Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport.

Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK). In turn, AMPK activates FOXO3A and its transcriptional target, PUMA, which induces anoikis to suppress PDAC tumor growth and metastasis. Pharmacological or genetic activation of AMPK, similar to PON2 inhibition, blocks PDAC tumor growth. Collectively, our results identify PON2 as a new modulator of glucose transport that regulates a pharmacologically tractable pathway necessary for PDAC tumor growth and metastasis.

Utility of a Benchmarking Report for Balancing Infection Prevention and Antimicrobial Stewardship in Children with Complicated Appendicitis.

OBJECTIVE: To develop a severity-adjusted, hospital-level benchmarking comparative performance report for postoperative organ space infection and antibiotic utilization in children with complicated appendicitis. BACKGROUND: No benchmarking data exist to aid hospitals in identifying and prioritizing opportunities for infection prevention or antimicrobial stewardship in children with complicated appendicitis. METHODS: This was a multicenter cohort study using NSQIP-Pediatric data from 16 hospitals participating in a regional research consortium, augmented with antibiotic utilization data obtained through supplemental chart review. Children with complicated appendicitis who underwent appendectomy from 07/01/2015 to 06/30/2020 were included. Thirty-day postoperative OSI rates and cumulative antibiotic utilization were compared between hospitals using observed-to-expected (O/E) ratios after adjusting for disease severity using mixed effects models. Hospitals were considered outliers if the 95% confidence interval for O/E ratios did not include 1.0. RESULTS: 1790 patients were included. Overall, the OSI rate was 15.6% (hospital range: 2.6-39.4%) and median cumulative antibiotic utilization was 9.0 days (range: 3.0-13.0). Across hospitals, adjusted O/E ratios ranged 5.7-fold for OSI (0.49-2.80, P=0.03) and 2.4-fold for antibiotic utilization (0.59-1.45, P<0.01). Three (19%) hospitals were outliers for OSI (1 high and 2 low performers), and eight (50%) were outliers for antibiotic utilization (5 high and 3 low utilizers). Ten (63%) hospitals were identified as outliers in one or both measures. CONCLUSIONS: A comparative performance benchmarking report may help hospitals identify and prioritize quality improvement opportunities for infection prevention and antimicrobial stewardship, as well as identify exemplar performers for dissemination of best practices.

Antibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner.

Regulation of small intestinal epithelial growth by endogenous and environmental factors is critical for intestinal homeostasis and recovery from insults. Depletion of the intestinal microbiome increases epithelial proliferation in small intestinal crypts, similar to the effects observed in animal models of serotonin potentiation. Based on prior evidence that the microbiome modulates serotonin activity, we hypothesized that microbial depletion-induced epithelial proliferation is dependent on host serotonin activity. A mouse model of antibiotic-induced microbial depletion (AIMD) was employed. Serotonin potentiation was achieved through either genetic knockout of the serotonin transporter (SERT) or pharmacological SERT inhibition, and inhibition of serotonin synthesis was achieved with para-chlorophenylalanine. AIMD and serotonin potentiation increased intestinal villus height and crypt proliferation in an additive manner, but the epithelial proliferation observed after AIMD was blocked in the absence of endogenous serotonin. Using Lgr5-EGFP-reporter mice, we evaluated intestinal stem cell (ISC) quantity and proliferation. AIMD increased the number of ISCs per crypt and ISC proliferation compared with controls, and changes in ISC number and proliferation were dependent on the presence of host serotonin. Furthermore, Western blotting demonstrated that AIMD reduced epithelial SERT protein expression compared with controls. In conclusion, host serotonin activity is necessary for microbial depletion-associated changes in villus height and ISC proliferation in crypts, and microbial depletion produces a functional serotonin-potentiated state through reduced SERT protein expression. These findings provide an understanding of how changes to the microbiome contribute to intestinal pathology and can be applied therapeutically.NEW & NOTEWORTHY Antibiotic-induced microbial depletion of the murine small intestine results in a state of potentiated serotonin activity through reduced epithelial expression of the serotonin transporter. Specifically, serotonin-dependent mechanisms lead to increased intestinal surface area and intestinal stem cell proliferation. Furthermore, the absence of endogenous serotonin leads to blunting of small intestinal villi, suggesting that serotonin signaling is required for epithelial homeostasis.

Association Between Antibiotic Redosing Before Incision and Risk of Incisional Site Infection in Children With Appendicitis.

