A Prospective Analysis of Efficacy and Long-Term Outcome of Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Background/Aims: Few studies exist on the efficacy and long-term outcome of radiation therapy (RT) for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: Twenty-two patients with stage I or stage II(1) disease were prospectively evaluated, including 14 patients without Helicobacter pylori(H. pylori) infection and 8 patients with persistent lymphoma after H. pylori eradication. RT dose was 30 Gy in daily fractions of 1.5 Gy. All patients underwent endoscopic and histological follow-up regularly. Results: The study included 22 patients with a mean age of 63 years. The t(11;18)(q21;q21) translocation occurred in 8 of the 22 cases. All patients showed complete remission without any serious toxicity. At a median follow-up evaluation 74 months (range 27-159) after completion of RT, the overall and relapse-free survival rates after 5 years were 91 and 84%, respectively. Although no patient showed local recurrence of lymphoma, distant recurrence was detected in 3 patients, all of whom were H. pylori negative; MALT lymphoma relapsed in two patients with the t(11;18)(q21;q21) translocation, and diffuse large-cell lymphoma developed in one patient without the translocation. Conclusion: RT provides excellent local control of the gastric MALT lymphoma. However, continuous follow-up is mandatory as relapse may occur in other sites.     

Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia with immunodeficiency

Somatic mosaicism has been described in several primary immunodeficiency diseases and causes modified phenotypes in affected patients. X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the NF-κB essential modulator (NEMO) gene and manifests clinically in various ways. We have previously reported a case of XL-EDA-ID with somatic mosaicism caused by a duplication mutation of the NEMO gene, but the frequency of somatic mosaicism of NEMO and its clinical impact on XL-EDA-ID is not fully understood. In this study, somatic mosaicism of NEMO was evaluated in XL-EDA-ID patients in Japan. Cells expressing wild-type NEMO, most of which were derived from the T-cell lineage, were detected in 9 of 10 XL-EDA-ID patients. These data indicate that the frequency of somatic mosaicism of NEMO is high in XL-ED-ID patients and that the presence of somatic mosaicism of NEMO could have an impact on the diagnosis and treatment of XL-ED-ID patients.     

Endoscopic submucosal dissection with sheath-assisted counter traction using a novel sheath for early gastric cancers

Background/Aims: Endoscopic submucosal dissection (ESD) is technically demanding and requires considerable skill. We previously described sheath-assisted counter traction ESD that uses simple materials and methods to improve cutting line visualization. We recently improved counter-traction of the submucosal layer using a novel chemically treated sheath that reduces slippage and maintains traction, and investigated the utility of the novel sheath for ESD. Methodology: Forty-three and 25 consecutive patients with early gastric carcinomas were treated by standard ESD and traction ESD assisted with novel sheaths, respectively. The mean duration of procedures relative to tumor size and location, as well as complications after ESD between the two groups were compared. Results: The mean duration of ESD procedures for lesions =20mm in diameter was significantly reduced using the novel sheath. The mean duration of procedures for all locations of resected tumors in the stomach was significantly reduced using the novel sheath. However, no perforation and delayed bleeding developed after treatment with the novel sheath. Conclusions: Sheath-assisted counter traction ESD by the novel sheath was technically simpler and thus less time-consuming regardless of the location of lesions, especially when =20mm in diameter. The traction ESD with the novel sheath is safe and not invasive, and it can be universally applied to standard ESD.     

Cerebral microhemorrhage in Marchiafava–Bignami disease detected by susceptibility-weighted imaging

Marchiafava–Bignami disease (MBD) is a rare alcohol-associated disorder. Clinical features include not only disturbed consciousness, dysarthria, tetraparesis, astasia-abasia, and symptoms of interhemispheric disconnection as initial symptoms but also cognitive deficits as clinical outcomes. The clinical significance of cerebral microhemorrhage (CMH) has been recognized in patients with cognitive deficits; however, the presence of CMH in patients with MBD has not been emphasized. The aim of the present study was to clarify the relationship between CMH and MBD. For this purpose, we report four patients with MBD, who showed asymmetrical hypointense areas in multiple cortico-subcortical regions on susceptibility-weighted imaging (SWI). All cases had a history of chronic alcohol abuse and symmetrical lesions in the entire corpus callosum. These patients’ clinical symptoms included not only coma, dysarthria, and astasia-abasia as initial symptoms but also dementia as a clinical outcome. SWI showed asymmetrical hypointense areas in the multiple cortico-subcortical regions, indicating the presence of CMH. Compared with patients with normal cognitive function, demented patients showed higher severity of CMH. Our report would indicate that CMH is an important factor indicating the severity of dementia in patients with MBD.     

