Inflammatory bowel disease increases the risk of hepatobiliary pancreatic cancer: A two-sample Mendelian randomization analysis of European and East Asian populations.

BACKGROUND: Both inflammatory bowel disease (IBD) and hepato-pancreato-biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC. METHODS: Herein, we utilized inverse-variance weighting to conduct a two-sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses. RESULTS: Compared to the general population, IBD patients in Europe exhibited a 1.22-fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022-1.4888 (p = 0.0475). We also found a 1.14-fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017-1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28-fold higher (95% CI = 1.0709-1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12-fold (95% CI: 1.1466-1.3334, p < 0.0001) and 1.31-fold (95% CI: 1.0983-1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19-fold higher in CD patients than in the general population (95% CI = 1.0741-1.3132, p = 0.0008). CONCLUSION: Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations.

Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts.

BACKGROUND: Neuronal signaling has been implicated in the pathophysiology of multiple malignancies. In biliary tract cancers (BTCs), tumor cell expression of nerve growth factor (NGF) and its receptor neurotrophic tropomyosin receptor kinase (NTRK) has been reported in Asian patients and linked to inferior clinical outcome. Furthermore, NTRK fusions have emerged as a promising target in various cancers. Expression patterns of these markers in Caucasian patients remain unknown. METHODS: In this study, 106 patients with BTCs were included. Immunohistochemistry for pan-NTRK and NGF-beta was performed on > 90 samples of this cohort. Additionally, samples from two independent cohorts, incorporating 254 cases, were used to confirm the findings of the original cohort. RESULTS: While expression of pan-NTRK and NGF-beta was readily detectable in peri-tumoral nerves, these markers were not detectable in malignant epithelial cells in our cohort. CONCLUSIONS: In a large cohort of Caucasian patients with BTC, NTRK and NGF-beta were not detectable, underscoring potential differences between Caucasian and Asian patient populations.

Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

OBJECTIVE: Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. METHODS: Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. RESULTS: Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). CONCLUSIONS: In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

Comparison of diets of urban American Indian and non-Hispanic whites: populations with a disparity for biliary tract cancer rates.

AIM: The incidnece of biliary tract cancer (BTC) is many-fold higher for American Indians (AI) relative to non-Hispanic whites (NHW). Neither gallstones nor genetics can account for this difference. There is speculation that certain fatty acids in bile may play a role in preventing BTC. Since diet may influence composition of bile, we compared the dietary intakes of urban AI and NHW adult women in New Mexico. METHODS: Design, a cross- sectional study of the diets of lactating AI and NHW women was conducted. Setting, the University of New Mexico Hospital. Participants, healthy lactating women 18 to 39 years of age were recruited. Main outcome measures, a three-day diet record for each participant was analyzed. RESULTS: The AI women consumed less calcium (p = 0.04) and significantly less short and intermediate chain-length fatty acids (C4-C12), but nearly twice as much proinflammatory arachidonic acid as the NHWs (p < 0.01). The intake of dairy products by AI women was less than NHW women (p = 0.01) while the intake of processed meat products was higher (p < 0.01). CONCLUSION: Dietary factors may account for the difference in the risk of BTC between AI and NHW women.

Diversification and trends in biliary tree cancer among the three major ethnic groups in the state of New Mexico.

BACKGROUND: New Mexico's population is composed of 45% non-Hispanic whites, 42% Hispanics, 10% American Indians, and 3% other minorities. The purpose of this study was to compare the trends of biliary tract cancer among these groups over the past 3 decades. METHODS: The state's tumor registry was used to ascertain the incidence of gallbladder cancer, extrahepatic bile duct cancer, and intrahepatic bile duct cancer. RESULTS: A total of 1,449 new biliary cancers were diagnosed between 1981 and 2008. The contemporary incidence of gallbladder cancer remains several times higher among American Indians than in other ethnicities: for men, 4.1%, 1.1%, and .8% for American Indians, Hispanics, and non-Hispanic whites, respectively, and for women, 8.1%, 2.1%, and 1.0%, respectively. CONCLUSIONS: Biliary malignancies are more prevalent among American Indians. Despite a decline in the incidence of gallbladder cancer among American Indians and Hispanics, it remains higher compared with the state's non-Hispanic white population.

Cancer of the digestive system in Circumpolar Inuit.

Cancer of the oesophagus, stomach, small intestine, colon, rectum, liver, gallbladder, biliary tract and pancreas was studied in the Inuit populations of Alaska, Canada and Greenland. Indirect standardization to the populations in Canada, Connecticut (USA) and Denmark was used. High risk of oesophageal cancer was observed in both sexes with standardized incidence ratios (SIRs) of up to 7. An increased risk of colon and rectum cancer occurred among Alaskan Inuit compared with the Inuit populations in Canada and Greenland, which had lower rates. Liver and gallbladder cancer rates were high, with SIRs of 1.5 to 4.1, whereas there were no differences in pancreatic cancer in the populations compared. Dietary habits, alcohol and tobacco consumption are believed to play an important role in most of the observed cancer patterns, but for liver cancer hepatitis B virus infection is also believed to have a causal role.

[Cancer of the extrahepatic biliary tracts and abnormality of the biliopancreatic junction]. / Cancer des voies biliaires extra-hépatiques et anomalie de la jonction bilio-pancréatique.

This retrospective study was undertaken to evaluate the incidence of an abnormal pancreaticobiliary ductal union (long common duct) in biliary tract carcinoma. Of 86 patients presenting with such a cancer, 67 had a pre- or intra-operative radiologic examination. An abnormal pancreaticobiliary ductal union was found in only one 60 year old woman having stones associated with invasive gallbladder carcinoma. Operative cholangiogram revealed an early and marked Wirsung opacification with a 1.5 cm long common duct. This low incidence in our study contrasts deeply with Japanese data and raises several questions about the correct evaluation of pancreaticobiliary ductal union, the true consequences of such an anomaly and possible interracial variations in incidence.