Lack of Routine Postoperative Labs Not Associated With Complications in Pediatric Perforated Appendicitis.

INTRODUCTION: Postoperative (postop) management of pediatric perforated appendicitis varies significantly, and postop intra-abdominal abscesses (IAA) remain a significant issue. Between 2019 and 2020, our standardized protocol included routine postop labs after an appendectomy for perforated appendicitis. However, given the lack of predictive utility of these routine labs, we discontinued this practice in 2021. We hypothesize that discontinuing routine postop labs will not be associated with an increase in complication rates after an appendectomy for pediatric perforated appendicitis. METHODS: A single-institution, retrospective review of all pediatric appendectomies for perforated appendicitis from January 2019 to December 2021 was conducted at University Hospitals Rainbow Babies and Children's Hospital in Cleveland, Ohio. Data were collected on rate of complications (IAA development, re-admissions, bowel obstructions, superficial surgical site infections, intensive care unit transfers, Clostridium difficile infections, allergic reactions, and transfusions), postop imaging, postop interventions, and length of stay. Statistical analysis was completed using Fisher's exact test and Mann-Whitney U-test. RESULTS: A total of 109 patients (2019-2020 n = 61, 2021 n = 48) were included in the study. All 61 patients from 2019 to 2020 had postop labs compared to only eight patients in 2021. There was no statistically significant difference between the two groups in overall complication rates, but there was a decrease in IAAs reported in 2021 (P = 0.03). There were no statistically significant differences in other complications, postop imaging usage, or postop interventions. The median length of stay was 4.5 d in 2021 compared to 6.0 d in 2019-2020 (P = 0.009). CONCLUSIONS: Discontinuing routine postop labs is not associated with an increase in overall complications rates. Further studies are needed to determine whether routine postop labs can be safely removed in pediatric patients with perforated appendicitis, which would reduce patient discomfort and care costs.

Labs Do Not Predict Postoperative Intra-abdominal Abscess in Pediatric Perforated Appendicitis.

INTRODUCTION: We aim to evaluate the utility of postoperative labs in predicting the development of an intra-abdominal abscess (IAA) in pediatric patients with perforated appendicitis. We hypothesize that postoperative labs are not predictive of IAA development. METHODS: This was a single-institution retrospective cohort study that included pediatric patients (n = 61) who underwent surgery for perforated appendicitis from January 1, 2019 to December 1, 2020. Patients were stratified into those who developed a postoperative IAA (n = 22) and those who did not (n = 39). Postoperative labs (white blood cell [WBC] count, absolute neutrophil count, platelet count, C-reactive protein) were examined. Mann-Whitney U tests and chi-square tests were used to assess for differences between groups. RESULTS: There was extensive heterogeneity and overlap in postoperative lab values between patients who developed an IAA and those who did not. Almost all patients who developed an IAA had clinical signs that were indicative of abscess formation regardless of their postoperative WBC count or change in WBC count. While patients who developed an IAA had a higher postoperative median WBC count (10.8 versus 8.4, P = 0.003) and a smaller WBC count decrease (-4.9 versus -7.4, P = 0.01), no cutoff value for any of the examined lab values specifically predicted abscess formation. Postoperative median absolute neutrophil count (7.4 versus 4.0, P = 0.15), platelet count (360 versus 353, P = 0.98), and C-reactive protein (8.20 versus 5.32, P = 0.06) did not differ significantly. CONCLUSIONS: We conclude that postoperative labs have limited clinical utility in evaluating IAA development in children with perforated appendicitis.

Neonatal Intensive Care Unit Mixed Lipid Emulsion Use Associated With Reduced Cholestasis at Discharge in Surgical Patients.

