[Expert consensus on the laparoscopic radical resection of gallbladder cancer(2023)].

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

Nomograms to predict long-term survival for patients with gallbladder carcinoma after resection.

BACKGROUND: Surgical resection remains the primary treatment option for gallbladder carcinoma (GBC). However, there is a pressing demand for prognostic tools that can refine patients' treatment choices and tailor personalized therapies accordingly. AIMS: The nomograms were constructed using the data of a training cohort (n = 378) of GBC patients at Eastern Hepatobiliary Surgery Hospital (EHBH) between 2008 and 2018. The model's performance was validated in GBC patients (n = 108) at Guangzhou Centre from 2007 to 2018. METHODS AND RESULTS: The 5-year overall survival (OS) rate in the training cohort was 24.4%. Multivariate analyses were performed using preoperative and postoperative data to identify independent predictors of OS. These predictors were then incorporated into preoperative and postoperative nomograms, respectively. The C-index of the preoperative nomogram was 0.661 (95% CI, 0.627 to 0.694) for OS prediction and correctly delineated four subgroups (5-year OS rates: 48.1%, 19.0%, 15.6%, and 8.1%, p < 0.001). The C-index of the postoperative nomogram was 0.778 (95%CI, 0.756 -0.800). Furthermore, this nomogram was superior to the 8th TNM system in both C-index and the net benefit on decision curve analysis. The results were externally validated. CONCLUSION: The two nomograms showed an optimally prognostic prediction in GBC patients after curative-intent resection.

Decoding the role of long non-coding RNAs in gallbladder cancer pathogenesis: A review focus on signaling pathways interplay.

Gallbladder cancer (GBC) is one of the most aggressive types of biliary tree cancers and the commonest despite its rarity. It is infrequently diagnosed at an early stage, further contributing to its poor prognosis and low survival rate. The lethal nature of the disease has underlined a crucial need to discern the underlying mechanisms of GBC carcinogenesis which are still largely unknown. However, with the continual evolution in the research of cancer biology and molecular genetics, studies have found that non-coding RNAs (ncRNAs) play an active role in the molecular pathophysiology of GBC development. Dysregulated long non-coding RNAs (lncRNAs) and their interaction with intracellular signaling pathways contribute to malignancy and disease development. LncRNAs, a subclass of ncRNAs with over 200 nucleotides, regulate gene expression at transcriptional, translational, and post-translational levels and especially as epigenetic modulators. Thus, their expression abnormalities have been linked to malignancy and therapeutic resistance. lnsRNAs have also been found in GBC patients' serum and tumor tissue biopsies, highlighting their potential as novel biomarkers and for targeted therapy. This review will examine the growing involvement of lncRNAs in GBC pathophysiology, including related signaling pathways and their wider clinical use.

Referral rate of patients with incidental gallbladder cancer and survival: outcomes of a multicentre retrospective study.

BACKGROUND: Treatment outcomes of incidental gallbladder cancer generally stem from tertiary referral centres, while many patients are initially diagnosed and managed in secondary care centres. Referral patterns of patients with incidental gallbladder cancer are poorly reported. This study aimed to evaluate incidental gallbladder cancer treatment in secondary centres, rates of referral to tertiary centres and its impact on survival. METHODS: Medical records of patients with incidental gallbladder cancer diagnosed between 2000 and 2019 in 27 Dutch secondary centres were retrospectively reviewed. Patient characteristics, surgical treatment, tumour characteristics, referral pattern and survival were assessed. Predictors for overall survival were determined using multivariable Cox regression. RESULTS: In total, 382 patients with incidental gallbladder cancer were included. Of 243 patients eligible for re-resection (pT1b-pT3, M0), 131 (53.9%) were referred to a tertiary centre. The reason not to refer, despite indication for re-resection, was not documented for 52 of 112 non-referred patients (46.4%). In total, 98 patients underwent additional surgery with curative intent (40.3%), 12 of these in the secondary centre. Median overall survival was 33 months (95% c.i. 24 to 42 months) in referred patients versus 17 months (95% c.i. 3 to 31 months) in the non-referred group (P = 0.019). Referral to a tertiary centre was independently associated with improved survival after correction for age, ASA classification, tumour stage and resection margin (HR 0.60, 95% c.i. 0.38 to 0.97; P = 0.037). CONCLUSION: Poor incidental gallbladder cancer referral rates were associated with worse survival. Age, performance status, resection margin or tumour stage should not preclude referral of a patient with incidental gallbladder cancer to a tertiary centre.

