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PubMed - Cholangiocarcinoma (100 unread)

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5-aminolevulinic acid-incorporated poly(vinyl alcohol) nanofiber-coated metal stent for application in photodynamic therapy.

Fetched: May 25th, 2012, 11:00pm MDT

5-aminolevulinic acid-incorporated poly(vinyl alcohol) nanofiber-coated metal stent for application in photodynamic therapy.

Int J Nanomedicine. 2012;7:1997-2005

Authors: Yoo JJ, Kim C, Chung CW, Jeong YI, Kang DH

Abstract
BACKGROUND: The study investigated the use of combined photodynamic therapy (PDT) and stent placement for the treatment of cholangiocarcinoma (CC). For this purpose, 5-aminolevulinic acid (ALA) was incorporated into poly(vinyl alcohol) (PVA) nanofiber, and coated onto metal stents. Their efficacy was assessed in PDT towards HuCC-T1 CC cells.
METHODS: Fabrication of ALA-PVA nanofiber, and simultaneous coating onto metal stents, was performed through electrospinning. The dark-toxicity, generation of protoporphyrin IX (PpIX), and PDT effect of ALA and ALA-PVA nanofiber were studied in vitro, using HuCC-T1 CC cells.
RESULTS: The ALA-PVA nanofibers were coated onto metal stents less than 1000 nm in diameter. ALA-only displayed marginal cytotoxicity; ALA-PVA nanofiber showed less cytotoxicity. PpIX generation was not sigficantly different between ALA and ALA-PVA nanofiber treatments. PVA itself did not generate PpIX in tumor cells. ALA and ALA-PVA nanofiber displayed a similar PDT effect on tumor cells. Cell viability was decreased, dose-dependently, until ALA concentration reached 100 μg/mL. Necrosis and apoptosis of tumor cells occurred similarly for ALA and ALA- PVA nanofiber treatments.
CONCLUSION: The ALA-PVA nanofiber-coated stent is a promising candidate for therapeutic use with cholangiocarcinoma.

PMID: 22619537 [PubMed - in process]

Scalp and chest cutaneous metastases of cholangiocarcinoma.

Fetched: May 24th, 2012, 11:00pm MDT

Scalp and chest cutaneous metastases of cholangiocarcinoma.

Int J Dermatol. 2012 May 22;

Authors: Pasquali P, Fortuño A, Casañas C, Fonoll M, Landeyro J, Gonzalez J

PMID: 22612588 [PubMed - as supplied by publisher]

Synthesis and evaluation of [(18)F]Fluorobutyl ethacrynic amide: A potential PET tracer for studying glutathione transferase.

Fetched: May 24th, 2012, 11:00pm MDT

Synthesis and evaluation of [(18)F]Fluorobutyl ethacrynic amide: A potential PET tracer for studying glutathione transferase.

Bioorg Med Chem Lett. 2012 Apr 30;

Authors: Huang HL, Yeh CN, Chang KW, Chen JT, Lin KJ, Chiang LW, Jeng KC, Wang WT, Lim KH, Chen CG, Lin KI, Huang YC, Lin WJ, Yen TC, Yu CS

Abstract
[(18)F]Flurobutyl ethacrynic amide ([(18)F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl]ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48GBq/μmol and radiochemical purity of 98%. Chemical conjugation of [(18)F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [(18)F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [(18)F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [(18)F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [(18)F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.

PMID: 22607679 [PubMed - as supplied by publisher]

Efficacy of metal and plastic stents in unresectable complex hilar cholangiocarcinoma: a randomized controlled trial.

Fetched: May 20th, 2012, 11:00pm MDT

Efficacy of metal and plastic stents in unresectable complex hilar cholangiocarcinoma: a randomized controlled trial.

Gastrointest Endosc. 2012 May 15;

Authors: Sangchan A, Kongkasame W, Pugkhem A, Jenwitheesuk K, Mairiang P

Abstract
BACKGROUND: Endoscopic biliary stent drainage is effective in the palliative treatment of patients with hilar cholangiocarcinoma (HCA). However, no randomized controlled trial comparing the efficacy of the self-expandable metal stent (SEMS) and the plastic stent (PS) in patients with unresectable complex HCA is available. OBJECTIVE: To compare the successful drainage rates of endoscopic SEMSs and PSs. DESIGN: A single-center, open-label randomized controlled trial. SETTING: University hospital in KhonKaen, Thailand. PATIENTS: One hundred eight patients with unresectable complex, Bismuth type II-IV HCA. INTERVENTIONS: Endoscopic retrograde cholangiography with unilateral SEMS or PS insertion. MAIN OUTCOME MEASUREMENTS: Successful drainage rate. LIMITATIONS: Diagnosis of HCA was made by clinical presentations, imaging studies, and clinical outcome during follow-up. RESULTS: One hundred eight patients were randomly allocated to the SEMS and PS groups. Intention-to-treat analysis revealed that the successful drainage rate in the SEMS group was higher than in the PS group (70.4% vs 46.3%, P = .011). The median survival times were 126 and 49 days, respectively, in the SEMS and PS groups. The overall survival rates of the patients in both groups were statistically different by log-rank test (P = .002). CONCLUSIONS: Endoscopic biliary drainage with the SEMS provides better adequacy of drainage and longer survival compared with the PS in patients with unresectable complex HCA. (Clinical trial registration number: NCT00721175.).

PMID: 22595446 [PubMed - as supplied by publisher]

IDH mutations: new genetic signatures in cholangiocarcinoma and therapeutic implications.

Fetched: May 20th, 2012, 11:00pm MDT

IDH mutations: new genetic signatures in cholangiocarcinoma and therapeutic implications.

Expert Rev Anticancer Ther. 2012 May;12(5):543-6

Authors: Borger DR, Zhu AX

PMID: 22594888 [PubMed - in process]

Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis.

Fetched: May 20th, 2012, 11:00pm MDT

Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis.

Histopathology. 2012 May 17;

Authors: Igarashi S, Matsubara T, Harada K, Ikeda H, Sato Y, Sasaki M, Matsui O, Nakanuma Y

Abstract
Igarashi S, Matsubara T, Harada K, Ikeda H, Sato Y, Sasaki M, Matsui O & Nakanuma Y (2012) Histopathology Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis Aims: Pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that is crucial in embryogenic development and differentiation of pancreas, and its overexpression is reportedly involved in the progression of many malignancies, including pancreatic carcinoma. In this study, the role of Pdx1 was examined in cholangiocarcinogenesis. Methods and results: Forty-three cases of human cholangiocarcinoma (CC) and 66 cases of hepatolithiasis or primary sclerosing cholangitis (PSC) with biliary intraepithelial neoplasia (BilIN) lesions and also eight fetal and 20 adult normal livers were examined immunohistochemically. Pdx1 was constantly expressed in the nuclei of fetal bile ducts, but was virtually absent in the large bile ducts of adults. By contrast, Hairy and enhancer of split 1 (Hes1), which represses pancreatic exocrine and endocrine differentiation, was expressed frequently in the adult bile ducts. Pdx1 was expressed in 67% of invasive CCs. In large bile ducts, expression of Pdx1 increased while that of Hes1 decreased during the progression of BilIN lesions to CC. Expression of Pdx1 correlated with proliferative activities in CCs. In an in vitro study, all three CC cell lines expressed Pdx1 mRNA and protein. Conclusion: Up-regulation of Pdx1 is a feature of cholangiocarcinogenesis associated with chronic cholangitis. Furthermore, expression of Pdx1 in CC is related to increased proliferative activity in CCs.

PMID: 22594685 [PubMed - as supplied by publisher]

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells.

Fetched: May 20th, 2012, 11:00pm MDT

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells.

Oncogene. 2012 Mar 15;31(11):1376-88

Authors: Clapéron A, Guedj N, Mergey M, Vignjevic D, Desbois-Mouthon C, Boissan M, Saubaméa B, Paradis V, Housset C, Fouassier L

Abstract
Scaffold proteins form multiprotein complexes that are central to the regulation of intracellular signaling. The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is highly expressed at the plasma membrane of normal biliary epithelial cells and binds epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with oncogenic properties. This study investigated EBP50-EGFR interplay in biliary cancer. We report that in a collection of 106 cholangiocarcinomas, EBP50 was delocalized to the cytoplasm of tumor cells in 66% of the cases. Ectopic expression of EBP50 was correlated with the presence of satellite nodules and with the expression of EGFR, which was at the plasma membrane, implying a loss of interaction with EBP50 in these cases. In vitro, loss of interaction between EBP50 and EGFR was mimicked by EBP50 depletion using a small interfering RNA approach in human biliary carcinoma cells co-expressing the two proteins at their plasma membrane, and in which interaction between EBP50 and EGFR was validated. EBP50 depletion caused an increase in EGFR expression at their surface, and a sustained activation of the receptor and of its downstream effectors (extracellular signal-regulated kinase 1/2, signal transducer and activator of transcription 3) in both basal and EGF-stimulated conditions. Cells lacking EBP50 showed epithelial-to-mesenchymal transition-associated features, including reduction in E-cadherin and cytokeratin-19 expression, induction of S100A4 and of the E-cadherin transcriptional repressor, Slug, and loss of cell polarity. Accordingly, depletion of EBP50 induced the disruption of adherens junctional complexes, the development of lamellipodia structures and the subsequent acquisition of motility properties. All these phenotypic changes were prevented upon inhibition of EGFR tyrosine kinase by gefitinib. These findings indicate that loss of EBP50 at the plasma membrane in tumor cells may contribute to biliary carcinogenesis through EGFR activation.

PMID: 21822312 [PubMed - indexed for MEDLINE]

Permalink for 'Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells.'

Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells.

Fetched: May 19th, 2012, 11:00pm MDT

Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells.

BMC Cancer. 2012 May 16;12(1):179

Authors: Gui A, Kobayashi A, Motoyama H, Kitazawa M, Takeoka M, Miyagawa S

Abstract
ABSTRACT: BACKGROUND: Since cholangiocarcinoma has a poor prognosis, several epidermal growth factor receptor (EGFR)-targeted therapies with antibody or small molecule inhibitor treatment have been proposed. However, their effect remains limited. The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR, with emphasis on its degradation and recycling. METHODS: We evaluated EGFR expression and colocalization by immunoblotting and immunofluorescence, cell surface EGFR expression by fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein binding by immunoprecipitation in the human cholangiocarcinoma RBE and immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a depletion by siRNA were adopted for inhibition of EGFR recycling. RESULTS: Upon stimulation with EGF, ligand-induced EGFR degradation was impaired and the expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting for lysosomal degradation was blocked at the early endosome stage, and non-degradated EGFR was recycled to the cell surface. A disrupted association between EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR at tyrosine 1045 (Tyr1045), were also observed in RBE cells. CONCLUSION: In RBE cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful molecular alteration in EGFR-targeted therapy. The combination of molecular-targeted therapy determined by the characteristics of individual EGFR phosphorylation events and EGFR recycling inhibition show promise in future treatments of cholangiocarcinoma.

PMID: 22591401 [PubMed - as supplied by publisher]

Evaluation of mass-forming intrahepatic cholangiocarcinoma with viral hepatitis.

Fetched: May 17th, 2012, 11:00pm MDT

Evaluation of mass-forming intrahepatic cholangiocarcinoma with viral hepatitis.

Hepatogastroenterology. 2012 Jul-Aug;59(116):1217-9

Authors: Horino K, Beppu T, Komori H, Masuda T, Hayashi H, Okabe H, Takamori H, Baba H

Abstract
Background/Aims: The correlation between the mass-forming type of intrahepatic cholangiocarcinoma (ICC) and the infection of the hepatitis B virus and hepatitis C virus are poorly understood. In this study, the clinical features of 34 patients with the mass-forming type ICC were reviewed to evaluate prognostic determinants. Methodology: Between January 1997 and December 2007, 34 patients underwent surgical resection for the mass-forming type of ICC in Kumamoto University Hospital. The significance of 14 clinicopathological factors consisting of age, gender, CA19-9 levels, CEA levels, size, intrahepatic metastases, portal vein invasion, bile duct invasion, histological differentiation, lymph node involvement, type B or C hepatitis, lymph node dissection, Sirius Red score of the tumor and platelet count in peripheral blood were analyzed, with regard to prognostic aspect. Results: Univariate analysis showed that significant risk factors for poor survival included age =65 years, CEA levels =1.6ng/mL and pathological lymph node involvement. Multivariate analysis revealed that age, CEA levels and lymph node involvement were independent and significant poor prognostic factors. Conclusions: It was concluded that age, CEA levels and lymph node involvement were significantly poor prognostic factors. However, the infection with type B or C hepatitis was not a prognostic factor of the mass forming type ICC.

PMID: 22580675 [PubMed - in process]

Permalink for 'Co-treatment of dichloroacetate, omeprazole and tamoxifen exhibited synergistically antiproliferative effect on malignant tumors: in vivo experiments and a case report.'

Co-treatment of dichloroacetate, omeprazole and tamoxifen exhibited synergistically antiproliferative effect on malignant tumors: in vivo experiments and a case report.

Fetched: May 17th, 2012, 11:00pm MDT

Co-treatment of dichloroacetate, omeprazole and tamoxifen exhibited synergistically antiproliferative effect on malignant tumors: in vivo experiments and a case report.

Hepatogastroenterology. 2012 Jul-Aug;59(116):994-6

Authors: Ishiguro T, Ishiguro R, Ishiguro M, Iwai S

Abstract
Background/Aims: Omeprazole (OPZ) and tamoxifen (TAM) strengthen the effects of anticancer drugs and dichloroacetate (DCA) inhibits tumor growth. This study assesses the synergistic effects of these drugs. Methodology: HT1080 human fibrosarcoma cells and WI-38 human fibroblasts were used as test and control cells, respectively. DCA, OPZ and TAM alone or in combination were applied and cells were counted after a one week culture. The combination of these drugs was prescribed to a cholangiocarcinoma patient and serum CA19-9 was monitored. Results: DCA combined with OPZ and TAM exhibited more potent antitumor activity than DCA alone in HT1080 fibrosarcoma cells, but did not influence proliferation of WI-38 human fibroblasts. All these drugs induce caspase-dependent cell growth inhibition through superoxide production. Since they can be taken orally and have been used clinically without major side effects, it was thought that this combination therapy would be a readily translated strategy to treat malignant tumors. Under the patient's consent these three drugs were prescribed to a 51-year old female cholangiocarcinoma patient to whom neither gemcitabine+S-1 nor adoptive immunotherapy with natural killer cells was effective. Disease progression was successfully blocked (the rise of serum CA19-9 value) for three months, also confirmed by CT. Conclusions: Although findings are preliminary, this study is a sample of translational research. Since there is no consensus regarding treatment strategy of cholangiocarcinoma and chemotherapy has only limited efficacy, it is expected that it might open a new possibility of treatment.

PMID: 22580646 [PubMed - in process]

Permalink for 'Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders.'

Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders.

Fetched: May 17th, 2012, 11:00pm MDT

Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders.

Gut. 2012 May 12;

Authors: Metzger J, Negm AA, Plentz RR, Weismüller TJ, Wedemeyer J, Karlsen TH, Dakna M, Mullen W, Mischak H, Manns MP, Lankisch TO

Abstract
BackgroundDiagnosis and curative treatment of cholangiocarcinoma (CC) often comes too late due to the lack of reliable tumour markers especially in patients with primary sclerosing cholangitis (PSC). The authors recently introduced bile proteomic analysis for CC diagnosis. Nevertheless, bile collection depends on invasive endoscopic retrograde cholangiography. The authors therefore evaluated urine proteomic analysis for non-invasive CC diagnosis.MethodsUsing capillary electrophoresis mass spectrometry the authors established a CC-specific peptide marker model based on the distribution of 42 peptides in 14 CC, 13 PSC and 14 benign biliary disorder (BBD) patients.ResultsIn cross-sectional validation of 123 patients, the urine peptide marker model correctly classified 35 of 42 CC patients and 64 of 81 PSC and BBD patients with an area under the curve value of 0.87 (95% CI 0.80 to 0.92, p=0.0001, 83% sensitivity, 79% specificity). Evaluation of 101 normal controls resulted in 86% specificity. All 10 patients with CC on top of PSC were correctly classified. The majority of sequence-identified peptides are fragments of interstitial collagens with some of them also detected in blood indicating their extra-renal origin. Immunostaining of liver sections for matrix metallopeptidase 1 indicated increased activity of the interstitial collagenase in liver epithelial cells of CC patients.ConclusionThe urine test differentiates CC from PSC and other BBD and may provide a new diagnostic non-invasive tool for PSC surveillance and CC detection.

PMID: 22580416 [PubMed - as supplied by publisher]

A novel use for the round ligament of the liver in a complicated bile duct operation.

Fetched: May 17th, 2012, 11:00pm MDT

A novel use for the round ligament of the liver in a complicated bile duct operation.

ANZ J Surg. 2011 Jul-Aug;81(7-8):572-3

Authors: Zhang CH, Yang XY, Chen X, Zhou CC, Zhou HB, Jiang JB

PMID: 22295406 [PubMed - indexed for MEDLINE]

Cholangiocarcinoma: a 10-year experience of a single tertiary centre in the multi ethnicity-Malaysia.

Fetched: May 17th, 2012, 11:00pm MDT

Cholangiocarcinoma: a 10-year experience of a single tertiary centre in the multi ethnicity-Malaysia.

Med J Malaysia. 2012 Feb;67(1):45-51

Authors: Yusoff AR, Siti ZM, Muzammil AR, Yoong BK, Vijeyasingam R

Abstract
Cholangiocarcinoma (CCA) is a rare biliary tract epithelial malignancy. We described the clinical features of CCA patients in our institution. A 10-year retrospective study of patients with cholangiocarcinoma in University Malaya Medical Centre was conducted. Clinical data and outcomes in relation to the three anatomical groups of CCA were collected and analysed. Of the 69 patients that were included 55% were male. Mean age was 61 years. Twelve (17%) had intrahepatic, 38 (55%) perihilar and 19 (28%) distal tumour. Mean age (p=0.043), median duration of symptoms (p=0.011), jaundice (p<0.001), total bilirubin level (p=0.003), INR (p=0.005) and mean tumour size (p=0.048) were significantly related to the site of tumour. Only 12 patients had curative resection with seven R0 resections. Cholangiocarcinoma is increasingly diagnosed in our population. Despite that, the diagnosis is still often late. Age, jaundice and tumour size may predict anatomical location of CCA.

PMID: 22582548 [PubMed - in process]

Effects of Helicobacter pylori γ-Glutamyltranspeptidase on Apoptosis and Inflammation in Human Biliary Cells.

Fetched: May 17th, 2012, 11:00pm MDT

Effects of Helicobacter pylori γ-Glutamyltranspeptidase on Apoptosis and Inflammation in Human Biliary Cells.

