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PubMed - Bile Duct Cancer (40 unread)

Lapatinib/gemcitabine and lapatinib/gemcitabine/oxaliplatin: a phase I study for advanced pancreaticobiliary cancer.

Fetched: April 30th, 2008, 9:00pm EDT

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Lapatinib/gemcitabine and lapatinib/gemcitabine/oxaliplatin: a phase I study for advanced pancreaticobiliary cancer.

Am J Clin Oncol. 2008 Apr;31(2):140-4

Authors: Safran H, Miner T, Resnick M, Dipetrillo T, McNulty B, Evans D, Joseph P, Plette A, Millis R, Sears D, Gutman N, Kennedy T

OBJECTIVE: To evaluate the safety/tolerability and potential antitumor activity of lapatinib, at dose ranges of 1000 to 1500 mg/d, in combination with gemcitabine and gemcitabine/oxaliplatin (GEMOX) in patients with advanced pancreaticobiliary cancer. MATERIALS AND METHODS: Patients with advanced pancreaticobiliary cancer were assigned to 1 of 4 cohorts of lapatinib administered once daily. Toxicities, response, and survival were assessed. RESULTS: Twenty-five patients were enrolled, 18 with pancreatic cancer and 7 with biliary cancer. Lapatinib, 1500 mg/d, was successfully administered with weekly gemcitabine. Dose limiting toxicities of nausea and anorexia occurred in 2 of 5 patients receiving 1500 mg/d lapatinib with GEMOX. The median survival of all patients was 11 months and the 1-year survival was 48%. CONCLUSION: Lapatinib, 1500 mg/d, can be administered with weekly gemcitabine. The maximum tolerated dose of lapatinib is 1000 mg/d with GEMOX. A phase II study of lapatinib and gemcitabine for metastatic pancreatic cancer will be initiated.

PMID: 18391597 [PubMed - indexed for MEDLINE]
Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver.

Fetched: April 30th, 2008, 9:00pm EDT

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Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver.

Mod Pathol. 2008 Feb;21(2):125-30

Authors: Fujii T, Zen Y, Sato Y, Sasaki M, Enomae M, Minato H, Masuda S, Uehara T, Katsuyama T, Nakanuma Y

Podoplanin, which is immunoreactive to D2-40 antibody, is reportedly expressed in lymphatic vessels in non-neoplastic tissues, and also in vascular and non-vascular tumors. However, its expression in non-neoplastic and neoplastic liver tissues has not been well documented. In this study, we examined podoplanin expression in specimens from 10 normal livers and 73 cases of liver tumors: hemangioma (16 cases), epithelioid hemangioendothelioma (9 cases), angiosarcoma (4 cases), angiomyolipoma (7 cases), hepatocellular carcinoma (11 cases), intrahepatic cholangiocarcinoma (11 cases), and metastatic liver cancer (15 cases). We compared levels of podoplanin and other endothelial markers (CD31, CD34, and factor VIII) in liver tumors. In the normal liver, podoplanin was expressed in lymphatic endothelium, nerve fibers, and mesothelium in the hepatic capsule, but not observed in any cells within hepatic lobules. Among liver tumors, podoplanin was specifically expressed in seven of nine cases (78%) of epithelioid hemangioendothelioma but not in other hepatic tumors. The expression of CD31, CD34, and factor VIII was observed in endothelial cells in all cases of hemangioma, epithelioid hemangioendothelioma, angiosarcoma, and angiomyolipoma with one exception, a case of epithelioid hemangioendothelioma which was without CD31 expression. Interestingly, the intensity of podoplanin expression was negatively correlated with the expression of CD34 and factor VIII. In conclusion, podoplanin would be useful as a diagnostic marker for epithelioid hemangioendothelioma in liver tumors.

PMID: 18084256 [PubMed - indexed for MEDLINE]
Management of hilar biliary strictures.

Fetched: April 29th, 2008, 9:00pm EDT

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Management of hilar biliary strictures.

Am J Gastroenterol. 2008 Feb;103(2):458-73

Authors: Larghi A, Tringali A, Lecca PG, Giordano M, Costamagna G

Biliary strictures at the liver hilum are caused by a heterogeneous group of benign and malignant conditions. In the absence of a clear-cut benign etiology, i.e. bile duct damage during surgery, hilar biliary strictures remain a diagnostic and therapeutic challenge for which a multidisciplinary approach is often necessary. A definitive diagnosis can be achieved in only 40-60% of the patients, while in all the other cases strictures are treated as though they are malignant until surgical pathology determines otherwise. Surgical resection is the only treatment that prolongs survival in patients with malignant strictures. Because these tumors frequently extend longitudinally via the hepatic ducts into the liver parenchyma, partial hepatic resection has been gradually added to biliary resection to ensure tumor-free surgical margins. For unresectable cases, endoscopic stenting of biliary obstruction is considered the preferred palliation modality to relieve pruritus, cholangitis, pain and jaundice, while the percutaneous approach has been reserved for cases of failure. Other modalities of treatment such as radiotherapy, chemotherapy, and photodynamic therapy currently remain investigational. For benign post surgical hilar strictures, surgical repair can be difficult and requires specific skills and experience. As an alternative, a multi-stent technique with endoscopic placement of an increasing number of stents over time until complete resolution of the stricture has been proposed.

