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Lv TR, Wang JK, Li FY, Hu HJ. Prognostic factors for resected cases with gallbladder carcinoma: a systematic review and meta-analysis. Int J Surg 2024; 110:4342-4355. [PMID: 38537060 PMCID: PMC11254228 DOI: 10.1097/js9.0000000000001403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 03/11/2024] [Indexed: 07/19/2024]
Abstract
OBJECTIVE Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival among resected cases with gallbladder carcinoma. METHODS PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. RESULTS A total of 36 studies with 11 502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P =0.00020), concurrent gallstone disease (HR=1.22, P =0.00200), elevated preoperative CA199 level (HR=1.93, P <0.00001), advanced T stage (HR=3.09, P <0.00001), lymph node metastasis (HR=2.78, P <0.00001), peri-neural invasion (HR=2.20, P <0.00001), lymph-vascular invasion (HR=2.37, P <0.00001), vascular invasion (HR=2.28, P <0.00001), poorly differentiated tumor (HR=3.22, P <0.00001), hepatic side tumor (HR=1.85, P <0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P <0.00001), combined bile duct resection (HR=1.45, P <0.00001), and positive surgical margin (HR=2.90, P <0.00001) were well-established prognostic factors. Pathological subtypes ( P =0.53000) and postoperative adjuvant chemotherapy ( P =0.70000) were not prognostic factors. Pooled results of multivariate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. CONCLUSION Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.
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Affiliation(s)
- Tian-Run Lv
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jun-Ke Wang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Fu-Yu Li
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hai-Jie Hu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Lv TR, Hu HJ, Liu F, Ma WJ, Jin YW, Li FY. The role of extra-hepatic bile duct resection in patients with gallbladder carcinoma with peri-neural invasion: A ten-year experience in China. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 49:1009-1015. [PMID: 36604233 DOI: 10.1016/j.ejso.2022.12.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/19/2022] [Accepted: 12/30/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND Peri-neural invasion (PNI) in gallbladder carcinoma (GBC) has been demonstrated as a vital prognostic factor. However, whether PNI in patients with GBC can be regarded as a surgical indication of bile duct resection (BDR) remains controversial. METHODS GBC patients with pathologically-confirmed PNI between September 2010 and September 2020 were retrospectively reviewed. Comparative analyses were performed in patients with PNI according to the performance of BDR. SPSS 25.0 software and Graph pad PRISMA 7.0 software were used for statistical analyses. RESULTS A total of 70 patients GBC patients with PNI were incorporated. The results of comparative analyses indicated that patients who received BDR were generally in a more advanced stage and often required a more extended radical cholecystectomy. Higher incidences of preoperative jaundice (48.6% vs 2.9%, P < 0.0001), major hepatectomy (25.7% vs 8.6%, P = 0.055), combined multi-visceral resections (48.6% vs 5.7%, P < 0.0001), combined major vascular reconstruction (22.9% vs 2.9%, P = 0.014), and a lower R0 rate (68.6% vs 88.6%, P = 0.039) were detected in patients who received BDR. Even after propensity score matching (PSM), BDR still had no significant survival advantage but only increased the length of postoperative stay and the frequency of postoperative morbidities. CONCLUSION BDR seemed to have no significant survival advantage in GBC patients with PNI and was only correlated with a longer postoperative hospital stay and a higher rate of morbidities. PNI should not be regarded as a surgical indication of BDR in patients with GBC.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Yan-Wen Jin
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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Yuan Z, Shui Y, Liu L, Guo Y, Wei Q. Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy. Radiat Oncol 2022; 17:118. [PMID: 35799270 PMCID: PMC9264693 DOI: 10.1186/s13014-022-02091-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 06/27/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy. METHODS Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis. RESULTS The median follow-up time is 34 months (IQR: 11-64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis. CONCLUSION The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.
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Affiliation(s)
- Zhijun Yuan
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yongjie Shui
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lihong Liu
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yinglu Guo
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qichun Wei
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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Lv TR, Liu F, Hu HJ, Regmi P, Ma WJ, Yang Q, Jin YW, Li FY. The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:482-491. [PMID: 34955314 DOI: 10.1016/j.ejso.2021.11.131] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 10/06/2021] [Accepted: 11/26/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients. METHODS PubMed, EMBASE and the Cochrane Library were searched up to March 1st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses. RESULTS EHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01). CONCLUSION EHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - Parbatraj Regmi
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Qing Yang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Yan-Wen Jin
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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Xu L, Tan H, Liu X, Huang J, Liu L, Si S, Sun Y, Zhou W, Yang Z. Survival benefits of simple versus extended cholecystectomy and lymphadenectomy for patients with T1b gallbladder cancer: An analysis of the surveillance, epidemiology, and end results database (2004 to 2013). Cancer Med 2020; 9:3668-3679. [PMID: 32233076 PMCID: PMC7286443 DOI: 10.1002/cam4.2989] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 02/17/2020] [Accepted: 03/01/2020] [Indexed: 12/12/2022] Open
Abstract
Although guidelines recommend extended surgical resection, radical resection and lymphadenectomy for patients with tumor stage (T)1b gallbladder cancer, these procedures are substantially underutilized. This population‐based, retrospective cohort study aimed to evaluate treatment patterns and outcomes of 401 patients using the US Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013. Results showed that median overall survival (OS) was 69 months for lymphadenectomy patients and 37 months for those without lymphadenectomy. Lymphadenectomy also tended to prolong cancer‐specific survival (CSS), although the differences were not statistically significant. OS and CSS were similar for patients who received simple cholecystectomy and extended surgical resection. Cox proportional hazards regression models revealed survival advantages in patients with stage T1bN0 gallbladder cancer compared to those with stage T1bN1, and patients who received simple cholecystectomy plus lymphadenectomy compared to those who did not receive lymph node dissection. In further analyses, patients undergoing simple cholecystectomy who had five or more lymph nodes excised had better OS and CSS than those without lymph node dissection. In conclusion, survival advantages are shown for patients with T1b gallbladder cancer undergoing surgeries with lymphadenectomy. Future studies with longer follow‐up and control of potential confounders are highly warranted.
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Affiliation(s)
- Li Xu
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Haidong Tan
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Xiaolei Liu
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Jia Huang
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Liguo Liu
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Shuang Si
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Yongliang Sun
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Wenying Zhou
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Zhiying Yang
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, Beijing, China
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Who benefits from R0 resection? A single-center analysis of patients with stage Ⅳ gallbladder cancer. Chronic Dis Transl Med 2019; 5:188-196. [PMID: 31891130 PMCID: PMC6926113 DOI: 10.1016/j.cdtm.2019.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Indexed: 12/12/2022] Open
Abstract
Objectives Most patients with gallbladder cancer (GBC) present with advanced-stage disease and have a poor prognosis. Radical resection remains the only therapeutic option to improve survival in patients with GBC. This study aimed to analyze the prognostic factors in patients with stage Ⅳ GBC and to identify a subgroup of patients who might benefit from R0 resection. Methods A total of 285 patients with stage Ⅳ GBC were retrospectively analyzed at our institution from January 2008 to December 2012. Factors potentially influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analyses. Results The 1-, 3-, and 5-year overall survival rates were 6.6% (15/229), 0.9% (2/229), and 0 (0/229), respectively. Ascites (relative risk [RR] = 1.631, 95% confidence interval [CI]: 1.221-2.180, P = 0.001), pathological grade (RR = 1.337, 95% CI: 1.050-1.702, P = 0.018), T stage (RR = 1.421, 95% CI: 1.099-1.837, P = 0.000), M stage (RR = 1.896, 95% CI: 1.409-2.552, P = 0.000), and surgery (RR = 1.542, 95% CI: 1.022-2.327, P = 0.039) were identified as independent risk factors influencing prognosis. The median survival time (MST) was significantly higher in patients undergoing R0 resection than in those undergoing R1/R2 resection (6.0 vs. 2.7 months; P < 0.001). In subgroup analyses, stage ⅣA patients benefited from R0 resection (MST for R0 vs. R1/R2, 11.0 vs. 4.0 months; P = 0.003), while R0 resection had a significant survival benefit than R1/R2 resection in patient with stage ⅣB GBC without distant metastasis (MST for R0 vs. R1/R2, 6.0 vs. 3.0 months; P = 0.007). Conclusion Ascites, pathological grade, T stage, M stage, and surgery were independent risk factors influencing prognosis in patients with stage IV GBC. N2 lymph node metastasis did not preclude curative resection, and radical resection should be considered in patients with stage Ⅳ GBC without distant metastasis once R0 margin was achieved.
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Chun YJ, Jeung HC, Park HS, Park JS, Rha SY, Choi HJ, Lee JH, Jeon TJ. Significance of Metabolic Tumor Volume and Total Lesion Glycolysis Measured Using ¹⁸F-FDG PET/CT in Locally Advanced and Metastatic Gallbladder Carcinoma. Yonsei Med J 2019; 60:604-610. [PMID: 31250573 PMCID: PMC6597472 DOI: 10.3349/ymj.2019.60.7.604] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 04/20/2019] [Accepted: 04/25/2019] [Indexed: 12/22/2022] Open
Abstract
PURPOSE This study aimed to determine the prognostic value of new quantitative parameters of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), including metabolic tumor volume (MTV), in patients with locally advanced and metastatic gallbladder cancer (GBC). MATERIALS AND METHODS In total, 83 patients initially diagnosed with locally advanced and metastatic GBC and who underwent ¹⁸F-FDG PET/CT at the time of initial diagnosis were retrospectively reviewed. The metabolic volume-based PET parameters of primary tumors and metastatic lesions were measured, including maximum and average standardized uptake values (SUV), MTV, and total lesion glycolysis. An overall survival (OS) analysis was performed using the Kaplan-Meier method with PET and clinical parameters. A Cox proportional hazards regression analysis was performed to determine independent prognostic factors. RESULTS In univariate analysis, pathologic differentiation (p<0.001), performance status (PS; p=0.003), C-reactive protein (CRP) level (p=0.009), and PET-related SUVmt max (the highest SUV among the metastatic lesions) (p=0.040) and MTVtotal (the sum of the MTVs of both the primary and metastatic lesions) (p=0.031), were significant for OS. In multivariate analysis, MTVtotal (hazard ratio: 2.07; 95% confidence interval: 1.23-3.48; p=0.006) remained significant for the prediction of OS, as did differentiation (p=0.001), PS (p=0.001), and CRP (p=0.039). CONCLUSION In locally advanced and metastatic GBC, volume-based PET/CT parameters of the total tumor burden of malignancy, such as MTVtotal, were found to be useful for the identification of patients with poor prognosis.