OBJECTIVE: To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis. BACKGROUND: Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing before incision. METHODS: This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from July 2016 to June 2020 who received antibiotics upon diagnosis of appendicitis between 1 and 6 hours before incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within 1 hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events. RESULTS: A total of 3533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P <0.001) and iSSI rates were similar between groups [redosed: 1.2% vs non-redosed: 1.3%; odds ratio (OR) 0.84, (95%,CI, 0.39-1.83)]. In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs nonredosed: 2.5%; OR: 0.38, (95% CI, 0.17-0.84)], but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity. CONCLUSIONS: Redosing of antibiotics within 1 hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.

Use of Antipseudomonal Antibiotics is not Associated with Lower Rates of Postoperative Drainage Procedures or More Favorable Culture Profiles in Children with Complicated Appendicitis: Results from a Multicenter Regional Research Consortium.

OBJECTIVE: To compare rates of postoperative drainage and culture profiles in children with complicated appendicitis treated with the two most common antibiotic regimens with and without antipseudomonal activity (piperacillin-tazobactam [PT] and ceftriaxone with metronidazole [CM]). SUMMARY OF BACKGROUND DATA: Variation in use of antipseudomonal antibiotics has been driven by a paucity of multicenter data reporting clinically relevant, culture-based outcomes. METHODS: Retrospective cohort study of patients with complicated appendicitis (7/2015-6/2020) using NSQIP-Pediatric data from 15 hospitals participating in a regional research consortium. Operative report details, antibiotic utilization, and culture data were obtained through supplemental chart review. Rates of 30-day postoperative drainage and organism-specific culture positivity were compared between groups using mixed effects regression to adjust for clustering after propensity matching on measures of disease severity. RESULTS: 1002 children met criteria for matching (58.9% received CM and 41.1% received PT). In the matched sample of 778 patients, children treated with PT had similar rates of drainage overall (PT: 11.8%, CM: 12.1%; OR 1.44 [OR:0.71-2.94]) and higher rates of drainage associated with growth of any organism (PT: 7.7%, CM: 4.6%; OR 2.41 [95%CI:1.08-5.39]) and Escherichia coli (PT: 4.6%, CM: 1.8%; OR 3.42 [95%CI:1.07-10.92]) compared to treatment with CM. Rates were similar between groups for drainage associated with multiple organisms (PT: 2.6%, CM: 1.5%; OR 3.81 [95%CI:0.96-15.08]) and Pseudomonas (PT: 1.0%, CM: 1.3%; OR 3.42 [95%CI:0.55-21.28]). CONCLUSIONS AND RELEVANCE: Use of antipseudomonal antibiotics is not associated with lower rates of postoperative drainage procedures or more favorable culture profiles in children with complicated appendicitis.

Comparing Serum Matrix Metalloproteinase-7 in Parenteral Nutrition-Associated Liver Disease and Biliary Atresia.

In this cross-sectional study, serum matrix metalloproteinase-7 levels were significantly lower in infants with jaundice and parenteral nutrition-associated liver disease compared with those with confirmed biliary atresia. Serum metalloproteinase-7 may aid in excluding biliary atresia and thus may minimize invasive testing in infants with a history of parenteral nutrition.

Point-of-Care Ultrasound to Evaluate the Acute Abdomen: A Case of Bowel Perforation After Unknown Single Magnet Ingestion.

ABSTRACT: We report the case of a 3-year-old boy who presented to the pediatric emergency department in undifferentiated shock with an acute abdomen. Point-of-care ultrasound revealed viscous perforation with a large amount of free fluid. Intraoperatively, a single magnet was discovered as the likely cause of bowel perforation and the resulting state of shock.

Reducing Underdiagnosis of Hirschsprung-Associated Enterocolitis: A Novel Scoring System.