PMID: 18028506 [PubMed - indexed for MEDLINE]
Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging.

Fetched: April 26th, 2008, 9:00pm EDT

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Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging.

Radiol Med (Torino). 2008 Feb;113(1):76-86

Authors: D'Onofrio M, Vecchiato F, Cantisani V, Barbi E, Passamonti M, Ricci P, Malagò R, Faccioli N, Zamboni G, Pozzi Mucelli R

PURPOSE: This study was done to compare the perfusion patterns of intrahepatic peripheral cholangiocarcinoma (IPCC) on contrast-enhanced ultrasound (CEUS) and dynamic computed tomography (CT). MATERIALS AND METHODS: We retrospectively reviewed 23 histologically proven cases of IPCC. All lesions were studied by CEUS with sulfur hexafluoride-filled microbubbles coated with a phospholipid capsule, and by dynamic CT. Contrast-enhancement patterns were evaluated in the arterial phase (CEUS 10-20 s after the injection; CT 25-30 s after the injection) and in the delayed phase (CEUS 120 s after the injection; CT>2-3 min after the injection). RESULTS: Lesions were single in 18/23 cases (78%), single with nearby satellite lesions in 1/23 (4%) cases and multifocal with distant secondary lesions in 4/23 (17%) cases. Lesion diameter was 2-5 cm in 7/23 cases (30%), 5-7 cm in 13/23 cases (57%) and >7 cm in 3/23 (13%) cases. On CEUS, lesions were hypervascular in 16/23 cases (70%). On delayed-phase CEUS, 22/23 lesions (96%) were markedly hypoechoic. CT showed that the lesions were hypovascular in the arterial phase in 15/23 cases (66%) and hypervascular in 7/23 (30%) cases; one lesion (1/23; 4%) was isovascular. On delayed-phase CT, lesions were hyperdense in 17/23 cases (74%), hypodense in 5/23 (22%) cases and isodense in 1/23 (43%) cases. CONCLUSIONS: Enhancement discrepancy between delayed-phase CEUS (hypoechogenicity) and CT (hyperdensity) is common semiological findings in the study of IPCC.

PMID: 18338129 [PubMed - indexed for MEDLINE]
Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

Fetched: April 25th, 2008, 9:00pm EDT

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Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

Gastroenterology. 2008 Apr;134(4):1203-14

Authors: Strautnieks SS, Byrne JA, Pawlikowska L, Cebecauerová D, Rayner A, Dutton L, Meier Y, Antoniou A, Stieger B, Arnell H, Ozçay F, Al-Hussaini HF, Bassas AF, Verkade HJ, Fischler B, Németh A, Kotalová R, Shneider BL, Cielecka-Kuszyk J, McClean P, Whitington PF, Sokal E, Jirsa M, Wali SH, Jankowska I, Pawłowska J, Mieli-Vergani G, Knisely AS, Bull LN, Thompson RJ

BACKGROUND & AIMS: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. METHODS: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely phenotypic severity were correlated with data on BSEP immunohistochemistry and clinical outcome. RESULTS: Eighty-two different mutations (52 novel) were identified in 109 families (9 nonsense mutations, 10 small insertions and deletions, 15 splice-site changes, 3 whole-gene deletions, 45 missense changes). In 7 families, only a single heterozygous mutation was identified despite complete sequence analysis. Thirty-two percent of mutations occurred in >1 family, with E297G and/or D482G present in 58% of European families (52/89). On immunohistochemical analysis (88 patients), 93% had abnormal or absent BSEP staining. Expression varied most for E297G and D482G, with some BSEP detected in 45% of patients (19/42) with these mutations. Hepatocellular carcinoma or cholangiocarcinoma developed in 15% of patients (19/128). Two protein-truncating mutations conferred particular risk; 38% (8/21) of such patients developed malignancy versus 10% (11/107) with potentially less severe genotypes (relative risk, 3.7 [confidence limits, 1.7-8.1; P = .003]). CONCLUSIONS: With this study, >100 ABCB11 mutations are now identified. Immunohistochemically detectable BSEP is typically absent, or much reduced, in severe disease. BSEP deficiency confers risk of hepatobiliary malignancy. Close surveillance of BSEP-deficient patients retaining their native liver, particularly those carrying 2 null mutations, is essential.

PMID: 18395098 [PubMed - indexed for MEDLINE]
Bile tract adenomyoma: a case report.

Fetched: April 25th, 2008, 9:00pm EDT

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Bile tract adenomyoma: a case report.

World J Gastroenterol. 2008 Jan 28;14(4):647-50

Authors: Shu GM, Wang YJ, Du Z, Li DY, Liu CL

This paper described a rare case of adenomyoma of common bile duct. The case is a 51-year-old man who was hospitalized for yellow color skin and sclera and itching for 2 mo without abdominal pain. Nothing special was found in physical examination except yellowish skin and sclera. The clinical presentation and Computerized Tomography (CT), Magnetic resonance cholangiopancreatography (MRCP), and ultrasonography suspected a tumor of the distal bile duct. The patient was treated successfully by pancreaticoduodenectomy. Histologically, the lesion consisted of adenoid and myofibrous tissue and moderate atypia. The immunophenotype of the epithelial component was cytokeratin 7+/cytokeratin 20-. The patient has been well without any evidence of recurrence for 12 mo since his operation.

