Hilar cholangiocarcinoma still has a poor prognosis and a relatively low 5-year survival rate despite improvement of the resection rate and curative resection rate. Optimal surgical strategies should be chosen according to the balance between operation safety and curative resection. Extended resection and dissection of lymph nodes do not always ensure successful treatment. Preoperative evaluation of liver function should be carefully carried out. For patients with severe jaundice or those who undergo extensive hepatic resection, preoperative biliary drainage, portal vein embolization and a precise hepatec-tomy technique should be carried out to improve the safety of the operation. Assessment of resectability should be carried out to avoid unnecessary laparotomy, and endoscopic drainage is preferable in dealing with unresectable tumors. The aim of palliative treatment is to relieve biliary obstruction, prolong life and improve the quality of life. Biological characteristics of hilar cholangiocarcinoma need to be taken into account and multi-modality therapy is required to improve treatment. The survival rate of patients with hilar cholangiocarcinoma may be improved by comprehensive treatment. Populations with high risks should be monitored and screened to find patients at early stages of the disease.

Cholangiocarcinoma is rare. It is highly malignant and early diagnosis is difficult. Various risk facts have been linked to the carcinogenesis and development of cholangiocarcinoma. Chronic inflammation and cholestasis are the two common pathways in the malignant transformation of cholangial cells. We reviewed the molecular biological researches of cholangiocarcinoma from two aspects: its risk factors and related pathomechanism.

Objective: To compare the efficiency between the transhepatic hilar approach and conventional approach for the surgical treatment of Bismuth type Ⅲ and Ⅳ hilar cholangiocarcinoma. Methods: There were 42 consecutive patients with hilar cholangiocarcinoma of Bismuth type Ⅲ and Ⅳ who underwent surgical treatment at Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from January 2008 to December 2013.The transhepatic hilar approach was used in 19 patients and conventional approach was performed in 23 patients.There were no differences in clinical parameters between the two groups(all P>0.05). The t-test was used to analyze the measurement data, and the χ² test was used to analyze the count data.Kaplan-Meier analysis was used to analyze the survival period.Multivariate COX regression analysis was used to analyze the prognosis factors. Results: Among the 19 patients who underwent transhepatic hilar approach, 3 patients changed the operative planning after reevaluated by exposing the hepatic hilus.The intraoperative blood was 300(250-400)ml in the transhepatic hilar approach group, which was significantly less than the conventional approach group, 800(450-1 300)ml(t=4.276, P=0.00 1), meanwhile, the R0 resection rate was significantly higher in the transhepatic hilar approach group than in the conventional approach group(89.4% vs. 52.2; χ²=6.773, P=0.009) and the 3-year and 5-year cumulative survival rate was better in the transhepatic hilar approach group than in the conventional approach group(63.2% vs. 47.8%, 26.3% vs. 0; χ²=66.363, 127.185, P=0.000). On univariate analysis, transhepatic hilar approach, intraoperative blood loss, intraoperative blood transfusion, R0 resection and lymph node metastasis were significant risk factors for patient survival(all P<0.05). On multivariate analysis, use of transhepatic hilar approach, intraoperative blood loss, R0 resection and lymph node metastasis were significant independent risk factors for patient survival(all P<0.05). Conclusion The transhepatic hilar approach is the preferred technique for surgical treatment for hilar cholangiocarcinoma because it can improve accuracy of surgical planning, safety of operation, R0 resection rate and survival rate compared with the conventional approach.

SUMOylation is recently found to function as a targeting signal for the degradation of substrates through the ubiquitin-proteasome system. RNF4 is the most studied human SUMO-targeted ubiquitin E3 ligase. However, the relationship between SUMO proteases, SENPs, and RNF4 remains obscure. There are limited examples of the SENP regulation of SUMO2/3-targeted proteolysis mediated by RNF4. The present study investigated the role of SENP3 in the global protein turnover related to SUMO2/3-targeted ubiquitination and focused in particular on the SENP3 regulation of the stability of Sp1. Our data demonstrated that SENP3 impaired the global ubiquitination profile and promoted the accumulation of many proteins. Sp1, a cancer-associated transcription factor, was among these proteins. SENP3 increased the level of Sp1 protein via antagonizing the SUMO2/3-targeted ubiquitination and the consequent proteasome-dependent degradation that was mediated by RNF4. De-conjugation of SUMO2/3 by SENP3 attenuated the interaction of Sp1 with RNF4. In gastric cancer cell lines and specimens derived from patients and nude mice, the level of Sp1 was generally increased in parallel to the level of SENP3. These results provided a new explanation for the enrichment of the Sp1 protein in various cancers, and revealed a regulation of SUMO2/3 conjugated proteins whose levels may be tightly controlled by SENP3 and RNF4.
Animals ; Cysteine Endopeptidases ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Prognosis ; Protein Processing, Post-Translational ; Proteolysis ; RNA, Messenger ; genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Small Ubiquitin-Related Modifier Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Sp1 Transcription Factor ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Sumoylation ; Tumor Cells, Cultured ; Ubiquitination ; Ubiquitins ; antagonists & inhibitors ; genetics ; metabolism ; Xenograft Model Antitumor Assays