INTRODUCTION: Parenteral nutrition associated cholestasis (PNAC) is a common morbidity in neonates requiring total parenteral nutrition (TPN). Previous studies in infants with intestinal failure have shown a benefit of mixed lipid emulsion (MLE) in reducing PNAC. It is not known whether this benefit extends to a general neonatal intensive care unit (NICU) population, where MLE is used on a selective basis. The objective of this study is to examine associations between MLE use and PNAC rate in the general NICU setting. METHODS: This is a retrospective review of NICU patients who received TPN for 7 or more days. We compared patients born between 1/1/2014 and 12/31/2015 (pre-MLE) to patients born between 7/1/2017 and 12/31/2018 (post-MLE). Fisher's exact test and two-sample t-test were used to compare the two groups. RESULTS: There were 353 patients in 2014-2015 and 271 patients in 2017-2018. Demographics were similar between the two groups, but there were more patients with congenital heart disease in the MLE era (P < 0.001). Mortality was similar (6.2% pre-MLE versus 6.3% post-MLE). There was no significant difference in PNAC rate between the pre-MLE (11.5%) and post-MLE (14.1%) patient cohorts (P = 0.342). Among patients receiving MLE (n = 38), 58% developed PNAC, while only 6.4% of the post-MLE cohort not receiving MLE developed PNAC. Of the patients coded with a surgical diagnosis, there was no significant difference in PNAC rates between pre-MLE and post-MLE groups. Discharge rates of PNAC did differ between pre-MLE surgical patients (13.0%) and post-MLE surgical patients (8.2%). In the subgroup of post-MLE surgical patients, PNAC rate differed significantly between those receiving MLE (43.5%) and not receiving MLE (15.4%). However, this difference was resolved by discharge (8.7% versus 7.7%). CONCLUSIONS: There were no significant differences in PNAC rates between the pre-MLE and post-MLE cohorts. However, in surgical patients, MLE was associated with reduced PNAC at discharge, with levels equivalent to those seen in neonates receiving TPN for 7 or more days, despite having a higher starting rate of PNAC. Further studies are needed to determine whether the general NICU population may benefit from MLE or certain selective subpopulations like surgical patients.

Wilms Tumor in Child With Trisomy 18 and Horseshoe Kidney.

Trisomy 18 is associated with several congenital malformations, including horseshoe kidney. It can be full, partial, or mosaic, and mosaicism is often associated with lesser severity and longer life expectancy, placing patients at greater risk of developing neoplasms or malignancies. One common tumor among children with Trisomy 18 is Wilms tumor, which is also associated with renal congenital abnormalities such as horseshoe kidney. We present a case describing the occurrence of these three characteristics: development of Wilms tumor in a patient with Trisomy 18 and a horseshoe kidney and discuss treatment with regards to these conditions.

Total parenteral nutrition-associated lamina propria inflammation in mice is mediated by a MyD88-dependent mechanism.

Enteral nutrient deprivation via total parenteral nutrition (TPN) administration leads to local mucosal inflammatory responses, but the underlying mechanisms are unknown. Wild-type (WT) and MyD88(-/-) mice underwent jugular vein cannulation. One group received TPN without chow, and controls received standard chow. After 7 d, we harvested intestinal mucosally associated bacteria and isolated small-bowel lamina propria (LP) cells. Bacterial populations were analyzed using 454 pyrosequencing. LP cells were analyzed using quantitative PCR and multicolor flow cytometry. WT, control mucosally associated microbiota were Firmicutes-dominant, whereas WT TPN mice were Proteobacteria-domiant. Similar changes were observed in MyD88(-/-) mice with TPN administration. UniFrac analysis showed divergent small bowel and colonic bacterial communities in controls, merging toward similar microbiota (but distinct from controls) with TPN. The percentage of LP T regulatory cells significantly decreased with TPN in WT mice. F4/80(+)CD11b(+)CD11c(dull/-) macrophage-derived proinflammatory cytokines significantly increased with TPN. These proinflammatory immunologic changes were significantly abrogated in MyD88(-/-) TPN mice. Thus, TPN administration is associated with significant expansion of Proteobacteria within the intestinal microbiota and increased proinflammatory LP cytokines. Additionally, MyD88 signaling blockade abrogated decline in epithelial cell proliferation and epithelial barrier function loss.

