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Varshney P, Baghmar S, Sirohi B, Abou-Alfa GK, Cao HT, Sharma LM, Javle M, Goetze T, Kapoor VK. Neoadjuvant treatment for incidental gallbladder cancer: A systematic review. Ann Hepatobiliary Pancreat Surg 2025; 29:113-120. [PMID: 40064481 PMCID: PMC12093237 DOI: 10.14701/ahbps.24-223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/09/2025] [Accepted: 01/22/2025] [Indexed: 05/15/2025] Open
Abstract
Incidental gallbladder cancer (iGBC) diagnosed post-histopathological examination of gallbladders removed assuming benign gallstone disease constitutes a significant proportion of GBC patients. Most iGBC patients present with early-stage disease. The standard care for localized (non-metastatic) iGBC includes a reoperation for complete extended (radical) cholecystectomy involving liver resection and lymphadenectomy, followed by postoperative adjuvant systemic therapy. However, a major drawback of this approach is the high recurrence rate within six months post-radical surgery, which undermines the benefits of the extensive procedure; notably, most recurrences are distant, highlighting the efficacy of systemic therapy. Similar to other gastrointestinal cancers, there appears to be a potential for neoadjuvant systemic therapy (chemotherapy) before reoperative surgery in iGBC cases. The premise that neoadjuvant systemic therapy aids in selecting diseases with more favorable biological characteristics and addresses micro-metastatic disease appears applicable to iGBC as well. This systematic review examines the current evidence supporting or refuting neoadjuvant therapy and discusses criteria for selecting patients who would derive significant benefit, along with proposing an optimal chemotherapy regimen for iGBC patients. Improved outcomes have been reported in patients undergoing reoperation after 4 to 14 weeks following the initial cholecystectomy compared to immediate reoperation. Limited, yet promising, evidence supports the use of 3 to 4 cycles of gemcitabine-based neoadjuvant chemotherapy prior to reoperative surgery in select high-risk iGBC cases.
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Affiliation(s)
- Peeyush Varshney
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Jodhpur, India
| | - Saphalta Baghmar
- Department of Medical Oncology, Amrita Institute of Medical Sciences, Faridabad, India
| | - Bhawna Sirohi
- Department of Medical Oncology, Vedanta Medical Research Foundation, Balco Medical Center, Raipur, India
| | - Ghassan K Abou-Alfa
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Department of Medical Oncology, Weill Cornell College at Cornell University, New York, NY, United States
- Department of Medical Oncology, Trinity College Dublin, Dublin, Ireland
| | - Hop Tran Cao
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Lalit Mohan Sharma
- Department of Medical Oncology, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Milind Javle
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Thorsten Goetze
- Department of Visceral Surgery, Krankenhaus Nordwest, Frankfurt, Germany
- Department of Visceral Surgery, University Cancer Center Frankfurt, Frankfurt, Germany
| | - Vinay K Kapoor
- Department of Surgical Gastroenterology, Mahatma Gandhi Medical College and Hospital, Jaipur, India
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Waller GC, Sarpel U. Gallbladder Cancer. Surg Clin North Am 2024; 104:1263-1280. [PMID: 39448127 DOI: 10.1016/j.suc.2024.03.006] [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] [Indexed: 10/26/2024]
Abstract
Gallbladder cancer is the most common biliary tract malignancy, often detected incidentally post-cholecystectomy or at an advanced stage, historically linked to a poor prognosis. Advances in minimally invasive surgery and systemic therapies have improved outcomes. Global incidence varies, with risk factors including gender, age, gallbladder disease history, and polyp size influencing malignancy risks. Management involves cross-sectional imaging, staging laparoscopy in select cases, and radical cholecystectomy with lymphadenectomy and adjuvant therapy, though its use is limited. Trials are ongoing assessing the role of neoadjuvant therapy. Prognosis depends on the tumor stage, with early detection crucial for long-term survival.
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Affiliation(s)
- Giacomo C Waller
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Suite B17, Box #1259, New York, NY 10029-6574, USA. https://twitter.com/gwallermd
| | - Umut Sarpel
- Division of Surgical Oncology, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Shapiro Clinical Building, Boston, MA 02215, USA.
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3
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Marino R, Ratti F, Casadei-Gardini A, Rimini M, Pedica F, Clocchiatti L, Aldrighetti L. The oncologic burden of residual disease in incidental gallbladder cancer: An elastic net regression model to profile high-risk features. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108397. [PMID: 38815335 DOI: 10.1016/j.ejso.2024.108397] [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: 02/10/2024] [Revised: 05/04/2024] [Accepted: 05/07/2024] [Indexed: 06/01/2024]
Abstract
INTRODUCTION Incidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection's role as a modifying factor in the natural history of IGBC. METHODS All patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD. RESULTS Among the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38-60) for IGBC patients with no evidence of RD, compared to 31 months (23-42) for those with RD (p < 0.001). CONCLUSION Re-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.
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Affiliation(s)
- Rebecca Marino
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy
| | - Francesca Ratti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy; University Vita-Salute San Raffaele, 20132, Milan, Italy.
| | | | - Margherita Rimini
- Department of Medical Oncology, IRCCS San Raffaele Hospital, 20132, Milan, Italy
| | - Federica Pedica
- Department of Experimental Oncology, Pathology Unit, San Raffaele Hospital, 20132, Milan, Italy
| | - Lucrezia Clocchiatti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy
| | - Luca Aldrighetti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy; University Vita-Salute San Raffaele, 20132, Milan, Italy
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Patkar S, Kunte A, Chaudhari V, Goel M. Outcomes of incidental versus non-incidental T2 gallbladder cancer: A single-institute experience of 425 cases. J Surg Oncol 2024; 129:754-764. [PMID: 38088226 DOI: 10.1002/jso.27562] [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: 07/26/2023] [Revised: 11/07/2023] [Accepted: 11/30/2023] [Indexed: 02/17/2024]
Abstract
BACKGROUND Up to 60% of incidentally detected gallbladder cancers (GBCs) have a primary stage of pathologic T2 stage (pT2), defined by invasion of the peri-adventitial tissue by the tumour, a plane breached during a simple cholecystectomy. This study assesses the impact of incidental detection of pT2 GBCs on survival outcomes. METHODS Retrospective analysis of pT2 GBCs undergoing a curative resection was performed. Patients who received neoadjuvant chemotherapy before an upfront radical resection were excluded. Outcomes of patients undergoing upfront surgery (uGBC) and incidentally detected tumours (iGBC) were compared. RESULTS From a total of 1356 patients, 425 patients with pT2 GBCs were included. Of these, 118 (27.7%) and 307 (72.23%) patients were in the uGBC and iGBC groups, respectively. Patients with iGBC had significantly higher locoregional, (62 [19.8%] vs. 11 [9.3%]; p = 0.009), liver, (36 [11.5%] vs. 4 [3.4%]; p = 0.01), and abdominal wall recurrences (23 [7.4%] vs. 1 [0.8%]; p = 0.009). Five-year disease free survival rates were 68.7% and 49.2% in the uGBC and iGBC groups, respectively (p = 0.013). Five-year overall survival rates were 71.7% and 64.6% in the uGBC and iGBC groups, respectively (p = 0.317). CONCLUSIONS Incidentally detected pT2 GBCs have significantly poorer outcomes compared to similarly staged patients undergoing an upfront radical cholecystectomy.
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Affiliation(s)
- Shraddha Patkar
- Department of Surgical Oncology, GI & HPB Services, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Aditya Kunte
- Department of Surgical Oncology, GI & HPB Services, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Vikram Chaudhari
- Department of Surgical Oncology, GI & HPB Services, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Mahesh Goel
- Department of Surgical Oncology, GI & HPB Services, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
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Kim M, Stroever S, Aploks K, Ostapenko A, Dong XD, Seshadri R. Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis. World J Gastrointest Surg 2024; 16:95-102. [PMID: 38328312 PMCID: PMC10845287 DOI: 10.4240/wjgs.v16.i1.95] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 11/27/2023] [Accepted: 12/18/2023] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract. Neoadjuvant chemotherapy (NACT) has improved overall survival by enabling R0 resection. Currently, there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer. As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients, we examined American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to determine if there was higher morbidity among the neoadjuvant group within the 30-day post-operative period. We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity. AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery. METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity (bile leak, infection rate, rate of converting to open surgery, etc.) compared to the group who only had surgery. To calculate the odds ratio for the primary and secondary outcomes, a crude logistic regression was performed. RESULTS Of the 452 patients, 52 patients received NACT prior to surgery. There were no statistically significant differences in the odds of morbidity between the two groups, including bile leak [odds ratio (OR), 0.69; 95% confidence interval (95%CI): 0.16-2.10; P = 0.55], superficial wound infection (OR, 0.58; 95%CI: 0.03-3.02; P = 0.61), and organ space wound infection (OR, 0.63; 95%CI: 0.18-1.63; P = 0.61). CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.
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Affiliation(s)
- Minha Kim
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Stephanie Stroever
- Department of Research and Innovation, Nuvance Health, Danbury, CT 06810, United States
| | - Krist Aploks
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Alexander Ostapenko
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Xiang Da Dong
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Ramanathan Seshadri
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
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Lv TR, Liu F, Jin YW, Li FY. Comparative analyses between radically re-resected incidental gallbladder carcinoma and primary radically resected gallbladder carcinoma: a single-center experience in China. Langenbecks Arch Surg 2023; 409:2. [PMID: 38087066 DOI: 10.1007/s00423-023-03199-3] [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: 09/11/2023] [Accepted: 12/05/2023] [Indexed: 12/18/2023]
Abstract
PURPOSES The current study was performed to comparatively evaluate the similarities and differences between cases with radically re-resected incidental gallbladder carcinoma (RRIGBC) and those with primary radically resected gallbladder carcinoma (PRGBC). METHODS Comparative analysis between patients with RRIGBC and those with PRGBC were performed in terms of clinic-pathological features and long-terms survival. RESULTS A total of 330 surgically treated GBC patients with 110 patients with IGBC were identified. PRGBCs were generally in a more advanced tumor stage, sharing more aggressive tumor biological features and worse prognosis than those with RRIGBC. Subgroup analyses indicated a comparable prognosis among T1-2 patients between RRIGBC and PRGBC groups. However, among T3-4 patients, patients in the PRGBC group shared a much worse prognosis. Moreover, IGBC itself can be regarded as a prognostic factor but cannot be regarded as an independent prognostic factor. It is the tumor stage which really determined the overall prognosis. CONCLUSION Patients with RRIGBC were generally in a much earlier tumor stage and shared a much better prognosis than those with PRGBC. IGBC itself can be regarded as a prognostic factor but cannot be regarded as the independent prognostic factors. It is the tumor stage which really determine the overall prognosis.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China
| | - Fei Liu
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China
| | - Yan-Wen Jin
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China.
| | - Fu-Yu Li
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China.
