| BackgroundPart1The inflammation and immune response produced by HBV infection is an important cause of occurrence and development of HCC. Some studies have reported that IL-22had protective and pathological properties in liver diseases recently. As for liver tumors, some research have shown that IL-22played an important role in the process of hepatocarcinogenesis and metastasis, other studies have pointed out that the level of serum IL-22were negative associated with prognosis of HCC patients. However, there is no report about the changes of IL-22in patients with CHB progressing from AH to HCC. Thus, in this study we try to clear the importance of IL-22in occurrence and development of HCC, also clear the relationship between tissue IL-22levels and the prognosis of HCC. We further investigate the feasibility of IL-22as a therapeutic target for HCC.Part2For HCC conforming to Milan criteria, treatment is still controversial. Surgical resection (RES) is widely accepted as first-line treatment. Recently, microwave ablation (MWA) has gained great attention because of advances in microwave technology. However, there were no studies comparing MWA and RES. The aim of this study was to compare the efficacy and safety of MWA and RES in the treatment of HCC meeting Milan criteria.ObjectivePart11. The aim of the present study was to evaluate the importance of IL-22+T cells in liver tissue. IL-22in plasma in patients with CHB progressing from AH to HCC.2. We also explored the effect of IL-22on proliferation and apoptosis of hepatoma cells in vitro.Part2The present study was to compare the efficacy and safety of MWA and RES in the treatment of HCC conforming to the Milan criteria, with the aim of providing basis for clinical selection of proper treatments.MethodsPart11.136liver biopsies specimens from46patients with CHB,37with AH,53with HCC and56sets of patient-matched tumors and peritumoral surgical specimens from HCC patients were enrolled. The expressions of IL-22and CD8in liver tissue were measured by immunochemistry.2. IL-22in plasma of patients in each group was detected by ELISA.3. CCK-8and BrdU/DAPI assays were performed to determine the effect of IL-22on proliferation of SMMC-7721cells, Hoechst33342/PI immunofluorescence staining and Cell-IQ system were performed to detect the effect of IL-22on apoptosis of SMMC-7721cells.Part2224HCC patients were enrolled in the study,117patients were initially treated with MWA,107patients were initially treated with RES. We compared overall survival (OS) rates, disease-free survival (DFS) rates, overall recurrence rates and complications between the two groups. Patients were divided into three subgroups according to diameter and number of the tumor. We also explored the survival of patients in different subgroups.ResultsPart11. The density of liver infiltrated IL-22+T cells was increased in a stepwise manner from CHB to AH and HCC (CHB vs AH, P=0.002; AH vs HCC, P=0.010). In surgical specimens, the density of tumor infiltrated IL-22+T cells was increased in a stepwise manner from well differentiated HCC to middle differentiated HCC and poorly differentiated HCC (WD vs MD, P=0.007; MD vs PD, P=0.008). The density of tumor infiltrated IL-22+T cells was an independent prognostic factor for OS and DFS of HCC patients.2. The level of IL-22in plasma was increased in a stepwise manner from CHB to AH and HCC (CHB vs AH, P=0.024; AH vs HCC, P=0.026). IL-22in plasma correlated with histologic grade of HCC (P=0.033). The level of IL-22in plasma was an independent prognostic factor for OS and DFS of HCC patients.3.1-10ng/mL recombinant IL-22could promote proliferation of hepatoma cells, but IL-22did not inhibit apoptosis of them.Part2For HCC conforming to Milan criteria, there was no significant differences in OS rates between MWA group and RES group (P=0.513), the DFS rates was significantly higher in the RES group than in the MWA group (P=0.005). In subgroup analyses of patients with solitary HCC≤3cm, there were no significant differences in OS rates and DFS rates between the two groups (P=0.577and P=0.140). For patients with solitary HCC3to5cm, there was no significant differences in OS rates between the two groups (P=0.820), the DFS rates was significantly higher in the RES group than in the MWA group (P=0.014). For patients with multifocal HCCs<3cm, the OS rates and DFS rates between the two groups were similar (P=0.702and P=0.327).ConclusionsPart11. Our findings suggested that intrahepatic IL-22+T cells might promote the occurrence and progression of HCC, high intratumoral IL-22+T cells showed a significantly lower survival rate.2. IL-22in plasma may promote the occurrence and progression of HCC. high level of IL-22in plasma showed a significantly lower survival rate.3. Recombinant IL-22could promote proliferation of hepatoma cells but did not inhibit apoptosis of them.Part2MWA resulted in lower DFS rates and higher tumor recurrence than RES for HCC conforming to Milan criteria. However, the OS rates were comparable between the two therapies. For solitary HCC≤3cm and multiple (2-3) HCCs<3cm, MWA was as effective as RES. |