Dig Dis Sci. 2012 May 13;

Authors: Boonyanugomol W, Chomvarin C, Song JY, Kim KM, Kim JM, Cho MJ, Lee WK, Kang HL, Rhee KH, Sripa B, Hahnvajanawong C, Baik SC

Abstract
BACKGROUND: Several studies have reported the presence of H. pylori in individuals with hepatobiliary diseases, but in vitro and in vivo studies are still needed. Here, we determined the effects of H. pylori γ-glutamyltranspeptidase (GGT) on the induction of apoptosis and IL-8 production in a human cholangiocarcinoma cell line (KKU-100 cells). METHODS: Cell viability and DNA synthesis were examined by MTT and BrdU assays, respectively. RT-PCR and western blot analysis were performed to assess gene and protein expression, respectively. IL-8 secretion in KKU-100 cells was measured by ELISA. RESULTS: Exposure to the H. pylori ggt (+) strain decreased KKU-100 cell survival and DNA synthesis when compared with cells exposed to the H. pylori ggt mutant strain. Treatment with recombinant H. pylori GGT (rHP-GGT) dramatically decreased cell survival and DNA synthesis, and stimulated apoptosis; these features corresponded to an increased level of iNOS gene expression in KKU-100 cells treated with rHP-GGT. RT-PCR and western blot analyses revealed that rHP-GGT treatment enhanced the expression of pro-apoptotic molecules (Bax, Caspase-9, and Caspase-3) and down-regulated the expression of anti-apoptotic molecules (Bcl-2 and Bcl-xL). The extrinsic-mediated apoptosis molecules, including Fas and activated Caspase-8, were not expressed after treatment with rHP-GGT. Furthermore, rHP-GGT significantly stimulated IL-8 secretion in KKU-100 cells. CONCLUSION: Our data indicate that H. pylori GGT might be involved in the development of cancer in hepatobiliary cells by altering cell kinetics and promoting inflammation.

PMID: 22581342 [PubMed - as supplied by publisher]

Permalink for 'Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Advanced Cholangiocarcinoma Patients Treated With Gemcitabine-Based Adjuvant Chemotherapy After Surgical Resection.'

Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Advanced Cholangiocarcinoma Patients Treated With Gemcitabine-Based Adjuvant Chemotherapy After Surgical Resection.

Fetched: May 17th, 2012, 11:00pm MDT

Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Advanced Cholangiocarcinoma Patients Treated With Gemcitabine-Based Adjuvant Chemotherapy After Surgical Resection.

Ann Surg. 2012 May 10;

Authors: Kobayashi H, Murakami Y, Uemura K, Sudo T, Hashimoto Y, Kondo N, Sueda T

Abstract
OBJECTIVE:: The aim of this study was to evaluate whether intratumoral human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. BACKGROUND:: There have been no reports concerning a useful predictive biomarker in patients with cholangiocarcinoma treated with adjuvant gemcitabine chemotherapy. METHODS:: Intratumoral hENT1 expression was investigated immunohistochemically in 105 patients with resected advanced cholangiocarcinoma. Relationships between intratumoral hENT1 expression and clinicopathological factors were evaluated by univariate and multivariate analyses. This study was a retrospective analysis on retrospectively collected tissue and data. RESULTS:: Fifty-one patients received AGC, and 54 did not. High and low intratumoral hENT1 expression was found in 74 (70%) and 31 patients (30%), respectively. There were no significant differences in clinicopathological factors between patients with high hENT1 expression and those with low hENT1 expression. Survival patients with high hENT1 expression were significantly better than those with low hENT1 expression among patients who received AGC (P = 0.008), but not among patients who did not (P = 0.894). Moreover, a significant difference in survival between patients who received AGC and those who did not was observed among patients with high hENT1 expression (P = 0.002), but not among patients with low hENT1 expression (P = 0.525). Intratumoral hENT1 expression was only an independent predictive factor for patients treated with AGC by multivariate analysis (P = 0.027). CONCLUSIONS:: Intratumoral hENT1 expression may be a potent predictive marker for advanced cholangiocarcinoma patients treated with AGC.

PMID: 22580938 [PubMed - as supplied by publisher]

Cholangiocarcinoma or IgG4-Associated Cholangitis: How Feasible It Is to Avoid Unnecessary Surgical Interventions?

Fetched: May 17th, 2012, 11:00pm MDT

Cholangiocarcinoma or IgG4-Associated Cholangitis: How Feasible It Is to Avoid Unnecessary Surgical Interventions?

Ann Surg. 2012 May 10;

Authors: Lytras D, Kalaitzakis E, Webster GJ, Imber CJ, Amin Z, Rodriguez-Justo M, Pereira SP, Olde Damink SW, Malago' M

Abstract
OBJECTIVE:: To evaluate the experience of a tertiary hepatopancreaticobiliary (HPB) center in the diagnostic approach and management of patients with suspicion of cholangiocarcinoma (CCa), focusing on excluding patients with IgG4-associated cholangitis (IAC) from unnecessary major surgical interventions. METHODS:: Between January 2008 and September 2010, a total number of 152 patients with suspicion of CCa underwent evaluation through a HPB multidisciplinary team meeting. Patients without tissue diagnosis were managed surgically or medically on the basis of probable presence of IAC as underlying pathology. Serology, immunostaining, and imaging were reviewed and analyzed according to the HISORt (Histology, Imaging, Serology, Other organ involvement, Response to therapy) criteria for IAC. RESULTS:: Tissue diagnosis during the diagnostic workup was achieved in 104 patients (68%), whereas the remaining 48 were classified as "highly suspicious for CCa" (n = 35) or as "probable IAC" (n = 13). Among 16 "highly suspicious for CCa" patients who underwent surgery, pathology revealed 2 patients harboring IAC (n = 1) and a benign chronic inflammatory biliary stricture (n = 1), respectively. Among the 13 patients with primarily medical management as "probable IAC," final diagnosis was CCa (n = 3) and IAC (n = 9), while 1 patient had no proven diagnosis. The accuracy of serum IgG4 for diagnosis of IAC reached 60%. Sensitivity and specificity of immunostaining for IAC in biopsy specimens were 56% and 89%, respectively. Imaging features suggesting IAC yielded sensitivity, specificity, and accuracy of 75%, 89%, and 83%, respectively. Initial imaging was revised at the referral institute in 75% of IAC patients (P = 0.009), while an isolated stricture (P = 0.038), a biliary mass (P = 0.006), and normal pancreas on computed tomography (P = 0.01) were statistically significant parameters for distinguishing between CCa and IAC. The mean time for establishing a diagnosis of IAC was 12.4 months (range: 2.5-32 months) CONCLUSIONS:: Differential diagnosis between CCa and IAC mandates high index of suspicion and low threshold for referral in high volume institutes. The delayed establishment of diagnosis particularly for CCa needs to be balanced versus avoiding unnecessary surgery for IAC. Imaging features may be most helpful for optimal management.

PMID: 22580936 [PubMed - as supplied by publisher]

Permalink for 'Chemotherapy for Inoperable Advanced or Metastatic Cholangiocarcinoma: Retrospective Analysis of 78 Cases in a Single Center over Four Years.'

Chemotherapy for Inoperable Advanced or Metastatic Cholangiocarcinoma: Retrospective Analysis of 78 Cases in a Single Center over Four Years.

Fetched: May 12th, 2012, 11:00pm MDT

Chemotherapy for Inoperable Advanced or Metastatic Cholangiocarcinoma: Retrospective Analysis of 78 Cases in a Single Center over Four Years.

Chemotherapy. 2012 May 10;58(2):134-141

Authors: Pracht M, Le Roux G, Sulpice L, Mesbah H, Manfredi S, Audrain O, Boudjema K, Raoul JL, Boucher E

Abstract
Background: Systemic chemotherapy is the treatment of choice for inoperable (advanced or metastatic) cholangiocarcinoma. According to phase II and III trials, regimens combining 5-fluorouracil (5FU) or gemcitabine with a platinum salt have provided an overall response rate of 12-50% with a median overall survival of 5-16 months. Methods: This was a retrospective analysis of 78 consecutive cases of inoperable cholangiocarcinoma treated by palliative chemotherapy from July 2005 to November 2009 in one center. We firstly aimed to evaluate the impact of palliative chemotherapy in terms of survival and secondly to analyze possible related prognostic factors. Results: This cohort included 25 female and 53 male patients, with a mean age of 60.8 ± 11.4 years. Intrahepatic and extrahepatic cholangiocarcinoma were observed in 57 and 21 patients, respectively. First-line chemotherapy regimens were as follows: gemcitabine (n = 7), gemcitabine plus oxaliplatin (with or without cetuximab; n = 62) and 5FU plus cisplatin (n = 9). None of the patients achieved a complete response. The partial response rate was 35.9% (27/78), and the stable disease rate was 26.9% (21/78), giving a disease control rate of 62.8%. At the time of this analysis, with a median follow-up of 18 months, 13 patients were survivors. Median overall survival was 10 months [95% confidence interval (CI) 7-12], and median progression-free survival was 7 months (95% CI 6-8). Upon univariate analysis, only the distribution of the disease was significantly linked with prognosis, with a median overall survival of 10 months (95% CI 10-24) for solitary tumors versus 7 months (95% CI 6-11) in the case of infiltrative or multifocal tumors (p = 0.039). Conclusion: The disease control rate, overall survival and progression free-survival in this single-center retrospective study were in agreement with earlier reports. Specific features of this cohort were a large proportion of cholangiocarcinoma with associated cirrhosis (n = 30/78, 38.5%), mostly intrahepatic (n = 25/30, 83.5%). This confirms the increasing incidence of intrahepatic localization and the epidemiological link recently reported between intrahepatic biliary tract carcinoma and cirrhosis.

PMID: 22572213 [PubMed - as supplied by publisher]

Hepatocellular carcinoma in a low-endemic area: rising incidence and improved survival.

Fetched: May 12th, 2012, 11:00pm MDT

Hepatocellular carcinoma in a low-endemic area: rising incidence and improved survival.

Eur J Gastroenterol Hepatol. 2012 Apr;24(4):450-7

Authors: Witjes CD, Karim-Kos HE, Visser O, van den Akker SA, de Vries E, Ijzermans JN, de Man RA, Coebergh JW, Verhoef C

Abstract
OBJECTIVE: To examine recent trends in incidence and outcome among patients with hepatocellular carcinoma (HCC) in an unselected population in Western Europe.
METHODS: Data from the nationwide Netherlands Cancer Registry were used to estimate trends in incidence for all 6514 patients newly diagnosed with primary liver cancer between 1989 and 2009. Trends in incidence, treatment, and relative survival according to sex and age were estimated in 5143 patients with HCC, also using the European Standardized Rates (ESR).
RESULTS: The ESR for all primary liver cancers combined increased significantly between 1989 and 2009 as did the ESR for HCC among men (estimated annual percentage change: 2.2%, 95% confidence interval: 1.6-2.7) and for women aged below 60 years, suggesting etiological influences in these groups. Especially, the nonhistologically confirmed HCC incidence increased. More patients underwent surgery for HCC, from 9% in 1989-1994 to 23% in 2005-2009, as well as chemotherapy and/or irradiation, from 6 to 11% in the same period. At the end of the study period, only 66% of patients received noncancer-related HCC therapy, that is, best supportive care, compared with 85% in 1989-1994. The 1 and 5-year relative survival for patients with HCC increased significantly (P<0.001 and P<0.001).
CONCLUSION: In as much as the modest increase in the incidence of HCC was a matter of better detection, due to improved imaging techniques, which may have affected the overall relative survival for HCC patients, the increasing trend in survival is likely to be, in the absence of other explanations, due to better treatment of the underlying liver cirrhosis.

PMID: 22273986 [PubMed - indexed for MEDLINE]

Prognostic significance of snail expression in hilar cholangiocarcinoma.

Fetched: May 11th, 2012, 11:00pm MDT

Prognostic significance of snail expression in hilar cholangiocarcinoma.

Braz J Med Biol Res. 2012 May 10;

Authors: Dalu K, Liang J, Rong L, Shihai L, Jigang W, Kejun Z, Dong C

PMID: 22570087 [PubMed - as supplied by publisher]

Long-term Survival in Hilar Cholangiocarcinoma also Possible in Unresectable Patients.

Fetched: May 11th, 2012, 11:00pm MDT

Long-term Survival in Hilar Cholangiocarcinoma also Possible in Unresectable Patients.

World J Surg. 2012 May 9;

Authors: Ruys AT, van Haelst S, Busch OR, Rauws EA, Gouma DJ, van Gulik TM

Abstract
BACKGROUND: Radical resection remains the only curative treatment for hilar cholangiocarcinoma (HCCA). Only a limited proportion of patients, however, are eligible for resection. The survival and prognostic factors of these patients are largely unknown. The aim of this study was to evaluate survival and prognostic factors in unresectable patients presenting with HCCA. METHODS: We performed a cohort study of the denominator of HCCA patients seen in a tertiary referral center between March 2003 and March 2009. Demographics, treatment, pathology results, and survival were analyzed. RESULTS: A total of 217 patients with suspected HCCA were identified. Ninety-five patients (40 %) underwent laparotomy, and in 57 (63 %) of these patients resection was performed. Overall median and 5-year survival of resected patients were 37 months and 43 %, respectively, as compared to 13 months and 7 % in unresectable patients. In unresectable patients, median survival was better in patients with locally advanced disease (16 months) as compared to patients with hepatic and extrahepatic metastases (5 and 3 months, p < 0.001). Of the 160 unresectable patients, 17 (10 %) survived longer than 3 years. CONCLUSION: Of the patients presenting with HCCA in our center, 26 % proved resectable. The 7 % long-term survival rate of unresectable patients is remarkable and emphasizes the indolent growth of some of these tumors. Patients with metastases had a much worse prognosis with a median of 4 months.

PMID: 22569746 [PubMed - as supplied by publisher]

Validation of methylation-sensitive high resolution melting for the detection of DNA methylation in cholangiocarcinoma.

Fetched: May 11th, 2012, 11:00pm MDT

Validation of methylation-sensitive high resolution melting for the detection of DNA methylation in cholangiocarcinoma.

Clin Biochem. 2012 May 5;

Authors: Amornpisutt R, Sriraksa R, Limpaiboon T

Abstract
OBJECTIVES: To validate methylation-sensitive high resolution melting (MS-HRM) for detection of DNA methylation. Design and Methods Methylation of two independent loci, OPCML and DcR1, was analyzed in cholangiocarcinoma and adjacent normal samples by using MS-HRM, methylation-specific PCR and pyrosequencing. RESULTS: There was significant agreement between methods at both loci. CONCLUSIONS: MS-HRM represents the excellent potential and reliability for quantifying DNA methylation levels in clinical samples.

PMID: 22569599 [PubMed - as supplied by publisher]

Novel organotypic culture model of cholangiocarcinoma progression.

Fetched: May 11th, 2012, 11:00pm MDT

Novel organotypic culture model of cholangiocarcinoma progression.

Hepatol Res. 2012 Apr 19;

Authors: Campbell DJ, Dumur CI, Lamour NF, Dewitt JL, Sirica AE

Abstract
Aim: Recent studies have suggested that increased α-smooth muscle-actin positive myofibroblastic cells (α-SMA positive CAF) in the desmoplastic stroma may relate to a more aggressive cancer and worse survival outcomes for intrahepatic cholangiocarcinoma (ICC) patients. To facilitate investigating cellular and molecular interactions between α-SMA positive CAF and cholangiocarcinoma cells related to ICC progression, we developed a novel 3-D organotypic culture model of cholangiocarcinoma that more accurately mimics the stromal microenvironment, gene expression profile and select pathophysiological characteristics of desmoplastic ICC in vivo. Methods: This unique model was established by co-culturing within a type I collagen gel matrix, a strain of cholangiocarcinoma cells (derived from an ICC formed in syngeneic rat liver following bile duct inoculation of spontaneously-transformed rat cholangiocytes) with varying numbers of clonal α-SMA positive CAF established from the same tumor type. Results: Cholangiocarcinoma cells and α-SMA positive CAF in monoculture each exhibited cell-specific biomarker gene expression profiles characteristic of stromal myofibroblastic cell versus malignant cholangiocyte cell types. In comparison, the gene expression profile and histopathological characteristics exhibited by the organotypic co-culture closely resembled those of whole tissue samples of the parent orthotopic ICC. We further showed α-SMA positive CAF to significantly enhance cholangiocarcinoma cell "ductal-like" growth and cancer cell migration/invasiveness in vitro, as well as to promote upregulated expression of select genes known to be associated with ICC invasion. Conclusion: This novel organotypic model provides an important new resource for studying the effects of microenvironment on cholangiocarcinoma progression in vitro and may have potential as a preclinical model for identifying molecularly targeted therapies.

PMID: 22568523 [PubMed - as supplied by publisher]

Exome sequencing of liver fluke-associated cholangiocarcinoma.

Fetched: May 10th, 2012, 11:00pm MDT

Exome sequencing of liver fluke-associated cholangiocarcinoma.

Nat Genet. 2012 May 6;

Authors: Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W, McPherson JR, Allen GE, Ng CC, Wong BH, Myint SS, Rajasegaran V, Heng HL, Gan A, Zang ZJ, Wu Y, Wu J, Lee MH, Huang D, Ong P, Chan-On W, Cao Y, Qian CN, Lim KH, Ooi A, Dykema K, Furge K, Kukongviriyapan V, Sripa B, Wongkham C, Yongvanit P, Futreal PA, Bhudhisawasdi V, Rozen S, Tan P, Teh BT

Abstract
Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.

PMID: 22561520 [PubMed - as supplied by publisher]

Hepatic hilar transection method for liver surgery (with video).

Fetched: May 10th, 2012, 11:00pm MDT

Hepatic hilar transection method for liver surgery (with video).

J Hepatobiliary Pancreat Sci. 2012 Jan;19(1):9-14

Authors: Kokudo N, Aoki T

Abstract
The procedure used to isolate the hepatic artery, the portal vein and the bile duct separately at the hepatic hilum was first reported in the 1940s, and remains significant as an essential technique for liver surgery in the era of more complicated liver surgery and liver transplantation. The anatomy of the vessels at the hepatic hilum is highly variable; therefore, preoperative imaging studies are indispensable for understanding the anatomy in each individual patient. The minimal extent of the transection should be defined according to the operative procedure, as excessive disruption of the blood flow and lymphatic vessels can induce postoperative complications. When isolating the vessels, gentle handling and appropriate ligation/division of the vessels are required to avoid bleeding and injuries to the vessels to be preserved. The bile duct is wrapped with perivascular connective tissue and is difficult to isolate separately. Therefore, the hilar plate should be divided together with the bile duct, under the guidance of intraoperative cholangiography.

PMID: 21959896 [PubMed - indexed for MEDLINE]

A common language to describe perihilar cholangiocarcinoma.

Fetched: May 6th, 2012, 11:00pm MDT

A common language to describe perihilar cholangiocarcinoma.