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7
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Shah S, Sweeney R, Wegner RE. Survival Benefit with Re-resection and Optimal Time to Re-resection in Gallbladder Cancer: a National Cancer Database Study. J Gastrointest Cancer 2023; 54:1331-1337. [PMID: 37231186 DOI: 10.1007/s12029-023-00934-3] [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] [Accepted: 03/29/2023] [Indexed: 05/27/2023]
Abstract
PURPOSE Gallbladder cancer is often diagnosed incidentally after cholecystectomy. Most patients will then undergo re-resection for potential residual disease; however, overall survival (OS) benefit data in this scenario is variable. This National Cancer Database analysis (NCDB) compared OS in patients with T1b-T3 gallbladder cancer who underwent re-resection and evaluated if time to resection impacts OS. METHODS We reviewed the NCDB for patients who received initial cholecystectomy for gallbladder cancer and were subsequently eligible for re-resection based on tumor stage (T1b-T3 disease). Patients with re-resection were subdivided into four cohorts based on time to re-resection: 0-4 weeks, 5-8 weeks, 9-12 weeks, and > 12 weeks. We used a Cox proportional hazards ratio to identify factors associated with worse survival and logistic regression to evaluate characteristics associated with re-resection. OS was calculated using Kaplan Meier curves. RESULTS A total of 791 (5.82%) patients received re-resection. Cox proportional hazards analysis showed a comorbidity score of 1 was associated with worse survival. Patients with higher comorbidity scores and treatment at comprehensive community, integrated, or academic cancer programs were less likely to undergo re-resection. Re-resection showed significantly improved OS [HR 0.87; 95 CI 0.77-0.98; p = 0.0203]. Improved survival was appreciated when re-resection was completed at 5-8 weeks [HR 0.67; CI 0.57-0.81], 9-12 weeks [HR 0.64; CI 0.52-0.79], or > 12 weeks [HR 0.61; CI 0.47-0.78] compared to 0-4 weeks. CONCLUSION Optimal timing to re-resection in gallbladder cancer supports previous data showing benefit at > 4 weeks. However, there was no significant survival difference as to whether re-resection was completed at 5-8 weeks, 9-12 weeks, or > 12 weeks post initial cholecystectomy.
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Affiliation(s)
- Shivani Shah
- Department of Internal Medicine, Allegheny Health Network, 320 E. North Avenue, Pittsburgh, PA, 15212, USA.
| | - Ryan Sweeney
- Department of Internal Medicine, Allegheny Health Network, 320 E. North Avenue, Pittsburgh, PA, 15212, USA
| | - Rodney E Wegner
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, 320 E. North Avenue, Pittsburgh, PA, 15212, USA
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Sun J, Xie TG, Ma ZY, Wu X, Li BL. Current status and progress in laparoscopic surgery for gallbladder carcinoma. World J Gastroenterol 2023; 29:2369-2379. [PMID: 37179580 PMCID: PMC10167897 DOI: 10.3748/wjg.v29.i16.2369] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/01/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Gallbladder carcinoma (GBC) is the most common biliary tract malignancy associated with a concealed onset, high invasiveness and poor prognosis. Radical surgery remains the only curative treatment for GBC, and the optimal extent of surgery depends on the tumor stage. Radical resection can be achieved by simple cholecystectomy for Tis and T1a GBC. However, whether simple cholecystectomy or extended cholecystectomy, including regional lymph node dissection and hepatectomy, is the standard surgical extent for T1b GBC remains controversial. Extended cholecystectomy should be performed for T2 and some T3 GBC without distant metastasis. Secondary radical surgery is essential for incidental gall-bladder cancer diagnosed after cholecystectomy. For locally advanced GBC, hepatopancreatoduodenectomy may achieve R0 resection and improve long-term survival outcomes, but the extremely high risk of the surgery limits its implementation. Laparoscopic surgery has been widely used in the treatment of gastrointestinal malignancies. GBC was once regarded as a contraindication of laparoscopic surgery. However, with improvements in surgical instruments and skills, studies have shown that laparoscopic surgery will not result in a poorer prognosis for selected patients with GBC compared with open surgery. Moreover, laparoscopic surgery is associated with enhanced recovery after surgery since it is minimally invasive.
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Affiliation(s)
- Jia Sun
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Tian-Ge Xie
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Zu-Yi Ma
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Xin Wu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Bing-Lu Li
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
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Gholami S, Colby S, Horowitz DP, Guthrie KA, Ben-Josef E, El-Khoueiry AB, Blanke CD, Philip PA, Kachnic LA, Ahmad SA, Rocha FG. Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers: Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809). Ann Surg Oncol 2023; 30:1354-1363. [PMID: 36622529 PMCID: PMC10695673 DOI: 10.1245/s10434-022-12863-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/10/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND SWOG 0809 is the only prospective study of adjuvant chemotherapy followed by chemoradiation focusing on margin status in patients with extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBCA); however, the effects of adjuvant therapy by nodal status have never been reported in this population. METHODS Patients with resected EHCC and GBCA, stage pT2-4, node-positive (N+) or margin-positive (R1) who completed four cycles of chemotherapy followed by radiotherapy were included. Cox regression was used to compare overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis by nodal status. DFS rates were compared with historical data via a one-sample t-test. RESULTS Sixty-nine patients [EHCC, n = 46 (66%); GBCA, n = 23 (33%)] were evaluated, with a median age of 61.7 years and an R0 rate of 66.7% and R1 rate of 33.3%. EHCC versus GBCA was more likely to be N+ (73.9% vs. 47.8%, p = 0.03). Nodal status did not significantly impact OS (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.86-4.54, p = 0.11) or DFS (HR 1.63, 95% CI 0.77-3.44, p = 0.20). Two-year OS was 70.6% for node-negative (N0) disease and 60.9% for N+ disease, while 2-year DFS was 62.5% for N0 tumors and 49.8% for N+ tumors. N+ versus N0 tumors showed higher rates of distant failure (42.2% vs. 25.0%, p = 0.04). The 2-year DFS rate in N+ tumors was significantly higher than in historical controls (49.8% vs. 29.7%, p = 0.004). CONCLUSIONS Adjuvant therapy is associated with favorable outcome independent of nodal status and may impact local control in N+ patients. These data could serve as a benchmark for future adjuvant trials, including molecular-targeted agents.
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Affiliation(s)
- Sepideh Gholami
- Department of Surgery, University of California, Davis, CA, USA.
| | - Sarah Colby
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - David P Horowitz
- Department of Radiation Oncology, Columbia University Irving Medical Center, New York City, NY, USA
- Herbert Irving Comprehensive Cancer Center, New York City, NY, USA
| | - Katherine A Guthrie
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Edgar Ben-Josef
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA
| | - Anthony B El-Khoueiry
- Department of Clinical Medicine, University of Southern California, Los Angeles, CA, USA
| | - Charles D Blanke
- SWOG Group Chair's Office, Oregon Health Sciences University, Knight Cancer Institute, Portland, OR, USA
| | - Philip A Philip
- Department of Oncology and Department of Pharmacology, School of Medicine, Wayne State University, Karmanos Cancer Center, Detroit, MI, USA
| | - Lisa A Kachnic
- Department of Radiation Oncology, Columbia University Irving Medical Center, New York City, NY, USA
- Herbert Irving Comprehensive Cancer Center, New York City, NY, USA
| | - Syed A Ahmad
- Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Flavio G Rocha
- Division of Surgical Oncology, Oregon Health Sciences University, Knight Cancer Institute, Portland, OR, USA
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10
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Li C, Luan X, Bi X, Chen S, Pan Y, Zhang J, Han Y, Xu X, Wang G, Xu B. Multiparameter diagnostic model based on 18F-FDG PET metabolic parameters and clinical variables can differentiate nonmetastatic gallbladder cancer and cholecystitis. BMC Cancer 2023; 23:119. [PMID: 36747196 PMCID: PMC9901059 DOI: 10.1186/s12885-023-10599-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To evaluate the diagnostic value of a multiparameter model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters and clinical variables in differentiating nonmetastatic gallbladder cancer (GBC) from cholecystitis. PATIENTS AND METHODS In total, 122 patients (88 GBC nonmetastatic patients and 34 cholecystitis patients) with gallbladder space-occupying lesions who underwent 18F-FDG PET/CT were included. All patients received surgery and pathology, and baseline characteristics and clinical data were also collected. The metabolic parameters of 18F-FDG PET, including SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), SUVpeak (peak standard uptake value), MTV (metabolic tumour volume), TLG (total lesion glycolysis) and SUVR (tumour-to-normal liver standard uptake value ratio), were evaluated. The differential diagnostic efficacy of each independent parameter and multiparameter combination model was evaluated using the receiver operating characteristic (ROC) curve. The improvement in diagnostic efficacy using a combination of the above multiple parameters was evaluated by integrated discriminatory improvement (IDI), net reclassification improvement (NRI) and bootstrap test. Decision curve analysis (DCA) was used to evaluate clinical efficacy. RESULTS The ROC curve showed that SUVR had the highest diagnostic ability among the 18F-FDG PET metabolic parameters (area under the curve [AUC] = 0.698; sensitivity = 0.341; specificity = 0.971; positive predictive value [PPV] = 0.968; negative predictive value [NPV] = 0.363). The combined diagnostic model of cholecystolithiasis, fever, CEA > 5 ng/ml and SUVR showed an AUC of 0.899 (sensitivity = 0.909, specificity = 0.735, PPV = 0.899, NPV = 0.758). The diagnostic efficiency of the model was improved significantly compared with SUVR. The clinical efficacy of the model was confirmed by DCA. CONCLUSIONS The multiparameter diagnostic model composed of 18F-FDG PET metabolic parameters (SUVR) and clinical variables, including patient signs (fever), medical history (cholecystolithiasis) and laboratory examination (CEA > 5 ng/ml), has good diagnostic efficacy in the differential diagnosis of nonmetastatic GBC and cholecystitis.
