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Sample records for type peripheral cholangiocarcinoma

  1. Hepatic abscess versus peripheral cholangiocarcinoma: Sonographic differentiation

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    Chung, Hwan Hoon; Kim, Yun Hwan; Kang, Chang Ho; Chung, Kyoo Byung; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of); Lee, Chang Hee [Kunkuk University College of Medicine, Chung-Ju Hospital, Chung-Ju (Korea, Republic of)

    2000-12-15

    To find out the sonographic findings that are useful to differentiate hepatic abscess from peripheral cholangiocarcinoma. Twenty-two hepatic abscesses and 22 peripheral cholangiocarcinomas which had been confirmed histologically were included in this study. Objective points were echo characteristics of the lesion, internal septation, presence of peripheral low echoic rim, demarcation from normal liver(well or poorly defined), posterior enhancement, multiplicity, dilatation of bile duct(obstructive or non-obstructive), intrahepatic duct stone, pleural effusion, and intra-abdominal fluid collection. Echo characteristics of the lesion were classified in-to four types. Type I; Predominantly echogenic with hypoechoic portion, type II; Echogenic without hypoechoic portion, type III; Predominantly hypoechoic with echogenic portion, type IV; Hypoechoic without echogenic portion. 1)Nine abscesses and 2 peripheral cholangiocarcinomas were type I(p=0.037), 2)One abscess and 18 peripheral cholangiocarcinomas were type II(p=0.001), 3)Seven abscesses and none of peripheral cholangiocarcinomas were type III(p=0.001), 4)Five abscesses and 2 peripheral cholangiocarcinomas were type IV(p=0.410). Only 7 abscesses showed internal septations(p=0.013). One abscess and 9 peripheral cholangiocarcinomas showed peripheral hypoechoic halos(p=0.012). Only 9 peripheral cholangiocarcinomas showed obstructive bile duct dilatation (p=0.001). There were no statistically significant differences between abscess and peripheral cholangiocarcinoma on other objective points. Predominantly echogenic with hypoechoic portion, predominantly hypoechoic with echogenic portion, and internal septation are the features suggestive of hepatic abscess, and echogenic without hypoechoic portion, peripheral hypoechoic halo, obstructive bile duct dilatation are suggestive of peripheral cholangiocarcinoma. Therefore these sonographic findings are helpful to differentiate hepatic abscess from peripheral

  2. Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.

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    Zhang, Xu-Feng; Bagante, Fabio; Chen, Qinyu; Beal, Eliza W; Lv, Yi; Weiss, Matthew; Popescu, Irinel; Marques, Hugo P; Aldrighetti, Luca; Maithel, Shishir K; Pulitano, Carlo; Bauer, Todd W; Shen, Feng; Poultsides, George A; Soubrane, Olivier; Martel, Guillaume; Koerkamp, B Groot; Guglielmi, Alfredo; Itaru, Endo; Pawlik, Timothy M

    2018-05-01

    Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. A total of 912 patients with mass-forming peripheral intrahepatic cholangiocarcinoma, 101 patients with hilar type intrahepatic cholangiocarcinoma, and 159 patients with hilar cholangiocarcinoma undergoing curative resection from 2000 to 2015 were included from two multi-institutional databases. Clinicopathologic characteristics and short- and long-term outcomes were compared among the 3 groups. Patients with hilar type intrahepatic cholangiocarcinoma had more aggressive tumor characteristics (eg, higher frequency of vascular invasion and lymph nodes metastasis) and experienced more extensive resections in comparison with either peripheral intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma patients. The odds of lymphadenectomy and R0 resection rate among patients with hilar type intrahepatic cholangiocarcinoma were comparable with hilar cholangiocarcinoma patients, but higher than peripheral intrahepatic cholangiocarcinoma patients (lymphadenectomy incidence, 85.1% vs 42.5%, P hilar type intrahepatic cholangiocarcinoma experienced a higher rate of technical-related complications compared with peripheral intrahepatic cholangiocarcinoma patients. Of note, hilar type intrahepatic cholangiocarcinoma was associated with worse disease-specific survival and recurrence-free survival after curative resection versus peripheral intrahepatic cholangiocarcinoma (median disease-specific survival, 26.0 vs 54.0 months, P hilar cholangiocarcinoma (median disease-specific survival, 26.0 vs 49.0 months, P = .003; median recurrence-free survival

  3. Computed tomographic findings of intrahepatic peripheral cholangiocarcinoma

    International Nuclear Information System (INIS)

    Woo, Seong Ku; Suh, Soo Jhi; Kim, Ho Joon; Chun, Byung Hee

    1986-01-01

    Cholangiocarcinoma is synonymous with bile duct carcinoma, and can originate in a small intrahepatic bile duct (peripheral type), a major intrahepatic duct including the hepatic hills, an extrahepatic duct, or near the papilla of Vater (central type). In a sense bile duct carcinoma of the peripheral type is cholangiocarcinoma of the liver; it has the same gross configuration as hepatocellular carcinoma, resulting in difficulty to differentiate on the CT. The authors studied CT findings of 14 cases of pathologically proven peripheral type cholangiocarcinoma of the liver during the last 4 years. The results were as follows: 1. Of 14 cases, 8 were female and 6 were male, and the age ranged from 5th to 7th decades. 2. Preoperative clinical diagnosis were as follows: hepatoma 8 cases, abscess 5 cases and metastasis 1 case in order of frequency. 3. Diagnosis were confirmed by hepatic lobectomy in 7 cases, wedge resection in 5 cases and needle biopsy in 2 case. 4. Laboratory findings were not specific, but there were only 2 cases with elevated alpha-fetoprotein level. 5. Associated diseases were gallstones in 1 case, intrahepatic duct stones in 1 case, extrahepatic duct stones in 2 cases, acute or chronic cholecystitis in 5 cases and CS in 3 cases. 6. Angiographic and scintigraphic findings were helpful in differential diagnosis from hepatoma but ultrasonography was non-specific. 7. The number of tumor were solitary in 12 cases and multiple in 2 cases. Among solitary cases, the site of involvement of the liver were right lobe in 8 cases and left lobe in 4 cases. 8. Common CT features of the intrahepatic peripheral cholangiocinoma of the liver were irregular, inhomogeneous, occasionally peripherally enhancing, low density liver mass, frequently accompanied by diffuse or segmental dilatation of the intrahepatic bile duct. If there were normal alpha fetoprotein level, positive skin and/or stool examination for CS and diffuse or segmental dilatation of the intrahepatic duct

  4. Computed tomography of intrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Kamimura, Ryoichi; Takashima, Tsutomu; Matsui, Osamu; Tsuji, Masahiko; Hirose, Shoichiro.

    1983-01-01

    Intrahepatic cholangiocarcinoma is an uncommon tumor as primary hepatic neoplasm. Five cases of cholangiocarcinoma, mass forming peripheral type, are reported about its CT findings. They were manifested as a poorly marginated low density mass with a irregular stellate area. In one case, a cut section of the gross specimen following surgery showed a central callagenous scar and vessels within the necrotic tumor. (author)

  5. Bile Duct Cancer (Cholangiocarcinoma)

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    ... Home > Types of Cancer > Bile Duct Cancer (Cholangiocarcinoma) Bile Duct Cancer (Cholangiocarcinoma) This is Cancer.Net’s Guide to Bile Duct Cancer (Cholangiocarcinoma). Use the menu below to ...

  6. Pure laparoscopic radical resection for type IIIa hilar cholangiocarcinoma.

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    Zhang, Cheng-Wu; Liu, Jie; Hong, De-Fei; Wang, Zhi-Fei; Hu, Zhi-Ming; Huang, Dong-Shen; Shang, Min-Jie; Yao, Wei-Feng

    2018-03-01

    Pure laparoscopic radical resection of hilar cholangiocarcinoma is still a challenging procedure, in which laparoscopic lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy were included [1-4]. Relative report is rare in the world up to now. Hilar cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis or vessel invasion [5, 6]. We recently had a patient who underwent a pure laparoscopic extended right hepatectomy and lymph node dissection and hepaticojejunostomy for a type IIIa hilar cholangiocarcinoma. The tumor was 20 × 15 × 12 mm in diameter and located in the right bile duct and common hepatic duct. Radiological examination showed that hepatic artery and portal vein was not invaded. After the division and mutilation of the right hepatic artery and the right portal vein, short hepatic veins were divided and cut off with clip and ultrasound knife from the anterior face of the vena cava. Mobilization was performed after the devascularization of the right liver, followed by the transection of liver parenchymal with CUSA and ultrasound knife. Finally, left hepatic bile duct jejunum Roux-en-Y reconstruction was performed. This patient underwent successfully with a totally laparoscopic procedure. An extended right hepatectomy (right hemihepatectomy combined with caudate lobectomy) and complete lymph node dissection and hepaticojejunostomy were performed in this operation. The operation time was nearly 590 min, and the intraoperative blood loss was about 300 ml. No obvious complication was observed and the postoperative hospital stay was 11 days. The final diagnosis of the hilar cholangiocarcinoma with no lymph node metastasis was pT2bN0M0 stage II (American Joint Committee on Cancer, AJCC). Pure laparoscopic resection for hilar cholangiocarcinoma was proved safe and feasible, which enabled the patient to recover early and have an opportunity to receive chemotherapy as soon as possible. We

  7. Laparoscopic resection of hilar cholangiocarcinoma.

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    Lee, Woohyung; Han, Ho-Seong; Yoon, Yoo-Seok; Cho, Jai Young; Choi, YoungRok; Shin, Hong Kyung; Jang, Jae Yool; Choi, Hanlim

    2015-10-01

    Laparoscopic resection of hilar cholangiocarcinoma is technically challenging because it involves complicated laparoscopic procedures that include laparoscopic hepatoduodenal lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy. There are currently very few reports describing this type of surgery. Between August 2014 and December 2014, 5 patients underwent total laparoscopic or laparoscopic-assisted surgery for hilar cholangiocarcinoma. Two patients with type I or II hilar cholangiocarcinoma underwent radical hilar resection. Three patients with type IIIa or IIIb cholangiocarcinoma underwent extended hemihepatectomy together with caudate lobectomy. The median (range) age, operation time, blood loss, and length of hospital stay were 63 years (43-76 years), 610 minutes (410-665 minutes), 650 mL (450-1,300 mL), and 12 days (9-21 days), respectively. Four patients had a negative margin, but 1 patient was diagnosed with high-grade dysplasia on the proximal resection margin. The median tumor size was 3.0 cm. One patient experienced postoperative biliary leakage, which resolved spontaneously. Laparoscopic resection is a feasible surgical approach in selected patients with hilar cholangiocarcinoma.

  8. Palliative treatment with radiation-emitting metallic stents in unresectable Bismuth type III or IV hilar cholangiocarcinoma.

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    Lu, Jian; Guo, Jin-He; Zhu, Hai-Dong; Zhu, Guang-Yu; Wang, Yong; Zhang, Qi; Chen, Li; Wang, Chao; Pan, Tian-Fan; Teng, Gao-Jun

    2017-01-01

    The emerging data for stenting in combination with brachytherapy in unresectable hilar cholangiocarcinoma are encouraging. The aim of this study was to evaluate the efficacy and safety of radiation-emitting metallic stents (REMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma. Consecutive patients who underwent percutaneous placement with REMS or uncovered self-expandable metallic stent (SEMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma between September 2011 and April 2016 were identified into this retrospective study. Data on patient demographics and overall survival, functional success, stent patency and complications were collected at the authors' hospital. A total of 59 patients were included: 33 (55.9%) in the REMS group and 26 (44.1%) in the SEMS group. The median overall survival was 338 days in the REMS group and 141 days in the SEMS group (philar cholangiocarcinoma, and seems to prolong survival as well as patency of stent in these patients.

  9. [Clinical value of MRI united-sequences examination in diagnosis and differentiation of morphological sub-type of hilar and extrahepatic big bile duct cholangiocarcinoma].

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    Yin, Long-Lin; Song, Bin; Guan, Ying; Li, Ying-Chun; Chen, Guang-Wen; Zhao, Li-Ming; Lai, Li

    2014-09-01

    To investigate MRI features and associated histological and pathological changes of hilar and extrahepatic big bile duct cholangiocarcinoma with different morphological sub-types, and its value in differentiating between nodular cholangiocarcinoma (NCC) and intraductal growing cholangiocarcinoma (IDCC). Imaging data of 152 patients with pathologically confirmed hilar and extrahepatic big bile duct cholangiocarcinoma were reviewed, which included 86 periductal infiltrating cholangiocarcinoma (PDCC), 55 NCC, and 11 IDCC. Imaging features of the three morphological sub-types were compared. Each of the subtypes demonstrated its unique imaging features. Significant differences (P big bile duct cholangiocarcinoma. MRI united-sequences examination can accurately describe those imaging features for differentiation diagnosis.

  10. [Clinical value of "Kou mode of hepatic hilar anastomosis" in resection of type III or IV hepatic hilar cholangiocarcinoma].

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    He, Xiao-dong; Liu, Wei; Tao, Lian-yuan; Zhang, Zhen-huan; Cai, Lei; Zhang, Shuang-min

    2009-08-01

    To evaluate the surgical technique of "Kou mode of hepatic hilar anastomosis" in the treatment for type III or IV hilar cholangiocarcinoma. The clinical data of 89 patients with type III or IV hilar cholangiocarcinoma surgically treated in our department between Jan. 1990 and Jan. 2008 were retrospectively analyzed. Since January 2000, "Kou mode of hepatic hilar anastomosis" was performed for some patients with advanced hilar cholangiocarcinoma. The patients were divided into two groups: group A treated between 1990 and 1999, group B between 2000 and 2008. The rate of resection, therapeutic efficacy and complications in these two groups were compared, respectively. Of the 37 cases with hilar cholangiocarcinoma in group A, 4 were surgically treated (10.8%), with 1 (2.7%) radical resection and 3 (8.1%) palliative resection. Among the 52 cases with hilar cholangiocarcinoma in the group B, 35 (67.3%) received surgical resection, of them 15 (28.8%) underwent radical resection and 20 (38.5%) had palliative resection. Twenty-eight of these 35 cases underwent the "Kou mode of hepatic hilar anastomosis". The resection rate of advanced hilar cholangiocarcinoma in the group B was significantly higher than that in group A (P anastomosis" developed bile leakage to a varying degree and recovered after drainage and symptomatic treatment. The resection rate of type III or IV advanced hilar cholangiocarcinoma can be remarkably improved by using a novel alternative surgical technique called "Kou mode of hepatic hilar anastomosis". However, the long-term outcome still needs to be determined by close follow-up and further observation.

  11. Interventional therapy of hilar cholangiocarcinoma in type III and IV

    International Nuclear Information System (INIS)

    Fan Weijun; Wu Peihong; Zhang Liang; Huang Jinhua; Zhang Fujun; Gu Yangkui; Zhao Ming; Huang Xianglong; Guo Changyu

    2005-01-01

    Objective: To explore the role of synthetic interventional therapy for hilar cholangiocarcinoma in type III and IV. Methods: Twenty-one patients with obstructive cholestasis were pathological confirmed as cholangioadenocarcinoma, and they were classified as type III and IV cholangioadenocarcinoma by CT, MRCP, and percutaneous transhepatic cholangiography. Percutaneous transhepatic cholangiography with internal and external drainage (PTCD), multipolar radiofrequency (RF) ablation, biliary stent endoprosthesis, and interventional adjuvant chemotherapy were applied sequentially. Results: All masses presented with density diminution in CT one month after RF ablation, in which 13 masses had about 30% reduction in size, 4 masses had about 20% reduction in size, and 4 masses remained unchanged. All the masses presented with size reduction with an average of 37% in follow-up CT after 6 months, and the most remarkable size reduction was 60%. The direct and indirect bilirubin levels prompt returned to normal range in 17 cases one month after synthetic interventional therapy and returned to normal range in all cases 6 months later. All patients survived with the follow-up period ranging from 9 to 24 months, with the mean survival time of 14 months. Conclusion: Synthetic interventional therapy is a micro-invasive and effective treatment for type III and IV cholangiocarcinoma. (authors)

  12. MDCT assessment of resectability in hilar cholangiocarcinoma.

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    Ni, Qihong; Wang, Haolu; Zhang, Yunhe; Qian, Lijun; Chi, Jiachang; Liang, Xiaowen; Chen, Tao; Wang, Jian

    2017-03-01

    The purpose of this study is to investigate the value of multidetector computed tomography (MDCT) assessment of resectability in hilar cholangiocarcinoma, and to identify the factors associated with unresectability and accurate evaluation of resectability. From January 2007 to June 2015, a total of 77 consecutive patients were included. All patients had preoperative MDCT (with MPR and MinIP) and surgical treatment, and were pathologically proven with hilar cholangiocarcinoma. The MDCT images were reviewed retrospectively by two senior radiologists and one hepatobiliary surgeon. The surgical findings and pathologic results were considered to be the gold standard. The Chi square test was used to identify factors associated with unresectability and accurate evaluation of resectability. The sensitivity, specificity, and overall accuracy of MDCT assessment were 83.3 %, 75.9 %, and 80.5 %, respectively. The main causes of inaccuracy were incorrect evaluation of N2 lymph node metastasis (4/15) and distant metastasis (4/15). Bismuth type IV tumor, main or bilateral hepatic artery involvement, and main or bilateral portal vein involvement were highly associated with unresectability (P hilar cholangiocarcinoma. Bismuth type IV tumor and main or bilateral vascular involvement highly suggest the unresectability of hilar cholangiocarcinoma. Patients without biliary drainage have a more accurate MDCT evaluation of resectability. We suggest MDCT should be performed before biliary drainage to achieve an accurate evaluation of resectability in hilar cholangiocarcinoma.

  13. Genetics Home Reference: cholangiocarcinoma

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    ... year in the United States. This type of cancer occurs much more frequently in Southeast Asian countries such as Thailand, where it is related to infection with a parasite that is common there. For unknown reasons, cholangiocarcinoma ...

  14. Risk factors and classifications of hilar cholangiocarcinoma.

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    Suarez-Munoz, Miguel Angel; Fernandez-Aguilar, Jose Luis; Sanchez-Perez, Belinda; Perez-Daga, Jose Antonio; Garcia-Albiach, Beatriz; Pulido-Roa, Ysabel; Marin-Camero, Naiara; Santoyo-Santoyo, Julio

    2013-07-15

    Cholangiocarcinoma is the second most common primary malignant tumor of the liver. Perihilar cholangiocarcinoma or Klatskin tumor represents more than 50% of all biliary tract cholangiocarcinomas. A wide range of risk factors have been identified among patients with Perihilar cholangiocarcinoma including advanced age, male gender, primary sclerosing cholangitis, choledochal cysts, cholelithiasis, cholecystitis, parasitic infection (Opisthorchis viverrini and Clonorchis sinensis), inflammatory bowel disease, alcoholic cirrhosis, nonalcoholic cirrhosis, chronic pancreatitis and metabolic syndrome. Various classifications have been used to describe the pathologic and radiologic appearance of cholangiocarcinoma. The three systems most commonly used to evaluate Perihilar cholangiocarcinoma are the Bismuth-Corlette (BC) system, the Memorial Sloan-Kettering Cancer Center and the TNM classification. The BC classification provides preoperative assessment of local spread. The Memorial Sloan-Kettering cancer center proposes a staging system according to three factors related to local tumor extent: the location and extent of bile duct involvement, the presence or absence of portal venous invasion, and the presence or absence of hepatic lobar atrophy. The TNM classification, besides the usual descriptors, tumor, node and metastases, provides additional information concerning the possibility for the residual tumor (R) and the histological grade (G). Recently, in 2011, a new consensus classification for the Perihilar cholangiocarcinoma had been published. The consensus was organised by the European Hepato-Pancreato-Biliary Association which identified the need for a new staging system for this type of tumors. The classification includes information concerning biliary or vascular (portal or arterial) involvement, lymph node status or metastases, but also other essential aspects related to the surgical risk, such as remnant hepatic volume or the possibility of underlying disease.

  15. Hepatic Artery Resection for Bismuth Type III and IV Hilar Cholangiocarcinoma: Is Reconstruction Always Required?

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    Hu, Hai-Jie; Jin, Yan-Wen; Zhou, Rong-Xing; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Liu, Fei; Cheng, Nan-Sheng; Li, Fu-Yu

    2018-03-06

    The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma. We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups. There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6 ± 143.1 min vs. 656.3 ± 192.8 min; P = 0.013) and smaller tumor size (3.0 ± 1.1 cm vs. 2.5 ± 0.9 cm; P = 0.036). The R0 resection margin was comparable between the HAR group and HAR + RCS group (86.2 vs. 85.3%; P > 0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR + RCS group were recorded (P = 0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR + RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P = 0.928). Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma.

  16. Percutaneous intraductal radiofrequency ablation in the management of unresectable Bismuth types III and IV hilar cholangiocarcinoma.

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    Wang, Yu; Cui, Wei; Fan, Wenzhe; Zhang, Yingqiang; Yao, Wang; Huang, Kunbo; Li, Jiaping

    2016-08-16

    To assess the feasibility and safety of percutaneous intraductal radiofrequency ablation (RFA) for unresectable Bismuth types III and IV hilar cholangiocarcinoma. Percutaneous intraductal RFA combined with metal stent placement was successful in all patients without any technical problems; the technical success rate was 100%. Chemotherapy was administered to two patients. After treatment, serum direct bilirubin levels were notably decreased. Six patients died during the follow-up period. Median stent patency from the time of the first RFA and survival from the time of diagnosis were 100 days (95% confidence interval (CI), 85-115 days) and 5.3 months (95% CI, 2.5-8.1 months), respectively. No acute pancreatitis, bile duct bleeding and perforation, bile leakage, or other severe complications occurred. Four cases of procedure-related cholangitis, three cases of postoperative abdominal pain, and five cases of asymptomatic transient increase in serum amylase were observed. One patient who presented with stent blockage 252 days' post-procedure underwent repeat ablation. Between September 2013 and May 2015, nine patients with unresectable Bismuth types III and IV hilar cholangiocarcinoma who were treated with percutaneous intraductal RFA combined with metal stent placement after the percutaneous transhepatic cholangial drainage were included in the retrospective analysis. Procedure-related complications, stent patency, and survival after treatment were investigated. Percutaneous intraductal RFA combined with metal stent placement is a technically safe and feasible therapeutic option for the palliative treatment of unresectable Bismuth types III and IV hilar cholangiocarcinoma. Its long-term efficacy and safety is promising, but needs further study via randomized and prospective trials that include a greater number of patients.

  17. Multidetector Computed Tomography in the Preoperative Workup of Hilar Cholangiocarcinoma

    International Nuclear Information System (INIS)

    Kim, Hyoung Jung; Lee, Dong Ho; Lim, Joo Won; Ko, Young Tae

    2009-01-01

    Hilar cholangiocarcinoma is associated with a dismal prognosis; however, curative resection may offer a chance of cure. Various factors should be considered in the surgical planning for curative resection. These factors include extent of bile duct involvement, relationship between portal vein and tumor involvement, diffuse hepato duodenal ligament infiltration, vascular invasion, lymph node metastasis, peritoneal seeding, and hepatic volume. Using high-quality volume data from multidetector-row computed tomography (MDCT) and adequate postprocessing images, radiologists can provide various types of information, imperative for curative resection of a hilar cholangiocarcinoma. This review illustrates the role of MDCT in the preoperative workup of hilar cholangiocarcinoma

  18. Preoperative biliary drainage in hilar cholangiocarcinoma: When and how?

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    Paik, Woo Hyun; Loganathan, Nerenthran; Hwang, Jin-Hyeok

    2014-01-01

    Hilar cholangiocarcinoma is a tumor of the extrahepatic bile duct involving the left main hepatic duct, the right main hepatic duct, or their confluence. Biliary drainage in hilar cholangiocarcinoma is sometimes clinically challenging because of complexities associated with the level of biliary obstruction. This may result in some adverse events, especially acute cholangitis. Hence the decision on the indication and methods of biliary drainage in patients with hilar cholangiocarcinoma should be carefully evaluated. This review focuses on the optimal method and duration of preoperative biliary drainage (PBD) in resectable hilar cholangiocarcinoma. Under certain special indications such as right lobectomy for Bismuth type IIIA or IV hilar cholangiocarcinoma, or preoperative portal vein embolization with chemoradiation therapy, PBD should be strongly recommended. Generally, selective biliary drainage is enough before surgery, however, in the cases of development of cholangitis after unilateral drainage or slow resolving hyperbilirubinemia, total biliary drainage may be considered. Although the optimal preoperative bilirubin level is still a matter of debate, the shortest possible duration of PBD is recommended. Endoscopic nasobiliary drainage seems to be the most appropriate method of PBD in terms of minimizing the risks of tract seeding and inflammatory reactions. PMID:24634710

  19. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

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    Chantragan Srisomsap

    2010-01-01

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

  20. Percutaneous transhepatic biliary drainage for hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Qian Xiaojun; Jin Wenhui; Dai Dingke; Yu Ping; Gao Kun; Zhai Renyou

    2007-01-01

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

  1. Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma

    International Nuclear Information System (INIS)

    Makita, Chiyoko; Kikuchi, Yasuhiro; Hareyama, Masato; Murakami, Masao; Fuwa, Nobukazu; Hata, Masaharu; Inoue, Tomio; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Suzuki, Motohisa; Ishikawa, Yojiro; Azami, Yusuke; Kato, Takahiro; Tsukiyama, Iwao

    2014-01-01

    We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma. The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement. Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal

  2. Intrahepatic cholangiocarcinoma : gross appearance and corresponding pathologic and radiologic features

    International Nuclear Information System (INIS)

    Yoon, Kwon Ha; Kim, Chang Guhn; Lee, Moon Gyu; Ha, Hyun Kwon; Auh, Yong Ho; Lim, Jae Hoon

    1999-01-01

    To assess the clinical and pathologic features of each type of intrahepatic cholangiocarcinoma, which is divided into three types according to gross appearance, and to determine the efficacy of CT in detecting this tumor. The pathologic and CT features of 53 surgically proven cases of intrahepatic cholangio-carcinoma were reviewed. On the basis of their gross appearance, the tumors were divided into three types, as follows : mass forming (n=33), periductal infiltrating (n=6), and intraductal growth type (n=14). CT scans were analyzed for sensitivity of detection and correlation between a tumors appearance and its histopathology. The most common histopathologic feature of mass forming and periductal infiltrating type was tubular adenocarcinoma, while in the intraductal growth type, papillary adenocarcinoma (100%) was common. With regard to pattern of tumor spread, intrahepatic and lymph node metastasis were more common in the mass forming and periductal infiltrating type than in the intraductal growth type. CT findings including intrahepatic mass, ductal wall thickening or intraductal mass associated with segmental dilatation of intrahepataic bile ducts, corresponded with these morphologic types. This classification according to gross appearance is of considerable value when interpreting the pathologic features of intrahepatic cholangiocarcinoma. CT seems to be a useful modality for the detection of tumors and may be consistent with their gross morphologic findings

  3. Perioperative Management of Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Poruk, Katherine E; Pawlik, Timothy M; Weiss, Matthew J

    2015-10-01

    Cholangiocarcinoma is the most common primary tumor of the biliary tract although it accounts for only 2 % of all human malignancies. We herein review hilar cholangiocarcinoma including its risk factors, the main classification systems for tumors, current surgical management of the disease, and the role chemotherapy and liver transplantation may play in selected patients. We performed a comprehensive literature search using PubMed, Medline, and the Cochrane library for the period 1980-2015 using the following MeSH terms: "hilar cholangiocarcinoma", "biliary cancer", and "cholangiocarcinoma". Only recent studies that were published in English and in peer reviewed journals were included. Hilar cholangiocarcinoma is a disease of advanced age with an unclear etiology, most frequently found in Southeast Asia and relatively rare in Western countries. The best chance of long-term survival and potential cure is surgical resection with negative surgical margins, but many patients are unresectable due to locally advanced or metastatic disease at diagnosis. As a result of recent efforts, new methods of management have been identified for these patients, including preoperative portal vein embolism and biliary drainage, neoadjuvant chemotherapy with subsequent transplantation, and chemoradiation therapy. Current management of hilar cholangiocarcinoma depends on extent of the tumor at presentation and includes surgical resection, liver transplantation, portal vein embolization, and chemoradiation therapy. Our understanding of hilar cholangiocarcinoma has improved in recent years and further research offers hope to improve the outcome in patients with these rare tumors.

  4. Expression of an Intestine-Specific Transcription Factor (CDX1) in Intestinal Metaplasia and in Subsequently Developed Intestinal Type of Cholangiocarcinoma in Rat Liver

    Science.gov (United States)

    Ren, Ping; Silberg, Debra G.; Sirica, Alphonse E.

    2000-01-01

    CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478–486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats. PMID:10666391

  5. IgG4-associated sclerosing cholangitis masquerading as hilar cholangiocarcinoma.

    Science.gov (United States)

    Yadav, Kamal Sunder; Sali, Priyanka Akhilesh; Mansukhani, Verushka M; Shah, Rajiv; Jagannath, P

    2016-07-01

    IgG4-sclerosing cholangitis (IgG4-SC) commonly presents with type 1 autoimmune pancreatitis. Isolated IgG4-SC is rare. Differentiating IgG4-SC from cholangiocarcinoma preoperatively is challenging due to overlapping radio-clinical manifestations and difficult preoperative histology. We present three cases preoperatively diagnosed and surgically treated as hilar cholangiocarcinoma. First and second cases presented with cholangiocarcinoma with portal vein involvement and third with a malignant-appearing hilar stricture. On histopathology, IgG4-SC was diagnosed in the first two cases. Third patient had raised serum IgG4, and histopathology was inconclusive for IgG4-SC and negative for malignancy. However, she responded to steroid therapy.

  6. Endoscopic tissue diagnosis of cholangiocarcinoma.

    LENUS (Irish Health Repository)

    Harewood, Gavin C

    2008-09-01

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

  7. Role of hilar resection in the treatment of hilar cholangiocarcinoma.

    Science.gov (United States)

    Otani, Kazuhiro; Chijiiwa, Kazuo; Kai, Masahiro; Ohuchida, Jiro; Nagano, Motoaki; Kondo, Kazuhiro

    2012-05-01

    The aim of this study was to clarify the role of bile duct resection without hepatectomy (hilar resection) in hilar cholangiocarcinoma. We retrospectively compared surgical results for hilar cholangiocarcinoma between 8 patients treated with hilar resection and 21 patients treated with hepatectomy. All hilar resections were performed for Bismuth type I or II tumors with T2 or less lesions, whereas hepatectomy was done for type III or IV tumors excluding one type II tumor. R0 resection was equally achieved in both groups (62.5% in hilar resection group and 76.2% in hepatectomy group, p=0.469) and overall 5-year survival rates were comparable (21.9% vs. 23.6%, p=0.874). With respect to gross tumor appearance, R0 resection was achieved in all patients with papillary tumor in both groups with the excellent 5-year survivals (100% vs. 100%). In patients with nodular and flat tumors, R0 resection was achieved less frequently in the hilar resection vs. hepatectomy group (50% vs. 77.8%) mainly due to failure to clear the proximal ductal margin, resulting in poorer 5-year survival (0% vs. 18.7%). Hilar resection may be indicated for papillary T1 or 2 tumors in Bismuth type I or II cholangiocarcinoma.

  8. Palliative treatment in patients with unresectable hilar cholangiocarcinoma: results of endoscopic drainage in patients with type III and IV hilar cholangiocarcinoma

    NARCIS (Netherlands)

    Gerhards, M. F.; den Hartog, D.; Rauws, E. A.; van Gulik, T. M.; González González, D.; Lameris, J. S.; de Wit, L. T.; Gouma, D. J.

    2001-01-01

    OBJECTIVE: To find out how patients fared after palliative endoscopic biliary drainage for inoperable hilar cholangiocarcinoma. DESIGN: Retrospective study. SETTING: University hospital, the Netherlands. SUBJECTS: Between 1992 and 1999, 41 patients who were referred for resection had tumours that

  9. Value of multi-slice CT in the classification diagnosis of hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Qian Yi; Zeng Mengsu; Ling Zhiqing; Rao Shengxiang; Liu Yalan

    2008-01-01

    Objective: To evaluate the value of multi-slice CT (MSCT) classification in the assessment of the hilar cholangiocarcinoma resectability. Methods: Thirty patients with surgically and histopathologically proved hilar cholangiocarcinomas who underwent preoperative MSCT and were diagnosed correctly were included in present study. Transverse images and reconstructed MPR images were reviewed for Bismuth-Corlette classification and morphological classification of hilar cholangiocarcinoma. Then MSCT classification was compared with findings of surgery and histopathology. Curative resectabilty of different types according to Bismuth-Corlette classification and morphological classification were analyzed with chi-square test. Results: In 30 cases, the numbers of Type I, II, IIIa, IIIb and IV according to Bismuth-Corlette classification were 1, 3, 4, 5 and 17. Seventeen patients underwent curative resections, among which 1, 2, 1, 4 and 9 belonged to Type I, II, IIIa, IIIb and IV respectively. However, there was no significant difference in curative resectability among different types of Bismuth-Corlette classification (χ 2 = 0.9875, P>0.05). In present study, the accuracy of MSCT in Bismuth-Corlette classification reached 86.7% (26/30). The numbers of periductal infiltrating, mass forming and intraductal growing type were 13, 13 and 4, while 6, 8 and 3 cases of each type underwent curative resections. There was no significant difference in curative resectability among different types of morphological classification (χ 2 =1.2583, P>0.05). The accuracy of MSCT in morphological classification was 100% (30/30) in this study group. Conclusion: MSCT can make accurate diagnosis of Bismuth-Corlette classification and morphological classification, which is helpful in preoperative respectability assessment of hilar cholangiocarcinoma. (authors)

  10. Preoperative assessment of hilar cholangiocarcinoma using multidetector-row CT. Correlation with histopathological findings

    International Nuclear Information System (INIS)

    Watadani, Takeyuki; Akahane, Masaaki; Ohtomo, Kuni; Yoshikawa, Takeharu

    2008-01-01

    Our aim was to investigate the diagnostic reliability of multidetector-row computed tomography (MDCT) for preoperative assessment of local tumoral spread in hilar cholangiocarcinoma. Thirteen of 30 consecutive patients with hilar cholangiocarcinoma who underwent surgery, excluding 17 patients who underwent biliary drainage or preoperative portal embolization, were retrospectively evaluated. Using MDCT systems of 4 detector rows or 16 detector rows, plain and dynamic contrast-enhanced images of three phases were obtained. Extent of tumor spread and lymph node metastasis were assessed with MDCT and compared with histopathological findings. The Bismuth-Corlette classification of hilar cholangiocarcinoma with MDCT were type I, 1 patient; type IIIa, 3 patients; type IIIb, 4 patients; and type IV, 5 patients; those with histopathological findings were type I, 1 patient; type IIIa, 2 patients; type IIIb, 4 patients; and type IV, 6 patients. One patient diagnosed as type IIIa with MDCT was pathologically diagnosed as type IV. Accuracy of MDCT in tumoral spread was 92.3%, although that of lymph node metastasis was 54%. MDCT is likely to play an important role in evaluation of focal lesion spread especially in intrapancreatic tumor invasion, although a greater number of cohort cases are necessary to clearly define its role. (author)

  11. A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma

    International Nuclear Information System (INIS)

    Palumbo, Tiziana; Poultsides, George A.; Kouraklis, Grigorios; Liakakos, Theodore; Drakaki, Alexandra; Peros, George; Hatziapostolou, Maria; Iliopoulos, Dimitrios

    2016-01-01

    Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma. The online version of this article (doi:10.1186/s12885-016-2384-0) contains supplementary material, which is available to authorized users

  12. Computed tomography of hilar cholangiocarcinoma: a new sign

    International Nuclear Information System (INIS)

    Carr, D.H.; Hadjis, N.S.; Banks, L.M.; Hemingway, A.P.; Blumgart, L.H.

    1985-01-01

    Thirty-seven patients with histologic proof of cholangiocarcinoma at the confluence were examined by computed tomography (CT) to determine whether this examination is of value in the assessment of these patients for surgery and whether there are any features specific to this type of tumor. Thirty-two patients showed intrahepatic duct dilatation; six of these showed dilatation of ducts in one lobe only. Eighteen patients had intrahepatic low-attenuation areas, while eight had a mass lesion in the porta hepatis. The results of this study show that CT provides useful anatomic information preoperatively but that the appearances are nonspecific. Lobar atrophy is highly suggestive of hilar cholangiocarcinoma, either of long-standing or with unilateral portal venous involvement

  13. XIAP antagonist embelin inhibited proliferation of cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Cody J Wehrkamp

    Full Text Available Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentration-dependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL. However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis.

  14. Hilar cholangiocarcinoma: controversies on the extent of surgical resection aiming at cure.

    Science.gov (United States)

    Xiang, Shuai; Lau, Wan Yee; Chen, Xiao-ping

    2015-02-01

    Hilar cholangiocarcinoma is the most common malignant tumor affecting the extrahepatic bile duct. Surgical treatment offers the only possibility of cure, and it requires removal of all tumoral tissues with adequate resection margins. The aims of this review are to summarize the findings and to discuss the controversies on the extent of surgical resection aiming at cure for hilar cholangiocarcinoma. The English medical literatures on hilar cholangiocarcinoma were studied to review on the relevance of adequate resection margins, routine caudate lobe resection, extent of liver resection, and combined vascular resection on perioperative and long-term survival outcomes of patients with resectable hilar cholangiocarcinoma. Complete resection of tumor represents the most important prognostic factor of long-term survival for hilar cholangiocarcinoma. The primary aim of surgery is to achieve R0 resection. When R1 resection is shown intraoperatively, further resection is recommended. Combined hepatic resection is now generally accepted as a standard procedure even for Bismuth type I/II tumors. Routine caudate lobe resection is also advocated for cure. The extent of hepatic resection remains controversial. Most surgeons recommend major hepatic resection. However, minor hepatic resection has also been advocated in most patients. The decision to carry out right- or left-sided hepatectomy is made according to the predominant site of the lesion. Portal vein resection should be considered when its involvement by tumor is suspected. The curative treatment of hilar cholangiocarcinoma remains challenging. Advances in hepatobiliary techniques have improved the perioperative and long-term survival outcomes of this tumor.

  15. Clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Lee, Kyung-Hun; Lee, Kyoung-Bun; Kim, Tae-Yong; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk; Jang, Ja-June; Bang, Yung-Jue

    2015-01-01

    More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. One hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC). ROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (−) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377–0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples. ROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples

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

    Directory of Open Access Journals (Sweden)

    Yao X

    2012-10-01

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

  17. Downregulation of the expression of HDGF attenuates malignant biological behaviors of hilar cholangiocarcinoma cells.

    Science.gov (United States)

    Liu, Yanfeng; Sun, Jingxian; Yang, Guangyun; Liu, Zhaojian; Guo, Sen; Zhao, Rui; Xu, Kesen; Wu, Xiaopeng; Zhang, Zhaoyang

    2015-09-01

    Hepatoma-derived growth factor (HDGF) has been reported to be a potential predictive and prognostic marker for several types of cancer and important in malignant biological behaviors. However, its role in human hilar cholangiocarcinoma remains to be elucidated. Our previous study demonstrated that high expression levels of HDGF in hilar cholangiocarcinoma tissues correlates with tumor progression and patient outcome. The present study aimed to elucidate the detailed functions of the HDGF protein. This was performed by downregulating the protein expression of HDGF in the FRH0201 hilar cholangiocarcinoma cell line by RNA interference (RNAi) in vitro, and revealed that downregulation of the HDGF protein significantly inhibited the malignant biological behavior of the FRH0201 cells. In addition, further investigation revealed that downregulation of the protein expression of HDGF significantly decreased the secretion of vascular endothelial growth factor, which may be the mechanism partially responsible for the inhibition of malignant biological behaviors. These findings demonstrated that HDGF is important in promoting malignant biological behaviors, including proliferation, migration and invasion of hilar cholangiocarcinoma FRH0201 cells. Inhibition of the expression of HDGF downregulated the malignant biological behaviors, suggesting that downregulation of the protein expression of HDGF by RNAi may be a novel therapeutic approach to inhibit the progression of hilar cholangiocarcinoma.

  18. Peritoneal seeding of cholangiocarcinoma in patients with percutaneous biliary drainage

    International Nuclear Information System (INIS)

    Miller, G.A. Jr.; Heaston, D.K.; Moore, A.V. Jr.; Mills, S.R.; Dunnick, N.R.

    1983-01-01

    Percutaneous transhepatic catheter decompression is performed increasingly as an adjunct or alternative to surgery in patients with benign or malignant biliary obstruction. The authors recently saw three patients with cholangiocarcinoma in whom metastatic seeding of the peritoneal serosa was identified some months after initial percutaneous transhepatic biliary drainage. Although no tumor was found along the hepatic tract of the biliary drainage catheters to implicate the drainage tubes as the direct source of peritoneal spread, the occurrence of this rare type of metastasis of cholangiocarcinoma in patients with potential access of tumor cells to the peritoneal cavity via the catheter tracts does suggest such a relation. The clinical history of one patient is presented

  19. Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression

    DEFF Research Database (Denmark)

    Erice, O; Labiano, I; Arbelaiz, A

    2018-01-01

    BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangioc...

  20. Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells.

    Science.gov (United States)

    Kwak, Tae Won; Kim, Do Hyung; Jeong, Young-Il; Kang, Dae Hwan

    2015-09-26

    The aim of this study is to evaluate the anticancer activity of vorinostat-incorporated nanoparticles (vorinostat-NPs) against HuCC-T1 human cholangiocarcinoma cells. Vorinostat-NPs were fabricated by a nanoprecipitation method using poly(DL-lactide-co-glycolide)/poly(ethylene glycol) copolymer. Vorinostat-NPs exhibited spherical shapes with sizes Vorinostat-NPs have anticancer activity similar to that of vorinostat in vitro. Vorinostat-NPs as well as vorinostat itself increased acetylation of histone-H3. Furthermore, vorinostat-NPs have similar effectiveness in the suppression or expression of histone deacetylase, mutant type p53, p21, and PARP/cleaved caspase-3. However, vorinostat-NPs showed improved antitumor activity against HuCC-T1 cancer cell-bearing mice compared to vorinostat, whereas empty nanoparticles had no effect on tumor growth. Furthermore, vorinostat-NPs increased the expression of acetylated histone H3 in tumor tissue and suppressed histone deacetylase (HDAC) expression in vivo. The improved antitumor activity of vorinostat-NPs can be explained by molecular imaging studies using near-infrared (NIR) dye-incorporated nanoparticles, i.e. NIR-dye-incorporated nanoparticles were intensively accumulated in the tumor region rather than normal one. Our results demonstrate that vorinostat and vorinostat-NPs exert anticancer activity against HuCC-T1 cholangiocarcinoma cells by specific inhibition of HDAC expression. Thus, we suggest that vorinostat-NPs are a promising candidate for anticancer chemotherapy in cholangiocarcinoma. Graphical abstract Local delivery strategy of vorinostat-NPs against cholangiocarcinomas.

  1. Lower incidence of complications in endoscopic nasobiliary drainage for hilar cholangiocarcinoma.

    Science.gov (United States)

    Kawakubo, Kazumichi; Kawakami, Hiroshi; Kuwatani, Masaki; Haba, Shin; Kudo, Taiki; Taya, Yoko A; Kawahata, Shuhei; Kubota, Yoshimasa; Kubo, Kimitoshi; Eto, Kazunori; Ehira, Nobuyuki; Yamato, Hiroaki; Onodera, Manabu; Sakamoto, Naoya

    2016-05-10

    To identify the most effective endoscopic biliary drainage technique for patients with hilar cholangiocarcinoma. In total, 118 patients with hilar cholangiocarcinoma underwent endoscopic management [endoscopic nasobiliary drainage (ENBD) or endoscopic biliary stenting] as a temporary drainage in our institution between 2009 and 2014. We retrospectively evaluated all complications from initial endoscopic drainage to surgery or palliative treatment. The risk factors for biliary reintervention, post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis, and percutaneous transhepatic biliary drainage (PTBD) were also analyzed using patient- and procedure-related characteristics. The risk factors for bilateral drainage were examined in a subgroup analysis of patients who underwent initial unilateral drainage. In total, 137 complications were observed in 92 (78%) patients. Biliary reintervention was required in 83 (70%) patients. ENBD was significantly associated with a low risk of biliary reintervention [odds ratio (OR) = 0.26, 95%CI: 0.08-0.76, P = 0.012]. Post-ERCP pancreatitis was observed in 19 (16%) patients. An absence of endoscopic sphincterotomy was significantly associated with post-ERCP pancreatitis (OR = 3.46, 95%CI: 1.19-10.87, P = 0.023). PTBD was required in 16 (14%) patients, and Bismuth type III or IV cholangiocarcinoma was a significant risk factor (OR = 7.88, 95%CI: 1.33-155.0, P = 0.010). Of 102 patients with initial unilateral drainage, 49 (48%) required bilateral drainage. Endoscopic sphincterotomy (OR = 3.24, 95%CI: 1.27-8.78, P = 0.004) and Bismuth II, III, or IV cholangiocarcinoma (OR = 34.69, 95%CI: 4.88-736.7, P hilar cholangiocarcinoma is challenging. ENBD should be selected as a temporary drainage method because of its low risk of complications.

  2. Risk assessment and perioperative care in perihilar cholangiocarcinoma

    NARCIS (Netherlands)

    Coelen, R.J.S.

    2016-01-01

    Perihilar cholangiocarcinoma is one of the most complex gastrointestinal malignancies due to the many pitfalls encountered at various stages of its management. Despite several techniques to optimize the patient for operation, liver surgery for perihilar cholangiocarcinoma remains a hazardous

  3. Results of postoperative radiotherapy for resectable hilar cholangiocarcinoma

    NARCIS (Netherlands)

    Gerhards, Michael F.; van Gulik, Thomas M.; González González, Dioniso; Rauws, Erik A. J.; Gouma, Dirk J.

    2003-01-01

    The aim of this study was to assess the value of radiotherapy, and especially intraluminal brachytherapy, after resection of hilar cholangio-carcinoma by analyzing long-term complications and survival. Between 1983 and 1998, 112 patients underwent resection of a hilar cholangio-carcinoma. Of the 91

  4. Multislice helical CT in the diagnosis of hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Yang Li; Zhao Shaohong; Nie Yongkang; Zhao Hong; Fang Jie; Cai Zulong; Yang Zhou; Ying Yifeng

    2005-01-01

    Objective: To investigate the value ofMSCT in observing the direct findings of hilar cholangiocarcinoma1Methods Multislice helical CT studies were performed on the upper abdomen in 19 consecutive patientswith painless jaundice1 Precontrast and dynamic contrast enhanced (25 s phase and 60 s phase) scanswere conducted, and 3D imageswere reconstructed using enhanced raw data in 15 cases1 The direct CT findings of hilar cholangiocarcinoma were studied by three radiologists respectively in a 32scale strategy1 The morphological features and extension of bile duct involvement by hilar cholangiocarcinoma were analyzed1 All the 19 caseswere pathologically p roved as hilar cholangiocarcinoma by surgery (15 cases) and ERCP ( 4 cases) 1 Results The direct findings and extension of hilar cholangiocarcinoma could be demonstrated in 14 out of 15 3D reconstruction images, 8 out of 19 in 25 s phase, and 7 out of 19 in 60 s phase of contrast enhancement scans, respectively ( P < 0105 ) 1 The tumor involving the bile duct was enhanced most remarkablely on 25 s phase, and the bile duct wall thickening, bile duct narrowing or occlusion were demonstrated as the p rimary findings of hilar cholangiocarcinoma1 The intraductal sp read of tumor could be demonstrated as small nodules on the bile duct wall p roximal or distal to the tumor1 Conclusion. The tumor involving the bile duct can be enhanced most remarkablely on 25 s phase after contrast injection1 Multislice helical CT, especially 3D reconstructed images, can be used to detect the direct findings of hilar cholangiocarcinomas and the extension of tumor involving the bile duct. (authors)

  5. Bile Duct Cancer (Cholangiocarcinoma) Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Bile duct cancer (also called cholangiocarcinoma) can occur in the bile ducts in the liver (intrahepatic) or outside the liver (perihilar or distal extrahepatic). Learn about the types of bile duct cancer, risk factors, clinical features, staging, and treatment for bile duct cancer in this expert-reviewed summary.

  6. [A Case of Intrahepatic Cholangiocarcinoma with Invasion to the Transverse Colon and Gallbladder, Forming an Intra-Tumor Abscess].

    Science.gov (United States)

    Okada, Nami; Kametaka, Hisashi; Koyama, Takashi; Seike, Kazuhiro; Makino, Hironobu; Fukada, Tadaomi; Sato, Yutaka; Miyazaki, Masaru

    2015-11-01

    An 81-year-old man was referred to our institution for evaluation of high fever and a liver tumor that had been detected by ultrasonography. Computed tomography revealed a low-density mass with peripheral ring-like enhancement in S5 of the liver. The liver mass was in contact with the gallbladder, and the boundary between the mass and the gallbladder was unclear. On the suspicion of liver abscess, percutaneous transhepatic drainage was performed. The cavity of the abscess communicated with the gallbladder. Because the cavity had no tendency to reduce in size, we performed surgical resection under a preoperative diagnosis of liver abscess or primary liver carcinoma invading to the gallbladder. Intraoperative findings revealed a liver tumor invading the transverse colon and gallbladder. Subsegmentectomy of S4a and S5 of the liver combined with gallbladder and transverse colon resection was performed. Histopathological findings indicated the growth of a mass forming type intrahepatic cholangiocarcinoma with invasion to the transverse colon and gallbladder, and the pathological stage of the tumor was pT3N0M0, fStage Ⅲ. Thus far, the patient is alive without recurrence 9 months after surgery. Here, we report an extremely rare case of intrahepatic cholangiocarcinoma that invaded other organs and was associated with an intra-tumor abscess.

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

    International Nuclear Information System (INIS)

    Lu Zaiming; Liang Hongyuan; Guo Qiyong; Wen Feng; Liu Zhaoyu; Zhang Jun

    2007-01-01

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

  8. Risk Factors for Cholangiocarcinoma in Thailand: A Systematic

    Science.gov (United States)

    Kamsa-ard, Siriporn; Kamsa-ard, Supot; Luvira, Vor; Suwanrungruang, Krittika; Vatanasapt, Patravoot; Wiangnon, Surapon

    2018-03-27

    Background and objective: Cholangiocarcinoma remains a serious public health concern in Thailand. While many of the risk factors for cholangiocarcinoma in western countries are well-recognized, it remains unclear whether they are the same in Thailand. We set out to investigate the risk factors for cholangiocarcinoma in Thailand. Methods: Starting March 4, 2016, we reviewed studies found using pre-specified keywords on SCOPUS, Pro Quest Science Direct, PubMed, and online public access catalog of Khon Kaen University. Two review authors independently screened studies for inclusion criteria, extracted data, and assessed the studied Risk of Bias. The Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Tools were used to assess the quality of included studies. The risk effects of factors were estimated as a pooled adjusted odds ratio with a 95% confidence interval. The heterogeneity of results was considered using the I-square, Tau-square and Chi-square statistics. Results: A strong association was found between cholangiocarcinoma and age, Opisthorchis viverrini infection, eating raw cyprinoid fish, family history of cancer, liquor consumption, and taking praziquantel. There was only a mild association found between eating nitrite-containing foods, fresh vegetables, education, smoking behavior, and sex. No association was found between cholangiocarcinoma and eating fermented fish (Pla-ra), northeastern Thai or Chinese sausage, sticky rice, meat, chewing betel nut, or eating fruit. There were two protective factors including fresh vegetables consumption and education attainment. Conclusion: There are unique risk factors of cholangiocarcinoma in Thailand, including age, Opisthorchis viverrini infection, eating raw cyprinoid fish, family history of cancer, liquor consumption, and taking praziquantel. Creative Commons Attribution License

  9. Hilar cholangiocarcinoma: expert consensus statement.

    Science.gov (United States)

    Mansour, John C; Aloia, Thomas A; Crane, Christopher H; Heimbach, Julie K; Nagino, Masato; Vauthey, Jean-Nicolas

    2015-08-01

    An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of hilar cholangiocarcinoma in order to establish practice guidelines and to agree consensus statements. It was established that the treatment of patients with hilar cholangiocarcinoma requires a coordinated, multidisciplinary approach to optimize the chances for both durable survival and effective palliation. An adequate diagnostic and staging work-up includes high-quality cross-sectional imaging; however, pathologic confirmation is not required prior to resection or initiation of a liver transplant trimodal treatment protocol. The ideal treatment for suitable patients with resectable hilar malignancy is resection of the intra- and extrahepatic bile ducts, as well as resection of the involved ipsilateral liver. Preoperative biliary drainage is best achieved with percutaneous transhepatic approaches and may be indicated for patients with cholangitis, malnutrition or hepatic insufficiency. Portal vein embolization is a safe and effective strategy for increasing the future liver remnant (FLR) and is particularly useful for patients with an FLR of hilar cholangiocarcinoma should be evaluated for a standard trimodal protocol incorporating external beam and endoluminal radiation therapy, systemic chemotherapy and liver transplantation. Post-resection chemoradiation should be offered to patients who show high-risk features on surgical pathology. Chemoradiation is also recommended for patients with locally advanced, unresectable hilar cancers. For patients with locally recurrent or metastatic hilar cholangiocarcinoma, first-line chemotherapy with gemcitabine and cisplatin is recommended based on multiple Phase II trials and a large randomized controlled trial including a heterogeneous population of patients with biliary cancers. © 2015 International Hepato-Pancreato-Biliary Association.

  10. Expression and clinical significance of PIWIL2 in hilar cholangiocarcinoma tissues and cell lines.

    Science.gov (United States)

    Chen, Y J; Xiong, X F; Wen, S Q; Tian, L; Cheng, W L; Qi, Y Q

    2015-06-26

    The objective of this study was to explore the relationship between PIWI-like protein 2 (PIWIL2) and clinicopathological charac-teristics and prognosis after radical resection. To accomplish this, we analyzed PIWIL2 expression in hilar cholangiocarcinoma tissues and cell lines. PIWIL2 expression was detected by immunohistochemistry in 41 hilar cholangiocarcinoma samples and 10 control tissues. Western blotting and immunocytofluorescence were used to investigate PIWIL2 expression in the cholangiocarcinoma cell line QBC939 and the bile duct epithelial cell line HIBEpic. Univariate and multivariate surviv-al analyses were performed using the Kaplan-Meier method for hilar cholangiocarcinoma patients who underwent radical resection. PIWIL2 expression was significantly higher in the hilar cholangiocarcinoma tissues and QBC939 cells than in control tissues and HIBEpic cells, respectively (P hilar cholangiocarcinoma (P hilar cholangiocarcinoma.

  11. [The safety and effect of transhepatic hilar approach for the treatment of bismuth type Ⅲ and Ⅳ hilar cholangiocarcinoma].

