Cholangiocellular carcinoma (CCC) is a malignant tumor harboring a poor prognosis, occurring in the liver, gallbladder and in extra- or intrahepatic biliary ducts. The article reviews the topic concerning CCC from the point of view of a surgical pathologist. The paper deals with classification of CCC into an intrahepatic/peripheral and hilar/extrahepatic subtype with different morphology, molecular features and prognosis; together with classical gross pathology, histopathology and natural history of CCC. Hilar and extrahepatic CCC share some biological characteristics with pancreatic ductal adenocarcinoma. The review comprises various types of precancerous lesions of biliary tract, summarizes updates in 8th edition of TNM classification and describes the routine issues concerning histopathological diagnostics of CCC, including immunohistochemistry and frozen section methods.

• Klíčová slova
• cholangiocellular carcinoma, extrahepatic, hilar, intrahepatic, pathology,
• MeSH
• cholangiokarcinom * patologie   MeSH
• duktální karcinom slinivky břišní * patologie   MeSH
• lidé MeSH
• nádory žlučových cest * patologie   MeSH
• prognóza MeSH
• žlučové cesty intrahepatální * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cholangiocellular carcinoma is a relatively rare malignant tumor, originating from cholangiocytes, with poor prognosis and late diagnosis. It is a malignancy with a variable biological etiology, numerous genetic and epigenetic changes. Its incidence in the Czech Republic is about 1.4 per 100,000 people per year. For good prognosis and long-term survival, early diagnosis with surgical treatment is important. In these cases, a 5-year survival rate is about 20-40 %. In the early diagnosis imaging methods and histopathological verification play an essential role, whereas laboratory oncomarkers are not yet sufficiently accurate. The same applies for genetic markers. This leads to the search of new molecular targets and the high effort in the introduction of cytological and molecular-biological methods with high specificity and sensitivity into routine practice. Current early diagnosis is based on the use of efficient imaging methods. The use of genetic testing, and especially knowledge of the molecular basis of this disease, will be of a great benefit. The observation of the association between the genetic pathways, IDH1, RAS-MAPK etc., and genetic mutations of genes, such as TP53, KRAS, SMAD4, BRAF, IDH1/2, may be significant. From the molecular point of view, it is also interesting to monitor oncogenic potential in HBV/HCV infection.

• Klíčová slova
• KRAS, cholangiocellular carcinoma, mutation of genes, oncomarkers, p53,
• MeSH
• cholangiokarcinom * diagnóza   genetika   MeSH
• genetické testování MeSH
• geny nádorové MeSH
• lidé MeSH
• molekulární patologie MeSH
• mutace MeSH
• nádory žlučových cest * diagnóza   genetika   MeSH
• žlučové cesty intrahepatální * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND/AIM: The behavior of tumor markers in biliary tract malignancies is not well-known and has been scarcely studied. Such markers could play important roles in diagnostic and prognostic schemes as well as in decision-making about the best treatment strategies. This study analyzed the preoperative serum levels of conventional tumor markers (AFP, CEA, CA 19-9, CA 72-4), proliferative marker thymidine kinase (TK) and cytokeratins (TPA, TPS and CYFRA 21.1) in patients with gallbladder carcinoma, bile duct carcinoma (Klatskin) and cholangiocellular carcinoma, in relation to the patient prognosis. The study aimed in finding the role of tumor markers in not properly investigated diseases, where their importance is often marginalized. MATERIALS AND METHODS: The study included 43 patients, who underwent either radical surgical procedure (n=21) or explorative laparotomy without any surgical treatment (n=22) for gallbladder carcinoma, bile duct carcinoma (Klatskin tumor) and cholangiocellular carcinoma (24, 8 and 11 patients, respectively) between 2003 and 2010 at our Department. The association of serum tumor markers and patients' prognosis were assessed for the entire cohort and for each cancer type and also with regard to treatment (radical surgery versus explorative laparotomy). Overall survival (OS) and disease-free interval (DFI) were estimated by the Kaplan-Meier method and statistically evaluated using the LogRank test. DFI was computed only in the subgroup of patients treated by radical surgery. RESULTS: The statistical analysis of tumor markers revealed TK as a poor prognostic factor for shorter DFI (HR=3.5, 95%CI=0.6-21.3, p<0.05) and also OS (HR=4.6, 95%CI=1.0-4.7, p<0.05) in patients with gallbladder carcinoma treated with radical surgery. TPS was demonstrated as a poor prognostic factor for OS in patients with gallbladder carcinoma (HR=12.7, 95%CI=1.4-117.7, p<0.05). CEA was proven to be a factor of poor prognosis with shorter OS in patients after explorative laparotomy for all cumulated studied diagnoses (HR=9.8, 95%CI=1.05-92.7, p<0.05). CONCLUSION: The results of this study suggested the importance of tumor markers for assessment of prognosis (OS or DFI) in patients with gallbladder carcinoma, bile duct carcinoma, and cholangiocellular carcinoma.

