Annals of Case Reports

Summary of demographic data, initial presentation, duration of untreated gallstone persistence until GBC diagnosis, recent detection modalities, reasons for medical consultation, and overall survival (OS) status. “Time untreated to GBC diagnosis” denotes the interval between initial imaging detection of gallstones (ultrasonography [USG], magnetic resonance imaging [MRI], or computed tomography [CT]) and subsequent diagnosis of GBC. “Vital Status/Overall Survival (OS)” reflects patient status censored on 31 August 2025.

USG accounted for the initial detection in six cases, CT scan in two and MRI in two. Informational gaps accounted for the obstacles to cholecystectomy in seven cases, followed by financial burdens in two cases, poor access to healthcare in one, and clinical oversight in another [22]. Based on multimodal imaging (magnetic resonance cholangiopancreatography in four cases, contrast-enhanced CT in two cases, composite USG/CT/MRI), GBC diagnoses occurred between December 2024 and May 2025, consistently confirming stage IV dissemination.

Advanced disease was supported by symptom profiles that included widespread abdominal pain and vomiting in eight cases, jaundice in half of cases, and pyrexia in one case. Although prior imaging indicated chronicity, gallstone diameters >3 cm were documented in only half of the cases [8]. Prognostic indices were poor: Half of the patients died within 1-3 months post-diagnosis (June–August 2025), while the remaining survivors required palliative support as of August 30, 2025 [19]. These findings highlight both the heterogeneity of latency periods and the rapid downhill course once symptoms emerge. Notably, even patients with relatively short untreated intervals (<12 months) progressed to advanced disease, underscoring the urgent need for early intervention.

Discussion

This case series provides the first empirical timelines in an indigenous Indian paradigm, enabling unique longitudinal documenting of cholelithiasis-mediated transition to stage IV GBC among 10 West Bengal residents [19,23]. With shortened trajectories (1-6 years in 7 out of 10 patients), the mean untreated interval of 8.8 years (range 1-28 years) is consistent with existing literature suggesting a 5-20-year latency for metaplasia-dysplasiacarcinoma sequelae [24-26]. The findings in these 10 cases suggest an accelerated oncogenesis in genotypically or phenotypically vulnerable subpopulations, such as residents of the Gangetic basin [6,20,13]. The majority of the case series were women, who resembled the demographics of Indian GBC, where cholelithiasisrelated inflammatory diatheses are exacerbated by estrogenic effects and gestational parity [12, 22]. These findings reflect global patterns, where gallstones increase GBC risk by 0.3-3% but account for 80% of cases in high-risk areas [13, 19, 20].

GBC develops slowly, often only presenting symptomatically, e.g. with jaundice or abdominal pain at advanced disease stages, with a 50% death rate soon after clinical diagnosis and a 5 year survival rate of only about 2% for advanced metastatic disease highlights the need for early prevention [19, 27]. Prior studies show that carefully performed prophylactic cholecystectomy for gallstones larger than 3 cm or that are present for over 5 years can reduce mortality by 80-90% [14,15,11]. To prevent gallbladder cancer in resourcelimited areas like West Bengal, community-based efforts should focus on raising awareness about symptoms, using cost-effective ultrasound screening for high-risk groups (such as women over 40 with gallstones), and providing affordable access to surgical removal. Encouraging regular doctor visits and checkups at nearby government hospitals or health centers is crucial to overcome educational and financial barriers [3]. Excisional therapies may be accelerated by integrating GBC risk categorization into cholelithiasis care, supplemented by inflammatory biomarker surveillance [4]. Recent evidence also suggests that peri-operative chemotherapy may improve outcomes for advanced GBC, though prevention remains critical given the poor prognosis [27].

This study has inherent limitations, including a restricted sample size, retrospective provenance, and lacunae in genomic profiling or gallstone mensuration. While prospective expansive inquiries would provide the optimal scientific design, they are largely impracticable due to the long follow-up required and the likelihood of substantial patient attrition. Moreover, such non-interventional studies would raise ethical concerns, as withholding treatment in high-risk gallstone carriers would be indefensible given the established natural history of disease progression from gall stone etiology to GBC. In this context, the present study assumes significant value by offering real-world longitudinal insights that directly inform prevention-oriented public health and clinical strategies, motivating a paradigm shift toward preventative elimination in hyperendemic domains to attenuate GBC lethality [21,23].

In conclusion, the initial case series from West Bengal supports the inevitable progression from untreated cholelithiasis to advanced GBC over a period of 1-28 years. This progression can be interrupted with preventative cholecystectomy, supported by various awareness strategies and socioeconomic factors that mitigate [14,15, 22]. In endemic areas, GBC is transformed from an undetected fatality to a treatable illness by clinicians and policymakers emphasizing patient education and prompt intervention [19, 20].

Ethics, Consent to Participate, and Consent to Publish declarations

The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The study was approved by the Human Research Ethics Committee (HREC) of the Indian Institute of Liver and Digestive Sciences (IILDS), (HREC Approval #IILDS/2024-R38) and ratified by JCMLRI and IPGMER. Moffitt Cancer Center did not have access to private health information. All participants included in the study gave their written informed consent including consent for publication. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Consent for publication

Not applicable.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declaration of Interest Statement

The authors declare no competing interests.

Funding Declaration

This research received no external funding.

Authors’ contributions

Z.W, K.M, S.N participated in collecting the clinical data. S.M, C.C, A.C, B.C, R.G, R.S clinically reviewed the cases.  S.D and M.P.H wrote and edited the manuscript. S.D and M.P.H were involved in data analysis.  All authors read and approved the final manuscript.

Acknowledgements

We sincerely thank the patients and their families for their trust, cooperation, and consent to share their clinical information, which made this study possible. We also acknowledge the medical and nursing staff of the Institute of Post Graduate Medical Education & Research (IPGMER), Kolkata, and the Indian Institute of Liver and Digestive Sciences (IILDS).

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