BACKGROUND: Hirschsprung-Associated Enterocolitis (HAEC) is a life-threatening and difficult to diagnose complication of Hirschsprung Disease (HSCR). The goal of this study was to evaluate existing HAEC scoring systems and develop a new scoring system. METHODS: Retrospective, multi-institutional data collection was performed. For each patient, all encounters were analyzed. Data included demographics, symptomatology, laboratory and radiographic findings, and treatments received. A "true" diagnosis of HAEC was defined as receipt of treatment with rectal irrigations, antibiotics, and bowel rest. The Pastor and Frykman scoring systems were evaluated for sensitivity/specificity and univariate and multivariate logistic regression performed to create a new scoring system. RESULTS: Four centers worldwide provided data on 200 patients with 1450 encounters and 369 HAEC episodes. Fifty-seven percent of patients experienced one or more episodes of HAEC. Long-segment colonic disease was associated with a higher risk of HAEC on univariate analysis (OR 1.92, 95% CI 1.43-2.57). Six variables were significantly associated with HAEC on multivariate analysis. Using published diagnostic cutoffs, sensitivity/specificity for existing systems were found to be 38.2%/96% for Pastor's and 56.4%/86.9% for Frykman's score. A new scoring system with a sensitivity/specificity of 67.8%/87.9% was created by stepwise multivariate analysis. The new score outperformed the existing scores by decreasing underdiagnosis in this patient cohort. CONCLUSIONS: Existing scoring systems perform poorly in identifying episodes of HAEC, resulting in significant underdiagnosis. The proposed scoring system may be better at identifying those underdiagnosed in the clinical setting. Head-to-head comparison of HAEC scoring systems using prospective data collection may be beneficial to achieve standardization in the field.

Orally Dosed Citalopram Stimulates Small Intestinal Mucosal Growth.

BACKGROUND: Parenterally administered selective serotonin reuptake inhibitors, such as citalopram, increase intestinal mucosal absorptive surface by day 7 of treatment. We hypothesized that enteral citalopram would also induce intestinal mucosal growth, thus allowing for therapy with an oral agent. MATERIALS AND METHODS: Following a habituation period, C57BL/6 mice received peanut butter pellets containing 10, 50, or 100 mg/kg/d citalopram for 7 d (n = 5); or 25 mg/kg/d citalopram for 14 (n = 3) or 21 (n = 5) d; or plain peanut butter pellets for 7 (n = 2), 14 (n = 2), or 21 d (n = 3). Two-centimeter ileal segments were harvested and prepared for microscopic assessment of villus height (VH), crypt depth, villus width (VW), and crypt width. Mucosal surface area (MSA) was calculated and data were compared using Student's t-test. RESULTS: Enteral administration of citalopram had virtually no effect on VH, VW, or crypt depth after 7 d; crypt width decreased significantly (P value range 0.0002 to <0.0001), likely contributing to the increases in MSA (P value range 0.0578 to 0.0006). After 14 d of treatment, citalopram significantly increased VH (P < 0.0001), VW (P = 0.0058), and ileal MSA per mm2 (P = 0.0007). The increase in MSA was sustained at 21 d (P < 0.0001). CONCLUSIONS: Enteral citalopram given for 14 d results in increased VH and ileal MSA, which remains increased by day 21. Selective serotonin reuptake inhibitors show potential as oral therapy for serious intestinal disorders such as short bowel syndrome.

The Limited Utility of Routine Culture in Pediatric Pilonidal, Gluteal, and Perianal Abscesses.

BACKGROUND: Pilonidal, buttock, and perianal abscesses are common reasons for surgical consultation in the pediatric emergency department. Treatment typically includes a bedside incision and drainage, often followed by an abscess culture, and a course of oral antibiotics. We aimed to study the impact of culture data on changes in management and clinical outcomes. We hypothesized that management is unaffected by culture data, and therefore, fluid culture from pilonidal, buttock, and perianal abscesses in the pediatric population may represent an unnecessary laboratory test and cost. MATERIALS AND METHODS: A single institution's electronic medical record was searched between February 1, 2013 and August 1, 2017, identifying 249 pediatric patients meeting the inclusion criteria: age 0 to 18 y; diagnosis of pilonidal, buttock, or perianal abscess; bedside incision and drainage. Patients were divided into two different comparison groups for data analysis based on the presence or absence of culture and recurrence or no recurrence. RESULTS: Culture results directly altered management in only 5 patient encounters (2.7% of all cultured). When comparing groups by culture or no culture, no statistically significant difference in recurrence rate (P = 0.4) was noted. When comparing groups by recurrence versus no recurrence, we found no statistically significant difference between sex, resident type, vessel loop use, packing use, or antibiotic use (P > 0.05). CONCLUSIONS: We conclude that microbiological culture results are of limited utility in the management of pediatric pilonidal, buttock, and perianal abscesses as they do not appear to alter treatment, and omission of culture is not associated with failure of surgical management.

The Impact of Pediatric Surgical Specialty Meetings: A 5-year Analysis of Presented Abstracts.

