[Expression and significance of PD-1 and PD-L1 in the specimens of epithelial ovarian cancer].

Objective: To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. Methods: The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ，included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. Results: （1） PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC （type Ⅱ） than those of low-grade （type Ⅰ） and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (P<0.05). Conclusions: The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.

Establishment of a simple living donor liver transplantation dog model using a two-step nonvenous bypass hepatectomy.

AIM: Dogs are an ideal model for studying living donor liver transplantation (LDLT). However, due to their poor tolerance to congestion and acidosis during portal vein blockage, current LDLT dog models with long operation times have high mortality. To address the issue, we designed a novel simplified operation with two-step nonvenous bypass (NVB) hepatectomy. METHODS: Eighty dogs were evenly randomized to the living liver donor (LLD) or the recipient (LLR) groups. A standard lobectomy of I, II, and III lobes was performed in the LLD group. In the LLR group, first only I, II, and III lobes were resected using NVB; the residual lobes were resected off just after donor lobes were implanted. RESULTS: For the LLD group, the operation time was 172.67 ± 20.98 minutes, amount of blood loss was 71.39 ± 13.59 mL, and 2-week survival rate was 85.00%. For the LLR group, the operation time was 251.61 ± 22.87 minutes, amount of blood loss was 220.00 ± 96.40 mL, amount of blood transfusion was 163.89 ± 44.74 mL, and 48-hour survival rate was 77.14%. In the LLR group, the mean arterial and central venous pressures decreased after organ implantion, but gradually recovered to normal levels after surgery. The liver function biochemical parameters recovered to preoperational levels after 14 days in the LLD group; in the LLR group, they gradually increased during 48 hours after operation. CONCLUSION: The present method with two-step NVB hepatectomy can be used efficiently and safely for establishing LDLT dog model.