Prognostic Insights and Survival Analysis of Gallbladder Cancer in Bihar, India: A Prospective Observational Study Emphasizing the Impact of Surgical Intervention on Overall Survival

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Methods: This prospective observational study was conducted at a tertiary care center in Bihar state, India. Results: 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 three-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 three-year OS for surgical intervention were 95% and 11%, while for inoperable cases, they were 41% and 0%, respectively. Conclusion: 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. Outcome of Gallbladder cancer survival in Gallbladder cancer Surgery in Gallbladder cancer Overall survival in Gallbladder cancer in India Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Gallbladder cancer (GBC) has a marked variation of incidence around the globe. It is an aggressive and highly lethal neoplasm of the biliary tract [ 1 ]. GBC constitutes the most common biliary tract malignancy, and 7th most common amongst gastrointestinal neoplasms and accounts for 80%-95% of the biliary tract cancer [ 2 , 3 ]. The incidence of GBC is notably higher among the Indian population when compared to global statistics as a whole. In terms of GBC, the population in North and Northeast India exhibits a notably higher incidence rate compared to Chile and Bolivia [ 4 , 5 ]. According to GLOBOCON 2020 data, GBC accounts for 84,695 deaths in 2020, and 115,949 new cases globally [ 6 ]. GBC accounts for 14,736 deaths and 19,570 new cases in 2020 in India [ 7 ]. The regions near the river Ganges in the eastern part of Uttar Pradesh and western Bihar are identified as the highest-risk areas for GBC [ 8 ]. One possible explanation for this disparity could be the significant impact of environmental factors on the development of GBC etiology in these regions [ 9 ]. Carcinogens such as heavy metals and azo dyes are known to enhance the risk of cancer in this region, possibly due to mutation in oncogenes and tumor suppressor genes [ 10 , 11 ]. The clinical presentation is often non-specific resulting in a significant delay in diagnosis. Most of the time, GBC is detected incidentally at the time of cholecystectomy or due to symptoms advanced disease such as jaundice, ascites or obstruction [ 12 ]. The management of GBC continues to pose challenges due to the vague and nonspecific nature of its signs, symptoms, and the delay in diagnosis. Surgery remains the sole potential cure for GBC, but its effectiveness is limited to patients diagnosed in the early stages of the disease. Patients with advanced-stage GBC often cannot undergo radical resection due to the frequent metastasis of tumors to nearby organs [ 13 ]. The objective of this study is to assess the prognostic factors influencing survival and examine the survival outcomes of patients with GBC residing in state of Bihar, India. Methods This prospective observational study conducted at department of radiotherapy at All India Institute of Medical Sciences (AIIMS), Patna, Bihar. The study was spanned a period of 3 years, from January 2017 to December 2019. The workup and diagnosis of the GBC included history and clinical examination of the patients, ultrasonography (USG) of whole abdomen, contrast enhanced computed tomography (CECT) whole abdomen, CT scan thorax, contrast enhanced magnetic resonance imaging (CEMRI) abdomen when needed. USG/CT-guided fine-needle aspiration cytology (FNAC) was performed on the gallbladder lesion/mass. Patients with obstructive jaundice underwent percutaneous transhepatic biliary drainage (PTBD) or endoscopic retrograde cholahgiopancreatography (ERCP) stenting if possible. Workup of haematological and biochemical parameters included complete blood count (CBC), liver function test (LFT), kidney function test (KFT), prothrombin time (PT), international normalised ratio (INR), and CA19.9. Following multidisciplinary tumor board discussion operable cases underwent extended cholecystectomy and post operative cases were advised for adjuvant chemotherapy. Patients were staged according to AJCC TNM (American Joint Committee on Cancer) staging system 8th edition [ 14 ]. Incidental diagnosis of GBC following open cholecystectomy or laparoscopic cholecystectomy patients were considered for extended cholecystectomy with port site excision if operable and followed by adjuvant chemotherapy. Advanced GBC or patients with poor Eastern Cooperative Oncology Group (ECOG) performance status were considered for best supportive care. Objective: To find out the one-and three-years overall survival (OS) and factors influencing it. Inclusion criteria: age > 18 years of age, histopathologically or cytopathologically confirmed cases of GBC. Exclusion criteria: age < 18 years, pregnancy or lactation, residence outside of Bihar, diagnosed with concurrent second primary. Variables: demographic data, clinicopathological information of GBC, management of GBC, follow up (survival status). Outcome variable included the overall survival (the length of time from the diagnosis of GBC until the death due to progression of the GBC. Progression of GBC included the evidence of progressive disease (radiological or biochemical) after the intended completion of treatment. Data analysis: Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM® SPSS® Inc; Chicago, USA). Descriptive statistics were employed to describe the patient demographics. Cox regression model was utilized for univariate analysis of OS, variables having statistically significant influence on OS were included in Cox regression model for multivariate analysis to identify independent factors affecting OS. The Kaplan-Meier method was employed to determine the cumulative survival rate, and group comparisons were made using the Log-rank test. Statistical significance was set at p < 0.05 for all tests. Result Clinicopathological characteristics: Two hundred and twenty-eight patients meeting the inclusion and exclusion criteria were analyzed. The median age at diagnosis was 55 ± 12.05 years, with a majority falling within the 50–60 years age group (30.70%). The female-to-male ratio was 2.86:1, with females constituting 74.1% of the total patients. Geographical distribution in Bihar state is depicted in heat map Fig-1. The most common presenting symptom was upper abdominal pain (26.3%), followed by weight loss (14%) and ascites (13.6%). Thirty-seven point three percent (37.3%) of patients presented with an ECOG performance status of 2. Gallbladder stones were noted in 57% of patients at presentation, and surgical intervention was feasible in only 27.6% of cases. Histopathologically, adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma were observed in 95.6%, 3.5%, and 0.9% of cases, respectively. Most patients presented at stage IV (72.8%). Immunohistochemistry confirmed that all three patients with undifferentiated carcinoma had neuroendocrine tumors. Liver (61.4%) was the most common site of metastasis, followed by omental deposits (3.1%) at the presentation of metastatic gallbladder cancer. Interventional biliary drainage, either in