The impact of abdominal compression on outcome in patients treated with stereotactic body radiotherapy for primary lung cancer

The aim of this study was to evaluate the impact of abdominal compression (AC) on outcome in patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer. We retrospectively reviewed data for 47 patients with histologically proven non-small cell lung cancer and lung tumour motion ≥8 mm treated with SBRT. Setup error was corrected based on bony structure. The differences in overall survival (OS), local control (LC) and disease-free survival (DFS) were evaluated to compare patients treated with AC (n = 22) and without AC (n = 25). The median follow-up was 42.6 months (range, 1.4–94.6 months). The differences in the 3-year OS, LC and DFS rate between the two groups were not statistically significant (P = 0.909, 0.209 and 0.639, respectively). However, the largest difference was observed in the LC rate, which was 82.5% (95% CI, 54.9–94.0%) for patients treated without AC and 65.4% (95% CI, 40.2–82.0%) for those treated with AC. After stratifying the patients into prognostic groups based on sex and T-stage, the LC difference increased in the group with an unfavourable prognosis. The present study suggests that AC might be associated with a worse LC rate after SBRT using a bony-structure-based set-up.     

Nardilysin prevents amyloid plaque formation by enhancing α-secretase activity in an Alzheimer's disease mouse model

Amyloid beta (Aβ) peptide, the main component of senile plaques in patients with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Alpha-cleavage of APP by α-secretase has a potential to preclude the generation of Aβ because it occurs within the Aβ domain. We previously reported that a metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances α-cleavage of APP, which results in the decreased generation of Aβ in vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that the neuron-specific overexpression of NRDc prevents Aβ deposition in the AD mouse model. The activity of α-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. However, reactive gliosis adjacent to the Aβ plaques, one of the pathological features of AD, was not affected by the overexpression of NRDc. Taken together, our results indicate that NRDc controls Aβ formation through the regulation of α-secretase.     

Intraductal dissemination of papillary adenocarcinoma of the ampulla of Vater in the pancreatic duct

It has been speculated that intraductal dissemination, via the pancreatic duct, bile duct, or mammary duct, is a unique form of cancer cell spread. However, clinical evidence to confirm this form of dissemination has been lacking. Here we report a case of papillary adenocarcinoma of the ampulla of Vater in which retrograde dissemination to the pancreatic duct was strongly suggested. A 79‐year‐old woman underwent pancreatoduodenectomy for a 22 mm microinvasive papillary adenocarcinoma of the ampulla. Multiple carcinomas in situ were found in the pancreatic duct distant from the ampulla. Seven months later, she underwent a second operation for a recurrent papillary adenocarcinoma at the pancreato‐jejunal anastomosis showing exophytic and expansive growth into the jejunal lumen that connected to an intraductal adenocarcinoma in the pancreatic body. None of these tumors showed invasive growth, or vascular or neural invasion, being separate from each other but sharing identical histological, immunohistochemical, and molecular features; papillary growth, a pancreatobiliary phenotype, the same pattern of genomic loss of heterozygosity, and no mutation of the KRAS, TP53, and GNAS genes. These results imply that this papillary adenocarcinoma of the ampulla of Vater had disseminated to the pancreatic duct in a retrograde manner and recurred in the remnant pancreas.     

Aerobic Exercise Attenuates the Loss of Skeletal Muscle during Energy Restriction in Adults with Visceral Adiposity

ObjectiveTo evaluate the effects of energy restriction with or without aerobic exercise on thigh muscle mass and quality in adults with visceral adiposity.Methods75 males and females were randomly assigned to the groups ‘diet only’ (DO; n = 42) or ‘diet plus aerobic exercise’ (D/Ex; n = 33) for 12 weeks. The target energy intake in both groups was 25 kcal/kg of ideal body weight. Subjects in the D/Ex group were instructed to exercise for ≥300 min/week at lactate threshold. Computed tomography was used to measure thigh muscle cross-sectional area (CSA), normal-density muscle area (NDMA), and visceral fat area.ResultsTotal body weight (DO: −6.6 ± 3.6%; D/Ex: −7.3 ± 4.6%) and visceral fat (DO: −16.0 ± 13.8%; D/Ex: −23.1 ± 14.7%) decreased significantly in both groups; however, the changes were not significantly different between the two groups. The decrease in muscle CSA was significantly greater in the DO group (-5.1 ± 4.5%) compared with the D/Ex group (-2.5 ± 5.0%). NDMA decreased significantly in the DO (-4.9 ± 4.9%) but not in the D/Ex group (-1.4 ± 5.0%).ConclusionAerobic exercise attenuated the loss of skeletal muscle during energy restriction in adults with visceral adiposity.Key Words: Aerobic exercise, Skeletal muscle, Normal density muscle, Visceral adiposity, Energy restriction     

