Early Hepatic Artery Thrombosis After Pediatric Living Donor Liver Transplantation.

AIM: Hepatic artery thrombosis is one of the major complications affecting patient and graft survival after liver transplantation. In this study, we analyzed the factors affecting the development of early hepatic artery thrombosis (eHAT) and its outcomes in pediatric liver transplantation. METHODS: A total of 175 pediatric patients underwent living donor liver transplantation between January 2013 and November 2018. Factors affecting eHAT and its outcomes were examined. RESULTS: Nine patients (5.1%) developed eHAT. In multivariate analysis, intraoperative hepatic artery revision and Roux-en-Y hepaticojejunostomy biliary reconstruction type were statistically significant (all, P < .05). Thrombectomy and reanastomosis was performed in 5 patients. Two of them were successful. In total, 3 retransplantations were performed and all of those patients are still alive. CONCLUSION: The factors affecting eHAT are still a matter of debate. Intraoperative hepatic artery anastomosis revision and Roux-en-Y hepaticojejunostomy reconstruction were independent risk factors for development of eHAT. In the present study, the confidence interval of the variables is high, therefore exact determination of the risk factors may not be possible. Early detection and thrombectomy and reanastomosis may be the first treatment of choice to rescue the patient and graft. When it fails, retransplantation must be an alternative. The results of the present study state that at least once a day the vascular anastomosis must be examined by Doppler ultrasonography in the post-transplant first week. It must be repeated when liver enzymes increase. The patients under high risk for eHAT may be followed up closer.

Significance and outcome of living-donor liver transplantation in acute mushroom intoxication.

INTRODUCTION: Mushroom intoxication (MT) can lead to acute liver injury which may result in Mushroom intoxication-related liver failure (M-ALF) requiring liver transplantation (LT). In the present study, we want to share the experience of our institute regarding living-donor LT (LDLT) due to mushroom poisoning. AIM: The aim of this study is to identify the predictors of poor prognosis in patients with ALF secondary to mushroom intoxication requiring LDLT. MATERIALS AND METHODS: All patients with MT between 2008 and 2016 were evaluated. Demographics, symptoms, interval between symptoms and admission to our institute, laboratory data, model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) scores, clinical course, and outcomes of supportive therapy and LT were evaluated. There were two groups in the study: Group A = responsive to supportive therapy (n = 9) versus Group B = unresponsive to supportive therapy (n = 9). RESULTS: During the study, a total of 18 patients were admitted with M-ALF. Twelve (66.7%) of them were female, and the mean age was 39.9 ± 18.2 years. All of the nine patients in Group A fully recovered with supportive therapy. In Group B, one patient died during waiting period for LT and 8 patients received LDLT LDLT. Three of the eight patients who were transplanted died in the postoperative early period within postoperative 5 days. The patients in Group B had significantly higher MELD/PELD scores and encephalopathy rate than in Group A (P < 0.05). International normalized ratio (INR), bilirubin, ammonium levels, and platelet count were significantly different between groups (P < 0.05). The patients in Group B had significantly longer interval before admission to our institute (P < 0.05). CONCLUSION: The presence of encephalopathy, higher MELD/PELD, INR, bilirubin, ammonium levels, and lower platelet count was related to poor prognosis in MT. LDLT provides a good therapeutic option in patients with M-ALF. The time is a crucial factor in successful treatment of MT. Early admission to a tertiary referral center with expertise in LT results in a better prognosis and increased survival following M-ALF.

Candesartan mediates microcirculation in acute necrotizing pancreatitis.

