Incidence Of Gallbladder Cancer Research Articles

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.

RpoS activates formation of Salmonella Typhi biofilms and drives persistence in the gall bladder.

The development of strategies for targeting the asymptomatic carriage of Salmonella Typhi in chronic typhoid patients has suffered owing to our basic lack of understanding of the molecular mechanisms that enable the formation of S. Typhi biofilms. Traditionally, studies have relied on cholesterol-attached biofilms formed by a closely related serovar, Typhimurium, to mimic multicellular Typhi communities formed on human gallstones. In long-term infections, S. Typhi adopts the biofilm lifestyle to persist in vivo and survive in the carrier state, ultimately leading to the spread of infections via the fecal-oral route of transmission. In the present work, we studied S. Typhi biofilms directly, applied targeted as well as genome-wide genetic approaches to uncover unique biofilm components that do not conform to the CsgD-dependent pathway established in S. Typhimurium. We undertook a genome-wide Tn5 mutation screen in H58, a clinically relevant multidrug resistance strain of S. Typhi, in gallstone-mimicking conditions. We generated New Generation Sequencing libraries based on the ClickSeq technology to identify the key regulators, IraP and RpoS, and the matrix components Sth fimbriae, Vi capsule and lipopolysaccharide. We discovered that the starvation sigma factor, RpoS, was required for the transcriptional activation of matrix-encoding genes in vitro, and for S. Typhi colonization in persistent infections in vivo, using a heterologous fish larval model. An rpoS null mutant failed to colonize the gall bladder in chronic zebrafish infections. Overall, our work uncovered a novel RpoS-driven, CsgD-independent paradigm for the formation of cholesterol-attached Typhi biofilms, and emphasized the role(s) of stress signaling pathways for adaptation in chronic infections. Our identification of the biofilm regulators in S. Typhi paves the way for the development of drugs against typhoid carriage, which will ultimately control the increased incidence of gall bladder cancer in typhoid carriers.

Clinical and Genomic Characterization of ERBB2-Altered Gallbladder Cancer: Exploring Differences Between an American and a Chilean Cohort.

Gallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on ERBB2 alterations. Patients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets. A total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% v 44%; P = .0003). The prevalence of ERBB2 alterations was comparable between the two cohorts (15% v 9%; P = .42). Overall, ERBB2 alterations were present in 14% of patients (8% with ERBB2 amplification, 4% ERBB2 mutation, 1.5% concurrent amplification and mutation, and 0.4% ERBB2 fusion). Notably, patients with GBC that harbored ERBB2 alterations had better overall survival (OS) versus their ERBB2-wild type counterparts (22.3 months v 11.8 months; P = .024). The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.

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.

