The Chile Biliary Longitudinal Study: A Gallstone Cohort.

Gallbladder cancer (GBC) is a highly fatal cancer that can be cured through cholecystectomy if identified early. The presence of gallstones is the primary risk factor for GBC, but few people with gallstones develop GBC. A key question is what drives the development of GBC among persons with gallstones. We initiated the Chile Biliary Longitudinal Study (Chile BiLS) to address this question. From 2016 to 2019, Chile BiLS enrolled 4,726 women aged 50-74 years with ultrasound-detected gallstones from southern-central Chile, accounting for an estimated 36% of eligible women with gallstones in the study area. The median age was 59 years; 25% of the women were Amerindian (Mapuche), 60% were obese, 25% had diabetes, and 6% had cardiovascular disease. Participants will be followed for gallbladder dysplasia or cancer for 6 years. As of April 30, 2020, over 91% of those eligible completed the year 2 follow-up visit. Data being collected include epidemiologic and sociodemographic information, anthropometric measurements, blood pressure, and tooth counts. Biosamples being taken include baseline plasma, buffy coat, red blood cells, serum, blood clot from serum, and PAXgene whole blood (PreAnalytiX GmbH, Hombrechtikon, Switzerland). Complete gallbladder sampling is conducted for most participants undergoing cholecystectomy. The Chile BiLS cohort study will increase our understanding of GBC etiology and could identify potential risk stratification and early detection strategies in high-risk areas.

Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry.

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10-5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10-8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10-7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

Gallbladder carcinoma: An analysis of the national cancer data base to examine hispanic influence.

BACKGROUND: Gallbladder cancer (GBC) is a lethal disease with high incidence among Hispanics. Overall survival (OS) among races/ethnicities has not been described using the most recent National Cancer Database. This study hypothesized that prognosis is worse for Hispanics compared to similar non-Hispanic populations. METHODS: Patients with GBC were identified from the National Cancer Database and categorized as White, Black, Hispanic, and Other. Descriptive statistics, OS, and Cox regression were examined. RESULTS: The study identified 12 952 patients. Median age was 71 years and 68.8% were female. The study characterized 69.8% White, 13.9% Black, 11.0% Hispanic, and 5.4% other patients. A 5-year OS curves differed, with survival highest in Hispanic patients (27% vs 23% Other, 18% White, and 17% Black, P < 0.001). Hispanics presented at younger ages (67 vs 72 years, P < 0.001), were more likely to be uninsured (17.3% vs 3.9% P < 0.001), had lower income (P < 0.001), and education levels (P < 0.001) compared to Whites. Following multivariable modeling, treatment at an academic facility (HR 0.90, 95%CI 0.84-0.97) and year of diagnosis (HR 0.90, 95%CI 0.88-0.92) related to survival. Hispanic ethnicity did not show significance (P = 0.207). DISCUSSION: Hispanic ethnicity exhibits the highest OS for GBC, but after adjusting for covariates, this influence is not significant.

[Disparities of sex on cancer incidence and mortality in Jiashan county, Zhejiang province,1990-2014].

Objective: This study aimed to describe the sex disparities on cancer incidence and mortality in Jiashan population. Methods: All data concerning incident and death cases of cancers were gathered from the database of Cancer Registry in Jiashan county. Data from the 2010 China census was used as the standard population. Sex-specific age-standardized incidence rates (ASIRs), mortality rates (ASMRs) per 100 000 persons for all cancers and types of each cancer were calculated for the years of 1990 to 1999, 2000 to 2009, 2010 to 2014, and 1990 to 2014. In addition, the corresponding male-to-female incidence rate ratios (IRRs) and mortality rate ratios (MRRs) were also calculated. Results: The ASIR of all cancers was 226.13/10(5) for the whole period of 1990 to 2014, with 266.04/10(5) for males and 187.22/10(5) for females, respectively. The corresponding IRR was 1.42 (95%CI: 1.39-1.46), with significant difference noticed in the incidence rates between males and females (P<0.05). The ASMR of all cancers was 155.39/10(5), with 206.55/10(5) for males and 104.98/10(5) for females, respectively. The corresponding MRR was 1.97 (95% CI: 1.91-2.03), with significant difference between males and females (P<0.05). Among all the cancer types, only gallbladder cancer and thyroid cancer showed female predominance in both incidence and mortality, with male predominance in all the remaining cancers. Conclusion: Finding from our study suggested that a male predominance in both incidence and mortality for a majority of cancers in Jiashan population.

