Gallstones are a common disease of the digestive system, and its complications pose serious risks to human health and impose a significant economic burden on society. Inadequate dietary potassium intake may be associated with the development of gallstones, however, there is a lack of current epidemiological research on this topic.

The purpose of this research was a preliminarily exploration of the relationship between dietary potassium intake and the prevalence of gallstones, providing direction for the next step of quantitativeanalysis on the association between dietary potassium intake and the prevalence of gallstones.

Data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017 to 2020 were used for a cross-sectional analysis. The presence of gallstones was assessed based on the NHANES questionnaire data for the corresponding time frame. To investigate the link between dietary potassium consumption and the likelihood of developing gallstones, multiple logistic regression models were used. Subgroup analyses were conducted based on variables such as age, gender, poverty-to-income ratio (PIR), body mass index (BMI), hypertension, diabetes, dietary supplement use, and physical activity. An analysis of linear associations was carried out using smoothing curves.

The study comprised 6,223 participants aged 20 years and older, excluding pregnant individuals. Among these participants, 671 were diagnosed with gallstones. In the final adjusted model, with a 95% confidence interval (CI) of 0.70 to 0.93, it was determined that dietary potassium intake and gallstone incidence were negatively correlated (OR = 0.81, p = 0.003). Individuals in the highest tertile of dietary potassium intake experienced a 31% lower risk of developing gallstones compare to those in the lowest tertile (OR = 0.69, 95% CI: 0.51-0.94, p = 0.017). In Model 1, the prevalence of gallstones exhibited an inverse relationship with dietary potassium intake. This negative association persisted even after stratifying by variables such as age, gender, PIR, BMI, hypertension, diabetes, dietary supplement use, and physical activity. Sensitivity analyses demonstrated the stability of this relationship.

Our research revealed that increased dietary potassium intake is associated with a lower prevalence of gallstones. Nevertheless, additional prospective studies are required to confirm a precise dietary potassium intake level and the long-term effects of potassium metabolism on gallstone formation.

This study aims to provide updated estimate on the global burden of Gallbladder cancer (GBC) in 2022 and to predict the trends through the year 2042.

Data were extracted from GLOBOCAN 2022 database. Incidence and mortality rates were calculated by sex, country, world region and Human Development Index (HDI). Trends up to the year 2042 were predicted based on global demographic projections by HDI.

Worldwide, there were 122,469 new GBC cases and 89,045 deaths identified in 2022. While the highest absolute number was observed in South Central Asia and Eastern Asia, particularly India and China, countries in South America, particularly Bolivia, showed the highest age-standardised rate. Medium HDI countries showed more than double the incidence and mortality rates compared to low HDI countries. Over half of GBC cases and deaths occurred in individuals aged 50-74 years. Predictions indicate a 65.3 % increase in new cases and a 67.6 % increase in deaths by 2042, with High HDI countries and Low HDI countries experiencing the largest absolute and percentage increases, respectively.

The global burden of GBC is substantial, especially concentrated in South Central Asia, Eastern Asia and South America. With significant increase of burden over the next 20 years, there is an urgent need for effective cancer control strategies in regions exhibiting great GBC burden.

Background and Objectives: Gallbladder cancer (GBC) is a biologically aggressive malignancy characterised by poor survival outcomes often attributed to delayed diagnosis due to nonspecific clinical presentations. Paraneoplastic syndromes (PNSs), atypical symptoms caused by cancer itself, may serve as valuable indicators for timely diagnosis, particularly in malignancies with nonspecific features. Understanding the manifestations of PNSs in GBC is, therefore, critical. This systematic review collates case studies documenting the association of PNS with GBC, including subsequent management and clinical outcomes. Materials and Methods: A comprehensive search of PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases yielded 49 relevant articles. Upon searching other information sources, two more relevant articles were identified via citation sources. Results: The paraneoplastic syndromes were classified according to haematological (leukocytosis), dermatological (inflammatory myositis like dermatomyositis and polymyositis, acanthosis nigricans, Sweet's syndrome, exfoliative dermatitis), neurological, metabolic (hypercalcemia, hyponatremia), and others (chorea). The analysis included the age, sex, and country of origin of the patient, as well as the time of PNS diagnosis relative to GBC diagnosis. Furthermore, common presenting complaints, investigations, and effectiveness of treatment modalities using survival time were assessed. Conclusions: While PNS management can offer some benefits, oncologic outcomes of GBC are largely poor. The majority of PNS in GBC are reported in advanced stages, and, hence, PNS has a minimal role in early diagnosis. PNS management can improve a patient's quality of life, and thus recognition and treatment are important considerations in the holistic management of GBC patients.

Gallstones (GS) are one of the most common gastrointestinal diseases. Till date medical cure for gallstones is not available. Unlike kidney stones, GS need cholecystectomy, i.e. surgical removal of the gallbladder (GB). GS are asymptomatic in most of the cases. They are the cause of GB inflammation that is chronic cholecystitis. GS have been supposed to be an important risk factor for causing gallbladder cancer (GBC). But the exact relationship between GS and GBC is not clear till date. In this study, we have compared the gallstones from cholelithiasis patients with those from patients with GBC. The size, volume and weight of these GS were comparatively analyzed. We have performed compositional as well as heavy metal analysis of the GS for both groups of patients by FTIR, FESEM and ICP-MS. The size and volume of gallstones from GBC patients was found to be on the higher side. We found that the GS from GBC patients were only of cholesterol type while those from cholelithiasis patients were mixed and pigment type. Heavy metals such as As, Pb, Fe were detected in higher concentration in GS from GBC patients. Thus, heavy metals detected in the gallstones could be regarded as the contributing factors to GBC. Further the mechanism of initiation of cancer by heavy metals in presence of cholesterol GS needs to be studied, so that novel strategies can be developed for the prevention of GBC.