Br J Surg. 2012 May 3;

Authors: Deoliveira ML, Clavien PA

PMID: 22556154 [PubMed - as supplied by publisher]

Genetics in primary sclerosing cholangitis.

Fetched: May 6th, 2012, 11:00pm MDT

Genetics in primary sclerosing cholangitis.

Clin Res Hepatol Gastroenterol. 2012 May 1;

Authors: Næss S, Shiryaev A, Hov JR, Franke A, Karlsen TH

Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder with a progressive course. PSC is strongly associated with inflammatory bowel disease and is often complicated by cholangiocarcinoma development. Etiology and pathogenesis remain obscure, but the diverse clinical manifestation of the disease might, to some extent, indicate different genetic susceptibility in subgroups of patients. In recent years, genome-wide association studies performed in PSC have identified a number of genetic susceptibility loci. In this mini-review, we suggest that the genetic associations established can be grouped according to four pathogenic aspects relating to inflammation, cholangiocyte function, fibrosis and carcinogenesis. Subclassification of PSC patients according to their genetic predisposition could be a valuable tool in future functional and clinical studies.

PMID: 22554879 [PubMed - as supplied by publisher]

Clinical outcomes and toxicity using Stereotactic Body Radiotherapy (SBRT) for advanced cholangiocarcinoma.

Fetched: May 6th, 2012, 11:00pm MDT

Clinical outcomes and toxicity using Stereotactic Body Radiotherapy (SBRT) for advanced cholangiocarcinoma.

Radiat Oncol. 2012 May 3;7(1):67

Authors: Barney BM, Olivier KR, Miller RC, Haddock MG

Abstract
ABSTRACT: BACKGROUND: To report single-institutional clinical outcomes and toxicity with SBRT for cholangiocarcinoma. METHODS: From March 2009 to July 2011, 10 patients with 12 unresectable primary (n = 6) or recurrent (n = 6) cholangiocarcinoma lesions underwent abdominal SBRT. Sites treated included liver (n = 10), abdominal lymph nodes (n = 1), and adrenal gland (n = 1). SBRT was delivered in three (n = 2) or five (n = 10) consecutive daily fractions over one week. The median prescription dose was 55 Gy (range, 45-60). Treatment response was graded by RECIST v.1.1, and toxicities were scored by CTCAE v.4.0. Data was analyzed using the Kaplan- Meier method to determine rates of local control (LC), freedom from distant progression (FFDM) and overall survival (OS). RESULTS: The median follow-up was 14 months (range, 2-26 months). LC, defined as freedom from progression within the SBRT field, was 100%, but four patients treated to intrahepatic sites experienced progression elsewhere in the liver. Estimates for FFDM at 6 and 12 months were 73% and 31%, respectively. Sites of disease relapse included liver (n = 3), liver and lymph nodes (n = 1), liver and lungs (n = 1), lymph nodes (n = 1), and mesentery (n = 1). OS estimates for the cohort at 6 and 12 months were 83% and 73%, respectively. The most common Grade [greater than or equal to]2 early toxicities were Grade 2 nausea and vomiting (n = 5) and gastrointestinal pain (n = 2). Late [greater than or equal to]2 toxicities included Grade 2 gastrointestinal pain (n = 3), Grade 3 biliary stenosis (n = 1), and Grade 5 liver failure (n = 1). CONCLUSIONS: SBRT shows promise as an effective local therapy for properly-selected patients with cholangiocarcinoma. Further follow-up is needed to better quantify the risk of late complications associated with SBRT.

PMID: 22553982 [PubMed - as supplied by publisher]

Cutaneous paraneoplastic syndrome presenting with wartylike oral lesions.

Fetched: May 6th, 2012, 11:00pm MDT

Cutaneous paraneoplastic syndrome presenting with wartylike oral lesions.

Cutis. 2012 Jan;89(1):14-6

Authors: Pagnini F, Giomi B, Delfino C, Tiradritti L, Fattorini L, Zuccati G

PMID: 22439304 [PubMed - indexed for MEDLINE]

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini.

Fetched: May 6th, 2012, 11:00pm MDT

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini.

Parasitol Int. 2011 Sep;60(3):283-8

Authors: Sripa J, Pinlaor P, Brindley PJ, Sripa B, Kaewkes S, Robinson MW, Young ND, Gasser RB, Loukas A, Laha T

Abstract
Functional genomics have not been reported for Opisthorchis viverrini or the related fish-borne fluke, Clonorchis sinensis. Here we describe the introduction by square wave electroporation of Cy3-labeled small RNA into adult O. viverrini worms. Adult flukes were subjected to square wave electroporation employing a single pulse for 20 ms of 125V in the presence of 50 μg/ml of Cy3-siRNA. The parasites tolerated this manipulation and, at 24 and 48 h after electroporation, fluorescence from the Cy3-siRNA was evident throughout the parenchyma of the worms, with strong fluorescence evident in the guts and reproductive organs of the adult worms. Second, other worms were treated using the same electroporation settings with double stranded RNA targeting an endogenous papain-like cysteine protease, cathepsin B. This manipulation resulted in a significant reduction in specific mRNA levels encoding cathepsin B, and a significant reduction in cathepsin B activity against the diagnostic peptide, Z-Arg-Arg-AMC. This appears to be the first report of introduction of reporter genes into O. viverrini and the first report of experimental RNA interference (RNAi) in this fluke. The findings indicated the presence of an intact RNAi pathway in these parasites which, in turn, provides an opportunity to probe gene functions in this neglected tropical disease pathogen.

PMID: 21565281 [PubMed - indexed for MEDLINE]

Proteomics-based identification of α-enolase as a potential prognostic marker in cholangiocarcinoma.

Fetched: May 5th, 2012, 11:00pm MDT

Proteomics-based identification of α-enolase as a potential prognostic marker in cholangiocarcinoma.

Clin Biochem. 2012 Apr 19;

Authors: Yonglitthipagon P, Pairojkul C, Bhudhisawasdi V, Mulvenna J, Loukas A, Sripa B

Abstract
OBJECTIVES: To investigate the association of expression status of α-enolase (ENO1) and clinicopathological outcomes of CCA patients. DESIGN AND METHODS: Two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to compare differential expressed protein profiles of four human CCA cell lines and H69, a non-malignant biliary cell line, as a control. Immunohistochemical analysis was carried out in tissue-microarray of human CCA tissues (n=301). RESULTS: We identified ENO1 in all CCA cell lines but not H69 by proteomics based. About 75% of patients with CCA showed over-expression of ENO1 in hyperplastic bile duct and the tumors compared with that in tumor-adjacent normal tissue counterparts. Moreover, over-expression of ENO1 is significantly associated with poor prognosis and tumor invasion of CCA patients. CONCLUSIONS: ENO1 may serve as a prognostic marker to monitor the disease progression of these patients.

PMID: 22552009 [PubMed - as supplied by publisher]

Clinicopathologic study of mixed adenoneuroendocrine carcinomas of hepatobiliary organs.

Fetched: May 4th, 2012, 11:00pm MDT

Clinicopathologic study of mixed adenoneuroendocrine carcinomas of hepatobiliary organs.

Virchows Arch. 2012 Mar;460(3):281-9

Authors: Harada K, Sato Y, Ikeda H, Maylee H, Igarashi S, Okamura A, Masuda S, Nakanuma Y

Abstract
Neuroendocrine neoplasms in hepatobiliary organs are very rare, but several cases of mixed adenoneuroendocrine carcinoma (MANEC) have been reported. In this study, we characterized the neuroendocrine component of biliary MANEC. A total of 274 cases of biliary cancer including 17 intrahepatic cholangiocarcinomas (CCs), 15 hepatic hilar CCs without preceding hepatobiliary disease, 55 hepatic hilar CCs with hepatolithiasis, 49 gallbladder cancers, 53 extrahepatic CCs, and 85 hepatocellular carcinomas were examined for a neuroendocrine component using immunohistochemistry with neuroendocrine markers (chromogranin A and synaptophysin). In the MANEC cases, in addition to a close histological examination, the proliferative activity and the expression of somatostatin receptor 2A were also evaluated. In addition to an ordinary adenocarcinoma, a neuroendocrine component occupying more than 30% of the entire tumor was also found in 4% (2/55 cases) of hepatic hilar cholangiocarcinomas with hepatolithiasis, 10% (5/49 cases) of gallbladder cancers, and 4% (2/53 cases) of extrahepatic cholangiocarcinomas, but not in the intrahepatic cholangiocarcinomas, hilar cholangiocarcinomas without preceding hepatobiliary disease, and hepatocellular carcinomas. Two cases were positive for somatostatin receptor 2A. The adenocarcinoma components were predominately located at the surface of the tumors, and the majority of stromal and vascular invasion and lymph node metastasis involved neuroendocrine components, showing the features of neuroendocrine tumor G2 or neuroendocrine carcinomas (NECs). NEC components showed higher proliferative activity on Ki67 immunostaining, compared to the adenocarcinoma components. Biliary MANECs are found in hepatic hilar cholangiocarcinomas with hepatolithiasis, gallbladder cancers, and extrahepatic cholangiocarcinomas and show a characteristic histology. Since the neuroendocrine component in biliary MANEC defines the prognosis, it is important to identify it and consider the indications for adjunctive therapy with somatostatin analogues.

PMID: 22358181 [PubMed - indexed for MEDLINE]

Downregulated miR-214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist.

Fetched: May 2nd, 2012, 11:00pm MDT

Downregulated miR-214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist.

FEBS J. 2012 Apr 27;

Authors: Li B, Han Q, Zhu Y, Yu Y, Wang J, Jiang X

Abstract
microRNAs (miRNAs) play an important role in many human diseases, including cancer metastasis. However, the mechanisms by which miRNAs regulate intrahepatic cholangiocarcinoma metastasis remain poorly understood. In the current study we assayed the expression level of miR-214 in intrahepatic cholangiocarcinoma tissues by real-time PCR, and defined the target gene and biologically functional effect by luciferase reporter assay and western blot analysis. We found that the miR-214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non-metastatic tissues. Inhibition of miR-214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cell. We further demonstrated that downregulated miR-214 increased the levels of the EMT-associated genes Twist, and decreased E-cadherin levels. We confirmed that downregulated miR-214 promoted EMT by directly targeting Twist gene. These results suggest an important role of miR-214 in regulating metastasis of intrahepatic cholangiocarcinoma and implicate the potential application of miR-214 in intrahepatic cholangiocarcinoma therapy.

PMID: 22540680 [PubMed - as supplied by publisher]

Polysomy and p16 deletion by fluorescence in situ hybridization in the diagnosis of indeterminate biliary strictures.

Fetched: May 2nd, 2012, 11:00pm MDT

Polysomy and p16 deletion by fluorescence in situ hybridization in the diagnosis of indeterminate biliary strictures.

Gastrointest Endosc. 2012 Jan;75(1):74-9

Authors: Gonda TA, Glick MP, Sethi A, Poneros JM, Palmas W, Iqbal S, Gonzalez S, Nandula SV, Emond JC, Brown RS, Murty VV, Stevens PD

Abstract
BACKGROUND: The diagnosis of indeterminate biliary strictures is limited because of the low sensitivity of cytology. However, an accurate diagnosis of malignancy is critical in the management of patients with suspected biliary malignancy. Testing for chromosomal aneuploidy by fluorescence in situ hybridization (FISH) may increase the yield.
OBJECTIVE: To evaluate the diagnostic accuracy of FISH in indeterminate biliary strictures and the additional value of including deletion of 9p21 (p16) in the diagnostic criteria of malignant biliary strictures.
DESIGN: Retrospective review.
SETTING: Academic medical center.
PATIENTS: This study involved 76 consecutive patients who were seen for the evaluation of indeterminate strictures at our institution. These patients were screened, and 50 patients with either a final pathologic diagnosis or ≥ 12 months' conclusive follow-up were included in the analysis.
MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, and area under the curve (AUC) analysis of cytology alone compared with the presence of FISH polysomy versus FISH polysomy and 9p21 deletion.
RESULTS: The presence of increased copy numbers (polysomy) of chromosome 3, 7, or 17 by FISH increased the sensitivity of brush cytology from 21% to 58%, and when the presence of 9p21 deletion was included, the sensitivity increased to 89%. The specificity of FISH was 97% (vs 100% for cytology). The accuracy of cytology combined with FISH polysomy (AUC = 0.93) or p16 deletion was significantly greater than the accuracy of cytology alone (AUC 0.6; P < .001) or even cytology combined with FISH polysomy (AUC = 0.77; P ≤ .05).
LIMITATIONS: Sample size. There is a relatively high incidence of malignant biliary strictures in the entire cohort but low incidence among primary sclerosing cholangitis patients, and the majority of cancers are cholangiocarcinomas (as opposed to pancreatic).
CONCLUSION: FISH significantly improves the diagnostic accuracy of brush cytology in indeterminate biliary strictures. In our series, the addition of 9p21 deletion to FISH polysomy and cytology further improved sensitivity. This suggests that 9p21 deletion may be added to the diagnostic criteria in indeterminate strictures.

PMID: 22100297 [PubMed - indexed for MEDLINE]

Expression and roles of NUPR1 in cholangiocarcinoma cells.

Fetched: April 28th, 2012, 11:00pm MDT

Expression and roles of NUPR1 in cholangiocarcinoma cells.

Anat Cell Biol. 2012 Mar;45(1):17-25

Authors: Kim KS, Jin DI, Yoon S, Baek SY, Kim BS, Oh SO

Abstract
Nuclear protein-1 (NUPR1) is a small nuclear protein that is responsive to various stress stimuli. Although NUPR1 has been associated with cancer development, its expression and roles in cholangiocarcinoma have not yet been described. In the present study, we found that NUPR1 was over-expressed in human cholangiocarcinoma tissues, using immunohistochemistry. The role of NUPR1 in cholangiocarcinoma was examined by its specific siRNA. NUPR1 siRNA decreased proliferation, migration and invasion of human cholangiocarcinoma cell lines (HuCCT1 and SNU1196 cells). From these results, we conclude that NUPR1 is over-expressed in cholangiocarcinoma and regulates the proliferation and motility of cancer cells.

PMID: 22536548 [PubMed - in process]

Origin and pathological characteristics of Klatskin tumor: a case report and literature review.

Fetched: April 28th, 2012, 11:00pm MDT

Origin and pathological characteristics of Klatskin tumor: a case report and literature review.

Pol J Pathol. 2012;63(1):65-70

Authors: Somer L, Andrejić B, Milošević P

Abstract
Hilar cholangiocarcinomas involving the bifurcation of the hepatic duct are called Klatskin tumors. A resected specimen of the hilar hepatic region with Klatskin tumor was analyzed. The lining epithelium of major biliary ducts was regular, while the majority of epithelial cells lining the excretory ducts of peribiliary glands (PBGs) exhibited malignant features. The connective tissue surrounding the PBGs was infiltrated by mucinous malignant epithelial cells, sometimes in a signet-ring cell form, with perineural invasion. The tumor epithelial cells showed distinct CK 7 and CA 19-9 positivity. The described cholangiocarcinoma was classified as the Bismuth-Corlette type IIIb and originated from the excretory ducts and acinar cells of PBGs.

PMID: 22535609 [PubMed - in process]

Permalink for 'Early massive bleeding after duodenal self-expandable metal stent placement for palliation of malignant gastric outlet obstruction (with video).'

Early massive bleeding after duodenal self-expandable metal stent placement for palliation of malignant gastric outlet obstruction (with video).

Fetched: April 28th, 2012, 11:00pm MDT

Early massive bleeding after duodenal self-expandable metal stent placement for palliation of malignant gastric outlet obstruction (with video).

Gastrointest Endosc. 2011 Dec;74(6):1426-7

Authors: Saleem A, Bakken J, Baron TH

PMID: 21429490 [PubMed - indexed for MEDLINE]

Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma.

Fetched: April 27th, 2012, 11:00pm MDT

Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma.

Ann Oncol. 2012 Apr 24;

Authors: van der Gaag NA, Kloek JJ, de Bakker JK, Musters B, Geskus RB, Busch OR, Bosma A, Gouma DJ, van Gulik TM

Abstract
BACKGROUND: Tumor location of extrahepatic cholangiocarcinoma (CCA) might influence survival after resection. METHODS: A consecutive series of 175 patients who had undergone a potentially curative resection of extrahepatic CCA was analyzed. We calculated concordance indices of different constructed prognostic models for survival including TNM (tumour-node-metastasis) staging and developed a nomogram of the most sensitive model. RESULTS: Overall cancer-specific survival rates were 83%, 58%, and 26% at 1, 2, and 5 years, respectively. Cancer-specific survival according to location was 42% for proximal, 23% for mid, and 19% for distal CCA after 5 years. Tumor location was not an independent significant predictor (P = 0.06). A prognostic model using all potential prognostic variables predicted survival better compared with TNM staging (concordance index 0.65 versus 0.63). A reduced model containing only lymph node status, microscopically residual tumor status, and tumor differentiation grade, also outperformed TNM staging (concordance index 0.66). CONCLUSIONS: Tumor location of extrahepatic CCA does not independently predict cancer-specific survival after resection. We developed a nomogram, based on a prognostic model with lymph node status, microscopically residual tumor status of resection margins, and tumor differentiation grade, that predicted survival better than TNM staging.

PMID: 22532585 [PubMed - as supplied by publisher]

The prognosis of perihilar cholangiocarcinoma after radical treatments.

Fetched: April 27th, 2012, 11:00pm MDT

The prognosis of perihilar cholangiocarcinoma after radical treatments.

Hepatology. 2012 Apr 24;

Authors: Fabris L, Alvaro D

PMID: 22532318 [PubMed - as supplied by publisher]

Permalink for 'Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection : Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation.'

Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection : Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation.

Fetched: April 27th, 2012, 11:00pm MDT

Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection : Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation.

Strahlenther Onkol. 2012 Apr 13;

Authors: Habermehl D, Lindel K, Rieken S, Haase K, Goeppert B, Büchler MW, Schirmacher P, Welzel T, Debus J, Combs SE

Abstract
BACKGROUND: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. PATIENTS AND METHODS: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. RESULTS: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. CONCLUSION: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials.

PMID: 22526232 [PubMed - as supplied by publisher]

Radiofrequency ablation in the management of unresectable intrahepatic cholangiocarcinoma.

Fetched: April 27th, 2012, 11:00pm MDT

Radiofrequency ablation in the management of unresectable intrahepatic cholangiocarcinoma.