Trend analysis and survival of primary gallbladder cancer in the United States: a 1973-2009 population-based study.

Primary gallbladder cancer is an aggressive and uncommon cancer with poor outcomes. Our study examines epidemiology, trend, and survival of gallbladder cancer in the United States from 1973 to 2009. We utilized the Surveillance Epidemiology and End Results database (SEER). Frequency and rate analyses on demographics, stage, and survival were compared among non-Hispanic whites, Hispanics, African American, and Asian/Pacific Islanders. A total of 18,124 cases were reported in SEER from 1973 to 2009 comprising 1.4% of all reported gastrointestinal cancers. Gallbladder cancer was more common in females than males (71 vs. 29%, respectively). The age-adjusted incidence rate was 1.4 per 100,000, significantly higher in females than males (1.7 vs. 1.0). Trend analysis showed that the incidence rate has been decreasing over the last three decades for males. However, among females, the incidence rate had decreased from 1973 to mid-90s but has remained stable since then. Trend analysis for stage at diagnosis showed that the proportion of late-stage cases has been increasing significantly since 2001 after a decreasing pattern since 1973. Survival has improved considerably over time, and survival is better in females than males and in Asian/Pacific Islanders than other racial groups. The highest survival was in patients who received both surgery and radiation. Trend analysis revealed a recent increase of the incidence of late-stage gallbladder cancer. Highest survival was associated with receiving both surgery and radiation.

Management and follow-up of gallbladder polyps : Joint guidelines between the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery - European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE).

OBJECTIVES: The management of incidentally detected gallbladder polyps on radiological examinations is contentious. The incidental radiological finding of a gallbladder polyp can therefore be problematic for the radiologist and the clinician who referred the patient for the radiological examination. To address this a joint guideline was created by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery - European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE). METHODS: A targeted literature search was performed and consensus guidelines were created using a series of Delphi questionnaires and a seven-point Likert scale. RESULTS: A total of three Delphi rounds were performed. Consensus regarding which patients should have cholecystectomy, which patients should have ultrasound follow-up and the nature and duration of that follow-up was established. The full recommendations as well as a summary algorithm are provided. CONCLUSIONS: These expert consensus recommendations can be used as guidance when a gallbladder polyp is encountered in clinical practice. KEY POINTS: • Management of gallbladder polyps is contentious • Cholecystectomy is recommended for gallbladder polyps >10 mm • Management of polyps <10 mm depends on patient and polyp characteristics • Further research is required to determine optimal management of gallbladder polyps.

Variants and haplotypes in Flap endonuclease 1 and risk of gallbladder cancer and gallstones: a population-based study in China.

The role of FEN1 genetic variants on gallstone and gallbladder cancer susceptibility is unknown. FEN1 SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method in blood samples from 341 gallbladder cancer patients and 339 healthy controls. The distribution of FEN1-69G > A genotypes among controls (AA, 20.6%; GA, 47.2% and GG 32.2%) was significantly different from that among gallbladder cancer cases (AA, 11.1%; GA, 48.1% and GG, 40.8%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-69G > A GA (OR = 1.73, 95% CI = 1.01-2.63) and the FEN1-69G > A GG (OR = 2.29, 95% CI = 1.31-3.9). The distribution of FEN1 -4150T genotypes among controls (TT, 21.8%;GT, 49.3% and GG 28.9%) was significantly different from that among gallbladder cancer cases (TT, 12.9%; GT, 48.4% and GG 38.7%), significantly increased association with gallbladder cancer was observed for subjects with both the FEN1-4150T GT(OR = 1.93, 95% CI = 1.04-2.91) and the FEN1-4150T GG(OR = 2.56, 95% CI = 1.37-5.39). A significant trend towards increased association with gallbladder cancer was observed with potentially higher-risk FEN1-69G > A genotypes (P < 0.001, χ2 trend test) and FEN14150G > T (P < 0.001, χ2 trend test) in gallstone presence but not in gallstone absence (P = 0.81, P = 0.89, respectively). In conclusion, this study revealed firstly that FEN1 polymorphisms and haplotypes are associated with gallbladder cancer risk.