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.

Identifying past, present, and future temporal trends in gallbladder and biliary tract cancer (GBTC) can increase public awareness and promote changes in prevention and treatment strategies.

The incidence and death rates of GBTC between 1990 and 2021 were extracted from the Global Burden of Disease study 2021 and assessed according to country, region, year, age, and sex. Time trends were measured using the average annual percentage change (AAPC) and projections of the burden of disease for 2022 to 2045 were made using the Bayesian age-period-cohort model.

In 2021, there were 216,768.3 new cases (95% uncertainty interval [UI], 181,888.0-245,237.6) and 171,961.2 deaths (95% UI, 142,351.8-194,238.4) in GBTC globally. The increases in incidence and deaths were 101.09% and 74.26%, respectively, compared with 1990. The GBTC burden was higher in females and older adults. However, age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) trended downward from 1990 to 2021, with AAPC at -0.39 (95% CI, -0.52 to -0.26) and -0.88 (95% CI, -0.96 to -0.79), respectively. Although the ASIR and ASDR for both sexes are projected to decline gradually from 2022 to 2045, the incidence and deaths are expected to increase steadily. In addition, the global proportion of GBTC deaths owing to high body mass index in 2021 was 12.66% for females and 10.48% for males, which did not change significantly from 1990.

GBTC is becoming a major global health burden, especially among females and older adults. Given the increasing burden of an aging population, there is a need to reduce the incidence of this disease by adopting effective strategies and measures targeting risk factors.

Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3-8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4-17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5-16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3-35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3-14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2-12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8-100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6-17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.

There is a paucity of literature regarding the effect of anesthetic techniques on antitumor immunity, especially in gall bladder malignancies. We designed a study to compare the effect of propofol-based total intravenous anesthesia and sevoflurane-based general anesthesia-on antitumor immunity, including tumor growth factor-β (TGF-β), T-helper cell profile, and inflammatory markers. A pilot prospective randomized trial was conducted in 64 patients undergoing surgery for gall bladder malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of ASA physical status I-III fulfilling the inclusion criteria were randomized to either group S (sevoflurane-based general anesthesia) or group T (propofol-based total intravenous anesthesia). Preoperative (morning of surgery) and postoperative (24 h and 1 month after surgery) blood samples were obtained. Demographic profile and preoperative parameters were comparable between both groups. There was a statistically significant difference in the postoperative value of TGF-β (higher in group T). There was a statistically significant difference in postoperative interleukin-17A value (indicative of TH17 cells), and it was found to be higher in group S. Propofol-based TIVA increases serum TGF-β levels. At the same time, Sevoflurane modulates T-helper cells-based immunity to increase TH17 cells in patients with gall bladder cancer. Multiple larger studies will be required to validate the results and provide useful recommendations.

Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.

This study evaluates the effectiveness of machine learning (ML) models that incorporate clinical and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG)-positron emission tomography (PET)-radiomic features for predicting outcomes in gallbladder cancer patients.

The study analyzed 52 gallbladder cancer patients who underwent pre-treatment [18F]-FDG-PET/CT scans between January 2011 and December 2021. Twenty-seven patients were assigned to the training cohort between January 2011 and January 2018, and the data randomly split into training (70%) and validation (30%) sets. The independent test cohort consisted of 25 patients between February 2018 and December 2021. Eight clinical features (T stage, N stage, M stage, Union for International Cancer Control [UICC] stage, histology, tumor size, carcinoembryonic antigen level, and carbohydrate antigen 19-9 level) and 49 radiomic features were used to forecast progression-free survival (PFS). Three feature selection methods were applied including the univariate statistical feature selection test method, least absolute shrinkage and selection operator Cox regression method and recursive feature elimination method, and two ML algorithms (Cox proportional hazard and random survival forest [RSF]) were employed. Predictive performance was assessed using the concordance index (C-index).

Two clinical variables (UICC stage, N stage) and three radiomic features (total lesion glycolysis, grey-level size-zone matrix_grey level non-uniformity and grey-level run-length matrix_run-length non-uniformity) were identified by the statistical feature selection method as significant for PFS prediction. The RSF model incorporating these features demonstrated strong predictive performance, with C-indices above 0.80 in both training and testing sets (training 0.81, testing 0.89). This model almost closely matched the actual and predicted progression timelines with a low mean absolute error of 1.435, a median absolute error of 0.082, and a root mean square error of 2.359.

This study highlights the potential of using ML approaches with clinical and pre-treatment [18F]-FDG-PET radiomic data for predicting the prognosis of gallbladder cancer.

Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis, often diagnosed at advanced stages due to subtle early symptoms. Recent studies have provided a comprehensive view of GBC's genetic and mutational landscape, uncovering crucial pathways involved in its pathogenesis. Environmental exposures, particularly to heavy metals, have been linked to elevated GBC risk. Established signaling pathways, including hormonal, apoptotic, metabolic, inflammatory, and DNA damage repair pathways, are integral to GBC progression, and evidence points to the involvement of specific germline and somatic mutations in its development. Key mutations in genes such as KRAS, TP53, IDH1/2, ERBB, PIK3CA, MET, MYC, BRAF, MGMT, CDKN2A and p16 have been identified as contributors to tumorigenesis, with additional alterations including chromosomal aberrations and epigenetic modifications. These molecular insights reveal several potential therapeutic targets that could address the limited treatment options for GBC. Promising therapeutic avenues under investigation include immune checkpoint inhibitors, tyrosine kinase inhibitors, tumor necrosis factor-related apoptosis-inducing ligands (TRAIL), and phytochemicals. Numerous clinical trials are assessing the efficacy of these targeted therapies. This review provides a detailed examination of GBC's genetic and mutational underpinnings, highlighting critical pathways and emerging therapeutic strategies. We discuss the implications of germline and somatic mutations for early detection and individualized treatment, aiming to bridge current knowledge gaps. By advancing our understanding of GBC's molecular profile, we hope to enhance diagnostic accuracy and improve treatment outcomes, ultimately paving the way for precision medicine approaches in managing GBC.

