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This document is a reply to a letter regarding a review on chronic intestinal pseudo-obstruction (CIPO) in adult patients. The authors express gratitude for the message that more effective treatments require a better understanding of the underlying causes of the disease. They discuss some clinical presentations of mitochondrial disease and the association of CIPO with familial degenerative intestinal neuropathy. However, they disagree with the list of genes and diseases that should be added to the causes of CIPO, stating that further investigation is needed to establish their relevance. They also mention that certain conditions and diseases associated with CIPO require clarification regarding their causal relationship. The authors hope that increased availability of genetic evaluations and histologic examinations will help in selecting more effective treatments and clarifying the role of causal factors in the pathophysiology of CIPO. [Extracted from the article]

Purpose: Surgery initiates pro-inflammatory mediator cascades leading to a variably pronounced sterile inflammation (SIRS). SIRS is associated with intestinal paralysis and breakdown of intestinal barrier and might result in abdominal sepsis. Technological progress led to the development of a neurostimulator for transcutaneous auricular vagal nerve stimulation (taVNS), which is associated with a decline in inflammatory parameters and peristalsis improvement in rodents and healthy subjects via activation of the cholinergic anti-inflammatory pathway. Therefore, taVNS might be a strategy for SIRS prophylaxis. Methods: The NeuroSIRS-Study is a prospective, randomized two-armed, sham-controlled, double-blind clinical trial. The study is registered at DRKS00016892 (09.07.2020). A controlled endotoxemia is used as a SIRS-mimicking model. 2 ng/kg bodyweight lipopolysaccharide (LPS) will be administered after taVNS or sham stimulation. The primary objective is a reduction of clinical symptoms of SIRS after taVNS compared to sham stimulation. Effects of taVNS on release of inflammatory cytokines, intestinal function, and vital parameters will be analyzed. Discussion: TaVNS is well-tolerated, with little to no side effects. Despite not fully mimicking postoperative inflammation, LPS challenge is the most used experimental tool to imitate SIRS and offers standardization and reproducibility. The restriction to healthy male volunteers exerts a certain bias limiting generalizability to the surgical population. Still, this pilot study aims to give first insights into taVNS as a prophylactic treatment in postoperative inflammation to pave the way for further clinical trials in patients at risk for SIRS. This would have major implications for future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Post-polypectomy syndrome (PPS) is a complication that may arise after some colonoscopy procedures that require electrocoagulation, due to a transmural burn, which irritates the serous membrane. Its clinical presentation is similar to the one of intestinal perforation, but it has a favorable prognosis, and does not require surgical treatment. We report the case of a 55-year-old woman diagnosed with a polyp in the ascending colon, who was admitted for an endoscopic resection. After the procedure, she complained of nausea, emesis and abdominal pain in the right iliac fossa. She was transferred to the emergency department. An abdominal tomography showed cecal wall thickening without pneumoperitoneum. Therefore, the diagnosis of PPS was made and was managed with bowel rest, parenteral fluids and antibiotics, with full recovery. Despite of its low incidence, it is important to suspect this syndrome to avoid unnecessary surgical treatment and initiate medical management right away. [ABSTRACT FROM AUTHOR]

Apple-peel (or Type IIIb) is an unusual and severe type of intestinal atresia that has generally been treated with anastomosis, entailing considerable morbidity. The aim of this case report is to present an alternative management option that allows intestinal adaptation before performing the anastomosis. We present a case of apple-peel atresia, born at 27 weeks, which during surgery presented a large discordance between the duodenum and the atretic segment. A jejunostomy of the distal atretic bowel was performed to initiate enteral trophic feeding and stimulate its growth. At 2 months of life, both anastomotic ends were similar in caliber and a side-to-side anastomosis was performed. Jejunostomy is an alternative management option that allows to perform a deferred anastomosis in better conditions. [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) is a syndrome in which a significant amount of intestine is lost due to functional or congenital anomalies, resulting in maldigestion, malabsorption, and malnutrition. Children with SBS rely on parenteral nutri tion (PN) for energy and growth. However, this life-sustaining treatment is associated with liver failure and intestinal atrophy, among other complications that can lead to morbidity and mortality. Thus, the goal of SBS therapy is to achieve enteral autonomy. The purpose of this article is to evaluate therapies aimed at protecting the bowel, promoting intestinal adaption, and increasing intestinal absorptive capabilities, with the goal of weaning PN support and achieving enteral autonomy in pediatric SBS. These therapies include bowel-lengthening procedures, bowel tissue engineering, and new hormonal treatments. Promising hormonal treatments include teduglutide, ghrelin, growth hormone, and glutamine. Additionally, new parenteral lipids formulations, Smoflipid® and Omegaven®, can result in improved long-term outcomes in children with SBS when compared to the current standard soy lipid. Nurses should consider these lipid options and therapies to help wean PN support and achieve enteral autonomy in pediatric SBS. [ABSTRACT FROM AUTHOR]

The importance for mortality and morbidity of an in-house pediatric surgery unit for premature infants with necrotizing enterocolitis (NEC) remains undefined. Data on 389 consecutive very low birth weight infants with a birth weight <1250 g admitted between 2009 and 2014 was retrospectively analyzed in two almost identical neonatal intensive care units. Epidemiological data (n=172 and n=217, respectively) were comparable. Incidence of NEC stage II+ was significantly higher in center 1 (15.1 versus 5.5%, n=18 versus 6). This correlated with a significantly lower rate of exclusive human milk feeding compared to center 2 (24.2 versus 59.3%). Probiotic treatment did not differ. Importantly, in case of surgery the length of removed intestine (49.9 versus 19.5 cm) and the rate of severe short-bowel syndrome (38.9 versus 0 %) were significantly higher in center 1 (no in-house pediatric surgery). Furthermore, long-term morbidity assessment revealed more impaired motoric (-4.2 versus -2.2 months, p=0.21) and psychologic (-4.3 versus -1.6 months, p=0.09) development in center 1. Mortality was similar in both centers. Conclusions. Short- and possibly also long-term morbidity of NEC is clearly associated with the presence of an on-site pediatric surgery unit. Enteral nutrition with human milk seems to be a strong protective factor against NEC. [ABSTRACT FROM AUTHOR]