Characteristics of and cost of care for children with impaired development and acute appendicitis: A study of two national databases.

BACKGROUND: Characteristics of children with impaired development who have acute appendicitis are not well described in the literature. METHODS: We reviewed the National Surgical Quality Improvement Program-Pediatric and the multicenter Pediatric Health Information System for patients with acute appendicitis. Comparisons for demographics, clinical outcomes, and hospital charges between children with impaired development versus neurotypical children were made using independent t test or Wilcoxon rank sum tests. The multivariable logistic regression model estimated the odds of complicated acute appendicitis in impaired development patients. Based on correlation analyses, hierarchical linear modeling was used to examine the extent to which impaired development influenced resource use. RESULTS: Patients with impaired development were younger, had higher comorbidities, and were more commonly male sex. In the National Surgical Quality Improvement Program-Pediatric database, impaired development was associated with higher rates of complicated acute appendicitis (33.6% vs 27.5, P < .001), particularly in older children, and higher usage of computed tomography at National Surgical Quality Improvement Program-Pediatric hospitals (23.1% vs 15.1%, P < .001). In the Pediatric Health Information System database, the adjusted odds of complicated acute appendicitis were significantly higher in patients with impaired development (1.20 [1.09-1.31]), low childhood opportunity level (1.39 [95% confidence interval: 1.31-1.47]), and Black race (1.25 [1.17-1.33]). Hierarchical adjusted linear modeling showed that impaired development was associated with significantly higher hospital charges (9% increase). CONCLUSION: Management of acute appendicitis in children with impaired development remains a challenge to clinicians, as evidenced by the higher rate of perforated appendicitis in older children, diagnostic computed tomography use at National Surgical Quality Improvement Program-Pediatric hospitals, postoperative computed tomography use, and increased costs.

Quadratus Lumborum Block as a Cornerstone for Neonatal Intestinal Surgery Enhanced Recovery (ERAS): A Case Series.

Purpose: Neonates present unique challenges for pediatric surgical teams. To optimize outcomes, it is imperative to standardize perioperative care by using early extubation and multimodal analgesic techniques. The quadratus lumborum (QL) block provides longer duration and superior pain relief than other single-injection abdominal fascial plane techniques. The purpose of this case series was to report our initial experience with QL blocks in neonatal patients treated with intestinal ERAS. Patients and Methods: Ten neonates requiring intestinal surgery at a single tertiary care center who received QL blocks between December 2019 and April 2022 for enhanced recovery were studied. Bilateral QL blocks were performed with 0.5 mL/kg of 0.25% ropivacaine per side with an adjuvant of 1 mcg/kg of dexmedetomidine. Results: Gestational age at birth ranged from 32.2 to 41 weeks. The median age, weight, and American Society of Anesthesiologists (ASA) score at the time of surgery was 5 days [range 7.5 hours, 60 days], 2.84 kg [range 1.5, 4.5], and 3, respectively. Bilateral QL blocks were performed without complications in all patients. Two patients were outside the neonatal range from birth to surgery, but were under 42 weeks gestational age when corrected for prematurity. All patients were extubated with well-controlled pain, and no patient required reintubation within the first 24 hours. Postoperatively, median cumulative morphine equivalents were 0.16 mg/kg [range 0, 0.79] and six patients received scheduled acetaminophen. Morphine (0.1 mg/kg) was administered to patients with a modified neonatal infant pain scale (NIPS) score greater than or equal to 4, and pain was reassessed 1 hour after administration (Appendix). Conclusion: When developing intestinal ERAS protocols, Bilateral QL blocks may be considered for postoperative analgesia in the neonatal population. Further prospective studies are required to validate this approach in neonates.

Successful implantation of bioengineered, intrinsically innervated, human internal anal sphincter.