Microbiome dysbiosis in gallbladder cancer: A systemic review

Gallbladder cancer (GBC) starts in the epithelial tissue (lining of the bile duct and gallbladder). It is a type of aggressive cancer called adenocarcinoma that can spread to other tissues. Among all cases of biliary tract cancer, 50% is from GBC. It is a deadly cancer with a survival rate of 17.6% between 2007 and 2013. GBC is rarely found in the Western world, but it is commonly found in South Asia. In Southeast Asian countries, GBC plays a significant role in cancer-related morbidity and mortality. GBC incidence exhibits marked regional variability, a rare condition in the western population but having a higher frequency in India, especially the Indo-Gangetic belt and some northeast districts excluding Nagaland. This might be attributed to the differences in environmental factors and genetic predisposition modulating carcinogenesis. In GBC, only 10% of cases are identified in the early stages. The low rate of early detection is due to the lack of screening techniques and the aggressive characteristics of the tumor. Various risk factors are associated with GBC, for example, chronic cholecystitis with or without gallstones, obesity, exposure to heavy metals such as lead and arsenic, bacterial infection, congenital biliary cysts, and abnormal pancreaticobiliary duct junction. The risk factors can cause chronic gallbladder mucosa irritation, leading to dysplasia and neoplasia. GBC can form metaplasia to dysplasia in a time span of 5–15 years, then to carcinoma in situ, and finally to invasive cancer. Dysbiosis is responsible for various diseases, including cancer. Multiple triggers can cause dysbiosis, for example, environmental changes, inflammation, infection, medications, dietary changes, or genetic predisposition. Various researches show that Helicobacter pylori, human papillomavirus, Hepatitis B virus, and Hepatitis C virus microbial species can cause cancer. They are the major species responsible for 90% of infection-associated cancers. Various studies demonstrate that the strains of Salmonella and Helicobacter colonize are linked to developing GBC. While the mechanisms linking gut microbiota to GBC are not fully understood, several studies have suggested a potential association. According to a study, certain gut microbiomes, such as Fusobacterium nucleatum, found glut in GBC tissues, compared to adjacent normal tissues. By evaluating gut microbiome dysbiosis, we can see the potential link between gut microbiome dysbiosis and GBC; it may provide valuable insights into the development and progression of GBC. It could lead to the identification of new diagnostic markers and the development of novel therapeutic strategies. In GBC, the evaluation of gut microbiome dysbiosis (involving evaluating the composition, diversity, and functional capacity of the gut microbiome in patients) has emerged as a promising method for understanding the molecular mechanisms and identifying biomarkers for early prevention and detection of GBC and also investigating the possibility of any link between the gut microbiome and host immune response. In conclusion, evaluating gut microbiome dysbiosis in GBC is a promising direction for identifying potential early detection and prevention biomarkers. Additional investigation is therefore needed to determine the role of gut microbiome dysbiosis in the development and progression of GBC and to identify reliable biomarkers for clinical use.

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.

Racial and ethnic disparities in gallbladder cancer: A two-decade analysis of incidence and mortality rates in the US.

Gallbladder cancer (GBC) is an aggressive malignancy that is usually diagnosed at a late stage. Prior data showed increasing incidence of GBC in the US. However, little is known about race/ethnic-specific incidence and mortality trends of GBC per stage at diagnosis. Therefore, we aimed to conduct a time-trend analysis of GBC incidence and mortality rates categorized by race/ethnicity and stage-at-diagnosis. Age-adjusted GBC incidence and mortality rates were calculated using SEER*Stat software from the United States Cancer Statistics database (covers ~98% of US population between 2001 and 2020) and NCHS (covers ~100% of the US population between 2000 and 2020) databases, respectively. Race/Ethnic groups were Non-Hispanic-White (NHW), Non-Hispanic-Black (NHB), Hispanic, Non-Hispanic-Asian/Pacific-Islander (NHAPI), and Non-Hispanic-American-Indian/Alaska-Native (NHAIAN). Stage-at-diagnoses were all stages, early, regional, and distant stages. Joinpoint regression was used to generate time-trends [annual percentage change (APC) and average APC (AAPC)] with parametric estimations and a two-sided t-test (p-value cut-off 0.05). 76,873 patients were diagnosed with GBC with decreasing incidence rates in all races/ethnicities except NHB who experienced an increasing trend between 2001 and 2014 (APC = 2.08, p < 0.01) and plateauing afterward (APC = -1.21, p = 0.31); (AAPC = 1.03, p = 0.03). Among early-stage tumors (9927 patients), incidence rates were decreasing only in Hispanic (AAPC = -4.24, p = 0.006) while stable in other races/ethnicities (NHW: AAPC = -2.61, p = 0.39; NHB: AAPC = -1.73, p = 0.36). For regional-stage tumors (29,690 patients), GBC incidence rates were decreasing only in NHW (AAPC = -1.61, p < 0.001) while stable in other races/ethnicities (NHB: AAPC = 0.73, p = 0.34; Hispanic: AAPC = -1.58, p = 0.24; NHAPI: AAPC = -1.22, p = 0.07). For distant-stage tumors (31,735 patients), incidence rates were increasing in NHB (AAPC = 2.72, p < 0.001), decreasing in Hispanic (AAPC = -0.64, p = 0.04), and stable in NHW (AAPC = 0.07, p = 0.84) and NHAPI (AAPC = 0.79, p = 0.13). There were 43,411 deaths attributed to GBC with decreasing mortality rates in all races/ethnicities except NHB who experienced a stable trend (AAPC = 0.25, p = 0.25). Nationwide data over the last two decades show that NHB patients experienced increasing GBC incidence between 2001 and 2014 followed by stabilization of the rates. This increase was driven by late-stage tumors and occurred in the first decade. NHB also experienced non-improving GBC mortality, compared to other race and ethnic groups who had decreasing mortality. This can be due to lack of timely-access to healthcare leading to delayed diagnosis and worse outcomes. Future studies are warranted to investigate contributions to the revealed racial and ethnic disparities, especially in NHB, to improve early detection.