    Science.gov (United States)

    He, M; Wang, H L; Yan, J Y; Xu, S W; Chen, W; Wang, J

    2018-05-01

    Objective: To compare the efficiency between the transhepatic hilar approach and conventional approach for the surgical treatment of Bismuth type Ⅲ and Ⅳ hilar cholangiocarcinoma. Methods: There were 42 consecutive patients with hilar cholangiocarcinoma of Bismuth type Ⅲ and Ⅳ who underwent surgical treatment at Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from January 2008 to December 2013.The transhepatic hilar approach was used in 19 patients and conventional approach was performed in 23 patients.There were no differences in clinical parameters between the two groups(all P >0.05). The t-test was used to analyze the measurement data, and the χ(2) test was used to analyze the count data.Kaplan-Meier analysis was used to analyze the survival period.Multivariate COX regression analysis was used to analyze the prognosis factors. Results: Among the 19 patients who underwent transhepatic hilar approach, 3 patients changed the operative planning after reevaluated by exposing the hepatic hilus.The intraoperative blood was 300(250-400)ml in the transhepatic hilar approach group, which was significantly less than the conventional approach group, 800(450-1 300)ml( t =4.276, P =0.00 1), meanwhile, the R0 resection rate was significantly higher in the transhepatic hilar approach group than in the conventional approach group(89.4% vs . 52.2; χ(2)=6.773, P =0.009) and the 3-year and 5-year cumulative survival rate was better in the transhepatic hilar approach group than in the conventional approach group(63.2% vs . 47.8%, 26.3% vs . 0; χ(2)=66.363, 127.185, P =0.000). On univariate analysis, transhepatic hilar approach, intraoperative blood loss, intraoperative blood transfusion, R0 resection and lymph node metastasis were significant risk factors for patient survival(all P hilar approach, intraoperative blood loss, R0 resection and lymph node metastasis were significant independent risk factors for

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

    Directory of Open Access Journals (Sweden)

    Jeffrey S Chang

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

  13. Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma.

    Science.gov (United States)

    Nooron, Nattakarn; Ohba, Koji; Takeda, Kazuhisa; Shibahara, Shigeki; Chiabchalard, Anchalee

    2017-08-01

    Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is over-expressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

  14. Use of an autologous liver round ligament flap zeros postoperative bile leak after curative resection of hilar cholangiocarcinoma.

    Science.gov (United States)

    Sun, Da-Xin; Tan, Xiao-Dong; Gao, Feng; Xu, Jin; Cui, Dong-Xu; Dai, Xian-Wei

    2015-01-01

    Postoperative bile leak is a major surgical morbidity after curative resection with hepaticojejunostomy for hilar cholangiocarcinoma, especially in Bismuth-Corlette types III and IV. This retrospective study assessed the effectiveness and safety of an autologous hepatic round ligament flap (AHRLF) for reducing bile leak after hilar hepaticojejunostomy. Nine type III and IV hilar cholangiocarcinoma patients were consecutively hospitalized for elective perihilar partial hepatectomy with hilar hepaticojejunostomy using an AHRLF between October 2009 and September 2013. The AHRLF was harvested to reinforce the perihilar hepaticojejunostomy. Main outcome measures included operative time, blood loss, postoperative recovery times, morbidity, bile leak, R0 resection rate, and overall survival. All patients underwent uneventful R0 resection with hilar hepaticojejunostomy. No patient experienced postoperative bile leak. The AHRLF was associated with lack of bile leak after curative perihilar hepatectomy with hepaticojejunostomy for hilar cholangiocarcinoma, without compromising oncologic safety, and is recommended in selected patients.

  15. Serum albumin predicts survival in patients with hilar cholangiocarcinoma.

    Science.gov (United States)

    Waghray, Abhijeet; Sobotka, Anastasia; Marrero, Carlos Romero; Estfan, Bassam; Aucejo, Federico; Narayanan Menon, K V

    2017-02-01

    Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P 3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14-0.70) with a survival benefit of 44 weeks. This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. © The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University.

  16. Mandibular metastasis of cholangiocarcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

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

    Science.gov (United States)

    Fattach, Hassan El; Dohan, Anthony; Guerrache, Youcef; Dautry, Raphael; Boudiaf, Mourad; Hoeffel, Christine; Soyer, Philippe

    2015-08-01

    To qualitatively and quantitatively analyze the presentation of intrahepatic and hilar mass-forming cholangiocarcinoma with diffusion-weighted magnetic resonance imaging (DW-MRI). Twenty-eight patients with histopathologically proven mass-forming cholangiocarcinoma (hilar, n=17; intrahepatic, n=11) underwent hepatic DW-MRI at 1.5-T using free-breathing acquisition and three b-values (0,400,800s/mm(2)). Cholangiocarcinomas were evaluated qualitatively using visual analysis of DW-MR images and quantitatively with conventional ADC and normalized ADC measurements using liver and spleen as reference organs. All cholangiocarcinomas (28/28; 100%) were visible on DW-MR images. DW-MRI yielded best conspicuity of cholangiocarcinomas than the other MRI sequences (Philar cholangiocarcinomas. The use of normalized ADC using the liver as reference organ resulted in the most restricted distribution of ADC values of cholangiocarcinomas (variation coefficient=16.6%). There is a trend towards a common appearance of intrahepatic and hilar mass-forming cholangiocarcinomas on DW-MRI but variations may be observed. Familiarity with these variations may improve the diagnosis of mass-forming cholangiocarcinoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Zaydfudim, Victor M; Wang, Andrew Y; de Lange, Eduard E; Zhao, Zimin; Moskaluk, Christopher A; Bauer, Todd W; Adams, Reid B

    2015-07-01

    IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

  19. Radiation therapy in the treatment of hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Jing Jin; Zhai Renyou

    2007-01-01

    The incidence of hilar cholangiocarcinoma is very rare worldwide. Radical resection is the only prognostic factor for long survival in patients with hilar cholangiocarcinoma. Postoperative radiation therapy can improve local control and survival rates for patients with palliative resection, but it remains controversial in patients with radical resection. Biliary drainage can effectively release bile duct obstruction for the majority of patients with locally advanced disease, and may even prolong survival when combined with radiation therapy. Radiation therapy includes extrernal beam therapy alone, external beam therapy with intraluminal brachytheapy and new radiation technique, such as three dimentional conformal therapy and intensity modulated radiation therapy. The propective randomized clinical study is needed for further investigation in the role of combined modality therapy especially for hilar cholangiocarcinoma. (authors)

  20. Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism.

    Science.gov (United States)

    Frampton, Gabriel; Invernizzi, Pietro; Bernuzzi, Francesca; Pae, Hae Yong; Quinn, Matthew; Horvat, Darijana; Galindo, Cheryl; Huang, Li; McMillin, Matthew; Cooper, Brandon; Rimassa, Lorenza; DeMorrow, Sharon

    2012-02-01

    Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. The growth factor, progranulin, is overexpressed in a number of tumours. The study aims were to assess the expression of progranulin in cholangiocarcinoma and to determine its effects on tumour growth. The expression and secretion of progranulin were evaluated in multiple cholangiocarcinoma cell lines and in clinical samples from patients with cholangiocarcinoma. The role of interleukin 6 (IL-6)-mediated signalling in the expression of progranulin was assessed using a combination of specific inhibitors and shRNA knockdown techniques. The effect of progranulin on proliferation and Akt activation and subsequent effects of FOXO1 phosphorylation were assessed in vitro. Progranulin knockdown cell lines were established, and the effects on cholangiocarcinoma growth were determined. Progranulin expression and secretion were upregulated in cholangiocarcinoma cell lines and tissue, which were in part via IL-6-mediated activation of the ERK1/2/RSK1/C/EBPβ pathway. Blocking any of these signalling molecules, by either pharmacological inhibitors or shRNA, prevented the IL-6-dependent activation of progranulin expression. Treatment of cholangiocarcinoma cells with recombinant progranulin increased cell proliferation in vitro by a mechanism involving Akt phosphorylation leading to phosphorylation and nuclear extrusion of FOXO1. Knockdown of progranulin expression in cholangiocarcinoma cells decreased the expression of proliferating cellular nuclear antigen, a marker of proliferative capacity, and slowed tumour growth in vivo. Evidence is presented for a role for progranulin as a novel growth factor regulating cholangiocarcinoma growth. Specific targeting of progranulin may represent an alternative for the development of therapeutic strategies.

  1. Pathomorphological study of Thorotrast-related intrahepatic cholangiocarcinoma with a comparison to non-Thorotrast cases

    International Nuclear Information System (INIS)

    Kojiro, Masamichi; Sugihara, Shigetaka; Ito, Yuji; Nakashima, Toshiro; Ikezaki, Hidefumi; Mori, Takesaburo; Kido, Choichiro.

    1986-01-01

    Thirty-five autopsy cases of Thorotrast (TH)-related intrahepatic cholangiocarcinoma were morphologically studied with a comparison to 45 non-TH cases. Latent periods ranged from 25 to 48 years, with a mean of 34.1 ± 6.6 years. As to tumor location, the peripheral-middle type, in which the main tumor was located in the peirphery to middle portion of the liver, was the most common (89.2 %) in the TH-related cases, and the hilar type, in which the main tumor was located in the hepatic hilum, was the most common (78.8 %) in the non-TH cases. However, there was no close relationship between the distribution of TH depositsoand tumor location by soft-X ray examination of the liver slices. Grossly, the massive type with an infiltrative growth was the most common both in the TH- and non-TH cases. Histologically, there were no remarkable differences between the two groups, and tubular adenocarcinoma with varying degrees of fibrous stroma was the most common. In noncancerous areas, proliferation of the bile ducts with slight to moderate atypism and ductular proliferation around Glisson's capsule were found in 30 %, and 10 %, respectively, of the TH-related cases. However, such changes were also found in the non-TH cases at almost the same incidence. (author)

  2. Metallic stent and stereotactic conformal radiotherapy for hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Li Yu; Wang Ning; Tian Qihe; Guo Zhanwen; Zhang Haibo; Song Liyan

    2005-01-01

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

  3. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Ting-Lei Gu

    Full Text Available Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23 of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted.

  4. Primary Hepatic Lymphoma Mimicking Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Foroogh Forghani1,

    2017-07-01

    Full Text Available Primary hepatic lymphoma (PHL presenting with obstructive jaundice is rare and can mimic a preoperative diagnosis of cholangiocarcinoma. We should consider PHL in patients with radiological hepatic disease with normal serum alpha-fetoprotein and carcinoembryonic antigen levels, and elevated lactate dehydrogenase. We present the case of a 67-year-old male with no significant medical history presented with abdominal pain, jaundice, fever, and abnormal liver function tests. Abdominal sonography and computed tomography scan suggested a diagnosis of obstructive jaundice and cholangitis due to cholangiocarcinoma (Klatskin tumor. A subsequent liver biopsy diagnosed PHL, and the patient was treated with combination chemotherapy, including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP. PHL should be considered in patients presenting with biliary obstruction.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-15

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

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

    International Nuclear Information System (INIS)

    Fattach, Hassan El; Dohan, Anthony; Guerrache, Youcef; Dautry, Raphael

    2015-01-01

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

  7. Usefulness of 18F-FDG PET in intrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Kim, Young-Jin; Yun, Mijin; Lee, Jong Doo; Lee, Woo Jung; Kim, Kyung Sik

    2003-01-01

    Surgical resection is the only curative treatment strategy for intrahepatic cholangiocarcinoma (CC). Therefore, accurate staging is essential for appropriate management of patients with CC. We assessed the usefulness of 2-[ 18 F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the staging of CC. We undertook a retrospective review of FDG PET images in 21 patients (10 female, 11 male; mean age 57 years) diagnosed with CC. Ten patients had hilar CC and 11, peripheral CC. Patients underwent abdominal magnetic resonance imaging (MRI) (n=20) and computed tomography (CT) (n=12) for the evaluation of primary tumours, and chest radiography and whole-body bone scintigraphy for work-up of distant metastases. For semi-quantitative analysis, the maximum voxel standardised uptake value (SUV max ) was obtained from the primary tumour. All peripheral CCs showed intensely increased FDG uptake, and some demonstrated ring-shaped uptake corresponding to peripheral rim enhancement on CT and/or MRI. In nine of the ten patients, hilar CCs demonstrated increased FDG uptake of a focal nodular or linear branching appearance. The remaining case was false negative on FDG PET. One patient with a false negative result on MRI demonstrated increased uptake on FDG PET. Among the ten hilar CCs, FDG uptake was intense in only two patients and was slightly higher than that of the hepatic parenchyma in the remaining patients. For the detection of lymph node metastasis, FDG PET and CT/MRI were concordant in 16 patients, and discordant in five (FDG PET was positive in three, and CT and MRI in two). FDG PET identified unsuspected distant metastases in four of the 21 patients; all of these patients had peripheral CC. FDG PET is useful in detecting the primary lesion in both hilar and peripheral CC and is of value in discovering unsuspected distant metastases in patients with peripheral CC. FDG PET could be useful in cases of suspected hilar CC with non-confirmatory biopsy and

  8. [Occupational cholangiocarcinoma in a printer that responded to neoadjuvant chemoradiotherapy].

    Science.gov (United States)

    Nakagawa, Kei; Katayose, Yu; Ishida, Kazuyuki; Hayashi, Hiroki; Morikawa, Takanori; Yoshida, Hiroshi; Motoi, Fuyuhiko; Naitoh, Takeshi; Kubo, Shoji; Unno, Michiaki

    2015-07-01

    A 42-year-old man working at a printing company was referred to our hospital for examination and treatment of icterus. We diagnosed resectable hilar cholangiocarcinoma and provided neoadjuvant chemoradiotherapy, extended right hepatectomy, and extrahepatic bile duct resection. A detailed history revealed that he had used 1,2-dichloropropane as part of his work as an offset colour proof-printer, and he has subsequently been recognized as having occupational cholangiocarcinoma. He has survived without recurrence for more than 2 and half years since the liver resection. In the present report, we describe our valuable experience of neoadjuvant chemoradiotherapy for occupational cholangiocarcinoma.

  9. TROP2 correlates with microvessel density and poor prognosis in hilar cholangiocarcinoma.

    Science.gov (United States)

    Ning, Shanglei; Guo, Sen; Xie, Jianjun; Xu, Yunfei; Lu, Xiaofei; Chen, Yuxin

    2013-02-01

    Trophoblast cell surface antigen 2 (TROP2) was found to be associated with tumor progression and poor prognosis in a variety of epithelial carcinomas. The aim of the study was to investigate TROP2 expression and its prognostic impact in hilar cholangiocarcinoma. Immunohistochemistry and quantitative real-time PCR were used to determine TROP2 expression in surgical specimens from 70 hilar cholangiocarcinoma patients receiving radical resection. The relationship between TROP2 expression and microvessel density was investigated and standard statistical analysis was used to evaluate TROP2 prognosis significance in hilar cholangiocarcinoma. High TROP2 expression by immunohistochemistry was found in 43 (61.4 %) of the 70 tumor specimens. Quantitative real-time PCR confirmed that TROP2 level in tumor was significantly higher than in non-tumoral biliary tissues (P = 0.001). Significant correlations were found between TROP2 expression and histological differentiation (P = 0.016) and tumor T stage (P = 0.031) in hilar cholangiocarcinoma. TROP2 expression correlated with microvessel density in hilar cholangiocarcinoma (P = 0.026). High TROP2 expression patients had a significantly poorer overall survival rate than those with low TROP2 expression (30 vs. 68.5 %, P = 0.001), and multivariate Cox regression analysis indicated TROP2 as an independent prognostic factor for hilar cholangiocarcinoma (P = 0.004). TROP2 expression correlates with microvessel density significantly and is an independent prognostic factor in human hilar cholangiocarcinoma.

  10. Exploring new strategies in diagnosis and treatment of hilar cholangiocarcinoma

    NARCIS (Netherlands)

    Mantel, Hendrik Teunis Johannes

    2016-01-01

    Hilar cholangiocarcinoma is a rare form of cancer arising at the confluence of the right and left bile duct. The disease is known for its difficult diagnosis and treatment. The chapters in this thesis describe different aspects of hilar cholangiocarcinoma with the aim to improve diagnosis and

  11. Plasma osteoprotegerin concentrations in peripheral sensory neuropathy in Type 1 and Type 2 diabetic patients

    DEFF Research Database (Denmark)

    Nybo, M; Poulsen, M K; Grauslund, J

    2010-01-01

    Osteoprotegerin (OPG) has been linked to different diabetes complications, including cardiovascular disease, and new findings have indicated a specific role in diabetic peripheral neuropathy, but the exact mechanism is unknown. To investigate a possible association between OPG and diabetic...... peripheral sensory neuropathy, we therefore analysed plasma OPG in Type 1 and Type 2 diabetic patients with and without peripheral neuropathy....

  12. Imaging and interventions in hilar cholangiocarcinoma: A review

    Science.gov (United States)

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

    2015-01-01

    Hilar cholangiocarcinoma is a common malignant tumor of the biliary tree. It has poor prognosis with very low 5-year survival rates. Various imaging modalities are available for detection and staging of the hilar cholangiocarcinoma. Although ultrasonography is the initial investigation of choice, imaging with contrast enhanced computed tomography scan or magnetic resonance imaging is needed prior to management. Surgery is curative wherever possible. Radiological interventions play a role in operable patients in the form of biliary drainage and/or portal vein embolization. In inoperable cases, palliative interventions include biliary drainage, biliary stenting and intra-biliary palliative treatment techniques. Complete knowledge of application of various imaging modalities available and about the possible radiological interventions is important for a radiologist to play a critical role in appropriate management of such patients.We review the various imaging techniques and appearances of hilar cholangiocarcinoma and the possible radiological interventions. PMID:25729485

  13. MOLECULAR MECHANISMS THAT LEAD TO CHOLANGIOCARCINOMA, DURING CHRONIC INFECTION OF LIVER FLUKES

    Directory of Open Access Journals (Sweden)

    A. O. Bogdanov

    2015-01-01

    Full Text Available Cholangiocarcinoma is a malignant tumor, characterized by poor prognosis and a low five-year survival rate. There is a clear correlation between the incidence of opisthorchiasis and high incidence of cholangiocarcinoma in South-East Asia. Liver flukes Clonorchis sinensis and Opisthorchis viverrini are I class carcinogens. There are some endemic regions of opisthorchiasis In the Russian Federation. The most important factor that leads to carcinogenesis during liver fluke infection is chronic inflammation. This review article focuses on the communication of chronic inflammation caused by invasion of liver flukes and cholangiocarcinoma. This paper summarizes the current knowledge about the risk factors for cholangiocarcinoma, as well as knowledge about the molecular aspects of the induction of carcinogenesis by liver flukes.

  14. Cholangiocarcinoma with respect to IgG4 Reaction

    Directory of Open Access Journals (Sweden)

    Kenichi Harada

    2014-01-01

    Full Text Available IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important.

  15. Treatment of hilar cholangiocarcinoma with inserting biliary double stents

    International Nuclear Information System (INIS)

    Jia Guangzhi; Zhang Zidong; Wang Xuejing; Yin Hua; Li Jianming

    2004-01-01

    Objective: To investigate the inserting technique of biliary double stents in treating hilar cholangiocarcinoma. Methods: 6 patients with hilar cholangiocarcinoma (Bismuth IV) were treated by percutaneous transhepatic insertion of biliary stents. Double stents were inserted in each patient. Different inserting methods were adopted according to the branch angles formed by left and right hepatic ducts. Results: The jaundice of all patients alleviated or disappeared obviously after stent implantation. The average difference between post-and pre-operation in the serum total bilirubin level was (104 ± 29) μmol/L (P<0.01). Stent obstruction was found in 2 cases after 4 and 6 months respectively. Conclusion: Double stents implantation is effective for the treatment of hilar cholangiocarcinoma. Beware of the angulation between main hepatic duct and adopting different inserting methods. (authors)

  16. Down-regulation of Gab1 inhibits cell proliferation and migration in hilar cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Haiquan Sang

    Full Text Available Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the hilar biliary duct epithelium. Due to few effective comprehensive treatments, the prognosis of hilar cholangiocarcinoma is poor. In this study, immunohistochemistry was first used to detect and analyze the expression of Gab1, VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly expressed and positively correlated with each other in hilar cholangiocarcinoma tissues, which were related to lymph node metastasis and differentiation. 2. After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9 levels were decreased in ICBD-1 cells. At the same time, cell proliferation decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and influences the invasion of tumor cells via MMP-9.

  17. Down-regulation of Gab1 inhibits cell proliferation and migration in hilar cholangiocarcinoma.

    Science.gov (United States)

    Sang, Haiquan; Li, Tingting; Li, Hangyu; Liu, Jingang

    2013-01-01

    Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the hilar biliary duct epithelium. Due to few effective comprehensive treatments, the prognosis of hilar cholangiocarcinoma is poor. In this study, immunohistochemistry was first used to detect and analyze the expression of Gab1, VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly expressed and positively correlated with each other in hilar cholangiocarcinoma tissues, which were related to lymph node metastasis and differentiation. 2. After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9 levels were decreased in ICBD-1 cells. At the same time, cell proliferation decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and influences the invasion of tumor cells via MMP-9.

  18. Expression of Her-2/neu in extrahepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Shamekh R

    2017-02-01

    Full Text Available Rania Shamekh,1,* Marilin Rosa,2,* Zena Sayegh,2 Masoumeh Ghayouri,2 Richard Kim,3 Mokenge P Malafa,3 Domenico Coppola2 1Department of Pathology, University of South Florida, 2Department of Anatomic Pathology, 3Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA *These authors contributed equally to this work Background: Receptor tyrosine-protein kinase erbB-2, which is also frequently called human epidermal growth factor receptor-2 (Her-2 or Her-2/neu, has been found to be overexpressed in various human cancers.Hypothesis: The aim of this pilot study was to explore the frequency of Her-2/neu gene amplification and protein expression in extrahepatic cholangiocarcinoma (EHBC. We used the World Health Organization classification criteria for EHBC.Materials and methods: This was a retrospective study using 88 tissue samples, including 45 samples from non-neoplastic biliary tissue (NNB and 43 samples of extrahepatic cholangiocarcinoma (EHBC. A tissue microarray including NNB and EHBC was constructed and analyzed by immunohistochemistry (IHC and dual in situ hybridization for Her-2/neu protein expression and amplification, respectively. The Her-2/neu expression was scored following the guidelines used for the ToGA study.Results: All NNB samples and all but one EHBC samples showed no expression of Her-2/neu by IHC. The one EHBC case immunohistochemically positive for Her-2/neu had an IHC score of 3+. Her-2/neu gene amplification was present in two EHBC samples only and included the case found to be positive by IHC.Conclusion: Our findings are similar to those reported in the literature. Although Her-2/neu overexpression has been documented in many types of cancer, Her-2/neu protein overexpression tends to have no role in the development and/or progression of EHBC. Keywords: extrahepatic, cholangiocarcinoma, Her-2/neu, ToGA, immunohistochemistry

  19. Diagnostic value of MRI for hepatic hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Wang Zhen; Zuo Yujiang; Sun Lihui; Zhou Jian; Shen Bingqi

    2010-01-01

    Objective: To investigate the value of MRI in the diagnosis of hepatic hilar cholangiocarcinoma. Methods: Sixty-four patients with hepatic hilar cholangiocarcinomas confirmed by surgery or pathology underwent MRI using a 1.5-T superconductive MR system including conventional unenhanced MRI, MRCP and dynamic contrast-enhanced MRI with Gd-DTPA. Results: Dilatation of the intrahepatic biliary tree with narrowing, occlusion or filling defects in the hepatic hilar bile ducts was noted in all 64 cases. Unenhanced MR[ showed T 1 - and T 2 -hyperintense hilar masses in 42 patients and was normal in the remaining 22 patients. The hilar masses demonstrated slow, progressive and delayed enhancement patterns. There was enhancement of the thickened bile duct wall with luminal narrowing in the 22 patients without hilar masses. Conclusion: The characteristic MRI findings of enhancing hepatic hilar mass and bile duct wall thickening together with MRCP are valuable for diagnosing hepatic hilar cholangiocarcinomas. (authors)

  20. Cholangiocarcinoma with Lymphoepithelioma-like Component not Associated with Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Wen-Han Chang

    2015-12-01

    Full Text Available Lymphoepithelioma-like cholangiocarcinoma (LELCC is a rare variant of intrahepatic cholangiocarcinoma. We herein have reported an unusual case of LELCC in a 71-year-old Taiwanese women with cirrhotic liver disease and chronic hepatitis C. The patient's liver tumor was unexpectedly discovered during a regular abdominal ultrasound exam without obvious clinical symptoms and signs; she thereafter received surgical resection. Histologically, the liver tumor showed lymphoepithelial-like appearance and features of cholangiocarcinoma without association with Epstein-Barr virus (EBV. We maintained regular follow-up with the patient for 3 years, who at that time was alive without tumor recurrence.

  1. Duct-to-duct biliary reconstruction after radical resection of Bismuth IIIa hilar cholangiocarcinoma.

    Science.gov (United States)

    Wu, Wen-Guang; Gu, Jun; Dong, Ping; Lu, Jian-Hua; Li, Mao-Lan; Wu, Xiang-Song; Yang, Jia-Hua; Zhang, Lin; Ding, Qi-Chen; Weng, Hao; Ding, Qian; Liu, Ying-Bin

    2013-04-21

    At present, radical resection remains the only effective treatment for patients with hilar cholangiocarcinoma. The surgical approach for R0 resection of hilar cholangiocarcinoma is complex and diverse, but for the biliary reconstruction after resection, almost all surgeons use Roux-en-Y hepaticojejunostomy. A viable alternative to Roux-en-Y reconstruction after radical resection of hilar cholangiocarcinoma has not yet been proposed. We report a case of performing duct-to-duct biliary reconstruction after radical resection of Bismuth IIIa hilar cholangiocarcinoma. End-to-end anastomosis between the left hepatic duct and the distal common bile duct was used for the biliary reconstruction, and a single-layer continuous suture was performed along the bile duct using 5-0 prolene. The patient was discharged favorably without biliary fistula 2 wk later. Evidence for tumor recurrence was not found after an 18 mo follow-up. Performing bile duct end-to-end anastomosis in hilar cholangiocarcinoma can simplify the complex digestive tract reconstruction process.

  2. Palliative management of hilar cholangiocarcinoma

    NARCIS (Netherlands)

    Singhal, D.; van Gulik, T. M.; Gouma, D. J.

    2005-01-01

    Around 80% of the patients with hilar cholangiocarcinoma are candidates for palliative management due to extensive co-morbidity for major surgery, metastases or advanced loco-regional disease. The primary aim of treatment is to provide biliary drainage with long-term relief from pruritis,

  3. Evaluation of delayed contrast-enhanced CT scan in diagnosing hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Li Jianding; Liang Chenyang; Zhang Hua; Zhang Yuezhen; Li Rui

    2001-01-01

    Objective: To assess the diagnostic value of delayed CT contrast enhancement patterns in hilar cholangiocarcinoma based on two-phased dynamic incremental CT scanning. Methods: Fifty-two patients with suspected hilar tumor and bile duct obstruction underwent spiral CT scan. The scan time for one revolution of the X-ray tube was 1 second. To elucidate the delay time for optimal imaging, all proved cholangiocarcinoma with delayed (6, 8, 10, 15, 20, 30 minutes) post-equilibrium-phase contrast-enhanced CT scans were acquired with unenhanced, dynamic contrast-enhanced, and delayed images. Degree of delayed enhancement was compared with that of surrounding liver parenchyma. Results: (1) 8-15 minutes after IV injection of contrast material was the delay time for optimal imaging. (2) Of 29 cholangiocarcinomas, the early CT showed hypo-attenuating (lower than that of liver parenchyma) in 23 tumors, iso-attenuating (equal to that of the liver) in 4 tumors, and hyper-attenuating (higher than that of liver) in 2 tumors. The delayed CT scan showed iso-attenuating in 8 tumors, hyper-attenuating in 21 tumors, and no hypo-attenuating. Most of delay imaging of hilar cholangiocarcinoma may appear hyper-attenuating (U = -4.3073, P 2 = 9.09, P < 0.01). Conclusion: When assessing hilar tumor, delayed CT contrast enhancement patterns based on two-phase dynamic incremental CT scans is useful in the detection and characterization of hilar cholangiocarcinoma

  4. A massive hepatic tumor demonstrating hepatocellular, cholangiocarcinoma and neuroendocrine lineages: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Rachel E. Beard

    2017-01-01

    Conclusion: This is one of the only reports of a hepatic tumor arising from hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine lineages. Increased awareness of this tumor type may optimize improve future management.

  5. Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels

    International Nuclear Information System (INIS)

    Lin, Zi-Ying; Liang, Zhen-Xing; Zhuang, Pei-Lin; Chen, Jie-Wei; Cao, Yun; Yan, Li-Xu; Yun, Jing-Ping; Xie, Dan; Cai, Mu-Yan

    2016-01-01

    Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients’ cancer-specific survival and recurrence-free survival rates. High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management

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

    International Nuclear Information System (INIS)

    Fan, Zhongqi; Yu, Huimei; Cui, Ni; Kong, Xianggui; Liu, Xiaomin; Chang, Yulei; Wu, Yao; Sun, Liankun; Wang, Guangyi

    2015-01-01

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

  7. Elevated AQP1 Expression Is Associated With Unfavorable Oncologic Outcome in Patients With Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Li, Chunxiang; Li, Xiaofu; Wu, Linfeng; Jiang, Zheng

    2017-08-01

    Hilar cholangiocarcinomas are malignant tumors with a poor prognosis. An early prediction of prognosis for patients may help us determine treatment strategies. Aquaporin 1 is a cell membrane channel involved in water transport, cell motility, and proliferation. Increasing evidences showed that aquaporin 1 played a role in tumor prognosis and diagnosis. The purpose of this study is to evaluate the role of aquaporin 1 in hilar cholangiocarcinoma. Here, we analyzed messenger RNA expression data of genes function as bile secretion in a data set of 169 samples using the R2 bioinformatic platform ( http://r2.amc.nl ). Quantitative polymerase chain reaction was performed to verify the gene expression in 17 hilar cholangiocarcinoma samples. Immunohistochemistry was also performed in a series of specimens from 62 hilar cholangiocarcinoma tissues, and its clinical significance was assessed by clinical correlation and Kaplan-Meier analyses. All data were analyzed using the R2 web application, aquaporin 1 was selected for further analysis. The significant expression variation of aquaporin 1 among 17 cases with cholangiocarcinoma was also found using quantitative polymerase chain reaction. The expression level of aquaporin 1 protein significantly correlated with tumor-node-metastasis stage ( P = .002) and overall survival time ( P = .010). Higher aquaporin 1 expression indicated poor prognostic outcomes ( P hilar cholangiocarcinoma ( P = .002). This study highlighted the prognostic value of aquaporin 1 in hilar cholangiocarcinoma. Strong aquaporin 1 expression predicts poor survival, regardless of pathological features. Immunohistochemical detection of aquaporin 1, as a prognostic marker, may contribute to predicting clinical outcome for patients with hilar cholangiocarcinoma.

  8. A case of distal extrahepatic cholangiocarcinoma with two positive resection margins.

    Science.gov (United States)

    Warner, Wayne A; Ramcharan, Wesley; Harnanan, Dave; Umakanthan, Srikanth; Maharaj, Ravi

    2016-11-01

    Cholangiocarcinoma is an uncommon primary malignancy of the biliary tract that is challenging to diagnose and treat effectively due to its relatively silent and late clinical presentation. The present study reports a case of a 60-year-old male with distal extrahepatic cholangiocarcinoma with a 3-week history of painless obstructive jaundice symptoms and subjective weight loss. Imaging revealed an obstructing lesion in the common bile duct, just distal to the entrance of the cystic duct. Pathology revealed moderately differentiated cholangiocarcinoma with two positive proximal resection margins. The two positive resection margins presented a challenge during surgery and points to an urgent need for further studies to better illuminate diagnostic and therapeutic options for patients with similar clinicopathological presentation.

  9. Percutaneous biliary drainage in patients with cholangiocarcinoma

    International Nuclear Information System (INIS)

    Mehta, A.C.; Gobel, R.J.; Rose, S.C.; Hayes, J.K.; Miller, F.J.

    1990-01-01

    This paper determines whether radiation therapy (RT) is a risk factor for infectious complications (particularly hepatic abscess formation) related to percutaneous biliary drainage (PBD). The authors retrospectively reviewed the charts of 98 consecutive patients who had undergone PBD for obstruction. In 34 patients with benign obstruction, three infectious complications occurred, none of which were hepatic abscess or fatal sepsis. In 39 patients who had malignant obstruction but did not have cholangiocarcinoma, 13 infectious complications occurred, including two hepatic abscesses and three cases of fatal sepsis. Of the 25 patients with cholangiocarcinoma, 15 underwent RT; in these 15 patients, 14 infectious complications occurred, including six hepatic abscesses and two cases of fatal sepsis

  10. High mobility group A1 enhances tumorigenicity of human cholangiocarcinoma and confers resistance to therapy

    DEFF Research Database (Denmark)

    Quintavalle, Cristina; Burmeister, Katharina; Piscuoglio, Salvatore

    2017-01-01

    High mobility group A1 (HMGA1) protein has been described to play an important role in numerous types of human carcinoma. By the modulation of several target genes HMGA1 promotes proliferation and epithelial-mesenchymal transition of tumor cells. However, its role in cholangiocarcinoma (CCA) has...

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

    Directory of Open Access Journals (Sweden)

    Liberato Manuel José

    2012-08-01

    Full Text Available Abstract Background Endoscopic biliary drainage of hilar cholangiocarcinoma is controversial with respect to the optimal types of stents and the extent of drainage. This study evaluated endoscopic palliation in patients with hilar cholangiocarcinoma using self-expandable metallic stents (SEMS and plastic stents (PS.We also compared unilateral and bilateral stent placement according to the Bismuth classification. Methods Data on 480 patients receiving endoscopic biliary drainage for hilar cholangiocarcinoma between September 1995 and December 2010 were retrospectively reviewed to evaluate the following outcome parameters: technical success (TS, functional success (FS, early and late complications, stent patency and survival. Patients were followed from stent insertion until death or stent occlusion. Patients were divided into 3 groups according to the Bismuth classification (Group 1, type I; Group 2, type II; Group 3, type > III. Results The initial stent insertion was successful in 450 (93.8% patients. TS was achieved in 204 (88.3% patients treated with PS and in 246 (98.8% patients palliated with SEMS (p P P  Conclusions SEMS insertion for the palliation of hilar cholangiocarcinoma offers higher technical and clinical success rates in the ITT analysis as well as lower complication rates and a superior cumulative stent patency when compared with PS placement in all Bismuth classifications. The cumulative patency of bilateral SEMS or PS stents was significantly higher than that of unilateral SEMS or PS stents, with lower occlusion rates in Bismuth II patients.

  12. Diffusion-weighted MR imaging for detection of extrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Cui, Xing-Yu; Chen, Hong-Wei; Cai, Song; Bao, Jian; Tang, Qun-Feng; Wu, Li-Yuan; Fang, Xiang-Ming

    2012-01-01

    Objectives: To measure the sensitivity of diffusion-weighted imaging (DWI) and determine the most appropriate b value for DWI; to explore the correlation between the apparent diffusion coefficient (ADC) value and the degree of extrahepatic cholangiocarcinoma differentiation. Methods: Preoperative diffusion-weighted imaging and magnetic resonance examinations were performed for 31 patients with extrahepatic cholangiocarcinoma. Tumor ADC values were measured, and the signal-to-noise ratio, contrast-to-noise ratio, and signal-intensity ratio between the diffusion-weighted images with various b values as well as the T2-weighted images were calculated. Pathologically confirmed patients were pathologically graded to compare the ADC value with different b values of tumor at different degrees of differentiation, and the results were statistically analyzed by using the Friedman test. Results: A total of 29 cases of extrahepatic cholangiocarcinoma were detected by DWI. As the b value increased, tumor signal-to-noise ratio and contrast-to-noise ratio between the tumor and normal liver gradually decreased, but the tumor signal-intensity ratio gradually increased. When b = 800 s/mm 2 , contrast-to-noise ratio between tumor and normal liver, tumor signal-intensity ratio, and tumor signal-to-noise ratio of diffusion-weighted images were all higher than those of T2-weighted images; the differences were statistically significant (P 2 was the best in DWI of extrahepatic cholangiocarcinoma; the lesion ADC value declined as the degree of cancerous tissue differentiation decreased.

  13. Intrahepatic cholangiocarcinoma--a rare indication for liver transplantation. Case report and review of the literature.

    Science.gov (United States)

    Hrehoreţ, D; Alexandrescu, S; Grigorie, R; Herlea, V; Anghel, R; Popescu, I

    2012-01-01

    While hepatocellular carcinoma is a common indication for liver transplantation, intrahepatic cholangiocarcinoma represents a controversial indication for this procedure, due to lower disease-free and overall survival rates achieved by liver transplantation in such patients. Hence, in the last years, few centers reported satisfactory survival rates after liver transplantation for cholangiocarcinoma, in highly selected groups of patients. Herein we present the clinicopathological characteristics, the pre- and postoperative management and the favorable outcome of a patient undergoing liver transplantation for an unresectable intrahepatic cholangiocarcinoma. We consider that reporting the patients with such favorable outcomes is useful, since collecting the data presented by different centers may contribute to identification of a selected group of patients with cholangiocarcinoma who may benefit from liver transplantation. A 62-year old female patient with a primary liver tumor developed on HBV liver cirrhosis, was admitted in our center for therapeutical management. Since preoperative work-up suggested that the tumor is an unresectable hepatocellular carcinoma (due to its location and underlying liver disease), we decided to perform liver transplantation. The pathological examination of the explanted liver revealed that the tumor was a stage I intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and in present, 15 months after transplantation, the patient is alive, without recurrence. Liver transplantation may represent a valid therapeutical option in selected patients with intrahepatic cholangiocarcinoma. Patients with early stage intrahepatic cholangiocarcinomas unresectable due to the underlying liver cirrhosis seem to benefit mostly by liver transplantation. Further studies are needed to identify the favorable prognostic factors in order to select the most appropriate candidates for liver transplantation. The most suitable immunosuppressive

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

    DEFF Research Database (Denmark)

    Grunnet, Mie; Christensen, I J; Lassen, Ulrik

    2014-01-01

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

  15. Current research in perineural invasion of cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Deng Xi-Yun

    2010-03-01

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

  16. Overexpression of Prdx1 in hilar cholangiocarcinoma: a predictor for recurrence and prognosis.

    Science.gov (United States)

    Zhou, Jie; Shen, Weiwen; He, Xiaojing; Qian, Jing; Liu, Shiyuan; Yu, Guanzhen

    2015-01-01

    Prdx1 is an important member of peroxiredoxins (Prdxs) regulating various cellular signaling and differentiation. Prdx1 confers an aggressive survival phenotype of cancer cells and drug-resistance, yet its role in hilar cholangiocarcinoma is not fully investigated. In present study, we detected the expression profile of Prdx1 in 88 hilar cholangiocarcinoma by tissue arrays and immunohistochemistry. Prdx1 level was down-regulated by specific Prdx1-shRNA in vitro and the possible mechanism was investigated. Overexpression of Prdx1 was observed in 53 of 88 cases (60.2%). Prdx1 expression was significantly associated with tumor invasion, nodal metastasis, advanced disease stage. Down-regulation of Prdx1 inhibited cell proliferation and colony formation of QBC939 cells and reduced the level of SNAT1 expression. Patients with Prdx1 overexpression had a shorter disease-free survival and overall survival than those without Prdx1 expression. Multivariate analysis showed that Prdx1 was an independent prognostic factor for patients with hilar cholangiocarcinoma. The data indicate that Prdx1 may contribute to the development and progression of hilar cholangiocarcinoma, partially through regulating SNAT1 expression, and may be used as a biomarker in predicting the outcome of patients with hilar cholangiocarcinoma.

  17. Mass-forming intrahepatic cholangiocarcinoma: Enhancement patterns in the arterial phase of dynamic hepatic CT - Correlation with clinicopathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Nobuhiro; Asayama, Yoshiki; Nishie, Akihiro; Ishigami, Kousei; Ushijima, Yasuhiro; Okamoto, Daisuke; Moirta, Koichiro; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan); Takayama, Yukihisa [Kyushu University, Department of Radiology Informatics and Network, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan); Shirabe, Ken [Kyushu University, Department of Surgery and Science, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan); Aishima, Shinichi [Saga University Hospital, Department of Pathology and Microbiology, Faculty of Medicine, Saga City, Saga (Japan); Wang, Huanlin; Oda, Yoshinao [Kyushu University, Department of Anatomic Pathology, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan)

    2017-02-15

    To evaluate the relationship between the enhancement pattern of intrahepatic cholangiocarcinomas (ICCs) in the hepatic arterial phase (HAP) of dynamic hepatic CT and the clinicopathological findings with special reference to the perihilar type and the peripheral type. Forty-seven patients with pathologically proven ICCs were enrolled. Based on the enhancement pattern in the HAP, the lesions were classified into three groups: a hypovascular group (n=13), rim-enhancement group (n=18), and hypervascular group (n=16). The clinicopathological findings were compared among the three groups. Perihilar-type ICCs were significantly more frequently observed in the hypovascular group than in the rim-enhancement and hypervascular groups (p=0.006 and p <0.001, respectively). Lymphatic invasion, perineural invasion, and biliary invasion were significantly more frequent in the hypovascular group than the rim- enhancement group (p=0.001, p=0.025 and p=0.029, respectively) or hypervascular group (p <0.001, p <0.001 and p=0.025, respectively). Patients with hypovascular lesions showed significantly poorer disease-free survival than patients with rim-enhancing or hypervascular lesions (p=0.001 and p=0.001, respectively). Hypovascularity was an independent preoperative prognostic factor for disease-free survival (p<0.001). Hypovascular ICCs in the HAP tend to be of perihilar type and to have more malignant potential than other ICCs. (orig.)

  18. Interleukin-8 is a prognostic indicator in human hilar cholangiocarcinoma

    Science.gov (United States)

    Sun, Qi; Li, Fanni; Sun, Fengkai; Niu, Jun

    2015-01-01

    Interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and neovascularization have been implicated to be associated with biological processes, especially cancer progression. However, few studies have investigated the role of IL-8 in human hilar cholangiocarcinoma. In this study we detected the expression of IL-8 combined with MMP-9 and microvessel density (MVD) in hilar cholangiocarcinoma to evaluate their clinicopathological significance and prognostic value. A total of 62 patients with hilar cholangiocarcinoma who underwent curative surgery were enrolled in this study. The expression of IL-8, MMP-9 and MVD were examined immunohistochemically. The correlation of IL-8 with MMP-9 expression, MVD, clinicopathological features and survival time of patients were then analyzed. Expression of IL-8 was observed in 56.5% tumors, which was related to advanced TNM stage (P = 0.026) and tumor recurrence (P = 0.018). IL-8 had a positive correlation with MMP-9 expression and MVD. Furthermore, patients with high IL-8 expression had a significantly shorter overall survival than those with low IL-8 expression (P = 0.01). Multivariate analysis confirmed IL-8 as an independent prognostic factor (P = 0.005). In conclusion, IL-8 expression significantly correlated with MMP-9 expression and MVD, and IL-8 was a valuable prognostic factor for human hilar cholangiocarcinoma. PMID:26339407

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

    Science.gov (United States)

    2012-01-01

    Background Endoscopic biliary drainage of hilar cholangiocarcinoma is controversial with respect to the optimal types of stents and the extent of drainage. This study evaluated endoscopic palliation in patients with hilar cholangiocarcinoma using self-expandable metallic stents (SEMS) and plastic stents (PS).We also compared unilateral and bilateral stent placement according to the Bismuth classification. Methods Data on 480 patients receiving endoscopic biliary drainage for hilar cholangiocarcinoma between September 1995 and December 2010 were retrospectively reviewed to evaluate the following outcome parameters: technical success (TS), functional success (FS), early and late complications, stent patency and survival. Patients were followed from stent insertion until death or stent occlusion. Patients were divided into 3 groups according to the Bismuth classification (Group 1, type I; Group 2, type II; Group 3, type > III). Results The initial stent insertion was successful in 450 (93.8%) patients. TS was achieved in 204 (88.3%) patients treated with PS and in 246 (98.8%) patients palliated with SEMS (p stent patency in weeks (w) were as follows: 20 w in patients palliated with PS and 27 w in patients treated with SEMS (p stent patency. Conclusions SEMS insertion for the palliation of hilar cholangiocarcinoma offers higher technical and clinical success rates in the ITT analysis as well as lower complication rates and a superior cumulative stent patency when compared with PS placement in all Bismuth classifications. The cumulative patency of bilateral SEMS or PS stents was significantly higher than that of unilateral SEMS or PS stents, with lower occlusion rates in Bismuth II patients. PMID:22873816

  20. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy.

    Science.gov (United States)

    Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K; van Wijk, Albert C; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C; van Gulik, Thomas M; Storm, Gert; Heger, Michal

    2016-01-19

    Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1β dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.

  1. Prevalence of nonalcoholic steatohepatitis among patients with resectable intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Reddy, Srinevas K; Hyder, Omar; Marsh, J Wallis; Sotiropoulos, Georgios C; Paul, Andreas; Alexandrescu, Sorin; Marques, Hugo; Pulitano, Carlo; Barroso, Eduardo; Aldrighetti, Luca; Geller, David A; Sempoux, Christine; Herlea, Vlad; Popescu, Irinel; Anders, Robert; Rubbia-Brandt, Laura; Gigot, Jean-Francois; Mentha, Giles; Pawlik, Timothy M

    2013-04-01

    The objective of this report was to determine the prevalence of underlying nonalcoholic steatohepatitis in resectable intrahepatic cholangiocarcinoma. Demographics, comorbidities, clinicopathologic characteristics, surgical treatments, and outcomes from patients who underwent resection of intrahepatic cholangiocarcinoma at one of eight hepatobiliary centers between 1991 and 2011 were reviewed. Of 181 patients who underwent resection for intrahepatic cholangiocarcinoma, 31 (17.1 %) had underlying nonalcoholic steatohepatitis. Patients with nonalcoholic steatohepatitis were more likely obese (median body mass index, 30.0 vs. 26.0 kg/m(2), p < 0.001) and had higher rates of diabetes mellitus (38.7 vs. 22.0 %, p = 0.05) and the metabolic syndrome (22.6 vs. 10.0 %, p = 0.05) compared with those without nonalcoholic steatohepatitis. Presence and severity of hepatic steatosis, lobular inflammation, and hepatocyte ballooning were more common among nonalcoholic steatohepatitis patients (all p < 0.001). Macrovascular (35.5 vs. 11.3 %, p = 0.01) and any vascular (48.4 vs. 26.7 %, p = 0.02) tumor invasion were more common among patients with nonalcoholic steatohepatitis. There were no differences in recurrence-free (median, 17.0 versus 19.4 months, p = 0.42) or overall (median, 31.5 versus 36.3 months, p = 0.97) survival after surgical resection between patients with and without nonalcoholic steatohepatitis. Nonalcoholic steatohepatitis affects up to 20 % of patients with resectable intrahepatic cholangiocarcinoma.

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

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Jakobsen, Anders

    2011-01-01

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

  3. Vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma

    OpenAIRE

    Baek, Sungmin; Lee, Young-Suk; Shim, Hye-Eun; Yoon, Sik; Baek, Sun-Yong; Kim, Bong-Seon; Oh, Sae-Ock

    2011-01-01

    A low serum level of vitamin D has been associated with an increased incidence of gastrointestinal tract cancers. However, the effects of vitamin D3 have not been investigated in gastric cancer and cholangiocarcinoma. In the present study, we found that vitamin D3 treatment significantly suppressed the viability of gastric cancer and cholangiocarcinoma cells. Moreover, vitamin D3 had a synergistic effect with other anti-cancer drugs, such as paclitaxel, adriamycin, and vinblastine, for suppre...

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

    International Nuclear Information System (INIS)

    Valek, Vlastimil; Kysela, Petr; Kala, Zdenek; Kiss, Igor; Tomasek, Jiri; Petera, Jiri

    2007-01-01

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

  5. Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves.

    Science.gov (United States)

    Anholt, R R; Murphy, K M; Mack, G E; Snyder, S H

    1984-02-01

    Binding levels of [3H]Ro5-4864, a ligand selective for peripheral-type benzodiazepine receptors, are substantially higher in homogenates of the olfactory bulb than in the rest of the brain. Among peripheral tissues evaluated, high levels of [3H]Ro5-4864 binding are found in the nasal epithelium. Drug displacement studies show that these binding sites are pharmacologically of the peripheral type. Their presence in the nasal epithelium and in the olfactory bulb can be demonstrated in several different mammalian species. Autoradiographic studies of murine nose reveal a bipolar staining pattern around the cell bodies of the olfactory receptor cells, suggesting the presence of peripheral-type benzodiazepine receptors on both processes of these bipolar neurons. In the brain a high density of [3H]Ro5-4864 binding sites occurs in the nerve fiber and glomerular layers of the olfactory bulb. Throughout the rest of the brain [3H]Ro5-4864-associated silver grains are diffusely distributed with intense staining over the choroid plexus and along the ependymal linings of the ventricles. Both the distribution and the ontogenic development of the peripheral-type benzodiazepine receptors differ from the central-type receptors. Intranasal irrigation with 5% ZnSO4 results in a 50% reduction of peripheral-type benzodiazepine receptors in the olfactory bulb without affecting the density of central-type benzodiazepine receptors. Thus, [3H]Ro5-4864 binding sites in the olfactory bulb appear in large part to be localized to olfactory nerves which originate in the nasal epithelium.

  6. Prognostic significance of macrophage invasion in hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Atanasov, Georgi; Hau, Hans-Michael; Dietel, Corinna; Benzing, Christian; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Matia, Ivan; Prager, Isabel; Schierle, Katrin; Robson, Simon C.; Reutzel-Selke, Anja; Pratschke, Johann; Schmelzle, Moritz; Jonas, Sven

    2015-01-01

    Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients’ survival. Statistical analysis was performed using SPSS software. Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6 % vs. 75.1 %; three-year 61.3 % vs. 42.4 %; both ρ < 0.05) and recurrence-free survival (one-year 93.9 % vs. 57.4 %; three-year 59.8 % vs. 26.2 %; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs

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

    Directory of Open Access Journals (Sweden)

    Maarten Criel

    2012-01-01

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

  8. Sonography-guided percutaneous microwave ablation of intrahepatic primary cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yu Mingan [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Liang Ping, E-mail: Liangping301@hotmail.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu Xiaoling; Cheng Zhigang; Han Zhiyu; Liu Fangyi; Yu Jie [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China)

    2011-11-15

    Objective: To evaluate the efficacy and safety of sonography-guided percutaneous microwave ablation of intrahepatic primary cholangiocarcinoma. Materials and methods: From May 2006 to March 2010, 15 patients (11 men, 4 women; mean age, 57.4 years) with 24 histologically proven intrahepatic primary cholangiocarcinoma lesions (mean tumor size, 3.2 {+-} 1.9 cm; range, 1.3-9.9 cm) were treated with microwave ablation. Results: Thirty-eight sessions were performed for 24 nodules in 15 patients. The follow-up period was 4-31 months (mean, 12.8 {+-} 8.0 months). The ablation success rate, the technique effectiveness rate, and the local tumor progression rate were 91.7% (22/24), 87.5% (21/24), and 25% (6/24) respectively according to the results of follow-up. The cumulative overall 6, 12, 24 month survival rates were 78.8%, 60.0%, and 60.0%, respectively. Major complication occurred including liver abscess in two patients (13.3%) and needle seeding in one patient (6.7%). Both complications were cured satisfied with antibiotic treatment combined to catheter drainage for abscess and resection for needle seeding. The minor complications and side effects were experienced by most patients which subsided with supportive treatment. Conclusion: Microwave ablation can be used as a safe and effective technique to treat intrahepatic primary cholangiocarcinoma.

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

    International Nuclear Information System (INIS)

    Kose, Fatih; Oguzkurt, Levent; Besen, Ayberk; Sumbul, Taner; Sezer, Ahmet; Karadeniz, Cemile; Disel, Umut; Mertsoylu, Huseyin; Ozyilkan, Ozgur

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-15

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

  11. Peripheral neuropathy in patients with myotonic dystrophy type 2.

    Science.gov (United States)

    Leonardis, L

    2017-05-01

    Myotonic dystrophy type 2 (dystrophia myotonica type 2-DM2) is an autosomal dominant multi-organ disorder. The involvement of the peripheral nervous system was found in 25%-45% of patients with myotonic dystrophy type 1, although limited data are available concerning polyneuropathy in patients with DM2, which was the aim of this study with a thorough presentation of the cases with peripheral neuropathy. Patients with genetically confirmed DM2 underwent motor nerve conduction studies of the median, ulnar, tibial and fibular nerves and sensory nerve conduction studies of the median (second finger), ulnar (fifth finger), radial (forearm) and sural nerves. Seventeen adult patients with DM2 participated in the study. Fifty-three percent (9/17) of our patients had abnormality of one or more attributes (latency, amplitude or conduction velocity) in two or more separate nerves. Four types of neuropathies were found: (i) predominantly axonal motor and sensory polyneuropathy, (ii) motor polyneuropathy, (iii) predominantly demyelinating motor and sensory polyneuropathy and (iv) mutilating polyneuropathy with ulcers. The most common forms are axonal motor and sensory polyneuropathy (29%) and motor neuropathy (18% of all examined patients). No correlations were found between the presence of neuropathy and age, CCTG repeats, blood glucose or HbA1C. Peripheral neuropathy is common in patients with DM2 and presents one of the multisystemic manifestations of DM2. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Recurrent thrombo-embolic episodes: the association of cholangiocarcinoma with antiphospholipid syndrome

    Science.gov (United States)

    Samadian, S; Estcourt, L

    1999-01-01

    Antiphospholipid syndrome is a disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently elevated levels of antiphospholipid antibodies. It was first described in a group of patients with systemic lupus erythematosus but has since been associated with a wide range of conditions, including other autoimmune disorders and malignancy. It can also occur in isolation, the so-called primary antiphospholipid syndrome. We describe an elderly woman with the antiphospholipid syndrome thought to be associated with a cholangiocarcinoma.


Keywords: antiphospholipid syndrome; cholangiocarcinoma; deep vein thrombosis PMID:10396590

  13. Pathological aspects of so called "hilar cholangiocarcinoma".

    Science.gov (United States)

    Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

    2013-07-15

    Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, "hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

  14. Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

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

    2016-01-01

    , the context of tumor plasticity and the causative features driving the disease. Molecular profiling and pathological techniques have begun to underline persistent alterations that may trigger inherited drug resistance (a hallmark of hepatobiliary and pancreatic cancers), metastasis and disease recurrence......Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic...... clinical strategies and patient outcome. This was achieved for other cancers, such as breast carcinoma, facilitated by the delineation of patient subsets and of precision therapies. In iCCA, many questions persevere as to the evolutionary process and cellular origin of the initial transforming event...

  15. Pathomorphological characteristics of 102 cases of Thorotrast-related hepatocellular carcinoma, cholangiocarcinoma, and hepatic angiosarcoma

    International Nuclear Information System (INIS)

    Nakashima, T.; Kojiro, M.; Ito, Y.; Mori, T.; Kido, C.