BACKGROUND & AIMS: To restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human IAS to emulate sphincteric physiology in vitro. METHODS: We cocultured human IAS circular smooth muscle with immortomouse fetal enteric neurons. We investigated the ability of bioengineered innervated human IAS, implanted in RAG1-/- mice, to undergo neovascularization and preserve the physiology of the constituent myogenic and neuronal components. RESULTS: The implanted IAS was neovascularized in vivo; numerous blood vessels were observed with no signs of inflammation or infection. Real-time force acquisition from implanted and preimplant IAS showed distinct characteristics of IAS physiology. Features included the development of spontaneous myogenic basal tone; relaxation of 100% of basal tone in response to inhibitory neurotransmitter vasoactive intestinal peptide (VIP) and direct electrical field stimulation of the intrinsic innervation; inhibition of nitrergic and VIPergic electrical field-induced relaxation (by antagonizing nitric oxide synthesis or receptor interaction); contraction in response to cholinergic stimulation with acetylcholine; and intact electromechanical coupling (evidenced by direct response to potassium chloride). Implanted, intrinsically innervated bioengineered human IAS tissue preserved the integrity and physiology of myogenic and neuronal components. CONCLUSIONS: Intrinsically innervated human IAS bioengineered tissue can be successfully implanted in mice. This approach might be used to treat patients with fecal incontinence.

Flow through a mechanical distraction enterogenesis device: a pilot test.

BACKGROUND: We tested the coupling portion of a prototype intraluminal distraction enterogenesis device to allow flow-through of simulated enteric contents (SEC) in both pig and human jejunum. MATERIALS AND METHODS: SEC was made using 80% corn syrup. Ten-cm pig and human intestinal segments had a spoke-shaped 2.2 cm coupling adaptor sutured in place, intraluminally. The adaptor had a flow-through area of 33.6 mm(2). SEC was pumped into the proximal part of the intestinal segment at 0.083 mL/s. The times to first passage of SEC through the coupler (first drop), 10 mL, and 20 mL of SEC eluted from the distal end were recorded. RESULTS: Mean time to first drop elution was 155 ± 38 s with pig, and 149 ± 22 s with human bowel (P = 0.8). This corresponded to a hydrostatic pressure of 37.5 mmHg before the initial drop passed through. Mean flow rates were 0.094 mL/s in pig bowel and 0.084 mL/s in human bowel (P = 0.09). To account for occlusion from luminal debris, a 75% occlusion of coupler holes was studied in the smaller pig bowel to investigate if reductions in flow-through area could be tolerated. Mean time to first drop increased slightly to 171 ± 15 s, but the elution rate stayed the same (P = 0.5). CONCLUSIONS: After a physiologic level of initial pressure buildup allowing the first drop of SEC to pass the coupling adaptor, our prototype intestinal coupling adaptor did not obstruct flow-through of SEC, even after a 75% decrease in flow-through area. This type of attachment represents a viable approach to placing a device in-continuity without obstructing flow of enteric contents.

In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival.

PURPOSE: Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality. METHODS: Bioengineered IAS rings were implanted subcutaneously into the dorsum of wildtype C57Bl/6 mice, with an osmotic pump dispensing FGF-2, vascular endothelial growth factor (VEGF), or platelet-derived growth factor (PDGF) (n = 4 per group). Control mice received IAS implants but no growth factor. The IAS was harvested approximately 25 days post-implantation. Tissue was subjected to physiologic testing, then histologically analyzed. Muscle phenotype was confirmed by immunofluorescence. RESULTS: All implants supplemented with growth factors maintained smooth muscle phenotype. Histological scores, blood vessel density and muscle fiber thickness were all markedly better with growth factors. Neovascularization was comparable between the three growth factors. Basal tonic force of the constructs was highest with VEGF or PDGF. CONCLUSION: All growth factors demonstrated excellent performance. As our ultimate goal is clinical implantation, our strong results with PDGF, a drug approved for use in the United States and the European Union, pave the way for translating bioengineered IAS implantation to the clinical realm.

Bladder Agenesis and Bilateral Ectopic Ureters in an Infant Male With Cystic Renal Dysplasia, Imperforate Anus, and Penoscrotal Transposition.

