Thoracoscopic Neonatal Congenital Diaphragmatic Hernia Repair: How We Do It.

Background: Congenital diaphragmatic hernia (CDH) is a relatively common congenital anomaly, typically requiring repair in the neonatal period. Approaches to surgical repair of a CDH are varied. A small defect may be repaired primarily while a large defect often requires a patch repair. Minimally invasive and open techniques have been reported to have varying benefits and outcomes. Materials and Methods: The authors describe their technique of CDH repair and present a review of the literature. Results: In a stabilized neonate with a small-to-moderate CDH defect, a thoracoscopic primary repair with biological mesh underlay (or a patch repair if needed to reduce tension) represents our approach of choice to treat this pathology. However, attention to specific technical details is required to minimize incidence of recurrence. Conclusions: The data favor a minimally invasive approach to CDH repair in the appropriate patients.

The International Pediatric Endosurgery Group Evidence-Based Guideline on Minimal Access Approaches to the Operative Management of Inguinal Hernia in Children.

Introduction: Minimally invasive surgery (MIS) for inguinal hernia repair (IHR) in children has been reported for more than two decades. The International Pediatric Endosurgery Group (IPEG) Evidence-Based Review Committee chose MIS IHR as the inaugural topic for review and presentation at the 2016 IPEG annual meeting. Materials and Methods: English language articles published between January 1, 2009, and December 31, 2015, were reviewed and included in this evidence-based review after searching PubMed, Cochrane Reviews, ClinicalTrials.gov, Google Scholar, and EMBASE. Results: Level 1a and 1b evidence supports the recommendations that operative time for bilateral IHRs should be considered shorter and postoperative complications rates should be considered lower in MIS repair over open. Recurrence rates are similar between the two methods (level 1a and 1b evidence). No level 1 evidence exists to support one MIS technique over another or that operating on a detected contralateral patent processus vaginalis during laparoscopy makes any difference in long-term outcome to the patient. Conclusions: The advantages of lower postoperative complications and shorter operative times have been found in studies of surgeons experienced in MIS repair and differences were small. The evidence in this review supports that MIS repair is a safe, effective method of IHR with proper training and mentorship.

Hemodialysis and peritoneal dialysis access related outcomes in the pediatric and adolescent population.

BACKGROUND: There is paucity of comparative data on the objective performance of arteriovenous fistulas (AVF), grafts (AVG), hemodialysis (HD) catheter and peritoneal dialysis (PD) catheter in the pediatric population. METHODS: A retrospective analysis of all patients <21 years in the United States Renal Database System who had an AVF, AVG, HD catheter or PD catheter placed for dialysis access between 1/2007 and 12/2014 was performed. Multivariable cox regression was used to evaluate mortality, patency (primary, primary-assisted and secondary), maturation and catheter survival. RESULTS: The 11,575 patients studied comprised of 9445 (82%) HD, 1435 (12%) PD, 528 (4.6%) HD to PD and 167 (1.4%) PD to HD patients. The HD subcohort comprised of 1296 (13.7%) AVF initiates, 199 (2.1%) AVG initiates, 1347 (14.3%) AVF converts after initial HD catheter use, 292 (3.1%) AVG converts and 6311 (67%) patients who persistently utilized HD catheters. There was no difference between PD and HD in patients 0-5 (aHR: 1.36; 95% CI: 0.89-2.07; P = 0.15) and 6-12 years (aHR: 1.05; 95% CI: 0.72-1.52; P = 0.8). However, PD was associated with 73% and 76% increase in mortality relative to HD among patients in the 13-17 (aHR: 1.73; 95% CI: 1.35-2.21; P < 0.001) and 18-20 (aHR: 1.76; 95% CI: 1.38-2.24; P < 0.001) age categories. AVG was associated with 78% increase in mortality compared to AVF (aHR: 1.78; 95% CI: 1.41-2.25; P < 0.001). Persistent use of HD catheters was associated with 29% increase in mortality (aHR: 1.29; 95% CI: 1.07-1.57; P = 0.009) compared to initiation and persistent use of AVF. Conversion from HD catheter to AVF was associated with 66% decrease in mortality compared to persistent HD catheter use (aHR: 0.34; 95% CI: 0.28-0.40; P < 0.001). Primary, primary assisted and secondary patency were higher for AVF compared to AVG. CONCLUSION: There was no difference in risk adjusted mortality between HD and PD in children less than 13 years. PD is associated with higher mortality compared to HD in adolescents. Initiation of HD with AVF is associated with better patency and patient survival relative to AVG and persistent use of HD catheters in pediatric patients irrespective of transplant potential. Conversion from HD catheter to AVF or AVG in patients who inevitably initiate HD with a catheter is associated with better survival compared to persistent HD catheter use. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level II.

