosis, and close monitoring of its evolution under treatment

  17. Gluconeogenesis in lethally X-irradiated rats

    International Nuclear Information System (INIS)

    Paulikova, E.; Ahlers, I.; Praslicka, M.

    1983-01-01

    The in vivo incorporation of U- 14 C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of 14 C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis. (author)

  18. Gluconeogenesis in lethally X-irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Paulikova, E.; Ahlers, I.; Praslicka, M. (Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie)

    1983-02-01

    The in vivo incorporation of U-/sup 14/C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of /sup 14/C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis.

  19. Ants defend aphids against lethal disease

    Science.gov (United States)

    Nielsen, Charlotte; Agrawal, Anurag A.; Hajek, Ann E.

    2010-01-01

    Social insects defend their own colonies and some species also protect their mutualist partners. In mutualisms with aphids, ants typically feed on honeydew produced by aphids and, in turn guard and shelter aphid colonies from insect natural enemies. Here we report that Formica podzolica ants tending milkweed aphids, Aphis asclepiadis, protect aphid colonies from lethal fungal infections caused by an obligate aphid pathogen, Pandora neoaphidis. In field experiments, bodies of fungal-killed aphids were quickly removed from ant-tended aphid colonies. Ant workers were also able to detect infective conidia on the cuticle of living aphids and responded by either removing or grooming these aphids. Our results extend the long-standing view of ants as mutualists and protectors of aphids by demonstrating focused sanitizing and quarantining behaviour that may lead to reduced disease transmission in aphid colonies. PMID:19923138

  20. Lethal photosensitization of biofilm-grown bacteria

    Science.gov (United States)

    Wilson, Michael

    1997-12-01

    Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

  1. Acute Pancreatitis and Ileus Postcolonoscopy

    Directory of Open Access Journals (Sweden)

    Hin Hin Ko

    2009-01-01

    Full Text Available Postpolypectomy bleeding and perforation are the most common complications of colonoscopy. A case of acute pancreatitis and ileus after colonoscopy is described. A 60-year-old woman underwent a gastroscopy and colonoscopy for investigation of iron deficiency anemia. Gastroscopy was normal; however, the colonoscope could not be advanced beyond the splenic flexure due to a tight angulation. Two polypectomies were performed in the descending colon. After the procedure, the patient developed a distended, tender abdomen. Bloodwork was remarkable for an elevated amylase level. An abdominal x-ray and computed tomography scan showed pancreatitis (particularly of the tail, a dilated cecum and a few air-fluid levels. The patient improved within 24 h of a repeat colonoscopy and decompression tube placement. The patient had no risk factors for pancreatitis. The causal mechanism of pancreatitis was uncertain but likely involved trauma to the tail of the pancreas during the procedure. Our patient developed ileus, likely secondary to pancreatitis. The present case is the first report of clinical pancreatitis and ileus associated with colonoscopy.

  2. Pancreatic Stones: Treat or Ignore?

    Directory of Open Access Journals (Sweden)

    DA Howell

    1999-01-01

    Full Text Available Painful, chronic pancreatitis is of complex etiology, but increasing clinical experience suggests that removal of pancreatic duct stones in many cases significantly improves patients’ symptoms. The development and refinement of therapeutic endoscopic retrograde choledochopancreatography have permitted improved access to the pancreatic duct, which makes the development of new techniques of stone fragmentation and fragment removal a much more successful nonsurgical intervention. A major step forward has been the understanding of the safety and efficacy of pancreatic sphincterotomy, which is necessary for the removal of these difficult stones. The recognition that extracorporeal shock wave lithotripsy can be delivered safely with good efficacy has revolutionized the nonsurgical management of pancreatic duct stones. Nevertheless, advanced and sophisticated therapeutic endoscopy is necessary to achieve clearance of the duct, which can generally be accomplished in the majority of selected patients. State-of-the-art treatments are described, and some new approaches using pancreatoscopy and electrohydrolic lithotripsy are discussed. Newly recognized long term complications are reviewed. Finally, it must be recognized that chronic pancreatitis is an ongoing disease that does not have a simple treatment or cure, and frequently represents a process of remissions and relapses requiring interventions and problem solving.

  3. Radiologic evaluation of pancreatic pseudocyst

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, T. H.; Kim, Y. J.; Hong, I. S.; Kim, M. S.; Sung, K. J. [Yeonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    1986-12-15

    Pancreatic pseudocyst is a collection of necrotic tissue, old blood and secretions that escaped from the pancreas damaged by pancreatitis, trauma and chronic alcoholism. There is no epithelial cell lining the cystic wall. With the advent of ultrasound and CT more accurate diagnosis can be made. Our study was carried out to analyse the radiological and clinical findings of 32 cases of pancreatic pseudocysts confirmed at Wonju College of Medicine Yonsei University from Jan. 1979 to Aug. 1986. The results are as follows: 1. Male to female ratio was 4.3:1 Incidence was the most common in 4th decades. 2. The most frequent symptom was epigastric pain (100%). 3. In a total of 32 cases, 15 cases had a underlying cause of pancreatitis, 9 cases abdominal trauma. 4. In laboratory findings, serum amylase level was elevated in 23 cases, leucocytosis in 10 cases. 5. On chest films, the lungs were mostly normal. Soft tissue mass density in 12 cases was the most common finding on abdomen films. 6. UGI series were helpful in directing attention by pancreatic pseudocysts' location and size. 7. Ultrasonogram using primary procedure for the detection of pseudocyst (23 cases) disclosed anechoic lesion in 8 cases, mixed echo lesion in 15 cases. Mixed echo patterns, in terms of internal echo patters, were echogenic spots (8 cases), septation and echogenic spots (3 cases), fluid-fluid level (3 cases), etc. 8. CT scanning is the best imaging procedure, providing detailed morphologic information about the pancreatic pseudocyst and surrounding tissue.

  4. Differentiation of Metastatic and Non-Metastatic Mesenteric Lymph Nodes by Strain Elastography in Surgical Specimens

    DEFF Research Database (Denmark)

    Havre, R F; Leh, S M; Gilja, O H

    2016-01-01

    Purpose: To investigate if strain elastography could differentiate between metastatic and non-metastatic mesenteric lymph nodes ex-vivo. Materials and Methods: 90 mesenteric lymph nodes were examined shortly after resection from 25 patients including 17 patients with colorectal cancer and 8...... patients with Crohn's disease. Ultrasound-based strain elastography was performed with a linear probe. Tissue hardness in lymph nodes was assessed using visual scales and measuring the strain ratio. B-mode characteristics were also recorded. Pathological diagnosis with grading of fibrosis served...... non-metastatic nodes, but the difference was not significant (65.5 vs. 55.0, p = 0.055). There was no difference between lymph nodes in Crohn's and non-metastatic cancer specimens. The metastatic lymph nodes were significantly more fibrotic than the non-metastatic lymph nodes by the ordinal fibrosis...

  5. Tityus serrulatus venom--A lethal cocktail.

    Science.gov (United States)

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

    2015-12-15

    Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Synergistic activity of troxacitabine (Troxatyl™ and gemcitabine in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Leblond Lorraine

    2007-07-01

    Full Text Available Abstract Background Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™ is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. Methods The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1 tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Results Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth. The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of

  7. Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

    International Nuclear Information System (INIS)

    Damaraju, Vijaya L; Bouffard, David Y; Wong, Clarence KW; Clarke, Marilyn L; Mackey, John R; Leblond, Lorraine; Cass, Carol E; Grey, Mike; Gourdeau, Henriette

    2007-01-01

    Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug

  8. Revaluation on detection of metastatic cancer of the colorectum with barium enema. Comparison with computed tomography and colonoscopy

    International Nuclear Information System (INIS)

    Watari, Jiro; Mizukami, Yusuke; Tanabe, Hirotaka

    1996-01-01

    The findings with barium enema were analyzed and compared to those with computed tomography and colonoscopy in 15 patients with metastatic cancer of the colorectum, which were from 8 gastric, 2 colonic, 2 ovarian, 1 pancreatic, 1 prostatic carcinomas and 1 unknown origin. Primary cancers of intra-abdominal cavity origin tended to make multiple colorectal metastases (91.7%). With barium enema colonic and rectal involvement was mostly expressed as the tethered type and the diffuse type by Ishikawa's classification, respectively. Computed tomography detected direct tumor invasion to the colorectum in 4 cases. Of the other 11 cases, 8 patients (72.3%) showed abnormally thickened colorectal wall. Colonoscopy detected only 3 (37.5%) out of 8 lesions seen in 4 patients who had undergone colonoscopy before barium enema. Many of the lesions missed were the tethered type involvement. Barium enema is the most sensitive method to detect metastatic cancer of the colorectum. (author)

  9. Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

    Science.gov (United States)

    Hu, Wenyan; Fu, Ling

    2013-05-01

    Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (ppancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

  10. Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria.