Cancer Incidence Trends in Successive Social Generations in the US

The incidence of some cancers in the US is increasing in younger age groups, but underlying trends in cancer patterns by birth year remain unclear. To estimate cancer incidence trends in successive social generations. In this cohort study, incident invasive cancers were ascertained from the Surveillance, Epidemiology, and End Results (SEER) program's 13-registry database (November 2020 submission, accessed August 14, 2023). Invasive cancers diagnosed at ages 35 to 84 years during 1992 to 2018 within 152 strata were defined by cancer site, sex, and race and ethnicity. Invasive cancer. Stratum-specific semiparametric age-period-cohort (SAGE) models were fitted and incidence per 100 000 person-years at the reference age of 60 years was calculated for single-year birth cohorts from 1908 through 1983 (fitted cohort patterns [FCPs]). The FCPs and FCP incidence rate ratios (IRRs) were compared by site for Generation X (born between 1965 and 1980) and Baby Boomers (born between 1946 and 1964). A total of 3.8 million individuals with invasive cancer (51.0% male; 8.6% Asian or Pacific Islander, 9.5% Hispanic, 10.4% non-Hispanic Black, and 71.5% non-Hispanic White) were included in the analysis. In Generation X vs Baby Boomers, FCP IRRs among women increased significantly for thyroid (2.76; 95% CI, 2.41-3.15), kidney (1.99; 95% CI, 1.70-2.32), rectal (1.84; 95% CI, 1.52-2.22), corpus uterine (1.75; 95% CI, 1.40-2.18), colon (1.56; 95% CI, 1.27-1.92), and pancreatic (1.39; 95% CI, 1.07-1.80) cancers; non-Hodgkins lymphoma (1.40; 95% CI, 1.08-1.82); and leukemia (1.27; 95% CI, 1.03-1.58). Among men, IRRs increased for thyroid (2.16; 95% CI, 1.87-2.50), kidney (2.14; 95% CI, 1.86-2.46), rectal (1.80; 95% CI, 1.52-2.12), colon (1.60; 95% CI, 1.32-1.94), and prostate (1.25; 95% CI, 1.03-1.52) cancers and leukemia (1.34; 95% CI, 1.08-1.66). Lung (IRR, 0.60; 95% CI, 0.50-0.72) and cervical (IRR, 0.71; 95% CI, 0.57-0.89) cancer incidence decreased among women, and lung (IRR, 0.51; 95% CI, 0.43-0.60), liver (IRR, 0.76; 95% CI, 0.63-0.91), and gallbladder (IRR, 0.85; 95% CI, 0.72-1.00) cancer and non-Hodgkins lymphoma (IRR, 0.75; 95% CI, 0.61-0.93) incidence decreased among men. For all cancers combined, FCPs were higher in Generation X than for Baby Boomers because gaining cancers numerically overtook falling cancers in all groups except Asian or Pacific Islander men. In this model-based cohort analysis of incident invasive cancer in the general population, decreases in lung and cervical cancers in Generation X may be offset by gains at other sites. Generation X may be experiencing larger per-capita increases in the incidence of leading cancers than any prior generation born in 1908 through 1964. On current trajectories, cancer incidence could remain high for decades.

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.