Objectives:  The aim of this study was to ascertain predictors of survival, liver disease (LD), and enteral autonomy 48 months after resection in neonatal short bowel syndrome (SBS) patients with residual small bowel length (SBL) ≤40 cm.Patients and Methods:  Medical records of all SBS patients followed up between 1996 and 2016 were retrospectively reviewed. Survival rate, prevalence of LD, and of enteral autonomy were evaluated.Results:  Forty-seven patients were included, and 43 were still alive at the end of the study period, with cumulative 48-month survival of 91.5%. Twenty-one (45%) patients developed LD, all within the first 6 months. On the final follow-up visit, three (6%) patients were still jaundiced and progressed toward end-stage LD. LD prevalence was higher in patients with recurrent bloodstream infections (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.5-19.3). Of the 43 surviving patients, 22 (51%) had enteral autonomy 48 months after resection. The probability of weaning off parenteral nutrition (PN) was strongly correlated with the remaining SBL.Conclusion:  Survival of patients who have undergone neonatal massive small bowel resection has improved in recent years. Multidisciplinary strategies can improve the course of LD, but not the probability of weaning off PN, which seems to be strongly dependent on the anatomical profile of residual bowel. Therefore, the primary surgical approach should be as conservative as possible to gain even small amounts of intestinal length, which may be crucial in promoting intestinal adaptation. [ABSTRACT FROM AUTHOR]

Spring-mediated distraction enterogenesis has been studied as a novel treatment for short bowel syndrome (SBS). Previous approaches are limited by multiple surgeries to restore intestinal continuity. Purely endoluminal devices require a period of intestinal attachment for enterogenesis. The purpose of this study is to modify the device to prevent premature spring migration in a porcine model. Two models were created in juvenile mini-Yucatan pigs for the placement of three-dimensionally printed springs. (1) Two Roux-en-y jejunojenostomies with two Roux limbs were made. A spring with bidirectional hooked surface features was placed in one Roux limb and a spring with smooth surface was placed in the other Roux limb. (2) The in-continuity model had both hooked and smooth surface springs placed directly in intestinal continuity. Spring location was evaluated by weekly radiographs, and the intestine was retrieved after 2 to 4 weeks. Springs with smooth surfaces migrated between 1 to 3 weeks after placement in both porcine models. Springs with bidirectional hooked surface features were anchored to the intestine for up to 4 weeks without migration. Histologically, the jejunal architecture showed significantly increased crypt depth and muscularis thickness compared to normal jejunum. Bidirectional features printed on springs prevented the premature migration of endoluminal springs. These novel spring anchors allowed for their endoluminal placement without any sutures. This approach may lead to the endoscopic placement of the device for patients with SBS. [ABSTRACT FROM AUTHOR]

Introduction:  Short bowel syndrome (SBS) is the main cause of intestinal failure (IF) in the pediatric population. To promote the standardization of care of these patients, the registry of Pediatric Intestinal Rehabilitation and Transplantation (PIRAT) has been established. The aim of this study is to describe patients with IF using PIRAT database.Materials and Methods:  Data from two tertiary care European referral Centers registered in PIRAT (https://www.studeon.eu/pirat) were analyzed (1994-2015). Neonatal SBS-related IF was defined as need for parenteral nutrition (PN) to sustain life and growth for more than 75 days, after extensive bowel resection during neonatal period. Data included patient demographics, disease at birth, residual small intestine, and intestinal autonomy (PN on/off).Results:  In this study, 114 children with SBS-related IF were identified (male 60%). Median gestational age was 35.3 weeks (interquartile range [IQR]: 33.0-38.0); median birth weight was 2,440 g (IQR: 1,700-2,990). The main causes of SBS were intestinal atresia in 31 (27%), midgut volvulus in 29 (25%), necrotizing enterocolitis in 23 (20%), and gastroschisis in 12 (11%). Nine (7.9%) patients died on PN (six sepsis, two IF-associated liver disease, and one multiorgan failure). Median residual small bowel length was 46 cm (IQR: 13.0-92.5). Ileocecal valve was resected in 48 patients (42%). Intestinal autonomy was achieved in 68% patients.Conclusion:  We present the web-based registry PIRAT and the first results of patients with IF registered from two European Centers. PIRAT could give the opportunity to create a dedicated international network (IF-net) to standardize, improve, and spread the therapeutic paths for the rare and heterogeneous condition of SBS-related IF. [ABSTRACT FROM AUTHOR]

Background: Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis.Methods: Wistar rats (n = 59) were distributed into four groups: "ileal resection" or "laparotomy", each one subdivided into "postoperative teduglutide administration" or "no treatment"; and sacrificed at the third or the seventh day, with ileal sample harvesting. Gene expression of insulin-like growth factor 1 (Igf1), vascular endothelial growth factor a (Vegfa), transforming growth factor β1 (Tgfβ1), connective tissue growth factor (Ctgf), fibroblast growth factor 2 (Fgf2), fibroblast growth factor 7 (Fgf7), epidermal growth factor (Egf), heparin-binding epidermal-like growth factor (Hbegf), platelet-derived growth factor b (Pdgfb) and glucagon-like peptide 2 receptor (Glp2r)was studied by real-time polymerase chain reaction.Results: Upregulation of Fgf7, Fgf2, Egf, Vegfaand Glp2rat the third day and of Pdgfat the seventh day was verified in the perianastomotic segment. Teduglutide administration was associated with higher fold-change of relative gene expression of Vegfa(3.6 ± 1.3 vs.1.9 ± 2.0, p = 0.0001), Hbegf(2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1(1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) and Ctgf(1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); and lower fold-change of Tgfβ1, Fgf7and Glp2r.Conclusions: Those results underscore the recognized role of Igf1and Hbegfas molecular mediators of the effects of teduglutide and suggest that other humoral factors, like Vegfand Ctgf, may also be relevant in the perioperative context. Induction of Vegfa, Igf1and Ctgfgene expressions might indicate a favorable influence of teduglutide on the intestinal anastomotic healing. [ABSTRACT FROM AUTHOR]

Background Improving treatment for short bowel syndrome requires a better understanding of how intestinal adaptation is affected by factors like mechanoluminal stimulation. We hypothesized that in mice, luminal diversion via an ileostomy would drive adaptive changes similar to those seen in human intestine after diversion while offering the opportunity to study the immediate events after resection that precede intestinal adaptation. Materials and methods With Institutional Animal Care and Use Committee approval, a distal ileostomy with a long distal Hartman's was created in 9- to 14-week-old C57/B6 mice ( n = 8). Control mice only had a midline laparotomy without stoma formation ( n = 5). A rim of tissue from the proximal stoma was resected as a historical control for the proximal segment. Postoperatively, mice received a high-protein liquid diet and water ad libitum . On day 3, tissue from both the proximal and distal limbs were collected for histologic and RNA analysis. Morphometric measures, immunofluorescent antigen detection, and RNA expression were compared with Student paired t -tests with a P value < 0.05 considered significant. Results At 3 d, survival for mice with an ileostomy was 87% and average weight loss was 12.5% of initial weight compared to 6.05% for control mice. Compared to the distal limb, the proximal limb in mice with an ileostomy demonstrated significantly taller villi with deeper and wider crypts. The proximal limb also had decreased expression of intestinal stem cell markers lgr5, bmi1, sox9 , and ascl2 . Fewer goblet and enteroendocrine cells per hemivillus were also noted in the proximal limb. In control mice, none of these measures were significant between proximal and distal ileum except for villus height. Conclusions This new murine ileostomy model allows study of intestinal adaptation without intestinal anastomosis, which can be technically challenging and morbid. [ABSTRACT FROM AUTHOR]