Lipocalin-type prostaglandin D2 synthase (L-PGDS) modulates beneficial metabolic effects of vertical sleeve gastrectomy.

BACKGROUND: Vertical sleeve gastrectomy (VSG) ameliorates metabolic complications in obese and diabetic patients through unknown mechanisms. OBJECTIVE: The objective of this study was to investigate the role of lipocalin-type prostaglandin D2 synthase (L-PGDS) in glucose regulation in response to VSG using L-PGDS knock-out (KO), knock-in (KI), and C57BL/6 (wild type) mice. SETTING: Winthrop University Hospital Research Institute. METHODS: Animals were divided into 6 groups: L-PGDS KO sham/VSG (n = 5), L-PGDS KI sham/VSG (n = 5), and C57BL/6 (wild type) sham/VSG (n = 5). Related parameters were measured in fasting animals after 10 weeks. RESULTS: Our intraperitoneal glucose tolerance tests and homeostatic model assessment insulin resistance results showed significant glycemic improvement 10 weeks post-VSG in both C57BL/6 and KI groups compared with the sham group. In contrast, the KO group developed glucose intolerance and insulin resistance similar to or greater than the sham group 10 weeks post-VSG. Interestingly, weight gain was insignificant 10 weeks post-VSG in all the groups and even trended higher in the KO group compared with sham. Peptide YY levels in the KO group post-VSG were slightly increased but significantly less than other groups. Similarly, the KO group showed significantly less leptin sensitivity in response to VSG compared with the KI group. Total cholesterol level remained unchanged in all groups irrespective of sham or surgery but interestingly, the KO group had significantly higher cholesterol levels. In parallel, adipocyte size was also found to be significantly increased in the KO group post-VSG compared with the sham group. CONCLUSION: Our findings propose that L-PGDS plays an important role in the beneficial metabolic effects observed after VSG.

Roux-en-Y gastric bypass attenuates the progression of cardiometabolic complications in obese diabetic rats via alteration in gastrointestinal hormones.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes (T2DM) and obesity through alteration in gastrointestinal (GI) hormones. OBJECTIVE: The objective of this study was to investigate the effect of RYGB on GI hormones and cardiometabolic parameters in Zucker diabetic fatty (ZDF) rodents. SETTING: Winthrop University Hospital, Research and Academic Center METHODS: Animals were divided into 3 groups, pair-fed (n = 4), ad lib (n = 4), and RYGB (n = 5). This study was carried out for 4 weeks and all related parameters were measured pre- and postsurgery in fasted obese diabetic Zucker rodents. RESULTS: Postoperatively, RYGB significantly decreased fasting blood glucose by 32% compared with ad lib. Plasma insulin and leptin levels were also found to be significantly decreased, by 66% and 38%, respectively, after surgery. Moreover, both glucose-dependent insulinotropic polypeptide (GIP) and peptide tyrosine-tyrosine (PYY) were significantly increased after RYGB-by 300% and 51%, respectively. Glucagon-like peptide-1 (GLP-1) levels were also increased, but the increase was not statistically significant. Total cholesterol levels of the RYGB group remained unchanged for 4 weeks. However, total cholesterol in the ad lib and pair-fed groups increased by 25% and 34%, respectively, compared with initial levels. The cholesterol/high-density lipoprotein (HDL) ratio was decreased in the RYGB group by 14% and 30% compared with the ad lib and pair-fed group, respectively. The RYGB group had a significant decrease in aortic wall thickness of 25% compared with the ad lib and pair-fed groups. Similarly, the RYGB group had a 20-unit (mm Hg) decrease in systolic blood pressure compared with the presurgical value. CONCLUSION: RYGB has beneficial cardiometabolic effects through alterations in GI hormones in a severely obese and diabetic rodent model.