Modifiable Factors and Genetic Predisposition Associated with Gallbladder Cancer. A Concise Review.

Gallbladder cancer (GbCa) is the most frequent malignancy of the biliary tract. It is also the 6th most common gastrointestinal tumor. It is associated with very high lethality, mainly due to the lack of symptoms up to a very late and thus incurable state. As many as 80% of patients are diagnosed at very late stages of disease, which allow only palliative therapy. As a result, most of the patients with GbCa will die within 6 months of the diagnosis, hence the average 5-year survival does not exceed 5%. Currently, surgical resection represents the only curative option in GbCa, but this approach is feasible only at an early stage of the disease. Other oncologic therapies are of limited use. The incidence of GbCa is remarkably increased in certain populations such as Native North Americans, South Indian females and, in Europe, in the Polish population. It is not clear to date if these enhanced risk populations are the result of common environmental exposure or of shared genetic risk factors. In this review we provide an overview of the state-of-art in GbCa research with the focus on the current knowledge concerning genetic and environmental triggers of this tumor.

Association between estrogen receptor 1 (ESR1) genetic variations and cancer risk: a meta-analysis.

PURPOSE: Emerging published reports on the association between estrogen receptor 1 (ESR1) genetic variation and cancer susceptibility are inconsistent. This review and meta- analysis was performed to achieve a more precise evaluation of this relationship. METHODS: A literature search of PubMed database was conducted from the inception of this study through April 1st 2014. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the association. RESULTS: 87 studies were enrolled in this meta-analysis. The results indicated that PvuII (T>C) polymorphism was associated with an increased risk of hepatocellular carcinoma (HCC) and prostate cancer, in contrast with the decreased risk of gallbladder cancer. No significant association was found in Asian and Caucasian populations. Furthermore, XbaI (A>G) genetic variation was only associated with an increased risk of prostate cancer, but was not related with race. In addition, T594T (G>A) polymorphisms were significantly associated with an increased risk of cancer, especially in Asian populations. CONCLUSIONS: This meta-analysis indicated that PvuII (T>C) genetic variation may be risk factor for HCC, prostate cancer and gallbladder cancer. Meanwhile, XbaI (A>G) polymorphism may be potential prognostic factor for prostate cancer. Furthermore, T594T (G>A) was closely related with cancer susceptibility, especially in Asian populations.

Vitamin D receptor genetic variants are associated with susceptibility of gallbladder adenocarcinoma in a Chinese cohort.

The aim of this study was to test for the possible association between vitamin D receptor (VDR) genetic variants and susceptibility to gallbladder cancer (GBC). A total of 291 GBC cases were recruited and 396 gender- and age-matched healthy volunteers were enrolled as controls. The VDR gene polymorphisms were determined in all subjects. The genotype and the allele frequencies of ApaI, BsmI, and TaqI polymorphisms were not significantly different between GBC subjects and controls. However, the genotype and allele frequencies of the FokI C>T polymorphism were significantly different between GBC subjects and controls. The FokI TT genotype was in markedly higher frequency in GBC subjects compared to controls (38.14 vs 22.73%, P < 0.001). Using TT as the reference genotype, multivariate logistic regression analysis showed that CC genotype carriers had a higher risk of GBC (adjusted odds ratio (OR) = 3.423, adjusted P = 0.001) with adjustment for age, gender, smoking status, alcohol use, and gallstone presence, as well as the serum 1,25(OH)2D level. Carriers of the CT genotype also had a higher risk of GBC (adjusted OR = 1.992, adjusted P = 0.003). Multivariate logistic regression analysis did not reveal any association between the ApaI, BsmI, and TaqI polymorphisms and GBC risk (all P > 0.05).