    Science.gov (United States)

    Schneider, Alexander; Michaely, Henrik; Rückert, Felix; Weiss, Christel; Ströbel, Philipp; Belle, Sebastian; Hirth, Michael; Wilhelm, Torsten J; Haas, Stephan L; Jesenofsky, Ralf; Schönberg, Stefan; Marx, Alexander; Singer, Manfred V; Ebert, Matthias P; Pfützer, Roland H; Löhr, J Matthias

    We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  11. The role of surgery in renal cell carcinoma with pancreatic metastasis

    Directory of Open Access Journals (Sweden)

    Ying-Hsu Chang

    2015-04-01

    Full Text Available Metastasis of renal cell carcinoma to the pancreas is uncommon and, in most cases, presents as a single pancreatic mass that shows a more favorable prognosis than primary pancreatic tumors. We examined patients with renal cell carcinoma metastatic to the pancreas, and discuss the clinical findings, treatment administered, and final outcomes. The present study is a retrospective analysis of renal cell carcinoma patients with pancreatic metastasis. Pancreatic tumor specimens were obtained by surgical excision, surgical biopsy, fine-needle biopsy, or endoscopic ultrasound biopsy. The surgical approaches included distal splenopancreatectomy, total pancreatectomy, or distal pancreatectomy. The physician determined the postoperative treatment regimen with interferon-α or targeted therapy on the basis of patient's performance. A total of six patients with median age of 50 years were included in the study. The median time from the primary nephrectomy to the development of pancreatic metastasis was 16 years. In the biopsy-only group, the mean stable disease period was 16.5 months. In the patients treated with surgery combined with interferon-α or targeted therapy, the mean stable disease period was 29.5 months. The patients treated with repeat mastectomy showed a mean stable disease period of 33.3 months. Aggressive surgical management is more effective than observation or immunotherapy. Recent advances in the design of targeted therapies may provide alternative treatment strategies. Combination therapy may play an important role in the future. Considering patient compliance and cost-effectiveness, resection of pancreatic metastasis is currently the first choice of treatment.

  12. Endocrine carcinoma of the pancreatic tail exhibiting gastric variceal bleeding

    Directory of Open Access Journals (Sweden)

    Si-Yuan Wu

    2014-01-01

    Full Text Available Nonfunctional endocrine carcinoma of the pancreas is uncommon. Without excess hormone secretion, it is clinically silent until the enlarging or metastatic tumor causes compressive symptoms. Epigastric pain, dyspepsia, jaundice, and abdominal mass are the usual symptoms, whereas upper gastrointestinal (GI bleeding is rare. Here, we describe the case of a 24-year-old man with the chief complaint of hematemesis. Upper GI panendoscopy revealed isolated gastric varices at the fundus and upper body. Ultrasonography and computed tomography showed a tumor mass at the pancreatic tail causing a splenic vein obstruction, engorged vessels near the fundus of the stomach, and splenomegaly. After distal pancreatectomy and splenectomy, the bleeding did not recur. The final pathologic diagnosis was endocrine carcinoma of the pancreas. Gastric variceal bleeding is a possible manifestation of nonfunctional endocrine carcinoma of the pancreas if the splenic vein is affected by a tumor. In non-cirrhotic patients with isolated gastric variceal bleeding, the differential diagnosis should include pancreatic disorders.

  13. Comparative proteomic investigation of metastatic and non-metastatic osteosarcoma cells of human and canine origin.

    Directory of Open Access Journals (Sweden)

    Jahnabi Roy

    Full Text Available Osteosarcoma is the most common bone cancer in dogs and people. In order to improve clinical outcomes, it is necessary to identify proteins that are differentially expressed by metastatic cells. Membrane bound proteins are responsible for multiple pro-metastatic functions. Therefore characterizing the differential expression of membranous proteins between metastatic and non-metastatic clonal variants will allow the discovery of druggable targets and consequently improve treatment methodology. The objective of this investigation was to systemically identify the membrane-associated proteomics of metastatic and non-metastatic variants of human and canine origin. Two clonal variants of divergent in vivo metastatic potential from human and canine origins were used. The plasma membranes were isolated and peptide fingerprinting was used to identify differentially expressed proteins. Selected proteins were further validated using western blotting, flow cytometry, confocal microscopy and immunohistochemistry. Over 500 proteins were identified for each cell line with nearly 40% of the proteins differentially regulated. Conserved between both species, metastatic variants demonstrated significant differences in expression of membrane proteins that are responsible for pro-metastatic functions. Additionally, CD147, CD44 and vimentin were validated using various biochemical techniques. Taken together, through a comparative proteomic approach we have identified several differentially expressed cell membrane proteins that will help in the development of future therapeutics.

  14. Comparative proteomic investigation of metastatic and non-metastatic osteosarcoma cells of human and canine origin.

    Science.gov (United States)

    Roy, Jahnabi; Wycislo, Kathryn L; Pondenis, Holly; Fan, Timothy M; Das, Aditi

    2017-01-01

    Osteosarcoma is the most common bone cancer in dogs and people. In order to improve clinical outcomes, it is necessary to identify proteins that are differentially expressed by metastatic cells. Membrane bound proteins are responsible for multiple pro-metastatic functions. Therefore characterizing the differential expression of membranous proteins between metastatic and non-metastatic clonal variants will allow the discovery of druggable targets and consequently improve treatment methodology. The objective of this investigation was to systemically identify the membrane-associated proteomics of metastatic and non-metastatic variants of human and canine origin. Two clonal variants of divergent in vivo metastatic potential from human and canine origins were used. The plasma membranes were isolated and peptide fingerprinting was used to identify differentially expressed proteins. Selected proteins were further validated using western blotting, flow cytometry, confocal microscopy and immunohistochemistry. Over 500 proteins were identified for each cell line with nearly 40% of the proteins differentially regulated. Conserved between both species, metastatic variants demonstrated significant differences in expression of membrane proteins that are responsible for pro-metastatic functions. Additionally, CD147, CD44 and vimentin were validated using various biochemical techniques. Taken together, through a comparative proteomic approach we have identified several differentially expressed cell membrane proteins that will help in the development of future therapeutics.

  15. Pancreatic endocrine tumor with neoplastic venous thrombus and bilobar liver metastasis. A case report.

    Science.gov (United States)

    Barbier, L; Turrini, O; Sarran, A; Delpero, J-R

    2010-02-01

    We report the case of an asymptomatic 56-year-old woman with a metastatic pancreatic endocrine tumor, fortuitously discovered by abdominal imaging. A CT-scan showed a large mass in the pancreatic tail invading the spleen and stomach; in addition, there was neoplastic thrombus within the spleno-mesentericoportal venous confluence and bilobar liver metastases. Surgical resection was performed in two stages. The first procedure was an extended left pancreatectomy with venous thrombectomy and "clearance" of the left hepatic lobe. During the interval, embolization of the right portal vein was carried out. Right hepatectomy and radiofrequency destruction of residual metastases was then performed. On the basis of completeness of the resection and the histopathological data, the patient did not undergo any adjuvant therapy, in accordance with French guidelines. At 1 year of follow-up, there was no evidence of recurrence. (c) 2010 Elsevier Masson SAS. All rights reserved.

  16. Two cases of pathological complete response to neoadjuvant chemoradiation therapy in pancreatic cancer

    International Nuclear Information System (INIS)

    Fujii-Nishimura, Yoko; Nishiyama, Ryo; Kitago, Minoru

    2015-01-01

    Neoadjuvant chemoradiation therapy (NACRT) is increasingly used in patients with a potentially or borderline resectable pancreatic ductal adenocarcinoma (PDA) and it has been shown to improve survival and reduce locoregional metastatic disease. It is rare for patients with PDA to have a pathological complete response (pCR) to NACRT, but such patients reportedly have a good prognosis. We report the clinicopathological findings of two cases of pCR to NACRT in PDA. Both patients underwent pancreatectomy after NACRT (5-fluorouracil, mitomycin C, cisplatin, and radiation). Neither had residual invasive carcinoma and both showed extensive fibrotic regions with several ducts regarded as having pancreatic intraepithelial neoplasia 3/carcinoma in situ in their post-therapy specimens. It is noteworthy that both patients had a history of a second primary cancer. They both had comparatively good outcomes: one lived for 9 years after the initial pancreatectomy and the other is still alive without recurrence after 2 years. (author)

  17. Pancreatic cancer cell detection by targeted lipid microbubbles and multiphoton imaging

    Science.gov (United States)

    Cromey, Benjamin; McDaniel, Ashley; Matsunaga, Terry; Vagner, Josef; Kieu, Khanh Quoc; Banerjee, Bhaskar

    2018-04-01

    Surgical resection of pancreatic cancer represents the only chance of cure and long-term survival in this common disease. Unfortunately, determination of a cancer-free margin at surgery is based on one or two tiny frozen section biopsies, which is far from ideal. Not surprisingly, cancer is usually left behind and is responsible for metastatic disease. We demonstrate a method of receptor-targeted imaging using peptide ligands, lipid microbubbles, and multiphoton microscopy that could lead to a fast and accurate way of examining the entire cut surface during surgery. Using a plectin-targeted microbubble, we performed a blinded in-vitro study to demonstrate avid binding of targeted microbubbles to pancreatic cancer cells but not noncancerous cell lines. Further work should lead to a much-needed point-of-care diagnostic test for determining clean margins in oncologic surgery.

