Faculty Bibliography

Despite the paucity of evidence on robotic ventral hernia repair (RVHR) in patients with obesity, the robotic platform is being used more frequently in hernia surgery. The impact of obesity on RVHR outcomes has not been thoroughly studied. Obesity is considered a major risk factor for the development of recurrent ventral hernias and postoperative complications; however, we hypothesize that patients undergoing robotic repairs will have similar complication profiles despite their body mass index (BMI). We performed a retrospective analysis of patients aged 18-90 years who underwent RVHR between 2013 and 2023 using data from the Abdominal Core Health Quality Collaborative registry. Preoperative, intraoperative, and postoperative characteristics were compared in non-obese and obese groups, determined using a univariate and logistic regression analysis to compare short-term outcomes. The registry identified 9742 patients; 3666 were non-obese; 6076 were classified as obese (BMI > 30 kg/m²). There was an increased odds of surgical site occurrence in patients with obesity, mostly seroma formation; however, obesity was not a significant factor for a complication requiring a procedural intervention after RVHR. In contrast, the hernia-specific quality-of-life scores significantly improved following surgery for all patients, with those with obesity having more substantial improvement from baseline. Obesity does increase the risk of certain complications following RVHR in a BMI-dependent fashion; however, the odds of requiring a procedural intervention are not significantly increased by BMI. Patients with obesity have a significant improvement in their quality of life, and RVHR should be carefully considered in this population.

Specific biomarkers of intestinal injury associated with necrotizing enterocolitis (NEC) are needed to diagnose and monitor intestinal mucosal injury and recovery. This study aims to develop and test a modified enzyme-linked immunosorbent assay (ELISA) protocol to detect the total keratin 8 (K8) in the stool of newborns with NEC and investigate the clinical value of fecal K8 as a marker of intestinal injury specifically associated with NEC. We collected fecal samples from five newborns with NEC and five gestational age-matched premature neonates without NEC at the Lucile Packard Children's Hospital Stanford and Washington University School of Medicine, respectively. Fecal K8 levels were measured using a modified ELISA protocol and Western blot, and fecal calprotectin was measured using a commercial ELISA kit. Clinical data, including gestational age, birth weight, Bell stage for NEC, feeding strategies, total white blood cell (WBC) count, and other pertinent clinical variables, were collected and analyzed. Fecal K8 levels were significantly higher in the pre-NEC group (1-2 days before diagnosis of NEC) and NEC group than those in the non-NEC group (p = 0.013, p = 0.041). Moreover, fecal K8 was relatively higher at the onset of NEC and declined after the resolution of the disease (p = 0.019). Results with similar trends to fecal K8 were also seen in fecal calprotectin (p = 0.046), but not seen in total WBC count (p = 0.182). In conclusion, a modified ELISA protocol for the total K8 protein was successfully developed for the detection of fecal K8 in the clinical setting of premature newborns with NEC. Fecal K8 is noted to be significantly increased in premature newborns with NEC and may, therefore, serve as a noninvasive and specific marker for intestinal epithelial injury associated with NEC.

BACKGROUND/PURPOSE/OBJECTIVE:Distraction enterogenesis with intraluminal spring technology has been successfully used to lengthen segments of murine small intestine. We hypothesized that biocompatible springs could also be used to lengthen murine large intestine. METHODS:Age and weight matched C57BL/6 mice underwent surgical insertion of nitinol spring-loaded capsules into the cecum. Segment lengths were measured at initial spring placement and at euthanasia after 7 and 14 days. Histologic adaptations were evaluated at scarification. RESULTS:Cecal segments loaded with compressed springs lengthened an average of 150%, which was significantly longer than control segments loaded with either empty capsules or uncompressed springs. Muscularis layers tended to be thicker in the compressed spring groups compared to control groups. CONCLUSIONS:Insertion of a compressed nitinol spring into the cecum results in significant colonic lengthening in a mouse model. The ability to increase cecum length serves as proof of concept that distraction enterogenesis technology may be feasibly applied to large intestinal models. The use of distraction enterogenesis technology shows promise for application to clinical models in the treatment of pediatric intestinal disease.

PURPOSE/OBJECTIVE:Children often require anesthesia for simple diagnostic and therapeutic procedures. The aim of this study was to evaluate the feasibility of using virtual reality (VR) to reduce sedation in children undergoing minor surgical procedures. METHOD/METHODS:In this prospective, non-randomized clinical trial, pediatric patients at a free-standing children's hospital undergoing hormone implant placement, removal, or exchange were recruited to use VR and local anesthesia instead of procedural sedation or general anesthesia (GA). Patients were enrolled between November 2017 and March 2020, and were compared to historic controls who underwent similar procedures without VR between April 2016 and February 2020. Primary outcome measure was successful procedure completion without sedation or GA. Secondary measures included assessments of pain, fear and anxiety, patient compliance, procedural and recovery times. RESULTS:Twenty-eight patients underwent 29 procedures with VR. Hormone implants (72%), removals (7%), or exchanges (21%) were completed without GA, sedation or IV placement. Procedure lengths and pain scores were similar between VR patients and historic controls, but recovery times were significantly shorter in VR patients (18 vs 65 min, p < 0.001). Participant satisfaction scores were high, with 95% recommending VR to others. CONCLUSIONS:VR is a feasible alternative to sedation or GA for select pediatric patients undergoing minor surgical procedures.