Primary cutaneous diffuse large B‐cell lymphoma,leg type,with features simulating POEMS syndrome

A 91‐year‐old woman presented with a rapidly proliferative cutaneous lesion on the left lower limb, which was identified as a primary cutaneous diffuse large B‐cell lymphoma (PCLBCL), leg type, on biopsy. The patient also showed complications of hepatomegaly, endocrinopathy, edema, skin change, and polyneuropathy without monoclonal plasma cell proliferative disorder, and was therefore diagnosed with POEMS‐like syndrome owing to the lack of monoclonal plasma cell proliferative disorder. Levels of serum vascular endothelial growth factor (VEGF) and interleukin‐6 (IL‐6) were high with the lymphoma cells immunostained positively for VEGF and IL‐6. To the best of our knowledge, this is the first case report of PCLBCL, leg type, with POEMS‐like syndrome. The findings in this case suggest that the symptoms of POEMS‐like syndrome might be caused by the cytokines produced by the lymphoma cells. Furthermore, a wider range of diagnostic criteria associated with the result of abnormal secretion of cytokine may have to be considered for the diagnosis and evaluation of patients with possible POEMS syndrome, as against the present criteria specifying monoclonal plasma cell proliferative disorder as the essential criterion.     

IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis

PURPOSE: Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted. EXPERIMENTAL DESIGN: Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of > or =2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes. RESULTS: SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis. CONCLUSION: Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.     

Changes of gene expression profiles in macrophages stimulated by angiotensin II--angiotensin II induces MCP-2 through AT1-receptor.

INTRODUCTION: Macrophages play critical roles in the development of atherosclerosis and diabetic nephropathy as well as many inflammatory diseases. Angiotensin II type 1 receptor antagonists (AIIA) are beneficial for the prevention of atherosclerosis and diabetic nephropathy suggesting that angiotensin II (Ang II) promotes the development of these diseases. It has recently been reported that Ang II exerts proinflammatory actions in vivo and in vitro. This study was aimed to clarify the direct effects of Ang II on monocytes/macrophages. MATERIALS AND METHODS: PMA-treated THP-1 cells, a human monocytic leukaemia cell line, were treated with Ang II (10-6 mol/L) for 24 hours with or without AIIA (CV11974). We evaluated gene expression profiles of these cells using DNA microarray system and quantified them by real-time RT-PCR. RESULTS: DNA microarray revealed that in total 19 genes, including monocyte chemoattractant protein (MCP)-2, were up-regulated by Ang II and down-regulated by AIIA. Real-time RT-PCR showed that up-regulation of MCP-2 with Ang II is blocked by the AIIA (CV11974) but not by an AT2-receptor antagonist. CONCLUSIONS: These results suggest that Ang II directly stimulates MCP-2 expression through AT1-receptors in activated macrophages. Ang II may contribute to the persistence or amplification of microinflammation in vessel walls, heart and kidney. Vasculoprotective or renoprotective effects of AIIA might partly depend on direct anti-inflammatory effects on macrophages.     

Urinary Fibrin and Fibrinogen Degradation Products and the Origin of Hematuria

We examined urinary fibrin and fibrinogen degradation product (U-FDP) concentrations in pediatric patients with hematuria using the rapid and highly-sensitive latex particle agglutination test (LPAT), and assessed the value of this test for the localization of the site of hematuria. Patients with hematuria were divided into two groups: 60 with glomerular hematuria and 46 with non-glomerular hematuria. If U-FDP concentrations less than 0.25 μg/ml are Accepted as an indicator of glomerular bleeding, the sensitivity and specificity of localization of glomerular hematuria in the present study were 78% (47/60) and 89% (41/46), respectively. The high U-FDP concentrations observed in patients with non-glomerular hematuria may reflect direct bleeding into the urinary tract. Since all 13 patients with glomerular hematuria and U-FDP concentrations of 0.25 μg/ml or more had coexistent erythrocyte cylindruria, the U-FDP test seems to be compensated with combined urinalysis for the relatively lower sensitivity. We conclude that a knowledge of U-FDP concentrations by LPAT can be of help in localizing the site of bleeding in hematuria.