Risk factors for diabetes mellitus and impaired glucose tolerance following allogeneic hematopoietic stem cell transplantation in pediatric patients with hematological malignancies

Long-term surviving recipients of allogeneic hematopoietic stem cell transplantation (HSCT) often suffer from diabetes mellitus (DM). We sought to identify risk factors for the development of post-transplant DM and impaired glucose tolerance (IGT) in pediatric HSCT patients. Glucose tolerance statuses were evaluated in 22 patients aged 6.3–21.8 years who had received allogeneic HSCT between the ages of 0.8–13.5 years. Five patients were diagnosed as having type 2 DM, and treated with insulin or oral hypoglycemic agents. Five patients were included in the IGT group, and the remaining 12 children were in the normal glucose tolerance (NGT) group. The cumulative incidence of DM plus IGT was 11.6 % at 5 years and 69.3 % at 10 years. None of the patients were obese/overweight and none had a family history of DM. There were no significant differences in serum levels of leptin and adiponectin between the DM + IGT and the NGT groups. An average preprandial glucose levels in the DM + IGT group were significantly higher than those in the NGT group from preparative conditioning to 60 days after HSCT. In multivariate analysis, an age of ≥6 years at the time of HSCT was significantly associated with the development of DM + IGT. Additionally, careful follow-up is necessary, even for NGT patients.     

Anti-erythropoietin receptor antibody-associated pure red cell aplasia accompanied by Coombs-negative autoimmune hemolytic anemia in a patient with T cell/histiocyte-rich large B cell lymphoma

A 79-year-old female diagnosed with T cell/histiocyte-rich large B cell lymphoma in complete remission after six cycles of rituximab-combined chemotherapy developed severe anemia, reticulocytopenia, and bone marrow erythroid hypoplasia. She was diagnosed with pure red cell aplasia (PRCA) accompanied by Coombs-negative autoimmune hemolytic anemia evidenced by a lack of glycophorin-A-positive cells in the bone marrow, haptoglobin under the detection level, and a high titer of RBC-bound IgG. Anti-erythropoietin receptor (EPOR) antibody was detected in the serum, and oligoclonal α/β and γ/δ T cells were also detected in her peripheral blood by Southern blotting analysis. Parvovirus B19 DNA was not detected by PCR. Although the treatment with rituximab had limited efficacy (specifically, only for hemolysis), subsequent cyclosporine therapy led to prompt recovery of erythropoiesis with the disappearance of anti-EPOR antibody and oligoclonal T cells. This is the first case report of anti-EPOR antibody-associated PRCA in a patient with malignant lymphoma treated successfully with cyclosporine.     

The Impact of Endogenous Breast Cancer Resistance Protein on Human P-Glycoprotein-Mediated Transport Assays Using LLC-PK1 Cells Transfected With Human P-Glycoprotein

Lilly Laboratories cell porcine kidney 1 (LLC-PK1) cells transfected with human P-glycoprotein (LLC-PK1-P-gp) are widely used in transport assays to identify drug candidates that function as substrates of this efflux transporter. Endogenous transporters expressed in LLC-PK1 cells may complicate the interpretation of findings from P-gp-mediated transport assays. We investigated the impact of porcine breast cancer resistance protein (Bcrp) in P-gp-mediated transport assays in LLC-PK1 cells. Porcine Bcrp mRNA was detected in both LLC-PK1 wildtype (WT) and LLC-PK1-P-gp cells by quantitative RT-PCR. To investigate the activity and impact of porcine Bcrp, we conducted transport assays using 6 typical BCRP substrates in LLC-PK1 cells. Efflux ratios (ER) of the 6 BCRP substrates in LLC-PK1 WT cells were >2, and were reduced in the presence of the BCRP inhibitor Ko143. The efflux activities of the 6 BCRP substrates were confirmed using MDCKII cells transfected with human BCRP. Net ERs of prazosin and fluvastatin, dual substrates of P-gp and BCRP, determined by dividing ERs in LLC-PK1-P-gp cells by those in LLC-PK1 WT cells, were <2, but increased to >2 in the presence of Ko143. These results indicated that endogenous Bcrp in LLC-PK1 cells was involved in the transport of BCRP substrates and may interfere with the identification of P-gp substrates.     

