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Role of common bile duct resection in T2 and T3 gallbladder cancer patients

Backgrounds/Aims Routine bile duct resection as part of the typical oncological resection for patients with advanced gallbladder cancer remains controversial with regard to, ultimately, curative value. The aim of this study was to compare oncological outcomes for patients undergoing surgery for gallbladder cancer with or without bile duct resection. Methods We recruited, for the purpose of this study, all patients who underwent surgical resection for T2 and T3 gallbladder cancer at Severance hospital, Seoul, Korea, during the period January 2000 and December of 2011. The patient data was reviewed retrospectively. Results The patients (n=149) recruited to participate in the study were divided into two groups according to their bile duct resection status: The bile duct resection group (BDR group, n=54); and, the bile duct non-resection group (BDNR group, n=95). Significant difference was found in lymph node retrieval between BDR and BDNR groups (15 vs. 5, respectively with p<0.001). There was no significant difference between the two groups with regard to the five year survival rate (43% in BDR group vs. 57% in BDNR group, p=0.339). Following multivariate analysis, lymph node metastasis, advanced T-stage, and total retrieved lymph nodes <6 were independent prognostic factors for poor survival in patients with T2 and T3 gallbladder cancer. Conclusions The findings revealed by the current study suggest that the role of bile duct resection might be limited to improved staging, and offers no advantage in long-term survival. However, in view of the foregoing and given the minimal increase in morbidity associated with BDR, it should be actively considered as a treatment option for patients who present with findings suspicious for invasion around hepatoduodenal ligament.


INTRODUCTION
Gallbladder adenocarcinoma, historically, has been considered an incurable malignancy with a dismal prognosis. 1,2 Complete surgical resection seems to represent the only potentially effective curative treatment for resectable gallbladder cancer. Regional lymph node dissection is indispensable and invaluable for the accurate staging of gallbladder cancer. 3,4 The extent of resection in gallbladder cancer is usually determined by the pre-and intraoperative assessment of the nature and extent of the tumor invasion.
According to the National Comprehensive Cancer Network (NCCN) guidelines, 5 simple cholecystectomy is considered appropriate to treat T1a gallbladder cancer. In patients with more advanced localized disease, en bloc hepatic resection and lymphadenectomy are recommended. 5 Whether routine bile duct resection is medically indicated and "should be performed", in many cases, remains a judgment call on the part of the surgeon because the surgical indication may remain unclear, even to direct inspection.
There is a lack of objective evidence to support an increased long-term survival rate after routine resection, while increased morbidity has been reported. [6][7][8] Several recent studies have focused on identifying prognostic factors conductive to long-term survival in those patients afflicted with advanced gallbladder cancer. Although several varia-bles such as lymphovascular invasion, the operative method and total lymph node count of ＜6 have been proposed no definitive consensus has ever been achieved. 3,9,10 Current guidelines 5 suggest that a selective approach to bile duct resection be implemented and utilized, with the aim of ensuring a negative margin. Despite the relative paucity of rarified, substantial medical evidence, others recommend routine bile duct resection in an effort to increase chances of disease-free survival. 9 The aim of this study was to more precisely assess and identify the role of bile duct resection for T2 and T3 gallbladder cancer, vis-à-vis the specific issues of oncological and long-term survival benefit.

RESULTS
Of the 271 patients who underwent surgery for gallbladder cancer within the study period, 211 (78%) patients underwent R0 resection. Of these 211 patients, 149 (55%) had T2 or T3 disease confirmed pathologically and were included for further analysis (Fig. 1).
Given the clinicopathologic heterogeneity (Table 1) among the two groups, a subgroup analysis was performed for those who underwent liver resection (n=89) with or without BDR (   According to the survival analysis for bile duct resection, there was no evidence of survival benefit of bile duct resection in each of cancer stage (Fig. 4). Further survival analysis for liver resected patients has also shown no significant role of bile duct resection in both overall survival and disease-free survival (Fig. 5).
In univariate analysis for disease-free survival, bile duct resection (p=0.048) was one indicator of poor survival outcome. However, in multivariate analyses, lymph node  (Table 3). In multivariate analysis for overall survival, lymph node metastasis, T3 stage, and the total number of retrieved lymph nodes ＜6 were the independent prognostic factors of poor survival outcome (Table 4).

DISCUSSION
The optimal extent of resection in advanced gallbladder cancer patients remains a debated issue. Chiefly, the clinical significance of concomitant bile duct resection remains controversial. Kokudo