Background and aims Patients on parenteral nutrition for short bowel syndrome (SBS) have a high risk of thrombotic complications and are often treated with parenteral anticoagulation. Direct oral anticoagulants are absorbed proximally in the digestive tract and may represent alternative regimens in selected SBS patients. In our pilot study, we provided pharmacokinetics parameters of dabigatran etexilate and rivaroxaban in this setting and compared peak (Cmax), trough (Ctrough) concentrations, and areas-under-the-concentration-time-curve (AUC 0 − t ) to reference values retrieved from phase I-III studies. Methods We enrolled 6 adults with a remaining small bowel length ≤ 200 cm, normal renal/hepatic function, and intact stomach. In our crossover study, patients were exposed to twice-daily dabigatran etexilate 150 mg and once-daily rivaroxaban 20 mg. Results After 5 days of dabigatran dosing, Ctrough and Cmax geometric means were 39 μg/L (90% CI: 23–66) and 88 μg/L (90% CI: 56–137), respectively; AUC 0–12 h was 958 μg ∗ h/L (90% CI: 635–1445). After 5 days of rivaroxaban dosing, Ctrough and Cmax geometric means were 9 μg/L (90% CI: 1–71) and 167 μg/L (90% CI: 102–276), respectively; AUC 0–24 h was 1720 μg ∗ h/L (90% CI: 899–3300). Absorption was negligible in one patient with ultra-short (~ 15 cm) bowel. For dabigatran, Cmax ratio was 0.57 (SD 0.33) and Ctrough ratio was 0.35 (SD 0.44). For rivaroxaban, the mean observed-to-reference ratios AUC 0–24 h and Cmax ratios were 0.73 (SD 0.32) and 0.76 (SD 0.34), respectively. Conclusions While in SBS patients there is some absorption of the oral anticoagulants dabigatran etexilate and rivaroxaban, it appears to be lower than reference values. Plasma drug levels showed significant inter-individual variability. [ABSTRACT FROM AUTHOR]

The discovery, characterization, and clinical development of glucagon-like-peptide-1 (GLP-1) spans more than 30 years and includes contributions from multiple investigators, science recognized by the 2017 Harrington Award Prize for Innovation in Medicine. Herein, we provide perspectives on the historical events and key experimental findings establishing the biology of GLP-1 as an insulin-stimulating glucoregulatory hormone. Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies. The discovery that GLP-2 promotes mucosal growth in the intestine is described, and key findings from both preclinical studies and the GLP-2 clinical development program for short bowel syndrome (SBS) are reviewed. Finally, we summarize recent progress in GLP biology, highlighting emerging concepts and scientific insights with translational relevance. [ABSTRACT FROM AUTHOR]

Background: extensive resection of the intestinal tract regularly results in insufficient digestion and absorption of nutrients, a condition identified as short bowel syndrome. This condition requests a devoted multidisciplinary collaboration to overcome the morbidity and mortality in these patients. With progresses in serious care management, an increased number of patients survive the prompt morbidity of massive intestinal resection present with short bowel syndrome. Some treatments, including parenteral nutrition and surgical methods to reconstruct bowel have been utilized in these patients. Dietary methods, pharmacotherapy and convenient surgical interventions have all added to the enhanced result in these patients. Nevertheless, increasing experience and promising outcomes of intestinal transplantation had added a new aspect to the administration of short bowel syndrome. [ABSTRACT FROM AUTHOR]

The article discusses the condition known as pediatric intestinal failure. Topics mention including the diseases under intestinal failure which include the short-bowel syndrome, congenital enterocyte disorders and gastrointestinal motility, needs for a parenteral nutrition and most often cause due to necrotizing enterocolitis.

Background The aim of this study was to ascertain if prospective determination of specific gut hormones and growth factors could predict bowel adaptation in children with short bowel syndrome ( SBS). Methods We studied independence from parenteral nutrition ( PN) as the short-term result and discontinuation of enteral nutrition ( EN) as the long-term result from a retrospective chart review of seven patients with SBS, who were managed in the absence of growth retardation. The correlation between increased number of enteral feeds or enteral nutrients and fasting serum gastrin, glucagon-like peptide 2 ( GLP-2), citrulline, and D-amino acid oxidase ( DAO) activity was analyzed. Five patients were weaned from PN, and two from EN. Results Fasting serum gastrin was significantly higher and serum GLP-2 lower in the PN-dependent patients than in the patients weaned from EN. The upper limit of fasting serum gastrin for PN independence and for EN independence was 300 and 200 pg/ mL, respectively. The lower limit of fasting serum citrulline for PN independence was 15 μmol/L. The relationship between serum citrulline and DAO and the course of bowel adaptation, however, was poor. Conclusions Serum citrulline is a predictor of PN independence in children with SBS. Fasting serum gastrin and GLP-2 are indicators for adaptation of the residual intestine, but this was a small study and further larger prospective trials are required to confirm these results. [ABSTRACT FROM AUTHOR]

