Protective effect of recombinant human IL-1Ra on CCl_4-induced acute liver injury in mice

AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl 4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl 4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl 4 treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1β, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1β, IL-1Ra and IL-6 expression during CCl 4-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl 4-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION: rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.

Surgical procedure determination based ontumor-node-metastasis staging of gallbladder cancer

AIM: To investigate the impact of surgical procedures on prognosis of gallbladder cancer patients classified with the latest tumor-node-metastasis(TNM) staging system.METHODS: A retrospective study was performed by reviewing 152 patients with primary gallbladder carcinoma treated at Peking Union Medical College Hospital from January 2003 to June 2013. Postsurgical follow-up was performed by telephone and outpatient visits. Clinical records were reviewed and patients were grouped based on the new edition of TNM staging system(AJCC, seventh edition, 2010). Prognoses were analyzed and compared based on surgical operations including simple cholecystectomy, radical cholecystectomy(or extended radical cholecystectomy), and palliative surgery. Simple cholecystectomy is, by definition, resection of the gallbladder fossa. Radical cholecystectomy involves a wedge resection of the gallbladder fossa with 2 cm nonneoplastic liver tissue; resection of a suprapancreatic segment of the extrahepatic bile duct and extended portal lymph node dissection may also be considered based on the patient's circumstance. Palliative surgery refers to cholecystectomy with biliary drainage. Data analysis was performed with SPSS 19.0 software. KaplanMeier survival analysis and Logrank test were used for survival rate comparison. P < 0.05 was consideredstatistically significant.RESULTS: Patients were grouped based on the new 7th edition of TNM staging system, including 8 cases of stage 0, 10 cases of stage Ⅰ, 25 cases of stage Ⅱ, 21 cases of stage ⅢA, 21 cases of stage ⅢB, 24 cases of stage ⅣA, 43 cases of stage ⅣB. Simple cholecystectomy was performed on 28 cases, radical cholecystectomy or expanded gallbladder radical resection on 57 cases, and palliative resection on 28 cases. Thirty-nine cases were not operated. Patients with stages 0 and Ⅰ disease demonstrated no statistical significant difference in survival time between those receiving radical cholecystectomy and simple cholecystectomy(P = 0.826). The prognosis of stage Ⅱ patients with radical cholecystectomy was better than that of simple cholecystectomy. For stage Ⅲ patients, radical cholecystectomy was significantly superior to other surgical options(P < 0.05). For stage ⅣA patients, radical cholecystectomy was not better than palliative resection and non-surgical treatment. For stage ⅣB, patients who underwent palliative resection significantly outlived those with non-surgical treatment(P < 0.01)CONCLUSION: For stages 0 and Ⅰ patients, simple cholecystectomy is the optimal surgical procedure, while radical cholecystectomy should be actively operated for stages Ⅱ and Ⅲ patients.