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Spontaneous esophageal perforation in Boerhaave's syndrome results in significant morbidity and mortality. The gold standard treatment for this disease is thoracotomy and laparotomy because it can be a life-saving procedure that can be performed in emergencies; however, minimally invasive surgery has recently been reported. This report describes three cases of Boerhaave's syndrome that were treated using laparoscopic transhiatal suture and omental patch. One patient recovered uneventfully and was discharged from the hospital after 12 days. The other 2 patients had postoperative complications, such as minor leakage and remnant abscess (Clavien-Dindo Grade II), but were discharged from the hospital after 17 days and 30 days, respectively. In the case of Boerhaave's syndrome with localized mediastinal collections, a good clinical course can be obtained by laparoscopic transhiatal esophageal repair to avoid surgical invasion due to thoracotomy. [ABSTRACT FROM AUTHOR]

Granulocyte-colony-stimulating factor(G-CSF) has been reported to improve cardiac function after myocardial infarction (MI). However, whether postinfarct acute effect of G-CSF is mediated through the same signaling pathways as those of ischemic postconditioning is still unclear. We examined the postinfarct acute effect of G-CSF on myocardial infarct size and its precise molecular mechanism. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Rabbits were intravenously injected 10 μg/kg of G-CSF (G-CSF group), saline (control group) immediately after reperfusion. The wortmannin+G-CSF, PD98059+G-CSF, Nω-nitro-L-arginine methyl ester (L-NAME) + G-CSF, and 5-HD+G-CSF groups were respectively injected with wortmannin(0.6mg/kg), PD98059(0.3mg/kg), L-NAME(10mg/kg) and 5-HD(5mg/kg), 5 min before G-CSF administration. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the signals such as Akt, ERK, eNOS, p70S6K and GSK3β in the ischemic myocardium after 48 hours of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7±2.7%) than in the control group (42.3±4.6%). The infarct size-reducing effect of G-CSF was completely blocked by wortmannin(44.7±4.8%), PD98059(38.3±3.9%), L-NAME (42.1±4.2%) and 5-HD (42.5±1.7%). Wortmannin, PD98059, L-NAME or 5HD alone did not affect the infarct size. Western blotting showed higher myocardial expression of phospho-Akt, phospho-ERK, phosho-eNOS, phosho-p70S6K and phosho-GSK3β at 10 min and 48 hours after reperfusion in the G-CSF group than in the control group. In conclusion, postreperfusion G-CSF administration reduces myocardial infarct size via activation of PI3K-Akt and ERK prosurvival signaling pathways and their down stream targets eNOS, p70S6K, GSK3β and mitochondrial KATP channels. [ABSTRACT FROM AUTHOR]

