Is Hepatic Resection Needed in the Patients with Peritoneal Side T2 Gallbladder Cancer?

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Is Hepatic Resection Needed in the Patients with Peritoneal Side T2 Gallbladder Cancer? Lee H, Park JY, Youn S, Kwon W, Heo JS, Choi SH, Choi DW Department of Surgery, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Introduction General approach to the treatment of gallbladder cancer AJCC staging (7 th ) TNM Treatment I II IIIA IIIB T1a-bN0M0 T2N0M0 T3N0M0 T1-3N1M0 Cholecystectomy with or without lymph node dissection Radical cholecystectomy Cholecystectomy Lymph node dissection Hepatic resection IVA T4N0-1M0 Palliative (Locally advanced) IVB T1-4N2M0 T1-4N0-2M1 Palliative (Distant metastasis)

Introduction Anatomical differences according to the location of gallbladder cancer Peritoneal side Hepatic side No Adjacent organ Liver Yes Serosa No Cystic artery Hepatic hilum Blood supply Venous drainage Cystic artery Arterial communication between gallbladder and liver Hepatic hilum Liver (gallbladder bed) Hepatic hilum Lymphatic drainage Hepatic hilum

Purpose Clinical question: Is Hepatic Resection Needed in the Patients with Peritoneal Side T2 Gallbladder Cancer? The aim of this study is to analyze the surgical outcomes of T2 gall bladder cancer according to the tumor location and extent of surgery.

Patients and Methods Study period January 2000 - December 2011 (retrospective study) Inclusion criteria Patients with T2 gallbladder cancer Underwent curative intent surgery (no gross residual tumor) Exclusion criteria Palliative surgery Distant LN metastasis Double primary cancer

Patients and Methods Divided by the location of tumor Peritoneal side Fundus or body Hepatic side Fundus, body or neck Computed tomographic imaging Operative finding Fundus Body Neck Surgery Hepatic resection group (cholecystectomy, lymph node dissection) No hepatic resection group (cholecystectomy, lymph node dissection) Oncologic outcomes Recurrence pattern Survival

Results Patients selection Tis: 18 T1: 67 T3: 86 T4: 26 Simple cholecystectomy 5 Major hepatectomy 11 Gallbladder cancer N = 429 T2 N = 179 Palliative: 39 Double primary: 14 Distant metastasis 5 Mortality 1 T2 GB cancer N = 157 Hepatic resection N = 122 No hepatic resection N = 35 Peritoneal side N = 33 Hepatic side N = 124 24 98 9 26 Median age: 62 years (range, 37 to 83), Median follow up: 40 months (range, 5 to 170)

Results Demographics (I) Category Hepatic resection (N = 122) (%) No hepatic resection (N = 35) (%) P value * Tumor location Sex Peritoneal side 24 (20) 9 (26) 0.439 Hepatic side 98 (80) 26 (74) Male 49 (40) 12 (34) 0.529 Female 73 (60) 23 (66) Age (years) (median, range) 60 (37 81) 71 (44 83) < 0.001 Tumor size (cm) (median, range) 3.0 (0.4 12.0) 3.0 (1.0 10.0) 0.968 Preoperative CA 19-9 (U/dl) 14.5 (0.1 2650.0) 18.5 (1.0 28404.0) 0.342 N stage N0 83 (68) 28 (80) 0.170 N1 39 (32) 7 (20) Cell differentiation Papillary, well or moderately Poorly or undifferentiated 88 (72) 26 (74) 0.614 34 (28) 8 (23) * Chi-square test, Fisher s exact test or Mann Whitney U test

Results Demographics (II) Category Hepatic resection (N = 122) (%) No hepatic resection (N = 35) (%) P value * American Society of Anesthesiologists (ASA) score I 56 (46) 8 (23) 0.022 II 63 (52) 24 (69) III 3 (2) 3 (9) Gross type Polypoid, nodular or fungating Ulcerofungating or infiltrative 86 (70) 29 (83) 0.121 33 (27) 5 (14) Lymphovascular invasion Perineural invasion Chemotherapy Yes 24 (20) 4 (11) 0.264 No 95 (78) 30 (86) Yes 6 (5) 5 (14) 0.054 No 113 (93) 29 (83) Yes 36 (30) 8 (23) 0.440 No 86 (70) 27 (77) * Chi-square test, Fisher s exact test or Mann Whitney U test

Results Kaplan Meyer survival analysis Overall survival (OS) curves T2 GB cancer N = 157 Peritoneal side N = 33 A Hepatic side N = 124 Hepatic resection N = 122 No hepatic resection N = 35 24 98 B C 9 26 Median age: 62 years (range, 37 to 83), Median follow up: 40 months (range, 5 to 170)

Results Recurrence pattern Peritoneal side N = 33 Hepatic side N = 124 Hepatic resection N = 24 No hepatic resection N = 9 Hepatic resection N = 98 No hepatic resection N = 26 1 recurrence No recurrence 36 recurrence 13 recurrence

Results Recurrence pattern Peritoneal side N = 33 Hepatic side N = 124 Hepatic resection N = 24 No hepatic resection N = 9 Hepatic resection N = 98 No hepatic resection N = 26 1 recurrence No recurrence 36 recurrences 13 recurrences Local recurrence 5 Local recurrence 4 LN metastasis 1 Liver 14 LN metastasis 13 Peritoneal seeding 5 Liver 4 LN metastasis 6 Peritoneal seeding 2 Others * 5 * Lung metastasis: 3 patients, extrahepatic bile duct recurrence: 2 patients

Results Recurrence pattern Hepatic side N = 124 Hepatic resection N = 98 No hepatic resection N = 26 36 recurrences 13 recurrences Others 12% Local recurrence 12% Peritoneal seeding 13% Local recurrence 25% Peritoneal seeding 14% Intrahepatic LN metastasis 30% recurrence 32% LN metastasis 37% Intrahepati c recurrence 25% * Lung metastasis: 3 patients, extrahepatic bile duct recurrence: 2 patients

Limitations Not a randomized controlled trial Information bias Selection bias Small patients number

Conclusion Surgical strategy for gallbladder cancer Location of tumor: Important prognostic factor in T2 GB cancer T1 Cholecystectomy with or without lymph node dissection T2 Peritoneal side Hepatic side Cholecystectomy with lymph node dissection Radical cholecystectomy (including hepatic resection) T3 Radical cholecystectomy (including hepatic resection)