Outcomes of patients with gallbladder cancer presenting with acute cholecystitis.

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

Large Cell Neuroendocrine Carcinoma of Gallbladder: A Case Report.

Large cell neuroendocrine carcinoma of the gallbladder is an extremely rare tumour with aggressive behaviour and a bad prognosis. Here, we report a case of a 65-year-old lady suspected of carcinoma of the gallbladder and underwent extended cholecystectomy. The histopathology report revealed neuroendocrine carcinoma of a large cell type of gall bladder infiltrating the liver and three periportal and pericholedochal lymph nodes. She had an uneventful perioperative period and was doing good till 6 months of follow-up. The only potentially curative treatment for large cell neuroendocrine carcinoma of the gallbladder is aggressive surgical resection, owing to its aggressive behaviour and bad prognosis. Keywords: carcinoma; case reports; cholecystectomy; gallbladder.

Comparative prognosis and risk assessment in gallbladder neuroendocrine neoplasms versus adenocarcinomas.

Background: Gallbladder neuroendocrine neoplasms (GB-NENs) are a rare malignant disease, with most cases diagnosed at advanced stages, often resulting in poor prognosis. However, studies regarding the prognosis of this condition and its comparison with gallbladder adenocarcinomas (GB-ADCs) have yet to yield convincing conclusions. Methods: We extracted cases of GB-NENs and GB-ADCs from the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Firstly, we corrected differences in clinical characteristics between the two groups using propensity score matching (PSM). Subsequently, we visualized and compared the survival outcomes of the two groups using the Kaplan-Meier method. Next, we employed the least absolute shrinkage and selection operator (LASSO) regression and Cox regression to identify prognostic factors for GB-NENs and constructed two nomograms for predicting prognosis. These nomograms were validated with an internal validation dataset from the SEER database and an external validation dataset from a hospital. Finally, we categorized patients into high-risk and low-risk groups based on their overall survival (OS) scores. Results: A total of 7,105 patients were enrolled in the study, comprising 287 GB-NENs patients and, 6,818 GB-ADCs patients. There were substantial differences in clinical characteristics between patients, and GB-NENs exhibited a significantly better prognosis. Even after balancing these differences using PSM, the superior prognosis of GB-NENs remained evident. Independent prognostic factors selected through LASSO and Cox regression were age, histology type, first primary malignancy, tumor size, and surgery. Two nomograms for prognosis were developed based on these factors, and their performance was verified from three perspectives: discrimination, calibration, and clinical applicability using training, internal validation, and external validation datasets, all of which exhibited excellent validation results. Using a cutoff value of 166.5 for the OS nomogram score, patient mortality risk can be identified effectively. Conclusion: Patients with GB-NENs have a better overall prognosis compared to those with GB-ADCs. Nomograms for GB-NENs prognosis have been effectively established and validated, making them a valuable tool for assessing the risk of mortality in clinical practice.

Malignant melanoma located in the ureter and gallbladder: A case report and literature review.

RATIONALE: Melanoma is one of a common cutaneous malignancy. Currently, metastatic malignant melanoma is difficult to be diagnosed through imaging examinations. Furthermore, the incidence of metastatic melanoma affecting the gallbladder and ureter is exceptionally rare. PATIENT CONCERNS: A 54-year-old female was admitted to the hospital with a half-month history of left lower back pain. Correlative examination revealed an occupying lesion in the mid-left ureter and the neck of the gallbladder. DIAGNOSES: The patient was initially diagnosed with gallbladder cancer and left ureteral carcinoma based on imaging. Following 2 operations, immunohistochemical staining confirmed the presence of metastatic melanoma involving both the gallbladder and ureter. INTERVENTION: After multidisciplinary consultation and obtaining consent from the patient and her family, the patient underwent left radical nephroureterectomy, radical cholecystectomy, laparoscopic partial hepatectomy (Hep IV, Hep V), and lymph node dissection of hepatoduodenal ligament. OUTCOMES: One month after treatment, the patient imaging showed no disease progression, and at 6 months of follow-up, the patient was still alive. LESSONS: It is difficult to distinguish metastatic melanoma from carcinoma in situ by imaging. In addition, metastatic malignant melanoma lacks specific clinical manifestations and is prone to misdiagnosis, which emphasizes the highly aggressive nature of malignant melanoma.

