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Background: Enteral drug therapy is challenging in short bowel syndrome with intestinal failure (SBS-IF) because of unpredictable absorption. SEFA-6179 is an enterally administered medium-chain fatty acid analogue under development for intestinal failure-associated liver disease. We investigate the pharmacokinetics of two SEFA-6179 formulations in two large-animal models of SBS-IF, including a new pseudojejunostomy model., Methods: Twenty Yucatan minipigs were obtained. Half underwent pre-resection pharmacokinetic study with single-dose SEFA-6179 administration. All minipigs then underwent 90% jejunoileal resection, with either a jejunoileal anastomosis or bypass of the intraperitoneal colon with anastomosis just proximal to the rectum (pseudojejunostomy). On postoperative day 3, a single-dose pharmacokinetic study was performed., Results: Both SBS-IF models were well tolerated. Compared with the jejunoileal anastomosis minipigs, pseudojejunostomy minipigs had a more severe malabsorptive phenotype with weight loss by postoperative day 4 (+0.1 vs -0.9 kg, P = 0.03) and liquid diarrhea (Bristol 5 vs Bristol 7, P = 0.0007). Compared with pre-resection minipigs, both jejunoileal and pseudojejunostomy minipigs had lower total plasma exposure of SEFA-6179 measured by area under the curve (jejunoileal: 37% less, P = 0.049; pseudojejunostomy: 74% less, P = 0.0001). Peak plasma concentration was also lower in the pseudojejunostomy group compared with pre-resection (65% less, P = 0.04), but not lower in the jejunoileal group (P = 0.47)., Conclusion: In two SBS-IF minipig models, SEFA-6179 had substantially decreased absorption compared with pre-resection minipigs. Dose optimization for different intestinal anatomy and function may be required. We describe a new SBS-IF pseudojejunostomy model that may improve the translation of preclinical research to patients with SBS-IF who have enterostomies., (© 2023 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Introduction: The International Intestinal Failure Registry (IIFR) is an international consortium to study intestinal failure (IF) outcomes in a large contemporary pediatric cohort. We aimed to identify predictors of early (1-year) enteral autonomy., Methods: We included IIFR pilot phase patients. IF was defined by a parenteral nutrition need for at least 60 days due to a primary gastrointestinal etiology. The primary outcome was time to enteral autonomy achievement. We built a mixed-effects Weibull accelerated failure time model with random effects by center to analyze variables associated with enteral autonomy achievement with a primary outcome of time ratio (TR)., Results: We included 189 patients (82% with short bowel syndrome) representing 11 international centers. Cumulative incidence of early enteral autonomy was 51.6%, and death was 6.5%. In multivariable analysis, ostomy presence (TR, 2.63; 95% CI, 1.41-4.90) was associated with increased time to enteral autonomy achievement, and Asian/Indian (TR, 0.28; 95% CI, 0.10-0.81) and Pacific Islander race (TR, 0.34; 95% CI, 0.13-0.90) were associated with decreased time to enteral autonomy achievement. In a second model in the subset with measured percentage of bowel length remaining, ostomy presence (TR, 4.21; 95% CI, 1.90-9.33) was associated with increased time to enteral autonomy achievement, whereas greater percentage of bowel remaining (TR, 0.96; 95% CI, 0.94-0.98) was associated with decreased time to enteral autonomy achievement., Conclusions: Minimizing bowel resection at initial surgery and establishing bowel continuity by ostomy reversal can effectively decrease the time to early enteral autonomy achievement in children with IF., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Patients with short bowel syndrome (SBS) are optimally managed in centers of expertise with dedicated multidisciplinary intestinal failure (IF) teams. Over the life of a patient with SBS, many different surgical concerns may arise requiring intervention. These can range from reasonably simple procedures, such as the creation or maintenance of gastrostomy tube and enterostomies, to complex reconstructions of multiple enterocutaneous fistulas or the performance of intestine-containing transplants. This review will cover the development of a surgeon's role on the IF team; common surgical issues arising in patients with SBS, with a focus on decision-making rather than technique; and, finally, a brief overview of transplantation and some related decision-making issues., (© 2023 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: We aimed to evaluate costs from transplant to discharge in children who had undergone intestine transplant., Methods: We performed a cross-sectional observational study of pediatric intestine transplant recipients from 2004 through 2020, utilizing the Pediatric Health Information System database. Standardized costs were applied to all charges and converted to 2021 US dollars. We analyzed the association of cost from transplant to discharge with age, sex, race and ethnicity, length of stay, insurance type, transplant year, short bowel syndrome diagnosis, liver-containing graft, hospitalization status, and immunosuppressive regimen. Predictors with a P value <0.20 in univariable analysis were included in a multivariable model, which was reduced using backwards selection with a P value of 0.05., Results: We identified 376 intestinal transplant recipients across nine centers (median age, 2 years; 44% female). Most patients had short bowel syndrome (294; 78%). The liver was included in 218 transplants (58%). Median posttransplant cost was $263,724 (interquartile range [IQR], $179,564-$384,147), and length of stay was 51.5 days (IQR, 34-77). In the final model, increased cost from transplant to hospital discharge was associated with liver-containing graft (+$31,805; P = 0.028), T-cell-depleting antibody use (+$77,004; P < 0.001), and mycophenolate mofetil use (+$50,514; P = 0.012) while controlling for insurance type and length of stay. A 60-day posttransplant hospital stay would cost an estimated $272,533., Conclusions: Intestine transplant has high immediate cost and long length of stay that varies by center, graft type, and immunosuppression regimen. Future work will examine the cost-effectiveness of various management strategies before and after transplant., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Objective: For the first time, we reported experiences with an intestinal rehabilitation unit (IRU) from a country without home parenteral nutrition (HPN)., Methods: We included patients with a diagnosis of intestinal failure (IF) since the establishment of our IRU from February 2018 to February 2020. We further report on our protocols for management of enterocutaneous fistulas (ECFs), short-bowel syndrome (SBS), chronic intestinal pseudo-obstruction and motility disorders., Results: Among a total of 349 patients who have been admitted, 100 patients had IF and were included . Mean (SD) age of patients was 46.3 ± 16.1 years. Most common cause of IF was ECFs (32%), SBS (24%), and SBS + fistula (22%). Most common causes of SBS were mesenteric ischemia (63.3%) and repeated surgery (22.4%). Median (interquartile range [IQR]) duration of parenteral nutrition (PN) for patients was 32 (18-60) days. The most common reconstructive surgery performed was resection and anastomosis (75.4%), followed by serial transverse enteroplasty procedure (10.5%) and closure of ostoma (7%). Patients were hospitalized for a median (IQR) of 33 (17.5-61) days. Most common complications were sepsis (45%), catheter infections (43%), and catheter thrombosis (20%), respectively. At the final follow-up, 61% stopped receiving PN, 23% became candidates for transplantation, and 16% died., Conclusion: Considering that most countries lack facilities for HPN, by establishing IRUs using specific treatment protocols and autologous gastrointestinal reconstruction techniques will provide a means to manage patients with IF, thus decreasing death rates and number of patients who require intestinal transplantations due to IF., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: In an era of improved management and treatment options, this study aims to describe the long-term outcomes and factors predictive of outcomes of neonatal-onset intestinal failure (IF) due to surgical short bowel syndrome (SBS)., Methods: Retrospective, single-center cohort study of infants born between January 2011 and December 2018 with