BACKGROUND: Abstracts presented at the American Academy of Pediatrics Section on Surgery (AAP) and American Pediatric Surgical Association (APSA) meetings can be taken as a reasonable representation of academic activity in pediatric surgery. We sought to assess ongoing trends in pediatric surgical research by analyzing the scientific content of each association's yearly meeting. METHODS: Abstracts presented at AAP and APSA between 2009 and 2013 were identified from the final printed programs (n = 910). Video abstracts (n = 34) were excluded. Collected data included title, authors, classification (basic science/clinical), presentation type (podium/poster), and topic. Publication as a journal article was determined using the abstract title/authors in a PubMed search. Journal impact factors were recorded for each journal and a composite impact factor (CIF) was calculated by dividing the sum of impact factors by the published articles per meeting. RESULTS: Number of abstracts presented, percentage published, abstract classifications, and presentation type remained consistent over the study period. The AAP meetings accepted a higher percentage of clinical abstracts: AAP 72.3 ± 3.4% versus APSA 65.9 ± 1.3%. The five most popular topics at both meetings were oncology, congenital diaphragmatic hernia, necrotizing enterocolitis, trauma, and appendicitis. The publication rate for clinical and basic science abstracts did not vary significantly over the study period, whereas CIFs were higher for basic science publications nearly every year. The percentage of podium abstracts published was significantly greater than poster abstracts, but no statistical difference in CIF was seen between podium- and poster-associated publications. CONCLUSIONS: Abstracts accepted and presented at the two major pediatric surgical specialty meetings more commonly involve clinical studies with a trend away from basic science. Despite this, basic science abstracts tended to be published in higher impact journals. This study attempts to quantify the quality of pediatric surgical research and serves as a baseline for future comparison.

Opioid Prescribing Habits of General Versus Pediatric Surgeons After Uncomplicated Laparoscopic Appendectomy.

BACKGROUND: Adolescents who use prescription opioids have an increased risk for future drug abuse and overdose, making them a high-risk population. Appendectomy is one of the most common surgical procedures in this age group, often requires opioid analgesia, and is performed by both pediatric and general surgeons. Prescription patterns comparing these two provider groups have not yet been evaluated; we hypothesize that general surgery providers prescribe more opioids for adolescent and young adult patients than do pediatric surgery providers. METHODS: A retrospective chart review was conducted across a single health system consisting of four hospitals. All uncomplicated laparoscopic appendectomies performed between January 1, 2016 and August 14, 2017 on patients aged 7-20 were included for analysis. Any case coded for multiple procedures, identified as converted to open, or had a length of stay >48 h were excluded. The primary outcome measure was amount of opioid prescribed postoperatively. To standardize different formulations and types of analgesia prescribed, prescriptions were converted into oral morphine equivalents (OMEs). For reference, one 5 mg pill of oxycodone equals 7.5 OME. Linear regression was performed controlling for patient weight, gender, race, insurance status, provider type (pediatric versus general surgery), and provider level (resident, advanced practice provider, and attending). RESULTS: A total of 336 pediatric laparoscopic appendectomies were analyzed, 148 by general surgeons and 188 by pediatric surgeons. Pediatric surgeons prescribed less opioid than general surgeons overall (59 OME versus 90 OME, P < 0.0001). For patients aged <13 y, there was no significant difference between pediatric (26 OME) and general (37 OME, P = 0.8921) surgeons. However, for the age group 13-20 y, pediatric surgeons prescribed 25% less opioid than general surgeons (90 OME versus 112.5 OME, P < 0.0001). Regression analysis demonstrated that being cared for by a general surgery service (+24.1 OME [95% confidence interval 9.8-38.3]) was associated with high prescribing, whereas having Medicaid was associated with lower prescription amounts (-16.4 OME [95% confidence interval -32.5 to -0.3]). CONCLUSIONS: After an uncomplicated laparoscopic appendectomy, general surgeons prescribe significantly more opioid to adolescent patients than do pediatric surgeons, even when controlling for age and weight. One substantial and modifiable contributor of the opioid epidemic is the amount of opioid prescribed. The variability of prescribing habits to adolescents and young adults demonstrates a clear need for increased education and guidelines on this topic, especially for surgeons who do not frequently treat the younger and more vulnerable population.

Mucosal homeostasis is altered in the ileum of gnotobiotic mice.