J Vasc Interv Radiol. 2012 May;23(5):642-9

Authors: Fu Y, Yang W, Wu W, Yan K, Xing BC, Chen MH

Abstract
PURPOSE: To evaluate the efficacy of radiofrequency (RF) ablation for treatment of unresectable intrahepatic cholangiocarcinoma (ICC) and to explore the impact of prognostic variables on outcomes.
MATERIALS AND METHODS: From 2000-2010, 17 patients with 26 ICCs underwent RF ablation at a single institution. None of the patients were surgery candidates. Seven patients had 15 primary ICCs, and 10 patients had 11 recurrent ICCs. The median largest diameter was 4.4 cm (range 2.1-6.8 cm). A percutaneous approach was used in 15 patients, and an open approach was used in 2 patients. Early tumor necrosis, recurrence-free survival, and overall survival were analyzed. Univariate analysis was performed to evaluate 12 clinicopathologic and treatment-related variables associated with recurrence-free survival and overall survival.
RESULTS: Early tumor necrosis was 96.2% (25 of 26 tumors). The median follow-up period after RF ablation was 29 months. The median recurrence-free survival and overall survival were 17 months and 33 months. The 1-year, 3-year, and 5-year survival rates were 84.6%, 43.3%, and 28.9%, with an overall complication rate of 3.6% (1 of 28 sessions). Three variables were found to be closely associated with recurrence-free survival: lymph node metastases (P = .023), tumor differentiation (P = .034), and tumor number (P = .035). The only variable significantly associated with overall survival was tumor differentiation (P = .033).
CONCLUSIONS: Preliminary results showed that RF ablation may be an effective treatment for ICC because it achieved an acceptable survival rate in a small population. Prognostic factors might allow better patient selection and outcomes.

PMID: 22525022 [PubMed - in process]

Diagnosis and cure experience of hepatolithiasis-associated intrahepatic cholangiocarcinoma in 66 patients.

Fetched: April 27th, 2012, 11:00pm MDT

Diagnosis and cure experience of hepatolithiasis-associated intrahepatic cholangiocarcinoma in 66 patients.

Asian Pac J Cancer Prev. 2012;13(2):725-9

Authors: Li HY, Zhou SJ, Li M, Xiong D, Singh A, Guo QX, Liu CA, Gong JP

Abstract
Background: The management of hepatolithiasis combined with intrahepatic cholangicarcinoma (IHHCC) remains a challenge due to poor prognosis. The aim of this study was to summarize our diagnosis and cure experience of IHHCC over the recent 10 years. Methods: From January 1996 to January 2006, 66 patients with IHHCC were reviewed retrospectively. Results: Of the 66 patients, 52 underwent surgical resection (radical resection in 38 and palliative in 14) and 8 patients abdominal exploration, while the other 6 cases received endoscopic retrograde biliary internal drainage and stent implantation. In this series, correct diagnosis of advanced stage was made during operation in 8 cases (8/60, 13.3%) and all of them (underwent unnecessary abdominal exploration, among them the positive rate of CA19-9 was 100%, and the positive rate of CEA was 87.6% (7/8), incidence rate of ascites was 100% and short-term significant weight loss was 100%, with median overall survival of only 4 months. Conclusion: Radical resection is mandatory for IHHCC patient to achieve long-term survival, the CT and MR imaging features of IHHCC being concentric enhancement. Patients with IHHCC have significant higher CA199 and significant higher CEA and short-term significant weight loss and ascites should be considered with advanced stage of IHHCC and unnecessary non-therapeutic laparotomies should be avoided.

PMID: 22524851 [PubMed - in process]

Duodenoportal fistula resulting from peptic ulcer after extended right hepatectomy for cholangiocarcinoma.

Fetched: April 27th, 2012, 11:00pm MDT

Duodenoportal fistula resulting from peptic ulcer after extended right hepatectomy for cholangiocarcinoma.

Am Surg. 2012 Mar;78(3):154-5

Authors: Fujiki M, Ramirez JR, Aucejo FN

PMID: 22524745 [PubMed - in process]

Acute inflammatory demyelinating polyradiculoneuropathy in a patient receiving oxaliplatin-based chemotherapy.

Fetched: April 27th, 2012, 11:00pm MDT

Acute inflammatory demyelinating polyradiculoneuropathy in a patient receiving oxaliplatin-based chemotherapy.

Asia Pac J Clin Oncol. 2012 Jun;8(2):201-4

Authors: Yoon JY, Nam TS, Kim MK, Hwang JE, Shim HJ, Cho SH, Chung IJ, Bae WK

Abstract
We report a case of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) that developed in a patient with cholangiocarcinoma after receiving oxaliplatin-based chemotherapy. A 62-year-old man had multiple hypodense lesions with delayed enhancement in the both lobes of the liver on abdominal computed tomography. He was treated with 5-fluorouracil, leucovorin and oxaliplatin (100 mg/m(2) ). After eight cycles of treatment and a cumulative oxaliplatin dose of 780 mg/m(2) , he developed an unsteady gait, dysphagia, weakness of both the upper and lower limbs and impairment of all sensory modalities. Nerve conduction studies confirmed the diagnosis of AIDP. Immunoglobulin G i.v. was administered for 5 days but the neurological deficits of both his upper and lower limbs did not improve. This case highlights unusual peripheral nervous system manifestations in a patient who received chemotherapy with oxaliplatin.

PMID: 22524580 [PubMed - in process]

No correlation between the expression of FXR and genes involved in multidrug resistance phenotype of primary liver tumors.

Fetched: April 27th, 2012, 11:00pm MDT

No correlation between the expression of FXR and genes involved in multidrug resistance phenotype of primary liver tumors.

Mol Pharm. 2012 Apr 23;

Authors: Martinez-Becerra P, Vaquero J, Romero MR, Lozano E, Anadon C, Macias RI, Serrano MA, Grañé-Boladeras N, Muñoz-Bellvis L, Alvarez L, Sangro B, Pastor-Anglada M, Marin JJ

Abstract
Farnesoid X receptor (FXR) has been recently reported to enhance chemoresistance through bile acid-independent mechanisms. Thus, FXR transfection plus activation with GW4060 resulted in reduced sensitivity to cisplatin-induced toxicity. This is interesting because primary tumors of the liver, an organ where FXR is expressed, exhibit marked refractoriness to pharmacological treatment. Here we have determined whether FXR is up-regulated in hepatocellular carcinoma (HCC), cholangiocarcinoma (CGC) and hepatoblastoma (HPB) and whether this is related with the expression of genes involved in mechanisms of chemoresistance. Using RT-QPCR and Taqman Low-Density Arrays we have analyzed biopsies from healthy livers or surgically removed tumors from naive patients and cell lines derived from HCC (SK-HEP-1, Alexander and Huh7), CGC (TFK1) and HPB (HepG2), before and after exposure to cisplatin at IC50 for 72 h. In liver tumors FXR expression was not enhanced but significantly decreased (healthy liver>HCC>HPB≈CGC). Except for CGC, this was not accompanied by changes in the proportions of FXR isoforms. Changes in 36 genes involved in drug uptake/efflux and metabolism, expression/function of molecular targets, and survival/apoptosis balance were found. Changes affecting SLC22A1, CYP2A1 and BIRC5 were shared by HCC, CGC and HPB. Similarity in gene expression profiles between cell lines and parent tumors was found. Pharmacological challenge with cisplatin induced changes that increased this resemblance. This was not dependent upon FXR expression. Thus, although FXR may play a role in inducing chemoresistance under certain circumstances, its up-regulation does not seem to be involved in the multidrug resistance phenotype characteristic of HCC, CGC and HPB.

PMID: 22524153 [PubMed - as supplied by publisher]

18F-FDG PET/CT predicts survival after radioembolization of hepatic metastases from breast cancer.

Fetched: April 27th, 2012, 11:00pm MDT

18F-FDG PET/CT predicts survival after radioembolization of hepatic metastases from breast cancer.

J Nucl Med. 2012 Mar;53(3):371-7

Authors: Haug AR, Tiega Donfack BP, Trumm C, Zech CJ, Michl M, Paul Laubender R, Uebleis C, Bartenstein P, Heinemann V, Hacker M

Abstract
UNLABELLED: (90)Y radioembolization (selective internal radiation therapy [SIRT]) has emerged as a valuable therapeutic option in unresectable, chemotherapy-refractory hepatic metastases from breast cancer. The objective of the present study was to evaluate (18)F-FDG PET/CT for predicting survival in these patients.
METHODS: Fifty-eight consecutive patients with hepatic metastases from breast cancer were treated with SIRT. Before therapy, all patients underwent MRI of the liver. (18)F-FDG PET/CT was performed at baseline and 3 mo after SIRT to calculate percentage changes in maximum (18)F-FDG standardized uptake value (SUV(max)) relative to baseline. A decrease of more than 30% in the follow-up scan, compared with the baseline examination, indicated therapy response. Treatment response at 3 mo was also assessed in 43 patients using contrast-enhanced MRI and CT on the basis of the Response Evaluation Criteria in Solid Tumors. All patients were followed to complete survival data.
RESULTS: Overall median survival after SIRT was 47 wk. Response as assessed with SUV(max) correlated significantly with survival after radioembolization, with responders having significantly longer survival (65 wk) than nonresponders (43 wk; P < 0.05). In multivariate analysis the change in SUV(max) was identified as the only independent predictor of survival (hazard ratio, 0.23; P < 0.005). Furthermore, a high pretherapeutic SUV(max) (>20) was associated with a significantly shorter median survival than was an SUV(max) of 20 or less (21 vs. 52 wk; P < 0.005). The presence of extrahepatic metastases (mean survival in both groups, 47 wk; P = 0.92), hormone receptor status (estrogen, P = 0.53; progesterone, P = 0.79; Her-2/neu, P = 0.49), and MRI/CT response (P = 0.91) did not predict survival.
CONCLUSION: The change in SUV(max) as assessed by (18)F-FDG PET/CT before and 3 mo after SIRT was identified as the only independent predictor of survival in patients with hepatic metastases of breast cancer.

PMID: 22331219 [PubMed - indexed for MEDLINE]

Permalink for 'α-Fetoprotein-producing gastric carcinoma and combined hepatocellular and cholangiocarcinoma show similar morphology but different histogenesis with respect to SALL4 expression.'

α-Fetoprotein-producing gastric carcinoma and combined hepatocellular and cholangiocarcinoma show similar morphology but different histogenesis with respect to SALL4 expression.

Fetched: April 23rd, 2012, 11:00pm MDT

α-Fetoprotein-producing gastric carcinoma and combined hepatocellular and cholangiocarcinoma show similar morphology but different histogenesis with respect to SALL4 expression.

Hum Pathol. 2012 Apr 17;

Authors: Ikeda H, Sato Y, Yoneda N, Harada K, Sasaki M, Kitamura S, Sudo Y, Ooi A, Nakanuma Y

Abstract
α-Fetoprotein is expressed in hepatocellular carcinoma, yolk sac tumor, and some gastric carcinomas. The α-fetoprotein-producing gastric carcinoma composed of hepatoid and common adenocarcinoma shows morphological similarities to combined hepatocellular and cholangiocarcinoma. In this study, the expression of putative hepatic stem/progenitor markers (EpCAM, OV-6, DLK-1, and NCAM/CD56), hepatocyte markers (HepParI, α-fetoprotein, glypican 3), and the germ cell marker SALL4 was examined in α-fetoprotein-producing gastric carcinoma (20 cases) and combined hepatocellular and cholangiocarcinoma (20 cases) for evaluation of pathologic differentiation and also the histogenesis of both tumors. The SALL4 protein was expressed in 95% of α-fetoprotein-producing gastric carcinoma, including the hepatoid component (hepatoid gastric carcinoma), but was absent in combined hepatocellular and cholangiocarcinoma. Glypican 3 and α-fetoprotein were detected in all hepatoid-type α-fetoprotein-producing gastric carcinoma but variably in combined hepatocellular and cholangiocarcinoma. NCAM/CD56 was expressed focally in combined hepatocellular and cholangiocarcinoma but was rare in hepatoid gastric carcinoma. EpCAM, DLK-1, and OV6 were variably expressed in hepatoid gastric carcinoma and combined hepatocellular and cholangiocarcinoma. SALL4 was a useful differential marker for combined hepatocellular and cholangiocarcinoma and hepatoid gastric carcinoma. The histogenesis of hepatoid gastric carcinoma expressing SALL4 seems to reflect fetal gut differentiation or involve the germ cell lineage and may be different from that of combined hepatocellular and cholangiocarcinoma involving the hepatic stem cell or progenitor cell lineages. In conclusion, hepatoid gastric carcinoma and combined hepatocellular and cholangiocarcinoma shared morphologies, whereas the distinction of hepatoid gastric carcinoma from combined hepatocellular and cholangiocarcinoma is possible by immunostaining for SALL4. These 2 tumors seem to differ in their histogenesis with respect to SALL4 expression.1.

PMID: 22516245 [PubMed - as supplied by publisher]

Crucial role of heme oxygenase-1 on the sensitivity of cholangiocarcinoma cells to chemotherapeutic agents.

Fetched: April 21st, 2012, 11:00pm MDT

Crucial role of heme oxygenase-1 on the sensitivity of cholangiocarcinoma cells to chemotherapeutic agents.

PLoS One. 2012;7(4):e34994

Authors: Kongpetch S, Kukongviriyapan V, Prawan A, Senggunprai L, Kukongviriyapan U, Buranrat B

Abstract
Cancer cells acquire drug resistance via various mechanisms including enhanced cellular cytoprotective and antioxidant activities. Heme oxygenase-1 (HO-1) is a key enzyme exerting potent cytoprotection, cell proliferation and drug resistance. We aimed to investigate roles of HO-1 in human cholangiocarcinoma (CCA) cells for cytoprotection against chemotherapeutic agents. KKU-100 and KKU-M214 CCA cell lines with high and low HO-1 expression levels, respectively, were used to evaluate the sensitivity to chemotherapeutic agents, gemcitabine (Gem) and doxorubicin. Inhibition of HO-1 by zinc protoporphyrin IX (ZnPP) sensitized both cell types to the cytotoxicity of chemotherapeutic agents. HO-1 gene silencing by siRNA validated the cytoprotective effect of HO-1 on CCA cells against Gem. Induction of HO-1 protein expression by stannous chloride enhanced the cytoprotection and suppression of apoptosis caused by anticancer agents. The sensitizing effect of ZnPP was associated with increased ROS formation and loss of mitochondrial transmembrane potential, while Gem alone did not show any effects. A ROS scavenger, Tempol, abolished the sensitizing effect of ZnPP on Gem. Combination of ZnPP and Gem enhanced the release of cytochrome c and increased p21 levels. The results show that HO-1 played a critical role in cytoprotection in CCA cells against chemotherapeutic agents. Targeted inhibition of HO-1 may be a strategy to overcome drug resistance in chemotherapy of bile duct cancer.

PMID: 22514698 [PubMed - in process]

A case of emphysematous hepatitis with spontaneous pneumoperitoneum in a patient with hilar cholangiocarcinoma.

Fetched: April 21st, 2012, 11:00pm MDT

A case of emphysematous hepatitis with spontaneous pneumoperitoneum in a patient with hilar cholangiocarcinoma.

Korean J Hepatol. 2012 Mar;18(1):94-7

Authors: Kim JH, Jung ES, Jeong SH, Kim JS, Ku YS, Hahm KB, Kim JH, Kim YS

Abstract
An 80-year-old woman with hilar cholangiocarcinoma was hospitalized due to sudden-onset abdominal pain. Computed tomography revealed hepatic necrosis accompanied with emphysematous change in the superior segment of the right liver (S7/S8), implying spontaneous rupture, based on the presence of perihepatic free air. Although urgent percutaneous drainage was performed, neither pus nor fluids were drained. These findings suggest emphysematous hepatitis with a hepatic mass. Despite the application of intensive care, the patient's condition deteriorated rapidly, and she died 3 days after admission to hospital. Liver gas has been reported in some clinical diseases (e.g., liver abscess) to be caused by gas-forming organisms; however, emphysematous hepatitis simulating emphysematous pyelonephritis is very rare. The case reported here was of fatal emphysematous hepatitis in a patient with hilar cholangiocarcinoma.

PMID: 22511909 [PubMed - in process]

Permalink for 'Preexcisional artery reconstruction: A new strategy in multiple hepatic artery reconstruction for reducing ischemic injury of the liver.'

Preexcisional artery reconstruction: A new strategy in multiple hepatic artery reconstruction for reducing ischemic injury of the liver.

Fetched: April 21st, 2012, 11:00pm MDT

Preexcisional artery reconstruction: A new strategy in multiple hepatic artery reconstruction for reducing ischemic injury of the liver.

Microsurgery. 2012 Apr 18;

Authors: Iida T, Mihara M, Narushima M, Yoshimatsu H, Hara H, Koshima I

Abstract
Multiple reconstructions of the hepatic arteries (HA) after cancer resection presents a surgical challenge, not only because it is technically demanding, but also because attention must be paid to potential ischemic injury to the liver caused by the prolonged ischemia. We present a novel "preexcisional artery reconstruction" method for minimizing ischemic injury of the liver. A 65-year-old woman presented with cholangiocarcinoma invading the HA. Pancreatoduodenectomy, resection, and multiple reconstruction of the HA were performed. First, the left hepatic artery (LHA) was reconstructed prior to the tumor resection. During this procedure, blood supply was maintained to most of the liver via the right hepatic artery (RHA). Then, resection of the tumor en bloc with the HA was performed, followed by reconstruction of the RHA. During this procedure, blood supply was maintained via the already-reconstructed LHA, thereby limiting the ischemic area. Use of this method allowed the ischemia time and region to be divided and minimized, thereby leading to a reduced risk of ischemia-related complications. We believe that this method may be one of the useful approaches in multiple HA reconstruction. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.

PMID: 22511322 [PubMed - as supplied by publisher]

[Extrahepatic Cholangiocarcinoma: Current State of Palliation Therapy.]

Fetched: April 21st, 2012, 11:00pm MDT

[Extrahepatic Cholangiocarcinoma: Current State of Palliation Therapy.]

Zentralbl Chir. 2012 Apr 17;

Authors: Wolkersdörfer GW, Berr F, Nawara C, Emmanuel K

Abstract
Introduction: Decompression of bile ducts is the priority objective in the non-curative stage of hilar cholangiocarcinoma. Only this will prevent or slow down infectious complications and secondary biliary cirrhosis thereby sustaining the quality of life. Key Statements: At present, photodynamic therapy combined with insertion of an endoprosthesis seems to be best documented and most appropriate therapy.Methods: Data from a selective literature search combined with our clinical experience were evaluated. Conclusions: Therapeutic measures should match the dissemination and stage of the tumor: in locally advanced or progressing disease (stage III) a local ablating therapy, in systemically progressing disease (stage IV) systemic chemotherapy should be utilised.

PMID: 22511020 [PubMed - as supplied by publisher]

Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.

Fetched: April 21st, 2012, 11:00pm MDT

Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.