    1987-01-01

    We described the pathomorphological characteristics of 102 autopsy cases of Thorotrast (Th) related hepatic malignancies, and compared these to the features of non-Th-related cases. Among the 102 Th-related hepatic malignancies, 44 (43.1%) were cholangiocarcinoma (CHC), 39 (38.3%) were angiosarcoma (AGS), 16 (15.7%) were hepatocellular carcinoma (HCC), and 3 (2.9%) were double cancer. Grossly, the majority (91.7%) of Th-related CHC was located in the middle-peripheral portion of the liver. Th-related AGS was classified into four types: diffuse micronodular, multinodular, massive and mixed multinodular, and massive. Histologically, in CHC and HCC cases, there were no significant differences between Th-related and non-Th-related cases. AGS was characterized by two cell types (spindle-shaped cells and polyhedral cells) and three growth patterns (sinusoidal, carvernous, and solid). In non-cancerous areas, foci of varying degrees of sinusoidal dilatation with hyperplastic changes of sinusoidal lining cells were observed in all AGS cases and in some of the cases of Th-related CHC and HCC cases. In Th-related CHC cases, papillary proliferation of the epithelium of relatively large bile ducts was seen in 11 (29.7%) of the 37 cases, and proliferation of small bile ducts and/or bile ductules was seen in 9 (24.3%) of the 37 cases. However, similar histologic changes were also observed in the non-Th- related CHC cases. In Th-related HCC cases, mixed macro- and micronodular cirrhosis was superimposed on varying degrees of hepatic fibrosis related to Th deposition in 4 cases. (21.1%). (author)

  16. Desmoplastic Tumor Microenvironment and Immunotherapy in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Høgdall, Dan; Lewinska, Monika; Andersen, Jesper B

    2018-01-01

    connective tissue which surrounds and infiltrates the tumor epithelium. This desmoplastic environment presents a clinical challenge, limiting drug delivery and supporting the growth of the tumor mass. In this review we attempt to highlight key pathways involved in cell to cell communication between the tumor......Cholangiocarcinoma (CCA) is a dismal disease which often is diagnosed at a late stage where the tumor is locally advanced, metastatic, and, as a result, is associated with low resectability. The heterogeneity of this cancer type is a major reason why the majority of patients fail to respond...... to therapy, and surgery remains their only curative option. Among patients who undergo surgical intervention, such tumors typically recur in 50% of cases within 1year. Thus, CCA is among the most aggressive and chemoresistant malignancies. CCA is characterized by marked tumor reactive stroma, a fibrogenic...

  17. SPARCL1 is a novel predictor of tumor recurrence and survival in hilar cholangiocarcinoma.

    Science.gov (United States)

    Yu, Yang; Chen, Yan; Ma, Jianxia; Yu, Xiaofeng; Yu, Guanzhen; Li, Zhaoshen

    2016-03-01

    Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1) has been implicated in tumor initiation, formation, and progression of various cancers, yet its role in hilar cholangiocarcinoma remains largely uncharacterized. In the present study, tissue microarrays containing resected hilar cholangiocarcinoma specimens from 92 patients were used to evaluate the expression of SPARCL1 protein by immunohistochemistry (IHC). In vitro assays were used to determine the effect of SPARCL1 overexpression on cell growth and migration. Loss of SPARCL1 expression was observed in 46 (50.0 %) of the 92 primary tumors. SPARCL1 expression is inversely associated with poorly or undifferentiation specimens (P = 0.030) in addition to lymph node metastasis (P = 0.047). Survival analysis demonstrated that SPARCL1 is an independent factor in predicting the outcome of patients with hilar cholangiocarcinoma. SPARCL1 overexpression suppressed tumor cell migration in vitro by inhibiting MMP-9, MMP-2, Vimentin, and Fibronectin expression, whereas did not inhibit cell proliferation in vitro. Our results suggest that loss of SPARCL1 is involved in the tumorigenesis of hilar cholangiocarcinoma and may serve as a novel molecular biomarker for patients' outcome.

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

    Directory of Open Access Journals (Sweden)

    Itharat Arunporn

    2010-09-01

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

  19. Lymph node metastasis in the biliary tract carcinoma: CT evaluation

    International Nuclear Information System (INIS)

    Lee, Byung Hee; Lee, Ah Ra; Kim, Kie Hwan; Do, Young Soo; Chin, Soo Yil

    1994-01-01

    The primary biliary carcinoma is usually unresectable at presentation, because of early lymphatic spread. To determine the incidence and the spread pattern of lymph node metastases according to the location of the primary tumor, we analyzed the CT scans of the patients with primary biliary adenocarcinoma. We reviewed the CT scans of 92 patients with pathologically proven primary biliary adenocacinima, including 45 peripheral cholangiocarcinomas, 22 hilar cholangiocarcinomas, 18 gallbladder carcinomas, and 7 common bile duct carcinomas. Positive adenopathy was diagnosed when the node exceeded 10 mm in short axis. The overall incidence of nodal metastases was 59.8% (55/92); 66.7% in peripheral cholangiocarcinoma, 54.5% in hilar cholangiocarcinoma, 55.6% in gallbladder carcinoma, and 42.9% in common bile duct carcinoma. The most commonly involved nodal group was the lesser omentum, followed by the celiac, periaortic, and peripancreatic group. The phrenic node group was only involved in the cases with the peripheral or hilar cholangiocarcinoma. The primary biliary carcinoma has a high incidence of lymph node metastases at the time of diagnosis, and shows different nodal spread pattern according to the location of the primary tumor. Involvement of the phrenic node was limited to the peripheral and hilar cholangiocarcinoma

  20. Lymph node metastasis in the biliary tract carcinoma: CT evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Hee; Lee, Ah Ra; Kim, Kie Hwan; Do, Young Soo; Chin, Soo Yil [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1994-07-15

    The primary biliary carcinoma is usually unresectable at presentation, because of early lymphatic spread. To determine the incidence and the spread pattern of lymph node metastases according to the location of the primary tumor, we analyzed the CT scans of the patients with primary biliary adenocarcinoma. We reviewed the CT scans of 92 patients with pathologically proven primary biliary adenocacinima, including 45 peripheral cholangiocarcinomas, 22 hilar cholangiocarcinomas, 18 gallbladder carcinomas, and 7 common bile duct carcinomas. Positive adenopathy was diagnosed when the node exceeded 10 mm in short axis. The overall incidence of nodal metastases was 59.8% (55/92); 66.7% in peripheral cholangiocarcinoma, 54.5% in hilar cholangiocarcinoma, 55.6% in gallbladder carcinoma, and 42.9% in common bile duct carcinoma. The most commonly involved nodal group was the lesser omentum, followed by the celiac, periaortic, and peripancreatic group. The phrenic node group was only involved in the cases with the peripheral or hilar cholangiocarcinoma. The primary biliary carcinoma has a high incidence of lymph node metastases at the time of diagnosis, and shows different nodal spread pattern according to the location of the primary tumor. Involvement of the phrenic node was limited to the peripheral and hilar cholangiocarcinoma.

  1. Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integratio...

  2. Infiltration of peritumoural but tumour-free parenchyma with IgG4-positive plasma cells in hilar cholangiocarcinoma and pancreatic adenocarcinoma.

    Science.gov (United States)

    Resheq, Yazid J; Quaas, Alexander; von Renteln, Daniel; Schramm, Christoph; Lohse, Ansgar W; Lüth, Stefan

    2013-10-01

    Recently, new guidelines for diagnosing IgG4-associated cholangitis have been published devaluing the diagnostic significance of IgG4-positive plasma cells and steroid trials. We sought to evaluate the utility of IgG4-positive plasma cells in discriminating IgG4-associated cholangitis from hilar cholangiocarcinoma and autoimmune pancreatitis from pancreatic adenocarcinoma under conditions when malignancy is likely to be missed. Resection specimens obtained from patients with hilar cholangiocarcinoma, pancreatic adenocarcinoma or hepatocellular carcinoma were re-evaluated for IgG4-positivity. Histological analysis focussed on peritumoural but tumour-free sections. Perioperative biochemical and clinical data were reviewed. Nineteen patients with hilar cholangiocarcinoma and 29 patients with pancreatic adenocarcinoma were eligible for histological re-evaluation. Six of 19 (32%) patients with hilar cholangiocarcinoma and 5 of 29 (17%) patients with pancreatic adenocarcinoma were IgG4-positive (≥20 IgG4-positive plasma cells per high power field). Patients with IgG4-positive hilar cholangiocarcinoma showed significantly higher levels of serum total bilirubin (3.6mg/dl vs. 1.8mg/dl; Philar cholangiocarcinoma. IgG4-positive plasma cells are of limited utility especially in distinguishing hilar cholangiocarcinoma from IgG4-associated cholangitis even when combined with clinical parameters and may be misleading under conditions when malignancy is missed. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway

    OpenAIRE

    Jung, Dawoon E.; Park, Soo Been; Kim, Kahee; Kim, Chanyang; Song, Si Young

    2017-01-01

    Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with...

  4. Endoscopic palliation of patients with biliary obstruction caused by nonresectable hilar cholangiocarcinoma: efficacy of self-expandable metallic Wallstents

    NARCIS (Netherlands)

    Cheng, John L. S.; Bruno, Marco J.; Bergman, Jacques J.; Rauws, Erik A.; Tytgat, Guido N.; Huibregtse, Kees

    2002-01-01

    Background: The aim of this study was to evaluate the efficacy of an endoscopically inserted self-expandable metal stent for treatment of biliary obstruction caused by nonresectable hilar cholangiocarcinoma. Methods: Data on all patients with nonresectable hilar cholangiocarcinoma receiving

  5. Annexin II-Dependent Mechanism of Breast Cancer Progression

    Science.gov (United States)

    2010-11-01

    Guedj N, Zhan Q, Perigny M, et al. Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas. J Hepatol 2009; 51: 93...Guedj, N., et al., 2009. Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas. J. Hepatol. 51, 93–101. Hajjar

  6. Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

    Science.gov (United States)

    Telleman, Johan A; Stellingwerff, Menno D; Brekelmans, Geert J; Visser, Leo H

    2018-02-01

    Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018. © 2017 Wiley Periodicals, Inc.

  7. Identification of bile survivin and carbohydrate antigen 199 in distinguishing cholangiocarcinoma from benign obstructive jaundice.

    Science.gov (United States)

    Liu, Yanfeng; Sun, Jingxian; Zhang, Qiangbo; Jin, Bin; Zhu, Min; Zhang, Zongli

    2017-01-01

    To investigate whether bile survivin and carbohydrate antigen 199 (CA199) can be helpful in distinguishing cholangiocarcinoma (malignant obstructive jaundice) from benign obstructive jaundice. Receiver operating characteristic curve was used to evaluate the feasibility of bile survivin and CA199 in differentiating cholangiocarcinoma from benign obstructive jaundice. The area under the curve for survivin and CA199 in bile and serum were 0.780 (p jaundice.

  8. Genomic Perturbations Reveal Distinct Regulatory Networks in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Nepal, Chirag; O'Rourke, Colm J; Oliveira, Douglas Vnp

    2018-01-01

    Intrahepatic cholangiocarcinoma (iCCA) remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole-exome sequen...

  9. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...... and individualization for precision therapies. Many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of intratumoral plasticity and the causal driver action. Next-generation sequencing has begun to underline the persistent alterations, which may...

  10. Opisthorchiasis and cholangiocarcinoma in Southeast Asia: an unresolved problem

    Directory of Open Access Journals (Sweden)

    Hughes T

    2017-08-01

    Full Text Available Thomas Hughes,1,* Thomas O’Connor,1,* Anchalee Techasen,2,3 Nisana Namwat,2,3 Watcharin Loilome,2,3 Ross H Andrews,2–4 Narong Khuntikeo,3,5 Puangrat Yongvanit,3,6 Paiboon Sithithaworn,3,7 Simon D Taylor-Robinson1 1Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, London, UK; 2Department of Biochemistry, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Centre, 3Cholangiocarcinoma Screening and Care Program (CASCAP, Khon Kaen University, Khon Kaen, Thailand; 4Faculty of Medicine, St Mary’s Campus, Imperial College, London, UK; 5Department of Surgery, 6Department of Biochemistry, 7Department of Parasitology, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Centre, Khon Kaen University, Khon Kaen, Thailand *These authors contributed equally to this work Abstract: The prevalence of cholangiocarcinoma (CCA in Southeast Asia is much higher than other areas of the world. Eating raw, fermented, or undercooked cyprinid fish, infected with the liver fluke, Opisthorchis viverrini sensu lato (sl, results in chronic biliary inflammation, periductal fibrosis, and increased cancer risk. There may be associated glomerulonephritis. The process of infection is difficult to disrupt because eating practices have proven extremely difficult to change, and the life cycle of the fluke cannot be broken due to high prevalence in canine and feline reservoir hosts. Fecal analysis and enzyme-linked immunosorbent assay tests can be used to diagnose opisthorchiasis. Diagnosis of CCA is complex, partly due to the lack of definitive imaging characteristics but also due to the difficulty of obtaining samples for cytology or histology. This cancer has proven to be resistant to common chemotherapy treatments and so the two avenues of treatment available are surgical resection and liver transplantation, both requiring early detection of the tumor for the best chances of success. Late presentation of symptoms reduces the

  11. Staging of Klatskin tumours (hilar cholangiocarcinomas): comparison of MR cholangiography, MR imaging, and endoscopic retrograde cholangiography

    International Nuclear Information System (INIS)

    Vogl, Thomas J.; Schwarz, Wolfram O.; Heller, Matthias; Herzog, Christopher; Zangos, Stephan; Hammerstingl, Renate M.; Hintze, Rainer E.; Neuhaus, Peter

    2006-01-01

    The aim of the study was to compare prospectively magnetic resonance cholangiography (MRC) and magnetic resonance imaging (MRI) with endoscopic retrograde cholangiography (ERC) in the diagnosis and staging of Klatskin tumours of the biliary tree (hilar cholangiocarcinomas). Forty-six patients with suspected Klatskin tumours of the biliary tract underwent MRI and heavily T2-weighted, non-breathhold, respiratory-triggered fast spin-echo MRC. Forty-two patients underwent ERC within 24 h; in four patients, ERC was not feasible, and percutaneous trans-hepatic cholangiography (PTC) was carried out instead. Two independent investigators evaluated imaging results for the presence of tumour, bile duct dilatation, and stenosis. Clinical and histopathological correlation revealed Klatskin tumours in 33 patients. MRI revealed a slightly hyperintense signal of infiltrated bile ducts in T2-weighted fast spin-echo sequences. The malignant lesion was regularly visualized as a hypointense area in T1-weighted gradient-echo sequences with substantial contrast enhancement along the involved bile duct walls. MRC revealed the location and extension of the tumour in 31 of 33 cases correctly (sensitivity 94%, specificity 100%, diagnostic accuracy 95%). In 27 of 31 cases, ERC enabled accurate staging and diagnosis of Klatskin tumours with a sensitivity of 87%. ERC and PTC combined yielded a sensitivity of 84% and a specificity of 97%. Tumours were grouped according to the Bismuth classification, with MRC allowing correct identification of type I tumour in seven patients, type II tumour in four patients, type III tumour in 12 patients, and type IV tumour in ten patients. MRC provided superior visualization of completely obstructed peripheral systems. MRC in combination with MRI is a reliable non-invasive diagnostic method for the pre-therapeutic staging of Klatskin tumours. (orig.)

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

    NARCIS (Netherlands)

    Dinant, Sander; Gerhards, Michael F.; Rauws, E. A. J.; Busch, Olivier R. C.; Gouma, Dirk J.; van Gulik, Thomas M.

    2006-01-01

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

  13. Malignant peripheral nerve sheath tumor arisen from plexiform Neurofibromatosis type 1

    International Nuclear Information System (INIS)

    Kirova, G.; Penkov, M.; Hadjidekov, G.; Parvanova, V.

    2005-01-01

    Neurofibromatosis type 1 is multisystemic neurocutaneous disorder involving both neuroectodermal and mesenchymal texture and the most common familial cancer predisposing syndrome in humans. Tumors occurring in patients with NF1 are primarily peripheral neurofibromas. They can continue to develop throughout life and the rate of appearance may vary greatly from year to year. At the same time any new and rapid change noted at clinical examination - increase volume, pain or neurological deficit, requires biopsy because of potential malignant transformation of the neurofibroma into neurofibrosarcoma. The definitive treatment depends on the respectable character of the tumor. In this case the authors document two cases of malignant peripheral nerve sheath tumor occurring in the association with NF type l

  14. Enhancement pattern of hilar cholangiocarcinoma: Contrast-enhanced ultrasound versus contrast-enhanced computed tomography

    International Nuclear Information System (INIS)

    Xu Huixiong; Chen Lida; Xie Xiaoyan; Xie Xiaohua; Xu Zuofeng; Liu Guangjian; Lin Manxia; Wang Zhu; Lu Mingde

    2010-01-01

    Objective: To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods: Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results: In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P = 0.125). Conclusion: The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

  15. Enhancement pattern of hilar cholangiocarcinoma: Contrast-enhanced ultrasound versus contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huixiong, E-mail: xuhuixiong@hotmail.co [Department of Medical Ultrasonics, The First Affiliated Hospital, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China); Chen Lida; Xie Xiaoyan; Xie Xiaohua; Xu Zuofeng; Liu Guangjian; Lin Manxia; Wang Zhu [Department of Medical Ultrasonics, The First Affiliated Hospital, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China); Lu Mingde, E-mail: lumd@21cn.co [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China)

    2010-08-15

    Objective: To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods: Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results: In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P = 0.125). Conclusion: The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

  16. Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin

    2016-03-01

    Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

  17. CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway.

    Science.gov (United States)

    Jung, Dawoon E; Park, Soo Been; Kim, Kahee; Kim, Chanyang; Song, Si Young

    2017-09-07

    Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies.

  18. Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS.

    Directory of Open Access Journals (Sweden)

    Xianzhi Qu

    Full Text Available The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma.

  19. Peripheral-type benzodiazepine receptor: a protein of mitochondrial outer membranes utilizing porphyrins as endogenous ligands

    International Nuclear Information System (INIS)

    Snyder, S.H.; Verma, A.; Trifiletti, R.R.

    1987-01-01

    The peripheral-type benzodiazepine receptor is a site identified by its nanomolar affinity for [ 3 H]diazepam, similar to the affinity of diazepam for the central-type benzodiazepine receptor in the brain. The peripheral type benzodiazepine receptor occurs in many peripheral tissues but has discrete localizations as indicated by autoradiographic studies showing uniquely high densities of the receptors in the adrenal cortex and in Leydig cells of the testes. Subcellular localization studies reveal a selective association of the receptors with the outer membrane of mitochondria. Photoaffinity labeling of the mitochondrial receptor with [ 3 H]flunitrazepam reveals two discrete labeled protein bands of 30 and 35 kDa, respectively. The 35-kDa band appears to be identical with the voltage-dependent anion channel protein porin. Fractionation of numerous peripheral tissues reveals a single principal endogenous ligand for the receptor, consisting of porphyrins, which display nanomolar affinity. Interactions of porphyrins with the mitochondrial receptor may clarify its physiological role and account for many pharmacological actions of benzodiazepines

  20. Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Mantel, Hendrik T J; Wiggers, Jim K; Verheij, Joanne; Doff, Jan J; Sieders, Egbert; van Gulik, Thomas M; Gouw, Annette S H; Porte, Robert J

    2015-12-01

    Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.

  1. Effect of leptin on proliferation and apoptosis of cholangiocarcinoma QBC939 cells

    Directory of Open Access Journals (Sweden)

    DAI Kai

    2013-03-01

    Full Text Available ObjectiveTo determine whether leptin can exert anti-proliferative and pro-apoptotic effects on human cholangiocarcinoma cells and to investigate the underlying molecular mechanisms. MethodsHuman cholangiocarcinoma QBC939 cells were cultured and treated with different concentrations of leptin. Changes in the proliferation rate were measured by the MTT assay. Changes in cell cycle and in the apoptosis incidence rate were detected by flow cytometry. Changes in cyclin D1, bax and bcl-2 gene expression were detected by measuring mRNA levels by real-time quantitative reverse transcription-polymerase chain reaction (qPCR. Changes in caspase-3 protease activity were detected by fluorometric assay. ResultsLeptin treatment significantly increased the proliferation rate of QBC939 cells in a dose- and time-dependent manner. Compared to untreated QBC939 cells, leptin treatment led to significantly more G0/G1 to S phase transition and significantly lower apoptosis rate. In addition, leptin-treated QBC939 cells showed enhanced mRNA expression of cyclin D1 and bcl-2, but decreased mRNA expression of bax. The leptin treatment also led to decreased caspase-3 activity. ConclusionLeptin promotes S to G0/G1 phase transition and proliferation, but inhibits apoptosis, of human cholangiocarcinoma cells in vitro.

  2. [Clinical value of CT-guided high frequency-induced thermotherapy as a treatment for intrahepatic cholangiocarcinoma].

    Science.gov (United States)

    Fan, Wei-Jun; Zhang, Liang; Gu, Yang-Kui; Wang, Li-Gang; Ouyang, Yu-Shu

    2008-07-01

    To evaluate the therapeutic effect of CT-guided high frequency-induced thermotherapy (HiTT) for intrahepatic cholangiocarcinoma. Seventeen patients of intrahepatic cholangiocarcinoma with 21 lesions underwent comprehensive treatment with HiTT as the principle approach. As to the patients with obstructive jaundice, percutaneous trans-hepatic cholangial drainage (PTCD) or bile duct endoprosthesis placement was performed first to improve the liver function, then HiTT was performed; and patients without obstructive jaundice underwent CT-guided HiTT directly, 1-2 weeks later, chemotherapy was given for 4 - 6 courses. CT scan 1 week after HiTT showed a short-term achievement rate of 100% (17/17), and the single puncture in situ ablation rate was 76.1% (16/21). The average life span in the near future was 13.5 months. The adverse effects included topo-bleeding, pain after procedure, liver function damage, defervescence, etc. All the patients recovered after symptomatic treatment. The clinical value of CT-guided HiTT for intrahepatic cholangiocarcinoma is obvious.

  3. Anxiety and depression among patients with different types of vestibular peripheral vertigo.

    Science.gov (United States)

    Yuan, Qing; Yu, Lisheng; Shi, Dongmei; Ke, Xingxing; Zhang, Hua

    2015-02-01

    Numerous studies have been published on comorbid anxiety and depression in patients with vertigo. However, very few studies have separately described and analyzed anxiety or depression in patients with different types of vestibular peripheral vertigo. The present study investigated anxiety and depression among patients with 4 different types of peripheral vertigo. A total of 129 patients with 4 types of peripheral vertigo, namely, benign paroxysmal positional vertigo (BPPV, n = 49), migrainous vertigo (MV, n = 37), Menière disease (MD, n = 28), and vestibular neuritis (VN, n = 15), were included in the present study. Otological and neurootological examinations were carefully performed, and self-rating anxiety scale and self-rating depression scale were used to evaluate anxiety and depression. Patients were divided into 2 groups, according to the vestibular function: normal and abnormal vestibular function. There was no significant difference in the risk of anxiety/depression between these 2 groups. However, for patients with the 4 different vertigo types, the prevalence of anxiety (MV = 45.9%, MD = 50%) and depression (MV = 27%, MD = 28.6%) was significantly higher in the patients with MV or MD than those with BPPV or VN (P vertigo, as well as differences in the prevention and self-control of the patients against the vertigo.

  4. Sildenafil ameliorates long term peripheral neuropathy in type II diabetic mice.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve, concurrently with augmentation of intra-epidermal nerve fiber density in the skin and myelinated axons in the sciatic nerve. Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment. In vitro studies showed that mouse dermal endothelial cells (MDE cultured under high glucose levels exhibited significant down regulation of angiopoietin 1 (Ang1 expression and reduction of capillary-like tube formation, which were completely reversed by sildenafil. In addition, incubation of dorsal root ganglia (DRG neurons with conditioned medium harvested from MDE under high glucose levels suppressed neurite outgrowth, where as conditional medium harvested from MDE treated with sildenafil under high glucose levels did not inhibit neurite outgrowth of DRG neurons. Moreover, blockage of the Ang1 receptor, Tie2, with a neutralized antibody against Tie2 abolished the beneficial effect of sildenafil on tube formation and neurite outgrowth. Collectively, our data indicate that sildenafil has a therapeutic effect on long term peripheral neuropathy of middle aged diabetic mice and that improvement of neurovascular dysfunction by sildenafil likely contributes to the amelioration of nerve function. The Ang1/Tie2 signaling pathway may play an important role in these

  5. Two stents insertion via single tract for treatment of hepatic hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Xie Zonggui; Jin Peng; Xie Zhiyong; Yi Yuhai; Zhang Xuping

    2003-01-01

    Objective: To evaluate the feasibility and clinical application of two stents insertion via single tract for treatment of hepatic hilar cholangiocarcinoma. Methods: Eighteen patients with hepatic hilar cholangiocarcinoma who had left and right bile duct obstruction were treated with stents insertion via right bile duct puncturing routeway. These two stents were implanted between right and left bile duct, and between right bile duct and common bile duct. Results: Eighteen patients obtained successful two stents placement by right bile duct puncturing tract and succeeded with internal drainage for all biliary tree jaundice subsided distinctly. Conclusions: The technique of two stents insertion via single tract could predigest interventional drainage procedure of high bile duct obstruction, reduce operation trauma, shorten handling time and possess promising application value

  6. Impact of specialized multi-disciplinary approach and an integrated pathway on outcomes in hilar cholangiocarcinoma.

    Science.gov (United States)

    Gomez, D; Patel, P B; Lacasia-Purroy, C; Byrne, C; Sturgess, R P; Palmer, D; Fenwick, S; Poston, G J; Malik, H Z

    2014-01-01

    To assess the outcomes of patients with hilar cholangiocarcinoma following referral to a specialist multi-disciplinary team. Over an 11-year period, patients referred with hilar cholangiocarcinoma were identified from a prospectively maintained registry. Collated data included demographics, operative findings and histo-pathological data. Survival differences and prognostic factors were determined. 345 patients were referred with hilar cholangiocarcinoma, of which 57 (16.5%) patients had surgery. Prior to 2008, of 143 patients referred, only 17 (11.9%) patients underwent surgery, compared to 40 (19.8%) of 202 patients referred from 2008 onwards (p = 0.051). In the surgery group, the majority of patients underwent left hemi-hepatectomy (n = 19). In addition, portal vein (n = 5), hepatic artery (n = 2) and inferior vena cava (n = 3) resections were performed. The R0 resection rate was 73.7%. The morbidity and mortality rates were 59.6% and 14.0%, respectively. The median disease-free survival was 16 (4-101) months. The presence of lymph node metastasis (p = 0.002) was the only predictor of poorer disease-free survival. The 5-year overall survival was 39.5% and was significantly better than that of the palliative group (p hilar cholangiocarcinoma and is associated with better overall survival. Prompt referral to tertiary centres with a core team of clinicians to manage this difficult condition may allow more patients to come to potentially curative surgical resections. Copyright © 2013. Published by Elsevier Ltd.

  7. Case report: A female case of isolated IgG4-related sclerosing cholangitis mimicking cholangiocarcinoma.

    Science.gov (United States)

    Xiao, Jianchun; Li, Guanqiao; Yang, Gang; Jia, Congwei; Li, Binglu

    2017-04-01

    IgG4-related disease is a newly recognized fibroinflammatory disorder, characterized by tumefactive lesions, storiform fibrosis and IgG4-positive plasma cells infiltration. IgG4-related sclerosing cholangitis (IgG4-SC) is the most common extrapancreatic manifestation of IgG4-related disease, but it is frequently associated with autoimmune pancreatitis(AIP). Only few case was reported to be diagnosed with IgG4-SC in the absence of AIP, with a striking male preponderance. Here we report a female case of isolated IgG4 related sclerosing cholangitis mimicking cholangiocarcinoma. A 58-year-old woman complaint of one-month history of jaundice and right upper quadrant discomfort, and the biliary reconstruction showed full-length wall thickening and segmental stenosis. Cholangiocarcinoma was then diagnosed. Choledochoplasty was performed, followed by Roux-en-Y anastomosis. However, pathological examination revealed IgG4-related sclerosing cholangitis (IgG4-SC) and the retrospective measurement of serum IgG4 was 346 mg/dL post-operatively. The patient was followed for another nine monthswithout recurrence. The differential diagnosis between cholangiocarcinoma and IgG4-SC is challenging due to significant overlap of clinical manifestations, lab tests and imaging characteristics. However, as an afterthought of this case, typical cholangiocarcinoma rarely presents full-length wall thickening. What the case taught us was pre-operative IgG4 measurement for patients with long bile duct involvement was highly recommended in order to rule out IgG4-SC.

  8. Hilar anatomy of the hepatic artery and surgical procedure for hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Uesaka, Katsuhiko; Maeda, Atsuyuki; Kanamoto, Hideyuki; Matsunaga, Kazuya; Yuasa, Ichiro; Okamura, Yukiyasu; Yamaguchi, Shigeki; Bando, Etsuro; Furukawa, Hiroyoshi

    2006-01-01

    This paper describes the examination of findings by multi-detector-row CT (MDCT) and by surgery to obtain the anatomy of hilar arteries and portal vein, which is necessary for the procedure in the title. Subjects are those findings of 38 patients with hilar cholangiocarcinoma, who underwent its excision during the period of 1 year from 2002 Nov. Before operation, MDCT with 16-row detector was done 20-120 sec after infusion of a non-ionized contrast medium to compose the 3D images. The left hepatic arterial system was found to be classifiable in 3 types of common, anti-clockwise and clockwise one with the respective frequency of 63, 24 and 11%, and the right system, infra-portal (76%) and supra-portal (24%) types. It was concluded that to the arterial clockwise and supra-portal types, particular attention should be paid for the cancer invasion there and for avoidance of the artery damage during the operation. (T.I.)

  9. Does high location and thickness of the Wrisberg ligament affect discoid lateral meniscus tear type based on peripheral detachment?

    Science.gov (United States)

    Ahn, Jin Hwan; Wang, Joon Ho; Kim, Dong Uk; Lee, Do Kyung; Kim, Jun Ho

    2017-12-01

    The aim of this study was to evaluate the relationship between discoid lateral meniscus (DLM) types based on peripheral detachment and anatomic features of Wrisberg ligament (WL) such as location and thickness based on magnetic resonance image (MRI). A total of 322 knees in 292 patients were reviewed. Patients were divided into four DLM types according to peripheral detachment: no shift (type 1), anterocentral shift (type 2), posterocentral shift (type 3) and central shift (type 4). We reviewed all MRI concentrating on the presence, location (high or low location), running angle, thickness of WL, and WL/posterior cruciate ligament (PCL) thickness ratio. The relationship between DLM types and anatomic features of WL were analyzed using one-way analysis of variance and chi-square test. According to DLM types based on peripheral detachment, 149 knees were type 1, 38 were type 2, 79 were type 3, and 56 were type 4. Among the 322 knees, 302 (93.8%) had WL on MRI. In DLM patients, type 3 showed a statistically significant (Plocation of WL. In addition, type 3 had significantly larger (Plocation and thick WL are related to posterocentral shift type of DLM based on peripheral detachment. Based on our results, the high location and thick WL might provide information to surgeons in predicting the direction of peripheral detachment in symptomatic DLM patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Primary Follicular Lymphoma of the Common Bile Duct Mimicking Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Khaled Youssef Elbanna

    2014-01-01

    Full Text Available Primary non-Hodgkin′s lymphoma of the common bile duct is extremely rare. We present a case with history of inflammatory bowel disease and clinical manifestations of obstructive jaundice. Abdominal magnetic resonance imaging with magnetic resonance cholangiopancreatography (MRCP was done and demonstrated tight stricture at the middle part of common bile duct, and radiological findings were supportive of extra-hepatic cholangiocarcinoma. Whipple′s procedure was performed and the case was histopathologically proven to be non-Hodgkin′s lymphoma of follicular subtype involving the common bile duct. Lymphoma of the hepatobiliary system is usually present as secondary manifestation of systemic malignant lymphoma. However, primary malignant lymphomas arising from the hepatobiliary tree are extremely rare. The radiological appearance of common bile duct lymphoma is very similar to cholangiocarcinoma, making preoperative diagnosis very difficult, as in our present case. We also compare the imaging findings of our case to those seen in reported cases of follicular lymphoma of the common bile duct.

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

    International Nuclear Information System (INIS)

    Han Xinwei; Li Yongdong; Guan Sheng; Wu Gang; Xing Gusheng; Ma Bo

    2002-01-01

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

  12. Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series.

    Science.gov (United States)

    Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F

    2016-09-01

    Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    Directory of Open Access Journals (Sweden)

    Farshad Farshidfar

    2017-03-01

    Full Text Available Cholangiocarcinoma (CCA is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

  14. Dysregulation of Iron Metabolism in Cholangiocarcinoma Stem-like Cells

    DEFF Research Database (Denmark)

    Raggi, Chiara; Gammella, Elena; Correnti, Margherita

    2017-01-01

    Cholangiocarcinoma (CCA) is a devastating liver tumour arising from malignant transformation of bile duct epithelial cells. Cancer stem cells (CSC) are a subset of tumour cells endowed with stem-like properties, which play a role in tumour initiation, recurrence and metastasis. In appropriate con...... compartment as a novel metabolic factor involved in CCA growth, may have implications for a better therapeutic approach....

  15. Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Sang Youl Rhee

    2015-08-01

    Full Text Available Peripheral arterial disease (PAD in patients with type 2 diabetes mellitus (T2DM exhibits broad clinical characteristics and various consequences and is known as one of the major macrovascular complications of T2DM. Atherosclerosis is recognized as the most direct and important cause of PAD, but acute or chronic limb ischemia may be the result of various risk factors. In light of the increasing number of patients who undergo peripheral vascular procedures, the number of subjects who are exposed to the risks for PAD and related complications is increasing. In this review, we will discuss the clinical and epidemiological characteristics of PAD, as well as the clinical significance of PAD in T2DM subjects.

  16. Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

    LENUS (Irish Health Repository)

    Saeed, A

    2012-01-31

    Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

  17. Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells

    OpenAIRE

    Kwak, Tae Won; Kim, Do Hyung; Jeong, Young-Il; Kang, Dae Hwan

    2015-01-01

    Background The aim of this study is to evaluate the anticancer activity of vorinostat-incorporated nanoparticles (vorinostat-NPs) against HuCC-T1 human cholangiocarcinoma cells. Vorinostat-NPs were fabricated by a nanoprecipitation method using poly(dl-lactide-co-glycolide)/poly(ethylene glycol) copolymer. Results Vorinostat-NPs exhibited spherical shapes with sizes

  18. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    DEFF Research Database (Denmark)

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude

    2017-01-01

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahep...

  19. Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

    Science.gov (United States)

    Linnemann, Christoph; Tezenas du Montcel, Sophie; Rakowicz, Maryla; Schmitz-Hübsch, Tanja; Szymanski, Sandra; Berciano, Jose; van de Warrenburg, Bart P; Pedersen, Karine; Depondt, Chantal; Rola, Rafal; Klockgether, Thomas; García, Antonio; Mutlu, Gurkan; Schöls, Ludger

    2016-04-01

    Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

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

    Directory of Open Access Journals (Sweden)

    Takashi Yuri

    2014-05-01

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

  1. In-vivo monitoring of development of cholangiocarcinoma induced with C. sinensis and N-nitrosodimethylamine in Syrian golen hamsters using ultrasonography and magnetic resonance imaging: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Hyunsik [SMG-SNU Boramae Medical Center, Department of Radiology, Seoul (Korea, Republic of); Han, Joon Koo; Kim, Jung Hoon [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Hong, Sung-Tae [Seoul National University, Department of Parasitology, College of Medicine, Seoul (Korea, Republic of); Uddin, M.H. [Seoul National University, Adult Stem Cell Research Center, Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul (Korea, Republic of); Jang, Ja-June [Seoul National University, Department of Pathology, College of Medicine, Seoul (Korea, Republic of)

    2017-04-15

    The purpose of this study is to evaluate high-resolution ultrasound and magnetic resonance imaging (MRI) in monitoring of cholangiocarcinoma in the hamsters with C. sinensis infection and N-nitrosodimethylamine (NDMA). Twenty-four male Syrian golden hamsters of were divided into four groups composed of five hamsters as control, five hamsters receiving 30 metacercariae of C. sinensis per each hamster, five hamsters receiving NDMA in drinking water, and nine hamsters receiving both metacercariae and NDMA. Ultrasound was performed every other week from baseline to the 12th week of infection. MRI and histopathologic examination was done from the 4th week to 12th week. Cholangiocarcinomas appeared as early as the 6th week of infection. There were 12 cholangiocarcinomas, nine and ten of which were demonstrated by ultrasound and MRI, respectively. Ultrasound and MRI findings of cholangiocarcinomas in the hamsters were similar to those of the mass-forming intrahepatic cholangiocarcinomas in humans. Ultrasound and MRI also showed other findings of disease progression such as periductal increased echogenicity or signal intensity, ductal dilatation, complicated cysts, and sludges in the gallbladder. High-resolution ultrasound and MRI can monitor and detect the occurrence of cholangiocarcinoma in the hamsters non-invasively. (orig.)

  2. In-vivo monitoring of development of cholangiocarcinoma induced with C. sinensis and N-nitrosodimethylamine in Syrian golen hamsters using ultrasonography and magnetic resonance imaging: a preliminary study

    International Nuclear Information System (INIS)

    Woo, Hyunsik; Han, Joon Koo; Kim, Jung Hoon; Hong, Sung-Tae; Uddin, M.H.; Jang, Ja-June

    2017-01-01

    The purpose of this study is to evaluate high-resolution ultrasound and magnetic resonance imaging (MRI) in monitoring of cholangiocarcinoma in the hamsters with C. sinensis infection and N-nitrosodimethylamine (NDMA). Twenty-four male Syrian golden hamsters of were divided into four groups composed of five hamsters as control, five hamsters receiving 30 metacercariae of C. sinensis per each hamster, five hamsters receiving NDMA in drinking water, and nine hamsters receiving both metacercariae and NDMA. Ultrasound was performed every other week from baseline to the 12th week of infection. MRI and histopathologic examination was done from the 4th week to 12th week. Cholangiocarcinomas appeared as early as the 6th week of infection. There were 12 cholangiocarcinomas, nine and ten of which were demonstrated by ultrasound and MRI, respectively. Ultrasound and MRI findings of cholangiocarcinomas in the hamsters were similar to those of the mass-forming intrahepatic cholangiocarcinomas in humans. Ultrasound and MRI also showed other findings of disease progression such as periductal increased echogenicity or signal intensity, ductal dilatation, complicated cysts, and sludges in the gallbladder. High-resolution ultrasound and MRI can monitor and detect the occurrence of cholangiocarcinoma in the hamsters non-invasively. (orig.)

  3. Stage of hilar cholangiocarcinoma predicts recurrence of biliary obstruction in patients with metal stents.

    Science.gov (United States)

    Siddiqui, Ali; Shahid, Haroon; Sarkar, Avik; Cox, Kristen; Kowalski, Thomas E; Loren, David E; Sharma, Ashish; Laing, Patrick; Birch, Madeline; Adler, Douglas G

    2013-09-01

    Most patients with hilar cholangiocarcinomas present with unresectable tumors, so only palliative biliary drainage with self-expanding metal stents (SEMS) is possible. Stents eventually cease to function because of tumor overgrowth and/or other causes, so it is important to identify factors that affect stent patency and failure. We examined the patency of endoscopically placed SEMS in patients with hilar cholangiocarcinoma and factors associated with patency. We performed a retrospective study of 120 consecutive patients (mean age, 67 ± 14.6 years; 74 male) who presented with obstructive jaundice from hilar cholangiocarcinoma and underwent bilateral SEMS from September 2006 through April 2012 at 2 US tertiary medical centers. We collected data on patient demographics and survival, success of stent placement and function, and immediate adverse events. The primary outcome was duration of stent patency (time from insertion to failure). Thirty-eight patients had stage 1 hilar cholangiocarcinomas, 45 had stage 2, 12 had stage 3, and 25 had stage 4. The median length of the hilar stricture was 9 mm (range, 8-50 mm). The stent was successfully passaged across the stricture in all patients and was functional in 115; its median length was 8 mm (range, 8-10 mm), and diameter was 80 mm (range, 60-100 mm). Fourteen patients had immediate adverse events, including perforation (n = 2), bleeding (n = 2), pancreatitis (n = 9), and cholangitis (n = 1). Median survival was 17 weeks (range, 1-211 weeks), and 50 patients had stent occlusion. On Kaplan-Meier analysis, the median time from stent placement to occlusion was 17 weeks (range, 1-104 weeks). More patients with stage 3 or 4 tumors (64%) had SEMS occlusion than patients with stage 1 or 2 tumors (28%) in univariate analysis (P = .017). In multivariate analysis, only cancer stage was independently and significantly associated with patency (P = .006; hazard ratio, 2.77); age, sex, length of stricture, and SEMS diameter and

  4. Hilar cholangiocarcinoma: Cross sectional evaluation of disease spectrum

    Science.gov (United States)

    Mahajan, Mangal S; Moorthy, Srikanth; Karumathil, Sreekumar P; Rajeshkannan, R; Pothera, Ramchandran

    2015-01-01

    Although hilar cholangiocarcinoma is relatively rare, it can be diagnosed on imaging by identifying its typical pattern. In most cases, the tumor appears to be centered on the right or left hepatic duct with involvement of the ipsilateral portal vein, atrophy of hepatic lobe on that side, and invasion of adjacent liver parenchyma. Multi-detector computed tomography (MDCT) and magnetic resonance cholangiopancreatography (MRCP) are commonly used imaging modalities to assess the longitudinal and horizontal spread of tumor. PMID:25969643

  5. Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

    Science.gov (United States)

    Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

    2016-08-26

    Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

    Science.gov (United States)

    Pak, Jhang Ho; Shin, Jimin; Song, In-Sung; Shim, Sungbo; Jang, Sung-Wuk

    2017-01-01

    Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  7. Impaired peripheral nerve regeneration in type-2 diabetic mouse model.

    Science.gov (United States)

    Pham, Vuong M; Tu, Nguyen Huu; Katano, Tayo; Matsumura, Shinji; Saito, Akira; Yamada, Akihiro; Furue, Hidemasa; Ito, Seiji

    2018-01-01

    Peripheral neuropathy is one of the most common and serious complications of type-2 diabetes. Diabetic neuropathy is characterized by a distal symmetrical sensorimotor polyneuropathy, and its incidence increases in patients 40 years of age or older. In spite of extensive research over decades, there are few effective treatments for diabetic neuropathy besides glucose control and improved lifestyle. The earliest changes in diabetic neuropathy occur in sensory nerve fibers, with initial degeneration and regeneration resulting in pain. To seek its effective treatment, here we prepared a type-2 diabetic mouse model by giving mice 2 injections of streptozotocin and nicotinamide and examining the ability for nerve regeneration by using a sciatic nerve transection-regeneration model previously established by us. Seventeen weeks after the last injection, the mice exhibited symptoms of type-2 diabetes, that is, impaired glucose tolerance, decreased insulin level, mechanical hyperalgesia, and impaired sensory nerve fibers in the plantar skin. These mice showed delayed functional recovery and nerve regeneration by 2 weeks compared with young healthy mice and by 1 week compared with age-matched non-diabetic mice after axotomy. Furthermore, type-2 diabetic mice displayed increased expression of PTEN in their DRG neurons. Administration of a PTEN inhibitor at the cutting site of the nerve for 4 weeks promoted the axonal transport and functional recovery remarkably. This study demonstrates that peripheral nerve regeneration was impaired in type-2 diabetic model and that its combination with sciatic nerve transection is suitable for the study of the pathogenesis and treatment of early diabetic neuropathy. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Molecular profiling of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Oliveira, Douglas V N P; Zhang, Shanshan; Chen, Xin

    2017-01-01

    . Areas covered: The present review article outlines the main studies and resulting discoveries on the molecular profiling of iCCA, with a special emphasis on the different techniques used for this purpose, the diagnostic and prognostic markers identified, as well as the genes and pathways that could......INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary tumor of the liver and a highly lethal disease. Therapeutic options for advanced iCCA are limited and ineffective due to the largely incomplete understanding of the molecular pathogenesis of this deadly tumor...... be potentially targeted with innovative therapies. Expert commentary: Molecular profiling has led to the identification of distinct iCCA subtypes, characterized by peculiar genetic alterations and transcriptomic features. Targeted therapies against some of the identified genes are ongoing and hold great promise...

  9. Podoplanin is an important stromal prognostic marker in perihilar cholangiocarcinoma.

    Science.gov (United States)

    Obulkasim, Halmurat; Shi, Xiaolei; Wang, Jun; Li, Jun; Dai, Bo; Wu, Pengwen; Wang, Shuai; Wang, Xun; Ding, Yitao

    2018-01-01

    Cancer-associated fibroblasts (CAFs) exhibit various phenotypes and serve an important role in tumor progression. However, research on podoplanin expression in CAFs is limited, and its role in the cholangiocarcinoma microenvironment remains unclear. The present study analyzed the clinical and pathological records of 42 patients diagnosed with perihilar cholangiocarcinoma (pCCA) in The Affiliated Drum Tower Hospital of Nanjing University Medical School (Nanjing, China). Immunohistochemical staining was performed to evaluate the expression of podoplanin in CAFs in order to determine its association with clinicopathological parameters and survival rate. Podoplanin expression in the CAFs was associated with the tumor-node-metastasis staging system, and lymph node metastasis in pCCA. Tumor tissue demonstrated an increase in lymphatic vessel density (LVD) compared with para-tumor tissue. Podoplanin expression in CAFs was associated with LVD in tumor and para-tumor tissues. To examine the effect of podoplanin expression in CAFs on tumor progression, CAFs were isolated from tumor xenografts. Following transfection with an expression plasmid encoding podoplanin, the migratory ability of CAFs was significantly increased. Therefore, CAF-associated podoplanin expression in pCCA may serve as a potential biomarker to evaluate prognosis and provide a valuable target for anticancer therapy.

  10. Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma.

    Science.gov (United States)

    Nguyen Canh, Hiep; Harada, Kenichi

    2016-12-01

    Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.

  11. Inflammation-based prognostic score is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Oshiro, Yukio; Sasaki, Ryoko; Fukunaga, Kiyoshi; Kondo, Tadashi; Oda, Tatsuya; Takahashi, Hideto; Ohkohchi, Nobuhiro

    2013-03-01

    Recent studies have revealed that the Glasgow prognostic score (GPS), an inflammation-based prognostic score, is useful for predicting outcome in a variety of cancers. This study sought to investigate the significance of GPS for prognostication of patients who underwent surgery with extrahepatic cholangiocarcinoma. We retrospectively analyzed a total of 62 patients who underwent resection for extrahepatic cholangiocarcinoma. We calculated the GPS as follows: patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (L) were allocated a score of 2; patients with one or none of these abnormalities were allocated a s ore of 1 or 0, respectively. Prognostic significance was analyzed by the log-rank test and a Cox proportional hazards model. Overall survival rate was 25.5 % at 5 years for all 62 patients. Venous invasion (p = 0.01), pathological primary tumor category (p = 0.013), lymph node metastasis category (p GPS (p = 0.008) were significantly associated with survival by univariate analysis. A Cox model demonstrated that increased GPS was an independent predictive factor with poor prognosis. The preoperative GPS is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma.

  12. De-novo cholangiocarcinoma in native common bile duct remnant following OLT for primary sclerosing cholangitis.

    Science.gov (United States)

    Landaverde, Carmen; Ng, Vivian; Sato, Alisa; Tabibian, James; Durazo, Francisco; Busuttil, Ronald

    2009-01-01

    Primary sclerosing cholangitis (PSC) is a chronic, progressive, inflammatory and obstructive disease of the intra- and extra-hepatic bile ducts of unknown etiology. Currently, orthotopic liver transplantation (OLT) is the only definitive treatment for PSC-related end-stage liver disease. However, PSC has been known to recur in the grafted liver. Roux-en-Y hepaticojejunostomy is more commonly performed than choledochocholedochostomy for PSC, although choledochocholedochostomy has been found to be safe and efficacious for PSC if the distal common bile duct is uninvolved at the time of OLT. Our case is unique in that it describes a patient who developed de-novo cholangiocarcinoma in the remnant portion of the native common bile duct six years after OLT with choledochocholedochostomy for PSC-associated end-stage liver disease without having PSC recurrence. In conclusion, our case report indicates that choledochocholedochostomy may not be desirable in PSC due to an increased risk of developing cholangiocarcinoma in the native common bile duct. This risk exists as well with a Roux-en-Y hepaticojejunostomy in the remaining intra-duodenal and intra-pancreatic biliary epithelium, although in theory to a lesser extent. Therefore, the risk of developing cholangiocarcinoma in the recipient common bile duct can only be completely eliminated by performing a Whipple procedure at the time of OLT.

  13. Left hepatectomy combined with hepatic artery resection for hilar cholangiocarcinoma: A retrospective cohort study.

    Science.gov (United States)

    Peng, Chihan; Li, Chuan; Wen, Tianfu; Yan, Lvnan; Li, Bo

    2016-08-01

    To investigate the efficacy of our technique and policy on left hepatectomy (LH) with hepatic artery resection but without arterial reconstruction (HAR) in selected patients with hilar cholangiocarcinoma. From May 2005 to May 2012, 61 patients with hilar cholangiocarcinoma underwent left hepatectomy. These patients were divided into two groups: the LH with HAR group (n = 26) and the LH alone group (n = 35), based on whether hepatic artery resection was performed. We evaluated the serum total and direct bilirubin on postoperative day 7, length of hospital stay after surgery, postoperative complications, long-term postoperative survival and disease-free survival. The improvement in jaundice after surgery was comparable between the two groups (P = 0.837). There were no significant differences in the rates of postoperative complications or mortality between the LH with HAR group and the LH group (P = 0.654 and no assessment, respectively). The cumulative 1-, 2-, 3- and 5-year survival rates were 61.5%, 49%, 40.8% and 30.6% and 71.4%, 58.7%, 51.3% and 38.5%, respectively, in the LH with HAR group and the LH group (P = 0.383, including perioperative deaths). The cumulative 1-, 2-, 3- and 5-year disease-free survival rates were 61.9%, 41.6%, 29.7% and 14.8% and 58.2%, 50.7%, 44.3% and 23.6% in the LH with HAR group and the LH group, respectively (P = 0.695, including perioperative deaths). The postoperative complication rate was higher in patients with severe jaundice than those with non-severe jaundice, but no significant difference was detected (56.3% (9/16) vs. 46.7% (46.7%), P = 0.804). Similarly, 18.8% (3/16) postoperative mortality was found in patients with severe jaundice, compared to 4.4% (2/45) in those with non-severe jaundice. The difference was not significant (P = 0.139). For the cumulative 1-, 2-, 3- and 5-year survival and cumulative 1-, 2-, 3- and 5-year disease-free survival rates, patients with severe jaundice had poorer outcomes than

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

    Science.gov (United States)

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

    2016-08-01

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

  15. Extent of liver resection for hilar cholangiocarcinoma (Klatskin tumor): how much is enough?

    NARCIS (Netherlands)

    van Gulik, Thomas M.; Ruys, Anthony T.; Busch, Oliver R. C.; Rauws, Erik A. J.; Gouma, Dirk J.

    2011-01-01

    Hilar resection in combination with extended liver resections has resulted in a higher rate of R0 resections and increased survival in patients with hilar cholangiocarcinoma (HCCA). This aggressive surgical approach is, however, associated with high rates of operative morbidity and mortality,

  16. Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Stuti L. Misra

    2014-01-01

    Full Text Available Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Results. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P=0.12 and P=0.33, resp.. Tear lipid thickness (P=0.02, stability (P<0.0001, and quantity (P=0.01 were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P<0.001 and tear film stability was inversely associated with total neuropathy score (r=-0.29, P=0.03. Conclusion. The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.

  17. Synergistic Anticancer Effects of Vorinostat and Epigallocatechin-3-Gallate against HuCC-T1 Human Cholangiocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Tae Won Kwak

    2013-01-01

    Full Text Available The aim of this study was to investigate the effect of the combination of vorinostat and epigallocatechin-3-gallate against HuCC-T1 human cholangiocarcinoma cells. A novel chemotherapy strategy is required as cholangiocarcinomas rarely respond to conventional chemotherapeutic agents. Both vorinostat and EGCG induce apoptosis and suppress invasion, migration, and angiogenesis of tumor cells. The combination of vorinostat and EGCG showed synergistic growth inhibitory effects and induced apoptosis in tumor cells. The Bax/Bcl-2 expression ratio and caspase-3 and -7 activity increased, but poly (ADP-ribose polymerase expression decreased when compared to treatment with each agent alone. Furthermore, invasion, matrix metalloproteinase (MMP expression, and migration of tumor cells decreased following treatment with the vorinostat and EGCG combination compared to those of vorinostat or EGCG alone. Tube length and junction number of human umbilical vein endothelial cells (HUVECs decreased as well as vascular endothelial growth factor expression following vorinostat and EGCG combined treatment. These results indicate that the combination of vorinostat and EGCG had a synergistic effect on inhibiting tumor cell angiogenesis potential. We suggest that the combination of vorinostat and EGCG is a novel option for cholangiocarcinoma chemotherapy.

  18. The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas.

    Science.gov (United States)

    Stroescu, Cezar; Herlea, Vlad; Dragnea, Adrian; Popescu, Irinel

    2006-03-01

    To study the differences between the hepatocellular carcinoma (HCC) and peripheral type of cholangiocarcinoma (CHC) using cytokeratin (CK) and carcinoembryonic antigen (CEA) expressions and assessing their accuracy on paraffin sections in the differential diagnosis. The following antibodies were analyzed: AB1 complex (anti CK9-CK20), AB2 complex (anti CK1-CK8), pCEA, and the monoclonal antibodies against cytokeratins CK7, CK8/18, CK17 and CK19. In the mmunohistochemical studies, 15 selected surgically resected liver tumors, 10 HCCs and 5 CHCs, with well established diagnosis (by morphological criteria) were included. Other markers, such as AFP si CA 19-9, were not available. No CHC, but 50% of HCCs were positive for CEA, presenting a canalicular staining pattern. For CK 7, all but one (which was focally positive), meaning 80% of CHCs were diffusely positive, whereas only two HCCs were positive. For CK 19, 80% of CHCs were diffusely positive, while all but two HCCs (a moderately and a poorly differentiated tumor) were negative. For CK 8/18, 70% of HCCs were diffusely positive, whereas only 20% of CHCs were positive. For CK 17, 60% of CHCs were positive, while all HCCs were negative. 80% of CHCs were positive for AB1 anti-CKs complex, whereas only 50% of HCCs were positive, and relating to AB2 anti-CKs complex, 50% of HCCs were diffusely positive and only 20% of CHCs. The immunohistochemical expression of CKs and CEA might be considered helpful in addition to other diagnostic criteria for the differential diagnosis of primary carcinomas of the liver, especially in difficult cases.

  19. Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease.

