Cases Of Gallbladder Cancer Research Articles

Cost-effectiveness of trans-abdominal ultrasound for gallbladder cancer surveillance in patients with gallbladder polyps less than 10 mm in the United Kingdom

Abstract Objective Gallbladder polyps (GBPs) are commonly detected with trans-abdominal ultrasound (TAUS). Gallbladder cancer (GBC) is associated with GBPs but the risk of malignancy is low. International guidelines recommend ultrasound surveillance (USS) in selected cases of GBPs <10mm, with cholecystectomy advised if polyp size increases. USS (including potential surgeries) is resource intense. We evaluated the costs and potential cost-effectiveness of USS in a theoretical UK patient cohort with GBPs. Methods A health economic model mapped expected management pathways over 2-years for 1,000 GBP patients with and without USS, stratified by initial size of GBP (<6mm and 6-9mm). We estimated USS resource and costs under alternate thresholds for surgery. Clinical data were extracted from a large-scale cohort study. TAUS and surgery costs were based on NHS tariffs. GBC costs were estimated from the literature. Outcomes included USS costs, expected numbers of GBC and incremental cost for each case of GBC avoided. Results The 2-year additional cohort costs of USS (n=number of additional surgeries) were estimated between £213,441 (n = 50) and £750,045 (n = 253) in GBPs <6mm, and between £420,275 (n = 165) and £531,297 (n = 207) in GBPs 6-9mm, balanced against avoidance of 1.3 (<6mm) and 8.7 (6-9mm) cases of GBC. Model findings were robust to plausible changes in inputs. Conclusions Using published data, we demonstrated that, in patients with GBPs <10mm, the costs of USS to avoid GBC outweigh potential GBC cost offsets, and would result in high rates of cholecystectomy. Additional evidence is needed to establish the formal cost-effectiveness of GBP USS in the UK.

Human epidermal growth factor receptor-2/neu expression in gallbladder cancer is significantly associated with clinicopathological parameters and survival.

Anti-human epidermal growth factor receptor-2 (Her-2/neu) target therapy has substantially improved the disease outcome of patients with breast and gastric/gastroesophageal cancers characterized by Her-2/neu overexpression and/or amplification. Consequently, evaluating Her-2/neu expression in other cancers to predict response to Her-2/neu targeting agents emerges as a crucial approach. We aimed at investigating the positivity rate of this receptor in gallbladder cancer (GBC) and assess the relationship between Her-2/neu status, clinicopathological parameters and survival to identify patients who would benefit most from anti-Her-2/neu-targeted therapy. The Her-2/neu expression was correlated with clinicopathological parameters and survival of GBC cases. Total 235 surgically resected and histopathologically proven primary GBC cases were collected over a five-year period from January 1, 2017, and December 31, 2020. Her-2/neu expression in these cases was analyzed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Employing testing algorithms (IHC scoring based on gastric cancer criteria, followed by FISH in equivocal cases), Her-2/neu positivity was identified in 43 (18.29%) GBC cases and was significantly associated with grade I tumors, tumor stage > T2, perineural invasion, surgical margin positivity and advanced TNM stage. The mean survival time for Her-2/neu-positive cases was 14 months (SE, 1.1; 95%CI, 11.7-16.06), while it was 20 months (SE, 0.69; 95%CI, 18.1-20.9) for Her-2-negative cases (p < 0.001). Her-2/neu is expressed in about one-fifth of GBC patients and is significantly associated with tumor behavior and patient survival. Utilizing novel targeted agents may hold the key to improving the prognosis of these patients.

Defining the Role of Adjuvant Radiotherapy for Biliary Tract Cancers: A Site-Specific Propensity-Matched Analysis