inclusion criteria: <44 weeks postmenstrual age at SBS diagnosis, <28 days on admission, parenteral nutrition dependence >60 days, and documented intestinal resection. Primary outcomes included survival and achievement of enteral autonomy (EA). Data analysis utilized Fisher.s exact test, Kruskal-Wallis test, survival analysis methods, Cox proportional hazards regression, linear regression and logistic regression., Results: Ninety-five patients (males 56%) were studied with median follow-up of 38 months (IQR 19, 59). Survival at last follow-up was 96%, and EA was achieved in 85%. Forty-eight patients had documented residual bowel length (RBL) with median length of 49 cm (IQR 36, 80). Survival in patients with RBL of <30cm (n = 8), 30-59cm (n = 19), and >60cm (n = 21) was 100%, 95%, and 95% respectively. Shorter RBL was associated with longer time to achieve EA (p = 0.007), but not with survival (p = 0.81). Delay in achieving EA was associated with absence of ileocecal valve (p = 0.002) and bloodstream infections (p < 0.001). Peak conjugated bilirubin correlated with increased mortality (p = 0.002)., Conclusion: Overall high rate of survival and achievement of EA was found in neonatal onset IF due to SBS. EA but not survival was correlated with RBL. Ileocecal valve, bloodstream infections, and conjugated bilirubin levels were the other predictive factors of outcomes., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: It is challenging to provide optimum nutrition in low-birth-weight (LBW) infants with short-bowel syndrome (SBS) and ostomy. This study aims to evaluate the clinical course of LBW infants with SBS and ostomy in response to enteral feeds, recognize characteristics associated with achievement of enteral autonomy prior to reanastomosis, and evaluate associated short-term outcomes., Methods: A retrospective analysis of 52 LBW neonates with intestinal failure (IF) caused by SBS and ostomy treated in a neonatal intensive care unit from 2012 to 2018 was performed. Clinical characteristics and short-term outcomes were studied in relation to the location of the ostomy and the success with enteral feeding achieved prior to reanastomosis., Results: Of the 52 infants with SBS, jejunostomy, ileostomy, and colostomy were present in 9, 40, and 3 infants, respectively. Fourteen (26.92%) infants achieved enteral autonomy transiently, and 7 (13.46%) sustained until reanastomosis. All 9 infants with jejunostomy were parenteral nutrition dependent, compared with 22 with ileostomy and none with colostomy (P = 0.002). Infants who achieved enteral autonomy showed lower incidence of cholestasis (P = 0.038) and better growth velocity (P = 0.02) prior to reanastomosis., Conclusions: A minority of LBW infants with SBS and ostomy achieved enteral autonomy prior to reanastomosis. Distal ostomy (ileostomy and colostomy), reduced cholestasis, and better growth were associated with achievement of enteral autonomy. Our report highlights the challenges in establishing enteral autonomy in LBW infants with IF and ostomy, and the feasibility of that approach in a minority of patients, with tangible benefits., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Background: Minimal enteral nutrition (MEN) may induce a diet-dependent stimulation of gut adaptation following intestinal resection. Bovine colostrum is rich in growth factors, and we hypothesized that MEN with colostrum would stimulate intestinal adaptation, compared with formula, and would be well tolerated in patients with short bowel syndrome., Methods: In experiment 1, 3-day-old piglets with 50% distal small intestinal resection were fed parenteral nutrition (PN, n = 10) or PN plus MEN given as either colostrum (PN-COL, n = 5) or formula (PN-FORM, n = 9) for 7 days. Intestinal nutrient absorption and histomorphometry were performed. In experiment 2, tolerance and feasibility of colostrum supplementation were tested in a pilot study on 5 infants who had undergone intestinal resection, and they were compared with 5 resected infants who served as controls., Results: In experiment 1, relative wet-weight absorption and intestinal villus height were higher in PN-COL vs PN (53% vs 23% and 362 ± 13 vs 329 ± 7 µm, P < .05). Crypt depth and tissue protein synthesis were higher in PN-COL (233 ± 7 µm, 22%/d) and PN-FORM (262 ± 13 µm, 22%/d) vs PN (190 ± 4 µm, 9%/d, both P < .05). In experiment 2, enteral colostrum supplementation was well tolerated, and no infants developed clinical signs of cow's milk allergy., Conclusion: Minimal enteral nutrition feeding with bovine colostrum and formula induced similar intestinal adaptation after resection in piglets. Colostrum was well tolerated by newly resected infants, but the clinical indication for colostrum supplementation to infants subjected to intestinal resection remains to be determined., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: Fasting plasma citrulline (p-citrulline) is a marker of functional enterocyte mass. However, the optimal timing of measurement in relation to meals has yet to be clarified. Furthermore, p-citrulline has been proposed to be a surrogate marker for small bowel length and intestinal absorption parameters in short bowel syndrome patients with intestinal failure (SBS-IF)., Materials and Methods: Eight patients with SBS-IF and 8 healthy controls (HCs) were given a standardized mixed test meal, and p-citrulline was measured 15 minutes before and 60, 120, and 180 minutes after completion of the meal. The patients with SBS-IF had their intestinal absorption of wet weight, energy, macronutrients, and electrolytes measured in relation to 72-hour metabolic balance studies. We investigated the possible correlations between p-citrulline and short bowel length, absorptive parameters, and the dependence on parenteral support (PS)., Results: In the patients with SBS-IF, we found a 12% (P = .041) reduction in postprandial citrulline levels after 180 minutes. In the HCs, there was a 13% postprandial reduction at 60 minutes (P = .018). No significant correlations between fasting p-citrulline and bowel length, bowel absorptive function, or the dependence on PS were found. Even when excluding 2 patients in whom the intestinal absorption was adjacent to the intestinal insufficiency borderlines, these correlations were not significant., Conclusion: Based on findings in this small study, the optimal timing of p-citrulline measurement is on fasting samples. However, p-citrulline seems insufficiently discriminative to serve as a valid biomarker of bowel length, bowel absorptive function, or dependence on PS in patients with SBS-IF., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: An impaired hormonal "ileo-colonic brake" may contribute to rapid gastric emptying, gastric hypersecretion, high ostomy losses, and the need for parenteral support in end-jejunostomy short bowel syndrome (SBS) patients with intestinal failure (IF). Liraglutide, a glucagon-like peptide 1 receptor agonist, may reduce gastric hypersecretion and dampen gastric emptying, thereby improving conditions for intestinal absorption., Materials and Methods: In an 8-week, open-label pilot study, liraglutide was given subcutaneously once daily to 8 end-jejunostomy patients, aged 63.4 ± 10.9 years (mean ± SD) and with small bowel lengths of 110 ± 66 cm. The 72-hour metabolic balance studies were performed before and at the end of treatment. Food intake was unrestricted. Oral fluid intake and parenteral support volume were kept constant. The primary end point was change in the ostomy wet weight output., Results: Liraglutide reduced ostomy wet weight output by 474 ± 563 g/d from 3249 ± 1352 to 2775 ± 1187 g/d (P = .049, Student t test). Intestinal wet weight absorption tended to increase by 464 ± 557 g/d (P = .05), as did urine production by 765 ± 759 g/d (P = .02). Intestinal energy absorption improved by 902 ± 882 kJ/d (P = .02)., Conclusion: Liraglutide reduced ostomy wet weight output in end-jejunostomy patients with SBS-IF and increased their intestinal wet weight and energy absorption. If larger, randomized, placebo-controlled studies confirm these effects, it adds to the hypothesis that many ileo-colonic brake hormones in conjunction may be involved in the process of intestinal adaptation. By identification of key hormones and addressing their potential synergistic effects, better treatments may be provided to patients with SBS-IF. This trial was registered at clinicaltrialsregister.eu as 2013-005499-16., (© 2016 American Society for Parenteral and Enteral Nutrition.)