    Science.gov (United States)

    Sfyri, Peggy; Matsakas, Antonios

    2017-07-08

    Atherosclerosis is a chronic inflammatory process that, in the presence of hyperlipidaemia, promotes the formation of atheromatous plaques in large vessels of the cardiovascular system. It also affects peripheral arteries with major implications for a number of other non-vascular tissues such as the skeletal muscle, the liver and the kidney. The aim of this review is to critically discuss and assimilate current knowledge on the impact of peripheral atherosclerosis and its implications on skeletal muscle homeostasis. Accumulating data suggests that manifestations of peripheral atherosclerosis in skeletal muscle originates in a combination of increased i)-oxidative stress, ii)-inflammation, iii)-mitochondrial deficits, iv)-altered myofibre morphology and fibrosis, v)-chronic ischemia followed by impaired oxygen supply, vi)-reduced capillary density, vii)- proteolysis and viii)-apoptosis. These structural, biochemical and pathophysiological alterations impact on skeletal muscle metabolic and physiologic homeostasis and its capacity to generate force, which further affects the individual's quality of life. Particular emphasis is given on two major areas representing basic and applied science respectively: a)-the abundant evidence from a well-recognised atherogenic model; the Apolipoprotein E deficient mouse and the role of a western-type diet and b)-on skeletal myopathy and oxidative stress-induced myofibre damage from human studies on peripheral arterial disease. A significant source of reactive oxygen species production and oxidative stress in cardiovascular disease is the family of NADPH oxidases that contribute to several pathologies. Finally, strategies targeting NADPH oxidases in skeletal muscle in an attempt to attenuate cellular oxidative stress are highlighted, providing a better understanding of the crossroads between peripheral atherosclerosis and skeletal muscle pathophysiology.

  20. Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

    Science.gov (United States)

    Patzkowski, Michael S

    2016-03-01

    Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted. Published by Elsevier Inc.

  1. Histopathology of a benign bile duct lesion in the liver: Morphologic mimicker or precursor of intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Lee, Kyoung-Bun

    2016-09-01

    A bile duct lesion originating from intrahepatic bile ducts is generally regarded as an incidental pathologic finding in liver specimens. However, a recent study on the molecular classification of intrahepatic cholangiocarcinoma has focused on the heterogeneity of this carcinoma and has suggested that the cells of different origins present in the biliary tree may have a major role in the mechanism of oncogenesis. In this review, benign intrahepatic bile duct lesions-regarded in the past as reactive changes or remnant developmental anomalies and now noted to have potential for developing precursor lesions of intrahepatic cholangiocarcinoma-are discussed by focusing on the histopathologic features and its implications in clinical practice.

  2. Bile Duct Cancer (Cholangiocarcinoma) Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

    Science.gov (United States)

    Bile duct cancer, or cholangiocarcinoma, is rare. Bile ducts are tubes that carry bile between the liver, gallbladder, and small intestine. Bile duct cancer can occur in the intrahepatic, perihilar (Klatskin tumor), or distal extrahepatic area. Learn about tests to diagnose and the stages of bile duct cancer.

  3. Endoscopic and Photodynamic Therapy of Cholangiocarcinoma.

    Science.gov (United States)

    Meier, Benjamin; Caca, Karel

    2016-12-01

    Most patients with cholangiocarcinoma (CCA) have unresectable disease. Endoscopic bile duct drainage is one of the major objectives of palliation of obstructive jaundice. Stent implantation using endoscopic retrograde cholangiography is considered to be the standard technique. Unilateral versus bilateral stenting is associated with different advantages and disadvantages; however, a standard approach is still not defined. As there are various kinds of stents, there is an ongoing discussion on which stent to use in which situation. Palliation of obstructive jaundice can be augmented through the use of photodynamic therapy (PDT). Studies have shown a prolonged survival for the combinations of PDT and different stent applications as well as combinations of PDT and additional systemic chemotherapy. More well-designed studies are needed to better evaluate and standardize endoscopic treatment of unresectable CCA.

  4. Which Measurement of Blood Pressure Is More Associated With Albuminuria in Patients With Type 2 Diabetes: Central Blood Pressure or Peripheral Blood Pressure?

    Science.gov (United States)

    Kitagawa, Noriyuki; Okada, Hiroshi; Tanaka, Muhei; Hashimoto, Yoshitaka; Kimura, Toshihiro; Nakano, Koji; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

    2016-08-01

    The aim of this study was to investigate whether central systolic blood pressure (SBP) was associated with albuminuria, defined as urinary albumin excretion (UAE) ≥30 mg/g creatinine, and, if so, whether the relationship of central SBP with albuminuria was stronger than that of peripheral SBP in patients with type 2 diabetes. The authors performed a cross-sectional study in 294 outpatients with type 2 diabetes. The relationship between peripheral SBP or central SBP and UAE using regression analysis was evaluated, and the odds ratios of peripheral SBP or central SBP were calculated to identify albuminuria using logistic regression model. Moreover, the area under the receiver operating characteristic curve (AUC) of central SBP was compared with that of peripheral SBP to identify albuminuria. Multiple regression analysis demonstrated that peripheral SBP (β=0.255, PAUC of peripheral SBP was significantly greater than that of central SBP to identify albuminuria (P=0.035). Peripheral SBP is superior to central SBP in identifying albuminuria, although both peripheral and central SBP are associated with UAE in patients with type 2 diabetes. © 2016 Wiley Periodicals, Inc.

  5. Multidisciplinary management of intrahepatic cholangiocarcinoma: Current approaches.

    Science.gov (United States)

    Guro, Hanisah; Kim, Jin Won; Choi, YoungRok; Cho, Jai Young; Yoon, Yoo-Seok; Han, Ho-Seong

    2017-06-01

    Intrahepatic cholangiocarcinoma (ICC) is a common primary hepatic tumor. However, its outcomes are usually worse than those of hepatocellular carcinoma owing to its non-specific presentation and detection at an advanced stage. The most widely used serum marker, carbohydrate antigen 19-9, is non-specific. Furthermore, imaging studies rarely identify any pathognomonic features. Surgery is the only treatment option that offers a chance of long-term survival. However, the resectability rate is low owing to the high frequencies of intrahepatic metastases, peritoneal carcinomatosis, or extrahepatic metastases. Surgical treatment should be tailored according to the macroscopic classification of ICC (e.g. mass-forming, periductal infiltrating, and intraductal growth types) because it reflects the tumor's dissemination pattern. Although lymph node metastasis is a negative prognostic factor, the importance and extent of lymph node dissection is still controversial. To improve patient survival, liver transplantation is considered in some patients with unresectable ICC, especially in those with an insufficient remnant liver volume. Minimally invasive procedures, including laparoscopic and robotic liver resection, have been tested and achieved comparable outcomes to conventional surgery in preliminary studies. No randomized trials have confirmed the efficacy of adjuvant chemotherapy in ICC, and several trials have evaluated molecular-targeted agents as monotherapy or in combination with cytotoxic chemotherapy. Multidisciplinary approaches are necessary to improve the outcomes of ICC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Foot Kinetics and Kinematics Profile in Type 2 Diabetes Mellitus with Peripheral Neuropathy: A Hospital Based Study from South India.

    Science.gov (United States)

    Hazari, Animesh; Maiya, Arun G; N, Shivashankara K

    2018-02-01

    A kinetic change in thefoot like altered plantar pressure is the most common etiological risk factor for causing foot ulcers among people with diabetes mellitus. Kinematic alterations in joint angle and spatiotemporal parameters of the gait have also been frequently observed in participants with diabetes peripheral neuropathy. Diabetes peripheral neuropathy is the most common long-term standing complication of type 2 diabetes mellitus. It leads to various micro and macrovascular related complication of the foot. There is a gap in theliteraturefor biomechanical evaluation and assessment in type 2 diabetes mellitus with peripheral neuropathy in Indian population. The aim of the study was to assess and determine the biomechanical changes including kinetics and kinematics of foot among diabetic peripheral neuropathy. The cross-sectional study was conducted at Diabetic Foot Clinic, Kasturba Hospital, Manipal University, Manipal, Karnataka, India. A total of 120 participants with type 2 diabetes mellitus and peripheral neuropathywere recruited under the purposive sampling method. Participants with any active ulceration or amputation were excluded from the study. The mean age, height, weight, body mass index, duration of diabetes was 57±14 year, 164±11cm, 61±18kg, 24± 3, 12±7 year respectively. There were significant changes in overall biomechanical profile along with clinical manifestations of diabetes peripheral neuropathy.The regression analysis showed statistical significance for dynamic maximum plantar pressure at forefoot with age, weight, height, duration of diabetes, body mass index, knee & ankle joint angle at toe-off phase of gait cycle,pinprick sensation and ankle reflex (R=.71,R =.55, F (12, 108)=521.9 kPa, p=.002) Conclusions: From the present study, we conclude that people with type 2 diabetes mellitus and peripheral neuropathy have significant changes in their foot kinetics and kinematicsparameters. Therefore, they could be at higher risk of foot

  7. Analysis of different ways of drainage for obstructive jaundice caused by hilar cholangiocarcinoma.

    Science.gov (United States)

    Xu, Chuan; Lv, Peng-Hua; Huang, Xin-En; Wang, Shu-Xiang; Sun, Ling; Wang, Fu-An

    2014-01-01

    To evaluate the prognosis of different ways of drainage for patients with obstructive jaundice caused by hilar cholangiocarcinoma. During the period of January 2006- March 2012, percutaneous transhepatic catheter drainage (PTCD)/ percutaneous transhepatic biliary stenting (PTBS) were performed for 89 patients. According to percutaneous transhepatic cholangiography (PTC), external drainage was selected if the region of obstruction could not be passed by guide wire or a metallic stent was inserted if it could. External drainage was the first choice if infection was diagnosed before the procedure, and a metallic stent was inserted in one week after the infection was under control. Selection by new infections, the degree of bilirubin decrease, the change of ALT, the time of recurrence of obstruction, and the survival time of patients as the parameters was conducted to evaluate the methods of different interventional treatments regarding prognosis of patients with hilar obstruction caused by hilar cholangiocarcinoma. PTCD was conducted in 6 patients and PTBS in 7 (pPTBS was 243 days (pPTBS was found to be better than PTCD for prolonging the patient survival.

  8. [Clinical application of combined hepatic artery resection and reconstruction in surgical treatment for hilar cholangiocarcinoma].

    Science.gov (United States)

    Dai, H S; Bie, P; Wang, S G; He, Y; Li, D J; Tian, F; Zhao, X; Chen, Z Y

    2018-01-01

    Objective: To clarify whether the surgical treatment for hilar cholangiocarcinoma combined with artery reconstruction is optimistic to the patients with hilar cholangiocarcinoma with hepatic artery invasion. Methods: There were 384 patients who received treatment in the First Affiliated Hospital to Army Medical University from January 2008 to January 2016 analyzed retrospectively. There were 27 patients underwent palliative operation, 245 patients underwent radical operation, radical resection account for 63.8%. Patients were divided into four groups according to different operation method: routine radical resection group( n =174), portal vein reconstruction group ( n =47), hepatic artery reconstruction group ( n =24), palliative group( n =27). General information of patients who underwent radical operation treatment was analyzed by chi-square test and analysis of variance. The period of operation time, blood loss, the length of hospital stay and hospitalization expenses of the radical operation patients were analyzed by one-way ANOVA. Comparison among groups was analyzed by LSD- t test. Results: The follow-up ended up in June first, 2016. Each of patients followed for 6 to 60 months, the median follow-up period was 24 months. 1-, 3-, and 5-year survival rates were 81.3%, 44.9% and 13.5% of routine radical operation group, and were 83.0%, 44.7% and 15.1% of portal vein reconstruction group, and were 70.8%, 27.7% and 6.9% of hepatic artery reconstruction group, respectively. And 1-, 3-, and 5-year survival rates of hepatic artery reconstruction group was lower than routine radical group and portal vein reconstruction group significantly ( P 0.05). The data shows that the ratio of lymphatic metastasis in hepatic artery reconstruction group (70.8%) is much higher than them in routine radical operation group (20.1%) and portal vein reconstruction group (19.1%) significantly ( P hilar cholangiocarcinoma. Cox regression analysis indicate that hepatic artery resection and

  9. Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma

    NARCIS (Netherlands)

    Coelen, Robert J. S.; Gaspersz, Marcia P.; Labeur, Tim A.; van Vugt, Jeroen L. A.; van Dieren, Susan; Willemssen, François E. J. A.; Nio, Chung Y.; Ijzermans, Jan N. M.; Klümpen, Heinz-Josef; Groot Koerkamp, Bas; van Gulik, Thomas M.

    2017-01-01

    BACKGROUND & AIMS: Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We

  10. Robotic surgery twice performed in the treatment of hilar cholangiocarcinoma with deep jaundice: delayed right hemihepatectomy following the right-hepatic vascular control.

    Science.gov (United States)

    Zhu, Zhenyu; Liu, Quanda; Chen, Junzhou; Duan, Weihong; Dong, Maosheng; Mu, Peiyuan; Cheng, Di; Che, Honglei; Zhang, Tao; Xu, Xiaoya; Zhou, Ningxin

    2014-10-01

    To explore and find a new method to treat hilar cholangiocarcinoma with deep jaundice assisted by Da Vinci robot. A hilar cholangiocarcinoma patient of type Bismuch-Corlette IIIa was found with deep jaundice (total bilirubin: 635 µmol/L). On the first admission, we performed Da Vinci robotic surgery including drainage of left hepatic duct, dissection of right hepatic vessels (right portal vein and right hepatic artery), and placement of right-hepatic vascular control device. Three weeks later on the second admission when the jaundice disappeared we occluded right-hepatic vascular discontinuously for 6 days and then sustained later. On the third admission after 3 weeks of right-hepatic vascular control, the right hemihepatectomy was performed by Da Vinci robot for the second time. The future liver remnant after the right-hepatic vascular control increased from 35% to 47%. The volume of left lobe increased by 368 mL. When the total bilirubin and liver function were all normal, right hemihepatectomy was performed by Da Vinci robot 10 weeks after the first operation. The removal of atrophic right hepatic lobe with tumor in bile duct was found with no pathologic cancer remaining in the margin. The patient was followed up at our outpatient clinic every 3 months and no tumor recurrence occurs by now (1 y). Under the Da Vinci robotic surgical system, a programmed treatment can be achieved: first, the hepatic vessels were controlled gradually together with biliary drainage, which results in liver's partial atrophy and compensatory hypertrophy in the other part. Then a radical hepatectomy could be achieved. Such programmed hepatectomy provides a new treatment for patients of hilar cholangiocarcinoma with deep jaundice who have the possibility of radical heptolobectomy.

  11. Peripheral nerve tumors in neurofibromatosis type 1. Correlation of MR imaging and histopathologic findings

    International Nuclear Information System (INIS)

    Karube, Sachiko

    1995-01-01

    Magnetic resonance imaging (MRI) of peripheral nerve tumors in neurofibromatosis type I was correlated with histopathologic findings. MRI of 2 of 5 pachydermatoceles revealed T1-weighted image (T1WI) low-intensity and STIR high-intensity areas in the adipose tissue (fine marbled appearance) corresponding to mixtures of tumor and small amounts of adipose tissue. The pachydermatoceles in the 3 remaining cases showed coarse-marbled T1WI low, and STIR high areas reflecting histopathological changes due to proliferation of neurofibroma tissue mainly within the connective tissue septa between the fat lobules. All of the six plexiform neurofibromas exhibited central iso- to low-intensity, and peripheral high-intensity (target appearance) on STIR. Histopathologically, the tumors were composed of a central hypercellular area and peripheral myxomatous area. Low-grade neurofibrosarcoma showed the same MRI patterns as plexiform neurofibromas. High-grade neurofibrosarcoma showed heterogeneous signal intensity on T1WI and Gd-DTPA T1WI coincided with the histopathologic findings, such as necrosis and hemorrhage. (author)

  12. Tumor markers as a diagnostic key for hilar Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Juntermanns B

    2010-08-01

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

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

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    Bailey David M

    2007-08-01

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

  14. Surgical and Palliative Management and Outcome in 184 Patients With Hilar Cholangiocarcinoma

    Science.gov (United States)

    Witzigmann, Helmut; Berr, Frieder; Ringel, Ulrike; Caca, Karel; Uhlmann, Dirk; Schoppmeyer, Konrad; Tannapfel, Andrea; Wittekind, Christian; Mossner, Joachim; Hauss, Johann; Wiedmann, Marcus

    2006-01-01

    Objective: First, to analyze the strategy for 184 patients with hilar cholangiocarcinoma seen and treated at a single interdisciplinary hepatobiliary center during a 10-year period. Second, to compare long-term outcome in patients undergoing surgical or palliative treatment, and third to evaluate the role of photodynamic therapy in this concept. Summary Background Data: Tumor resection is attainable in a minority of patients (<30%). When resection is not possible, radiotherapy and/or chemotherapy have been found to be an ineffective palliative option. Recently, photodynamic therapy (PDT) has been evaluated as a palliative and neoadjuvant modality. Methods: Treatment and outcome data of 184 patients with hilar cholangiocarcinoma were analyzed prospectively between 1994 and 2004. Sixty patients underwent resection (8 after neoadjuvant PDT); 68 had PDT in addition to stenting and 56 had stenting alone. Results: The 30-day death rate after resection was 8.3%. Major complications occurred in 52%. The overall 1-, 3-, and 5-year survival rates were 69%, 30%, and 22%, respectively. R0, R1, and R2 resection resulted in 5-year survival rates of 27%, 10%, and 0%, respectively. Multivariate analysis identified R0 resection (P < 0.01), grading (P < 0.05), and on the limit to significance venous invasion (P = 0.06) as independent prognostic factors for survival. PDT and stenting resulted in longer median survival (12 vs. 6.4 months, P < 0.01), lower serum bilirubin levels (P < 0.05), and higher Karnofsky performance status (P < 0.01) as compared with stenting alone. Median survival after PDT and stenting, but not after stenting alone, did not differ from that after both R1 and R2 resection. Conclusion: Only complete tumor resection, including hepatic resection, enables long-term survival for patients with hilar cholangiocarcinoma. Palliative PDT and subsequent stenting resulted in longer survival than stenting alone and has a similar survival time compared with incomplete R1 and

  15. Peripheral artery disease in type II diabetes

    International Nuclear Information System (INIS)

    Ali, Z.; Ahmed, S.M.; Bhutto, A.R.; Chaudhry, A.; Munir, S.M.

    2012-01-01

    Objective: To determine the frequency of peripheral arterial disease (PAD) in type 2 diabetic patients. Study Design: Cross-sectional observational study. Place and Duration of Study: Diabetes Clinic, Medical Unit III, Jinnah Postgraduate Medical Centre, Karachi, from January to June 2010. Methodology:Three hundred and eighty seven (387) type II diabetic patients of either gender and any age were included. Patients with a previous history of trauma to the arterial vasculature, pregnancy and those who underwent in the study arterial graft procedures were excluded. Non-purposive convenient sampling technique was used to enroll patients in the study. PAD was diagnosed when ankle-brachial index (ABI) was less than 0.9. Ap-value of less than 0.05 was considered statistically significant. Results: Out of 387 studied patients, 128 were males (33.1%) and 259 were females (66.9%). Mean age was 52.22 +- 6.39 years. PAD was detected in 152 9.671 (22 - 76) years in the entire cohort. Mean duration of diabetes was 9.38 +- (39.28%) of the total study subjects. Thirty-one of 128 male patients (24.22%) had PAD disease while 121 out of 259 female patients (46.71%) had evidence of PAD (p = 0.001). Hypertension was a significantly associated factor (p = 0.002). Conclusion: A high frequency of PAD was observed in the diabetic population particularly with hypertension and more prevalent in females. (author)

  16. The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes

    Science.gov (United States)

    Fraser, David A.; Diep, Lien M.; Hovden, Inger Anette; Nilsen, Kristian B.; Sveen, Kari Anne; Seljeflot, Ingebjørg; Hanssen, Kristian F.

    2012-01-01

    OBJECTIVE To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. RESULTS Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes. PMID:22446172

  17. Vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Mona Amini

    2014-02-01

    Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

  18. Vascular access in neonatology: peripherally inserted central catheter and peripheral venous catheter

    Directory of Open Access Journals (Sweden)

    Marcia Lienemann

    2014-04-01

    The objective of this paper is to present aspects of peripherally inserted central catheter and peripheral venous catheter, highlighting important points in choosing the type of access. For the passage of peripherally inserted central catheter is previously performing specific course necessary, while the primary indication occurs when it is necessary to access the patient's stay for a long period of time. Whereas peripheral venipuncture is the most appropriate in cases of needing an IV line quickly and safely, for the administration of fluids, blood collection, blood transfusion and other.

  19. Cholangiocarcinoma in Cirrhosis: Value of Hepatocyte Specific Magnetic Resonance Imaging.

    Science.gov (United States)

    Piscaglia, Fabio; Iavarone, Massimo; Galassi, Marzia; Vavassori, Sara; Renzulli, Matteo; Forzenigo, Laura Virginia; Granito, Alessandro; Salvatore, Veronica; Sangiovanni, Angelo; Golfieri, Rita; Colombo, Massimo; Bolondi, Luigi

    2015-10-01

    The diagnosis of intrahepatic cholangiocellular carcinoma (ICC) remains elusive at imaging, which is a critical issue in cirrhotic patients in whom a diagnosis of hepatocellular carcinoma (HCC) can be established only by imaging. The aim of the study was to evaluate the potential of MRI in the diagnosis of ICC in cirrhosis using 'hepatocyte-specific' Gadolinium (Gd)-based contrast agents. Sixteen histologically proven and retrospectively identified ICCs on cirrhosis were investigated with hepatocyte-specific magnetic resonance contrast agents (6 in Bologna with Gd-EOB-DTPA and 10 in Milan with Gd-BOPTA). The control group consisted of 41 consecutively and prospectively collected nodules (31 HCCs) imaged with Gd-EOB-DTPA. Fifteen ICC nodules (94%) displayed hypointensity in the hepatobiliary phase, suggesting malignancy. Thirteen cholangiocarcinomas (81%) showed hyperenhancement in the venous phase. Only 2 cholangiocarcinoma nodules showed hypoenhancement in the venous phase, corresponding to washout, in both cases preceded by rim enhancement in arterial phase. All the hepatocarcinomas showed hypointensity in hepatobiliary phase, but was always preceded by hypointensity in the venous phase; arterial rim enhancement was never observed in any hepatocarcinoma or regenerative nodule. MRI with hepatocyte-specific Gd-based contrast agents showed a pattern of malignancy in almost all the ICCs, concurrently avoiding misdiagnosis with hepatocarcinoma. These findings suggest a greater diagnostic capacity for this technique compared with the results of MRI with conventional contrast agents reported in the literature in this setting. © 2015 S. Karger AG, Basel.

  20. Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma

    NARCIS (Netherlands)

    Mantel, Hendrik T. J.; Wiggers, Jim K.; Verheij, Joanne; Doff, Jan J.; Sieders, Egbert; van Gulik, Thomas M.; Gouw, Annette S. H.; Porte, Robert J.

    2015-01-01

    Background. Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The

  1. Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma

    NARCIS (Netherlands)

    Mantel, Hendrik T. J.; Wiggers, Jim K.; Verheij, Joanne; Doff, Jan J.; Sieders, Egbert; van Gulik, Thomas M.; Gouw, Annette S. H.; Porte, Robert J.

    2015-01-01

    Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of

  2. Combined hepatocellular-cholangiocarcinoma in a Yellow-headed Amazon (Amazona oratrix).

    Science.gov (United States)

    Tennakoon, Anusha Hemamali; Izawa, Takeshi; Fujita, Daisuke; Denda, Yuki; Seto, Eiko; Sasai, Hiroshi; Kuwamura, Mitsuru; Yamate, Jyoji

    2013-11-01

    A 9-year-old male Yellow-headed Amazon (Amazona oratrix) with a history of anorexia and vomiting died of a liver tumor. The tumor consisted of neoplastic cells with hepatocellular and cholangiocellular differentiations and their intermingled areas. Neoplastic hepatocytes showed islands or trabecular growth with vacuolated eosinophilic cytoplasm. Cells showing biliary differentiation formed ducts or tubules lined by cytokeratin AE1/AE3-positive epithelia, accompanied by desmoplasia consisting of myofibroblasts reacting to α-smooth muscle actin and desmin. The tumor was diagnosed as a combined hepatocellular-cholangiocarcinoma, which is very rare in the avian.

  3. Liver parenchyma transection-first approach in hemihepatectomy with en bloc caudate lobectomy for hilar cholangiocarcinoma: A safe technique to secure favorable surgical outcomes.

    Science.gov (United States)

    Kawabata, Yasunari; Hayashi, Hikota; Yano, Seiji; Tajima, Yoshitsugu

    2017-06-01

    Although hemihepatectomy with total caudate lobectomy (hemiHx-tc) is essential for the surgical treatment of hilar cholangiocarcinoma, the advantage of an anterior approach for hemiHx-tc has not been fully discussed technically; the significance of an anterior approach without liver mobilization for preventing infectious complications also remains unknown. The liver parenchyma transection-first approach (Hp-first) technique is an early transection of the hepatic parenchyma without mobilization of the liver that utilizes a modified liver-hanging maneuver to avoid damaging the future remnant liver. Between May 2010 and August 2016, a total of 40 consecutive patients underwent surgery for hilar cholangiocarcinoma. Of these, 19 patients underwent a conventional hemihepatectomy with total caudate lobectomy (cHx), while 21 patients received a Hp-first. The patients in the Hp-first group had significantly less intraoperative blood loss (P hilar cholangiocarcinoma because it resulted in improved surgical outcomes as compared with the conventional approach. © 2017 Wiley Periodicals, Inc.

  4. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Laurent Bochatay

    2016-10-01

    Full Text Available IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy.

  5. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

    NARCIS (Netherlands)

    Weijer, Ruud; Broekgaarden, Mans; Krekorian, Massis; Alles, Lindy K.; van Wijk, Albert C.; Mackaaij, Claire; Verheij, Joanne; van der Wal, Allard C.; van Gulik, Thomas M.; Storm, Gert; Heger, Michal

    2016-01-01

    Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of

  6. Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy

    NARCIS (Netherlands)

    Weijer, R.; Broekgaarden, M.; Krekorian, M.; Alles, L.K.; van Wijk, A.C; Mackaaij, C.; Verheij, J.; van der Wal, A.C.; van Gullik, T.M.; Storm, Gerrit; Heger, M.

    2016-01-01

    Background: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression

  7. Molecular alterations and clinical prognostic factors for cholangiocarcinoma in Thai population

    Directory of Open Access Journals (Sweden)

    Trachu N

    2017-10-01

    Full Text Available N Trachu,1,2 E Sirachainan,3 N Larbcharoensub,4 W Rattanadech,3 S Detarkom,3 N Monnamo,1 K Kamprerasart,4 D MunTham,5 C Sukasem,6,7 T Reungwetwattana3 1Research Center, Faculty of Medicine Ramathibodi Hospital, 2Molecular Medicine Program, Multidisciplinary Unit, Faculty of Science, 3Division of Medical Oncology, Department of Medicine, 4Division of Anatomical Pathology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 5Section for Mathematic, Faculty of Science and Technology, Rajamangala University of Technology Suvarnabhumi, 6Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, 7Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract: This study explores genomic alterations in cholangiocarcinoma (CCC tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was found. Patients with T790M mutation had a significantly longer overall survival (18.84 months than those with the other types of EGFR mutations (4.08  months; hazard ratio [HR]: 0.26, P=0.038 and also had a significantly lower median Ki-67 (22.5% vs 80%, P=0.025. Furthermore, patients with PIK3CA mutations had a significantly longer median progression-free survival (15.87 vs 7.01 months; HR: 0.46, P=0.043. Strongly positive HER2 expression was found in only 1 patient, whereas ALK expression was not found. The presence of EGFR

  8. Photodynamic Therapy in Patients with Advanced Hilar Cholangiocarcinoma: Percutaneous Cholangioscopic Versus Peroral Transpapillary Approach.

    Science.gov (United States)

    Lee, Tae Yoon; Cheon, Young Koog; Shim, Chan Sup

    2016-04-01

    This study aimed to compare the clinical outcomes of patients with advanced hilar cholangiocarcinoma (CC) who underwent photodynamic therapy (PDT) with either percutaneous transhepatic cholangioscopy (PTCS) or endoscopic retrograde cholangiopancreatography (ERCP). PDT has been proposed as a promising therapy for treatment of unresectable hilar CC that is resistant to conventional standard treatment. However, few studies have compared the delivery methods of PDT in unresectable hilar CC patients. Thirty-seven adult patients with advanced hilar CC were included in this study. Twenty-four patients treated with PTCS-directed PDT and 13 patients treated with ERCP-directed PDT were analyzed retrospectively. The PTCS- and ERCP-directed PDT groups were comparable with respect to age, gender, health status, pretreatment bilirubin levels, Bismuth type, and hilar CC stage. The length of hospital stay differed significantly (p hilar CC. Lower pre-PDT bilirubin levels were associated with longer survival in all patients.

  9. Autoimmune Hepatitis: A Risk Factor for Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Rajat Garg

    2017-11-01

    Full Text Available Cholangiocarcinoma (CCA is a very aggressive and lethal tumor, which arises from the epithelial cells of bile ducts. CCA comprises about 3% of all gastrointestinal malignancies and its incidence is on the rise in the recent years. Anatomically, it is classified into intrahepatic, perihilar, or extrahepatic (distal CCA. There are a number of risk factors associated with CCA including primary sclerosing cholangitis, fibropolycystic liver disease, parasitic infection, viral hepatitis, chronic liver disease, and genetic disorders like Lynch syndrome. Autoimmune hepatitis is also recently reported to have an association with development of CCA. We report an interesting case of perihilar CCA in the setting of autoimmune hepatitis along with a literature review. This case highlights the importance of early treatment and close clinical follow-up of patients with autoimmune hepatitis for development of CCA.

  10. Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Massimiliano Cadamuro

    2017-01-01

    Full Text Available Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and paracrine cues released in the tumor microenvironment. Here, recent evidence regarding molecular mechanisms of chemoresistance is reviewed, as well as associations between well-developed chemoresistance and activation of the cancer stem cell compartment. It is concluded that improved understanding of the complex interplay between apoptosis signaling and the promotion of cell survival represent potentially productive areas for active investigation, with the ultimate aim of encouraging future studies to unveil new, effective strategies able to overcome current limitations on treatment.

  11. Differentiating immunoglobulin g4-related sclerosing cholangitis from hilar cholangiocarcinoma.

    Science.gov (United States)

    Tabata, Taku; Kamisawa, Terumi; Hara, Seiichi; Kuruma, Sawako; Chiba, Kazuro; Kuwata, Go; Fujiwara, Takashi; Egashira, Hideto; Koizumi, Koichi; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Itoi, Takao

    2013-03-01

    Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. In patients with hilar CC, obstructive jaundice was more frequent (philar CC patients (philar or hepatic duct was completely obstructed in 83% of hilar CC patients (philar bile duct stenosis, was more frequent in IgG4-SC patients (philar CC.

  12. Kaempferol inhibits the growth and metastasis of cholangiocarcinoma in vitro and in vivo

    OpenAIRE

    Qin, Youyou; Cui, Wu; Yang, Xuewei; Tong, Baifeng

    2016-01-01

    Kaempferol is a flavonoid that has been reported to exhibit antitumor activity in various malignant tumors. However, the role of kaempferol on cholangiocarcinoma (CCA) is largely unknown. In this article, we found that kaempferol inhibited proliferation, reduced colony formation ability, and induced apoptosis in HCCC9810 and QBC939 cells in vitro. Results from transwell assay and wound-healing assay demonstrated that kaempferol significantly suppressed the migration and invasion abilities of ...

  13. Resection of hilar cholangiocarcinoma with left hepatectomy after pre-operative embolization of the proper hepatic artery

    DEFF Research Database (Denmark)

    Yasuda, Yoshikazu; Larsen, Peter N; Ishibashi, Toshimitsu

    2010-01-01

    Right or right-extended hepatectomy including the caudate lobe is the most common treatment for hilar cholangiocarcinoma (HC). A 5-year survival of up to 60% can be achieved using this procedure if R0-resection is obtained. However, for some patients a left-sided liver resection is necessary...

  14. Internal papillomatosis with intrahepatic cholangiocarcinoma and gastrointestinal adenocarcinoma in a peach-fronted conure (Aratinga aurea).

    Science.gov (United States)

    Gibbons, Paul M; Busch, Martin D; Tell, Lisa A; Graham, Jennifer E; Lowenstine, Linda J

    2002-01-01

    A 17-yr-old pet female peach-fronted conure (Aratinga aurea) was presented with the chief complaints of mild lethargy and weight loss with increased appetite. Antemortem diagnostics included complete blood count, plasma biochemistry, and radiography. Abnormal findings included elevated inflammatory parameters (hyperfibrinogenemia) and a space-occupying mass in the region of the liver. Histologic examination of a liver biopsy sample indicated bile duct hyperplasia leading to a presumptive diagnosis of hepatoxicosis. The bird initially showed moderate improvement with supportive care, but its condition declined 9 days after the liver biopsy. Supportive care was attempted a second time, but the bird did not improve and euthanasia was elected. Abnormal gross necropsy findings were confined to the liver, which contained multiple tan nodules that exuded yellowish fluid on cut section. Histopathologic examination revealed multicentric bile duct hyperplasia and cholangiocarcinoma as well as segmental papillary hyperplasia and adenocarcinoma in the proventriculus, ventriculus, and throughout the intestinal tract. This is the first report of concurrent internal papillomatosis, gastrointestinal adenocarcinoma, and cholangiocarcinoma in a peach-fronted conure.

  15. Palliation: Hilar cholangiocarcinoma

    Science.gov (United States)

    Goenka, Mahesh Kr; Goenka, Usha

    2014-01-01

    Hilar cholangiocarcinomas are common tumors of the bile duct that are often unresectable at presentation. Palliation, therefore, remains the goal in the majority of these patients. Palliative treatment is particularly indicated in the presence of cholangitis and pruritus but is often also offered for high-grade jaundice and abdominal pain. Endoscopic drainage by placing stents at endoscopic retrograde cholangio-pancreatography (ERCP) is usually the preferred modality of palliation. However, for advanced disease, percutaneous stenting has been shown to be superior to endoscopic stenting. Endosonography-guided biliary drainage is emerging as an alternative technique, particularly when ERCP is not possible or fails. Metal stents are usually preferred over plastic stents, both for ERCP and for percutaneous biliary drainage. There is no consensus as to whether it is necessary to place multiple stents within advanced hilar blocks or whether unilateral stenting would suffice. However, recent data have suggested that, contrary to previous belief, it is useful to drain more than 50% of the liver volume for favorable long-term results. In the presence of cholangitis, it is beneficial to drain all of the obstructed biliary segments. Surgical bypass plays a limited role in palliation and is offered primarily as a segment III bypass if, during a laparotomy for resection, the tumor is found to be unresectable. Photodynamic therapy and, more recently, radiofrequency ablation have been used as adjuvant therapies to improve the results of biliary stenting. The exact technique to be used for palliation is guided by the extent of the biliary involvement (Bismuth class) and the availability of local expertise. PMID:25232449

  16. Cancer review: Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Yezaz Ahmed Ghouri

    2015-01-01

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

  17. [The possibility of local control of cancer by neoadjuvant chemoradiation therapy with gemcitabine and surgical resection for advanced cholangiocarcinoma].

    Science.gov (United States)

    Nakagawa, Kei; Katayose, Yu; Rikiyama, Toshiki; Okaue, Adoru; Unno, Michiaki

    2009-11-01

    Surgical resection is the gold standard of treatment for cholangiocarcinoma. However, there are also many recurrences after operation, because of the anatomical background and the tendency of invasion. We thought that eliminating the remnant of the cancer could yield a better prognosis. Therefore, an introduction of the neoadjuvant chemoradiation therapy with gemcitabine and surgical resection for advanced cholangiocarcinoma patient (NACRAC) was planned. The safety of NACRAC was confirmed by a pilot study. The recommended dose of gemcitabine (600 mg/m2) was determined by a phase I study. A phase II study is now being performed for evaluating the effectiveness and safety. NACRAC may control the frontal part of the tumor with difficult distinctions made by MDCT, and abolishing the cancer remnant is expected. The possibility of extended prognosis by NACRAC can be considered.

  18. Angiographic Assessment of the Right Hepatic Artery for Encasement by Hilar Cholangiocarcinoma: Comparison Between Antero-Posterior and Right Anterior Oblique Projections

    International Nuclear Information System (INIS)

    Furukawa, Hiroyoshi; Iwata, Ryoko; Moriyama, Noriyuki

    2001-01-01

    Purpose: To evaluate the usefulness of right anterior oblique (RAO) arteriography for evaluating encasement of the right hepatic artery (RHA) by hilar cholangiocarcinoma.Methods: Celiac arteriography was performed in both the antero-posterior (AP) and RAO projection in ten patients with cholangiocarcinoma. The lengths of the arteries between the bifurcation of the anterior and posterior branch of the liver and the following points were measured: (a) the bifurcation of the left and right hepatic artery (AP-LR), (b) the bifurcation of the proper hepatic artery and the gastroduodenal artery (AP-PG). Additionally, image quality in investigating the invasion of the RHA was evaluated.Results: On the AP images, the average lengths of AP-LR and AP-PG were 24.5 ± 5.1 mm and 30.0 ± 4.9 mm, respectively. On RAO images, the lengths were 28.2 ± 4.6 mm and 32.7 ± 4.8 mm, respectively. Every length was different between the two projections (p < 0.01). In 6 of 10 patients with hilar cholangiocarcinoma, images in RAO projections were superior to AP images for evaluation of encasement.Conclusion: We conclude that angiography obtained in the RAO projection yields images that are superior to those obtained in the conventional AP projection for assessment of RHA encasement

  19. Extrahepatic bile duct resection in combination with liver resection for hilar cholangiocarcinoma : A report of 42 cases

    NARCIS (Netherlands)

    IJitsma, AJC; Appeltans, BMG; de Jong, KP; Porte, RJ; Peeters, PMJG; Slooff, MJH

    2004-01-01

    From September 1986 until December 2001, 42 patients (20 males and 22 females) underwent a combined extrahepatic bile duct resection (EHBDR) and liver resection (LR) for hilar cholangiocarcinoma (HC). The aim of this study was to analyze patient survival, morbidity, and mortality as well as to seek

  20. [Joint diagnostic value of four temperature sensation tests in elderly patients with type 2 diabetic peripheral neuropathy].

    Science.gov (United States)

    Guo, Wei; Li, Yun-Ming; Ai, Zhi-Hua; You, Zhi-Qing; Wan, Yong; Cheng, Ying; Lang, Hong-Mei

    2013-07-01

    To explore the joint diagnostic value of four temperature sensation tests in elderly patients with type 2 diabetic peripheral neuropathy. Thermal sensory analyzer-II were applied to measure cool sensation (CS), warm sensation (WS), cold pain sensation (CP)and heat pain sensation (HP) of 308 elderly patients with type 2 diabetes. Logistic regression model was adopted to create the new variable Temp4 from four temperature sensation tests to diagnose type 2 diabetic peripheral neuropathy. The ROC curve analysis was used to determine the best cut-off points of the four temperature sensation and Temp4, and the diagnostic value of it was evaluated. The means of temperature sensation tests of the diabetic peripheral neuropathy (DPN) group were significantly different from those of the non-DPN group (P sensation tests to diagnose the DPN, the sensitivity of WS test was the highest, and the value was 0.710; but the specificity, positive predictive value, negative predictive value, Youden index, diagnostic accuracy and Kappa value of cold sensation test were the highest, and the values were 0.842, 0.746, 0.799, 0.528, 77.92% and 0.535, respectively; the Kappa values of the other three temperature sensation tests were all greater than 0.4 (P sensation tests (P sensation quantitative tests were in good agreementand could be applied to diagnose DPN; the new variable Temp4 could be used for diagnosis of DPN with a higher diagnostic accuracy.

  1. Interactions of pyrethroid insecticides with GABAA and peripheral-type benzodiazepine receptors

    International Nuclear Information System (INIS)

    Devaud, L.L.

    1988-01-01

    Pyrethroid insecticides are potent proconvulsants in the rat. All pyrethroids evincing proconvulsant activity elicited a similar 25-30% maximal reduction of seizure threshold. The Type II pyrethroids were the most potent proconvulsants with 1RαS, cis cypermethrin having an ED 50 value of 6.3 nmol/kg. The proconvulsant activity of both Type I and Type II pyrenthroids was blocked by pretreatment with PK 11195, the peripheral-type benzodiazepine receptor (PTBR) antagonist. In contrast, phenytoin did not antagonize the proconvulsant activity of either deltamethrin or permethrin. Pyrethroids displaced the specific binding of [ 3 H]Ro5-4864 to rat brain membranes with a significant correlation between the log EC 50 values for their activities as proconvulsants and the log IC 50 values for their inhibition of [ 3 H]Ro5-4864 binding. Both Ro5-4864 and pyrethroid insecticides were found to influence specific [ 35 S]TBPS binding in a GABA-dependent manner. PK 11195 and the Type II pyrethroid, deltamethrin antagonized the Ro5-4864-induced modulation of [ 35 S]TBPS binding. Pyrethroid insecticides, Ro5-4864 and veratridine influenced GABA-gated 36 Chloride influx. Moreover, the Type II pyrethroids elicited an increase in 36 chloride influx in the absence of GABA-stimulation. Both of these actions were antagonized by PK 11195 and tetrodotoxin

  2. Association of peripheral neuropathy with circulating advanced glycation end products, soluble receptor for advanced glycation end products and other risk factors in patients with type 2 diabetes.

    Science.gov (United States)

    Aubert, C E; Michel, P-L; Gillery, P; Jaisson, S; Fonfrede, M; Morel, F; Hartemann, A; Bourron, O

    2014-11-01

    The pathogenesis of diabetic peripheral neuropathy remains uncertain and nonenzymatic glycoxidation is one of the contributing mechanisms. The aim of this study was to assess the respective relationship of diabetic peripheral neuropathy with glycoxidation, compared with other identified risk factors, in patients with type 2 diabetes. We included 198 patients with type 2 diabetes and high risk for vascular complications. Circulating concentrations of three advanced glycation end products (carboxymethyllysine, methyl-glyoxal-hydroimidazolone-1, pentosidine) and of their soluble receptor (sRAGE) were measured. Peripheral neuropathy was assessed by the neuropathy disability score and by the monofilament test and defined as either an abnormal monofilament test and/or a neuropathy disability score ≥6. Multivariate regression analyses were performed adjusting for potential confounding factors for neuropathy: age, gender, diabetes duration, current smoking, systolic blood pressure, waist circumference, height, peripheral arterial occlusive disease, glycated haemoglobin, estimated glomerular filtration rate and lipid profile. Prevalence of peripheral neuropathy was 20.7%. sRAGE and carboxymethyllysine were independently and positively associated with the presence of peripheral neuropathy. No significant association was found between peripheral neuropathy and methyl-glyoxal-hydroimidazolone-1 or pentosidine. Waist circumference, height and peripheral arterial occlusive disease were independently associated with peripheral neuropathy. Carboxymethyllysine and sRAGE were independently associated with peripheral neuropathy in patients with type 2 diabetes. Although the conclusions are limited by the absence of a healthy control population, this study confirms the relationship between advanced glycoxidation and diabetic peripheral neuropathy, independently of other risk factors. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Peripheral neuropathy in children with type 1 diabetes.

    Science.gov (United States)

    Louraki, M; Karayianni, C; Kanaka-Gantenbein, C; Katsalouli, M; Karavanaki, K

    2012-10-01

    Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Synergistic anticancer effects of cisplatin and histone deacetylase inhibitors (SAHA and TSA) on cholangiocarcinoma cell lines.

    Science.gov (United States)

    Asgar, Md Ali; Senawong, Gulsiri; Sripa, Banchob; Senawong, Thanaset

    2016-01-01

    Clinical application of cisplatin against cholangiocarcinoma is often associated with resistance and toxicity posing urgent demand for combination therapy. In this study, we evaluated the combined anticancer effect of cisplatin and histone deacetylase inhibitors (HDACIs), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), on the cholangiocarcinoma KKU-100 and KKU-M214 cell lines. Antiproliferative activity was evaluated using MTT assay. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. Cell cycle and apoptosis regulating proteins were evaluated by western blot analysis. MTT assay showed that cisplatin, SAHA and TSA dose-dependently reduced the viability of KKU-100 and KKU-M214 cells. The combination of cisplatin and HDACIs exerted significantly more cytotoxicity than the single drugs. Combination indices below 1.0 reflect synergism between cisplatin and HDACIs, leading to positive dose reductions of cisplatin and HDACIs. Cisplatin and HDACIs alone induced G0/G1 phase arrest in KKU-100 cells, but the drug combinations increased sub-G1 percent more than either drug. However, cisplatin and HDACIs alone or in combination increased only the sub-G1 percent in KKU-M214 cells. Annexin V-FITC staining revealed that cisplatin and HDACIs combinations induced more apoptotic cell death of both KKU-100 and KKU-M214 cells than the single drug. In KKU-100 cells, growth inhibition was accompanied by upregulation of p53 and p21 and downregulation of CDK4 and Bcl-2 due to exposure to cisplatin, SAHA and TSA alone or in combination. Moreover, combination of agents exerted higher impacts on protein expression. Single agents or combination did not affect p53 expression, however, combination of cisplatin and HDACIs increased the expression of p21 in KKU-M214 cells. Taken together, cisplatin and HDACIs combination may improve the therapeutic outcome in cholangiocarcinoma patients.

  5. Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma?

    Science.gov (United States)

    Wang, Jun-Ke; Hu, Hai-Jie; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Liu, Fei; Cheng, Nan-Sheng; Li, Fu-Yu

    2017-07-11

    To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216-9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391-28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107-14.459; P = 0.034). Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.

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

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

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

  7. Correct diagnosis of vascular encasement and longitudinal extension of hilar cholangiocarcinoma by four-channel multidetector-row computed tomography

    International Nuclear Information System (INIS)

    Okumoto, Tadayuki; Yamada, Takayuki; Sato, Akihiro

    2009-01-01

    Accurate diagnosis of local invasion of hilar cholangiocarcinomas is challenging due to their small size and the anatomic complexity of the hepatic hilar region. On the other hand, the correct diagnosis of local invasion is essential for assuring the possibility of curative surgery. The purpose of this study was to evaluate the feasibility of four-channel multidetector-row computed tomography (MDCT) in the assessment of vascular and bile duct involvement, by which we could obtain useful information for the surgical management of hilar cholangiocarcinoma. The subjects were 18 patients for whom the extent of tumor invasion was surgically and pathologically confirmed. All patients underwent preoperative multiphasic CT scanning by MDCT. Arterial and portal dominant phases were acquired using a detector configuration of 1.25 mm x 4 mm, and both axial and multiplanar reconstructed images were interpreted. Longitudinal extension was evaluated up to second-order branches. Vascular invasion is considered to be the degree of tumor contiguity to the hepatic arteries and portal vein and was graded by CT. The longitudinal extension was correctly diagnosed in 14 patients (77.8%). Hepatic artery invasion was correctly diagnosed in 17 patients with sensitivity of 100% and specificity of 90%, respectively. Portal vein invasion was correctly diagnosed in 47 of 51 branches with sensitivity and specificity of 92.3% and 90.2%, respectively. Multiplanar reconstructed images contributed to the correct diagnosis for both vascular encasement and longitudinal tumor extension. In conclusion, MDCT is useful in preoperative evaluation of hilar cholangiocarcinoma, especially when combined with multiplanar reconstructed images. (author)

  8. Case report combined hepatocellular and cholangiocarcinoma with sarcomatous transformation.

    Science.gov (United States)

    Boonsakan, Paisarn; Thangnapakorn, Orathai; Tapaneeyakorn, Jiemjit; Kositchaiwat, Sawit; Bunyaratvej, Sukhum

    2007-03-01

    Combined hepatocellular and cholangiocarcinoma with sarcomatous transformation was first recognized in Ramathibodi Hospital in 2005. This variant of carcinoma has been increasingly reported particularly from Asian countries. Dedifferentiation of the epithelial component to various sarcomatous components is likely the underlying mechanism. The causative factors of hepatocarcinogenesis in Thailand include chronic viral hepatitis B or C, exposures to aflatoxin B1 and nitrosamine(s) and occasionally some certain nodular hepatocellular lesions due to arterial hyperperfusion. It is suggested that the recent change of the Thai peoples' life style to an increased consumption of fast foods containing food preservatives especially nitrate or nitrite, the nitrosamine precursor may allow heavy exposure(s) to the chemical carcinogen(s) i.e. nitrosamine(s) leading to sarcomatous transformation of the carcinoma.

  9. Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

    Science.gov (United States)

    Hayashi-Takagi, Akiko; Vawter, Marquis P; Iwamoto, Kazuya

    2014-06-15

    Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  10. Preparation of a chlorophyll derivative and investigation of its photodynamic activities against cholangiocarcinoma.

    Science.gov (United States)

    Wu, Zhong-Ming; Wang, Li; Zhu, Wei; Gao, Ying-Hua; Wu, Hai-Ming; Wang, Mi; Hu, Tai-Shan; Yan, Yi-Jia; Chen, Zhi-Long

    2017-08-01

    Photodynamic therapy (PDT) is emerging as a promising method for the treatment of various cancer diseases. However, the clinical application of PDT is limited due to the lack of effective photosensitizers. In this study, a novel chlorophyll derivative, N,N-bis(2-carboxyethyl)pyropheophorbide a (BPPA), had been synthesized and characterized. BPPA had a characteristic long wavelength absorption peak at 669nm and a singlet oxygen quantum yield of 0.54. To investigate the photodynamic ability of BPPA against cholangiocarcinoma (CCA), cellular uptake, subcellular location and bio-distribution, in vitro and in vivo PDT efficacy of BPPA were studied. The results showed that BPPA could rapidly accumulate in QBC-939 cells and localize in the cytoplasm. BPPA- PDT was effective in reducing the cell viability in a drug dose- and light dose-dependent manner in vitro. In CCA xenograft nude mouse model, the concentration of BPPA in the plasma lowered rapidly, and the fluorescence signal peaked at 0.5h and 2h after injection in the skin and tumor, respectively. Significant quantities could be observed in the tumor. BPPA followed by irradiation could significantly inhibit growth of tumors, and histological examination revealed necrotic damage in PDT-treated tumors. These results suggested that BPPA could be a promising drug candidate for photodynamic therapy in cholangiocarcinoma. Published by Elsevier Masson SAS.

  11. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  12. Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case?control analysis

    OpenAIRE

    Brandi, Giovanni; Di Girolamo, Stefania; Farioli, Andrea; de Rosa, Francesco; Curti, Stefania; Pinna, Antonio Daniele; Ercolani, Giorgio; Violante, Francesco Saverio; Biasco, Guido; Mattioli, Stefano

    2013-01-01

    Purposes We conducted a case?control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC). Methods The study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant?Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population cont...

  13. Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

    Science.gov (United States)

    Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

    2018-05-01

    Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

  14. Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus.

    Science.gov (United States)

    Pai, Yen-Wei; Lin, Ching-Heng; Lee, I-Te; Chang, Ming-Hong

    To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese. A cross-sectional, hospital-based observational study was conducted. We enrolled 2837 adults with type 2 diabetes mellitus. Diabetic peripheral neuropathy with or without pain were diagnosed using 2 validated screening tools, namely the Michigan Neuropathy Screening Instrument and Douleur Neuropathique 4 questionnaire. In our sample, 2233 participants had no neuropathy, 476 had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral neuropathy with neuropathic pain, representing an overall diabetic peripheral neuropathy prevalence of 21.3%, and the prevalence of neuropathic pain in diabetic peripheral neuropathy was 21.2%. Multivariate analysis revealed that older age (Pperipheral neuropathy, whereas older age (Pperipheral neuropathy with neuropathic pain. During clinical visits involving biochemical studies, the risk for diabetic peripheral neuropathy with neuropathic pain should be considered for people with older age, elevated glycated haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with particular attention given to increased levels of albuminuria while concerning neuropathic pain. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  15. The impact of caudate lobe resection on margin status and outcomes in patients with hilar cholangiocarcinoma: a multi-institutional analysis from the US Extrahepatic Biliary Malignancy Consortium.

    Science.gov (United States)

    Bhutiani, Neal; Scoggins, Charles R; McMasters, Kelly M; Ethun, Cecilia G; Poultsides, George A; Pawlik, Timothy M; Weber, Sharon M; Schmidt, Carl R; Fields, Ryan C; Idrees, Kamran; Hatzaras, Ioannis; Shen, Perry; Maithel, Shishir K; Martin, Robert C G

    2018-04-01

    The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma. A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes. A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival. Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma.

    Science.gov (United States)

    Hu, Hai-Jie; Mao, Hui; Tan, Yong-Qiong; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

    2016-01-01

    To examine the predictive value of tumor markers for evaluating tumor resectability in patients with hilar cholangiocarcinoma and to explore the prognostic effect of various preoperative factors on resectability in patients with potentially resectable tumors. Patients with potentially resectable tumors judged by radiologic examination were included. The receiver operating characteristic (ROC) analysis was conducted to evaluate serum carbohydrate antigenic determinant 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125) and carcino embryonie antigen levels on tumor resectability. Univariate and multivariate logistic regression models were also conducted to analysis the correlation of preoperative factors with resectability. In patients with normal bilirubin levels, ROC curve analysis calculated the ideal CA 19-9 cut-off value of 203.96 U/ml in prediction of resectability, with a sensitivity of 83.7 %, specificity of 80 %, positive predictive value of 91.1 % and negative predictive value of 66.7 %. Meanwhile, the optimal cut-off value for CA 125 to predict resectability was 25.905 U/ml (sensitivity, 78.6 %; specificity, 67.5 %). In a multivariate logistic regression model, tumor size ≤3 cm (OR 4.149, 95 % CI 1.326-12.981, P = 0.015), preoperative CA 19-9 level ≤200 U/ml (OR 20.324, 95 % CI 6.509-63.467, P hilar cholangiocarcinoma. Preoperative CA 19-9 and CA 125 levels predict resectability in patients with radiological resectable hilar cholangiocarcinoma. Increased preoperative CA 19-9 levels and CA 125 levels are associated with poor resectability rate.

  17. Peripheral nerve conduits: technology update

    Science.gov (United States)

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  19. CT features of malignant hepatic tumors : the significance of capsular retraction

    International Nuclear Information System (INIS)

    Seo, Bo Kyoung; Rhee, Ji Yong; Seol, Hae Young; Lee, Ki Yeol; Park, Cheol Min; Chung, Kyoo Byung

    1998-01-01

    To evaluate the prevalence of capsular retraction in malignant hepatic tumors and the factors involved. Between January 1994 and December 1996, we retrospectively reviewed the CT scans of 152 patients with pathologically-proven, peripherally-located, malignant hepatic tumors. We evaluated size, site, portal and hepatic venous obstruction, bile duct dilatation, and liver atrophy in 18 cases involving capsular retraction. The overall prevalence of capsular retraction among malignant hepatic tumors was 18/152 (12 %); the prevalence was 9/129 (7%) in hepatocellular carcinoma, 6/14 (43 %) in cholangiocarcinoma and 3/9 (33 %) in metastatic cancer; among cases of cholangiocarcinoma and metastatic cancer, the prevalence was high (p<0.05). Portal venous obstruction was seen in six patients with hepatocellular carcinoma ( a high incidence; p=0.04) and one with cholangiocarcinoma. Hepatic venous obstruction was demonstrated in one patient with hepatocellular carcinoma and one with cholangiocarcinoma. Among cholangiocarcinoma patients, bile duct obstruction was seen in four and liver atrophy in three, but among metastatic cancer cases there were no similar findings. The main factors causing capsular retraction were portal venous obstruction in hepatocellular carcinoma and bile duct obstruction and liver atrophy in cholangiocarcinoma. (author). 16 refs., 3 figs

  20. Immunohistochemical Examination of a Resected Advanced Hilar Cholangiocarcinoma Arising in a 29-Year-Old Male without Primary Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    Taketoshi Suehiro

    2010-05-01

    Full Text Available A 29-year-old man with advanced hilar cholangiocarcinoma was successfully treated with an extended right lobectomy. The carbohydrate antigen 19-9 (CA19-9 level was elevated to 939 IU/l, and the pathological findings revealed moderately differentiated tubular adenocarcinoma which involved almost the entire thickness of the hepatic duct and the adjacent liver tissue (T3 and which was associated with lymph node metastasis (N1. It was a stage IIB (T3N1M0 tubular adenocarcinoma according to UICC pathological staging. Immunohistochemical examination revealed that Ki-67, cyclin D1, and MMP-7 were positive, and 14-3-3σ and p27 were negative. The pathological and immunohistochemical findings indicated high malignant potential indicating poor prognosis. We administrated the postoperative adjunct gemcitabine combined with S-1 chemotherapy. The patient is alive without recurrence and doing well two years after surgery. We also review other reports of cholangiocarcinoma patients aged less than 30 years.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-15

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

  2. [Curative effect analysis of bile reinfusion combined with enteral nutrition support before surgery of hilar cholangiocarcinoma].

