Persistent verbal and behavioral deficits after resection of the left supplementary motor area in epilepsy surgery

An 8-year-old boy underwent a resection for focal cortical dysplasia at the left supplementary motor area (SMA) for the treatment of intractable epilepsy. The manifestations of SMA syndrome, such as transient mutism and right hemiparesis, resolved within a few weeks. Verbal disfluency and impaired executive function, accompanied by impulsivity and distractibility, persisted for more than 12 months. The verbal and behavioral problems caused serious difficulties in the school life of the patient, until they became less evident at 18 months after surgery. Tractography performed 18 months after surgery revealed a defect in the subportion of fronto-parietal association fibers within the left superior longitudinal fascicles. Verbal influency can persist with unusually long duration after resection of SMA during childhood. Although not discernible on the routine neuroimaging, white matter damage beneath the SMA region could result in serious disabilities in executive function. These complications should be recognized for the prediction and assessment of deficits in children after surgical intervention involving this region.     

Verification of responses of Japanese medaka (Oryzias latipes) to anti‐androgens,vinclozolin and flutamide,in short‐term assays

Various testing methods for the detection of the endocrine disruptive activities of chemicals have been developed in freshwater fish species. However, a few relatively easier specific methods for detecting anti‐androgenic activities are available for fish. The aim of this study was to verify the papillary process in Japanese medaka (Oryzias latipes) as an indicator of the anti‐androgenic activity of chemicals. Japanese medaka were exposed to two types of anti‐androgenic compounds, vinclozolin and flutamide, using two short‐term assays; one was conformed to the existing short‐term reproduction assay using adult fish (adult test) and the other was a test based on the same methods but using juvenile fish at the beginning of exposure (juvenile test). Significant decreases in male papillary processes were observed in the juvenile test treated with the highest concentration of both antiandrogens (640 µg l^–1 vinclozolin and 1000 µg l^–1 flutamide); however, no significant effects were observed in the adult test. Consequently, our results indicate that papillary processes in Japanese medaka can be used as the end‐point for screening the anti‐androgenic activity of chemicals using juvenile fish for a specific period based on the existing short‐term reproduction assay. Copyright © 2013 John Wiley & Sons, Ltd.     

Sirolimus-eluting stents vs bare metal stents for coronary intervention in Japanese patients with renal failure on hemodialysis.

BACKGROUND: Accelerated atherosclerosis is a major risk for long-term survivors receiving hemodialysis (HD), with coronary events being the leading cause of mortality. METHODS AND RESULTS: A total of 88 consecutive patients on HD (121 lesions) who underwent percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) were compared with 78 patients on HD (95 lesions) who received bare metal stents (BMS) in the preceding 1 year. The primary endpoint was angiographic restenosis defined as > or =50% diameter stenosis at 6-8 months follow-up after PCI. The angiographic restenosis rate at follow-up was 22.2% in the SES group and 24.4% in the BMS group. No difference was detected in the restenosis rate between the 2 groups (p=0.73). When including both HD and non-HD patients, the independent predictors for restenosis after SES implantation were treatment with HD (hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.23-7.95; p=0.016), incidence of hyperlipidemia (HR 3.93; 95%CI 1.12-13.7; p=0.032), coronary calcification (HR 2.78; 95%CI 1.12-6.91; p=0.027), and implantation of multi-stents (HR 4.14; 95%CI 1.70-10.1; p=0.0017). CONCLUSIONS: Even if treated with SES, patients with end-stage renal failure on HD are at high risk of restenosis after PCI.     

Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low pathogenicity and emergence of an adaptive mutation

The identification of the hepatitis C virus (HCV) strain JFH-1 enabled the successful development of infectious cell culture systems. Although this strain replicates efficiently and produces infectious virus in cell culture, the replication capacity and pathogenesis in vivo are still undefined. To assess the in vivo phenotype of the JFH-1 virus, cell culture-generated JFH-1 virus (JFH-1cc) and patient serum from which JFH-1 was isolated were inoculated into chimpanzees. Both animals became HCV RNA-positive 3 days after inoculation but showed low-level viremia and no evidence of hepatitis. HCV viremia persisted 8 and 34 weeks in JFH-1cc and patient serum-infected chimpanzees, respectively. Immunological analysis revealed that HCV-specific immune responses were similarly induced in both animals. Sequencing of HCV at various times of infection indicated more substitutions in the patient serum-inoculated chimpanzee, and the higher level of sequence variations seemed to be associated with a prolonged infection in this animal. A common mutation G838R in the NS2 region emerged early in both chimpanzees. This mutation enhances viral assembly, leading to an increase in viral production in transfected or infected cells. CONCLUSION: Our study shows that the HCV JFH-1 strain causes attenuated infection and low pathogenicity in chimpanzees and is capable of adapting in vivo with a unique mutation conferring an enhanced replicative phenotype.     

