BACKGROUND: Lymphovascular invasion and perineural invasion are histopathological features associated with higher-risk colon cancer. OBJECTIVE: The purpose of this study was to quantify the impact of lymphovascular and perineural invasion on overall survival after diagnosis and to determine the protective effect of adjuvant chemotherapy for early adenocarcinoma with high-risk factors. DESIGN: This was a retrospective database review of the 2010–2014 National Cancer Database for colon cancer. SETTINGS: Individuals diagnosed with invasive adenocarcinoma of the colon (histology code 8140) with primary surgical resection with >12 nodes harvested and no positive nodes on pathological examination were included. PATIENTS: A total of 32,493 patients underwent surgical resection for stage II adenocarcinoma of the colon. INTERVENTIONS: The study involved multivariate Cox regression analysis of the impact of lymphovascular and perineural invasion and adjuvant chemotherapy on overall survival after a diagnosis of stage II adenocarcinoma of the colon. MAIN OUTCOME MEASURES: Survival after a diagnosis of stage II adenocarcinoma of the colon was measured. RESULTS: Five-year survival after diagnosis and surgical resection without adjuvant chemotherapy was lower for patients with lymphovascular (60.0%), perineural (56.9%), and lymphovascular and perineural invasion (55.8%) compared with double-negative disease (66.1%). Log-rank testing confirmed that adjuvant chemotherapy improved 5-year survival after diagnosis for lymphovascular (85.5%), perineural (83.6%), and lymphovascular and perineural invasion (74.3%). After controlling for differences in cohorts, Cox regression analysis showed an increased HR for mortality of 14.0% for lymphovascular (HR = 1.141 (95% CI, 1.060–1.228)), 32.1% for perineural (HR = 1.321 (95% CI, 1.176–1.483)), and 41.0% for lymphovascular and perineural invasion (HR = 1.409 (95% CI, 1.231–1.612)) compared with having neither. Chemotherapy showed a 43% reduction in hazard for mortality (HR = 0.570 (95% CI, 0.513–0.633)). LIMITATIONS: The study was limited by its retrospective review and observational bias. CONCLUSIONS: Lymphovascular and perineural invasion have a detrimental effect on survival after diagnosis of stage II adenocarcinoma of the colon. Chemotherapy may be protective specifically when lymphovascular and perineural invasion are present. See Video Abstract at http://links.lww.com/DCR/A786.

To date, no consensus exists regarding indication, technique, or efficacy of distal perfusion cannulae (DPC) in preventing limb ischemia among patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). We aim to examine the available literature and report association between DPC and risk of limb ischemia. PubMed/Medline, Scopus, Cochrane Central Register of Controlled Trials, Google Scholar, and bibliographies of included studies were searched from database inception until August 2016. Original studies describing the DPC placement technique and incidence of limb ischemia following DPC placement among VA-ECMO patients were included for systematic review. Studies with a comparison group of patients without DPC were included for meta-analysis. Two authors independently screened title/abstracts, reviewed full texts, and extracted data from the eligible studies. Meta-analysis was performed using the Mantel-Haenszel method under a random-effects model. Statistical heterogeneity was examined with the I2 statistic (RevMan Version 5.3). Of 542 title/abstracts screened, 62 full text articles were selected for review, yielding 22 retrospective observational studies, for a total of 779 patients with 132 limb ischemia events. There was significant variation in DPC indication, cannula type, and placement technique among the studies. Compared to no DPC, the presence of a DPC was associated with at least a 15.7% absolute reduction in the incidence of limb ischemia (9.74 vs. 25.42%; risk ratio 0.41; 95% confidence interval 0.26-0.65, P < 0.01; heterogeneity statistic I2 = 28%). There was no statistically significant difference in mortality in the pooled dataset comparing DPC versus no DPC. In adults treated with VA-ECMO, DPC placement was associated with a lower incidence of limb ischemia. Currently no consensus guidelines exist regarding indication for DPC placement. Given the association described in this analysis, future prospective trials are warranted to establish a causal relationship and optimal technique for the use of DPC in patients treated with VA-ECMO.