PMID: 18203305 [PubMed - indexed for MEDLINE]
Risk factors for intrahepatic cholangiocarcinoma: a case-control study in China.

Fetched: April 25th, 2008, 9:00pm EDT

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

World J Gastroenterol. 2008 Jan 28;14(4):632-5

Authors: Zhou YM, Yin ZF, Yang JM, Li B, Shao WY, Xu F, Wang YL, Li DQ

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

PMID: 18203300 [PubMed - indexed for MEDLINE]
Cholangioscopic removal of a dislocated stent from the cystic duct using a high pressure biliary dilation balloon.

Fetched: April 24th, 2008, 9:00pm EDT

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Cholangioscopic removal of a dislocated stent from the cystic duct using a high pressure biliary dilation balloon.

Endoscopy. 2007 Feb;39 Suppl 1:E337-8

Authors: Graepler F, Raible A, Neuhaus H, Gregor M

PMID: 18273785 [PubMed - indexed for MEDLINE]
Multiple stenting in a patient with a high-grade malignant hilar biliary stricture: endoscopic four-branched partial stent-in-stent deployment of metallic stents.

Fetched: April 24th, 2008, 9:00pm EDT

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Multiple stenting in a patient with a high-grade malignant hilar biliary stricture: endoscopic four-branched partial stent-in-stent deployment of metallic stents.

Endoscopy. 2007 Feb;39 Suppl 1:E167-8

Authors: Kawamoto H, Tsutsumi K, Fujii M, Harada R, Kato H, Hirao K, Kurihara N, Nakanishi T, Mizuno O, Ishida E, Ogawa T, Fukatsu H, Sakaguchi K

PMID: 17614071 [PubMed - indexed for MEDLINE]
Sump syndrome and biliary adenocarcinoma 40 years after surgical choledochoduodenal fistula.

Fetched: April 24th, 2008, 9:00pm EDT

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Sump syndrome and biliary adenocarcinoma 40 years after surgical choledochoduodenal fistula.

Endoscopy. 2007 Feb;39 Suppl 1:E194

Authors: Mecklenburg I, Scheubel R, Messmann H

PMID: 17614061 [PubMed - indexed for MEDLINE]
EUS-guided methylene blue injection into the pancreatic duct as a guide for pancreatic stenting after ampullectomy.

Fetched: April 24th, 2008, 9:00pm EDT

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EUS-guided methylene blue injection into the pancreatic duct as a guide for pancreatic stenting after ampullectomy.

Endoscopy. 2007 Feb;39 Suppl 1:E151-2

Authors: Carrara S, Arcidiacono PG, Diellou AM, Mezzi G, Rossi M, Boemo C, Masci E, Testoni PA

PMID: 17611896 [PubMed - indexed for MEDLINE]
Endoscopic ultrasound-guided pancreaticogastrostomy reconstruction.

Fetched: April 24th, 2008, 9:00pm EDT

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Endoscopic ultrasound-guided pancreaticogastrostomy reconstruction.

Endoscopy. 2007 Feb;39 Suppl 1:E70-1

Authors: Sakamoto H, Kitano M, Komaki T, Takeyama Y, Kudo M

PMID: 17354176 [PubMed - indexed for MEDLINE]
Biliorenous fistula related to self-expandable biliary metallic stent placement: a rare complication of endoscopic retrograde cholangiopancreatography.

Fetched: April 24th, 2008, 9:00pm EDT

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Biliorenous fistula related to self-expandable biliary metallic stent placement: a rare complication of endoscopic retrograde cholangiopancreatography.

Endoscopy. 2007 Feb;39 Suppl 1:E67-8

Authors: Vila JJ, Jiménez FJ, Irisarri R, Vicuña M, Martínez B, Borda F

PMID: 17354174 [PubMed - indexed for MEDLINE]
Periampullary carcinoid tumor.

Fetched: April 24th, 2008, 9:00pm EDT

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Periampullary carcinoid tumor.

Endoscopy. 2007 Feb;39 Suppl 1:E49-50

Authors: Fukatsu H, Kawamoto H, Fujii M, Tsutsumi K, Kato H, Hirao K, Kurihara N, Okamoto Y, Ogawa T, Ishida E, Okada H, Sakaguchi K

PMID: 17285506 [PubMed - indexed for MEDLINE]
Cancer of the papilla causing recurrent acute pancreatitis and mimicking a pancreatic stone.

Fetched: April 24th, 2008, 9:00pm EDT

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Cancer of the papilla causing recurrent acute pancreatitis and mimicking a pancreatic stone.

Endoscopy. 2007 Feb;39 Suppl 1:E2

Authors: Li ZS, Liao Z, Chen J, Wang LW, Wu XH

PMID: 17285500 [PubMed - indexed for MEDLINE]
A new biliary "Y" stent for hilar tumors.

Fetched: April 24th, 2008, 9:00pm EDT

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A new biliary "Y" stent for hilar tumors.