Background Distraction enterogenesis has been investigated as a novel treatment for short bowel syndrome (SBS). With variable intestinal sizes, it is critical to determine safe, translatable spring characteristics in differently sized animal models before clinical use. Nitinol springs have been shown to lengthen intestines in rats and pigs. Here, we show spring-mediated intestinal lengthening is scalable and feasible in a murine model. Materials and methods A 10-mm nitinol spring was compressed to 3 mm and placed in a 5-mm intestinal segment isolated from continuity in mice. A noncompressed spring placed in a similar fashion served as a control. Spring parameters were proportionally extrapolated from previous spring parameters to accommodate the smaller size of murine intestines. After 2-3 wk, the intestinal segments were examined for size and histology. Results Experimental group with spring constants, k = 0.2-1.4 N/m, showed intestinal lengthening from 5.0 ± 0.6 mm to 9.5 ± 0.8 mm ( P < 0.0001), whereas control segments lengthened from 5.3 ± 0.5 mm to 6.4 ± 1.0 mm ( P < 0.02). Diameter increased similarly in both groups. Isolated segment perforation was noted when k ≥ 0.8 N/m. Histologically, lengthened segments had increased muscularis thickness and crypt depth in comparison to normal intestine. Conclusions Nitinol springs with k ≤ 0.4 N/m can safely yield nearly 2-fold distraction enterogenesis in length and diameter in a scalable mouse model. Not only does this study derive the safe ranges and translatable spring characteristics in a scalable murine model for patients with short bowel syndrome, it also demonstrates the feasibility of spring-mediated intestinal lengthening in a mouse, which can be used to study underlying mechanisms in the future. [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) in neonates is an uncommon but highly morbid condition. As SBS survival increases, physiologic complications become more apparent. Few reports in the literature elucidate outcomes for adults with a pediatric history of SBS. We present a case report of a patient, born with complicated gastroschisis resulting in SBS at birth, who subsequently developed symptoms and pathologic changes of inflammatory bowel disease (IBD) as an adult. The patient lived from age 7, after a Bianchi intestinal lengthening procedure, to age 34 independent of parenteral nutrition (PN), but requiring hydration fluid via G-tube. He was then diagnosed with IBD, after presenting with weight loss, diarrhea, and malabsorption, which required resumption of PN and infliximab treatment. This report adds to a small body of the literature which points to a connection between SBS in neonates and subsequent diagnosis of IBD. Recent evidence suggests that SBS and IBD have shared features of mucosal immune dysfunction and altered intestinal microbiota. We review current treatment options for pediatric SBS as well as multidisciplinary and coordinated transition strategies. We conclude that there may be an etiologic connection between SBS and IBD and that this knowledge may impact outcomes and approaches to care. [ABSTRACT FROM AUTHOR]

Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and management of multiple intestinal diseases have been reported. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions. As glutamine stores are depleted during severe metabolic stress including trauma, sepsis, and inflammatory bowel diseases, glutamine supplementation has been examined in patients to improve their clinical outcomes. In this review, we discuss the physiological roles of glutamine for intestinal health and its underlying mechanisms. In addition, we discuss the current evidence for the efficacy of glutamine supplementation in intestinal diseases. [ABSTRACT FROM AUTHOR]

Background: Intestinal failure-associated liver disease (IFALD) remains a serious problem in the treatment of infants with nutritional problems and short bowel syndrome.Methods: A review of the recent literature from 2010 to 2016, concentrating on articles related to the pathophysiology of IFALD and to outcomes of novel nutritional and pharmacological therapies for neonatal cholestasis in the post-surgical neonate.Results: The pathophysiology of IFALD relates to an increase sensitivity of the neonatal liver to cholestasis in the non-fed state; prolonged cholestasis almost inevitably results in liver damage which will progress from fibrosis to cirrhosis. Clinically discerned risk factors include premature birth, inflammation, sepsis, disruption of the enterohepatic circulation by creation of a proximal stoma, and the duration and type of parenteral nutritional support. Within the hepatocyte, the regulatory enzyme farsanoid receptor X (FXR) appears to play a pivotal role in the development of cholestasis. Recent studies have shown that its activity is suppressed by sepsis, and by plant phytosterols found in soy-based lipid preparations. This paradigm is reflected in the emerging consensus for the care of post-surgical neonates, which is based around a multi-disciplinary team approach. Using an algorithm-driven approach, an appropriate balance between caloric support and prevention of IFALD can be achieved.Conclusions: Further prospective studies are required to further refine the optimal sequence of use of these therapies and the long-term effects on neurological development and hepatic function. However, with optimal care, the number of IF patients progressing to end-stage liver disease because of IFALD should be very low. [ABSTRACT FROM AUTHOR]

Extensive loss of small bowel in all age groups has significant morbidity and mortality consequences. Despite the astonishing ability of the small bowel to compensate for an extensive loss, long-term parenteral nutrition and enteral nutrition, tailored to the need of the patients in relation to the missing intestinal regions is needed. Organ-preserving surgical intervention becomes necessary in patients with a very short intestinal transit time and in an other group of patients with impaired propulsive peristalsis. Intestinal transplantation is indicated in recurrent septical infections or if nearly all of the small bowel is missing. This review discusses indications and risks of the organ-preserving surgical therapies in children with short bowel syndrome. [ABSTRACT FROM AUTHOR]

Subcutaneous teduglutide (Revestive), a glucagon-like peptide-2 analogue that increases intestinal absorption, is approved in the EU for the treatment of short bowel syndrome (SBS) in patients aged ≥1 year who are stable following a period of postsurgical intestinal adaptation. In a phase III trial in adults with SBS intestinal failure (IF) dependent on parenteral support (PS), a significantly greater proportion of teduglutide 0.05 mg/kg/day than placebo recipients achieved a ≥20% reduction in weekly PS volume from baseline to week 20 and maintained it to week 24. The proportion of patients who had a reduction in one or more days on PS was also significant with teduglutide compared with placebo. Improved intestinal absorption and reduced PS requirements were generally maintained in the longer term. Results from a phase III trial in paediatric patients with SBS-IF dependent on PS were consistent with those in adults. Adverse events were mostly of mild to moderate severity and generally consistent with the underlying condition or known mechanism of the drug (e.g. central line-related issues, gastrointestinal events). Teduglutide is therefore a useful treatment option in children (aged ≥1 year), adolescents and adults with SBS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Long-term parenteral nutrition following massive bowel resection causes liver dysfunction, such as intestinal failure-associated liver disease (IFALD). IFALD includes two different states, cholestasis and steatosis, which represents a life-threatening complication. The previous reports have shown the protective role of ghrelin in the liver. The aim of this study was to evaluate the effects of the administration of ghrelin in the liver in a parenterally fed rat model of short bowel syndrome (SBS).Methods: Rats underwent jugular vein catheterization, and were divided into three groups: 90 % small bowel resection (90 % SBR) and TPN (SBS/TPN group), 90 % SBR and TPN plus ghrelin (SBS/TPN/ghrelin group), and sham operation with normal chow (sham group). Ghrelin was administered continuously at a dose of 10 μg/kg/day. On day 13, all rats were euthanized. The serum chemistry was analyzed, the lipid content of the liver was measured, and the liver tissue was histologically analyzed.Result: The AST and LDH levels significantly increased, and the accumulation of lipids in the liver was observed in the TPN/SBS group. The accumulation of lipids in the liver of the rats in the SBS/TPN group was attenuated by the administration of ghrelin.Conclusion: The administration of ghrelin has a therapeutic potential for IFALD. [ABSTRACT FROM AUTHOR]