Background: Biliary tract cancers (BTCs) have distinct tumor biology but share a poor prognosis, with a 5-year-survival-rate of 5–19%. Surgical resection is the only potential cure, but recurrences are common. The role of adjuvant radiotherapy (XRT) remains unclear. Methods: Using the National Cancer Database (2006–2018), we analyzed resected non-metastatic BTCs. Patients who survived beyond 90 days post-surgery were included, while those with R2 resections or neoadjuvant therapy were excluded. Propensity matching was performed based on predictors of adjuvant radiation, age, and sex. Survival outcomes were compared between no adjuvant therapy, chemotherapy alone, and XRT ± chemotherapy. Results: Among 21,275 patients, including 5308 intrahepatic cholangiocarcinoma (IHC), 2689 perihilar cholangiocarcinoma (PHC), 3092 distal cholangiocarcinoma (DCC), and 10,186 gallbladder cancer (GBC) cases, adjuvant XRT did not improve survival for IHC. For PHC and DCC, XRT improved survival over no adjuvant therapy (PHC: 31.2 vs. 26.3 months, p = 0.004; DCC: 33.7 vs. 27.0 months, p = 0.015) but not over chemotherapy alone. For GBC, XRT significantly improved survival compared to both no adjuvant therapy and chemotherapy (30.2 vs. 26.6 and 24.6 months; p = 0.05 and p = 0.001). Conclusions: XRT provides a survival benefit for GBC, especially in node-positive and R1-resected patients. For PHC and DCC, XRT improves outcomes compared to no therapy, but its benefit over chemotherapy is uncertain. No benefit was observed for IHC.

Risk factors of gallbladder cancer in Nepal: A case control study.

Gallbladder cancer (GBC) is a rare, highly fatal disease with diagnosis in advanced stage and low survival rate. Nepal ranked 4th position with highest rates of GBC for 10 countries in 2020. To find the association between socio-demographic, behavioral and environmental factors associated with the development of GBC. A case-control study was conducted in 2021/22 with newly diagnosed gallbladder cancer cases from three cancer-specialized hospitals and one tertiary (superspeciality) hospital. Controls were selected from the same tertiary hospital and one additional hospital providing services to gallbladder pathologies for a huge population, making a total of five hospitals involved in the study. The ratio of cases to control was 1:1. The data collection was done through telephonic interviews using structured questionnaires. The risk factors for GBC were assessed by using unconditional logistic regression to find odds ratios and 95% confidence level for bivariate and multivariate analysis. The statistical analysis was carried out in STATA 18. A total of 240 respondents were enrolled in the study, among them half were GBC patients (cases) and half were gallbladder patients (controls). The average age of the respondents was 54.82±12.3 years, with female preponderance among both groups. On multivariate analysis, the risk factors studied were; parity ≥3 (AOR = 2.80, 95% CI: 1.17-6.66, P value 0.020), being ethnic group of Terai/Madhesi (AOR = 7.88, 95% CI: 3.16-19.66, P value <0.001), being Janajati (AOR = 3.36, 95% CI: 1.17-6.61, P value <0.001), having gallbladder related disease (AOR = 2.00, 95% CI:1.00-4.02, P value 0.049), consuming alcohol ≥100ml/day (AOR = 3.44, 95% CI:1.11-10.63, P value 0.032), exposed with pesticides ≥2 times in a year (AOR = 4.04, 95% CI: 1.27-12.89, P value 0.018) and consuming less vegetables and fruits (<1 times per day in a week) (AOR = 2.69, 95% CI:1.34-5.40, P value 0.005). The study reveals key GBC risk factors, offering vital insights for targeted screening, resource allocation, and public health measures to mitigate risks in Nepal.

Analysis of CD1a-Positive Monocyte-Derived Cells in the Regional Lymph Nodes of Patients with Gallbladder Cancer.

Dendritic cells (DCs) are known to be major antigen-presenting cells, and lymph nodes (LNs) play an important role in DC-mediated immune response. CD1a is known as a marker of monocyte-derived DCs. The present study focused on the infiltration of CD1a-positive DCs (CD1a-DCs) into regional LNs in 70 cases of gallbladder cancer (GBC). After univariate analyses, the results showed that LN infiltration by CD1a-DCs was associated with unfavorable clinical outcomes in patients with GBC, with all cases categorized in the CD1a-DCs high group had nodal metastasis. LN infiltration by CD1a-DCs was not an independent prognostic factor identified by multivariate analyses. After subgroup analyses of cases with LN metastasis (n = 32), no significant impacts of CD1a-DCs infiltration into metastatic LNs were observed. In contrast, CD1a-DCs infiltration into primary tumors had a significant impact on surgical outcomes. The results of strong confounding between CD1a-DCs and LN metastasis support the theory that CD1a-DCs are developed from monocytes at tumor sites. As the results of previous research focused on CD1a-DCs infiltration into regional LNs of other organs varied, the role and significance of CD1a-DCs infiltration in regional LNs may be different according to the tumor histology or its primary site. Thus, further studies are needed to clarify the role and significance of CD1a-DCs infiltration into regional LNs of solid cancers.