Background Gallbladder carcinoma (GBC) is a rare but highly aggressive malignancy, often discovered incidentally during cholecystectomy for symptomatic cholelithiasis. Despite significant geographic variation, the association between gallstones and GBC is well-documented, with chronic inflammation from gallstones potentially contributing to carcinogenesis. Objective This study aims to determine the prevalence of incidental GBC in patients undergoing cholecystectomy for symptomatic cholelithiasis at a tertiary care hospital in Peshawar, Pakistan. Materials and methods This retrospective cohort study was conducted at the General Surgery Department, Hayatabad Medical Complex, Peshawar, from February 2, 2021, to July 1, 2024. A total of 230 patients, aged 18-55 years and diagnosed with symptomatic cholelithiasis, were included. Cholecystectomy was performed, and all excised gallbladders were histopathologically examined for carcinoma. Statistical analysis was conducted using IBM SPSS (version 26), with a significance threshold of p ≤ 0.05. Results Out of 230 patients, 7 (3.04%) were found to have incidental GBC upon histopathological examination. Among these, five had adenocarcinoma, and two had papillary carcinoma. The carcinoma was confined to the mucosa (T1a) in four cases, while three cases had deeper invasion (T1b). Patients with incidental carcinoma had a significantly longer symptom duration (mean: 14.2 ± 3.1 months) and were older on average (mean age: 49.2 ± 4.3 years) compared to non-carcinoma patients (p = 0.001 and p = 0.002, respectively). No malignancy was suspected intraoperatively in any case. Conclusion Incidental GBC was present in 3.04% of patients undergoing cholecystectomy for symptomatic cholelithiasis, with longer symptom duration and older age as significant risk factors. The findings underscore the importance of histopathological examination of cholecystectomy specimens in regions with high gallstone prevalence, as early detection of incidental carcinoma can facilitate timely oncological intervention.

Gallbladder cancer is the most common biliary tract malignancy, often detected incidentally post-cholecystectomy or at an advanced stage, historically linked to a poor prognosis. Advances in minimally invasive surgery and systemic therapies have improved outcomes. Global incidence varies, with risk factors including gender, age, gallbladder disease history, and polyp size influencing malignancy risks. Management involves cross-sectional imaging, staging laparoscopy in select cases, and radical cholecystectomy with lymphadenectomy and adjuvant therapy, though its use is limited. Trials are ongoing assessing the role of neoadjuvant therapy. Prognosis depends on the tumor stage, with early detection crucial for long-term survival.

Pure gallbladder squamous cell carcinoma is rare. Adenocarcinoma is the foremost malignant pathology of gallbladder cancer. Simultaneously, squamous cell carcinoma accounts for only 1% of malignant gallbladder tumors. They are often advanced at diagnosis and associated with a poor prognosis. The patient was a 37-year-old man diagnosed with poorly differentiated squamous cell carcinoma of the gallbladder. Cholecystectomy, right hemicolectomy, hepatic wedge resection, and regional lymph node dissection were performed, and then he received six courses of adjuvant chemotherapy with the FOLFOX regimen. After 2 months, liver metastasis was diagnosed, and a chemotherapy regimen consisting of gemcitabine, cisplatin, and pembrolizumab was started. After three courses, stable disease was seen. Surgery is the main treatment. There is no consensus about the best adjuvant treatment. The results obtained from this patient might help elucidate the role of adjuvant therapies in treating this rare case report.

Treatment for advanced gallbladder cancer (GBC) remains controversial, with various recommendations regarding the choice and combination of surgery and adjuvant therapy. The present article is targeting for the exploration of optimal treatment models for advanced GBC.

AJCC (American Joint Committee on Cancer, 8th edition) stage III and stage IV GBC, were defined as advanced GBC. Patients with advanced GBC were identified using the Surveillance, Epidemiology, and End Results (SEER) database and departmental cohort. Because of the most representative, only gallbladder adenocarcinoma (GBAC) patients were selected. Based on their surgical status (No, Non-radical and Radical surgery), chemotherapy status (Chemotherapy, No chemotherapy), and radiotherapy status (Radiotherapy, No radiotherapy), treatment models were categorized. For the purposes of evaluating the treatment outcomes of various treatment models and determining the risk element for cancer-specific survival (CSS), Cox regression analysis was applied. Kaplan-Meier curves were used before and after adjusting for covariates, with log-rank tests used to analyze discrepancies between curves. Immunotherapy was analyzed using clinical data from departmental cohort. Finally, to compensate for the limitations of the database, a review examines the progress in treatment models for advanced GBC.

5,154 patients aged over 18 years with solitary primary advanced GBC were identified from the SEER database. In advanced GBC patients, the treatment model has emerged as a significant prognostic factor. "Radical surgery + Chemotherapy + Radiotherapy" models maximally improved the CSS of advanced GBC before and after adjusting for covariates, while "No surgery + No chemotherapy + No radiotherapy" model had the lowest CSS. The present conclusions were supported even after subgroup analysis by AJCC stage. The efficacy of immunotherapy was demonstrated in the departmental cohort analysis. Additionally, this article provides a comprehensive overview of recent advancements in various emerging treatment strategies.