Bladder agenesis is a rare congenital anomaly infrequently reported in the literature, with an incidence of 1/600,000 patients.1 Commonly associated with other fatal malformations, the condition is often incompatible with life.2 Prior reports estimate that over 90% of living children born with this malformation are female, owing to renal preservation resulting from low pressure drainage of urine into the vagina, uterus, and vestibule.3,4 Herein we report a rare case of an infant male born with penoscrotal transposition and end stage renal disease secondary to bilateral cystic renal dysplasia found to have concurrent bladder agenesis and bilateral ureteral ectopia.

Successful implantation of physiologically functional bioengineered mouse internal anal sphincter.

We have previously developed bioengineered three-dimensional internal anal sphincter (IAS) rings from circular smooth muscle cells isolated from rabbit and human IAS. We provide proof of concept that bioengineered mouse IAS rings are neovascularized upon implantation into mice of the same strain and maintain concentric smooth muscle alignment, phenotype, and IAS functionality. Rings were bioengineered by using smooth muscle cells from the IAS of C57BL/6J mice. Bioengineered mouse IAS rings were implanted subcutaneously on the dorsum of C57BL/6J mice along with a microosmotic pump delivering fibroblast growth factor-2. The mice remained healthy during the period of implantation, showing no external signs of rejection. Mice were killed 28 days postsurgery and implanted IAS rings were harvested. IAS rings showed muscle attachment, neovascularization, healthy color, and no external signs of infection or inflammation. Assessment of force generation on harvested IAS rings showed the following: 1) spontaneous basal tone was generated in the absence of external stimulation; 2) basal tone was relaxed by vasoactive intestinal peptide, nitric oxide donor, and nifedipine; 3) acetylcholine and phorbol dibutyrate elicited rapid-rising, dose-dependent, sustained contractions repeatedly over 30 min without signs of muscle fatigue; and 4) magnitudes of potassium chloride-induced contractions were 100% of peak maximal agonist-induced contractions. Our preliminary results confirm the proof of concept that bioengineered rings are neovascularized upon implantation. Harvested rings maintain smooth muscle alignment and phenotype. Our physiological studies confirm that implanted rings maintain 1) overall IAS physiology and develop basal tone, 2) integrity of membrane ionic characteristics, and 3) integrity of membrane associated intracellular signaling transduction pathways for contraction and relaxation by responding to cholinergic, nitrergic, and VIP-ergic stimulation. IAS smooth muscle tissue could thus be bioengineered for the purpose of implantation to serve as a potential graft therapy for dysfunctional internal anal sphincter in fecal incontinence.

Application of distractive forces to the small intestine: defining safe limits.

BACKGROUND: Distraction enterogenesis is a novel method for increasing small bowel length by the application of linearly directed forces. However, the magnitude of distractive forces that human and animal small bowel can safely withstand is unknown. METHODS: Acute ex vivo force-displacement curves for human (n = 5) and pig (n = 6) small intestine (with and without mesentery) were made by applying increasing amounts of distractive forces to bowel immersed in normal saline (39°C). Progressive load was applied until gross disruption of the tissue was detected, or the applied force reached 1000 gram-force (gf). Histology was used to detect evidence of load-induced damage. In vivo blood flow to pig bowel with distractive loads (30-200 gf) was measured by laser Doppler. RESULTS: The relationship between the level of force and degree of displacement was linear. The presence of a mesentery increased stiffness of pig bowel, but did not affect human bowel. Gross tissue disruption in pig and human tissue was seen at forces between 235 and 295 gf, respectively. However, in grossly undamaged areas, histology was unchanged even after application of higher loads. With in vivo testing, mesenteric blood flow was present up to 200 gf; however, blood flow to the bowel wall was reduced to undetectable levels at loads exceeding 100 gf. CONCLUSIONS: While whole bowel tissue may tolerate greater applied loads, blood flow to the bowel wall was compromised at loads over 100 gf, suggesting that any higher forces place the bowel at risk for ischemia. These measurements will help guide the clinical application of distraction enterogenesis.