Global variations in gallbladder cancer incidence: What do recorded data and national estimates tell us?

On a global scale, gallbladder cancer is a relatively rare cancer with a striking variability in incidence across countries and world regions. We examined recent geographic variations worldwide based on national gallbladder cancer incidence estimates for the year 2022 from the GLOBOCAN database for 185 countries alongside recorded incidence data from the most recent volume of Cancer Incidence in Five Continents. In 2022, 122,491 new gallbladder cancer cases and 89,055 deaths were estimated to occur worldwide, of which 64.5% and 64.7% respectively were among females. The highest reported rates (ASR per 100,000) were in subpopulations of Northeastern regions of India and Southern Chile in both males (ASR of 6.1 and 5.3, respectively) and in females, though rates were two times higher than males (ASR of 14.9 and 15.4). The lowest incidence rates were reported in subpopulations of Uganda for males and South Africa for females (0.21 and 0.14, respectively). Recorded gallbladder cancer incidence rates among subnational populations within countries differed considerably from their respective national estimates and revealed a 100-fold variation in gallbladder cancer, highlighting the importance of subnational population-based cancer registry data in pinpointing areas of high risk, driving research and prioritizing tailored public health actions.

HPB SO27 - Reconsidering Routine Histopathological Examination of Gallbladder Specimens in Cholecystectomy: Optimizing Clinical Practice and Resource Management

Abstract Background Cholecystectomy, the removal of the gallbladder, is a common surgery performed globally. Routine histopathological examination (HPE) of gallbladder specimens post-surgery aims to detect pathologies like gallbladder cancer (GBC). GBC incidence varies by region and ethnicity, with higher risks in women and those over 65. Advanced GBC stages often require surgery, while early stages may only need cholecystectomy. Global HPE practices differ based on resources and GBC rates. This study evaluates the necessity of routine HPE by examining the selective processing of specimens suspected of GBC, ensuring patient safety while potentially optimizing resource use. Method This retrospective cohort study conducted at Redland Hospital, a district general hospital in Australia, investigated the necessity of routine histopathological examination (HPE) for excised gallbladder specimens. Adhering to routine HPE policy, the study encompassed all elective and emergency cholecystectomies performed from January 2023 to December 2023, excluding pediatric cases, concurrent surgical procedures, and those with suspected malignancy. Demographic data, surgery indications, intraoperative findings, histopathological results, and incidental gallbladder cancer (IGC) outcomes were analyzed. Pathology reports and case documentation were reviewed for cancerous pathology indicators. Results Over the one-year study period from January 2023 to December 2023, a total of 266 gallbladder specimens were subjected to histopathological examination (HPE) post-cholecystectomy. Of these, 201 were female and 65 were male, yielding a male-to-female ratio of 3:1. Elective cholecystectomy was performed on 56.4% (150) of patients, while 43.6% (116) underwent emergency procedures. Laparoscopic cholecystectomy (LC) was the primary surgical approach, except for one case requiring conversion to an open procedure. None of the patients exhibited gallbladder carcinoma (GBC); however, 3.3% (9) displayed premalignant histopathological features in their specimens. Conclusion In conclusion, adopting a selective approach, where only gallbladder specimens with macroscopic abnormalities undergo histopathological examination (HPE), seems prudent, especially in regions with low gallbladder cancer (GBC) incidence. Our study, which revealed no cases of GBC, supports this approach. It not only reduces the risk of missing incidental carcinoma in clinically unsuspected cases but also proves cost-effective and reduces the histopathology department workload without compromising patient outcomes. Therefore, we advocate for routine macroscopic examination of gallbladder specimens for abnormalities before HPE submission, particularly in cholecystectomy patients with gallstone disease.

Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults: 30 years' overview and forecasted trends.