INTRODUCTION/BACKGROUND:short bowel syndrome is marked by inadequate intestinal surface area to absorb nutrients. Current treatments are focused on medical management and surgical reconfiguration of the dilated intestine. We propose the use of spring-mediated distraction enterogenesis as a novel intervention to increase intestinal length. Given our previous success lengthening intestinal segments using springs with spring constant ~7 N/m that exerts 0.46 N or higher, we sought to determine the minimal force needed to lengthen porcine small intestinal segments, and to explore effects on intestine over time. METHODS:Juvenile Yucatan pigs underwent laparotomy with enterotomy to introduce nitinol springs intraluminally (n = 21 springs). Bowel segments (control, spring-distracted) were retrieved on post-operative day (POD) 7 and 14, and lengths measured. Thickness of cross-sectional intestinal layers were measured using H&E, and submucosal collagen fiber orientation measured using trichrome stained sections. RESULTS:all pigs survived to POD7 and 14. Spring constants of at least 2 N/m exerting a minimum force of 0.10 N significantly lengthened intestinal segments (p <0.0001). The stronger the spring force, the greater the induced thickness of various intestinal layers at POD7 and 14. Collagen fiber orientation was also more disordered because of stronger springs. CONCLUSION/CONCLUSIONS:a spring constant of approximately 2 N/m exerting 0.10 N and greater significantly lengthens intestinal segments and stimulates intestinal structural changes at POD7 and 14. This suggests a decreased force is capable of inducing spring-mediated distraction enterogenesis.

INTRODUCTION/BACKGROUND:High-risk neuroblastoma is a deadly disease; poor prognosticators are MYCN-amplification and TERT-overexpression. We hypothesized that Gene Set Enrichment Analysis (GSEA) could identify pathways associated with MYCN-amplification and that inhibition of these pathways could decrease tumor growth. METHODS:We analyzed the Neuroblastoma-Kocak dataset (GSE45547, n = 649) and identified pathways associated with MYCN-amplification. Inhibitors were selected from upregulated gene sets for in vitro cytotoxicity testing using ST16-patient-derived primary neuroblastoma cells and in vivo testing using orthotopic ST16-patient-derived xenografts (PDX) in mice. Tumor volume was measured with ultrasound and tumor sections examined after H&E staining. RESULTS:GSEA identified significantly overexpressed gene sets in MYCN-amplified tumors including MYC targets, cell cycle mitotic genes, TERT associated genes, loss of RB1 gene sets, and E2Fs targets. Several genes were potential Bromodomain-containing protein 4 (Brd4) targets, making Brd4 inhibitors - JQ1, AZD5153 - and cyclin-dependent kinase (Brd4's binding partner) inhibitors - dinaciclib - potential therapeutic agents. JQ1 and dinaciclib were synergistic in inducing cytotoxicity in vitro. Dinaciclib-AZD5153 in vivo decreased tumor size compared to control, and increased tumor lymphocyte infiltration and necrosis on histology. CONCLUSIONS:GSEA is a powerful approach to identify upregulated genes and potential therapeutic targets. Dinaciclib-AZD5153 combination therapy can be effective against MYCN-amplified and TERT-overexpressing neuroblastoma tumors.

BACKGROUND:Ultrasound-guided (US) transversus abdominis plane (TAP) block is commonly utilized as part of a multi-modal approach for postoperative pain management. This study seeks to determine whether laparoscopic-guided TAP blocks are as effective as US-guided TAP blocks among pediatric patients. METHOD/METHODS:In this prospective, randomized controlled trial, pediatric patients undergoing laparoscopic procedures were randomly assigned to one of two treatment arms: US-guided TAP block (US-arm) or laparoscopic-guided TAP block (LAP-arm). Primary outcome was PACU pain scores. Secondary outcomes included PACU opioid consumption, block completion time and block accuracy. RESULTS:Twenty-five patients were enrolled in each arm. In the LAP-arm, 59% of blocks were in the transversus abdominis plane compared to 74% of TAP blocks in the US-arm (p = 0.18). Blocks were completed faster in the LAP-arm (2.1 ± 1.9 vs. 7.9 ± 3.4 min, p<0.001). The average highest PACU pain score was 3.4 ± 3.1 for the LAP-arm and 4.3 ± 3.8 for the US-arm (p = 0.37). Overall PACU pain scores and opioid consumption were similar between the groups (1.2 ± 1.3 vs. 1.6 ± 1.6, p = 0.24; 2.2 ± 5.8 vs. 0.9 ± 1.4MME, p = 0.26). CONCLUSION/CONCLUSIONS:Laparoscopic TAP blocks have equivalent efficacy in post-operative pain scores, narcotic use, and tissue plane accuracy as compared to US-guided TAP blocks. They are also completed faster and may result in less operating room and general anesthetic time for the pediatric patient.

BACKGROUND/PURPOSE/OBJECTIVE:Intraluminal springs have recently been shown to lengthen segments of intestine in a process known as distraction enterogenesis. We hypothesized that biocompatible springs could be used to lengthen defunctionalized murine small intestine and would lead to identifiable intestinal adaptations at the molecular level. METHODS:Age and weight matched C57BL/6 mice underwent surgical insertion of nitinol spring-loaded capsules into a Roux limb of jejunum. Segment lengths were measured at initial spring placement and at euthanasia after 14 and 21 days. Histology and gene expression of the Roux limb were evaluated at scarification and compared to untreated control segments. RESULTS:Intestinal segments loaded with compressed springs lengthened an average of 240%, which was significantly longer than control segments loaded with either empty capsules or uncompressed springs. Muscularis thickening was greater in spring-treated mice compared to controls without springs. Crypt depth and Lgr5+ expression was greater in mice that received compressed spring treatments when compared to control groups. CONCLUSIONS:Insertion of a compressed nitinol spring into a Roux limb results in significant intestinal lengthening, smooth muscle thickening, and Lgr5+ expression in a mouse model. The ability to increase small bowel length in a defunctionalized murine model may be used to understand the mechanism of distraction enterogenesis.