Angiosarcoma of gallbladder, a literature review.

BACKGROUND: Angiosarcoma of the gallbladder is a rare diagnostic entity rarely encountered by pathologists and has rarely been reported in literature. This review aimed to examine the clinicopathological features, immunohistochemistry, treatment, and outcomes of gallbladder angiosarcoma. METHODS: A search of the PubMed, Science Direct and Google Scholar was done with the search terms ("angiosarcoma" OR "angiosarcomas") AND ("gallbladder" OR "gallbladders"). Based on inclusion and exclusion criteria, only case reports could be used for this review. RESULT: 8 case reports were chosen in the end for analysis. The mean age of the patients at presentation was 65 years. It was most frequently observed in males. Abdominal pain and palpable mass were the most commonly reported symptoms. Cholelithiasis and anemia were also reported. On histopathology morphologically epithelioid appearance of angiosarcoma was evident. Cytokeratin (CK) AE1/AE3, Von willebrand factor, Factor VIII antigen, Vimentin, CD31 were positive. Meanwhile, UEA, CD34, CD117, S-100, Keratin, EMA, and CEA showed negative outcome. Surgery was the preferred method of treatment and a mean 10-months follow-up was done. CONCLUSION: Despite the unavailability of convincing data, histological and immunohistochemical analyses play a major role in the diagnosis of gallbladder angiosarcoma. Nevertheless, more comprehensive clinical studies are required to provide universal guidelines for the treatment and diagnosis of angiosarcoma of the gallbladder.

Diagnostic Utility of Next-Generation Sequencing in Circulating Free DNA and a Comparison With Matched Tissue in Gallbladder Carcinoma.

Mutation detection for therapy monitoring in cell-free DNA (cfDNA) is used clinically for some malignancies. Gallbladder carcinoma (GBC) presents a diagnostic challenge and has limited late-stage treatment options. To our knowledge, this novel study examines, for the first time, genomic alterations in cfDNA from GBC to assess diagnostic accuracy and therapeutic options. The concordance of somatic genomic changes in cfDNA and DNA from paired tumor tissue was analyzed. Paired serum and tissue samples from 40 histologically proven GBC, 20 cholecystitis, and 4 normal (noninflamed gallbladder) controls were included. Targeted next-generation sequencing with a 22-gene panel (Colon and Lung Cancer Research Panel v2, Thermo Scientific) in cfDNA and tumor tissue with high depth and uniform coverage on ION Personal Genome Machine (ION, PGM) was performed. A spectrum of 223 mutations in cfDNA and 225 mutations in formalin-fixed paraffin-embedded tissue DNA were identified in 22 genes. Mutations ranged from 1 to 17 per case. In cfDNA frequent alterations were in TP53 (85.0%), EGFR (52.5%), MET (35%) CTNNB1, SMAD4, BRAF (32.5%), PTEN (30%), FGFR3 and PIK3CA (27.5%), NOTCH1 (25.0%), and FBXW7 and ERBB4 (22.5%). At least one clinically actionable mutation was identified in all cfDNA samples. Paired samples shared 149 of 225 genetic abnormalities (66.2%). Individual gene mutation concordance ranged from 44.44% to 82.0% and was highest for EGFR (82.0%), BRAF and NOTCH1 (80.0%), TP53 (73.08%), MET (72.22%), and ERBB4 (71.42%) with a significant level of correlation (Spearman r = 0.91, P ≤ .0001). The sensitivity and specificity of the TP53 gene at the gene level was the highest (94.44% and 100.0%, respectively). Overall survival was higher for ERBB4 and ERBB2 mutant tumors. The adenocarcinoma subtype revealed specific genetic changes in ERBB4, SMAD4, ERBB2, PTEN, KRAS, and NRAS. NGS-based cfDNA mutation profiling can be used to diagnose GBC before surgery to guide treatment decisions. Targeted therapy identified in GBC included SMAD4, ERBB2, ERBB4, EGFR, KRAS, BRAF, PIK3CA, MET, and NRAS.

Is systematic histological examination of the cholecystectomy specimen always necessary?