Br J Cancer. 2012 Apr 17;

Authors: Prado CM, Bekaii-Saab T, Doyle LA, Shrestha S, Ghosh S, Baracos VE, Sawyer MB

Abstract
Background:Cancer cachexia is characterised by skeletal muscle wasting; however, potential for muscle anabolism in patients with advanced cancer is unproven.Methods:Quantitative analysis of computed tomography images for loss/gain of muscle in cholangiocarcinoma patients receiving selumetinib (AZD6244; ARRY-142886) in a Phase II study, compared with a separate standard therapy group. Selumetinib is an inhibitor of mitogen-activated protein/extracellular signal-regulated kinase and of interleukin-6 secretion, a putative mediator of muscle wasting.Results:Overall, 84.2% of patients gained muscle after initiating selumetinib; mean overall gain of total lumbar muscle cross-sectional area was 13.6 cm(2)/100 days (∼2.3 kg on a whole-body basis). Cholangiocarcinoma patients who began standard treatment were markedly catabolic, with overall muscle loss of -7.3 cm(2)/100 days (∼1.2 kg) and by contrast only 16.7% of these patients gained muscle.Conclusion:Our findings suggest that selumetinib promotes muscle gain in patients with cholangiocarcinoma. Specific mechanisms and relevance for cachexia therapy remain to be investigated.British Journal of Cancer advance online publication, 17 April 2012; doi:10.1038/bjc.2012.144 www.bjcancer.com.

PMID: 22510747 [PubMed - as supplied by publisher]

Permalink for 'Temporary endosonography-guided biliary drainage for transesophageal placement of a metal stent in recurrent cholangiocarcinoma.'

Temporary endosonography-guided biliary drainage for transesophageal placement of a metal stent in recurrent cholangiocarcinoma.

Fetched: April 19th, 2012, 11:00pm MDT

Temporary endosonography-guided biliary drainage for transesophageal placement of a metal stent in recurrent cholangiocarcinoma.

Dig Endosc. 2012 May;24(3):191

Authors: Ito K, Fujita N, Noda Y, Kobayashi G, Horaguchi J, Koshita S, Kanno Y, Ogawa T, Masu K

PMID: 22507098 [PubMed - in process]

Chromosomes and karyotype analysis of a liver fluke, Opisthorchis viverrini, by scanning electron microscopy.

Fetched: April 19th, 2012, 11:00pm MDT

Chromosomes and karyotype analysis of a liver fluke, Opisthorchis viverrini, by scanning electron microscopy.

Parasitol Int. 2012 Apr 4;

Authors: Kaewkong W, Choochote W, Kanla P, Maleewong W, Intapan PM, Wongkham S, Wongkham C

Abstract
Opisthorchis viverrini, a human liver fluke, has been categorized as the carcinogenic organism according to the strong association with carcinogenesis of cholangiocarcinoma (CCA). The infection of this food-borne parasite is a major impact on the health of humans, especially CCA patients in the northeast of Thailand. Taxonomy, morphology, epidemiology and molecular study of O. viverrini have been publicized increasingly but the precise karyotypic study is still incomplete. In this study, the chromosomes of O. viverrini were prepared from the testes of adult worms retrieved from metacercariae infected-hamsters. The chromosomes of O. viverrini were identified in haploid (n=6) meiotic metaphase and in diploid (2n=12) mitotic metaphase by light microscopy. The chromosome number, length and nomenclature of each chromosome were determined by scanning electron microscopy. The six chromosomes consist of one large-sized metacentric, one medium-sized metacentric, two small-sized metacentric, one small-sized submetacentric and one small-sized acrocentric chromosomes with the lengths of 2.84±0.03, 2.12±0.10, 1.71±0.13, 1.44±0.04, 1.23±0.03 and 0.84±0.13μm, respectively. This is the first karyotype analysis of O. viverrini with defined complete nomenclature.

PMID: 22504416 [PubMed - as supplied by publisher]

Efficacy of Neoadjuvant Chemoradiation, followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers.

Fetched: April 19th, 2012, 11:00pm MDT

Efficacy of Neoadjuvant Chemoradiation, followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers.

Gastroenterology. 2012 Apr 12;

Authors: Murad SD, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, Botha JF, Mezrich JD, Chapman WC, Schwartz JJ, Hong JC, Emond JC, Jeon H, Rosen CB, Gores GJ, Heimbach JK

Abstract
BACKGROUND & AIMS: Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing (UNOS) to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception. METHODS: We collected and analyzed data from 12 large-volume transplant centers in the US. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n=287 total patients). Center-specific protocols and medical charts were reviewed on-site. RESULTS: The patients completed external radiation (99%), brachytherapy (75%), radio-sensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate of 11.5% in 3 months). Intent-to-treat survival rates were 68% and 53%, 2 and 5 years after therapy, respectively; post-transplant, recurrence-free survival rates were 78% and 65%, respectively. Patients outside the UNOS criteria (those with tumor mass >3 cm, trans-peritoneal tumor biopsy, or metastatic disease) or with a prior malignancy had significantly shorter survival times (P<.001). There were no differences in outcomes among patients based on differences in operative staging or brachytherapy. Although most patients came from 1 center (n=193), the other 11 centers had similar survival times after therapy. CONCLUSION: Patients with perihilar cholangiocarcinoma who were treated with neoadjuvant therapy followed by liver transplantation at 12 US centers had a 65% rate of recurrence-free survival after 5 years, demonstrating this therapy to be highly effective. An 11.5% dropout rate after 3.5 months of therapy indicates the appropriateness of the MELD exception. Rigorous selection is important for the continued success of this treatment.

PMID: 22504095 [PubMed - as supplied by publisher]

Oriental cholangiohepatitis masquerading as cholangiocarcinoma: A rare presentation that surgeons need to know.

Fetched: April 19th, 2012, 11:00pm MDT

Oriental cholangiohepatitis masquerading as cholangiocarcinoma: A rare presentation that surgeons need to know.

Int J Surg Case Rep. 2012 Mar 16;3(7):235-237

Authors: Singla S, Warner AH, Jain A, Thomas RM, Karachristos A

Abstract
INTRODUCTION: The detection of an abnormal hepatic mass with ductal dilatation is highly concerning for malignancy. However, if such patients happen to be immigrants from endemic parts of Asia or South America, further investigations are necessary to rule out oriental cholangiohepatitis, a rare recurrent disease of the hepatobiliary system that can masquerade as cholangiocarcinoma. PRESENTATION OF CASE: We report a case of a patient of South Asian origin who presented to us with acute cholangitis and moderately dilated left hepatic ducts. The findings were highly suspicious for advanced hepatic malignancy; however the laboratory and pathological investigations remained normal. We suspected an unlikely etiology and proceeded with conservative hepatic resection. The histology revealed cholangiohepatitis without any evidence of malignancy. DISCUSSION: Cholangiohepatitis is a complex hepatobiliary disease that commonly manifests as recurrent cholangitis or overt biliary sepsis and can rarely present as an abnormal hepatic mass. It results from the development of intrahepatic or extrahepatic strictures that causes stone formation and biliary dilation in the absence of gallbladder disease. Although it is endemic in many parts of the world, it is rare in the western world, and therefore it can present as a significant diagnostic enigma. CONCLUSION: Cholangiohepatitis is a rare clinical entity that requires a multi-disciplinary team approach. Surgery plays a dominant role in the management of such patients and therefore surgeons need to be aware of this disease.

PMID: 22503913 [PubMed - as supplied by publisher]

Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma.

Fetched: April 19th, 2012, 11:00pm MDT

Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma.

Hum Pathol. 2012 Apr 11;

Authors: Kipp BR, Voss JS, Kerr SE, Barr Fritcher EG, Graham RP, Zhang L, Highsmith WE, Zhang J, Roberts LR, Gores GJ, Halling KC

Abstract
Somatic mutations in isocitrate dehydrogenase 1 and 2 genes are common in gliomas and help stratify patients with brain cancer into histologic and molecular subtypes. However, these mutations are considered rare in other solid tumors. The aims of this study were to determine the frequency of isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma and to assess histopathologic differences between specimens with and without an isocitrate dehydrogenase mutation. We sequenced 94 formalin-fixed, paraffin-embedded cholangiocarcinoma (67 intrahepatic and 27 extrahepatic) assessing for isocitrate dehydrogenase 1 (codon 132) and isocitrate dehydrogenase 2 (codons 140 and 172) mutations. Multiple histopathologic characteristics were also evaluated and compared with isocitrate dehydrogenase 1/2 mutation status. Of the 94 evaluated specimens, 21 (22%) had a mutation including 14 isocitrate dehydrogenase 1 and 7 isocitrate dehydrogenase 2 mutations. Isocitrate dehydrogenase mutations were more frequently observed in intrahepatic cholangiocarcinoma than in extrahepatic cholangiocarcinoma (28% versus 7%, respectively; P = .030). The 14 isocitrate dehydrogenase 1 mutations were R132C (n = 9), R132S (n = 2), R132G (n = 2), and R132L (n = 1). The 7 isocitrate dehydrogenase 2 mutations were R172K (n = 5), R172M (n = 1), and R172G (n = 1). Isocitrate dehydrogenase mutations were more frequently observed in tumors with clear cell change (P < .001) and poorly differentiated histology (P = .012). The results of this study show for the first time that isocitrate dehydrogenase 1 and 2 genes are mutated in cholangiocarcinoma. The results of this study are encouraging because it identifies a new potential target for genotype-directed therapeutic trials and may represent a potential biomarker for earlier detection of cholangiocarcinoma in a subset of cases.

PMID: 22503487 [PubMed - as supplied by publisher]

Permalink for 'Ultrasonography as a Tool for Monitoring the Development and Progression of Cholangiocarcinoma in Opisthorchis viverrini/ Dimethylnitrosamine-Induced Hamsters.'

Ultrasonography as a Tool for Monitoring the Development and Progression of Cholangiocarcinoma in Opisthorchis viverrini/ Dimethylnitrosamine-Induced Hamsters.

Fetched: April 19th, 2012, 11:00pm MDT

Ultrasonography as a Tool for Monitoring the Development and Progression of Cholangiocarcinoma in Opisthorchis viverrini/ Dimethylnitrosamine-Induced Hamsters.

Asian Pac J Cancer Prev. 2012;13(1):87-90

Authors: Plengsuriyakarn T, Eursitthichai V, Labbunruang N, Na-Bangchang K, Tesana S, Aumarm W, Pongpradit A, Viyanant V

Abstract
Cholangiocarcinoma (CCA) is the most common cancer in northeastern Thailand. At present, effective diagnosis of CCA either in humans or animals is not available. Monitoring the development and progression of CCA in animal models is essential for research and development of new promising chemotherapeutics. Ultrasonography has been widely used for screening of bile duct obstruction in CCA patients. In this study, we preliminarily investigated the applicability of ultrasonography to monitor the development and progression of CCA in Syrian golden hamsters (n=8) induced by Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN) administration. Ultrasonography and histopathological examination of hamsters was performed at week 0, 20, 24 and 28 of OV infection or at the start of water/Tween-80 administration to controls. The ultrasonographic images of liver parenchyma and gallbladders of OV/DMN-induced CCA hamsters showed sediments in gallbladder, thickening of gallbladder wall, and hypoechogenicity of liver parenchyma cells. The ultrasonographic images of liver tissues were found to correlate well with histopathological examination. Although ultrasonography does not directly detect the occurrence of CCA, it reflects the thickening of bile ducts and abnormality of liver tissues. It may be applied as a reliable tool for monitoring the development and progression of CCA in animal models in research and development of new promising chemotherapeutics for CCA.

PMID: 22502719 [PubMed - in process]

ROS1 as a 'druggable' receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway.

Fetched: April 19th, 2012, 11:00pm MDT

ROS1 as a 'druggable' receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway.

Expert Rev Anticancer Ther. 2012 Apr;12(4):447-56

Authors: Ou SH, Tan J, Yen Y, Soo RA

Abstract
ROS1 is one of 58 receptor tyrosine kinases, and one of two orphan receptor tyrosine kinases where its ligand is unknown. ROS1 is evolutionarily related to ALK. ROS1 rearrangement was discovered in glioblastoma in 1987, in non-small-cell lung cancer (NSCLC) in 2007, and in cholangiocarcinoma in 2011. While the clinicopathologic characteristics of ROS1-rearranged glioblastoma and cholangiocarcinoma patients remain to be defined, the clinicopathologic characteristics of ROS1-rearranged NSCLC patients have recently been described. Although ROS1 shares only 49% amino acid sequence homology with ALK in the kinase domains, several ALK inhibitors have demonstrated in vitro inhibitory activity against ROS1. With the recent US approval of crizotinib, a multi-targeted ALK/MET kinase inhibitor, for the treatment of ALK-rearranged NSCLC, attention has turned to ROS1-rearranged tumors, especially NSCLC. The next few years should witness a rapid pace of clinical research in ROS1-rearranged tumors utilizing available ALK inhibitors.

PMID: 22500682 [PubMed - in process]

Current management of cholangiocarcinoma.

Fetched: April 17th, 2012, 11:00pm MDT

Current management of cholangiocarcinoma.

Mt Sinai J Med. 2012 Mar;79(2):232-45

Authors: Singh MK, Facciuto ME

Abstract
Cholangiocarcinoma is the second most common primary hepatobiliary malignancy after hepatocellular carcinoma and remains among the most difficult management problems faced by surgeons. Curative surgery is achieved in only 25% to 30% of patients. Local tumor extent, such as portal vein invasion and hepatic lobar atrophy, does not preclude resection. Long-term survival has been seen only in patients who underwent extensive liver resections, suggesting that bile-duct excision alone is less effective. The majority of patients have unresectable disease, with 20% to 30% incidence of distant metastasis at presentation. Unresectable patients should be referred for nonsurgical biliary decompression, and in potential curative resection candidates the use of biliary stents should be reduced. Liver transplantation provides the option of wide resection margins, expanding the indication of surgical intervention for selected patients who otherwise are not surgical candidates due to lack of functional hepatic reserve. Mt Sinai J Med 79:232-245, 2012. © 2012 Mount Sinai School of Medicine.

PMID: 22499494 [PubMed - in process]

Intraoperative Assessment of the Resectability of Hilar Cholangiocarcinoma.

Fetched: April 17th, 2012, 11:00pm MDT

Intraoperative Assessment of the Resectability of Hilar Cholangiocarcinoma.

Hepatogastroenterology. 2012 Apr 12;59(120)

Authors: Shirai Y, Sakata J, Wakai T, Hatakeyama K

Abstract
Major hepatectomy combined with extrahepatic bile duct resection has gained acceptance as a standard radical procedure for hilar cholangiocarcinoma. Here, we describe an operative technique, "taping of the right hepatic artery behind Calot's triangle", for assessing the resectability of hilar lesions for which left-sided hepatectomy is planned. Briefly, after retracting the gallbladder anteriorly, the lateral peritoneum of the hepatoduodenal ligament is incised longitudinally (3-4cm in length) behind Calot's triangle and just to the left of the fissure of Ganz. By dividing the adipose tissue, the distal portion of the right hepatic artery is identified and secured with tape. Any suspicious tissues around the right hepatic artery should be submitted to frozen-section analysis. If no cancer cells were found, the planned resection goes ahead. Conversely, if they were found, the resection should be abandoned. Since 2003, 14 patients for whom left-sided hepatectomy was planned underwent this technique. Three patients were judged to have irresectable tumors and the planned resection could be avoided. In conclusion, this simple technique, isolation of the right hepatic artery behind Calot's triangle before starting resection, should be applied to all hilar malignancies when a left-sided hepatectomy is planned.

PMID: 22497948 [PubMed - as supplied by publisher]

Diagnosis and Surgical Treatment of Mucin-Producing Bile Duct Tumors.

Fetched: April 17th, 2012, 11:00pm MDT

Diagnosis and Surgical Treatment of Mucin-Producing Bile Duct Tumors.

Hepatogastroenterology. 2012 Apr 12;59(120)

Authors: Xin-Wei Y, Kui W, Jue Y, Xiao-Bo M, Bao-Hua Z, Feng S, Meng-Chao W

Abstract
Background/Aims: To summarize the experience of diagnosis and surgical treatment of mucin-producing bile duct tumors (MPBTs). Methodology: A retrospective analysis was undertaken to determine the radiography characteristics and results of surgical treatment of MPBTs over the past 9 years. Only eight patients underwent such treatment. The detailed data of diagnosis, treatment and prognosis were carefully studied. Results: Intermittent jaundice was the most frequently clinical manifestation of MPBTs, with unique characteristics on magnetic resonance cholangiopancreatography (MPCP) when compared with gallbladder carcinoma, hilar cholangiocarcinoma and distal bile duct cancer. All the 8 patients with MPBTs received appropriate surgical procedure and were cured. Conclusions: Appropriate diagnosis and curative hepatectomy for MPBTs made it possible to achieve long-term survival.

PMID: 22497947 [PubMed - as supplied by publisher]

DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells.

Fetched: April 14th, 2012, 11:00pm MDT

DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells.

Biochem Biophys Res Commun. 2012 Apr 3;

Authors: Saiki Y, Yoshino Y, Fujimura H, Manabe T, Kudo Y, Shimada M, Mano N, Nakano T, Lee Y, Shimizu S, Oba S, Fujiwara S, Shimizu H, Chen N, Nezhad ZK, Jin G, Fukushige S, Sunamura M, Ishida M, Motoi F, Egawa S, Unno M, Horii A

Abstract
Although gemcitabine is the most effective chemotherapeutic agent against pancreatic cancer, a growing concern is that a substantial number of patients acquire gemcitabine chemoresistance. To elucidate the mechanisms of acquisition of gemcitabine resistance, we developed gemcitabine-resistant cell lines from six human cancer cell lines; three pancreatic, one gastric, one colon, and one bile duct cancer. We first analyzed gemcitabine uptake using three paired parental and gemcitabine resistant pancreatic cancer cell lines (PK-1 and RPK-1, PK-9 and RPK-9, PK-59 and RPK-59) and found that uptake of gemcitabine was rapid. However, no DNA damage was induced in resistant cells. We further examined the microarray-based expression profiles of the cells to identify genes associated with gemcitabine resistance and found a remarkable reduction in the expression of deoxycytidine kinase (DCK). DCK is a key enzyme that activates gemcitabine by phosphorylation. Genetic alterations and expression of DCK were studied in these paired parental and derived gemcitabine-resistant cell lines, and inactivating mutations were found only in gemcitabine-resistant cell lines. Furthermore, siRNA-mediated knockdown of DCK in the parental cell lines yielded gemcitabine resistance, and introduction of DCK into gemcitabine-resistant cell lines invariably restored gemcitabine sensitivities. Mutation analyses were expanded to three other different paired cell lines, DLD-1 and RDLD-1 (colon cancer cell line), MKN-28 and RMKN-28 (gastric cancer cell line), and TFK-1 and RTFK -1 (cholangiocarcinoma cell line). We found inactivating mutations in RDLD-1 and RTFK-1 and decreased expression of DCK in RMKN-28. These results indicate that the inactivation of DCK is one of the crucial mechanisms in acquisition of gemcitabine resistance.

PMID: 22490663 [PubMed - as supplied by publisher]

Overexpression of ECM1 Contributes to Migration and Invasion in Cholangiocarcinoma Cell.

