Cholangiocarcinoma represents the second most common primary liver malignancy. Despite it comprises only 3 % of all gastrointestinal malignancies, its incidence has been increasing recently. Cholangiocarcinomas are hepatobiliary cancers with features of cholangiocyte differentiation and from clinical point of view they are classified anatomically as intrahepatic or extrahepatic form. The only curative treatment with aim of long term and disease-free survival is surgery - liver resection or liver transplantation. Current progress in perioperative treatment and increased surgical skills has changed old treatment algorithms and widen number of patients suitable for curative treatment. On the other hand, surgical intervention is connected with not negligible morbidity and mortality. A rigorous knowledge of the disease extent and all prognostic factors is main condition for proper treatment decision.

• Keywords
• Klatskin tumor, cholangiocarcinoma, liver resection, liver transplantation,
• MeSH
• Cholangiocarcinoma * surgery   MeSH
• Adult MeSH
• Hepatectomy MeSH
• Humans MeSH
• Liver Neoplasms * surgery   MeSH
• Bile Ducts, Intrahepatic * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH

Cholangiocarcinoma is a relatively rare malignant tumor arising from the biliary epithelium of the intra- and extrahepatic bile ducts, the gallbladder, and the ampulla of Vater. This review article presents cholangiocarcinoma from the routine histopathological point of view. In addition to an overview of basic morphological, immunohistochemical, and molecular genetic characteristics of cholangiocarcinoma subtypes and precancerous lesions, the article is focused on intraoperative biopsies and on changes in the 8th edition of the TNM classification. Macroscopic and microscopic photo documentation and a review of recent literature are included.

• Keywords
• cholangiocarcinoma, cholangiocellular carcinoma, extrahepatic, intrahepatic, perihilar,
• MeSH
• Cholangiocarcinoma * pathology   MeSH
• Humans MeSH
• Bile Duct Neoplasms * surgery   pathology   MeSH
• Pathologists MeSH
• Bile Ducts, Extrahepatic * pathology   MeSH
• Bile Ducts, Intrahepatic pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

INTRODUCTION: The aim of this study was to evaluate the results of surgical treatment of intrahepatic cholangiocarcinoma (IHCHCA) in terms of overall survival and disease-free survival, and to analyse and find potential prognostic factors affecting overall survival and disease-free survival. METHODS: Retrospective evaluation was performed of consecutively enrolled patients operated for IHCHCA from January 2005 to January 2022 (17 years) had undergone surgery. During the monitored period, 38 surgical procedures were performed, of which liver resection was done in 25 cases (65.8%). RESULTS: The 5-year survival in the radically resected group was 44%, and the 5-year disease-free survival was 32%. Based on univariate and multivariate analysis, radicality of surgery (p=0.01116) and lymph node involvement (p=0.00576) were assessed as negative prognostic factors for overall survival. Radicality of surgery (p=0.018) and administration of adjuvant chemotherapy (p=0.044) were significant negative prognostic factors affecting disease-free survival. However, they lost their significance in the multivariate analysis. CONCLUSION: Radical surgical resection of the liver remains an essential treatment option for intrahepatic cholangiocarcinoma aimed at achieving a radical procedure with microscopically negative margins. KEY WORDS: cholangiocarcinoma, resection, recurrence, survival.

• Keywords
• Prognosis, cholangiocarcinoma, heart failure, recurrence, resection, survival,
• MeSH
• Cholangiocarcinoma * surgery   pathology   MeSH
• Hepatectomy methods   MeSH
• Humans MeSH
• Survival Rate MeSH
• Bile Duct Neoplasms * surgery   pathology   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Treatment Outcome MeSH
• Bile Ducts, Intrahepatic pathology   surgery   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Cholangiocarcinoma is a cancer with very poor prognosis. The only potentially curative approach is surgical resection of tumor. However, the rate of local and distant recurrence after radical surgery is still high. Benefit of adjuvant therapy is not clearly defined, nevertheless patients at high risk of recurrence are indicated to chemotherapy or chemoradiotherapy. Locally advanced, unresectable disease can also be treated with chemotherapy alone, or with her combination with radiotherapy. Required radiation doses are relatively high, therefore it is necessary to use highly conformal radiation therapy. Treatment of metastatic disease is currently based on systemic therapy, combination of gemcitabine and cisplatin as standard of care. Benefit of targeted molecular therapy is not clear at present, but ongoing research in genetic profiling of tumor may help to improve current clinical practice. Patients with cholangiocarcinoma have to be discussed during multidisciplinary team meetings.