In the management of short bowel syndrome (SBS), the benefits of treatment with growth hormone (GH), glutamine, and enteral nutrition (EN) on intestinal adaptation among children patients is still controversial. The aim of present study is to determine whether GH, glutamine, and EN have positive effect on intestinal adaptation in children with SBS. Sixteen children with SBS (small bowel remnant length, 56.75 ± 8.09 cm; mean ± SE) were treated with GH (0.05 mg/kg/d), glutamine (0.45 mg/kg/d), plus EN-enriched fiber diet for four weeks. After four weeks of treatment, patients were discharged home; GH was discontinued, but the EN with glutamine was continued. Repeated treatment was performed if there were lose weight, dysplasia, or severe diarrhea. All patients completed the treatment. Body weight, intestinal absorptive capacity, and plasma levels of proteins were significantly improved after complete treatment, without any major adverse effects. On follow-up, no death was reported. Treatment with GH, glutamine, and EN in early stage significantly improved intestinal adaptation in pediatric patients with SBS. Furthermore, the positive effect of the treatment does not seem to be sustained once GH discontinued until the residual intestinal adaptation reaches its maximum. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-2 (GLP-2) is a gut hormone that promotes highly specific growth and function of the intestinal epithelium. Recent studies have begun to elucidate the complex mechanism of action of GLP-2, which is mediated indirectly through other intestinal factors. Although a long-acting GLP-2 analog has recently been approved for treatment of adult patients with short bowel syndrome, there remain numerous conditions characterized by intestinal insufficiency for which pre-clinical studies, as well as some limited clinical data, support further consideration of GLP-2 for expanded therapeutic use. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of an in vivo small bowel bioengineering model using allogeneic aortic grafts in pigs.Background: The best treatment for short bowel syndrome is still unclear. Intestinal transplantation, as well as lifelong parenteral nutrition is associated with a 5-year survival rate of less than 50 %. We have already used allogeneic arterial segments to replace the upper airway in sheep. The results were encouraging with an induced transformation of the aortic wall into tracheo-bronchial bronchial-type tissue.Methods: Seven young mini-pigs were used. A 10-cm-diameter, allogeneic, aortic graft was interposed in an excluded small bowel segment and wrapped by the neighboring omentum. Animals were autopsied at 1 (n = 2), 3 (n = 3), and 6 months (n = 2), respectively. Specimens were examined macroscopically and microscopically.Results: The overall survival rate of the animals was 71.4 %. No anastomotic leak occurred. Histologic analysis revealed intestinal-like wall transformation of the aortic graft in the surviving animals.Conclusion: Aortic-enteric anastomosis is feasible in a porcine model. Moreover, in vivo, bioengineered, intestinal-like transformation of the vascular wall was identified. [ABSTRACT FROM AUTHOR]

Surgical management of children with short bowel syndrome (SBS) changed with the introduction of the serial transverse enteroplasty procedure (STEP). We conducted a systematic review and meta-analysis using MEDLINE and SCOPUS to determine if children with SBS had improved enteral tolerance following STEP. Studies were included if information about a child's pre- and post-STEP enteral tolerance was provided. A random effects meta-analysis provided a summary estimate of the proportion of children with enteral tolerance increase following STEP. From 766 abstracts, seven case series involving 86 children were included. Mean percent tolerance of enteral nutrition improved from 35.1 to 69.5. Sixteen children had no enteral improvement following STEP. A summary estimate showed that 87 % (95 % CI 77-95 %) of children who underwent STEP had an increase in enteral tolerance. Compilation of the literature supports the belief that SBS subjects' enteral tolerance improves following STEP. Enteral nutritional tolerance is a measure of efficacy of STEP and should be presented as a primary or secondary outcome. By standardizing data collection on children undergoing STEP procedure, better determination of nutritional benefit from STEP can be ascertained. [ABSTRACT FROM AUTHOR]

Necrotising enterocolitis (NEC) is a neonatal surgical emergency. At its early stages, the management of NEC is largely medical using broad-spectrum antibiotics, gut rest and total parental nutrition. The only absolute indication for surgery is an intra-abdominal perforation. There are several relative indications for surgery based on clinical, biochemical and radiological parameters. Once the decision to intervene is made, several approaches may be taken. Peritoneal lavage can be used as a salvage procedure or definitive management in some cases. The most common approach taken is bowel resection with enterostomy formation. There is a role for primary anastomosis of bowel in limited NEC. In severe, multi-focal NEC a high diverting jejunostomy or "clip and drop technique" can be used. Laparoscopy has a limited role and is not widespread. The surgical complications of NEC include stoma related morbidity, anastomotic leak/stricture and short-bowel syndrome. Long-term data on neurodevelopmental outcomes is sparse but the present literature is suggestive of a negative impact in cases of surgically managed NEC. [ABSTRACT FROM AUTHOR]

Intestinal failure is a recognized complication of surgically-managed necrotizing enterocolitis (NEC). Functional adaptation of remaining bowel means that many children are eventually able to achieve enteral autonomy. Integrated multidisciplinary care in the early post-operative phase is key to long-term success. The objective of this review is to outline a clinical approach to management of intestinal and nutritional complications experienced by children following intestinal resection for NEC. [ABSTRACT FROM AUTHOR]

Necrotising enterocolitis (NEC) is a serious infection of the bowel that predominantly affects preterm infants and is a leading cause for mortality and morbidity in preterm infants. It involves a spectrum of pathology including widespread inflammation of the intestinal mucosa, invasion of the immature gut by enteric gas forming bacteria, dissection of the gut wall and portal veins by this gas, often culminating in ischemic necrosis of the intestine. This article provides an overview of the incidence, etio-pathological risk factors, preventive strategies and medical management of NEC. [ABSTRACT FROM AUTHOR]

Case Report Gastroschisis is the most frequent congenital abdominal wall defect. When associated with intestinal atresia (complex gastroschisis), short bowel syndrome may occur. Complicated gastroschisis is the most frequent cause of short bowel syndrome in our series. The serial transverse enteroplasty procedure has been used to lengthen the bowel and achieve intestinal rehabilitation in patients with dilated gut. The use of this technique in the newborn period, for tailoring the bowel while preserving absorptive mucosa, has been recently described. We present a video showing the surgical treatment of an intestinal obstruction produced by a complex intestinal atresia in a newborn baby in whom a primary closure of a gastroschisis had been done at birth. During laparotomy at the 21st day of life, a type IVa intestinal atresia was found, associated with a colonic stenosis. Proximal dilated jejunum was tailored with a serial transverse enteroplasty procedure, as shown in the video. End-to-end jejunal-ileal anastomosis was performed. Postoperative entero-cutaneous fistula occurred and was treated with vacuum-assisted therapy. Enteral feedings were initiated at 15 days after surgery. Parenteral nutrition was withdrawn at 30 days. After 16 months follow-up, actual weight was 8.7 kg (percentile 10% to 25%). The patient remained on full enteral feedings. Conclusions In cases of intestinal atresia, short bowel syndrome, and proximal dilated bowel, we propose an aggressive surgical approach to preserve bowel mucosal surface while tailoring the jejunal loop to improve motility. The serial transverse enteroplasty procedure is an acceptable alternative to tailoring methods that resect a segment of the bowel wall. [ABSTRACT FROM AUTHOR]