Exploratory Analysis to Find Unfavorable Subset of Stage II Gastric Cancer for Which Surgery Alone Is the Standard Treatment; Another Target for Adjuvant Chemotherapy

The aim of the present study was to explore the unfavorable subset of patients with Stage II gastric cancer for whom surgery alone is the standard treatment (T1N2M0, T1N3M0, and T3N0M0). Recurrence-free survival rates were examined in 52 patients with stage T1N2-3M0 and stage T3N0M0 gastric cancer between January 2000 and March 2010. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. The recurrence-free survival (RFS) rates of the patients with stages T1N2, T1N3, and T3N0 cancer were 80.0, 76.4, and 100% at 5 years, respectively. The only significant prognostic factor for the survival rates of the patients with stage pT1N2-3 cancer measured by univariate and multivariate analyses was pathological tumor diameter. The 5-year RFS rates of the patients with stage pT1N2-3 cancer were 60.0%, when the tumor diameters measured <30 mm, and 88.9% when the tumor diameters measured >30 mm (P = 0.0248). These data may suggest that pathological tumor diameter is associated with poor survival in patients with small T1N2-3 tumors. Because our study was a retrospective single-center study with a small sample size, a prospective multicenter study is necessary to confirm whether small tumors are risk factor for the RFS in T1N2-3 disease.Key words: Gastric cancer, Stage II, Adjuvant chemotherapyEvery year, more than 934,000 people develop gastric cancer worldwide. After lung cancer, gastric cancer is the second most frequent cancer-related cause of death.¹ Complete resection is essential to cure gastric cancer. Patients with stage II or stage III gastric cancer often develop tumor recurrence, even after complete curative resections.In 2007, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) phase III trial demonstrated that S-1 is effective as adjuvant chemotherapy in Japanese patients who have undergone curative D2 gastrectomy for advanced gastric cancer.² In general, patients eligible for ACTS-GC were those diagnosed with pathological stages II and III. However, patients classified with pathological (p) stages T1N2M0, T1N3M0, and T3N0M0—which are classified as part of stage II—were excluded from the ACTS-GC trial. Because in the prior phase III studies comparing surgery alone and adjuvant chemotherapy, patients with stages T1N+ and T2-3/N0 cancer had excellent prognoses with 5-year overall survival (OS) rates of more than 80% from surgery alone,^3,4 these patients were excluded from receiving adjuvant chemotherapy. Japanese Gastric Cancer Association (JGCA) guidelines clearly state that the standard treatment for these patients is surgery alone.⁵Therefore, patients with stage II gastric cancer have been divided into two groups: one for whom the standard treatment is surgery alone, and the other for whom the standard treatment is surgery and adjuvant chemotherapy with S-1. Before the advent of ACTS-GC, survival rates were poorer in the latter group than in the former. However, treatment with adjuvant chemotherapy with S-1 has reversed this trend. Now, patients in the latter group receiving S-1 adjuvant chemotherapy have 5-year OS rates of 84.2%.⁶ Therefore, it may be old rationale that dictates that patients in the former group should be excluded from receiving adjuvant chemotherapy, because the 5-year OS rates are now more than 80% by S-1 adjuvant chemotherapy in the latter group. Five-year OS rates of 80% would not be obtained by surgery alone. Among those patients with stage II gastric cancer assigned to the surgery alone group, some may have a poor prognosis and be good candidates for adjuvant chemotherapy. The aim of the present study was to explore the unfavorable subset of patients among those with stage II gastric cancer for whom surgery alone is the standard treatment (T1N2M0, T1N3M0, and T3N0M0).     

Basiliximab treatment for steroid‐resistant rejection in pediatric patients following liver transplantation for acute liver failure

An IL‐2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6–12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno‐occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.     

Hepatic artery reconstruction preserving the pancreaticoduodenal arcade in pediatric liver transplantation with celiac axis compression syndrome: Report of a case

CACS is rare, although it has been reported to be a potential risk factor for hepatic artery thrombosis following LT. We herein present the case of a 14‐yr‐old male with stenosis of the origin of the celiac trunk. Preoperative CT and color ultrasonography showed narrowing of the proximal celiac artery. The patient underwent DDLT with standard arterial reconstruction without dividing the gastroduodenal artery. His postoperative course was uneventful, with an excellent hepatic artery flow on Doppler ultrasonography. Applying a meticulous preoperative evaluation and the appropriate surgical technique is crucial in patients with CACS.     

Central pontine myelinolysis following pediatric living donor liver transplantation: A case report and review of literature

CPM is one of the most serious neurological complications that can occur after OLT and is characterized by symmetrical demyelinization in the basis pontis. The etiology of CPM remains unclear, although the rapid correction of the serum sodium and CNI concentrations may be associated with the development of CPM. With recent advances in MRI technology, early diagnosis of CPM has become possible. Here, we present the case of a five‐yr‐old female who developed CNI‐associated CPM after undergoing LDLT. A decreased level of consciousness and dysphasia was noted one wk after LDLT, and MRI revealed findings compatible with a diagnosis of CPM. The patient fully recovered from the neurological deficits related to CPM following the switch from the CNI to sirolimus. We propose MRI to be promptly considered for patients with abnormal neurological findings, together with the substitution of CNI with an mTOR inhibitor as a management regimen for CNI‐related CPM.