Even when optimal treatment model cannot be pursued, providing comprehensive combinations of treatments to advanced GBC patients whenever possible is always beneficial for their survival.

Gallbladder cancer is often associated with poor prognosis, especially when patients experience early recurrence after surgery. Machine learning may improve prediction accuracy by analysing complex non-linear relationships. The aim of this study was to develop and evaluate a machine learning model to predict early recurrence risk after resection of gallbladder cancer.

In this cross-sectional study, patients who underwent resection of gallbladder cancer with curative intent between 2001 and 2022 were identified using an international database. Patients were assigned randomly to a development and an evaluation cohort. Four machine learning models were trained to predict early recurrence (within 12 months) and compared using the area under the receiver operating curve (AUC).

Among 374 patients, 56 (15.0%) experienced early recurrence; most patients had T1 (51, 13.6%) or T2 (180, 48.1%) disease, and a subset had lymph node metastasis (120, 32.1%). In multivariable Cox analysis, resection margins (HR 2.34, 95% c.i. 1.55 to 3.80; P < 0.001), and greater AJCC T (HR 2.14, 1.41 to 3.25; P < 0.001) and N (HR 1.59, 1.05 to 2.42; P = 0.029) categories were independent predictors of early recurrence. The random forest model demonstrated the highest discrimination in the evaluation cohort (AUC 76.4, 95% c.i. 66.3 to 86.5), compared with XGBoost (AUC 74.4, 53.4 to 85.3), support vector machine (AUC 67.2, 54.4 to 80.0), and logistic regression (AUC 73.1, 60.6 to 85.7), as well as good accuracy after bootstrapping validation (AUC 75.3, 75.0 to 75.6). Patients classified as being at high versus low risk of early recurrence had much worse overall survival (36.1 versus 63.8% respectively; P < 0.001). An easy-to-use calculator was made available (https://catalano-giovanni.shinyapps.io/GallbladderER).

Machine learning-based prediction of early recurrence after resection of gallbladder cancer may help stratify patients, as well as help inform postoperative adjuvant therapy and surveillance strategies.

Gallbladder neuroendocrine carcinoma (GNEC) is indeed a relatively rare malignant tumor of the gallbladder with neuroendocrine differentiation and the ability to produce and secrete a number of neurotransmitters and hormones, characteristics that make its clinical presentation and biological behavior likely to be different from those of other types of gallbladder cancer. Current treatment mostly relies on surgery and adjuvant chemotherapy and radiotherapy.

We report a 53-year-old middle-aged male patient who underwent radical surgery for gallbladder malignancy after a diagnosis of neuroendocrine carcinoma of the gallbladder.

Diagnosis of neuroendocrine carcinoma of the gallbladder based on the return of pathologic findings.

After local progression of postoperative chemotherapy with the first-line regimen of etoposide + cisplatin, an immune checkpoint inhibitor (traplizumab) + FOLIFIRI (fluorouracil + calcium folinate + irinotecan) regimen was used.

The patient achieved 20 months of clinical survival and ultimately died of myelosuppression.

The use of immune checkpoint inhibitors may become an effective tool in the treatment of neuroendocrine carcinoma of the gallbladder.

Retroperitoneal lymphadenopathy is considered a metastatic disease in GBC; however, some surgical series of radical surgery with enlarged RPLN who underwent RPLN dissection have shown results marginally inferior to those without enlarged RPLN. Radiological RPLN comprises a major proportion of advanced non-metastatic GBC. There is dilemma in the intent of treatment to be offered in such cases. We are reporting our series of outcome of GBC with RPLN treated with first-line CT followed by consolidation CTRT.

Non-metastatic locally advanced GBC with good performance status (KPS ≥ 80) were initiated on first-line CT (cisplatin-gemcitabine), and thereafter, responders were evaluated by CECT-angiography and PET-CT scan for resectability. If found unresectable, they were offered consolidation CTRT to a dose of 45 Gy by conventional fractionation (3D-CRT technique) along with concurrent capecitabine at 1250 mg/m2 to GBC and regional lymphatics including RPLN. Thereafter, boost dose of 9 Gy/5# was given to GBC only. Response assessment was done using CECT abdomen by RECIST criteria v 1.1. Outcomes (overall survival) of the two groups (RPLN vs non-RPLN) were computed with Kaplan-Meier survival curves and chi-square tests using SPSS v 20.

Among 189 patients of advanced non-metastatic GBC recruited from 2011 to 2022, 80 had RPLN. The demographic features of both groups were comparable. Overall, 68% of the patients were women, 30% underwent upfront stenting for obstructive jaundice, and 90% had T3 and T4 disease. Only 10% had undergone upfront laparoscopic staging and had pathologically proven RPLN. Forty percent of the patients received four cycles of CT only and 50% of the patients received six cycles or more and 33% received CTRT. By RECIST criteria, 10% vs 16% achieved complete response (CR), 39% vs 41% achieved partial response (PR), 16% vs 15% achieved stable disease (SD), 2.7% vs 6% had disease progression (PD), and 14.5% vs 3.7% were non-evaluable in non-RPLN group vs RPLN group, respectively. 12% vs 6% could undergo radical surgery in non-RPLN group vs RPLN group (p = 0.03). The median OS was 9 months (95% CI 7.6-10.3 months) vs 10 months (95% CI 8-9.8 months) (p = NS) in non-RPLN group vs RPLN group, respectively. In those who received CT only, the median OS was 7 months vs 8 months, while in those who received CT followed by CTRT, the median OS was 14 months vs 13 months (p = 0.65) in non-RPLN group vs RPLN group, respectively.