Roux-en-Y gastric bypass alters tumor necrosis factor-α but not adiponectin signaling in immediate postoperative period in obese rats.

BACKGROUND: Adiponectin has anti-inflammatory properties and is increased with weight loss. Tumor necrosis factor (TNF)-α is a pro-inflammatory cytokine that negatively regulates adiponectin. Previously, we have demonstrated that Roux-en-Y gastric bypass (RYGB) induces weight loss and improves steatosis in obese rats. We hypothesized that RYGB would alter the interplay of TNF-α and adiponectin signaling in the postoperative period. METHODS: Obese Sprague-Dawley male rats that had undergone RYGB (n = 5) or sham (n = 4) were euthanatized at 9 weeks postoperatively. The adiponectin levels from serial serum samples were measured by enzyme-linked immunosorbent assay. Adiponectin, adiponectin receptor 2, and TNF-α mRNA from adipose and liver samples were quantified by reverse transcriptase-polymerase chain reaction. Data are presented as mean ± standard deviation; using a t test, P <.05 was significant. RESULTS: RYGB did not change the serum adiponectin, adipose tissue adiponectin mRNA, or hepatic adiponectin receptor 2 levels compared with the levels in the sham-operated rats (P >.05). However, the TNF-α mRNA levels had decreased in the adipose tissue (P >.05) but remained unchanged in the liver compared with the sham controls (P >.05). CONCLUSION: Surgically-induced weight loss in a rat model of RYGB did not increase adiponectin signaling in the immediate postoperative period but was associated with decreased pro-inflammatory signaling in the adipose tissue. During this period, pro-inflammatory signaling might play a more important role than adiponectin. Additional studies with longer follow-up are necessary to determine whether adiponectin plays a role in weight loss and improvement of steatosis after RYGB.

Does LKB1 mediate activation of hepatic AMP-protein kinase (AMPK) and sirtuin1 (SIRT1) after Roux-en-Y gastric bypass in obese rats?

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) improves steatosis and reduces liver triglycerides in obese rats. Sirtuin1 (SIRT1) and AMP-activated protein kinase (AMPK) are key metabolic regulators that reduce lipogenesis and increase fatty acid oxidation. LKB1 phosphorylates AMPK and may activate SIRT1. We hypothesize that RYGB in obese rats is associated with an upregulation of the LKB1-AMPK-SIRT1 signaling pathway. METHODS: Obese Sprague-Dawley male rats underwent RYGB or sham. Liver tissue was obtained at 9 weeks postoperatively. Protein levels of SIRT1, LKB1, p-LKB1, AMPKalpha, p-AMPKalpha, and p-protein kinase C-zeta (PKC-zeta ) were determined. Protein associations of LKB1 with each of SIRT1, AMPKalpha, and PKC-zeta were determined by coimmunoprecipitation.Data are mean +/- SD; for t test, p<0.05 was significant. RESULTS: RYGB increased protein levels of hepatic AMPKalpha, p-AMPKalpha, and SIRT1 (all p<0.001 vs. sham); p-LKB1 but not LKB1 increased after RYGB (p<0.001 vs. sham). Physical interactions of LKB1-AMPK and LKB1-SIRT1 increased after RYGB (p<0.001 vs. sham). Although PKC-zeta mRNA and p-PKC-zeta did not change, interactions between LKB1 and PKC-zeta increased after RYGB (p<0.001 vs. sham). CONCLUSION: RYGB increases hepatic levels of SIRT1, AMPK, and p-AMPK as well as increasing interactions of LKB1 with AMPK or SIRT1. p-PKC-zeta may play an intermediary role in the interaction between AMPK and SIRT. These findings demonstrate key signaling changes in powerful metabolic regulators that may account for the resolution of steatosis after RYGB.