Risk factors for gallbladder cancer: A case–control study

Risk factors for gallbladder cancer (GBC) except gallstones are not well known. The objective was to study the risk factors for GBC. In a case–control study, 200 patients with GBC, 200 healthy controls and 200 gallstones patients as diseased controls were included prospectively. The risk factors studied were related to socioeconomic profile, life style, reproduction, diet and bile acids. On comparing GBC patients (mean age 51.7 years; 130 females) with healthy controls, risk factors were chemical exposure [odd ratios (OR): 7.0 (2.7–18.2); p < 0.001)], family history of gallstones [OR: 5.3 (1.5–18.9); p < 0.01)], tobacco [OR: 4.1 (1.8–9.7); p < 0.001)], fried foods [OR: 3.1 (1.7–5.6); p < 0.001], joint family [OR: 3.2 (1.7–6.2); p < 0.001], long interval between meals [OR: 1.4 (1.2–1.6); p < 0.001] and residence in Gangetic belt [OR: 3.3 (1.8–6.2); p < 0.001]. On comparing GBC cases with gallstone controls, risk factors were female gender [OR: 2.4 (1.3–4.3); p = 0.004], residence in Gangetic belt [OR: 2.3 (1.2–4.4); p = 0.012], fried foods [OR: 2.5 (1.4–4.4); p < 0.001], diabetes [OR: 2.7 (1.2–6.4); p = 0.02)], tobacco [OR 3.8 (1.7–8.1); p < 0.001)] and joint family [OR: 2.1 (1.2–3.4); p = 0.004]. The ratio of secondary to primary bile acids was significantly higher in GBC cases than gallstone controls (20.8 vs. 0.44). Fried foods, tobacco, chemical exposure, family history of gallstones, residence in Gangetic belt and secondary bile acids were significant risk factors for GBC.     

胆囊癌与胆囊结石关系的临床分析

目的　探讨胆囊癌与胆囊结石的关系。方法　对所收集的胆囊癌病人 47例 ,胆囊结石病人 2 86 3例进行了分析。结果　 47例胆囊癌病人均伴有胆囊结石 ,全部经手术治疗。其生存率 :1年为 46例 ( 97.87% ) ,2年 32例 ( 6 8.0 8% ) ,3年 2 8例 ( 5 9.5 7% ) ,4年 12例 ( 2 5 .5 3% ) ,年 2例 ( 4 .2 5 % )。胆囊结石病人 2 86 3例 ,经手术治疗 10 6 9例。结论　胆囊癌与胆囊结石的关系极为密切 ,胆囊结石是诱发胆囊癌的重要因素之一。对胆囊结石的病人行胆囊切除是预防胆囊癌发生的较为有效的方法之一。     

原发性胆囊癌外科治疗(附34例分析)

目的:探讨胆囊癌的临床特点和提高疗效的途径。方法:对我院8年来收治的34例胆囊癌患者临床资料进行分析。结果:胆囊癌多见于中老年人,平均年龄64.61岁,34例患者中男12例,女22例,男女之比为1:1.83,胆囊癌合并胆囊结石者占65.71%,术前B超诊断符合率为82.14%。手术切除率为73.53%,根治性切除10例,根治率40%。1、3、5年生存率分别为58.82%、8.82%、2.94%。结论:B超、CT是常用的诊断方法,对易患胆囊癌高危人群应进行定期观察。手术方式及治疗效果取决于胆囊癌的分期。     

Gallstones and the risk of biliary tract cancer: a population-based study in China

We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0-33.4), 8.0 (95% CI 5.6-11.4), and 4.2 (95% CI 2.5-7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR=34.3, 95% CI 19.9-59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P<0.001). Gallstone weight in gallbladder cancer was significantly higher than in gallstone patients (4.9 vs 2.8 grams; P=0.001). We estimate that in Shanghai 80% (95% CI 75-84%), 59% (56-61%), and 41% (29-59%) of gallbladder, bile duct, and ampulla of Vater cancers, respectively, could be attributed to gallstones.     