• Keywords
• cholangiocarcinoma, drug therapy, radiotherapy adjuvant, targeted therapy,
• MeSH
• Chemoradiotherapy MeSH
• Cholangiocarcinoma * therapy   MeSH
• Adult MeSH
• Combined Modality Therapy MeSH
• Humans MeSH
• Liver Neoplasms * therapy   MeSH
• Bile Duct Neoplasms * therapy   MeSH
• Bile Ducts, Intrahepatic * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal cholangiocarcinoma (DCC) patients to identify potential prognostic factors. PATIENTS AND METHODS: A retrospective cohort study of 32 consecutive DCC patients treated with pancreaticoduodenectomy between 2009-2017. The clinicopathological and histopathological data were evaluated for prognostic factors using the univariable Cox regression analysis. The Overall Survival (OS) was estimated using the Kaplan-Meier analysis. RESULTS: The study comprised a total of 32 patients, with a mean age of 65.8 (± 9.0) years at the time of surgery. R0 resection was achieved in 25 (86.2%) patients, 19 (65.5%) patients received adjuvant oncological therapy. The OS rates at 1, 3 and 5 years were 62.5%, 37.5% and 21.9%, respectively. The 90-day mortality was 3/32 (9.4%) accounting for one-fourth of the first-year mortality rate. The median OS was 28.5 months. The only statistically significant prognostic factor was vascular resection, which was associated with worse OS in the univariable analysis (HR: 3.644; 95%-CI: 1.179-11.216, P=0.025). An age less than 65 years, ASA grade I/II, hospital stay of fewer than 15 days, R0 resection, lymph node ratio less than 0.2 and adjuvant oncological therapy tended to be associated with better OS but without statistically significant relevance. CONCLUSION: The main factor directly influencing the survival of DCC patients is surgical complications. Surgical mortality comprises a significant group of patients, who die in the first year following pancreaticoduodenectomy. Vascular resection is the most important negative prognostic factor for long-term survival.

• Keywords
• cholangiocarcinoma, long-term survival, pancreaticoduodenectomy, prognostic factor,
• MeSH
• Cholangiocarcinoma * surgery   pathology   MeSH
• Humans MeSH
• Bile Duct Neoplasms * surgery   pathology   MeSH
• Pancreaticoduodenectomy MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Bile Ducts, Intrahepatic pathology   MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The gut microbiota, composed by several species of microorganisms, works to preserve the liver-gut homeostasis and plays an important role during digestion and absorption of nutrients, and in the immune response of the host. In this review, we analyzed the influence of microbiota in patients with cholangiocarcinoma (CCA) who were candidates for elective surgery. METHODS: A literature review was conducted to identify papers that provided empiric evidence to support that the altered microbiota composition (dysbiosis) is related also to CCA development. RESULTS: Bacteria such as Helicobacter pylori, Helicobacter hepaticus, and Opisthorchis viverrini increase the risk of CCA. The most abundant genera were Enterococcus, Streptococcus, Bacteroides, Klebsiella, and Pyramidobacter in CCA's biliary microbiota. Additionally, levels of Bacteroides, Geobacillus, Meiothermus, and Anoxybacillus genera were significantly higher. An enrichment of Bifidobacteriaceae, Enterobacteriaceae, and Enterococcaceae families has also been observed in CCA tumor tissue. Microbiota is related to postoperative outcomes in abdominal surgery. The combination of caloric restriction diets in liver cancer or CCA increases the effect of the chemotherapy treatment. CONCLUSION: The correct use of nutrition for microbiota modulation according to each patient's needs could be a therapeutic tool in combination with elective surgery and chemotherapy to diminish side effects and improve prognosis. Further investigations are needed to fully understand the mechanisms by which they are related.

• Keywords
• Cholangiocarcinoma, Diet, Liver cancer, Microbiota, Surgery,
• MeSH
• Cholangiocarcinoma * surgery   pathology   MeSH
• Dysbiosis MeSH
• Humans MeSH
• Microbiota * MeSH
• Bile Duct Neoplasms * surgery   MeSH
• Opisthorchiasis * microbiology   MeSH
• Bile Ducts, Intrahepatic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Cholangiocarcinoma is a relatively rare, highly fatal neoplasm originating from the biliary epithelium. Its only potentially curative treatment option is a radical surgical resection. The aim of our work was to evaluate the feasibility and the safety of intraoperative ERCP and direct cholangioscopy (SpyGlass) to assess the intraductal border of cholangiocarcinoma proliferation. The study ran from November 2015 to January 2018. The group included patients with histologically verified cholangiocarcinoma and, based on available examinations, the resectability of the tumor was assessed by a multidisciplinary team. In cases of indicated surgical resection we peroperatively performed ERCP with cholangioscopy SpyGlass and "diaphanoscopy" in all patients. The resectability was assessed on the basis of these examinations and the peroperative surgical findings. The resection procedure itself was performed only in 2 out of the total of 14 patients, as other patients were indicated for the implantation of metallic SEMS within the ERCP procedure in the operating room instead. To validate the cholangioscopic findings, we used our own criteria based on both the Monaco and other criteria. We divided the findings according to the presence or absence of ulceration, prominent polyposis, pathological vascularization (4 types), pressure defect with a coagulum in the presence of previous stent implantation, papillomatous changes or discolorations of the mucosa. Out of the total number of 14 patients only two patients were indicated for resection and in both cases R0 resection was achieved. The remaining patients were intraoperatively indicated for palliative implantation of SEMS based on the same unresectable finding during cholangioscopy and laparotomy. We demonstrated the technical feasibility and safety of direct peroperative cholangioscopy. Our results show that direct perioperative cholangioscopy is one of the methods which can contribute to a more accurate determination of tumor spread margins.