Routine histological analysis of a macroscopically normal gallbladder--a review of the literature.

BACKGROUND: 70,000 cholecystectomies were performed in the United Kingdom in 2011-2012. Currently it is standard practice to submit all gallbladder specimens for routine histology to exclude malignancy. The aim of this systematic review was to establish whether a normal macroscopic appearance to the gallbladder at the time of cholecystectomy is sufficient to rule out malignancy and therefore negate the need for routine histology. METHODS: Relevant articles that were published between 1966 and January 2013 were identified through electronic databases. RESULTS: 21 studies reported on 34,499 histologically analysed specimens. 172/187 (92%) of gallbladder cancers demonstrated intra-operative macroscopic abnormality. Studies that opened the specimens intra-operatively identified all cancers, whereas gross macroscopic visualization resulted in 15 potentially missed cancers (p = 0.10). In patients of European ethnicity, gallbladder cancer in a macroscopically normal looking gallbladder was identified in only one study; however all of these patients were above the age of 60. The incidence of gallbladder cancer was significantly raised in ethnic groups from high risk areas (p = 0.0001). CONCLUSIONS: A macroscopically normal gallbladder in patients of European ethnicity under the age of 60 may not require formal histopathology. The best method for intra-operative examination may involve opening the specimen to allow inspection of the mucosa and wall, however this needs further investigation. In the context of the volume of gallbladder surgery being performed there is the potential for significant cost and time savings.

Death receptor (DR4) haplotypes are associated with increased susceptibility of gallbladder carcinoma in north Indian population.

BACKGROUND AND AIM: Defective apoptosis is a hallmark of cancer development and progression. Death receptors (DR4, FAS) and their ligands (TRAIL, FASL) are thought to mediate the major extrinsic apoptotic pathway in the cell. SNPs in these genes may lead to defective apoptosis. Hence, the present study aimed to investigate the association of functional SNPs of DR4 (rs20575, rs20576 and rs6557634), FAS (rs2234767) and FASL (rs763110) with gallbladder cancer (GBC) risk. METHODS: This case-control study included 400 GBC and 246 healthy controls (HC). Genotyping was carried out by Taqman genotyping assays. Statistical analysis was performed by using SPSS ver16. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) to systematically summarize the possible association of SNP with cancer risk. Functional prediction of these variants was carried out using Bioinformatics tools (FAST-SNP, F-SNP). False discovery rate (FDR test) was used in multiple comparisons. RESULTS: The DR4 C rs20575 A rs20576 A rs6557634, G rs20575 A rs20576 G rs6557634 and G rs20575 C rs20576 G rs6557634 haplotypes conferred two-fold increased risk for GBC. Among these, the DR4 C rs20575 A rs20576 A rs6557634 haplotype emerged as main factor influencing GBC susceptibility as the risk was not modulated by gender or gallstone stratification. Our meta-analysis results showed significant association of DR4 rs6557634 with overall cancer risk, GI cancers as well as in Caucasians. We didn't find any association of FAS and FASL SNPs with GBC susceptibility. CONCLUSIONS: The DR4 haplotype C rs20575 A rs20576 A rs6557634 represents an important factor accounting the patients susceptibility to GBC probably due to decreased apoptosis. However, additional well-designed studies with larger sample size focusing on different ethnicities are required to further validate the results.

Roles of ApoB-100 gene polymorphisms and the risks of gallstones and gallbladder cancer: a meta-analysis.