Fetched: April 14th, 2012, 11:00pm MDT

Overexpression of ECM1 Contributes to Migration and Invasion in Cholangiocarcinoma Cell.

Neoplasma. 2012 Apr 10;

Authors: P Xiong G, Zhang JX, P Gu S, Wu YB, Liu JF

Abstract
Although the expression of extracellular matrix protein-1 (ECM1) has been documented in several tumor models, the function of ECM1 has remained unclear. In this study, expression of ECM1 was detected by real time PCR and immunohistochemistry. The role and mechanism of ECM1 overexpression in cholangiocarcinoma (CCA) cells were assessed by wound-healing, matrigel invasion assay and Western blotting. Expression of ECM1 was significantly elevated in CCA tissues than that in adjacent noncancerous, cholangitis and normal bile duct tissues. Its overexpression was associated with poor differentiation, lymph node metastasis, poor prognosis, and the level of CA199, MMP-9, estrogen receptor. Knockdown of ECM1 suppressed migration and invasion of CCA cells. Using PI3K or IKK inhibitor reduced the level of phospho-Akt or phospho-IκBα as well as ECM1. Taken together, overexpression of ECM1 may contribute to CCA initiation and progression through promoting migration and invasion of CCA cells, its overexpression was associated with Akt/NF-κB signaling axis. Keywords: extracellular matrix protein 1; migration; invasion; Akt/NF-κB; cholangiocarcinoma.

PMID: 22489696 [PubMed - as supplied by publisher]

Permalink for 'Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART I: Diagnosis-clinical staging and pathology.'

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART I: Diagnosis-clinical staging and pathology.

Fetched: April 14th, 2012, 11:00pm MDT

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART I: Diagnosis-clinical staging and pathology.

J Surg Oncol. 2012 Apr 4;

Authors: Marsh RD, Alonzo M, Bajaj S, Baker M, Elton E, Farrell TA, Gore RM, Hall C, Nowak J, Roy H, Shaikh A, Talamonti MS

Abstract
Biliary tract cancers (gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma, and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.

PMID: 22488652 [PubMed - as supplied by publisher]

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART II: Multidisciplinary management.

Fetched: April 14th, 2012, 11:00pm MDT

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART II: Multidisciplinary management.

J Surg Oncol. 2012 Apr 4;

Authors: Marsh RD, Alonzo M, Bajaj S, Baker M, Elton E, Farrell TA, Gore RM, Hall C, Nowak J, Roy H, Shaikh A, Talamonti MS

Abstract
Biliary tract cancers (gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases. J. Surg. Oncol © 2012 Wiley Periodicals, Inc.

PMID: 22488601 [PubMed - as supplied by publisher]

Permalink for 'Clinical outcome in patients with hilar malignant strictures type II Bismuth-Corlette treated by minimally invasive unilateral versus bilateral endoscopic biliary drainage.'

Clinical outcome in patients with hilar malignant strictures type II Bismuth-Corlette treated by minimally invasive unilateral versus bilateral endoscopic biliary drainage.

Fetched: April 14th, 2012, 11:00pm MDT

Clinical outcome in patients with hilar malignant strictures type II Bismuth-Corlette treated by minimally invasive unilateral versus bilateral endoscopic biliary drainage.

Hepatobiliary Pancreat Dis Int. 2012 Apr;11(2):209-14

Authors: Bulajic M, Panic N, Radunovic M, Scepanovic R, Perunovic R, Stevanovic P, Ille T, Zilli M, Bulajic M

Abstract
BACKGROUND: Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors. The aim of this two-center prospective study was to compare unilateral versus bilateral drainage in hilar malignant stenosis Bismuth-Corlette type II.
METHODS: During a 3-year period, a total of 49 patients with hilar tumors (Bismuth-Corlette type II) were referred for endoscopic treatment, following the criteria of unresectability. Ultrasound, computed tomography scan and magnetic resonance cholangiopancreatography (MRCP) were previously performed in all patients in order to facilitate endoscopic retrograde cholangiopancreatography (ERCP). The stricture was first passed by the hydrophilic guide-wire and then contrast medium was injected. Mechanical bile duct dilation was performed, followed by plastic stent placement only in the liver lobe which was previously opacified. The procedures were performed under conscious sedation. The patients were followed up for the next 12 months with a stent exchange every 3 months. Primary outcome was assessed by patient survival in the first 12 months after the procedure.
RESULTS: All 49 patients were treated with ERCP while 39 (79.59%) had successful stent placement. Among these, 32 had hilar cholangiocarcinoma (82%) and 7 (18%) had gallbladder cancer. Two groups of patients had Bismuth II strictures: A, 21 patients (54%) with unilateral contrast injection and drainage, and B, 18 (46%) with bilateral contrast injection and drainage. A total of 57 plastic stents were used (10 Fr, 89%; 11.5 Fr, 11%). Group B showed a lower bilirubin level 7 days after the procedure (P=0.008). Early complications were cholangitis (3 patients, 2 in group A and 1 in group B) and acute pancreatitis (2 patients, 1 each in A and B) with no statistical difference between the groups. Late complications were stent migration (5 patients, 1 in A and 4 in B) and stent clogging (6 patients, 2 in A and 4 in B) showing a significant difference between the groups (P<0.01). The first stent replacement after 3 months was successful in 87% of patients (four died due to disease progression and one due to cardiopulmonary insufficiency) showing no statistical difference between the groups. At 6 months follow-up, 72% patients survived, with no statistical difference between the groups. A final follow-up (12 months) showed the survival rate of 18% (4 patients from group A and 3 from group B) (P>0.05).
CONCLUSIONS: A minimally invasive approach, based on the criterion that every bile duct being opacified needs to be drained, is associated with a lower incidence of early complications. Considering that the clinical outcome measured by bilirubin level was lower in patients with bilateral drainage 7 days after the procedure, we assumed that drainage of 50% or more of the liver volume leads to sufficient drainage effectiveness.

PMID: 22484591 [PubMed - in process]

MicroRNA-26a Promotes Cholangiocarcinoma Growth by Activating β-catenin.

Fetched: April 14th, 2012, 11:00pm MDT

MicroRNA-26a Promotes Cholangiocarcinoma Growth by Activating β-catenin.

Gastroenterology. 2012 Apr 3;

Authors: Zhang J, Han C, Wu T

Abstract
BACKGROUND & AIMS: MicroRNAs (miRNAs) have been implicated in the development and progression of human cancers. We investigate the roles and mechanisms of miR-26a in human cholangiocarcinoma. METHODS: We used in situ hybridization and quantitative reverse transcriptase-PCR to measure expression of miR-26a in human cholangiocarcinoma tissues and cell lines (CCLP1, SG231, HuCCT1, TFK1). Human cholangiocarcinoma cell lines were transduced with lentiviruses that expressed miR-26a1 or a scrambled sequence (control); proliferation and colony formation were analyzed. We analyzed growth of human cholangiocarcinoma cells that overexpress miR-26a or its inhibitor in SCID mice. Immunoblot, immunoprecipitation, DNA pull down, immunofluorescence, and luciferase reporter assays were used to measure expression and activity of glycogen synthase kinase (GSK)-3β, β-catenin, and related signaling molecules. RESULTS: Human cholangiocarcinoma tissues and cell lines had increased levels of miR-26a, compared with the non-cancerous biliary epithelial cells. Overexpression of miR-26a increased proliferation of cholangiocarcinoma cells and colony formation in vitro, whereas miR-26 depletion reduced these parameters. In SCID mice, overexpression of miR-26a by cholangiocarcinoma cells increased tumor growth whereas overexpression of the miR-26a inhibitor reduced it.GSK-3βmRNA was identified as a direct target of miR-26a by computational analysis and experimental assays. MiR-26a-mediated reduction of GSK-3β resulted in activation of β-catenin and induction of several downstream genes including c-Myc,cyclinD1,and PPARδ. Depletion of β-catenin partially prevented miR-26a-induced tumor cell proliferation and colony formation. CONCLUSIONS: MiR-26a promotes cholangiocarcinoma growth by inhibition of GSK-3β and subsequent activation of β-catenin. These signaling molecules might be targets for prevention or treatment of cholangiocarcinoma.

PMID: 22484120 [PubMed - as supplied by publisher]

Role of EUS/EUS-guided FNA in the management of proximal biliary strictures.

Fetched: April 7th, 2012, 11:00pm MDT

Role of EUS/EUS-guided FNA in the management of proximal biliary strictures.

Hepatogastroenterology. 2011 Nov-Dec;58(112):1862-5

Authors: Manu NK, Derek MM, Viney W, Kofi OE

Abstract
BACKGROUND/AIMS: Optimal management of proximal biliary strictures depends on staging and adequate tissue diagnosis of suspected malignant lesions. Sensitivity of ERCP brush cytology is poor. EUS/EUS-FNA of these lesions is challenging with limited data on its diagnostic accuracy. We report our experience of EUS/ EUS guided FNA of proximal biliary strictures in a tertiary referral centre.
METHODOLOGY: All patients who underwent EUS guided FNA of hilar lesions between October 2003 to July 2007 were identified. The final diagnosis was determined by surgical pathology, results of EUS-FNA or follow-up.
RESULTS: 32 patients underwent 36 procedures for hilar lesions during the study period. EUS detected a mass in 9/14 patients who did not have a mass seen on imaging. The mean followup period was 39.43 months. The cytological specimen was adequate in 26 patients. The final diagnosis was adenocarcinoma (24) and benign (8). The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EUS-FNA were 68%, 52 %, 100%, 100% and 54%, respectively. If only adequate aspirates were included in the analysis, the values were 74%, 60%, 100%, 100% and 55% respectively.
CONCLUSIONS: EUS guided FNA is a useful modality in the diagnosis and management of hilar lesions.

PMID: 22234054 [PubMed - indexed for MEDLINE]

Permalink for 'The utility of radial endosonographic features in the diagnosis of cholangio-carcinoma arising from the distal common bile duct.'

The utility of radial endosonographic features in the diagnosis of cholangio-carcinoma arising from the distal common bile duct.

Fetched: April 7th, 2012, 11:00pm MDT

The utility of radial endosonographic features in the diagnosis of cholangio-carcinoma arising from the distal common bile duct.

Minerva Gastroenterol Dietol. 2011 Dec;57(4):434-5

Authors: Alper E, Üstün Dao Y, Akca S, Arabul M, Buyrac Z, Baydar B

PMID: 22105733 [PubMed - indexed for MEDLINE]

Meta-analysis should be interpreted with caution.

Fetched: April 7th, 2012, 11:00pm MDT

Meta-analysis should be interpreted with caution.

Gastrointest Endosc. 2011 Nov;74(5):1172; author reply 1172-3

Authors: Shao F, Wang C, Qiu L, Huang Q, Hu Y

PMID: 22032322 [PubMed - indexed for MEDLINE]

Para-aortic lymph node micrometastasis in patients with node-negative biliary cancer.

Fetched: April 7th, 2012, 11:00pm MDT

Para-aortic lymph node micrometastasis in patients with node-negative biliary cancer.

Dig Surg. 2011;28(4):315-21

Authors: Yonemori A, Kondo S, Matsuno Y, Ito T, Tanaka E, Hirano S

Abstract
BACKGROUND/AIMS: The presence of para-aortic lymph node metastasis in biliary cancer negatively impacts prognosis. The present study aims to immunohistochemically identify and evaluate the clinical significance of para-aortic lymph node micrometastases in 66 patients who had undergone curative resection of biliary cancer.
METHODS: We used an antibody against cytokeratins 7 and 8 (CAM5.2) to immunostain 529 para-aortic lymph nodes that were negative according to conventional analysis from 66 patients with biliary cancer.
RESULTS: We detected CAM5.2-positive occult carcinoma cells in para-aortic lymph nodes from 3 (5%) of the 66 patients and in 3 (0.6%) of the 529 para-aortic lymph nodes. One of the 3 patients also had micrometastasis in the regional lymph nodes. All 3 patients with para-aortic lymph node micrometastasis are alive at 45, 48 and 90 months after surgery despite having locally advanced cancer.
CONCLUSIONS: Occult cancer cells were identified in para-aortic lymph nodes from 5% of patients with node-negative biliary cancer, yet these patients have survived over the long term. The presence of para-aortic nodal micrometastasis might not have an influence on survival. However, further studies using a greater number of patients are required to support this notion.

PMID: 21921633 [PubMed - indexed for MEDLINE]

The current status of opisthorchiasis and clonorchiasis in the Mekong Basin.

Fetched: April 7th, 2012, 11:00pm MDT

The current status of opisthorchiasis and clonorchiasis in the Mekong Basin.

Parasitol Int. 2012 Mar;61(1):10-6

Authors: Sithithaworn P, Andrews RH, Nguyen VD, Wongsaroj T, Sinuon M, Odermatt P, Nawa Y, Liang S, Brindley PJ, Sripa B

Abstract
This review highlights the current status and control of liver fluke infections in the Mekong Basin countries where Opisthorchis and Clonorchis are highly endemic. Updated data on prevalence and distribution have been summarized from presentations in the "96 Years of Opisthorchiasis. International Congress of Liver Flukes". It is disturbing that despite treatment and control programs have been in place for decades, all countries of the Lower Mekong Basin are still highly endemic with O. viverrini and/or C. sinensis as well as alarmingly high levels of CCA incidence. A common pattern that is emerging in each country is the difference in transmission of O. viverrini between lowlands which have high prevalence versus highlands which have low prevalence. This seems to be associated with wetlands, flooding patterns and human movement and settlement. A more concerted effort from all community, educational, public health and government sectors is necessary to successfully combat this fatal liver disease of the poor.

PMID: 21893213 [PubMed - indexed for MEDLINE]

Intraductal tubulopapillary neoplasm of the bile duct: potential origin from peribiliary cysts.

Fetched: April 7th, 2012, 11:00pm MDT

Intraductal tubulopapillary neoplasm of the bile duct: potential origin from peribiliary cysts.

Hum Pathol. 2012 Mar;43(3):440-5

Authors: Zen Y, Amarapurkar AD, Portmann BC

Abstract
We report two patients with unique biliary tumors histologically similar to pancreatic intraductal tubulopapillary neoplasm (ITPN). One patient underwent right hepatectomy for a partly cystic mass in the hepatic hilum. The other patient had liver transplantation for cryptogenic cirrhosis and multiple hilar cysts detected in the explanted liver, some obliterated by papillary nodules. Histologically both tumors consisted of intracystic non-invasive and well differentiated adenocarcinoma with a papillary and tubular architecture. Associated cysts were peribiliary cysts partly lined by carcinoma cells that were continuous with the intracystic papillotubular masses. Both tumors shared the same immunophenotype: K7(+)/K20(-)/MUC1(+)/MUC2(-)/MUC5AC(-)/MUC6(+). Genetic analysis of KRAS and BRAF revealed wild type genotypes. These pathological and genetic features are similar to those of pancreatic ITPNs. This report suggested that ITPNs may rarely develop in the bile duct seemingly in association with peribiliary cysts.

PMID: 21813159 [PubMed - indexed for MEDLINE]

Blumgart's technique of pancreaticojejunostomy: an appraisal.

Fetched: April 7th, 2012, 11:00pm MDT

Blumgart's technique of pancreaticojejunostomy: an appraisal.

Dig Surg. 2011;28(4):281-7

Authors: Mishra PK, Saluja SS, Gupta M, Rajalingam R, Pattnaik P

Abstract
BACKGROUND: Although mortality of Whipple's pancreaticoduodenectomy (WPD) is reduced to <5%, morbidity still remains between 30 and 50%. Pancreaticojejunal anastomosis remains the main cause of morbidity. Blumgart anastomosis using transpancreatic U sutures has been proposed to decrease the leak rate and its associated morbidity. We analyzed the results of Blumgart anastomosis applied in consecutive cases of WPD.
METHODS: Of 189 patients with periampullary or pancreatic cancer admitted, 100 patients underwent WPD. Except for 2 patients (no duct identified preoperatively), all patients underwent pancreaticojejunostomy by the Blumgart anastomotic technique. The records of 98 patients were analyzed for pancreatic leak and its related complications using the definitions given by the International Study Group for Pancreatic Surgery.
RESULTS: Of 98 patients, 63 were men. The mean operative time was 390 min (270-690 min) and blood loss was 275 ml (100-1,000 ml). Overall mortality was 3.06%. The clinically significant pancreatic anastomotic failure leak was seen in only 7 (7.14%) cases (grade B, n = 4; grade C, n = 3) with one patient requiring relaparotomy due to leak. Only one patient died due to a leak-related complication.
CONCLUSION: Blumgart pancreaticojejunal anastomosis can be routinely used for reconstruction in WPD. It is a technically simple procedure and is associated with low rates of fistula and its related complications.

PMID: 21811074 [PubMed - indexed for MEDLINE]

Laparoscopic resections for hilar cholangiocarcinomas: a critical appraisal.

Fetched: April 7th, 2012, 11:00pm MDT

Laparoscopic resections for hilar cholangiocarcinomas: a critical appraisal.

Dig Surg. 2011;28(4):277-8; author reply 279-80

Authors: Donati M, Stavrou GA, Oldhafer KJ

PMID: 21778727 [PubMed - indexed for MEDLINE]

Permalink for 'Percutaneous intervention strategies for the management of dysfunctioning biliary plastic endoprostheses in patients with malignant biliary obstruction.'

Percutaneous intervention strategies for the management of dysfunctioning biliary plastic endoprostheses in patients with malignant biliary obstruction.

Fetched: April 7th, 2012, 11:00pm MDT

Percutaneous intervention strategies for the management of dysfunctioning biliary plastic endoprostheses in patients with malignant biliary obstruction.

Diagn Interv Radiol. 2012 Apr 5;

Authors: Gumus B

Abstract
PURPOSE: To present our clinical experience and to suggest different strategies in the management of dysfunctioning plastic biliary stents in patients with malignant biliary obstruction. MATERIALS AND METHODS: Twenty females and 23 males with a mean age of 64.8 years (range, 30-89 years) with malignant obstructive jaundice were referred to the interventional radiology department due to previously inserted dysfunctioning plastic endoprostheses. Pancreatic carcinoma (n=12), duodenal carcinoma (n=5), cholangiocarcinoma (n=16), gallbladder cancer (n=4), and metastatic disease (n=6) had been previously stented endoscopically. Nine of the patients had two plastic endoprostheses in the biliary tree. Forty-nine endoprostheses were straight polyethylene stents, and three were double-J type plastic stents (52 endoprostheses in total). RESULTS: Forty-nine of the dysfunctioning plastic stents were cleared from the biliary tree. Of these, 31 were dislodged into the bowel with the help of a balloon catheter. Threading with an over-the-wire diagnostic and percutaneous biliary drainage catheter was performed in 12 of the plastic stents. Six dysfunctioning endoprostheses were removed by transhepatic access. Three plastic endoprostheses could not be removed or dislodged. No complication occurred due to intervention. The mean follow-up time was nine months (range, 1-19 months). All of the patients were evaluated in the first month, and then at three-month intervals. Percutaneous metallic stenting was performed on 29 patients. CONCLUSION: Percutaneous intervention should be considered as an alternative treatment when a need for eliminating the dysfunctioning plastic stent arises. Both removal of the dysfunctioning stent and dislodgement into the bowel are safe and efficient strategies in the management of malignant biliary obstructions.

