Primary Biliary Tract Cancer Research Articles

Primary Biliary Tract Cancers in Golestan, Iran: 13-Year Experience of Golestan Population-Based Cancer Registry.

Epidemiological research on the high-risk population might be helpful in early detection and prevention of biliary tract malignancies. This study assesses the prevalence of biliary tract cancer (BTC) in the Golestan province, northeastern Iran, between 2004 and 2016. The current study used information from the Golestan Population-based Cancer Registry (GPCR) to access the epidemiology of BTC across a 13-year period while taking into account temporal and geographic differences. The number of cases, crude rates, age-standardized incidence rates (ASRs) per 100,000 person-years, average annual percent change (AAPC), age-specific incidence rates, and 95% confidence intervals (CI) were reported for each year with respect to gender and place of residence. Totally, 224 instances of BTC overall (54% of whom were females) were reported throughout the research period. The ASR of BTC was 1.7 (95% CI: 1.4‒2) for females and 1.4 (95% CI: 1.1‒1.6) for men, respectively. Males exhibited a growing time trend in incidence (AAPC: 7.18; CI: 0.06‒14.81; P-value:0.048), whereas females had a decreasing trend (AAPC: 0.82; CI: -5.94‒4.57; P-value: 0.740). Both sexes saw an increase in age-specific incidence rates starting at the age of 45; however, males experienced a significant increase in incidence in the age group of 75 to 79 while the female rates grew steadily. The focus for cancer control in this region may be given to demographic groups with a combination of risk factors, including male gender, older age, and urban residence.

A prospective investigation of serum bile acids with risk of liver cancer, fatal liver disease, and biliary tract cancer.

Bile acids (BAs), major regulators of the gut microbiota, may play an important role in hepatobiliary cancer etiology. However, few epidemiologic studies have comprehensively examined associations between BAs and liver or biliary tract cancer. In the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) study, we designed 1:1 matched, nested, case–control studies of primary liver cancer (n = 201 cases), fatal liver disease (n = 261 cases), and primary biliary tract cancer (n = 138 cases). Using baseline serum collected ≤30 years before diagnosis or death, we measured concentrations of 15 BAs with liquid chromatography–tandem mass spectrometry. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable conditional logistic regression models, adjusted for age, education, diabetes status, smoking, alcohol intake, and body mass index. We accounted for multiple comparisons using a false discovery rate (FDR) correction. Comparing the highest to the lowest quartile, seven BAs were positively associated with liver cancer risk, including taurocholic acid (TCA) (OR, 5.62; 95% CI, 2.74–11.52; Q trend < 0.0001), taurochenodeoxycholic acid (TCDCA) (OR, 4.77; 95% CI, 2.26–10.08; Q trend < 0.0001), and glycocholic acid (GCA) OR, 5.30; 95% CI, 2.41–11.66; Q trend < 0.0001), and 11 were positively associated with fatal liver disease risk, including TCDCA (OR, 9.65; 95% CI, 4.41–21.14; Q trend < 0.0001), TCA (OR, 7.45; 95% CI, 3.70–14.97; Q trend < 0.0001), and GCA (OR, 6.98; 95% CI, 3.32–14.68; Q trend < 0.0001). For biliary tract cancer, associations were generally >1 but not significant after FDR correction. Conjugated BAs were strongly associated with increased risk of liver cancer and fatal liver disease, suggesting mechanistic links between BA metabolism and liver cancer or death from liver disease.

Frequency of BRCA mutation in biliary tract cancer and its correlation with tumor mutational burden (TMB) and microsatellite instability (MSI).

