Gallstone disease (cholelithiasis) is one of the most prevalent biliary tract disorders worldwide and represents a significant health problem in the Indian subcontinent, particularly among females and the elderly population [1,2]. Chronic irritation and inflammation of the gallbladder mucosa due to gallstones are considered important risk factors for the development of carcinoma of the gallbladder (CaGB) [3]. The relationship between gallstones and gallbladder carcinoma has been well established, with gallstones detected in approximately 70–90% of patients diagnosed with CaGB [4,5]. Carcinoma of the gallbladder is the most common malignancy of the biliary tract and one of the most aggressive cancers of the gastrointestinal system, often associated with poor prognosis due to late diagnosis [6]. The geographical variation in its incidence is striking—high rates are reported from North India, Pakistan, Chile, and certain regions of Eastern Europe, suggesting environmental, dietary, and genetic factors in its pathogenesis [7]. In India, particularly in the Gangetic belt, gallbladder cancer ranks among the leading causes of gastrointestinal malignancies in females [8]. Incidental carcinoma gallbladder (ICGB), defined as gallbladder cancer detected histopathologically after cholecystectomy performed for presumed benign gallstone disease, accounts for a considerable proportion of CaGB cases [9]. The reported incidence of ICGB varies from 0.2% to 2.9% in different series [10]. Given its asymptomatic nature in early stages and the overlap of symptoms with benign biliary disorders, routine histopathological examination of all cholecystectomy specimens is vital for early detection and improved outcomes. The present study aimed to determine the incidence of carcinoma gallbladder in patients undergoing simple cholecystectomy for gallstone disease and to analyze the demographic and clinicopathological profile of these cases.

Study design: It was a prospective observational study. Place of study: The Study was Conducted in Calcutta National Medical College & Hospital, In Department of General Surgery, Under Prof. Dr. R.N. Roy. Period of study: One and a half year, starting from November 2017 to April 2019. Study Variables: • Number of cases of Gallbladder carcinoma. • Age and sex of the patients. • Clinical presentation (Right upper quadrant pain) • Laboratory Data(CBC, LFT, Serum Amylase Lipase) • Pre-operative USG findings(cholelithiasis/cholecystitis/thick walled gallbladder) • Surgery(Open/Laparoscopic Cholecystectomy) • Intraoperative findings(severe adhesion in calots triangle/thickened GB adherent to Liver) • Post-operative histopathological findings. Sample size: 200 pediatric patients diagnosed with symptomatic gallstone disease undergoing elective simple cholecystectomy. Inclusion Criteria: • Symptomatic Gallstone disease (USG proven). • All age groups were included. • Both sexes of different religion and socio-economic background. • Selection was done randomly. Exclusion Criteria: • Patients not willing to participate in the study. • Patients medically unfit for surgery. • Patients unwilling to undergo operation. • Patients undergoing simple cholecystectomy for GB polyps, Adenomyomatosis, Porcelain gallbladder, Acute acalculous cholecystitis, i.e. Benign conditions other than gallstone disease leading to simple cholecystectomy. • Patients having pre-operative diagnosis of Carcinoma of Gallbladder. • Patients having concurrent bile duct stones in addition to Gallstones (proven cases by USG or MRCP). Statistical Analysis: Statistical interpretation was done by analysing the data obtained by study tools. Data analysis was done by SPSS™ (Version 23, SPSS Inc. Chicago IL.) software for Windows™ and the incidence as defined above was obtained. The analysis includes standard diagrams and graphs, and the findings were discussed in detail to draw appropriate conclusions. Application of statistical tests were done wherever necessary. All data thus obtained will be kept confidential and will be preserved for at least 3 years.