  18. Pancreatic HIF2α Stabilization Leads to Chronic Pancreatitis and Predisposes to Mucinous Cystic Neoplasm

    Directory of Open Access Journals (Sweden)

    Heather K. Schofield

    2018-01-01

    Conclusions: We show that pancreatic HIF2α stabilization disrupts pancreatic homeostasis, leading to chronic pancreatitis, and, in the context of oncogenic Kras, MCN formation. These findings provide new mouse models of both chronic pancreatitis and MCN, as well as illustrate the importance of hypoxia signaling in the pancreas.

  19. Enteric hyperoxaluria in chronic pancreatitis.

    Science.gov (United States)

    Demoulin, Nathalie; Issa, Zaina; Crott, Ralph; Morelle, Johann; Danse, Etienne; Wallemacq, Pierre; Jadoul, Michel; Deprez, Pierre H

    2017-05-01

    Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney damage. However, the prevalence and determinants of hyperoxaluria in chronic pancreatitis patients as well as its association with renal function decline have not been investigated.We performed an observational study. Urine oxalate to creatinine ratio was assessed on 2 independent random urine samples in consecutive adult patients with chronic pancreatitis followed at the outpatient clinic from March 1 to October 31, 2012. Baseline characteristics and annual estimated glomerular filtration rate (eGFR) change during follow-up were compared between patients with hyper- and normo-oxaluria.A total of 48 patients with chronic pancreatitis were included. The etiology of the disease was toxic (52%), idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%). Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found in 23% of patients. Multivariate regression analysis identified clinical steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent predictors of hyperoxaluria. Taken together, a combination of clinical steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a positive predictive value of 100% for hyperoxaluria. On the contrary, none of the patients with a fecal elastase-1 level >100 μg/g had hyperoxaluria. Longitudinal evolution of eGFR was available in 71% of the patients, with a mean follow-up of 904 days. After adjustment for established determinants of renal function decline (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis and associated with faster decline in renal function. A high urine oxalate to creatinine ratio in patients with chronic pancreatitis is best predicted by clinical steatorrhea, a high acid

  20. Proposed cut-off value of CA19-9 for detecting pancreatic cancer in patients with diabetes: a case-control study.

    Science.gov (United States)

    Murakami, Mariko; Nagai, Yoshio; Tenjin, Ayumi; Tanaka, Yasushi

    2018-04-11

    Pancreatic cancer is a highly lethal malignancy. CA19-9 is a well-known marker for diagnosis of pancreatic cancer, but the serum CA19-9 level is reported to be elevated in patients with poorly controlled diabetes. This study evaluated the sensitivity, specificity, and cut-off value of serum CA19-9 for detection of pancreatic cancer in patients with diabetes. A case-control study of 236 patients was performed. The case group was selected from diabetic patients with pancreatic cancer, while one control was selected for each case from among diabetic patients without pancreatic cancer during the same period. The case group (n = 118) and the control group (n = 118) were matched for age, sex, and pancreatic cancer risk factors. Receiver operating characteristic (ROC) curves were plotted to determine the serum CA19-9 level that predicted pancreatic cancer. Then the sensitivity and specificity of CA19-9 were calculated for the threshold value. There were no significant differences of age, sex, BMI, smoking, alcohol intake, and HbA1c between the case and control groups. According to ROC analysis, a serum CA19-9 level of 75 U/mL had the maximum sensitivity and specificity for separating diabetic patients with or without pancreatic cancer. Using this cut-off value, the sensitivity and specificity of CA19-9 for pancreatic cancer was 69.5% and 98.2%, respectively, while the area under the ROC curve was 0.875 [95%CI: 0.826-0.924]. We propose that a serum CA19-9 level of 75 U/mL should be used as the cut-off value when screening patients with diabetes for pancreatic cancer.

  1. Chronic exposure of corals to fine sediments: lethal and sub-lethal impacts.

    Directory of Open Access Journals (Sweden)

    Florita Flores

    Full Text Available Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata more than the upright branching species (Acropora millepora. The lowest sediment treatments that caused full colony mortality were 30 mg l(-1 TSS (25 mg cm(-2 day(-1 for M. aequituberculata and 100 mg l(-1 TSS (83 mg cm(-2 day(-1 for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue.

  2. Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts

    Science.gov (United States)

    Flores, Florita; Hoogenboom, Mia O.; Smith, Luke D.; Cooper, Timothy F.; Abrego, David; Negri, Andrew P.

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l−1 TSS (25 mg cm−2 day−1) for M. aequituberculata and 100 mg l−1 TSS (83 mg cm−2 day−1) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  3. Development of epidermal growth factor receptor targeted therapy in pancreatic cancer.

    Science.gov (United States)

    Qing, Liu; Qing, Wang

    2018-02-01

    The epidermal growth factor receptor (EGFR) family are a series of important cancer therapeutic targets involved in cancer biology. These genes play an important role in tumor biological characteristics including angiogenesis, cell survival, invasion and glucose metabolism. In recent years, progresses have been achieved upon the cellular and molecular biological characteristics of EGFR and its role in cancer development based on the study of tumor specimens and experimental animal model. EGFR(HER1/ErbB) is overexpressed in over sixty percent of triple-negative breast cancers and occurs in pancreatic, bladder, lung and head-and-neck cancers. Up to now, EGFR inhibitors have been applied in various of cancer, such as lung, breast, bladder and head and neck cancers etc., in which the combination of EGFR inhibitors plus chemotherapeutic agents is now seen as the standard of care for advanced/metastatic pancreatic cancer. For these reasons, EGFR inhibitors and their therapeutic effect for pancreatic cancer is becoming the focus in Laboratory and clinical research. In this paper, research progress of the development of epidermal growth factor receptor targeted therapy in pancreatic cancer is introduced.

  4. Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.

    Science.gov (United States)

    Sun, Xiangjie; Zuo, Ke; Huang, Dan; Yu, Baohua; Cheng, Yufan; Yang, Wentao

    2017-07-11

    Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare. We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast. To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.

  5. Emerging treatments for advanced pancreatic cancer: clinical potential of albumin-bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Fontana E

    2014-06-01

    Full Text Available Elisa Fontana, Francesco Sclafani, David Cunningham Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK Abstract: The management of pancreatic cancer has historically represented a major challenge for oncologists. The inherent aggressiveness of this tumor and the fibrotic features of the surrounding stromal tissue have significantly limited the impact of standard chemotherapy. Moreover, the paucity of available tumor tissue has hampered a better understanding of the biology of this disease as well as the development of new treatment strategies. Recently, the therapeutic landscape of metastatic pancreatic cancer has been enriched by two new combination regimens (FOLFIRINOX and gemcitabine-nab-paclitaxel which have been demonstrated to improve the outcome in patients with good performance status. Moreover, the peritumoral stroma has been increasingly recognized as a potential therapeutic target for this disease, and several new agents targeting stromal components are currently under investigation. In this paper, we review the current treatment options for advanced pancreatic cancer, highlight the role of the peritumoral stroma, and discuss the clinical potential of nab-paclitaxel and antistromal treatment strategies. Keywords: pancreatic cancer, nab-paclitaxel, stroma, SPARC

  6. Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection

    International Nuclear Information System (INIS)

    Delpero, J.R.; Turrini, O.