Background: Intestinal failure-associated liver disease (IFALD) causes significant morbidity in neonates with short bowel syndrome (SBS) dependent on parenteral nutrition (PN). Resected ileum, with loss of the ileocecal valve (ICV), is the most common anatomy in SBS, yet its impact on IFALD has not been adequately studied., Methods: Neonatal piglets were randomized to 75% intestinal resection with jejunocolic anastomosis (JC, n = 12), 75% resection with jejunoileal anastomosis and intact ICV (JI, n = 13), PN-fed sham (sham, n = 14), or sow-fed control (SF, n = 8). Surgical and sham piglets received 100% PN for 14 days before bile flow was measured and blood chemistry, liver pathology, jejunal permeability, and bacterial translocation were assessed., Results: Bile flow was lower for PN-fed compared with SF (P = .002) but not different between the PN-fed groups. Total bilirubin (P = .03) and liver pathology (P < .001) were greater in PN-fed than SF groups but not different between PN-fed groups. Serum bile acids were increased in sham (P = .01) but not different between SBS groups. PN-fed piglets with sepsis had lower bile flow (P = .001) and increased bilirubin (P = .04). Neither jejunal permeability nor bacterial translocation were different between JC, JI, or sham groups., Conclusion: Contrary to our hypothesis, the remnant anatomy does not appear to worsen the progression of IFALD. However, the role of sepsis in IFALD should be further explored, in addition to other mechanisms, including PN factors, host immune responses, and intestinal bacterial dysbiosis., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: Exogenous glucagon-like peptide 2 (GLP-2) stimulates intestinal adaptation after resection in animal models of pediatric short bowel syndrome (SBS). It is unknown whether the molecular mechanisms of such GLP-2 effects are similar to those of postresection spontaneous adaptation. Using preterm pigs as a model, we hypothesized that GLP-2 treatment would change the intestinal proteome within the first week after resection, relative to individuals not resected or resected without GLP-2 treatment., Materials and Methods: Two-day-old preterm pigs were subjected to resection of 50% distal small intestine and fed total parenteral nutrition without (SBS) or with GLP-2 infusion (3.5 µg/kg/h, SBS+GLP-2) for 5 days. The proteome of the remnant proximal intestine was compared among the SBS, SBS+GLP-2, and unresected pigs, through gel-based proteomics., Results: Thirty-two proteins with differential expression were identified. Ten of these proteins were affected by the resection alone (ie, SBS vs unresected pigs). Five of these resection-responsive proteins and another 22 proteins were affected by GLP-2 infusion (ie, SBS+GLP-2 vs SBS or unresected pigs). Resection alone mainly affected cellular structural proteins, while the added GLP-2 treatment affected proteins involved in protein processing and the metabolism of protein, carbohydrate, and sulphur., Conclusion: In the first days following resection, proteins affected by resection plus GLP-2 treatment differed markedly from those affected by the spontaneous intestinal adaptation following resection alone. Whether more long-term GLP-2 treatment may affect the intestinal proteome following intestinal resection remains unknown.