Gallbladder cancer: Incidence and survival in a high‐risk area of Chile

We assessed population incidence rates 1998–2002 and 5‐year survival rates of 317 primary gallbladder cancer (GBC) entered in the population‐based cancer registry in Valdivia. We analyzed GBC incidence (Poisson regression) and GBC survival (Cox regression). Cases were identified by histology (69.4%), clinical work‐up (21.8%), or death certificate only (8.8%). Main symptoms were abdominal pain (82.8%), jaundice (53.6%) nausea (42.6%), and weight loss (38.2%); at diagnosis, 64% had Stage TNM IV. In the period, 4% of histopathological studies from presumptively benign cholecystectomies presented GBC. GBC cases were mainly females (76.0%), urban residents (70.3%), Hispanic (83.7%) of low schooling <4 years (64.0%). GBC standardized incidence rate per 100,000 (SIR) were all 17.5 (95%CI: 15.5–19.4), women 24.3, and men 8.6 (p < 0.00001); Mapuche 25.0, Hispanic 16.2 (p = 0.09). The highest SIRs were in Mapuche (269.2) and Hispanic women (199.6) with <4 years of schooling. Lowest SIRs were among Hispanic men (19.8) and women (21.9) with >8 years of schooling. Low schooling, female and urban residence were independent risk factors. By December 31, 2007, 6 (1.9%) cases were living, 280 (88.3%) died from GBC, 32 (10.1%) were lost of follow‐up. Kaplan Meier Global 5‐year survival was: 10.3%, 85% at stage I and 1.9% at stage IV; median survival: 3.4 months. Independent poor prognostic factors were TNM IV, jaundice and nonincidental diagnoses. Our results suggest that women of Mapuche ancestry with low schooling (>50 years) are at the highest risk of presenting and dying from GBC and should be the target for early detection programs.     

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.     

Cholecystectomy,gallstones, tonsillectomy,and pancreatic cancer risk: a population-based case-control study in minnesota

Background:

Associations between medical conditions and pancreatic cancer risk are controversial and are thus evaluated in a study conducted during 1994–1998 in Minnesota.

Methods:

Cases (n=215) were ascertained from hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic. Controls (n=676) were randomly selected from the general population and frequency matched to cases by age and sex. The history of medical conditions was gathered with a questionnaire during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression.

Results:

After adjustment for confounders, subjects who had cholecystectomy or gallstones experienced a significantly higher risk of pancreatic cancer than those who did not (OR (95% CI): 2.11 (1.32–3.35) for cholecystectomy and 1.97 (1.23–3.12) for gallstones), whereas opposite results were observed for tonsillectomy (0.67 (0.48–0.94)). Increased risk associated with cholecystectomy was the greatest when it occurred ⩽2 years before the cancer diagnosis (5.93 (2.36–15.7)) but remained statistically significant when that interval was ⩾20 years (2.27 (1.16–4.32)).

Conclusions:

Cholecystectomy, gallstones, and tonsillectomy were associated with an altered risk of pancreatic cancer. Our study suggests that cholecystectomy increased risk but reverse causality may partially account for high risk associated with recent cholecystectomy.     

Body size and the risk of biliary tract cancer: a population-based study in China

Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case-control study of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index (BMI) at various ages and waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood (ages 20-29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (>or=25) was associated with a 1.6-fold risk of gall bladder cancer (95% CI 1.2-2.1, P for trend <0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI (>or=25) and a high WHR (>0.90) having the highest risk of gall bladder cancer (OR=12.6, 95% CI 4.8-33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai.     