• Klíčová slova
• Gall bladder carcinoma, bile duct carcinoma, cholangiocellular carcinoma, liver surgery, prognosis, tumor markers,
• MeSH
• antigen CA-19-9 krev   MeSH
• antigeny nádorové krev   MeSH
• cholangiokarcinom krev   patologie   MeSH
• dospělí MeSH
• imunoanalýza MeSH
• keratin-19 krev   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádorové biomarkery krev   MeSH
• nádory žlučníku krev   patologie   MeSH
• nádory žlučových cest krev   patologie   MeSH
• pilotní projekty MeSH
• prognóza MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• antigen CA-19-9 MeSH
• antigen CYFRA21.1 MeSH Prohlížeč
• antigeny nádorové MeSH
• keratin-19 MeSH
• nádorové biomarkery 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.

• Klíčová slova
• AGR3, GPC-3, Hepatocellular carcinoma, Immunohistochemistry, Intrahepatic cholangiocarcinoma, Mucopolysaccharides,
• MeSH
• cholangiokarcinom diagnóza   genetika   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• genetické markery MeSH
• glypikany genetika   metabolismus   MeSH
• hepatocelulární karcinom diagnóza   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové proteiny genetika   metabolismus   MeSH
• nádory jater diagnóza   genetika   MeSH
• nádory žlučových cest MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transportní proteiny genetika   metabolismus   MeSH
• žlučové cesty intrahepatální metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AGR3 protein, human MeSH Prohlížeč
• genetické markery MeSH
• glypikany MeSH
• GPC3 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• nádorové proteiny MeSH
• transportní proteiny 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.

• Klíčová slova
• cholangiocarcinoma, cholangiocellular carcinoma, extrahepatic, intrahepatic, perihilar,
• MeSH
• cholangiokarcinom * patologie   MeSH
• lidé MeSH
• nádory žlučových cest * chirurgie   patologie   MeSH
• patologové MeSH
• žlučové cesty extrahepatické * patologie   MeSH
• žlučové cesty intrahepatální patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

To achieve satisfactory results of liver transplantation, proper selection of transplant candidates is essential. Moreover, indication process is crucial regulator to solve disparity between need for transplantation and capacity of transplant services. Any patient entering the transplant waiting list must have a chance to achieve at least average transplant benefit, currently described as 50% chance to survive 5 years after liver replacement. Until now, liver transplantation is procedure designed to treat life threatening liver disorders with aim to offer long-term survival. Nevertheless, an increase in incidence of hepatocellular carcinoma, and nonalcoholic fatty liver disease caused changes in indication spectrum. Improvement in intensive care turned interest to patients with acute-on-chronic liver failure even caused by acute alcoholic hepatitis. Advances in surgery and oncology broadened indications of patients with hepatocellular carcinoma behind standard criteria, and reopened interest in field of cholangiocellular cancer and even liver metastases of colorectal cancer. These criteria are still under development, and full of controversies and broad local variation in clinical practice is present. Entity of futile transplantation is discussed recently with aim to define generally acceptable criteria to deny transplant treatment in too risky patients.

• Klíčová slova
• acute-on-chronic liver failure, cholangiocellular carcinoma, futile transplantation, hepatocellular carcinoma, indication of transplantation, liver transplantation, non-alcoholic fatty liver disease,
• MeSH
• hepatocelulární karcinom * chirurgie   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nádory jater * chirurgie   MeSH
• seznamy čekatelů MeSH
• transplantace jater * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The prognosis of extrahepatic cholangiocarcinoma is dismal and the only way to achieve long-term survival is surgical resection. While pancreatoduodenectomy (PD) is the standard procedure for distal cholangiocarcinoma (distal bile duct cancer; DBDC), bile duct segmental resection (BDR) can be used as an alternative approach for middle bile duct cholangiocarcinoma (middle bile duct cancer; MBDC). The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal bile duct cholangiocarcinoma patients. METHODS: A retrospective cohort study of consecutive patients treated for MBDC and DBDC with PD or BDR between 1/2009-12/2019. The patients were divided according to the type of surgical resection (PD and BDR group). Demographic, clinicopathological and histopathological data and overall survival (OS) were evaluated in both groups. OS was estimated using the Kaplan-Meier analysis. RESULTS: The study comprised a total of 62 patients - 45 patients (72.6%) in the PD group and 17 (27.4%) in the BDR group. Patients undergoing BDR were significantly older than those receiving PD (p=0.048). Men predominated in the PD group (N=34/45; 75.6%) while more women were included in the BDR group (N=10/17; 58.8%). Median age was higher in the BDR group (p=0.048). Serious morbidity (Clavien-Dindo III-V) (33.3% vs 11.8%), 30-day and 90-day mortality (4.4% vs 0.0% and 8.9% vs 5.9%, respectively) predominated in the PD group although the differences were not statistically significant, as well as a longer hospital stay (16.0 days vs 11.0 days; p=0.002). Pathological assessments revealed comparable numbers of positive lymph nodes in both groups, but a significantly higher number of total resected lymph nodes in the PD group (p.