Hepatobiliary and pancreatic (HBP) cancers impose a considerable burden on young populations (aged 15 to 49 years), resulting in a substantial number of new cases and fatalities each year. In young populations, the HBP cancers shows extensive variance worldwide and the updated data in China is lacking. To investigate the current status, trends, projections, and underlying risk factors of HBP cancers among young populations in China. The Global Burden of Disease Study 2019 provided data on the annual incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rate (ASIR), mortality rate (ASMR), and DALYs rate (ASDR) of HBP cancers in young Chinese adults between 1990 and 2019. Temporal trends were assessed using estimated annual percentage change and hierarchical clustering. Sex-specific mortality and DALYs caused by various risks were analyzed across China and other regions, with future trends until 2035 projected using the Bayesian age-period-cohort model. From 1990 to 2019, incident cases, deaths, DALYs, ASIR, ASMR, and ASDR for liver cancer (LC) in young Chinese individuals decreased, classified into 'significant decrease' group. Conversely, cases of gallbladder and biliary tract cancer and pancreatic cancer rose, categorized as either 'significant increase' or 'minor increase' groups. The contribution of risk factors to mortality and DALYs for HBP tumors increased to varying degrees. Healthy lifestyle behaviors, such as tobacco control, weight management, alcohol moderation, and drug avoidance, could lower HBP cancers incidence. Moreover, except for LC in females, which is likely to initially decline slightly and then rise, the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young adults. HBP cancers burden among young adults in China is expected to increase until 2035, necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these cancers.

Prediabetes persistence or remission and subsequent risk of gallbladder cancer: A nationwide cohort study

Background & aimsHyperglycemia is associated with an increased risk of gallbladder cancer (GBC), potentially by inhibiting gallbladder motility and inducing prolonged cholestasis. Although intermediate hyperglycemia (or prediabetes) is highly reversible, evidence is lacking about whether prediabetes persistence or remission is associated with an altered GBC risk. MethodsThis nationwide cohort study included 6058,662 adults without diabetes or cancer who underwent national health examinations twice in 2-year intervals between 2009 (S1) and 2011 (S2) and were followed-up until 2018. Prediabetes was defined as a fasting plasma glucose level of 100–125 mg/dL. We categorized changes in prediabetes status into: stable normoglycemia, new-onset prediabetes, prediabetes remission, and persistent prediabetes groups. GBC risk was estimated using Cox proportional hazards models, after adjusting for potential confounders. ResultsDuring 38.6 million person-years (median 6.4 years) of follow-up, 1349 new GBC cases were identified. Among 1409,474 individuals with prediabetes at S1, 768,515 achieved prediabetes remission at S2, outnumbering the 640,959 individuals with persistent prediabetes. GBC incidence probability was consistently higher among individuals with persistent prediabetes than in individuals with stable normoglycemia or prediabetes remission (all log-rank P < 0.01). Compared with stable normoglycemia, persistent prediabetes was associated with increased GBC risk (adjusted hazard ratio [aHR], 95 % CI: 1.21, 1.04 to 1.41). The aHRs of GBC were 1.14 (95 % CI, 0.99 to 1.33) and 1.03 (95 % CI, 0.88 to 1.21) for new-onset prediabetes and prediabetes remission, respectively. ConclusionsIndividuals with persistent prediabetes had a significantly increased risk of GBC, whereas those with prediabetes remission had no increased risk. Achieving prediabetes remission has a significant potential to reduce the risk of GBC.

Evaluation of malignancy in gallbladder tumors using the apparent diffusion coefficient obtained by diffusion‑weighted MRI.

The utility of the apparent diffusion coefficient (ADC) of diffusion-weighted image (DWI) magnetic resonance imaging was examined for evaluating malignancy and prognosis in gallbladder tumors. A total of 63 patients (benign tumors, n=33; cancer, n=30) were included after surgical resection for gallbladder tumors, and their mean ADC values by DWI were obtained. Cases of advanced gallbladder cancer (n=25) were divided into ADCHigh and ADCLow groups, and clinicopathological factors were compared. In 63 cases, ADC values in advanced gallbladder cancer were significantly lower compared with benign tumors and non-advanced gallbladder cancer (P<0.05), and ADC values in early gallbladder cancer were also significantly lower compared with benign tumors (P<0.05). In 25 advanced gallbladder cancer cases, the ADCLow group tended to have a higher rate of advanced stage disease (P=0.09). Disease-free survival and overall survival (OS) of the ADCLow group were worse compared with the ADCHigh group (P<0.01). In the multivariate analysis of OS, poor differentiation and low ADC value were independent prognostic factors. ADC values may be useful for evaluating tumor malignancies in gallbladder tumors.

Expression Pattern of Estrogen Receptor Alpha and Progesterone Receptor in Gallbladder Carcinoma and Their Association with Clinicopathological Parameters and Overall Survival.