BACKGROUND: The microbiome of the gastrointestinal tract is a vast collection of microorganisms implicated in numerous aspects of normal physiology and disease pathogenesis. The use of gnotobiotic mouse models, with single or specific communities of microbes comprising the microbiome, can enhance our understanding of the microbiome-host relationship. We hypothesized that gnotobiotic mice would exhibit differences in mucosal homeostasis when compared with mice with conventional flora (CF). MATERIALS AND METHODS: Single-organism gnotobiotic mice were generated containing Escherichia coli MG1655, Akkermansia muciniphila, Bacteroides eggerthii, and Clostridium symbiosum, representing four of the major phyla present in the gastrointestinal tract. Distal ileal segments were harvested from adult mice, and histologic sections were H&E stained and used to measure villus height and crypt depth. Immunohistochemistry was performed with Ki67 and TUNEL as markers of proliferation and apoptosis, respectively. RESULTS: When compared to the ileum from CF mice, the ileum from all groups of gnotobiotic mice had significant increases in nearly all measured parameters. In addition, significant differences were seen among certain gnotobiotic groups for villus height, crypt depth, and apoptosis. CONCLUSIONS: Single-organism gnotobiotic mice demonstrate enhanced morphometric parameters compared with mice with CF and show differences in growth patterns among bacterial species. These findings suggest unique interactions between individual bacteria and the host animal which hold potential for future therapeutic strategies aimed at mucosal restoration. The mechanisms involved in this process therefore warrant further study.

Enhanced serotonin signaling stimulates ordered intestinal mucosal growth.

BACKGROUND: Significant quantities of serotonin (5-hydroxytryptamine; 5-HT) are found in the intestine, and studies have demonstrated that 5-HT can stimulate enterocyte cell division, suggesting regulatory roles in mucosal homeostasis and intestinal adaptation. We hypothesized that excess enteric 5-HT signaling enhances mucosal growth without changing intestinal villous cellular makeup. METHODS: Mice lacking the serotonin reuptake transporter (SERT) and wild-type littermates (WTLM) were euthanized and their ileum analyzed. Villus height (VH), crypt depth (CD), and enterocyte height (EH) were measured. Enterocyte cell division was measured using Ki-67 immunofluorescence to calculate crypt proliferation index (CPI). Cellular distribution along villi was investigated by immunofluorescent staining for enterocytes, enteroendocrine cells, and goblet cells. Group measurements were compared using t-test and chi-squared test. RESULTS: SERT knock-out (SERTKO) mice had significantly taller villi, deeper crypts, and taller enterocytes compared with WTLM (P < 0.0001). Similarly, enterocyte proliferation was greater in SERTKO compared with WTLM (P < 0.01). For SERTKO, mean values were: VH, 255.6 µm; CD, 66.7 µm; EH, 21.2 µm; and CPI, 52.8%. For WTLM, corresponding values were: VH, 207.8 µm; CD, 56.1 µm; EH, 19.5 µm; and CPI, 31.9%. The cellular composition along villi was not significantly different between genotypes (P > 0.05). CONCLUSIONS: Enhancing 5-HT signaling in mice increases VH, CD, EH, and crypt cell proliferation in the intestinal mucosa. 5-HT-associated growth did not alter the cellular composition of the villi. Serotonin may represent an important physiologic regulator of intestinal growth and adaptation and holds promise as a target for therapies aimed at enhancing intestinal recovery after injury or mucosal surface area loss.

Surgical tray optimization as a simple means to decrease perioperative costs.