Endoscopy. 2007 Feb;39 Suppl 1:E47-8

Authors: Ramchandani M, Lakhtakia S, Gupta R, Tandan M, Rao GV, Reddy DN

PMID: 17285492 [PubMed - indexed for MEDLINE]
The utility of hepatocyte paraffin 1 antibody in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma.

Fetched: April 23rd, 2008, 9:00pm EDT

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The utility of hepatocyte paraffin 1 antibody in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma.

Malays J Pathol. 2006 Dec;28(2):87-92

Authors: Shiran MS, Isa MR, Sherina MS, Rampal L, Hairuszah I, Sabariah AR

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and its diagnosis on routine stains is usually straightforward, except in some cases where there may be difficulty in distinguishing HCCs from metastatic carcinomas (MC) and cholangiocarcinomas (CC). Hepatocyte Paraffin 1 antibody (Hep Par 1) is a new monoclonal antibody which reacts with normal and neoplastic hepatocytes, and this study aims to determine its specificity and sensitivity in distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic carcinomas (MC). Hep Par 1 antibody was applied to 28 cases of HCC, 22 cases of MC from varying sites and 8 CCs, and produced a strong, diffuse, granular, cytoplasmic staining of all benign hepatocytes. 23 out of 28 cases of HCC showed heterogeneously positive staining for Hep Par 1 irrespective of their degree of differentiation, while 2 out of 8 cases of cholangiocarcinoma were positive for Hep Par 1, and all 22 cases of metastatic carcinoma were negative. The sensitivity and specificity of Hep Par 1 for HCC was 82.1% and 93.3% respectively; whereby the antibody was noted to show occasional false positivity in cases of cholangiocarcinoma and non-neoplastic bowel mucosa, while its variable staining in HCC produced false negative results in some small biopsies. Thus, Hep Par 1 should be used in a panel with other antibodies to obtain useful information in distinguishing HCC from CC and MC.

PMID: 18376797 [PubMed - indexed for MEDLINE]
Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using [18F]-2-fluro-2-deoxy-D-glucose positron emission tomography.

Fetched: April 23rd, 2008, 9:00pm EDT

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Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using [18F]-2-fluro-2-deoxy-D-glucose positron emission tomography.

Cancer Sci. 2008 Feb;99(2):260-6

Authors: Paudyal B, Oriuchi N, Paudyal P, Higuchi T, Nakajima T, Endo K

Cholangiocellular carcinoma (CCC) has been reported to have a high glucose uptake; however, the mechanism of glucose entry into these cells is still unclear. We investigated the relationship between [(18)F]-2-fluro-2-deoxy-D-glucose ((18)F-FDG) uptake and the expression of facilitative glucose transporters (Glut) and hexokinase (HK) II, as well as the association between the expression of different histological types of CCC. The expression of Glut (1-5) and HK II was studied using immunohistochemistry of 26 patients with CCC who underwent whole-body (18)F-FDG positron emission tomography before surgery or biopsy. CCC expressed immunohistochemically detectable Glut 1 in 81%, Glut 2 in 54%, Glut 3 in 19%, and HK II in 77% of the total cases. Glut 1, Glut 2, Glut 3, and HK II were more often detected in moderately differentiated and poorly differentiated than in well-differentiated CCC. A significant correlation was observed between (18)F-FDG uptake and the staining scores of Glut 1 and HK II (P = 0.02, rho = 0.45 and P = 0.001, rho = 0.59). The staining scores of Glut 1 and HK II were also significantly correlated (P = 0.002, rho = 0.3). Multivariate regression analysis revealed that lymph-node metastasis was independently associated with (18)F-FDG uptake. Our study showed a significant association between the expression of Glut 1 and HK II with (18)F-FDG uptake, indicating that Glut 1 is a major glucose transporter expressed in CCC and that HK II contributes to the increased metabolism of glucose, especially in moderately and poorly differentiated CCC.

PMID: 18271924 [PubMed - indexed for MEDLINE]
Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines.

Fetched: April 21st, 2008, 9:00pm EDT

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Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines.

Int J Mol Med. 2007 Dec;20(6):801-8

Authors: Enomoto M, Tsuchida A, Miyazawa K, Yokoyama T, Kawakita H, Tokita H, Naito M, Itoh M, Ohyashiki K, Aoki T

Vitamin K2 (MK4) has antitumor effects on various types of cancer cell lines in vitro, and its efficacy has also been reported in clinical applications for patients with leukemia, myelodysplastic syndrome, and hepatocellular carcinoma (HCC). However, details of the mechanism of the antitumor effects of MK4 remain unclear. In the present study, we examined the antitumor effects of MK4 on cholangiocellular carcinoma (CCC) cell lines and its mechanism of action using the HL-60 leukemia cell line that exerts MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest as a control. MK4 exerted dose-dependent antitumor effects on all three types of CCC cell lines. However, apoptosis occurred in a smaller percentage of cells and there was less cell cycle arrest compared with other cancer cell lines studied previously, which suggested slight MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest. On the contrary, histopathological fidings showed a large number of cells containing vacuoles in their cytoplasm, and electron microscopic findings showed a large number of cytoplasmic autophagosomes and autolysosomes. These findings suggested evidence of autophagy-related cell death. Fluorescence microscopy following acridine orange staining revealed an increase in the number of cytoplasmic acidic vesicular organelles characteristic of autophagy. Moreover, there were few cells forming autophagic vesicles in the control group, while the percentage of cells containing vacuoles in the MK4-treated group increased with the duration of culture. These results suggested that, unlike in leukemia, gastric cancer, HCC, and other cancer cells, the antitumor effects of MK4 on CCC cells are induced via autophagy formation.