PMID: 22477647 [PubMed - as supplied by publisher]

Permalink for 'Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates invasion in cholangiocarcinoma cell lines in vitro.'

Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates invasion in cholangiocarcinoma cell lines in vitro.

Fetched: April 7th, 2012, 11:00pm MDT

Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates invasion in cholangiocarcinoma cell lines in vitro.

J Cancer Res Clin Oncol. 2012 Apr 3;

Authors: Hunsawong T, Singsuksawat E, In-Chon N, Chawengrattanachot W, Thuwajit C, Sripa B, Paupairoj A, Chau-In S, Thuwajit P

Abstract
PURPOSE: Cholangiocarcinoma is defined as a chronic liver disease with altered estrogen metabolism and could result in estrogen retention. Estrogenic response was known as a promoting factor in progression of some cancer. In this study, we determined the significant increase of estrogen level in cholangiocarcinoma patients' sera. METHODS: The estrogen levels in cholangiocarcinoma patients' sera were measured and correlated with clinical presentations. Estrogen receptor-α expressions in cholangiocarcinoma tissues were detected by immunohistochemistry method. KKU-100 and KKU-M213 cholangiocarcinoma cell lines were treated with 17β-estradiol and tested the proliferative and invasive effects. RESULTS: The estrogen levels showed positive correlations with serum bilirubin and alkaline phosphatase and a negative correlation with albumin. This study also showed an association with shorter survival times when patients with low and high serum estrogen levels were compared. In vitro studies demonstrated the effect of estrogen on cell proliferation and invasion in dose-dependent manners, which could be inhibited by tamoxifen, a clinical used estrogen antagonist. Invasion showed an association with the TFF1 gene expression and could be inhibited by small interfering RNA against TFF1 gene. Estrogen receptor-α was the main estrogen receptor that response to 17β-estradiol stimulation. CONCLUSIONS: TFF1 trefoil protein could be one of the effectors for estrogen-induced invasion in cholangiocarcinoma via the estrogen receptor-α. These findings could lead to an understanding of the mechanism of cholangiocarcinoma progression.

PMID: 22476540 [PubMed - as supplied by publisher]

The proximal margin of resected hilar cholangiocarcinoma: the effect of microscopic positive margin on long-term survival.

Fetched: April 7th, 2012, 11:00pm MDT

The proximal margin of resected hilar cholangiocarcinoma: the effect of microscopic positive margin on long-term survival.

Am Surg. 2012 Apr;78(4):471-7

Authors: Lee JH, Hwang DW, Lee SY, Park KM, Lee YJ

Abstract
Achieving an R0 resection can be difficult for hilar cholangiocarcinoma (HC) because of the anatomic structures of the hepatic hilum and frequent tumor infiltration. The aim of this study was to evaluate the margin status of bile duct resected in HC and prognostic impact of R1 resection. Between 2000 and 2009, 245 patients underwent operation for HC at Asan Medical Center. We retrospectively analyzed the clinicopathologic features and surgical outcomes, focusing on the proximal margin status, of 162 cases of patients with curative intention. Curative resections were achieved in 125 (52.1%) patients, and R1 resections were performed in 43 (26.5%). Proximal ductal margin states were classified as free margin (73.5%), carcinoma in situ (3.7%), and invasive carcinoma (22.8%). The 3- and 5-year survival rates of the R1 group (39.5% and 34.9%) were not significantly different from the rates of the R0 group (55.5% and 44.5%, respectively). Multivariate analysis showed lymph node metastasis (P = 0.001) and histologic differentiation (P = 0.001) were independent predictors of patient survival. The aggressive surgical approach based on liver resection including caudate lobe may increase the number of patients eligible for a curative chance and improve long-term survival even if the microscopically positive margin is still achieved.

PMID: 22472407 [PubMed - in process]

Role of hilar resection in the treatment of hilar cholangiocarcinoma.

Fetched: April 7th, 2012, 11:00pm MDT

Role of hilar resection in the treatment of hilar cholangiocarcinoma.

Hepatogastroenterology. 2012 May-Jun;59(115):696-700

Authors: Otani K, Chijiiwa K, Kai M, Ohuchida J, Nagano M, Kondo K

Abstract
Background/Aims: The aim of this study was to clarify the role of bile duct resection without hepatectomy (hilar resection) in hilar cholangiocarcinoma. Methodology: We retrospectively compared surgical results for hilar cholangiocarcinoma between 8 patients treated with hilar resection and 21 patients treated with hepatectomy. Results: 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%). Conclusions: Hilar resection may be indicated for papillary T1 or 2 tumors in Bismuth type I or II cholangiocarcinoma.

PMID: 22469711 [PubMed - in process]

Permalink for 'Safety and efficacy of primary metallic biliary stent placement with tract embolization in patients with massive ascites: a retrospective analysis of 16 patients.'

Safety and efficacy of primary metallic biliary stent placement with tract embolization in patients with massive ascites: a retrospective analysis of 16 patients.

Fetched: April 7th, 2012, 11:00pm MDT

Safety and efficacy of primary metallic biliary stent placement with tract embolization in patients with massive ascites: a retrospective analysis of 16 patients.

J Vasc Interv Radiol. 2012 Apr;23(4):521-7

Authors: Sofue K, Arai Y, Takeuchi Y, Fujiwara H, Tokue H, Sugimura K

Abstract
PURPOSE: To evaluate the safety and efficacy of primary metallic biliary stent placement with tract embolization in patients with massive ascites.
MATERIALS AND METHODS: Sixteen patients with malignant biliary obstruction and massive ascites (age range, 44-79 y; median age, 59 y) were treated with primary percutaneous stent placement with tract embolization. These patients were unsuitable candidates for endoscopic intervention. Etiologies of biliary obstruction were gastric cancer with hilar nodal metastases (n = 9), pancreatic carcinoma (n = 5), cholangiocarcinoma (n = 1), and gallbladder carcinoma (n = 1). Eight patients had nonhilar lesions and the remaining eight had hilar lesions. Percutaneous accesses to the biliary system and stent placements were performed in a one-step procedure, and catheters were removed with tract embolization with metallic coils.
RESULTS: Stent placement and tract embolization were successful in all patients, without external drainage catheters left in place. Significant reduction of serum bilirubin level was observed in 14 patients (87.5%). No bile peritonitis or intraperitoneal hemorrhage occurred. Major complications included postprocedural cholangitis (12.5%), bloody bowel discharge (6.2%), and right pleural effusion (25.0%). One patient who died 19 days after intervention was deemed to represent a procedure-related mortality. During the survival period (range, 19-175 d; median, 66 d), stent occlusion was noted in two patients at 6 and 159 days after the procedure. Primary stent patency was achieved in 14 patients (87.5%).
CONCLUSIONS: Primary biliary stent placement with tract embolization is technically safe and offers an effective palliative treatment option for patients with malignant biliary obstruction and massive ascites when endoscopic intervention is not possible.

PMID: 22464717 [PubMed - in process]

Positron emission tomography in hepatobiliary and pancreatic malignancies: a review.

Fetched: April 7th, 2012, 11:00pm MDT

Positron emission tomography in hepatobiliary and pancreatic malignancies: a review.

Am J Surg. 2012 Mar 29;

Authors: Lan BY, Kwee SA, Wong LL

Abstract
BACKGROUND: The prognosis for hepatobiliary and pancreatic malignancies is dismal. Surgery remains the primary curative option, but unresectable disease is often discovered during operative exploration. Positron emission tomography (PET) provides unique biological information different from current imaging modalities. The role of PET in detecting hepatobiliary and pancreatic malignancies has not yet been established. The purpose of this article was to review the literature on the use of PET in hepatobiliary and pancreatic malignancies. DATA SOURCES: We performed an extensive search on PubMed using PET and hepatocellular, pancreatic, gallbladder, and cholangiocarcinoma as keywords, excluding articles not written in English or on nonhuman subjects, case reports, and series with <5 patients. CONCLUSIONS: Although PET has shown usefulness in the diagnosis of certain cancers, current literature cautions against the use of PET for determining malignant potential of primary liver and pancreatic lesions. Literature on PET more strongly supports clinical roles for restaging of hepatobiliary and pancreatic malignancies, and for identifying metastatic disease.

PMID: 22464445 [PubMed - as supplied by publisher]

Surgical treatment of congenital biliary duct cyst.

Fetched: April 7th, 2012, 11:00pm MDT

Surgical treatment of congenital biliary duct cyst.

BMC Gastroenterol. 2012 Mar 30;12(1):29

Authors: Wang DC, Liu ZP, Li ZH, Li DJ, Chen J, Zheng SG, He Y, Bie P, Wang SG

Abstract
ABSTRACT: BACKGROUND: It is acknowledged that total cyst excision is a safe and ideal surgical treatment for congenital biliary duct cyst, compared to simple internal drainage. The aim of this study was to determine the optimal operation occasion and the effect of laparoscopy on congenital biliary duct cyst based upon total cyst excision. METHODS: From January 2002 to January 2011, 217 patients were admitted to Southwest Hospital for congenital biliary duct cyst. To determine the optimal surgery occasion, we divided these subjects into three groups, the infant group (age [less than or equal to] 3 years), the immaturity group (3 < age [less than or equal to] 18 years), and the maturity group (age > 18 years), and then evaluated the feasibility, risk and long-term outcome after surgery in the three groups. To analyze the effect of laparoscopic technique on congenital biliary duct cyst, we divided the patients into the laparoscopy and the open surgery groups. RESULTS: Among the three groups, the morbidity from cholangiolithiasis before surgical treatment had obvious discrepancy (p < 0.05) (lowest in the infant group), and intraoperative blood loss also had apparent diversity (p < 0.05). Furthermore, long-term outcomes (secondary cholangiolithiasis, stoma stenosis and cholangiocarcinoma) showed no significant difference between different groups (p >0.05). Similarly, no significant discrepancy was observed in the morbidity from postoperative complications or long-term postoperative complications (p >0.05) between the laparoscopic and the open surgery groups. CONCLUSIONS: We conclude that total cyst excision should be performed as early as possible. The optimal treatment occasion is the infant period, and laparoscopic resection may be a new safe and feasible minimally invasive surgery for this disease.

PMID: 22458359 [PubMed - as supplied by publisher]

Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Clinical Features, Treatment Modalities, and Prognosis.

Fetched: April 7th, 2012, 11:00pm MDT

Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Clinical Features, Treatment Modalities, and Prognosis.

Ann Surg Oncol. 2012 Mar 27;

Authors: Yin X, Zhang BH, Qiu SJ, Ren ZG, Zhou J, Chen XH, Zhou Y, Fan J

Abstract
BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary liver cancer that has rarely been reported in large-scale clinical studies. The aim of this study was to clarify the clinical features, treatment modalities, and prognosis of cHCC-CC. METHODS: Included in this study were 113 patients who were histologically diagnosed as having Allen type C cHCC-CC, 103 of whom received liver resection, 6 transarterial chemoembolization treatment, 3 radiofrequency ablation, and 1 palliative supportive treatment. Clinicopathologic features and prognosis of 103 cHCC-CC patients after liver resection were compared with those of 6,679 patients with hepatocellular carcinoma (HCC) and 386 patients with intrahepatic cholangiocarcinoma (ICC) who underwent liver resection during the same period. RESULTS: The proportion of cHCC-CC in primary liver cancers was 1.5 %. The 103 cases of cHCC-CC were characterized by male predominance, infection with hepatitis virus or presence of liver cirrhosis, and elevated alfa-fetoprotein-findings similar to HCC. However, serum CA19-9 elevation, incomplete capsules, and lymph node involvement were similar to ICC. The 1-, 3-, and 5-year overall survival rates after liver resection were 73.9, 41.4, and 36.4 %, respectively, for patients with cHCC-CC versus 77.5, 53.3, and 41.4 % for HCC patients, and 58.0, 29.1, and 22.3 % for ICC patients (χ(2) = 137.5, P < 0.001). Tumor, node, metastasis system stage (hazard ratio 1.27, 95 % confidence interval 1.08-1.49, P = 0.003) and radical liver resection (hazard ratio 0.31, 95 % confidence interval 0.14-0.68, P = 0.004) were independent prognostic factors for overall survival. CONCLUSIONS: cHCC-CC has biological behavior and prognosis that are intermediate between HCC and ICC. Radical liver resection can provide a better outcome for this uncommon malignancy.

PMID: 22451237 [PubMed - as supplied by publisher]

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

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

Fetched: April 7th, 2012, 11:00pm MDT

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

BMC Complement Altern Med. 2012 Mar 27;12(1):23

Authors: Plengsuriyakarn T, Viyanant V, Eursitthichai V, Picha P, Kupradinant P, Itharat A, Na-Bangchang K

Abstract
ABSTRACT: BACKGROUND: Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. METHODS: The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. RESULTS: Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities. CONCLUSION: Plants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA.

PMID: 22448640 [PubMed - as supplied by publisher]

Bile-Based Detection of Extrahepatic Cholangiocarcinoma with Quantitative DNA Methylation Markers and Its High Sensitivity.

Fetched: April 7th, 2012, 11:00pm MDT

Bile-Based Detection of Extrahepatic Cholangiocarcinoma with Quantitative DNA Methylation Markers and Its High Sensitivity.

J Mol Diagn. 2012 Mar 21;

Authors: Shin SH, Lee K, Kim BH, Cho NY, Jang JY, Kim YT, Kim D, Jang JJ, Kang GH

Abstract
Extrahepatic cholangiocarcinoma (EHC) is usually difficult to diagnose by bile cytology because of cellular disintegration. However, DNA samples from bile fluid can provide sufficient materials to screen for the presence of EHC. We developed DNA methylation marker panels that can be used for MethyLight assay-based detection of EHC in bile fluid specimens. The methylation status of 59 DNA methylation markers was investigated in 20 EHC and 20 non-neoplastic gallbladder tissue samples with MethyLight assay to determine cancer-specific DNA methylation markers. Through assaying cancer-specific DNA methylation markers in a training set (n = 40) and validation set (n = 45) of bile fluid specimens from patients with EHC or those without cancer, we selected suitable marker panels that were assessed for their performance in a third set (test set; n = 40). Four marker panels showed a sensitivity of 60% or more and a specificity of 100% in both the training and validation sets, whereas bile cytology displayed a sensitivity of 40% to 46% and a specificity of 100%. In an independent test set of bile fluid samples, a five-gene panel (CCND2, CDH13, GRIN2B, RUNX3, and TWIST1) detected EHC at a sensitivity of 83%, which was far higher than that of bile cytology (46%, P = 0.004). Using bile fluids, a methylation assay consisting of a five-gene panel may be useful for detecting EHC and in helping to increase the sensitivity of preoperative diagnoses.

PMID: 22446083 [PubMed - as supplied by publisher]

Prognostic significance of peroxiredoxin 1 and ezrin-radixin-moesin-binding phosphoprotein 50 in cholangiocarcinoma.

Fetched: April 7th, 2012, 11:00pm MDT

Prognostic significance of peroxiredoxin 1 and ezrin-radixin-moesin-binding phosphoprotein 50 in cholangiocarcinoma.

Hum Pathol. 2012 Mar 23;

Authors: Yonglitthipagon P, Pairojkul C, Chamgramol Y, Loukas A, Mulvenna J, Bethony J, Bhudhisawasdi V, Sripa B

Abstract
We performed a comparative proteomic analysis of protein expression profiles in 4 cholangiocarcinoma cell lines: K100, M156, M213, and M139. The H69 biliary cell line was used as a control. Peroxiredoxin 1 and ezrin-radixin-moesin-binding phosphoprotein 50 were selected for further validation by immunohistochemistry using a cholangiocarcinoma tissue microarray (n = 301) to assess their prognostic value in this cancer. Both peroxiredoxin 1 and ezrin-radixin-moesin-binding phosphoprotein 50 were overexpressed in cholangiocarcinoma tissues compared with normal liver tissues. Of the 301 cholangiocarcinoma cases, overexpression of peroxiredoxin 1 in 103 (34.3%) was associated with an age-related effect in young patients (P = .011) and the absence of cholangiocarcinoma in lymphatic vessels and perineural tissues (P = .004 and P = .037, respectively). Expression of radixin-moesin-binding phosphoprotein 50 correlated with histopathologic type, with 180 (59.8%) of moderately or poorly differentiated tumors (P = .039) being higher, and was associated with the presence of cholangiocarcinoma in lymphatic and vascular vessels (P < .001 and P < .001, respectively). The high expression of radixin-moesin-binding phosphoprotein 50 and the low expression of peroxiredoxin 1 correlated with reduced survival by univariate analysis (P = .017 and P = .048, respectively). Moreover, the impact of peroxiredoxin 1 and radixin-moesin-binding phosphoprotein 50 expression on patient survival was an independent predictor in multivariate analyses (P = .004 and P = .025, respectively). Therefore, altered expression of peroxiredoxin 1 and radixin-moesin-binding phosphoprotein 50 may be used as prognostic markers in cholangiocarcinoma.

PMID: 22446018 [PubMed - as supplied by publisher]

Permalink for 'Gadobenate dimeglumine-enhanced liver magnetic resonance imaging: value of hepatobiliary phase for the detection of focal liver lesions.'

Gadobenate dimeglumine-enhanced liver magnetic resonance imaging: value of hepatobiliary phase for the detection of focal liver lesions.

Fetched: April 7th, 2012, 11:00pm MDT

Gadobenate dimeglumine-enhanced liver magnetic resonance imaging: value of hepatobiliary phase for the detection of focal liver lesions.

J Comput Assist Tomogr. 2012 Jan-Feb;36(1):14-9

Authors: Fu GL, Du Y, Zee CS, Yang HF, Li Y, Duan RG, Zeng NL, Xiao DM

Abstract
OBJECTIVE: The objective of the study was to determine the value of addition of hepatobiliary phase to dynamic gadobenate dimeglumine (Gd-BOPTA)-enhanced imaging for the detection of focal liver lesions (nodules with diameter ≤3.0 cm).
METHODS: Routine nonenhanced magnetic resonance images were obtained in 25 patients with focal liver lesions suggested by ultrasonography and/or computed tomography.T1-weighted dynamic gradient-echo images were acquired immediately and 100 minutes after bolus injection of Gd-BOPTA. The number of the lesions detected by T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced, and delayed hepatobiliary-phase imaging was counted, respectively. Contrast-to-noise ratios were measured for all the sequences including delayed hepatobiliary-phase imaging. The signal intensity and morphologic features of liver parenchyma and lesions were recorded and analyzed.
RESULTS: There were 7 patients with hepatocellular carcinomas, 6 with hemangiomas, 7 with metastases, and 5 with cholangiocarcinomas. The delayed hepatobiliary-phase imaging showed a homogeneous enhancement of liver parenchyma and distinctive enhancement features of focal liver lesions. The delayed hepatobiliary-phase imaging was better than diffusion-weighted imaging for the detection of focal liver lesions (P < 0.05).
CONCLUSION: The addition of hepatobiliary-phase imaging to Gd-BOPTA-enhanced dynamic imaging increased the sensitivity and accuracy for the detection of focal hepatic lesions.