Functional relevance of MMP2 promoter variants in gallbladder cancer: A case-control study in an Eastern Indian Population

Gallbladder cancer (GBC) is a prevalent and deadly form of bile duct cancer, associated with poor prognosis. This study aimed to investigate the genetic factors contributing to the high incidence of GBC in certain geographical regions, particularly in the Northern and Eastern parts of India. The present case-control study focused on MMP2, a gene involved in tumor progression and metastasis, as a potential candidate in GBC pathogenesis.We scanned MMP2 promoter for twelve SNPs using Sanger’s sequencing and carried out a case-control study in 300 cases and 300 control samples. We found five rare variants (rs1961998763, rs1961996235, rs1391392808, rs1488656253, and rs17859816) and one nonpolymorphic SNP (rs17859817). Our results revealed a significant association between GBC and MMP2 promoter SNPs, rs243865 (Allelic-Padjusted = 0.0353) and g.55477735G > A (Allelic-Padjusted = 9.22E-05). Moreover, the haplotype “C-C-A-C-C” exhibited a significant association with GBC (P = 4.23E-05). Genotype-phenotype correlation for variant rs243865, in the GBC patient tissue samples, established that 'T' risk allele carriers had higher expression levels of MMP2. Additionally, luciferase reporter assay in HEK293T cells revealed the probable regulatory role of rs243865 variant allele 'T' in MMP2 expression. Our study uncovers the association of MMP2 promoter SNPs with GBC and their role in regulating its expression.

Expert consensus on the laparoscopic radical resection of gallbladder cancer

The incidence of gallbladder cancer has been increasing. Radial resection is still the most promising curable treatment for patients with gallbladder cancer. Although the techniques required for laparoscopic radical resection of gallbladder cancer have matured, the number of reports is also on the rise, and laparoscopic radical resection of gallbladder cancer is still controversial. To standardize laparoscopic radical resection of gallbladder cancer, the Biliary Surgery Branch, Chinese Society of Surgery, Chinese Medical Association, together with the Chinese Medical Doctor Association in Chinese Committee of Biliary Surgeons, gathered experts to formulate recommendations and consensus on laparoscopic radical resection of gallbladder cancer. This consensus includes several parts: safety, preoperative evaluation, indications, surgical team, positioning of patient and trocars, intraoperative frozen examination, lymph node dissection, liver resection,bile duct resection, etc. Furthermore, suggestions on the principle of treatment, surgical procedures, and precautions were also provided for patients with delayed diagnoses of gallbladder cancer undergoing resection. This consensus aims to offer valuable suggestions for the standardization of laparoscopic radical resection of gallbladder cancer.

Outcomes of patients with gallbladder cancer presenting with acute cholecystitis

The main purpose of this study is to explore the outcomes of patients found to have gallbladder cancer during investigation and diagnosis of acute cholecystitis. The incidence of primary gallbladder cancer co-existing in acute cholecystitis is not well defined in the literature, with anecdotal reports suggesting that they experience worse outcomes than patients with gallbladder cancer found incidentally.MethodsA retrospective review of all patients with gallbladder cancer managed at the Canberra Health Service between 1998 and May 2022 were identified and reviewed.ResultsA total of 65 patients were diagnosed with primary gallbladder cancer during the study period with a mean age of 70.4 years (SD 11.4, range 59–81.8 years) and a female preponderance (74% versus 26%) with a ratio of 2.8. Twenty (31%) patients presented with acute calculus cholecystitis and were found to have a primary gallbladder cancer. This group of patients were older and predominantly female, but the difference was not statistically significant. The overall 5-year survival in the cohort was 20% (stage 1 63%, stage 2 23%, stage 3 16%, and stage 4 0%). There was no statistically significant difference in survival between those who presented with acute cholecystitis vs other presentations.ConclusionsA third of the patients with gallbladder cancer presented with acute cholecystitis. There was no statistically significant difference in survival in those with bile spillage during cholecystectomy as well those presenting with acute cholecystitis.