AIM: In the present study we aimed to determine the effect of an AT-II antagonist candesartan on pancreatic microcirculation in an experimental model of acute necrotizing pancreatitis. MATERIALS AND METHODS: There were five study groups with 10 animals in each. Pancreatitis was induced by intravenous infusion of cerulein and coadministration of glycodeoxycholate into biliopancreatic canal. Candesartan is given at 6th and 18th hour to the 24th and 48th hour groups, respectively. At 24th and 48th hours; following anaesthesia laparotomy was performed and laser Doppler flowmetry was performed in the pancreatic tissue of the animals. Following scarification blood samples were obtained for amylase, myeloperoxidase, IL-6 and tumour necrosis factor alpha. Tissue samples from the pancreas were obtained for histopathological analysis, endothelial cell apoptosis (TUNEL assay) and matrix metalloproteinase-9 immunohistochemistry. RESULTS: Pancreatic microcirculation was higher in the candesartan treated groups (p < 0.05). Myeloperoxidase, IL-6 and tumour necrosis factor alpha was found to be lower in the candesartan treated groups (p < 0.05). The pancreatic edema and inflammation were found to be reduced in the candesartan treated groups (p < 0.05). Endothelial apoptosis was found to be reduced by cadesartan treatment but it did not reach statistical significance (p > 0.05). Tissue matrix metalloproteinase -9 levels were found to be reduced with candesartan treatment (p < 0.05). CONCLUSION: Treatment with candesartan in the early phases of acute necrotizing pancreatitis effective on microcirculation of pancreatic tissue (Tab. 3, Fig. 6, Ref. 28).

Antitumor efficacy of oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes.

Although several studies have reported that locally administering oncolytic viruses effectively targets malignancies, the efficacy of systemically administered oncolytic viruses is restricted. Recently, however, it was reported that systemic administration of oncolytic vesicular stomatitis virus adsorbed onto antigen-specific lymphocytes was effective against malignancies. We hypothesized that intravenously administering such virus might have significant potential in treatment of the malignant tumors. We adsorbed oncolytic herpes simplex virus-1 mutant R3616 onto lymphocytes harvested from mice with acquired antitumor immunity. We administered adsorbed R3616 to peritoneally disseminated tumors and analyzed the efficacy of this treatment. Mice administered adsorbed R3616 survived significantly longer than mice administered R3616 adsorbed onto non-specific lymphocytes, or mice administered either virus or tumor antigen-specific lymphocytes alone. In this context, herpes oncolytic virus is a promising treatment not only for primary lesions, but also for multiple metastasizing lesions. This treatment strategy may become one of the most effective methods for systemic virus delivery.

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer.

Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P=0.016). Angiogenesis was significantly higher in treatment group (P=0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P=0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.

A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer.

In 2005, we initiated a clinical trial that examined the efficacy of the oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to have a high mortality rate, despite multimodal treatments for patients, and new therapeutic methods are greatly needed. The current mainstream methods for cancer treatment include biological therapeutics such as trastuzumab (Herceptin) for breast cancer or erlotinib (Tarceva) for non-small cell lung cancer. Oncolytic virus therapy is a new and promising treatment strategy for cancer. Oncolytic viruses are novel biological therapeutics for advanced cancer that appear to have a wide spectrum of anticancer activity with minimal human toxicity. To examine the efficacy of oncolytic virus therapy for pancreatic cancer, we initiated pilot studies by injecting six patients with non-resectable pancreatic cancer with three doses of HF10. All patients were monitored for 30 days for local and systemic adverse effects and were not administered any other therapeutics during this period. There were no adverse side-effects, and we observed some therapeutic potential based on tumor marker levels, survival, pathological findings and diagnostic radiography. The tumors were classified as stable disease in three patients, partial response in one patient and progressive disease in two patients.

Is neopterin level a predictive and differential biomarker in patients with thyroid disorders?

Neopterin production provides information about the extent of cellular immune activation. Measurement of neopterin levels may also provide predictive and prognostic information in patients with malignant thyroid diseases. In the present study, neopterin levels were investigated in patients with thyroid disorders (no.=68). Twenty-four patients had papillary thyroid cancers and the rest of them benign thyroid disorders. Results were compared with a healthy control group (no.=30). It was observed that there was a significant difference in neopterin levels between the control group and the thyroid disorders group (p<0.05). The mean neopterin levels in malignant and benign patients were also significantly different (p<0.05). Monitoring of urinary neopterin profile may be used in early diagnosis of papillary thyroid cancer. Neopterin seems to be a differential biomarker for malignant and benign thyroid disorders.