BACKGROUND: Gallstones (GS) is the major manifestation of gallbladder disease, and is the most common risk factor for gallbladder cancer (GBC). Previous studies investigating the association between ApoB-100 gene polymorphisms and the risks of GS and GBC have yielded conflicting results. Therefore, we performed a meta-analysis to clarify the effects of ApoB-100 gene polymorphisms on the risks of GS and GBC. METHODS: A computerized literature search was conducted to identify the relevant studies from PubMed and Embase. Fixed or random effects model was selected based on heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS: A total of 10, 3, and 3 studies were included in the analyses of the association between ApoB-100 XbaI, EcoRI, or insertion/deletion (ID) polymorphisms and the GS risks, respectively, while 3 studies were included in the analysis for the association between XbaI polymorphism and GBC risk. The combined results showed a significant association in Chinese (X+ vs. X-, OR = 2.37, 95%CI 1.52-3.70; X+X+/X+X- vs. X+X+, OR = 2.47, 95%CI 1.55-3.92), but not in Indians or Caucasians. Null association was observed between EcoRI or ID polymorphisms and GS risks. With regard to the association between XbaI polymorphism and GBC risk, a significant association was detected when GBC patients were compared with healthy persons and when GBC patients were compared with GS patients. A significant association was still detected when GBC patients (with GS) were compared with the GS patients (X+X+ vs. X-X-, OR = 0.33, 95%CI 0.12-0.90). CONCLUSION: The results of this meta-analysis suggest that the ApoB-100 X+ allele might be associated with increased risk of GS in Chinese but not in other populations, while the ApoB-100 X+X+ genotype might be associated with reduced risk of GBC. Further studies with larger sample sizes are needed to confirm these results.

Incidence of gastrointestinal cancers by ethnic group in England, 2001-2007.

OBJECTIVE: To compare the incidence of six gastrointestinal cancers (colorectal, oesophageal, gastric, liver, gallbladder and pancreatic) among the six main 'non-White' ethnic groups in England (Indian, Pakistani, Bangladeshi, Black African, Black Caribbean and Chinese) to each other and to Whites. METHODS: We analysed all 378 511 gastrointestinal cancer registrations from 2001-2007 in England. Ethnicity was obtained by linkage to the Hospital Episodes Statistics database and we used mid-year population estimates from 2001-2007. Incidence rate ratios adjusted for age, sex and income were calculated, comparing the six ethnic groups (and combined 'South Asian' and 'Black' groups) to Whites and to each other. RESULTS: There were significant differences in the incidence of all six cancers between the ethnic groups (all p<0.001). In general, the 'non-White' groups had a lower incidence of colorectal, oesophageal and pancreatic cancer compared to Whites and a higher incidence of liver and gallbladder cancer. Gastric cancer incidence was lower in South Asians but higher in Blacks and Chinese. There was strong evidence of differences in risk between Indians, Pakistanis and Bangladeshis for cancer of the oesophagus, stomach, liver and gallbladder (all p<0.001) and between Black Africans and Black Caribbeans for liver and gallbladder cancer (both p<0.001). CONCLUSIONS: The risk of gastrointestinal cancers varies greatly by individual ethnic group, including within those groups that have traditionally been grouped together (South Asians and Blacks). Many of these differences are not readily explained by known risk factors and suggest that important, potentially modifiable causes of these cancers are still to be discovered.

Treatment and surveillance of polypoid lesions of the gallbladder in the United Kingdom.

OBJECTIVES: The increase in the routine use of abdominal imaging has led to a parallel surge in the identification of polypoid lesions in the gallbladder. True gallbladder polyps (GBP) have malignant potential and surgery can prevent or treat early gallbladder cancer. In an era of constraint on health care resources, it is important to ensure that surgery is offered only to patients who have appropriate indications. The aim of this study was to assess treatment and surveillance policies for GBP among hepatobiliary and upper gastrointestinal tract surgeons in the UK in the light of published evidence. METHODS: A questionnaire on the management of GBP was devised and sent to consultant surgeon members of the Association of Upper Gastrointestinal Surgeons (AUGIS) of Great Britain and Ireland with the approval of the AUGIS Committee. It included eight questions on indications for laparoscopic cholecystectomy and surveillance based on GBP (size, number, growth rate) and patient (age, comorbidities, ethnicity) characteristics. RESULTS: A total of 79 completed questionnaires were returned. The vast majority of surgeons (>75%) stated that they would perform surgery when a single GBP reached 10 mm in size. However, there was a lack of uniformity in the management of multiple polyps and polyp growth rate, with different surveillance protocols for patients treated conservatively. CONCLUSIONS: Gallbladder polyps are a relatively common finding on abdominal ultrasound scans. The survey showed considerable heterogeneity among surgeons regarding treatment and surveillance protocols. Although no randomized controlled trials exist, national guidelines would facilitate standardization, the formulation of an appropriate algorithm and appropriate use of resources.

The impact of routine histopathological examination on cholecystectomy specimens from an Asian demographic.

INTRODUCTION: Most gallbladder carcinoma cases are suspected pre-operatively or intra-operatively. In Malaysia histopathological examination of cholecystectomy specimens has become routine practice. The aim of this study was to assess the impact of routine histological examinations on cholecystectomy specimens from an Asian demographic, which may differ from a Caucasian demographic. METHODS: A retrospective study was performed of all histopathology reports for cholecystectomies (laparoscopic and open) undertaken over a period of 12 years (1997-2008) in a single teaching hospital. RESULTS: A total of 1,375 gallbladder specimens were sent for histopathological analysis, with 7 (0.5%) being reported as malignant while only three (0.2%) were found to contain primary gallbladder carcinoma. Other premalignant findings included two specimens with dysplastic changes of the mucosa and one tubulovillous adenoma with a dysplastic epithelium. From the ten malignant and premalignant specimens, seven were diagnosed pre-operatively, two were suspected intra-operatively and one was diagnosed with dysplastic changes on the histopathology report post-operatively. CONCLUSIONS: This study supports earlier research carried out in the UK and the demographic difference does not affect the impact of the histology examination on cholecystectomy specimens in diagnosing this disease. A selective policy is recommended in Malaysia.

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.

Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

AIM: To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC). METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffin block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping Assays. RESULTS: The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (OR: 0.14, 95% CI: 0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (OR: 5.04, 95% CI: 1.43-17.8). CONCLUSION: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs708272 polymorphisms may be related to the risk of developing GBC in Chilean women.

The risk of gallbladder cancer from polyps in a large multiethnic series.

BACKGROUND: The aim of this study is assess whether patients with Indian ethnic background are at an increased risk of developing gallbladder cancer (GBC) if they have been diagnosed with ultrasonic abnormalities of the gallbladder. METHODS: Between January 1998 and July 2006, 137,655 abdominal ultrasound examinations were performed in Leeds Teaching Hospitals NHS Trust. After the exclusion of repeat scans and those performed for renal or pelvic disease, 71,431 reports were included in this analysis. Patients in whom the diagnosis of GBC has been made without histology have been identified from the database of Northern and Yorkshire Cancer Registry and the presence of GBC was correlated with ultrasonic gallbladder abnormalities. RESULTS: Gallbladder polyps (GBP) were detected in 3.3% of patients and these were larger than 10 mm in 0.1% of the cases. Age above 60 years, Indian ethnic background, single GBP larger than 10mm, the presence of gallstones, severe gallbladder wall thickening and irregular thickening were independently associated with the higher odds of developing GBC. The prevalence of malignancy in those with GBP was significantly higher among patients with Indian ethnic background compared to Caucasian patients, 5.5% versus 0.08%, p<0.001. CONCLUSIONS: The presence of GBP, irrelevant of size, amongst patients of Indian ethnic decent, is an indication for further investigation and/or cholecystectomy.