This was a large sample study and confirmed that jaundice was a predictor of advanced gallbladder cancer. The three-year survival rate and median survival time were 13.0% and 18.0 months for the 54 jaundiced patients, respectively, and 40.9% and 40.8 months for the 213 non-jaundiced ones, respectively (p < 0.001). The jaundiced patients had significantly lower survival rates than the non-jaundiced patients. In this study, the impact of preoperative jaundice on the prognosis of GBC patients after R0 resection was thoroughly evaluated. So far, no other report is known to be published. This study provided a basis and data support for clinical prognostic evaluation of GBC patients after R0 resection.
In previous reports, preoperative jaundice was an important predictor of advanced gallbladder carcinoma, and the median survival in the presence of jaundice was poorer that of non-jaundiced patients (11 vs. 36 months; p < 0.0001) . In the first report on the prognostic impact of jaundice in gallbladder carcinoma , the rate of R0 resection was only 5%, and the prognosis was very poor. However, the result of the low R0 resection rate was calculated by taking all 82 GBC patients as base number, rather than the patients who went through surgical resection. Previous studies have found that the rate of surgical resection was higher in non-jaundice patients (64% vs 45%), although there was no significant difference of R0 resection between the jaundice group and the non-jaundice group . In contrast, Agarwal et al found no significant difference in surgical resection rates between the jaundice group and the non-jaundice group (27% vs 36%, P>0.05) . At present, with the advancement of imaging technology, especially the extensive application of laparoscopic exploration, the rate of surgical resection (R0 resection) was expected to be significantly improved, especially in GBC patients with preoperative jaundice [16,17].
However, jaundice can cause a series of pathophysiological changes, including hyperbilirubinemia, endotoxemia, bleeding tendency, and immune dysfunction . Effective and rapid biliary drainage before surgery was very important . The routine biliary drainage includes PTBD (percutaneous transhepatic biliary drainage) and endoscopic biliary drainage (EBD). Although both methods were effective for biliary decompression, there were significant differences in pathophysiology between internal drainage and external drainage. There was still some controversy about which drainage method should be preferentially used [19,20]. According to our previous research, compared with factors such as intestinal bacterial translocation and pancreatitis associated with EBD, PTBD was simpler and less expensive. However, there were many problems such as nutritional status and decreased immune function after bile wastage in PTBD. To our experience, we recommend that PTBD combined with oral bile before surgery was an effective method. Furthermore, this treatment did not increase the incidence of postoperative abdominal infection . In the present study, the decrease in the bilirubin level after preoperative biliary drainage was statistically relevant (p < 0.001). However, this benefit was not associated with a longer survival time (p = 0.151).
Although the surgical prognosis of advanced gallbladder cancer was not satisfactory, it was the only expected treatment to be cured [6,8]. Advanced gallbladder carcinoma was usually accompanied with adjacent organ invasion, such as the liver, transverse colon, duodenum, extrahepatic bile duct, hepatic artery, and portal vein. Enlarged surgical resection was required for radical resection. The morbidity and mortality of this operation were still high. It was reported that the postoperative complication rate was as high as 53% and the mortality was 4%-27% in extended hepatectomy . With the advent of preoperative biliary drainage and portal vein embolization (PVE), extended hemihepatectomy, mainly extended right hepatectomy, was safer and more feasible. Although extended hemihepatectomy was expected to remove tumor lesions radically, the postoperative mortality was higher and survival benefits remained controversial . In addition, the local radical resection with more liver parenchyma reservation was expected to achieve similar prognosis . In short, the advantages and disadvantages of extended surgery should be carefully weighed. This study has found that the jaundiced group had a worse prognosis than the non-jaundiced group, suggesting that preoperative jaundice was identified as advanced stage. However, there was no specific correlation between preoperative jaundice and long-term survival. The mechanism between preoperative jaundice and prognosis remained unclear. In conclusion, advanced GBC with extrahepatic bile duct invasion and/or jaundice was a candidate for resection when R0 resection was achievable. However, the radical resection of advanced gallbladder carcinoma was still challenging with high postoperative morbidity and poor prognosis. In our opinion, the scope of surgical resection should not be blindly expanded. Patient benefit was the most important evaluation index.
In previous reports, hilar invasion was identified as an important prognostic factor [10,23]. The clinical manifestation of hilar invasion was jaundice, which was an independent factor for poor prognosis [10,23]. In our previous study, the jaundiced patients had lower survival rates than the non-jaundiced patients (p < 0.001). The lymph node metastasis and gallbladder neck tumors were the only significant risk factors of poor prognosis in GBC patients who underwent surgical resection with curative intent (R0 and R1 resection). However, in this study, preoperative jaundice and gallbladder neck tumors were not the independent factors associated with poor prognosis after R0 resection, which suggested that GBC patients with preoperative jaundice and gallbladder neck tumors should be actively given surgery, if R0 resection was expected. This was different from previous research results. This again emphasized the clinical importance of radical resection.
In addition, another important predictor of poor prognosis in gallbladder cancer was lymph node metastasis [23,24,25]. In a report, the authors insisted that radical resection can be only acquired in GBC patients with regional lymph node metastasis . In contrast, reports from the Japanese Society of Biliary Surgery, have found that GBC patients with extensive lymph node metastasis were also benefit from lymphadenectomy [10,25]. The univariate analysis of this study has found that lymph node metastasis was closely associated with survival (P < 0.001). At the same time, the para-aortic lymph nodes are considered to be distant metastasis . Kondo et al  insisted that surgery can not improve the prognosis of gallbladder cancer patients with lymph node metastasis around the abdominal aorta. The multivariate analysis of this study has found that regional lymph node involvement was not an independent prognostic factor for long-term survival, and only pT stage was a key prognostic factor. With the continuous advancement of imaging technologies such as CT, MRI, and PET-CT , the pT stage can be more accurately evaluated before surgery. Therefore, once more advanced pT stage (pT4) was suggested by preoperative imaging, the choice of surgical indications and multidisciplinary treatment should be more cautious. The pT stage was the most important long-term prognostic factor of gallbladder cancer, which should be paid attention to clinical assessment.
This was a study from a famous hepatobiliary surgery center in China. The univariate and multivariate analysis of GBC patients showed that preoperative jaundice did not affect long-term survival after R0 resection. The independent prognostic factor was precisely the pT stage in TNM staging. This study confirmed the absolute authority of TNM staging in the evaluation of tumor prognosis.
The limitation of this study is the limited amount of cases. Further multi-center studies are needed to confirm this conclusion. In addition, there are limitations in retrospective research itself. However, this study suggested that there was no absolute relation between preoperative jaundice and poor long-term prognosis. The pT staging was a key long-term prognostic factor for gallbladder carcinoma after R0 resection.
In conclusion, unilateral and multivariate analyses of 267 GBC patients showed that the depth of tumor invasion (pT stage), lymphatic metastasis, and hepatic invasion were independent prognostic factors. The univariate and multivariate analysis of 54 GBC patients with preoperative jaundice showed that only pT staging was an independent factor for prognosis. In the 54 GBC patients with preoperative jaundice, intraoperative blood transfusion and pT stage were significantly different between long-term survival (survival for more than 3 years) and those who died within 3 years. Preoperative jaundice and gallbladder neck tumors were not the independent factors affecting the long-term prognosis of gallbladder carcinoma after R0 resection. The pT staging was the only long-term prognostic factor for both GBC patients with and without preoperative jaundice. Once advanced pT staging was suspected preoperatively, we should be prudent in deciding whether surgery is indicated so as to avoid unnecessary surgery. This study confirmed the absolute authority of TNM staging in the evaluation of long-term prognosis.