    2006-01-01

    Induction chemoradiotherapy (CRT) may down-stage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a RO resection. Patients and methods. We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neo-adjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. Results. The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The RO resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. Conclusion. Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic disease

  7. Preventive medicine for von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Krauss, Tobias; Ferrara, Alfonso Massimiliano; Links, Thera P; Wellner, Ulrich; Bancos, Irina; Kvachenyuk, Andrey; Villar Gómez de Las Heras, Karina; Yukina, Marina; Petrov, Roman; Bullivant, Garrett; von Duecker, Laura; Jadhav, Swati S; Ploeckinger, Ursula; Welin, Staffan; Schalin-Jantti, Camilla; Gimm, Oliver; Pfeifer, Marija; Ngeow, Joanne; Hasse-Lazar, Kornelia; Sanso, Gabriela; Qi, Xiao-Ping; Ugurlu, Umit; Diaz, Rene Eduardo; Wohllk, Nelson; Peczkowska, Mariola; Aberle, Jens; Lourenço, Delmar Muniz; Pereira, Maria Adelaide; Fragoso, Maria Candida Barisson Villares; Hoff, Ana O; Almeida, Madson Queiroz; Violante, Alice H D; Quidute, Ana R P; Zhang, Zheiwei; Recasens, Monica; Robles Diaz, Luis; Kunavisarut, Tada; Wannachalee, Taweesak; Sirinvaravong, Sirinart; Jonasch, Eric; Grozinsky-Glasberg, Simona; Fraenkel, Merav; Beltsevich, Dmitry; Egorov, Viacheslav I; Bausch, Dirk; Schott, Matthias; Tiling, Nikolaus; Pennelli, Gianmaria; Zschiedrich, Stefan; Därr, Roland; Ruf, Juri; Denecke, Timm; Link, Karl-Heinrich; Zovato, Stefania; von Dobschuetz, Ernst; Yaremchuk, Svetlana; Amthauer, Holger; Makay, Ozer; Patocs, Attila; Walz, Martin K; Huber, Tobias B; Seufert, Jochen; Hellman, Per; Kim, Raymond H; Kuchinskaya, Ekaterina; Schiavi, Francesca; Malinoc, Angelica; Reisch, Nicole; Jarzab, Barbara; Barontini, Marta; Januszewicz, Andrzej; Shah, Nalini; Young, William; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P H; Bausch, Birke

    2018-05-10

    Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2,330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8cm vs ≥2.8 cm (94% vs 85% by 10 years; P=0.020; 80% vs 50% at 10 years; P=0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

  8. Treatment of metastatic brain lesion

    Directory of Open Access Journals (Sweden)

    A. M. Zaytsev

    2015-01-01

    Full Text Available Objective. Increasing survival in patients with secondary brain damage, and identifying the factors of favorable and adverse prognosis.Material and method. In P. A. Hertsen Moscow Oncology Research Institute from 2007 to 2013 there were treated 268 patients with brain metastases. The mean age was 55.8 years (from 24 to 81 years. Metastases of colorectal cancer identified in 7.8%, cases of lung cancer in 34%, melanoma 9.3 %, breast cancer in 26%, kidney cancer in 11%, with non-identified primary tumor in 4.5%, other tumors accounted for 6.7%. Solitary metastasis was diagnosed in 164 (61,19% patients, oligometastasis (2-3 - 72 (26,87% patients with polymetastasis (more than 3 – 32 (11,94% patients. In 106 (39,55% of patients with brain metastases it was the only manifestation of the generalization process. To control the radical removal of the tumor in 93 (34,7% patients we used the method of fluorescence navigation (FN with the drug Alasens. In 66 (24,6% patients intraoperatively was held a session of photodynamic therapy (PDT. In 212 (79,1% cases, the removal of metastasis performed totally, 55 (20,9% patients stated Subtotal removal.Results. The observation period for the patients ranged from 3 to 79 months. Survival median among the entire group of patients with metastatic brain lesion was 12 months. Overall survival was significantly dependent on RPA class, the volume of postoperative treatment, histological type of primary tumor, number of intracerebral metastases and the timing of the relapse-free period.Conclusions. Factors that affects the overall survival are the features of the histology of the primary lesion, multiplicity of metastatic lesions, RPA class and the synchronous nature of the metastasis. The median of overall survival of patients who did not receive after surgical treatment of a particular type of therapy was only 4 months. If to use the combined treatment (surgical treatment with the irradiation of the whole brain median

  9. Experimental study of the intra-operative radiation therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Kodera, Taro; Matsuno, Seiki; Kobari, Masao; Akaishi, Satoshi; Sakamoto, Kiyohiko

    1988-01-01

    The radiosensitivity of pancreatic cancer, optimum dose of irradiation and the effect of 1-[4'-Hydroxy-2'-Butenoxy) Methyl]-2-Nitrosoimidaole (RK-28) on irradiation were investigated using an experimental pancreatic cancer of hamster and the following results were obtained: i) The mean lethal dose (Do) and the 50 % tumor control dose (TCD 50 ) against the pancreatic cancer were 3.5 Gy and 73.7 ± 6.9 Gy, respectively. These results indicate that the pancreatic cancer is resistant to irradiation, which could be explained by the existence of hypoxic cells consisting of 35 % of the tumor. ii) The dose of intraoperative irradiation (10 - 40 Gy) seemed to be insufficient to bring long-term anti-tumor effect and long-term survival since that dose resulted in only temporary regression of the tumor. iii) The hypoxic cell sensitizer (RK28), which is known to specifically enhance the sensitivity of hypoxic cells to irradiation, lowered TCD 50 of the pancreatic cancer to 53.8 ± 1.57 Gy. Therefore, RK-28 was effective in the treatment of the experimental pancreatic cancer (the enhancement ratio : 1.37). When combined with 30 or 40 Gy of irradiation, which is applicable to intraoperative irradiation, RK-28 induced a longer period of tumor suppression and a higher tumor regression ratio than irradiation alone. These results indicate that RK-28 significantly increases the effect of intraoperative irradiation and this combination therapy could possibly induce remarkable effect on tumor regression and long-term survival. (author)

  10. Autoimmune pancreatitis : Diagnostic and immunological aspects

    NARCIS (Netherlands)

    M.J. van Heerde (Marianne)

    2013-01-01

    textabstractAutoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic fibro- inflammatory disease, characterized by infiltration with lymphoplasmacytic cells and extensive fibrosis, which leads to morphological changes (swelling, mass forming) and organ dysfunction. Often, but

  11. Acute and chronic pancreatitis: surgical management.

    Science.gov (United States)

    Dzakovic, Alexander; Superina, Riccardo

    2012-08-01

    Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function. Copyright © 2012. Published by Elsevier Inc.

  12. Asparaginase-associated pancreatitis in children.

    Science.gov (United States)

    Raja, Raheel Altaf; Schmiegelow, Kjeld; Frandsen, Thomas Leth

    2012-10-01

    l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis. © 2012 Blackwell Publishing Ltd.

  13. Targeting ROCK activity to disrupt and prime pancreatic cancer for chemotherapy.

    Science.gov (United States)

    Vennin, Claire; Rath, Nicola; Pajic, Marina; Olson, Michael F; Timpson, Paul

    2017-10-03

    Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease; the identification of novel targets and development of effective treatment strategies are urgently needed to improve patient outcomes. Remodeling of the pancreatic stroma occurs during PDAC development, which drives disease progression and impairs responses to therapy. The actomyosin regulatory ROCK1 and ROCK2 kinases govern cell motility and contractility, and have been suggested to be potential targets for cancer therapy, particularly to reduce the metastatic spread of tumor cells. However, ROCK inhibitors are not currently used for cancer patient treatment, largely due to the overwhelming challenge faced in the development of anti-metastatic drugs, and a lack of clarity as to the cancer types most likely to benefit from ROCK inhibitor therapy. In 2 recent publications, we discovered that ROCK1 and ROCK2 expression were increased in PDAC, and that increased ROCK activity was associated with reduced survival and PDAC progression by enabling extracellular matrix (ECM) remodeling and invasive growth of pancreatic cancer cells. We also used intravital imaging to optimize ROCK inhibition using the pharmacological ROCK inhibitor fasudil (HA-1077), and demonstrated that short-term ROCK targeting, or 'priming', improved chemotherapy efficacy, disrupted cancer cell collective movement, and impaired metastasis. This body of work strongly indicates that the use of ROCK inhibitors in pancreatic cancer therapy as 'priming' agents warrants further consideration, and provides insights as to how transient mechanical manipulation, or fine-tuning the ECM, rather than chronic stromal ablation might be beneficial for improving chemotherapeutic efficacy in the treatment of this deadly disease.

  14. Role of pancreatic fat in the outcomes of pancreatitis.

    Science.gov (United States)

    Acharya, Chathur; Navina, Sarah; Singh, Vijay P

    2014-01-01

    The role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP).The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [9-11]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  15. Hypothermia-Related Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Kyawzaw Lin

    2018-05-01

    Full Text Available Acute pancreatitis (AP is an inflammatory disease presenting from mild localized inflammation to severe infected necrotic pancreatic tissue. In the literature, there are a few cases of hypothermia-induced AP. However, the association between hypothermia and AP is still a myth. Generally, mortality from acute pancreatitis is nearly 3–6%. Here, we present a 40-year-old chronic alcoholic female who presented with acute pancreatitis induced by transient hypothermia. A 40-year-old chronic alcoholic female was hypothermic at 81°F on arrival which was improved to 91.7°F with warming blanket and then around 97°F in 8 h. Laboratory tests including complete blood count, lipid panel, and comprehensive metabolic panels were within the normal limit. Serum alcohol level was 0.01, amylase 498, lipase 1,200, ammonia 26, serum carboxyhemoglobin level 2.4, and β-HCG was negative. The entire sepsis workup was negative. During rewarming period, she had one episode of witnessed generalized tonic-clonic seizure. It was followed by transient hypotension. Fluid challenge was successful with 2 L of normal saline. Sonogram (abdomen showed fatty liver and trace ascites. CAT scan (abdomen and pelvis showed evidence of acute pancreatitis without necrosis, peripancreatic abscess, pancreatic mass, or radiopaque gallstones. The patient was managed medically and later discharged from the hospital on the 4th day as she tolerated a normal low-fat diet. In our patient, transient hypothermia from chronic alcohol abuse and her social circumstances might predispose to microcirculatory disturbance resulting in acute pancreatitis. Early and aggressive fluid resuscitation prevents complications.