    Science.gov (United States)

    Song, P; Mao, L; Bian, X J; Zhou, T; Fan, Y Y; Zhang, J; Xie, M; Qiu, Y D

    2018-05-01

    Objective: To investigate the clinical effect of bile reinfusion combined with enteral nutrition support before surgery for hilar cholangiocarcinoma. Methods: A retrospective analysis of patients with hilar cholangiocarcinoma who underwent surgical treatment at Nanjing Drum Tower Hospital Hepato-biliary-pancreatic Surgery Department from July 2010 to August 2017 was completed.A total of 52 cases were finally enrolled in our study.All the patients included, on the basis of whether they received preoperative drainage and bile reinfusion, were divided into non-drainage group( n =15) and drainage group( n =37). Differences of clinical indicators, including operation time, intraoperative bleeding and serum liver function index levels at day 1, 3, 7 postoperative, postoperative complications(liver failure, biliary fistula, pleural effusion, peritoneal effusion, abdominal cavity infection, death in hospital), tumor classification, R0 resection, postoperative hospitalization time between the 2 groups were analyzed. At the same time, in the drainage group, patients were divided into non-enteral nutrition subgroup( n =13) and enteral nutrition subgroup( n =24) according to whether they received enteral nutrition before operation. The normal distribution data of the group was statistically analyzed by independent sample t test, the non-normal distribution data of the group was statistically analyzed by rank-sum test. The count data was statistically analyzed by non-calibration and correction of the square test. Results: There was no statistically significant difference in general infomation such as age, gender, and serum liver function between non-drainage group and drainage group( P >0.05). There was no statistically significant difference in general information such as age, gender, and serum liver function between non-enteral nutrition group and enteral nutrition group( P >0.05). The rate of vascular resection and reconstruction(33.3%) and operating time(10.8(2.2)h) in

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

    Directory of Open Access Journals (Sweden)

    Amir Houshang Mohammad Alizadeh

    2011-10-01

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

  4. MRCP and 3D LAVA imaging of extrahepatic cholangiocarcinoma at 3 T MRI

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    Li, N.; Liu, C.; Bi, W.; Lin, X.; Jiao, H. [Shandong Medical Imaging Research Institute, Shandong University, Jinan (China); Zhao, P., E-mail: Gavinsdu@163.com [Department of Radiology, Shandong Provincial Hospital, Shandong University, Jinan (China)

    2012-06-15

    Extrahepatic cholangiocarcinoma (CCA) is a primary bile duct malignant tumour with poor prognosis. Familiarity with their varied imaging characteristics can be helpful in developing a correct diagnosis and in optimal treatment planning, and thus contribute to a better prognosis. The purpose of this article is to illustrate the typical appearances of extrahepatic CCA on magnetic resonance cholangiopancreatography (MRCP) and three-dimensional (3D) LAVA (liver acquisition with volume acceleration) sequences at 3 T magnetic resonance imaging (MRI), and to discuss the superiority of the two techniques in the diagnosis of CCA.

  5. Relationships between Brachial-Ankle Pulse Wave Velocity and Peripheral Neuropathy in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Byung Kil Ha

    2012-12-01

    Full Text Available BackgroundBrachial-ankle pulse wave velocity (baPWV is known to be a good surrogate marker of clinical atherosclerosis. Atherosclerosis is a major predictor for developing neuropathy. The goal of this study was to determine the relationship between baPWV and diabetic peripheral neuropathy (DPN in patients with type 2 diabetes.MethodsA retrospective cross-sectional study was conducted involving 692 patients with type 2 diabetes. The correlation between increased baPWV and DPN, neurological symptoms, and neurological assessment was analyzed. DPN was examined using the total symptom score (TSS, ankle reflexes, the vibration test, and the 10-g monofilament test. DPN was defined as TSS ≥2 and an abnormal neurological assessment. Data were expressed as means±standard deviation for normally distributed data and as median (interquartile range for non-normally distributed data. Independent t-tests or chi-square tests were used to make comparisons between groups, and a multiple logistic regression test was used to evaluate independent predictors of DPN. The Mantel-Haenszel chi-square test was used to adjust for age.ResultsPatients with DPN had higher baPWV and systolic blood pressure, and were more likely to be older and female, when compared to the control group. According to univariate analysis of risk factors for DPN, the odds ratio of the baPWV ≥1,600 cm/sec was 1.611 (95% confidence interval [CI], 1.072 to 2.422; P=0.021 and the odds ratio in female was 1.816 (95% CI, 1.195 to 2.760; P=0.005.ConclusionIncreased baPWV was significantly correlated with peripheral neuropathy in patients with type 2 diabetes.

  6. Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.

    Science.gov (United States)

    Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

    2014-09-01

    The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

  7. High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study.

    Science.gov (United States)

    Walter-Höliner, Isabella; Barbarini, Daniela Seick; Lütschg, Jürg; Blassnig-Ezeh, Anya; Zanier, Ulrike; Saely, Christoph H; Simma, Burkhard

    2018-03-01

    In this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. A total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. At baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). The prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Beauty and cuteness in peripheral vision

    Science.gov (United States)

    Kuraguchi, Kana; Ashida, Hiroshi

    2015-01-01

    Guo et al. (2011) showed that attractiveness was detectable in peripheral vision. Since there are different types of attractiveness (Rhodes, 2006), we investigated how beauty and cuteness are detected in peripheral vision with a brief presentation. Participants (n = 45) observed two Japanese female faces for 100 ms, then were asked to respond which face was more beautiful (or cuter). The results indicated that both beauty and cuteness were detectable in peripheral vision, but not in the same manner. Discrimination rates for judging beauty were invariant in peripheral and central vision, while discrimination rates for judging cuteness declined in peripheral vision as compared with central vision. This was not explained by lower resolution in peripheral vision. In addition, for male participants, it was more difficult to judge cuteness than beauty in peripheral vision, thus suggesting that gender differences can have a certain effect when judging cuteness. Therefore, central vision might be suitable for judging cuteness while judging beauty might not be affected by either central or peripheral vision. This might be related with the functional difference between beauty and cuteness. PMID:25999883

  9. [Retrospective analysis of 47 cases with hilar cholangiocarcinoma using T-staging system].

    Science.gov (United States)

    Peng, Cheng-hong; Zhao, Zhi-ming; Peng, Shu-you; Liu, Ying-bin; Wu, Yü-lian; Fang, He-qing; Jiang, Xian-chuan

    2005-01-01

    To evaluate the clinical value of T-staging system for hilar cholangiocarcinoma which was adopted in memorial Sloan-Kettering cancer center of New York. The image data of these 47 patients were analyzed retrospectively from December 1997 to December 2002 whose data were according with our demand, and they were staged into three-stage according to the criteria of the T-staging system. The difference of respectability, ratio of tumor-free resection margin and actuarial survival rate were analyzed for different T-staging. And the coincident ratio of three different kinds of imaging methods was also analyzed. Twenty patients had T(1) tumors, twenty three had T(2) tumors and four had T(3) tumors. The resectability of the three stage was 60%, 39% and 0% respectively, and the difference was significant (P = 0.013). The likelihood of achieving tumor-free margin decreased progressively with increasing T stage (P = 0.018). The cumulative 1-year survival rates of T(1), T(2) and T(3) patients were 60%, 39% and 0% respectively, and the cumulative 3-year survival rate was 35%, 9% and 0% respectively, the survival of different stage patients differed markedly (P = 0.0103). The coincident ratio of combined using MRCP and color Doppler-ultrasonography was higher than that of combined using MRCP and B-ultrasonography or combined using CT/SCT and color Doppler-ultrasonography (P = 0.007). The T-staging system has a better value for preoperative assessment, and can be used to judge resectability and survival of hilar cholangiocarcinoma. It will be helpful to use MRCP and color Doppler-Ultrasonography combined to verdict the coverage of the tumor and the T-staging preoperatively.

  10. Transhepatic Hilar Approach for Perihilar Cholangiocarcinoma: Significance of Early Judgment of Resectability and Safe Vascular Reconstruction.

    Science.gov (United States)

    Kuriyama, Naohisa; Isaji, Shuji; Tanemura, Akihiro; Iizawa, Yusuke; Kato, Hiroyuki; Murata, Yasuhiro; Azumi, Yoshinori; Kishiwada, Masashi; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki

    2017-03-01

    In the most common surgical procedure for perihilar cholangiocarcinoma, the margin status of the proximal bile duct is determined at the final step. Our procedure, the transhepatic hilar approach, confirms a cancer-negative margin status of the proximal bile duct first. We first performed a partial hepatic parenchymal transection to expose the hilar plate, and then transected the proximal bile duct to confirm margin status. Then, divisions of the hepatic artery and portal vein of the future resected liver are performed, followed by the residual hepatic parenchymal transection. The transhepatic hilar approach offers a wide surgical field for safe resection and reconstruction of the portal vein in the middle of the hepatectomy. We reviewed 23 patients with perihilar cholangiocarcinoma who underwent major hepatectomy using our procedure from 2011 to 2015. A combined vascular resection and reconstruction was carried out in 14 patients (60.9%). R0 resection was achieved in 17 patients (73.9%), and the overall 3-year survival rate was 52.9% (median survival time 52.4 months). The transhepatic hilar approach is useful and practicable regardless of local tumor extension, enabling us to determine tumor resectability and perform safe resection and reconstruction of the portal vein early in the operation.

  11. [The impact of preoperative biliary drainage on surgical morbidity in hilar cholangiocarcinoma patients].

    Science.gov (United States)

    Li, Shao-qiang; Chen, Dong; Liang, Li-jian; Peng, Bao-gang; Yin, Xiao-yu

    2009-08-01

    To evaluate the impact of preoperative biliary drainage on surgical morbidity in hilar cholangiocarcinoma patients underwent surgery. One hundred and eleven consecutive patients with hilar cholangiocarcinoma whose serum total bilirubin (TBIL) level > 85 micromol/L and underwent surgery in the period from June 1998 to August 2007 were enrolled. There were 67 male and 44 female patients, aged from 26 to 82 years old with a mean of 56 years old. Fifty-five patients underwent preoperative biliary drainage with a mean of 11.4 d of drainage period (drainage group), the other (n = 56) were the non-drainage group. The preoperative TBIL level of drainage group was (154 +/- 69) micromol/L, which was significantly lower than the value of pre-drainage (256 +/- 136) micromol/L (P = 0.000) and the value of non-drainage group (268 +/- 174) micromol/L (P = 0.005). ALT and GGT levels could be lowered by preoperative biliary drainage. The postoperative complications of these two groups were comparable (36.3% vs. 28.6%, P = 0.381). Four patients in drainage group and 5 patients in non-drainage group died of liver failure. Multivariate logistic regression indicated that hepatectomy (OR = 0.284, P = 0.003) was the independent risk factor associated with postoperative morbidity. Bismuth-Corlette classification (OR = 0.211, P = 0.028) was the independent risk factor linked to postoperative mortality. Preoperative biliary drainage could alleviate liver injury due to hyperbilirubin, but it could not decrease the surgical morbidity and postoperative mortality. Concomitant hepatectomy and Bismuth-Corlette classification were independent risk factors linked to surgical risks.

  12. Hilar cholangiocarcinoma is pathologically similar to pancreatic duct adenocarcinoma: suggestions of similar background and development.

    Science.gov (United States)

    Nakanuma, Yasuni; Sato, Yasunori

    2014-07-01

    Routine experiences suggest that cholangiocarcinomas (CCAs) show different clinicopathological behaviors along the biliary tree, and hilar CCA apparently resembles pancreatic duct adenocarcinoma (PDAC). Herein, the backgrounds for these similarities were reviewed. While all cases of PDAC, hilar CCA, intrahepatic CCA (ICCA) and CCA components of combined hepatocellular-cholangiocarcinoma (cHC-CCA) were adenocarcinomas, micropapillary patterns and columnar carcinoma cells were common in PDAC and hilar CCA, and trabecular components and cuboidal carcinoma cells were common in ICCA and CCA components of cHC-CCA. Anterior gradient protein-2 and S100P were frequently expressed in perihilar CCA and PDAC, while neural cell adhesion molecule and luminal epithelial membrane antigen were common in CCA components of c-HC-CCA. Pdx1 and Hes1 were frequently and markedly expressed aberrantly in PDAC and perihilar CCA, although their expression was rare and mild in CCA components in cHC-CCA and ICCA. Hilar CCA showed a similar postoperative prognosis to PDAC but differed from ICCA and cHC-CCA. Taken together, hilar CCA may differ from ICCA and CCA components of cHC-CCA but have a similar development to PDAC. These similarities may be explained by the unique anatomical, embryological and reactive nature of the pancreatobiliary tract. Further studies of these intractable malignancies are warranted. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  13. Hsa-circRNA11783-2 in peripheral blood is correlated with coronary artery disease and type 2 diabetes mellitus.

    Science.gov (United States)

    Li, Xuejie; Zhao, Zhenzhou; Jian, Dongdong; Li, Wentao; Tang, Haiyu; Li, Muwei

    2017-11-01

    The purpose of this study was to identify the expression characteristics of circular RNAs in the peripheral blood of coronary artery disease patients and type 2 diabetes mellitus patients. Circular RNA in the peripheral blood from 6 control individuals, 6 coronary artery disease patients, 6 type 2 diabetes mellitus patients and 6 coronary artery disease combined with type 2 diabetes mellitus patients was collected for microarray analysis, and a further independent cohort consisting of 20 normal individuals, 20 type 2 diabetes mellitus subjects and 20 coronary artery disease subjects was used to verify the expression of five circular RNAs chosen for further analysis. The findings were then tested in a third cohort using quantitative real-time polymerase chain reaction. In total, 40 circular RNAs differentially expressed between the three experimental groups and the control group were identified by microarray analysis: 13 were upregulated in the experimental groups, while 27 were downregulated. Of the five circular RNAs chosen for further analysis, three were significantly downregulated in the experimental groups. The crude odds ratios and adjusted odds ratios of hsa-circRNA11783-2 showed significant differences in both the coronary artery disease group and type 2 diabetes mellitus group. We then verified hsa-circRNA11783-2 in the third cohort, and it remained closely related to both coronary artery disease and type 2 diabetes mellitus. Hsa-circRNA11783-2 is closely related to both coronary artery disease and type 2 diabetes mellitus.

  14. Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): Design and rationale of a randomized controlled trial

    NARCIS (Netherlands)

    J.K. Wiggers (Jimme K.); R.J. Coelen (Robert J.); E.A.J. Rauws (Erik); O.M. van Delden (Otto); C.H.J. van Eijck (Casper); J. de Jonge (Jeroen); R.J. Porte (Robert); C.I. Buis (Carlijn I.); C.H. Dejong (Cees); I.Q. Molenaar (I. Quintus); M.G. Besselink (Marc); O.R.C. Busch (Olivier); M.G.W. Dijkgraaf (Marcel); T.M. van Gulik (Thomas)

    2015-01-01

    textabstractBackground: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be

  15. Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial

    NARCIS (Netherlands)

    Wiggers, Jimme K.; Coelen, Robert J. S.; Rauws, Erik A. J.; van Delden, Otto M.; van Eijck, Casper H. J.; de Jonge, Jeroen; Porte, Robert J.; Buis, Carlijn I.; Dejong, Cornelis H. C.; Molenaar, I. Quintus; Besselink, Marc G. H.; Busch, Olivier R. C.; Dijkgraaf, Marcel G. W.; van Gulik, Thomas M.

    2015-01-01

    Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when

  16. Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial) : design and rationale of a randomized controlled trial

    NARCIS (Netherlands)

    Wiggers, Jimme K.; Coelen, Robert J. S.; Rauws, Erik A. J.; van Delden, Otto M.; van Eijck, Casper H. J.; de Jonge, Jeroen; Porte, Robert J.; Buis, Carlijn I.; Dejong, Cornelis H. C.; Molenaar, I. Quintus; Besselink, Marc G. H.; Busch, Olivier R. C.; Dijkgraaf, Marcel G. W.; van Gulik, Thomas M.

    2015-01-01

    Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when

  17. The prognostic potential and carcinogenesis of long non-coding RNA TUG1 in human cholangiocarcinoma

    OpenAIRE

    Xu, Yi; Leng, Kaiming; Li, Zhenglong; Zhang, Fumin; Zhong, Xiangyu; Kang, Pengcheng; Jiang, Xingming; Cui, Yunfu

    2017-01-01

    Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pa...

  18. Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway

    Directory of Open Access Journals (Sweden)

    Daya M

    2018-01-01

    Full Text Available Minerva Daya,1–3 Watcharin Loilome,1,3 Anchalee Techasen,3,4 Malinee Thanee,3 Prakasit Sa-Ngiamwibool,4,5 Attapol Titapun,5,6 Puangrat Yongvanit,3 Nisana Namwat1,31Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 2Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Sampaloc, Manila, Philippines; 3Cholangiocarcinoma Research Institute, 4Faculty of Associated Medical Science, 5Department of Pathology, 6Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand Abstract: Progranulin (PGRN is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA. However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility. We found that CCA tissues with high PGRN expression were correlated with poor prognosis and likelihood of metastasis. PGRN knockdown KKU-100 and KKU-213 cells demonstrated a reduced rate of proliferation and colony formation and decreased levels of phosphatidyl inositol-3-kinase (PI3K and phosphorylated Akt (pAkt proteins. Accumulation of cells at the G1 phase was observed and was accompanied by a reduction of cyclin D1 and CDK4 protein levels. Knockdown cells also induced apoptosis by increasing the Bax-to-Bcl-2 ratio. Increased cell apoptosis was confirmed by annexin V-FITC/PI staining. Moreover, suppression of PGRN reduced CCA cell migration and invasion in vitro. Investigating the biomarkers in epithelial–mesenchymal transition (EMT revealed a decrease in the expression of vimentin, snail, and metalloproteinase-9. In

  19. Detection of Cholangiocarcinoma with Magnetic Resonance Spectroscopy of Bile in Patients with and without Primary Sclerosing Cholangitis

    International Nuclear Information System (INIS)

    Albiin, N.; Smith, I.C.P.; Arnelo, U.; Lindberg, B.; Bergquist, A.; Dolenko, B.; Bryksina, N.; Bezabeh, T.

    2008-01-01

    Background: Early detection of cholangiocarcinoma (CC) is very difficult, especially in patients with primary sclerosing cholangitis (PSC) who are at increased risk of developing CC. Purpose: To evaluate 1 H magnetic resonance spectroscopy ( 1 H-MRS) of bile as a diagnostic marker for CC in patients with and without PSC. Material and Methods: The institutional review board approved the study, and all patients gave informed consent. Bile from 49 patients was sampled and investigated using 1 H-MRS. MR spectra of bile samples from 45 patients (18 female; age range 22-87 years, mean age 57 years) were analyzed both conventionally and using computerized multivariate analysis. Sixteen of the patients had CC, 18 had PSC, and 11 had other benign findings. Results: The spectra of bile from CC patients differed from the benign group in the levels of phosphatidylcholine, bile acids, lipid, and cholesterol. It was possible to distinguish CC from benign conditions in all patients with malignancy. Two benign non-PSC patients were misclassified as malignant. The sensitivity, specificity, and accuracy were 88.9%, 87.1%, and 87.8%, respectively. Conclusion: With 1 H-MRS of bile, cholangiocarcinoma could be discriminated from benign biliary conditions with or without PSC

  20. Oncological superiority of hilar en bloc resection for the treatment of hilar cholangiocarcinoma.

    Science.gov (United States)

    Neuhaus, Peter; Thelen, Armin; Jonas, Sven; Puhl, Gero; Denecke, Timm; Veltzke-Schlieker, Wilfried; Seehofer, Daniel

    2012-05-01

    Long-term results after liver resection for hilar cholangiocarcinoma are still not satisfactory. Previously, we described a survival advantage of patients who undergo combined right trisectionectomy and portal vein resection, a procedure termed "hilar en bloc resection." The present study was conducted to analyze its oncological effectiveness compared to conventional hepatectomy. During hilar en bloc resection, the extrahepatic bile ducts were resected en bloc with the portal vein bifurcation, the right hepatic artery, and liver segments 1 and 4 to 8. With this "no-touch" technique, preparation of the hilar vessels in the vicinity of the tumor was avoided. The long-term outcome of 50 consecutive patients who underwent curative (R0) hilar en bloc resection between 1990 and 2004 was compared to that of 50 consecutive patients who received curative conventional major hepatectomy for hilar cholangiocarcinoma (perioperative deaths excluded). The 1-, 3-, and 5-year survival rates after hilar en bloc resection were 87%, 70%, and 58%, respectively, which was significantly higher than after conventional major hepatectomy. In the latter group, 1-, 3-, and 5-year survival rates were 79%, 40%, and 29%, respectively (P = 0.021). Tumor characteristics were comparable in both groups. A high number of pT3 and pT4 tumors and patients with positive regional lymph nodes were present in both groups. Multivariate analysis identified hilar en bloc resection as an independent prognostic factor for long-term survival (P = 0.036). In patients with central bile duct carcinomas, hilar en bloc resection is oncologically superior to conventional major hepatectomy, providing a chance of long-term survival even in advanced tumors.

  1. Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

    Science.gov (United States)

    Castro-Sánchez, Adelaida María; Moreno-Lorenzo, Carmen; Matarán-Peñarrocha, Guillermo A.; Feriche-Fernández-Castanys, Belen; Granados-Gámez, Genoveva; Quesada-Rubio, José Manuel

    2011-01-01

    The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD) (Leriche-Fontaine classification) were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P < .05) in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg) and left lower limb (lower one-third of thigh and upper and lower one-third of leg). A significant difference (P < .05) was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P < .05) for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD. PMID:19933770

  2. Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Adelaida María Castro-Sánchez

    2011-01-01

    Full Text Available The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD (Leriche-Fontaine classification were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P<.05 in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg and left lower limb (lower one-third of thigh and upper and lower one-third of leg. A significant difference (P<.05 was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P<.05 for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD.

  3. Peripheral facial nerve dysfunction: CT evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Disbro, M.A.; Harnsberger, H.R.; Osborn, A.G.

    1985-06-01

    Peripheral facial nerve dysfunction may have a clinically apparent or occult cause. The authors reviewed the clinical and radiographic records of 36 patients with peripheral facial nerve dysfunction to obtain information on the location of the suspected lesion and the number, sequence, and type of radiographic evaluations performed. Inadequate clinical evaluations before computed tomography (CT) was done and unnecessary CT examinations were also noted. They have suggested a practical clinical and radiographic scheme to evaluate progressive peripheral facial dysfunction with no apparent cause. If this scheme is applied, unnecessary radiologic tests and delays in diagnosis and treatment may be avoided.

  4. The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

    Science.gov (United States)

    Kim, Minjoo; Kim, Minkyung; Han, Ji Yun; Lee, Sang-Hyun; Jee, Sun Ha; Lee, Jong Ho

    2017-03-01

    To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A 2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A 2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A 2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

  5. The effects of long-term oral benfotiamine supplementation on peripheral nerve function and inflammatory markers in patients with type 1 diabetes: a 24-month, double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Fraser, David A; Diep, Lien M; Hovden, Inger Anette; Nilsen, Kristian B; Sveen, Kari Anne; Seljeflot, Ingebjørg; Hanssen, Kristian F

    2012-05-01

    To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes.

  6. CA 19-9 as a Marker of Survival and a Predictor of Metastization in Cholangiocarcinoma

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    Rosa Coelho

    2017-02-01

    Full Text Available Background: Cholangiocarcinoma is the second most frequent primitive liver malignancy and is responsible for 3% of the malignant gastrointestinal neoplasms. The aims of this study were to determine the association of serum levels of CA 19-9 at diagnosis with other clinical data and serum liver function tests and to identify possible factors that influence the survival rates during follow-up. Methods: Retrospective observational study of 89 patients with a diagnosis of cholangiocarcinoma followed at the Department of Gastroenterology during 5 years. Statistical analyses were performed using SPSS version 20.0. Results: Patients were followed up for a median time of 127 days (IQR: 48-564, and the median age at diagnosis was 71.0 years (IQR: 62.0-77.5. The median survival rate was 14.0 months (IQR: 4.3-23.7, and the mortality rate was 79%. Patients with CA 19-9 levels ≥103 U/L had lower albumin levels and higher levels of alanine aminotransferase and γ-glutamyltransferase. CA 19-9 levels ≥103 U/L were associated with a higher probability of metastization (p = 0.001 and lower rates of treatment with curative intent (p = 0.024. In a multivariate analysis, CA 19-9 levels Conclusion: Predictive factors for overall survival were identified, namely presence of metastasis, surgery, and chemotherapy. CA 19-9 levels ≥103 U/L were predictive factors for survival and metastization.

  7. Clonorchis sinensis infestation promotes three-dimensional aggregation and invasion of cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jihee Won

    Full Text Available Numerous experimental and epidemiological studies have demonstrated a correlation between Clonorchis sinensis (C. sinensis infestation and cholangiocarcinoma (CCA. However, the role of C. sinensis in the increased invasiveness and proliferation involved in the malignancy of CCA has not been addressed yet. Here, we investigated the possibility that C. sinensis infestation promotes expression of focal and cell-cell adhesion proteins in CCA cells and secretion of matrix metalloproteinases (MMPs. Adhesion proteins help maintain cell aggregates, and MMPs promote the three-dimensional invasion of cells into the neighboring extracellular matrix (ECM. Using a novel microfluidic assay, we quantitatively addressed the role of excretory-secretory products (ESPs gradients from C. sinensis in promoting the invasion of cells into the neighboring ECM.

  8. MR imaging and MR cholangiopancreatography in the preoperative evaluation of hilar cholangiocarcinoma: correlation with surgical and pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Masselli, Gabriele; Gualdi, Gianfranco [Umberto I Hospital-La Sapienza University Rome, Department of Radiology, Rome (Italy); Manfredi, Riccardo [University of Verona, Department of Radiology, Verona (Italy); Vecchioli, Amorino [A. Gemelli Hospital-University of Sacred Heart, Department of Radiology, Rome (Italy)

    2008-10-15

    The primary aim was to evaluate delayed contrast-enhanced MRI in depicting perineural spread of hilar cholangiocarcinoma (CCC) and consequently to determine the capability of MRI/MRCP for staging CCC. Fifteen patients that underwent MRI/MRCP and surgical treatment were retrospectively included. Two radiologists evaluated MR images to assess delayed periductal enhancement, extent of bile duct stenosis, liver parenchymal and vascular involvement and presence of liver atrophy. An agreement between delayed enhancement of the bile duct walls and perineural neoplastic spread showed a very good correlation factor (0.93). The overall accuracy in detecting biliary neoplastic invasion was higher for delayed T1-weighted images (93.3%) than for the MRCP images (80%), and T1-delayed image increased the MR accuracy in assessing the neoplastic resectability (p < 0.05). MRI correctly predicted vascular involvement in 73% and liver involvement in 80% of the cases. The number of overall correctly assessed patients with regard to resectability was 11 true positive, 1 false positive and 3 true negative. The combination of MRI/MRCP is a reliable diagnostic method for staging hilar cholangiocarcinomas. Delayed periductal enhancement is accurate in the evaluation of neoplastic perineural spread, and it can improve diagnostic accuracy to identify resectable and unresectable tumours. (orig.)

  9. Peripheral neuropathy

    Science.gov (United States)

    ... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  10. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    Energy Technology Data Exchange (ETDEWEB)

    Frampton, Gabriel; Coufal, Monique [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Li, Huang [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Ramirez, Jonathan [Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States); DeMorrow, Sharon, E-mail: demorrow@medicine.tamhsc.edu [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States)

    2010-05-15

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the {gamma}-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-{gamma}-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the {gamma}-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  11. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    International Nuclear Information System (INIS)

    Frampton, Gabriel; Coufal, Monique; Li, Huang; Ramirez, Jonathan; DeMorrow, Sharon

    2010-01-01

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the γ-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-γ-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the γ-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  12. Two Cases of Type Va Extrahepatic Bile Duct Duplication With Distal Klatskin Tumor Surgically Treated with Whipple Procedure and Hepaticojejunostomy.

    Science.gov (United States)

    Hammad, Tariq A; Alastal, Yaseen; Khan, Muhammad Ali; Hammad, Mohammad; Alaradi, Osama; Nigam, Ankesh; Sodeman, Thomas C; Nawras, Ali

    2015-10-01

    We describe the diagnostic and therapeutic challenges of a type Va extrahepatic bile duct duplication coexistent with distally located hilar cholangiocarcinoma (Klatskin tumor). We present 2 cases that were diagnosed preoperatively and treated with a modified surgical technique of a combined pylorus-preserving Whipple procedure and hepaticojejunostomy.

  13. Photodynamic Therapy Plus Chemotherapy Compared with Photodynamic Therapy Alone in Hilar Nonresectable Cholangiocarcinoma.

    Science.gov (United States)

    Wentrup, Robert; Winkelmann, Nicola; Mitroshkin, Andrey; Prager, Matthias; Voderholzer, Winfried; Schachschal, Guido; Jürgensen, Christian; Büning, Carsten

    2016-05-23

    Standard treatments are not available for hilar nonresectable cholangiocarcinoma (NCC). It is unknown whether combination therapy of photodynamic therapy (PDT) plus systemic chemotherapy is superior to PDT alone. We retrospectively reviewed 68 patients with hilar NCC treated with either PDT plus chemotherapy (PTD-C) or PDT monotherapy (PDT-M). The primary endpoint was the mean overall survival rate. Secondary endpoints included the 1-year survival rate, risk of cholangitic complications, and outcomes, which were evaluated according to the chemotherapy protocol. More than 90% of the study population had advanced hilar NCC Bismuth type III or IV. In the PDT-M group (n=35), the mean survival time was 374 days compared with 520 days in the PDT-C group (n=33, p=0.021). The 1-year survival rate was significantly higher in the PDT-C group compared with the PDT-M group (88% vs 58%, p=0.001) with a significant reduction of mortality (hazard ratio, 0.20; 95% confidence interval, 0.07 to 0.58; p=0.003). Gemcitabine monotherapy resulted in a shorter survival time compared with the gemcitabine combination therapy (mean, 395 days vs 566 days; p=0.09). Cholangitic complications were observed at a similar frequency in the PDT-C and PDT-M groups. Combining repeated PDT with a gemcitabine-based combination therapy might offer a significant survival benefit in patients with hilar NCC.

  14. An inguinal hernia sac tumor of extrahepatic cholangiocarcinoma origin

    Directory of Open Access Journals (Sweden)

    Yamazaki Hidehiro

    2006-03-01

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

  15. The type I interferon signature in leukocyte subsets from peripheral blood of patients with early arthritis: a major contribution by granulocytes.

    Science.gov (United States)

    de Jong, Tamarah D; Lübbers, Joyce; Turk, Samina; Vosslamber, Saskia; Mantel, Elise; Bontkes, Hetty J; van der Laken, Conny J; Bijlsma, Johannes W; van Schaardenburg, Dirkjan; Verweij, Cornelis L

    2016-07-13

    The type I interferon (IFN) signature in rheumatoid arthritis (RA) has shown clinical relevance in relation to disease onset and therapeutic response. Identification of the cell type(s) contributing to this IFN signature could provide insight into the signature's functional consequences. The aim of this study was to investigate the contribution of peripheral leukocyte subsets to the IFN signature in early arthritis. Blood was collected from 26 patients with early arthritis and lysed directly or separated into peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). PBMCs were sorted into CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes by flow cytometry. Messenger RNA expression of three interferon response genes (IRGs RSAD2, IFI44L, and MX1) and type I interferon receptors (IFNAR1 and IFNAR2) was determined in whole blood and blood cell subsets by quantitative polymerase chain reaction. IRG expression was averaged to calculate an IFN score for each sample. Patients were designated "IFN(high)" (n = 8) or "IFN(low)" (n = 18) on the basis of an IFN score cutoff in whole peripheral blood from healthy control subjects. The difference in IFN score between IFN(high) and IFN(low) patients was remarkably large for the PMN fraction (mean 25-fold) compared with the other subsets (mean 6- to 9-fold), indicating that PMNs are the main inducers of IRGs. Moreover, the relative contribution of the PMN fraction to the whole-blood IFN score was threefold higher than expected from its abundance in blood (p = 0.008), whereas it was three- to sixfold lower for the other subsets (p ≤ 0.063), implying that the PMNs are most sensitive to IFN signaling. Concordantly, IFNAR1 and IFNAR2 were upregulated compared with healthy controls selectively in patient PMNs (p ≤ 0.0077) but not in PBMCs. PMNs are the main contributors to the whole-blood type I IFN signature in patients with early arthritis, which seems due to

  16. Peripheral Osteoma of the Mandibular Notch: Report of a Case

    International Nuclear Information System (INIS)

    Iwai, Toshinori; Izumi, Toshiharu; Baba, Junichi; Maegawa, Jiro; Mitsudo, Kenji; Tohnai, Iwai

    2013-01-01

    Osteoma is a benign, slow-growing osteogenic tumor that sometimes arises from the craniomaxillofacial region, such as the sinus, temporal or jaw bones. Osteoma consists of compact or cancellous bone that may be peripheral, central or extraskeletal type. Peripheral osteoma arises from the periosteum and is commonly a unilateral, pedunculated mushroom-like mass. Peripheral osteoma of the mandible is relatively uncommon, and peripheral osteoma of the mandibular notch is extremely rare, although many cases arise from the mandibular body, angle, condyle, or coronoid process. We report here an unusual peripheral osteoma of the mandibular notch in a 78-year-old nonsyndromic female

  17. Cholangiocarcinoma stem-like subset shapes tumor-initiating niche by educating associated macrophages

    DEFF Research Database (Denmark)

    Raggi, Chiara; Correnti, Margherita; Sica, Antonio

    2017-01-01

    BACKGROUND AND AIMS: Therapeutically challenging subset, termed cancer stem cells (CSCs) are responsible for cholangiocarcinoma (CCA) clinical severity. Presence of tumor-associated macrophages (TAMs) has prognostic significance in CCA and other malignancies. Thus, we hypothesized that CSCs may......-activator. Gene expression profile of CCA-SPH activated MØ (SPH MØ) revealed unique molecular TAM-like features confirmed by high invasion capacity. Also, freshly isolated MØs from CCA-resections recapitulated similar molecular phenotype of in vitro educated-MØs. Consistently with invasive features, largest CD163...... providing a rationale for a synergistic therapeutic strategy for CCA-disease. LAY SUMMARY: Immune plasticity represents an important hallmark of tumor outcome. Since cancer stem cells are able to manipulate stromal cells to their needs, a better definition of key deregulated immune subtype responsible...

  18. Attempts to increase a scarce peripheral population of the Red-breasted Flycatcher (Ficedula parva using a new type of nestbox

    Directory of Open Access Journals (Sweden)

    Deme Tamás

    2016-12-01

    Full Text Available The Red-breasted Flycatcher has a large and stable global population widespread through much of the Western Palearctic. Contrarily, however, it is a very scarce breeding bird in the forested montane habitats of Hungary. The few pairs breeding here represent a peripheral population on the very edge of the species’ geographic area. This peripheral population declined considerably (from 3–500 to 100 pairs during the past decades likely due to the degradation of suitable habitat patches including the loss of appropriate nesting sites. To reverse this trend, we applied a new type of artificial nestbox developed specifically for this species. Occupancy rate was very low and breeding success was also low unless applying a protective wire mesh to reduce predation pressure.

  19. Peripheral nerve conduits: technology update

    Directory of Open Access Journals (Sweden)

    Arslantunali D

    2014-12-01

    Full Text Available D Arslantunali,1–3,* T Dursun,1,2,* D Yucel,1,4,5 N Hasirci,1,2,6 V Hasirci,1,2,7 1BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University (METU, Ankara, Turkey; 2Department of Biotechnology, METU, Ankara, Turkey; 3Department of Bioengineering, Gumushane University, Gumushane, Turkey; 4Faculty of Engineering, Department of Medical Engineering, Acibadem University, Istanbul, Turkey; 5School of Medicine, Department of Histology and Embryology, Acibadem University, Istanbul, Turkey; 6Department of Chemistry, Faculty of Arts and Sciences, METU, Ankara, Turkey; 7Department of Biological Sciences, Faculty of Arts and Sciences, METU, Ankara, Turkey *These authors have contributed equally to this work Abstract: Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers and designs (tubular, fibrous, and matrix type are being presented. Keywords: peripheral nerve injury, natural biomaterials, synthetic biomaterials

  20. SOX17 Regulates Cholangiocyte Differentiation and Acts as a Tumor Suppressor in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Merino-Azpitarte, M; Lozano, E; Perugorria, M J

    2017-01-01

    /function was evaluated along the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation process of normal human cholangiocytes (NHC) in culture and in cholangiocarcinogenesis. Lentiviruses for SOX17 overexpression or knock-down were used. Gene expression and DNA......BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a biliary malignancy linked to genetic and epigenetic abnormalities, such as hypermethylation of SOX17 promoter. Here, the role of SOX17 in cholangiocyte differentiation and cholangiocarcinogenesis was studied. METHODS: SOX17 expression...... methylation profiling were performed. RESULTS: SOX17 expression is induced in the last stage of cholangiocyte differentiation from iPSC and regulates the acquisition of biliary markers. SOX17 becomes downregulated in NHC undergoing dedifferentiation; experimental SOX17 knock-down in differentiated NHC...

  1. Yttrium-90 resin microspheres and their use in the treatment of intrahepatic cholangiocarcinoma.

    Science.gov (United States)

    Filippi, Luca; Schillaci, Orazio; Cianni, Roberto; Bagni, Oreste

    2018-04-01

    Intrahepatic cholangiocarcinoma (ICC) is a severe and rapidly progressive hepatic tumor. Surgery is often impracticable due to locally advanced presentation. On the other hand, chemotherapy has demonstrated only limited effectiveness. For these reasons, liver-directed therapies have been successfully applied for treating ICC. In particular, radioembolization with Yttrium-90 ( 90 Y)-labeled spheres has been reported to be a promising therapeutic approach for this neoplasia. Two commercial forms of 90 Y-labeled spheres are available: glass (TheraSphere ® ) and resin (SIR-Spheres ® ) microspheres. The aim of the present paper is to review the existing literature on the use of the resin microspheres for the treatment of unresectable and chemorefractory ICC, focusing on the methodology, clinical applications and side effects.

  2. Does Peripheral Neuropathy Associate with Cranial Nerves Neuropathy in Type 2 diabetes Patients?

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    Walaa Fadhil Jalal

    2017-02-01

    Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication of type 2 diabetes mellitus. Cranial neuropathies is usually presenting as mononeuropathies coexist with DPN either presented clinically or in subclinical form. The aim of this study is to detect cranial neuropathy in diabetic patients. Eighty three patients with type 2 diabetes mellitus (T2DM with an age range of 30-69 years were included in the study. The study also involved normal healthy persons whose age and gender are harmonized with that of our patients that were deliberated as control group (60 persons. Diabetic patients with DPN had significant difference in age, highly significant difference in the duration of the disease and highly significance difference in BMI had poor glycemic control reflected by high FBS and HbA1c, while lipid profile picture showed insignificant difference when compared with diabetic patients without DPN. Nerve conduction study (sensory and motor showed a significant difference regarding latency, amplitude, and conduction velocity between diabetic patients with DPN and those without DPN. The results of blink reflex showed highly significant difference between diabetic patients and controls.

  3. Cost utility analysis of endoscopic biliary stent in unresectable hilar cholangiocarcinoma: decision analytic modeling approach.

    Science.gov (United States)

    Sangchan, Apichat; Chaiyakunapruk, Nathorn; Supakankunti, Siripen; Pugkhem, Ake; Mairiang, Pisaln

    2014-01-01

    Endoscopic biliary drainage using metal and plastic stent in unresectable hilar cholangiocarcinoma (HCA) is widely used but little is known about their cost-effectiveness. This study evaluated the cost-utility of endoscopic metal and plastic stent drainage in unresectable complex, Bismuth type II-IV, HCA patients. Decision analytic model, Markov model, was used to evaluate cost and quality-adjusted life year (QALY) of endoscopic biliary drainage in unresectable HCA. Costs of treatment and utilities of each Markov state were retrieved from hospital charges and unresectable HCA patients from tertiary care hospital in Thailand, respectively. Transition probabilities were derived from international literature. Base case analyses and sensitivity analyses were performed. Under the base-case analysis, metal stent is more effective but more expensive than plastic stent. An incremental cost per additional QALY gained is 192,650 baht (US$ 6,318). From probabilistic sensitivity analysis, at the willingness to pay threshold of one and three times GDP per capita or 158,000 baht (US$ 5,182) and 474,000 baht (US$ 15,546), the probability of metal stent being cost-effective is 26.4% and 99.8%, respectively. Based on the WHO recommendation regarding the cost-effectiveness threshold criteria, endoscopic metal stent drainage is cost-effective compared to plastic stent in unresectable complex HCA.

  4. Study on the peripheral white blood cell count in patients with type 2 diabetes complicated with microangiopathy

    International Nuclear Information System (INIS)

    Cai Wenpin; Zhu Pinghui

    2010-01-01

    Objective: To study the possible role played by peripheral white blood cells in the development of type 2 diabetes (DM2) and complication of microvascular pathological changes. Methods: White blood cell count and metabolism related parameters (FBG, 2hPBG, 2h Pinsulin, TCH, HDL, LDL, TG, HbA1c, BMI, age) were examined in 33 DM2 patients without complication, 41 DM2 patients with micro-angiopathy and 31 controls. Results: The white blood cell counts in both DM2 patients with no complication and the DM2 with microvascular pathological changes were significantly higher than those in controls (P 0.05). The white blood cell counts were positively correlated with age,body metabolism index (BMI), triglyceride (TG), 2h glucose (PBG) and 2h insulin (the r value 0.248, 0.201, 0.435, 0.225, 0.352 respectively, P<0.05). Conclusion: Peripheral white blood cells possibly played some role in development of DM2 and microvascular pathological changes and might be of some predictive importance. (authors)

  5. Cholangiocarcinoma of intrahepatic bile ducts with disseminated metastases in an African lion (Panthera leo).

    Science.gov (United States)

    Lepri, Elvio; Sforna, Monica; Brachelente, Chiara; Chiara, Brachelente; Vitellozzi, Giovanni; Giovanni, Vitellozzi

    2013-06-01

    A cholangiocarcinoma is reported in an 18-yr-old, female African lion (Panthera leo). The primary tumor consisted of multifocal to coalescing, hepatic, white-yellow masses distributed throughout the liver lobes. Metastases were present in regional lymph nodes, peritoneal surface, and lungs. Histologically, the tumor was characterized by a tubular pattern with alcian- and periodic acid-Schiff-positive secretory material in cystic spaces. The neoplastic cells were positive to broad-spectrum cytokeratins. Histochemical and immunohistochemical stains were consistent with bile duct carcinoma. Biliary tumors arising from the gallbladder have been reported in lions. However, to the authors' knowledge, this is the first case of intrahepatic bile duct carcinoma reported in an African lion.

  6. Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

    Directory of Open Access Journals (Sweden)

    Araki Nobuhito

    2010-01-01

    Full Text Available Abstract A rare case is presented of a 61-year-old man with a malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart. The primary tumor originated in the right thigh in 1982. Since then, the patient has had repeated local recurrences in spite of repeated surgical treatment and adjuvant chemotherapy. He has developed previous metastases of the lung and heart. The patient died of cardiac involvement.

  7. [Ultrasound-guided peripheral catheterization].

    Science.gov (United States)

    Salleras-Duran, Laia; Fuentes-Pumarola, Concepció

    2016-01-01

    Peripheral catheterization is a technique that can be difficult in some patients. Some studies have recently described the use of ultrasound to guide the venous catheterization. To describe the success rate, time required, complications of ultrasound-guided peripheral venous catheterization. and patients and professionals satisfaction The search was performed in databases (Medline-PubMed, Cochrane Library, CINAHL and Cuiden Plus) for studies published about ultrasound-guided peripheral venous catheterization performed on patients that provided results on the success of the technique, complications, time used, patient satisfaction and the type of professional who performed the technique. A total of 21 studies were included. Most of them get a higher success rate 80% in the catheterization ecoguide and time it is not higher than the traditional technique. The Technical complications analyzed were arterial puncture rates and lower nerve 10%. In all studies measuring and comparing patient satisfaction in the art ecoguide is greater. Various professional groups perform the technique. The use of ultrasound for peripheral pipes has a high success rate, complications are rare and the time used is similar to that of the traditional technique. The technique of inserting catheters through ultrasound may be learned by any professional group performing venipuncture. Finally, it gets underscores the high patient satisfaction with the use of this technique. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  8. The anticancer effects of Resina Draconis extract on cholangiocarcinoma.

    Science.gov (United States)

    Wen, Feng; Zhao, Xiangxuan; Zhao, Yun; Lu, Zaiming; Guo, Qiyong

    2016-11-01

    Cholangiocarcinoma (CCA) is a relatively rare, heterogeneous malignant tumor with poor clinical outcomes. Because of high insensitivity to chemotherapy and radiotherapy, there are no effective treatment options. Efforts to identify and develop new agents for prevention and treatment of this deadly disease are urgent. Here, we assessed the apoptotic cytotoxicity of Resina Draconis extract (RDE) using in vitro and in vivo assays and identified the mechanisms underlying antitumor effects of RDE. RDE was obtained via vacuum distillation of Resina Draconis with 75 % ethanol. The ethanol extract could inhibit CCA cell proliferation and trigger apoptotic cell death in both QBC939 and HCCC9810 cell lines in a time- and concentration-dependent manner. RDE treatment resulted in intracellular caspase-8 and poly (ADP-ribose) polymerase protease activation. RDE significantly downregulated antiapoptotic protein survivin expression and upregulated proapoptotic protein Bak expression. RDE also inhibited CCA tumor growth in vivo. We observed that human CCA tissues had much higher survivin expression than did paired adjacent normal tissue. Taken together, the current data suggested that RDE has anticancer effects on CCA, and that RDE could function as a novel anticancer agent to benefit patients with CCA.

  9. Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications.

    Science.gov (United States)

    Blocki, Anna; Wang, Yingting; Koch, Maria; Goralczyk, Anna; Beyer, Sebastian; Agarwal, Nikita; Lee, Michelle; Moonshi, Shehzahdi; Dewavrin, Jean-Yves; Peh, Priscilla; Schwarz, Herbert; Bhakoo, Kishore; Raghunath, Michael

    2015-03-01

    Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10-40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-β and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies.

  10. C-Reactive Protein Predicts Progression of Peripheral Arterial Disease in Patients with Type 2 Diabetes: A 5-Year Follow-Up Study

    Directory of Open Access Journals (Sweden)

    Popović Ljiljana

    2014-09-01

    Full Text Available Background: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP is a risk factor for the peripheral arterial disease (PAD in diabetes. This study aimed to evaluate the possible predictive significance of hs-CRP for the development and progression of PAD in patients with type 2 diabetes (T2D.

  11. Peripheral neuropathy in prediabetes and the metabolic syndrome.

    Science.gov (United States)

    Stino, Amro M; Smith, Albert G

    2017-09-01

    Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  12. Role of sigma 1 receptor in high fat diet-induced peripheral neuropathy.

    Science.gov (United States)

    Song, Tieying; Zhao, Jianhui; Ma, Xiaojing; Zhang, Zaiwang; Jiang, Bo; Yang, Yunliang

    2017-09-26

    The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDAR subunits GluN2A and GluN2B along with postsynaptic density protein 95 (PSD-95) in the spinal cord after 24-week HFD treatment in both wild-type and Sig-1R-/- mice. Finally, we examined the effects of repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice on peripheral neuropathy. Wild-type mice developed tactile allodynia and thermal hypoalgesia after 24-week HFD treatment. HFD-induced peripheral neuropathy correlated with increased expression of GluN2A and GluN2B subunits of NMDARs, PDS-95, and Sig-1R, as well as increased Sig-1R-NMDAR interaction in the spinal cord. In contrast, Sig-1R-/- mice did not develop thermal hypoalgesia or tactile allodynia after 24-week HFD treatment, and the levels of GluN2A, GluN2B, and PSD-95 were not altered in the spinal cord of HFD-fed Sig-1R-/- mice. Finally, repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice attenuated peripheral neuropathy. Our results suggest that obesity-associated peripheral neuropathy may involve Sig-1R-mediated enhancement of NMDAR expression in the spinal cord.

  13. Large Peripheral Osteoma of the Mandible: A Case Report

    Directory of Open Access Journals (Sweden)

    Emel Bulut

    2010-01-01

    Full Text Available Osteomas are benign, slow-growing osteogenic tumors commonly occurring in the craniofacial bones. Osteomas are characterized by the proliferation of compact and/or cancellous bone. It can be of a central, peripheral, or extraskeletal type. The peripheral type arises from the periosteum and is rarely seen in the mandible. The lingual surface and lower border of the body are the most common locations of these lesions. They are usually asymptomatic and can be discovered in routine clinical and radiographic examination. In this paper, we presented a large solitary peripheral osteoma located in the buccal surface of the left posterior mandible and causing facial deformity in a 37-year-old woman. Radiographic examination by computed tomography revealed radiopacity with a well-circumscribed, pedunculated mass approximately 3 cm in size. The osteoma was removed surgically, and no recurrence has been observed.

  14. Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial

    OpenAIRE

    Wiggers, Jimme K; Coelen, Robert JS; Rauws, Erik AJ; van Delden, Otto M; van Eijck, Casper HJ; de Jonge, Jeroen; Porte, Robert J; Buis, Carlijn I; Dejong, Cornelis HC; Molenaar, I Quintus; Besselink, Marc GH; Busch, Olivier RC; Dijkgraaf, Marcel GW; van Gulik, Thomas M

    2015-01-01

    Background Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients? condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorr...

  15. Evaluation of peripheral vasodilative indices in skin tissue of type 1 diabetic rats by use of RGB images

    Science.gov (United States)

    Tanaka, Noriyuki; Nishidate, Izumi; Nakano, Kazuya; Aizu, Yoshihisa; Niizeki, Kyuichi

    2016-04-01

    We investigated a method to evaluate the arterial inflow and the venous capacitance in the skin tissue of streptozotocin-induced type 1 diabetic rats from RGB digital color images. The arterial inflow and the venous capacitance in the dorsal reversed McFarlane skin flap are calculated based on the responses of change in the total blood concentration to occlusion of blood flow to and from the flap tissues at a pressure of 50 mmHg. The arterial inflow and the venous capacitance in the skin flap tissue were significantly reduced in type 1 diabetic rat group compared with the non-diabetic rat group. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular dysfunctions in diabetes mellitus.

  16. In vivo labelling in several rat tissues of 'peripheral type' benzodiazepine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Benavides, J.; Guilloux, F.; Rufat, P.; Uzan, A.; Renault, C.; Dubroeucq, M.C.; Gueremy, C.; Le Fur, G. (Pharmuka Laboratoires, 92 - Gennevilliers (France))

    1984-03-16

    'Peripheral type' benzodiazepine binding sites in several rat tissues were labelled by intravenous injection of (/sup 3/H)PK 11195 and (/sup 3/H)RO5-4864. Binding was saturable in all tissues studied and regional distribution paralleled the in vitro binding. A similar potency order of displacing compounds was found in vivo and in vitro PK 11195 > PK 11211 > RO5-4864 > diazepam > dipyridamole > clonazepam. These results demonstrate the feasibility of using this technique to examine the effects of pharmacological manipulation on the binding sites in their native state. However, some properties (broader maximum during time course, higher percentage of particulate binding in the brain and independence of temperature) make (/sup 3/H)PK 11195 the most suitable ligand for this kind of studies.

  17. Use of betahistine in the treatment of peripheral vertigo.

    Science.gov (United States)

    Ramos Alcocer, Rubén; Ledezma Rodríguez, José Gregorio; Navas Romero, Antonio; Cardenas Nuñez, José Luis; Rodríguez Montoya, Vicente; Deschamps, Jose Junior; Liviac Ticse, Jorge Anibal

    2015-01-01

    Clinical studies and meta-analyses demonstrated that betahistine is effective and safe in the treatment of Ménière's disease, BPPV (benign paroxysmal positional vertigo), vestibular neuronitis, and other types of peripheral vertigo. The goal of this paper is to review the pharmacological profile of betahistine and the evidence for its effectiveness and safety in the treatment of peripheral vertigo. Selection criteria for the publications on betahistine included randomized clinical trials that evaluated the effectiveness and safety of betahistine vs placebo or active control in the treatment of peripheral vertigo. Recent meta-analyses were also included. Databases searched included PubMed, the Cochrane Ear, Nose and Throat Disorders Group Trials Register, and ICTRP. The review also presents an update on the mechanisms of action, pharmacodynamics, and pharmacokinetics of betahistine. Efficacy and safety of betahistine has been demonstrated in numerous clinical trials. The precise mechanism of action of betahistine is still not completely understood, but the clinical experience demonstrated the benefit of betahistine in different types of peripheral vertigo. In more than 40 years of clinical use, betahistine has shown an excellent safety profile with the usual dose range from 8-48 mg daily. According to clinical studies, betahistine 48 mg daily during 3 months is an effective and safe option for the treatment of peripheral vertigo.

  18. PERIPHERAL BLOCK ANESTHESIA OF UPPER EXTREMITY AND ITS COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Hakan Tapar

    2012-09-01

    Full Text Available Successful peripheral blocks and selection of appropriate technique according to surgery is possible with a good knowledge of anatomy. Regional peripheral block anesthesia of upper extremity which applied by single injection to plexus brachialis is the most recommended method of anesthesia in daily surgical procedures. The most important advantages of peripheral nerve blocks which are type of regional anesthesia according to general anesthesia and central blocks are less effect to respiration and hemodynamics and shortness of recovery time. If a plexus brachialis catheter is placed, control of pain is provided without using systemic narcotic analgesic. With these advantages; rare life threatening potential complications can be seen which are pneumothorax, hematoma, neuritis, allergy, systemic and neurologic complications. In this compilation we aimed to review again the complications of upper extremity nerve blocks according to block type. [J Contemp Med 2012; 2(3.000: 195-200

  19. [Correlation between typing of peripheral neuroblastic tumors and prognosis: a clinicopathologic study of 135 cases].

