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Objective:To explore the mechanism of biliary fibrosis after end to end anastomosis of bile duct.Methods:12 Neijiang miniature pigs (6-8 months old, weight 30-40 kg) were divided into experimental group ( n=6) and control group ( n=6). The model of end to end anastomosis after transection of the common bile duct was established in experimental group. Control group was a sham operation group, and only T tube was placed. After 9 months, Masson staining, fluorescence quantitative PCR and immunohistochemistry were used to analyze the expressing changes of pro-fibrotic factor transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and epithelial-mesenchymal transition (EMT) markers, including cytokeratin-19 (CK19), E-cadherin (E-Cad) and fibroblast specific protein-1 (S100A4), α-smooth muscle actin (α-SMA) and collagen components Collagen I (COL-1), collagen III (COL-3) and fibronectin (FN) in the anastomotic bile duct tissues. Results:Masson staining showed that the submucosal collagen fibers increased significantly in the experimental group. Compared with the control group, the mRNA expression of TGF-β1 [(3.482±0.313) vs. (1.000±0.102), t=18.43, P<0.001], CTGF [(2.160±0.287) vs. (1.000±0.103), t=9.32, P<0.001] were increased, the difference was statistically significant. Compared with control group, the mRNA and protein expression of CK19 and E-Cad were decreased in the experimental group, while the mRNA and protein expression of S100A4 and α-SMA were increased in the experimental group (all P<0.01). Conclusion:It was feasible in the short term to perform an end-to-end anastomosis after transection of the common bile duct, but there was an obvious fibrosis in the anastomotic bile duct tissue at later time.
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Objective:To study the impact of additional resection of an intraoperative proximal bile duct positive margin on the survival rate of patients with hilar cholangiocarcinoma (HCCA).Methods:The clinical data of 214 patients with HCCA treated at the First Affiliated Hospital of Zhengzhou University from January 2000 to January 2017 were analyzed. There were 126 males and 88 females, aged (62.3±17.1) years. These patients were divided into three groups according to the pathological status of bile duct margins and whether the proximal bile duct was further resected. Group A consisted of patients with negative margins without additional resection (161 cases). Group B consisted of patients with negative margins after additional resection (21 cases). Group C consisted of patients with R 1 resections (32 cases). The Kaplan-Meier method was used for survival analysis and log-rank test was used for inter-group comparison. Univariate and multivariate Cox regression analysis were used to analyze prognostic factors. Results:The 3-year and 5-year survival rates of patients in groups A, B, and C were 37.1%, 28.6%, 0 and 18.5%, 10.7%, 0, respectively. The cumulative survival rates of patients in group A and group B were significantly higher than that in group C (all P<0.05). Multivariate Cox regression analysis showed that R 1 proximal bile duct margin ( HR=3.728, 95% CI: 2.531-4.936), margin width >5 mm ( HR=0.534, 95% CI: 0.224-0.857), and T 3-4 staging ( HR=5.655, 95% CI: 3.174-8.203) were independent influencing factors for overall survival of patients with HCCA after attempted radical surgery. Conclusion:The survival rate of patients with HCCA with a positive proximal bile duct margin was significantly improved by further resecting the bile duct to obtain a negative margin. The R 1 proximal bile duct margin was an independent risk factor for prognosis in patients with HCCA after attempted radical resection.
