Summary Background Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles. On the basis of promising results from a phase 1/2 trial ...assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer (NSCLC), we aimed to assess efficacy and safety of this combination in a phase 3 trial. Methods In our double-blind, placebo-controlled, randomised phase 3 trial (BeTa), we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment. Patients were randomly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab (bevacizumab group) or erlotinib plus placebo (control group) according to a computer-generated randomisation sequence by use of an interactive voice response system. The primary endpoint was overall survival in all enrolled patients. Patients, study staff, and investigators were masked to treatment assignment. We assessed safety by calculation of incidence of adverse events and tissue was collected for biomarker analyses. This trial is registered with ClinicalTrials.gov , number NCT00130728. Findings Overall survival did not differ between 317 controls and 319 patients in the bevacizumab group (hazard ratio HR 0·97, 95% CI 0·80–1·18, p=0·7583). Median overall survival was 9·3 months (IQR 4·1–21·6) for patients in the bevacizumab group compared with 9·2 months (3·8–20·2) for controls. Progression-free survival seemed to be longer in the bevacizumab group (3·4 months 1·4–8·4) than in the control group (1·7 months 1·3–4·1; HR 0·62, 95% CI 0·52–0·75) and objective response rate suggested some clinical activity of bevacizumab and erlotinib. However, these secondary endpoint differences could not be defined as significant because the study prespecified that the primary endpoint had to be significant before testing of secondary endpoints could be done, to control type I error rate. In the bevacizumab group, 130 (42%) of 313 patients with safety data had a serious adverse event, compared with 114 (36%) controls. There were 20 (6%) grade 5 adverse events, including two arterial thromboembolic events, in the bevacizumab group, and 14 (4%) in the control group. Interpretation Addition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC. Funding Genentech.
Abstract Objective To provide recommendations for the comprehensive management of young infants who present with signs or symptoms concerning for laryngomalacia. Methods Expert opinion by the members ...of the International Pediatric Otolaryngology Group (IPOG). Results Consensus recommendations include initial care and triage recommendations for health care providers who commonly evaluate young infants with noisy breathing. The consensus statement also provides comprehensive care recommendations for otolaryngologists who manage young infants with laryngomalacia including: evaluation and treatment considerations for commonly debated issues in laryngomalacia, initial work-up of infants presenting with inspiratory stridor, treatment recommendations based on disease severity, management of the infant with feeding difficulties, post-surgical treatment management recommendations, and suggestions for acid suppression therapy. Conclusion Laryngomalacia care consensus recommendations are aimed at improving patient-centered care in infants with laryngomalacia. Level of evidence 5
Background and Aims EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical ...histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis. Methods Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval CI), and intraobserver reliability (IOR, mean ± standard deviation SD) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used. Results A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively. Conclusions EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488 .)
Abstract We queried the National Surgical Quality Improvement Program to compare the rate of 30-day readmissions and major complications between simultaneous bilateral and unilateral total knee ...arthroplasty (TKA). We identified 1771 patients who underwent simultaneous (same-day) bilateral TKA and matched them to a control group of 6790 patients who underwent unilateral TKA. The simultaneous bilateral TKA patients had longer surgery, were more commonly performed under general anesthesia, had a higher rate of postoperative transfusion, and a greater proportion of patients discharged to rehabilitation facilities. Simultaneous bilateral TKA has a low incidence of major complications and was not associated with more readmissions as compared to unilateral TKA (3.6% versus 3.5% respectively). Nonetheless, the odds of major complications was slightly higher following simultaneous bilateral TKA (OR = 1.58).
Background and Aims Serrated epithelial change (SEC) is a histologic finding in longstanding colitis that may be associated with dysplasia. Our primary aim was to determine the incidence of dysplasia ...and colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients with SEC. Secondary aims were to determine the rate of location concordance between SEC and dysplasia/CRC and to identify other risk factors associated with dysplasia in IBD patients with SEC. Methods A retrospective, descriptive, observational study was performed by searching the Pathology Data System at a single tertiary referral center for a histologic finding of “serrated epithelial change.” The patient’s first pathology specimen with SEC was designated the index SEC. All subsequent pathology reports were evaluated for the occurrence and location of dysplasia or CRC. Univariable and multivariable logistic regression were performed to identify predictors of dysplasia. Results There were 187 patients with confirmed IBD and 1 or more histologic findings of SEC without prior dysplasia. Mean IBD duration was 16 years, and median follow-up time was 28 months. The rate of high-grade dysplasia or CRC was 17 per 1000 patient-years. Thirty-nine of 187 patients (21%) had synchronous or metachronous dysplasia or CRC. Location concordance was 68%. Multivariable analysis found SEC on follow-up examinations, older age at IBD diagnosis, male gender, and a first-degree relative with CRC were associated with dysplasia in IBD patients with SEC. Conclusions This uncontrolled study describes a high frequency of dysplasia in patients with a histologic finding of SEC. SEC seen on successive endoscopic examinations further increased the risk of dysplasia. Further controlled studies are needed to determine if SEC is a precancerous lesion in IBD patients and if SEC can be endoscopically identified.