    Science.gov (United States)

    YIN, Min-zhi; ZHANG, Zhong-de; MA, Jing; SHEN, Ping; CHEN, Jie-feng; ZHANG, Hui-zhen

    2011-03-01

    To study the clinicopathologic characteristics of peripheral neuroblastic tumors and to investigate the prognostic significance of International Neuroblastoma Pathology Classification (INPC). One hundred and thirty-five cases of peripheral neuroblastic tumors encountered in Shanghai Children's Medical Center were enrolled into the study. All the cases were classified according to INPC and International Neuroblastoma Staging System (INSS). The follow-up data were analyzed. The consensus diagnoses of the 135 cases were as follows: 80 cases (59.2%) of neuroblastoma, 24 cases (17.8%) of ganglioneuroblastoma, intermixed, 17 cases (12.6%) of ganglioneuroma and 14 cases (10.4%) of ganglioneuroblastoma, nodular. The cases were subdivided into 2 subgroups: favorable histology (number = 90, 66.7%) and unfavorable histology (number = 45, 33.3%). According to INSS, the number of cases in stages I, II, III and IV was 22 (16.3%), 24 (17.8%), 34 (25.2%) and 55 (40.7%), respectively. The survival of peripheral neuroblastic tumors correlated with histologic diagnosis, INPC and INSS (P < 0.05). Diagnostic categorization of peripheral neuroblastic tumors according to INPC is of prognostic value.

  20. Cooperative Effects of Corticosteroids and Catecholamines upon Immune Deviation of the Type-1/Type-2 Cytokine Balance in Favor of Type-2 Expression in Human Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Salicru, A. N.; Sams, Clarence F.; Marshall, G. D.

    2007-01-01

    A growing number of studies show strong associations between stress and altered immune function. In vivo studies of chronic and acute stress have demonstrated that cognitive stressors are strongly correlated with high levels of catecholamines (CT) and corticosteroids (CS). Although both CS and CT individually can inhibit the production of T-helper 1 (TH1, type-1 like) cytokines and simultaneously promote the production of T-helper 2 (TH2, type-2 like) cytokines in antigen-specific and mitogen stimulated human leukocyte cultures in vitro, little attention has been focused on the effects of combination CT and CS in immune responses that may be more physiologically relevant. We therefore investigated the combined effects of in vitro CT and CS upon the type-1/type-2 cytokine balance of human peripheral blood mononuclear cells (PBMC) as a model to study the immunomodulatory effects of superimposed acute and chronic stress. Results demonstrated a significant decrease in type-1 cytokine production (IFN-gamma) and a significant increase in type-2 cytokine production (IL-4, IL-10) in our CS+CT incubated cultures when compared to either CT or CS agents alone. Furthermore, variable enhancement of type-1/type-2 immune deviation occurred depending upon when the CT was added. The data suggest that CS can increase the sensitivity of PBMC to the immunomodulatory effects of CT and establishes an in vitro model to study the combined effects of in vivo type-1/type-2 cytokine alterations observed in acute and chronic stress.

  1. Histological heterogeneity in primary and metastatic classic combined hepatocellular-cholangiocarcinoma: a case series.

    Science.gov (United States)

    De Vito, Claudio; Sarker, Debashis; Ross, Paul; Heaton, Nigel; Quaglia, Alberto

    2017-11-01

    Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare and aggressive primary liver cancer with both hepatocellular and cholangiocellular differentiation. Due to its bi-phenotypic component, cHCC-CC is a heterogeneous tumour and histopathological analysis of metastatic deposits is poorly characterized. In this retrospective study, we describe four patients in whom the histology from resected specimens of both primary and recurrent and/or metastatic tumour was available for comparison and immunohistochemical characterization. Our study shows that recurrent or metastatic deposits replicate the heterogeneity of the primary cHCC-CC, that even originally small foci of divergent differentiation can become predominant later on and that hepatocellular and cholangiocellular components can show different tropism in distant organs. In our experience, the behaviour of recurrent/metastatic cHCC-CC is unpredictable and histological examination is necessary to guide treatment options at present.

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

    Directory of Open Access Journals (Sweden)

    Jean Amede Roch

    2008-10-01

    Full Text Available

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

  3. Peripheral facial palsy in children.

    Science.gov (United States)

    Yılmaz, Unsal; Cubukçu, Duygu; Yılmaz, Tuba Sevim; Akıncı, Gülçin; Ozcan, Muazzez; Güzel, Orkide

    2014-11-01

    The aim of this study is to evaluate the types and clinical characteristics of peripheral facial palsy in children. The hospital charts of children diagnosed with peripheral facial palsy were reviewed retrospectively. A total of 81 children (42 female and 39 male) with a mean age of 9.2 ± 4.3 years were included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma, congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%) patients had recurrent attacks. In patients with Bell palsy, female/male and right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a history of preceding infection. The overall rate of complete recovery was 98.4%. A wide variety of disorders can present with peripheral facial palsy in children. Therefore, careful investigation and differential diagnosis is essential. © The Author(s) 2013.

  4. 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

  5. Prognostic Value of Bismuth Typing and Modified T-stage in Hilar Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Shengen Yi

    2015-01-01

    Conclusion: The majority of our patients with HCC were characterized as Subtype IV in Bismuth typing and Stage T3 in modified T-stage. Both Bismuth typing and modified T-stage showed prognostic value in HCC. Compared with Bismuth typing, modified T-stage is a better indicator of the resectability of HCC.

  6. Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients with Cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keunyoung; Kim, Seongjang; Kim, Injoo; Kim, Dong Uk; Kim, Heeyoung; Kim, Sojung; Ahn, Sang Hyun [Pusan National Univ. Hospital, Busan (Korea, Republic of)

    2014-06-15

    Although diffuse splenic {sup 18}F-fluorodeoxyglucose (F-18 FDG) uptake exceeding hepatic activity, is considered abnormal, its clinical significance is rarely discussed in the literature. The aim of this study was to determine the contributing factors causing diffusely increased splenic FDG uptake in patients with cholangiocarcinoma. From January 2010 to March 2013, 140 patients (84 men, 56 women) were enrolled in this study. All patients had been diagnosed with cholangiocarcinoma and underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) for the pretreatment staging work up. Clinical records were reviewed retrospectively. Various hematological parameters, C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver function tests were conducted within 2 days after the F-18 FDG PET/CT study. Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19 patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP) 7 days before F-18 FDG PET/CT. The CRP level (p <0.001) and white blood cell count (p =0.023) were significantly higher in the group of patients with diffuse splenic FDG uptake. The hemoglobin (p <0.001) and the hematocrit (p <0.001) were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic enzymes, liver function test results, and tumor markers were not significantly different between the patients who did or did not have diffusely increased splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR, 1.211; 95% CI, 1.051-1.871). In conclusion, our study demonstrated that concurrent inflammation could be associated with diffusely increased splenic FDG uptake. We suggest that performing ERCP before F-18 FDG PET

  7. Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients with Cholangiocarcinoma

    International Nuclear Information System (INIS)

    Kim, Keunyoung; Kim, Seongjang; Kim, Injoo; Kim, Dong Uk; Kim, Heeyoung; Kim, Sojung; Ahn, Sang Hyun

    2014-01-01

    Although diffuse splenic 18 F-fluorodeoxyglucose (F-18 FDG) uptake exceeding hepatic activity, is considered abnormal, its clinical significance is rarely discussed in the literature. The aim of this study was to determine the contributing factors causing diffusely increased splenic FDG uptake in patients with cholangiocarcinoma. From January 2010 to March 2013, 140 patients (84 men, 56 women) were enrolled in this study. All patients had been diagnosed with cholangiocarcinoma and underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) for the pretreatment staging work up. Clinical records were reviewed retrospectively. Various hematological parameters, C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver function tests were conducted within 2 days after the F-18 FDG PET/CT study. Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19 patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP) 7 days before F-18 FDG PET/CT. The CRP level (p <0.001) and white blood cell count (p =0.023) were significantly higher in the group of patients with diffuse splenic FDG uptake. The hemoglobin (p <0.001) and the hematocrit (p <0.001) were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic enzymes, liver function test results, and tumor markers were not significantly different between the patients who did or did not have diffusely increased splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR, 1.211; 95% CI, 1.051-1.871). In conclusion, our study demonstrated that concurrent inflammation could be associated with diffusely increased splenic FDG uptake. We suggest that performing ERCP before F-18 FDG PET

  8. Mitochondrial dysfunction in calf muscles of patients with combined peripheral arterial disease and diabetes type 2

    DEFF Research Database (Denmark)

    Lindegaard Pedersen, Brian; Bækgaard, Niels; Quistorff, Bjørn

    2017-01-01

    BACKGROUND: This study elucidate the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment. METHODS: Near Infra Red Spectroscopy (NIRS) calf muscle exercise tests...... were conducted on Forty subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~ 80 mg) (Gastrocnemius and Anterior tibial muscles) were sampled and mitochondrial function...... group. This was confirmed by a ~30% reduction in oxygen consumption in the muscle biopsy tests for the PAD+T2D compared to the PAD group (P

  9. Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

    Science.gov (United States)

    Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

    2016-12-01

    Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The Effects of Tai Chi on Peripheral Somatosensation, Balance, and Fitness in Hispanic Older Adults with Type 2 Diabetes: A Pilot and Feasibility Study

    Directory of Open Access Journals (Sweden)

    Elisabeth I. Cavegn

    2015-01-01

    Full Text Available Peripheral neuropathy and loss of somatosensation in older adults with type 2 diabetes can increase risk of falls and disability. In nondiabetic older adult population Tai Chi has been shown to enhance balance and fitness through improvements in somatosensation and neuromuscular control, and it is unclear if Tai Chi would elicit similar benefits in older adults with diabetes. Therefore, the purpose of this study was to investigate the effects of an 8-week, three-hour-per-week Tai Chi intervention on peripheral somatosensation in older adults with type 2 diabetes. Participants were eight Hispanic older adults with type 2 diabetes who participated in the Tai Chi intervention and a convenience sample of Hispanic older adults as a referent group. Baseline and postintervention assessments included ankle proprioception, foot tactile sense, plantar pressure distribution, balance, and fitness. After intervention, older adults with type 2 diabetes showed significant improvements in ankle proprioception and fitness and decreased plantar pressure in the forefoot, with no statistical effect noted in balance or tactile sensation. Study results suggest that Tai Chi may be beneficial for older adults with diabetes as it improves ankle proprioception; however, study findings need to be confirmed in a larger sample size randomized controlled trial.

  11. [Anti-tumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line in vitro].

    Science.gov (United States)

    Li, Maolan; Lu, Wei; Zhang, Fei; Ding, Qichen; Wu, Xiangsong; Tan, Zhujun; Wu, Wenguang; Weng, Hao; Wang, Xuefeng; Shi, Weibin; Dong, Ping; Gu, Jun; Liu, Yingbin

    2014-11-04

    To explore the antitumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line. DDP-PLLA-CNTs were prepared with the method of ultrasound emulsification. The morphology of DDP-PLLA-CNTs was determined by scanning electron microscope (SEM). And its drug loading and drug release curve in vitro was detected by UV-Vis-NIR spectrophotometer. CCK8 was used to test the cytotoxic effects of DDP-PLLA-CNTs at different concentrations on QBC939 cell proliferation.Flow cytometry was employed to measure the changes of apoptotic rate. With excellent controlled-release characteristic of in vitro drug release, DDP-PLLA-CNTs inhibited the proliferation and significantly increased the apoptotic rate of QBC939 cell line. DDP-PLLA-CNTs have drug sustained-release characteristics and can significantly inhibit the proliferation of QBC939 cell line.

  12. Expression profiling feline peripheral blood monocytes identifies a transcriptional signature associated with type two diabetes mellitus.

    Science.gov (United States)

    O'Leary, Caroline A; Sedhom, Mamdouh; Reeve-Johnson, Mia; Mallyon, John; Irvine, Katharine M

    2017-04-01

    Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes (T2D) in humans, especially with respect to the role of obesity-induced insulin resistance, glucose toxicity, decreased number of pancreatic β-cells and pancreatic amyloid deposition. Cats have thus been proposed as a valuable translational model of T2D. In humans, inflammation associated with adipose tissue is believed to be central to T2D development, and peripheral blood monocytes (PBM) are important in the inflammatory cascade which leads to insulin resistance and β-cell failure. PBM may thus provide a useful window to study the pathogenesis of diabetes mellitus in cats, however feline monocytes are poorly characterised. In this study, we used the Affymetrix Feline 1.0ST array to profile peripheral blood monocytes from 3 domestic cats with T2D and 3 cats with normal glucose tolerance. Feline monocytes were enriched for genes expressed in human monocytes, and, despite heterogeneous gene expression, we identified a T2D-associated expression signature associated with cell cycle perturbations, DNA repair and the unfolded protein response, oxidative phosphorylation and inflammatory responses. Our data provide novel insights into the feline monocyte transcriptome, and support the hypothesis that inflammatory monocytes contribute to T2D pathogenesis in cats as well as in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

    2011-01-01

    for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

  14. Nuclear NF-κB p65 in peripheral blood mononuclear cells correlates with urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Bin Yi

    Full Text Available AIMS: To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. METHODS: According to their urinary albumin-to-creatinine ratio (uACR, 107 patients with type 2 diabetes (eGFR >60 ml/min were divided into normal albuminuria group (DN0 group, 38 cases, microalbuminuria group (DN1 group, 38 cases, and macroalbuminuria group (DN2 group, 31 cases, compared with matched healthy normal control group (NC group, 30 cases. Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS: Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION: Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

  15. Evaluation of small peripheral pulmonary lesions with thin slice computed tomography

    International Nuclear Information System (INIS)

    Yamada, Kouzo

    1992-01-01

    To evaluate the morphology of small peripheral pulmonary lesions, we studied thin-slice CT (TS-CT) images of 47 small peripheral pulmonary lesions (24 lung cancers, 23 benign lesions) in 47 patients. CT images were examined by two different window and level settings (window level; -600, window width; 1900 and window level; 50, window width; 300). In TS-CT images, findings of all lesions were classified into 3 different patterns (infiltrative type, solid with air-bronchogram type, homogeneous solid type) which were useful in diagnosing histology based on the growth pattern of the lesion. There was no lung cancer case in which calcification was diagnosed to be present on TS-CT. On the other hand, 5 of 9 inflammatory granulomas were recognized to contain calcium which was never seen on conventional CT. The results suggest that TS-CT may have a significant clinical role in diagnosing small peripheral pulmonary lesion by demonstrating macroscopic features and calcification. (author)

  16. Transcriptomic profiles of peripheral white blood cells in type II diabetes and racial differences in expression profiles

    Directory of Open Access Journals (Sweden)

    Mao Jinghe

    2011-12-01

    Full Text Available Abstract Background Along with obesity, physical inactivity, and family history of metabolic disorders, African American ethnicity is a risk factor for type 2 diabetes (T2D in the United States. However, little is known about the differences in gene expression and transcriptomic profiles of blood in T2D between African Americans (AA and Caucasians (CAU, and microarray analysis of peripheral white blood cells (WBCs from these two ethnic groups will facilitate our understanding of the underlying molecular mechanism in T2D and identify genetic biomarkers responsible for the disparities. Results A whole human genome oligomicroarray of peripheral WBCs was performed on 144 samples obtained from 84 patients with T2D (44 AA and 40 CAU and 60 healthy controls (28 AA and 32 CAU. The results showed that 30 genes had significant difference in expression between patients and controls (a fold change of 1.4 with a P value Conclusions These newly identified genetic markers in WBCs provide valuable information about the pathophysiology of T2D and can be used for diagnosis and pharmaceutical drug design. Our results also found that AA and CAU patients with T2D express genes and pathways differently.

  17. Clinical case

    International Nuclear Information System (INIS)

    Garcia Fontes, M

    2012-01-01

    This presentation is about a case of a patient with liver tumor. The ultrasound scan and Tc technique were used for the diagnosis and treatment. The application of PET - CT FDG contributed to detect peripheral cholangiocarcinoma, the lymph node distance to guide the therapeutic and the recurrence in case of a negative morphological methods.

  18. Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients.

    Science.gov (United States)

    Tamasawa, Atsuko; Mochizuki, Kazuki; Hariya, Natsuyo; Saito, Miyoko; Ishida, Hidenori; Doguchi, Satako; Yanagiya, Syoko; Osonoi, Takeshi

    2015-09-05

    Acarbose, an α-glucosidase inhibitor, leads to the production of hydrogen gas, which reduces oxidative stress. In this study, we examined the effects of a single dose of acarbose immediately before a test meal on postprandial hydrogen gas in breath and peripheral blood interleukin (IL)-1β mRNA expression in Japanese type 2 diabetic patients. Sixteen Japanese patients (14 men, 2 women) participated in this study. The mean±standard deviation age, hemoglobin A1c and body mass index were 52.1±15.4 years, 10.2±2.0%, and 27.7±8.0kg/m(2), respectively. The patients were admitted into our hospital for 2 days and underwent test meals at breakfast without (day 1) or with acarbose (day 2). We performed continuous glucose monitoring and measured hydrogen gas levels in breath, and peripheral blood IL-1β mRNA levels before (0min) and after the test meal (hydrogen gas: 60, 120, 180, and 300min; IL-1β: 180min). The induction of hydrogen gas production and the reduction in peripheral blood IL-1β mRNA after the test meal were not significant between days 1 (without acarbose) and 2 (with acarbose). However, the changes in total hydrogen gas production from day 1 to day 2 were closely and inversely associated with the changes in peripheral blood IL-1β mRNA levels. Our results suggest that an increase in hydrogen gas production is inversely associated with a reduction of the peripheral blood IL-1β mRNA level after a single dose of acarbose in Japanese type 2 diabetic patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Peripheral blood count in preoperative radiotherapy (with radiomodificators) of lung cancer

    International Nuclear Information System (INIS)

    Demidchik, Yu.E.; Zharkov, V.V.; Prokhorova, V.I.; Rubanova, C.Z.

    1989-01-01

    Indices of peripheral blood in 215 patients with lung cancer during preoperative radiation using hyperglycemia or metronidazole are studied. It is shown that after preoperative radiotherapy, when radiomodifying effects are not used, the content of erythrocytes, thrombocytes, leukocytes, the concentration of hemoglobin in peripheral blood, as well as erythrocyte sedimentation rare didn't change. Functional disorders of the leukopoietic function and the thrombopoietic function of bone marrow when using metronidazole are registered when applying various types of preoperative radiotherapy. Lymphopenia is established when using various types of radiotherapy with radiomodificators

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

    Directory of Open Access Journals (Sweden)

    Ting-Ting Liu

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

  1. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models.

    Science.gov (United States)

    Plengsuriyakarn, Tullayakorn; Viyanant, Vithoon; Eursitthichai, Veerachai; Picha, Porntipa; Kupradinun, Piengchai; Itharat, Arunporn; Na-Bangchang, Kesara

    2012-03-27

    Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO

  2. Vorinostat-eluting poly(DL-lactide-co-glycolide nanofiber-coated stent for inhibition of cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Kwak TW

    2017-10-01

    Full Text Available Tae Won Kwak,1,* Hye Lim Lee,2,* Yeon Hui Song,2 Chan Kim,3 Jungsoo Kim,2 Sol-Ji Seo,2 Young-Il Jeong,2 Dae Hwan Kang2,4 1Medical Convergence Textile Center, Gyeongbuk, Republic of Korea; 2Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea; 3Amogreentech Co. Ltd. Gyeonggi-do, Republic of Korea; 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea *These authors contributed equally to this work Purpose: The aim of this study was to fabricate a vorinostat (Zolinza™-eluting nanofiber membrane-coated gastrointestinal (GI stent and to study its antitumor activity against cholangiocarcinoma (CCA cells in vitro and in vivo. Methods: Vorinostat and poly(DL-lactide-co-glycolide dissolved in an organic solvent was sprayed onto a GI stent to make a nanofiber-coated stent using an electro-spinning machine. Intact vorinostat and vorinostat released from nanofibers was used to assess anticancer activity in vitro against various CCA cells. The antitumor activity of the vorinostat-eluting nanofiber membrane-coated stent was evaluated using HuCC-T1 bearing mice. Results: A vorinostat-incorporated polymer nanofiber membrane was formed on the surface of the GI stent. Vorinostat was continuously released from the nanofiber membrane over 10 days, and its release rate was higher in cell culture media than in phosphate-buffered saline. Released vorinostat showed similar anticancer activity against various CCA cells in vitro compared to that of vorinostat. Like vorinostat, vorinostat released from nanofibers induced acetylation of histone H4 and inhibited histone deacetylases 1·3·4/5/7 expression in vitro and in vivo. Furthermore, vorinostat nanofibers showed a higher tumor growth inhibition rate in HuCC-T1 bearing mice than vorinostat injections. Conclusion: Vorinostat-eluting nanofiber membranes showed significant antitumor

  3. Chronic obstructive pulmonary disease and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Gupta Prem

    2006-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death world-wide and a further increase in the prevalence as well as mortality of the disease is predicted for coming decades. There is now an increased appreciation for the need to build awareness regarding COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its associated complication(s. Peripheral neuropathy in COPD has received scanty attention despite the fact that very often clinicians come across COPD patients having clinical features suggestive of peripheral neuropathy. Electrophysiological tests like nerve conduction studies are required to distinguish between axonal and demyelinating type of disorder that cannot be analyzed by clinical examination alone. However, various studies addressing peripheral neuropathy in COPD carried out so far have included patients with COPD having markedly varying baseline characteristics like severe hypoxemia, elderly patients, those with long duration of illness, etc. that are not uniform across the studies and make it difficult to interpret the results to a consistent conclusion. Almost one-third of COPD patients have clinical evidence of peripheral neuropathy and two-thirds have electrophysiological abnormalities. Some patients with no clinical indication of peripheral neuropathy do have electrophysiological deficit suggestive of peripheral neuropathy. The more frequent presentation consists of a polyneuropathy that is subclinical or with predominantly sensory signs, and the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke, alcoholism, malnutrition and adverse effects of certain drugs.

  4. Determination of malignancy and characterization of hepatic tumor type with diffusion-weighted magnetic resonance imaging: comparison of apparent diffusion coefficient and intravoxel incoherent motion-derived measurements.

    Science.gov (United States)

    Doblas, Sabrina; Wagner, Mathilde; Leitao, Helena S; Daire, Jean-Luc; Sinkus, Ralph; Vilgrain, Valérie; Van Beers, Bernard E

    2013-10-01

    The objective of this study was to compare the value of the apparent diffusion coefficient (ADC) determined with 3 b values and the intravoxel incoherent motion (IVIM)-derived parameters in the determination of malignancy and characterization of hepatic tumor type. Seventy-six patients with 86 solid hepatic lesions, including 8 hemangiomas, 20 lesions of focal nodular hyperplasia, 9 adenomas, 30 hepatocellular carcinomas, 13 metastases, and 6 cholangiocarcinomas, were assessed in this prospective study. Diffusion-weighted images were acquired with 11 b values to measure the ADCs (with b = 0, 150, and 500 s/mm) and the IVIM-derived parameters, namely, the pure diffusion coefficient and the perfusion-related diffusion fraction and coefficient. The diffusion parameters were compared between benign and malignant tumors and between tumor types, and their diagnostic value in identifying tumor malignancy was assessed. The apparent and pure diffusion coefficients were significantly higher in benign than in malignant tumors (benign: 2.32 [0.87] × 10 mm/s and 1.42 [0.37] × 10 mm/s vs malignant: 1.64 [0.51] × 10 mm/s and 1.14 [0.28] × 10 mm/s, respectively; P coefficients provided similar accuracy in assessing tumor malignancy (areas under the receiver operating characteristic curve of 0.770 and 0.723, respectively). In the multigroup analysis, the ADC was found to be significantly higher in hemangiomas than in hepatocellular carcinomas, metastases, and cholangiocarcinomas. In the same manner, it was higher in lesions of focal nodular hyperplasia than in metastases and cholangiocarcinomas. However, the pure diffusion coefficient was significantly higher only in hemangiomas versus hepatocellular and cholangiocellular carcinomas. Compared with the ADC, the diffusion parameters derived from the IVIM model did not improve the determination of malignancy and characterization of hepatic tumor type.

  5. ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

    Science.gov (United States)

    Jiao, Xiaodong; Yu, Wenlong; Qian, Jianxin; Chen, Ying; Wei, Peilian; Fang, Wenzheng; Yu, Guanzhen

    2018-05-18

    A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

  6. Newly diagnosed type 1 diabetes complicated by ketoacidosis and peripheral thrombosis leading to transfemoral amputation

    DEFF Research Database (Denmark)

    Bisgaard Jørgensen, Line; Skov, Ole; Yderstræde, Knud Bonnet

    2014-01-01

    Peripheral vascular thromboembolism is a rarely described complication of diabetic ketoacidosis. We report a 41-year-old otherwise healthy man admitted with ketoacidosis and ischaemia of the left foot. The patient was unsuccessfully treated with thromboendarterectomy, and the extremity was ultima...... was ultimately amputated. The patient had no family history of cardiovascular disease, and all blood sample analyses for hypercoagulability were negative. We recommend an increased focus on peripheral thromboembolism, when treating patients with severe ketoacidosis....

  7. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function

    DEFF Research Database (Denmark)

    Kallestrup, M; Møller, Holger Jon; Tankisi, H

    2015-01-01

    and serum in participants with neuropathy than in those without neuropathy [cerebrospinal fluid: median (range) 131 (86-173) vs 101 (70-190) μg/l, P = 0.08 and serum: 3725 (920-7060) vs 2220 (1130-4780), P = 0.06). CONCLUSIONS: Cerebrospinal fluid soluble CD163 level is associated with impaired peripheral......AIMS: To measure soluble CD163 levels in the cerebrospinal fluid and serum of people with Type 2 diabetes, with and without polyneuropathy, and to relate the findings to peripheral nerve function. METHODS: A total of 22 people with Type 2 diabetes and 12 control subjects without diabetes were...... included in this case-control study. Participants with diabetes were divided into those with neuropathy (n = 8) and those without neuropathy (n = 14) based on clinical examination, vibratory perception thresholds and nerve conduction studies. Serum and cerebrospinal fluid soluble CD163 levels were analysed...

  8. Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis

    International Nuclear Information System (INIS)

    Vern-Gross, Tamara Z.; Shivnani, Anand T.; Chen, Ke; Lee, Christopher M.; Tward, Jonathan D.; MacDonald, O. Kenneth; Crane, Christopher H.; Talamonti, Mark S.; Munoz, Louis L.; Small, William

    2011-01-01

    Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p < .001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

  9. A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Mengmeng; Gao, Yuzhen; Feng, Huijuan; Warner, Elisa; An, Mingrui; Jia, Jian'an; Chen, Shipeng; Fang, Meng; Ji, Jun; Gu, Xing; Gao, Chunfang

    2018-03-01

    Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer (PLC). Although ICC and HCC share similar risk factors and clinical manifestations, ICC usually bears poorer prognosis than HCC. Confidently discriminating ICC and HCC before surgery is beneficial to both treatment and prognosis. Given the lack of effective differential diagnosis biomarkers and methods, construction of models based on available clinicopathological characteristics is in need. Nomograms present a simple and efficient way to make a discrimination. A total of 2894 patients who underwent surgery for PLC were collected. Of these, 1614 patients formed the training cohort for nomogram construction, and thereafter, 1280 patients formed the validation cohort to confirm the model's performance. Histopathologically confirmed ICC was diagnosed in 401 (24.8%) and 296 (23.1%) patients in these two cohorts, respectively. A nomogram integrating six easily obtained variables (Gender, Hepatitis B surface antigen, Aspartate aminotransferase, Alpha-fetoprotein, Carcinoembryonic antigen, Carbohydrate antigen 19-9) is proposed in accordance with Akaike's Information Criterion (AIC). A score of 15 was determined as the cut-off value, and the corresponding discrimination efficacy was sufficient. Additionally, patients who scored higher than 15 suffered poorer prognosis than those with lower scores, regardless of the subtype of PLC. A nomogram for clinical discrimination of ICC and HCC has been established, where a higher score indicates ICC and poor prognosis. Further application of this nomogram in multicenter investigations may confirm the practicality of this tool for future clinical use. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. Serum levels of TGF-β1 in patients of diabetic peripheral neuropathy and its correlation with nerve conduction velocity in type 2 diabetes mellitus.

    Science.gov (United States)

    Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal

    2016-01-01

    To correlate serum levels of TGF-β1 with motor and sensory nerve conduction velocities in patients of type 2 diabetes mellitus The study was conducted in diagnosed type 2 diabetes mellitus patients which were divided in patients with clinically detectable peripheral neuropathy of shorter duration (n=37) and longer duration (n=27). They were compared with patients without clinical neuropathy (n=22). Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TGF-β1. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study In patients of type 2 diabetes mellitus with clinically detectable and serum TGF-β1 showed positive correlation with nerve conduction velocities High level of TGF-β1 in serum of T2DM patients with neuropathy show possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  11. Deep convolutional neural network for the classification of hepatocellular carcinoma and intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Midya, Abhishek; Chakraborty, Jayasree; Pak, Linda M.; Zheng, Jian; Jarnagin, William R.; Do, Richard K. G.; Simpson, Amber L.

    2018-02-01

    Liver cancer is the second leading cause of cancer-related death worldwide.1 Hepatocellular carcinoma (HCC) is the most common primary liver cancer accounting for approximately 80% of cases. Intrahepatic cholangiocarcinoma (ICC) is a rare liver cancer, arising in patients with the same risk factors as HCC, but treatment options and prognosis differ. The diagnosis of HCC is based primarily on imaging but distinguishing between HCC and ICC is challenging due to common radiographic features.2-4 The aim of the present study is to classify HCC and ICC in portal venous phase CT. 107 patients with resected ICC and 116 patients with resected HCC were included in our analysis. We developed a deep neural network by modifying a pre-trained Inception network by retraining the final layers. The proposed method achieved the best accuracy and area under the receiver operating characteristics curve of 69.70% and 0.72, respectively on the test data.

  12. Peripheral endocannabinoids regulate skeletal muscle development and maintenance

    Directory of Open Access Journals (Sweden)

    Dongjiao Zhao

    2010-12-01

    Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

  13. [Peripheral intravenous catheter-related phlebitis].

    Science.gov (United States)

    van der Sar-van der Brugge, Simone; Posthuma, E F M Ward

    2011-01-01

    Phlebitis is a very common complication of the use of intravenous catheters. Two patients with an i.v. catheter complicated by thrombophlebitis are described. Patient A was immunocompromised due to chronic lymphatic leukaemia and developed septic thrombophlebitis with positive blood cultures for S. Aureus. Patient B was being treated with flucloxacillin because of an S. Aureus infection and developed chemical phlebitis. Septic phlebitis is rare, but potentially serious. Chemical or mechanical types of thrombophlebitis are usually less severe, but happen very frequently. Risk factors include: female sex, previous episode of phlebitis, insertion at (ventral) forearm, emergency placement and administration of antibiotics. Until recently, routine replacement of peripheral intravenous catheters after 72-96 h was recommended, but randomised controlled trials have not shown any benefit of this routine. A recent Cochrane Review recommends replacement of peripheral intravenous catheters when clinically indicated only.

  14. Advances in endoscopic retrograde cholangiopancreatography for the treatment of cholangiocarcinoma.

    Science.gov (United States)

    Uppal, Dushant S; Wang, Andrew Y

    2015-06-25

    Cholangiocarcinoma (CCA) is a malignancy of the bile ducts that carries high morbidity and mortality. Patients with CCA typically present with obstructive jaundice, and associated complications of CCA include cholangitis and biliary sepsis. Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable treatment modality for patients with CCA, as it enables internal drainage of blocked bile ducts and hepatic segments by using plastic or metal stents. While there remains debate as to if bilateral (or multi-segmental) hepatic drainage is required and/or superior to unilateral drainage, the underlying tenant of draining any persistently opacified bile ducts is paramount to good ERCP practice and good clinical outcomes. Endoscopic therapy for malignant biliary strictures from CCA has advanced to include ablative therapies via ERCP-directed photodynamic therapy (PDT) or radiofrequency ablation (RFA). While ERCP techniques cannot cure CCA, advancements in the field of ERCP have enabled us to improve upon the quality of life of patients with inoperable and incurable disease. ERCP-directed PDT has been used in lieu of brachytherapy to provide neoadjuvant local tumor control in patients with CCA who are awaiting liver transplantation. Lastly, mounting evidence suggests that palliative ERCP-directed PDT, and probably ERCP-directed RFA as well, offer a survival advantage to patients with this difficult-to-treat malignancy.

  15. Hedgehog pathway as a potential treatment target in human cholangiocarcinoma.

    Science.gov (United States)

    Riedlinger, Dorothee; Bahra, Marcus; Boas-Knoop, Sabine; Lippert, Steffen; Bradtmöller, Maren; Guse, Katrin; Seehofer, Daniel; Bova, Roberta; Sauer, Igor M; Neuhaus, Peter; Koch, Arend; Kamphues, Carsten

    2014-08-01

    Innovative treatment concepts targeting essential signaling pathways may offer new chances for patients suffering from cholangiocarcinoma (CCC). For that, we performed a systematic molecular genetic analysis concerning the Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition on CCC cells in vitro and in vivo. Activation of the Hh pathway was analyzed in 50 human CCC samples using quantitative polymerase chain reaction (qPCR). The efficacy of Hh inhibition using cyclopamine and BMS-833923 was evaluated in vitro. In addition, the effect of BMS-833923, alone or in combination with gemcitabine, was analyzed in vivo in a murine subcutaneous xenograft model. Expression analysis revealed a significant activation of the Hh-signaling pathway in nearly 50% of CCCs. Hh inhibition resulted in a significant decrease in cell proliferation of CCC cells. Moreover, a distinct inhibition of tumor growth could be seen as a result of a combined therapy with BMS-833923 and gemcitabine in CCC xenografts. The results of our study suggest that the Hh pathway plays a relevant role at least in a subset of human CCC. Inhibition of this pathway may represent a possible treatment option for CCC patients in which the Hh pathway is activated. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  16. Multifragmentation in peripheral nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Trautmann, W.; Adloff, J.C.; Bouissou, P.; Hubele, J.; Imme, G.; Iori, I.; Kreutz, P.; Leray, S.; Lindenstruth, V.; Liu, Z.; Lynen, U.; Meijer, R.J.; Milkau, U.; Moroni, A.; Mueller, W.F.J.; Ngo, C.; Ogilvie, C.A.; Pochodzalla, J.; Raciti, G.; Rudolf, G.; Schuettauf, A.; Stuttge, L.

    1993-10-01

    The complete fragmentation of highly excited nuclear systems into fragments of intermediate mass is observed in heavy-ion reactions at relativistic bombarding energies in the range of several hundreds of MeV per nucleon. Similar features are found for peripheral collisions between heavy nuclei and for more central collisions between a heavy and a light nucleus. The partition space explored in multifragment decays is well described by the statistical multifragmentation models. The expansion before breakup is confirmed by the analysis of the measured fragment energies of ternary events in their own rest frame. Collective radial flow is confined to rather small values in these peripheral-type reactions. Many conceptually different models seem to be capable of reproducing the charge correlations measured for the multifragment decays. (orig.)

  17. Vitamin B supplementation for diabetic peripheral neuropathy.

    Science.gov (United States)

    Jayabalan, Bhavani; Low, Lian Leng

    2016-02-01

    Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association.

  18. Peripheral vascular disease is associated with reduced glycosuria in newly diagnosed type 2 diabetic patients

    DEFF Research Database (Denmark)

    Olivarius, Niels de Fine; Holstein-Rathlou, N H; Siersma, V

    2004-01-01

    was 65.2 years. Urinary glucose concentration (UGC) was determined quantitatively in a freshly voided morning urine specimen. RESULTS: The over-all prevalence of peripheral vascular disease (PVD) was 16.5%. Bivariately, high values of UGC were associated with low prevalence of PVD (p...). The predictive value of PVD--together with HbA1c, glomerular filtration rate (GFR) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (Y/N) as outcome variable (p=0.0004). CONCLUSION: Surprisingly, type 2 diabetic patients with PVD tend not to have glycosuria...... as compared to patients without PVD. PVD may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. This could lead to a lowering of GFR and thereby of the amount of glucose filtered. Assuming no, or only a minor direct effect of PVD on tubular function...

  19. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions.

    Science.gov (United States)

    Bertram, Stefanie; Padden, Juliet; Kälsch, Julia; Ahrens, Maike; Pott, Leona; Canbay, Ali; Weber, Frank; Fingas, Christian; Hoffmann, Andreas C; Vietor, Antonie; Schlaak, Joerg F; Eisenacher, Martin; Reis, Henning; Sitek, Barbara; Baba, Hideo A

    2016-07-01

    The distinction between intrahepatic cholangiocarcinoma (ICC) and benign bile duct lesions can be challenging. Using our previously identified potential biomarkers for ICC, we examined whether these are useful for the differential diagnosis of ICC, bile duct adenoma and reactive bile duct proliferations in an immunohistochemical approach and identified a diagnostic marker panel including known biomarkers. Subjects included samples from 77 patients with ICC, 33 patients with bile duct adenoma and 47 patients with ductular reactions in liver cirrhosis. Our previously identified biomarkers (stress-induced phosphoprotein 1 (STIP1), SerpinH1, 14-3-3Sigma) were tested immunohistochemically following comparison with candidates from the literature (cluster of differentiation 56, heat shock protein (HSP)27, HSP70, B-cell-lymphoma2, p53, ki67). The expression of SerpinH1 and 14-3-3Sigma was significantly higher in ICC than in bile duct adenomas and ductular reactions (p5% might be used for the distinction of malignant and non-malignant lesions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Hilar cholangiocarcinoma: diagnosis, treatment options, and management

    Science.gov (United States)

    Soares, Kevin C.; Kamel, Ihab; Cosgrove, David P.; Herman, Joseph M.

    2014-01-01

    Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6th decade of life. Of the 3,000 cases seen annually in the United States, less than one half of these tumors are resectable. A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. Patients typically present with abdominal pain, pruritis, weight loss, and jaundice. Computed topography (CT), magnetic resonance imaging (MRI), and ultrasound (US) are used to characterize biliary lesions. Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) assess local ductal extent of the tumor while allowing for therapeutic biliary drainage. MRCP has demonstrated similar efficacies to PTC and ERCP in identifying anatomic extension of tumors with less complications. Treatment consists of surgery, radiation, chemotherapy and photodynamic therapy. Biliary drainage of the future liver remnant should be performed to decrease bilirubin levels thereby facilitating future liver hypertrophy. Standard therapy consists of surgical margin-negative (R0) resection with extrahepatic bile duct resection, hepatectomy and en bloc lymphadenectomy. Local resection should not be undertaken. Lymph node invasion, tumor grade and negative margins are important prognostic indicators. In instances where curative resection is not possible, liver transplantation has demonstrated acceptable outcomes in highly selected patients. Despite the limited data, chemotherapy is indicated for patients with unresectable tumors and adequate functional status. Five-year survival after surgical resection of HC ranges from 10% to 40% however, recurrence can be as high as 50-70% even after R0 resection. Due to the complexity of this disease, a multi-disciplinary approach with multimodal treatment is recommended for this complex disease. PMID:24696835

  1. The thin-section CT, pathological and clinical findings of peripheral small squamous cell lung carcinomas

    International Nuclear Information System (INIS)

    Yamamoto, Takahito; Saito, Haruhiro; Kondo, Tetsuro

    2010-01-01

    We analyzed thin-section CT, pathological, and clinical findings of peripheral lung squamous cell carcinomas, with diameters of less than 20 mm and compared these findings with solid type adenocarcinomas. CT findings of polygonal shapes, notches, pleural thickness, and cavities are more frequently found in squamous cell carcinomas than in adenocarcinomas. The pathological types can be classified in two groups: Solid types, Scirrhous types. The 5 year survival rate after resection is 64.5%, which is poorer than survival rate for solid type adenocarcinomas. It is vital to diagnose and treat peripheral squamous cell carcinomas as early as possible. (author)

  2. Repair of the Peripheral Nerve—Remyelination that Works

    DEFF Research Database (Denmark)

    Fex Svenningsen, Åsa; Dahlin, Lars

    2013-01-01

    outcome, is emphasized throughout the review. The review concludes by describing the target re-innervation, which today is one of the most serious problems for nerve regeneration. It is clear, compiling this data, that even though regeneration of the peripheral nervous system is possible, more research......Abstract: In this review we summarize the events known to occur after an injury in the peripheral nervous system. We have focused on the Schwann cells, as they are the most important cells for the repair process and facilitate axonal outgrowth. The environment created by this cell type is essential...

  3. Normal and sonographic anatomy of selected peripheral nerves. Part II: Peripheral nerves of the upper limb

    Directory of Open Access Journals (Sweden)

    Berta Kowalska

    2012-06-01

    Full Text Available The ultrasonographic examination is frequently used for imaging peripheral nerves. It serves to supplement the physical examination, electromyography, and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive, well-tolerated by patients, and relatively inexpensive. Part I of this article series described in detail the characteristic USG picture of peripheral nerves and the proper examination technique, following the example of the median nerve. This nerve is among the most often examined peripheral nerves of the upper limb. This part presents describes the normal anatomy and ultrasound picture of the remaining large nerve branches in the upper extremity and neck – the spinal accessory nerve, the brachial plexus, the suprascapular, axillary, musculocutaneous, radial and ulnar nerves. Their normal anatomy and ultrasonographic appearance have been described, including the division into individual branches. For each of them, specific reference points have been presented, to facilitate the location of the set trunk and its further monitoring. Sites for the application of the ultrasonographic probe at each reference point have been indicated. In the case of the ulnar nerve, the dynamic component of the examination was emphasized. The text is illustrated with images of probe positioning, diagrams of the normal course of the nerves as well as a series of ultrasonographic pictures of normal nerves of the upper limb. This article aims to serve as a guide in the ultrasound examination of the peripheral nerves of the upper extremity. It should be remembered that a thorough knowledge of the area’s topographic anatomy is required for this type of examination.

  4. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  5. Deployment of spatial attention to words in central and peripheral vision.

    Science.gov (United States)

    Ducrot, Stéphanie; Grainger, Jonathan

    2007-05-01

    Four perceptual identification experiments examined the influence of spatial cues on the recognition of words presented in central vision (with fixation on either the first or last letter of the target word) and in peripheral vision (displaced left or right of a central fixation point). Stimulus location had a strong effect on word identification accuracy in both central and peripheral vision, showing a strong right visual field superiority that did not depend on eccentricity. Valid spatial cues improved word identification for peripherally presented targets but were largely ineffective for centrally presented targets. Effects of spatial cuing interacted with visual field effects in Experiment 1, with valid cues reducing the right visual field superiority for peripherally located targets, but this interaction was shown to depend on the type of neutral cue. These results provide further support for the role of attentional factors in visual field asymmetries obtained with targets in peripheral vision but not with centrally presented targets.

  6. Right trisectionectomy with principle en bloc portal vein resection for right-sided hilar cholangiocarcinoma: no-touch technique.

    Science.gov (United States)

    Machado, Marcel Autran; Makdissi, Fabio F; Surjan, Rodrigo C

    2012-04-01

    The most favorable long-term survival rate for hilar cholangiocarcinoma is achieved by a R0 resection. A surgical concept involving a no-touch technique, with extended right hepatic resections and principle en bloc portal vein resection was described by Neuhaus et al. According to Neuhaus et al., their technique may increase the chance of R0, because the right branch of the portal vein and hepatic artery is in close contact with the tumor and is frequently infiltrated. The left artery runs on the left margin of the hilum and often is free. The 5-year survival rate for their patients is 61% but 60-day mortality rate is 8%. Given the increased morbidity, some authors do not agree with routine resection of portal vein and may perform the resection of portal vein only on demand, after intraoperative assessment and confirmation of portal vein invasion. This video shows en bloc resection of extrahepatic bile ducts, portal vein bifurcation, and right hepatic artery, together with extended right trisectionectomy (removal of segments 1, 4, 5, 6, 7, and 8). A 75-year-old man with progressive jaundice due to right-sided hilar cholangiocarcinoma underwent percutaneous biliary drainage with metallic stents for palliation. The patient was referred for a second opinion. Serum bilirubin levels were normal, and CT scan showed a resectable tumor, but volumetry showed a small left liver remnant. Right portal vein embolization was then performed, and CT scan performed after 4 weeks showed adequate compensatory hypertrophy of the future liver remnant (segments 2 and 3). Surgical decision was to perform a right trisectionectomy with en bloc portal vein and bile duct resection using the no-touch technique. The operation began with hilar lymphadenectomy. The common bile duct is sectioned. Right hepatic artery is ligated. Left hepatic artery is encircled. Portal vein is dissected and encircled. Right liver is mobilized and detached from retrohepatic vena cava. Right and middle hepatic

  7. Peripheral reactions

    International Nuclear Information System (INIS)

    Greiner, D.

    1978-01-01

    Peripheral collisions, that is, collisions involving a small amount of overlap of nuclear matter, are discussed including inclusive interactions, the magnitude of the peripheral cross section, fragmentation, a compilation of experiments and available data, limiting fragmentation, factorization, some models, fragment momentum distributions, and future research directions

  8. Development and characterization of a hydrogen peroxide-resistant cholangiocyte cell line: A novel model of oxidative stress-related cholangiocarcinoma genesis

    Energy Technology Data Exchange (ETDEWEB)

    Thanan, Raynoo [Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Techasen, Anchalee [Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Hou, Bo [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan); Jamnongkan, Wassana; Armartmuntree, Napat [Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Yongvanit, Puangrat, E-mail: puangrat@kku.ac.th [Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Murata, Mariko, E-mail: mmurata@doc.medic.mie-u.ac.jp [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan)

    2015-08-14

    Oxidative stress is a cause of inflammation–related diseases, including cancers. Cholangiocarcinoma is a liver cancer with bile duct epithelial cell phenotypes. Our previous studies in animal and human models indicated that oxidative stress is a major cause of cholangiocarcinoma development. Hydrogen peroxide (H{sub 2}O{sub 2}) can generate hydroxyl radicals, which damage lipids, proteins, and nucleic acids, leading to cell death. However, some cells can survive by adapting to oxidative stress conditions, and selective clonal expansion of these resistant cells would be involved in oxidative stress-related carcinogenesis. The present study aimed to establish H{sub 2}O{sub 2}-resistant cell line from an immortal cholangiocyte cell line (MMNK1) by chronic treatment with low-concentration H{sub 2}O{sub 2} (25 μM). After 72 days of induction, H{sub 2}O{sub 2}-resistant cell lines (ox-MMNK1-L) were obtained. The ox-MMNK1-L cell line showed H{sub 2}O{sub 2}-resistant properties, increasing the expression of the anti-oxidant genes catalase (CAT), superoxide dismutase-1 (SOD1), superoxide dismutase-2 (SOD2), and superoxide dismutase-3 (SOD3) and the enzyme activities of CAT and intracellular SODs. Furthermore, the resistant cells showed increased expression levels of an epigenetics-related gene, DNA methyltransferase-1 (DNMT1), when compared to the parental cells. Interestingly, the ox-MMNK1-L cell line had a significantly higher cell proliferation rate than the MMNK1 normal cell line. Moreover, ox-MMNK1-L cells showed pseudopodia formation and the loss of cell-to-cell adhesion (multi-layers) under additional oxidative stress (100 μM H{sub 2}O{sub 2}). These findings suggest that H{sub 2}O{sub 2}-resistant cells can be used as a model of oxidative stress-related cholangiocarcinoma genesis through molecular changes such as alteration of gene expression and epigenetic changes. - Highlights: • An H{sub 2}O{sub 2}-resistant ox-MMNK1-L cells was established from

  9. Hilar cholangiocarcinoma: MR correlation with surgical and histological findings

    Energy Technology Data Exchange (ETDEWEB)

    Chryssou, E. [MRI Department, Clinical Radiology, St James' s University Hospital, Beckett Street, Leeds LS9 7TF (United Kingdom); Guthrie, J.A., E-mail: ashguthrie@hotmail.co [MRI Department, Clinical Radiology, St James' s University Hospital, Beckett Street, Leeds LS9 7TF (United Kingdom); Ward, J.; Robinson, P.J. [MRI Department, Clinical Radiology, St James' s University Hospital, Beckett Street, Leeds LS9 7TF (United Kingdom)

    2010-10-15

    Aim: To evaluate magnetic resonance cholangiography (MRC) with high-resolution dynamic gadolinium-enhanced magnetic resonance imaging (MRI) in determining the imaging features of hilar cholangiocarcinoma that relate to tumour extent and influence resectability. Materials and methods: Twenty-six patients that underwent resection were reviewed. Tumour location and extent, lobar atrophy, the degree of portal vein and hepatic artery involvement were recorded. The findings were correlated with surgical and histopathological findings. Results: Biliary assessment was concordant in 14 and discordant in eight of 14 stented and four of 12 non-stented patients. In 63/82 veins and 43/74 arteries results were fully concordant. The mean sensitivity, specificity, positive and negative predictive values (PPV, NPV) in predicting involvement of the main portal vein (MPV) at surgery were 83.3, 100, 100, and 92.5%; of the left main branch of the portal vein (LPV) were 100, 91.6, 93.3, and 100%; and of the right branch of the portal vein (RPV) were 87.5, 100, 100, and 87.5%. The sensitivity, specificity, PPV and NPV of MRI in determining histological involvement of the MPV was 75, 90.9, 60, and 92.5%; 100, 73.3, 73, and 100% for the LPV, and 100, 66.6, 42.8, and 100% for the RPV, respectively. Conclusion: MRC with high-resolution dynamic gadolinium-enhanced MRI is effective in determining tumour extent and vascular involvement, but prior stenting may lead to overestimation.

  10. Hilar cholangiocarcinoma: MR correlation with surgical and histological findings

    International Nuclear Information System (INIS)

    Chryssou, E.; Guthrie, J.A.; Ward, J.; Robinson, P.J.

    2010-01-01

    Aim: To evaluate magnetic resonance cholangiography (MRC) with high-resolution dynamic gadolinium-enhanced magnetic resonance imaging (MRI) in determining the imaging features of hilar cholangiocarcinoma that relate to tumour extent and influence resectability. Materials and methods: Twenty-six patients that underwent resection were reviewed. Tumour location and extent, lobar atrophy, the degree of portal vein and hepatic artery involvement were recorded. The findings were correlated with surgical and histopathological findings. Results: Biliary assessment was concordant in 14 and discordant in eight of 14 stented and four of 12 non-stented patients. In 63/82 veins and 43/74 arteries results were fully concordant. The mean sensitivity, specificity, positive and negative predictive values (PPV, NPV) in predicting involvement of the main portal vein (MPV) at surgery were 83.3, 100, 100, and 92.5%; of the left main branch of the portal vein (LPV) were 100, 91.6, 93.3, and 100%; and of the right branch of the portal vein (RPV) were 87.5, 100, 100, and 87.5%. The sensitivity, specificity, PPV and NPV of MRI in determining histological involvement of the MPV was 75, 90.9, 60, and 92.5%; 100, 73.3, 73, and 100% for the LPV, and 100, 66.6, 42.8, and 100% for the RPV, respectively. Conclusion: MRC with high-resolution dynamic gadolinium-enhanced MRI is effective in determining tumour extent and vascular involvement, but prior stenting may lead to overestimation.

  11. UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes.

    Science.gov (United States)

    Adler, Amanda I; Stevens, Richard J; Neil, Andrew; Stratton, Irene M; Boulton, Andrew J M; Holman, Rury R

    2002-05-01

    To determine the role of hyperglycemia in prospective analyses of peripheral vascular disease (PVD) in type 2 diabetes, taking into account other potential risk factors. Potential risk factors for the development of PVD were examined in 3,834 of 5,102 individuals enrolled in the U.K. Prospective Diabetes Study (UKPDS) without PVD at diagnosis of diabetes, followed for 6 years, and for whom relevant data were available. PVD was defined as two of the following: ankle-arm blood pressure index < 0.8, absence of both dorsalis pedis and posterior tibial pulses to palpation in one or both legs, and intermittent claudication. Logistic regression was used to estimate the association between potential risk factors measured 3-4 months after diagnosis of diabetes and incident PVD. The prevalence of PVD at 3-year intervals to 18 years was determined. Hyperglycemia, assessed as HbA(1c), was associated with an increased risk for incident PVD, independent of other risk factors including age, increased systolic blood pressure, reduced HDL cholesterol, smoking, prior cardiovascular disease, peripheral sensory neuropathy, and retinopathy. Each 1% increase in HbA(1c) was associated with a 28% increased risk of PVD (95% CI 12-46), and each 10-mmHg increase in systolic blood pressure with a 25% increase in risk (95% CI 10-43). Hyperglycemia, as well as smoking, dyslipidemia, and blood pressure are potentially modifiable risk factors for the development of PVD.

  12. A New Surgical Procedure "Dumbbell-Form Resection" for Selected Hilar Cholangiocarcinomas With Severe Jaundice: Comparison With Hemihepatectomy.

    Science.gov (United States)

    Wang, Shuguang; Tian, Feng; Zhao, Xin; Li, Dajiang; He, Yu; Li, Zhihua; Chen, Jian

    2016-01-01

    The aim of the study is to evaluate the therapeutic effect of a new surgical procedure, dumbbell-form resection (DFR), for hilar cholangiocarcinoma (HCCA) with severe jaundice. In DFR, liver segments I, IVb, and partial V above the right hepatic pedicle are resected.Hemihepatectomy is recognized as the preferred procedure; however, its application is limited in HCCAs with severe jaundice.Thirty-eight HCCA patients with severe jaundice receiving DFR and 70 receiving hemihepatectomy from January 2008 to January 2013 were included. Perioperative parameters, operation-related morbidity and mortality, and post-operative survival were analyzed.A total of 21.1% patients (8/38) in the DFR group received percutaneous transhepatic biliary drainage (PTBD), which was significantly jaundice. However, its indications should be restricted.

  13. Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1.

    Science.gov (United States)

    Sarmento, Dmitry José de Santana; Carvalho, Sérgio Henrique Gonçalves de; Araújo, José Cadmo Wanderley Peregrino de; Carvalho, Marianne de Vasconcelos; Silveira, Éricka Janine Dantas da

    2017-01-01

    We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia.

  14. Phytohemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell take

    Energy Technology Data Exchange (ETDEWEB)

    Astaldi, G [Blood Research Foundation Center, Tortona, Italy; Karanovic, D; Vettori, P P; Karanovic, J; Piletic, O

    1974-01-01

    The effect of PHA-stimulation of peripheral-blood lymphocytes on the spleen-colony formation in irradiated rats was examined. 25-day old Wistar rats underwent total-body irradiation (600 R), and they were used as recipients. On the other hand, 2 and /sup 1///sub 2/ month old untreated Wistar rats were used as donors of peripheral-blood lymphocytes, which were obtained by sedimentation with Dextraven from defibrinated blood. Four rat lots were used. The 1st one did not receive irradiation, and was kept as ''blank control.'' The 2nd one was just irradiated and kept as ''radiated control.'' The 3rd and the 4th rat lots of the series were irradiated, but the former lot was injected i.v. with 5 x 10/sup 7/ peripheral-blood untreated lymphocytes, whereas the fourth lot was injected i.v. with the same amount of lymphocytes, which were previously incubated in vitro for 24 hrs with PHA-M (Difco). The results showed that the PHA-incubation of transplanted peripheral-blood lymphocytes significantly increases the number and size of the macroscopic spleen colonies, in relationship to the colonies which occurs after transplantation of untreated lymphocytes. Histo-cytological observation clearly showed that the colonies formed after injection of mitogen-pretreated peripheral-blood lymphocytes were predominantly of erythroid type and, then, of non-differentiated cells. Only a few of them were of a mixed type, consisting of both undifferentiated cells and erythroid cells.