INTRODUCTION: The histological examination (HE) of all cholecystectomy specimens removed for cholelithiasis is a widespread practice to rule out unrecognized gallbladder cancer. (GBC). But this dogmatic practice has been called into question by recent published data. The aim of this literature review was to answer two questions: (1) can HE be omitted in specific cases; (2) under what conditions is a selective strategy indicated? METHODS: A review of the literature was carried out that included selected multicenter studies, registry studies, or meta-analyses. A reliable technique for the surgeon's macroscopic examination of the specimen would allow the selection of dubious cases for HE. The cost-effectiveness of selective HE was discussed. The PICO methodology (population, intervention, comparator, outcome) was used in the selection of articles that compared routine and selective histological examination. RESULTS: If cases from countries with a high prevalence of gallbladder cancer are excluded and in the absence of high-risk situations (advanced age, female gender, calcified or porcelain gallbladder, acute cholecystitis, polyps, abnormalities noted intra-operatively), the macroscopic examination of the gallbladder in the operating room has a reliability approaching 100% in the majority of published studies. This would make it possible to omit systematic HE without compromising the diagnosis and prognosis of patients with unsuspected GBC and with a very favorable cost-effectiveness ratio. CONCLUSION: Through a selection of patients at very low risk of incidentally-discovered cancer and a routine macroscopic examination of the opened gallbladder, the strategy of selective HE could prove useful in both clinical and economic terms.

The risk and predictors of gallbladder cancer in patients with gallbladder polyps: A retrospective cohort study with an insight into confounding by indication.

BACKGROUND AND AIM: We aimed to determine the risk and predictors of gallbladder cancer in all individuals with gallbladder polyps (GP) including those who did not have cholecystectomy. METHODS: The STROCSS guideline was followed to conduct a retrospective cohort study. All individuals with GP between 2010 and 2019 were followed up to determine the risk and predictors of gallbladder cancer. The primary outcomes were gallbladder cancer and gallbladder dysplasia, and the secondary outcomes included polyp growth rate and polyp disappearance rate. Binary logistic regression analysis and receiver operating characteristic curve analysis were conducted to evaluate the outcomes. RESULTS: Analysis of 438 patients showed risk of gallbladder cancer was 0.7% in all polyps (0% in polyps < 10 mm; 5.9% in polyps ≥ 10 mm). The risk of gallbladder dysplasia or cancer was 1.1% in all polyps (0% in polyps < 10 mm; 10% in polyps ≥ 10 mm). The polyp size (P = 0.0001) was predictor of cancer; however, patient's age (P = 0.1085), number of polyps (P = 0.9983), symptomatic polyps (P = 0.3267), and change in size (P = 0.9012) were not. Size of 21 mm was cut-off for risk of cancer (area under the curve [AUC]: 0.995, P < 0.001) and 11.8 mm for risk of dysplasia or cancer (AUC: 0.986, P < 0.001). The mean polyp growth rate was 0.3 mm/year and polyp disappearance rate was 16%. CONCLUSIONS: The GP size remains the only predictor of malignant changes regardless of patient's age, patient's symptoms and number of polyps. The polyp growth rate is unremarkable, and a significant proportion disappears during follow-up. We changed our follow-up protocol with reduced number of scans and early discharge policy.

Melanoma of the gallbladder.

Melanoma is a highly malignant neoplasm with the most typical primary locations in the skin and eyeball and rarely reported in the other organs, including the gallbladder. More commonly metastases of melanoma of various primary sites to the gallbladder are observed. However, generally melanoma of the gallbladder is a rare entity with only 217 cases reported in the literature up to date. The paper summarizes knowledge on epidemiology, symptoms, laboratory and imaging findings, morphology, treatment options, and outcome of patients with both primary and metastatic melanoma to the gallbladder.

The value of the preoperative Naples prognostic score in predicting prognosis in gallbladder cancer surgery patients.