Background Challenges in EUS-guided FNA (EUS-FNA) include sampling error, nondiagnostic cytology, and limited on-site cytological evaluation. A prototype needle-based confocal laser endomicroscopy ...(nCLE) probe is a submillimeter probe that provides real-time imaging at the microscopic level through the FNA needle. Objective To evaluate the feasibility of nCLE during EUS-FNA of pancreatic lesions. Design Feasibility study. Setting Multicenter, tertiary care. Patients Eighteen patients presenting for EUS-FNA. Interventions Patients were injected with 2.5 mL of 10% fluorescein. The lesion was interrogated with the nCLE probe positioned at the tip of a 19-gauge FNA needle. Main Outcome Measurements Device integrity, technical ease, safety, and image acquisition. Results Cases included 16 cysts and 2 masses. There were no device malfunctions. Technical challenges were encountered in 6 of 18 attempts to image and reflected challenges with a postloading technique, the longer ferule tip, and a transduodenal approach. Technical feasibility to perform imaging with nCLE during a pancreatic EUS-FNA procedure was achieved in 17 of 18 cases. Ten cases had good to very good image quality. Two serious adverse events occurred; both were pancreatitis requiring hospitalization. Limitations Limited sample size, small number of patients with confirmed pathological diagnosis, lack of coregistered pathology and images. Conclusions nCLE in the pancreas is technically feasible via a 19-gauge needle under endosonographic guidance. Future studies will address identification of structures, diagnostic accuracy, and complication profiles. The rate of pancreatitis needs to be further clarified and mitigated.
Background and Aims EMR is increasingly used for resection of sporadic, nonampullary duodenal adenomas (SNDAs), but there are no guidelines for the management of these lesions. The aims of this study ...were to evaluate the safety and efficacy of EMR exclusively for SNDAs and to determine the factors predictive of outcomes. Methods We performed a retrospective review of patients with SNDAs referred for endoscopic therapy from 2006 to 2013. The outcomes studied were successful endoscopic resection, major adverse events, early and late recurrences, and clinical remission. Results Sixty-eight patients with SNDAs were included and 51 (75%) underwent EMR. The mean adenoma size was 22.0 ± 8.9 mm. Successful resection was achieved in 49 of 51 patients (96.1%), and major adverse events were noted in 8 of 51 patients (15.7%). Early and late recurrences were noted in 25.6% and 5.2% of patients, respectively, and were treated endoscopically. Clinical remission was achieved in 89.7% of patients after a median follow-up of 15 months. Presence of villous histology was associated with increased recurrence ( P = .019), but no association of recurrence was noted with other endoscopic features or resection technique. Large adenoma size ( P = .0057) and need for intraprocedural hemostasis ( P = .006) were associated with increased adverse events, but no association of adverse events was noted with location or resection technique. Conclusions Large duodenal adenomas can be effectively managed with EMR at a referral center with experienced endoscopists. However, EMR has a significant recurrence rate, especially early recurrence, and the risk of adverse events is not negligible. Endoscopic therapy is successful in managing recurrent adenomas.
The term "alcoholic liver disease" encompasses a spectrum of pathologic conditions ranging from isolated steatosis to established cirrhosis. Within this spectrum, varying degrees of inflammation, ...hepatocellular ballooning degeneration, hepatocyte necrosis, cholestasis, and fibrosis may be encountered. This article reviews the characteristic histologic features of the many forms of alcoholic liver disease. Histologic scoring systems are described, and diseases with overlapping morphologic features and comorbid conditions are also discussed.
Background Treatment options for periprosthetic distal femur fractures include open reduction and internal fixation (ORIF) and distal femoral replacement (DFR). The purpose of this study was to ...evaluate the complications, and functional recovery (ambulatory status, living situation, mortality) in patients undergoing operative treatment (DFR and ORIF) of periprosthetic distal femur fractures. Methods A retrospective review of 58 patients with distal femoral periprosthetic fractures treated with either ORIF or DFR was conducted. Surgical complications, discharge disposition, ambulatory status, living situation at one-year, and mortality at one-year were compared between patients treated with ORIF and DFR. Outcomes at one-year were also compared between patients older and younger than 85 years of age. Results 58 patients with a mean age of 80 years (range 61-95) met inclusion criteria. The mean follow-up was 29.5 (5-81) months. Patients undergoing DFR were significantly older than those who underwent ORIF (83 vs 78, p<.01). The one-year mortality rate was 20.6%. There was no difference between groups with respect to mortality, complications, discharge disposition, or ambulatory status and living situation at one-year. Patients who lost the ability to ambulate at one-year were significantly older than patients who maintained the ability to ambulate (87.5 vs 76.4 years, p<.05). Patients over the age of 85 were more likely to lose the ability to ambulate and to live in a skilled nursing facility at one-year (p<.01). Conclusion Distal femoral periprosthetic fractures have a high morbidity and mortality. Age at time of injury, not treatment rendered, is predictive of ambulatory status and living independence after periprosthetic distal femur fractures.
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