  15. Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

    Directory of Open Access Journals (Sweden)

    Steven M. Horton

    2017-11-01

    Full Text Available The pannexin family of channels consists of three members—pannexin-1 (Panx1, pannexin-2 (Panx2, and pannexin-3 (Panx3 that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system and PNS (peripheral nervous system, coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

  16. Peripheral Developing Odontoma or Peripheral Ameloblastic Fibroodontoma: A Rare Challenging Case

    Directory of Open Access Journals (Sweden)

    Saede Atarbashi Moghadam

    2016-01-01

    Full Text Available Peripheral odontogenic lesions are considered to be rare within the classification of odontogenic tumors. They share the same microscopic characteristics of their central counterparts. Here, we report an ulcerated mass of the maxillary gingiva that on histopathological examination was diagnosed as peripheral developing odontoma or peripheral ameloblastic fibroodontoma. The diagnosis of this tumor is challenging and may lead to unnecessary treatment.

  17. The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy

    DEFF Research Database (Denmark)

    Hansen, C.S.; Jensen, T.M.; Jensen, J.S.

    2015-01-01

    AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...

  18. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  19. Peripheral neuropathy as a complication of diabetic ketoacidosis in a child with newly diagnosed diabetes type 1 - case report.

    Science.gov (United States)

    Baszyńska-Wilk, Marta; Wysocka-Mincewicz, Marta; Świercz, Anna; Świderska, Jolanta; Marszał, Magdalena; Szalecki, Mieczysław

    2017-12-08

    Neurological complications of diabetic ketoacidosis are considered to be very serious clinical problem. The most common complication is cerebral edema. However this group includes also less common syndromes such as ischemic or hemorrhagic stroke, cerebral venous and sinus thrombosis or very rare peripheral neuropathy. We present a case of 9-year old girl with new onset type 1 diabetes, diabetic ketoacidosis, cerebral edema, multifocal vasogenic brain lesions and lower limbs peripheral paresis. The patient developed polydipsia and polyuria one week before admission to the hospital. In laboratory tests initial blood glucose level 1136 mg/dl and acidosis (pH 7.1; BE-25.9) were noted. She was admitted to the hospital in a critical condition and required treatment in intensive care unit. Computed tomography scan showed brain edema and hipodense lesion in the left temporal region. Brain MRI revealed more advanced multifocal brain lesions Nerve conduction studies demonstrated damage of the motor neuron in both lower extremities with dysfunction in both peroneal nerves and the right tibial nerve. As a result of diabetological, neurological treatment and physiotherapy patient's health state gradually improved. Acute neuropathy after ketoacidosis is rare complication and its pathomechanism is not clear. Patients with DKA require careful monitoring of neurological functions even after normalization of glycemic parameters.

  20. Effects of the L/N-type calcium channel antagonist cilnidipine on morning blood pressure control and peripheral edema formation.

    Science.gov (United States)

    Narita, Sumito; Yoshioka, Yasuko; Ide, Atsumi; Kadokami, Toshiaki; Momii, Hidetoshi; Yoshida, Masayoshi; Ando, Shin-ichi

    2011-01-01

    The L/N-type calcium channel blocker cilnidipine has unique effects including sympathetic nerve suppression and the balanced vasodilatation of arteries and veins that may alleviate morning hypertension (MHT) or peripheral edema caused by calcium channel antagonists. We used ambulatory blood pressure monitoring (ABPM) and a unique peripheral edema measurement to evaluate the effect of morning and bedtime cilnidipine in patients with MHT. Forty-three patients with MHT (60 ± 12 years) were randomly assigned to a morning or bedtime cilnidipine (10-20 mg/day). MHT was defined as a mean systolic blood pressure (SBP) ≥ 135 mm Hg by ABPM within 2 hours after awaking. After 3 months, greater SBP reductions were observed in the bedtime administration group (versus the morning administration group) at 3:30-6:00 AM (-24 ± 20 mm Hg vs. -10 ± 4 mm Hg; P < .05) and at 6:30-9:00 AM (-26 ± 15 mm Hg vs. -14 ± 17 mm Hg; P < .05). Although physical examinations showed leg edema in 16% of the patients, quantitative evaluations did not reveal significant volume gains. Cilnidipine had a greater effect on MHT, without causing significant leg edema, when administered at bedtime. Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  1. Cholangiocarcinoma

    Science.gov (United States)

    ... of the ducts that carries bile from the liver to the small intestine. ... Updated December 9, 2015. www.cancer.gov/types/liver/hp/bile-duct-treatment-pdq . Accessed July 8, 2016. Zani S, Pappas ...

  2. Prognostic significance of snail expression in hilar cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Dalu [Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Hexi District, Tianjin (China); Liang, Jun [Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China); Li, Rong [Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Hexi District, Tianjin (China); Liu, Shihai [Department of Laboratory Center, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China); Wang, Jigang [Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China); Zhang, Kejun; Chen, Dong [Department of General Surgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China)

    2012-05-11

    Many patients with hilar cholangiocarcinoma (HC) have a poor prognosis. Snail, a transcription factor and E-cadherin repressor, is a novel prognostic factor in many cancers. The aim of this study was to evaluate the relationship between snail and E-cadherin protein expression and the prognostic significance of snail expression in HC. We examined the protein expression of snail and E-cadherin in HC tissues from 47 patients (22 males and 25 females, mean age 61.2 years) using immunohistochemistry and RT-PCR. Proliferation rate was also evaluated in the same cases by the MIB1 index. High, low and negative snail protein expression was recorded in 18 (38%), 17 (36%), and 12 (26%) cases, respectively, and 40.4% (19/47) cases showed reduced E-cadherin protein expression in HC samples. No significant correlation was found between snail and E-cadherin protein expression levels (P = 0.056). No significant correlation was found between snail protein expression levels and gender, age, tumor grade, vascular or perineural invasion, nodal metastasis and invasion, or proliferative index. Cancer samples with positive snail protein expression were associated with poor survival compared with the negative expresser groups. Kaplan-Meier curves comparing different snail protein expression levels to survival showed highly significant separation (P < 0.0001, log-rank test). With multivariate analysis, only snail protein expression among all parameters was found to influence survival (P = 0.0003). We suggest that snail expression levels can predict poor survival regardless of pathological features and tumor proliferation. Immunohistochemical detection of snail protein expression levels in routine sections may provide the first biological prognostic marker.

  3. The relationship between the peripheral lung cancer and the bronchi, pulmonary artery and vein: a multislice helical CT observation

    International Nuclear Information System (INIS)

    Liu Xueguo; Liang Mingzhu; Chen Cuifen; Qin Peixin; Zhong Guomei; He Yanguo; Liu Xiaobing; Han Mingqun; Yi Xianping; Wang Yong; Zhang Hao

    2008-01-01

    Objective: To investigate the relationships between the peripheral lung cancer and pulmonary vessels or bronchi by 16-row multislice computed tomography (MSCT) and analyze the related factors. Methods: Fifty-four patients with peripheral lung cancer confirmed pathologically underwent contrast-enhanced MSCT. Multiplanar reformation (MPR) and maximum intensity projection (MIP) in all patients were used to demonstrate the relationships between the peripheral lung cancer and pulmonary vessels, bronchi. The relationships were categorized five types: Type 1, erupted at the edge of nodule. Type 2, erupted at the center of nodule. Type 3, penetrated through the nodule. Type 4, contacting the nodule but stretched or encased. Type 5, contacting the nodule but smoothly compressed. The pathology type, stage, size, density and location of the peripheral lung cancer were recorded and the relationships with five types were evaluated by using Chi-square test and correlation analysis. Results: (1) Tumor-bronchi relationship: type 1 (33,61.1%) was more often seen in ≥2.0 cm and solid lesions with stage II-IV, while Type 2(14,25.9%) was often seen in < 2.0 cm and part-solid or non-solid lesions with stage I. (2) Tumor-PA relationship: Type 1 was more often seen in ≥2.0 cm and solid lesions with stage II-IV, while Type 2 was often seen in part-solid or non-solid lesions with stage I. (3) Tumor-PV relationship: type 4 was the most common type (29, 53.7%). Type 2 (13, 24.1%) was more often seen in part-solid or non-solid lesions. (4) Tumor-bronchi relationship and tumor-PA relationship had a positive correlation (r0.5265, P<0.01). Conclusions: MSCT can demonstrate the relations between the peripheral lung cancer and bronchi, PA and PV. It is useful for the differential diagnosis and prognosis evaluation of the lung cancer. (authors)

  4. Management of empyema of gallbladder with percutaneous cholecysto-duodenal stenting in a case of hilar cholangiocarcinoma treated with common bile duct metallic stenting

    Directory of Open Access Journals (Sweden)

    Sheo Kumar

    2011-01-01

    Full Text Available Empyema of the gallbladder develops when the gallbladder neck is obstructed in the presence of infection, preventing pus from draining via the cystic duct. Treatment options include cholecystectomy or, in patients with comorbidities, drainage via percutaneous cholecystostomy, later followed by cholecystectomy. Here, we describe a 59-year-old man who presented with complaints of recurrent hiccups and was found to have cholangiocarcinoma causing obstruction to cystic duct drainage. The patient was managed successfully by percutaneous transhepatic cholecysto-duodenal self-expandable covered metal stent.

  5. Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Asayama, Yoshiki [Kyushu University, Department of Advanced Imaging and Interventional Radiology, Graduate School of Medical Sciences, Fukuoka (Japan); Nishie, Akihiro; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Honda, Hiroshi [Kyushu University, Departments of Clinical Radiology, Fukuoka (Japan); Ohtsuka, Takao [Kyushu University, Departments of Surgery and Oncology, Fukuoka (Japan); Yoshizumi, Tomoharu [Kyushu University, Departments of Surgery and Sciences, Fukuoka (Japan); Aishima, Shinichi [Saga University, Pathology and Microbiology, Faculty of Medicine, Saga (Japan); Kyushu University, Departments of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan); Oda, Yoshinao [Kyushu University, Departments of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan)

    2017-06-15

    To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] x 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. (orig.)

  6. Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders

    International Nuclear Information System (INIS)

    Reddy, E.P.; Mettus, R.V.; DeFreitas, E.; Wroblewska, Z.; Cisco, M.; Koprowski, H.

    1988-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, the authors have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. They have clones the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome

  7. Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1*

    Science.gov (United States)

    Sarmento, Dmitry José de Santana; de Carvalho, Sérgio Henrique Gonçalves; de Araújo Filho, José Cadmo Wanderley Peregrino; Carvalho, Marianne de Vasconcelos; da Silveira, Éricka Janine Dantas

    2017-01-01

    We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia. PMID:28538890

  8. Circulating Plasma Levels of MicroRNA-21 and MicroRNA-221 Are Potential Diagnostic Markers for Primary Intrahepatic Cholangiocarcinoma

    Science.gov (United States)

    Kemeny, Nancy; Kingham, T. Peter; Allen, Peter J.; D’Angelica, Michael I.; DeMatteo, Ronald P.; Betel, Doron; Klimstra, David; Jarnagin, William R.; Ventura, Andrea

    2016-01-01

    Background MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility. Methods Using deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers. The discriminatory ability of the evaluated plasma miRNAs between patients and controls was evaluated with receiving operating characteristic (ROC) curves. Results Small RNAs from 12 ICC and 11 tumor-free liver samples were evaluated. Unsupervised hierarchical clustering using the miRNA expression data showed clear grouping of ICC vs. non-neoplastic liver parenchyma. We identified 134 down-regulated and 128 upregulated miRNAs. Based on overexpression and high fold-change, miR21, miR200b, miR221, and miR34c were measured in plasma from an independent cohort of patients with ICC (n = 25) and healthy controls (n = 7). Significant overexpression of miR-21 and miR-221 was found in plasma from ICC patients. Furthermore, circulating miR-21 demonstrated a high discriminatory ability between patients with ICC and healthy controls (AUC: 0.94). Conclusion Among the differentially expressed miRNAs in ICC, miR-21 and miR-221 are overexpressed and detectable in the circulation. Plasma expression levels of these miRNAs, particularly miR-21, accurately differentiates patients with ICC from healthy controls and could potentially serve as adjuncts in diagnosis. Prospective validation and comparison with other hepatobiliary malignancies is required to establish their potential role as diagnostic and prognostic biomarkers. PMID:27685844

  9. Phytohemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell take

    Energy Technology Data Exchange (ETDEWEB)

    Astaldi, G. (Blood Research Foundation Center, Tortona, Italy); Karanovic, D.; Vettori, P.P.; Karanovic, J.; Piletic, O.

    1974-01-01

    The effect of PHA-stimulation of peripheral-blood lymphocytes on the spleen-colony formation in irradiated rats was examined. 25-day old Wistar rats underwent total-body irradiation (600 R), and they were used as recipients. On the other hand, 2 and /sup 1///sub 2/ month old untreated Wistar rats were used as donors of peripheral-blood lymphocytes, which were obtained by sedimentation with Dextraven from defibrinated blood. Four rat lots were used. The 1st one did not receive irradiation, and was kept as ''blank control.'' The 2nd one was just irradiated and kept as ''radiated control.'' The 3rd and the 4th rat lots of the series were irradiated, but the former lot was injected i.v. with 5 x 10/sup 7/ peripheral-blood untreated lymphocytes, whereas the fourth lot was injected i.v. with the same amount of lymphocytes, which were previously incubated in vitro for 24 hrs with PHA-M (Difco). The results showed that the PHA-incubation of transplanted peripheral-blood lymphocytes significantly increases the number and size of the macroscopic spleen colonies, in relationship to the colonies which occurs after transplantation of untreated lymphocytes. Histo-cytological observation clearly showed that the colonies formed after injection of mitogen-pretreated peripheral-blood lymphocytes were predominantly of erythroid type and, then, of non-differentiated cells. Only a few of them were of a mixed type, consisting of both undifferentiated cells and erythroid cells.

  10. Spatial distribution of cannabinoid receptor type 1 (CB1 in normal canine central and peripheral nervous system.

    Directory of Open Access Journals (Sweden)

    Jessica Freundt-Revilla

    Full Text Available The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2 and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of several regions of the brain, spinal cord and peripheral nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten-year-old dog revealed strong dot-like immunoreactivity in the neuropil of the cerebral cortex, Cornu Ammonis (CA and dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense CB1 expression was found in fibres of the globus pallidus and substantia nigra surrounding immunonegative neurons. Astrocytes were constantly positive in all examined regions. CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These results can be used as a basis for further studies aiming to elucidate the physiological consequences of this particular anatomical and cellular distribution.

  11. Ultra-peripheral collisions of heavy ions at RHIC and the LHC

    CERN Document Server

    Nystrand, J

    2007-01-01

    This paper deals with so-called Ultra-Peripheral Collisions (UPCs) of heavy ions. These can be defined as collisions in which no hadronic interactions occur because of the large spatial separation between the projectile and target. The interactions are instead mediated by the electromagnetic field. Two types of ultra-peripheral collisions can be distinguished: purely electro-magnetic interactions (two-photon interactions) and photonuclear interactions, in which a photon from the projectile interacts with the hadronic component of the target.

  12. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  13. THE INFLUENCE OF PERIPHERAL NEUROPATHY AND PERIPHERAL VASCULAR DISEASE IN THE OUTCOME OF DIABETIC FOOT MANAGEMENT – A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Sundar Prakash S, Krishnakumar, Chandra Prabha

    2015-04-01

    Full Text Available Objective: Peripheral neuropathy and Peripheral Vascular Disease are the risk factors for the development of diabetic foot. The aim of this study was to evaluate differences and predictors of outcome parameters in patients with diabetic foot by stratifying these subjects according to the severity of these risk factors. Materials and methods: This is a prospective study conducted in 70 patients in the age group of 30-90 years diagnosed as Type II Diabetes with foot ulcers. After detailed clinical examination the following tests were conducted in all the patients: Complete blood count (CBC, Haemoglobin (Hb, Random Blood Sugar (RBS, Erythrocyte Sedimentation rate (ESR, Chest X-ray(CXR, Electrocardiography (ECG, foot X-ray, pus culture, Neuropathy testing by Semmes Weinstein Monofilament Test and Vibration Perception Threshold and Peripheral vascularity assessment by Duplex Doppler. Then grading of the ulcers was done using Wagner’s Grade. The outcome of the patients was assessed by recording the healing time, mode of surgery and amputation rates of the patients. Results: A total of 70 patients with diabetic foot were consecutively included into the study (65.7% male, age (31% in 51-60 years, mean diabetes duration (5.2 years, Ulcer Grade (37% in Grade IV, Foot lesions (45.7% in toe, Blood sugar levels (64% in 300-400 mg/dl, Neuropathy (84%, Peripheral vascular disease (67%, major amputation (7% and mortality (1.4%. Conclusion: All diabetic patients should undergo testing for neuropathy and peripheral vascular disease apart from doing other tests.

  14. Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

    Science.gov (United States)

    Tshering, Gyem; Dorji, Palden Wangyel; Chaijaroenkul, Wanna; Na-Bangchang, Kesara

    2018-06-01

    Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

  15. Peripheral mononuclear cell resistin mRNA expression is increased in type 2 diabetic women.

    Science.gov (United States)

    Tsiotra, Panayoula C; Tsigos, Constantine; Anastasiou, Eleni; Yfanti, Eleni; Boutati, Eleni; Souvatzoglou, Emmanouil; Kyrou, Ioannis; Raptis, Sotirios A

    2008-01-01

    Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P = .05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 were all significantly higher in DM2 compared to control women (P DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1beta, TNF-alpha, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

  16. Motor-commands decoding using peripheral nerve signals: a review

    Science.gov (United States)

    Hong, Keum-Shik; Aziz, Nida; Ghafoor, Usman

    2018-06-01

    During the last few decades, substantial scientific and technological efforts have been focused on the development of neuroprostheses. The major emphasis has been on techniques for connecting the human nervous system with a robotic prosthesis via natural-feeling interfaces. The peripheral nerves provide access to highly processed and segregated neural command signals from the brain that can in principle be used to determine user intent and control muscles. If these signals could be used, they might allow near-natural and intuitive control of prosthetic limbs with multiple degrees of freedom. This review summarizes the history of neuroprosthetic interfaces and their ability to record from and stimulate peripheral nerves. We also discuss the types of interfaces available and their applications, the kinds of peripheral nerve signals that are used, and the algorithms used to decode them. Finally, we explore the prospects for future development in this area.

  17. Statin use and peripheral sensory perception: a pilot study.

    Science.gov (United States)

    West, Brenton; Williams, Cylie M; Jilbert, Elise; James, Alicia M; Haines, Terry P

    2014-06-01

    Peripheral sensory neuropathy is a neurological deficit resulting in decreased detection of sensation through the peripheral nervous system. Peripheral sensory neuropathy is commonly diagnosed with the use of a monofilament and either a tuning fork or neurothesiometer. Statins are a widely used medication and there has been some debate of association with their use and peripheral sensory neuropathy. This pilot study aimed to test the sensory perception of participants with long-term statin use and compare these results to their peers who were not taking statins. Thirty participants were recruited and equally divided into a statin and non-statin group. Healthy participants were screened by their medical and medication history, Australian Type 2 Diabetes Risk assessment, and random blood glucose level. An assessor who was blinded to the participant group conducted sensory assessments using a 10 g monofilament and neurothesiometer. There was no difference in monofilament testing results between the groups. The statin group was less sensate at the styloid process (p = 0.031) and medial malleolus (p = 0.003) than the control group. Results at the hallux were not statistically significant (p = 0.183). This result is suggestive of a potential association between long-term statin use and a decrease in peripheral sensory perception. This may be because of peripheral sensory neuropathy. Limitations such as consideration of participant height, participant numbers, and inability to analyze results against statin groups are reported. As statins are a life-saving medication, careful consideration should be applied to these results and further research be conducted to determine if these results are applicable to larger populations.

  18. Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

    Science.gov (United States)

    Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

    2018-03-28

    Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

  19. Ultrasound-guided peripheral nerve blocks: what are the benefits?

    DEFF Research Database (Denmark)

    Nielsen, Zbigniew Jerzy Koscielniak

    2008-01-01

    with the MESH terms 'nerve block' and 'ultrasonography'. The following limits were applied: studies with abstracts, only in humans, published in core clinical journals. Trial type: meta-analysis, randomized-controlled trial and clinical trial. RESULTS: When peripheral nerves are adequately imaged by ultrasound...

  20. Fruit and Vegetables Consumption: A Pointer for Cholangiocarcinoma Prevention in Northeast Thailand, the Highest Incidence Area in the World.

    Science.gov (United States)

    Songserm, Nopparat; Woradet, Somkiattiyos; Charoenbut, Pattaraporn

    2016-01-01

    Cholangiocarcinoma (CCA) caused by opisthorchiasis is a specific public health problem in the Greater Mekong subregional countries. The Northeast Thailand is considered a world's prime area of CCA. Many epidemiological studies found the association between fruit and vegetables consumption and CCA, but their results were inconclusive. Therefore, this meta-analysis aimed to investigate the relationship between fruit and vegetables consumption and CCA prevention in the Northeast Thailand. The authors conducted a comprehensive search of scholarships on MEDLINE, EMBASE, and SCOPUS published during 1990 and 2015. Selected studies about fruit and vegetables consumption and CCA were analyzed. The fixed-effect model was used to estimate pool odds ratios for the consumption vs. nonconsumption. Based on a meta-analysis, consumption of mixed fruit [odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.65-0.96], mixed vegetables (OR = 0.61; 95% CI: 0.50-0.75), and combined fruit and vegetables (OR = 0.68; 95% CI: 0.57-0.80) was associated with the reduction of CCA risk statistically. These findings support that fruit and vegetables consumption is associated with CCA risk reduction. If implemented in a larger geographical area, the study will shed light on possibilities to future reduction of CCA. Educators can replicate the study to solve CCA or other types of cancer and discover the best practice.

  1. Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus.

    Science.gov (United States)

    Khattab, Salma A; Abo-Elmatty, Dina M; Ghattas, Maivel H; Mesbah, Noha M; Mehanna, Eman T

    2017-09-01

    Intestinal fatty acid-binding protein 2 (FABP2) is expressed in enterocytes and binds saturated and unsaturated long-chain fatty acids. The FABP2 Ala54Thr polymorphism has been reported to effect lipid metabolism. The aim of the present study was to assess the relationship between this polymorphism and peripheral atherosclerosis combined with type 2 diabetes mellitus (T2DM) in an Egyptian population. The study was performed on 100 T2DM patients with peripheral atherosclerosis and 100 control subjects. The Ala54Thr polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism, whereas serum FABP2 levels were determined using ELISA. Fasting blood glucose, fasting serum insulin concentrations, HbA1c, lipid profile, body mass index (BMI) and systolic and diastolic blood pressure (SBP and DBP, respectively) were determined. There was a higher frequency of the Thr54 allele among the patient group (P = 0.002). In Ala54/Thr54 heterozygotes and carriers of the rare Thr54/Thr54 genotype, there were significant increases in BMI and FABP2. Those with the Thr54/Thr54 genotype had significantly decreased high-density lipoprotein cholesterol (HDL-C) concentrations; in addition, those with the Thr54/Thr54 genotype had significantly higher SBP and DBP than subjects with the Ala54/Ala54 and Ala54/Thr54 genotypes. There was a positive correlation between FABP2 levels and BMI, SBP and DBP, and a negative correlation with HDL-C. The Thr54 allele of the FABP2 Ala54Thr polymorphism was associated with an increased incidence of peripheral atherosclerosis combined with T2DM in the population studied. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  2. Mutation inactivation of Nijmegen breakage syndrome gene (NBS1 in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Yan Wang

    Full Text Available Nijmegen breakage syndrome (NBS with NBS1 germ-line mutation is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition. The NBS1 gene codes for a protein, Nbs1(p95/Nibrin, involved in the processing/repair of DNA double-strand breaks. Hepatocellular carcinoma (HCC is a complex and heterogeneous tumor with several genomic alterations. Recent studies have shown that heterozygous NBS1 mice exhibited a higher incidence of HCC than did wild-type mice. The objective of the present study is to assess whether NBS1 mutations play a role in the pathogenesis of human primary liver cancer, including HBV-associated HCC and intrahepatic cholangiocarcinoma (ICC. Eight missense NBS1 mutations were identified in six of 64 (9.4% HCCs and two of 18 (11.1% ICCs, whereas only one synonymous mutation was found in 89 control cases of cirrhosis and chronic hepatitis B. Analysis of the functional consequences of the identified NBS1 mutations in Mre11-binding domain showed loss of nuclear localization of Nbs1 partner Mre11, one of the hallmarks for Nbs1 deficiency, in one HCC and two ICCs with NBS1 mutations. Moreover, seven of the eight tumors with NBS1 mutations had at least one genetic alteration in the TP53 pathway, including TP53 mutation, MDM2 amplification, p14ARF homozygous deletion and promoter methylation, implying a synergistic effect of Nbs1 disruption and p53 inactivation. Our findings provide novel insight on the molecular pathogenesis of primary liver cancer characterized by mutation inactivation of NBS1, a DNA repair associated gene.

  3. Diagnostics of peripheric plasma in thermonuclear devices

    International Nuclear Information System (INIS)

    Vojtsenya, V.S.; Tereshin, V.I.

    1986-01-01

    Review of basic methods, applied or developed for peripheral plasma diagnostics is given, including electric probes of various types, collecting probes for studying impurity ion and main plasma component characteristics, spectroscopic and corpuscular-optical methods, laser fluorescence spectroscopy, mass-spectrometry, heavy ion and atom (lithium and hydrogen) beam methods. Ranges of plasma parameters their measurements being provided by the methods indicated are presented

  4. The association between pulse wave velocity and peripheral neuropathy in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Tentolouris, Anastasios; Eleftheriadou, Ioanna; Grigoropoulou, Pinelopi; Kokkinos, Alexander; Siasos, Gerasimos; Ntanasis-Stathopoulos, Ioannis; Tentolouris, Nikolaos

    2017-11-01

    Diabetic peripheral neuropathy (DPN) is the most common diabetic complication, affecting up to half of the patients with type 2 diabetes mellitus (T2DM). Increased aortic stiffness, measured with the carotid-femoral pulse wave velocity (PWV), has been associated with incidence of cardiovascular disease independently of traditional risk factors. Previous data showed associations between risk factors for macroangiopathy and DPN in diabetes. However, the association between PWV and DPN is not well known. In this study we examined the association between PWV and presence as well as severity of DPN in subjects with T2DM. A total of 381 patients with T2DM were recruited. Participants were classified as having DPN and not having DPN. PWV was measured at the carotid-femoral segment with a non-invasive method using applanation tonometry. DPN was assessed by determination of the Neuropathy Symptom Score (NSS) and the Neuropathy Disability Score (NDS). A hundred and seven participants (28.1%) had DPN. Patients with DPN were significantly more often male and older, had longer diabetes duration, higher height, larger waist circumference, higher systolic arterial blood pressure (SBP) and higher PWV (all Pperipheral arterial disease. Multivariate logistic regression analysis, after adjustment for age, gender, waist circumference, SBP, nephropathy and use of b-blockers, demonstrated that the odds [OR (95% confidence intervals)] of peripheral neuropathy were associated significantly and independently only with diabetes duration [1.044 (1.009-1.081), P=0.013], height [1.075 (1.041-1.110), Pperipheral arterial disease [4.658 (2.264-9.584), Pperipheral arterial disease (beta=0.374, P<0.001). Increased PWV is associated strongly and independently not only with the presence but also with the severity of DPN in patients with T2DM, irrespective of known risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Control of peripheral units by satellite computer

    International Nuclear Information System (INIS)

    Tran, K.T.

    1974-01-01

    A computer system was developed allowing the control of nuclear physics experiments, and use of the results by means of graphical and conversational assemblies. This system which is made of two computers, one IBM-370/135 and one Telemecanique Electrique T1600, controls the conventional IBM peripherals and also the special ones made in the laboratory, such as data acquisition display and graphics units. The visual display is implemented by a scanning-type television, equipped with a light-pen. These units in themselves are universal, but their specifications were established to meet the requirements of nuclear physics experiments. The input-output channels of the two computers have been connected together by an interface, designed and implemented in the Laboratory. This interface allows the exchange of control signals and data (the data are changed from bytes into word and vice-versa). The T1600 controls the peripherals mentionned above according to the commands of the IBM370. Hence the T1600 has here the part of a satellite computer which allows conversation with the main computer and also insures the control of its special peripheral units [fr

  6. Virtual bronchoscopy-guided transbronchial biopsy for aiding the diagnosis of peripheral lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iwano, Shingo, E-mail: iwano45@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi (Japan); Imaizumi, Kazuyoshi [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550 (Japan); Okada, Tohru [Research Center for Charged Particle Therapy, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba 2638555 (Japan); Hasegawa, Yoshinori [Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550 (Japan); Naganawa, Shinji [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi (Japan)

    2011-07-15

    Objective: The aim of this study was to evaluate the clinical value of virtual bronchoscopy (VB) in aiding diagnosis of peripheral lung cancer by transbronchial biopsy (TBB). In addition, we sought to systematically analyze the factors that affect the diagnostic sensitivity of VB-guided TBB for the evaluation of peripheral lung cancers. Materials and methods: A hundred and twenty-two peripheral lung cancers from 122 patients (82 men and 40 women, 38-84 years; median 68.5 years) who were performed VB-guided TBB were evaluated retrospectively. VB was reconstructed from 1- or 0.5-mm slice thickness images of multi-detector CT (MDCT). Experienced pulmonologists inserted the conventional and ultrathin bronchoscopes into the target bronchus under direct vision following the VB image. Results: A definitive diagnosis was established by VB-guided TBB in 96 lesions (79%). The diagnostic sensitivity of small pulmonary lesions {<=}30 mm in maximal diameter (71%) was significantly lower than that of lesions >30 mm (91%, p = 0.008). For small pulmonary lesions {<=}30 mm (n = 76), internal opacity of the lesion was the independent predictor of diagnostic sensitivity by VB-guided TBB, and the non-solid type lung cancers were significantly lower than the solid type and part-solid type lung cancers for diagnostic sensitivity (odds ratio = 0.161; 95% confidence interval = 0.033-0.780; p = 0.023). Conclusion: Use of an ultrathin bronchoscope and simulation with VB reconstructed by high quality MDCT images is thought to improve pathological diagnosis of peripheral lung cancers, especially for solid and partly solid types. For small pulmonary lesions {<=}30 mm, the lesion internal opacity is a significant factor for predicting the diagnostic sensitivity, and the sensitivity was low for small non-solid type of lung cancers.

  7. Augmented reality navigation in open surgery for hilar cholangiocarcinoma resection with hemihepatectomy using video-based in situ three-dimensional anatomical modeling: A case report.

    Science.gov (United States)

    Tang, Rui; Ma, Longfei; Xiang, Canhong; Wang, Xuedong; Li, Ang; Liao, Hongen; Dong, Jiahong

    2017-09-01

    Patients who undergo hilar cholangiocarcinoma (HCAC) resection with concomitant hepatectomy have a high risk of postoperative morbidity and mortality due to surgical trauma to the hepatic and biliary vasculature. A 58-year-old Chinese man with yellowing skin and sclera, abdominal distension, pruritus, and anorexia for approximately 3 weeks. Magnetic resonance cholangiopancreatography and enhanced computed tomography (CT) scanning revealed a mass over the biliary tree at the porta hepatis, which diagnosed to be s a hilar cholangiocarcinoma. Three-dimensional (3D) images of the patient's hepatic and biliary structures were reconstructed preoperatively from CT data, and the 3D images were used for preoperative planning and augmented reality (AR)-assisted intraoperative navigation during open HCAC resection with hemihepatectomy. A 3D-printed model of the patient's biliary structures was also used intraoperatively as a visual reference. No serious postoperative complications occurred, and the patient was tumor-free at the 9-month follow-up examination based on CT results. AR-assisted preoperative planning and intraoperative navigation might be beneficial in other patients with HCAC patients to reduce postoperative complications and ensure disease-free survival. In our postoperative analysis, we also found that, when the3D images were superimposed 3D-printed model using a see-through integral video graphy display device, our senses of depth perception and motion parallax were improved, compared with that which we had experienced intraoperatively using the videobased AR display system.

  8. Propylthiouracil and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Valentina Van Boekel

    1992-06-01

    Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

  9. Peripheral Neuropathy: Symptoms and Signs

    Science.gov (United States)

    ... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

  10. Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.

    Science.gov (United States)

    Kawamoto, Makoto; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Sinichiro; Kawabe, Ken; Onishi, Hideya; Nakamura, Masafumi; Morisaki, Takashi

    2018-05-01

    Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Effect of blocking Rac1 expression in cholangiocarcinoma QBC939 cells

    Directory of Open Access Journals (Sweden)

    Liu Xudong

    2011-05-01

    Full Text Available Cholangiocarcinomas (CCs are malignant tumors that originate from epithelial cells lining the biliary tree and gallbladder. Ras correlative C3 creotoxin substrate 1 (Rac1, a small guanosine triphosphatase, is a critical mediator of various aspects of endothelial cell functions. The objective of the present investigation was to study the effect of blocking Rac1 expression in CCs. Seventy-four extrahepatic CC (ECC specimens and matched adjacent normal mucosa were obtained from the Department of Pathology, Inner Mongolia Medicine Hospital, between 2007 and 2009. Our results showed that the expression of Rac1 was significantly higher (53.12% in tumor tissues than in normal tissues. Western blotting data indicated a significant reduction in Rac1-miRNA cell protein levels. Rac1-miRNA cell growth rate was significantly different at 24, 48, and 72 h after transfection. Flow cytometry analysis showed that Rac1-miRNA cells undergo apoptosis more effectively than control QBC939 cells. Blocking Rac1 expression by RNAi effectively inhibits the growth of CCs. miRNA silencing of the Rac1 gene suppresses proliferation and induces apoptosis of QBC939 cells. These results suggest that Rac1 may be a new gene therapy target for CC. Blocking Rac1 expression in CC cells induces apoptosis of these tumor cells and may thus represent a new therapeutic approach.

  12. Peripheral circulatory disorders in essential thrombocythemia.

    Science.gov (United States)

    Małecki, Rafał; Gacka, Małgorzata; Fiodorenko-Dumas, Żanna; Dumas, Ilias; Kwiatkowski, Jacek; Adamiec, Rajmund; Kuliszkiewicz-Janus, Małgorzata

    2018-03-01

    A significant number of patients with essential thrombocythemia (ET) complain of symptoms including distal parts of the extremities (e.g., paresthesias or Raynaud's phenomenon). The aim of the present study was to examine peripheral circulation in the upper extremities of individuals with ET. The study included 45 ET patients and 30 control subjects. All participants were subjected to thermography, photoplethysmography, impedance plethysmography, and applanation tonometry pulse wave analysis. The patients with ET differed significantly from the control subjects in terms of 3rd finger skin temperature (mean 31.04 vs. 32.45°C), skin temperature gradient (mean 1.82 vs. 0.11°C), photoplethysmographic amplitude (median 0.25 vs. 0.74%), and pulse waveform in the radial artery (more frequent occurrence of type B waveform). Pulse wave parameters correlated with the skin temperature gradient. The study findings imply the altered regulation of peripheral circulation in ET, including a decreased flow and an increased resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Discussion of vascular vagovagal reflexes in interventional approach of peripheral arterial diseases

    International Nuclear Information System (INIS)

    Zhuang Baixi; Yu Chunli; Ma Lubo; Yang Miao; Shi Bo

    2007-01-01

    Objective: To investigate the vascular vagovagal reflexes (VVRs) during interventional approach of peripheral arterial disease (PAD). Methods: Twelve patients with VVRs during intervention of 528 patients with peripheral arterial diseases were analyzed retrospectively. Results: The 12 patients with VVRs belonging to mixed type, included 2 cases of occurrence during intervention and 10 cases after intervention. All patients recovered well without adverse reaction. Conclusion: VVRs should always be looking after and prompt management be ready in hand. (authors)

  14. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

  15. Prognostic factors and long-term outcomes of hilar cholangiocarcinoma: A single-institution experience in China

    Science.gov (United States)

    Hu, Hai-Jie; Mao, Hui; Shrestha, Anuj; Tan, Yong-Qiong; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

    2016-01-01

    AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution. METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated by univariate and multivariate analyses. RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio (HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease (HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation (HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion (HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins (HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease (HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation (HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion (HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins (HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio (OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter (OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures (OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage (OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion (OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumor-free margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent

  16. Peripheral Mononuclear Cell Resistin mRNA Expression Is Increased in Type 2 Diabetic Women

    Directory of Open Access Journals (Sweden)

    Panayoula C. Tsiotra

    2008-01-01

    Full Text Available Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P=.05. Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 were all significantly higher in DM2 compared to control women (P<.001. The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women (P=.051, and overall, they correlated significantly with BMI (r=0.406, P=.010 and waist circumference (r=0.516, P=.003, but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1β, TNF-α, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

  17. Nootropic nefiracetam inhibits proconvulsant action of peripheral-type benzodiazepines in epileptic mutant EL mice.

    Science.gov (United States)

    Nakamoto, Yurie; Shiotani, Tadashi; Watabe, Shigeo; Nabeshima, Toshitaka; Yoshii, Mitsunobu

    2004-10-01

    Piracetam and structurally related nootropics are known to potentiate the anticonvulsant effects of antiepileptic drugs. It remains to be seen, however, whether these nootropics inhibit proconvulsant actions of many toxic agents including Ro 5-4864, a specific agonist for peripheral-type benzodiazepine receptors (PBR). The present study was designed to address this issue using EL mice, an animal model of epilepsy. In behavioral pharmacological experiments, EL mice were highly susceptible to convulsions induced by Ro 5-4864 (i.p.) in comparison with nonepileptic DDY mice. Nefiracetam administered orally to EL mice inhibited spontaneous seizures. In DDY mice, convulsions induced by Ro 5-4864 were prevented by nefiracetam when administered by i.v. injection. Aniracetam (i.v.) was partially effective, but piracetam and oxiracetam were ineffective as anticonvulsants. Binding assay for brain tissues revealed a higher density of mitochondrial PBR in EL mice compared with DDY mice. Binding of the PBR ligands Ro 5-4864 to either EL or DDY mouse brain was inhibited by micromolar concentrations of these nootropic agents in the sequence of nefiracetam > aniracetam > oxiracetam, piracetam. This rank order is identical to potency as anticonvulsants. These data suggest that nefiracetam may prevent toxic effects of PBR agonists through interacting with PBR.

  18. Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

    Science.gov (United States)

    Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

    2015-10-01

    Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Expression and localization of sterile alpha motif domain containing 5 is associated with cell type and malignancy of biliary tree.

    Directory of Open Access Journals (Sweden)

    Tomoki Yagai

    Full Text Available Cholangiocarcinoma (CC is a type of relatively rare neoplasm in adenocarcinoma. The characteristics of CCs as well as biliary epithelial cells are heterogeneous at the different portion of the biliary tree. There are two candidate stem/progenitor cells of the biliary tree, i.e., biliary tree stem/progenitor cell (BTSC at the peribiliary gland (PBG of large bile ducts and liver stem/progenitor cell (LPC at the canals of Hering of peripheral small bile duct. Although previous reports suggest that intrahepatic CC (ICC can arise from such stem/progenitor cells, the characteristic difference between BTSC and LPC in pathological process needs further investigation, and the etiology of CC remains poorly understood. Here we show that Sterile alpha motif domain containing 5 (SAMD5 is exclusively expressed in PBGs of large bile ducts in normal mice. Using a mouse model of cholestatic liver disease, we demonstrated that SAMD5 expression was upregulated in the large bile duct at the hepatic hilum, the extrahepatic bile duct and PBGs, but not in proliferating intrahepatic ductules, suggesting that SAMD5 is expressed in BTSC but not LPC. Intriguingly, human ICCs and extrahepatic CCs exhibited striking nuclear localization of SAMD5 while the normal hilar large bile duct displayed slight-to-moderate expression in cytoplasm. In vitro experiments using siRNA for SAMD5 revealed that SAMD5 expression was associated with the cell cycle regulation of CC cell lines.SAMD5 is a novel marker for PBG but not LPC in mice. In humans, the expression and location of SAMD5 could become a promising diagnostic marker for the cell type as well as malignancy of bile ducts and CCs.

  20. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

    Science.gov (United States)

    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  1. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  2. Taste buds as peripheral chemosensory processors.

    Science.gov (United States)

    Roper, Stephen D

    2013-01-01

    Taste buds are peripheral chemosensory organs situated in the oral cavity. Each taste bud consists of a community of 50-100 cells that interact synaptically during gustatory stimulation. At least three distinct cell types are found in mammalian taste buds - Type I cells, Receptor (Type II) cells, and Presynaptic (Type III) cells. Type I cells appear to be glial-like cells. Receptor cells express G protein-coupled taste receptors for sweet, bitter, or umami compounds. Presynaptic cells transduce acid stimuli (sour taste). Cells that sense salt (NaCl) taste have not yet been confidently identified in terms of these cell types. During gustatory stimulation, taste bud cells secrete synaptic, autocrine, and paracrine transmitters. These transmitters include ATP, acetylcholine (ACh), serotonin (5-HT), norepinephrine (NE), and GABA. Glutamate is an efferent transmitter that stimulates Presynaptic cells to release 5-HT. This chapter discusses these transmitters, which cells release them, the postsynaptic targets for the transmitters, and how cell-cell communication shapes taste bud signaling via these transmitters. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas

    International Nuclear Information System (INIS)

    Yanagisawa, Nobuyuki; Hana, Kiyomi; Nakada, Norihiro; Ichinoe, Masaaki; Koizumi, Wasaburo; Endou, Hitoshi; Okayasu, Isao; Murakumo, Yoshiki

    2014-01-01

    Oncocytic L-type amino acid transporter (LAT) 1 may be a prognostic indicator and target of new molecular therapeutic agents against malignancies. To investigate whether LAT1 expression influence the outcomes of patients with bile duct cancer, the expression of LAT1, LAT2, CD98, and Ki-67 was investigated immunohistochemically in 134 surgically resected bile duct adenocarcinomas, including 84 distal extrahepatic bile duct adenocarcinomas, 21 hilar cholangiocarcinomas, 15 intrahepatic cholangiocarcinomas, and 14 ampullary adenocarcinomas. LAT1 expression was weakly correlated with CD98 expression and Ki-67 labeling index (LI). Kaplan–Meier analysis showed a significant difference in prognosis between patients with bile duct adenocarcinomas having LAT1-high and -low scores, whereas LAT2 and CD98 expression and Ki-67 LI were not predictive of poor prognosis. Prognosis tended to be worse in patients having tumors with LAT1-high/LAT2-low than LAT1-low/LAT2-high scores (P = 0.0686). Multivariable analyses revealed that LAT1 expression, surgical margin, pT stage were independent prognostic factors. In conclusion, aberrant overexpression of LAT1 in bile duct adenocarcinoma predicts poor prognosis, suggesting that LAT1 may be a potential target of anticancer therapy

  4. Induction of sustained aberration and SCE in peripheral blood lymphocytes by internal contamination of fragment 147Pm

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Cao Genfa; Sun Baofu

    1994-12-01

    The purpose of this study is to ascertain the induction of sustained aberration and SCE in peripheral blood lymphocytes by 147 Pm retention in the body. The retention process of 147 Pm in the body fitted an equation which consists of two components, fast and slow. The half-time of the fast component is T 1 = 4.77 d and that of the slow component is T 2 = 816.3 d. When 147 Pm was accumulated in the body, it caused chromosome aberrations in peripheral blood lymphocytes. Among the different types of aberration induced by 147 Pm, the predominant type was aberration of chromatid, accompanied by a few chromosome breakage and translocation. The experimental results indicated that SCE of peripheral blood lymphocytes increased significantly after different periods of 147 Pm exposures. It should be noted that after exposure for 30 d, a peak elevation of SCE in peripheral blood lymphocytes was observed. (8 figs., 3 tabs.)

  5. High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.

    Science.gov (United States)

    Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

    2017-12-01

    High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm 2 ) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score ( p peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm 2 ) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm 2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

  6. Prevalence of peripheral arterial disease and related risk factors in Turkish elders

    Directory of Open Access Journals (Sweden)

    Yesilkayali Teoman

    2011-09-01

    Full Text Available Abstract Background It is known that prevalence of peripheral arterial disease being a widespread atherosclerotic vascular disease increases by age. On the other hand, no comprehensive study showing the prevalence of peripheral arterial disease in Turkish elders is seen. In this study, it is aimed to assess prevalence of peripheral arterial disease and related risk factors in Turkish elders in primary health center. Methods 507 elderly staying at Narlidere Geriatric Care Center and Residential Home and accepting to participate in the study were included in the study. Epidemiological data for diagnosis of peripheral arterial disease, risk factors, findings of physical examination and ankle brachial index measurements were assessed in the study. Data were analyzed in terms of prevalence of peripheral arterial disease, age and gender relation and other cardiovascular risk factors. Results Of the participants, 317 (62.5% were female. The mean age was 77.61 ± 6.93 years (62-102. The most wide-spread chronic diseases in elderly included hypertension, coronary artery disease, hyperlipidemia and Type 2 DM, respectively. On the other hand, only 7 (1.4% elderly were diagnosed with peripheral arterial disease. The number of elderly ABI of whom was measured as Conclusions Peripheral arterial disease is expected to be seen prevailing in elderly. However, it was determined at very low rate before the study due to the fact that the disease cannot be diagnosed clinically especially in early-period. Peripheral arterial disease determined in the study is lower than expected as per the age group. This can be associated with practices of geriatrics nursing and family practice including continuous care to reduce cardiovascular risk factors of patients staying at the unit.

  7. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

    Science.gov (United States)

    Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

    2018-01-01

    AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy

  8. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

    Science.gov (United States)

    Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

    2018-03-28

    To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12

  9. Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

    National Research Council Canada - National Science Library

    Sherman, Larry

    2003-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are aggressive, difficult to treat tumors that occur in type I neurofibromatosis patients with an increased incidence compared to the general population...

  10. Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

    National Research Council Canada - National Science Library

    Sherman, Larry

    2001-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are aggressive, difficult to treat tumors that occur in type I neurofibromatosis patients with an increased incidence compared to the general population...

  11. Radiological diagnosis and intervention of cholangiocarcinomas (CC); Radiologische Diagnostik und Intervention von Cholangiokarzinomen (CC)

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Zangos, S.; Eichler, K.; Gruber-Rouh, T.; Hammerstingl, R.M.; Weisser, P. [Frankfurt Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Trojan, J. [Frankfurt Univ. (Germany). Medizinische Klinik I: Gastroenterologie, Endokrinologie, Pneumologie/Allergologie

    2012-10-15

    To present current data on diagnosis, indication and different therapy options in patients with cholangiocarcinoma (CC) based on an analysis of the current literature and clinical experience. The diagnostic routine includes laboratory investigations with parameters of cholestasis and also serum tumor markers CA19 - 9 and CEA. After ultrasound for clarifying a tumor and/or dilated bile ducts, contrast-enhanced magnetic resonance imaging (MRI) should be performed with magnetic resonance cholangiography (MRCP). The accuracy (positive predictive value) for diagnosing a CC is 37 - 84 % (depending on the location) for ultrasound, 79 - 94 % for computed tomography (CT), and 95 % for MRI and MRCP. An endoscopic retrograde cholangiography (ERCP) can then be planned, especially if biliary drainage or cytological or histological specimen sampling is intended. A curative approach can be achieved by surgical resection, rarely by liver transplantation. However, many patients are not eligible for surgery. In addition to systemic chemotherapy, locoregional therapies such as transarterial chemoembolization (TACE), hepatic arterial infusion (HAI) - also known as chemoperfusion -, drug eluting beads-therapy (DEB) as well as thermoablative procedures, such as laser-induced thermotherapy (LITT), microwave ablation (MWA) and radiofrequency ablation (RFA) can be provided with a palliative intention.

  12. Disruption of endocytic trafficking protein Rab7 impairs invasiveness of cholangiocarcinoma cells.

    Science.gov (United States)

    Suwandittakul, Nantana; Reamtong, Onrapak; Molee, Pattamaporn; Maneewatchararangsri, Santi; Sutherat, Maleerat; Chaisri, Urai; Wongkham, Sopit; Adisakwattana, Poom

    2017-09-07

    Alterations and mutations of endo-lysosomal trafficking proteins have been associated with cancer progression. Identification and characterization of endo-lysosomal trafficking proteins in invasive cholangiocarcinoma (CCA) cells may benefit prognosis and drug design for CCA. To identify and characterize endo-lysosomal trafficking proteins in invasive CCA. A lysosomal-enriched fraction was isolated from a TNF-α induced invasive CCA cell line (KKU-100) and uninduced control cells and protein identification was performed with nano-LC MS/MS. Novel lysosomal proteins that were upregulated in invasive CCA cells were validated by real-time RT-PCR. We selected Rab7 for further studies of protein level using western blotting and subcellular localization using immunofluorescence. The role of Rab7 in CCA invasion was determined by siRNA gene knockdown and matrigel transwell assay. Rab7 mRNA and protein were upregulated in invasive CCA cells compared with non-treated controls. Immunofluorescence studies demonstrated that Rab7 was expressed predominantly in invasive CCA cells and was localized in the cytoplasm and lysosomes. Suppression of Rab7 translation significantly inhibited TNF-α-induced cell invasion compared to non-treated control (p= 0.044). Overexpression of Rab7 in CCA cells was associated with cell invasion, supporting Rab7 as a novel candidate for the development of diagnostic and therapeutic strategies for CCA.

  13. The Relationship between Peripheral Nerve Conduction Velocity and Ophthalmological Findings in Type 2 Diabetes Patients with Early Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Azusa Ito

    2018-01-01

    Full Text Available Purpose. Nerve conduction velocity (NCV is an indicator of neuronal damage in the distal segment of the peripheral nerves. Here, we determined the association between NCV and other systemic and ocular clinical findings, in type 2 diabetes patients with early diabetic retinopathy (DR. Methods. This study included 42 eyes of 42 type 2 diabetes patients (median age: 54 years with no DR or with mild nonproliferative DR. Standard statistical techniques were used to determine associations between clinical findings. Results. Sural sensory conduction velocity (SCV and tibial motor conduction velocity (MCV were significantly lower in mild nonproliferative DR patients than patients with no DR (P=0.008 and P=0.01, resp.. Furthermore, logistic regression analyses revealed that sural SCV and tibial MCV were independent factors contributing to the presence of mild nonproliferative DR (OR 0.83, P=0.012 and OR 0.69 P=0.02, resp.. Tibial MCV was correlated with choroidal thickness (CT (P=0.01, and a multiple regression analysis revealed that age, tibial MCV, and carotid intima-media thickness were independent associating factors with CT (P=0.035, P=0.015, and P=0.008, resp.. Conclusions. Our findings suggest that reduced NCV may be closely associated with early DR in type 2 diabetes patients. Thus, reduced nerve conduction is a potential early biomarker of DR.

  14. 25-Hydroxyvitamin D and Peripheral Immune Mediators

    DEFF Research Database (Denmark)

    Thorsen, Steffen; Pipper, Christian; Skogstrand, Kristin

    2017-01-01

    Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470...... patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981–1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997–2005. A variety of peripheral immune mediators were measured and compared...... to total 25(OH)D levels (25(OH)D2 + 25(OH)D3). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH...

  15. Predicting IDH mutation status of intrahepatic cholangiocarcinomas based on contrast-enhanced CT features

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Yong [Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Department of Radiology, Nanjing, Jiangsu Province (China); Chen, Jun [Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Department of Pathology, Nanjing, Jiangsu Province (China); Kong, Weiwei [Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Department of Oncology, Nanjing, Jiangsu Province (China); Mao, Liang; Qiu, Yudong [Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Department of Hepatopancreatobiliary Surgery, Nanjing, Jiangsu Province (China); Kong, Wentao [Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Department of Ultrasonography, Nanjing, Jiangsu Province (China); Zhou, Qun [Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu Province (China); Zhou, Zhengyang; Zhu, Bin; He, Jian [Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Department of Radiology, Nanjing, Jiangsu Province (China); Wang, Zhongqiu [Jiangsu Province Hospital of Traditional Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing, Jiangsu Province (China)

    2018-01-15

    To explore the difference in contrast-enhanced computed tomography (CT) features of intrahepatic cholangiocarcinomas (ICCs) with different isocitrate dehydrogenase (IDH) mutation status. Clinicopathological and contrast-enhanced CT features of 78 patients with 78 ICCs were retrospectively analysed and compared based on IDH mutation status. There were 11 ICCs with IDH mutation (11/78, 14.1%) and 67 ICCs without IDH mutation (67/78, 85.9%). IDH-mutated ICCs showed intratumoral artery more often than IDH-wild ICCs (p = 0.023). Most ICCs with IDH mutation showed rim and internal enhancement (10/11, 90.9%), while ICCs without IDH mutation often appeared diffuse (26/67, 38.8%) or with no enhancement (4/67, 6.0%) in the arterial phase (p = 0.009). IDH-mutated ICCs showed significantly higher CT values, enhancement degrees and enhancement ratios in arterial and portal venous phases than IDH-wild ICCs (all p < 0.05). The CT value of tumours in the portal venous phase performed best in distinguishing ICCs with and without IDH mutation, with an area under the curve of 0.798 (p = 0.002). ICCs with and without IDH mutation differed significantly in arterial enhancement mode, and the tumour enhancement degree on multiphase contrast-enhanced CT was helpful in predicting IDH mutation status. (orig.)

  16. Integration of the Residual Limb with Prostheses via Direct Skin-Bone-Peripheral Nerve Interface

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0791 TITLE: Integration of the Residual Limb with Prostheses via Direct Skin- Bone-Peripheral Nerve Interface...ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Integration of the...translational study to develop Skin and Bone Integrated Pylon with Peripheral Neural Interface (SBIP-PNI) directly attached to the residuum and the

  17. Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT).

    Science.gov (United States)

    Chan, C Y; Molrine, D C; Antin, J H; Wheeler, C; Guinan, E C; Weinstein, H J; Phillips, N R; McGarigle, C; Harvey, S; Schnipper, C; Ambrosino, D M

    1997-07-01

    Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented. We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines. IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups. Geometric mean IgG anti-HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P = 0.006). Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039). Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients. PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations. These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization.

  18. Characterization of glucocerebrosidase in peripheral blood cells and cultured blastoid cells

    NARCIS (Netherlands)

    Aerts, J. M.; Heikoop, J.; van Weely, S.; Donker-Koopman, W. E.; Barranger, J. A.; Tager, J. M.; Schram, A. W.