4085 Background: Biliary tract cancers constitute ~3% of cancers worldwide with incidence increasing, especially for intrahepatic cholangiocarcinoma (IHC). The prognosis of these tumors remains dismal and novel treatment strategies are needed to improve overall survival. BRCA mutations occur in biliary tract cancers but their frequency in distinct sites of biliary tract cancer is unknown. Moreover, no data are available correlating BRCA mutation with immunogenic markers such as TMB, MSI, or PD-L1 expression. Methods: Tumor samples from 1288 primary biliary tract cancers, comprising IHC (n = 746), extrahepatic cholangiocarcinoma (EHC) (n = 189), gallbladder (GBC) (n=353) were profiled at Caris Life Sciences, Phoenix, AZ. Testing included NextGen SEQ (MiSeq on 47 genes, NextSeq on 592 genes) and PD-L1 IHC (SP142). TMB was calculated based on somatic nonsynonymous missense mutations, and MSI was evaluated by NGS of known MSI loci. Results: BRCA mutations were detected in 3.6% (N = 46) of samples ( BRCA1 0.6%, BRCA2 3%), no differences were seen based on the site of the tumor. In GBC and IHC BRCA2 mutations (4.0% and 2.7%) were more frequent than BRCA1 (0.3% and 0.4, p &lt; 0.05) while in EHC, similar frequency was observed ( BRCA1: 2.1%; BRCA2: 2.6%). There was no significant association with gender or age. In BRCA-mutant biliary tract cancer the most frequently mutated genes were TP53 (55.6%), ARID1A (52.2%) and KRAS (26.1%), KMT2D/C (20%, 13%) and CDKN2A(13%). Overall, BRCA mutations were associated with a higher rate of MSI-H (19.5% vs 1.7%, p = 0.001) and higher TMB in both MSI-H and MSS tumors (p&lt;0.05). When investigated separately, BRCA association with elevated TMB was seen in IHC and EHC, but not in GBC. No correlation was seen with PD-L1 expression. TP53, KMT2D/C, RB1, PTEN, KDM6A mutations and FGFR1 amplifications were significantly higher in BRCA mutated tumors (p &lt; 0.05). Conclusions: BRCA mutations are found in a significant subgroup of biliary tract tumors and are associated with an immunogenic tumor profile. These data provide rationale for trials testing PARP inhibitors in combination with immunotherapy and targeted therapies in patients with BRCA-mutant biliary tract cancers that are MSS.

Methylated promoter DNA of CDO1 gene and preoperative serum CA19-9 are prognostic biomarkers in primary extrahepatic cholangiocarcinoma.

BackgroundPromoter DNA methylation of Cysteine dioxygenase type1 (CDO1) gene has been clarified as a molecular diagnostic and prognostic indicator in various human cancers. The aim of this study is to investigate the clinical relevance of CDO1 methylation in primary biliary tract cancer (BTC).MethodsCDO1 DNA methylation was assessed by quantitative methylation-specific PCR in 108 BTC tumor tissues and 101 corresponding normal tissues. BTC was composed of extrahepatic cholangiocarcinoma (EHCC) (n = 81) and ampullary carcinoma (AC) (n = 27).ResultsThe CDO1 methylation value in the tumor tissues was significantly higher than that in the corresponding normal tissues (p<0.0001). The overall survival (OS) in EHCC patients with hypermethylation was poorer than those with hypomethylation (p = 0.0018), whereas there was no significant difference in AC patients. Multivariate analysis identified that CDO1 hypermethylation, preoperative serum CA19-9 and perineural invasion were independent prognostic factors in EHCC. The EHCC patients with CDO1 hypermethylation exhibited more dismal prognosis than those with hypomethylation even in low group of CA19-9 level (p = 0.0006).ConclusionsOur study provided evidence that promoter DNA methylation of CDO1 gene could be an excellent molecular diagnostic and prognostic biomarker in primary EHCC. The combination of CDO1 methylation and preoperative serum CA19-9 effectively enriched EHCC patients who showed the most dismal prognosis. These markers would be beneficial for clinical clarification of the optimal strategies in EHCC.

Endoscopic inside stent placement is suitable as a bridging treatment for preoperative biliary tract cancer.

BackgroundEndoscopic biliary stenting (EBS) is one of the most important palliative treatments for biliary tract cancer. However, reflux cholangitis arising from bacterial adherence to the inner wall of the stent must be avoided. We evaluated the use of EBS above the sphincter of Oddi to determine whether reflux cholangitis could be prevented in preoperative cases.MethodsFifty-seven patients with primary biliary tract cancer were retrospectively recruited for the evaluation of stent placement either above (n = 25; inside stent group) or across (n = 32; conventional stent group) the sphincter of Oddi. We compared the stent patency periods prior to the time of surgical resection.ResultsThe preoperative periods were 96.3 days in the conventional stent group and 96.8 days in the inside stent group (P = 0.979). Obstructive jaundice and/or acute cholangitis occurred in 7 patients (28.0%) in the inside stent group and in 15 patients (46.9%) in the conventional stent group during the preoperative period (P = 0.150). The average patency periods of the stents were 85.2 days (range, 13–387 days) for the inside stent group and 49.1 days (range, 9–136 days) for the conventional stent group (log-rank test: P = 0.009). The mean numbers of re-interventions because of stent occlusion were 0.32 for the inside stent group and 1.03 for the conventional stent group (P = 0.026). Post-endoscopic retrograde cholangiopancreatography complications occurred in 2 patients in the inside stent group and 4 patients in the conventional stent group (P = 0.516). Postoperative liver abscess occurred in 1 patient in the inside stent group and 5 patients in the conventional stent group (P = 0.968). Inside stent placement was the only significant preventative factor associated with stent obstruction based on univariate (hazard ratio [HR], 0.286; 95% confidence interval [CI], 0.114-0.719; P = 0.008) and multivariate (HR, 0.292; 95% CI, 0.114-0.750; P = 0.011) analyses.ConclusionTemporary plastic stent placement above the sphincter of Oddi is a better bridging treatment than conventional stent placement in preoperative primary biliary tract cancer.