the form of percutaneous transhepatic biliary drainage or stenting at endoscopic retrograde cholangiopancreatography, was performed in 9.6% of patients. The median value of CA 19.9 was 366.60, with its distribution among patients categorized as 400–600, and > 600 showing percentages of 9.6%, 48.7%, 25.9%, and 15.8%, respectively. Systemic chemotherapy, either with adjuvant intent or palliative intent, was received by 84.64% of patients, while 15.36% were considered for best supportive care. None of the patients received adjuvant radiotherapy. During data analysis, 221 (96.9%) patients showed disease progression, and among those with progressive disease, 206 patients died. Table 1 illustrates the clinicopathological characteristics of patients with gallbladder carcinoma. Table 1 Clinicopathological characteristics of patients with gallbladder carcinoma. Count Table N % Age group 20–30 years 6 2.6% > 30–40 years 27 11.8% > 40–50 years 61 26.8% > 50–60 years 70 30.7% > 60–70 years 44 19.3% > 70 years 20 8.8% Gender Female 169 74.1% Male 59 25.9% Presenting features Abdominal lump 30 13.2% Ascites 31 13.6% Fever 23 10.1% Jaundice 27 11.8% Weight loss/loss of appetite 32 14.0% Nausea and vomiting 25 11.0% Upper abdominal pain 60 26.3% CA 19.9 group 400–600 59 25.9% > 600 36 15.8% ECOG performance status ECOG 1 69 30.3% ECOG 2 85 37.3% ECOG 3 32 14.0% ECOG 4 42 18.4% Stage Stage II 29 12.7% Stage III 33 14.5% Stage IV 166 72.8% Gall stone on USG Yes 130 57.0% No 98 43.0% Histopathological subtypes Adenocarcinoma 218 95.6% Squamous cell carcinoma 8 3.5% Undifferentiated carcinoma 2 0.9% Surgical intervention Yes 63 27.6% No 165 72.4% Types of surgery Cholecystectomy 24 10.5% Radical cholecystectomy 39 17.1% Inoperable 165 72.4% Site of metastasis Abdominal wall 1 0.6% Bone 2 0.9% Liver 140 61.4% Liver and bone 2 0.9% Liver and lung 4 1.8% Omentum 7 3.1% Ovary 5 2.2% SCLN 5 2.2% ECOG- Eastern Cooperative Oncology Group performance status; USG- Ultra sonography; SCLN- Supraclavicular lymph node. Clinical characteristics and survival: The overall median survival was 14 months (95% CI 12.518–15.482), as depicted in figure-2. One- and three-years OS rates were 57% and 3%, respectively. The Kaplan-Meier survival analysis showed that the survival rates of the patients with different categorical variables progressively decreases with the increase in the duration of follow-up in months. The result of Log-rank test showed a statistically significant difference (Log-rank test; χ 2 = 132.45; p = < 0.001) in OS when comparing the stage of the GBC. The median OS in stage II, stage III, and stage IV was 30 months (95% CI of 26.501–33.499), 26 months (95% CI of 23.255–28.745), and 12 months (95% CI of 11.473–12.527) shown in Figure-3. One-year OS in stage II, stage III, and stage IV was 100%, 97%, and 44%, respectively, while the three-years OS in stage II, stage III, and stage IV was 29%, 4%, and 0%. A statistically significant difference (Log-rank test; χ2 = 128.87; p < 0.001) in OS was observed when comparing the surgical interventions (radical cholecystectomy and cholecystectomy), as depicted in Fig. 4 . The OS in patients who underwent surgical intervention was 28 months (95% CI of 25.195–30.805), while the OS in patients with inoperable gallbladder carcinoma was 12 months (95% CI of 11.473–12.527). The one- and three-year OS for patients who underwent surgical intervention were 95% and 11%, respectively, whereas the one- and three-year OS for patients with inoperable gallbladder carcinoma were 41% and 0%, respectively. No difference in OS was observed when comparing the values of CA19.9 among groups at the time of diagnosis. Risk factors and overall survival: Univariate and multivariate Cox regression analyses were performed to analyze the hazard ratio (HR). The results of Cox regression univariate analysis indicated that ECOG performance status (p < 0.001), stage (p < 0.001), gallstone disease (p < 0.001), and surgical intervention (p < 0.001) at diagnosis were the risk factors influencing the OS in gallbladder carcinoma. Age group (p = 0.168), gender (p = 0.921), histopathological subtypes (p = 0.855), and CA19.9 group (p = 0.061) did not influence the OS in gallbladder carcinoma. The multivariate Cox regression analysis demonstrated that ECOG performance status (p < 0.001), stage (p = 0.039), and surgical intervention (p = 0.038) were the independent factors influencing the OS in gallbladder carcinoma. The univariate and multivariate Cox regression analyses are depicted in Table 2 . Table 2 Univariate and multivariate Cox regression analysis Variables Univariate analysis Multivariate analysis Exp(B) 95% CI p value Exp(B) 95% CI p value Age Group 1.085 0.966–1.219 0.168 Gender 0.984 0.717–1.351 0.921 ECOG 2.667 2.217–3.209 < 0.001 1.847 1.498–2.279 < 0.001 Stage 4.423 3.235–6.047 < 0.001 1.783 1.029–3.091 0.039 Gall stone disease 2.596 1.919–3.512 < 0.001 1.266 0.920–1.742 0.147 CA 19.9 category 1.168 0.993–1.375 0.061 Surgical intervention 11.213 6.923–18.161 < 0.001 2.672 1.057–6.752 0.038 Histopathological subtypes 0.943 0.502–1.770 0.855 ECOG- Eastern Cooperative Oncology Group performance status Discussion Gallbladder carcinoma is the predominant malignancy in the biliary tract system, with the highest incidence observed in northern and central India. In developing nations, it commonly presents in advanced stages, significantly diminishing the chances of successful curative resection [ 15 – 18 ]. The median age at presentation was 67 years in a Memorial Sloan–Kettering report of 435 GBC patients [ 19 ]. In our study, the median age is 55 years, suggesting that the incidence of GBC increases with age. These findings align with previous studies conducted in India [ 20 – 22 ]. GBC exhibits a higher incidence in females globally, ranging from 2 to 6 times more than in males. This trend is particularly notable in the northern part of India, Pakistan, and among American-Indian females. In our study, the female-to-male ratio is 3.53:1 [ 23 – 24 ]. A previous study from New Delhi reported GBC incidence as 1/100,000 in males and 3.3/100,000 in females during 1987–1996, with a female-to-male ratio of 3.3:1 [ 25 – 26 ]. Our study similarly highlights GBC as predominantly affecting females, with a female-to-male ratio of 2.8:1. This observation aligns with other studies reporting a female-to-male ratio of 2.5-3:1 [ 27 – 28 ]. Upper abdominal pain emerged as the most common presenting symptom in our study. The clinical signs mimic those of benign gallbladder disease until the invasion of surrounding structures provides a clue leading to an accurate diagnosis [ 29 ]. Similar observations were reported by other studies [ 30 – 32 ]. In our study, adenocarcinoma (95.6%) was the most common histology, followed by squamous cell carcinoma (3.5%). Lal et al. reported 89.15% adenocarcinoma and 2.4% squamous cell carcinoma in their study. Hamdani et al. and Beltz et al., in their studies, also reported a similar distribution of histopathological types of GBC [ 33 , 34 ]. In this study, the majority of patients presented in stage IV (72.8%), with the liver (61.4%) being the most common site of