Background: Data are limited on how short bowel syndrome (SBS) affects the healthy developing intestinal microbiome, with even less assessing different SBS anatomical surgical models. This study was conducted to describe the "ileal" and "colonic" microflora in 2 surgical models of SBS., Materials and Methods: Neonatal piglets (2-5 days old) underwent intestinal resection, leaving the ileum (JI anatomy, n = 6) or removing the ileum and ileocecal valve (JC anatomy, n = 5), or sham surgery (sham; n = 4). JI, JC, and sham piglets commenced parenteral nutrition on day 0 and received ampicillin and trimethoprim-sulfadoxine on days 0-4 for prevention of line sepsis. At day 7, ileal and colonic digesta were collected, and they were also collected from age-matched sow-fed piglets (n = 6). DNA extraction, sequencing, and annotation followed standard procedures., Results: Colonic and ileal bacterial genus diversity and relative bacterial abundance were greater ( P < .05) in sow-fed compared with JI, JC, and sham piglets; however, minor differences were observed in either location between sham, JI, and JC piglets and within the surgical model. In the colon, sow-fed piglets had higher ( P < .05) abundance of Lactobacillus (26%) and tended to have lower ( P = .06) abundance of Enterococcus (<.1%) than JI, JC, or sham piglets, in which Lactobacillus and Enterococcus abundance averaged <.1% and 9%, respectively., Conclusions: Intestinal resection reduces bacterial diversity in the large bowel, and the difference is associated with the presence/absence of the ileum and ileocecal valve. The lack of enteral nutrition and antibiotic administration (ie, sow-fed vs surgery) had a greater influence on the observed shift in diversity and relative abundance than intestinal resection.

Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

Obesity is a major chronic disease affecting the U.S. population. Bariatric surgery has consistently shown greater weight loss and improved outcomes compared with conservative therapy. However, complications after bariatric surgery can be catastrophic, resulting in short bowel syndrome with a potential risk of intestinal failure, ultimately resulting in the need for a small bowel transplant. A total of 6 patients became dependent on home parenteral nutrition (HPN) after undergoing bariatric surgery at an outside facility. Four of the 6 patients required evaluation for small bowel transplant; 2 of the 6 patients were successfully managed with parenteral nutrition and did not require further small bowel transplant evaluation. Catheter-related bloodstream infection, a serious complication of HPN, occurred in 3 patients despite extensive patient education on catheter care and use of ethanol lock. Two patients underwent successful small bowel transplantation, 1 died before transplant could be performed, and 1 was listed for a multivisceral transplantation. Surgical procedures to treat morbid obesity are common and growing in popularity but are not without risk of serious complications, including intestinal failure and HPN dependency. Despite methods to prevent complications, failure of HPN may lead to the need for transplant evaluation. In selected cases, the best therapeutic treatment may be a small bowel transplant to resolve irreversible, post-bariatric surgery intestinal failure.

For patients with short bowel syndrome (SBS), surgery can play an important role in preventing, mitigating, and, in some cases, reversing intestinal failure (IF). During intestinal resection, bowel length should be conserved to the fullest extent possible to avoid dependence on parenteral nutrition (PN). Bowel salvage may be improved by initially preserving tissue of questionable viability and later reevaluating during "second-look" procedures. Once the patient is stabilized, ostomy reversal and recruitment of distal unused bowel should be prioritized whenever feasible. Following progression to IF, surgical management of SBS depends on the symptoms and anatomical characteristics of the individual patient. For carefully selected patients with rapid intestinal transit and dilated bowel, longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) procedures may provide benefit. Outcomes following STEP and LILT are generally similar, and the choice between these procedures may rest on surgeon preference. For patients with rapid intestinal transit in the absence of bowel dilation, segmental reversal of the small bowel may reduce PN requirements. Intestinal transplantation is the standard of care for patients in whom intestinal rehabilitation attempts have failed and who are at risk of life-threatening complications of PN. Because patients awaiting isolated intestine transplant show increased survival compared with patients awaiting combined intestine-liver transplant, early referral of appropriate patients, before the development of advanced liver disease, is critical to enhancing patient outcomes.