Based on this analysis, we conclude that RPLN constitutes a major proportion of advanced non-metastatic GBC and has outcomes similar to those without RPLN if treated with radical intent. RPLN should not be considered a metastatic disease and should be treated with radical intent.

BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC.

Cholelithiasis is the most well-recognized risk factor for gallbladder cancer (GBC), the predominant biliary-tract malignancy; however, credibility on other modifiable exposures remains uncertain. We performed a field-wide systematic review and meta-analysis on environmental factors associated with GBC.

We systematically searched Medline/PubMed and Embase up to May 8, 2023, to identify randomized and nonrandomized studies examining environmental factors for GBC. We conducted random-effects meta-analyses focusing on longitudinal studies. Evidence from case-control studies was considered complementary. Evidence credibility was graded by prespecified criteria including the random-effects estimate, 95% confidence interval (CI), P value, statistical heterogeneity, small-study effects, and robustness to unmeasured confounding.

We identified 215 eligible primary studies and performed 350 meta-analyses across 7 domains: lifestyle, reproductive, metabolic, dietary, infections, interventions, and contaminants and occupational exposures. Based on longitudinal evidence, body mass index (relative risk [RR] per 5-unit increase, 1.27; 95% CI, 1.21‒1.33), hip circumference (RR per 5-cm increase, 1.16; 95% CI, 1.11‒1.22), infection of bile ducts (RR, 31.7; 95% CI, 24.8-40.6), high parity (RR, 1.48; 95% CI, 1.30‒1.68), obesity (RR, 1.70; 95% CI, 1.44‒2.01), overweight (RR, 1.28; 95% CI, 1.14‒1.43), waist circumference (RR per 5-cm increase, 1.14; 95% CI, 1.10‒1.18), and waist-to-height ratio (RR per 0.1 increase, 1.49; 95% CI, 1.36‒1.64) were robustly associated with increased GBC risk, whereas high education (RR, 0.63; 95% CI, 0.49‒0.82) was associated with reduced risk (moderate-to-high credibility). Another 39 significant associations showed lower credibility, including different exposure scenarios of tobacco smoking, alcohol consumption, and insufficient physical activity.

This study offers a detailed appraisal and mapping of the evidence on modifiable factors for GBC. Further high-quality prospective studies are essential to validate emerging associations and inform preventive strategies in high-incidence areas. (Systematic review registration: CRD42023434673.).

Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021).

The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI).

In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors.

The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors.

Gallbladder cancers (GBCs) occur a decade earlier in India in comparison to the global occurrence, limiting the applicability of existing literature on age adjusted outcomes.

Patients who underwent surgery between 01.01.2010 and 31.12.2020 for GBC were analyzed. Patients were divided into three age groups: group 1(≤40 years), group 2(41-60 years), group 3(>60 years) and their outcomes were compared.

Total of 6190 patients were treated for suspected or diagnosed GBC with a median age of 57 years. Curative resection was performed in 749 (67.9%) patients, of whom 114 (16.2%), 471 (62.9%), and 164 (21.9%) patients were in groups 1, 2, and 3, respectively. 5-year disease-free survival (DFS) [46.8% vs. 58.5%, p = 0.031] and overall survival (OS)[53.5% vs. 66.6%, p = 0.05] of group 3 were significantly lower than group 1. Patient age (HR 1.021), AJCC stage (HR 6.413), pathologic residual disease in the gallbladder fossa (HR 2.44), and extranodal tumor deposits (HR 1.762) were identified as independent predictors of poor OS.

Gallbladder cancers in the Indian population show poorer outcomes with advancing age. Higher proportion of males in the elderly group with a more advanced stage at presentation are plausible reasons for poorer outcomes.

This research aimed to create a predictive model and an innovative risk classification system for patients with gallbladder cancer who undergo radical surgery.

A cohort of 1387 patients diagnosed with gallbladder cancer was selected from the SEER database. The researchers devised a prognostic tool known as a nomogram, which was subjected to assessment and fine-tuning using various statistical measures such as the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve, decision curve analysis (DCA), and risk stratification were included in the catalog of comparisons. An external validation set comprising 93 patients from Nanchong Central Hospital was gathered for evaluation purposes.

The nomogram effectively incorporated seven variables and demonstrated satisfactory discriminatory ability, as evidenced by the C-index (training cohort: 0.737, validation cohort: 0.730) and time-dependent AUC (>0.7). Additionally, calibration plots confirmed the excellent alignment between the nomogram and actual observations. Our investigation unveiled NRI scores of 0.79, 0.81, and 0.81 in the training group, while the validation group exhibited NRI values of 0.82, 0.77, and 0.78. Additionally, when evaluating CSS at three-, six-, and nine-year intervals using DCA curves, our established nomograms demonstrated significantly improved performance compared to the old model (P < 0.05), showcasing enhanced discriminatory ability. The results of the external validation set proved the above results.

The current investigation has devised a practical prognostic nomogram and risk stratification framework to aid healthcare practitioners in evaluating the postoperative outlook of individuals who have received extensive surgical treatment for gallbladder carcinoma.

Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention.

We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc. Further molecular mechanism was demonstrated with in vitro and in vivo studies.