metastasis. Dubey et al., in their study, reported almost similar findings, with 72.06% of patients in stage IV, and 57.14% having metastasis to the liver [ 35 ]. Batra et al. reported in their study that about 76% of GBC patients presented with stage IV [ 36 ]. Similarly, Gupta et al. reported findings consistent with our study, where 71.4% of patients presented in stage IV [ 37 ]. In our study, the median value of CA 19.9 was 366.60 U/mL, with 48.7% of patients having CA19.9 levels within the range of 200–400. Sinha SR et al. reported a median value of CA 19.9 of 112.9 U/mL in their study [ 38 ], while Zhijian et al. reported a median value of CA 19.9 of 278 U/mL [39]. Elevated CA19.9 levels in patients with GBC without jaundice have been associated with metastatic disease, showing high specificity and potential for prognostication. CA19.9 was found to be superior to CEA in predicting tumor burden and recurrence [ 40 ]. In our study, 15.36% of patients were considered for best supportive care due to their poor ECOG performance status. Singh SK et al. reported a similar finding in their study, with 18.6% of patients considered for best supportive care due to poor performance status [ 41 ]. Gallstones have been reported to be present in 61–90% of patients with gallbladder cancer [ 42 ]. However, the incidence of GBC in a population with gallstones varies from 0.3 to 3% only. In our study, 57% of patients had evidence of gallstones, aligning with the existing literature. Our study demonstrated that surgical intervention was associated with improved OS. Surgery remains the sole treatment modality offering a survival benefit in cases of GBC. Over the past decade, various studies have shown a significant increase in 5-year survival rates, rising from 5–12% and even up to 38%. In contrast, palliative chemotherapy or radiotherapy has shown limited effectiveness for GBC, providing only a few months of survival benefit, if any. Given this situation, an aggressive surgical approach for locally confined disease is entirely justified. There is a lack of consensus worldwide on what constitutes aggressive surgery for a given stage of GBC [ 43 ]. Surgeons must exercise heightened caution when overseeing patients who have fortuitously discovered gallbladder cancers subsequent to laparoscopic cholecystectomy. During laparoscopic removal of the gallbladder, it is essential to use a protective bag to prevent the potential dissemination and implantation of tumor cells. Surgeons should consistently document instances of gallbladder wall breach and whether the specimen was enclosed within a bag before extraction during the cholecystectomy procedure [ 44 , 45 , 46 , 47 ]. In this study, the OS was 14 months, with one and three-year OS rates of 53% and 3%, respectively. Patients who underwent surgical intervention experienced significantly improved OS compared to those who were unable to undergo surgical intervention. The one-year OS rates in stage II, stage III, and stage IV were 100%, 97%, and 44%, respectively. The three-year OS rates in stage II, stage III, and stage IV were 29%, 4%, and 0%. A study by Singh SK et al. reported one-year survival rates of 100%, 76%, and 36.6% in stage II, III, and IV, respectively [ 48 ], and similar findings were observed in the study by Principe A et al. [ 49 ]. Conclusion The survival of GBC patients is very poor, especially for those diagnosed with advanced disease. The geographical region of the patients, namely the Gangetic plains of Bihar, is one of the areas with a high incidence of GBC. Patients with gallstone disease should be considered at high risk for developing GBC, especially in the context of this geographical area and the age group at risk. It is essential to provide adequate workup and surgical intervention for these high-risk group patients. While adequate surgical intervention is associated with improved OS, there is room for improvement in the treatment strategies for locally advanced GBC. More focused efforts are needed to enhance the outcomes for patients facing locally advanced GBC Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dr Dharmendra Singh, Dr Pritanjali Singh, Dr Avik Mandal and Dr Amrita Rakesh. The first draft of the manuscript was written by Dr Dharmendra Singh and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of All India Institute of Medical Sciences, Patna (IEC/2018/315 dated 04/10/2018). Consent to participate: Informed consent was obtained from all individual participants included in the study. References Feroz, Z., Gautam, P., Tiwari, S. et al. Survival analysis and prognostic factors of the carcinoma of gallbladder. World J Surg Onc 20 , 403 (2022). https://doi.org/10.1186/s12957-022-02857-y Donohue JH, Stewart AK, Menck HR. The national cancer data base report on carcinoma of the gall bladder, 1989-1995. Cancer 1998;83:2618-28. Hundal R, Shaffer EA. Gallbladder cancer: Epidemiology and outcome. Clin Epidemiol 2014;6:99-109. Schmidt MA, Marcano-Bonilla L, Roberts LR. 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DOI: 10.1007/s12029-017-9940-y. PMID: 28367607. Principe A, Del Gaudio M, Ercoloni G, Golfieri R, Cucchetti A, Pinna AD. Radical surgery for gallbladder carcinoma: possibilities of survival. Hepato-Gastroenterology. 2006;53(71):660–4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Mar, 2024 Read the published version in Indian Journal of Surgical Oncology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3825287","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264684479,"identity":"36cc45e5-4ff5-4a60-a4f7-dddaeb3c9f51","order_by":0,"name":"Dharmendra Singh","email":"data:image/png;base64,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","orcid":"","institution":"All India Institute of Medical Sciences, Deoghar","correspondingAuthor":true,"prefix":"","firstName":"Dharmendra","middleName":"","lastName":"Singh","suffix":""},{"id":264684480,"identity":"9a2aa387-3056-4f31-958d-4a9dffb2b69b","order_by":1,"name":"Pritanjali Singh","email":"","orcid":"","institution":"All India Institute of Medical Sciences, Patna","correspondingAuthor":false,"prefix":"","firstName":"Pritanjali","middleName":"","lastName":"Singh","suffix":""},{"id":264684481,"identity":"c364ed6d-e87b-4142-8470-42e3695e051e","order_by":2,"name":"Avik Mandal","email":"","orcid":"","institution":"Medella Karkinos Oncology Institute, Kolkata","correspondingAuthor":false,"prefix":"","firstName":"Avik","middleName":"","lastName":"Mandal","suffix":""},{"id":264684482,"identity":"958a1e46-5439-47ba-a9cb-d552e05e2783","order_by":3,"name":"Amrita Rakesh","email":"","orcid":"","institution":"SAVERA Cancer and Multispeciality Hospital, Patna","correspondingAuthor":false,"prefix":"","firstName":"Amrita","middleName":"","lastName":"Rakesh","suffix":""}],"badges":[],"createdAt":"2023-12-31 06:44:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3825287/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3825287/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s13193-024-01925-x","type":"published","date":"2024-03-18T08:34:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49143034,"identity":"3b101cbf-c7d4-45a1-a8b5-24e8cabe7c6c","added_by":"auto","created_at":"2024-01-03 18:47:08","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":116597,"visible":true,"origin":"","legend":"\u003cp\u003eHeat map of different districts of Bihar state (not to scale) showing distribution of GBC patients around Gangetic river basin system (light blue colour)\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3825287/v1/331ea2f062565a40716ce685.jpeg"},{"id":49143036,"identity":"8db1c180-3840-4ca4-b3b2-c507e25f6698","added_by":"auto","created_at":"2024-01-03 18:47:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11433,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier Survival curve showing overall survival (OS).