Background: Intestinal adaptation is important for recovery in short bowel syndrome (SBS). This process is dependent on the presence of enteral nutrition (EN) and trophic factors, such as glucagon-like peptide-2 (GLP-2). In clinical practice, elemental formula is often used to feed neonates with SBS, whereas animal studies suggest polymeric formula promotes better intestinal adaptation. In neonatal piglet models of SBS, with or without ileum, we compared the elemental with the polymeric formula, including the effect on endogenous GLP-2., Materials and Methods: Forty-eight piglets underwent 75% mid-intestinal resection with jejunoileal anastomosis, 75% distal-intestinal resection with jejunocolic anastomosis (JC), or sham without resection. Parenteral nutrition (PN) started postoperatively, tapering as EN was increased, according to clinical criteria, based on diarrhea and weight. Within groups, piglets were randomized to an isocaloric/isonitrogenous elemental (amino acid) or polymeric (intact protein) diet. Plasma GLP-2 and histology for adaptation were measured at 14 days., Results: Within both SBS and control groups, no difference in adaptation was observed according to diet. A difference was observed only within the JC piglet group with regard to clinical outcomes. In these piglets, compared with elemental formula, the polymeric formula was associated with more diarrhea ( P = .023) and longer duration of PN support (P = .047)., Conclusion: An overall benefit of the polymeric formula over the elemental formula on gut adaptation was not observed. Furthermore, SBS piglets without ileum had less ability to tolerate polymeric formula, contributing to more days of PN support.

Appropriate nutrition recommendations are important for the successful management of the infant with an injured gastrointestinal tract postsurgery who is at risk for intestinal failure. Management strategies that can be used to augment successful adaptation and prevent liver disease are summarized in this review. These include appropriate postoperative fluid and electrolyte management, modification of parenteral nutrition to minimize intestinal failure-associated liver disease, early and aggressive enteral feeding advancement, the use of hormonal and trophic agents, prevention of central line-associated bloodstream infections using ethanol lock, appropriate treatment, and prevention of pathologic small bowel bacterial overgrowth.

Short bowel syndrome-associated intestinal failure (SBS-IF) as a consequence of extensive surgical resection of the gastrointestinal (GI) tract results in a chronic reduction in intestinal absorption. The ensuing malabsorption of a conventional diet with associated diarrhea and weight loss results in a dependency on parenteral nutrition and/or intravenous fluids (PN/IV). A natural compensatory process of intestinal adaptation occurs in the years after bowel resection as the body responds to a lack of sufficient functional nutrient-processing intestinal surface area. The adaptive process improves bowel function but is a highly variable process, yielding different levels of symptom control and PN/IV independence among patients. Intestinal rehabilitation is the strategy of maximizing the absorptive capacity of the remnant GI tract. The approaches for achieving this goal have been limited to dietary intervention, antidiarrheal and antisecretory medications, and surgical bowel reconstruction. A targeted pharmacotherapy has now been developed that improves intestinal absorption. Teduglutide is a human recombinant analogue of glucagon-like peptide 2 that promotes the expansion of the intestinal surface area and increases the intestinal absorptive capacity. Enhanced absorption has been shown in clinical trials by a reduction in PN/IV requirements in patients with SBS-IF. This article details the clinical considerations and best-practice recommendations for intestinal rehabilitation, including optimization of fluids, electrolytes, and nutrients; the integration of teduglutide therapy; and approaches to PN/IV weaning.

Short bowel syndrome (SBS) results in loss of absorptive capacity of the development of gut, leading to malabsorption due to protein, energy, fluid, and electrolyte loss and imbalance while on enteral diet alone. Various nonsurgical and surgical therapeutic options that have emerged improve the survival outcome following SBS in both children and adults. An individualized, complex multidisciplinary approach to medical and surgical intestinal rehabilitation is needed to provide an opportunity for enteral autonomy to be possible in a patient with SBS. The remnant bowel plays a very pivotal role in autologous gastrointestinal reconstruction (AGIR) surgery. Intestinal transplantation, although promising and potentially life-saving for SBS, should be reserved for patients with failed AGIR or those who have no prospect for autologous enteral autonomy. This article reviews the evolution of nontransplant surgical management of patients with SBS.

