Abstract: Objective:To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).
Methods:The retrospective case-control study was conducted. The clinicopathological data of 305 patients with primary GBC who underwent radical R0 resection in the First Affiliated Hospital of Xi′an Jiaotong University from 2013 to 2017 were collected, including 108 males and 197 females, aged from 30 to 88 years, with a median age of 62 years. According to the different tumor staging, patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy. Observation indicators: (1) results of imaging and laboratory examinations; (2) treatment situations: ① surgical situations, ② postoperative adjuvant treatment; (3) results of postoperative pathological examination; (4) follow-up; (5) prognostic factors analysis. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5, 2018, and death was used as the end point. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were described as M (range). Count data were represented as percentage. The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method. The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.
Results:(1) Results of imaging and laboratory examinations: results of imaging examination showed that diagnostic rates of ultrasound, CT and MRI examination were respectively 84.06%(174/207), 85.71%(168/196) and 63.11%(65/103). Results of laboratory examination showed that the positive rates of CA19-9, CA125 and carcinoembryonic antigen (CEA) were respectively 55.34%(145/262), 48.06%(124/258) and 46.15%(126/273). (2) Treatment situations: ① surgical situations: 305 patients underwent radical R0 resection for primary GBC, including 145 undergoing liver wedge resection + D₂ lymph node dissection, 61 undergoing liver wedge resection + D₁ lymph node dissection, 55 undergoing liver ⅣB and Ⅴ segmentectomy + D₂ lymph node dissection, 11 undergoing liver ⅣB and Ⅴ segmentectomy + D₁ lymph node dissection, 9 undergoing right hepatectomy + D₂ lymph node dissection, 5 undergoing liver wedge resection + D₂ lymph node dissection+partial colectomy, 4 undergoing pancreatico-duodenectomy, 3 undergoing simple cholecystectomy in Tis stage, 3 undergoing right hepatectomy + D₁ lymph node dissection, 2 undergoing liver ⅣB and Ⅴ segmentectomy + D₂ lymph node dissection + partial colectomy, 1 undergoing liver ⅣB and Ⅴ segmentectomy + resection and reconstruction of portal vein + D₂ lymph node dissection, 1 undergoing liver ⅣB and Ⅴ segmentectomy + D₂ lymph node dissection + partial resection of the stomach or duodenum, 1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein, 1 undergoing right hepatectomy + pancreaticoduodenectomy, 1 undergoing right hepatic lobectomy + partial gastrectomy + D₂ lymph node dissection, 1 undergoing right hepatic lobectomy + D₁ lymph node dissection and 1 undergoing right hepatic trilobectomy + D₂ lymph node dissection. Of 94 patients with unsuspected GBC, 78 who were diagnosed in the other hospitals received salvage surgery in the authors′ center. Twenty-one patients had postoperative surgery-related complications, including 11 with bile leakage, 8 with pulmonary infection and 2 with abdominal bleeding. Two patients died in the perioperative period. ② Postoperative adjuvant treatment: 26 patients underwent postoperative adjuvant chemotherapy. Chemotherapy regimen: gemcitabine + oxaliplatin were used in 12 patients, gemcitabine + tegafur in 7 patients, gemcitabine + cisplatin in 6 patients, oxaliplatin + tegafur in 1 patient. (3) Results of postoperative pathological examination. The postoperative pathological type of 305 patients: 257, 23, 6, 5, 4, 3, 3, 2, 1 and 1 patients were respectively confirmed as pure adenocarcinoma, adenocarcinoma combined with squamous cell carcinoma, adenocarcinoma combined with neuroendocrine carcinoma, mucinous adenocarcinoma, neuroendocrine carcinoma, adenocarcinoma combined with mucinous carcinoma, squamous cell carcinoma, sarcomatoid carcinoma, adenocarcinoma combined with sarcomatoid carcinoma, adenocarcinoma combined with signet-ring cell carcinoma. Degree of tumor differentiation: high-differentiated, moderate-differentiated and low-differentiated tumors were detected in 37, 130 and 121 patients, respectively, 17 with unknown differentiated degree. Of 305 patients, 16 and 32 patients had respectively vascular invasion and nerve invasion. The number of lymph node dissected of 305 patients was 8±5, with positive lymph node of 0 (range, 0-9), including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis). TNM staging of 305 patients: stage 0, Ⅰ, Ⅱ, ⅢA, ⅢB, ⅣA and ⅣB were detected in 7, 18, 13, 137, 57, 11 and 62 patients, respectively. (4) Follow-up: 245 of 305 patients were followed up for 18.0 months (range, 6.0-70.0 months). The survival time, 1- and 3-year survival rates were respectively 29.5 months (range, 0.5-69.9 months), 71.6% and 45.8%. One hundred and twenty-two patients died during the follow-up. (5) Prognostic factors analysis: the results of univariate analysis showed that preoperative level of bilirubin, pathological type, degree of tumor differentiation, liver invasion, vascular invasion, nerve invasion, T staging, N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (χ²=10.26, 3.96, 45.89, 34.64, 12.75, 27.05, 35.09, 39.44, 4.40, P<0.05). The results of multivariate analysis showed that low-differentiated tumor, liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC ［odds ratio (OR)=1.90, 1.71, 1.46, 95% confidence interval (CI): 1.34-2.70, 1.15-2.52, 1.17-1.82, P<0.05］, and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35，95% CI: 0.15-0.82, P<0.05).
Conclusions:For patients with primary GBC undergoing radical resection, D₂ lymph node dissection should be performed routinely. The low-differentiated tumor, liver invasion and N2 staging are independent risk factors affecting prognosis of patients, and postoperative chemotherapy is a protective factor.