Gallbladder cancer (GBC) is a highly aggressive malignant tumor with a poor prognosis. Despite being first described two centuries ago, there are no targeted therapies available beyond conventional cytotoxic therapy. Epidemiological studies have shown that the incidence of gallbladder cancer is higher in females than males. This suggests that the gallbladder may be a female sex hormone-responsive organ, and these hormones might be involved in the pathogenesis of gallbladder cancer. Therefore, we aimed to analyze the expression of ERα and PR in GBC and correlate their expression with clinicopathological variables and overall survival. A total of 235 histopathologically diagnosed GBC cases were included in this hospital-based cross-sectional study. Clinicopathological data were collected, and the expression of ERα and PR was evaluated by immunohistochemistry. The mean age of this study population was 55.47 ± 8.45 with range 28-87years. Females were predominated over male with a male-to-female ratio of 1:3.5. Positive nuclear expression of the ERα and PR was found in 13 (5.5%) and eight (3.4%) cases, respectively. Apart from nuclear staining, cytoplasmic expression of ERα and PR was found in three (1.2%) and 31 (13.2%) cases, respectively. Higher percentage of positive nuclear expression of ER was found in < 50years age (p value = 0.04), parity > 4 (p value = 0.02), advanced pT stage (T3) (p value = 0.01), lymphovascular invasion (p value = 0.02), and liver invasion (p value = 0.04) which were statistically significant. Higher percentage of PR expression was also observed in < 50years age (p value = 0.01), and tumor associated with gallstone (p value = 0.04). There was no significant correlation between cytoplasmic expression of ER, PR, and clinicopathological variables. In multivariate analysis, there was no significant correlation between ER or PR positive expression and overall survival. Although nuclear expression of ERα was significantly associated with progressive disease factors but the positive expression was found in very small percentage of GBC cases. So anti-hormone therapy might be an option in patient with ER α positive gallbladder carcinoma.

Reconsidering Routine Histopathological Examination of Gallbladder Specimens in Cholecystectomy: Optimizing Clinical Practice and Resource Management.

Introduction Cholecystectomy, the surgical removal of the gallbladder, is a common procedure worldwide. Despite no visible anomalies, routine histopathological examination (HPE) of gallbladder specimens post-surgery is standard practice to exclude pathologies, notably gallbladder cancer (GBC). Incidence rates of GBC vary geographically and ethnically. Surgical intervention is recommended for advanced GBC stages, while early stages may require cholecystectomy alone. Although rare, GBC and bile duct cancers pose increased risks in certain demographics, such as women and individuals over 65. Routine HPE practices vary globally based on resource availability and GBC incidence. This study assesses the necessity of routine HPE by evaluating the selective processing of gallbladder specimens suspected of GBC, prioritizing patient safety. Materials and methods This retrospective cohort study conducted at Redland Hospital, a district general hospital in Australia, investigated the necessity of routine HPEfor excised gallbladder specimens. Adhering to routine HPE policy, the study encompassed all elective and emergency cholecystectomies performed from January 2023 to December 2023, excluding pediatric cases, concurrent surgical procedures, and those with suspected malignancy. Demographic data, surgery indications, intraoperative findings, histopathological results, and incidental gallbladder cancer (IGC)outcomes were analyzed. Pathology reports and case documentation were reviewed for cancerous pathology indicators. Results Over the one-year study period from January 2023 to December 2023, a total of 266 gallbladder specimens were subjected to HPEpost-cholecystectomy. Of these, 201 were female and 65 were male, yielding a male-to-female ratio of 3:1. Elective cholecystectomy was performed on 56.4% (150) of patients, while 43.6% (116) underwent emergency procedures. Laparoscopic cholecystectomy (LC) was the primary surgical approach, except for one case requiring conversion to an open procedure. None of the patients exhibited GBC; however, 3.3% (9) displayed premalignant histopathological features in their specimens. Conclusion In conclusion, adopting a selective approach, where only gallbladder specimens with macroscopic abnormalities undergo HPE, seems prudent, especially in regions with low GBCincidence. Our study, which revealed no cases of GBC, supports this approach. It not only reduces the risk of missing incidental carcinoma in clinically unsuspected cases but also proves cost-effective and reduces the histopathology department workload without compromising patient outcomes. Therefore, we advocate for routine macroscopic examination of gallbladder specimens for abnormalities before HPE submission, particularly in cholecystectomy patients with gallstone disease.