PMID: 17982686 [PubMed - indexed for MEDLINE]
Progenitor gene DLK1 might be an independent prognostic factor of liver cancer.

Fetched: April 18th, 2008, 9:00pm EDT

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Progenitor gene DLK1 might be an independent prognostic factor of liver cancer.

Expert Opin Biol Ther. 2008 Apr;8(4):371-7

Authors: Jin ZH, Yang RJ, Dong B, Xing BC

BACKGROUND: Delta-like 1 homolog (DLK1) is a marker for progenitor cells of the liver. The gene encoding DLK1 is expressed early during embryonic development but, importantly, it is also expressed in some human liver cancers. However, the prognostic value of the DLK1 gene has not been investigated. OBJECTIVES: To examine the association between the DLK1 gene and survival time and whether high levels of expression of DLK1 are a prognostic factor for liver cancer. METHODS: We evaluated 60 cases of primary liver cancer, and investigated the link between the expression of DLK1 and patient survival. Clinical characteristics of the cases used for our study, such as tumor size, differentiation and staging, are statistically evenly distributed. Using RT-PCR, western blotting and immunohistochemistry, we analyzed the expression of DLK1 in the tumor samples and evaluated the results statistically. RESULTS: DLK1 was expressed in 22 of the 60 cases (36.7%), and analysis of the survival of the patients revealed that DLK1-positive patients had a shorter survival time than DLK1-negative patients. Cox regression analysis also showed that DLK1 is a risk factor. However, DLK1 expression does not seem to correlate with other classic prognostic factors such as alpha-fetoprotein (AFP), tumor-node-metastasis (TNM) and vascular invasion, which implies that it is an independent prognostic factor.

PMID: 18352842 [PubMed - indexed for MEDLINE]
Photodynamic therapy: standard of care for palliation of cholangiocarcinoma?

Fetched: April 18th, 2008, 9:00pm EDT

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Photodynamic therapy: standard of care for palliation of cholangiocarcinoma?

Clin Gastroenterol Hepatol. 2008 Mar;6(3):266-7

Authors: Baron TH

PMID: 18328433 [PubMed - indexed for MEDLINE]
Unresectable cholangiocarcinoma: comparison of survival in biliary stenting alone versus stenting with photodynamic therapy.

Fetched: April 18th, 2008, 9:00pm EDT

Unresectable cholangiocarcinoma: comparison of survival in biliary stenting alone versus stenting with photodynamic therapy.

Clin Gastroenterol Hepatol. 2008 Mar;6(3):290-7

Authors: Kahaleh M, Mishra R, Shami VM, Northup PG, Berg CL, Bashlor P, Jones P, Ellen K, Weiss GR, Brenin CM, Kurth BE, Rich TA, Adams RB, Yeaton P

BACKGROUND & AIMS: Photodynamic therapy (PDT) for unresectable cholangiocarcinoma is associated with improvement in cholestasis, quality of life, and potentially survival. We compared survival in patients with unresectable cholangiocarcinoma undergoing endoscopic retrograde cholangiopancreatography (ERCP) with PDT and stent placement with a group undergoing ERCP with stent placement alone. METHODS: Forty-eight patients were palliated for unresectable cholangiocarcinoma during a 5-year period. Nineteen were treated with PDT and stents; 29 patients treated with biliary stents alone served as a control group. Multivariate analysis was performed by using Model for End-Stage Liver Disease score, age, treatment by chemotherapy or radiation, and number of ERCP procedures and PDT sessions to detect predictors of survival. RESULTS: Kaplan-Meier analysis demonstrated improved survival in the PDT group compared with the stent only group (16.2 vs 7.4 months, P<.004). Mortality in the PDT group at 3, 6, and 12 months was 0%, 16%, and 56%, respectively. The corresponding mortality in the stent group was 28%, 52%, and 82%, respectively. The difference between the 2 groups was significant at 3 months and 6 months but not at 12 months. Only the number of ERCP procedures and number of PDT sessions were significant on multivariate analysis. Adverse events specific to PDT included 3 patients with skin phototoxicity requiring topical therapy only. CONCLUSIONS: ERCP with PDT seems to increase survival in patients with unresectable cholangiocarcinoma when compared with ERCP alone. It remains to be proved whether this effect is attributable to PDT or the number of ERCP sessions. A prospective randomized multicenter study is required to confirm these data.

PMID: 18255347 [PubMed - indexed for MEDLINE]
Human equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer.

Fetched: April 17th, 2008, 9:00pm EDT

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Human equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer.

Ann Oncol. 2008 Apr;19(4):724-8

Authors: Santini D, Perrone G, Vincenzi B, Lai R, Cass C, Alloni R, Rabitti C, Antinori A, Vecchio F, Morini S, Magistrelli P, Coppola R, Mackey JR, Tonini G

BACKGROUND: Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors. Materials and methods: We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes. RESULTS: In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor-node-metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05). CONCLUSIONS: hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.

