Background A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. Objective We aimed for assessment of ...the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. Methods Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis–free, and overall survivals. Results GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB ( P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis–free, and overall survivals were 35%, 49%, and 54%, respectively. Limitations Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. Conclusions In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients.
Background The prognosis of esophageal cancer (EC) depends on the depth of tumor invasion and lymph node metastasis. EC limited to the mucosa (T1a) can be treated effectively with minimally invasive ...endoscopic therapy, whereas submucosal (T1b) EC carries relatively high risk of lymph node metastasis and requires surgical resection. Objective To determine the diagnostic accuracy of EUS in differentiating T1a EC from T1b EC. Design We performed a comprehensive search of MEDLINE, SCOPUS, Cochrane, and CINAHL Plus databases to identify studies in which results of EUS-based staging of EC were compared with the results of histopathology of EMR or surgically resected esophageal lesions. DerSimonian-Laird random-effects model was used to estimate the pooled sensitivity, specificity, and likelihood ratio, and a summary receiver operating characteristic (SROC) curve was created. Setting Meta-analysis of 19 international studies. Patients Total of 1019 patients with superficial EC (SEC). Interventions EUS and EMR or surgical resection of SEC. Main Outcome Measurements Sensitivity and specificity of EUS in accurately staging SEC. Results The pooled sensitivity, specificity, and positive and negative likelihood ratio of EUS for T1a staging were 0.85 (95% CI, 0.82-0.88), 0.87 (95% CI, 0.84-0.90), 6.62 (95% CI, 3.61-12.12), and 0.20 (95% CI, 0.14-0.30), respectively. For T1b staging, these results were 0.86 (95% CI, 0.82-0.89), 0.86 (95% CI, 0.83-0.89), 5.13 (95% CI, 3.36-7.82), and 0.17 (95% CI, 0.09-0.30), respectively. The area under the curve was at least 0.93 for both mucosal and submucosal lesions. Limitations Heterogeneity was present among the studies. Conclusion Overall EUS has good accuracy (area under the curve ≥0.93) in staging SECs. Heterogeneity among the included studies suggests that multiple factors including the location and type of lesion, method and frequency of EUS probe, and the experience of the endosonographer can affect the diagnostic accuracy of EUS.
Summary Background The Solitaire Flow Restoration Device is a novel, self-expanding stent retriever designed to yield rapid flow restoration in acute cerebral ischaemia. We compared the efficacy and ...safety of Solitaire with the standard, predicate mechanical thrombectomy device, the Merci Retrieval System. Methods In this randomised, parallel-group, non-inferiority trial, we enrolled patients from 18 sites (17 in the USA and one in France). Patients were eligible for inclusion if they had acute ischaemic stroke with moderate to severe neurological deficits and were treatable by thrombectomy within 8 h of stroke symptom onset. We used a computer-generated randomisation sequence to randomly allocate patients to receive thrombectomy treatment with either Solitaire or Merci (1:1; block sizes of four and stratified by centre and stroke severity). The primary endpoint was Thrombolysis In Myocardial Ischemia (TIMI) scale 2 or 3 flow in all treatable vessels without symptomatic intracranial haemorrhage, after up to three passes of the assigned device, as assessed by an independent core laboratory, which was masked to study assignment. Primary analysis was done by intention to treat. A prespecified efficacy stopping rule triggered an early halt to the trial. The study is registered with ClinicalTrials.gov , number NCT 01054560. Results Between February, 2010, and February, 2011, we randomly allocated 58 patients to the Solitaire group and 55 patients to the Merci group. The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group (61% vs 24%; difference 37% 95% CI 19–53, odds ratio OR 4·87 95% CI 2·14–11·10; pnon-inferiority <0·0001, psuperiority =0·0001). More patients had good 3-month neurological outcome with Solitaire than with Merci (58% vs 33%; difference 25% 6–43, OR 2·78 1·25–6·22; pnon-inferiority =0·0001, psuperiority =0·02). 90-day mortality was lower in the Solitaire group than it was in the Merci group (17 vs 38; difference −21% –39 to −3, OR 0·34 0·14–0·81; pnon-inferiority =0·0001, psuperiority =0·02). Interpretation The Solitaire Flow Restoration Device achieved substantially better angiographic, safety, and clinical outcomes than did the Merci Retrieval System. The Solitaire device might be a future treatment of choice for endovascular recanalisation in acute ischaemic stroke. Funding Covidien/ev3.