• Klíčová slova
• bile duct resection, distal bile duct cancer, middle bile duct cancer, pancreatoduodenectomy,
• MeSH
• cholangiokarcinom * chirurgie   patologie   MeSH
• lidé MeSH
• nádory žlučových cest * chirurgie   patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• žlučové cesty extrahepatické * patologie   chirurgie   MeSH
• žlučové cesty intrahepatální patologie   chirurgie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.

• Klíčová slova
• alcohol, comorbidity, familial risk, hepatocellular carcinoma, risk factor, smoking,
• MeSH
• ampulla Vateri * patologie   MeSH
• autoimunitní nemoci * MeSH
• cholangiokarcinom * epidemiologie   etiologie   diagnóza   MeSH
• cholelitiáza * komplikace   patologie   MeSH
• hepatocelulární karcinom * patologie   MeSH
• lidé MeSH
• nádory ductus choledochus * komplikace   patologie   MeSH
• nádory jater * epidemiologie   etiologie   patologie   MeSH
• nádory žlučníku * etiologie   komplikace   MeSH
• nádory žlučových cest * epidemiologie   etiologie   patologie   MeSH
• zánět patologie   MeSH
• žlučové cesty intrahepatální patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND/AIMS: The aim of our study was to evaluate preliminary results of intensity modulated radiotherapy (IMRT) in patients with inoperable subhepatic tumors. METHODOLOGY: Thirteen patients with inoperable cholangiocarcinoma or gall bladder carcinoma were treated by biliary drainage and intensity modulated radiotherapy. In patients with tumors limited to the biliary duct only tumor stenosis was irradiated to the dose of 50-60 Gy. In patients with bulky extraductal tumors the dose was 50 Gy/25 fractions to the whole tumor and an integrated boost was used to raise the dose to the malignant stenosis to 60 Gy/25 fractions. RESULTS: Doses to organs at risk (duodenum, small intestine, liver) were in tolerable limits. In four patients transient fever occurred; one patient had duodenal bleeding that resolved after conservative treatment. Recurrent dilatation of the biliary tract was observed in 4 patients and was managed by exchange of the internal biliary drainage. Median survival was 10.4 months, 5 patients survived for more than one year following diagnosis. CONCLUSIONS: IMRT of inoperable extrahepatic biliary tract tumors allows application of high doses of radiation to the tumor with effective sparing of healthy tissues. The control of jaundice is good. In selected cases IMRT may prolong overall survival.

• MeSH
• celková dávka radioterapie MeSH
• cholangiokarcinom radioterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory žlučníku radioterapie   MeSH
• nádory žlučových cest radioterapie   MeSH
• radioterapie s modulovanou intenzitou metody   MeSH
• senioři MeSH
• žlučové cesty intrahepatální * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bile duct malignancies include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma of Vater's ampulla (ampulloma). Bile duct neoplasms are rare tumours with overall poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000 persons. The incidence and mortality have been remarkably stable over the past 3 decades. The survival rate of patients with these tumours is poor, usually not exceeding 12 months. The diagnostic process is complex, uneasy and usually late. Most cases are diagnosed when unresectable, and palliative treatment is the main approach of medical care for these tumours. The treatment remains very challenging. New approaches have not brought much improvement in this field. Standards of palliative care are lacking and quality of life assessments are surprisingly not common. From the scarce data it seems, however, that multimodal individually tailored treatment can prolong patients'survival and improve the health-related quality of life. The care in specialized centres offers methods of surgery, interventional radiology, clinical oncology and high quality supportive care. These methods are discussed in the article in greater detail. Improvements in this field can be sought in new diagnostic methods and new procedures in surgery and interventional radiology. Understanding the tumour biology on the molecular level could shift the strategy to a more successful one, resulting in more cured patients. Further improvements in palliative care can be sought by defining new targets and new drug development. The lack of patients with bile duct neoplasms has been the limiting factor for any improvements. A new design of larger randomized international multicentric clinical trials with prompt data sharing could help to overcome this major problem. Defining standards of palliative care is a necessity. Addressing health-related quality of life could help to assess the real benefit of palliative treatment.

• MeSH
• cholangiokarcinom diagnóza   epidemiologie   terapie   MeSH
• lidé MeSH
• nádory ductus choledochus diagnóza   terapie   MeSH
• nádory žlučníku diagnóza   terapie   MeSH
• nádory žlučových cest * diagnóza   epidemiologie   terapie   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH