Prevalence of gallbladder cancer in cholecystectomized patients in Sulaymaniyah city.

Gallbladder cancers (GBC) are rare, and they are one of lethal neoplasms of biliary system. The diagnosis is either incidentally during histopathological examinations after cholecystectomy or due to complications of local or systemic spread of the malignancy. The incidence differs ethnically and geographically. The aim was to identify increase risk of cancer in the Kurdistan region by searching for the number of GBC cases among cholecystectomy patients in Sulaymaniyah governorate. This study is laboratory-based retrospective study, including data obtained from 8315 cholecystectomized patients in Sulaymaniyah governorate from 2017- 2021. The information within the questionnaire included: age, sex, clinical notes and histopathological findings; including GBC. The total of 8315 cases; were 2149 males (25.8%) and 6166 females (74.2%). The mean age was (44.67+/-15.18) years. Forty-five cases have been reported as adenocarcinoma of GB and one case of Carcinosarcoma. Among the patients, 875 cases (10.50%) had acute cholecystitis. A significant relationship was found between the findings and the age and gender of the patients. GBC is not common and is mainly diagnosed incidentally after routine post-operative histopathological examination, and mainly affects old ages.

Insights for clinical management from the real-life data of the centralized West of Scotland biliary cancer clinic.

BACKGROUND: With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations. METHODS AND RESULTS: We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT. CONCLUSIONS: About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.

Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Geo-spatial epidemiology of gallbladder cancer in Bihar, India.

Recently, a substantial increase in gallbladder cancer (GBC) cases has been reported in Bihar, India. The region's groundwater can naturally contain harmful concentrations of arsenic, which appears to be epidemiologically linked to the unusually high incidence. However, the root causes remain largely unexplored. Recent findings of uranium in the state's groundwater may also have associations. This study investigates the geo-spatial epidemiology of GBC in Bihar, India-with a focus on the correlation between environmental carcinogens, particularly arsenic and uranium in groundwater, and the incidence of GBC. Utilizing data from 8460 GBC patients' registration records over an 11-year period at a single health center, the research employs Semi-parametric Geographically Weighted Poisson Regression (S-GWPR) to account for non-stationarity associations and explores significant factors contributing to GBC prevalence at a subdistrict level. The S-GWPR model outperformed the standard Poisson regression model. The estimates suggest that arsenic and uranium concentrations in groundwater did not present significant associations; however, this could be due to the lower resolution of this data at the district level, necessitating higher resolution data for accurate estimates. Other socio-environmental factors included demonstrated significant regional heterogeneity in their association with GBC prevalence. Notably, each 1 % increase in the coverage of well- and canal-irrigated areas is associated with a maximum of 3.0 % and 5.2 % rise in the GBC incidence rate, respectively, likely attributable to carcinogen exposure from irrigation water. Moreover, distance to the health center and domestic electricity connections appear to influence the number of reported GBC cases. The latter suggests that access to electricity might have facilitated the use of groundwater pumps-increasing exposure to carcinogens. The results underscore the necessity for targeted health policies and interventions based on fine-resolution spatial analysis, as well as ongoing environmental monitoring and research to better understand the multifaceted risk factors contributing to GBC.

Referral rate of patients with incidental gallbladder cancer and survival: outcomes of a multicentre retrospective study.

BACKGROUND: Treatment outcomes of incidental gallbladder cancer generally stem from tertiary referral centres, while many patients are initially diagnosed and managed in secondary care centres. Referral patterns of patients with incidental gallbladder cancer are poorly reported. This study aimed to evaluate incidental gallbladder cancer treatment in secondary centres, rates of referral to tertiary centres and its impact on survival. METHODS: Medical records of patients with incidental gallbladder cancer diagnosed between 2000 and 2019 in 27 Dutch secondary centres were retrospectively reviewed. Patient characteristics, surgical treatment, tumour characteristics, referral pattern and survival were assessed. Predictors for overall survival were determined using multivariable Cox regression. RESULTS: In total, 382 patients with incidental gallbladder cancer were included. Of 243 patients eligible for re-resection (pT1b-pT3, M0), 131 (53.9%) were referred to a tertiary centre. The reason not to refer, despite indication for re-resection, was not documented for 52 of 112 non-referred patients (46.4%). In total, 98 patients underwent additional surgery with curative intent (40.3%), 12 of these in the secondary centre. Median overall survival was 33 months (95% c.i. 24 to 42 months) in referred patients versus 17 months (95% c.i. 3 to 31 months) in the non-referred group (P = 0.019). Referral to a tertiary centre was independently associated with improved survival after correction for age, ASA classification, tumour stage and resection margin (HR 0.60, 95% c.i. 0.38 to 0.97; P = 0.037). CONCLUSION: Poor incidental gallbladder cancer referral rates were associated with worse survival. Age, performance status, resection margin or tumour stage should not preclude referral of a patient with incidental gallbladder cancer to a tertiary centre.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Age and incidence of occult pancreaticobiliary reflux in patients with benign gallbladder diseases.

BACKGROUND: Occult pancreaticobiliary reflux (OPBR) has a significant correlation with diseases of the gallbladder and biliary system. This study examined the incidence of OPBR by age in patients with benign gallbladder diseases. METHODS: We assessed 475 patients with benign gallbladder diseases who underwent surgery at Shanghai East Hospital from December 2020 to December 2021. Bile samples collected during surgery were tested for amylase. Patients with bile amylase >110 U/L (n = 64) were classified as the OPBR group; the rest (n = 411) as controls. RESULTS: Of the participants, 375 had gallbladder stone (GS), 170 had gallbladder polyp (GP), and 49 had gallbladder adenomyomatosis (GA). The OPBR group was generally older, with OPBR incidence increasing with age, peaking post-45. Rates by age were: 4.9% (<35), 5.2% (35-44), 20.7% (45-54), 22.5% (55-64) and 17.6% (≥65), mainly in GS patients. ROC analysis for predicting OPBR by age yielded an area under the curve of 0.656, optimal cut-off at 45 years. Logistic regression indicated age > 45, GP, male gender, and BMI ≥ 24 kg*m-2 as independent OPBR predictors in GS patients. Based on these variables, a predictive nomogram was constructed, and its effectiveness was validated using the ROC curve, calibration curve and decision curve analysis (DCA). Further stratification revealed that among GS patients ≤ 45, concurrent GA was an OPBR risk; for > 45, it was GP and male gender. CONCLUSIONS: The incidence of OPBR in GS patients is notably influenced by age, with those over 45, especially males without GP, being at heightened risk.

Household cooking fuel and gallbladder cancer risk: a multi-centre case-control study in India.

PURPOSE: Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors. METHODS: We evaluated the association between household cooking fuel and GBC risk in a hospital-based case-control study conducted in the North-East and East Indian states of Assam and Bihar. We explored the potential mediation by diet, fire-vents, 'daily exposure duration' and parity (among women). We recruited biopsy-confirmed GBC (n = 214) men and women aged 30-69 years between 2019 and 2021, and controls frequency-matched by age, sex and region (n = 166). Information about cooking fuel, lifestyle, personal and family history, female reproductive factors, socio-demographics, and anthropometrics was collected. We tested associations using multivariable logistic regression analyses. RESULTS: All participants (73.4% women) were categorised based on predominant cooking fuel use. Group-1: LPG (Liquefied Petroleum Gas) users in the previous 20 years and above without concurrent biomass use (26.15%); Group-2: LPG users in the previous 20 years and above with concurrent secondary biomass use (15.9%); Group-3: Biomass users for ≥ 20 years (57.95%). Compared to group-1, accounting for confounders, GBC risk was higher in group-2 [OR: 2.02; 95% CI: 1.00-4.07] and group-3 [OR: 2.01; 95% CI: 1.08-3.73] (p-trend:0.020). These associations strengthened among women that attenuated with high daily consumption of fruits-vegetables but not with fire-vents, 'daily exposure duration' or parity. CONCLUSION: Biomass burning was associated with a high-risk for GBC and should be considered as a modifiable risk factor for GBC. Clean cooking fuel can potentially mitigate, and a healthy diet can partially reduce the risk among women.

Association of aflatoxin with gallbladder cancer in a case-control study nested within a Chinese cohort.

We evaluated whether aflatoxin B1 (AFB1 ) exposure was associated with later risk of developing gallbladder cancer (GBC). We measured AFB1 -lysine albumin adducts in baseline samples from the Shanghai Cohort Study of 18 244 men aged 45 to 64 years (recruited 1986-1989). We included 84 GBC cases with sufficient serum and 168 controls matched on age at sample collection, date of blood draw and residence. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for detectable vs non-detectable AFB1 -lysine albumin adducts and gallbladder cancer. AFB1 -lysine albumin adducts were detected in 50.0% of GBC cases, and risk of GBC was twice as high in those with detectable vs undetectable levels (OR = 2.0, 95% CI = 1.0-3.9). ORs ranged from 1.8 (95% CI = 0.75-4.3) for 0.5 to <1.75 pg/mg vs undetectable adduct levels to 2.2 (95% CI = 0.91-5.6) for >3.36 pg/mg vs undetectable, suggesting a dose-response (Ptrend = .05). When restricted to cases diagnosed before the median time to diagnosis after blood draw (18.4 years), results were similar (OR = 2.2, 95% CI = 0.80-5.8) to those for the entire follow-up duration. The OR was 9.4 (95% CI = 1.7-51.1) for individuals with detectable AFB1 -lysine albumin adducts and self-reported gallstones compared to individuals with neither. Participants with detectable AFB1 -lysine albumin adducts at baseline had increased risk of developing GBC, replicating the previously observed association between AFB1 exposure and providing the first evidence of temporality.

The risk and predictors of gallbladder cancer in patients with gallbladder polyps: A retrospective cohort study with an insight into confounding by indication.

BACKGROUND AND AIM: We aimed to determine the risk and predictors of gallbladder cancer in all individuals with gallbladder polyps (GP) including those who did not have cholecystectomy. METHODS: The STROCSS guideline was followed to conduct a retrospective cohort study. All individuals with GP between 2010 and 2019 were followed up to determine the risk and predictors of gallbladder cancer. The primary outcomes were gallbladder cancer and gallbladder dysplasia, and the secondary outcomes included polyp growth rate and polyp disappearance rate. Binary logistic regression analysis and receiver operating characteristic curve analysis were conducted to evaluate the outcomes. RESULTS: Analysis of 438 patients showed risk of gallbladder cancer was 0.7% in all polyps (0% in polyps < 10 mm; 5.9% in polyps ≥ 10 mm). The risk of gallbladder dysplasia or cancer was 1.1% in all polyps (0% in polyps < 10 mm; 10% in polyps ≥ 10 mm). The polyp size (P = 0.0001) was predictor of cancer; however, patient's age (P = 0.1085), number of polyps (P = 0.9983), symptomatic polyps (P = 0.3267), and change in size (P = 0.9012) were not. Size of 21 mm was cut-off for risk of cancer (area under the curve [AUC]: 0.995, P < 0.001) and 11.8 mm for risk of dysplasia or cancer (AUC: 0.986, P < 0.001). The mean polyp growth rate was 0.3 mm/year and polyp disappearance rate was 16%. CONCLUSIONS: The GP size remains the only predictor of malignant changes regardless of patient's age, patient's symptoms and number of polyps. The polyp growth rate is unremarkable, and a significant proportion disappears during follow-up. We changed our follow-up protocol with reduced number of scans and early discharge policy.

Global epidemiological trends and variations in the burden of gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is a rare but lethal malignancy with a dismal prognosis. The aim of this study is to analyze the burdens and trends of GBC across the world based on geography, socioeconomic development (based on human development index [HDI]), and gender. METHODS: GLOBOCAN 2020 database was used to extract data (2020-2040) relating to the incidence and mortality of GBC across the world. RESULTS: Asia had the highest burden of GBC with India and China contributing to majority of the absolute burden. The burden of GBC by age standardized rate was highest in Latin America (Bolivia and Chile) and Southeast Asia (Bangladesh and Nepal). Medium HDI countries had a higher mortality rate compared to very high HDI countries. Females had a higher predilection for GBC across different regions and socioeconomic groups. GBC burden is expected to significantly increase across the world by 2040 with variable trends across different regions, age groups, and genders. CONCLUSION: The global burden of GBC will significantly increase over the next two decades with marked regional and demographic variations. The results of this study will empower national and global health leaders to develop policies to address the increasing burden of this lethal malignancy.

Non cancer causes of death after gallbladder cancer diagnosis: a population-based analysis.

Mortality from non cancer causes in patients with gallbladder cancer (GBC) still unclear. This study evaluated the causes and risk factors of non cancer death during different follow-up periods after GBC diagnosis. Non cancer causes of death for GBC patients diagnosed between 2000 and 2017 in Surveillance, Epidemiology and End Results database were analyzed and standardized mortality rates (SMR) for each non cancer death were calculated. Predictors for non cancer death were identified through multivariate competing risk analysis. A total 11,927 GBC patients were identified for further analysis, 9393 died during follow up. The largest proportion of non cancer deaths occurred > 3 years after diagnosis (39.4%). Most common non cancer cause were cardiovascular disease (43.3%), followed by other cause of death (34.4%) and infectious diseases (8.6%). Compared with US general population, GBC patients has higher risk of death from disease of heart (SMR, 1.58; 95%CI, 1.41-1.75), septicemia (SMR,3.21; 95%CI, 2.27-4.40), diabetes mellitus (SMR,1.97; 95%CI, 1.43-2.63), alone with other causes. Non cancer causes accounted for a significant proportion of deaths during the follow-up period after GBC diagnosis. The risk of non cancer death is higher in GBC patients than in the general population. Our study provides comprehensive assessment of death from non cancer cause in GBC patients, which has important implications for health management in GBC patients.

Temporal Trends of Stages and Survival of Biliary Tract Cancers in the United States and Associations with Demographic Factors.

BACKGROUND: The incidence of cholangiocarcinoma and gallbladder cancer has been increasing and decreasing respectively in the United States, whereas their mortality has been declining since 1980, which suggests improved overall survival of biliary tract cancers (BTC). We aimed to investigate temporal trends of BTC stages and survival and their associations with demographic factors. METHODS: A total of 55,163 patients with BTC collected from 2000 to 2018 from the NCI Surveillance, Epidemiology, and End Results 18 registry were included in this study. We assessed the temporal trend of BTC stages with diagnosis years using the annual percentage of change (APC) in the proportion of the stages. We estimated the association of BTC survival and stages with diagnosis years and demographic factors using the Cox regression models. RESULTS: While localized BTC proportion remained little changed from 2006 to 2018, the proportion of regional and distant BTCs significantly decreased (APC = -2.3%) and increased (APC = 2.7%), respectively, through the years. The overall and cancer-specific survival increased from 41.0% and 47.3% in 2000 to 2004 to 51.2% and 53.8% in 2015 to 2018, respectively. Patients with BTC who were older, Black, unmarried, or had lower socioeconomic status (SES) had significantly poorer overall survival. CONCLUSIONS: We found that distant and regional BTC significantly increased and decreased, respectively, and the BTC survival significantly improved over time. Age, sex, race, SES, and marital status were significantly associated with overall survival and less evidently with cancer-specific survival of patients with BTC. IMPACT: Our findings suggest that demographic factors were associated with BTC stages and BTC survival.

Ultrasound Surveillance of Small, Incidentally Detected Gallbladder Polyps: Projected Benefits by Sex, Age, and Comorbidity Level.

OBJECTIVE: Incidentally detected gallbladder polyps are commonly encountered when performing upper abdominal ultrasound. Our purpose was to estimate the life expectancy (LE) benefit of ultrasound-based gallbladder surveillance in patients with small (6-7 to <10 mm), incidentally detected gallbladder polyps, accounting for patient sex, age, and comorbidity level. METHODS: We developed a decision-analytic Markov model to evaluate hypothetical cohorts of women and men with small gallbladder polyps, with varying age (66-80 years) and comorbidity level (none, mild, moderate, severe). Drawing from current evidence, in the base case, we assumed no increased risk of gallbladder cancer in patients with small gallbladder polyps. To estimate maximal possible LE gains from surveillance, we assumed perfect cancer control consequent to 5 years of surveillance. We varied key assumptions including cancer risk and test performance characteristics in sensitivity analysis. RESULTS: Projected LE gains from surveillance were <3 days across most cohorts and scenarios evaluated. For 66- and 80-year-olds with no comorbidities, LE gains were 1.46 and 1.45 days, respectively, for women, and 0.67 and 0.75 days for men. With 10 years of surveillance, LE gains increased to 2.94 days for 66-year-old women with no comorbidities (men: 1.35 days). If we assumed a 10% increase in gallbladder cancer risk among individuals with polyps, LE gains increased slightly to 1.60 days for 66-year-old women with no comorbidities (men: 0.74 days). Results were sensitive to test performance and surgical mortality. DISCUSSION: Even under unrealistic, optimistic assumptions of cancer control, ultrasound surveillance of incidentally detected small gallbladder polyps provided limited benefit.

The Impact of a History of Different Other Cancers on the Long-Term Outcomes of Patients with Gallbladder Cancer: A Propensity Score-Adjusted, Population-Based Study.

BACKGROUND: As the number of cancer survivors increases, the prevalence of the second type of primary cancer will increase. In clinical trials, patients with a history of malignant tumors in the past are usually excluded. It is unknown whether previous cancers affect survival outcomes. The purpose of this study was to investigate the impact of previous malignant tumors on the long-term prognosis of patients with gallbladder cancer. METHODS: By using the Surveillance, Epidemiology and END Results (SEER) database, we collect patient data and obtain patients who had gallbladder cancer diagnosed in 2004-2015 and had an adaption and contrast 1:1 with cases. We applied the Kaplan-Meier analysis and Cox regression models to assess the influence of prior malignancy on gallbladder cancer survival outcomes. RESULTS: Among 8338 patients who had mainly gallbladder cancer, 525 (6.3%) suffered prior cancer. Prostate cancer (22.29%), Breast cancer (21.14%), and Genitourinary (14.67%) are the most common types. Before propensity score matching (PSM), two groups of different Kaplan-Meier curves were obtained by classifying previous cancer history, and by comparison, the all-cause difference in the group with previous cancer history was not salience (P = 0.31), but there is a protective effect on the Cancer-specific fatality rate (p < 0.001). Similar results were obtained after propensity score matching (PSM). Among the multivariate Cox analysis, previous malignancy had no obvious relation, including all causes (HR = 0.98, 95% CI: 0.86-1.12, p = 0.70) but a better gallbladder cancer-specific survival (HR =0.64, 95% CI: 0.55-0.75, P < 0.001). CONCLUSION: Prior cancer may not be an obvious factor impacting the survival of cancers of all-cause including the gallbladder. In clinical trials of gallbladder cancer, exclusion criteria based on cancer history should be assessed.

Incidence and management of gallbladder cancer in cholecystectomy specimens: a 5-year tertiary centre experience.

BACKGROUND: Gallbladder cancer (GBC) is an uncommon, but highly aggressive cancer. Half of these cases are diagnosed pre-operatively, and the remaining cases are discovered incidentally on post-cholecystectomy specimens. There is a significant geographical variability in GBC incidence, with increasing age, female sex, and prolonged duration of cholelithiasis being risk factors for GBC. The primary aim was to define the overall local incidence of GBC incidental GBC and management of these cases. The secondary aim was to determine any pertinent risk factors in our case population. METHODS: A retrospective observational study was performed on all the cholecystectomy specimens at the Gold Coast Hospital and Health Service from 1 January 2016 to 2 December 2021. Data was collected via the electronic medical record. The incidence and management of gallbladder cancers was calculated, and association with body mass index (BMI), smoking status, diabetes, inflammatory bowel disease (IBD) was identified. RESULTS: 3904 cholecystectomy specimens were reviewed. GBC was identified in 0.46% of cholecystectomies. 50% of these cases were found incidentally. Abdominal pain was the most common presenting complaint (94.4%). GBC was associated with increased age and BMI and female sex. There was no association between smoking status, diabetes or IBD with an increased incidence of cancer. Tumour staging guided surgical and/or adjuvant chemotherapy. CONCLUSION: GBC is rare. Patients with symptoms are associated with a poor prognosis. Incidental cancers are common, and negative margin resection based on the T stage of the cancer is the most reliable curative option.

The inverse association between fasting blood glucose and the occurrence of gallbladder cancer in type 2 diabetes mellitus patients: a case-control study.

OBJECTIVE: This study aimed to explore the correlation between diabetes mellitus (DM) and gallbladder cancer (GBC) in an epidemiological setting. METHODS: The study summarized the clinical and laboratory data of 2210 GBC Chinese patients in the authors' hospital. A total of 17 influencing factors for GBC, including gender, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FINS), the homeostasis model assessment of insulin resistance (HOMA-IR), retinol-binding protein 4 (RBP4), and lipid indexes were analyzed using unconditional logistic regression analysis. RESULTS: Based on the results of univariate logistic regression, the risk of GBC was significantly and positively correlated with serum triglyceride, low-density lipoprotein, FINS, HOMA-IR, being female, BMI, DM, non-alcoholic fatty liver disease, and gallbladder stone disease (GSD), and significantly negatively correlated with high-density lipoprotein and FBG concentrations in serum, as well as hypertension. According to multivariate analysis, FINS was significantly positively associated with GBC risk, while DM showed an insignificant negative association; FBG was also not important. The most significant independent factor of GBC risk in patients with DM was HOMA-IR. Fasting blood glucose levels showed a significant negative relationship with GBC in patients with DM. In addition, this study indicated a significantly negative association between serum RBP levels and GBC. CONCLUSIONS: The findings of the current study revealed that the efficient treatment of insulin resistance is an important approach for decreasing GBC risk, as opposed to lowering blood sugar only, particularly in patients with DM. Interestingly, FBG may have had an inverse association with the development of GBC in patients with type 2 DM. Of note, the study found that a dramatic initial drop in RBP may help predict the occurrence of GBC.

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.

Incidence, Mortality, and Survival Trends in Cancer of the Gallbladder and Extrahepatic Bile Ducts in Lithuania.

Background and Objectives: Gallbladder cancer is a rare type of cancer, with aggressive clinical behavior. Limited treatment options provide poor survival prognosis. We aimed to investigate the incidence, mortality trends, and survival of gallbladder and extrahepatic bile duct cancer in Lithuania between 1998 and 2017. Materials and Methods: The study was based on the Lithuanian Cancer Registry database. The study included all cases of cancer of the gallbladder and extrahepatic bile ducts reported to the Registry in the period 1998-2017. Age-specific and age-standardized incidence rates were calculated. In addition, 95% confidence intervals for APC (Annual Percent Change) were calculated. Changes were considered statistically significant if p was <0.05. Relative survival estimates were calculated using period analysis according to the Ederer II method. Results: Age-standardized rates for gallbladder cancer and extrahepatic bile duct cancer among females decreased from 3.91 to 1.93 cases per 100.000 individuals between 1998 and 2017, and from 2.32 to 1.59 cases per 100.000 individuals between 1998 and 2017 among males. The highest incidence rates were found in the 85+ group with 27.5/100,000 individuals in females and 26.8/100,000 individuals in males. The 1-year as well as 5-year relative survival rates of both genders were 34.29% (95% CI 32.12-36.48) and 16.29% (95% CI 14.40-18.27), respectively. Conclusions: Incidence and mortality from gallbladder and extrahepatic bile duct cancer decreased in both sexes in Lithuania. Incidence and mortality rates were higher in females than in males. Relative 1-year and 5-year survival rates showed a steady increase during the study period among males and females.