Elipse, the first procedureless gastric balloon for weight loss: a prospective, observational, open-label, multicenter study.

Background and study aims Conventional gastric balloons for weight loss require endoscopy for placement and removal. The Elipse device is swallowed, resides in the stomach for 4 months, and is then expelled. The objectives of this study were to assess the safety of Elipse and to measure its effects on weight loss, metabolic parameters, and quality of life. Methods Each participant swallowed one Elipse device, which was filled with 550 mL of filling fluid through a thin delivery catheter that was then removed. Weight was measured every 2 weeks, and metabolic parameters and quality of life were assessed at baseline and at trial exit. Results 34 patients, with a mean body mass index of 34.8 kg/m2, were enrolled. All 34 patients successfully swallowed the Elipse device. All adverse events were either self-limiting or resolved with medication. All balloons were safely excreted. At 4 months, the mean percent total body weight loss was 10 %. Mean waist circumference was reduced by 8.4 cm. Improvements were also seen in hemoglobin A1c, triglycerides, low density lipoprotein, and blood pressure. At trial exit, quality of life measures had improved across all domains. Conclusion These results demonstrate clinically significant weight loss with the Elipse, the first procedureless gastric balloon. The weight loss was similar to that seen in previous studies of endoscopically placed balloons. In addition, Elipse therapy led to improvements in waist circumference, several metabolic parameters, and overall quality of life.ClinicalTrials.gov identifier: NCT 02802007.

Prediction of Low versus High Recurrence Scores in Estrogen Receptor-Positive, Lymph Node-Negative Invasive Breast Cancer on the Basis of Radiologic-Pathologic Features: Comparison with Oncotype DX Test Recurrence Scores.

Purpose To review mammographic, ultrasonographic (US), and magnetic resonance (MR) imaging features and pathologic characteristics of estrogen receptor (ER)-positive, lymph node-negative invasive breast cancer and to determine the relationship of these characteristics to Oncotype DX (Genomic Health, Redwood City, Calif) test recurrence scores (ODRS) for breast cancer recurrence. Materials and Methods This institutional review board-approved retrospective study was performed in a single large academic medical center. The study population included patients with ER-positive, lymph node-negative invasive breast cancer who underwent genomic testing from January 1, 2009, to December 31, 2013. Imaging features of the tumor were classified according to the Breast Imaging Reporting and Data System lexicon by breast imagers who were blinded to the ODRS. Mammography was performed in 86% of patients, US was performed in 84%, and MR imaging was performed in 33%, including morphologic and kinetic evaluation. Images from each imaging modality were evaluated. Each imaging finding, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, and tumor grade were then individually correlated with ODRS. Analysis of variance was used to determine differences for each imaging feature. Regression analysis was used to calculate prediction of recurrence on the basis of imaging features combined with histopathologic features. Results The 319 patients had a mean age ± standard deviation of 55 years ± 8.7 (range, 31-82 years). Imaging features with a positive correlation with ODRS included a well-circumscribed oval mass (P = .024) at mammography, vascularity (P = .047) and posterior enhancement (P = .004) at US, and lobulated mass (P = .002) at MR imaging. Recurrence scores were predicted by using these features in combination with PR and HER2 status and tumor grade by using the threshold of more than 30 as a high recurrence score. With a regression tree, there was correlation (r = 0.79) with 89% sensitivity and 83% specificity. Conclusion On the basis of preliminary data, information obtained routinely for breast cancer diagnosis can reliably be used to predict the ODRS with high sensitivity and specificity. (©) RSNA, 2016.

Role of videourodynamics in the identification of causes of lower urinary tract symptoms and low uroflow in young men.

Introduction: The etiology of lower urinary tract symptoms (LUTS) is multifactorial with causes attributed either to the dysfunction of the bladder or its outlet. Although the etiologies are well studied in aged men, very limited research trials are available in young men with LUTS. Most of the time young men presenting with chronic irritative or obstructive symptoms are labeled with chronic prostatitis or prostatodynia and are treated empirically. In this study using videourodynamics, we prospectively investigated the etiologies of LUTS and low uroflow in young men. Materials and Methods: Fifty male patients, 18-50 years of age attending the urology outpatient department at a tertiary care center from January 2021 to December 2021 with symptoms suggestive of chronic LUTS and low uroflow (maximum urinary flow rate [Qmax] <15 ml/s at a voided volume >150 ml) were included in the study and underwent multichannel videourodynamic study (VUDS). Clinical characteristics and urodynamic results in different diagnostic groups were tabulated and analyzed. The P ≤ 0.05 was considered statistically significant. Results: Out of 50 enrolled patients, primary bladder neck obstruction was seen in 21 patients (42%), dysfunctional voiding in 14 (28%), impaired detrusor contractility (IDC) in 9 (18%), and benign prostatic obstruction (BPO) was noted in 6 patients (12%). The mean age and size of the prostate of patients with BPO were greater than those in the remaining groups and patients with IDC had lower Qmax and Pdet at Qmax than those in the remaining patients. Conclusion: Chronic LUTS in young men has a variety of underlying etiologies and VUDS in this population is helpful in attaining an accurate diagnosis and thus may guide toward efficient management.