PURPOSE: The Naples prognostic score (NPS) is a comprehensive prognostic model that includes inflammatory and nutrition-related indicators and is increasingly used as a prognostic score for various malignant tumors. Given its predictive effect on prognosis in patients with gallbladder cancer, it is currently unclear. This study aimed to investigate the role of preoperative NPS in predicting prognosis in gallbladder cancer surgery patients. PATIENTS AND METHODS: A retrospective analysis was performed for 135 patients who underwent radical surgery for gallbladder cancer without preoperative treatment between March 2011 and January 2020. NPS was calculated by measuring the preoperative total cholesterol value, serum albumin value, neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). They were then divided into 3 groups (groups 0, 1, and 2) based on NPS scores. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Plot time-dependent receiver operating characteristic (ROC) curves to compare the prognostic value of scoring systems. Finally, a nomogram model was developed with independent prognostic factors. RESULTS: Multivariate analysis showed that NPS was an independent risk factor affecting OS (HR = 3.417, p < 0.05). The time-dependent ROC curve results showed that NPS had a better predictive value on survival prognosis than other indicators. The nomogram constructed according to independent factors such as NPS has a good predictive ability for OS. CONCLUSION: As a simple and reliable tool, the NPS has important predictive value in the survival prognosis of gallbladder cancer patients. The nomogram model constructed by NPS will help determine prognosis and make individualized treatment decisions.

Gallbladder cancer mimicking perihilar cholangiocarcinoma-considerable rate of postoperative reclassification with implications for prognosis.

BACKGROUND: For some patients undergoing resection under the suspicion of a perihilar cholangiocarcinoma (pCCA), postoperative diagnosis may differ from the preoperative diagnosis. While a postoperative finding of benign bile duct stricture is known to affect 3-15% of patients, less has been described about the consequences of finding other biliary tract cancers postoperatively. This study compared pre- and postoperative diagnoses, risk characteristics, and outcomes after surgery for suspected pCCA. METHODS: Retrospective single-center study, Karolinska University Hospital, Stockholm, Sweden (January 2009-May 2017). The primary postoperative outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. Survival analysis was performed by the Kaplan-Meier method. RESULTS: Seventy-one patients underwent resection for suspected pCCA. pCCA was confirmed in 48 patients (68%). Ten patients had benign lesions (14%), 2 (3%) were diagnosed with other types of cholangiocarcinoma (CCA, distal n = 1, intrahepatic n = 1), while 11 (15%) were diagnosed with gallbladder cancer (GBC). GBC patients were older than patients with pCCA (median age 71 versus 58 years, p = 0.015), with a large proportion of patients with a high tumor extension stage (≥ T3, 91%). Median overall survival was 20 months (95% CI 15-25 months) for patients with pCCA and 17 months (95% CI 11-23 months) for patients with GBC (p = 0.135). Patients with GBC had significantly shorter median disease-free survival (DFS), 10 months (95% CI 3-17 months) compared 17 months (95% CI 15-19 months) for patients with pCCA (p = 0.010). CONCLUSIONS: At a large tertiary referral center, 15% of patients resected for suspected pCCA were postoperatively diagnosed with GBC. Compared to patients with pCCA, GBC patients were older, with advanced tumors and shorter DFS. The considerable rate of re-classification stresses the need for improved preoperative staging, as these prognostic differences could have implications for treatment strategies.

[Efficacy analysis of surgical combined with postoperative adjuvant therapy for T3 gallbladder carcinoma: a multicenter retrospective study].

Objective: To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection. Methods: Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A,n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B,n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results: After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A (χ2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% (χ2=4.042,P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% (χ2=0.992,P=0.319). Conclusions: Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Non cancer causes of death after gallbladder cancer diagnosis: a population-based analysis.

Mortality from non cancer causes in patients with gallbladder cancer (GBC) still unclear. This study evaluated the causes and risk factors of non cancer death during different follow-up periods after GBC diagnosis. Non cancer causes of death for GBC patients diagnosed between 2000 and 2017 in Surveillance, Epidemiology and End Results database were analyzed and standardized mortality rates (SMR) for each non cancer death were calculated. Predictors for non cancer death were identified through multivariate competing risk analysis. A total 11,927 GBC patients were identified for further analysis, 9393 died during follow up. The largest proportion of non cancer deaths occurred > 3 years after diagnosis (39.4%). Most common non cancer cause were cardiovascular disease (43.3%), followed by other cause of death (34.4%) and infectious diseases (8.6%). Compared with US general population, GBC patients has higher risk of death from disease of heart (SMR, 1.58; 95%CI, 1.41-1.75), septicemia (SMR,3.21; 95%CI, 2.27-4.40), diabetes mellitus (SMR,1.97; 95%CI, 1.43-2.63), alone with other causes. Non cancer causes accounted for a significant proportion of deaths during the follow-up period after GBC diagnosis. The risk of non cancer death is higher in GBC patients than in the general population. Our study provides comprehensive assessment of death from non cancer cause in GBC patients, which has important implications for health management in GBC patients.