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Affiliation(s)
- Can Li
- grid.414252.40000 0004 1761 8894Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Xiaohui Luan
- grid.414252.40000 0004 1761 8894Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China ,grid.414252.40000 0004 1761 8894Graduate School, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Xiao Bi
- grid.414252.40000 0004 1761 8894Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Shengxin Chen
- grid.414252.40000 0004 1761 8894Graduate School, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China ,grid.414252.40000 0004 1761 8894Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Yue Pan
- grid.414252.40000 0004 1761 8894Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China ,grid.414252.40000 0004 1761 8894Graduate School, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Jingfeng Zhang
- grid.414252.40000 0004 1761 8894Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China ,grid.414252.40000 0004 1761 8894Graduate School, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Yun Han
- grid.414252.40000 0004 1761 8894Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China ,grid.414252.40000 0004 1761 8894Graduate School, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Xiaodan Xu
- grid.414252.40000 0004 1761 8894Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853 China
| | - Guanyun Wang
- Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China. .,Nuclear Medicine Department, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Road, Xicheng District, Beijing, 100050, China.
| | - Baixuan Xu
- Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.
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11
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Pehlivanoglu B, Akkas G, Memis B, Basturk O, Reid MD, Saka B, Dursun N, Bagci P, Balci S, Sarmiento J, Maithel SK, Bandyopadhyay S, Escalona OT, Araya JC, Losada H, Goodman M, Knight JH, Roa JC, Adsay V. Reappraisal of T1b gallbladder cancer (GBC): clinicopathologic analysis of 473 in situ and invasive GBCs and critical review of the literature highlights its rarity, and that it has a very good prognosis. Virchows Arch 2023; 482:311-323. [PMID: 36580138 DOI: 10.1007/s00428-022-03482-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 12/05/2022] [Accepted: 12/17/2022] [Indexed: 12/30/2022]
Abstract
There are highly conflicting data on relative frequency (2-32%), prognosis, and management of pT1b-gallbladder carcinoma (GBC), with 5-year survival ranging from > 90% in East/Chile where cholecystectomy is regarded as curative, versus < 50% in the West, with radical operations post-cholecystectomy being recommended by guidelines. A total of 473 in situ and invasive extensively sampled GBCs from the USA (n = 225) and Chile (n = 248) were re-evaluated histopathologically per Western invasiveness criteria. 349 had invasive carcinoma, and only 24 were pT1. Seven cases previously staged as pT1b were re-classified as pT2. There were 19 cases (5% of all invasive GBCs) qualified as pT1b and most pT1b carcinomas were minute (< 1mm). One patient with extensive pTis at margins (but pT1b focus away from the margins) died of GBC at 27 months, two died of other causes, and the remainder were alive without disease (median follow-up 69.9 months; 5-year disease-specific survival, 92%). In conclusion, careful pathologic analysis of well-sampled cases reveals that only 5% of invasive GBCs are pT1b, with a 5-year disease-specific survival of > 90%, similar to findings in the East. This supports the inclusion of pT1b in the "early GBC" category, as is typically done in high-incidence regions. Pathologic mis-staging of pT2 as pT1 is not uncommon. Cases should not be classified as pT1b unless extensive, preferably total, sampling of the gallbladder to rule out a subtle pT2 is performed. Critical appraisal of the literature reveals that the Western guidelines are based on either SEER or mis-interpretation of stage IB cases as "pT1b." Although the prognosis of pT1b-GBC is very good, additional surgery (radical cholecystectomy) may be indicated, and long-term surveillance of the biliary tract is warranted.
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Affiliation(s)
- Burcin Pehlivanoglu
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
- Current affiliation: Department of Pathology, Dokuz Eylul University, Izmir, Turkey
| | - Gizem Akkas
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
- Current affiliation: Department of Pathology, Faculty of Medicine, Kutahya University of Health Sciences, Kutahya, Turkey
| | - Bahar Memis
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michelle D Reid
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Burcu Saka
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Nevra Dursun
- Department of Pathology, University of Health Sciences, Istanbul Education and Research Hospital, Istanbul, Turkey
| | - Pelin Bagci
- Department of Pathology, Marmara University School of Medicine, Istanbul, Turkey
| | - Serdar Balci
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Juan Sarmiento
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Shishir K Maithel
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | | | | | - Juan Carlos Araya
- Department of Pathology, Hospital Dr. Hernan Henriquez Aravena, Temuco, Chile
| | - Hector Losada
- Department of Surgery and Traumatology, Universidad de La Frontera, Temuco, Chile
| | - Michael Goodman
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA
| | - Jessica Holley Knight
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA
| | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital, Davutpaşa Caddesi No:4, Topkapi, 34010, Istanbul, Turkey.
- Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.
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12
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Abstract
Gallbladder cancer (GBC) is the most common cancer of the biliary tract, characterized by a very poor prognosis when diagnosed at advanced stages owing to its aggressive behaviour and limited therapeutic options. Early detection at a curable stage remains challenging because patients rarely exhibit symptoms; indeed, most GBCs are discovered incidentally following cholecystectomy for symptomatic gallbladder stones. Long-standing chronic inflammation is an important driver of GBC, regardless of the lithiasic or non-lithiasic origin. Advances in omics technologies have provided a deeper understanding of GBC pathogenesis, uncovering mechanisms associated with inflammation-driven tumour initiation and progression. Surgical resection is the only treatment with curative intent for GBC but very few cases are suitable for resection and most adjuvant therapy has a very low response rate. Several unmet clinical needs require to be addressed to improve GBC management, including discovery and validation of reliable biomarkers for screening, therapy selection and prognosis. Standardization of preneoplastic and neoplastic lesion nomenclature, as well as surgical specimen processing and sampling, now provides reproducible and comparable research data that provide a basis for identifying and implementing early detection strategies and improving drug discovery. Advances in the understanding of next-generation sequencing, multidisciplinary care for GBC, neoadjuvant and adjuvant strategies, and novel systemic therapies including chemotherapy and immunotherapies are gradually changing the treatment paradigm and prognosis of this recalcitrant cancer.
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Affiliation(s)
- Juan C Roa
- Department of Pathology, Millennium Institute on Immunology and Immunotherapy, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Patricia García
- Department of Pathology, Millennium Institute on Immunology and Immunotherapy, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Vinay K Kapoor
- Department of Hepato-pancreato-biliary (HPB) Surgery, Mahatma Gandhi Medical College & Hospital (MGMCH), Jaipur, India
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, UT M.D. Anderson Cancer Center, Houston, TX, USA
| | - Jill Koshiol
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
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13
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Rahul R, Haldenia K, Singh A, Kapoor V, Singh RK, Saxena R. Does Timing of Completion Radical Cholecystectomy Determine the Survival Outcome in Incidental Carcinoma Gallbladder: A Single-Center Retrospective Analysis. Cureus 2022; 14:e26653. [PMID: 35949769 PMCID: PMC9357255 DOI: 10.7759/cureus.26653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2022] [Indexed: 12/03/2022] Open
Abstract
Introduction Incidental discovery of gallbladder cancer (GBC) on postoperative histopathology or intra-operative suspicion is becoming increasingly frequent since laparoscopic cholecystectomy became the standard of care for gallstone disease. Incidental GBC (IGBC) portends a better survival than primarily detected GBC. Various factors affect the outcome of re-resection with the timing of re-intervention an important determinant of survival. Methods All patients of IGBC who underwent curative resection from January 2009 to December 2018 were considered for analysis. Details of demographic profile, index surgery, and operative findings on re-resection, histopathology and follow-up were retrieved from the prospectively maintained database. Patients were evaluated in three groups based on the interval between index cholecystectomy and re-resection: Early (<4 weeks), Intermediate (4-12 weeks) and Late (>12 weeks), using appropriate statistical tests. Results Ninety-one patients were admitted with IGBC during the study period of which 48 underwent re-resection with curative intent. The median age of presentation was 55 years (31-77 years). The median duration of follow-up was 40.6 months (Range: 1.2-130.6 months). Overall and disease-free survival among the above-mentioned three groups was the best in the early group (104 and 102 months) as compared to the intermediate (84 and 83 months) and late groups (75 and 73 months), though the difference failed to achieve statistical significance (p=0.588 and 0.581). On univariate analysis, factors associated with poor outcome were node metastasis, need for common bile duct (CBD) excision and high-grade tumor. However, on multivariate analysis, poor differentiation was the only independent factor affecting survival. Conclusion Early surgery, preferably within four weeks, possibly entails better survival in incidentally detected GBC. The grade of a tumor, however, is the most important determinant of survival in IGBC.
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14
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Vega EA, Mellado S, Salehi O, Freeman R, Conrad C. Treatment of Resectable Gallbladder Cancer. Cancers (Basel) 2022; 14:1413. [PMID: 35326566 PMCID: PMC8945892 DOI: 10.3390/cancers14061413] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/18/2022] [Accepted: 03/06/2022] [Indexed: 02/04/2023] Open
Abstract
Gallbladder cancer (GBC) is the most common biliary tract cancer worldwide and its incidence has significant geographic variation. A unique combination of predisposing factors includes genetic predisposition, geographic distribution, female gender, chronic inflammation, and congenital developmental abnormalities. Today, incidental GBC is the most common presentation of resectable gallbladder cancer, and surgery (minimally invasive or open) remains the only curative treatment available. Encouragingly, there is an important emerging role for systemic treatment for patients who have R1 resection or present with stage III-IV. In this article, we describe the pathogenesis, surgical and systemic treatment, and prognosis.
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Affiliation(s)
- Eduardo A. Vega
- Department of Surgery, St. Elizabeth’s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA; (E.A.V.); (O.S.); (R.F.)
| | | | - Omid Salehi
- Department of Surgery, St. Elizabeth’s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA; (E.A.V.); (O.S.); (R.F.)
| | - Richard Freeman
- Department of Surgery, St. Elizabeth’s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA; (E.A.V.); (O.S.); (R.F.)
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth’s Medical Center, Boston University School of Medicine, Boston, MA 02135, USA; (E.A.V.); (O.S.); (R.F.)
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15
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Feo CF, Ginesu GC, Fancellu A, Perra T, Ninniri C, Deiana G, Scanu AM, Porcu A. Current management of incidental gallbladder cancer: A review. Int J Surg 2022; 98:106234. [PMID: 35074510 DOI: 10.1016/j.ijsu.2022.106234] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/11/2022] [Accepted: 01/12/2022] [Indexed: 02/05/2023]
Abstract
Early-stage gallbladder cancer (GBC) is mostly discovered incidentally by the pathologist after cholecystectomy for a presumed benign disease. It is the most common malignancy of the biliary tract with a variable incidence rate all over the World. The majority of patients with GBC remain asymptomatic for a long time and diagnosis is usually late when the disease is at an advanced stage. Radical surgery consisting in resection of the gallbladder liver bed and regional lymph nodes seems to be the best treatment option for incidental GBC. However, recurrence rates after salvage surgery are still high and the addition of neoadjuvant/adjuvant chemotherapy may improve outcomes. The aim of the present review is to evaluate current literature for advances in management of incidental GBC, with particular focus on staging techniques and surgical options.