MicroRNA-34a-5p: A pivotal therapeutic target in gallbladder cancer

Gallbladder cancer incidence has been increasing globally, andit remains challenging to expect long prognosis with the current systemic chemotherapy. We identified a novel nucleic acid-mediated therapeutic target against gallbladder cancer by using innovative organoid-based gallbladder cancer models generated from KrasLSL-G12D/+; Trp53f/f mice. Using comprehensive microRNA expression analyses and a bioinformatics approach, we identified significant microRNA-34a-5p downregulation in both murine gallbladder cancer organoids and resected human gallbladder cancer specimens. In three different human gallbladder cancer cell lines, forced microRNA-34a-5p expression inhibited cell proliferation and induced cell-cycle arrest at the G1 phase by suppressing direct target (CDK6) expression. Furthermore, comprehensive RNA sequencing revealed the significant enrichment of gene sets related to the cell-cycle regulators after microRNA-34a-5p expression in gallbladder cancer cells. In a murine xenograft model, locally injected microRNA-34a-5p mimics significantly inhibited gallbladder cancer progression and downregulated CDK6 expression. These results provide a rationale for promising therapeutics against gallbladder cancer by microRNA-34a-5p injection, as well as a strategy to explore therapeutic targets against cancers using organoid-based models, especially for those lacking useful genetically engineered murine models, such as gallbladder cancer.

Projected Incidence of Hepatobiliary Cancers and Trends Based on Age, Race, and Gender in the United States.

Identifying the projected incidence of hepatobiliary cancers and recognizing patient cohorts at increased risk can help develop targeted interventions and resource allocation. The expected incidence of subtypes of hepatobiliary cancers in different age groups, races, and genders remains unknown. Historical epidemiological data from the Surveillance, Epidemiology, and End Results (SEER) database was used to project future incidence of hepatobiliary malignancies in the United States and identify trends by age, race, and gender. Patients ≥18 years of age diagnosed with a hepatobiliary malignancy between 2001 and 2017 were included. US Census Bureau 2017 National Population projects provided the projected population from 2017 to 2029. Age-Period-Cohort forecasting model was used to estimate future births cohort-specific incidence. All analyses were completed using R Statistical Software. We included 110381 historical patients diagnosed with a hepatobiliary malignancy between 2001 and 2017 with the following subtypes: hepatocellular cancer (HCC) (68%), intrahepatic cholangiocarcinoma (iCCA) (11.5%), gallbladder cancer (GC) (8%), extrahepatic cholangiocarcinoma (eCCA) (7.6%), and ampullary cancer (AC) (4%). Our models predict the incidence of HCC to double (2001 to 2029) from 4.5 to 9.03 per 100,000, with the most significant increase anticipated in patients 70-79 years of age. In contrast, incidence is expected to continue to decline among the Asian population. Incidence of iCCA is projected to increase, especially in the white population, with rates in 2029 double those in 2001 (2.13 vs. 0.88 per 100,000, respectively; p < 0.001). The incidence of GC among the black population is expected to increase. The incidence of eCCA is expected to significantly increase, especially among the Hispanic population, while that of AC will remain stable. The overall incidence of hepatobiliary malignancies is expected to increase in the coming years, with certain groups at increased risk. These findings may help with resource allocation when considering screening, treatment, and research in the coming years.

Development of the EULAT eCollect application for electronic data collection within the European-Latin American consortium towards eradication of preventable gallbladder cancer - EULAT Eradicate GBC

The European-Latin American Consortium towards Eradication of Preventable Gallbladder Cancer (GBC) - EULAT Eradicate CVB is collecting high-quality data and samples in four Latin American countries with a high incidence of GBC: Argentina, Bolivia, Chile and Peru. The goal is to build a unique biorepository integrated with a customized informatics platform, identify, validate, and functionally characterize novel GBC risk biomarkers, and develop GBC prediction models integrating epidemiological and genetic-molecular risk factors. We decided to develop the electronic data collection application EULAT eCollect to facilitate the retrieval of socio-demographic, clinical, lifestyle, nutritional, and sample information from the 15,000 Latin Americans we are enrolling. The EULAT eCollect app reduces the time spent by study participants, limits the use of paper and ink, minimizes the costs and errors associated with completing written forms and their subsequent digitization, and allows close monitoring of local recruitment rates and data quality. We describe in this article the design and implementation of EULAT eCollect, which started with the specification of functional and non-functional requirements and ended with the implementation and subsequent validation of the four application modules: I Socio-demographic interview, II Sample information, III Case report form, and IV Food frequency questionnaire. We present both general and technical results and our experience with the Open Data Kit software, which may be of interest for future research projects, especially those on personalized cancer prevention conducted in low- and middle-income regions.

Gastrointestinal cancer trends in the Hispanic population: A SEER database population study (2000-2019).