Background: Successful small intestinal (SI) adaptation following surgical resection is essential for optimizing newborn growth and development, but the potential for adaptation is unknown. The authors developed an SI resection model in neonatal piglets supported by intravenous and enteral nutrition., Methods: Piglets (n = 33, 12-13 days old) were randomized to 80% SI resection with parenteral nutrition feeding (R-PN), 80% SI resection with PN + enteral feeding (R-EN), or sham SI transection with PN + enteral feeding (sham-EN). In resected pigs, the distal 100 cm of ileum (residual SI) and 30 cm of proximal SI were left intact. All pigs received parenteral nutrition postsurgery. Enteral nutrition piglets received continuous gastric infusion of elemental diet from day 3 (40:60 parenteral nutrition:enteral nutrition). Piglets were killed 4, 6, or 10 days postsurgery., Results: By 10 days, R-EN piglets had longer residual SI than R-PN and sham-EN pigs (P < .05). At days 6 and 10, R-EN piglets had greater weight per length of intact SI (P < .05) and isolated mucosa (P < .05) compared to other groups. Greater gut weight in R-EN piglets was facilitated by a greater cellular proliferation index (P < .01) by 4 days compared to other groups and greater overall ornithine decarboxylase activity vs R-PN piglets (P < .05)., Conclusions: This new model demonstrated profound SI adaptation, initiated early postsurgery by polyamine synthesis and crypt cell proliferation and only in response to enteral feeding. These changes translated to greater gut mass and length within days, likely improving functional capacity long term.

A 22-year-old man suffered an acute small bowel infarct leading to extensive bowel resection, resulting in only 20 cm of jejunum to a jejunostomy, although he also had 50 cm of residual colon with a mucous fistula. The patient was out on long-term home parenteral nutrition (PN) but endured high stomal losses of 5-6 L per day and, despite all conventional measures, required 6.1 L of fluid (including PN) and 555 mmol sodium per day. Although body mass index was maintained, he suffered debilitating malaise and recurrent episodes of catheter-related sepsis and also developed persistently abnormal liver function tests. He was considered a potential intestinal transplant patient, but before taking that step, he opted for reanastomosis of his residual colon to his jejunum, ending in a colostomy. At surgery, only 30 cm of additional bowel lengthening could be achieved, but despite this, the patient's stomal losses reduced to 2.5 L per day, intravenous fluid requirements reduced to 4.1 L per day, and liver function normalized. The patient also gained 7.5 kg despite no change in PN caloric prescription, and his quality of life was dramatically enhanced. The case illustrates that even a small length of colon can grant significant improvements, probably via improvements in small bowel transit and adaptive changes, better sodium and water resorption with decreased hyperaldosteronism, and enhanced energy and nitrogen recovery. Reanastomosis of defunctioned colon should therefore always be considered a management option in short bowel syndrome.

Background: The purpose of the present study was to evaluate the effects of ω-3 fatty acids (Omegaven) on early intestinal adaptation in rats with short bowel syndrome (SBS)., Methods: Male Sprague-Dawley rats were randomly assigned to 1 of 4 groups: sham rats underwent bowel transection; SBS rats underwent 75% bowel resection; SBS-O ω-3 rats underwent bowel resection and were treated with oral Omegaven given by gavage; and SBS-I ω-3 rats underwent bowel resection and were treated with Omegaven given intraperitoneally. Rats were killed on day 14. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depths, cell proliferation and apoptosis) were determined at time of death. Real-time polymerase chain reaction was used to determine the level of Bax and Bcl-2 messenger RNA (mRNA). Statistical analysis was performed using Kruskal-Wallis test followed by post hoc test, with P < .05 considered statistically significant., Results: Oral ω-3 supplementation did not significantly change intestinal regrowth. In contrast, parenteral ω-3 in rats that underwent resection resulted in higher bowel and mucosal weights, mucosal DNA and protein in ileum, villus height in ileum, crypt depth in jejunum and ileum, and greater rates of cell proliferation in jejunum and ileum compared with SBS animals. The initial decreased levels of apoptosis corresponded with the early decrease in Bax and increase in Bcl-2 mRNA levels., Conclusions: Parenteral but not enteral Omegaven augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased apoptosis reflect increased cell turnover in Omegaven-treated animals.