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Objective To investigate the influence factors of tumor diameter and related prognostic factors on the prognosis of hilar cholangiocarcinoma.Methods The retrospective case-control study was conducted.The clinicopathological data of 240 patients who underwent resection of hilar cholangiocarcinoma in the West China Hospital of Sichuan University between January 1995 and January 2013 were collected,including 104 patients with tumor diameter ≤ 2 cm (8 with tumor diameter ≤ 1 cm and 96 with 1 cm ＜ tumor diameter ≤ 2 cm),85 with 2 cm ＜ tumor diameter ≤ 3 cm and 51 with tumor diameter ＞ 3 cm (40 with 3 cm ＜ tumor diameter ≤ 4 cm and 11 with tumor diameter ＞ 4 cm).Observation indicators:(1) surgical situations;(2) follow-up situations;(3) risk factors analysis affecting the prognosis of patients;(4) correlation analysis between related prognostic indicators and tumor diameter.The follow-up using outpatient examination and telephone interview was performed to detect the survival up to August 2016.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.The prognostic factors and correlation between related prognostic indicators and tumor diameter were respectively analyzed using the COX proportional hazard model and logistic regression model.Results (1) Surgical situations:240 patients underwent successful resection of hilar cholangiocarcinoma and lymph node dissection.Of 73 patients with postoperative complications,1 died of intraperitoneal infection induced to systemic infection and multiple organ failure,1 diel of renal failure,and other patients were cured by symptomatic treatment.(2) Follow-up situations:240 patients were followed up for 12.0-98.0 months,with a median time of 47.4 months.The overall median survival time,1-,3-and 5-year overall survival rates were respectively 30.6 months,81％,47％ and 29％.The median survival time and 5-year survival rate were 46.5 months,34％ in patients with tumor diameter ≤ 2 cm and 30.5 months,30％ in patients with 2 cm ＜ tumor diameter ≤ 3 cm and 13.8 months,20％ in patients with tumor diameter ＞ 3 cm,respectively,with a statistically significant difference (x2 =17.83,P＜0.05).Results of further analysis showed the median survival time and 5-year survival rate were 31.3 months,38％ in patients with tumor diameter ≤ 1 cm and 46.5 months,34％ in patients with 1 cm ＜ tumor diameter ≤ 2 cm,respectively,with no statistically significant difference (x2=1.16,P＞O.05).The median survival time and 1-year survival rate were 14.7 months,62％ in patients with 3 cm ＜ tumor diameter ≤ 4 cm and 13.0 months,55％ in patients with tumor diameter ＞ 4 cm,respectively,with no statistically significant difference (x2 =2.34,P＞O.05).(3) Risk factors analysis affecting the prognosis of patients:univariate analysis showed that tumor diameter,surgical margin,lymph node metastasis,vascular invasion and histological differentiation were the related factors affecting patients' prognosis [hazard ratio (HR)=1.456,8.714,1.737,2.246,1.665;95％ confidence interval (C I):1.212-1.748,5.558-13.663,1.311-2.301,1.494-3.378,1.375-2.016,P ＜ 0.05].The multivariate analysis showed that 2 cm ＜ tumor diameter ≤ 3 cm,tumor diameter ＞ 3 cm,R1 resection,lymph node metastasis and low-differentiated tumor were the independent risk factors affecting poor prognosis of patients (HR =1.559,1.868,7.410,1.521,2.274,95％ CI:1.125-2.160,1.265-2.759,4.497-12.212,1.136-2.037,1.525-3.390,P＜0.05).(4) Correlation analysis between related prognostic indicators and tumor diameter:the results of univariate analysis showed that there was a correlation between lymph node metastasis,vascular invasion,histological differentiation and T staging of American Joint Committee on Cancer (AJCC) and tumor diameter of 2 cm as a cut-off point (x2 =6.063,4.950,8.770,9.069,P＜0.05).There was a correlation between surgical margin,lymph node metastasis,vascular invasion and histological differentiation and tumor diameter of 3 cm as a cut-off point (x2=10.251,9.919,5.485,15.632,P＜0.05).The results of multivariate analysis showed that lymph node metastasis and T staging of AJCC were independent related factors affecting tumor diameter of 2 cm as a cut-off point[odds ratio (OR) =1.882,2.104,95 ％CI:1.075-3.293,1.220-3.631,P＜0.05];surgical margin and lymph node metastasis were independent related factors affecting tumor diameter of 3 cm as a cut-off point (OR=3.187,2.211,95 ％CI:1.377-7.379,1.133-4.314,P＜0.05).Conclusions The 2 cm ＜ tumor diameter ≤ 3 cm,tumor diameter ＞ 3 cm,R1 resection,lymph node metastasis and low-differentiated tumor are the independent risk factors affecting the prognosis of patients with hilar cholangiocarcinoma.Three cm (T staging in De Oliveira staging system) as the second cut-off point is feasible,meanwhile,2 cm cut-off point may be become another potential tumor dividing point described in De Oliveira staging system.