BACKGROUND: Health care spending in the US remains excessively high. Aside from complicated, large-scale efforts at health care cost reduction, there are still relatively simple ways in which individual hospitals can cut unnecessary costs from everyday operations. Inspired by recent publications, our group sought to decrease the costs associated with surgical instrument processing at a large, multihospital academic center. METHODS: This was a single-site observational study conducted at a large academic medical center. At the study start, all attending surgeons within the section of pediatric surgery agreed to standardize the pediatric surgery trays and to eliminate instruments that were deemed unnecessary from each tray. A multidisciplinary start-up meeting was held, and this meeting included stakeholders from central sterile processing, operating room nursing, scrub technicians, and materials management along with all five pediatric surgeons. Each tray was addressed individually. Instruments were eliminated from trays only if there was unanimous agreement among all the surgeons in the group. If no instruments in a given surgical tray were deemed necessary, the entire tray was eliminated from sterile processing rotation. Feedback questionnaires were drafted by the multidisciplinary team that participated in the start-up meeting. Surgeons were allowed to request for certain instruments to be placed back into the trays at any time, and the questionnaires also allowed for free-hand comments. Surgical kit preparation time was obtained from the institutional barcode scanning system. The cost per second of sterile processing labor was calculated using regional median salary for sterile processing technicians in the state of Connecticut. Using the pediatric surgery section as the model unit, this method was then applied to pediatric urology, neurosurgery, spine surgery, and orthopedics. RESULTS: The pediatric surgery section eliminated an average of 59.5% of instruments per tray, resulting in an overall reduction of 1826 (39.5%) instruments from rotation, 45,856 fewer instruments processed per year, and nine trays eliminated completely from regular rotation. Processing time for six commonly used trays was reduced by an average of 28.7%. The urology section eliminated 18 trays from regular rotation and 179 (10.1%) instruments in total. Pediatric orthopedics, neurosurgery, and spine sections eliminated 708 (17.1%), 560 (92.7%), and 31 (32.2%) instruments, respectively, resulting in approximately 18,804 fewer instruments processed per year. Among all five surgical sections, annual instrument cost avoidance after tray optimization was estimated at $53,193 to $531,929 using average instrument life spans ranging from 1-10 y. Negative feedback and requests for instrument replacement were both minimal on feedback questionnaires. CONCLUSIONS: Surgical tray optimization represents a relatively simple microsystem improvement that could result in significant hospital cost reduction. Although difficult to quantify, other gains from surgical kit optimization include decreased weight per tray, decreased materials cost, and decreased labor required to count, decontaminate, and pack surgical trays.

Guidelines for the diagnosis and management of Hirschsprung-associated enterocolitis.

BACKGROUND: Patients with Hirschsprung disease are at risk for Hirschsprung-associated enterocolitis (HAEC), an inflammatory disorder of the bowel that represents the leading cause of serious morbidity and death in these patients. The diagnosis of HAEC is made based on clinical signs and symptoms which are often non-specific, making it difficult to establish a definitive diagnosis in many patients. The purpose of this guideline is to present a rational, expert-based approach to the diagnosis and management of HAEC. METHODS: The American Pediatric Surgical Association Board of Governors established a Hirschsprung Disease Interest Group. Group discussions, literature review, and expert consensus were then used to summarize the current state of knowledge regarding diagnosis, management, and prevention of Hirschsprung-associated enterocolitis (HAEC). RESULTS: Guidelines for the diagnosis of HAEC and its clinical grade, utilizing clinical history, physical examination findings, and radiographic findings, are presented. Treatment guidelines, including patient disposition, diet, antibiotics, rectal irrigations and surgery, are presented. CONCLUSIONS: Clear, standardized definitions of Hirschsprung-associated enterocolitis and its treatment are lacking in the literature. This guideline serves as a first step toward standardization of diagnosis and management. LEVEL OF EVIDENCE: V.

A comparison of suction and full-thickness rectal biopsy in children.

BACKGROUND: Rectal biopsy evaluation by an experienced pathologist is the gold standard in diagnosis of Hirschsprung's disease (HD). Although both suction rectal biopsy (SRB) and full-thickness (FTRB) rectal biopsy are performed, the ability for SRB to obtain adequate tissue in older children has been questioned. We hypothesized that SRB and FTRB yield tissue specimens of different size but are equally adequate for diagnosis. METHODS: Records of children who underwent rectal biopsy to evaluate for HD between January 2007 and July 2014 were reviewed. Volume, percent submucosa, and specimen adequacy were compared between biopsy techniques, and the effect of age on biopsy adequacy was assessed. Data were analyzed by mixed-effects models with covariate adjustment for age at biopsy and Fisher's exact test. RESULTS: Forty-seven children underwent a total of 58 biopsies, 45 SRB and 13 FTRB. Thirty-seven were performed before 12 mo of age, and 21 after 12 mo of age. Volume of SRB specimens was significantly smaller than FTRB across ages (14.8 ± 7.8 mm(3)versus 121.3 ± 13.8 mm(3), P = 0.0001). Percent submucosa did not differ significantly between SRB and FTRB specimens across ages (63.8 ± 2.7% versus 66.5 ± 4.3%, P = 0.575). The number of inadequate biopsies was low and not significantly different across ages (P = 0.345), or when comparing by biopsy method (P = 0.689). All biopsies were clinically diagnostic. There were no complications. CONCLUSIONS: Tissue specimens obtained by SRB are smaller than those obtained by FTRB, especially in older children. SRB and FTRB appear equivalent in their ability to provide adequate submucosa. Differences in cost and patient satisfaction between rectal biopsy techniques must be studied to further define the best overall technique.