Background Minimally invasive inguinal lymphadenectomy (MILND) is a novel procedure with the potential to decrease surgical morbidity compared with the traditional open approach. The current study ...examined the feasibility of a combined didactic and hands-on training program to prepare high-volume melanoma surgeons to perform this procedure safely and proficiently. Study Design A select group of melanoma surgeons with no MILND experience were recruited. After completing a structured training program, surgeons enrolled patients with melanoma who required inguinal lymphadenectomy and performed the procedure in the minimally invasive fashion. A proficiency score composed of lymph node yield, operative time, and blood loss (or adverse events) was assigned for each case. After performing six cases, surgeons meeting a threshold score were considered proficient in the procedure. Results Twelve surgeons from 10 institutions enrolled 88 patients. The majority of surgeons were deemed proficient within 6 cases (83%). No differences in operative time or lymph node yield were noted during the course of the study. The rate of conversion was higher during an individual surgeon's early experience (9 of 49 18%), and only 1 procedure was converted in the 39 cases performed after a surgeon had performed 5 cases (late conversion rate, 3%; p = 0.038); however, this did not remain significant after controlling for surgeon. Conclusions After a structured training program, experienced melanoma surgeons adopted a novel surgical technique with acceptable operative times, conversions, and lymph node yield. Eighty-four percent of the surgeons who completed at least 6 MILND procedures were considered proficient based on our predetermined definition.
Abstract Objective Substantial controversy surrounds the choice between a mechanical versus bioprosthetic prosthesis for aortic valve replacement (AVR), based on age. This study aims to investigate ...national trends and in-hospital outcomes of the 2 prosthesis choices. Methods All patients aged >18 years in the National Inpatient Sample who received an AVR between 1998 and 2011 were considered. Valve-type use was examined by patient, procedural, and hospital characteristics, after which we matched patients based on their propensity score for receiving a bioprosthetic valve and compared their in-hospital outcomes. Results Bioprosthetic valves comprised 53.3% of 767,375 implanted valves, an increase in use from 37.7% in the period 1998 to 2001 to 63.6% in the period 2007 to 2011. The median age was 74 years for patients receiving bioprosthetic valves, and 67 years for those receiving mechanical valves. Use of bioprosthetic valves increased across all age groups, most markedly in patients age 55 to 64 years. Compared with patients receiving mechanical valves, these patients had a higher incidence of renal disease (8.0% vs 4.2%), coronary artery disease (58.5% vs 50.5%), concomitant coronary artery bypass grafting (46.7% vs 41.9%), and having surgery in a high-volume (>250 cases per year) center (31.3% vs 18.5%). Patients receiving bioprosthetic valves had a higher occurrence of in-hospital complications (55.9% vs 48.6%), but lower in-hospital mortality (4.4% vs 4.9%) than patients receiving mechanical valves. This difference was confirmed in propensity-matched analyses (complications: 52.7% vs 51.5%; mortality: 4.3% vs 5.2%). Conclusions Use of bioprosthetic valves in AVR increased dramatically from 1998 to 2011, particularly in patients age 55 to 64 years. Prosthesis selection varied significantly by facility, with low-volume facilities favoring mechanical valves. Aortic valve replacement with a bioprosthetic valve, compared with a mechanical valve, was associated with lower in-hospital mortality.
Outcomes of salvage esophagectomy after definitive chemoradiation (CRT) for squamous cell carcinoma are well defined. Previous reports of salvage esophagectomy in patients with recurrent ...adenocarcinoma after definitive CRT are limited by small numbers and high morbidity and mortality rates.
We reviewed our experience of 65 patients with esophageal adenocarcinoma treated from 1997 to 2010 who underwent salvage esophagectomy after failed definitive CRT. We then compared this group to 65 matched patients of 521 total patients with esophageal adenocarcinoma who received preoperative CRT followed by planned esophagectomy. Propensity matching and multivariable analysis were performed.
Median time to surgery from completion of therapy for the salvage group was 216 days. Major postoperative events (major pulmonary event, conduit loss, leak, readmission to intensive care unit) occurred in 35% (23 of 65) of salvage patients and 31% (20 of 65) of the planned resection matched group. Anastomotic leak occurred in 18.5% (12 of 65) and 11.3 (59 of 521) of salvage and planned groups, respectively. Thirty-day mortality was 3.1% (2 of 65) after salvage resection and 4.6% (3 of 65) after planned resection. There was no difference in 3-year overall or median survival between the two groups of patients (32 months, 48% salvage, versus 40 months, 57% planned resection). Multivariable analysis did not identify salvage strategy or time from completion of therapy to resection as a predictor of major event or death.
Postoperative morbidity, mortality, and overall survival of patients after salvage esophagectomy are comparable to matched patients after planned resection. These results suggest that patients with esophageal adenocarcinoma who fail definitive CRT and recur locoregionally should be considered for salvage esophagectomy at experienced esophageal centers.
Abstract The American College of Cardiology Adult Congenital and Pediatric Cardiology (ACPC) Section had attempted to create quality metrics (QM) for ambulatory pediatric practice, but limited ...evidence made the process difficult. The ACPC sought to develop QMs for ambulatory pediatric cardiology practice. Five areas of interest were identified, and QMs were developed in a 2-step review process. In the first step, an expert panel, using the modified RAND-UCLA methodology, rated each QM for feasibility and validity. The second step sought input from ACPC Section members; final approval was by a vote of the ACPC Council. Work groups proposed a total of 44 QMs. Thirty-one metrics passed the RAND process and, after the open comment period, the ACPC council approved 18 metrics. The project resulted in successful development of QMs in ambulatory pediatric cardiology for a range of ambulatory domains.