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Affiliation(s)
- You Jin Chun
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Hei Cheul Jeung
- Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyung Soon Park
- Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea
| | - Ji Soo Park
- Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Sun Young Rha
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Jin Choi
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hoon Lee
- Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Joo Jeon
- Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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Wang JK, Ma WJ, Wu ZR, Yang Q, Hu HJ, Liu F, Li FY. Is combined extra-hepatic bile-duct resection justified for advanced gallbladder carcinoma? Gastroenterol Rep (Oxf) 2019; 7:426-433. [PMID: 31857904 PMCID: PMC6911994 DOI: 10.1093/gastro/goz018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 02/26/2019] [Accepted: 04/08/2019] [Indexed: 02/05/2023] Open
Abstract
Background Whether the extra-hepatic bile duct (EHBD) should be routinely resected for gallbladder carcinoma (GBC) remains controversial. The current study aimed to determine the clinical impact of combined EHBD resection during curative surgery for advanced GBC. Methods In total, 213 patients who underwent curative surgery for T2, T3 or T4 GBC were enrolled. The clinicopathological features were compared between the patients treated with EHBD resection and those without EHBD resection. Meanwhile, univariable and multivariable Cox-proportional hazards regression models were used to identify risk factors for overall survival (OS). Results Among the 213 patients identified, 87 (40.8%) underwent combined EHBD resection. Compared with patients without EHBD resection, patients with EHBD resection suffered more post-operative complications (33.3% vs. 21.4%, P = 0.046). However, the median OS of the EHBD resection group was longer than that of the non-EHBD resection group (25 vs. 11 months, P = 0.008). Subgroup analyses were also performed according to tumor (T) category and lymph-node metastasis. The median OS was significantly longer in the EHBD resection group than in the non-EHBD resection group for patients with T3 lesion (15 vs. 7 months, P = 0.002), T4 lesion (11 vs. 6 months, P = 0.021) or lymph-node metastasis (12 vs. 7 months, P < 0.001). No survival benefit of EHBD resection was observed in GBC patients with T2 lesion or without lymph-node metastasis. T category, lymph-node metastasis, margin status, pre-operative CA19-9 level and EHBD resection were identified as independent prognostic factors for OS of patients with advanced GBC (all P values <0.05). Conclusions EHBD resection can independently affect the OS in advanced GBC. For GBC patients with T3 lesion, T4 lesion and lymph-node metastasis, combined EHBD resection is justified and may improve OS.
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Affiliation(s)
- Jun-Ke Wang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China
| | - Zhen-Ru Wu
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China
| | - Qin Yang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China
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Gupta A, Gupta A, Gupta S, Chauhan U, Joshua LM. Are incidentally detected gall bladder cancers really incidental? A report of two cases from a developing nation. Trop Doct 2018; 48:355-358. [PMID: 30089420 DOI: 10.1177/0049475518788486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Gallbladder cancer (GBC) is a rare gastrointestinal tumour. It occurs in women with pre-existing cholelithiasis. These tumours pose therapeutic as well as diagnostic challenges to treating clinicians. Early suspicion and optimal surgery for suspected GBC results in the best outcome. We describe two cases of metastatic GBC initially treated by simple cholecystectomy for gallstone despite disease pointers towards a malignant pathology. Subsequent presentation was with histopathologically proven metastatic GBC. In an area of high gallsone prevalence, a high index of suspicion and correct management of patients with suspicion of GBC is mandatory.
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Affiliation(s)
- Ashish Gupta
- 1 Assistant Professor, Department of Surgery, AIIMS, Rishikesh, India
| | - Amit Gupta
- 2 Additional Professor, Department of Surgery AIIMS, Rishikesh, India
| | - Sweety Gupta
- 3 Assistant Professor, Department of Radiotherapy, AIIMS, Rishikesh, India
| | - Udit Chauhan
- 4 Assistant Professor, Department of Radiology, AIIMS, Rishikesh, India
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Imaoka Y, Kuranishi F, Miyazaki T, Yasuda H, Ohno T. Long-lasting complete response status of advanced stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine: two case reports. World J Surg Oncol 2017; 15:170. [PMID: 28893260 PMCID: PMC5594464 DOI: 10.1186/s12957-017-1245-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 09/03/2017] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND The prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer. CASE PRESENTATION Case 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years. Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years. CONCLUSION We report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs.
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Affiliation(s)
- Yuki Imaoka
- Department of Surgery, Innoshima Ishikai Hospital, 1962, Nakanosho, Innoshima, Onomichi, 722-7221, Japan.
| | - Fumito Kuranishi
- Department of Surgery, Innoshima Ishikai Hospital, 1962, Nakanosho, Innoshima, Onomichi, 722-7221, Japan
| | - Tsubasa Miyazaki
- Cell-Medicine Inc, 2-1-6-C-B-1, Sengen, Tsukuba, Tsukuba, Ibaraki, 305-0047, Japan
| | - Hiroko Yasuda
- Cell-Medicine Inc, 2-1-6-C-B-1, Sengen, Tsukuba, Tsukuba, Ibaraki, 305-0047, Japan
| | - Tadao Ohno
- Cell-Medicine Inc, 2-1-6-C-B-1, Sengen, Tsukuba, Tsukuba, Ibaraki, 305-0047, Japan
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11
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Gavriilidis P, Askari A, Azoulay D. To Resect or Not to Resect Extrahepatic Bile Duct in Gallbladder Cancer? J Clin Med Res 2016; 9:81-91. [PMID: 28090223 PMCID: PMC5215011 DOI: 10.14740/jocmr2804w] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2016] [Indexed: 12/18/2022] Open
Abstract
The indications for and limitations of extrahepatic bile duct resection (EHBDR) in the context of gallbladder (GB) cancer are unclear. The purpose of this review was to examine the current literature to determine the impact of EHBDR on loco-regional recurrence and survival in GB cancer. The EMBASE and Medline databases were searched up to February 2016 using the terms: extrahepatic bile duct resection and gallbladder cancer. Studies published in the last 20 years were eligible for inclusion. Given the heterogeneity of the population and the study methodologies employed, qualitative data synthesis in the form of meta-analysis was deemed implausible. Twenty-four studies fulfilled the inclusion criteria. The selected studies include 6,722 (55%) EHBDRs in a total of 12,251 GB cancer operations. The 25 studies were categorized into seven groups: 1) cancer survival all stages; 2) hepatoduodenal ligament invasion; 3) outcome in EHBDR and EHBDNR; 4) pT1b tumors; 5) pT2 tumors; 6) pT3/T4 tumors; and 7) incidental GB cancer. Radical cholecystectomy with EHBDR should be used as a standard operation for tumors involving the neck or the cystic duct of the GB (either macroscopically or microscopically). In all other cases, operative strategy should be individualized to the patient.
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Affiliation(s)
- Paschalis Gavriilidis
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France
| | - Alan Askari
- Department of Surgery, Ipswich Hospital, NHS Trust Ipswich, Heath Rd IP4 5PD, UK
| | - Daniel Azoulay
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France; INSERM U 955, Creteil, France
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12
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Lu W, Hu Y, Ma Q, Zhou L, Jiang L, Li Z, Zhao S, Xu Y, Shi W, Li S, Liu Y. miR-223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1. Oncotarget 2016; 7:62364-62376. [PMID: 27577078 PMCID: PMC5308733 DOI: 10.18632/oncotarget.11634] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 08/23/2016] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND MicroRNAs (miRs) are involved in cancer carcinogenesis, and certain regulatory miRs could provide promising therapeutic methods for refractory malignancies, such as gallbladder cancer (GBC). miR-223 was found to play a pivotal role in enhancing chemotherapeutic effects, therefore evoking interest in the role of miR-223 in GBC. RESULTS miR-223 was decreased in GBC tissues and cell lines, and ectopic miR- 223 expression exhibited multiple anti-tumorigenic effects in GBC cells, including decreased proliferation, migration and invasion in vitro. However, treatment with a miR-223 inhibitor increased cell viability. We determined that STMN1 was negatively correlated with and regulated by miR-223 in GBC. miR-223 increased GBC sensitivity to docetaxel in vitro and in vivo, and the induced sensitivity to docetaxel was suppressed by the restoration of STMN1 expression. METHODS We examined miR-223 expression in GBC tissue and GBC cell lines using qRT-PCR. The effects of modulated miR-223 expression in GBC cells were assayed using Cell Counting Kit-8 (CCK8), flow cytometry, and wound-healing and invasion assays. Susceptibility to docetaxel was evaluated in miR-223/STMN1-modulated GBC cells and xenograft tumor models. The protein expression of relevant genes was examined by Western blotting. CONCLUSIONS These findings indicated that miR-223 might serve as an onco-suppressor that enhances susceptibility to docetaxel by downregulating STMN1 in GBC, highlighting its promising therapeutic value.
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Affiliation(s)
- Wei Lu
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yunping Hu
- Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiang Ma
- Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Linzhu Zhou
- Institute of Chemistry, Shanghai Jiao Tong University, Shanghai, China
| | - Lin Jiang
- Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhizhen Li
- Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuai Zhao
- Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuzhen Xu
- Department of Gastrointestinal Surgery, Xu Zhou Center Hospital, Affiliated to Medical College of Southeast University, Jiangsu, China
| | - Weibin Shi
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Sheng Li
- Department of Biochemistry, Dalian Medical University, Liaoning, China
| | - Yingbin Liu
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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13
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Ahn Y, Park CS, Hwang S, Jang HJ, Choi KM, Lee SG. Incidental gallbladder cancer after routine cholecystectomy: when should we suspect it preoperatively and what are predictors of patient survival? Ann Surg Treat Res 2016; 90:131-8. [PMID: 26942156 PMCID: PMC4773457 DOI: 10.4174/astr.2016.90.3.131] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 10/05/2015] [Accepted: 11/04/2015] [Indexed: 12/11/2022] Open
Abstract
Purpose In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. Methods Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. Results The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). Conclusion Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts.