Intragastric balloons in high-risk obese patients in a Brazilian center: initial experience.

OBJECTIVE: to assess the short-term efficacy, tolerance and complications in high-risk morbidly obese patients treated with an intragastric balloon as a bridge for surgery. METHODS: we conducted a post-hoc analysis study in a Brazilian teaching hospital from 2010 to 2014, with 23 adult patients with a BMI of 48kg/m2, who received a single intragastric air or liquid balloon. We defined efficacy as 10% excess weight loss, and complications, as adverse events consequent to the intragastric balloon diagnosed after the initial accommodative period. We expressed the anthropometric results as means ± standard deviation, comparing the groups with paired T / Student's T tests, when appropriate, with p<0.05 considered statistically significant. RESULTS: the balloons were effective in 91.3% of the patients, remained in situ for an average of 5.5 months and most of them (65.2%) were air-filled, with a mean excess weight loss of 23.7kg±9.7 (excess weight loss 21.7%±8.9) and mean BMI reduction of 8.3kg/m2±3.3. Complications (17.3%) included abdominal discomfort, balloon deflation and late intolerance, without severe cases. Most of the participants (82.7%) did not experience adverse effects. We removed the intragastric balloons in time, without intercurrences, and 52.2% of these patients underwent bariatric surgery within one month. CONCLUSION: in our center, intragastric balloons can be successfully used as an initial weight loss procedure, with good tolerance and acceptable complications rates.

Elipse™, a Procedureless Gastric Balloon for Weight Loss: a Proof-of-Concept Pilot Study.

BACKGROUND: Endoscopic gastric balloons have been used effectively as weight loss devices for decades, but the requirement for endoscopy and sedation poses several limitations. The goal of this pilot study was to evaluate the safety and performance of a prototype version of Elipse™, a procedureless gastric balloon. METHODS: Eight patients (mean BMI = 31.0 kg/m(2)) participated in this study. Each patient swallowed one Elipse™ balloon intended to remain in the stomach for 6 weeks, self-empty, and then pass. Each balloon was filled with 450 mL of filling fluid. Patients returned every 2 weeks for abdominal ultrasound. No specific diet or exercise plan was prescribed. RESULTS: All eight patients successfully swallowed the device. The most common adverse events were nausea and vomiting. There were no serious adverse events, and all balloons were excreted safely. Despite not being prescribed a diet or exercise plan, all eight patients lost weight. In 6/8 patients, the balloon remained full through 6 weeks, self-emptied, and passed. In one patient, the balloon appeared partially collapsed on ultrasound after 11 days and was endoscopically punctured. One asymptomatic patient elected to have the balloon endoscopically punctured after 19 days. Both balloons passed in the stool after 4 days. In both cases, endoscopic examination of the upper GI tract showed no abnormalities. CONCLUSIONS: This pilot study demonstrates the safety and performance of Elipse™, a procedureless gastric balloon for weight loss. Future studies will test a commercial design filled to 550 mL intended to last in the stomach for at least 12 weeks.

Intragastric balloons in high-risk obese patients in a Brazilian center: initial experience / Balões intragástricos em obesos de alto risco em um centro brasileiro: experiência inicial

ABSTRACT Objective: to assess the short-term efficacy, tolerance and complications in high-risk morbidly obese patients treated with an intragastric balloon as a bridge for surgery. Methods: we conducted a post-hoc analysis study in a Brazilian teaching hospital from 2010 to 2014, with 23 adult patients with a BMI of 48kg/m2, who received a single intragastric air or liquid balloon. We defined efficacy as 10% excess weight loss, and complications, as adverse events consequent to the intragastric balloon diagnosed after the initial accommodative period. We expressed the anthropometric results as means ± standard deviation, comparing the groups with paired T / Student's T tests, when appropriate, with p<0.05 considered statistically significant. Results: the balloons were effective in 91.3% of the patients, remained in situ for an average of 5.5 months and most of them (65.2%) were air-filled, with a mean excess weight loss of 23.7kg±9.7 (excess weight loss 21.7%±8.9) and mean BMI reduction of 8.3kg/m2±3.3. Complications (17.3%) included abdominal discomfort, balloon deflation and late intolerance, without severe cases. Most of the participants (82.7%) did not experience adverse effects. We removed the intragastric balloons in time, without intercurrences, and 52.2% of these patients underwent bariatric surgery within one month. Conclusion: in our center, intragastric balloons can be successfully used as an initial weight loss procedure, with good tolerance and acceptable complications rates.