Background: institutions with multidisciplinary teams have shown improvements in patient outcomes with intestinal failure. Multidisciplinary approach allows an integral management and effective communication between families and care teams.Objective: describe the multidisciplinary management and outcome in pediatric patients with intestinal failure.Methods: retrospective study in patients 18 years old or less, with intestinal failure and Total Parenteral Nutrition (TPN) required. Simple frequencies and percentages were used for qualitative variables, and central tendency and dispersion measures were used for quantitative variables.Results: 33 patients with a median follow up of 281 days were evaluated. The median duration of the TPN was 68 days and the mean of catheter-related infections was 2.26 per patient. In 31 patients oral or enteral nutrition was provided, starting in 61.3% of cases through tube and continuous infusion. As concomitant treatment 72.7% of children received ursodeoxycholic acid, 67.7%, cholestyramine 57.6% loperamide, 48.5% antibiotics and 36.4% probiotic. The families of 24 patients were evaluated by social work professionals. Intestinal autonomy was achieved in 69.7% of cases, 72.7% of them showed an improvement in the score z of weight and showed an end albumin significantly higher than the initial (p value: 0.012).Conclusions: the management of patients with intestinal failure is a challenge for health institutions and require care based on a standardized protocol and a multidisciplinary group. [ABSTRACT FROM AUTHOR]

Aim: We investigated the role and outcome of a planned second-look laparotomy (SLL) in preserving bowel in extensive necrotizing enterocolitis (NEC). Methods: Extensive NECs managed surgically in a tertiary centre in 2006-2009 were retrospectively studied to include patients planned for an SLL. End points were bowel salvage rate and survival outcomes. Results were median (ranges), and statistical significance was P < 0.05. Main results: In 4 years, 34 NECs required a laparotomy, and 9 extensive NECs who required an SLL were included. The gestation at birth was 27 (24-38) weeks, birth weight was 1120 (580-2835) g, and first laparotomy performed on day 34 (2-77) of life, with SLL performed 2 (1-3) days after initial laparotomy. Commonest indications for SLL were doubtful bowel viability and physiological instability. 3 died before SLL. Patients who survived to have an SLL ( n = 6) had remaining small bowel length of 41 (25-70) cm, overall small bowel salvage rate 51 % (0-100 %), and 30-day survival 5/6 (83 %). Four patients survived for 1 year, their length of NICU stay was 114 (76-120) postoperative days, time on PN was 84 postoperative days (71 days-17 months), including one patient with short bowel syndrome who achieved enteral autonomy at 17 months; one late mortality had short bowel syndrome after further bowel resection for bowel obstruction, developed intestinal failure associated liver disease, and died before 1 year of life following liver transplant. Conclusion: SLL is a viable approach for extensive NEC. It offered bowel salvage rate of 51 % and long-term PN-free survival of 44 %, in the patient group who would have had significant risk of mortality and major morbidity. [ABSTRACT FROM AUTHOR]

Intestinal failure is a complicated long-term condition that can have profound physical and psychosocial consequences for a patient's life. Hospitalisation can be long, with many distressing and unpleasant medical procedures being endured. Patients often have to deal with large volumes of unmanageable faecal fluid from stomas or fistulae and usually require home parenteral nutrition (HPN) for the remainder of their life. The literature focuses on how patients often have to tolerate long periods of suffering, which can be the basis for significant emotional anguish. It also addresses how the condition can contribute to myriad psychosocial difficulties, which can have devastating effects on their body image and quality of life. However, there is a lack of information regarding the effects of this condition on the family, who not only have to provide ongoing support for the patient, but also have to attempt to function normally while coping with their own fears and emotions. This article reviews the experiences of two patients, father and daughter, living with intestinal failure; it discusses their experiences and reveals how they cope with the physical aspects. It also addresses how the condition can effect psychosocial disturbances, not only for them but for those living closely with them. The article addresses ways that nurses could develop their relationship with the patient, enabling them to recognise and act early on signs of emotional malady. [ABSTRACT FROM AUTHOR]

We present a case where the glucagon-like peptide 2 (GLP-2) analog teduglutide was used successfully to decrease high ostomy output due to short bowel syndrome in a patient not entirely dependent on parenteral nutrition. Short bowel syndrome is known to decrease quality of life and is associated with high health care costs. Although use has been limited by cost, teduglutide appears to be a treatment option for palliative care practice if patients suffer from short bowel syndrome. [ABSTRACT FROM AUTHOR]

Malabsorption is a major and common clinical characteristics of short bowel syndrome (SBS) and inflammatory bowel diseases (IBD). Traditional treatment opportunities have focused on decreasing malabsorptive losses via dietary modifications and antisecretory/antidiarrheal agents. However, novel therapeutic modalities aim to enhance the absorptive capacity of the residual bowel by the administration of different intestinal growth factors including teduglutide. In a current study the existence of two distinct functional putative epithelial stem cell subpopulations (i.e. Lgr5+/Bmi1− and Lgr5−/Bmi1+) have been described in a rat model of ileal resection and anastomosis. The described epithelial stem cell subpopulations displayed distinct behaviour after surgical injury and teduglutide administration. Though teduglutide was found to be clinically effective, we must keep in mind that growth factors theoretically may provoke adenoma development and subsequent malignant transformation. The present results give us a better insight into the role of stem cell modulation in intestinal repair. Based on these results new perioperative adjuvant pharmacological approaches may be developed for SBS and IBD patients to reduce the clinical symptoms and complications of associated malabsorption. [ABSTRACT FROM AUTHOR]

Background: Factitious fever is extremely challenging to diagnose in patients with complicated chronic medical problems, and represents as much as 10% of fevers of unknown origin. Factitious fever caused by self-injecting oral medications through indwelling central catheters is a diagnostic challenge. Case presentation: We present a 32-year-old Caucasian female with history of short gut syndrome, malnutrition requiring total parental nutrition, and pancreatic auto-islet transplant with fever of unknown origin. Multiple episodes of bacteremia occurred with atypical pathogens, including α-hemolytic Streptococcus, Achromobacter xylosoxidans, and Mycobacterium mucogenicum. Chest computed tomography was notable for extensive tree-in-bud infiltrates. Sudden cardiac arrest with right-sided heart failure following acute hypoxemia led to her death. Diffuse microcrystalline cellulose emboli with foreign body granulomatosis was found on autopsy. Circumstantial evidence indicated that this patient suffered from factitious disorder, and was self-injecting oral medications through her central catheter. Conclusion: A high index of suspicion, early recognition, and multifaceted team support is essential to detect and manage patients with factitious disorders before fatal events occur. [ABSTRACT FROM AUTHOR]