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Affiliation(s)
- Yongchel Ahn
- Department of Hematology-Oncology, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Cheon-Soo Park
- Department of Surgery, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyuk-Jai Jang
- Department of Surgery, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Kun-Moo Choi
- Department of Surgery, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Igami T, Ebata T, Yokoyama Y, Sugawara G, Mizuno T, Yamaguchi J, Shimoyama Y, Nagino M. Combined extrahepatic bile duct resection for locally advanced gallbladder carcinoma: does it work? World J Surg 2016; 39:1810-7. [PMID: 25663014 DOI: 10.1007/s00268-015-3011-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Prophylactic combined extrahepatic bile duct resection remains controversial for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion. The aim of this study is to resolve this issue and establish an appropriate surgery for locally advanced gallbladder carcinoma. METHODS A total of 52 patients underwent surgical resection combined with extrahepatic bile duct resection for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion, and their medical records were retrospectively reviewed for microvessel invasion (MVI), including lymphatic, venous, and/or perineural invasions, around the extrahepatic bile duct. RESULTS Of the 52 patients, 8 (15 %) had MVI around the extrahepatic bile duct. All of the 8 patients had Stage IV disease. According to a survival analysis of the 50 patients who tolerated surgery, MVIs around the extrahepatic bile duct and distant metastasis were identified as independent prognostic factors. Survival for patients with MVI around the extrahepatic bile duct was dismal, with a lack of 2-year survivors. CONCLUSIONS MVI around the extrahepatic bile duct is a sign of extremely locally advanced gallbladder carcinoma; therefore, prophylactic combined bile duct resection has no survival impact for patients without extrahepatic bile duct invasion.
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Affiliation(s)
- Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
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15
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Parikh U, Marcus C, Sarangi R, Taghipour M, Subramaniam RM. FDG PET/CT in Pancreatic and Hepatobiliary Carcinomas: Value to Patient Management and Patient Outcomes. PET Clin 2015; 10:327-43. [PMID: 26099670 DOI: 10.1016/j.cpet.2015.03.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Fludeoxyglucose F 18 ((18)F-FDG) PET/CT has not been shown to offer additional benefit in the initial diagnosis of pancreatic cancer, but studies show benefit of (18)F-FDG PET/CT in initial staging and patient prognosis. There is evidence for (18)F-FDG PET and (18)F-FDG PET/CT in staging and prognosis of cholangiocarcinoma and gallbladder cancer. (18)F-FDG PET/CT has shown promise in staging liver malignancies by detecting extrahepatic metastasis. There is evidence supporting the ability of PET/CT in predicting prognosis in patients with hepatocellular carcinoma. Evidence is evolving for the role of (18)F-FDGPET/CT in predicting prognosis and survival in patients with colorectal liver metastasis.
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Affiliation(s)
- Ujas Parikh
- Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, JHOC 3230, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Charles Marcus
- Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, JHOC 3230, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Rutuparna Sarangi
- Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, JHOC 3230, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Mehdi Taghipour
- Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, JHOC 3230, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Rathan M Subramaniam
- Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, JHOC 3230, 601 North Caroline Street, Baltimore, MD 21287, USA; Department of Oncology, Johns Hopkins School of Medicine, 401 North Broadway, Baltimore, MD 21231, USA; Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, 624 North Broadway, Baltimore, MD 21205, USA.
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Hong EK, Kim KK, Lee JN, Lee WK, Chung M, Kim YS, Park YH. Surgical outcome and prognostic factors in patients with gallbladder carcinoma. KOREAN JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2014; 18:129-37. [PMID: 26155265 PMCID: PMC4492352 DOI: 10.14701/kjhbps.2014.18.4.129] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Revised: 11/15/2014] [Accepted: 11/22/2014] [Indexed: 12/22/2022]
Abstract
BACKGROUNDS/AIMS Gallbladder carcinoma is usually associated with an unfavorable prognosis, and the clinical outcome has not improved much. This study was conducted to evaluate outcomes with gallbladder carcinoma according to the type of surgery performed, and the prognostic factors for survival. METHODS One hundred and six patients with gallbladder carcinoma, who underwent surgery for the purpose of curative resection between January 1999 and June 2012 were reviewed retrospectively. RESULTS Out of 106 patients, curative resection was achieved in 75 (70.8%). The cumulative 1-, 2- and 5-year survival rates of the gallbladder carcinoma patients were 93.4%, 80.9% and 63.0%, respectively. Radical resections, including extended cholecystectomy, were more beneficial for long term survival of patients. The 5-year survival rate in patients who underwent curative resection (56.9%) was significantly higher than in those who underwent palliative resection (0%, p=0.000). Multivariate analysis revealed that curative resection, preoperative CA19-9, T-stage, N-stage and differentiation of histology were independently significant prognostic factors. CONCLUSIONS Curative resection and early detection of patients with gallbladder carcinoma were the most important factors for long term survival. Radical resection improves survival for patients with localized gallbladder carcinoma and can help to access exact prognosis and treatments.
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Affiliation(s)
- Eun Kyung Hong
- Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Kun Kuk Kim
- Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Jung Nam Lee
- Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Woon Kee Lee
- Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Min Chung
- Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea
| | - Yeon Suk Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Yeon Ho Park
- Department of Surgery, Gachon University Gil Medical Center, Incheon, Korea
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Immunohistochemical Expression of Vascular Endothelial Growth Factor A in Advanced Gallbladder Carcinoma. Appl Immunohistochem Mol Morphol 2014; 22:530-6. [DOI: 10.1097/pai.0b013e3182a318a9] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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18
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Roa I, Ibacache G, Muñoz S, de Aretxabala X. Gallbladder cancer in Chile: Pathologic characteristics of survival and prognostic factors: analysis of 1,366 cases. Am J Clin Pathol 2014; 141:675-82. [PMID: 24713738 DOI: 10.1309/ajcpqt3eln2bbcka] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES To explore gallbladder cancer (GBC), the second leading cause of cancer-related death in women in Chile. METHODS Analysis of macroscopic and microscopic variables, morphometry, and survival in 1,366 patients with GBC. RESULTS Patients comprised 1,138 women and 228 men; diagnoses included 213 (15.6%) cases of mucosal carcinoma, 132 (9.7%) cases of muscular carcinoma, 316 (23.1%) cases of subserosal carcinoma, 382 (28.0%) cases of serosal carcinoma, and 323 (23.6%) cases beyond the serosa. Women older than 55 years with a gallbladder length greater than 9.5 cm had a five-times-greater relative risk of cancer. Those with a gallbladder wall thickness less than 7 mm had a better 5-year survival rate than those with a gallbladder wall thickness greater than 10 mm (P = .0001). Patients who had cholesterolosis of the gallbladder had 9.2 times less probability of having cancer. The infiltration level of the gallbladder wall was the most important independent prognostic factor (P < .001), followed by differentiation and lymphatic involvement (P < .001 and P = .05, respectively). Vascular infiltration had a mortality rate of 100%. CONCLUSIONS Morphologic features are strongly associated with the prognosis of GBC and must be taken into consideration when supplementary treatment is recommended.
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Affiliation(s)
- Iván Roa
- Molecular Laboratory, Creative Bioscience, Santiago, Chile
- Histopathology and Cytopathology Diagnosis Center, Temuco, Chile
| | - Gilda Ibacache
- Histopathology and Cytopathology Diagnosis Center, Temuco, Chile
| | - Sergio Muñoz
- CIGES Faculty of Medicine, Universidad de la Frontera, Temuco, Chile
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Hwang JP, Lim I, Na III, Cho EH, Kim BII, Choi CW, Lim SM. Prognostic Value of SUVmax Measured by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography in Patients with Gallbladder Cancer. Nucl Med Mol Imaging 2013; 48:114-20. [PMID: 24900151 PMCID: PMC4028469 DOI: 10.1007/s13139-013-0255-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Revised: 11/16/2013] [Accepted: 11/20/2013] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE The aim of this study is to investigate the prognostic value of F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder cancer patients. METHODS From June 2004 to June 2010, a total of 50 patients with gallbladder cancer who underwent diagnostic staging with F-18 FDG PET/CT following curative or palliative treatments were retrospectively evaluated. For the analysis, all patients were classified by age, sex, maximum standardized uptake value (SUVmax), lymph node (LN) or distant metastasis, serum level of CA19-9 and CEA, type of treatment and American Joint Committee on Cancer (AJCC) stage. RESULTS The median survival for the 50 patients was 245 days and the median SUVmax in PET/CT was 8.3 (range, 0-19.7). Patients with SUVmax < 6 survived significantly longer than patients with SUVmax ≥ 6 (median 405 days vs 203 days, p = 0.0400). On Kaplan-Meier analysis, SUVmax (p = 0.0400), stage (p = 0.0001), CA19-9 (p = 0.013), CEA (p = 0.006), LN metastasis (p = 0.0001), distant metastasis (p = 0.0020), type of treatment (p = 0.0001) were significantly associated with overall survival. Multivariate analysis study revealed that the patients with lower SUVmax measured from initial staging PET/CT (p = 0.0380), no LN metastasis (p = 0.0260), a lower stage (p = 0.026) and curative treatment (p = 0.0005) had longer survivals. CONCLUSIONS The present study shows that SUVmax on F-18 FDG PET/CT can provide prognostic information in patients with gallbladder cancer.