Table 1: Distribution of Study Participants According to Demographic and Clinical Parameters Study Participants Frequency (N) Percentage (%) P-Value Age (years) Up to 25 28 14 <0.0001 26–35 53 26.5 36–45 49 24.5 46–55 37 18.5 56–65 25 12.5 >65 8 4 Total 200 100 Gender Female 137 68.5 <0.0001 Male 63 31.5 Total 200 100 Duration < 6 months 115 57.5 <0.0001 6–12 months 37 18.5 > 12 months 48 24 Total 200 100 Type of Surgery Laparoscopic Cholecystectomy 97 48.5 0.5485 Open Cholecystectomy 103 51.5 Total 200 100 Findings Normal Anatomy 179 89.5 <0.0001 Complicated anatomy 21 10.5 Total 200 100 Table 2: Distribution of Study Participants According to Histopathological Findings Histopathological Finding Frequency (N) Percentage (%) P-Value Chronic Cholecystitis with Cholesterosis 15 7.5 <0.0001 Acute on Chronic Cholecystitis 17 8.5 Chronic Cholecystitis 152 76 Chronic Cholecystitis with Adenomatous Hyperplasia 4 2 Adenocarcinoma Gallbladder 4 2 Empyema Gallbladder 1 0.5 Chronic Cholecystitis with Mild Dysplasia 1 0.5 Chronic Cholecystitis with Cholegranuloma 4 2 Chronic Cholecystitis with Goblet Cell Metaplasia 1 0.5 Xanthogranulomatous Cholecystitis 1 0.5 Total 200 100 Table 3: Association of Age, Gender, and Duration of Gallstone Disease with Incidence of Incidental Gall Bladder Carcinoma (IGBC) IGBC Yes IGBC No Total P-Value Age ≤45 years 2 128 130 0.525 >45 years 2 68 70 Total 4 196 200 Gender Male 0 63 63 0.7 Female 4 133 137 Total 4 196 200 Duration ≤12 Months 1 151 152 0.015 >12 Months 3 45 48 Total 4 196 200 In the present study, the majority of patients (26.5%) were aged between 26–35 years, and the mean age distribution showed a highly significant variation (p < 0.0001). Females constituted 68.5% of the cases, showing a statistically significant female predominance (p < 0.0001). More than half of the patients (57.5%) had symptoms for less than 6 months (p < 0.0001). Open cholecystectomy (51.5%) was slightly more common than laparoscopic cholecystectomy (48.5%), with no significant difference (p = 0.5485). Intraoperatively, normal Calot’s triangle anatomy and gallbladder morphology were observed in 89.5% of cases, whereas 10.5% showed complicated anatomy, which was statistically significant (p < 0.0001). Histopathological evaluation revealed that chronic cholecystitis was the most common finding, observed in 76% of cases, and followed by acute on chronic cholecystitis (8.5%) and chronic cholecystitis with cholesterosis (7.5%). Less frequent findings included adenomatous hyperplasia, adenocarcinoma, and other rare variants such as xanthogranulomatous cholecystitis and dysplastic changes. The distribution of histopathological findings was statistically significant (p < 0.0001). In the present study, out of 200 patients undergoing cholecystectomy for gallstone disease, incidental gall bladder carcinoma (IGBC) was detected in 4 cases (2%). The occurrence of IGBC was same among patients aged >45 years (2 cases) compared to those aged ≤45 years (2 cases), (p = 0.525). All four IGBC cases were females, while none were males, indicating a female predominance; however, this association was also not statistically significant (p = 0.7). A significant association was observed with the duration of gallstone disease, as patients with a disease duration of more than 12 months had a higher incidence of IGBC (3 out of 48 cases) compared to those with a duration ≤12 months (1 out of 152 cases), and this association was statistically significant (p = 0.015).

The present study revealed that the majority of patients with gallstone disease were within the 26–35-year age group, with a mean age showing significant variation (p < 0.0001). Similar age distributions were reported by Sharma et al. [11] and Mehta et al. [12], who found the peak incidence of gallstone disease in the third and fourth decades of life. In contrast, studies from northern India by Gupta et al. [13] noted a slightly higher mean age, suggesting regional and lifestyle variations in disease onset. The predominance of females (68.5%) in the present study aligns with the findings of Singh et al. [14] and Choudhury et al. [15], who attributed the higher prevalence in women to hormonal influences, multiparity, and sedentary lifestyle factors. In this study, 57.5% of patients presented with symptoms for less than 6 months, comparable to observations made by Das et al. [16], who reported a majority of symptomatic gallstone cases presenting within 3–6 months of onset. The proportion of open versus laparoscopic cholecystectomy in the current study (51.5% vs. 48.5%) is consistent with the trend reported by Reddy et al. [17], where open cholecystectomy was more frequent in complicated cases or where resource limitations existed. Histopathological evaluation revealed chronic cholecystitis as the predominant lesion (76%), corroborating findings by Bhattacharya et al. [18] and Nandyal et al. [19], who reported chronic inflammatory pathology as the most frequent outcome in gallbladder specimens following cholecystectomy. Less common findings, such as adenomatous hyperplasia, xanthogranulomatous cholecystitis, and dysplasia, were also comparable to the data published by Jain et al. [20]. Importantly, incidental gall bladder carcinoma (IGBC) was detected in 2% of cases, which is consistent with previous reports ranging between 0.5% and 2.5% in cholecystectomy specimens [3,8,9]. In our study, the incidence was higher in females, though not statistically significant, echoing findings by Sharma et al. [11] and Mehta et al. [12]. However, a significant correlation was observed between longer duration of gallstone disease (>12 months) and the presence of IGBC (p = 0.015), which supports the hypothesis proposed by chronic gallstone irritation over time may induce mucosal dysplasia and malignant transformation.

The present study that gallstone disease predominantly affects females in the third to fourth decades of life, with chronic cholecystitis being the most common histopathological finding. Although incidental gall bladder carcinoma (IGBC) was observed in only 2% of cases, its significant association with longer disease duration underscores the importance of routine histopathological examination of all cholecystectomy specimens to enable early detection of unsuspected malignancies and improve patient outcomes.

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