Chronic typhoid infection and the risk of biliary tract cancer and stones in Shanghai, China

Previous studies have shown a positive association between chronic typhoid carriage and biliary cancers. We compared serum Salmonella enterica serovar Typhi antibody titers between biliary tract cancer cases, biliary stone cases without evidence of cancer, and healthy subjects in a large population-based case-control study in Shanghai, China.Participants included 627 newly diagnosed primary biliary tract cancer patients; 1,037 biliary stone cases (774 gallbladder and 263 bile-duct) and 959 healthy subjects without a history of cancer, randomly selected from the Shanghai Resident Registry.Overall only 6/2,293 (0.26%) were Typhi positive. The prevalence of Typhi was 1/457 (0.22%), 4/977 (0.41%), and 1/859 (0.12%) among cancer cases, biliary-stone cases, and population controls, respectively.We did not find an association between Typhi and biliary cancer in Shanghai, due to the very low prevalence of chronic carriers in this population.The low seroprevalence of S. Typhi in Shanghai is unlikely to explain the high incidence of biliary cancers in this population.

Prognostic Significance of CD44s Expression in Biliary Tract Cancers

CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers. Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed. Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37-86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211-.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630-3.393; P = .377) had no prognostic significance for survival. CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.

Risk factors for biliary tract cancers

Objective: Little is known regarding risk factors for biliary tract cancer, i.e., gallbladder carcinoma and extrahepatic bile duct carcinoma. This is the first case-control study conducted in the U.S. regarding risk factors for these cancers. Methods: In this hospital-based case-control study, we reviewed the medical records of 69 patients with primary biliary tract cancer who were admitted to Columbia-Presbyterian Medical Center for surgery between January 1, 1980, and April 4, 1994, and of 138 controls, consisting of patients admitted for surgery for benign conditions. Results: We found a significant association between cholelithiasis and biliary tract cancers (odds ratio, 19.5; 95% confidence interval, 6.4–59.4). Risk factors associated with gallbladder cancer included female gender, age, cigarette smoking, and postmenopausal status in women. Risk factors associated with extrahepatic bile duct cancer included history of cholecystectomy and hysterectomy in women. Conclusion: The risk factors for biliary tract cancers that have been identified in our study delineate a high-risk population, which in the future may be targeted for preventive measures.

Risk factors for biliary tract cancers.

Little is known regarding risk factors for biliary tract cancer, i.e., gallbladder carcinoma and extrahepatic bile duct carcinoma. This is the first case-control study conducted in the U.S. regarding risk factors for these cancers. In this hospital-based case-control study, we reviewed the medical records of 69 patients with primary biliary tract cancer who were admitted to Columbia-Presbyterian Medical Center for surgery between January 1, 1980, and April 4, 1994, and of 138 controls, consisting of patients admitted for surgery for benign conditions. We found a significant association between cholelithiasis and biliary tract cancers (odds ratio, 19.5; 95% confidence interval, 6.4-59.4). Risk factors associated with gallbladder cancer included female gender, age, cigarette smoking, and postmenopausal status in women. Risk factors associated with extrahepatic bile duct cancer included history of cholecystectomy and hysterectomy in women. The risk factors for biliary tract cancers that have been identified in our study delineate a high-risk population, which in the future may be targeted for preventive measures.

Comparison between metastatic vs primary biliary tract cancer in their response to the Wallstent

Comparison between metastatic vs primary biliary tract cancer in their response to the Wallstent

Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.