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Affiliation(s)
- Jae Pil Hwang
- />Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowongil, Nowon Gu, Seoul 139-706 Republic of Korea
| | - Ilhan Lim
- />Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowongil, Nowon Gu, Seoul 139-706 Republic of Korea
- />Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon Gu, Seoul Republic of Korea
| | - Im II Na
- />Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon Gu, Seoul Republic of Korea
| | - Eung Ho Cho
- />Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon Gu, Seoul Republic of Korea
| | - Byung II Kim
- />Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowongil, Nowon Gu, Seoul 139-706 Republic of Korea
- />Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon Gu, Seoul Republic of Korea
| | - Chang Woon Choi
- />Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowongil, Nowon Gu, Seoul 139-706 Republic of Korea
- />Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon Gu, Seoul Republic of Korea
| | - Sang Moo Lim
- />Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowongil, Nowon Gu, Seoul 139-706 Republic of Korea
- />Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon Gu, Seoul Republic of Korea
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Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer. Tumour Biol 2013; 35:419-23. [PMID: 23918306 DOI: 10.1007/s13277-013-1058-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2013] [Accepted: 07/24/2013] [Indexed: 12/16/2022] Open
Abstract
Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.
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21
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[Prevalence and sequence of metaplasia-dysplasia-carcinoma of the gallbladder. A single centre retrospective study]. Cir Esp 2013; 91:672-5. [PMID: 23706727 DOI: 10.1016/j.ciresp.2012.10.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2012] [Accepted: 10/01/2012] [Indexed: 11/20/2022]
Abstract
INTRODUCTION We report the frequency and age of metaplasia, dysplasia and carcinoma of the gallbladder, and seek to establish a sequence of progression of these, since several studies suggest that this is the carcinogenesis pathway. MATERIAL AND METHODS Descriptive retrospective cross-sectional study over a period of 4 years, with an analytical component of 1,514 patients with cholelithiasis, in whom cholecystectomy were performed. RESULTS The mean age of the sample was 46 years and 72% of patients were female. The prevalence (and mean age) of pyloric metaplasia, intestinal metaplasia, dysplasia and carcinoma was 22.6 (47), 2.1 (46), 0.2 (54) and 0.6% (63 years), respectively. There was a significant association between intestinal and pyloric metaplasia (P<.001, chi(2)) and between dysplasia and carcinoma (P<.005, Yates), but not between metaplasia and dysplasia. CONCLUSION Improved studies should be conducted for the correct interpretation of the pathogenesis of gallbladder cancer.
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Prognostic factors in patients with gallbladder cancer after surgical resection: analysis of 279 operated patients. J Clin Gastroenterol 2013. [PMID: 23188077 DOI: 10.1097/mcg.0b013e3182703409] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Identification of prognostic factors can help predict life expectancy and decide treatment plan. We evaluated prognostic factors in patients with gallbladder cancer (GBC) after surgical resection. STUDY Data from 279 patients with GBC who underwent surgery between January 1999 and February 2009 were reviewed retrospectively. RESULTS Of the 279 patients, 127 (45.5%) were male; median age was 63 years. R0 resection was achieved in 164 (58.8%) patients, 35 by cholecystectomy and 129 by extended resection. Chemotherapy and radiotherapy were performed in 72 (25.8%) and 55 (19.7%) patients. At a median follow-up of 17.0 months, median overall survival (OS) was 26.0 months. Five-year survival rates for stages I, II, IIIA, IIIB, IVA, and IVB GBC were 94.7%, 75.7%, 44.5%, 21.7%, 4.7%, and 2.6%, respectively. Compared with cholecystectomy, extended resection showed improved OS in all T stages, but statistical significance was observed only in T3 (P<0.001) and T4 (P=0.007). Although OS was similar in patients who received chemotherapy or radiotherapy, radiotherapy significantly improved OS in patients with positive resection margin (P=0.023). Low-grade histologic type (P=0.047) and clear resection margin (P=0.002) were significant predictors of increased OS, but epidemiological factors such as gallstones and anomalous pancreaticobiliary ductal union were not. CONCLUSIONS In patients with GBC after surgical resection, TNM stage was the most important prognostic factor. Prognosis was also associated with extent of resection, histologic differentiation, and involvement of resection margin. In patients with positive resection margin, radiotherapy seems to prolong OS.
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Garcia P, Leal P, Ili C, Brebi P, Alvarez H, Roa JC. Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro. Int J Exp Pathol 2013; 94:195-202. [PMID: 23593935 DOI: 10.1111/iep.12023] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2012] [Accepted: 02/21/2013] [Indexed: 01/28/2023] Open
Abstract
Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P < 0.05). An increased p27 expression was observed in G-415 cells with loss of CTGF function. Our results suggest that high expression of this protein in gallbladder cancer may confer a growth advantage for neoplastic cells.
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Affiliation(s)
- Patricia Garcia
- Department of Pathology, School of Medicine, BIOREN-CEGIN, Universidad de La Frontera, Temuco, Chile
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Lee HK, Cho MS, Kim TH. Prognostic significance of muc4 expression in gallbladder carcinoma. World J Surg Oncol 2012; 10:224. [PMID: 23101681 PMCID: PMC3500712 DOI: 10.1186/1477-7819-10-224] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Accepted: 10/15/2012] [Indexed: 12/15/2022] Open
Abstract
Background Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis. Methods The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining. Results For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05). Conclusions MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression.
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Affiliation(s)
- Hyeon Kook Lee
- Department of Surgery, School of Medicine Ewha Womans University, 911-1 Mok-dong, Yangcheon-gu, Seoul, 158-710 South Korea.
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Yoo J, Choi JY, Lee KT, Heo JS, Park SB, Moon SH, Choe YS, Lee KH, Kim BT. Prognostic Significance of Volume-based Metabolic Parameters by (18)F-FDG PET/CT in Gallbladder Carcinoma. Nucl Med Mol Imaging 2012; 46:201-206. [PMID: 24900061 PMCID: PMC4043037 DOI: 10.1007/s13139-012-0147-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Revised: 05/24/2012] [Accepted: 05/29/2012] [Indexed: 11/30/2022] Open
Abstract
PURPOSE We investigated the prognostic values of volume-based metabolic parameters by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder carcinoma patients and compared them with other prognostic parameters. MATERIALS AND METHODS We enrolled 44 patients, who were initially diagnosed with gallbladder carcinoma and undergoing (18)F-FDG PET/CT. Various metabolic volume-based PET parameters of primary tumors, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured in gallbladder carcinoma patients using mediastinal blood pool activity as a threshold SUV for determining the tumor boundaries. Overall survival analysis was performed using the Kaplan-Meier method with PET parameters and other clinical variables. For determining independent prognostic factors, Cox proportional hazards regression analysis was performed. RESULTS Of the 44 enrolled patients, cancer- or treatment-related death occurred in 30 (68.2 %). The mean clinical follow-up period was 22.2 ± 10.4 m (range, 0.6-35.9 m). Univariate analysis demonstrated that clinical or pathologic TNM stage (P < 0.001), treatment modality (P < 0.001), MTV (cutoff = 135 cm(3), P = 0.001), and TLG (cutoff = 7,090, P < 0.05) were significant prognostic factors. In multivariate analysis, both clinical or pathologic TNM stage [hazard ratio (HR) = 2.019 (I vs II), 21.287 (I vs III), and 24.354 (I vs IV); P = 0.001) and TLG (HR = 2.930; P < 0.05) were independent prognostic factors for predicting overall survival. CONCLUSIONS In gallbladder cancer, TLG of the primary tumor, a volume-based metabolic parameter, is a significant independent prognostic factor for overall survival in conjunction with the clinical or pathological TNM stage.
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Affiliation(s)
- Jang Yoo
- />Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 Korea
| | - Joon Young Choi
- />Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 Korea
| | - Kyu Taek Lee
- />Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Seok Heo
- />Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Bin Park
- />Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 Korea
| | - Seung Hwan Moon
- />Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 Korea
| | - Yearn Seong Choe
- />Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 Korea
| | - Kyung-Han Lee
- />Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 Korea
| | - Byung-Tae Kim
- />Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710 Korea
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Invasion of the hepatic artery is a crucial predictor of poor outcomes in gallbladder carcinoma. World J Surg 2012; 36:645-50. [PMID: 22270983 DOI: 10.1007/s00268-011-1413-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND In the present study we undertook a retrospective analysis of gallbladder carcinoma to assess whether histologically determined hepatic artery (HA) invasion and portal vein (PV) invasion can be considered prognostic factors. METHODS Seventy-one patients who had undergone radical resection for gallbladder carcinoma between 1995 and 2008 at University of Tsukuba were selected from the database for analysis. Patients who required extended surgery for para-aortic lymph node metastasis were also included. Correlation between invasion of the HA and the PV and prognosis and other clinicopathologic factors were analyzed. RESULTS There were two postoperative deaths among the 71 patients. Pathological invasion of the HA was confirmed in 16 (22.5%) cases and PV invasion was confirmed in 15 patients. Patients with invasion of the HA had a significantly poorer prognosis than those without HA invasion (P < 0.0001). Additionally, in univariate analysis, gender (male), positive para-aortic lymph node metastasis, PV invasion, and HA invasion were identified as significant poor prognostic factors. In multivariate analysis, only HA invasion was an independent prognostic factor (Odds Ratio 0.323; P = 0.029). CONCLUSIONS Invasion of the HA is a crucial prognostic factor in patients with gallbladder carcinoma.
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Kim K, Chie EK, Jang JY, Kim SW, Han SW, Oh DY, Im SA, Kim TY, Bang YJ, Ha SW. Postoperative chemoradiotherapy for gallbladder cancer. Strahlenther Onkol 2012; 188:388-392. [PMID: 22402869 DOI: 10.1007/s00066-012-0074-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2011] [Accepted: 01/11/2012] [Indexed: 10/28/2022]
Abstract
PURPOSE The goal of this work was to analyze the outcome of adjuvant chemoradiotherapy for patients with gallbladder cancer who underwent surgical resection and to identify the prognostic factors for these patients. PATIENTS AND METHODS Between August 1989 and November 2006, 47 patients with gallbladder cancer underwent surgical resection followed by adjuvant radiotherapy. There were 21 males and 26 females, and median age was 60 years (range 44-75 years). Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to 40-50 Gy at 2 Gy/fraction; 41 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 48 months for survivors. RESULTS There were 2 isolated locoregional recurrences, 14 isolated distant metastases, and 7 combined locoregional and distant relapses. The 5-year overall survival rate was 43.7%. According to the extent of resection, the 5-year overall survival rates were 52.8%, 20.0%, and 0% in R0-, R1-, and R2-resected patients, respectively (p = 0.0038). On multivariate analysis incorporating extent of resection, T stage, N stage, performance of lymph node dissection, and histologic differentiation, extent of resection was the only prognostic factor associated with overall survival (p = 0.0075). Among the 37 patients with R0 resection, there was no difference of 5-year overall survival rates in patients with N0, N1, and Nx diseases (46.2%, 60.0%, and 44.4%, respectively, p = 0.6246). As for significant treatment-related morbidity, there was only 1 patient with grade 4 gastric ulcer. CONCLUSION Adjuvant chemoradiotherapy after R0 resection can achieve a good long-term survival rate in gallbladder cancer patients, even in those with lymph node metastases, and may play a role for patients who underwent R0 resection of primary tumor without lymph node dissection.