  16. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO.

    Science.gov (United States)

    Ramadani, Naser; Dedushi, Kreshnike; Muçaj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-04-01

    The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, 2011-2015 at the University Clinical Center of Kosovo in Pristina. The main important factors included in this study are: age, sex and risk factors that altogether have considerable influence in incidence of pancreatic cancer. The imaging diagnostics are performed with the use of 2D ECHO Phillips, MSCT Sensation 64 and 6 and 1.5T MRI Symphony Siemens that are situated in the Radiologic Clinic of UCCK. The statistic data were obtained from NIPH of Kosovo and Agency of Statistics of Kosovo. Out of the total number of the 362 patients diagnosed with pancreatic cancer, the mortality in all age groups was higher at male patients-61.6 % of cases (n=223) with the highest number found at 51-60 years age group. The 38.4 % (n= 139) were female patients with the highest incidence frequency at F 61-70 years age group. The F/M ratio is 1:1.6. The "plane" nicotine users were found at 34 % (n=123) while the joined, nicotine/alcohol addiction was detected at 26 % (n= 94). The 18.5% (n=67) have had established diagnose of the diabetes mellitus tip II and 9.6 % (n=35) have undergone the medical treatment of the gastroduodenal peptic ulcerations. The total number of deaths is 310 (85.6%) and there are only 52 patients (14.4%) still alive. The mortality rate of the pancreatic cancer in Kosovo was 17.2 in 100.000 residents while the morbidity rate was 2.8 in 100.000 residents. This retrospective research study intends to present the role of the risk factor, that

  17. THE FREQUENCY OF RISK FACTORS ON TRENDS OF PANCREATIC CANCER IN KOSOVO

    Science.gov (United States)

    Ramadani, Naser; Dedushi, Kreshnike; Muçaj, Sefedin; Kabashi, Serbeze; Jerliu, Naim; Hoxhaj, Astrit

    2016-01-01

    The aim: The aim of this paper is to analyze different factors that influence the trends of pancreatic cancer mortality and morbidity of patients treated at the UCCK of Kosovo. Within this study, we have evaluated pancreatic cancer risk factors, durability and lethality regarding Kosovan patients who have been diagnosed and treated within Kosovo. The study in question is that of retrospective research traversing the period of 2011-2015. Materials and methodology: This retrospective research study includes 362 patients recently diagnosed with pancreatic cancer, 2011-2015 at the University Clinical Center of Kosovo in Pristina. The main important factors included in this study are: age, sex and risk factors that altogether have considerable influence in incidence of pancreatic cancer. The imaging diagnostics are performed with the use of 2D ECHO Phillips, MSCT Sensation 64 and 6 and 1.5T MRI Symphony Siemens that are situated in the Radiologic Clinic of UCCK. The statistic data were obtained from NIPH of Kosovo and Agency of Statistics of Kosovo. Results: Out of the total number of the 362 patients diagnosed with pancreatic cancer, the mortality in all age groups was higher at male patients–61.6 % of cases (n=223) with the highest number found at 51–60 years age group. The 38.4 % (n= 139) were female patients with the highest incidence frequency at F 61–70 years age group. The F/M ratio is 1:1.6. The “plane” nicotine users were found at 34 % (n=123) while the joined, nicotine/alcohol addiction was detected at 26 % (n= 94). The 18.5% (n=67) have had established diagnose of the diabetes mellitus tip II and 9.6 % (n=35) have undergone the medical treatment of the gastroduodenal peptic ulcerations. The total number of deaths is 310 (85.6%) and there are only 52 patients (14.4%) still alive. The mortality rate of the pancreatic cancer in Kosovo was 17.2 in 100.000 residents while the morbidity rate was 2.8 in 100.000 residents. Discussion and conclusion: This

  18. Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Enza Lonardo

    Full Text Available Pancreatic ductal adenocarcinomas contain a subset of exclusively tumorigenic cancer stem cells (CSCs, which are capable of repopulating the entire heterogeneous cancer cell populations and are highly resistant to standard chemotherapy. Here we demonstrate that metformin selectively ablated pancreatic CSCs as evidenced by diminished expression of pluripotency-associated genes and CSC-associated surface markers. Subsequently, the ability of metformin-treated CSCs to clonally expand in vitro was irreversibly abrogated by inducing apoptosis. In contrast, non-CSCs preferentially responded by cell cycle arrest, but were not eliminated by metformin treatment. Mechanistically, metformin increased reactive oxygen species production in CSC and reduced their mitochondrial transmembrane potential. The subsequent induction of lethal energy crisis in CSCs was independent of AMPK/mTOR. Finally, in primary cancer tissue xenograft models metformin effectively reduced tumor burden and prevented disease progression; if combined with a stroma-targeting smoothened inhibitor for enhanced tissue penetration, while gemcitabine actually appeared dispensable.

  19. Pathophysiology of alcoholic pancreatitis: An overview

    Institute of Scientific and Technical Information of China (English)

    Parimal Chowdhury; Priya Gupta

    2006-01-01

    Use of alcohol is a worldwide habit regardless of socioeconomic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented.

  20. A case of severe acute pancreatitis with near total pancreatic necrosis diagnosed by dynamic CT scanning

    International Nuclear Information System (INIS)

    Takeda, Kazunori; Kakugawa, Yoichiro; Amikura, Katsumi; Miyagawa, Kikuo; Matsuno, Seiki; Sato, Toshio

    1987-01-01

    A 42 year-old woman with severe acute pancreatitis had drainage of the pancreatic bed, cholecystostomy and jejunostomy on admission, but symptoms were not improved. Fourteen days after admission, clinical sepsis and septisemia were recognized. Dynamic CT scanning of the pancreas showed near total pancreatic necrosis. Symptoms were improved after necrosectomy of the pancreas and debridement of the peripancreatic necrotic tissue were performed. Our experience suggests the usefulness of dynamic CT scanning for detection of pancreatic necrosis in severe acute pancreatitis. (author)

  1. The role of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in resectable pancreatic cancer.

    Science.gov (United States)

    Crippa, Stefano; Salgarello, Matteo; Laiti, Silvia; Partelli, Stefano; Castelli, Paola; Spinelli, Antonello E; Tamburrino, Domenico; Zamboni, Giuseppe; Falconi, Massimo

    2014-08-01

    The role of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in pancreatic ductal adenocarcinoma is debated. We retrospectively assessed the value of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in addition to conventional imaging as a staging modality in pancreatic cancer. (18)Fluoro-deoxyglucose positron emission tomography/computed tomography was performed in 72 patients with resectable pancreatic carcinoma after multi-detector computed tomography positron emission tomography was considered positive for a maximum standardized uptake value >3. Overall, 21% of patients had a maximum standardized uptake value ≤ 3, and 60% of those had undergone neoadjuvant treatment (P=0.0001). Furthermore, 11% of patients were spared unwarranted surgery since positron emission tomography/computed tomography detected metastatic disease. All liver metastases were subsequently identified with contrast-enhanced ultrasound. Sensitivity and specificity of positron emission tomography/computed tomography for distant metastases were 78% and 100%. The median CA19.9 concentration was 48.8 U/mL for the entire cohort and 292 U/mL for metastatic patients (P=0.112). The widespread application of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in patients with resectable pancreatic carcinoma seems not justified. It should be considered in selected patients at higher risk of metastatic disease (i.e. CA19.9>200 U/mL) after undergoing other imaging tests. Neoadjuvant treatment is significantly associated with low metabolic activity, limiting the value of positron emission tomography in this setting. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  2. Role of {sup 68}Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rakesh; Sharma, Punit; Karunanithi, Sellam; Naswa, Niraj; Lata, Sneh; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Garg, Pramod [All India Institute of Medical Sciences, Department of Gastroenterology and Human Nutrition, New Delhi (India); Sharma, Raju; Thulkar, Sanjay [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India)