PMID: 18187485 [PubMed - indexed for MEDLINE]
Cholangiocarcinoma: lessons from Thailand.

Fetched: April 15th, 2008, 9:00pm EDT

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Cholangiocarcinoma: lessons from Thailand.

Curr Opin Gastroenterol. 2008 May;24(3):349-56

Authors: Sripa B, Pairojkul C

PURPOSE OF REVIEW: To present the background of liver fluke-associated cholangiocarcinoma in Thailand focusing on recent epidemiological data and pathogenesis of this bile duct cancer. RECENT FINDINGS: More systematic tumor registration in Thailand nowadays uncovers new high-incidence areas that are confined to not only the northeastern part but also some provinces in northern Thailand. The link between the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma, particularly in terms of cellular and molecular pathogenesis, is further elucidated. SUMMARY: Thailand is still the country with the highest incidence of cholangiocarcinoma in the world. Liver fluke induces chronic inflammation leading to oxidative DNA damage of the infected biliary epithelium and malignant transformation. Eradication of the fluke and identification of high-risk populations are urgently needed.

PMID: 18408464 [PubMed - in process]
Persistent erythema multiforme in a patient with extrahepatic cholangiocarcinoma.

Fetched: April 15th, 2008, 9:00pm EDT

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Persistent erythema multiforme in a patient with extrahepatic cholangiocarcinoma.

Oncology. 2007;73(1-2):127-9

Authors: Tzovaras V, Liberopoulos EN, Zioga A, Pavlidis N, Elisaf M

Presented in this report is a 66-year-old male with a widespread persistent erythema multiforme mostly atypical in appearance, which was detected well before the diagnosis of underlying extrahepatic cholangiocarcinoma. The lesions regressed in response to chemotherapy, but they appeared again in connection with tumor relapse. Clinicians should recognize persistent erythema multiforme as one of the paraneoplastic dermatoses and efforts should be made to detect internal malignancies in patients with these skin lesions.

PMID: 18337625 [PubMed - indexed for MEDLINE]
Does HepPar-1 immunoexpression have a role in differential diagnosis of periampullary cancer?

Fetched: April 15th, 2008, 9:00pm EDT

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Does HepPar-1 immunoexpression have a role in differential diagnosis of periampullary cancer?

Pathology. 2008 Jan;40(1):35-41

Authors: Gulluoglu MG, Karayigit E, Ozden I, Kapran Y, Dizdaroglu F

AIMS: Histological subtyping of periampullary carcinomas is considered as a criterion for prognosis and therapeutic implications of these tumours. We assessed the immunoexpression rates of HepPar-1, CDX2 and MUC2 antibodies in different subtypes of periampullary adenocarcinomas (PAC), intestinal and pancreatobiliary, in order to assess their impact on differential diagnosis of this group of cancers. The expression of antibodies was also measured in ductal adenocarcinoma of the pancreatic head (DAPH). METHODS: Sixty-five patients with PAC and DAPH who underwent pancreatic Whipple resection constituted the study cohort. Of these, 46 (71%) had PAC, and 19 (29%) had DAPH. Among PACs, 20 (44%) were intestinal and 26 (56%) were pancreatobiliary type. RESULTS: HepPar-1 immunoreactivity was detected in 18 (39%) of all PACs. The rate of HepPar-1 expression was significantly higher in intestinal type PAC (75%) than it was in pancreatobiliary type (12%). The sensitivity, specificity, and accuracy of HepPar-1 immunoexpression for diagnosing intestinal type PAC were 75% , 89%, and 83%, respectively. Similarly, the rates of both CDX2 and MUC2 expressions were significantly higher in intestinal type PAC (80%) than they were in pancreatobiliary type (8%). The sensitivity, specificity, and accuracy of both CDX2 and MUC2 immunoexpressions for intestinal type PAC were 80%, 92%, and 87%, respectively. CONCLUSION: HepPar-1 antibody was found to be a highly sensitive and specific marker for distinguishing intestinal type from pancreatobiliary type among PACs. In addition to CDX2 and MUC2 antibodies, HepPar-1 immunoexpression seems to have a potential role in differential diagnosis of PACs.

PMID: 18038313 [PubMed - indexed for MEDLINE]
[Endoscopic examination for diagnosis of cancer of major duodenal papilla]

Fetched: April 12th, 2008, 9:00pm EDT

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[Endoscopic examination for diagnosis of cancer of major duodenal papilla]

Khirurgiia (Mosk). 2007;(12):15-7

Authors: Shuleshova AG, Brekhov EI, Nikiforov PA, Minushkin ON

Endoscopic procedures were used for diagnosis and treatment of cancer of major duodenal papilla (MDP) at 31 patients. Gastroduodenoscopy (with visual assessment) and endoscopic retrograde cholangiopancreatography were performed at all the patients. Morphological study of tissue sampling permitted to confirm preliminary visual diagnosis only in half of patients. Detection of x-ray symptoms and bile passage disorders at retrograde cholangiopancreatography were high informative. All the patients underwent endoscopic papillosphincterotomy which was effective at 26 (83.9%) patients.

PMID: 18163108 [PubMed - indexed for MEDLINE]
Original article: New surgical approaches to the Klatskin tumour.

