Minimum-Dose,Short-Term Methotrexate With Tacrolimus for Graft-vs-Host Disease Prophylaxis Following Unrelated Cord Blood Transplantation in Adults: A Retrospective Analysis at a Single Institution

BackgroundMethotrexate (MTX) or mycophenolate mofetil with tacrolimus (TAC) is used for graft-vs-host disease (GVHD) prophylaxis in unrelated cord blood transplantation (CBT). However, there is no consensus regimen for GVHD prophylaxis in CBT. We aimed to assess the efficacy and feasibility of minimum-dose, short-term MTX (MS-MTX) for GVHD prophylaxis in CBT.MethodsWe retrospectively evaluated 35 consecutive adult patients who underwent CBT and received MS-MTX (6 mg/m² day 1; 3 mg/m² days 3 and 6, intravenously) with TAC for GVHD prophylaxis in our hospital between 2015 and 2019. Transplantation outcomes with respect to time to hematopoietic recovery, engraftment, incidence and severity of GVHD, adverse events, relapse, nonrelapse mortality (NRM), and overall survival were evaluated.ResultsThe median time to neutrophil, platelet, and reticulocyte recovery was 22, 38, and 32 days, respectively. Cumulative neutrophil engraftment was 91.4%. After a median 3.2-year follow-up, the 2-year overall survival was 64.3%. The 2-year cumulative incidence of relapse and NRM was 20.4% and 14.9%, respectively. The 100-day cumulative incidence of grade II-IV acute GVHD and 2-year cumulative incidence of chronic GVHD were 28.6% and 36.6%, respectively. No grade IV acute GVHD was observed. Sixteen patients experienced oral mucositis and/or pharyngeal pain (46%; grades 1-2, n = 15; grade 3 pharyngeal pain, n = 1). No patients suffered from human herpesvirus 6 encephalitis/myelitis.ConclusionsMS-MTX with TAC is feasible and safe and yields lower rates of severe oropharyngeal mucositis and human herpesvirus 6 encephalitis/myelitis without increasing GVHD, graft failure, relapse, or NRM.     

ASO Visual Abstract: Influence of Damaged Stomach on Anastomotic Leakage After Cervical Esophagogastrostomy for Patients with Esophageal Cancer

Annals of Surgical Oncology -     

All-case Japanese post-marketing surveillance of the real-world safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome

Clinical and Experimental Nephrology - Rituximab is conditionally approved in Japan for use in patients with refractory nephrotic syndrome. To meet the conditions of approval, an all-case...     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.     

Osteosarcoma occurring in osteogenesis imperfecta

We describe a case history of a 24-year-old male with osteogenesis imperfecta (OI) who developed osteosarcoma of the left thigh. High-dose ifosfamide therapy caused marked tumor regression of multiple lung metastases. Immunohistochemically, the tumor cells were diffusely positive for the p53 protein. Mutation of the p53 gene was not detected by direct genomic sequencing of exons 4–8. The radiographic characteristics, including irregularly distributed osteolytic lesions and cortical discontinuity, should not be confused with hyperplastic callus formation, a benign process. A biopsy is critical to establish the differential diagnosis between osteosarcoma and common hyperplastic callus formation in OI; however, it must be applied with great care.     

Structure and expression of tomato mitochondrial genes coding for tRNACys (GCA), tRNAAsn (GUU) and tRNATyr (GUA): A native tRNACys gene is present in dicot plants but absent in monocot plants

Summary The nucleotide sequences of tRNA^Asn (GUU) and tRNA^Tyr (GUA) genes from tomato mitochondria and their flanking regions have been determined. The tomato mitochondrial tRNA^Asn gene is located 2.1 kb downstream from the tRNA^Cys gene reported previously (Izuchi and Sugita 1989) and shows a nearly complete identity with the corresponding chloroplast gene. The tRNA^Tyr gene, which shows only 73% homology with the corresponding chloroplast gene, has to be considered a native mitochondrial tRNA gene and is 535 bp from the chloroplast-like tRNA^Asn gene on the same strand. Northern hybridization analysis revealed that the three tRNA genes are transcribed in tomato mitochondria. Southern hybridization analysis of tomato, sugar beet, rice and wheat mitochondrial DNAs, with oligonucleotide probes for mitochondrial or chloroplast tRNA genes, demonstrated that the mitochondrial tRNA^Cys gene found in tomato is present in dicot plants but not in monocots. On the other hand, a chloroplast-like tRNA^Cys gene exists in monocot plants.     

Identification of α1-adrenoceptor subtypes in the dog prostate

Summary The ₁-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [³H]prazosin bound to ₁-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [³H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct ₁-adrenoceptor subtypes was suggested: presumably subtypes _1A (high affinity for prazosin and WB4101), _1N (high affinity for only HV723) and _1L (low affinity for the three antagonists) according to the recently proposed ₁-adrenoceptor subclassification. The density of subtype _1L was much higher than that of subtypes _1A and _1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the _1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through _1L subtype -adrenoceptors.