Differences in the ultrastructural localization of sulfated glycoconjugates between dentine and bone in the ganoid scales of Polypterus senegalus

ObjectivesSulfated glycoconjugates (S-GCs) are essential components of dentinogenesis and osteogenesis, and are involved in the regulation of the mineralization process. The scales of Polypterus senegalus, which are homologous to teeth and phylogenetically derived from ancestral dermal skeleton, comprise true enamel, dentine, and bone. As part of the phylogenic evolutional studies on mesenchyme-derived hard tissues, we investigated the ultrastructural distribution patterns and histochemical properties of S-GCs in the dentine and bone of scales.MethodsFor detection of S-GCs, a high iron diamine–thiocarbohydrazide–silver proteinate (HID–TCH–SP) staining technique was used.ResultsS-GCs were observed in unmineralized predentine and osteoid, mineralized dentine, osteocyte pericellular matrix, but not in mineralized bone and isopedine. Most S-GCs in the dentine and osteoid were susceptible to testicular hyaluronidase, indicating that they are chondroitin sulfates.ConclusionDistinct differences in the S-GC distribution pattern between the dentine and bone were observed. The S-GC distribution pattern associated with the dentinogenesis of scales is very similar to that of mammalian mantle dentine.     

Impact of Pump Replacement on Outcome in Advanced Heart Failure Patients With Left Ventricular Assist System

Pump thrombosis is one of the major adverse events associated with the use of a left ventricular assist system (LVAS) in patients with advanced heart failure. We investigated the clinical implication of pump replacement because of thrombus formation. This study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal LVAS intended as a bridge to transplantation and were alive more than 3 months after implantation. The pump of this device is translucent, and daily evaluation for signs of thrombus formation was performed. Pump replacement was performed for significant thrombus formation that became visible. Data collection including demographics as well as hematologic values were performed 1 day before (baseline) and 3 months after implantation, and all patients were followed for 2 years or until death. At 3 months after LVAS implantation, 41 patients (47.1%) had undergone pump replacement because of pump thrombus. Baseline body surface area <1.63 m² was a significant predictor of pump replacement (hazard ratio [HR] 2.15, P = 0.04). At 3 months after implantation, there was a significantly higher incidence of stroke (P < 0.05) as well as a significantly greater decrease in body weight (F = 4.92, P = 0.03) in patients who underwent pump replacement as compared to those without. The 2‐year mortality after implantation was 26.4%. Multivariate Cox regression analysis showed that pump replacement within 3 months after implantation was an independent predictor of mortality (HR 2.50, P = 0.03). In conclusion, pump replacement for thrombus formation may have a strong association with worse outcome. Our results reconfirm the clinical importance of device thrombus in the management of LVAS.     

Pathophysiological analysis of nonalcoholic fatty liver disease by evaluation of fatty liver changes and blood flow using xenon computed tomography: can early-stage nonalcoholic steatohepatitis be distinguished from simple steatosis?

Introduction

Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS.

Materials and methods

We used Fick’s principle and the Kety–Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt’s classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups.

Results

LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups.

Conclusions

In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means.     

One Injection of DsRed Followed by Bites from Transgenic Mosquitoes Producing DsRed in the Saliva Elicits a High Titer of Antibody in Mice

It has been proposed that transgenic mosquitoes can be used as a “flying syringe” for infectious disease control. We succeeded in generating a transgenic (TG) mosquito, Anopheles stephensi, excreting and discharging DsRed in saliva. DsRed was deposited on the membrane where the TG mosquito probed with its proboscis. Repeated feeding by the TG mosquitoes induced anti-DeRed as well as anti-SG antibodies in mice. This indicates that the TG mosquitoes can immunize the animal. Moreover, in this report, we employed a pre-immunization method before exposing mice to the TG mosquitoes. We injected DsRed to mice to prepare memory B cells and exposed the mice to bites by the TG mosquitoes excreting DsRed. The mice produced a higher titer of antibody to DsRed, suggesting that the bites from TG mosquitoes act as a booster and that primary immunization with a vaccine protein and exposure to TG mosquitoes excreting the vaccine protein in the saliva produces a synergistic effect.     

A longitudinal study of age‐ and gender‐related annual rate of volume changes in regional gray matter in healthy adults

The aim of this study was to analyze correlations among the annual rate of gray matter volume change, age, gender, and cerebrovascular risk factors in 381 healthy community‐dwelling subjects with a large age range by applying a longitudinal design over 6 years using brain magnetic resonance images (MRIs). Brain MRI data were processed with voxel‐based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. The annual rate of regional gray matter volume change showed significant positive correlations with age in several regions, including the bilateral temporal pole, caudate nucleus, ventral and dorsolateral prefrontal cortices, insula, hippocampus, and temporoparietal cortex, whereas significant negative correlations with age were observed in several regions including the bilateral cingulate gyri and anterior lobe of the cerebellum. Additionally, a significant age‐by‐gender interaction was found for the annual rate of regional gray matter volume change in the bilateral hippocampus. No significant correlations were observed between the annual rate of regional gray matter volume change and body mass index or systolic blood pressure. A significant positive correlation between the annual rate of gray matter volume change and age indicates that the region shows not linear but accelerated gray matter loss with age. Therefore, evaluating the annual rate of the gray matter volume change with age in healthy subjects is important in understanding how gray matter volume changes with aging in each brain region and in anticipating what cognitive functions are likely to show accelerated decline with aging. Hum Brain Mapp 34:2292–2301, 2013. © 2012 Wiley Periodicals, Inc.     

Evaluation of a newly proposed renal risk score for Japanese patients with ANCA-associated glomerulonephritis

Clinical and Experimental Nephrology - We determined the usefulness and prognostic ability of the renal risk score (RRS), proposed in Europe, for Japanese patients with antineutrophil cytoplasmic...