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
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.
- Klíčová slova
- ERCP, cholangiocarcinoma, direct cholangioscopy, intraductal ultrasonography,
- MeSH
- biopsie MeSH
- cholangiokarcinom * diagnóza MeSH
- dospělí MeSH
- endoskopie trávicího systému MeSH
- lidé MeSH
- nádory žlučových cest * diagnóza MeSH
- pilotní projekty MeSH
- proliferace buněk MeSH
- žlučové cesty intrahepatální * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články 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
Sclerosing cholangitides represent a group of chronic biliary obstructive diseases which include primary sclerosing cholangitis (PSC), IgG4 associated sclerosing cholangitis (IgG4-SC) and secondary sclerosing cholangitis (SSC). The manifestations of the diseases are similar, but their asymptomatic course is also frequent. IgG4-SC belongs to the group of IgG4 associated diseases and it is the most frequently related to type 1 autoimmune pancreatitis. Diagnosing of IgG4-SC is based on typical histopathological images, shape changes revealed by diagnostic imaging, serological tests, concurrent impairment of other organs and response to therapy, where IgG4-SC responds well to treatment with corticoids, whereas the only possibility for the remaining units is endoscopic intervention or liver transplantation. Secondary sclerosing cholangitis may develop as a result of many different insults affecting the biliary tree. Among them, the most frequently described include long-lasting biliary obstruction, surgical injury of the biliary tree, and ischemic cholangitis in liver allotransplants or recurrent pancreatitis. We use serological and imaging examination in PSC diagnostics, sometimes we have to resort to liver biopsy. PSC is to a significant degree accompanied by the presence of idiopathic bowel disease, typically ulcerative colitis. As a result, PSC may lead to cirrhosis of the liver and it is a precancerous condition of several malignancies. With regard to variable locations of the biliary tree injuries concerning the aforementioned units, also certain malignancies in subhepatic landscape need to be considered in the differential diagnosis: pancreatic cancer and cholangiogenous carcinoma.Key words: genetic factors - IBD - IgG4 cholangitis - liver transplantation - bile duct cancer - ursodeoxycholic acid - primary sclerosing cholangitis - secondary cholangitis - sclerosing cholangitis.
- MeSH
- autoimunitní nemoci diagnóza imunologie MeSH
- biopsie MeSH
- cholangiokarcinom diagnóza MeSH
- cholestáza komplikace diagnóza MeSH
- diferenciální diagnóza MeSH
- imunoglobulin G imunologie MeSH
- ischemie komplikace diagnóza MeSH
- játra patologie MeSH
- lidé MeSH
- nádory slinivky břišní diagnóza MeSH
- nádory žlučových cest diagnóza MeSH
- sklerozující cholangitida diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- imunoglobulin G MeSH
Cholangiocarcinoma (CC) is a rare malignant tumour arising from cholangiocytes, and its prognosis is usually unfavourable, mostly as a result of late diagnosis of the tumour. The current incidence of cholangiocarcinoma in the Czech Republic is 1.4/100,000 inhabitants per year; in less than 30 % of patients with CC, one of the known risk factors can be identified, most frequently, primary sclerosing cholangitis. Only patients with early diagnosed and surgically amenable cholangiocarcinoma are likely to have a longer survival time; in their case, survival for more than five years has been achieved in 20 % to 40 %. From the perspective of the need for early diagnosis of CC, a significant part is played by imaging and histopathologic evaluation; the early diagnostic significance of oncomarkers is limited. The rational early diagnosis of CC consists in effective use of differentiated advantages of different imaging modalities - MRI with DSA appears to be the optimal method, endosonography is a sensitive method for the identification of malignancy in the hepatic hilum or distal common bile duct, MRCP (magnetic resonance cholangiopancreatography) is used to display pathological changes in the biliary tree, ERCP (endoscopic retrograde cholangiopancreatography) allows material removal for histopathological examination. Other new approaches are also beneficial, such as IDUS - intraductal ultrasonography of biliary tract or SPY-GLASS, enabling examination of the bile ducts by direct view with the possibility of taking targeted biopsies. Sensitivity and specificity of histology and cytology can be increased by using the molecular cytogenetic FISH method, i.e. fluorescence in situ by hybridization, with a specificity of 97 %.
- MeSH
- časná detekce nádoru MeSH
- cholangiokarcinom diagnóza epidemiologie MeSH
- diagnostické zobrazování MeSH
- hybridizace in situ fluorescenční MeSH
- lidé MeSH
- multimodální zobrazování MeSH
- nádory žlučových cest diagnóza epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie 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
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
Activity of beta-glucuronidase (GL), placentar izoenzyme of alkaline phosphatase (PLAP), cathepsin B (CB) and concentrations of carcinoembryonic antigen (CEA) were determined in serums and bile of pigs with experimental cholangiocarcinoma and in control animals. No differences in serum GL, PLAP, CB activities or CEA were observed. The same was found in bile for GL, PLAP and CEA. However, in bile the situation was different for CB. In all the tumour bearing animals we were able to demonstrate in the course of tumour development a stricking progression in CB activity. Very impressive was namely an elevation of CB alkaline-stable form, generated (according also to the chromatographic studies of the bile) from primary cholangiocarcinoma tissue.
- MeSH
- alkalická fosfatasa analýza MeSH
- cholangiokarcinom chemicky indukované diagnóza MeSH
- glukuronidasa analýza MeSH
- izoenzymy analýza MeSH
- karcinoembryonální antigen analýza MeSH
- kathepsin B analýza MeSH
- nádorové biomarkery analýza MeSH
- nádory žlučových cest chemicky indukované diagnóza MeSH
- prasata MeSH
- žluč chemie MeSH
- žlučové cesty intrahepatální * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- glukuronidasa MeSH
- izoenzymy MeSH
- karcinoembryonální antigen MeSH
- kathepsin B MeSH
- nádorové biomarkery MeSH
Concentrations of CA 19-9, CA 50, CA 195 and DUPAN-2 were followed in serum, bile and pancreatic juice of 65 patients with malignant or benign lesions of CBD and/or pancrease. In sera, significant differences between neoplasias and benign lesions were seen only in patients with tumors in stages III. and IV. In the bile, however, the significant increase of DUPAN-2 and CA 195 were present in all stages of cholangiocarcinoma when compared with benign CBD lesions. In the pancreatic juice, the significant increase on of CA 19-9, CA 50 and DUPAN-2 in patients with pancreatic cancer (stages I-IV) could also be evidenced.
- MeSH
- antigeny nádorové analýza MeSH
- antigeny sacharidové asociované s nádorem analýza MeSH
- cholangiokarcinom diagnóza MeSH
- dospělí MeSH
- karcinoembryonální antigen analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory slinivky břišní diagnóza MeSH
- nádory žlučových cest diagnóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- žlučové cesty intrahepatální * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- antigeny nádorové MeSH
- antigeny sacharidové asociované s nádorem MeSH
- DU-PAN-2 antigen, human MeSH Prohlížeč
- karcinoembryonální antigen MeSH
- nádorové biomarkery MeSH