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Affiliation(s)
- Claudio F Feo
- Unit of General Surgery 2, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100, Sassari, Italy
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16
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Altiok M, Özdemir HG, Kurt F, Gul MO, Gumus S. Incidental gallbladder cancer: a retrospective clinical study of 40 cases. Ann Surg Treat Res 2022; 102:185-192. [PMID: 35475225 PMCID: PMC9010968 DOI: 10.4174/astr.2022.102.4.185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/23/2022] [Accepted: 02/10/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose Methods Results Conclusion
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Affiliation(s)
- Merih Altiok
- Department of Surgical Oncology, Balcalı Training and Research Hospital, Cukurova University, Adana, Turkey
| | - Hanife Gülnihal Özdemir
- Department of Pathology, Cengiz Gokcek Gynecology, Obstetrics, and Pediatrics Hospital, Gaziantep, Turkey
| | - Feyzi Kurt
- Department of General Surgery, Seyhan Government Hospital, Adana, Turkey
| | - Mehmet Onur Gul
- Department of Surgical Oncology, Balcalı Training and Research Hospital, Cukurova University, Adana, Turkey
| | - Serdar Gumus
- Department of Surgical Oncology, Hatay Training and Research Hospital, Hatay, Turkey
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17
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Medin CR, Maithel SK. Neoadjuvant therapy trials in biliary tract malignancies. J Surg Oncol 2022; 125:84-88. [PMID: 34897705 PMCID: PMC9059554 DOI: 10.1002/jso.26714] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 10/03/2021] [Indexed: 01/03/2023]
Affiliation(s)
- Caroline R Medin
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
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18
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Teng TZJ, Chua BQY, Shelat VG. Carcinosarcoma of gallbladder: A world review. World J Clin Oncol 2021; 12:1244-1263. [PMID: 35070742 PMCID: PMC8716988 DOI: 10.5306/wjco.v12.i12.1244] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 05/14/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gallbladder carcinosarcoma is a rare hepatobiliary tumor comprising of both carcinomatous and sarcomatous components. Due to its rarity, the literature with regards to the topic is scarce and currently lacking, spanning less than 100 cases. AIM To summarize the current literature on gallbladder carcinosarcoma. METHODS A literature review was performed on the PubMed database using the keywords "Gallbladder" AND "Carcinosarcoma" from 1970 to 2021. Additionally, similar searches were performed on MEDLINE and Web of Science. RESULTS Risk factors noted include female gender, gallstones and chronic cholecystitis. In the absence of any diagnostic biochemical testing or tumor markers, imaging modality serves as the key initial impression tool, which can be histologically confirmed only post-resection. While surgery is the only curative option, the use of adjunctive chemotherapy has been considered on top of excision in recent years, with some success. CONCLUSION While this study has taken steps to bridge the gap in the literature, more cases should be reported to further ascertain the current associations and management potential for gallbladder carcinosarcoma.
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Affiliation(s)
- Thomas Zheng Jie Teng
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Undergraduate Medicine, Lee Kong Chian School of Medicine, Singapore 308232, Singapore
| | - Branden Qi Yu Chua
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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19
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Đokic M, Stupan U, Licen S, Trotovsek B. Residual disease in lymph nodes has no influence on survival in patients with incidental gallbladder cancer - institution experience with literature review. Radiol Oncol 2021; 56:208-215. [PMID: 34957726 PMCID: PMC9122290 DOI: 10.2478/raon-2021-0048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 10/27/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND A better appreciation of the course and factors that influence incidental gallbladder cancer (iGBC) is needed to develop treatment strategies aimed to improve outcomes. The purpose of the study was to determine the influence of residual disease in the liver and lymph nodes on overall survival in re-resected patients with iGBC. PATIENTS AND METHODS Patients undergoing radical re-resection for iGBC from January 2012 to December 2018 were retrospectively identified. Patients with a 5-year follow-up and submitted to complete resection with stage I, II and III disease were analysed. The influence of residual disease (RD) in liver and lymph nodes on survival was assessed using the Kaplan-Meier curves. In addition, the rest of the group was assessed based on type of primary/secondary procedure, number of harvested lymph nodes and RD in liver and/or lymph nodes. RESULTS In this retrospective study 48 out of 58 (83%) patients underwent re-resection. Among the group with a 5-year follow-up (re-operation between 2012-2014), 22 patients out of 28 (79%) were re-resected. Survival analysis showed that patients with no RD in the liver and lymph nodes had statistically significant better 5-year survival than those with RD. Comparing 5-year survival rate in patients with RD in the liver or lymph nodes against no RD group, patients with RD in the liver had statistically significantly worse 5-year survival, while lymph node metastases did not show any statistically significant different in 5-year survival. Besides, a statistically significant better prognosis was found in stage II disease compared to stage III, as expected. CONCLUSIONS The most important predictors of a 5-year survival in our study were RD in liver and stage of the disease. Lymph node metastases did not have any impact on the overall 5-year survival rate.
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Affiliation(s)
- Mihajlo Đokic
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Abdominal Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Urban Stupan
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Abdominal Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Sabina Licen
- Nursing Department, Faculty of Health Sciences, University of Primorska, Izola, Slovenia
| | - Blaz Trotovsek
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Abdominal Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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20
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Okumura K, Gogna S, Gachabayov M, Felsenreich DM, McGuirk M, Rojas A, Quintero L, Seshadri R, Gu K, Dong XD. Gallbladder cancer: Historical treatment and new management options. World J Gastrointest Oncol 2021; 13:1317-1335. [PMID: 34721769 PMCID: PMC8529935 DOI: 10.4251/wjgo.v13.i10.1317] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 06/19/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
Gallbladder cancer is a rare, aggressive malignancy that has a poor overall prognosis. Effective treatment consists of early detection and surgical treatment. With the wide spread treatment of gallbladder disease with minimally invasive techniques, the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease. Although the treatment remains mostly surgical, newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease. We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Shekhar Gogna
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Mahir Gachabayov
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | | | - Matthew McGuirk
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Aram Rojas
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Luis Quintero
- Department of Surgery, New York Medical College, Valhalla, NY 10595, United States
| | - Ramanathan Seshadri
- Division of Surgical Oncology, Nuvance Health, Norwalk, CT 06856, United States
| | - Katie Gu
- Division of Surgical Oncology, Nuvance Health, Norwalk, CT 06856, United States
| | - Xiang Da Dong
- Division of Surgical Oncology, Nuvance Health, Norwalk, CT 06856, United States
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21
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Chaudhari VA, Bhandare MS, Shrikhande SV. Incidental Gallbladder Cancer—Current Recommendations and Management Protocols. Indian J Surg 2021. [DOI: 10.1007/s12262-021-02828-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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22
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Ando T, Sakata J, Nomura T, Takano K, Takizawa K, Miura K, Hirose Y, Kobayashi T, Ichikawa H, Hanyu T, Shimada Y, Nagahashi M, Kosugi SI, Wakai T. Anatomic location of residual disease after initial cholecystectomy independently determines outcomes after re-resection for incidental gallbladder cancer. Langenbecks Arch Surg 2021; 406:1521-1532. [PMID: 33839959 DOI: 10.1007/s00423-021-02165-1] [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: 11/23/2020] [Accepted: 03/29/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). METHODS Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). RESULTS Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). CONCLUSION The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.
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Affiliation(s)
- Takuya Ando
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan.
| | - Tatsuya Nomura
- Department of Gastrointestinal Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan
| | - Kabuto Takano
- Department of Gastrointestinal Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan
| | - Kazuyasu Takizawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Kohei Miura
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Takashi Kobayashi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Hiroshi Ichikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Takaaki Hanyu
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Yoshifumi Shimada
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Masayuki Nagahashi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
| | - Shin-Ichi Kosugi
- Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, Niigata, 949-7302, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan
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Matsuyama R, Matsuo K, Mori R, Sugita M, Yamaguchi N, Kubota T, Kameda K, Mochizuki Y, Takagawa R, Kadokura T, Matsuda G, Kamiya N, Endo I. Incidental Gallbladder Cancer on Cholecystectomy: Strategy for Re-resection of Presumed Benign Diseases from a Retrospective Multicenter Study by the Yokohama Clinical Oncology Group. In Vivo 2021; 35:1217-1225. [PMID: 33622924 DOI: 10.21873/invivo.12372] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND/AIM Current expert consensus recommends re-resection for incidental gallbladder cancer (IGBC) of pT1b-3. This study examined whether this consensus was reasonably applicable to patients with IGBC in one Japanese region. PATIENTS AND METHODS This was a multicenter, retrospective analysis of cholecystectomies for presumed benign diseases between January 2000 and December 2009. RESULTS IGBC was diagnosed in 70 (1.0%) out of 6,775 patients undergoing cholecystectomy. Five-year disease-specific cumulative survival was 100% in 19 patients with pT1a, 80.0% in five with pT1b, 49.5% in 33 with pT2, and 23.1% in 13 with pT3. Re-resection was not performed for the 24 patients with pT1a/1b disease, whereas 24 out of 46 patients with pT2/3 underwent re-resection. Regardless of re-resection, independent factors associated with a poor prognosis on multivariate analysis were grade 2 or poorer disease and bile spillage at prior cholecystectomy. In the 24 patients with pT2/3 re-resection, 11 patients without either of these two factors had significantly better 5-year disease-specific cumulative survival than the 13 patients with one or two independent factors associated with a poor prognosis (72.7% vs. 30.8%, p=0.009). CONCLUSION This Japanese regional study suggests that indication of re-resection for IGBC should not be determined by pT-factor alone and that much more attention should be paid to pathological and intraoperative findings at prior cholecystectomy.