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3825287/v1/d7878dc8c6dea6b3bd0c4b82.png"},{"id":49143037,"identity":"c7e63877-86dc-4c26-accf-6f2aa7a610f9","added_by":"auto","created_at":"2024-01-03 18:47:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":17074,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve showing statistically significant survival difference in overall survival (OS) in gallbladder carcinoma comparing the stage (p\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3825287/v1/921d8c7719d25c34d47bcfdf.png"},{"id":49143035,"identity":"0a9c3a6c-b46a-4252-9826-ad655516cd6c","added_by":"auto","created_at":"2024-01-03 18:47:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":15204,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve showing statistically significant survival difference in overall survival (OS) in gallbladder carcinoma comparing the surgical intervention (p\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3825287/v1/8d2f8ccb41f825035d064967.png"},{"id":53150993,"identity":"8e49b3dc-a2bf-4ac8-8624-47d0e1f65778","added_by":"auto","created_at":"2024-03-21 08:34:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":387496,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3825287/v1/eadbd226-bad7-41f2-b715-1f87b8ef349b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Insights and Survival Analysis of Gallbladder Cancer in Bihar, India: A Prospective Observational Study Emphasizing the Impact of Surgical Intervention on Overall Survival","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGallbladder cancer (GBC) has a marked variation of incidence around the globe. It is an aggressive and highly lethal neoplasm of the biliary tract [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. GBC constitutes the most common biliary tract malignancy, and 7th most common amongst gastrointestinal neoplasms and accounts for 80%-95% of the biliary tract cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The incidence of GBC is notably higher among the Indian population when compared to global statistics as a whole. In terms of GBC, the population in North and Northeast India exhibits a notably higher incidence rate compared to Chile and Bolivia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. According to GLOBOCON 2020 data, GBC accounts for 84,695 deaths in 2020, and 115,949 new cases globally [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. GBC accounts for 14,736 deaths and 19,570 new cases in 2020 in India [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The regions near the river Ganges in the eastern part of Uttar Pradesh and western Bihar are identified as the highest-risk areas for GBC [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. One possible explanation for this disparity could be the significant impact of environmental factors on the development of GBC etiology in these regions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Carcinogens such as heavy metals and azo dyes are known to enhance the risk of cancer in this region, possibly due to mutation in oncogenes and tumor suppressor genes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The clinical presentation is often non-specific resulting in a significant delay in diagnosis. Most of the time, GBC is detected incidentally at the time of cholecystectomy or due to symptoms advanced disease such as jaundice, ascites or obstruction [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The management of GBC continues to pose challenges due to the vague and nonspecific nature of its signs, symptoms, and the delay in diagnosis. Surgery remains the sole potential cure for GBC, but its effectiveness is limited to patients diagnosed in the early stages of the disease. Patients with advanced-stage GBC often cannot undergo radical resection due to the frequent metastasis of tumors to nearby organs [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The objective of this study is to assess the prognostic factors influencing survival and examine the survival outcomes of patients with GBC residing in state of Bihar, India.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis prospective observational study conducted at department of radiotherapy at All India Institute of Medical Sciences (AIIMS), Patna, Bihar. The study was spanned a period of 3 years, from January 2017 to December 2019. The workup and diagnosis of the GBC included history and clinical examination of the patients, ultrasonography (USG) of whole abdomen, contrast enhanced computed tomography (CECT) whole abdomen, CT scan thorax, contrast enhanced magnetic resonance imaging (CEMRI) abdomen when needed. USG/CT-guided fine-needle aspiration cytology (FNAC) was performed on the gallbladder lesion/mass. Patients with obstructive jaundice underwent percutaneous transhepatic biliary drainage (PTBD) or endoscopic retrograde cholahgiopancreatography (ERCP) stenting if possible. Workup of haematological and biochemical parameters included complete blood count (CBC), liver function test (LFT), kidney function test (KFT), prothrombin time (PT), international normalised ratio (INR), and CA19.9. Following multidisciplinary tumor board discussion operable cases underwent extended cholecystectomy and post operative cases were advised for adjuvant chemotherapy. Patients were staged according to AJCC TNM (American Joint Committee on Cancer) staging system 8th edition [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Incidental diagnosis of GBC following open cholecystectomy or laparoscopic cholecystectomy patients were considered for extended cholecystectomy with port site excision if operable and followed by adjuvant chemotherapy. Advanced GBC or patients with poor Eastern Cooperative Oncology Group (ECOG) performance status were considered for best supportive care.\u003c/p\u003e \u003cp\u003eObjective: To find out the one-and three-years overall survival (OS) and factors influencing it.\u003c/p\u003e \u003cp\u003eInclusion criteria: age\u0026thinsp;\u0026gt;\u0026thinsp;18 years of age, histopathologically or cytopathologically confirmed cases of GBC. Exclusion criteria: age\u0026thinsp;\u0026lt;\u0026thinsp;18 years, pregnancy or lactation, residence outside of Bihar, diagnosed with concurrent second primary.