Hepatitis B and C virus infection and the risk of biliary tract cancer: a population-based study in China

Emerging data suggest that chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may also play a role in extrahepatic bile duct cancers. To test the HBV hypothesis, we examined the relationship of HBV/HCV infection with risks of biliary tract cancer and biliary stones in a population-based case-control study conducted in Shanghai, China. Standard assays were used to detect HBV surface antigen (HBsAg) and antibodies against HBV core antigen (anti-HBc) and hepatitis C virus (anti-HCV) in sera from 417 patients with biliary tract cancers, 517 with biliary stones, and 762 healthy controls randomly selected from the population. Unconditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for each disease type. HBsAg seroprevalence was 7.3% among population controls and 14.2% among patients with extrahepatic bile duct cancer, resulting in a 2.4-fold risk of extrahepatic bile duct cancer (95% CI 1.2-4.5). No association was found for cancers of the gallbladder (prevalence 8.2%) or the ampulla of Vater (6.1%), or for stones in the gallbladder (10.1%) or bile duct (9.3%). Further adjustment for education, smoking, body mass index, diabetes and gallstones did not materially change the results. Prevalence of HCV infection in this population was low (2%), limiting our ability to detect an association with biliary diseases. In Shanghai, an HBV endemic area, chronic HBV infection was associated with a 2.4-fold risk of extrahepatic bile duct cancer. These results should be confirmed in other populations with varying risks of HBV and HCV infection.     

Prognostic factors in gallbladder and biliary tract cancer

Background. Cancers of the gallbladder and bile ducts are uncommon neoplasms with poor survival. Prognostic factors are not well defined because of the scant number of patients reported through series of cases. Methods. We reviewed the medical records of patients with cancer of the bile ducts and gallbladder between the years 1979 and 1998, and analyzed their characteristics according to location (gallbladder, extrahepatic biliary tract, intrahepatic biliary tract, and Klatskin tumors). Results. One hundred and sixty-eight patients were included; the mean follow-up time was 238 ± 54 d. The tumor found at more advanced stages was the biliary tract tumor. Overall survival time was 254 ± 40 d. Location did not influence survival. The factors significantly associated to increased survival were age at diagnosis less than 50 yr (p=0.0065), surgical treatment (p<0.001), adjuvant chemotherapy and radiotherapy (p<0.001 and p=0.0072, respectively), surgical treatment with curative purpose (p<0.001), stage of the disease (p<0.0001), absence of jaundice (p=0.0425), and absence of weight loss (p=0.0446). In the multivariate analysis the significant variables were age, surgical treatment, adjuvant chemotherapy, surgery with curative purpose, stage of the disease, and absence of jaundice. Conclusions. Cancers of the bile ducts are neoplasms known to have a poor prognosis. Chemotherapy was an independent survival factor despite the context, there is need of future studies to define its role on this disease.     

Cigarette smoking, alcohol drinking and the risk of gallbladder cancer death: a prospective cohort study in Japan

Gallbladder cancer is a rare cancer with a poor prognosis, and few risk factors have been identified to date. This prospective study was conducted to evaluate the association of cigarette smoking and alcohol consumption with the risk of gallbladder cancer death. A baseline survey in 45 areas throughout Japan was conducted from 1988 to 1990 using a self-administered questionnaire, and a total of 113,496 participants (65,740 women) aged 40-89 years at entry were followed for 15 years. During the follow-up period, 165 gallbladder cancer deaths (95 women) were observed. Among women, the hazard ratio (HR) [95 percent confidence interval: 95% CI] of current smoker was 2.00 [0.91-4.42], when adjusted for age and drinking. There was no clear association between alcohol consumption and the risk. Among men, HR of current smoker was 2.27 [1.05-4.90]. HRs of those who smoked 21 cigarettes or more per day and those with 801-1,000 cigarette-years were 3.18 [1.18-8.53] and 3.44 [1.40-8.45], respectively, and positive linear associations were observed between that risk and the number of cigarettes per day (p for trend = 0.007) or "cigarette-years" (p for trend = 0.012). The alcohol dose was linearly associated with risk (p for trend = 0.004), where the HR among those who consumed 72.0 g or more of alcohol per day was 3.60 [1.29-9.85]. Among both men and women, cigarette smoking may elevate the risk of death from gallbladder cancer. Drinking may pose an elevated risk among men, but that seems to be less true among women.     