• Keywords
• ERCP, cholangiocarcinoma, direct cholangioscopy, intraductal ultrasonography,
• MeSH
• Biopsy MeSH
• Cholangiocarcinoma * diagnosis   MeSH
• Adult MeSH
• Endoscopy, Digestive System MeSH
• Humans MeSH
• Bile Duct Neoplasms * diagnosis   MeSH
• Pilot Projects MeSH
• Cell Proliferation MeSH
• Bile Ducts, Intrahepatic * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH

AIMS AND BACKGROUND: Conventional radiotherapy in inoperable cholangiocarcinoma is limited by radiotolerance of the surrounding tissues. The aim of our dosimetric study was an evaluation of intensity-modulated radiotherapy in the treatment of inoperable bile duct carcinoma. METHODS: Four patients with inoperable cholangiocarcinoma treated by self-expandable stent placed to the biliary tree and radiotherapy were studied. The rotational technique, conformal 3D BOX technique and intensity-modulated radiotherapy plan were compared. Dose volume histograms and the normal tissue complication probability concept were used for comparison. The stent was used for target motion verification. RESULTS: The intensity-modulated radiotherapy plans showed favorable dose distribution in planning target volume and remarkable sparing of organs at risk. CONCLUSIONS: The intensity-modulated radiotherapy technique in bile duct carcinomas deserves further research and clinical evaluation.

• MeSH
• Radiotherapy Dosage MeSH
• Cholangiocarcinoma radiotherapy   therapy   MeSH
• Combined Modality Therapy MeSH
• Humans MeSH
• Bile Duct Neoplasms radiotherapy   therapy   MeSH
• Palliative Care MeSH
• Computer Simulation MeSH
• Radiotherapy, Intensity-Modulated methods   MeSH
• Stents MeSH
• Bile Ducts, Extrahepatic * MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer next to hepatocellular carcinoma (HCC). Despite the significant difference of the therapeutic strategy for both diseases, their histological appearance may be very similar. Thus the correct diagnosis is crucial for treatment choice but is often difficult to achieve. The aim of our study was to evaluate anterior gradient 3 (AGR3) as a new diagnostic marker helping to distinguish between ICC and HCC. AGR3 is a putative transmembrane protein implicated in breast, prostate and ovary tumorigenesis and belongs to the family of protein disulfide isomerases. Since there is little information on how AGR3 is expressed in normal and diseased tissues and what its exact function is, we analyzed its expression pattern in normal liver and tumor tissue of ICC and HCC. The immunohistochemical analysis in normal tissue revealed specific AGR3 expression in intrahepatic bile duct cholangiocytes which was not present in liver hepatocytes. Consequently we analyzed AGR3 expression in 74 representative samples of puncture biopsies, tissue excisions and resection specimens from which 48 samples were diagnosed as HCC and 26 as ICC. Our results showed AGR3 expression negative and weakly positive respectively in hepatocellular carcinomas compared to stronger AGR3 positivity in cholangiocellular carcinomas. AGR3 expression statistically significantly correlated to acid mucopolysaccharide expression and negatively correlated to glypican-3 expression. We conclude that according to receiver operating characteristics (ROC) analysis AGR3 expression is relatively specific for ICC and is potentially linked to mucosecretion, which may indicate potential implication in treatment resistance.

• Keywords
• AGR3, GPC-3, Hepatocellular carcinoma, Immunohistochemistry, Intrahepatic cholangiocarcinoma, Mucopolysaccharides,
• MeSH
• Cholangiocarcinoma diagnosis   genetics   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Genetic Markers MeSH
• Glypicans genetics   metabolism   MeSH
• Carcinoma, Hepatocellular diagnosis   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Biomarkers, Tumor genetics   metabolism   MeSH
• Neoplasm Proteins genetics   metabolism   MeSH
• Liver Neoplasms diagnosis   genetics   MeSH
• Bile Duct Neoplasms MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Carrier Proteins genetics   metabolism   MeSH
• Bile Ducts, Intrahepatic metabolism   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• AGR3 protein, human MeSH Browser
• Genetic Markers MeSH
• Glypicans MeSH
• GPC3 protein, human MeSH Browser
• Biomarkers, Tumor MeSH
• Neoplasm Proteins MeSH
• Carrier Proteins MeSH

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

• MeSH
• Brachytherapy * methods   MeSH
• Radiotherapy Dosage MeSH
• Biliary Tract Surgical Procedures instrumentation   MeSH
• Cholangiocarcinoma radiotherapy   surgery   MeSH
• Adult MeSH
• Kaplan-Meier Estimate MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Bile Duct Neoplasms radiotherapy   surgery   MeSH
• Follow-Up Studies MeSH
• Prospective Studies MeSH
• Iridium Radioisotopes therapeutic use   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Stents * MeSH
• Treatment Outcome MeSH
• Bile Ducts, Intrahepatic pathology   radiation effects   surgery   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Iridium Radioisotopes MeSH