Evaluation of safety of endoscopic biopsy without cessation of antithrombotic agents in Japan

Background

Although guidelines in Japan recommend the cessation of antithrombotic agents before endoscopic biopsy, the safety of biopsy without the cessation of these agents has not been evaluated to date in this country. Therefore, we aimed to assess the feasibility of biopsy without cessation of antithrombotic agents in Japan.

Methods

This was a prospective single-arm study from a single institution. From May 2010 to November 2011, 112 outpatients who were receiving antithrombotic agents because of their high-risk status for a thromboembolic event (after implantation of coronary stent, after valve replacement, or a previous history of thromboembolic event or heart failure due to atrial fibrillation) were enrolled. We evaluated the rate of severe bleeding complications within 2?weeks after endoscopy and the endoscopic bleeding time (EBT) after biopsy in patients who underwent biopsy for endoscopic findings requiring pathology assessment.

Results

Among the 112 participants, 101 biopsies were performed for 48 and 12 outpatients who had had esophagogastroduodenoscopy and colonoscopy, respectively. All the biopsies provided enough specimens to evaluate pathologically. Hemostasis after biopsy was confirmed for all biopsies during endoscopic observation. No patients complained of any bleeding symptoms in the 2-week observation period after biopsy (0/101; 95% confidence interval [CI] 0–3.6%). Concerning the EBT (median 2.2?±?1.8?min, range 0.5–9?min), there were no significant differences between patients receiving single antithrombotic agents and those receiving multiple agents (2.4?±?1.4 vs. 2.1?±?2.1?min), nor were there any significant differences between patients not receiving and receiving warfarin (2.3?±?1.8 vs. 2.2?±?1.8?min).

Conclusion

Biopsy without cessation of antithrombotic agents, as recommended in Western guidelines, can also be acceptable for Japanese people if performed carefully.     

Monosomy 13 in metaphase spreads is a predictor of poor long-term outcome after bortezomib plus dexamethasone treatment for relapsed/refractory multiple myeloma

We retrospectively investigated the prognostic impact of high-risk cytogenetic abnormalities (CAs) on the outcome of treatment with bortezomib plus dexamethasone (BD) in 43 relapsed/refractory (Rel/Ref) multiple myeloma patients. Fluorescence in situ hybridization (FISH) analysis identified del(13q) in 25 patients, t(4;14) in 14, t(14;16) in 4, 1q21 abnormality in 12 and del(17p) in 2, while G-banding also detected chromosome 13 monosomy (-13) in metaphase spreads from 7 patients. Eighteen of 25 patients with FISH-detected chromosome 13 abnormalities also exhibited other abnormalities. Median observation period was 510 days, and median overall survival (OS) and progression-free survival (PFS) were 912 days and 162 days, respectively. Detection of del(13q), t(4;14), t(14;16) or 1q21 abnormalities by FISH and co-occurrence of chromosome 13 abnormality with other abnormalities were not associated with poorer outcomes. In contrast, detection of -13 by G-banding in metaphase spreads showed significant association with shorter OS, although the overall response rate and PFS were not inferior to those for patients without -13 detected by G-banding. BD therapy may be a potent weapon for overcoming most classical high-risk CAs, while the detection of -13 in metaphase spreads may serve as a predictor of highly progressive disease, even when treated with BD.     

Risk Stratification for Serious Arrhythmic Events Using Nonsustained Ventricular Tachycardia and Heart Rate Turbulence Detected by 24‐Hour Holter Electrocardiograms in Patients with Left Ventricular Dysfunction