饮食与胆囊癌关系的流行病学研究

目的探讨饮食因素与胆囊癌发病的关联,为采取预防措施提供科学依据.方法采用全人群病例对照研究,研究对象为1997年6月～2001年5月期间确诊的、年龄在35～74岁的上海市区368例胆囊癌新发病例以及按性别、年龄(5岁一组)频数配对的895例人群对照.采用非条件logistic回归模型分析饮食各因素与胆囊癌的关系.结果女性中,与最低四分位数组相比,葱属类蔬菜年摄入次数最高四分位组的调整OR为0.55(95%CI:0.31～0.97;Ptrend=0.06);与不吃组比较,大蒜头和洋葱最高摄入组的调整OR分别为0.59(95%CI:0.34～0.99;Ptrend=0.03)和0.52(95%CI:0.30～0.91;Ptrend=0.01).与最低四分位组比较,腌制品摄入其余各组调整OR在女性中依次为1.06、1.88、2.31,Ptrend＜0.001;与不吃乳腐组比较,余三组的调整OR依次为1.19、1.47、1.88,Ptrend＜0.01.男性结果与女性类似,腌制品和葱属类蔬菜摄入的各组OR都有不显著的升高和降低.结论新鲜蔬菜,尤其是葱属类蔬菜对胆囊癌的保护作用在女性比男性明显,而且以大蒜头、洋葱的保护作用较为显著.而腌制品摄入,尤其是乳腐,可能会增加胆囊癌的发病风险.     

Obesity and the risk of gallbladder cancer: a meta-analysis

We performed a meta-analysis of studies of the association between excess body weight and risk of gallbladder cancer identified from MEDLINE and EMBASE databases from 1966 to February 2007 and the references of retrieved articles. A random-effects model was used to combine results from eight cohort studies and three case-control studies, with a total of 3288 cases. Compared with individuals of 'normal weight', the summary relative risk of gallbladder cancer for those who were overweight or obese was 1.15 (95% CI, 1.01-1.30) and 1.66 (95% CI, 1.47-1.88) respectively. The association with obesity was stronger for women (relative risk, 1.88; 95% CI, 1.66-2.13) than for men (relative risk, 1.35; 95% CI, 1.09-1.68). There was no statistically significant heterogeneity among the results of individual studies. This meta-analysis confirms the association between excess body weight and risk of gallbladder cancer.     

Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan

Background: High incidence of gallbladder cancer (GBC) is reported from North India, with elevatedconcentrations of heavy metals in water and soil. This Indo-Japan collaborative study compared presence ofheavy metals in gallbladder tissues. Methods: Heavy metal concentrations were estimated in Indian GBC andcholecystitis tissues and compared with Japanese GBC and cholecystitis tissues. Spectrophotometry was donefor 13 Indian gallbladder tissues (8 GBC, 5 cholecystitis) and 9 Japanese (5 GBC, 4 cholecystitis). Transmissionelectron microscopy (TEM) thin foil element analysis was done in 10 Indian samples (6 GBC, 4 cholecystitis).Results: Chromium, lead, arsenic and zinc were significantly high in Indian GBC compared with Japanese GBC.Chromium, lead and arsenic were significantly high in the Indian cholecystitis tissues compared to the Japanese.TEM of Indian tissues demonstrated electron dense deposits in GBC. Conclusion: Heavy metals- chromium,lead, arsenic and zinc are potential carcinogens in Indian GBC from endemic areas. This preliminary studylinks presence of heavy metals in gallbladder cancer tissues in endemic areas.     

Polymorphisms in ERCC2, MSH2, and OGG1 DNA repair genes and gallbladder cancer risk in a population of Northern India

BACKGROUND:

Genetic variants of DNA repair enzymes may lead to genetic instability and contribute to gallbladder (GB) carcinogenesis.

METHODS:

A case‐control study (230 GB carcinogenesis patients and 230 controls) was undertaken to evaluate whether genetic variations in 3 DNA repair genes ERCC2 (Asp312Asn [rs1799793] and Lys751Gln [rs13181]), MSH2 (?118T>C [rs2303425] and IVS1 + 9G>C [rs2303426]), and OGG1 (Ser326Cys [rs1052133] and 748‐15C>G [rs2072668]) are associated with GB carcinogenesis risk in a North Indian population.