Intestinal microbial diversity and perioperative complications.

BACKGROUND AND AIMS: Enteral nutrient deprivation via parenteral nutrition (PN) in a mouse model leads to a local mucosal inflammatory response. This proinflammatory response leads to a loss of epithelial barrier function and atrophy of the intestine. Although the underlying mechanisms are unknown, a potential contributing factor is the impact PN has on the intestinal microbiome. We recently identified a shift in the intestinal microbial community in mice given PN; however, it is unknown whether such changes occur in humans. We hypothesized that similar microbial changes occur in humans during periods of enteral nutrient deprivation. METHODS: A series of small bowel specimens were obtained from pediatric and adult patients undergoing small intestinal resection. Mucosally associated bacteria were harvested and analyzed using 454 pyrosequencing techniques. Statistical analysis of microbial diversity and differences in microbial characteristics were assessed between enterally fed and enterally deprived portions of the intestine. Occurrence of postoperative infectious and anastomotic complications was also examined. RESULTS: Pyrosequencing demonstrated a wide variability in microbial diversity within all groups. Principal coordinate analysis demonstrated only a partial stratification of microbial communities between fed and enterally deprived groups. Interestingly, a tight correlation was identified in patients who had a low level of enteric microbial diversity and those who developed postoperative enteric-derived infections or intestinal anastomotic disruption. CONCLUSIONS: Loss of enteral nutrients and systemic antibiotic therapy in humans is associated with a significant loss of microbial biodiversity within the small bowel mucosa. These changes were associated with a number of enteric-derived intestinal infections and intestinal anastomotic disruptions.

Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells.

BACKGROUND: The internal anal sphincter (IAS) is a major contributing factor to pressure within the anal canal and is required for maintenance of rectoanal continence. IAS damage or weakening results in fecal incontinence. We have demonstrated that bioengineered, intrinsically innervated, human IAS tissue replacements possess key aspects of IAS physiology, such as the generation of spontaneous basal tone and contraction/relaxation in response to neurotransmitters. The objective of this study is to demonstrate the feasibility of implantation of bioengineered IAS constructs in the perianal region of athymic rats. METHODS: Human IAS tissue constructs were bioengineered from isolated human IAS circular smooth muscle cells and human enteric neuronal progenitor cells. After maturation of the bioengineered constructs in culture, they were implanted operatively into the perianal region of athymic rats. Platelet-derived growth factor was delivered to the implanted constructs through a microosmotic pump. Implanted constructs were retrieved from the animals 4 weeks postimplantation. RESULTS: Animals tolerated the implantation well, and there were no early postoperative complications. Normal stooling was observed during the implantation period. At harvest, implanted constructs were adherent to the perirectal rat tissue and appeared healthy and pink. Immunohistochemical analysis revealed neovascularization. Implanted smooth muscle cells maintained contractile phenotype. Bioengineered constructs responded in vitro in a tissue chamber to neuronally evoked relaxation in response to electrical field stimulation and vasoactive intestinal peptide, indicating the preservation of neuronal networks. CONCLUSION: Our results indicate that bioengineered innervated IAS constructs can be used to augment IAS function in an animal model. This is a regenerative medicine based therapy for fecal incontinence that would directly address the dysfunction of the IAS muscle.

Intestinal epithelial cell apoptosis and loss of barrier function in the setting of altered microbiota with enteral nutrient deprivation.

Total parenteral nutrition (TPN), a commonly used treatment for patients who cannot receive enteral nutrition, is associated with significant septic complications due in part to a loss of epithelial barrier function (EBF). While the underlying mechanisms of TPN-related epithelial changes are poorly understood, a mouse model of TPN-dependence has helped identify several contributing factors. Enteral deprivation leads to a shift in intestinal microbiota to predominantly Gram-negative Proteobacteria. This is associated with an increase in expression of proinflammatory cytokines within the mucosa, including interferon-γ and tumor necrosis factor-α. A concomitant loss of epithelial growth factors leads to a decrease in epithelial cell proliferation and increased apoptosis. The resulting loss of epithelial tight junction proteins contributes to EBF dysfunction. These mechanisms identify potential strategies of protecting against TPN-related complications, such as modification of luminal bacteria, blockade of proinflammatory cytokines, or growth factor replacement.