The balance of sympathetic and parasympathetic tone provides exquisite control of heart rate and contractility and has also been shown to modulate coronary flow and inflammation. Understanding how autonomic balance is altered by cardiac disease is an active area of research, and developing new ways to control this balance provides insights into disease therapies. However, achieving acute neuron-specific stimulation of autonomic neurons can be difficult in experiments that measure the acute effects of nerve stimulation on the heart. Conventional electrical and pharmacological approaches can be spatially and temporally non-selective. Cell-specific expression of light-activated channels (channelrhodopsin, ChR2) is a powerful approach that enables control of the timing and distribution of cellular stimulation using light. We present such an optogenetic approach where parasympathetic cardiac neurons are selectively photoactivated at high temporal precision to initiate cholinergic-mediated slowing of heart rate. Mice were crossbred to express ChR2 in peripheral cholinergic neurons using Cre-Lox recombination driven by a choline acetyltransferase (ChAT) promoter. Hearts from adult mice were excised, perfused, and the epicardium was illuminated (peak 460–465 nm) to photoactivate ChR2. In one set of studies, hearts were illuminated using a large-field LED light source. In other studies, a micro LED was placed on the right atrium to selectively illuminate the junction of the superior vena cava (SVC) and right atrium. The ECG was acquired before, during, and after tissue illumination to measure changes in heart rate. Upon illumination, hearts exhibited sudden and dramatic reductions in heart rate with restoration of normal heart rate after cessation of illumination. Delays in atrioventricular conduction were also observed. Heart rate reductions at the highest irradiance levels were similar to heart rate reductions caused by application of bethanechol (10 μM) or acetylcholine (800 μM). Atropine (50 nM) completely blocked the effect of ChR2 photoactivation, confirming cholinergic mediation. Optogenetic activation of intrinsic parasympathetic neurons reduced heart rate in an immediate, dose-dependent fashion, resembling the slowing of sinus rate in response to acetylcholine. Our results demonstrate a new approach for controlling parasympathetic modulation of cardiac function by selectively activating the endogenous release of acetylcholine from intrinsic cardiac cholinergic neurons.Key Message: Optogenetic photoactivation of intrinsic cardiac neurons provides immediate, tissue-specific stimulation with minimal cross-reactivity. Our results demonstrate that selective expression of channelrhodopsin within cardiac cholinergic neurons enables photoactivated release of acetylcholine, thereby instantaneously slowing sinus rate and altering atrioventricular conduction. This provides for in-depth examination of the endogenous interplay between cardiac autonomic neurons and the functional outcomes of downstream post-synaptic receptor ac...

Patients who undergo elective stoma reversal have a higher incidence of postoperative C difficile infection compared with patients who undergo an elective colectomy. Given the impact of postoperative C difficile infection, a heightened sense of suspicion should be given to symptomatic patients after stoma reversal. See at Video Abstract at http://links.lww.com/DCR/A553.

Objective Microtia is treated with rib cartilage sculpting and staged procedures; though aesthetically pleasing, these constructs lack native ear flexibility. Tissue-engineered (TE) elastic cartilage may bridge this gap; however, TE cartilage implants lead to hypertrophic changes with calcification and loss of flexibility. Retaining flexibility in TE cartilage must focus on increased elastin, maintained collagen II, decreased collagen X, with prevention of calcification. This study compares biochemical properties of human cartilage to TE cartilage from umbilical cord mesenchymal stem cells (UCMSCs). Our goal is to establish a baseline for clinically useful TE cartilage. Methods Discarded cartilage from conchal bowl, microtic ears, pre-auricular tags, rib, and TE cartilage were evaluated for collagen I, II, X, calcium, glycosaminoglycans, elastin, fibrillin I and III. Human UCMSCs were chondroinduced on 2-D surfaces and 3-D D, L-lactide-co-glycolic acid (PLGA) fibers. Results Cartilage samples demonstrated similar staining for collagens I, II, X, elastin, fibrillin I, and III, but differed from rib. TE pellets and PLGA-supported cartilage were similar to auricular samples in elastin and fibrillin I staining. TE samples exclusively stained for fibrillin III. Only microtic samples demonstrated calcium staining. Conclusions TE cartilage expressed similar levels of elastin, fibrillin I, collagens I and X when compared to native cartilage. Microtic cartilage demonstrated elevated calcium, suggesting this abnormal tissue may not be a viable cell source for TE cartilage. TE cartilage appears to recapitulate the embryonic development of fibrillin III, which is not expressed in adult tissue, possibly providing a strategy to control TE elastic cartilage phenotype.