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Affiliation(s)
- Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
| | - Kenichi Matsuo
- Department of Surgery, Fujisawa Municipal Hospital, Fujisawa, Japan
| | - Ryutaro Mori
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Mitsutaka Sugita
- Department of Surgery, Yokosuka Kyousai Hospital, Yokosuka, Japan
| | - Naotaka Yamaguchi
- Department of Surgery, Yokohama City Minato Red-Cross Hospital, Yokohama, Japan
| | - Toru Kubota
- Department of Surgery, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan
| | - Kunio Kameda
- Department of Surgery, Yokosuka Municipal Hospital, Yokosuka, Japan
| | - Yasuhisa Mochizuki
- Department of Surgery, Yokohama Municipal Citizens Hospital, Yokohama, Japan
| | - Ryo Takagawa
- Department of Surgery, Saiseikai Wakakusa Hospital, Yokohama, Japan
| | - Toshiaki Kadokura
- Department of Surgery, Yokohama Senin Hoken Hospital, Yokohama, Japan
| | - Goro Matsuda
- Department of Surgery, Yokohama Medical Center, Yokohama, Japan
| | | | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Keilson JM, Maithel SK. The Undertreatment of Gallbladder Cancer: Gaps in Seeking, Reaching, and Receiving Care. Ann Surg Oncol 2021; 28:2925-2927. [PMID: 33661462 PMCID: PMC7931778 DOI: 10.1245/s10434-021-09761-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 02/09/2021] [Indexed: 12/14/2022]
Affiliation(s)
- Jessica M Keilson
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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25
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Papageorge MV, de Geus SWL, Woods AP, Ng SC, Drake FT, Cassidy MR, McAneny DB, Tseng JF, Sachs TE. Undertreatment of Gallbladder Cancer: A Nationwide Analysis. Ann Surg Oncol 2021; 28:2949-2957. [PMID: 33566241 DOI: 10.1245/s10434-021-09607-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 11/23/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gallbladder cancer has a high mortality rate and an increasing incidence. The current National Comprehensive Cancer Network (NCCN) guidelines recommend resection for all T1b and higher-stage cancers. This study aimed to evaluate re-resection rates and the associated survival impact for patients with gallbladder cancer. METHODS Patients with gallbladder adenocarcinoma who underwent resection were identified from the National Cancer Database (2004-2015). Re-resection was defined as definitive surgery within 180 days after the first operation. Propensity scores were created for the odds of a patient having a re-resection. Patients were matched 1:2. Survival analyses were performed using the Kaplan-Meier and Cox proportional hazard methods. RESULTS The study identified 6175 patients, and 466 of these patients (7.6%) underwent re-resection. Re-resection was associated with younger median age (65 vs 72 years; p < 0.0001), private insurance (41.6% vs 27.1%; p < 0.0001), academic centers (50.4% vs 29.7%; p < 0.0001), and treatment location in the Northeast (22.8% vs 20.4%; p = 0.0011). Compared with no re-resection, re-resection was associated with pT stage (pT2: 47.6% vs 42.8%; p = 0.0139) and pN stage (pN1-2: 28.1% vs 20.7%; p < 0.0001), negative margins on final pathology (90.1% vs 72.6%; p < 0.0001), and receipt of chemotherapy (53.7% vs 35.8%; p < 0.0001). The patients who underwent re-resection demonstrated significantly longer overall survival (OS) than the patients who did not undergo re-resection (median OS, 44.0 vs 23.0 months; p < 0.0001). After propensity score-matching, re-resection remained associated with superior survival (median OS, 44.0 vs 31.0 months; p = 0.0004). CONCLUSIONS Re-resection for gallbladder cancer is associated with improved survival but remains underused, particularly for early-stage disease.
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Affiliation(s)
- Marianna V Papageorge
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Susanna W L de Geus
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Alison P Woods
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.,Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sing Chau Ng
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Frederick T Drake
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Michael R Cassidy
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - David B McAneny
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Jennifer F Tseng
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
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26
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Kingham TP, Aveson VG, Wei AC, Castellanos JA, Allen PJ, Nussbaum DP, Hu Y, D'Angelica MI. Surgical management of biliary malignancy. Curr Probl Surg 2021; 58:100854. [PMID: 33531120 PMCID: PMC8022290 DOI: 10.1016/j.cpsurg.2020.100854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Victoria G Aveson
- New York Presbyterian Hospital-Weill Cornel Medical Center, New York, NY
| | - Alice C Wei
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Duke Cancer Center, Chief, Division of Surgical Oncology, Duke University School of Medicine, Durham, NC
| | | | - Yinin Hu
- Division of Surgical Oncology, University of Maryland, Baltimore, MD
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, Professor of Surgery, Weill Medical College of Cornell University, New York, NY..
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27
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He S, Yu T, Khadaroo PA, Cai L, Chu Y, Wei F, Liang X. A Comparison Between the Prognosis of Simultaneous and Salvage Radical Resection in Incidental Gallbladder Cancer. Cancer Manag Res 2020; 12:13469-13478. [PMID: 33408519 PMCID: PMC7779289 DOI: 10.2147/cmar.s286292] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 12/08/2020] [Indexed: 12/25/2022] Open
Abstract
Purpose Incidental gallbladder cancer (IGBC) is defined as gallbladder cancer (GBC) that is accidentally discovered during cholecystectomy to treat benign lesions. We aimed to compare the prognosis of IGBC patients who underwent simultaneous radical resection (SIR) vs salvage radical resection (SAR). Patients and Methods We retrospectively reviewed data for IGBC patients admitted to Sir Run Run Shaw Hospital from January 2000 to May 2016. Survival analysis was performed using Kaplan–Meier (univariate) and COX regression (multivariate) analyses. Results Eighty-four patients with IGBC underwent radical resection; 43/84 underwent SIR, and 41/84 underwent SAR. Compared with SIR, the SAR group was more likely to receive comprehensive preoperative radiographic evaluation, port-site excision, and have more lymph nodes excised (all P < 0.05). Kaplan–Meier analysis indicated that the prognosis in the SAR group was better than that in SIR (overall survival: P = 0.050, recurrence-free survival: P = 0.028). Regression analysis indicated that the type of radical resection (SIR/SAR) was not an independent prognostic factor (overall survival: P = 0.737, recurrence-free survival: P = 0.957). Conclusion Patients undergoing SAR had non-inferior survival compared with SIR. It is possible that patients in SAR underwent preoperative radiographical evaluations more comprehensively and the surgical operations were more well performed.
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Affiliation(s)
- Shilin He
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Tunan Yu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Parikshit Asutosh Khadaroo
- Monash University, School of Medicine, Nursing and Health Sciences, Melbourne, Australia.,School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Liuxin Cai
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Yeyuan Chu
- School of Nursing, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Fangqiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, People's Republic of China
| | - Xiao Liang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
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Qin JM. Causes of misdiagnosis and missed diagnosis and therapeutic and preventive strategies for unexpected gallbladder carcinoma. Shijie Huaren Xiaohua Zazhi 2020; 28:1167-1176. [DOI: 10.11569/wcjd.v28.i23.1167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Laparoscopic cholecystectomy (LC) has been widely used in the treatment of gallbladder diseases. Since the indications for operation are constantly expanding, the intraoperative or postoperative incidence of unexpected gallbladder carcinoma (UGC) is gradually increasing. The incidence of UGC in LC and open cholecystectomy is 2.09% and 0.91%, respectively. Because gallbladder carcinoma is often accompanied by gallstones or inflammation and lacks specific clinical manifestations, imaging features, and specific serum tumor markers, the preoperative diagnostic rate of gallbladder carcinoma is only 30%, and 30% of cases of gallbladder carcinoma are diagnosed intraoperatively or postoperatively. Pathological T stage, lymph node metastasis, and gallbladder rupture are independent risk factors for the prognosis of patients with UGC. Preoperative imaging combined with serological tumor markers, intraoperative careful exploration, and rapid pathological examination are important measures to reduce the misdiagnosis and missed diagnosis of UGC. For patients with benign gallbladder diseases with a high potential of canceration, performing cholecystectomy in time and strictly grasping the indications for preserving gallbladder for benign gallbladder diseases are important preventive measures to reduce the incidence of UGC.
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Affiliation(s)
- Jian-Min Qin
- Department of General Surgery, The Third Hospital Affiliated to Naval Military Medical University, Shanghai 201805, China
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García P, Lamarca A, Díaz J, Carrera E, Roa JC, on behalf of the European-Latin American ESCALON Consortium. Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients. Cancers (Basel) 2020; 12:E3670. [PMID: 33297469 PMCID: PMC7762341 DOI: 10.3390/cancers12123670] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/06/2020] [Accepted: 11/11/2020] [Indexed: 01/17/2023] Open
Abstract
Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.
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Affiliation(s)
- Patricia García
- Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK;
| | - Javier Díaz
- Departamento del Aparato Digestivo, Hospital Nacional Edgardo Rebagliati Martins-Essalud, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru;
| | - Enrique Carrera
- Department of Gastroenterology, Hospital Especialidades Eugenio Espejo, Universidad San Francisco de Quito, Quito 170136, Ecuador;
| | - Juan Carlos Roa
- Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;
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Abstract
Managing patients with incidental gallbladder cancer requires stratifying patients risk for recurrence and an appreciation for the recurrence patterns characterizing this malignancy. Although standard management includes reresection to remove sites at risk of harboring residual disease and to achieve negative resection margin status, the decision to perform surgery is tempered by an early and frequent distant recurrence, the most common cause of surgical failure. High-risk patients may benefit from neoadjuvant chemotherapy before reresection. The goal of curative-intent reresection is achieving R0 margin status and optimal staging while limiting morbidity and mortality.
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31
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Vega EA, De Aretxabala X, Qiao W, Newhook TE, Okuno M, Castillo F, Sanhueza M, Diaz C, Cavada G, Jarufe N, Munoz C, Rencoret G, Vivanco M, Joechle K, Tzeng CWD, Vauthey JN, Vinuela E, Conrad C. Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer. Br J Surg 2020; 107:289-300. [PMID: 31873948 PMCID: PMC11844344 DOI: 10.1002/bjs.11379] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 03/22/2019] [Accepted: 09/04/2019] [Indexed: 02/03/2023]
Abstract
BACKGROUND The safety and oncological efficacy of laparoscopic re-resection of incidental gallbladder cancer have not been studied. This study aimed to compare laparoscopic with open re-resection of incidentally discovered gallbladder cancer while minimizing selection bias. METHODS This was a multicentre retrospective observational cohort study of patients with incidental gallbladder cancer who underwent re-resection with curative intent at four centres between 2000 and 2017. Overall survival (OS) and recurrence-free survival (RFS) were analysed by intention to treat. Inverse probability of surgery treatment weighting using propensity scoring was undertaken. RESULTS A total of 255 patients underwent re-resection (190 open, 65 laparoscopic). Nineteen laparoscopic procedures were converted to open operation. Surgery before 2011 was the only factor associated with conversion. Duration of hospital stay was shorter after laparoscopic re-resection (median 4 versus 6 days; P < 0·001). Three-year OS rates for laparoscopic and open re-resection were 87 and 62 per cent respectively (P = 0·502). Independent predictors of worse OS were residual cancer found at re-resection (hazard ratio (HR) 1·91, 95 per cent c.i. 1·17 to 3·11), blood loss of at least 500 ml (HR 1·83, 1·23 to 2·74) and at least four positive nodes (HR 3·11, 1·46 to 6·65). In competing-risks analysis, the RFS incidence was higher for laparoscopic re-resection (P = 0·038), but OS did not differ between groups. Independent predictors of worse RFS were one to three positive nodes (HR 2·16, 1·29 to 3·60), at least four positive nodes (HR 4·39, 1·96 to 9·82) and residual cancer (HR 2·42, 1·46 to 4·00). CONCLUSION Laparoscopic re-resection for selected patients with incidental gallbladder cancer is oncologically non-inferior to an open approach. Dissemination of advanced laparoscopic skills and timely referral of patients with incidental gallbladder cancer to specialized centres may allow more patients to benefit from this operation.
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Affiliation(s)
- E A Vega
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - X De Aretxabala
- Department of Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Clinica Alemana, Santiago, Chile
| | - W Qiao
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - T E Newhook
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - M Okuno
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - F Castillo
- Department of Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Clinica Alemana, Santiago, Chile
| | - M Sanhueza
- Department of Digestive Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Surgery Service, Hospital Sotero Del Rio, Santiago, Chile
- Department of Digestive Surgery, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - C Diaz
- Department of Digestive Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Surgery Service, Hospital Sotero Del Rio, Santiago, Chile
- Department of Digestive Surgery, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - G Cavada
- Department of Biostatistics, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile
| | - N Jarufe
- Department of Digestive Surgery, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - C Munoz
- Department of Digestive Surgery, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - G Rencoret
- Department of Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Clinica Alemana, Santiago, Chile
| | - M Vivanco
- Department of Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Clinica Alemana, Santiago, Chile
| | - K Joechle
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - C-W D Tzeng
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - J-N Vauthey
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - E Vinuela
- Department of Digestive Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Surgery Service, Hospital Sotero Del Rio, Santiago, Chile
- Department of Digestive Surgery, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - C Conrad
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Ramos E, Lluis N, Llado L, Torras J, Busquets J, Rafecas A, Serrano T, Mils K, Leiva D, Fabregat J. Prognostic value and risk stratification of residual disease in patients with incidental gallbladder cancer. World J Surg Oncol 2020; 18:18. [PMID: 31980034 PMCID: PMC6982379 DOI: 10.1186/s12957-020-1794-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 01/16/2020] [Indexed: 12/13/2022] Open
Abstract
Background and aim Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. Material and methods A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher’s exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. Results RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). Conclusion RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD.
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Affiliation(s)
- Emilio Ramos
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
| | - Nuria Lluis
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Laura Llado
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Jaume Torras
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Juli Busquets
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Antoni Rafecas
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Teresa Serrano
- Department of Pathology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Spain
| | - Kristel Mils
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain
| | - David Leiva
- Department of Radiology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Spain
| | - Joan Fabregat
- Department of Surgery, IDIBELL, Hospital Universitario de Bellvitge, CIBERehd, Servicio de Cirugía General y Digestiva, Universidad de Barcelona, Av Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain
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Abou-Alfa GK, Jarnagin W, El Dika I, D'Angelica M, Lowery M, Brown K, Ludwig E, Kemeny N, Covey A, Crane CH, Harding J, Shia J, O'Reilly EM. Liver and Bile Duct Cancer. ABELOFF'S CLINICAL ONCOLOGY 2020:1314-1341.e11. [DOI: 10.1016/b978-0-323-47674-4.00077-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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de Savornin Lohman EAJ, van der Geest LG, de Bitter TJJ, Nagtegaal ID, van Laarhoven CJHM, van den Boezem P, van der Post CS, de Reuver PR. Re-resection in Incidental Gallbladder Cancer: Survival and the Incidence of Residual Disease. Ann Surg Oncol 2019; 27:1132-1142. [PMID: 31741109 PMCID: PMC7060151 DOI: 10.1245/s10434-019-08074-4] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Indexed: 12/11/2022]
Abstract
Background Re-resection for incidental gallbladder cancer (iGBC) is associated with improved survival but little is known about residual disease (RD) and prognostic factors. In this study, survival after re-resection, RD, and prognostic factors are analyzed. Methods Patients with iGBC were identified from the Netherlands Cancer Registry, and pathology reports of re-resected patients were reviewed. Survival and prognostic factors were analyzed. Results Overall, 463 patients were included; 24% (n = 110) underwent re-resection after a median interval of 66 days. RD was present in 35% of patients and was most frequently found in the lymph nodes (23%). R0 resection was achieved in 93 patients (92%). Median overall survival (OS) of patients without re-resection was 13.7 (95% confidence interval [CI] 11.6–15.6), compared with 52.6 months (95% CI 36.3–68.8) in re-resected patients (p < 0.001). After re-resection, median OS was superior in patients without RD versus patients with RD (not reached vs. 23.1 months; p < 0.001). In patients who underwent re-resection, RD in the liver (hazard ratio [HR] 5.54; p < 0.001) and lymph nodes (HR 2.35; p = 0.005) were the only significant prognostic factors in multivariable analysis. Predictive factors for the presence of RD were pT3 stage (HR 25.3; p = 0.003) and pN1 stage (HR 23.0; p = 0.022). Conclusion Re-resection for iGBC is associated with improved survival but remains infrequently used and is often performed after the optimal timing interval. RD is the only significant prognostic factor for survival after re-resection and can be predicted by pT and pN stages. Electronic supplementary material The online version of this article (10.1245/s10434-019-08074-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | | | | | | | | | | | | | - Philip R de Reuver
- Department of Surgery, Route 618, Radboudumc, Nijmegen, The Netherlands.
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Creasy JM, Goldman DA, Gonen M, Dudeja V, O’Reilly EM, Abou-Alfa GK, Cercek A, Harding JJ, Balachandran VP, Drebin JA, Allen PJ, Kingham TP, D’Angelica MI, Jarnagin WR. Evolution of surgical management of gallbladder carcinoma and impact on outcome: results from two decades at a single-institution. HPB (Oxford) 2019; 21:1541-1551. [PMID: 31027875 PMCID: PMC6812599 DOI: 10.1016/j.hpb.2019.03.370] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 03/01/2019] [Accepted: 03/22/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND The surgical approach to gallbladder cancer (GBCA) has evolved in recent years, but the impact on outcomes is unknown. This study describes differences in presentation, surgery, chemotherapy strategy, and survival for patients with GBCA over two decades at a tertiary referral center. METHODS A single-institution database was queried for patients with GBCA who underwent surgical evaluation and exploration and was studied retrospectively. Univariate logistic regression was used to assess the relationship between time and treatment. Univariate Cox proportional hazard regression assessed the association between year of diagnosis and survival. RESULTS From 1992 to 2015, 675 patients with GBCA were evaluated and 437 underwent exploration. Complete resection rates increased over time (p < 0.001). In those submitted to complete resection (n = 255, 58.4%), more recent years were associated with lower likelihood of bile duct resection and major hepatectomy but greater odds of neoadjuvant and adjuvant chemotherapy (p < 0.05). No significant association was found between year of diagnosis and OS or RFS (p > 0.05) for patients with complete resection. CONCLUSION Over the study period, GBCA treatment evolved to include fewer biliary and major hepatic resections with no apparent adverse impact on outcome. Further prospective trials, specifically limited to GBCA, are needed to determine the impact of adjuvant chemotherapy.
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Affiliation(s)
- John M. Creasy
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Debra A. Goldman
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Vikas Dudeja
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Eileen M. O’Reilly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - James J. Harding
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Jeffrey A. Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Peter J. Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
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Blakely AM, Wong P, Chu P, Warner SG, Raoof M, Singh G, Fong Y, Melstrom LG. Intraoperative bile spillage is associated with worse survival in gallbladder adenocarcinoma. J Surg Oncol 2019; 120:603-610. [PMID: 31292970 DOI: 10.1002/jso.25617] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 06/21/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Gallbladder adenocarcinoma is often incidentally identified following cholecystectomy. We hypothesized that intraoperative bile spillage would be a negative prognostic factor. METHODS A retrospective review of patients treated at a cancer center with histologically confirmed gallbladder adenocarcinoma, 2009-2017, was performed. Patient, disease, and treatment factors were analyzed in terms of progression-free survival (PFS) and overall survival (OS). RESULTS Sixty-six patients were identified. Tumor stage was T1 (n = 8, 12%), T2 (n = 23, 35%), T3 (n = 35, 53%). Node stage was N0 (n = 22, 33%), N1+ (n = 26, 39%), Nx (n = 18, 27%). Operations included cholecystectomy alone (n = 27, 36%), cholecystectomy and partial hepatectomy (n = 30, 45%), or hepaticojejunostomy (n = 9, 14%). Median PFS was 7 months (interquartile range [IQR], 2-19); median OS was 16 months (IQR, 10-31). Subset multivariate proportional hazards regression of 41 patients who underwent initial cholecystectomy showed decreased PFS was associated with intraoperative spillage (n = 12, 29%; hazard ratio [HR], 5.5; P = .0014); decreased OS was associated with drain placement (n = 21, 51%; HR, 8.1; P = .006). CONCLUSIONS Intraoperative bile spillage and surgical drain placement at initial cholecystectomy are negatively associated with PFS and OS in gallbladder adenocarcinoma. Explicit documentation of spillage and drain placement rationale is critical, possibly indicating locally advanced disease and prompting stronger consideration of systemic therapy before definitive resection.
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Affiliation(s)
- Andrew M Blakely
- Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Paul Wong
- Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Peiguo Chu
- Department of Pathology, City of Hope National Medical Center, Duarte, California
| | - Susanne G Warner
- Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Mustafa Raoof
- Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Gagandeep Singh
- Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Laleh G Melstrom
- Department of Surgery, City of Hope National Medical Center, Duarte, California
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Lundgren L, Muszynska C, Ros A, Persson G, Gimm O, Andersson B, Sandström P. Management of incidental gallbladder cancer in a national cohort. Br J Surg 2019; 106:1216-1227. [DOI: 10.1002/bjs.11205] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 02/19/2019] [Accepted: 03/14/2019] [Indexed: 12/13/2022]
Abstract
Abstract
Background
Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade.
Methods
Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007–2011 and 2012–2016) to evaluate changes over time.
Results
In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030).
Conclusion
Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.