    2011-11-15

    The objective of the present study was to evaluate the role of {sup 68}Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide ({sup 68}Ga-DOTATOC) positron emission tomography computed tomography (PET-CT) for detection and staging of pancreatic neuroendocrine tumours (NETs). Twenty patients with clinically suspected and/or histopathologically proven pancreatic NET underwent {sup 68}Ga-DOTATOC PET-CT imaging for staging and /or localisation of primary lesion. They also underwent contrast enhanced CT (CECT) and 8 patients underwent {sup 18}F-FDG PET-CT. SUVmax of primary and metastatic lesions were measured. Results were verified with histopathology for primary tumour and with clinical follow up/MRI and /or biopsy for metastatic disease. Results of {sup 68}Ga-DOTATOC PET-CT were compared to CECT and {sup 18}F-FDG PET-CT. {sup 68}Ga-DOTATOC PET-CT correctly localised primary in all 20, CECT in 15 and {sup 18}F-FDG PET-CT in 2 patients. {sup 68}Ga-DOTATOC PET-CT demonstrated metastases in 13 patients, CECT in 7 and {sup 18}F-FDG PET-CT in 2. {sup 68}Ga-DOTATOC PET-CT emerged as the best investigation with 100% sensitivity and PPV for detecting primary tumour and metastatic disease. The detection rate of CECT was lower than {sup 68}Ga-DOTATOC PET-CT, both for primary tumour (20vs.15) or metastatic disease (13vs.7). {sup 18}F-FDG PET-CT performed poorly for primary and metastasis. Ga-DOTATOC PET-CT is a very useful imaging investigation for diagnosing and staging pancreatic NET. (orig.)

  3. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida

    NARCIS (Netherlands)

    Rico, Andreu; Sabater, Consuelo; Castillo, María Ángeles

    2016-01-01

    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure

  4. Pancreatitis in a high HIV prevalence environment

    African Journals Online (AJOL)

    In environments with low HIV infection rates, acute pancreatitis is ... The serum amylase level was used to confirm acute pancreatitis in 50 patients, with a ..... Mortier E, Gaba S, Mari I, Vinceneux P, Pouchot J. Acute pancreatitis during primary ...

  5. Genetic Risk for Alcoholic Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Flair José Carrilho

    2011-06-01

    Full Text Available In recent years many studies have examined the genetic predisposition to pancreatic diseases. Pancreatic disease of an alcoholic etiology was determined to be a multi-factorial disease, where environmental factors interact with the genetic profile of the individual. In this review we discuss the main results from studies examining the frequency of genetic mutations in alcoholic chronic pancreatitis.

  6. The management of complex pancreatic injuries

    African Journals Online (AJOL)

    Nicky

    pancreatic injuries. Leakage of pancreatic exocrine secre- ... gland damage and the likelihood of duct injury is usually sufficient to ..... creatic function. The decision to resort to pancreaticoduo- denectomy is based upon the extent of the pancreatic injury, the size and vascular status of any duodenal injury, the integrity of the ...

  7. Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis.

    Science.gov (United States)

    Rijkers, Anton P; Bakker, Olaf J; Ahmed Ali, Usama; Hagenaars, Julia C J P; van Santvoort, Hjalmar C; Besselink, Marc G; Bollen, Thomas L; van Eijck, Casper H

    2017-09-01

    Acute pancreatitis may be the first manifestation of pancreatic cancer. The aim of this study was to assess the risk of pancreatic cancer after a first episode of acute pancreatitis. Between March 2004 and March 2007, all consecutive patients with a first episode of acute pancreatitis were prospectively registered. Follow-up was based on hospital records audit, radiological imaging, and patient questionnaires. Outcome was stratified based on the development of chronic pancreatitis. We included 731 patients. The median follow-up time was 55 months. Progression to chronic pancreatitis was diagnosed in 51 patients (7.0%). In this group, the incidence rate per 1000 person-years for developing pancreatic cancer was 9.0 (95% confidence interval, 2.3-35.7). In the group of 680 patients who did not develop chronic pancreatitis, the incidence rate per 1000 person-years for developing pancreatic cancer in this group was 1.1 (95% confidence interval, 0.3-3.3). Hence, the rate ratio of pancreatic cancer was almost 9 times higher in patients who developed chronic pancreatitis compared with those who did not (P = 0.049). Although a first episode of acute pancreatitis may be related to pancreatic cancer, this risk is mainly present in patients who progress to chronic pancreatitis.

  8. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  9. CT manifestations of pancreatic tuberculosis

    International Nuclear Information System (INIS)

    Yu Risheng; Zheng Ji'ai; Li Rongfen

    2001-01-01

    Objective: To assess the CT manifestations and diagnostic value in the pancreatic tuberculosis(PTB)with review of the literatures. Methods: All cases of PTB proved by surgery or biopsy were examined with plain and enhanced CT scans. Results: The CT findings in one case with multiple-nodular type of PTB were diffuse enlargement of the pancreas with multiple, nodular, and low-density lesions; The nodular lesions had peripheral enhancement. 7 cases of local type of PTB encroached on pancreatic head. 4 cases showed local soft tissue masses with multiple flecked calcifications in 2 cases and mild enhancement in one case; Cystic masses was found in 2 cases, with mural calcification in 1 case and multi-loculated cystic mass in 1 case, respectively; Massive pancreatic head calcification was demonstrated in one case. In these 8 cases of PTB, the lesion extended out of pancreas in 4 cases, including abdominal tuberculous lymph nodes, tuberculous peritonitis, and hepatosplenic tuberculosis. Conclusion: CT findings of PTB were various but had some characteristics. Pancreatic masses with multiple flecked calcification or mild enhancement could suggest the diagnosis. Abdominal tuberculosis accompanied with the pancreatic lesion, especially tuberculous lymph nodes, was highly suggestive of the diagnosis of PTB

  10. Cystic Lesions in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Macarena Gompertz

    2015-11-01

    Full Text Available Autoimmune pancreatitis (AIP can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

  11. Radiological aspect of pancreatic pseudocysts

    International Nuclear Information System (INIS)

    Chung, Tae Sub; Lim, Sue Jin; Yoo, Hyung Sik; Suh, Jung Ho; Park, Chang Yun

    1982-01-01

    Pancreatic pseudocyst occurs as a complication of pancreatitis or trauma, which results in the escape of pancreatitis enzymes from the parenchyma or ductal system of pancreas. At that time, serum amylase may have retuned to normal level, and the patient may be subjectively asymptomatic. In this phase, the radiologic findings are relatively greater significance than laboratory data. In the conventional radiologic study, pancreatic pseudocyst have been frequently confused with other retroperitoneal mass, but recently with clinical application of ultrasound and CT scan, more accurate diagnosis can be obtained. The brief results are as follows: 1. Male to female ratio was 3 : 2 in 15 patients. Incidence was more common in young adult age. Most frequent symptom was epigastric pain, and which was noted in 11 cases of patients. 7 cases of patients had past history of abdominal trauma and past history of pancreatitis was only in 1 case. Most common laboratory findings was leukocytosis in 8 cases of patients and elevated serum amylase was also noted in 7 cases. 2. In each 5 cases of patients, plain chest roentgenologic evidence of left side pleural effusion and hemidiaphragm elevation were observed. 3. On flat abdomen film, soft mass shadow was visualized in 8 cases of patients. On UGI series, evidence of retrogastric space widening was observed in 11 cases of patients. 4. The location of pseudocyst is mainly in body and tail of pancrease in 11 cases of patients. 5. More accureable diagnosis can be obtained through application of ultrasound and CT scan

  12. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations.

    Science.gov (United States)

    Toouli, James; Biankin, Andrew V; Oliver, Mark R; Pearce, Callum B; Wilson, Jeremy S; Wray, Nicholas H

    2010-10-18

    Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.

  13. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Science.gov (United States)

    Greco, Stephanie H; Tomkötter, Lena; Vahle, Anne-Kristin; Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  14. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Directory of Open Access Journals (Sweden)

    Stephanie H Greco

    Full Text Available Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  15. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia

    Science.gov (United States)

    Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H. Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival. PMID:26172047

  16. Lethal endomyocarditis caused by chronic "Krokodil" intoxication.

    Science.gov (United States)

    Sorrentino, Antonella; Trotta, Silvia; Colucci, Anna Pia; Aventaggiato, Lucia; Marzullo, Andrea; Solarino, Biagio

    2018-03-19

    "Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.

  17. Human cooperation by lethal group competition.

    Science.gov (United States)

    Egas, Martijn; Kats, Ralph; van der Sar, Xander; Reuben, Ernesto; Sabelis, Maurice W

    2013-01-01

    Why humans are prone to cooperate puzzles biologists, psychologists and economists alike. Between-group conflict has been hypothesized to drive within-group cooperation. However, such conflicts did not have lasting effects in laboratory experiments, because they were about luxury goods, not needed for survival ("looting"). Here, we find within-group cooperation to last when between-group conflict is implemented as "all-out war" (eliminating the weakest groups). Human subjects invested in helping group members to avoid having the lowest collective pay-off, whereas they failed to cooperate in control treatments with random group elimination or with no subdivision in groups. When the game was repeated, experience was found to promote helping. Thus, not within-group interactions alone, not random group elimination, but pay-off-dependent group elimination was found to drive within-group cooperation in our experiment. We suggest that some forms of human cooperation are maintained by multi-level selection: reciprocity within groups and lethal competition among groups acting together.