The cell atlas unveiled an altered immune landscape across different pathological states of gallbladder diseases. GBC featured a more suppressive immune microenvironment with distinct T-cell proliferation patterns and macrophage attributions in different GBC subtypes. Notably, mutual exclusivity between stromal and immune cells was identified and remarkable stromal ecosystem (SC) heterogeneity during GBC progression was unveiled. Specifically, SC1 demonstrated active interaction between Fibro-iCAF and Endo-Tip cells, correlating with poor prognosis. Moreover, epithelium genetic variations within adenocarcinoma (AC) indicated an evolutionary similarity between adenoma and AC. Importantly, our study identified elevated olfactomedin 4 (OLFM4) in epithelial cells as a central player in GBC progression. OLFM4 was related to T-cell malfunction and tumour-associated macrophage infiltration, leading to a worse prognosis in GBC. Further investigations revealed that OLFM4 upregulated programmed death-ligand 1 (PD-L1) expression through the MAPK-AP1 axis, facilitating tumour cell immune evasion.

These findings offer a valuable resource for understanding the pathogenesis of gallbladder diseases and indicate OLFM4 as a potential biomarker and therapeutic target for GBC.

Lymph node metastasis (LNM) is one of the major prognostic factors in human gastrointestinal carcinomas (GICs). The lymph node-positive patients have poorer survival than node-negative patients. LNM is directly associated with the recurrence and poor survival of patients with GICs. The early detection of LNM in patients and designing effective therapies to suppress LNM may significantly impact the survival of these patients. The rapid progress made in proteomic technologies could be successfully applied to identify molecular targets for cancers at high-throughput levels. LC-MS/MS analysis enables the identification of proteins involved in LN metastasis, which can be utilized for diagnostic and therapeutic applications. This review summarizes the studies on LN metastasis in GICs using proteomic approaches to date.

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.

Gallbladder and biliary tract tumors are rare but highly fatal cancers. In patients diagnosed with unresectable/metastatic gallbladder cancer and cholangiocarcinomas, systemic chemotherapy is recommended if the patient's performance is good. Randomized studies on this subject are limited, and there is no standard treatment choice. The prognostic nutritional index (PNI) is a measurement calculated using albumin and absolute lymphocyte value, reflecting the immunological and nutritional status of the cancer patient. The aim of our study is to evaluate the prognostic effectiveness of PNI in unresectable/metastatic gallbladder and biliary tract cancers. The PNI was calculated using albumin and lymphocyte values at the time of diagnosis (10 x albumin g/dL + 0.005 x total lymphocyte/mm3). The relationship between PNI and overall survival (OS) and progression-free survival was examined. The prognostic nutritional index means of the patients included in the study was 44.8 (95% CI: 42.9-46.7), and the median was 44.77 (minimum: 22, maximum: 61.4). Receiver operating characteristic (ROC) analysis demonstrated a statistically significant prediction of patients' OS when the prognostic nutritional index was < 44 (AUC: 0.715, sensitivity: 54.8%, specificity: 33.3%; p=0.08). We evaluated the prognostic effectiveness of PNI in the subgroup of patients who could receive chemotherapy. In patients receiving chemotherapy, median survival was found to be 8.93 months in the PNI < 44 groups, while median survival was found to be 12.58 months in the PNI ≥ 44 group. The difference between both groups was statistically significant (p = 0.01). In univariate analysis, the Eastern Cooperative Oncology Group (ECOG) performance status, cancer antigen 19.9 (Ca 19.9), and PNI were statistically significant variables in predicting OS (p < 0.05). In multivariate analysis, the ECOG performance status, cancer antigen 19.9 (Ca 19.9), and PNI were found to be independent factors in predicting OS (p < 0.05). We believe that PNI can be used as a marker to assist the clinician in evaluating the prognosis of patients in the clinic and predicting treatment tolerance.

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.

Triglyceride glucose (TyG) index combined with obesity-related indicators [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC)], represents emerging methodologies for assessing insulin resistance. The objective of this investigation was to explore the correlation between TyG-related indices and gallstone disease.

The study included 3740 adults from the 2017-2020 period of the National Health and Nutrition Examination Survey. TyG-BMI, TyG-WC, and TyG-WHtR were integrated as both continuous and categorical variables within the multivariate logistic model, respectively to evaluate the connection between various TyG-related indices and gallstone disease. Additionally, restriction cubic splines and subgroup analysis were employed to deepen our understanding of this relationship.

When analyzed as continuous variables, positive correlations were observed between TyG-BMI, TyG-WC, TyG-WHtR and gallstone disease. The OR(95%CI) were 1.063(1.045,1.082) for TyG-BMI (per 10-unit), 1.026(1.018,1.034) for TyG-WC (per 10-unit) and 1.483(1.314,1.676) for TyG-WHtR (per 1-unit), respectively. When categorized into quartiles, these three TyG-related indices still show statistically significant associations with gallstone disease. Descending in order, the diagnostic capability for gallstone disease is demonstrated as follows: TyG-WHtR (AUC = 0.667), TyG-BMI (AUC = 0.647), and TyG-WC (AUC = 0.640).

There were significantly positive associations between TyG-related indices, including TyG-BMI, TyG-WC, and TyG-WHtR, and gallstone disease. Of these indices, TyG-WHtR demonstrated the most favorable performance in identifying the risk of gallstone disease.

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.