RESULTS:

The authors found that the ERCC2 Asp312Asn AA, MSH2 IVS1 + 9G>C CC, OGG1 Ser326Cys GG and CG + GG, and OGG1 748‐15C>G GG and CG + GG genotypes were significantly associated with an increased risk of GB carcinogenesis (odds ratio [OR], 2.1, 1.8, 2.5, 1.8, 2.0, and 1.6, respectively). In contrast, ERCC2 Lys751Gln, and MSH2 ?118T>C markers showed no significant associations with GB carcinogenesis risk, although because of the small sample size their effects cannot be ruled out. Female GB carcinogenesis patients with the OGG1 748‐15C>G GG, OGG1 Ser326Cys GG, and ERCC2 Asp312Asn genotypes had a greater risk for developing the disease (OR, 3.6, 7.7, and 2.7, respectively). There was a significant interaction between MSH2 IVS1 + 9G>C and OGG1 748‐15C>G polymorphisms (P = .001). Furthermore, individuals with >6 variant alleles of the studied polymorphisms were at 4‐fold increased risk for developing GB carcinogenesis. Classification and Regression Tree analysis revealed potential higher‐order gene‐gene interactions and categorized a few higher‐risk subgroups for GB carcinogenesis.

CONCLUSIONS:

These results suggest that genetic variants in the DNA repair pathways may be involved in GB carcinogenesis etiology. Cancer 2010. © 2010 American Cancer Society.     

Post-menopausal hormonal therapy and gallbladder cancer risk

The relation between post-menopausal hormone replacement therapy (HRT) and gallbladder cancer was analyzed in women above age 45 years, using data of a case-control study conducted in Italy between 1985 and 1997, on 31 incident, histologically confirmed cases and 3,702 controls in hospital for acute, non-neoplastic conditions. The multivariate odds ratio (OR) was 3.2 (95% confidence interval: 1.1-9.3) for those who had ever used HRT and the OR tended to rise with longer duration. Although based on small numbers, due to the rarity of the disease, these findings provide the first direct epidemiological evidence of an association between HRT and gallbladder cancer.     

Alcoholism and cancer risk: a population-based cohort study

The incidence of cancer was studied in a population-based cohort of 9,353 individuals (8,340 men and 1,013 women) with a discharge diagnosis of alcoholism in 1965–83, followed up for 19 years (mean 7.7). After exclusion of cancers in the first year of follow-up, 491 cancers were observed cf 343.2 expected through 1984 (standardized incidence ratio [SIR] = 1.4,95 percent confidence interval [CI] = 1.3–1.6). A similar excess risk of cancer was seen among men (SIR = 1.4, CI = 1.3–1.6) and among women (SIR = 1.5, CI = 1.1–2.0). We observed the established associations with cancers of the oral cavity and pharynx (SIR = 4.1, CI = 2.9–5.7), esophagus (SIR = 6.8, CI = 4.5–9.9), larynx (SIR = 3.3, CI = 1.7–6.0), and lung (SIR = 2.1, CI = 1.7–2.6), although confounding by smoking likely increased these risk estimates. While there was evidence of increased risk for pancreatic cancer (SIR = 1.5, CI = 0.9–2.3), alcoholism did not elevate the incidence of cancer of the stomach (SIR = 0.9, CI = 6–1.4), large bowel (SIR = 1.1, CI = 0.8–1.5), prostate (SIR = 1.0, CI = 0.8–1.3), urinary bladder (SIR = 1.0, CI = 0.6–1.5), or of malignant melanoma (SIR = 0.9, CI = 0.3–1.9). Among women, the number of breast cancers observed was close to expected (SIR = 1.2, CI = 0.6–2.2), although a significant excess number of cervical cancers occurred (SIR = 4.2, CI = 1.5–9.1). The results of this study, one of the first to evaluate the incidence of cancer in a population-based cohort of alcoholics of both sexes, are consistent with smaller previous studies, which were usually limited to cancer mortality and of short follow-up.Dr Adami is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Drs McLaughlin and Hsing are with the Biostatistics Branch, National Cancer Institute, Bethesda, MD, USA. Dr Wolk is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Ekbom is with the Department of Surgery and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Persson is with the Department of Obstetrics and Gynaecology and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Address correspondence to Dr Adami, Cancer Epidemiology Unit, University Hospital, S-751 85 Uppsala, Sweden. The work was performed at the Cancer Epidemiology Unit, Uppsala University, Sweden; the research was supported by grants from the Swedish Cancer Society.     