725 Background: Cancer continues to be the leading cause of death in the Hispanic population. Gastrointestinal cancer surveillance data in Hispanic individuals has only recently become available in the last 3 decades. Differences in incidence rates among Hispanics and Non-Hispanic Whites (NHWs) need further elucidation. In this study, we analyzed trends in Hispanics and NHW populations across multiple gastrointestinal cancers. Methods: Gastrointestinal cancers (liver, colon and rectum, pancreas, esophagus, gallbladder, stomach, small intestine, anus, anal canal and anorectum) diagnosed between 2000-2019 were identified in the Surveillance, Epidemiology, and End Results Program (SEER) Database. We calculated incidence rates, confidence intervals and incidence rate ratios. Rates are per 100,000 and age adjusted to the 2000 US standard population. Rate ratios are the rounded rates in Hispanic individuals divided by the rounded rates in NHWs. Results: There was a higher incidence of liver, gallbladder, and stomach cancers among Hispanics when compared to NHWs between the years 2000-2019. Liver cancer incidence rate is (11.5 per 100,000) in Hispanics compared with (6.3 per 100, 000) in NHWs with an incidence rate ratio of 1.8. Gallbladder cancer incidence rate is (2.2 per 100,000) in Hispanics compared with (0.9 per 100,000) in NHWs with an incidence rate ratio of 2.4. Stomach cancer is (10.9 per 100,000) in Hispanics compared with (5.7 per 100,000) in NHWs with an incidence rate ratio of 1.9. The lowest incidence rate ratio was seen for anus, anal canal and anorectum cancers in Hispanics compared to NHWs. The incidence rate is (1.2 per 100,000) in Hispanics compared with (2.1 per 100,000) in NHWs with an incidence rate ratio of 0.6. Remaining cancers had incidence rate ratios less than 1.0 and were more likely to occur in NHWs. Conclusions: This study illustrates differing incidence rates of multiple gastrointestinal cancers among Hispanics compared to NHWs. Liver, gallbladder and stomach cancer incidence rates in Hispanics is double that of NHWs. Interestingly, the remaining gastrointestinal cancers had higher incidence rates among NHWs. Further research is warranted to understand the differences in cancer risk within the Hispanic population as well as healthcare access, language barriers and cultural differences that may play a role.[Table: see text]

Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors.

Risk factors of gallbladder cancer (GBC) are not well-defined resulting in greater than 60% of GBCs being diagnosed incidentally following cholecystectomy performed for presumed benign indications. As most localized GBCs require more extensive oncologic surgery beyond cholecystectomy, this study aims to examine factors associated with incidentally found GBC to improve preoperative and intraoperative diagnoses. The American College of Surgeons National Surgical Quality Improvement Program Database from 2007 to 2017 was used to identify cholecystectomies performed with and without a final diagnosis of GBC. Univariate and multivariable logistic regressions were used to compare demographic, intraoperative, and postoperative characteristics among those with and without a diagnosis of GBC. The incidence of GBC was observed to be 0.11% (441/403,443). Preoperative factors associated with risk of GBC included age > 60 (OR 6.51, p < .001), female sex (OR 1.75, p < .001), history of weight loss (2.58, p < .001), and elevated preoperative alkaline phosphatase level (OR 1.67, p = .001). Open approach was associated with 7 times increased risk of GBC compared to laparoscopic approach (OR 7.33, p < .001). In addition to preoperative factors and surgical approach, longer mean operative times (127min vs 70.7min, p < .001) were significantly associated with increased risk of GBC compared to benign final pathology. This study demonstrates that those with incidentally discovered GBC at cholecystectomy are unique from those undergoing cholecystectomy for benign indications. By identifying predictors of GBC, surgeons can choose high risk individuals for pre-operative oncologic evaluation and consider better tools for identifying GBC such as intraoperative frozen pathology.