Introduction Gallbladder carcinoma is a rare but aggressive cancer of adults that affects females more than males. Its occurrence is more common in the regions of South America and Asia. Chronic inflammation and cholelithiasis are frequently associated risk factors of gallbladder carcinoma. The incidental discovery of a gallbladder carcinoma during cholecystectomy, gross or microscopic examination of the unsuspected gallbladder specimens is termed incidental gallbladder carcinoma (IGBC). Considering the lack of extensive studies on gallbladder carcinoma in the Eastern region of India, especially in Jharkhand, this study has been done to present the demographic and clinicopathological characteristics of gallbladder carcinoma in this region. Methods A retrospective and descriptive study was done at Rajendra Institute of Medical Sciences (RIMS), Ranchi, a tertiary care center in Jharkhand. The study sample comprised 2386 gall bladder cases received in the Department of Pathology over five years, from December 2018 to December 2023. Results Of 2368 specimens, 25 cases (n=25) were reported as primary gallbladder carcinoma. The female-to-male ratio was 4:1. Pain was the most common complaint by the patients. Of the 25 cases, 12 were suspected intra-operatively or diagnosed microscopically (IGBC). Most showed a mass at the neck. In six cases, no gross mass/lesion was seen. Cholelithiasis is present in 19/25 cases. Most cases showed adenocarcinoma (not otherwise specified). Out of the adenocarcinoma cases, most were well differentiated. At the time of diagnosis, most were at the pT2 stage. Twelve cases of IGBC were found. Eight out of 12 IGBC were early-stage carcinoma when diagnosed. Conclusion Twenty-five cases of gallbladder carcinoma were diagnosed in the last five years in our center, with 19 (76%) of them associated with cholelithiasis. Twelve (48%) of the cases were incidentally diagnosed either preoperatively or during gross/microscopic examination, and eight (66%) of those were discovered early, out of which five (62.5%) were observed to be in the T1b stage. At this stage, there is a diversion from the general surgical management of gallbladder carcinoma for a better prognosis. This underscores the significance of routine histopathological examination of gallbladder specimens, even if there is no preoperative suspicion of gallbladder carcinoma.

The aim of this study was to determine the 1- and 3-year overall survival rates. This prospective observational study was conducted at a tertiary care center in Bihar state, India. The study analyzed 228 patients in Bihar with a median age at diagnosis of 55 ± 12.05 years. The most common symptoms included upper abdominal pain (26.3%), weight loss (14%), and ascites (13.6%). The majority of patients presented at stage IV (72.8%), with liver metastasis being prevalent (61.4%). Interventional biliary drainage was performed in 9.6% of cases, and systemic chemotherapy was received by 84.64%, while 15.36% opted for best supportive care. Univariate Cox regression analysis identified Eastern Cooperative Oncology Group (ECOG) performance status, stage, gallstone disease, and surgical intervention as significant risk factors influencing overall survival (OS) (p < 0.001). Multivariate Cox regression analysis confirmed ECOG performance status (p < 0.001), stage (p = 0.039), and surgical intervention (p = 0.038) as independent factors impacting OS. One-year OS rates for stages II, III, and IV were 100%, 97%, and 44%, respectively, while 3-year OS rates were 29%, 4%, and 0%. Surgical intervention significantly influenced OS (p < 0.001). OS for surgical intervention was 28 months, and for inoperable cases, it was 12 months. One- and 3-year OS for surgical intervention were 95% and 11%, while for inoperable cases, they were 41% and 0%, respectively. Patients with gallbladder cancer, particularly in Bihar's Gangetic plains, face poor survival, especially with advanced disease. Adequate surgery improves outcomes, prompting a call for enhanced strategies, particularly for locally advanced GBC.

Our aim was to explore the disease burden caused by gallbladder and biliary tract cancer globally, regionally, and nationally, by age and sex.

The absolute number of cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) due to gallbladder and biliary tract cancer were extracted from the Global Burden of Disease (GBD) Study 2019. We estimated the trends in disease burden by calculating the percentage change in the absolute number of cases and the estimated annual percentage change (EAPC) in ASR, by social development index (SDI), region, nation, sex, and age.

From 1990 to 2019, the number of incident cases, prevalent cases, deaths, and DALYs worldwide significantly increased by 1.85-fold, 1.92-fold, 1.82-fold, and 1.68-fold, respectively. However, the age-standardized rates of incidence, prevalence, mortality, and DALYs tend to decrease globally over time. Nevertheless, heterogeneous disease burden patterns exist between geographic regions due to different geographical risk factors, distinct epidemiologically predominant gallbladder and biliary tract cancer subtypes, and potential genetic predispositions or ethnicity. Additionally, socioeconomic status mediates the regional variation in disease burden, with increasing SDI or HDI scores associated with downward trends in the age-standardized rates of incidence, prevalence, mortality, and DALYs. Older individuals and females are at higher risk of gallbladder and biliary tract cancer, but the increasing burden of early-onset gallbladder and biliary tract cancer is a cause for concern, especially for those living in lower SDI areas and males. High BMI is the primary risk factors underlying gallbladder and biliary tract cancer, accounted for 15.2% of deaths and 15.7% DALYs globally in 2019.

Our study comprehensively elucidated the distribution and dynamic trends of gallbladder and biliary tract cancer burden over the past three decades, from multiple dimensions. These findings emphasize the importance of promoting a healthy lifestyle as a population-level cancer prevention strategy and tailoring cancer control actions based on localized risk factors and the epidemic profiles of gallbladder and biliary tract cancer by anatomical subtype.

Dyslipidemia and abnormalities in cholesterol metabolism are commonly observed in individuals with gallstone disease. Previous research has demonstrated that dietary magnesium can influence lipid metabolism. The atherogenic index of plasma (AIP) has emerged as a novel lipid marker. This study aimed to examine the possible correlation between dietary magnesium intake and gallstones and the potential mediating role of AIP in US adults.

A total of 4,841 adults were included in this study from the National Health and Nutrition Examination Survey (NHANES) conducted from 2017 to 2020. A variety of statistical techniques such as logistic regression, subgroup analysis, smoothed curve fitting, and causal mediation analysis were utilized to analyze the information collected from the participants.

In the fully adjusted model, a statistically noteworthy inverse relationship was observed between dietary magnesium intake and the presence of gallstones, as indicated by an odds ratio (OR) of 0.58 and a 95% confidence interval (CI) of (0.42, 0.81). Causal intermediary analysis revealed that the association between magnesium intake and gallstones was partially mediated by AIP, with a mediation ratio of 3.2%.