Xanthogranulomatous cholecystitis. A rare case of chronic cholecystitis simulated gallbladder cancer

Xanthogranulomatous cholecystitis. A rare case of chronic cholecystitis simulated gallbladder cancer

Survival of primary gallbladder cancer in the United States: SEER database analysis from 2000-2020.

e16210 Background: Primary gallbladder cancer is a rare but aggressive cancer with poor outcomes. Our study aims to understand the survival trends of patients with Primary gallbladder cancer (PGC) and analyze the prognosis factors based on cases registered in the SEER database from 2000 to 2020. Methods: We usedSEER*Stat Version 8.4.3 software to extract primary gallbladder carcinoma cases from SEER 17 registries (2000-2020). 20,143 patients were included in the study. Those with unconfirmed histology were excluded. We analyzed overall mortality and primary gallbladder cancer-specific mortality (CSM) using a Cox proportional hazards model. The survival analysis was carried out using the Kaplan–Meier method and the log-rank test was used to compare survival curves. Results: There was an overall increase in gallbladder cancer cases by 23% in 2010-2020 compared to 2000-2010. There was no significant cancer-specific mortality difference identified between males and females (HR = 1.009; CI: 0.972-1.046). Non-Hispanic blacks had higher overall mortality (HR = 1.134; CI: 1.010-1.273) amongst different ethnicities. Crude analysis revealed overall mortality was higher among patients aged above 80 years (HR = 9.857; CI: 6.257-15.528). Crude analysis also revealed significantly higher cancer-specific mortality for cholangiocarcinoma (HR = 1.622; CI:1.509-1.744) amongst histological subtypes. Gallbladder cancer-specific mortality was high with regional disease (HR = 3.115; CI: 2.839-3.419) and increased significantly with distant metastases (HR = 7.169; CI 6.512-7.891). Treatment with surgery, chemotherapy, or radiation alone or in combination improved survival among patients. Conclusions: There is a significant increase in gallbladder carcinoma mortality even among patients with regional disease, and it was worse with metastatic disease. With limited early-stage diagnoses and poor overall survival rates, we recommend further research to develop effective screening methods, understand risk factors, and explore effective preventive and therapeutic strategies for primary gallbladder cancer.

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.

Projection of the number of new cases of gallbladder cancer in the world.

Projection of the number of new cases of gallbladder cancer in the world.

Abstract 3446: Associations of non-steroidal anti-inflammatory drug use and circulating inflammatory proteins with gallbladder dysplasia

Abstract Background: Most gallbladder cancer (GBC) cases arise from the metaplasia-dysplasia-GBC sequence, and chronic inflammation has been associated with its development. The use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of GBC; however, little is known about these associations with preneoplastic lesions. We thus aimed to study the associations of the use of NSAIDs and inflammatory proteins with gallbladder dysplasia, a precursor to GBC. Methods: Associations of NSAIDs and gallbladder dysplasia were evaluated in 1,925 Chilean cholecystectomy patients, 82 with dysplasia and 1,843 with gallstones but not dysplasia. In addition, we measured 33 circulating inflammatory proteins in a subsample of 68 dysplasia cases diagnosed at the time of sample selection and 136 gallstone controls. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and associations of inflammatory proteins and gallbladder dysplasia were analyzed. Results: NSAID use was inversely associated with gallbladder dysplasia (OR: 0.48, 95% CI: 0.26-0.83). Comparing the highest versus lowest category of each immune-related protein, eight proteins were inversely associated with dysplasia with ORs ranging from 0.30 (95%CI: 0.12-0.77) for IL-33 to 0.76 (95%CI: 0.59-0.99) for MIP-1B. Of those, GRO remained associated with dysplasia (OR: 0.64, 95%CI: 0.45-0.91) and BCA-1 was borderline-associated (OR: 0.74, 95%CI: 0.54-1.01) in the multivariable logistic regression model additionally adjusted for sex, age and NSAID use. Conclusion: NSAID users were less likely to have gallbladder dysplasia, suggesting that NSAIDs might be beneficial for gallstones patients. Prospective studies are needed to understand the inverse association of immune-related markers and dysplasia, and to evaluate the biological effect of NSAIDs in GBC. Research supported by general funds from the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the Office of Research on Women’s Health, National Institutes of Health. Citation Format: Lorena Rosa, Paz Cook, Ruth M. Pfeiffer, Troy J. Kemp, Allan Hildesheim, Burcin Pehlivanoglu, Volkan Adsay, Enrique Bellolio, Juan Carlos Araya, Ligia Pinto, Catterina Ferreccio, Gloria Aguayo, Eduardo Viñuela, Jill Koshiol. Associations of non-steroidal anti-inflammatory drug use and circulating inflammatory proteins with gallbladder dysplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3446.