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Original article: New surgical approaches to the Klatskin tumour.

Aliment Pharmacol Ther. 2007 Dec;26 Suppl 2:127-32

Authors: Van Gulik TM, Dinant S, Busch OR, Rauws EA, Obertop H, Gouma DJ

BACKGROUND: Surgical treatment of hilar cholangiocarcinoma (Klatskin tumours) is difficult because of its central location in the liver hilum. Recent developments in surgical techniques have improved the outcome after resection. AIM: To describe the surgical approaches currently applied in our centre and the impact of these strategies on outcome and criteria for resection. METHODS: From 1988 to 2003, 99 consecutive patients underwent resection for hilar cholangiocarcinoma. Patients were analysed for rate of R0 resections in relation with Bismuth classification. Morbidity, mortality and survival were assessed. RESULTS: The rate of hilar resections in combination with (extended) liver resections for type III and IV tumours increased from 24% to 95% in the last 5 years of the study period. Eight patients (8%) had Bismuth type IV tumours. Four of these patients underwent palliative local excisions of the hepatic duct confluence whereas the other four patients underwent hilar resection in combination with partial liver resection, resulting in microscopically radical resections. There was no mortality in this group. Overall postoperative morbidity and mortality were 68% and 10%, respectively. CONCLUSIONS: An aggressive surgical approach consisting of hilar resections combined with partial liver resections including segments 1 and 4, resulted in a higher rate of R0 resections. Even Bismuth type IV tumours may be resectable depending on the biliary anatomy of the hepatic duct confluence.

PMID: 18081656 [PubMed - indexed for MEDLINE]
[Interdisciplinary diagnosis of and therapy for cholangiocarcinoma]

Fetched: April 10th, 2008, 9:00pm EDT

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[Interdisciplinary diagnosis of and therapy for cholangiocarcinoma]

Z Gastroenterol. 2008 Jan;46(1):58-68

Authors: Kolligs FT, Zech CJ, Schönberg SO, Schirra J, Thasler W, Graeb C, Beuers U, Wilkowski R, Jacobs T, Böck S, Berster J, Heinemann V, Schäfer C

The diagnosis of and therapy for cholangiocarcinomas still remains an interdisciplinary challenge. For diagnostic and therapeutic purposes intra- and extrahepatic cholangiocarcinomas need to be distinguished. Multiple imaging tools such as sonography, multidetector computer tomography, magnetic resonance tomography as well as endoscopic ultrasound and endoscopic retrograde cholangiography for the diagnosis and localisation of these tumours are available. To date, surgical resection is the only curative treatment. At the time of diagnosis, most of the tumours are advanced. Therefore, only a small percentage of patients are suitable for curative surgery. Infiltration of the portal vein no longer constitutes a contraindication for surgery. Liver transplantation is not a reasonable option for intrahepatic cholangiocarcinomas but may be of advantage for perihilar Klatskin tumours. Severe cholangitis is the main cause of death of patients with obstructive cholangiocarcinomas. Drainage of the biliary tree system or surgery with construction of a biliary-digestive anastomosis is often necessary. If possible, a photodynamic therapy (PDT) should be performed in addition to biliary drainage. PDT has been shown to facilitate biliary drainage and to improve survival. The value of radiologist-assisted interventional procedures as well as percutaneous ablation and radiochemotherapy is not well established. In addition, so far, there is no standardised chemotherapy in a palliative situation established but there is some evidence for a benefit of gemcitabine-based chemotherapy. For the best care and treatment of patients with cholangiocarcinomas an interdisciplinary approach is required and to achieve progress in the therapy patients should be included in prospective clinical trials to test new approaches.

PMID: 18188818 [PubMed - indexed for MEDLINE]
Carcinomatous meningitis secondary to cholangiocarcinoma without other systemic metastasis.

Fetched: April 9th, 2008, 9:00pm EDT

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Carcinomatous meningitis secondary to cholangiocarcinoma without other systemic metastasis.

J Hepatobiliary Pancreat Surg. 2008;15(2):237-9

Authors: Okamura Y, Harada A, Maeda A, Fujioka A, Horiba T, Ishigure K, Hirai A, Ito Y, Uesaka K

Carcinomatous meningitis is clinically less common than brain metastasis or spinal cord compression, but has dire consequences for both the quality of life and the overall survival of patients with various kinds of malignancies. It occurs in about 5% of all adult cancer patients, though autopsies may double this number. The primary tumors that frequently cause carcinomatous meningitis include lung cancer, breast cancer, leukemia, lymphoma, and melanoma. Carcinomatous meningitis secondary to primary tumors in the gastrointestinal tract is clinically infrequent. In this report, we describe a 73-year-old man with lower bile duct cancer, who developed carcinomatous meningitis following surgical resection of the primary cancer. To our knowledge, this is the third case of carcinomatous meningitis secondary to cholangiocarcinoma described in the literature so far.

PMID: 18392723 [PubMed - in process]
Bile duct carcinoma in a gelding.

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Bile duct carcinoma in a gelding.

Vet Rec. 2008 Mar 1;162(9):281-2

Authors: Habershon-Butcher JL, Smyth JB, Hallowell GD

PMID: 18310563 [PubMed - indexed for MEDLINE]
Field defects in progression to gastrointestinal tract cancers.