Controversy currently exists about the optimum preoperative treatment platform for locoregionally advanced esophageal cancer, namely, preoperative chemoradiotherapy (preoperative C/RT) or ...preoperative chemotherapy alone. We therefore reviewed sequential phase II/III trials performed at a single institution to assess the impact of preoperative chemotherapy versus preoperative C/RT strategies.
In all, 157 esophageal cancer patients were sequentially enrolled in phase II/III trials at the University of Texas M.D. Anderson Cancer Center from March 27, 1990, to March 8, 2005. The treatment approaches included preoperative chemotherapy, n = 76 (INT 113 and ID90-01); preoperative C/RT, n = 81 (ID96-189 and DM98-349). Analysis was by intention to treat. Factors evaluated included demographics, preoperative staging, type of surgery, pathology, adjuvant therapies, and long-term outcome.
Adenocarcinoma predominated (85%), with cT3 (73%) and cN1 (43%). No significant difference was noted between groups in demographics or perioperative mortality. More patients with preoperative C/RT were staged with endoscopic ultrasound (52% versus 9%, p < 0.001). Preoperative C/RT demonstrated increased pathologic complete response (28% versus 4%, p < 0.001) and overall survival (3 years, 48% versus 29%, p = 0.04). Preoperative C/RT was a significant independent predictor of improved overall survival (hazard ratio 0.58, 95% confidence interval: 0.37 to 0.90, p = 0.015) and disease-free survival (hazard ratio 0.55, 95% confidence interval: 0.35 to 0.85, p = 0.007) in multivariable regression.
In sequential phase II/III trials involving locoregionally advanced esophageal cancer patients, preoperative C/RT was associated with improved overall and disease-free survival rates (p = 0.046 and p = 0.015, respectively) and increased pathologic complete response (p < 0.001) compared with preoperative chemotherapy.
Abstract Introduction Aging worsens outcome in traumatic brain injury (TBI), but available studies may not provide accurate outcome predictions due to confounding associated injuries. Our goal was to ...develop a predictive tool using variables available at admission to predict outcome related to severity of brain injury in aging patients. Methods Characteristics and outcomes of blunt trauma patients with isolated TBI of ages ≥ 50 in National Trauma Data Bank (NTDB) were evaluated. Equations predicting survival and independence at DC (IDC) were developed and validated using patients from our trauma registry, comparing predicted to actual outcomes. Results Logistic regression for survival and IDC was performed in 57,588 patients using age, gender, Glasgow Coma Scale score (GCS), and revised trauma score (RTS). All variables were independent predictors of outcome. Two models were developed using these data. The first included age, gender, and GCS. The second substituted RTS for GCS. C statistics from the models for survival and IDC were 0.90 and 0.82 in the GCS model. In the RTS model, C statistics were 0.80 and 0.67. The use of GCS provided better discrimination, and was chosen for further examination. Using the predictive equation derived from the logistic regression model, outcome probabilities were calculated for 894 similar patients from our trauma registry (1/12-3/16). The survival and IDC models both showed excellent discrimination (p<0.0001). IDC and survival generally decreased by decade: Age 50-59 (80% IDC, 6.5% mortality), 60-69 (82%, 7.0%), 70-79 (76%, 8.9%), and 80-89 (67%, 13.4%). Conclusion These models can assist in predicting the probability of survival and IDC for aging patients with TBI. This provides important data for loved ones of these patients when addressing goals of care.
To the Editor: Inducible T-cell costimulator (ICOS) is a costimulatory receptor upregulated on activated T cells.1ICOS mutations have been identified in 11 patients, 9 of whom share the same ...mutation.2 These patients have a common variable immunodeficiency (CVID) phenotype, with recurrent sinopulmonary and gastrointestinal infections, autoimmunity, inflammatory bowel disease, and granulomatous disease.1 ICOS deficiency is characterized by defective class-switching with hypogammaglobulinemia, absent antigen responses, and impaired germinal center formation.2 We report a novel ICOS mutation resulting in opportunistic infections and colitis responsive to hematopoietic stem cell transplant (HSCT). Myeloid-derived dendritic cells contribute to microbial surveillance in the gastrointestinal tract and express both ICOS and ICOSL, an interaction critical for the cytokine response to nucleotide-binding oligomerization domain 2 and Toll-like receptor stimulation.12 Furthermore, an ICOSL polymorphism (rs7282490) is associated with reduced ICOSL expression, decreased nucleotide-binding oligomerization domain 2-mediated signaling, and an increased risk of Crohn disease.
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