Clinicopathological and prognostic significance of VEGF, PDGF-B, and HER2/neu expression in gallbladder cancer.

Gallbladder cancer (GBC) is usually diagnosed in advanced stages with poor survival. The molecular mechanisms of GBC still remain unexplored. Several angiogenesis factors play a pivotal role in tumor progression. We aimed to study the expression of VEGF, PDGF-B, and human epidermal growth factor receptor 2 (HER2/neu) and its association with clinicopathological features and survival in GBC. VEGF, PDGF-B, and HER2/neu expression was studied by immunohistochemistry (IHC) after histological evaluation in 91 GBC cases. The relationship between these markers and clinicopathological features and survival was explained through the Cox regression model and Kaplan-Meier method. VEGF, PDGF-B, and HER2/neu overexpressed in 45, 79, and 68% GBC cases, respectively. VEGF was significantly overexpressed in GBC without gall stones (GS) (p = 0.007) and with moderately and poorly differentiated tumors (p = 0.012). HER2/neu was significantly overexpressed in GBC with GS (p = 0.022). Median overall survival (OS) was 39 months (95% CI: 23-55). In univariate analysis, histological type (adenocarcinoma and papillary) vs. others (signet ring/mucinous/adenosquamous) (p = 0.004), depth of tumor infiltration (p = 0.017), distant metastasis (p = 0.012), and adjuvant therapies (chemotherapy/radiotherapy) (p = 0.083) were associated with poor prognosis. Multivariate survival analysis showed histological type (p = 0.004) and distant metastasis (p = 0.032) to be independent prognostic factors for OS. Histological type (p = 0.002), distant metastasis (p = 0.003), and depth of tumor infiltration (T3-T4) (p = 0.012) showed poor median survival. Poor survival was seen in VEGF and HER2/neu positive cases. Overexpression of VEGF, PDGF-B, and HER2/neu might be possible prognostic biomarkers in GBC. Poor survival of VEGF and HER2/neu positive cases indicates the possibilities of using their blockers as therapeutic agents.

Uninvited Guest in the H ouse: A Rare Case of Metastatic Gallbladder Cancer

Gallbladder cancer is a rare malignancy. About 1–2% of surgical specimens demonstrated a gallbladder cancer as an incidental finding. Metastasis to ovaries by biliary origin, known as Krukenberg tumour, though known, is infrequent. It can mimic clinically and morphologically, as a primary ovarian tumour challenging the diagnosis. Diagnosis of secondary ovarian tumours though its challenging often misdiagnosed as primary ovarian cancer, specifically mucinous adenocarcinomas. The distinction from the latter is essential, as it requires different treatment. Immunohistochemistry plays an important role in distinguishing primary ovarian tumours from extra-ovarian metastases. Detailed diagnostic laparotomy with examination of upper abdomen , IHC and UGI scopy evaluation plays a major role in identifying the primary tumour and make the correct diagnosis. As treatment varies according to primary, detailed evaluation might help in deciding appropriate palliative chemotherapy. Keywords: Krukenberg tumour, Gall bladder cancer, Immunohistochemistry, UGI scopy, Metastatic gallbladder cancer, Ovarian metastasis, Ovarian mass

Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer.

Gall bladder cancer (GBC) is becoming a very devastating form of hepatobiliary cancer in India. Every year new cases of GBC are quite high in India. Despite recent advanced multimodality treatment options, the survival of GBC patients is very low. If the disease is diagnosed at the advanced stage (with local nodal metastasis or distant metastasis) or surgical resection is inoperable, the prognosis of those patients is very poor. So, perspectives of targeted therapy are being taken. Targeted therapy includes hormone therapy, proteasome inhibitors, signal transduction and apoptosis inhibitors, angiogenesis inhibitors, and immunotherapeutic agents. One such signal transduction inhibitor is the specific short interfering RNA (siRNA) or short hairpin RNA (shRNA). For developing siRNA-mediated therapy shRNA, although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells, many more clinical trials are required. To date, many such genes have been identified. This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.