PMID: 22261765 [PubMed - indexed for MEDLINE]

Permalink for 'Portal Vein Embolization before Extended Hepatectomy for Biliary Cancer: Current Technique and Review of 494 Consecutive Embolizations.'

Portal Vein Embolization before Extended Hepatectomy for Biliary Cancer: Current Technique and Review of 494 Consecutive Embolizations.

Fetched: March 26th, 2012, 11:00pm MDT

Portal Vein Embolization before Extended Hepatectomy for Biliary Cancer: Current Technique and Review of 494 Consecutive Embolizations.

Dig Surg. 2012;29(1):23-29

Authors: Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, Nagino M

Abstract
Backgrounds: Portal vein embolization (PVE) has been widely applied before extended hepatectomy; however, its clinical utility for patients with biliary cancer has not been fully addressed. Methods: Between 1991 and 2010, 494 patients with cholangiocarcinoma (n = 353) or gallbladder cancer (n = 141) underwent PVE before extended hepatectomy. PVE was performed by a transhepatic ipsilateral approach using fibrin glue or absolute ethanol with steel coils. Surgical outcomes of this cohort were retrospectively reviewed. Results: PVE-related complications requiring interventions were found in 3 (0.6%) of the 494 patients; no patient died of these complications. Among the 494 patients, 122 (24.7%) did not undergo subsequent hepatectomy. The unresectability rate was significantly higher in patients with gallbladder cancer than in those with cholangiocarcinoma [43.2% (61/141) and 17.3% (61/353), respectively, p < 0.001]. The remaining 372 patients underwent hepatectomy, and 24 (6.5%) died of postoperative complications [13 of 80 (16.3%) with gallbladder cancer vs. 11 of 292 (3.8%) with cholangiocarcinoma, p < 0.05]. The overall survival for patients with cholangiocarcinoma was significantly better than that for patients with gallbladder cancer, where the 5-year survival rate was 39 and 23%, respectively (p < 0.001). Thirty-six patients with cholangiocarcinoma and 10 patients with gallbladder cancer survived more than 5 years after extended surgery. Conclusion: PVE can be performed safely in patients with cholestatic liver, and it has a potential benefit for patients with advanced biliary cancer who are to undergo extended, difficult hepatectomy.

PMID: 22441616 [PubMed - as supplied by publisher]

$Permalink for 'Growth inhibition and mechanism of action of p-dodecylaminophenol against refractory human pancreatic cancer and cholangiocarcinoma.'$

Growth inhibition and mechanism of action of p-dodecylaminophenol against refractory human pancreatic cancer and cholangiocarcinoma.

Fetched: March 26th, 2012, 11:00pm MDT

Growth inhibition and mechanism of action of p-dodecylaminophenol against refractory human pancreatic cancer and cholangiocarcinoma.

Bioorg Med Chem. 2012 Mar 7;

Authors: Imai M, Takahashi N

Abstract
Pancreatic cancer and cholangiocarcinoma are aggressive and drug-resistant refractory cancers. Based on N-(4-hydroxyphenyl)retinamide (3), a synthetic amide of all-trans-retinoic acid (RA), p-dodecylaminophenol (1) was developed to be an effective anticancer agent without key side-effects of these agents. Compound 1 suppresses cell growth of pancreatic cancer (MIA Paca2) and cholangiocarcinoma (HuCCT1), potentially by inhibiting ras expression and signaling through ERK pathways in MIA Paca2 cells and both ERK and Akt pathways in HuCCT1 cells. Compound 1 inhibits proliferation of these cells to a greater extent than either RA or 3. Compound 1 may represent a potent and useful anti-cancer drug for use against pancreatic cancer and cholangiocarcinoma that lacks their key side-effects.

PMID: 22440084 [PubMed - as supplied by publisher]

Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies.

Fetched: March 26th, 2012, 11:00pm MDT

Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies.

Hum Pathol. 2012 Mar 19;

Authors: Bai H, Gayyed MF, Lam-Himlin DM, Klein AP, Nayar SK, Xu Y, Khan M, Argani P, Pan D, Anders RA

Abstract
Hepatocellular carcinoma and intrahepatic cholangiocarcinoma account for 95% of primary liver cancer. For each of these malignancies, the outcome is dismal; incidence is rapidly increasing, and mechanistic understanding is limited. We observed abnormal proliferation of both biliary epithelium and hepatocytes in mice after genetic manipulation of Yes-associated protein, a transcription coactivator. Here, we comprehensively documented Yes-associated protein expression in the human liver and primary liver cancers. We showed that nuclear Yes-associated protein expression is significantly increased in human intrahepatic cholangiocarcinoma and hepatocellular carcinoma. We found that increased Yes-associated protein levels in hepatocellular carcinoma are due to multiple mechanisms including gene amplification and transcriptional and posttranscriptional regulation. Survivin, a member of the inhibitors-of-apoptosis protein family, has been reported as an independent prognostic factor for poor survival in both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We found that nuclear Yes-associated protein expression correlates significantly with nuclear Survivin expression for both intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Furthermore, using mice engineered to conditionally overexpress Yes-associated protein in the liver, we found that Survivin messenger RNA expression depends upon Yes-associated protein levels. Our findings suggested that Yes-associated protein contributes to primary liver tumorigenesis and likely mediates its oncogenic effects through modulating Survivin expression.

PMID: 22436626 [PubMed - as supplied by publisher]

CT appearances of post-radiation livers in patients with unresectable cholangiocarcinoma.

Fetched: March 26th, 2012, 11:00pm MDT

CT appearances of post-radiation livers in patients with unresectable cholangiocarcinoma.

J Med Assoc Thai. 2012 Feb;95(2):221-8

Authors: Apisarnthanarak P, Kanchanarat K, Muangsomboon K, Chaiyasoot W, Ieumwananonthachai N, Pattaranutaporn P

Abstract
OBJECTIVE: To characterize the computed tomographic (CT) findings of post-radiation livers and the interval changes in patients with unresectable cholangiocarcinoma.
MATERIAL AND METHOD: Thirteen patients with unresectable cholangiocarcinoma who received concurrent chemoradiation with conformal radiotherapy technique (50 to 66 Gy, 2 Gy/fraction) were included in the present study. CT at pre-radiation and sequential follow-up at 1, 3, 6, 9 and 12 months were retrospectively reviewed by two abdominal radiologists to identify CT characteristics of post-radiation liver and the interval changes.
RESULTS: CT at pre-radiation and sequential follow-up at 1, 3, 6, 9 and 12 months were available in 92.3%, 100%, 76.9%, 53.8%, 30.8% and 23.1%, respectively. Post-radiation livers showed sharply-delineated, hypodense radiation areas, which were well related with the isodose line of 35 to 56 Gy (mean = 44.4 +/- 6.55 Gy). These radiation areas were mostly appreciated on portal venous phase at 1-month follow-up study in 12 of 13 (92.3%) patients and these were gradually less defined in subsequent studies. Progressive decrease size of radiation areas with persistent enhancement on delayed phase images were recognized. Progression of hepatic cortical irregularity was seen in four (30.8%) patients, as well as pulmonary fibrosis of lung bases.
CONCLUSION: Post-radiation liver in patients with unresectable cholangiocarcinoma showed a sharply-defined, hypodense radiation area, which was mostly appreciated in 1-month follow-up CT and was gradually less defined in subsequent studies with evidence of progressive atrophic change.

PMID: 22435253 [PubMed - in process]

Cholangiocarcinoma in a 17-year-old boy with primary sclerosing cholangitis and UroVysion™ fluorescent in situ hybridization.

Fetched: March 26th, 2012, 11:00pm MDT

Cholangiocarcinoma in a 17-year-old boy with primary sclerosing cholangitis and UroVysion™ fluorescent in situ hybridization.

Diagn Cytopathol. 2012 Apr;40(4):337-41

Authors: Huddleston BJ, Lamb RD, Gopez EV, Adler DG, Collins BT

Abstract
Primary sclerosing cholangitis (PSC) is uncommon in the younger age range and bile duct brushing cytology can present unique challenges. We describe the case of a 17-year-old boy with a new diagnosis of PSC who presented with cholangiocarcinoma. The clinical history, endoscopic features, cytomorphologic findings, and results of UroVysion™ fluorescent in situ hybridization (FISH) on the bile duct brush are described. UroVysion FISH on bile duct brushings is an ancillary study that can improve the diagnostic sensitivity for malignancy, specially in challenging cases where the cytomorphologic or clinical characteristics of the case are not typical. The occurrence of cholangiocarcinoma in young age group with PSC is uncommon, and the utilization of UroVysion FISH has been rarely described. Diagn. Cytopathol.2011; © 2011 Wiley-Liss, Inc.

PMID: 22431323 [PubMed - in process]

Permalink for 'Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma.'

Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma.

Fetched: March 26th, 2012, 11:00pm MDT

Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma.

Med Mol Morphol. 2012 Dec;45(1):7-13

Authors: Itoyama M, Hata M, Yamanegi K, Yamada N, Ohyama H, Hirano H, Terada N, Nakasho K

Abstract
Expression of phenotype markers of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) in HCC and CC components of 20 combined hepatocellular and cholangiocarcinomas (CHCs) of the liver was investigated immunohistochemically. Both HCC and CC components of all CHCs expressed at least one of the CC phenotype markers [cytokeratin (CK)-7, CK-19, and carbohydrate (CA) 19-9]. HCC components in 90% of CHCs and CC components in 95% of CHCs expressed at least one of these CC phenotype markers in more than 40% of cancer cells. HCC components in all CHCs expressed at least one of the HCC phenotype markers [hepatocyte antigen (HA), α-fetoprotein (AFP), and canalicular carcinoembryonic antigen]. HCC components in 90% of CHCs and CC components in 75% of CHCs expressed HA, AFP, or both. HCC components in 75% of CHCs and CC components in 60% of CHCs expressed HA, AFP, or both in more than 10% of cancer cells. The present results show that both HCC and CC components of most of the CHCs expressed both HCC and CC phenotypes, supporting the hypothesis that CHC originates from a hepatic progenitor cell capable of differentiating into hepatocytes and cholangiocytes.

PMID: 22431178 [PubMed - in process]

Permalink for 'Targeted Drug Regulation on Methylation of p53-BAX Mitochondrial Apoptosis Pathway Affects the Growth of Cholangiocarcinoma Cells.'

Targeted Drug Regulation on Methylation of p53-BAX Mitochondrial Apoptosis Pathway Affects the Growth of Cholangiocarcinoma Cells.

Fetched: March 26th, 2012, 11:00pm MDT

Targeted Drug Regulation on Methylation of p53-BAX Mitochondrial Apoptosis Pathway Affects the Growth of Cholangiocarcinoma Cells.

J Int Med Res. 2012;40(1):67-75

Authors: Liu XF, Jiang H, Zhang CS, Yu SP, Wang ZQ, Su HL

Abstract
OBJECTIVE: To study the mechanism of 5-aza-2-deoxycytidine (DAC; a methylation inhibitor) on growth of the human cholangiocarcinoma QBC939 cell line.
METHODS: A colourimetric assay was used to detect growth of QBC939 cells treated with DAC (0.1 - 100 μmol/l) over 24 h, 48 h and 72 h. Cell morphology was observed by transmission electron microscopy (TEM). The cell cycle and apoptosis were analysed by flow cytometry. Hypermethylation of the promoters of the p53-BAX mitochondrial apoptosis genes cyclin-dependent kinase inhibitor 2A (CDKN2A), death-associated protein kinase 1 (DAPK1) and PYD and CARD domain containing (PYCARD) was detected by methylation-specific polymerase chain reaction, with and without DAC treatment.
RESULTS: DAC inhibited QBC939 cell growth with a half maximal inhibitory concentration of 5 μmol/l at 72 h. After DAC treatment, apoptosis was observed by TEM. Flow cytometric analysis of propidium iodide-positive cells demonstrated increased apoptosis of DAC-treated QBC939 cells (43.04%) compared with untreated cells (4.31%). DAC treatment resulted in demethylation of the gene promoters of CDKN2A and DAPK1 in QBC939 cells.
CONCLUSIONS: DAC induces apoptosis of QBC939 cells by reactivation of hypermethylated p53-BAX mitchondrial apoptosis genes in cholangiocarcinoma cells.

PMID: 22429346 [PubMed - in process]

Erratum to: Photodynamic Therapy for Unresectable Cholangiocarcinoma.

Fetched: March 26th, 2012, 11:00pm MDT

Erratum to: Photodynamic Therapy for Unresectable Cholangiocarcinoma.

Dig Dis Sci. 2012 Mar 17;

Authors: Tomizawa Y, Tian J

PMID: 22427132 [PubMed - as supplied by publisher]

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

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

Fetched: March 26th, 2012, 11:00pm MDT

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

Clin Radiol. 2012 Mar 15;

Authors: Chong YS, Kim YK, Lee MW, Kim SH, Lee WJ, Rhim HC, Lee SJ

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

PMID: 22425613 [PubMed - as supplied by publisher]

Lobaplatin induces apoptosis and arrests cell cycle progression in human cholangiocarcinoma cell line RBE.

Fetched: March 26th, 2012, 11:00pm MDT

Lobaplatin induces apoptosis and arrests cell cycle progression in human cholangiocarcinoma cell line RBE.

Biomed Pharmacother. 2011 Dec 29;

Authors: Wang Z, Tang X, Zhang Y, Qi R, Li Z, Zhang K, Liu Z, Yang X

Abstract
The aim of this study was to determine the anticancer effects of lobaplatin in cholangiocarcinoma (CCA) RBE cells. We also explored the mechanism of action of lobaplatin by analyzing its influence on apoptosis and cell cycle. Our findings have shown that lobaplatin inhibits cell proliferations in human CCA cells with an IC50 value of approximately 5.26±0.63 μg/mL. Flowcytometry assay confirmed that lobaplatin affected CCA cell survival by blocking cell cycle progression and inducing apoptosis. Lobaplatin treatment reduced Cyclin D1, CDK4, and CDK6 expression, which led to the blocking of G0/G1 transition. In addition, lobaplatin increased p53, Bax expression, caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage, and reduced Bcl-2 expression, which contributed to the apoptosis of CCA cells. Lobaplatin showed a good anti-tumour activity in in vitro models of human CCA cells. These results indicate that Lobaplatin, as the third-generation platinum antineoplastic agent, could be an effective chemotherapeutic agent in human CCA treatment through induction apoptosis and cell cycle arrest.

PMID: 22425181 [PubMed - as supplied by publisher]

Permalink for 'Pretransplant psychiatric and substance use comorbidity in patients with cholangiocarcinoma who received a liver transplant.'

Pretransplant psychiatric and substance use comorbidity in patients with cholangiocarcinoma who received a liver transplant.

Fetched: March 26th, 2012, 11:00pm MDT

Pretransplant psychiatric and substance use comorbidity in patients with cholangiocarcinoma who received a liver transplant.

Psychosomatics. 2012 Mar;53(2):116-22

Authors: Schneekloth TD, Jowsey SG, Biernacka JM, Burton MC, Vasquez AR, Bergquist T, Drews MS, Gores GJ

Abstract
BACKGROUND: Psychopathology has been commonly observed in liver transplant candidates, and up to 40% have comorbid psychiatric disorders. This illness burden may negatively impact quality of life and transplant outcome. Liver transplantation for cholangiocarcinoma remains uncommon due to the complex treatment protocol. We assessed for pretransplant psychopathology and substance use disorders in liver transplant recipients with cholangiocarcinoma to better characterize this patient group.
METHODS: We retrospectively reviewed the records of 143 liver transplant recipients who completed pretransplant psychological screening with the PAS, BDI-FS, BSI-18, and the SAAST between 2000 and 2004. The majority completed an evaluation by a transplant psychiatrist. Rates of pretransplant psychiatric and substance use symptoms and disorders were compared between 26 patients with cholangiocarcinoma and 117 other liver recipients using χ(2) or Fisher's exact tests.
RESULTS: Of the total cohort, 35% had a pretransplant psychiatric diagnosis, 35% had a substance use disorder, and 43% were current or former smokers. The cholangiocarcinoma cohort had significantly lower scores on the PAS, BDI-FS, and the BSI-18. On interview, the cholangiocarcinoma group was less likely to have an alcohol use disorder (P = 0.03) or any substance use disorder (P = 0.04), but the two groups did not differ significantly in the likelihood of having a psychiatric disorder or smoking history.
CONCLUSIONS: This study suggests that patients with cholangiocarcinoma have lower rates of alcohol and drug use disorders than other liver transplant recipients. They do not differ in rates of psychiatric disorders or smoking. Psychosocial assessment and support are recommended throughout the transplant process.

PMID: 22424159 [PubMed - in process]

Biliary-tract cancer: improving therapy by adding molecularly targeted agents.

Fetched: March 26th, 2012, 11:00pm MDT

Biliary-tract cancer: improving therapy by adding molecularly targeted agents.

Lancet Oncol. 2012 Feb;13(2):118-9

Authors: Jensen LH

PMID: 22192730 [PubMed - indexed for MEDLINE]

MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression.

Fetched: March 26th, 2012, 11:00pm MDT

MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression.

Gene. 2012 Feb 1;493(1):44-51

Authors: Zhong XY, Yu JH, Zhang WG, Wang ZD, Dong Q, Tai S, Cui YF, Li H

Abstract
MicroRNAs (miRNAs) are involved in the development of most cancers. However, few studies have been conducted to determine their relationship to biliary tract cancer (BTC). Farnesoid X receptor (FXR) has been reported to be a tumor suppressor for hepatocellular carcinoma and breast cancer; but few studies have focused on its correlation with BTC. In this study, we identified miR-421 as a potential regulator of FXR expression. We found that their expression amount was inversely correlated as FXR was aberrantly down-regulated in both primary tumor specimens and cell lines; while miR-421 was significantly up-regulated. Ectopic expression of miR-421 significantly decreased FXR protein concentration in BTC cells and promoted cell proliferation, colony formation and migration in vitro. Furthermore, a decrease in miR-421 expression induced G(0)/G(1) cell cycle arrest. In conclusion, our study identified microRNA-421 functions as an oncomiR in BTC by targeting FXR. This finding may provide a novel therapeutic strategy for treatment of biliary tract cancer.

PMID: 22146319 [PubMed - indexed for MEDLINE]

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Rare Cancer News & Clinical Trials » PubMed - Cholangiocarcinoma

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PubMed - Cholangiocarcinoma (100 unread)

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