Fetched: April 9th, 2008, 9:00pm EDT

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Field defects in progression to gastrointestinal tract cancers.

Cancer Lett. 2008 Feb 18;260(1-2):1-10

Authors: Bernstein C, Bernstein H, Payne CM, Dvorak K, Garewal H

A field of defective tissue may represent a pre-malignant stage in progression to many cancers. However, field defects are often overlooked in studies of cancer progression through assuming tissue at some distance from the cancer is normal. We indicate, however, the generality of field defects in gastrointestinal cancers, including cancers of the oropharynx, esophagus, stomach, bile duct, pancreas, small intestine and colon/rectum. Common features of these field defects are reduced apoptosis competence, aberrant proliferation and genomic instability. These features are often associated with high bile acid exposure and may explain the association of dietary-related factors with cancer progression.

PMID: 18164807 [PubMed - indexed for MEDLINE]
[A Klatskin tumor?]

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[A Klatskin tumor?]

J Chir (Paris). 2007 Nov-Dec;144(6):546-51

Authors: Leclercq P, Meurisse N

PMID: 18235372 [PubMed - indexed for MEDLINE]
Estimate of radiobiologic parameters from clinical data for biologically based treatment planning for liver irradiation.

Fetched: April 4th, 2008, 9:00pm EDT

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Estimate of radiobiologic parameters from clinical data for biologically based treatment planning for liver irradiation.

Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):900-7

Authors: Tai A, Erickson B, Khater KA, Li XA

PURPOSE: The Radiation Therapy Oncology Group (RTOG) is initiating a few new hypofractionation regimens (RTOG 0438) to treat liver cancer patients. To evaluate the radiobiologic equivalence between different regimens requires reliable radiobiologic parameters. The purpose of this work is to estimate a plausible set of such parameters for liver tumors and to design new optimized dose fractionation schemes to increase patient survival. METHODS AND MATERIALS: A model was developed to fit clinical survival data from irradiation of a series of primary liver patients. The model consists of six parameters including radiosensitivity parameters alpha and alpha/beta, potential doubling time T(d). Using this model together with the Lyman model for calculations of the normal tissue complication probability, we designed a series of hypofractionated treatment strategies for liver irradiation. RESULTS: The radiobiologic parameters for liver tumors were estimated to be: alpha/beta = 15.0 +/- 2.0 Gy, alpha = 0.010 +/- 0.001 Gy (-1), T(d) = 128 +/- 12 day. By calculating the biologically effective dose using the obtained parameters, it is found that for liver patients with an effective liver volume of approximately 45% the dose fractionation regimens suggested in RTOG 0438 can be escalated to higher dose for improved patient survival ( approximately 80% at 1 year) while keeping the normal tissue complication probability to less than 10%. CONCLUSIONS: A plausible set of radiobiologic parameters has been obtained based on clinical data. These parameters may be used for radiation treatment planning of liver tumors, in particular, for the design of new treatment regimens aimed at dose escalation.

PMID: 18262101 [PubMed - indexed for MEDLINE]
Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater.

Fetched: April 4th, 2008, 9:00pm EDT

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Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater.

Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):735-43

Authors: Krishnan S, Rana V, Evans DB, Varadhachary G, Das P, Bhatia S, Delclos ME, Janjan NA, Wolff RA, Crane CH, Pisters PW

PURPOSE: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. METHODS AND MATERIALS: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). RESULTS: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). CONCLUSIONS: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

PMID: 17980502 [PubMed - indexed for MEDLINE]
Ectopic pancreas presenting as ampulla of Vater tumor.

Fetched: April 2nd, 2008, 9:00pm EDT

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Ectopic pancreas presenting as ampulla of Vater tumor.

Am J Surg. 2008 Apr;195(4):498-500

Authors: Hsu SD, Chan DC, Hsieh HF, Chen TW, Yu JC, Chou SJ

Ectopic pancreas is relatively rare and is defined as pancreatic tissue that is situated abnormally, has no contact with the normal pancreas, and has its own ductal system and blood supply. It is usually an incidental finding in clinical practice. Most patients with an ectopic pancreas are asymptomatic, and, if present, symptoms are nonspecific and depend on the site of the lesion and the different complications encountered. Heterotopic pancreatic tissue has been found in several abdominal and intrathoracic locations, most frequently in the stomach (25%-60%) or the duodenum (25%-35%). Herein, we report a patient presenting with symptoms of ampullary tumor with obstructive jaundice, but the imaging study did not suggest the possibility of ectopic pancreas preoperatively.

PMID: 18304504 [PubMed - indexed for MEDLINE]
Cholangiocarcinoma: natural history, treatment, and strategies for surveillance in high-risk patients.

Fetched: April 2nd, 2008, 9:00pm EDT

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Cholangiocarcinoma: natural history, treatment, and strategies for surveillance in high-risk patients.

J Clin Gastroenterol. 2008 Feb;42(2):178-90

Authors: Yachimski P, Pratt DS

Cholangiocarcinoma is a primary malignancy of biliary epithelium. Risk factors for cholangiocarcinoma include primary sclerosing cholangitis and othe

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