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Affiliation(s)
- K Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, 110-744, Seoul, Korea
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Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Sakabe R, Kobayashi H, Sueda T. Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection. J Gastrointest Surg 2011; 15:1007-16. [PMID: 21547707 DOI: 10.1007/s11605-011-1479-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2011] [Accepted: 02/27/2011] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prognosis for patients with advanced gallbladder carcinoma is dismal despite aggressive surgical resection. The aim of this study is to determine useful prognostic factors for patients with gallbladder carcinoma following aggressive surgical resection. METHODS Medical records of 62 patients with gallbladder carcinoma who underwent surgical resection were retrospectively reviewed. Univariate and multivariate models were used to analyze the effect of clinicopathological factors on long-term survival. RESULTS According to the UICC staging system, ten (16%), 11 (18%), eight (13%), 16 (25%), nine (15%), and eight patients (13%) were diagnosed with stages I, II, IIIA, IIIB, IVA, and IVB disease, respectively. Partial hepatectomy and pancreatoduodenectomy were performed for 43 (69%) and 11 (18%) patients, respectively. Overall survival rates of all 62 and 41 patients with UICC stages III and IV disease were 71% and 56% at 1 year, 48% and 23% at 3 years, and 48% and 23% at 5 years, respectively (median survival time, 15.8 and 12.7 months, respectively). Multivariate analysis revealed that independent prognostic factors included tumor differentiation (p = 0.006), hepatic invasion (p = 0.002), lymph node metastasis (p = 0.009), and surgical margin status (p = 0.002) for all patients, and adjuvant chemotherapy (p = 0.005), tumor differentiation (p = 0.008), hepatic invasion (p = 0.001), and surgical margin status (p = 0.022) for patients with UICC stages III and IV disease. CONCLUSIONS R0 resection and adjuvant chemotherapy are significant prognostic factors in advanced gallbladder carcinoma and should be performed to improve survival.
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Affiliation(s)
- Yoshiaki Murakami
- Department of Surgery, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
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Regimbeau JM, Fuks D, Bachellier P, Le Treut YP, Pruvot FR, Navarro F, Chiche L, Farges O. Prognostic value of jaundice in patients with gallbladder cancer by the AFC-GBC-2009 study group. Eur J Surg Oncol 2011; 37:505-12. [PMID: 21514090 DOI: 10.1016/j.ejso.2011.03.135] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2010] [Revised: 02/23/2011] [Accepted: 03/28/2011] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION Jaundice is frequent in patients with gallbladder cancer (GBC) and indicates advanced disease and, according to some teams, precludes routine operative exploration. The present study was designed to re-assess the prognostic value of jaundice in patients with GBC. METHODS Patients with GBC operated from 1998 to 2008 were included in a retrospective multicenter study (AFC). The main outcome measured was the prognostic value of jaundice in patients with GBC focusing on morbidity, mortality and survival. RESULTS A total of 110 of 429 patients with GBC presented with jaundice, with a median age of 66 years (range: 31-88). The resectability rate was 45% (n=50) and the postoperative mortality and morbidity rates were 16% and 62%, respectively; 71% had R0 resection and 46% had lymph node involvement. Overall 1- and 3-year survivals of the 110 jaundiced patients were 41% and 15%, respectively. For the 50 resected patients, 1- and 3-year survivals were 48% and 19%, respectively (real 5-year survivors n=4) which were significantly higher than that of the 60 non-resected patients (31%, 0%, p=0.001). Among the resected jaundiced patients, T-stage, N and M status were found to have a significant impact on survival. R0 resection did not increase the overall survival in all resected patients, but R0 increased median survival in the subgroup of N0 patients (20 months versus 6 months, p=0.01). CONCLUSION This series confirms that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (N0).
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Affiliation(s)
- J M Regimbeau
- Department of Digestive Surgery, Amiens North Hospital, University of Picardy Medical Centre, Place Victor Pauchet, Amiens Cedex 01, France.
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Gallbladder carcinoma incidentally encountered during laparoscopic cholecystectomy: how to deal with it. Clin Transl Oncol 2011; 13:25-33. [DOI: 10.1007/s12094-011-0613-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Shukla PJ, Barreto SG. Systematic review: should routine resection of the extra-hepatic bile duct be performed in gallbladder cancer? Saudi J Gastroenterol 2010; 16:161-167. [PMID: 20616410 PMCID: PMC3003211 DOI: 10.4103/1319-3767.65184] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2009] [Accepted: 01/07/2010] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND/AIM Complete surgical resection is associated with improved outcomes in gallbladder cancer. Whether the extra-hepatic bile duct (EHBD) should be routinely excised for gallbladder cancer is unclear. OBJECTIVE To analyze literature concerning EHBD excision to determine if it is associated with survival advantage and hence can be routinely recommended. MATERIALS AND METHODS A systematic search using Medline, Embase, and Cochrane Central Register of Controlled Trials for the years 1988-2008. RESULTS EHBD excision was reported to be performed routinely for T1-4 in some studies, while others reported resection to facilitate lymph node clearance or if the EHBD was grossly involved by disease that remained otherwise resectable. While one study demonstrated 100% survival in T1 disease, other reports do not demonstrate any survival benefit of EHBD excision in T1 disease. Four studies (level IV-V) demonstrated 60% to 90% five-year survival for routine excision in T2 disease, while three other studies demonstrated no survival advantage but increased morbidity due to the procedure. In T3/4 disease, one study (level IV-V) demonstrated a benefit in T4 disease only, and another study (level IV-V) reported a survival advantage in patients in whom the bile duct was not involved; five other studies showed no impact of routine EHBD excision on survival but reported morbidity following anastomotic leaks. CONCLUSIONS Available evidence does not support routine resection of EHBD in gallbladder cancer. EHBD excision should be performed in the presence of specific indications, viz., to achieve an R0 resection of the primary tumor and/ or to aid complete lymph node dissection that would compromise the EHBD by devascularization.
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Affiliation(s)
- Parul J. Shukla
- Department of Gastrointestinal Surgical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Savio G. Barreto
- Department of General and Digestive Surgery, Flinders Medical Center, Adelaide, Australia
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Kim WS, Choi DW, You DD, Ho CY, Heo JS, Choi SH. Risk factors influencing recurrence, patterns of recurrence, and the efficacy of adjuvant therapy after radical resection for gallbladder carcinoma. J Gastrointest Surg 2010; 14:679-87. [PMID: 20094817 DOI: 10.1007/s11605-009-1140-z] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2009] [Accepted: 12/14/2009] [Indexed: 01/31/2023]
Abstract
BACKGROUNDS Gallbladder carcinoma (GBC) is an aggressive neoplasm, and resection is the only curative modality. Recurrence frequently occurs after the curative resection of advanced GBC. Adjuvant treatment, particularly radiotherapy, is recommended and is used without any evidence of a beneficial effect. The aim of this study was to characterize patterns of recurrence and to identify the factors that influence recurrence and the efficacy of adjuvant therapy after the curative resection of GBC. METHODS The records of patients that underwent surgical resection with curative intent for gallbladder carcinoma from October 1994 and August 2007 were retrospectively reviewed. Recurrence patterns, times to recurrence, and survival rates were analyzed. Sites of recurrence were identified retrospectively and categorized as locoregional or distant. RESULTS One hundred sixty-six patients underwent surgical resection with curative intent for gallbladder adenocarcinoma. The 5-year recurrence rates of stages IA, IB, IIA, and IIB patients were 0%, 24.3%, 44.9%, and 58.3%, retrospectively. Positivity for lymph node metastases was found to have predictive significance for disease-free survival (p = 0.009). Regional lymph node recurrence (27.7%) was observed most frequently. There was no significant disease-free survival rates between the no adjuvant therapy and the adjuvant therapy groups. CONCLUSIONS The regional lymph nodes and the liver were found to be the most common sites of recurrence after curative resection. Lymph node metastases were identified as an independent predictor of tumor recurrence by multivariate analysis. Based on the disease-free survivals observed in this study, the authors find it would be difficult to advocate the routine use of adjuvant radiotherapy and/or chemotherapy.
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Affiliation(s)
- Woo Seok Kim
- Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
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Differential diagnostic and staging accuracies of high resolution ultrasonography, endoscopic ultrasonography, and multidetector computed tomography for gallbladder polypoid lesions and gallbladder cancer. Ann Surg 2010; 250:943-9. [PMID: 19855259 DOI: 10.1097/sla.0b013e3181b5d5fc] [Citation(s) in RCA: 96] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE The authors undertook to investigate the diagnostic performance of high-resolution ultrasound (HRUS), and to compare the differential diagnostic and staging accuracies of endoscopic ultrasonography (EUS), HRUS, and multidetector computed tomography for gallbladder (GB) polypoid lesions and GB cancer. SUMMARY OF BACKGROUND DATA Endoscopic ultrasonography was considered the most sensitive diagnostic modality for GB polypoid lesions. However, recent technical advancements in other image modalities including conventional sonography (US) allow the production of comparable images. METHODS A total of 170 patients, with a more than 1-cm sized polypoid GB lesion, and without evidence of definite local invasion to adjacent organs during primary screening, were consecutively enrolled in this prospective, blind, comparative study. After excluding 26 patients with inappropriate medical histories, 144 patients were finally enrolled. All patients underwent surgical resection. Clinical diagnoses were compared with histopathologic findings by diagnostic modality. RESULTS Of the 144 patients, there were 115 (79.8%) cases of benign GB polypoid lesions and 29 (20.2%) cases of GB cancers. Diagnostic sensitivities for malignancy were 90% for HRUS, 86% for EUS, and 72% for CT. When evaluating the abilities of these modalities to predict GB cancer depth of invasion, we excluded 2 unusual GB malignancies (melanoma and lymphoma), HRUS was found to have the highest diagnostic accuracy of 62.9%; EUS and CT had accuracies of 55.5% and 44.4%, respectively. CONCLUSIONS The diagnostic accuracies of HRUS and EUS for the differential diagnosis of GB polypoid lesions were comparable. In view of patient comfort and no requirement for sedation, we consider that HRUS is likely to become an important diagnostic modality for the differential diagnosis and staging of GB polypoid lesions and early GB cancer.
