Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats

AIM:To investigate oxidative stress(OS)-mediated damage and the behavior of extracellular matrices in various rat models because shear stress with portal hypertension and cold ischemia/warm reperfusion injury trigger the liver regeneration cascade after surgery. These injuries also cause fatal liver damage.METHODS: Rats were divided into four groups according to the surgery performed: control; hepatectomy with 40% liver remnant(60% hepatectomy); orthotopic liver transplantation(OLT) with whole liver graft(100% OLT); and split OLT(SOLT) with 40% graft(40% SOLT). Survival was evaluated. Blood and liver samples were collected at 6 h after surgery. Biochemical and histopathological examinations were performed. OSinduced damage, 4-hydroxynonenal, ataxia-telangiectasia mutated kinase, histone H2AX, phosphatidylinositol 3-kinase(PI3K) and Akt were evaluated by western blotting. Behavior of extracellular matrices, matrix metalloproteinase(MMP)-9, MMP-2, tissue inhibitor of metalloproteinase(TIMP)-1 and TIMP-2 were also evaluated by western blotting and zymography. RESULTS: Although 100% OLT survived, 60% hepatectomy and 40% SOLT showed poor survival. Histopathological, immunohistological, biochemical and protein assays revealed that 60% hepatectomy, 100% OLT and 40% SOLT showed liver damage. PI3K and Akt were decreased in 60% hepatectomy and 40% SOLT. For protein expression, 40% SOLT showed differences in MMP-9, MMP-2 and TIMP-2. TIMP-1 showed differences in 60% hepatectomy and 40% SOLT. For protein activity, MMP-9 demonstrated significant differences in 60% hepatectomy, 100% OLT and 40% SOLT. CONCLUSION: Under conditions with an insufficient liver remnant, prevention of OS-induced damage via the Akt/PI3K pathway may be key to improve the postoperative course. MMP-9 may be also a therapeutic target after surgery.

Living-related liver transplantation in patients with variceal bleeding:outcome and prognostic factors

BACKGROUND:Liver transplantation currently represents the ultimate therapy for bleeding esophageal varices in patients with liver cirrhosis.It is the only therapy that cures both portal hypertension and the underlying liver disease.The outcome of liver transplantation is thought to be correlated with several factors.In this study,the clinical outcome of living-related liver transplantation(LRLT) was evaluated in patients with variceal bleeding,and the prognostic indicators of short-term survival in these patients were identified. METHODS:We reviewed retrospectively 121 patients with a history of variceal bleeding who had received LRLT from 1998 to 2006.The clinical outcomes were analyzed,and the risk factors for short-term survival were defined. RESULTS:The 3-month survival rate of patients with variceal bleeding was 83.4%,while that of non-bleeders was 87%.Sepsis was the commonest cause of death in both groups.Portal vein diameter and blood transfusion were the only independent prognostic factors for short-term survival among variceal bleeders. CONCLUSION:The outcome of LRLT in recipients with variceal bleeding is based on the improvement of portal hemodynamics,by minimizing intraoperative blood loss and subsequent blood transfusion.

Recent evolution of living donor liver transplantation at Kyoto University:How to achieve a one-year overall survival rate of 99%?

Previously,living donor liver transplantation was considered as a“high-risk,high-return”medical treatment due to the relatively high short-term mortality.It is our task to change“high-risk,high-return”into a“low-risk,high-return”situation.In this review article,the recent evolutions in living donor liver transplantation for both donors and recipients at Kyoto University such as portal vein pressure modulation,hybrid donor operation,and perioperative management considering sarcopenia,focusing on improvement of short-term outcomes are described.Under a paradigm of“marketing and innovation”,various innovations and efforts have been made over the last decade aiming at improving the short-term outcomes of both donors and recipients.By doing so,excellent short-term results after living donor liver transplantation have been achieved,along with a potentially epoch-making discoveries.

Simple and reproducible hepatectomy in the mouse using the clip technique

AIM: To investigate the reliability of massive hepatectomy models by using clip techniques. METHODS: We analyzed anatomical findings in 100 mice following massive hepatectomy induced by liver reduction > 70%. The impact of various factors in the different models was also analyzed, including learning curves, operative time, survival curves, and histopathological findings.RESULTS: According to anatomical results, models with 75%, 80%, and 90% hepatectomy produced massive hepatectomy. Learning curves and operative times were most optimal with the clip technique. Each hepatectomy performed using the clip technique produced a reasonable survival curve, and there were no differences in histopathological findings between the suture and clip techniques. CONCLUSION: Massive hepatectomy by the clip technique is simple and can provide reliable and relevant data.

Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment:A case report

BACKGROUND Lenvatinib has been shown to be noninferior to sorafenib regarding prognosis and recurrence rate in patients with unresectable hepatocellular carcinoma(HCC)who have not received prior systemic chemotherapy.In patients treated with lenvatinib,40%of cases achieved sufficient tumor reduction to make potential surgery possible.However,the outcomes of such surgery are unknown.We report a successful case of hepatic resection for recurrent HCC after lenvatinib treatment.CASE SUMMARY A 69-year-old man underwent right anterior sectionectomy for HCC in segment 8 of the liver.Ten months later,he was found to have an intrahepatic HCC recurrence that grew rapidly to 10 cm in diameter with sternal bone metastases.After confirming partial response to lenvatinib administration for 2 mo,a second hepatectomy was performed.Pathological examination showed that 80%of the tumor was necrotic.The patient did not develop any adverse effects under lenvatinib treatment.He was discharged at 25 d after surgery.Radiation therapy for bone metastases continued to be given under lenvatinib,and the patient has remained alive for 1 year after the second hepatectomy.CONCLUSION The prognosis of patients with recurrent HCC may be improved by liver resection combined with prior lenvatinib therapy.

Screening for hilar biliary invasion in ampullary cancer patients

BACKGROUND The treatment for ampullary cancer is pancreatoduodenectomy or local ampullectomy.However,effective methods for the preoperative investigation of hilar biliary invasion in ampullary cancer patients have not yet been identified.AIM To determine the necessity of and an appropriate method for investigating hilar biliary invasion of ampullary cancer.METHODS Among 43 ampullary cancer patients,34 underwent endoscopic treatment(n=9)or surgery(n=25).The use of imaging findings(thickening and enhancement of the bile duct wall on contrast-enhanced computed tomography,irregularity on endoscopic retrograde cholangiography,thickening of the entire bile duct wall on intraductal ultrasonography(IDUS),and partial thickening of the bile duct wall on IDUS)and biliary biopsy results for diagnosing hilar biliary invasion of ampullary cancer was compared.RESULTS Hilar invasion was not observed in every patient.Among the patients who did not undergo biliary stent insertion,the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results showed the highest accuracy(100%)for diagnosing hilar biliary invasion.However,each imaging method and biliary biopsy yielded some false-positive results.CONCLUSION Although some false-positive results were obtained with each method,the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results was useful for diagnosing hilar biliary invasion of ampullary cancer.However,hilar invasion of ampullary cancer is rare;therefore,the investigation of hilar biliary invasion of ampullary cancer might be unnecessary.

HER2-positive adenocarcinoma arising from heterotopic pancreas tissue in the duodenum:A case report

BACKGROUND Adenocarcinoma originating from heterotopic pancreas tissue is a rare disease.Furthermore,to our knowledge,no HER2-positive cases in the duodenum have been reported in the scientific literature nor has the efficacy of trastuzumab treatment for the disease been reported.CASE SUMMARY A 65-year-old woman whose clinical diagnosis was unresectable advanced duodenal cancer with HER2 overexpression responded well to trastuzumab chemotherapy.The main tumor in the duodenum reduced drastically.The patient underwent pancreaticoduodenectomy and lymph node dissection.A small number of cancer cells remained in the submucosal layer of the duodenum and pancreas head.After histological and immunohistochemical examination,the patient was diagnosed with duodenal adenocarcinoma originating from heterotopic pancreas tissue.CONCLUSION Trastuzumab treatment is effective in HER2-positive adenocarcinoma originating from heterotopic pancreas tissue in the duodenum.

Development and validation of an artificial intelligence model for predicting post-transplant hepatocellular cancer recurrence

Dear Editor,In recent years,criteria based on the combinationof morphology and biology have been proposed forimproving the selection of hepatocellular cancer(HCC)patients waiting for liver transplantation(LT)[1,2].Since all the proposed models showed suboptimalresults in predicting the risk of postLT recurrence,aprediction model constructed using artificial intelligence(Al)could be an attractive way to surpass this limit[3,4].Therefore,the Time_Radiological-response_Alpha-fetoproteIN_Artificial-Intelligence(TRAIN-AI)modelwas developed,combining morphology and biology tumorvariables.

Significance of preoperative sarcopenia to liver surgery

Sarcopenia,characterized by a decline in skeletal muscle mass and muscle strength or physical activity,is now accepted worldwide as a new geriatric syndrome.Recent studies have identified significant associations between sarcopenia and poor outcomes of various diseases including liver diseases(1-3).This article reviews the significance of preoperative sarcopenia to liver surgery,particularly liver transplantation(LT).