The aim of this study was to review the management of Short Bowel Syndrome, focusing on the current trends regarding non-transplant, autologous surgical reconstructive techniques. Management of severe Short Bowel Syndrome is still one of the greatest challenges of medicine. Paediatricians and paediatric surgeons may face this challenge often because of the relatively common occurrence of necrotizing enterocolitis, intestinal malrotation, volvulus, gastroschisis and "apple peel" atresia. Although the short term results of intestinal transplantation are improving, the long term results are still disappointing. On the other hand an increasing number of patients have been saved through modern intestinal bowel rehabilitation programs and autologous intestinal reconstructive surgeries in the last decade. This review summarizes the main medical elements of these programs, such as the control of gastric hypersecretion, inhibition of intestinal motility, elemental enteral feeding, low fat (home) parenteral nutrition and hormonal enhancement of intestinal adaptation. It focuses on nontransplant surgical management of short bowel patients, such as accurate vascular access surgery, controlled bowel expansion program, extracorporeal stool recycling and intestinal lengthening techniques. Conclusion - Intestinal bowel rehabilitation and autologous intestinal reconstruction should be considered as first line management in short bowel patients. The establishment of national bowel rehabilitation centres should be considered. Intestinal transplantation should be reserved for unsuccessful cases and considered as a last resort. [ABSTRACT FROM AUTHOR]

Background Treatment of short bowel syndrome (SBS) remains difficult, entailing severe morbidity and mortality. Accepted surgical treatment modalities for SBS are the Bianchi intestinal lengthening procedure and reversed-segment procedure. We seek to investigate the short-term effects regarding growth, nutrition, and microscopic and functional adaptation after the intestinal lengthening and RS procedures in a piglet SBS-model. Material and methods Twenty-four piglets (Sus scrofa, ±30 kg) were divided into four groups ( n = 6 each) as follows: sham, SBS, Bianchi lengthening procedure (BIA), and reversed-segment (RS). At day one either sham laparotomy (sham) or 75% small bowel resection (SBS, BIA, and RS) was performed. After 2 wk sham laparotomy (sham and SBS), BIA, or RS procedure was performed. After 8 wk all animals were terminated. During the experimental time course, the following parameters were assessed: body weight, intestinal length, diameter, and weight, fat absorption, and biochemical parameters from serum and urine. Citrulline was used as a marker of absorptive enteral mass to demonstrate massive functional bowel loss. Intestinal biopsies were obtained for histologic analysis and electrophysiological measurements to analyze glucose absorptive capacity. Results Eight weeks after bowel resection, piglet growth was reduced in SBS, BIA, and RS piglets as demonstrated by reduced weight (51 ± 4 kg, 47 ± 2 kg, and 53 ± 1 kg, respectively) compared with sham (69 ± 3 kg; P < 0.01), with no demonstrable difference between SBS and treatment groups. Malabsorption and malnutrition occurred in SBS, BIA, and RS piglets reflected by increased fecal fat loss per 24 h (35 ± 4%, 30 ± 2%, and 32 ± 4%, respectively versus 18 ± 1% in sham; P < 0.01) and reduced serum albumin levels (24 ± 1 g/L, 22 ± 1 g/L, and 24 ± 1 g/L, respectively versus sham 33 ± 1 g/L; P < 0.01), but there was no significant difference between SBS and treatment groups. Serum citrulline levels reflected massive functional bowel loss (SBS 36 ± 7 μmol/L, BIA 23 ± 1 μmol/L, and RS 24 ± 2 μmol/L) compared with sham (64 ± 5 μmol/L; P < 0.01). Electrophysiological measurements demonstrated reduced glucose absorption after intestinal resection, which did not return to base levels within the experimental time course. However, the intestine of BIA and RS piglets adapted more profoundly than SBS piglets, as reflected by a greater crypt depth (490 ± 25 μm and 492 ± 21 μm versus 388 ± 20 μm; P < 0.01); and BIA piglets showed greater villus length (884 ± 58 μm) than RS or SBS piglets (715 ± 30 μm and 737 ± 64 μm, respectively; P < 0.01) after 8 wk. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide 2 (GLP-2) is a potent intestinotrophic growth factor with therapeutic potential in the treatment of intestinal deficiencies. It has recently been approved for the treatment of short bowel syndrome. The effects of GLP-2 are mediated by specific binding of the hormone to the GLP-2 receptor (GLP-2R) which was cloned in 1999. However, consensus about the exact receptor localization in the intestine has never been established. By physical, chemical and enzymatic tissue fragmentation, we were able to divide rat jejunum into different compartments consisting of: (1) epithelium alone, (2) mucosa with lamina propria and epithelium, (3) the external muscle coat including myenteric plexus, (4) a compartment enriched for the myenteric plexus and (5) intestine without epithelium. Expression of Glp2r ; chromogranin A ; tubulin , beta 3 ; actin , gamma 2 , smooth muscle , enteric and glial fibrillary acidic protein in these isolated tissue fractions was quantified with qRT-PCR. Expression of the Glp2r was confined to compartments containing enteric neurons and receptor expression was absent in the epithelium. Our findings provide evidence for the expression of the GLP-2R in intestinal compartments rich in enteric neurons and, importantly they exclude significant expression in the epithelium of rat jejunal mucosa. [ABSTRACT FROM AUTHOR]

Teduglutide (Gattex) is a recombinant analogue of human glucagon-like peptide-2 and is indicated for the treatment of adults with short bowel syndrome (SBS) dependent on parenteral support (PS). In a pivotal, 24-week clinical trial in SBS patients, subcutaneous teduglutide 0.05 mg/kg once daily increased absorption from the remnant intestine as evidenced by significant reductions in PS volume requirements versus placebo. Improvements attained in absorption in the first 6 months of therapy were maintained during the extension trial (total teduglutide treatment periods of up to 30 months), with evidence indicating that benefits accrue over time. Among patients who received teduglutide treatment for up to 30 months, 11 of 30 were able to achieve at least one additional day off PS and another ten achieved complete independence from PS. Subcutaneous teduglutide was generally well tolerated in clinical trials, including over the long term, with most adverse events that led to study discontinuation being gastrointestinal in origin. [ABSTRACT FROM AUTHOR]

D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be discussed subsequently. [ABSTRACT FROM AUTHOR]