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Tamura H, Ohtsuka M, Washiro M, Kimura F, Shimizu H, Yoshidome H, Kato A, Seki N, Miyazaki M. Reg IV expression and clinicopathologic features of gallbladder carcinoma. Hum Pathol 2009; 40:1686-92. [DOI: 10.1016/j.humpath.2009.06.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2009] [Revised: 06/02/2009] [Accepted: 06/11/2009] [Indexed: 10/20/2022]
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Slim K, Blay JY, Brouquet A, Chatelain D, Comy M, Delpero JR, Denet C, Elias D, Fléjou JF, Fourquier P, Fuks D, Glehen O, Karoui M, Kohneh-Shahri N, Lesurtel M, Mariette C, Mauvais F, Nicolet J, Perniceni T, Piessen G, Regimbeau JM, Rouanet P, sauvanet A, Schmitt G, Vons C, Lasser P, Belghiti J, Berdah S, Champault G, Chiche L, Chipponi J, Chollet P, De Baère T, Déchelotte P, Garcier JM, Gayet B, Gouillat C, Kianmanesh R, Laurent C, Meyer C, Millat B, Msika S, Nordlinger B, Paraf F, Partensky C, Peschaud F, Pocard M, Sastre B, Scoazec JY, Scotté M, Triboulet JP, Trillaud H, Valleur P. [Digestive oncology: surgical practices]. ACTA ACUST UNITED AC 2009; 146 Suppl 2:S11-80. [PMID: 19435621 DOI: 10.1016/s0021-7697(09)72398-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- K Slim
- Chirurgien Clermont-Ferrand.
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Mucin-producing carcinoma of the gallbladder associated with primary sclerosing cholangitis and ulcerative colitis. ACTA ACUST UNITED AC 2008; 16:83-5. [PMID: 19096754 DOI: 10.1007/s00534-008-0001-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2007] [Accepted: 10/25/2007] [Indexed: 10/21/2022]
Abstract
Mucin-producing carcinoma of the gallbladder is very rare. We report here a case of mucin-producing carcinoma of the gallbladder associated with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). A 74-year-old female had been treated with salazosulfapyridine and ursodesoxycholic acid becase of UC and PSC. After 7 years of treatment, laboratory data showed that the liver function took a turn for the worse, and the patient was admitted to our hospital for further examination. Enhanced computed tomography and ultrasonography showed an enlarged gallbladder associated with wall thickening and diffuse papillary protrusion. Endoscopic retrograde cholangiography showed stenosis and dilatation of the bile duct, which were compatible with PSC. Under the diagnosis of an early carcinoma of the gallbladder, we performed simple cholecystectomy. The tumor showed a papillary growth pattern located diffusely in the gallbladder with a massive amount of mucin filling the gallbladder. Histologically, it was diagnosed as a papillary adenocarcinoma localized in the mucosal layer. To the best of our knowledge, this is the first case of mucin-producing carcinoma of the gallbladder associated with PSC and UC. PSC and UC patients should be regarded as a high-risk group not only for cholangiocarcinoma but also carcinoma of the gallbladder.
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Abstract
OBJECTIVE The objective of this study was to evaluate prognostic predictors for patients with gallbladder cancer (GBC) in a Japanese nationwide data base. SUMMARY BACKGROUND DATA GBC is the most common cancer of the biliary tract in Japan. Differences in the survival rates between Japan and other countries have been noted. METHODS The authors analyzed 4424 patients with GBC in Japan between 1988 and 1997. Staging was determined in accordance with American Joint Committee on Cancer stage. RESULTS Survival is related closely to the surgical stage. Five-year survival rates for stage I, II, III, IVA, and IVB (5th edition) were 83%, 70%, 45%, 23%, and 9%, respectively. These differences were significant (P < 0.0001). The survival rate for patients aged <60 years was significantly better (P < 0.05). The survival rate for patients aged >69 years was significantly worse (P < 0.01). The cholecystectomy plus combined resection of bile duct and/or liver bed resection had an effect on prolonging the survival in stage II or III disease, but extended resection did not. The patients with anomalous pancreaticobiliary ductal junction had a survival advantage over those with cholelithiasis by univariate analysis. However, multivariate analyses indicated that only age, sex, stage, operative procedures were independent prognostic factors. Stage was the strongest covariate; patients diagnosed with stage II, III, IVA, or IVB disease were 2.2, 4.2, 8.1, and 13.6 times, respectively, were more likely to die. CONCLUSIONS Staging is the strongest prognostic factor for GBC, but patient outcomes were also affected by age, sex, and operative procedures. The data do not support any advantage for extended resection. Neither gallstones nor anomalous pancreaticobiliary ductal junction influenced the GBC patient outcome.
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Abstract
AIM Gallbladder cancer is the fifth most common cancer involving the gastrointestinal tract, but it is the most common malignant tumour of the biliary tract worldwide. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. This tumour is traditionally regarded as a highly lethal disease with an overall 5-year survival of less than 5%. The marked improvement in the outcome of patients with gallbladder cancer in the last decade is because of the aggressive radical surgical approach that has been adopted, and improvements in surgical techniques and peri-operative care. This article aims to review the current approach to the management of gallbladder cancer. METHODS A Medline, PubMed database search was performed to identify articles published from 1990 to 2007 using the keywords 'carcinoma of gallbladder', 'gallbladder cancer', 'gallbladder neoplasm' and 'cholecystectomy'. RESULTS AND CONCLUSIONS The overall 5-year survival for patients with gallbladder cancer who underwent Ro curative resection was reported to range from 21% to 69%. Laparoscopic cholecystectomy is absolutely contraindicated when gallbladder cancer is known or suspected pre-operatively. Patients with a pre-operative suspicion of gallbladder cancer should undergo open exploration and cholecystectomy after proper pre-operative assessment. For patients whose cancer is an incidental finding on pathological review, a second radical resection is indicated except for Tis and T1a disease. There is still controversy for the optimal management of T1b disease. Although the role of surgery for advanced disease remains controversial, patients with advanced gallbladder cancer can benefit from radical resection, provided a potentially curative Ro resection is possible. There is still no effective adjuvant therapy for gallbladder cancer.
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Affiliation(s)
- C H Eric Lai
- Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
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Otero JCR, Proske A, Vallilengua C, Luján M, Poletto L, Otero JR, Pezzotto SM, Celoria G. Gallbladder carcinoma: intraoperative imprint cytology, a helpful and valuable screening procedure. ACTA ACUST UNITED AC 2008; 15:157-60. [PMID: 18392708 DOI: 10.1007/s00534-007-1253-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2007] [Accepted: 07/08/2007] [Indexed: 12/20/2022]
Abstract
BACKGROUND/PURPOSE A major problem arises when a tumor is not readily recognized at the time of cholecystectomy. A carcinoma at early stages or one hidden by acute or chronic inflammation can be overlooked during surgery, and the diagnosis would then be made only after microscopic examination of paraffin-embedded tissue. The purpose of the present report is to communicate the results of 10 years' experience with the use of imprint cytology for the intraoperative diagnosis of gallbladder carcinoma. METHODS During the period June 1994 to June 2004, 525 imprint cytologies of gallbladder mucosa were performed after 160 open cholecystectomies and 365 laparoscopic cholecystectomies. The patients had been operated on for acute or chronic cholecystitis due to lithiasis. Only 18 patients had a preoperative diagnosis of gallbladder carcinoma. The sensitivity, specificity, predictive values, accuracy, and their confidence intervals (95% CIs), of intraoperative imprint cytology for the diagnosis of carcinoma were analyzed. RESULTS The average time employed for each procedure was 10 min. Patients' mean age was 69.2 years with a range of 24 to 92 years. Three hundred and forty-two patients (65.1%) were women and 183 (34.9%) were men. The imprint cytology method was positive in 44 of 58 gallbladder carcinomas diagnosed, with a sensitivity of 75.9% (44/58 patients) and a specificity of 99.8% (466/467). Only 1 case (1/525; 0.2%) was a false-positive; this was due to reactive changes. The positive predictive value was 97.8% (44/45; 95% CI = 86.8-99.9), negative predictive value was 97.1% (466/480; 95% CI = 95.0-98.3), and accuracy was 97.1% ([44 + 466]/525; 95% CI = 95.2-98.3). There was insufficient or inadequate material in 4 cases. CONCLUSIONS Imprint cytology of the gallbladder mucosa is an easy, rapid, and high-quality method for detecting gallbladder carcinoma.