Serum lipid levels and the risk of biliary tract cancers and biliary stones: A population-based study in China

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. Gallstones, the predominant risk factor for biliary cancers, are linked with hyperlipidemia. As part of a population-based case-control study conducted in Shanghai, China, we examined the associations of serum lipid levels with biliary stones and cancers. We included 460 biliary cancer cases (264 gallbladder, 141 extrahepatic bile duct, and 55 ampulla of Vater), 981 biliary stone cases and 858 healthy individuals randomly selected from the population. Participants completed an in-person interview and gave overnight fasting blood samples. Participants in the highest quintile of triglycerides (>/=160 mg/dl) had a 1.4-fold risk of biliary stones (95% CI = 1.1-1.9), a 1.9-fold risk of gallbladder cancer (95% CI = 1.3-2.8), and a 4.8-fold risk of bile duct cancer (95% CI = 2.8-8.1), compared to the reference group (third quintile: 90-124 mg/dl). Participants in the lowest quintile of high-density lipoprotein (HDL) (<30 mg/dl) had a 4.2-fold risk of biliary stones (95% CI = 3.0-6.0), an 11.6-fold risk of gallbladder cancer (95% CI = 7.3-18.5), and a 16.8-fold risk of bile duct cancer (95% CI = 9.1-30.9), relative to the reference group (third quintile: 40-49 mg/dl). In addition, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A (apo A) were inversely associated with biliary stones; whereas low levels as well as high levels of total cholesterol, LDL, apo A and apolipoprotein B (apo B) were associated with excess risks of biliary tract cancers. Our findings support a role for serum lipids in gallstone development and biliary carcinogenesis.     

Occult pancreaticobiliary reflux in gallbladder cancer and benign gallbladder diseases

BACKGROUND AND OBJECTIVES: It was proposed that occult pancreaticobiliary reflux (OPBR) was associated with precancerous mucosal changes in the gallbladder, hence the importance of this disorder. There are no published reports investigating the incidence of OPBR in patients operated on for the entire spectrum of benign gallbladder diseases and gallbladder cancer. Our aim was to determine the incidence of OPBR and measure the levels of active pancreatic enzymes (amylase and lipase) in gallbladder bile of patients undergoing cholecystectomy for benign and malignant gallbladder diseases. METHODS: One hundred eight patients with normal pancreaticobiliary junction evidenced by operative cholangiography were included in the study. RESULTS: According to gallbladder bile amylase and lipase levels, 84.2% and 89% patients respectively had OPBR. OPBR was present in all gallbladder cancer patients; in these patients the biliary levels of amylase and lipase were significantly higher than the levels found in patients with benign gallbladder pathology (P < 0.0001). CONCLUSIONS: OPBR could lead to inflammatory changes of the biliary epithelium and progress towards the development of precancerous mucosal changes and gallbladder cancer. The reason why such high levels of pancreatic enzymes are regurgitated into the biliary tree of patients with gallbladder cancer should be clarified.     

Nonsurgical management of gallbladder cancer: cytotoxic treatment and radiotherapy

Carcinoma of the gallbladder is a rare tumor entity. Apart from surgical intervention, there is no therapeutic measure with curative potential. Therefore, patients with advanced – i.e., unresectable or metastatic – disease present a difficult problem to clinicians, whether to choose a strictly symptomatic treatment or expose the patient to the side effects of potentially ineffective treatment. Despite anecdotal reports about symptomatic palliation and survival advantages, only unrandomized Phase II studies too small to draw meaningful conclusions have been published thus far. Since there is no standard therapy for advanced gallbladder cancer, patients should be offered the opportunity to participate in controlled clinical trials.