Introduction: Short bowel syndrome (SBS) is a morbid clinical condition that results from massive small-bowel resection (SBR). After SBR, there is a dramatic weight loss in the acute postoperative period. Our aim was to determine the impact of a high-protein diet (HPD) on weight gain and body composition in mice after SBR. Methods: C57BL/6 mice underwent 50 % proximal SBR. Postoperatively, mice were randomly selected to receive standard rodent liquid diet (LD) ( n = 6) or an isocaloric HPD ( n = 9) for 28 days. Mice weights were recorded daily. Body composition analyses were obtained weekly. Student's t test was used for statistical comparisons with p < 0.05 considered significant. Results: Mice that were fed HPD after SBR returned to baseline weight on average at postoperative day (POD) 8 versus mice that were fed LD that returned to baseline weight on average at POD 22. Total fat mass and lean mass were significantly greater by POD 14 within the HPD group. Both groups of mice demonstrated normal structural adaptation. Conclusion: HPD results in greater weight gain and improved body composition in mice after SBR. This finding may be clinically important for patients with SBS since improved weight gain may reduce the time needed for parenteral nutrition. [ABSTRACT FROM AUTHOR]

Aims. This is a descriptive study aiming to compare outcomes of intestinal rehabilitation surgery among pediatric and adult intestinal failure (IF) patients with either primary intestinal motility disorders or short bowel syndrome (SBS) treated by our nationwide program. Methods. Medical records of IF patients ( n = 31, 71% children) having undergone autologous intestinal reconstructions (AIR) ( n = 25), intestinal transplantation (ITx) ( n = 5), or being listed for ITx ( n = 2) between 1994 and 2014 were reviewed. Results. At surgery, median age was 3.4 (interquartile range, 1.0-22.1) in SBS ( n = 22) and 16.5 (3.2-26.7) years in dysmotility patients ( n = 9) who received median 60% and 83% of energy requirement parenterally, respectively. Median small bowel length was shorter in SBS than dysmotility patients (34 versus 157 cm, p < 0.001). Following AIR, none of the dysmotility patients achieved permanent intestinal autonomy, whereas 68% of SBS patients weaned off parenteral nutrition (PN) ( p = 0.022) and none required listing for ITx. Five dysmotility patients who underwent ITx achieved intestinal autonomy. Regarding both AIR and ITx procedures, no significant difference in PN weaning was observed between the two subgroups. At last follow-up, 3.3 (0.6-8.0) years postoperatively, median plasma bilirubin was 6 (4-16) µmol/l, while liver biopsy showed fibrosis (Metavir stage 1-2) in 50% and cholestasis in 8%. Proportion of PN energy requirement had reduced significantly ( p = 0.043) among PN-dependent SBS ( n = 7) but not among dysmotility patients ( n = 5). Overall survival was 90%. Conclusion. AIR surgery was beneficial among selected SBS patients, whereas in intestinal dysmotility disorders, permanent PN weaning was only achieved by ITx. [ABSTRACT FROM AUTHOR]

Objective: Distraction enterogenesis may provide a novel therapy for short bowel syndrome (SBS). Previously described methods have relied upon isolated intestinal segments or transmural fixation. Our objective was to develop a novel, fully endoluminal device, permitting placement and removal through an enteral stoma or orifice. Methods: A flexible device was designed consisting of two latex balloons mounted on coaxial catheters. The inner catheter allowed longitudinal force transmission from an external spring. Yorkshire pigs underwent jejunal Roux limb creation with device placement via jejunostomy. Balloons were inflated to 52 mmHg without significant reduction in bowel perfusion as measured by laser Doppler. The device was explanted after 7 days. Results: Distracted bowel achieved an increase in length of 26.1 ± 6.1 % vs nondistracted fed bowel. As the device resided in unfed bowel, a 66.7 ± 14.5 % increase vs unfed bowel was noted. These corresponded to a gain of 6.3 ± 2.3 cm (0.9 ± 0.3 cm/day) and 12.9 ± 7.6 cm (1.8 ± 1.1 cm/day), respectively. Attachment sites demonstrated occasional epithelial sloughing with no balloon-associated perforation. Conclusion: A novel double-balloon catheter device allows for fully endoluminal distraction enterogenesis. This approach may allow development of clinically applicable technology for the treatment of patients with SBS. [ABSTRACT FROM AUTHOR]

Aim: Spiral Intestinal Lengthening and Tailoring (SILT) invented by our team is a new technique that offers minimal mesenteric handling and a more physiological result compared to the STEP procedure. Its feasibility has been tested in animal models and now we report the first successful human application in extreme short bowel syndrome. Materials and Methods: A 3-year-old girl suffered subtotal loss of her small bowel and ileocaecal junction as a result of midgut volvulus. Only 15 cm of jejunum remained intact. Parenteral nutrition (PN), gastrostomy feeding, controlled bowel expansion and SILT procedure were applied. Results: The length of the jejunum increased from the initial 15 to 22 cm during 12 months of PN and bowel expansion. Eleven centimeter of distended bowel was further lengthened up to 20 cm by SILT giving a total small bowel length of 31 cm. Oral and gastrostomy feedings were commenced 5 days postoperatively. There were no surgical complications 6 months after the procedure. The patient's liver function was preserved, she was weaned off PN, discharged from hospital, but remained on gastrostomy top up feeding. The net weight gain of the patient was 1,800 g 6 months after the procedure. Conclusion: SILT procedure is a safe and feasible technique for human intestinal lengthening and tailoring. [ABSTRACT FROM AUTHOR]

Background Intestinal transplant in infants with severe short bowel syndrome (SBS) is an emerging therapy, yet without sufficient long-term data or established guidelines, resulting in possible variation in practice. Objectives To assess current attitudes and counselling practices among physicians regarding intestinal transplant in infants with SBS, and to determine whether counselling and management vary between subspecialists or centres. Methods A national sample of practicing paediatric surgeons and neonatologists was surveyed via the American Academy of Paediatrics listserves. Results were analysed by physician subspecialty and again by presence or absence of intestinal transplant at respondent's centre. Results The survey was completed by 433 respondents, consisting of 363 neonatologists and 70 paediatric surgeons. Fifty-seven respondents (13.2%) practiced at a centre that performed intestinal transplants in children. The vast majority of respondents (91% for preterm, 95% for term neonates) felt that maintaining a neonate with SBS on total parenteral nutrition for intestinal transplant was ethically optional (neither impermissible nor obligatory), and that parents should be given an informed choice whether to pursue that option. However, only 33% indicated they often/always offer intestinal transplant as a treatment option to families in this situation. Conclusions There is a marked disparity between individual physicians' beliefs regarding the acceptability of intestinal transplant for severe SBS and their reported practice. Wide variability exists among physicians with respect to their knowledge, beliefs and practice regarding severe SBS, raising concerns about transparency and justice. Survival data prior to transplant, currently unavailable, are essential to rational decision making and informed parental permission. [ABSTRACT FROM AUTHOR]