Accurate assessment of bowel length: the method of measurement matters.

PURPOSE: Small intestinal length has prognostic significance for patients with short bowel syndrome, and accurate measurement of Roux-en-Y limbs is considered important. The flexible elasticity of bowel makes its measurement highly subjective, yet a recommended method for intestinal measurement allowing accurate comparisons between surgeons remains undefined. Measurement of intestinal length has been described, but no comparison of the fidelity of measurement technique has been made. We hypothesized that silk suture and umbilical tape would yield the most consistent measurements. METHODS: This institutional review board-approved prospective trial enrolled 12 volunteer surgeons and two Institutional Animal Care and Use Committee-donated rabbits. Participants were asked to measure short, medium, and long segments of small intestine in a euthanized rabbit using common operating room tools: 18-in silk suture, 75-cm umbilical tape, 15-cm straight ruler, laparoscopic Dorsey bowel graspers. Data were analyzed by analysis of variance repeated measures model. RESULTS: Over short segments, intestinal measurements by grasper were significantly shorter than those by tape (P = 0.002) and ruler (P = 0.039). Over medium lengths of bowel, measurements by grasper were significantly shorter than those by suture (P = 0.032) and tape (P = 0.046), and measurements by ruler also were significantly shorter than those by suture (P = 0.008). Over the long intestinal segment, measurements by ruler resulted in the greatest variability, and comparison of variance across all possible pairs of groups found significant difference by method of measurement (P = 0.049). There was a significant difference in measurements taken along the mesenteric border compared with those taken along the antimesenteric border (P = 0.001). CONCLUSIONS: Measurement technique along short segments matters less; however, rigid tools underestimate length, and smaller variances in measurement by silk suture and umbilical tape suggest that these methods are more reliable across longer distances.

Enhanced serotonin signaling increases intestinal neuroplasticity.

BACKGROUND: The intestinal mucosa recovers from injury by accelerating enterocyte proliferation resulting in villus growth. A similar phenomenon is seen after massive bowel resection. Serotonin (5-HT) has been implicated as an important regulator of mucosal homeostasis by promoting growth in the epithelium. The impact of 5-HT on other components of growing villi is not known. We hypothesized that 5-HT-stimulated growth in the intestinal epithelium would be associated with growth in other components of the villus such as enteric neural axonal processes. MATERIALS AND METHODS: Enteric serotonergic signaling is inactivated by the serotonin reuptake transporter, or SERT, molecule. Enhanced serotonin signaling was achieved via SERT knockout (SERTKO) and administration of selective serotonin reuptake inhibitors (SSRI) to wild-type mice (WT-SSRI). 5-HT synthesis inhibition was achieved with administration of 4-chloro-L-phenylalanine (PCPA). Intestinal segments from age-matched WT, SERTKO, WT-SSRI, and corresponding PCPA-treated animals were assessed via villus height, crypt depth, and crypt proliferation. Gap 43, a marker of neuroplasticity, was assessed via immunofluorescence and Western blot. RESULTS: SERTKO and WT-SSRI mice had taller villi, deeper crypts, and increased enterocyte proliferation compared with WT mice. Gap 43 expression via immunofluorescence was significantly increased in SERTKO and WT-SSRI samples, as well as in Western blot analysis. PCPA-treated SERTKO and WT-SSRI animals demonstrated reversal of 5-HT-induced growth and Gap 43 expression. CONCLUSIONS: Enhanced 5-HT signaling results in intestinal mucosal growth in both the epithelial cell compartment and the enteric nervous system. Furthermore, 5-HT synthesis inhibition resulted in reversal of effects, suggesting that 5-HT is a critically important regulator of intestinal mucosal growth and neuronal plasticity.

Duodenal intussusception secondary to web presenting as recurrent pancreatitis in a 7-year-old girl.

Duodenal intussusception is a rare entity in children, with 32 cases reported in the English literature to our knowledge. Most reported cases are associated with endoluminal tubes or polyps, and the presenting symptoms are chronic and nonspecific. We report a case of duodenal intussusception in a 7-year-old girl secondary to a duodenal web and review the imaging findings.