\u003c/p\u003e \u003cp\u003eVariables: demographic data, clinicopathological information of GBC, management of GBC, follow up (survival status). Outcome variable included the overall survival (the length of time from the diagnosis of GBC until the death due to progression of the GBC. Progression of GBC included the evidence of progressive disease (radiological or biochemical) after the intended completion of treatment.\u003c/p\u003e \u003cp\u003eData analysis: Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM\u0026reg; SPSS\u0026reg; Inc; Chicago, USA). Descriptive statistics were employed to describe the patient demographics. Cox regression model was utilized for univariate analysis of OS, variables having statistically significant influence on OS were included in Cox regression model for multivariate analysis to identify independent factors affecting OS. The Kaplan-Meier method was employed to determine the cumulative survival rate, and group comparisons were made using the Log-rank test. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for all tests.\u003c/p\u003e"},{"header":"Result","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eClinicopathological characteristics:\u003c/h2\u003e \u003cp\u003eTwo hundred and twenty-eight patients meeting the inclusion and exclusion criteria were analyzed. The median age at diagnosis was 55\u0026thinsp;\u0026plusmn;\u0026thinsp;12.05 years, with a majority falling within the 50\u0026ndash;60 years age group (30.70%). The female-to-male ratio was 2.86:1, with females constituting 74.1% of the total patients. Geographical distribution in Bihar state is depicted in heat map Fig-1.\u003c/p\u003e \u003cp\u003eThe most common presenting symptom was upper abdominal pain (26.3%), followed by weight loss (14%) and ascites (13.6%). Thirty-seven point three percent (37.3%) of patients presented with an ECOG performance status of 2. Gallbladder stones were noted in 57% of patients at presentation, and surgical intervention was feasible in only 27.6% of cases. Histopathologically, adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma were observed in 95.6%, 3.5%, and 0.9% of cases, respectively. Most patients presented at stage IV (72.8%). Immunohistochemistry confirmed that all three patients with undifferentiated carcinoma had neuroendocrine tumors. Liver (61.4%) was the most common site of metastasis, followed by omental deposits (3.1%) at the presentation of metastatic gallbladder cancer.\u003c/p\u003e \u003cp\u003eInterventional biliary drainage, either in the form of percutaneous transhepatic biliary drainage or stenting at endoscopic retrograde cholangiopancreatography, was performed in 9.6% of patients. The median value of CA 19.9 was 366.60, with its distribution among patients categorized as \u0026lt;\u0026thinsp;200, 200\u0026ndash;400, \u0026gt;\u0026thinsp;400\u0026ndash;600, and \u0026gt;\u0026thinsp;600 showing percentages of 9.6%, 48.7%, 25.9%, and 15.8%, respectively. Systemic chemotherapy, either with adjuvant intent or palliative intent, was received by 84.64% of patients, while 15.36% were considered for best supportive care. None of the patients received adjuvant radiotherapy.\u003c/p\u003e \u003cp\u003eDuring data analysis, 221 (96.9%) patients showed disease progression, and among those with progressive disease, 206 patients died. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the clinicopathological characteristics of patients with gallbladder carcinoma.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathological characteristics of patients with gallbladder carcinoma.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCount\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTable N %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eAge group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u0026ndash;30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30\u0026ndash;40 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;40\u0026ndash;50 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u0026ndash;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;60\u0026ndash;70 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;70 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003ePresenting features\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbdominal lump\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAscites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJaundice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeight loss/loss of appetite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNausea and vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUpper abdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eCA 19.9 group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200\u0026ndash;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;400\u0026ndash;600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eECOG performance status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eECOG 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eECOG 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eECOG 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eECOG 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGall stone on USG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eHistopathological subtypes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSquamous cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUndifferentiated carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSurgical intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eTypes of surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCholecystectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRadical cholecystectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInoperable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eSite of metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbdominal wall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLiver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLiver and bone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLiver and lung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOmentum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOvary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSCLN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eECOG- Eastern Cooperative Oncology Group performance status; USG- Ultra sonography; SCLN- Supraclavicular lymph node.