The oriental herbal formulation inchin-ko-to (ICKT) inhibits liver cell apoptosis induced by transforming growth factor-beta 1 (TGF-beta1). This study evaluated the effect of ICKT on serum markers of liver function and liver fibrosis in postoperative biliary atresia (BA) patients. Twenty-one postoperative BA patients with elevated GOT, GPT and gamma-GTP, but normal serum total bilirubin levels, were divided into two groups arbitrarily; an ICKT group (n = 12), and a no-ICKT group (n = 9). Serum markers of liver function [GOT, GPT, gamma-GTP, total bile acids (TBA)], and serum markers of liver fibrosis [hyaluronic acid (HA), type IV collagen (C-IV)], were measured in both groups at the beginning of the study, and at 1, and 3 years after the beginning of the study and the results compared statistically. All patients tolerated ICKT well, and there were no side effects. In the ICKT group, mean serum HA levels were significantly decreased at 1 year (P < 0.012), and at 3 years, both mean serum HA and C-IV were significantly decreased (P < 0.001 and P < 0.003, respectively). However, mean serum levels of GOT, GPT, gamma-GTP, and TBA did not change significantly following ICKT use for any length of time (all P > 0.05). Administration of ICKT in postoperative BA patients appears to lower the serum levels of markers of fibrosis in the medium-term. Whether this in fact correlates with prevention cannot be determined from this paper, but ICKT would appear to protect against liver fibrosis. Long-term studies are required to determine the exact role ICKT plays in prognosis of BA patients. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy. Methods: We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy. Results: Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3–5 resection, preoperative Karnofsky Performance status < = 70%, and MIB-1 labeling index > = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group. Conclusion: We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Atypical teratoid/rhabdoid tumor (AT/RT) occurring in the central nervous system is a high-grade malignant tumor, and its prognosis is poor for patients younger than 3 years of age. In this article, we present a case of infant AT/RT in the cervical spine and its successful treatment by intensive chemotherapy. The patient, a 1.75-year-old girl, developed an acute, progressive tetraparesis. MRI revealed a large, intradural mass in the cervical spine.Total surgical resection was performed, and the specimen was diagnosed as AT/RT. Continuously, she received intensive chemotherapy using thiotepa with autologous bone marrow transplantation. At the age of nearly 3 years, she received radiation therapy to the local tumor bed and craniospinal axis. She is now 4 years old and has been maintained in complete remission with a good clinical course and no neurological deficit. The success of this treatment for the patient was that we could prevent tumor recurrence until she was able to receive radiotherapy. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We investigate the incidence, treatment, and implications of intrahepatic bile duct (IHBD) dilatation debris in 42 patients with choledochal cyst treated over a recent 8-year period. Mean age at cyst excision was 6.9 years, and mean follow-up period was 5.4 years. Intraoperative endoscopy (IOE) was performed at the time of cyst excision using a pediatric cystoscope, which identified IHBD debris in 11/42 (26.2%), and massive debris in 4/42 (9.5%). In all cases, IHBD debris was successfully washed out with normal saline through the cystoscope. There was no postoperative IHBD stone formation or cholangitis except for one case of cholangitis in a patient undergoing chemotherapy for acute myelocytic leukemia. Debris left in the IHBD during cyst excision is probably one of the primary causes of postoperative IHBD stone formation and can be prevented by washing during IOE. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as “allied disorders of Hirschsprung's disease” and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. Methods: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis‐microcolon‐intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo‐obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese‐ and English‐language articles in PubMed and Ichu‐Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. Results: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full‐thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. Conclusions: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between the pharmacokinetics and effects of gefitinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is unknown. In this study, we examined the correlation between gefitinib plasma concentration and progression-free survival (PFS) in patients with two common types of EGFR mutations: a deletion in exon 19 and point mutations in exon 21 L858R.Methods: The retrospective analysis examined 40 patients who were administered 250 mg of gefitinib daily. All patients were diagnosed with and treated for advanced non-small cell lung carcinoma with sensitive EGFR mutations between January 2011 and November 2013 at Akita University Hospital, Akita, Japan. The 40 patients were divided into four groups by trough plasma concentration (high or low) and mutation type (exon 19 deletions or exon 21 L858R point mutations). PFS, response rate, and toxic effects were analyzed in all four groups.Results: After excluding 5 patients, the remaining 35 were successfully analyzed. For the patients with exon 19 deletions, there was no significant difference in PFS between the high and low plasma concentration groups (median survival: 12.0 vs. 17.0 months, P = 0.9548). In contrast, the PFS was significantly shorter for patients with exon 21 point mutations and low vs. high concentrations of gefitinib (median survival: 8.0 vs. 16.0 months, P < 0.05).Conclusions: The results suggest that low gefitinib plasma concentrations in patients with exon 21 L858R point mutations may be associated with shorter PFS in NSCLC patients. [ABSTRACT FROM AUTHOR]