According to this study, dietary magnesium intake had a significant linear negative association with the prevalence of gallstones, in which AIP played a mediating role. This discovery offers novel perspectives on the prevention and management of gallstones.

Gallbladder cancer (GBC) stands out as one of the most widespread malignancies impacting the biliary tract globally. Despite increasing interest, to the best of our knowledge, no meta-analysis has been undertaken to amalgamate the existing data concerning the prognostic significance of micro-RNAs (miRNAs) in GBC in comparison to studies on miRNAs in other cancers. Hence, this systematic review and meta-analysis aimed at determining the prognostic significance of miRNAs in GBC patients. Comprehensive literature searches were conducted across PubMed, Cochrane Library, Ovid, Scopus, and Science Direct databases. Studies that evaluated the association between miRNAs and overall survival in GBC patients were included. Random-effect meta-analysis was employed to pool hazard ratios (HRs) and their 95% confidence intervals (CIs) across studies. A total of 15 studies, encompassing 16 miRs, were included for our analysis. The pooled analysis revealed that a high expression of miR-204, miR-7-2-3p, miR-29c-3p, miR-125b, miR-20a, miR-139-5p, miR-141, miR-92b-3p, miR-335, and miR-372 was significantly associated with poor prognosis and increased risk (HR>1 and the upper bound of the 95% CI>1). Additionally, these miRNAs were associated with the overall survival (HR = 1.56, 95% CI = 0.91-2.20, I2 = 91.82%). Significant heterogeneity was observed and could be attributed to the limited number of studies available on the GBC and significant reliance on quantitative real-time PCR for the detection of miRNAs. In conclusion, specific miRNAs exhibit prognostic significance in GBC, with potential implications for patient stratification and targeted therapeutic interventions. However, due to the heterogeneity among studies, these findings should be interpreted cautiously and validated in larger cohorts.

Locally advanced, inoperable, or metastatic gallbladder cancers (GBC) are treated with either gemcitabine-platinum combinations or gemcitabine alone based on physician discretion. However, the combination of gemcitabine, cisplatin, and nab-paclitaxel (GCNP) has shown increased response rates and prolonged survival in a phase II trial of biliary tract patients.

Consecutive series of patients diagnosed with locally advanced (liver infiltration > 5 cm, large nodes at porta, abutting duodenum), inoperable, and metastatic biliary tract patients between January 2018 and August 2022 were evaluated for first-line chemotherapy GCNP, in the multidisciplinary joint clinic (MDJC). The primary endpoint was ORR, and the major secondary endpoint was event-free survival (EFS).

A total of 142 patients received GCNP during the specified time period. The median age of the cohort was 52 years (range: 21-79), the majority were females (61.3%), and the majority were GB (81.7%). Response rates were available in 137 patients. Complete response, partial response, and stable disease were seen in 9 (6.3%), 87 (61.3%), and 24 (16.9%), respectively, for an ORR of 67.6% and a clinical benefit rate of 84.5%. The median EFS was 9.92 (95% CI, 7.69-12.14) months. Of the 52 patients in whom GCNP was given with NACT intent for locally advanced GBC, 17 patients underwent surgery (34%).

Our study indicates that GCNP leads to improved response rates, increased chances of resectability, and possibly better survival in patients with GBC.

Xanthogranulomatous cholecystitis (XGC) and gallbladder carcinoma (GBC) share similar imaging and serological profiles, posing significant challenges in accurate preoperative diagnosis. This study aimed to identify reliable indicators and develop a predictive model to differentiate between XGC and GBC.

This retrospective study involved 436 patients from Zhejiang Provincial People's Hospital and The Affiliated Lihuili Hospital of Ningbo University. Comprehensive preoperative imaging, including ultrasound, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and blood tests, were analyzed. Machine learning (Random Forest method) was employed for variable selection, and a multivariate logistic regression analysis was used to construct a nomogram for predicting GBC. Statistical analyses were performed using SPSS and RStudio software.

The study identified gender, Murphy's sign, absolute neutrophil count, glutamyl transpeptidase level, carcinoembryonic antigen level, and comprehensive imaging diagnosis as potential risk factors for GBC. A nomogram incorporating these factors demonstrated high predictive accuracy for GBC, outperforming individual or combined traditional diagnostic methods. External validation of the nomogram showed consistent results.

The study successfully developed a predictive nomogram for distinguishing GBC from XGC with high accuracy. This model, integrating multiple clinical and imaging indicators, offers a valuable tool for clinicians in making informed diagnostic decisions. The findings advocate for the use of comprehensive preoperative evaluations combined with advanced analytical tools to improve diagnostic accuracy in complex medical conditions.

Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors.

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.

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.

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.

The weight-adjusted-waist index (WWI) is a novel obesity index, and gallstones are associated with obesity. This study aimed to investigate the possible relationship between WWI and gallstones.

The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between WWI and gallstones incidence. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship.

The study comprised 8004 participants over the age of 20, including 833 reported with gallstones. Participants in the higher WWI tertile tended to have a higher gallstones prevalence. In the final adjusted model, a positive association between WWI and gallstones prevalence was observed (OR = 1.34, 95% CI: 1.20‒1.49). Participants in the highest WWI tertile had a significantly 71% higher risk of gallstones than those in the lowest WWI tertile (OR = 1.71, 95% CI: 1.35‒2.17). A nonlinear correlation was found between the WWI and gallstones prevalence, with an inflection point of 12.7.

Our study found that higher WWI levels connected with increased prevalence of gallstones. However, more prospective studies are needed to validate our findings.