  18. A diagnostic pitfall: pancreatic tuberculosis, not pancreatic cancer

    International Nuclear Information System (INIS)

    Samuel, D.O.; Mukhtar, A.A.M.; Philip, I.O.

    2013-01-01

    Abdominal tuberculosis (TB) is one of the most common forms of extra-pulmonary tuberculosis and is responsible for considerable morbidity and mortality globally. Tuberculosis can involve any part of the gastrointestinal tract from mouth to anus, the peritoneum, liver, spleen and the pancreatobiliary system. The occurrence of abdominal TB is independent of pulmonary disease in most patients, with a reported incidence of co-existing pulmonary disease varying from 6 to 38% worldwide. We report a case of pancreatic tuberculosis also involving the vertebrae, which was initially treated as a case of pancreatic cancer. (author)

  19. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Ozaki, Yayoi; Hamano, Hideaki; Oguchi, Kazuhiro

    2008-01-01

    Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis. FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis. (author)

  20. The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets.

    Science.gov (United States)

    Li, Shuang; Li, Rui; Wang, Heping; Li, Lisha; Li, Huiyu; Li, Yulin

    2018-04-01

    An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

  1. Emphysematous pancreatitis predisposed by Olanzapine

    Directory of Open Access Journals (Sweden)

    Sukhen Samanta

    2014-01-01

    Full Text Available A 32-year-old male presented to our intensive care unit with severe abdominal pain and was diagnosed as acute pancreatitis after 2 months of olanzapine therapy for bipolar disorder. His serum lipase was 900 u/L, serum triglyceride 560 mg/dL, and blood sugar, fasting and postprandial were 230 and 478 mg/dL, respectively on admission. Contrast enhanced computed tomography (CECT of abdomen was suggestive of acute pancreatitis. Repeat CECT showed gas inside pancreas and collection in peripancreatic area and patient underwent percutaneous drainage and antibiotics irrigation through the drain into pancreas. We describe the rare case of emphysematous pancreatitis due to development of diabetes, hypertriglyceridemia and immunosuppression predisposed by short duration olanzapine therapy.

  2. Dynamic MRI of pancreatic neoplasms

    International Nuclear Information System (INIS)

    Furukawa, Nobuyoshi; Takayasu, Ken-ichi; Muramatu, Yukio

    1995-01-01

    The usefulness of dynamic MRI study using contrast media is studied on pancreatic tumors. This method was useful in detecting small lesion of pancreatic tumor, however, T1-weighted SE method was more useful in detecting swelling lesions or diagnosing degree of tumors. Although endocrine tumors are depicted by contrast media, careful attention is needed since there are some hypovascular cases. T2-weighted image is commonly performed to detect the morphology of cystic content and the correlation between the pancreas and bile duct in cystic tumors, however, dynamic study was more useful in proving vascularity of serous cystadenoma and differentiating malignant or benign mucous cystic tumors by depicting intracystic torous components. In performing MR imaging on pancreatic diseases, it is necessary to select appropriate imaging procedure, and dynamic study should be included and used in a rational manner. (S.Y.)

  3. Pancreatic effects of GLP-1

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Albrechtsen, Nicolai Jacob Wewer; Holst, Jens Juul

    2014-01-01

    -dependent manner. But perhaps equally importantly, GLP-1’s glucose lowering effects are attributable to a strong inhibition of glucagon secretion, and, thereby, a reduction of hepatic glucose output. The effects of GLP-1 on insulin secretion are mediated by binding of the hormone to the receptor (GLP-1r......) on the pancreatic β-cell, which increases intracellular cAMP levels and sets in motion a plethora of events that lead to secretion. In contrast, the inhibitory effect of GLP-1 on the α-cell may be indirect, involving paracrine intra-islet regulation by somatostatin and possibly also insulin, although GLP-1 also...... inhibits glucagon secretion in patients with type 1 diabetes mellitus. Besides these acute effects on the endocrine pancreas, GLP-1 also appears to have a positive effect on β-cell mass. In the following we will review GLP-1’s pancreatic effects with particular focus on its effects on pancreatic islets...

  4. Comprehensive proteomic analysis of human pancreatic juice

    DEFF Research Database (Denmark)

    Grønborg, Mads; Bunkenborg, Jakob; Kristiansen, Troels Zakarias

    2004-01-01

    Proteomic technologies provide an excellent means for analysis of body fluids for cataloging protein constituents and identifying biomarkers for early detection of cancers. The biomarkers currently available for pancreatic cancer, such as CA19-9, lack adequate sensitivity and specificity...... contributing to late diagnosis of this deadly disease. In this study, we carried out a comprehensive characterization of the "pancreatic juice proteome" in patients with pancreatic adenocarcinoma. Pancreatic juice was first fractionated by 1-dimensional gel electrophoresis and subsequently analyzed by liquid...... in this study could be directly assessed for their potential as biomarkers for pancreatic cancer by quantitative proteomics methods or immunoassays....

  5. Concurrent AURKA and MYCN Gene Amplifications Are Harbingers of Lethal TreatmentRelated Neuroendocrine Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Juan Miguel Mosquera

    2013-01-01

    Full Text Available Neuroendocrine prostate cancer (NEPC, also referred to as anaplastic prostate cancer, is a lethal tumor that most commonly arises in late stages of prostate adenocarcinoma (PCA with predilection to metastasize to visceral organs. In the current study, we explore for evidence that Aurora kinase A (AURKA and N-myc (MYCN gene abnormalities are harbingers of treatment-related NEPC (t-NEPC. We studied primary prostate tissue from 15 hormone naïve PCAs, 51 castration-resistant prostate cancers, and 15 metastatic tumors from 72 patients at different stages of disease progression to t-NEPC, some with multiple specimens. Histologic evaluation, immunohistochemistry, and fluorescence in situ hybridization were performed and correlated with clinical variables. AURKA amplification was identified in overall 65% of PCAs (hormone naïve and treated from patients that developed t-NEPC and in 86% of metastases. Concurrent amplification of MYCN was present in 70% of primary PCAs, 69% of treated PCAs, and 83% of metastases. In contrast, in an unselected PCA cohort, AURKA and MYCN amplifications were identified in only 5% of 169 cases. When metastatic t-NEPC was compared to primary PCA from the same patients, there was 100% concordance of ERG rearrangement, 100% concordance of AURKA amplification, and 60% concordance of MYCN amplification. In tumors with mixed features, there was also 100% concordance of ERG rearrangement and 94% concordance of AURKA and MYCN co-amplification between areas of NEPC and adenocarcinoma. AURKA and MYCN amplifications may be prognostic and predictive biomarkers, as they are harbingers of tumors at risk of progressing to t-NEPC after hormonal therapy.

  6. A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

    Science.gov (United States)

    Cohen, Steven J; Zalupski, Mark M; Modiano, Manuel R; Conkling, Paul; Patt, Yehuda Z; Davis, Peg; Dorr, Robert T; Boytim, Michelle L; Hersh, Evan M

    2010-07-01

    Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). One hundred five patients received 340 treatment cycles (median 2, range 1-16). median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.

  7. Acute Pancreatitis and Pancreatic Cancer Risk: A Nationwide Matched-cohort Study in Denmark

    DEFF Research Database (Denmark)

    Kirkegård, Jakob; Cronin Fenton, Deirdre; Heide-Jørgensen, Uffe

    2018-01-01

    . Pancreatic cancer risk was expressed as hazard ratios (HRs) with 95% CIs, calculated using the Cox proportional hazards model. Cox models were stratified by age, sex, and year of pancreatitis diagnosis and adjusted for alcohol- and smoking-related conditions, and Charlson Comorbidity Index score. Results We...... included 41,669 patients diagnosed with incident acute pancreatitis and 208,340 comparison individuals. Patients with acute pancreatitis had an increased risk of pancreatic cancer compared with the age- and sex-matched general population throughout the follow-up period. The risk decreased over time......Background & Aims Acute pancreatitis may be a risk factor for pancreatic cancer. However, findings from studies on this association are conflicting. We investigated the association between acute pancreatitis and increased risk of pancreatic cancer. Methods We conducted a nationwide, population...