Рак желчного пузыря: заболеваемость, факторы риска, диагностика

Aim. To analyze current data on the incidence, risk factors, diagnostic methods and prevention of gallbladder cancer (GBC). Key points. GBC is a malignant tumor arising from the epithelium of the gallbladder, characterized by local and vascular invasion, extensive regional lymphogenous and hematogenous metastasis. GBC is the most common malignant tumor of the biliary tract, characterized by high malignancy and low 5-year survival rate. In international recommendations, gastrointestinal tract is considered as a natural stage of the course of biliary pathology: dyskinesia — cholecystitis — cholelithiasis — GBC. Globally, the incidence of GBC varies significantly among different geographic regions, reaching 27 per 100,000 population in Chile. In Russia, according to the Federal State Statistics Service, the incidence of GBC in 2019 was 1.4 per 100 thousand among men, and 2.5 per 100 thousand among women. The incidence of GBC is associated with female gender and increasing age. In the pathogenesis of gallstones, decisive importance is attached to long-term inflammatory changes in the epithelium due to mechanical trauma to the mucous membrane of the gallbladder by stones and a probable increase in the proportion of secondary bile acids in the bile. In the diagnosis of GBC, the recommendations of the Japanese Society of Hepato-Biliary-Pancreatic Surgery, in the first step, particular importance is attached to ultrasound examination of the abdominal organs and biochemical blood test. For a more detailed study, computed tomography, magnetic resonance imaging, magnetic resonance cholangiopancreatography, endosonography, retrograde cholangiopancreatography, oral cholangioscopy and positron emission tomography are useful. Gallstone disease is one of the five most significant risk factors. The remaining 4 leading risk factors for GBC — ethnicity, genetic predisposition, lifestyle factors (excess weight) and biliary tract infections — are common risk factors for patients with cholelithiasis. The risk of developing GBC increases significantly in patients with stones larger than 2 cm and with the duration of the pathology for more than 5 years. Another significant risk factor for GBC is patients with gallbladder polyps, therefore the article presents the main recommendations of European associations for the management of patients with gallbladder polyps. Conclusion. GBC is currently considered as a possible and natural stage in the course of cholelithiasis. The risk of developing GBC increases significantly in patients with cholelithiasis and gallbladder polyps. Considering the above, diagnosis of possible complications in elderly patients with cholecystitis and gallstone disease should include a thorough clinical, laboratory and instrumental examination. Preventive measures for people with risk factors for GBC should include optimizing diet, weight loss, and, if possible, expanding the physical activity regime. Taking ursodeoxycholic acid preparations helps reduce the content of hydrophobic bile acids in bile and reduces the likelihood of complications of biliary pathology. Keywords: gallbladder cancer, cholelithiasis, gallbladder polyps, diagnosis, morbidity.

Epidemiology of gallbladder cancer in India 2018–2023

ABSTRACT India is a high-incidence area for gallbladder cancer (GBC), contributing approximately 10% of the global GBC burden. Within the country, the incidence is notably high in North, North-East, Central, and Eastern regions, whereas it is less common in South and West India. The incidence has been steadily rising in both genders. Patients often present with advanced disease, which carries a dismal prognosis. Unlike the West, GBC in India typically affects younger patients in their fifth and sixth decades of life. Gallstones are present in 80% of Indian GBC patients, increasing the vulnerability of the gallbladder to mucosal injury. However, the incidence of GBC is disproportionate to the prevalence of gallstones in the country. Additional cofactors such as older age, lower socioeconomic status, chronic Salmonella typhi infection, Helicobacter pylori infection, exposure to pollutants, heavy metals, chemicals, adulterated mustard oil, and smoking in patients with gallstones have been identified as promoters of carcinogenesis. These risk factors act additively, resulting in a higher incidence of GBC and accelerating its development. Environmental risk factors, including soil and water contamination by industrial wastes, agricultural effluents, and human sewage, have also been identified as putative risk factors. The combination of a toxic environment, a vulnerable gallbladder, and a susceptible host plays a key role in the pathogenesis of GBC in India. Large multicentric comprehensive studies are required to assess the attributable risk of each identified putative risk factor. This will aid in formulating cost-effective national strategies to prevent GBC-related mortality in the country. Meanwhile, maintaining a high index of suspicion to detect incidental GBC and improving access to health-care facilities for appropriate management of gallstones will help reduce GBC-related mortality.

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

Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. 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. 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.