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Affiliation(s)
- Juan C Rodríguez Otero
- Surgical Oncology, Hospital del Centenario, Facultad de Ciencias Médicas, Universidad Nacional de Rosario and Instituto Cardiovascular de Rosario, Humboldt 4032, 2000 Rosario, Argentina
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Aldouri AQ, Malik HZ, Waytt J, Khan S, Ranganathan K, Kummaraganti S, Hamilton W, Dexter S, Menon K, Lodge JP, Prasad KR, Toogood GJ. The risk of gallbladder cancer from polyps in a large multiethnic series. Eur J Surg Oncol 2008; 35:48-51. [PMID: 18339513 DOI: 10.1016/j.ejso.2008.01.036] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2007] [Accepted: 01/31/2008] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The aim of this study is assess whether patients with Indian ethnic background are at an increased risk of developing gallbladder cancer (GBC) if they have been diagnosed with ultrasonic abnormalities of the gallbladder. METHODS Between January 1998 and July 2006, 137,655 abdominal ultrasound examinations were performed in Leeds Teaching Hospitals NHS Trust. After the exclusion of repeat scans and those performed for renal or pelvic disease, 71,431 reports were included in this analysis. Patients in whom the diagnosis of GBC has been made without histology have been identified from the database of Northern and Yorkshire Cancer Registry and the presence of GBC was correlated with ultrasonic gallbladder abnormalities. RESULTS Gallbladder polyps (GBP) were detected in 3.3% of patients and these were larger than 10 mm in 0.1% of the cases. Age above 60 years, Indian ethnic background, single GBP larger than 10mm, the presence of gallstones, severe gallbladder wall thickening and irregular thickening were independently associated with the higher odds of developing GBC. The prevalence of malignancy in those with GBP was significantly higher among patients with Indian ethnic background compared to Caucasian patients, 5.5% versus 0.08%, p<0.001. CONCLUSIONS The presence of GBP, irrelevant of size, amongst patients of Indian ethnic decent, is an indication for further investigation and/or cholecystectomy.
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Affiliation(s)
- A Q Aldouri
- HPB and Transplant Unit, St James's University Hospital, Leeds, UK
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Upregulation of topoisomerase IIalpha expression in advanced gallbladder carcinoma: a potential chemotherapeutic target. J Cancer Res Clin Oncol 2008; 134:793-801. [PMID: 18204862 DOI: 10.1007/s00432-007-0348-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2007] [Accepted: 12/10/2007] [Indexed: 12/16/2022]
Abstract
PURPOSE The lack of treatment options other than surgical resection results in unfavourable prognosis of advanced gallbladder carcinoma. The aim of this study was to identify cancer-specific cellular targets that would form the basis for some therapeutic approaches for this disease. METHODS Twelve advanced gallbladder carcinoma tissue samples and three samples of normal gallbladder epithelium were screened to identify differentially expressed genes by DNA microarray analysis. The results obtained were validated in an independent sample set by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Among the genes picked-up, one molecule, topoisomerase IIalpha (TOPO IIalpha), was further assessed immunohistochemically as a potential chemotherapeutic target, and the growth inhibitory effects of etoposide, doxorubicin and idarubicin, representative TOPO IIalpha inhibitors, on two different gallbladder carcinoma cell lines were compared with that of gemcitabine and 5-fulorouracil. RESULTS Five upregulated genes were identified: four cell cycle-related genes (TOPO IIalpha, cyclin B2, CDC28 protein kinase regulatory subunit 2, ubiquitin-conjugating enzyme E2C) and a metabolism-related gene (gamma-glutamyl hydrolase). Immunohistochemically, TOPO IIalpha was expressed in gallbladder cancer cells, and 16 of 35 cases (46%) had strong TOPO IIalpha expression defined as having a labeling index of >50%. In in vitro growth inhibition assay, etoposide, as well as doxorubicin and idarubicin, was the most effective for OCUG-1 cells that had strong TOPO IIalpha expression, while gemicitabine was the most effective for NOZ cells with weak TOPO IIalpha expression. Etoposide induced apoptosis of OCUG-1 cells. CONCLUSIONS TOPO IIalpha might be an effective chemotherapeutic target in advanced gallbladder carcinoma, especially when it is expressed strongly.
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Shukla PJ, Barreto SG, Arya S, Shrikhande SV, Hawaldar R, Purandare N, Rangarajan V. Does PET-CT scan have a role prior to radical re-resection for incidental gallbladder cancer? HPB (Oxford) 2008; 10:439-445. [PMID: 19088931 PMCID: PMC2597311 DOI: 10.1080/13651820802286910] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2008] [Indexed: 02/07/2023]
Abstract
BACKGROUND Radical re-resection is offered to patients with non-metastatic, invasive, incidental gallbladder cancer. Data evaluating (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in patients with incidental gallbladder cancer is sparse. AIM To evaluate the efficacy of integrated (18)F-FDG PET-CT in determining occult metastatic or residual local-regional disease in patients with incidental gallbladder cancer. METHODS Patients referred with incidental gallbladder cancer for radical re-resection were evaluated using multidetector computed tomography (MDCT) and PET-CT. Based on preoperative imaging, 24 out of 92 patients were found suitable for surgery. The two imaging modalities were evaluated with respect to residual and resectable disease. RESULTS In determining residual disease, MDCT had a sensitivity and positive predictive value (PPV) of 42.8%, each, while PET-CT had a sensitivity and PPV of 28.5 and 20%, respectively. In determining resectability, MDCT had a sensitivity, PPV, and accuracy of 100, 87.5, and 87.5%, respectively, as compared to PET-CT (sensitivity=100%, PPV=91.3%, accuracy=91.6%). CONCLUSIONS From our study, it appears that in patients with incidental gall bladder cancer without metastatic disease, PET-CT and MDCT seem to have roles complementing each other. PET-CT was able to detect occult metastatic or residual local-regional disease in some of these patients, and seems to be useful in the preoperative diagnostic algorithm of patients whose MDCT is normal or indicates locally advanced disease.
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Affiliation(s)
- Parul J Shukla
- Department of Gastrointestinal Surgical Oncology, Tata Memorial Hospital, Parel, Mumbai, India.
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Kayahara M, Nagakawa T. Recent trends of gallbladder cancer in Japan: an analysis of 4,770 patients. Cancer 2007; 110:572-80. [PMID: 17594719 DOI: 10.1002/cncr.22815] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Gallbladder cancer is the most common cancer of the biliary tract and has a particularly high incidence in Chile, Japan, and northern India. Many Japanese surgeons have reported that aggressive surgery improves the outcome of patients with gallbladder cancer. Differences in survival rates between Japan and other countries have been noted. The objective of this study was to determine whether there were any changes over time in the incidence, therapeutic approach, stage at diagnosis, or prognosis of gallbladder cancer in an unselected, community-based series of patients in Japan. METHODS In total, 4,774 patients with gallbladder cancer were analyzed between 1988 and 1997 based on data from the Biliary Tract Cancer Registration Committee of the Japanese Society of Biliary Surgery. RESULTS Survival was related closely to surgical stage, with 5-year survival rates of 77% for patients with stage I disease, 60% for patients with stage II disease, 29% for patients with stage III disease, 12% for patients with stage IVA disease, and 3% for patients with stage IVB disease. Patient age also affected survival. The survival rate for patients aged <49 years was significantly better compared with the survival rate for patients in the other groups (P < .05). The 5-year survival rate for patients aged <49 years was 38%. The survival rate for patients aged >79 years was significantly worse compared with the survival rate for patients in the other 4 groups (P < .01). The 5-year survival rate for patients aged >79 years was 21%. Stratifying patients by stage according to the Japanese Society of Biliary Surgery classification showed that women maintained a survival advantage over men among patients with stage I and II disease. Adjuvant chemotherapy did not provide a survival benefit. There were no apparent changes in patient demographics between the period from 1988 to 1992 and the period from 1993 to 1997. CONCLUSIONS For this study, the authors evaluated the gallbladder cancer trends in Japan. The Classification of Biliary Tract Carcinoma proposed by the Japanese Society of Biliary Surgery reflected the prognosis of patients with gallbladder cancer. Patient outcomes were affected by patient age and sex. No substantial differences in patient survival were apparent over the 10-year study period. The data did not support any advantage for aggressive surgical resection and adjuvant chemotherapy. Further analysis of operative procedures will be necessary to determine conclusively whether there is any survival advantage from aggressive surgery in patients with advanced gallbladder cancer.
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Affiliation(s)
- Masato Kayahara
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
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Ai Z, Lu W, Ton S, Liu H, Sou T, Shen Z, Qin X. Arsenic trioxide-mediated growth inhibition in gallbladder carcinoma cells via down-regulation of Cyclin D1 transcription mediated by Sp1 transcription factor. Biochem Biophys Res Commun 2007; 360:684-689. [PMID: 17617380 DOI: 10.1016/j.bbrc.2007.06.123] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2007] [Accepted: 06/23/2007] [Indexed: 02/03/2023]
Abstract
Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of drug stimuli. Here, we demonstrated that arsenic trioxide inhibited the proliferation of gallbladder carcinoma in vivo and in vitro as well as the transcription of cell cycle-related protein Cyclin D1. And, Cyclin D1 overexpression inhibited the negative role of arsenic trioxide in cell cycle progression. We further explored the mechanisms by which arsenic trioxide affected Cyclin D1 transcription and found that the Sp1 transcription factor was down-regulated by arsenic trioxide, with a corresponding decrease in Cyclin D1 promoter activity. Taken together, these results suggested that arsenic trioxide inhibited gallbladder carcinoma cell proliferation via down-regulation of Cyclin D1 transcription in a Sp1-dependent manner, which provided a new mechanism of arsenic trioxide-involved cell proliferation and may have important therapeutic implications in gallbladder carcinoma patients.