Although microvascular decompression (MVD) is a reliable treatment for hemifacial spasm (HFS), the postoperative course is varied. We retrospectively analyzed the resolution pattern of the spasm and specified predictors for delayed cure after MVD. This study included 114 consecutive patients with typical HFS. All of them were followed up for at least 1 year after operation. Patients were divided into three groups depending on the postoperative course: immediate cure, delayed cure, and failure. To identify the predictive factors for delayed cure after MVD, logistic regression analyses were applied using candidate clinical factors, such as duration of symptom, the tendency of the spasm, preoperative medical treatment, and offending vessels. Among the 114 patients, 107 patients were cured. For those cured, 65 patients were classified as immediate cure and 42 patients were classified as delayed cure. Cumulative spasm-free rates after 1 week, 1 month, and 3 months after MVD were 70, 88, and 97 %, respectively. No predictive factors between the cured and failure groups were observed. According to multivariate analysis, preoperative anticonvulsant therapy was found to be the sole significant predictive factor for delayed cure after MVD ( p = 0.025). A significant correlation between delayed cure and preoperative anticonvulsant therapy was found in our study, which suggests that hyperexcitation of the facial nucleus plays an important role in pathogenesis of delayed cure. Therefore, if a patient demonstrating a positive response to preoperative anticonvulsant therapy showed a persistent spasm after MVD, reoperation should be delayed for at least 3 months after the initial operation. [ABSTRACT FROM AUTHOR]

Background: Patients with hypoalbuminemia often fail to respond to increased doses of loop diuretics. We therefore performed a post hoc analysis to investigate the pharmacological action of tolvaptan and whether it is dependent on the serum albumin level.Methods: This analysis was based on four previous clinical trials of tolvaptan in patients with liver cirrhosis who exhibited insufficient response to conventional diuretics. We analyzed the correlation between the change in the initial 24-h cumulative urine volume from baseline and the serum albumin level at baseline, and assessed potential predictive factors of response to tolvaptan.Results: The correlation coefficient was 0.029 in the placebo group and -0.112 in the 7.5 mg tolvaptan group of patients with liver cirrhosis. Administration of tolvaptan provoked a stable response regardless of the serum albumin level. Tolvaptan use was identified as a significant predictor of pharmacological action, and was shown to change the initial urine volume by 885 mL (P < 0.0001) in liver cirrhosis patients.Conclusions: In this post hoc analysis, tolvaptan increased the initial urine volume from baseline regardless of serum albumin levels. Use of tolvaptan as an add-on therapy to loop diuretics can be considered an optimal therapeutic option in patients with insufficient response to loop diuretics. [ABSTRACT FROM AUTHOR]

Objectives: We hypothesized that erythropoietin (EPO)-immersed gelatin hydrogel microspheres (GHM) injected into ischemic legs might continuously release a small amount of EPO to locally stimulate angiogenesis without unfavorable systemic effects. Background: EPO is a potent angiogenic factor, but its use for relieving ischemic organs is limited because of the untoward systemic erythrogenic effect and its short half-life in plasma. Methods: The right femoral arteries of BALB/c mice were ligated. Recombinant human EPO (5,000 IU/kg)-immersed GHM was injected into the right hind limb muscles (n = 12); the control groups included a saline-injected group (n = 12), an EPO-injected group (n = 8), and an empty GHM-injected group (n = 8). Results: Eight weeks later, improvement of blood perfusion to the ischemic limb was significantly augmented in the EPO-GHM group compared with any of the control groups. There was no increase in the hemoglobin level, nor was there any increase in endothelial progenitor cells. However, capillary and arteriolar densities were significantly increased in this group. Although the treatment did not affect the levels of vascular endothelial growth factor or interleukin-1 beta, it up-regulated the EPO receptor and matrix metalloproteinase-2 and activated the downstream signaling of Akt and also endothelial nitric oxide synthase in ischemic limbs, which might have been associated with the evident angiogenic and arteriogenic effects in the present system. Conclusions: The present drug delivery system is suggested to have potential as a novel noninvasive therapy for ischemic peripheral artery disease. [Copyright &y& Elsevier]