Risk Factors for Lymphatic Metastasis of Malignant Bone and Soft-Tissue Tumors: A Retrospective Cohort Study of 242 Patients

Metastasis to the lymph nodes is relatively rare in malignant bone and soft-tissue tumors, and its risk factors remains unknown, except for tumors of the lymphogenous histotype, including rhabdomyosarcoma, epithelioid sarcoma, and clear cell sarcoma. The purpose of this study was to identify the risk factors for lymph node metastasis of malignant bone and soft-tissue tumors.We retrospectively reviewed 242 patients with malignant bone and soft-tissue tumors. The predictors of interest for the risk of lymph node metastasis included age, sex, histopathological diagnosis, location(s) of the primary tumor(s), local recurrence, residual tumor(s), and the size of the primary tumors. To identify the risk factors for lymph node metastasis, Cox regression analyses were performed.Among the 242 patients with malignant bone and soft-tissue tumors in the current study, 60, 29, and 28 were detected to have lung, lymph node, and bone metastases, respectively. In the univariate analyses, the lymphogenous histotype and a primary tumor invading the subcutis were the risk factors for lymph node metastasis. In the multivariate analysis, the lymphogenous histotype (P < 0.01) and a primary tumor in the subcutis (P < 0.01) remained significantly associated with a higher risk of lymph node metastasis with 5.15 and 3.48 of hazard ratios, respectively.Lymph node metastasis was detected in malignant bone and soft-tissue tumors more frequently than that has been previously reported, and the risk factors for lymph node metastasis were the lymphogenous histotype and primary tumors invading the subcutis.     

Improvement of region of interest extraction and scanning method of computer-aided diagnosis system for osteoporosis using panoramic radiographs

Objectives

Patients undergoing osteoporosis treatment benefit greatly from early detection. We previously developed a computer-aided diagnosis (CAD) system to identify osteoporosis using panoramic radiographs. However, the region of interest (ROI) was relatively small, and the method to select suitable ROIs was labor-intensive. This study aimed to expand the ROI and perform semi-automatized extraction of ROIs. The diagnostic performance and operating time were also assessed.

Methods

We used panoramic radiographs and skeletal bone mineral density data of 200 postmenopausal women. Using the reference point that we defined by averaging 100 panoramic images as the lower mandibular border under the mental foramen, a 400?×?100-pixel ROI was automatically extracted and divided into four 100?×?100-pixel blocks. Valid blocks were analyzed using program 1, which examined each block separately, and program 2, which divided the blocks into smaller segments and performed scans/analyses across blocks. Diagnostic performance was evaluated using another set of 100 panoramic images.

Results

Most ROIs (97.0%) were correctly extracted. The operation time decreased to 51.4% for program 1 and to 69.3% for program 2. The sensitivity, specificity, and accuracy for identifying osteoporosis were 84.0, 68.0, and 72.0% for program 1 and 92.0, 62.7, and 70.0% for program 2, respectively. Compared with the previous conventional system, program 2 recorded a slightly higher sensitivity, although it occasionally also elicited false positives.

Conclusions

Patients at risk for osteoporosis can be identified more rapidly using this new CAD system, which may contribute to earlier detection and intervention and improved medical care.

     

Japan Gastroenterological Endoscopy Society guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection

Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also several types of precarcinomatous adenomas. It is important to establish practical guidelines wherein preoperative diagnosis of colorectal neoplasia and selection of endoscopic treatment procedures are appropriately outlined and to ensure that actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society compiled colorectal endoscopic submucosal dissection/endoscopic mucosal resection guidelines by using evidence-based methods in 2014. The first edition of these guidelines was published 5 years ago. Accordingly, we have published the second edition of these guidelines based on recent new knowledge and evidence.     

Efficacy of enteral nutrition in patients with Crohn’s disease on maintenance anti-TNF-alpha antibody therapy: a meta-analysis

Enteral nutrition (EN) is effective in Crohn’s disease (CD) patients and has been shown to have an inhibitory effect on loss of response to anti-tumor necrosis factor (TNF)-alpha antibody therapy; however, the current level of evidence is not sufficient. The objective of this meta-analysis was to determine whether EN in combination anti-TNF-alpha antibody therapy is useful in maintaining remission. PubMed was used to identify all relevant studies. A total of nine articles were identified including one randomized control trial, two prospective cohort studies, and six retrospective cohort studies. We performed a meta-analysis on all these articles to assess the remission maintenance effect of EN (n = 857). The remission or response maintenance effect in the EN group was 203/288 (70.5%), which was higher than 306/569 (53.8%) in the non-EN group. The odds ratio for long-term remission or response using fixed effects model and random effects model were 2.23 (95% CI 1.60–3.10) and 2.19 (95% CI 1.49–3.22), respectively. The usefulness of EN was unclear in two prospective studies that were conducted immediately after remission induction with anti-TNF-alpha antibody therapy was detected. Differences in the definition of relapse and the observation period among articles were considered to be limitations. This analysis suggests that EN is effective for maintaining remission in patients already in remission or response as a result of anti-TNF-alpha antibody maintenance therapy.