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Affiliation(s)
- L Lundgren
- Department of Surgery, County Council of Östergötland and Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - C Muszynska
- Department of Surgery, Skåne University Hospital and Department of Clinical Sciences, Lund University, Lund, Sweden
| | - A Ros
- Jönköping Academy for Improvement of Health and Welfare, Jönköping University, Jönköping, Sweden
| | - G Persson
- Department of Surgery, Ryhov Hospital, Jönköping, Sweden
| | - O Gimm
- Department of Surgery, County Council of Östergötland and Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - B Andersson
- Department of Surgery, Skåne University Hospital and Department of Clinical Sciences, Lund University, Lund, Sweden
| | - P Sandström
- Department of Surgery, County Council of Östergötland and Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
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Cherkassky L, Jarnagin W. Selecting treatment sequence for patients with incidental gallbladder cancer: a neoadjuvant approach versus upfront surgery. Updates Surg 2019; 71:217-225. [PMID: 31254234 DOI: 10.1007/s13304-019-00670-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 06/22/2019] [Indexed: 02/07/2023]
Abstract
At MSKCC, over 50% of the patients presenting with gallbladder cancer have been diagnosed incidentally following elective cholecystectomy for presumed benign disease. While traditional management of incidental gallbladder cancer (IGBC) dictates re-resection with the ultimate goal of achieving cure, surgical decision-making must take into account that this malignancy is characterized by poor tumor biology with frequent distant recurrence. Since early and frequent distant recurrence is the most common cause of surgical failure, the surgical oncologist's goal should be to selectively re-resect only those patients most likely to benefit from an operation. The astute surgeon recognizes the high-risk patients who likely have micrometastatic disease at the time of diagnosis and alters the treatment sequence, delivering neoadjuvant chemotherapy. This strategy acts as a selection tool, as those progressing at distant sites during therapy are spared the morbidity and mortality of surgery and furthermore has the potential to treat micrometastatic disease. However, a chemotherapy first approach must be applied selectively since a poor response risks local progression to unresectability and a decrease in functional status that comes from the toxicities of dual agent chemotherapy that can impair surgical candidacy. To balance these risks and benefits, two other criteria for a neoadjuvant approach must be met: i) reliable identification of those patients who are at high risk of distant recurrence and who are, therefore, most likely to benefit from a systemic therapy first approach and ii) availability of effective chemotherapy options. In this review, we will outline the data and judgement we use to select a treatment sequence at our institution.
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Affiliation(s)
- Leonid Cherkassky
- Clinical Fellow in Complex General Surgical Oncology, Department of Surgical Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - William Jarnagin
- Leslie Blumgart Chair in Surgery, Department of Surgical Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
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Vega EA, Sanhueza M, Viñuela E. Minimally Invasive Surgery for Gallbladder Cancer. Surg Oncol Clin N Am 2019; 28:243-253. [DOI: 10.1016/j.soc.2018.11.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Hickman L, Contreras C. Gallbladder Cancer: Diagnosis, Surgical Management, and Adjuvant Therapies. Surg Clin North Am 2019; 99:337-355. [PMID: 30846038 DOI: 10.1016/j.suc.2018.12.008] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gallbladder cancer (GBC) is an often lethal disease, but surgical resection is potentially curative. Symptoms may be misdiagnosed as biliary colic; over half of new diagnoses are made after laparoscopic cholecystectomy for presumed benign disease. Gallbladder polyps >1 cm should prompt additional imaging and cholecystectomy. For GBC diagnosed after cholecystectomy, tumors T1b and greater necessitate radical cholecystectomy. Radical cholecystectomy includes staging laparoscopy, hepatic resection, and locoregional lymph node clearance to achieve R0 resection. Patients with locally advanced disease (T3 or T4), hepatic-sided T2 tumors, node positivity, or R1 resection may benefit from adjuvant chemotherapy. Chemotherapy increases survival in unresectable disease.
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Affiliation(s)
- Laura Hickman
- Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Carlo Contreras
- Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
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Vega EA, Vinuela E, Sanhueza M, Mege R, Caracci M, Diaz C, Diaz A, Okuno M, Joechle K, Goumard C, Chun YS, Tzeng CWD, Lee JE, Vauthey JN, Conrad C. Positive cystic duct margin at index cholecystectomy in incidental gallbladder cancer is an important negative prognosticator. Eur J Surg Oncol 2019; 45:1061-1068. [PMID: 30704808 DOI: 10.1016/j.ejso.2019.01.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 01/10/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Prognostic factors following index-cholecystectomy in patients with incidental gallbladder cancer (IGBC) are poorly understood. The aim of this study was to assess the value of the initial cystic duct margin status as a prognosticator factor and to aid in clinical decision making to move forward with curative intent oncologic extended resection (OER). METHODS This retrospective study included patients with IGBC who underwent subsequent OER with curative intent at 2 centers (USA and Chile) between 1999 and 2016., Patients with and without evidence of residual cancer (RC) at OER were included. Pathologic features were examined, and predictors of overall survival (OS) were analyzed. RESULTS The study included 179 patients. Thirty-three patients (17%) had a positive cystic duct margin at the index cholecystectomy. Forty-two patients (23%) underwent resection of the common bile duct. OS was significantly worse in the patients with a positive cystic duct margin at index cholecystectomy (OS rates at 5 years, 34% vs 57%; p = 0.032). Following multivariate analysis, only a positive cystic duct margin at index cholecystectomy was predictive of worse OS in patients with no evidence of residual cancer (RC) at OER (hazard ratio, 1.7 95%CI 1.04-2.78; p = 0.034). CONCLUSIONS A positive cystic duct margin at index-cholecystectomy is a strong independent predictor of worse OS even if no further cancer is found at OER. In patients with positive cystic duct margin and no RC at OER common bile duct resection leads to improved outcomes.
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Affiliation(s)
- Eduardo A Vega
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Digestive Surgery, Hepato-Pancreato-Biliary Surgery Unit, Surgery Service, Sotero del Rio Hospital, Santiago, Chile
| | - Eduardo Vinuela
- Department of Digestive Surgery, Hepato-Pancreato-Biliary Surgery Unit, Surgery Service, Sotero del Rio Hospital, Santiago, Chile; Department of Digestive Surgery, Faculty of Medicine, Catholic University of Chile, Santiago, Chile
| | - Marcel Sanhueza
- Department of Digestive Surgery, Hepato-Pancreato-Biliary Surgery Unit, Surgery Service, Sotero del Rio Hospital, Santiago, Chile; Department of Digestive Surgery, Faculty of Medicine, Catholic University of Chile, Santiago, Chile
| | - Rosemarie Mege
- Department of Digestive Surgery, Hepato-Pancreato-Biliary Surgery Unit, Surgery Service, Sotero del Rio Hospital, Santiago, Chile; Department of Digestive Surgery, Faculty of Medicine, Catholic University of Chile, Santiago, Chile
| | - Mario Caracci
- Department of Digestive Surgery, Hepato-Pancreato-Biliary Surgery Unit, Surgery Service, Sotero del Rio Hospital, Santiago, Chile; Department of Digestive Surgery, Faculty of Medicine, Catholic University of Chile, Santiago, Chile
| | - Cristian Diaz
- Department of Digestive Surgery, Hepato-Pancreato-Biliary Surgery Unit, Surgery Service, Sotero del Rio Hospital, Santiago, Chile; Department of Digestive Surgery, Faculty of Medicine, Catholic University of Chile, Santiago, Chile
| | - Alfonso Diaz
- Department of Digestive Surgery, Hepato-Pancreato-Biliary Surgery Unit, Surgery Service, Sotero del Rio Hospital, Santiago, Chile; Department of Digestive Surgery, Faculty of Medicine, Catholic University of Chile, Santiago, Chile
| | - Masayuki Okuno
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Katharina Joechle
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Claire Goumard
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Fujii Y, Nanashima A, Hiyoshi M, Imamura N, Yano K, Hamada T. Significance of bile duct resection for advanced gallbladder cancer without biliary infiltration. Am J Surg 2018; 216:1122-1126. [DOI: 10.1016/j.amjsurg.2018.07.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 07/06/2018] [Accepted: 07/17/2018] [Indexed: 02/06/2023]
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Incidental Gallbladder Cancer: How Residual Disease Affects Outcome in Two Referral HPB Centers from South America. World J Surg 2018; 43:214-220. [DOI: 10.1007/s00268-018-4762-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Mochizuki T, Abe T, Amano H, Hanada K, Hattori M, Kobayashi T, Nakahara M, Ohdan H, Noriyuki T. Efficacy of the Gallbladder Cancer Predictive Risk Score Based on Pathological Findings: A Propensity Score-Matched Analysis. Ann Surg Oncol 2018; 25:1699-1708. [DOI: 10.1245/s10434-018-6444-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Indexed: 08/30/2023]
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Lopez-Aguiar AG, Ethun CG, McInnis MR, Pawlik TM, Poultsides G, Tran T, Idrees K, Isom CA, Fields RC, Krasnick BA, Weber SM, Salem A, Martin RCG, Scoggins CR, Shen P, Mogal HD, Schmidt C, Beal EW, Hatzaras I, Shenoy R, Cardona K, Maithel SK. Association of perioperative transfusion with survival and recurrence after resection of gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium. J Surg Oncol 2018; 117:1638-1647. [PMID: 29761515 PMCID: PMC10182890 DOI: 10.1002/jso.25086] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 04/02/2018] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND OBJECTIVES Perioperative blood transfusion is associated with poor outcomes in several malignancies. Its effect in gallbladder cancer (GBC) is unknown. METHODS All patients with GBC who underwent curative-intent resection at 10-institutions from 2000 to 2015 were included. The effect of blood transfusion on overall survival (OS) and recurrence-free (RFS) was evaluated. RESULTS Of 262 patients with curative-intent resection for GBC, 61 patients (23%) received blood transfusions. Radical cholecystectomy was the most common procedure (80%), but major hepatectomy was more frequent in the transfusion versus no-transfusion group (13% vs 4%; P = 0.02). The transfusion group was less likely to have incidentally discovered disease (57% vs 74%) and receive adjuvant therapy (29% vs 48%), but more likely to have preoperative jaundice (23% vs 11%), T3/T4 tumors (60% vs 39%), LVI (71% vs 40%), PNI (71% vs 48%), and major complications (39% vs 12%) (all P < 0.05). Transfusion was associated with lower median OS compared to no-transfusion (20 vs 32 mos; P < 0.001), which persisted on multivariable (MV) analysis (HR:1.9; 95%CI 1.1-3.5; P = 0.035), controlling for comorbidities, serum albumin, INR, preoperative jaundice, major hepatectomy, incidental discovery, margin status, T-Stage, LN status, and major complications. Median RFS of transfused patients was 13mo compared to 49mo for non-transfused patients (P = 0.1). Transfusion, however, was an independent predictor of decreased RFS on MV analysis (HR:2.3; 95%CI 1.1-5.1; P = 0.035). CONCLUSIONS Perioperative blood transfusion is associated with decreased OS and RFS after resection for GCC, accounting for other adverse factors. Transfusions should thus be administered with well-defined protocols.