A review of 100 consecutive cases of congenital diaphragmatic hernia (CDH) treated at our institute focusing on the efficacy of protocolized management (PM) was conducted. Of the 100 cases, 14 who became symptomatic more than 24 h after birth, and seven with fatal anomalies (four cardiac and three chromosomal) were excluded, leaving 79 subjects for this study. Of these, 41 were diagnosed prenatally (PD). Subjects were divided into four groups. Group I: No PD, no PM (n = 34), Group II: No PD, PM (n = 4), Group III: PD, no PM (n = 21), and Group IV: PD, PM (n = 20). PM includes criteria for planned delivery, use of high frequency oxygenation, nitric oxide, echocardiography (EC), and a medication schedule. Overall survival rates for Groups I, II, III, and IV were 73.5% (25/34), 75% (3/4), 38.1% (8/21), and 70.0% (14/20), respectively. Survival rates were higher when PM was used: 70.8% (Groups II, IV) versus 60.0% (Groups I, III). Survival rates were significantly lower if diagnosed prenatally (PD+): 53.7% (Groups III, IV) versus 73.7% (Groups I, II) (P < 0.01). However, in PD+ groups, survival was significantly higher if PM was used (P < 0.05). PM significantly reduced length of hospital stay (35.5 vs. 52.0 days: P < 0.05). EC was found to be a predictor for survival while post-ductal AaDO(2) was not. In 17 cases with cardiac anomalies, PM did not affect survival. Our study suggests that use of PM for prenatally diagnosed CDH cases is associated with improved outcome, although the components of PM need to be tested in prospective trials to determine their true value. [ABSTRACT FROM AUTHOR]

Cathelicidins are a family of antibacterial peptides. Human cathelicidin LL-37 inhibits the binding of endotoxin lipopolysaccharide (LPS) to CD14-positive cells and could ameliorate sepsis. The aim of this study was to observe the effect of LL-37 on sepsis in neonatal rats. Intraperitoneal injection (IPI) of LPS was used to create sepsis in suckling rats. Group 1 rats were given LPS with LL-37, group 2 rats were given LL-37 2 h after LPS, and group 3 rats were given LPS without LL-37. Control group rats were given isovolemic normal saline by IPI. Rats given LL-37 IPI were divided into seven subgroups. Following IPI, an overall assessment score (OAS) and rectal temperature (RT) were assessed hourly. Serum C-reactive protein (CRP) was also assessed at death or at sacrifice 10 h after IPI. All rats in group 3 died. For rats receiving lower doses of LL-37 in groups 1 and 2, mortality was decreased. No deaths occurred among those receiving higher doses of LL-37 in group 1; however, mortality increased in group 2. In group 1, OAS and RT deteriorated initially for those receiving lower doses of LL-37, then improved. OAS and RT did not deteriorate throughout the study in rats given higher doses of LL-37. In group 2 rats given higher doses of LL-37, OAS and RT were not significantly different from rats in group 3. CRP was significantly decreased in group 1 compared with group 3, and decreased in group 2 for lower doses only. We conclude that LL-37 may prevent sepsis and be useful in lower doses for treating sepsis. However, LL-37 appears to have adverse effects when used at higher doses for treating sepsis. [ABSTRACT FROM AUTHOR]

Treatment of "forme fruste" choledochal cyst (FFCC) where pancreaticobiliary malunion (PBMU) is associated with minimal dilatation of the common bile duct (CBD) remains controversial. PBMU allows pancreaticobiliary reflux to occur, which causes complications such as recurrent pancreatitis and gallbladder cancer. Therefore, some surgeons opt to treat FFCC by cholecystectomy alone in order to prevent gallbladder cancer, with the result that pancreaticobiliary reflux could still occur. Our treatment of choice-excision of both the CBD and the gallbladder, followed by Roux-en-Y hepatico-jejunostomy-can eliminate pancreaticobiliary reflux and prevent complications. Our case, a 2-year-old boy, initially presented to a hospital abroad with recurrent abdominal pain. Endoscopic retrograde cholangiopancreatography showed massive protein plugs impacted in the papilla of Vater and mild CBD dilatation, but PBMU was not identified. Intraoperative cholangiography performed during laparotomy 5 days later suggested PBMU with minimal CBD dilatation. Despite these findings, cholecystectomy with T-tube drainage was performed rather than CBD excision with biliary reconstruction. Postoperative T-tube cholangiography clearly showed PBMU. The T-tube was removed after 2 weeks, and 3 months later the boy was referred to us because of recurrent pancreatitis. We performed CBD excision and Roux-en-Y hepatico-jejunostomy. His postoperative course was uneventful, and he is well after 10 years of follow-up. This case provides strong evidence that CBD excision with biliary reconstruction is mandatory for treating FFCC and, conversely, that cholecystectomy alone is inadequate for treating children with FFCC. [ABSTRACT FROM AUTHOR]