  8. Chronic Pancreatitis: A Changing Etiology?

    OpenAIRE

    Raffaele Pezzilli; Andrea Lioce; Luca Frulloni

    2008-01-01

    In 1998, Lankisch and Banks reported that the prevalence of chronic pancreatitis appeared to be in the range of 3-10 per 100,000 people in many parts of the world [1]. They also emphasized that the most important medical problems associated with the disease included abdominal pain, steatorrhea, diabetes mellitus and the possibility that chronic pancreatitis may be considered a premalignant condition [2, 3]. In 2002, in a well-written review, Banks pointed out that the two important forms were...

  9. Differential diagnosis of groove pancreatic carcinomas vs. groove pancreatitis: Usefulness of the portal venous phase

    International Nuclear Information System (INIS)

    Ishigami, Kousei; Tajima, Tsuyoshi; Nishie, Akihiro; Kakihara, Daisuke; Fujita, Nobuhiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Irie, Hiroyuki; Nakamura, Masafumi; Takahata, Shunichi; Ito, Tetsuhide; Honda, Hiroshi

    2010-01-01

    Purpose: To clarify if the portal venous phase is helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis. Materials and methods: MDCT and MRI of groove pancreatic carcinomas (n = 7) and groove pancreatitis (n = 15) were retrospectively reviewed by two radiologists independently. The signal intensity on T2-weighted images was subjectively assessed. The presence or absence of common bile duct (CBD) and main pancreatic duct (MPD) strictures, calcifications, and cystic lesions was evaluated. Additionally, the appearance of groove pancreatic carcinoma and that of groove pancreatitis in the portal venous phase on dynamic MDCT and MRI were compared. Results: There were no significant differences in the signal intensity on T2-weighted images and in the presence or absence of CBD and MPD strictures, calcifications, and cystic lesions between groove pancreatic carcinomas and groove pancreatitis. However, patchy focal enhancement in the portal venous phase was more commonly observed in groove pancreatitis than groove pancreatic carcinoma (Reviewers 1 and 2: 14/15 [93.3%] vs. 1/7 [14.3%], P < 0.0001). In addition, peripheral enhancement was only seen in groove pancreatic carcinomas (Reviewer 1: 4/7 [57.1%] vs. 0/15 [0%], P < 0.005, and Reviewer 2: 3/7 [42.9%] vs. 0/15 [0%], P < 0.05). Conclusion: The portal venous phase may be helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis.

  10. A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer.

    Science.gov (United States)

    Perán, Macarena; López-Ruiz, Elena; García, María Ángel; Nadaraia-Hoke, Shorena; Brandt, Ralf; Marchal, Juan A; Kenyon, Julian

    2017-10-25

    Proteolytic enzymes have shown efficacy in cancer therapy. We present a combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP) using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed by matrigel-based tube formation and by fibrous capsule formation assays. Furthermore, cell invasion and wound healing assays together with qRT-PCR determination of epithelial-to-mesenchymal transition (EMT) markers were performed on human cancer cells treated with PRP. Additionally, in vivo pharmacokinetic studies were implemented and the PRP's anti-tumour efficacy was explored against orthotopic pancreatic and ovarian cancer tumours. PRP formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer cell migration and invasiveness; and to be an effective and well tolerated in vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository formulation containing both pancreatic pro-enzymes in the context of a UK Pharmaceuticals Special Scheme was evaluated in advanced cancer patients. Consequently, PRP could have relevant oncological clinical applications for the treatment of advanced or metastatic pancreatic adenocarcinoma and advanced epithelial ovarian cancer.

  11. Acute pancreatitis in cats with hepatic lipidosis.

    Science.gov (United States)

    Akol, K G; Washabau, R J; Saunders, H M; Hendrick, M J

    1993-01-01

    The purpose of this study was to characterize the incidence, clinical features, and prognosis of acute pancreatitis in cats with hepatic lipidosis. Of 13 cats histologically diagnosed with hepatic lipidosis between July 1988, and November 1989, 5(38%) were also histologically diagnosed with acute pancreatitis. In cats with hepatic lipidosis alone, the signalment, history, physical examination, and clinicopathologic findings were generally indistinguishable from those of cats with concurrent acute pancreatitis except that cats with acute pancreatitis were more likely to be cachectic and to have coagulation abnormalities. Hepatomegaly was seen on abdominal radiographs in both groups. Of the 5 cats with concurrent acute pancreatitis, abdominal ultrasonography detected 1 cat with a hypoechoic pancreas and 5 with peritoneal effusion; those abnormalities were not seen in cats without concurrent acute pancreatitis. Cats with concurrent acute pancreatitis had only a 20% recovery rate, compared with a 50% recovery rate in cats with hepatic lipidosis alone. We conclude that cats with hepatic lipidosis should be rigorously evaluated for concurrent acute pancreatitis because of 1) the rate of disease coincidence, 2) the inability of signalment, history, physical examination, and clinicopathologic findings to adequately distinguish between hepatic lipidosis and acute pancreatitis, 3) the worse prognosis associated with concurrent acute pancreatitis, and 4) the opposing nutritional strategies for hepatic lipidosis and acute pancreatitis.

  12. New Insights into the Pathogenesis of Pancreatitis

    Science.gov (United States)

    Sah, Raghuwansh P.; Dawra, Rajinder K.; Saluja, Ashok K.

    2014-01-01

    Purpose of review In this article, we review important advances in our understanding of the mechanisms of pancreatitis. Recent Findings The relative contribution of intra-pancreatic trypsinogen activation and NFκB activation, the two major early independent cellular events in the etiology of pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as it is believed to be the central pathogenic event of pancreatitis However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis through NFκB activation. Further, chronic pancreatitis in the caerulein model develops independently of typsinogen activation. Sustained activation of the NFκB pathway, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. IL-6 was identified as a key cytokine mediating pancreatitis-associated lung injury. Summary Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis. PMID:23892538

  13. Epidemiology and therapies for metastatic sarcoma

    Science.gov (United States)

    Amankwah, Ernest K; Conley, Anthony P; Reed, Damon R

    2013-01-01

    Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma), adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor) and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma) in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. PMID:23700373

  14. Metastatic neoplasms of the central nervous system

    International Nuclear Information System (INIS)

    Fenner, W.R.

    1990-01-01

    Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of ''metastatic neoplasm.'' In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed

  15. Emerging Therapies in Metastatic Prostate Cancer.

    Science.gov (United States)

    Sonnenburg, Daniel W; Morgans, Alicia K

    2018-04-11

    In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.

  16. Imaging in the diagnosis of chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Vasile D. Balaban

    2014-12-01

    Full Text Available Chronic pancreatitis is characterised by progressive and irreversible damage of the pancreatic parenchyma and ductal system, which leads to chronic pain, loss of endocrine and exocrine functions. Clinically, pancreatic exocrine insufficiency becomes apparent only after 90% of the parenchima has been lost. Despite the simple definition, diagnosing chronic pancreatitis remains a challenge, especially for early stage disease. Because pancreatic function tests can be normal until late stages and have significant limitations, there is an incresing interest in the role of imaging techniques for the diagnosis of chronic pancreatitis. In this article we review the utility and accuracy of different imaging methods in the diagnosis of chronic pancreatitis, focusing on the role of advanced imaging (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

  17. [Tropical chronic pancreatitis in a young patient].

    Science.gov (United States)

    Reyes, J; Ginard, D; Barranco, L; Riera, J; Obrador, A

    2001-11-01

    Tropical chronic pancreatitis is a form of idiopathic chronic pancreatitis that has not previously been described in Spain. Typically it is related to dietary factors and malnutrition, although genetic factors may also play a significant role in the development of the disease. We report a case of chronic tropical pancreatitis in a 27-year-old woman from the Dominican Republic domiciled in Spain since 1992. The patient was admitted to our hospital for acute pancreatitis that fulfilled the diagnostic criteria (clinical and radiological) for chronic tropical pancreatitis. This case has led us to review this uncommon entity. Because of the increasing number of immigrants from tropical countries, chronic tropical pancreatitis will probably need to be taken into account in the differential diagnosis of chronic pancreatitis in our patients.

  18. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

    2017-09-01

    Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.

  19. Pancreatic pseudocysts in chronic pancreatitis. Surgical or interventional drainage?

    NARCIS (Netherlands)

    Boerma, D.; Obertop, H.; Gouma, D. J.

    2000-01-01

    Pseudocyst formation is a well-known complication of acute and chronic pancreatitis. Many pseudocysts are asymptomatic and may resolve without intervention. For a symptomatic pseudocyst drainage is indicated. Although surgical cystoenterostomy has been the treatment of choice for many years,

  20. Elevation of serum pancreatic amylase and distortion of pancreatic ...

    African Journals Online (AJOL)

    Background: Diabetes mellitus has been shown to cause severe impairment in exocrine pancreatic function and cyto-architecture. Ocimum grattissimum has been reported to lower blood glucose levels in experimental diabetic animals. This study, therefore, aims to investigate if treatment with O. grattissimum can alleviate ...