    1988-01-01

    We have characterized glucocerebrosidase in various cell types of peripheral blood of control subjects and in cultured human blastoid cells. The intracellular level of glucocerebrosidase in cultured blastoid cells (10-30 nmol substrate hydrolyzed/h.mg protein) resembles closely values observed for

  19. Peripheral visual performance enhancement by neurofeedback training.

    Science.gov (United States)

    Nan, Wenya; Wan, Feng; Lou, Chin Ian; Vai, Mang I; Rosa, Agostinho

    2013-12-01

    Peripheral visual performance is an important ability for everyone, and a positive inter-individual correlation is found between the peripheral visual performance and the alpha amplitude during the performance test. This study investigated the effect of alpha neurofeedback training on the peripheral visual performance. A neurofeedback group of 13 subjects finished 20 sessions of alpha enhancement feedback within 20 days. The peripheral visual performance was assessed by a new dynamic peripheral visual test on the first and last training day. The results revealed that the neurofeedback group showed significant enhancement of the peripheral visual performance as well as the relative alpha amplitude during the peripheral visual test. It was not the case in the non-neurofeedback control group, which performed the tests within the same time frame as the neurofeedback group but without any training sessions. These findings suggest that alpha neurofeedback training was effective in improving peripheral visual performance. To the best of our knowledge, this is the first study to show evidence for performance improvement in peripheral vision via alpha neurofeedback training.

  20. APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.

    Science.gov (United States)

    Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Paly, Evelyn; London, Jacqueline

    2010-03-16

    Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of APP overexpressing and FVB/N wild-type mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4-week follow up. We found no autotomy behavior as well as less significant atrophy of denervated muscles in APP overexpressing animals when compared to wild-type ones. Sciatic nerve function index outcome did not differ between groups. Histological evaluation revealed that the intensity of regeneration features, including GAP-43-positive growth cones and Schwann cells number in the distal stump of the transected nerve, was also similar in both groups. However, the regenerating fibers were organized more chaotically in wild-type mice and neuromas were much more often seen in this group. The number of macrophages infiltrating the injury site was significantly higher in control group. The number of surviving motoneurons was higher in transgenic mice than in control animals. Taken together, our findings suggest that APP overexpression is beneficial for nerve regeneration processes due to better organization of regenerating fibers, increased survival of motoneurons after autotomy and prevention of neuropathic pain. Copyright 2009 Elsevier Inc. All rights reserved.

  1. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  2. Peripheral Circulatory Features during High-Frequency Jet Ventilation

    Directory of Open Access Journals (Sweden)

    M. B. Kontorovich

    2010-01-01

    Full Text Available The paper gives the results of a study of peripheral circulatory features during high-frequency jet ventilation (HFJV. The main specific features of peripheral circulation and oxygen transport during HFJV are formulated on the basis of a study of cardiac output (impedance cardiography, peripheral vascular resistance, peripheral vascular blood filling (photoplethysmogram analysis, adaptive peripheral blood flow reactions (spectral analysis of peripheral vascular pulsation. HFJV gives rise to the peculiar pattern of peripheral hemodynamics and tissue gas exchange, which is characterized by higher oxygen uptake without a decrease in mixed venous blood saturation, with normal extraction coefficient and preserved low peripheral vascular resistance. During HFJV, unlike traditional ventilation, the main peripheral hemodynamic feature is the increased capillary bed blood volume caused by the blood flow involvement of reserve capillaries under control of volume (parasympathetic regulation of adaptive peripheral hemodynamic reactions. Key words: high-frequency jet ventilation, oxygen transport, peripheral hemodynamics.

  3. FLUORESCENCE DIAGNOSIS AND PHOTODYNAMIC THERAPY IN COMBINED TREATMENT OF CHOLANGIOCARCINOMA

    Directory of Open Access Journals (Sweden)

    A. A. Shiryaev

    2016-01-01

    Full Text Available The results of the pilot study of combined treatment for non-resectable cholangiocarcinoma complicated with obstructive jaundice are represented this paper. Method included percutaneous transhepatic biliary drainage, endoscopic fluorescence diagnosis, photodynamic therapy of tumor stricture, and stenting of bile ducts. Fourteen patients who underwent the treatment in the surgery department clinic of I.M. Sechenov First Moscow State Medical University were enrolled in the study. Fluorescence diagnosis and photodynamic therapy were carried out using photosensitizers photosens (0.5 mg/kg, fotolon (1 mg/kg, and radachlorin (1 mg/kg. The average light dose for one session was 115±5 J/cm2. Fluorescence diagnosis using endoscopic video-fluorescence system for endoscopy and minimally invasive surgery allowed to obtain videoassisted fluorescence image of the tumor and to measure level of photosensitizer fluorescence in tumor in all patients. Malignant tumor was confirmed by morphological study in 12 patients, biopsy of material for morphological study failed in 2 patients with Klatskin tumor. The preliminary results of combined minimally invasive treatment were assessed as promising. The survival time in 4 patients after treatment accounted for 21, 17, 13 and 11 months, respectively. For now 5 patients are under follow-up. Follow-up periods are 13 and 19 months in 2 of them and from 4 to 6 months in 3 of them. Five patients with multiple distant metastases before the treatment died in 3±1 months after therapy. The average lifetime in the treatment group is 9.5 months up to date, however the duration is expected to belonger because 5 of 14 patients are alive.

  4. Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review

    Directory of Open Access Journals (Sweden)

    Usman Ghafoor

    2017-10-01

    Full Text Available For those individuals with upper-extremity amputation, a daily normal living activity is no longer possible or it requires additional effort and time. With the aim of restoring their sensory and motor functions, theoretical and technological investigations have been carried out in the field of neuroprosthetic systems. For transmission of sensory feedback, several interfacing modalities including indirect (non-invasive, direct-to-peripheral-nerve (invasive, and cortical stimulation have been applied. Peripheral nerve interfaces demonstrate an edge over the cortical interfaces due to the sensitivity in attaining cortical brain signals. The peripheral nerve interfaces are highly dependent on interface designs and are required to be biocompatible with the nerves to achieve prolonged stability and longevity. Another criterion is the selection of nerves that allows minimal invasiveness and damages as well as high selectivity for a large number of nerve fascicles. In this paper, we review the nerve-machine interface modalities noted above with more focus on peripheral nerve interfaces, which are responsible for provision of sensory feedback. The invasive interfaces for recording and stimulation of electro-neurographic signals include intra-fascicular, regenerative-type interfaces that provide multiple contact channels to a group of axons inside the nerve and the extra-neural-cuff-type interfaces that enable interaction with many axons around the periphery of the nerve. Section Current Prosthetic Technology summarizes the advancements made to date in the field of neuroprosthetics toward the achievement of a bidirectional nerve-machine interface with more focus on sensory feedback. In the Discussion section, the authors propose a hybrid interface technique for achieving better selectivity and long-term stability using the available nerve interfacing techniques.

  5. Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review

    Science.gov (United States)

    Ghafoor, Usman; Kim, Sohee; Hong, Keum-Shik

    2017-01-01

    For those individuals with upper-extremity amputation, a daily normal living activity is no longer possible or it requires additional effort and time. With the aim of restoring their sensory and motor functions, theoretical and technological investigations have been carried out in the field of neuroprosthetic systems. For transmission of sensory feedback, several interfacing modalities including indirect (non-invasive), direct-to-peripheral-nerve (invasive), and cortical stimulation have been applied. Peripheral nerve interfaces demonstrate an edge over the cortical interfaces due to the sensitivity in attaining cortical brain signals. The peripheral nerve interfaces are highly dependent on interface designs and are required to be biocompatible with the nerves to achieve prolonged stability and longevity. Another criterion is the selection of nerves that allows minimal invasiveness and damages as well as high selectivity for a large number of nerve fascicles. In this paper, we review the nerve-machine interface modalities noted above with more focus on peripheral nerve interfaces, which are responsible for provision of sensory feedback. The invasive interfaces for recording and stimulation of electro-neurographic signals include intra-fascicular, regenerative-type interfaces that provide multiple contact channels to a group of axons inside the nerve and the extra-neural-cuff-type interfaces that enable interaction with many axons around the periphery of the nerve. Section Current Prosthetic Technology summarizes the advancements made to date in the field of neuroprosthetics toward the achievement of a bidirectional nerve-machine interface with more focus on sensory feedback. In the Discussion section, the authors propose a hybrid interface technique for achieving better selectivity and long-term stability using the available nerve interfacing techniques. PMID:29163122

  6. Incidence of local complications and risk factors associated with peripheral intravenous catheter in neonates

    Directory of Open Access Journals (Sweden)

    Mitzy Tannia Reichembach Danski

    2016-02-01

    Full Text Available Abstract OBJECTIVE To evaluate the incidence of complications related to the use of peripheral intravenous catheter in neonates and identify the associated risk factors. METHOD Prospective cohort study conducted in a Neonatal Intensive Care Unit. Participants were the hospitalized neonates undergoing peripheral intravenous puncture in the period from February to June 2013. RESULTS The incidence of complications was 63.15%, being infiltration/extravasation (69.89%, phlebitis (17.84% and obstruction (12.27%. The risk factors were the presence of infection (p = 0.0192 and weight at the puncture day (p = 0.0093, type of intermittent infusion associated with continuous infusion (p <0.0001, endotracheal intubation (p = 0.0008, infusion of basic plan (p = 0.0027, total parenteral nutrition (P = 0.0002, blood transfusion associated with other infusions (p = 0.0003 and other drugs (p = 0.0004. Higher risk of developing complications in the first 48 hours after puncture. CONCLUSION A high rate of complications related to the use of peripheral intravenous catheter, and risk factors associated with infection, weight, drugs and infused solutions, and type of infusion.

  7. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

    Nielsen, B N; Henneberg, S W; Schmiegelow, K

    2015-01-01

    BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June...... 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity...... difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved...

  8. Fisetin Reduces Cell Viability Through Up-Regulation of Phosphorylation of ERK1/2 in Cholangiocarcinoma Cells.

    Science.gov (United States)

    Kim, Nayoung; Lee, Sang Hyub; Son, Jun Hyuk; Lee, Jae Min; Kang, Min-Jung; Kim, Bo Hye; Lee, Jung-Su; Ryu, Ji Kon; Kim, Yong-Tae

    2016-11-01

    Cholangiocarcinoma (CCA) is a malignancy with poor prognosis and limited therapeutic options. Effective prevention and treatment of CCA require developing novel anticancer agents and improved therapeutic regimens. As natural products are concidered a rich source of potential anticancer agents, we investigated the anticancer effect of fisetin in combination with gemcitabine. Cytotoxic effect of fisetin and gemcitabine on a human CCA cell line SNU-308 was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay using propidium iodine and annexin V. Molecular mechanisms of fisetin action in CCA were investigated by western blotting. Fisetin was found to inhibit survival of CCA cells, through strongly phosphorylating ERK. It also induced cellular apoptosis additively in combination with gemcitabine. Expression of cellular proliferative markers, such as phospho-p65 and myelocytomatosis (MYC), were reduced by fisetin. These results suggest fisetin in combination with gemcitabine as a candidate for use in improved anticancer regimens. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma.

    Science.gov (United States)

    Tian, Meng-Xin; He, Wen-Jun; Liu, Wei-Ren; Yin, Jia-Cheng; Jin, Lei; Tang, Zheng; Jiang, Xi-Fei; Wang, Han; Zhou, Pei-Yun; Tao, Chen-Yang; Ding, Zhen-Bin; Peng, Yuan-Fei; Dai, Zhi; Qiu, Shuang-Jian; Zhou, Jian; Fan, Jia; Shi, Ying-Hong

    2018-01-01

    Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables ( P model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.

  10. Carcinoma with shared pathologic characteristics of both hepatocellular carcinoma and cholangiocarcinoma

    Science.gov (United States)

    Hiraoka, Atsushi; Kurose, Kiyotaka; Kumagi, Teru; Hirooka, Masashi; Yokota, Tomoyuki; Fujiwara, Toshiteru; Utsunomiya, Sachiko; Hirata, Mami; Ohtani, Hiromi; Michitaka, Kojiro; Horiike, Norio; Kobayashi, Nobuaki; Onji, Morikazu

    2005-01-01

    Background: α-Fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), and protein induced by vitamin K absence or antagonist II (PIVKA-II) and fucosylated AFP (AFP-L3) are specific tumor markers. Objective: The aim of this article was to report a case of intrahepatic cholangiocarcinoma (CC) with high levels of expression of AFP, AFP-L3, and PIVKA-II. Methods: A 70-year-old man weighing 66 kg with a diagnosis of intrahepatic CC presented with a liver tumor 4.0 cm in diameter and elevated concentrations of carbohydrate antigen 19-9 (575 U/mL), PIVKA-II (379 mAU/mL), and AFP (497 ng/mL; AFP-L3, 88.1%). On extended medial hepatic segmentectomy, microscopy showed that the tumor was a CC without HCC. The patient subsequently underwent immunohistochemical assessments using cytokeratin-19, epithelial membrane antigen (EMA), hepatocyte paraffin-1 (HP-1), PIVKA-II, and AFP. Results: In all specimens, desmoplasia was observed. However, results of immunohistochemistry showed positive results for cytokeratin-19 and EMA; HP-1 results were negative. Results of PIVKA-II and AFP testing in the tumor were positive. Conclusions: The case presented here showed characteristics of CC and HCC, whereas the histologic expression of the tumor suggested CC. Based on the literature search, this is the first known report of a case of a CC expressing AFP and PIVKA-II confirmed on immunohistochemical staining. This case is interesting with regard to the ability of the progenitor cells to differentiate HCC and CC. PMID:24678077

  11. Burn-related peripheral neuropathy: A systematic review.

    Science.gov (United States)

    Tu, Yiji; Lineaweaver, William C; Zheng, Xianyou; Chen, Zenggan; Mullins, Fred; Zhang, Feng

    2017-06-01

    Peripheral neuropathy is the most frequent disabling neuromuscular complication of burns. However, the insidious and progressive onset of burn neuropathy makes it often undiagnosed or overlooked. In our study, we reviewed the current studies on the burn-related peripheral neuropathy to summarize the morbidity, mechanism, detecting method and management of peripheral neuropathy in burn patients. Of the 1533 burn patients included in our study, 98 cases (6.39%) were presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies. Surgical procedures, especially nerve decompression, showed good effect on functional recovery of both acute and delayed peripheral neuropathy in burn patients. It is noteworthy that, for early detection and prevention of peripheral neuropathy, electrodiagnostic examinations should be performed on burn patients independent of symptoms. Still, the underlying mechanisms of burn-related peripheral neuropathy remain to be clarified. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  12. Association of glycaemic variability evaluated by continuous glucose monitoring with diabetic peripheral neuropathy in type 2 diabetic patients.

    Science.gov (United States)

    Hu, Yu-Ming; Zhao, Li-Hua; Zhang, Xiu-Lin; Cai, Hong-Li; Huang, Hai-Yan; Xu, Feng; Chen, Tong; Wang, Xue-Qin; Guo, Ai-Song; Li, Jian-An; Su, Jian-Bin

    2018-05-01

    Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes, is linked to glycaemic derangements. Glycaemic variability, as a pattern of glycaemic derangements, is a key risk factor for diabetic complications. We investigated the association of glycaemic variability with DPN in a large-scale sample of type 2 diabetic patients. In this cross-sectional study, we enrolled 982 type 2 diabetic patients who were screened for DPN and monitored by a continuous glucose monitoring (CGM) system between February 2011 and January 2017. Multiple glycaemic variability parameters, including the mean amplitude of glycaemic excursions (MAGE), mean of daily differences (MODD), standard deviation of glucose (SD), and 24-h mean glucose (24-h MG), were calculated from glucose profiles obtained from CGM. Other possible risks for DPN were also examined. Of the recruited type 2 diabetic patients, 20.1% (n = 197) presented with DPN, and these patients also had a higher MAGE, MODD, SD, and 24-h MG than patients without DPN (p diabetic duration, HOMA-IR, and hemoglobin A1c (HbA1c) were found to be independent contributors to DPN, and the corresponding odds ratios (95% confidence interval) were 4.57 (3.48-6.01), 1.10 (1.03-1.17), 1.24 (1.09-1.41), and 1.33 (1.15-1.53), respectively. Receiver operating characteristic analysis indicated that the optimal MAGE cutoff value for predicting DPN was 4.60 mmol/L; the corresponding sensitivity was 64.47%, and the specificity was 75.54%. In addition to conventional risks including diabetic duration, HOMA-IR and HbA1c, increased glycaemic variability assessed by MAGE is a significant independent contributor to DPN in type 2 diabetic patients.

  13. MR Angiography of Peripheral Arterial Stents: In Vitro Evaluation of 22 Different Stent Types

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    Matthias C. Burg

    2011-01-01

    Full Text Available Purpose. To evaluate stent lumen visibility of a large sample of different peripheral arterial (iliac, renal, carotid stents using magnetic resonance angiography in vitro. Materials and Methods. 21 different stents and one stentgraft (10 nitinol, 7 316L, 2 tantalum, 1 cobalt superalloy, 1 PET + cobalt superalloy, and 1 platinum alloy were examined in a vessel phantom (vessel diameters ranging from 5 to 13 mm filled with a solution of Gd-DTPA. Stents were imaged at 1.5 Tesla using a T1-weighted 3D spoiled gradient-echo sequence. Image analysis was performed measuring three categories: Signal intensity in the stent lumen, lumen visibility of the stented lumen, and homogeneity of the stented lumen. The results were classified using a 3-point scale (good, intermediate, and poor results. Results. 7 stents showed good MR lumen visibility (4x nitinol, 2x tantalum, and 1x cobalt superalloy. 9 stents showed intermediate results (5x nitinol, 2x 316L, 1x PET + cobalt superalloy, and 1x platinum alloy and 6 stents showed poor results (1x nitinol, and 5x 316L. Conclusion. Stent lumen visibility varies depending on the stent material and type. Some products show good lumen visibility which may allow the detection of stenoses inside the lumen, while other products cause artifacts which prevent reliable evaluation of the stent lumen with this technique.

  14. Selective pharmacological modulation of renal peripheral-type benzodiazepine binding by treatment with diuretic drugs

    International Nuclear Information System (INIS)

    Lukeman, D.S.; Vaughn, D.A.; Fanestil, D.D.

    1988-01-01

    The authors have assessed the effects of in vivo administration of different classes of diuretic drugs on the expression of the peripheral-type benzodiazepine binding site (PBBS) in crude membranes derived from the cortex and outer medulla of rat kidney by saturation analysis with the PBBS-selective ligands [ 3 H]RO5-4864 and [ 3 H]PH 11195 in cortex and [ 3 H]RO5-4864 in outer medulla. Administration for 14-15 days of furosemide, a drug that blocks NaCl-KCl coupled transport in the thick ascending limb of the loop of Henle, produced a significant doubling in the PBBS density (B/sub max/) in outer medulla, a region of the kidney rich in thick ascending limbs, and produced a lesser but significant increase in PBBS density in the cortex. Conversely, administration for 14-15 days of the carbonic anhydrase inhibitor acetazolamide, which acts predominantly in the proximal tubule, and hydrochlorothiazide, which acts predominantly in the early distal tubule, elicited statistically significant increases in PBBS density in renal cortex but not in renal outer medulla. Furthermore, all drug treatments were without effect on the equilibrium dissociation constants (K/sub d/s) of [ 3 H]RO5-4864 and [ 3 H]PK 11195 binding to cortical and outer medullary membrane preparations. These findings demonstrate that the PBBS can be selectively up-regulated in different regions of the kidney by diuretic drugs with different modes/sites of action. 50 references, 1 table

  15. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

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    Yan Cao

    2017-01-01

    Full Text Available Peripheral ulcerative keratitis (PUK is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Wegener granulomatosis (WG, relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.

  16. Profile of peripheral blood neutrophil cytokines in diabetes type 1 pregnant women and its correlation with selected parameters in the newborns.

    Science.gov (United States)

    Pertyńska-Marczewska, Magdalena; Głowacka, Ewa; Grodzicka, Alicja; Sobczak, Małgorzata; Cypryk, Katarzyna; Wilczyński, Jacek R; Wilczyński, Jan

    2010-02-01

    Interleukin (IL)-12, IL-10, tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 alter as pregnancy progresses, implying continuous immune regulation associated with the maintenance of pregnancy. We aimed to evaluate the peripheral blood neutrophil-derived production of these cytokines in the course of pregnancy complicated by type 1 diabetes. of study These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (P) and pregnant diabetic (PD) women. Neutrophil-derived secretion of TNF-alpha and IL-12 increased along with progression of pregnancy in PD and P groups. The concentration of IL-10 from lipopolysaccharide (LPS)-stimulated neutrophils increased during the course of uncomplicated pregnancy but decreased in diabetic pregnancy. Concentration of IL-8 decreased with the advancing gestational age in P and PD groups. LPS-stimulated neutrophil-derived IL-6 concentration increased only in PD patients. Our results show that diabetes creates pro-inflammatory environment thus potentially influencing the outcome of pregnancy. We conclude that neutrophil-derived cytokine production could contribute to the complications seen in pregnant women with type 1 diabetes.

  17. Peripheral Nerve Repair and Prevention of Neuroma Formation

    Science.gov (United States)

    2014-09-01

    bone disease in Neurofibromatosis type I. Molecular genetics and metabolism . 2008;94(1):105-11. doi: 10.1016/j.ymgme.2007.12.004. PubMed PMID...isolated from dog, and continue to develop them in a canine model of peripheral nerve extension- repair as well as characterize their contribution...Task 1: To test the functional contribution of the mouse/human cells (athymic rats) and their canine counterpart ( canine ) in critical size nerve

  18. Complementary therapies for peripheral arterial disease: systematic review.

    Science.gov (United States)

    Pittler, Max H; Ernst, Edzard

    2005-07-01

    While peripheral arterial disease (PAD) affects a considerable proportion of patients in the primary care setting, there is a high level of use of complementary treatment options. The aim was to assess the effectiveness of any type of complementary therapy for peripheral arterial disease. A systematic review was performed. Literature searches were conducted on Medline, Embase, Amed, and the Cochrane Library until December 2004. Hand-searches of medical journals and bibliographies were conducted. There were no restrictions regarding the language of publication. The screening of studies, selection, data extraction, the assessment of methodologic quality and validation were performed independently by the two reviewers. Data from randomized controlled trials, and systematic reviews and meta-analyses, which based their findings on the results of randomized controlled trials were included. Seven systematic reviews and meta-analyses and three additional randomized controlled trials met the inclusion criteria and were reviewed. The evidence relates to acupuncture, biofeedback, chelation therapy, CO(2)-applications and the dietary supplements Allium sativum (garlic), Ginkgo biloba (ginkgo), omega-3 fatty acids, padma 28 and Vitamin E. Most studies included only patients with peripheral arterial disease in Fontaine stage II (intermittent claudication). The reviewed RCTs, systematic reviews and meta-analyses which based their findings on the results of RCTs suggest that G. biloba is effective compared with placebo for patients with intermittent claudication. Evidence also suggests that padma 28 is effective for intermittent claudication, although more data are required to confirm these findings. For all other complementary treatment options there is no evidence beyond reasonable doubt to suggest effectiveness for patients with peripheral arterial disease.

  19. Peripheral nerve blocks in pediatric anesthesia

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    Novaković Dejan

    2009-01-01

    Full Text Available Introduction Most children undergoing surgery can benefit from regional anesthetic techniques, either as the sole anesthetic regimen or, as usual in pediatric practice, in combination with general anesthesia. The use of peripheral nerve blocks (PNBs in pediatric anesthesia is an effective way to decrease the side-effects and complications associated with central blocks. In spite of their many advantages, including easy performance end efficacy, peripheral nerve blocks are still underused. Objective This article discusses a general approach to PNBs in children and provides data concerning the practice of this regional technique in different age groups. Methods Data from 1,650 procedures were prospectively collected during the period from March 1, 2007 to February 29, 2008. The type of PNB, if any, as well as the patient age were noted. Our patients were divided into four groups: 0-3 years, 4-7 years, 8-12 years and 13-18 years. Results During the investigated period, PNBs as a sole technique or in anesthetized children were performed in 7.45% of cases. Ilioingunal/iliohypogastric nerve block and penile block were the most common (70% of all PNBs distributed mainly among the children between 4-7 years of age (p<0.05. In older children, extremity PNBs predominate in regard to other types of blocks. PNBs are most frequently performed under general anesthesia (85%, so the perineural approach requires a safe technique to avoid nerve damage. Conclusion The observed differences in PNB usage seem to be related to patient age and correlate with common pathology and also with technical availability of PNB performance.

  20. Silencing of CXCR4 inhibits tumor cell proliferation and neural invasion in human hilar cholangiocarcinoma.

    Science.gov (United States)

    Tan, Xin-Yu; Chang, Shi; Liu, Wei; Tang, Hui-Huan

    2014-03-01

    To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (philar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.

  1. Mass-forming cholangiocarcinoma and adenocarcinoma of unknown primary: can they be distinguished on liver MRI?

    Science.gov (United States)

    Al Ansari, Najwa; Kim, Bong Soo; Srirattanapong, Saowanee; Semelka, Charles T A; Ramalho, Miguel; Altun, Ersan; Woosley, John T; Calvo, Benjamin; Semelka, Richard C

    2014-12-01

    To determine MR features suggestive of mass-forming cholangiocarcinoma (CCA) or liver metastases of adenocarcinoma of unknown primary (AUP), and to compare the ability of two experienced radiologists to establish the correct diagnosis. 61 patients with CCA or AUP, with MRIs were placed into two groups: population 1, 28 patients with certain diagnosis of either CCA or AUP; and population 2, 33 patients with uncertain diagnosis. Using population 1 with known diagnosis, two investigators formulated imaging criteria for CCA or AUP, which represented phase 1 of the study. In phase 2, two independent radiologists categorized the patients in populations 1 and 2 as CCA or AUP using the formulated criteria. This categorization was compared with the patient medical records and pathologist review. Findings were tested for statistical significance. In phase 1, solitary lesion, multifocal lesions with dominant lesion, capsule retraction, and porta hepatis lymphadenopathy were features of CCA; multifocal lesions with similar size, and ring enhancement were features of AUP. The number of lesions, capsule retraction, and early tumor enhancement pattern were observed to be significant features (P AUP are identifiable on MRI images, which may aid the radiologist to establish the correct diagnosis.

  2. Intraoperative Ultrasound for Peripheral Nerve Applications.

    Science.gov (United States)

    Willsey, Matthew; Wilson, Thomas J; Henning, Phillip Troy; Yang, Lynda J-S

    2017-10-01

    Offering real-time, high-resolution images via intraoperative ultrasound is advantageous for a variety of peripheral nerve applications. To highlight the advantages of ultrasound, its extraoperative uses are reviewed. The current intraoperative uses, including nerve localization, real-time evaluation of peripheral nerve tumors, and implantation of leads for peripheral nerve stimulation, are reviewed. Although intraoperative peripheral nerve localization has been performed previously using guide wires and surgical dyes, the authors' approach using ultrasound-guided instrument clamps helps guide surgical dissection to the target nerve, which could lead to more timely operations and shorter incisions. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Plain radiologic findings of primary lung cancer by histologic types

    International Nuclear Information System (INIS)

    Lee, Young Seok; Park, Jae Hyung; Choi, Byung In; Yeon, Kyung Mo; Kim, Chu Wan

    1983-01-01

    Plain chest films are the most useful modality in diagnosis of primary lung cancer, but it is difficult to interpret the radiologic findings by histological types. Authors reviewed chest films of 324 cases of histologically confirmed primary lung cancer from January 1974 to April 1982 at Seoul National University. The results are as follows; 1. Incidence was most common in the 6th decade as 34.4%. Male to female sex radio was 3.8 : 1 and there was no sex difference in Adenocarcinoma. 2. Distribution of histologic types of primary lung cancers as follows; Squamous cell carcinoma 50.6%, Small cell carcinoma 22.5%, Large cell carcinoma 9.3%, Bronchogenic adeno carcinoma 10.5%, Bronchioloalveolar cell carcinoma 1.9%, Adenosquamous carcinoma 0.6%, Carcinoid tumor 0.3%, Adenoid cystic carcinoma 0.3%. 3. Radiologic findings by histologic types are follows; a) Squamous cell carcinoma commonly present as collapse (51.8%), peripheral mass (40.8%), pneumonitis (37.2%), hilar involvement (34.8%), and in single abnormality, peripheral mass (44.4%). b) Small cell carcinoma commonly present as hilar involvement (78.1%), mediastinal widening or mass (53.4%) and in single abnormality, hilar involvement (58.3%). c) Large cell carcinoma commonly present as hilar involvement (50%), pneumonia (46.7%), collapse (40%), peripheral mass (36.7%) and in single abnormality, large peripheral mass (33.3%). d) Bronchogenic adenocarcinoma commonly present as peripheral mass (44.1%), collapse (41.2%), pleural effusion (35.2%) and in single abnormality, peripheral mass (50%). e) Solitary peripheral mass commonly present as lobulation (48%) and spiculated margin (51%), but no specific findings by histologic types. Cavitary formation was most common in Squamous cell carcinoma

  4. Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy

    OpenAIRE

    Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J.

    2011-01-01

    Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicati...

  5. Mini-review: Far peripheral vision.

    Science.gov (United States)

    Simpson, Michael J

    2017-11-01

    The region of far peripheral vision, beyond 60 degrees of visual angle, is important to the evaluation of peripheral dark shadows (negative dysphotopsia) seen by some intraocular lens (IOL) patients. Theoretical calculations show that the limited diameter of an IOL affects ray paths at large angles, leading to a dimming of the main image for small pupils, and to peripheral illumination by light bypassing the IOL for larger pupils. These effects are rarely bothersome, and cataract surgery is highly successful, but there is a need to improve the characterization of far peripheral vision, for both pseudophakic and phakic eyes. Perimetry is the main quantitative test, but the purpose is to evaluate pathologies rather than characterize vision (and object and image regions are no longer uniquely related in the pseudophakic eye). The maximum visual angle is approximately 105 0 , but there is limited information about variations with age, race, or refractive error (in case there is an unexpected link with the development of myopia), or about how clear cornea, iris location, and the limiting retina are related. Also, the detection of peripheral motion is widely recognized to be important, yet rarely evaluated. Overall, people rarely complain specifically about this visual region, but with "normal" vision including an IOL for >5% of people, and increasing interest in virtual reality and augmented reality, there are new reasons to characterize peripheral vision more completely. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Acute injury in the peripheral nervous system triggers an alternative macrophage response

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    Ydens Elke

    2012-07-01

    Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

  7. A case of autoimmune cholangitis misdiagnosed for cholangiocarcinoma: How to avoid unnecessary surgical intervention?

    Directory of Open Access Journals (Sweden)

    Ignjatović Igor I.

    2015-01-01

    Full Text Available Introduction. Autoimmune cholangitis or immunoglobulin G4-associated cholangitis (IAC has been recently regarded as a new clinical and histopathological entity and is a part of a complex autoimmune disorder - IgG4-related systemic disease (ISD. ISD is an autoimmune disease with multi-organic involvement, characterized with IgG4-positive plasmocytic infiltration of various tissues and organs with a consequent sclerosis, which responds well to steroid therapy. Most commonly affected organs are the pancreas (autoimmune pancreatitis, [AIP] and the common bile duct (IAC. IAC and cholangiocarcinoma (CCA share many clinical, laboratory and imaging findings. Case Outline. We present a case of a 60-year-old male with a biliary stricture of a common bile duct, which was clinically considered as a bile duct carcinoma and treated surgically. Definite histopathological findings and immunohistochemistry revealed profound chronic inflammation, showing lymphoplasmacytic IgG-positive infiltration of a resected part of a common bile duct, highly suggestive for the diagnosis of IAC. In addition, postoperative IgG4 serum levels were also increased. Conclusion. It is of primary clinical importance to make a difference between IAC and CCA, in order to avoid unnecessary surgical intervention. Therefore, IAC should be considered in differential diagnosis in similar cases.

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

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    Zhou Yanming

    2012-07-01

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

  9. Tenascin-C in peripheral nerve morphogenesis.

    Science.gov (United States)

    Chiquet, M; Wehrle-Haller, B

    1994-01-01

    The extracellular matrix (ECM) molecule tenascin/cytotactin (TN-C) is expressed at a high level by satellite (glial precursor) cells in developing peripheral nerves of the chick embryo; synthesis of its mRNA peaks at the time period when axonal growth is maximal. When offered as a substrate in vitro, TN-C mediates neurite outgrowth by both motor and sensory neurons. The ability to grow neurites on TN-C is developmentally regulated: sensory neurons from 4-day chick embryos (the stage at which peripheral nerves start to develop) grow immediately and rapidly, whereas neurons from older embryos respond with a long delay. A TN-C domain responsible for this activity is located within the C-terminal (distal) portion of TN-C subunits. Integrin receptors seem to be involved on peripheral neurites because their growth on TN-C is completely blocked by antibodies to beta 1 integrins. In striking contrast to neuronal processes, nerve satellite cells can attach to a TN-C substrate but are completely inhibited in their migratory activity. Artificial substrate borders between tenascin and fibronectin or laminin act as selective barriers that allow neurites to pass while holding up satellite cells. The repulsive action of TN-C on satellite cells is similar to that observed for other cell types and is likely to be mediated by additional TN-C domains. In view of these data, it is surprising that mice seem to develop normally without a functional TN-C gene. TN-C is likely to be redundant, that is, its dual action on cell adhesion is shared by other molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects.

    Science.gov (United States)

    Savic, Lynn Jeanette; Chapiro, Julius; Geschwind, Jean-François H

    2017-02-01

    Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed.

  11. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Chan-on W

    2015-04-01

    Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

  12. Oral warfarin affects peripheral blood leukocyte IL-6 and TNFα production in rats.

    Science.gov (United States)

    Popov, Aleksandra; Belij, Sandra; Subota, Vesna; Zolotarevski, Lidija; Mirkov, Ivana; Kataranovski, Dragan; Kataranovski, Milena

    2013-01-01

    Warfarin is a Vitamin K (VK) antagonist that affects Vitamin K-dependent (VKD) processes, including blood coagulation, as well as processes unrelated to hemostasis such as bone growth, calcification, and growth of some cell types. In addition, warfarin exerts influence on some non-VKD-related activities, including anti-tumor and immunomodulating activity. With respect to the latter, both immune stimulating and suppressive effects have been noted in different experimental systems. To explore the in vivo immunomodulatory potential of warfarin on one type of activity (i.e., cytokine production) in two different immune cell populations (i.e., mononuclear or polymorphonuclear cells), effects of subchronic oral warfarin intake in rats on pro-inflammatory cytokine (i.e., TNFα, IL-6) production by peripheral blood mononuclear and polymorphonuclear cells (granulocytes) was examined. Differential effects of warfarin intake on TNFα and IL-6 were noted, depending on the type of peripheral blood leukocytes and on the cytokine examined. Specifically, a lack of effect on TNFα and a priming of IL-6 production by mononuclear cells along with a decrease in TNFα and a lack of effect on IL-6 in polymorphonuclear cells were seen in warfarin-exposed hosts. The cell- and cytokine-dependent effects from subchronic oral warfarin intake on peripheral blood leukocytes demonstrated in this study could, possibly, differentially affect reactions mediated by these cells. Ultimately, the observed effects in rats might have implications for those humans who are on long-term/prolonged warfarin therapy.

  13. Isolation, propagation, and titration of human immunodeficiency virus type 1 from peripheral blood of infected individuals

    NARCIS (Netherlands)

    Schuitemaker, Hanneke; Kootstra, Neeltje A.

    2005-01-01

    HIV-1 can be isolated from peripheral blood mononuclear cells and is easily propagated on primary cells in vitro. Here we describe the method for bulk isolation of the HIV-1 quasispecies and a limiting dilution virus isolation protocol by which single coexisting clones can be obtained. In addition,

  14. Long term clinical outcome of peripheral nerve stimulation in patients with chronic peripheral neuropathic pain

    DEFF Research Database (Denmark)

    Calenbergh, F. Van; Gybels, J.; Laere, K. Van

    2009-01-01

    BACKGROUND: Chronic neuropathic pain after injury to a peripheral nerve is known to be resistant to treatment. Peripheral nerve stimulation is one of the possible treatment options, which is, however, not performed frequently. In recent years we have witnessed a renewed interest for PNS. The aim...... of the present study was to evaluate the long-term clinical efficacy of PNS in a group of patients with peripheral neuropathic pain treated with PNS since the 1980s. METHODS: Of an original series of 11 patients, 5 patients could be invited for clinical examination, detailed assessment of clinical pain and QST...... functioning) also showed positive effects. Quantitative Sensory Testing results did not show significant differences in cold pain and heat pain thresholds between the "ON" and "OFF" conditions. CONCLUSION: In selected patients with peripheral neuropathic pain PNS remains effective even after more than 20...

  15. Effect of insulin-induced hypoglycaemia on the peripheral nervous system

    DEFF Research Database (Denmark)

    Jensen, Vivi Flou Hjorth; Mølck, A.-M.; Bøgh, I. B.

    2014-01-01

    Insulin-induced hypoglycaemia (IIH) is a common acute side effect in type 1 and type 2 diabetic patients, especially during intensive insulin therapy. The peripheral nervous system (PNS) depends on glucose as its primary energy source during normoglycaemia and, consequently, it may be particularly...... state exceeds a certain level of severity and duration, resulting in a sensory-motor neuropathy with associated skeletal muscle atrophy. Large myelinated motor fibres appear to be particularly vulnerable. Thus, although the PNS is not an obligate glucose consumer, as is the brain, it appears to be more...

  16. Analysis of changes of serum leptin, C-peptide levels and peripheral fat tissue leptin receptor expression in obesity

    International Nuclear Information System (INIS)

    Du Tongxin; Sun Junjiang; Wang Shukui; Fu Lei

    2002-01-01

    Objective: To explore the mechanism of obesity and obesity accompanied type two diabetes mellitus by investigating changes of serum leptin, C-peptide (C-P) levels and leptin receptor expression in peripheral adipose tissues. Methods: Peripheral leptin receptor density was measured via radio-ligand binding method, serum leptin and C - P levels were measured via radioimmunoassay in 91 cases (38 in obesity group, 23 in over weight, and 30 in normal controls). Results: With the increase of body mass index (BMI), the peripheral leptin receptor density of the over weight and obese cases decreased and was mash less than that of normal cases (both p<0.01, respectively). There was no statistical differences for Kd value among the three groups, suggesting no associated change between the binding ability of leptin receptor to its ligand. There was a negative correlation between BMI and leptin receptor density (r = -0.70, p < 0.01). The serum leptin and C-P levels in weight excess and obese subjects with type two DM were both increased, but significantly higher in obese group than those in weight excess group (p < 0.01). The increase of C-P was much marked than that of leptin. Serum C-P level was positively correlated with BMI. Conclusion: Changes of serum leptin, C-P levels and peripheral leptin receptor expression in cases with simple obesity and obesity accompanied with type two DM were related closely with BMI. Type 2 DM in obese subjects was related with leptin resistance and insulin resistance

  17. The heat shock protein 90 inhibitor 17-AAG suppresses growth and induces apoptosis in human cholangiocarcinoma cells.

    Science.gov (United States)

    Zhang, Jianjun; Zheng, Zhichao; Zhao, Yan; Zhang, Tao; Gu, Xiaohu; Yang, Wei

    2013-11-01

    The aim of this study was to investigate the effects of 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, on the proliferation, cell cycle, and apoptosis of human cholangiocarcinoma (CCA) cells. Cell proliferation and cell cycle distribution were measured by the MTT assay and flow cytometry analysis, respectively. Induction of apoptosis was determined by flow cytometry and Hoechst staining. The expressions of cleaved poly ADP-ribose polymerase (PARP), Bcl-2, Survivin, and Cyclin B1 were detected by Western blot analysis. The activity of caspase-3 was also examined. We found that 17-AAG inhibited cell growth and induced G2/M cell cycle arrest and apoptosis in CCA cells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the up-regulation of cleaved PARP. Moreover, increased caspase-3 activity was also observed in CCA cells treated with 17-AAG. In conclusion, our data suggest that the inhibition of HSP90 function by 17-AAG may provide a promising therapeutic strategy for the treatment of human CCA.

  18. Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

    Science.gov (United States)

    Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

    2016-03-01

    favor of peripheral nerve injury of various types and optic neuropathy of the axonal type.

  19. Motives for moving to rural, peripheral areas - work, “rural idyll” or “income transfer”

    DEFF Research Database (Denmark)

    Andersen, Hans Skifter; Nørgaard, Helle

    2012-01-01

    Much interest is given to attracting new settlement in rural, peripheral areas due to long-term population loss. The ideal type of settler is identified as families with young children. However, various studies on rural migration show that migrants are a mixed group of young, middle aged and older...... couples and individuals as well as families with children. A large part of the migrants have jobs while other are unemployed or on other types of social welfare. In a Danish context a key hypothesis is that especially welfare recipients and those outside the labor market settle in the countryside due...... to low housing prices. This article explores which groups of people move to rural, peripheral areas and why they chose to do so....

  20. Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb.

    Science.gov (United States)

    Kowalska, Berta; Sudoł-Szopińska, Iwona

    2012-06-01

    The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the "elevator technique". All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the "Journal of Ultrasonography".

  1. Modeling peripheral olfactory coding in Drosophila larvae.

    Directory of Open Access Journals (Sweden)

    Derek J Hoare

    Full Text Available The Drosophila larva possesses just 21 unique and identifiable pairs of olfactory sensory neurons (OSNs, enabling investigation of the contribution of individual OSN classes to the peripheral olfactory code. We combined electrophysiological and computational modeling to explore the nature of the peripheral olfactory code in situ. We recorded firing responses of 19/21 OSNs to a panel of 19 odors. This was achieved by creating larvae expressing just one functioning class of odorant receptor, and hence OSN. Odor response profiles of each OSN class were highly specific and unique. However many OSN-odor pairs yielded variable responses, some of which were statistically indistinguishable from background activity. We used these electrophysiological data, incorporating both responses and spontaneous firing activity, to develop a bayesian decoding model of olfactory processing. The model was able to accurately predict odor identity from raw OSN responses; prediction accuracy ranged from 12%-77% (mean for all odors 45.2% but was always significantly above chance (5.6%. However, there was no correlation between prediction accuracy for a given odor and the strength of responses of wild-type larvae to the same odor in a behavioral assay. We also used the model to predict the ability of the code to discriminate between pairs of odors. Some of these predictions were supported in a behavioral discrimination (masking assay but others were not. We conclude that our model of the peripheral code represents basic features of odor detection and discrimination, yielding insights into the information available to higher processing structures in the brain.

  2. Treatment of painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Rosenberg, Casandra J; Watson, James C

    2015-02-01

    Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

  3. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Peripheral neuropathy in HIV: prevalence and risk factors

    Science.gov (United States)

    Evans, Scott R.; Ellis, Ronald J.; Chen, Huichao; Yeh, Tzu-min; Lee, Anthony J.; Schifitto, Giovanni; Wu, Kunling; Bosch, Ronald J.; McArthur, Justin C.; Simpson, David M.; Clifford, David B.

    2011-01-01

    Objectives To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. Design AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Methods Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Results Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/µl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Conclusion Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for

  5. Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus.

    Science.gov (United States)

    Zhao, Zhenzhou; Li, Xuejie; Jian, Dongdong; Hao, Peiyuan; Rao, Lixin; Li, Muwei

    2017-03-01

    The purpose of the current study was to investigate the characteristic expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre-diabetes and T2DM. CircRNAs in the peripheral blood from six healthy individuals and six T2DM patients were collected for microarray analysis, and an independent cohort study consisting of 20 normal cases, 20 pre-diabetes patients and 20 T2DM patients was conducted to verify the five chosen circRNAs. We then tested hsa_circ_0054633 in a third cohort (control group, n = 60; pre-diabetes group, n = 63; and T2DM group, n = 64) by quantitative real-time polymerase chain reaction (Q-PCR). In total, 489 circRNAs were discovered to be differentially expressed between the two groups, and of these, 78 were upregulated and 411 were downregulated in the T2DM group. Five circRNAs were then selected as candidate biomarkers and further verified in a second cohort. Hsa_circ_0054633 was found to have the largest area under the curve (AUC). The diagnostic capacity of hsa_circ_0054633 was tested in a third cohort. After introducing the risk factors of T2DM, the hsa_circ_0054633 AUCs for the diagnosis of pre-diabetes and T2DM slightly increased from 0.751 (95% confidence interval [0.666-0.835], P diabetes and T2DM.

  6. Peripheral Vestibular System Disease in Vestibular Schwannomas

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Hansen, Søren; Caye-Thomasen, Per

    2015-01-01

    density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. CONCLUSION: Vestibular schwannomas...... are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which...

  7. Tension type headaches: a review

    African Journals Online (AJOL)

    Location of the pain:There is often a typical location for tension- type headaches, as ... Cranial nerve abnormalities, including papilloedema. • Signs of ... peripheral and central mechanisms underlie tension-type ... Physiotherapy has been shown to be an effective management option for .... Acupuncture in primary headache.

  8. Cutaneous manifestations of diabetic peripheral neuropathy.

    Science.gov (United States)

    Dogiparthi, S N; Muralidhar, K; Seshadri, K G; Rangarajan, S

    2017-01-01

    There is a rise in number of people diagnosed with Diabetes Mellitus. The incidence is rising in modern Indian society because of Industrial development and drastically changing lifestyles. Diabetic neuropathies are microvascular disorders that are usually associated with the duration of Diabetes. Among the various forms, the most common is Diabetic Peripheral Neuropathy. The disease if neglected leads to chronic ulcer formation leading to amputations frequently. Hence the aim of this study is to document the early cutaneous changes and create an early awareness in the importance of controlling Diabetes. The study consisted of 205 patients with Type 2 DM. Participant's neuropathy status was determined based on Neuropathy Disability Score and Diabetic Neuropathy Symptom Score. Among the Skin changes documented, the common changes seen were: Peripheral hair loss in 185 (90.2%), Xerosis in 168 (82%), Anhydrosis in 162 (79%), Plantar Fissures in 136 (66.3%), Plantar Ulcer in 80 (39%), common nail changes documented were Onychomycosis in 165 (80.5%) and Onychauxis in 53 (25.8%) patients in relation to the occupation and duration of Diabetes mellitus. In conclusion, it is important to control glycemic levels in the all stages of Diabetes and institute foot care measures to prevent the complications of neuropathy.

  9. Elevated levels of peripheral blood CD14(bright) CD16+ and CD14(dim) CD16+ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes.

    Science.gov (United States)

    Ryba-Stanisławowska, Monika; Myśliwska, Jolanta; Juhas, Ulana; Myśliwiec, Małgorzata

    2015-09-01

    The study aimed to analyze the CD14(bright) CD16(+) and CD14(dim) CD16(+) monocyte subsets in juvenile-onset complication-free diabetes mellitus type 1 in the context of their association with microvascular complications. 61 children with type 1 diabetes and 30 healthy individuals were enrolled in a study. CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes were quantified in peripheral blood by means of flow cytometry. At the time of sampling blood glucose concentration was taken along with biochemical measurement of renal function, CRP and glycosylated hemoglobin. The Spearman's correlations were used to compare the relationship between CD16(+) monocyte subsets and the clinical parameters that can predict the development of microangiopathies. The flow cytometric analysis of monocyte subsets in peripheral blood of analyzed subjects revealed that the numbers of CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes were significantly higher in patients with type 1 diabetes than in the healthy individuals. As to the relationship between CD16(+) monocyte subsets and the clinical parameters that can predict development of microangiopathies, it was shown that both CD16(+) subsets were associated with increased risk of retinopathy development, defined as retinopathy development value. Elevated levels of intermediate CD14(bright) CD16(+) and non-classical CD14(dim) CD16(+) monocytes predict development of diabetic retinopathy in patients with type 1 diabetes. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  10. Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

    KAUST Repository

    Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothsteinb, Jeffrey D.

    2015-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21. days in wild-type mice to greater than 38. days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote mice have no recovery of CMAP at 42. days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42. days post-crush in the MCT1 heterozygote mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote mice at 4. weeks and tibial mixed sensory and motor nerve at 3. weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush.

  11. Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status.

    LENUS (Irish Health Repository)

    O'Sullivan, Eoin P

    2010-12-01

    Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)\\/RANKL\\/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking.

  12. Toll-Like Receptor-Mediated Free Radical Generation in Clonorchis sinensis Excretory-Secretory Product-Treated Cholangiocarcinoma Cells.

    Science.gov (United States)

    Bahk, Young Yil; Pak, Jhang Ho

    2016-10-01

    Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-κB-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.

  13. Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma

    International Nuclear Information System (INIS)

    Seol, Min-A; Kim, Dae-Ghon; Chu, In-Sun; Lee, Mi-Jin; Yu, Goung-Ran; Cui, Xiang-Dan; Cho, Baik-Hwan; Ahn, Eun-Kyung; Leem, Sun-Hee; Kim, In-Hee

    2011-01-01

    The molecular mechanisms of CC (cholangiocarcinoma) oncogenesis and progression are poorly understood. This study aimed to determine the genome-wide expression of genes related to CC oncogenesis and sarcomatous transdifferentiation. Genes that were differentially expressed between CC cell lines or tissues and cultured normal biliary epithelial (NBE) cells were identified using DNA microarray technology. Expressions were validated in human CC tissues and cells. Using unsupervised hierarchical clustering analysis of the cell line and tissue samples, we identified a set of 342 commonly regulated (>2-fold change) genes. Of these, 53, including tumor-related genes, were upregulated, and 289, including tumor suppressor genes, were downregulated (<0.5 fold change). Expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPARγ, KRT17, UCHL1, IGFBP7 and SPARC proteins was immunohistochemically verified in human and hamster CC tissues. Additional unsupervised hierarchical clustering analysis of sarcomatoid CC cells compared to three adenocarcinomatous CC cell lines revealed 292 differentially upregulated genes (>4-fold change), and 267 differentially downregulated genes (<0.25 fold change). The expression of 12 proteins was validated in the CC cell lines by immunoblot analysis and immunohistochemical staining. Of the proteins analyzed, we found upregulation of the expression of the epithelial-mesenchymal transition (EMT)-related proteins VIM and TWIST1, and restoration of the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 during sarcomatoid transdifferentiation of CC. The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis

  14. Neovascular Glaucoma Induced by Peripheral Retinal Ischemia in Neurofibromatosis Type 1: Management and Imaging Features

    Directory of Open Access Journals (Sweden)

    Francesco Pichi

    2013-04-01

    Full Text Available Purpose: To report the case of a young patient affected by neurofibromatosis 1 (NF-1 with peripheral retinal ischemia-induced neovascular glaucoma and the peculiar spectral-domain optical coherence tomography (SD-OCT features. Material and Methods: A 13-year-old boy affected by NF-1, as diagnosed according to established criteria, was referred with a diagnosis of hypertensive uveitis in his left eye. He underwent a complete ophthalmic examination and comprehensive blood work with viral and immunological tests. The case was documented with fluorescein angiography (FA and SD-OCT. When the intraocular pressure (IOP of the left eye decreased and the cornea cleared, FA revealed retinal ischemia and leakage from pathologic retinal vessels. SD-OCT revealed foveal hypoplasia secondary to the complete absence of the retinal nerve fiber layer. Results: Peripheral retinal ischemia-induced neovascular glaucoma was diagnosed. The patient underwent Ahmed valve implantation to control his IOP, and subsequent retinal photocoagulation by argon laser and intravitreal bevacizumab injection were performed to control neovascularization. Discussion: Retinal ischemia in NF-1 might lead to neovascular glaucoma: lowering of the IOP with surgical implantation of an Ahmed valve, regression of neovascularization by argon laser panretinal photocoagulation and intravitreal injection of bevacizumab can be a helpful way to control such a complication.

  15. The interventional treatment for recurrent jaundice after palliative bilio-intestinal anastomosis in patients with malignant obstructive jaundice due to cholangiocarcinoma

    International Nuclear Information System (INIS)

    Han Xinwei; Li Yongdong; Li Tianxiao; Ma Bo; Xing Gusheng; Wu Gang

    2002-01-01

    Objective: To explore the interventional methods to treat recurrent jaundice after palliative bilio-intestinal anastomosis in patients with malignant obstructive jaundice due to cholangiocarcinoma. Methods: Ten patients with recurrent jaundice after bilio-intestinal anastomosis were retrospectively evaluated. Nine of ten underwent PTCD with metallic stent placement, one underwent the inner-outer draining catheter procedure. The patients were evaluated with comparison in regard to preoperative conditions, TBIL, ALT, GTP and AKP values. Results: Stent placement was successful only once in all 10 cases with successful rate of 100%. TBIL, ALT, GTP and AKP values were significantly lower 7 days postoperative than that preoperation. Subsidence of jaundice was satisfactory for 100% in all patients after the treatment. Conclusions: Percutaneous placement of biliary metallic stents is a safety, simple, low complication method for managing recurrent jaundice after palliative bilio-intestinal anastomosis for the terminal stage of malignant obstructive jaundice

  16. Hypothyroidism: Can It Cause Peripheral Neuropathy?

    Science.gov (United States)

    Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

  17. Peripheral ameloblastic fibro-odontoma or peripheral developing complex odontoma: report of a case

    DEFF Research Database (Denmark)

    Reibel, Jesper; Grønbæk, Anni Birgitte; Poulsen, Sven

    2011-01-01

    BACKGROUND. Peripheral (extraosseous) odontogenic tumors are rare. CASE REPORT. This report describes a case which illustrates the clinical and histopathological features of a lesion in an 8-year-old, healthy Caucasian girl that on purely morphological grounds would seem to be an ameloblastic fibro-odontoma......, but may represent a case of a peripheral developing complex odontoma. CONCLUSION. Conservative surgical enucleation of the lesion was followed by unbcomplicated healing and no recurrence was seen....

  18. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  19. Peripheral cemento-ossifying fibroma of maxilla.

    Science.gov (United States)

    Chatterjee, Anirban; Ajmera, Neha; Singh, Amit

    2010-07-01

    Peripheral cemento-ossifying fibroma is a reactive gingival overgrowth occurring frequently in anterior maxilla. It is a slow-growing benign tumor which may lead to pathologic migration and other periodontal problems, so it should be excised as soon as possible. The recurrence rate of peripheral cemento-ossifying fibroma is reported to be 8% to 20%, so a close postoperative follow-up is required. Herein, we are reporting a similar case of peripheral cemento-ossifying fibroma in the maxillary anterior region.

  20. Type-I interferon receptor expression: its circadian rhythm and downregulation after interferon-alpha administration in peripheral blood cells from renal cancer patients.

    Science.gov (United States)

    Shiba, Masahiro; Nonomura, Norio; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Inoue, Hitoshi; Tsujimura, Akira; Nishimura, Kazuo; Okuyama, Akihiko

    2009-04-01

    To investigate the regulation of interferon-alpha (IFN-alpha) receptor expression in metastatic renal cell carcinoma (RCC) after IFN-alpha administration. Blood sampling was carried out in eight patients with metastatic RCC and six healthy volunteers. Flow-cytometric analysis using a monoclonal antibody against the active subunit of the type-I IFN-alpha receptor (IFNAR2) was carried out to examine the circadian rhythm of IFNAR2 expression in peripheral blood mononuclear cells (PBMC) as well as its downregulation after IFN-alpha administration. According to its circadian rhythm IFNAR2 in PBMC had a peak expression at night. Once IFN-alpha is administered, IFNAR2 levels in PBMC showed downregulation within 48 h and recovered within another 48 h. Our findings might support the establishment of an optimal schedule for IFN-alpha administration.