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics and survival:\u003c/h2\u003e \u003cp\u003eThe overall median survival was 14 months (95% CI 12.518\u0026ndash;15.482), as depicted in figure-2. One- and three-years OS rates were 57% and 3%, respectively. The Kaplan-Meier survival analysis showed that the survival rates of the patients with different categorical variables progressively decreases with the increase in the duration of follow-up in months. The result of Log-rank test showed a statistically significant difference (Log-rank test; χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;132.45; p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in OS when comparing the stage of the GBC. The median OS in stage II, stage III, and stage IV was 30 months (95% CI of 26.501\u0026ndash;33.499), 26 months (95% CI of 23.255\u0026ndash;28.745), and 12 months (95% CI of 11.473\u0026ndash;12.527) shown in Figure-3. One-year OS in stage II, stage III, and stage IV was 100%, 97%, and 44%, respectively, while the three-years OS in stage II, stage III, and stage IV was 29%, 4%, and 0%. A statistically significant difference (Log-rank test; χ2\u0026thinsp;=\u0026thinsp;128.87; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in OS was observed when comparing the surgical interventions (radical cholecystectomy and cholecystectomy), as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The OS in patients who underwent surgical intervention was 28 months (95% CI of 25.195\u0026ndash;30.805), while the OS in patients with inoperable gallbladder carcinoma was 12 months (95% CI of 11.473\u0026ndash;12.527). The one- and three-year OS for patients who underwent surgical intervention were 95% and 11%, respectively, whereas the one- and three-year OS for patients with inoperable gallbladder carcinoma were 41% and 0%, respectively. No difference in OS was observed when comparing the values of CA19.9 among groups at the time of diagnosis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eRisk factors and overall survival:\u003c/h2\u003e \u003cp\u003eUnivariate and multivariate Cox regression analyses were performed to analyze the hazard ratio (HR). The results of Cox regression univariate analysis indicated that ECOG performance status (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), stage (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), gallstone disease (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and surgical intervention (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at diagnosis were the risk factors influencing the OS in gallbladder carcinoma. Age group (p\u0026thinsp;=\u0026thinsp;0.168), gender (p\u0026thinsp;=\u0026thinsp;0.921), histopathological subtypes (p\u0026thinsp;=\u0026thinsp;0.855), and CA19.9 group (p\u0026thinsp;=\u0026thinsp;0.061) did not influence the OS in gallbladder carcinoma.\u003c/p\u003e \u003cp\u003eThe multivariate Cox regression analysis demonstrated that ECOG performance status (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), stage (p\u0026thinsp;=\u0026thinsp;0.039), and surgical intervention (p\u0026thinsp;=\u0026thinsp;0.038) were the independent factors influencing the OS in gallbladder carcinoma. The univariate and multivariate Cox regression analyses are depicted in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate Cox regression analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExp(B)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eExp(B)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge Group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.966\u0026ndash;1.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.984\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.717\u0026ndash;1.351\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.921\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.667\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.217\u0026ndash;3.209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.847\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.498\u0026ndash;2.279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.423\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.235\u0026ndash;6.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.029\u0026ndash;3.091\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGall stone disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.919\u0026ndash;3.512\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.920\u0026ndash;1.742\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA 19.9 category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.993\u0026ndash;1.375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.923\u0026ndash;18.161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.672\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.057\u0026ndash;6.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistopathological subtypes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.943\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.502\u0026ndash;1.770\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eECOG- Eastern Cooperative Oncology Group performance status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eGallbladder carcinoma is the predominant malignancy in the biliary tract system, with the highest incidence observed in northern and central India. In developing nations, it commonly presents in advanced stages, significantly diminishing the chances of successful curative resection [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe median age at presentation was 67 years in a Memorial Sloan\u0026ndash;Kettering report of 435 GBC patients [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In our study, the median age is 55 years, suggesting that the incidence of GBC increases with age. These findings align with previous studies conducted in India [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGBC exhibits a higher incidence in females globally, ranging from 2 to 6 times more than in males. This trend is particularly notable in the northern part of India, Pakistan, and among American-Indian females. In our study, the female-to-male ratio is 3.53:1 [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A previous study from New Delhi reported GBC incidence as 1/100,000 in males and 3.3/100,000 in females during 1987\u0026ndash;1996, with a female-to-male ratio of 3.3:1 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Our study similarly highlights GBC as predominantly affecting females, with a female-to-male ratio of 2.8:1. This observation aligns with other studies reporting a female-to-male ratio of 2.5-3:1 [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUpper abdominal pain emerged as the most common presenting symptom in our study. The clinical signs mimic those of benign gallbladder disease until the invasion of surrounding structures provides a clue leading to an accurate diagnosis [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Similar observations were reported by other studies [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In our study, adenocarcinoma (95.6%) was the most common histology, followed by squamous cell carcinoma (3.5%). Lal et al. reported 89.15% adenocarcinoma and 2.4% squamous cell carcinoma in their study. Hamdani et al. and Beltz et al., in their studies, also reported a similar distribution of histopathological types of GBC [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, the majority of patients presented in stage IV (72.8%), with the liver (61.4%) being the most common site of metastasis. Dubey et al., in their study, reported almost similar findings, with 72.06% of patients in stage IV, and 57.14% having metastasis to the liver [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Batra et al. reported in their study that about 76% of GBC patients presented with stage IV [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Similarly, Gupta et al. reported findings consistent with our study, where 71.4% of patients presented in stage IV [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, the