BACKGROUND: Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to evaluate the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR. METHODS: Plasma bile salts, FGF19, and C4 (bile salt synthesis marker) were assessed in patients with pCCA and controls (colorectal liver metastases), before and after resection on postoperative days (PODs) 1, 3, and 7. Hepatic bile salts were determined in intraoperative liver biopsies. RESULTS: Partial liver resection in pCCA elicited a sharp decline in bile salt and FGF19 plasma levels on POD 1 and remained low thereafter, unlike in controls, where bile salts rose gradually. Preoperatively, suppressed C4 in pCCA normalized postoperatively to levels similar to those in the controls. The remnant liver volume and postoperative bilirubin levels were negatively associated with postoperative C4 levels. Furthermore, patients who developed postoperative liver failure had nearly undetectable C4 levels on POD 7. Hepatic bile salts strongly predicted hyperbilirubinemia on POD 7 in both groups. Finally, postoperative bile salt levels on day 7 were an independent predictor of LR. CONCLUSIONS: Partial liver resection alters the bile salt-FGF19 axis, but its derailment is unrelated to LR in pCCA. Postoperative monitoring of circulating bile salts and their production may be useful for monitoring LR.
- MeSH
- fibroblastové růstové faktory * krev MeSH
- hepatektomie * MeSH
- játra metabolismus chirurgie MeSH
- Klatskinův nádor * chirurgie patologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory žlučových cest * chirurgie patologie krev MeSH
- regenerace jater * fyziologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- žlučové kyseliny a soli * krev metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- FGF19 protein, human MeSH Prohlížeč
- fibroblastové růstové faktory * MeSH
- žlučové kyseliny a soli * MeSH
BACKGROUND: Endoluminal radiofrequency ablation (RFA) has been promoted as palliative treatment for patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) in order to improve biliary drainage and eventually prolong survival. No high level evidence is, however, available on this technique. DESIGN: In this randomised controlled study, we compared endoluminal RFA plus stenting with stenting alone (control group) in patients with malignant biliary obstruction; metal stents were primarily placed. Primary outcome was overall survival; secondary outcomes were stent patency, quality of life and adverse events. In a superiority design, survival was assumed to be doubled by RFA as compared with 6.4 months in the control group (n=280). RESULTS: A total of 161 patients (male:female 90:71, mean age 71±9 years) were randomised before recruitment was terminated for futility after an interim analysis. Eighty-five patients had CCA (73 hilar, 12 distal) and 76 had pancreatic cancer. There was no difference in survival in both subgroups: for patients with CCA, median survival was 10.5 months (95% CI 6.7 to 18.3) in the RFA group vs 10.6 months (95% CI 9.0 to 24.8), p=0.58)) in the control group. In the subgroup with pancreatic cancer, median survival was 6.4 months (95% CI 4.3 to 9.7) for the RFA vs 7.7 months (95% CI 5.6 to 11.3), p=0.73) for the control group. No benefit was seen in the RFA group with regard to stent patency (at 12 months 40% vs 36% in CCA and 66% vs 65% in PDAC), and quality of life was unchanged by either treatment and comparable between the groups. Adverse events occurred in seven patients in each groups. CONCLUSION: A combination of endoluminal RFA and stenting was not superior to stenting alone in prolonging survival or improving stent patency in patients with malignant biliary obstruction. TRIAL REGISTRATION NUMBER: NCT03166436.
- Klíčová slova
- biliary obstruction, cholangiocarcinoma, pancreatic cancer, stents,
- MeSH
- cholangiokarcinom * MeSH
- cholestáza * etiologie chirurgie MeSH
- katetrizační ablace * škodlivé účinky metody MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní * komplikace chirurgie MeSH
- nádory žlučových cest * komplikace chirurgie MeSH
- radiofrekvenční ablace * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stenty škodlivé účinky MeSH
- výsledek terapie MeSH
- žlučové cesty intrahepatální chirurgie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie 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.
- Klíčová slova
- Cholangiocarcinoma, Diet, Liver cancer, Microbiota, Surgery,
- MeSH
- cholangiokarcinom * chirurgie patologie MeSH
- dysbióza MeSH
- lidé MeSH
- mikrobiota * MeSH
- nádory žlučových cest * chirurgie MeSH
- opistorchióza * mikrobiologie MeSH
- žlučové cesty intrahepatální MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy 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: 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.
- Klíčová slova
- cholangiocarcinoma, long-term survival, pancreaticoduodenectomy, prognostic factor,
- MeSH
- cholangiokarcinom * chirurgie patologie MeSH
- lidé MeSH
- nádory žlučových cest * chirurgie patologie MeSH
- pankreatoduodenektomie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- žlučové cesty intrahepatální patologie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články 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
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
Extrahepatic cholangiocarcinoma is a rare disease with poor prognosis, requiring comprehensive multidisciplinary management. Only radical resection gives hope for long-term survival. Most patients have either an unresectable disease or their condition does not allow for radical surgery. The method of choice for resectable perihilar cholangiocarcinoma is en-block liver resection including the extrahepatic bile duct, or pancreatoduodenectomy for distal cholangiocarcinoma. Hepatopancreatoduodenectomy can be performed in selected patients if the entire hepato-choledochus is affected. Liver transplantation after neoadjuvant treatment can be also considered in highly selected patients with unresectable perihilar cholangiocarcinoma. These procedures are technically demanding, are associated with high morbidity and relevant mortality, and must be concentrated in tertiary hepatobiliary centers. Preoperative optimization (bile duct drainage, nutrition, portal venous embolization, etc.) plays a crucial role in reducing postoperative morbidity and mortality.
- Klíčová slova
- Hepatectomy, bile duct, cholangiocarcinoma, extrahepatic, pancreatoduodenectomy,
- MeSH
- cholangiokarcinom * patologie chirurgie MeSH
- hepatektomie metody MeSH
- Klatskinův nádor * chirurgie MeSH
- lidé MeSH
- nádory žlučových cest * chirurgie patologie MeSH
- žlučové cesty extrahepatické * chirurgie patologie MeSH
- žlučové cesty intrahepatální patologie chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články 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.
- Klíčová slova
- Prognosis, cholangiocarcinoma, heart failure, recurrence, resection, survival,
- MeSH
- cholangiokarcinom * chirurgie patologie MeSH
- hepatektomie metody MeSH
- lidé MeSH
- míra přežití MeSH
- nádory žlučových cest * chirurgie patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- výsledek terapie MeSH
- žlučové cesty intrahepatální patologie chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC (p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively (p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA.
- Klíčová slova
- Foxf1, cholangiocarcinoma, extrahepatic, hilar, intrahepatic cholangiocarcinoma, peripheral,
- MeSH
- dospělí MeSH
- duktální karcinom pankreatu metabolismus sekundární MeSH
- forkhead transkripční faktory metabolismus MeSH
- hepatocelulární karcinom metabolismus patologie MeSH
- imunohistochemie MeSH
- Klatskinův nádor metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádorové biomarkery metabolismus MeSH
- nádory jater metabolismus sekundární MeSH
- nádory slinivky břišní metabolismus patologie MeSH
- nádory žlučových cest metabolismus patologie MeSH
- následné studie MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři 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
- časopisecké články MeSH
- Názvy látek
- forkhead transkripční faktory MeSH
- FOXF1 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