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Affiliation(s)
- Zhilong Ai
- Zhongshan Hospital, Fudan University, Shanghai 200032, People's Republic of China
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Kai M, Chijiiwa K, Ohuchida J, Nagano M, Hiyoshi M, Kondo K. A curative resection improves the postoperative survival rate even in patients with advanced gallbladder carcinoma. J Gastrointest Surg 2007; 11:1025-32. [PMID: 17508256 DOI: 10.1007/s11605-007-0181-4] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The aim of this study was to evaluate the results of our series of 90 operations for gallbladder carcinoma according to the Japanese Society of Biliary Surgery (JSBS) classification system and to clarify the appropriate surgical strategy for advanced gallbladder carcinoma based on the depth of primary tumor invasion and lymph node metastasis. Generally, only a surgical resection can achieve a prognostic improvement of the advanced gallbladder carcinoma. The survival of patients with this neoplasm depends strictly on the depth of histological primary tumor invasion and lymph node metastasis. A retrospective analysis was conducted on 90 patients from 1990 to 2004 who underwent a surgical resection of gallbladder carcinoma. The factors influencing survival were examined. Thirty-nine patients with palliative treatment (not resected cases), which was diagnosed as T3 or T4 by preoperative imagings, were also included in this study. The significance of the variables for survival was examined by the Kaplan-Meier method and the log-rank test followed by multivariate analyses using Cox's proportional hazard model. Portal invasion, lymph node metastasis, the surgical margin (+ vs. -) and the final curability (fCurA, B vs. C) were all found to be independent prognostic factors in the multivariate analysis. In pT2 gallbladder carcinoma, a better survival was achieved in an aggressive surgical approach, in order of a S4a+S5 hepatic resection, an extended cholecystectomy and a cholecystectomy. In pT3 and pT4, although radical extended surgery did not provide the opportunity for good survival even after lobectomy of the liver, the survival of patients with curative surgery was statistically better than in those without curative surgery. In addition, the nodal involvement of pN1 to pN2 was better than that with pN3. A S4a+S5 hepatectomy, therefore, appears to be adequate for the treatment of pT2 gallbladder carcinoma. Even in patients with pT3 and pT4 gallbladder carcinoma, long-term survival can be expected by an operation with a tumor-free surgical margin. The role of radical surgery, however, is considered to be limited in patients with pN3 lymph node metastasis.
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Affiliation(s)
- Masahiro Kai
- Department of Surgical Oncology and Regulation of Organ Function, Miyazaki University School of Medicine, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
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Reid KM, Ramos-De la Medina A, Donohue JH. Diagnosis and surgical management of gallbladder cancer: a review. J Gastrointest Surg 2007; 11:671-81. [PMID: 17468929 DOI: 10.1007/s11605-006-0075-x] [Citation(s) in RCA: 170] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gallbladder cancer is one of the most lethal carcinomas and continues to pose many challenges for surgeons. Identifiable risk factors for carcinoma of the gallbladder include cholelithiasis, an anomalous pancreaticobiliary junction, and focal mucosal microcalcifications. Adenocarcinoma is the primary histologic type in most patients and the tumor is frequently associated with Kras and p53 mutations. Radiologic and endoscopic advances in endoscopic ultrasonography and magnetic resonance cholangiopancreatogram, plus helical computed tomography, have enhanced preoperative staging. Surgical options include cholecystectomy for disease limited to the mucosa (Tis/T1) or a radical cholecystectomy (subsegmental resection of segments IVB and V plus a hepatoduodenal ligament lymphadenectomy) for advanced disease without signs of distant metastasis (T2-4/N0-N2). Some surgeons have advocated more radical hepatic resection including extended right hepatectomy or central bisegmentectomy plus caudate lobectomy. Japanese surgeons have reported studies that included patients having a pancreaticoduodenectomy to improve distal ductal margins and lymphadenectomy for T3 and T4 cancers. These patients have a lower rate of local recurrence but no survival advantage. Options for adjuvant therapy remain limited. Radiation therapy with fluorouracil radiosensitization is the most commonly used postoperative treatments. Current trials are investigating the role of capecitabine, oxaliplatin, and bevacizumab in the management of gallbladder carcinoma.
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Affiliation(s)
- Kaye M Reid
- Department of Surgery, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA.
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Otero JCR, Proske A, Vallilengua C, Luján M, Poletto L, Pezzotto SM, Fein L, Otero JR, Celoria G. Gallbladder cancer: surgical results after cholecystectomy in 25 patients with lamina propria invasion and 26 patients with muscular layer invasion. ACTA ACUST UNITED AC 2006; 13:562-6. [PMID: 17139432 DOI: 10.1007/s00534-006-1123-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2005] [Accepted: 03/08/2006] [Indexed: 02/08/2023]
Abstract
BACKGROUND/PURPOSE It has been stated that simple cholecystectomy is sufficient treatment for all patients with pT1 gallbladder cancer. However, other authors note the necessity of carrying out extended surgery when there is muscular-layer involvement. METHODS A consecutive series of gallbladder carcinomas with lamina propria or muscular layer invasion were analyzed. Between July 1982 and December 2000, 51 patients with pT1 gallbladder carcinomas were treated with simple cholecystectomy (group A, 25 patients with lamina propria-invasion; group B, 26 patients with muscular-layer invasion). Patients with intraepithelial carcinomas were excluded from the study. RESULTS There were no differences between the groups in average age, sex ratios, association with other tumors, histologic type, malignancy grade, cholecystitis type, macroscopic aspects, lymph node status, or treatment applied. After an average of 6 years' follow-up, no patients in group A and nine patients (34.6%) in group B died due to gallbladder carcinoma. Cystic lymph nodes could be studied in five of these nine patients who relapsed, and the results were negative for metastasis. Lymphatic or venous invasion was observed in five of these nine patients. CONCLUSIONS According to these results, cholecystectomy is not sufficient treatment for gallbladder carcinoma with muscular-layer invasion.
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Affiliation(s)
- Juan C Rodríguez Otero
- Surgical Oncology, Hospital del Centenario, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Humboldt 4032, 2000 Rosario, Argentina
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Yagi H, Shimazu M, Kawachi S, Tanabe M, Aiura K, Wakabayashi G, Ueda M, Nakamura Y, Kitajima M. Retrospective analysis of outcome in 63 gallbladder carcinoma patients after radical resection. ACTA ACUST UNITED AC 2006; 13:530-6. [PMID: 17139427 DOI: 10.1007/s00534-006-1104-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2005] [Accepted: 02/03/2006] [Indexed: 12/19/2022]
Abstract
BACKGROUND/PURPOSE The aim of this study was to evaluate factors influencing outcome in gallbladder carcinoma after radical resection, in order to identify those patients benefiting from radical surgery. METHODS Sixty-three patients (13 pT1, 28 pT2, 14 pT3, and 8 pT4) who underwent surgical resection for gallbladder carcinoma were retrospectively reviewed. Correlations were sought between survival and factors such as the depth of invasion (pT) including the status of infiltration of the hepatoduodenal ligament (pBinf) and liver bed (pHinf), the extent of lymph node metastasis, and other pathologic factors. RESULTS Multivariate analysis showed that pBinf, pHinf, and lymph node metastasis were significant prognostic factors. We also analyzed survival rates for each operative procedure. There was no difference in survival between patients with or without bile duct resection for lymph node metastasis. The 5-year survival rates of pHinf-negative patients with stage 1B or more advanced disease after gallbladder bed resection or bisegmentectomy 4a,5 versus those without liver resection were 66% and 0%, respectively. Twelve patients survived for more than 5 years after surgery, including one patient undergoing HPD (liver resection with pancreatoduodenectomy) with positive lymph node metastasis; none was pBinf-positive. CONCLUSIONS Several factyors were identified as having prognostic significance for survival in patients with gallbladder carcinomas, and we suggest that radical surgery may be indicated for selected patients with advanced disease.
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Affiliation(s)
- Hiroshi Yagi
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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Cangemi V, Fiori E, Picchi C, De Cesare A, Cangemi R, Galati G, Volpino P. Early gallbladder carcinoma: a single-center experience. TUMORI JOURNAL 2006; 92:487-490. [PMID: 17260488 DOI: 10.1177/030089160609200604] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
AIMS AND BACKGROUND Controversy continues regarding the best surgical treatment for early gallbladder carcinoma defined as a tumor confined to the mucosa (pT1a) or to the muscularis propria (pT1b) according to the TNM classification. This study evaluates the effectiveness of different surgical approaches in patients with early gallbladder carcinoma in terms of long-term survival. MATERIALS AND METHODS From 1980 to 2001, 175 patients with gallbladder carcinoma were admitted to our department. Fifteen of them underwent resections for early gallbladder carcinoma: 4 patients for pT1a tumors and 11 patients for pT1b tumors. All patients with pT1a tumors and 8 patients with pT1b tumors underwent simple cholecystectomy. The remaining 3 patients with pT1b tumors underwent extended cholecystectomy. RESULTS The 5-10 year cumulative survival rate was 100% for patients with pT1a tumors, 37.5% for patients with pT1b tumors who underwent simple cholecystectomy, and 100% for patients with pT1b tumors who underwent extended cholecystectomy. CONCLUSIONS Simple cholecystectomy is the appropriate treatment for patients with pT1a tumors, whereas patients with pT1b tumors require an extended cholecystectomy.
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Affiliation(s)
- Vincenzo Cangemi
- Department of Surgery "Pietro Valdoni", Policlinico Umberto I, University La Sapienza, Rome, Italy.
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Abstract
BACKGROUND Gallbladder cancer is an uncommon disease except in countries like Chile and areas of India and Japan. The knowledge regarding the etiology and mechanisms through which this neoplasia is developed is significantly less compared to other malignant tumors. RESULTS The epithelial lesions involved in gallbladder carcinogenesis are dysplasia and adenomas that represent two biologically distinct carcinogenetic models. Dysplasia progresses to carcinoma in situ (CIS) and subsequently becomes invasive. Over 80% of invasive gallbladder cancers present areas adjacent to the CIS and epithelial dysplasia. Other authors have demonstrated adenomatous areas in carcinomas, or malignant transformation in an adenoma. The low incidence of gallbladder adenomas (0.14% of cholecystectomies) and the presence of adenomatous remnants in the neighboring mucosa to early carcinomas in less than 3% of the cases suggest the limited importance of this carcinogenic pathway. Epithelial dysplasia which is not associated with gallbladder cancer is observed in approximately 1% of cholecystectomies for symptomatic lithiasis. Metaplasia, dysplasia, and CIS are present in the mucosa adjacent to the cancer in 66%, 81.3%, and 69%, respectively. The average ages of patients with dysplasia not associated to cancer (51.9 years), early carcinomas (56.8 years), and advanced carcinomas (62.9 years) demonstrate a gradient which suggests the progression of these lesions. CONCLUSIONS From the morphological point of view, the dysplasia-carcinoma sequence is the most plausible carcinogenic pathway for gallbladder cancer, a process which would require a period of approximately 10 years.
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Affiliation(s)
- Iván Roa
- Department of Pathology, Faculty of Medicine, Universidad de la Frontera, Temuco, Chile
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