median value of CA 19.9 was 366.60 U/mL, with 48.7% of patients having CA19.9 levels within the range of 200\u0026ndash;400. Sinha SR et al. reported a median value of CA 19.9 of 112.9 U/mL in their study [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], while Zhijian et al. reported a median value of CA 19.9 of 278 U/mL [39]. Elevated CA19.9 levels in patients with GBC without jaundice have been associated with metastatic disease, showing high specificity and potential for prognostication. CA19.9 was found to be superior to CEA in predicting tumor burden and recurrence [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, 15.36% of patients were considered for best supportive care due to their poor ECOG performance status. Singh SK et al. reported a similar finding in their study, with 18.6% of patients considered for best supportive care due to poor performance status [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGallstones have been reported to be present in 61\u0026ndash;90% of patients with gallbladder cancer [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. However, the incidence of GBC in a population with gallstones varies from 0.3 to 3% only. In our study, 57% of patients had evidence of gallstones, aligning with the existing literature.\u003c/p\u003e \u003cp\u003eOur study demonstrated that surgical intervention was associated with improved OS. Surgery remains the sole treatment modality offering a survival benefit in cases of GBC. Over the past decade, various studies have shown a significant increase in 5-year survival rates, rising from 5\u0026ndash;12% and even up to 38%. In contrast, palliative chemotherapy or radiotherapy has shown limited effectiveness for GBC, providing only a few months of survival benefit, if any. Given this situation, an aggressive surgical approach for locally confined disease is entirely justified. There is a lack of consensus worldwide on what constitutes aggressive surgery for a given stage of GBC [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Surgeons must exercise heightened caution when overseeing patients who have fortuitously discovered gallbladder cancers subsequent to laparoscopic cholecystectomy. During laparoscopic removal of the gallbladder, it is essential to use a protective bag to prevent the potential dissemination and implantation of tumor cells. Surgeons should consistently document instances of gallbladder wall breach and whether the specimen was enclosed within a bag before extraction during the cholecystectomy procedure [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, the OS was 14 months, with one and three-year OS rates of 53% and 3%, respectively. Patients who underwent surgical intervention experienced significantly improved OS compared to those who were unable to undergo surgical intervention. The one-year OS rates in stage II, stage III, and stage IV were 100%, 97%, and 44%, respectively. The three-year OS rates in stage II, stage III, and stage IV were 29%, 4%, and 0%. A study by Singh SK et al. reported one-year survival rates of 100%, 76%, and 36.6% in stage II, III, and IV, respectively [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e48\u003c/span\u003e], and similar findings were observed in the study by Principe A et al. [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe survival of GBC patients is very poor, especially for those diagnosed with advanced disease. The geographical region of the patients, namely the Gangetic plains of Bihar, is one of the areas with a high incidence of GBC. Patients with gallstone disease should be considered at high risk for developing GBC, especially in the context of this geographical area and the age group at risk. It is essential to provide adequate workup and surgical intervention for these high-risk group patients. While adequate surgical intervention is associated with improved OS, there is room for improvement in the treatment strategies for locally advanced GBC. More focused efforts are needed to enhance the outcomes for patients facing locally advanced GBC\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAuthor contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dr Dharmendra Singh, Dr Pritanjali Singh, Dr Avik Mandal and Dr Amrita Rakesh. The first draft of the manuscript was written by Dr Dharmendra Singh and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eData Availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eEthics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of All India Institute of Medical Sciences, Patna (IEC/2018/315 dated 04/10/2018).\u003c/p\u003e\n\u003cp\u003eConsent to participate: Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFeroz, Z., Gautam, P., Tiwari, S.\u0026nbsp;\u003cem\u003eet al.\u003c/em\u003eSurvival analysis and prognostic factors of the carcinoma of gallbladder.\u0026nbsp;\u003cem\u003eWorld J Surg Onc\u003c/em\u003e\u003cstrong\u003e20\u003c/strong\u003e, 403 (2022). \u003ca href=\"https://doi.org/10.1186/s12957-022-02857-y\"\u003ehttps://doi.org/10.1186/s12957-022-02857-y\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eDonohue JH, Stewart AK, Menck HR. The national cancer data base report on carcinoma of the gall bladder, 1989-1995. Cancer 1998;83:2618-28.\u003c/li\u003e\n\u003cli\u003eHundal R, Shaffer EA. Gallbladder cancer: Epidemiology and outcome. 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In book: Perspectives in Cancer Prevention-Translational Cancer Research; 2014. p. 145\u0026ndash;51.\u003c/li\u003e\n\u003cli\u003eP\u0026eacute;rez-Moreno P, Riquelme I, Garc\u0026iacute;a P, Brebi P, Roa JC. Environmental and lifestyle risk factors in the carcinogenesis of gallbladder cancer. J Pers Med. 2022;12:234\u003c/li\u003e\n\u003cli\u003eDwivedi S, Mishra S, Tripathi RD. Ganga water pollution: a potential health threat to inhabitants of Ganga basin. Environ Int. 2018;117:327\u0026ndash;38.\u003c/li\u003e\n\u003cli\u003eSoliman AS, Lo AC, Banerjee M, El-Ghawalby N, Khaled HM, Bayoumi S, et al. Diferences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution. Carcinogenesis. 2007;28:1794\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eBatra Y, Pal S, Dutta U, et al. Gallbladder cancer in India: A dismal picture. 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The Nat Med Jour India 16: 209-213.\u003c/li\u003e\n\u003cli\u003eDuffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, et al. Gallbladder cancer (GBC): 10-year experience at memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol 2008;98:485-9.\u003c/li\u003e\n\u003cli\u003eKapoor VK, McMichael AJ (2003) Gallbladder cancer: An \u0026lsquo;Indian\u0026rsquo; disease. The Nat Med Jour India 16: 209-213.\u003c/li\u003e\n\u003cli\u003eShukla VK, Khandelwal C, Roy SK (1985) Primary carcinoma of the gallbladder: a review of a 16 year period at the University hospital. J Surg Oncol 28: 32-35.\u003c/li\u003e\n\u003cli\u003ePandey M, Pathak AK, Gautam A (2001) Carcinoma of the gallbladder: a retrospective review of 99 cases. Digest Dis and Sci 46: 1145-1151.