Loss of enteral nutrition in a mouse model results in intestinal epithelial barrier dysfunction.

Total parenteral nutrition (TPN) administration in a mouse model leads to a local mucosal inflammatory response, resulting in a loss of epithelial barrier function (EBF). Although, the underlying mechanisms are unknown, a major contributing factor is a loss of growth factors and subsequent critical downstream signaling. An important component of these is the p-Akt pathway. An additional contributing factor to the loss of EBF with TPN is an increase in proinflammatory cytokine abundance within the mucosal epithelium, including TNF-α and IFN-γ. Loss of critical nutrients, including glutamine and glutamate, may affect EBF, contributing to the loss of tight junction proteins. Finding protective modalities for the small intestine during TPN administration may have important clinical applications. Supplemental glutamine and glutamate may be examples of such agents.

Redilation of bowel after intestinal lengthening procedures--an indicator for poor outcome.

BACKGROUND/PURPOSE: Despite a good understanding of short-term outcomes of the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) procedures, limited data exist on long-term complications. METHODS: This is a 15-year single-institution retrospective chart review of patients who underwent an intestinal lengthening procedure (ILP). Long-term ILP-related complications, their interval to development, patients' ability to wean off parenteral nutrition (PN), and the need for further procedures were analyzed. RESULTS: Of 119 patients with short bowel syndrome, 14 had undergone an ILP. Seven patients had an LILT, and 9 patients had a STEP, including repeat ILPs on the same patient. Overall, 93% of patients had complications. Four patients in the LILT group and 3 patients in the STEP group weaned off PN. Eight patients (57%) experienced bowel redilation after their ILP. The 2 deaths in the study came from this group. Seven required another abdominal operation and only one weaned off PN. There were no significant differences in mean bowel length between the redilated group and the non-re-dilated group. CONCLUSIONS: Complications are common after ILPs, and patients who redilated their bowel after ILP did clinically worse than those who did not.

Glutamine prevents total parenteral nutrition-associated changes to intraepithelial lymphocyte phenotype and function: a potential mechanism for the preservation of epithelial barrier function.

Total parenteral nutrition (TPN) results in a number of derangements to the intestinal epithelium, including a loss of epithelial barrier function (EBF). As TPN supplemented with glutamine has been thought to prevent this loss, this article further defined the impact of glutamine on EBF, and investigated potential mechanisms that contributed to the preservation of EBF. C57BL/6J male mice were randomized to enteral nutrition (control), TPN, or TPN supplemented with glutamine (TPN+GLN). Changes in intraepithelial lymphocyte (IEL)-derived cytokine expression were measured, and EBF was assessed with electrophysiologic methods and assessment of junctional protein expression. TPN resulted in a significant decline in EBF, and this loss of EBF was significantly prevented in the TPN+GLN group. Coincident with these changes was a loss of intraepithelial lymphocyte (IEL, mucosal lymphocyte)-derived IL-10 and increase in interferon-gamma (IFN-gamma) expression, and a decline in IEL numbers in the TPN group. A prevention in the increase in IFN-gamma and decline in IL-10 expression was seen in the TPN+GLN group. To determine the mechanism responsible for these glutamine-associated cytokine changes, we tested whether blockade of the IL-7 signaling pathway between epithelial cells (EC) and IEL would prevent these changes; however, blockade failed to influence IEL-derived cytokine changes. Glutamine-supplemented TPN leads to a specific IEL-derived cytokine profile, which may account for the preservation of EBF; and such action may be due to a direct action of glutamine on the IEL.