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Affiliation(s)
- Alexandra G. Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery; Winship Cancer Institute, Emory University; Atlanta Georgia
| | - Cecilia G. Ethun
- Division of Surgical Oncology, Department of Surgery; Winship Cancer Institute, Emory University; Atlanta Georgia
| | - Mia R. McInnis
- Division of Surgical Oncology, Department of Surgery; Winship Cancer Institute, Emory University; Atlanta Georgia
| | - Timothy M. Pawlik
- Division of Surgical Oncology, Department of Surgery; The Johns Hopkins Hospital; Baltimore Maryland
- Division of Surgical Oncology; The Ohio State University Comprehensive Cancer Center; Columbus Ohio
| | - George Poultsides
- Department of Surgery; Stanford University Medical Center; Stanford California
| | - Thuy Tran
- Department of Surgery; Stanford University Medical Center; Stanford California
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery; Vanderbilt University Medical Center; Nashville Tennessee
| | - Chelsea A. Isom
- Division of Surgical Oncology, Department of Surgery; Vanderbilt University Medical Center; Nashville Tennessee
| | - Ryan C. Fields
- Department of Surgery; Washington University School of Medicine; St Louis Missouri
| | - Bradley A. Krasnick
- Department of Surgery; Washington University School of Medicine; St Louis Missouri
| | - Sharon M. Weber
- Department of Surgery; University of Wisconsin School of Medicine and Public Health; Madison Wisconsin
| | - Ahmed Salem
- Department of Surgery; University of Wisconsin School of Medicine and Public Health; Madison Wisconsin
| | - Robert C. G. Martin
- Division of Surgical Oncology; Department of Surgery, University of Louisville; Louisville Kentucky
| | - Charles R. Scoggins
- Division of Surgical Oncology; Department of Surgery, University of Louisville; Louisville Kentucky
| | - Perry Shen
- Department of Surgery; Wake Forest University; Winston-Salem North Carolina
| | - Harveshp D. Mogal
- Department of Surgery; Wake Forest University; Winston-Salem North Carolina
| | - Carl Schmidt
- Division of Surgical Oncology; The Ohio State University Comprehensive Cancer Center; Columbus Ohio
| | - Eliza W. Beal
- Division of Surgical Oncology; The Ohio State University Comprehensive Cancer Center; Columbus Ohio
| | | | - Rivfka Shenoy
- Department of Surgery; New York University; New York New York
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery; Winship Cancer Institute, Emory University; Atlanta Georgia
| | - Shishir K. Maithel
- Division of Surgical Oncology, Department of Surgery; Winship Cancer Institute, Emory University; Atlanta Georgia
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Abstract
PURPOSE OF REVIEW We will review the current standard of care management for metastatic gallbladder cancer (GBC), recommendations for resection of incidentally or non-incidentally diagnosed GBC, and developments in preoperative risk stratification and adjuvant chemotherapy. RECENT FINDINGS Gemcitabine-cisplatin is the standard of care therapy for advanced-stage disease. Patients with incidentally diagnosed GBC should undergo re-resection for T1b, T2, or T3 disease. The presence of residual disease is associated with decreased survival. Diagnostic laparoscopy should be used in select patients to avoid unnecessary laparotomy. Major hepatectomy and common bile duct excision should only be performed in select cases. Current standard of care for adjuvant therapy includes 6 months of oral capecitabine. Gallbladder cancer continues to carry high mortality rates due to its aggressive course and early spread. Recent developments in preoperative risk stratification, surgical resection, and chemotherapy have greatly shaped management of this malignancy in the current era.
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Affiliation(s)
- Mohammad Yahya Zaidi
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE Building C, 2nd Floor, Atlanta, GA, 30322, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE Building C, 2nd Floor, Atlanta, GA, 30322, USA.
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Creasy JM, Goldman DA, Gonen M, Dudeja V, Askan G, Basturk O, Balachandran VP, Allen PJ, DeMatteo RP, D’Angelica MI, Jarnagin WR, Kingham TP. Predicting Residual Disease in Incidental Gallbladder Cancer: Risk Stratification for Modified Treatment Strategies. J Gastrointest Surg 2017; 21:1254-1261. [PMID: 28484891 PMCID: PMC5521173 DOI: 10.1007/s11605-017-3436-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 04/26/2017] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Re-operation is advised for patients with T1b or greater incidental gallbladder cancer (GBCA). The presence of residual disease (RD) impacts resectability, chemotherapy, and survival. This study created a preoperative model to predict RD at re-operation. METHODS Patients with re-operation for incidental GBCA from 1992-2015 were included. The relationship between pathology data from initial cholecystectomy and RD at re-operation was assessed with logistic regression and classification and regression tree (CART) analysis. RESULTS Two hundred fifty-four patients were included and 188 underwent definitive re-resection (74.0%). Distant RD was identified in 69 (27.2%) patients and locoregional only RD in 82 (32.3%). On multivariate analysis, T3 (OR 22.7, 95% CI 5.5-94.4) and poorly differentiated tumors (OR 4.3, 95% CI 1.4-13.3) were associated with RD (p < 0.001-0.012). AUC of multivariate model was 0.78 (95% CI 0.72-0.83). CART analysis split patients into groups based on percentage with RD: 87% RD with T3, 67% RD with T1b/T2 and poorly differentiated, and 35% RD with T1b/T2 and well/moderate differentiated tumors. CONCLUSION Based on T stage and grade from cholecystectomy, this study developed a model for predicting RD at re-operation in incidental GBCA. This model delineates patient groups with variable percentages of RD and could be used to stratify high-risk patients for prospective trials.
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Affiliation(s)
- John M. Creasy
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Debra A. Goldman
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gonen
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vikas Dudeja
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Gokce Askan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P. Balachandran
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter J. Allen
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ronald P. DeMatteo
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael I. D’Angelica
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R. Jarnagin
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T. Peter Kingham
- Department of Surgery, Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Kim SH, Jung D, Ahn JH, Kim KS. Differentiation between gallbladder cancer with acute cholecystitis: Considerations for surgeons during emergency cholecystectomy, a cohort study. Int J Surg 2017; 45:1-7. [PMID: 28716660 DOI: 10.1016/j.ijsu.2017.07.046] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 07/11/2017] [Accepted: 07/12/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE Gallbladder cancer (GBCA) is an uncommon malignancy with vague and non-specific symptoms. GBCA is sometimes diagnosed after emergency cholecystectomy for acute cholecystitis. We investigated the differential diagnosis between GBCA with acute cholecystitis. MATERIALS AND METHODS Thirteen patients were diagnosed with GBCA after emergency cholecystectomy carried out for acute cholecystitis. A radiologist who was blinded to the final diagnoses retrospectively reviewed the computed tomography (CT) scans of the patients with GBCA and 25 patients with acute cholecystitis. We retrospectively reviewed the medical records of these patients and compared the clinical characteristics and CT findings between patients with GBCA and those with acute cholecystitis. We also investigated the prognostic factors in patients with GBCA who underwent emergency cholecystectomy. RESULTS Gallbladder (GB) stones were found more often in patients with acute cholecystitis (n = 17, 68%) than in patients with GBCA (n = 7, 53.8%) (p = 0.486). Patients with GBCA showed typical GB masses or focal enhanced wall thickening when compared to diffuse wall thickening in patients with acute cholecystitis. Some GBCA patients showed irregular mural thickening and GB enhancement. Differentiating carcinoma from acute cholecystitis might sometimes not possible, but the latter group of patients had significantly lower C-reactive protein (CRP) levels (p = 0.033) and less regional fat stranding (p = 0.047). Survival was significantly affected by aggressive tumor characteristics (lymphatic invasion [p = 0.025], depth of tumor invasion [p = 0.004]) or R0 resection (p = 0.013) rather than bile spillage (p = 0.112). CONCLUSIONS Surgeons deciding on emergency cholecystectomy for elderly patients with acute cholecystitis must suspect GBCA in patients with a low CRP level, irregular mural thickening or enhancement of GB without regional fat stranding.
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Affiliation(s)
- Sung Hoon Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju, South Korea
| | - Dawn Jung
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju, South Korea
| | - Jhii-Hyun Ahn
- Department of Radiology, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju, South Korea.
| | - Kyung Sik Kim
- Department of Surgery, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
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Ethun CG, Postlewait LM, Le N, Pawlik TM, Buettner S, Poultsides G, Tran T, Idrees K, Isom CA, Fields RC, Jin LX, Weber SM, Salem A, Martin RCG, Scoggins C, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, Kooby DA, Maithel SK. Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium. JAMA Surg 2017; 152:143-149. [PMID: 27784058 DOI: 10.1001/jamasurg.2016.3642] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Importance The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known. Objective To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival. Design, Setting, and Participants This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included. Exposures Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks. Main Outcomes and Measures Primary outcome was overall survival. Results Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis. Conclusions and Relevance The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy.
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Affiliation(s)
- Cecilia G Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Lauren M Postlewait
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Nina Le
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland3Deputy Editor, JAMA Surgery
| | - Stefan Buettner
- Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland
| | - George Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, California
| | - Thuy Tran
- Department of Surgery, Stanford University Medical Center, Stanford, California
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Chelsea A Isom
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Linda X Jin
- Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Sharon M Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison
| | - Ahmed Salem
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Charles Scoggins
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Perry Shen
- Department of Surgery, Wake Forest University, Winston-Salem, North Carolina
| | - Harveshp D Mogal
- Department of Surgery, Wake Forest University, Winston-Salem, North Carolina
| | - Carl Schmidt
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus
| | - Eliza Beal
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus
| | | | - Rivfka Shenoy
- Department of Surgery, New York University, New York
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
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50
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Ethun CG, Postlewait LM, Le N, Pawlik TM, Buettner S, Poultsides G, Tran T, Idrees K, Isom CA, Fields RC, Jin LX, Weber SM, Salem A, Martin RCG, Scoggins C, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, Merchant N, Cardona K, Maithel SK. A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium. Ann Surg Oncol 2017; 24:1343-1350. [PMID: 27812827 PMCID: PMC6054592 DOI: 10.1245/s10434-016-5637-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes. METHODS All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS). RESULTS Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3-4, intermediate: 5-7, high: 8-10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS. CONCLUSIONS By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.
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Affiliation(s)
- Cecilia G. Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Lauren M. Postlewait
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Nina Le
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Timothy M. Pawlik
- Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD
| | - Stefan Buettner
- Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD
| | - George Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Thuy Tran
- Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Chelsea A. Isom
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
| | - Ryan C. Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Linda X. Jin
- Department of Surgery, Washington University School of Medicine, St Louis, MO
| | - Sharon M. Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Ahmed Salem
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Robert C. G. Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY
| | - Charles Scoggins
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY
| | - Perry Shen
- Department of Surgery, Wake Forest University, Winston-Salem, NC
| | | | - Carl Schmidt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | - Eliza Beal
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | | | - Rivfka Shenoy
- Department of Surgery, New York University, New York, NY
| | - Nipun Merchant
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN,Division of Surgical Oncology, Department of Surgery, University of Miami, Miami, FL
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Shishir K. Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA
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