\u003c/li\u003e\n\u003cli\u003eRandi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer 2006;118:1591-602\u003c/li\u003e\n\u003cli\u003eKonstantinidis IT, Deshpande V, Genevay M, Berger D, Fernandez-del Castillo C, Tanabe KK, et al. Trends in presentation and survival for gallbladder cancer during a period of more than 4 decades: A single-institution experience. Arch Surg 2009;144:441-7.\u003c/li\u003e\n\u003cli\u003eRai A, Mohanpatra SC, Shukla HS (2004) A review of association of dietary factors in gallbladder cancer. Indian J Cancer 41: 147-151.\u003c/li\u003e\n\u003cli\u003eShukla VK, Khandelwal C, Roy SK (1985) Primary carcinoma of the gallbladder: a review of a 16 year period at the University hospital. J Surg Oncol 28: 32-35.\u003c/li\u003e\n\u003cli\u003eNandakumar A (2001) National Cancer Registry Programme. Consolidated Report of the Population Based Cancer Registries. Incidence and distribution of cancer: 1990\u0026ndash;96. 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J Pak Med Assoc 60: 217-219.\u003c/li\u003e\n\u003cli\u003eLal M, Raheja S, Bhowmik KT (2018) Carcinoma Gallbladder-Epidemiological Trends in a Tertiary Hospital in North India. Arch Surg Oncol 4: 131. doi: 10.4172/2471-2671.1000131.\u003c/li\u003e\n\u003cli\u003eHamdani NH, Qadri SK, Aggarwalla R (2012) Clinicopathological study of gall bladder carcinoma with special reference to gallstones: our 8-year experience from Eastern India. Asian Pac J Cancer Prev 13: 5613-5617.\u003c/li\u003e\n\u003cli\u003eBeltz WR, Condon RE (1974) Primary carcinoma of the gallbladder. Ann Surg 180: 180-184.\u003c/li\u003e\n\u003cli\u003eDubey AP, Rawat K, Pathi N, Viswanath S, Rathore A, Kapoor R, Pathak A. Carcinoma of gall bladder: Demographic and clinicopathological profile in Indian patients. Oncology. 2018 Jan;2(1).\u003c/li\u003e\n\u003cli\u003eBatra Y, Pal S, Dutta U, et al. Gallbladder cancer in India: A dismal picture. 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PMID: 34321956; PMCID: PMC8312375.\u003c/li\u003e\n\u003cli\u003eSinha SR, Prakash P, Singh RK, Sinha DK.\u0026nbsp;Assessment of tumor markers CA 19-9, CEA, CA 125, and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer.\u0026nbsp;World J Gastrointest Surg\u0026nbsp;2022;\u0026nbsp;14(11): 1272-1284\u003c/li\u003e\n\u003cli\u003e\u0026nbsp;Zhijian Wen, Anfeng Si, Jue Yang, Pinghua Yang, Xinwei Yang, Hu Liu, Xingzhou Yan, Wengang Li, Baohua Zhang, Elevation of CA19-9 and CEA is associated with a poor prognosis in patients with resectable gallbladder carcinoma, HPB, Volume 19, Issue 11, 2017, Pages 951-956.\u003c/li\u003e\n\u003cli\u003eSachan A, Saluja SS, Nekarakanti PK, Nimisha, Mahajan B, Nag HH, Mishra PK. Raised CA19-9 and CEA have prognostic relevance in gallbladder carcinoma. BMC Cancer. 2020 Aug 31;20(1):826. doi: 10.1186/s12885-020-07334-x. PMID: 32867709; PMCID: PMC7457344.\u003c/li\u003e\n\u003cli\u003eSingh SK, Talwar R, Kannan N, et al. Patterns of Presentation, Treatment, and Survival Rates of Gallbladder Cancer: a Prospective Study at a Tertiary Care Centre. Journal of Gastrointestinal Cancer. 2018 Sep;49(3):268-274. DOI: 10.1007/s12029-017-9940-y. PMID: 28367607.\u003c/li\u003e\n\u003cli\u003eReid KM, Ramos-De la Medina A, Donohue JH. Diagnosis and surgical management of gallbladder cancer: a review. J Gastrointest Surg. 2007;11:671\u0026ndash;81.\u003c/li\u003e\n\u003cli\u003eSingh SK, Talwar R, Kannan N, et al. Patterns of Presentation, Treatment, and Survival Rates of Gallbladder Cancer: a Prospective Study at a Tertiary Care Centre. Journal of Gastrointestinal Cancer. 2018 Sep;49(3):268-274. DOI: 10.1007/s12029-017-9940-y. PMID: 28367607.\u003c/li\u003e\n\u003cli\u003eMishra S, Chaturvedi A, Mishra NC (2003) Carcinoma of the gallbladder. Lancet Oncol 4: 167-176.\u003c/li\u003e\n\u003cli\u003eZhu AX, Hong TS, Hazel AF (2010) Current Management of Gallbladder Carcinoma. The Oncol 15: 168-181.\u003c/li\u003e\n\u003cli\u003eGiuliante F, Ardito F, Vellone M (2006) Port-sites excision for gallbladder cancer incidentally found after laparoscopic cholecystectomy. Am J Surg 191: 114-116.\u003c/li\u003e\n\u003cli\u003eSteinert R, Nestler G, Sagynaliev E (2006) Laparoscopic cholecystectomy and gallbladder cancer. J Surg Oncol 93: 682-689.\u003c/li\u003e\n\u003cli\u003eSingh SK, Talwar R, Kannan N, et al. Patterns of Presentation, Treatment, and Survival Rates of Gallbladder Cancer: a Prospective Study at a Tertiary Care Centre. Journal of Gastrointestinal Cancer. 2018 Sep;49(3):268-274. DOI: 10.1007/s12029-017-9940-y. PMID: 28367607.\u003c/li\u003e\n\u003cli\u003ePrincipe A, Del Gaudio M, Ercoloni G, Golfieri R, Cucchetti A, Pinna AD. Radical surgery for gallbladder carcinoma: possibilities of survival. Hepato-Gastroenterology. 2006;53(71):660\u0026ndash;4.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Outcome of Gallbladder cancer, survival in Gallbladder cancer, Surgery in Gallbladder cancer, Overall survival in Gallbladder cancer in India","lastPublishedDoi":"10.21203/rs.3.rs-3825287/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3825287/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose: The aim of this study was to determine the one- and three-year overall survival rates. Methods: This prospective observational study was conducted at a tertiary care center in Bihar state, India. Results: 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\u0026lt;0.001). Multivariate Cox regression analysis confirmed ECOG performance status (p\u0026lt;0.001), stage (p=0.039), and surgical intervention (p=0.038) as independent factors impacting OS.\u003c/p\u003e\n\u003cp\u003eOne-year OS rates for stages II, III, and IV were 100%, 97%, and 44%, respectively, while three-year OS rates were 29%, 4%, and 0%. Surgical intervention significantly influenced OS (p\u0026lt;0.001). OS for surgical intervention was 28 months, and for inoperable cases, it was 12 months. One and three-year OS for surgical intervention were 95% and 11%, while for inoperable cases, they were 41% and 0%, respectively. Conclusion: 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.\u003c/p\u003e","manuscriptTitle":"Prognostic Insights and Survival Analysis of Gallbladder Cancer in Bihar, India: A Prospective Observational Study Emphasizing the Impact of Surgical Intervention on Overall Survival","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 18:47:03","doi":"10.21203/rs.3.rs-3825287/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8d92f0f6-ddb1-4477-bc08-e143a70cf955","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-03-21T08:34:28+00:00","versionOfRecord":{"articleIdentity":"rs-3825287","link":"https://doi.org/10.1007/s13193-024-01925-x","journal":{"identity":"indian-journal-of-surgical-oncology","isVorOnly":false,"title":"Indian Journal of Surgical Oncology"},"publishedOn":"2024-03-18 08:34:28","publishedOnDateReadable":"March 18th, 2024"},"versionCreatedAt":"2024-01-03 18:47:03","video":"","vorDoi":"10.1007/s13193-024-01925-x","vorDoiUrl":"https://doi.org/10.1007/s13193-024-01925-x","workflowStages":[]},"version":"v1","identity":"rs-3825287","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3825287","identity":"rs-3825287","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}