The Prognostic Role Of Regional Lymph Node Metastasis And Lymphadenectomy Of Gallbladder Cancer

Background Lymph node metastasis is the major route for gallbladder cancer(GBC)metastasis and predicts dismal prognosis.Lymph node staging helps predict patients' survival and guides systematic treatment.Lymphadenectomy is an essential part of curative-intent surgery for GBC.However,the definition of regional lymph nodes of GBC,the benefit of lymphadenectomy in T1 b GBC patients,and novel staging systems are still controversial.Aims 1.Discover whether No.13 a lymph nodes(postsuperior pancreatic lymph nodes)belongs to the regional lymph nodes of GBC;2.Discover the prognostic role of regional lymphadenectomy in T1 b GBC patients;3.Establish the workflow of developing nodal staging score system,and apply the system in GBC.Methods & Results The Chinese Research Group of Gallbladder Cancer(CRGGC)is a national multicentre cancer registry cohort study.Launched by Shanghai Key Laboratory of Biliary Tract Disease Research,the cohort has built collaboration with 28 hospitals in 16 provinces in China.1.From CRGGC database,we retrieved primary GBC patients from 2008 to 2016 who underwent radical surgery and discovered lymph node metastasis.In the 257 patients,206(35.1%)had hepatoduodenal ligament lymph nodes metastasis(classified as Na),and 51 had No.13 a nodes metastasis(Nb).For further comparison,we identified 555 GBC patients underwent palliative surgery with distant metastasis(M1).Kaplan-Meier curve showed that the prognosis for Na patients were significantly better than Nb patients(3-year overall survival: 31.5% vs.19.7%,P= 0.03),while Nb patients had comparable prognosis with M1 patients(3-year overall survival: 19.7% vs.15.8%,P = 0.10).After adjusted for age,sex,hospital volume,T stage,resection margin,microvascular invasion,and perineural invasion,the Cox regression showed Nb an independent risk factor for prognosis(HR = 1.56,95% CI =1.03-2.36).With propensity score matching,we balanced age,sex,hospital volume,number of positive nodes,number of nodes examined,T stage,and resection margin.The survival difference persisted(P = 0.03).2.From the CRGGC we retrieved T1 b GBC patients from 2008 to 2016 who underwent surgical treatment.A total of 141 patients were involved,56(39.7%)underwent cholecystectomy(Ch),85(60.3%)underwent cholecystectomy combined with regional lymphadenectomy(Ch+RL).From KaplanMeier curve we observed significant better prognosis in patients underwent Ch+RL(5-year survival: 76.3% vs.56.8%,P = 0.04).We performed Cox regression to adjust for age,sex,hospital volume,and resection margion,Ch+RL was a protective factor for prognosis(HR = 0.51,95% CI = 0.26-0.99).3.After establishing the workflow of developing the nodal staging score system,we applied the system in 910 GBC patients in CRGGC,in which 442(48.6%)were node-positive.The ? and ? of the model were1.32(95% CI,1.11-1.53)and 1.29(95% CI,0.99-1.59).To achieve 90% confidence in a p N0 patient,6 lymph nodes would need to be examined.Nodal staging score showed limited efficacy in discrimination of patient prognosis(P=0.32).Conclusions 1.No.13 a lymph node metastasis predicts worse prognosis than hepatoduodenal ligament lymph node metastasis in GBC,but comparable prognosis with distant metastasis.No 13 a lymph nodes shouldn't be classified as the regional lymph nodes of GBC.2.Combined regional lymphadenectomy promotes the survival of T1 b GBC patients,and should be recommended in routine practice.3.To achieve 90%confidence in a p N0 patient,6 lymph nodes would need to be examined for gallbladder cancer.