RESUMO Objetivo: identificar a eficácia em curto prazo, a tolerância e as complicações em obesos mórbidos de alto risco, tratados com balão intragástrico como ponte para cirurgia. Métodos: estudo de análise post-hoc em um hospital acadêmico brasileiro durante o período de 2010 a 2014, de 23 pacientes adultos com IMC de 48kg/m2 que receberam um único balão intragástrico de ar ou líquido. Eficácia foi definida como perda de excesso de peso de 10%, e complicações como eventos adversos consequentes ao balão intragástrico diagnosticados após o período acomodativo inicial. Expressaram-se os resultados antropométricos com média ± desvio padrão, comparando os grupos com testes T Pareado / T de Student, quando apropriado, com p<0,05 considerado estatisticamente significante. Resultados: os balões foram efetivos em 91,3% dos pacientes, permaneceram in situ por em média 5,5 meses e a maioria deles (65,2%) era de ar, com perda média de excesso peso de 23,7kg±9,7 (perda de excesso de peso de 21,7%±8,9) e redução média de IMC de 8,3kg/m2±3,3. As complicações (17,3%) compreenderam desconforto abdominal, deflação do balão e intolerância tardia, sem casos graves. A maioria dos participantes (82,7%) não experimentou efeitos adversos, seus balões intragástricos foram extraídos em tempo, sem intercorrências e 52,2% desses pacientes submeteram-se à cirurgia bariátrica no intervalo de um mês. Conclusão: no nosso centro, balões intragástricos podem ser usados com sucesso como procedimento inicial de perda ponderal, com boa tolerância e taxas aceitáveis de complicações.

Hepatic arterial chemoembolization using drug-eluting beads in gastrointestinal neuroendocrine tumor metastatic to the liver.

PURPOSE: This study was designed to evaluate short (<3 months) and intermediate-term (>3 months) follow-up in patients with metastatic neuroendocrine tumor to the liver who underwent hepatic arterial chemoembolization with drug-eluting beads at a single institution. METHODS: Institutional review board approval was obtained for this retrospective review. All patients who were treated with 100-300 or 300-500 µm drug-eluting LC Beads (Biocompatibles, UK) preloaded with doxorubicin (range, 50-100 mg) for GI neuroendocrine tumor metastatic to the liver from June 2004 to June 2009 were included. CT and MRI were evaluated for progression using Response Evaluation Criteria In Solid Tumors (RECIST) or European Association for the Study of the Liver (EASL) criteria. Short-term (<3 months) and intermediate-term (>3 months) imaging response was determined and Kaplan-Meier survival curves were plotted. RESULTS: Thirty-eight drug-eluting bead chemoembolization procedures were performed on 32 hepatic lobes, comprising 21 treatment cycles in 18 patients. All procedures were technically successful with two major complications (biliary injuries). At short-term follow-up (<3 months), 22 of 38 (58%) procedures and 10 of 21 (48%) treatment cycles produced an objective response (OR) with the remainder having stable disease (SD). At intermediate-term follow-up (mean, 445 days; range, 163-1247), 17 of 26 (65%) procedures and 8 of 14 (57%) treatment cycles produced an OR. Probability of progressing was approximately 52% at 1 year with a median time to progression of 419 days. CONCLUSIONS: Drug-eluting bead chemoembolization is a reasonable alternative to hepatic arterial embolization and chemoembolization for the treatment of metastatic neuroendocrine tumor to the liver.

Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage.

Microtubule inhibitors are important cancer drugs that induce mitotic arrest by activating the spindle assembly checkpoint (SAC), which, in turn, inhibits the ubiquitin ligase activity of the anaphase-promoting complex (APC). Here, we report a small molecule, tosyl-L-arginine methyl ester (TAME), which binds to the APC and prevents its activation by Cdc20 and Cdh1. A prodrug of TAME arrests cells in metaphase without perturbing the spindle, but nonetheless the arrest is dependent on the SAC. Metaphase arrest induced by a proteasome inhibitor is also SAC dependent, suggesting that APC-dependent proteolysis is required to inactivate the SAC. We propose that mutual antagonism between the APC and the SAC yields a positive feedback loop that amplifies the ability of TAME to induce mitotic arrest.

Disease-associated mutations affect GPR56 protein trafficking and cell surface expression.

Bilateral frontoparietal polymicrogyria (BFPP) is a congenital brain malformation resulting in irregularities on the surface of the cortex, where normally convoluted gyri are replaced by numerous (poly) and noticeably smaller (micro) gyri. Individuals with BFPP suffer from epilepsy, mental retardation, language impairment and motor developmental delay. Mutations in the gene-encoding G protein-coupled receptor 56 (GPR56) cause BFPP; however, it remains unclear how these mutations affect GPR56 function. Here, we examine the biochemical properties and protein trafficking of wild-type and mutant GPR56. We demonstrate that GPR56 protein undergoes two major modifications, GPS domain-mediated protein cleavage and N-glycosylation, and that the N-terminal fragment can be released from the cell surface. In contrast to the wild-type protein, disease-associated GPR56 missense mutations in the tip of the N-terminal domain (R38Q, R38W, Y88C and C91S) produce proteins with reduced intracellular trafficking and poor cell surface expression, whereas the two mutations in the GPS domain (C346S and W349S) produce proteins with dramatically impaired cleavage that fail to traffic beyond the endoplasmic reticulum. Cell-trafficking impairments are abrogated in part by pharmacological chaperones that can partially rescue mutant GPR56 cell surface expression. These data demonstrate that some BFPP-associated mutations in GPR56 impair trafficking of the mutant protein to the plasma membrane, thus providing insights into how BFPP-associated mutations affect GPR56 function.