Background: Previous studies have described the clinical usefulness of the presence of nonsustained ventricular tachycardia (NSVT) and defined heart rate turbulence (HRT) in stratifying patients at risk. We prospectively assessed whether HRT can facilitate the predictive accuracy of NSVT for identifying patients at risk for serious arrhythmic events in patients with left ventricular (LV) dysfunction. Methods: We enrolled 299 consecutive patients with LV dysfunction (ejection fraction ≤ 40%) including ischemic (n = 184) and nonischemic causes (n = 115). The presence of NSVT was assessed on Holter electrocardiograms (ECGs). HRT was simultaneously measured from Holter ECGs, assessing two parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO and TS were abnormal. The end point was defined as of sudden cardiac death (SCD) and sustained ventricular tachyarrhythmias (VTs). Results: NSVT was documented in 93 patients (32.7%). For HRT assessment, 17 patients (5.6%) were not utilized. Of 282 patients, 68 (24.1%) were HRT positive. During follow‐up of 960 ± 444 days, 14 patients (5.0%) reached the end point. NSVT, HRT, and diabetes were significantly associated with the end point. On multivariate analysis, NSVT had the strongest value for the end point, with an HR of 4.4 (95%CI, 1.4–14.3; P = 0.0138). When NSVT combined with HRT, the predictive accuracy is more increased, with an HR of 8.2 (95%CI, 2.9–23.3; P < 0.0001). The predictive values of the combination were higher than single use of NSVT or HRT. Conclusions: HRT can facilitate the predictive accuracy of NSVT for identifying patients at risk for serious arrhythmic events in patients with LV dysfunction.     

A newly designed bioabsorbable substitute for the treatment of diaphragmatic defects

Purpose

Earlier studies have investigated the suitability of various materials and autologous grafts for the repair of diaphragmatic defects. Our group investigated the feasibility of using an artificial diaphragm (AD) to repair wide diaphragmatic defects.

Methods

Twelve pigs were laparotomized and, in each pig, a defect was fashioned by resecting a round 8-cm diameter hole in the left diaphragm. Next, the defect was repaired by implanting an AD. The animals were relaparotomized 8 or 24 weeks after implantation for gross, histological and radiological observation of the implanted sites.

Results

All recipient animals survived until killing for evaluation. Chest X-ray examinations showed no differences between the preoperative diaphragms and the grafted diaphragms at 8 and 24 weeks after implantation. At 8 weeks after implantation, the implanted sites exhibited fibrous adhesions to the liver and lungs without deformities or penetrations. Parts of the surface tissue at the graft sites had a varnished appearance similar to those of the native diaphragm. Histology performed at 8 weeks detected no trace of the ADs in the graft sites; however, numerous inflammatory cells and profuse fibrous connective tissue were observed. At 24 weeks after implantation, no differences were found in the thorax between the areas with the grafts and the unaffected areas. Histology of the graft sites in the thorax confirmed growth of mesothelial cells similar to that observed in the native diaphragm.

Conclusions

Artificial diaphragms can be a novel substitute for diaphragmatic repair.     

Eating Behavior and Glucagon-Like Peptide-1-Producing Cells in Interposed Ileum and Pancreatic Islets in Rats Subjected to Ileal Interposition Associated with Sleeve Gastrectomy

Background

Ileal interposition–sleeve gastrectomy (II–SG) has been developed as a metabolic surgery based on the hindgut hypothesis. The aim of the present study was to test this hypothesis by studying the eating behavior, metabolic changes, and glucagon-like peptide-1 (GLP-1)-producing cells in rat models.

Methods

Male Sprague–Dawley rats were subjected to laparotomy, II, SG, or II–SG. Eating behavior and metabolic parameters were monitored by an open-circuit indirect calorimeter designed for a comprehensive laboratory animal monitoring system. GLP-1-producing cells were examined by quantitative immunohistochemistry.

Results

After II alone, satiety ratio, i.e., intermeal interval/meal size, was reduced, while calorie intake was increased at 2 and 6 weeks postoperatively. Respiratory exchange ratio, VCO₂/VO₂, was increased to above 1.0 (i.e., carbohydrate metabolism) during both daytime and nighttime at 2 weeks postoperatively. After SG alone, GLP-1-producing cells were increased in the pancreatic islets (in terms of volume density), but not in the ileum (number/mm). After II–SG, the rate of eating was reduced, while meal duration (min) was increased during both daytime and nighttime at 2 weeks postoperatively. GLP-1-producing cells were increased by about 2.5-fold in the interposed ileum and also increased to the same extent in the pancreatic islets as seen after SG alone. The increased GLP-1-producing cells in the pancreatic islets after SG or II–SG were located around the insulin-producing β cells.

Conclusions

The present study provides evidence supporting the hindgut hypothesis. II–SG increased GLP-1 production both in the interposed ileum and in the pancreatic islets, leading to metabolic beneficial effects and altered eating behavior.