Background: Colostrum protein concentrate (CPC) contains a high level of insulin-like growth factor-1 (IGF-1). IGF-1 and IGF binding protein (IGFBPs) may play an important role during the postresection adaptation response. As smooth muscle is an important site for IGF-1 action in the intestine, this study aims to (1) investigate the effect of CPC supplementation on circulating levels and tissue expression of IGF-1, IGF-1 receptor, and IGFBPs following massive small bowel resection (MSBR), and (2) characterize the effect of CPC on the muscular adaptation response following MSBR., Methods: Four-week-old piglets underwent either a 75% MSBR or sham operation. Piglets received either a polymeric infant formula (PIF) diet or PIF supplemented with CPC for 8 weeks. Serum was analyzed by enzyme-linked immunosorbent assay, and ileal tissue assessed by molecular and histological analysis., Results: There was no difference in IGF-1 or IGFBPs mRNA among groups. CPC treatment resulted in significant increases in circulating levels of IGF-1 and IGFBPs and a concurrent increase in muscle width and the number of muscle cells, but did not alter muscle cell size., Conclusions: Strategies aimed at increasing muscular adaptation may decrease Gl transit and allow greater mucosal contact time for absorption. We have shown that CPC supplementation following resection results in increased levels of circulating IGF-1, IGFBP-2, and IGFBP-3 and muscular hypertrophy. Our results suggest that IGF-1 and its mediators may play a role in the muscular adaptation response and warrant further exploration as a treatment option for short bowel syndrome.

Intestinal failure (IF) is a condition where there is insufficient functional bowel to allow for adequate nutrient and fluid absorption to sustain adequate growth in children. Several etiologies can predispose to IF, including necrotizing enterocolitis, gastroschisis, and intestinal atresias. Intestinal rehabilitation can be seen as a 3-pronged strategy merging nutrition, pharmacologic, and surgical approaches to achieve the ultimate goal of enteral nutrition. Nutrition approaches should seek to facilitate transition from parenteral nutrition (PN) to enteral nutrition because prolonged use of PN is associated with severe morbidity and mortality. Enteral nutrition, on the other hand, promotes and enhances an adaptive response in the intestine. Medications used in the treatment of IF may help alleviate symptoms of diarrhea, bacterial overgrowth, and gastrointestinal dysmotility. Surgical procedures, such as longitudinal intestinal lengthening and tapering (LILT) or serial transverse enteroplasty (STEP), can increase mucosal surface area and may enhance intestinal adaptation. IF is a difficult disease process with a complex patient population and is best guided through this 3-pronged approach by a multidisciplinary team featuring surgeons, gastroenterologists, dietitians, pharmacists, and nurses.

Nutrition management of intestinal transplant recipients continues to be a challenging and essential component of the early postoperative care of this patient population. The absorptive capacity of the graft can be affected by immunologic and nonimmunologic factors, including enteric lymphatic disruption, preservation injury, central denervation, viral enteritis, systemic infections, and rejection. Chylous ascites, the extravasation of milky chyle into the peritoneal fluid, defined by elevated triglycerides levels of > or = 200 mg/dL, can occur as a result of trauma, obstruction, or interruption of the lymphatic system. It seems the incidence of chylous ascites after small bowel transplantation is low; however, this may be due in part to the limitation of enteral long-chain triglycerides in the early posttransplant period of 2-6 weeks. After this time frame, clinical evidence suggests that fat assimilation normalizes. In the event that chylous ascites develop as a posttransplant complication, limitation of oral or enteral nutrition support to a very-low-fat regimen may be required, or parenteral nutrition (PN) will need to be provided until clinical status improves. Long-term posttransplant, lymphatic regeneration generally occurs and the majority of intestinal transplant recipients achieve the ultimate goal of nutrition autonomy.

Background: Using a massively bowel-resected rat model, our previous study demonstrated that small bowel segment reversal stimulates jejunal hyperplasia but may also increase the possibility of bacterial translocation and the elevation of circulating white blood cells and serum interleukin-6 that may reduce the whole-body anabolism. The aim of this study is to investigate whether oral antibiotics might attenuate the inflammatory responses and might therefore facilitate the beneficial effects of bowel segment reversal., Methods: Male Wistar rats (approximately 270 g) underwent a 70% small bowel resection with (REV group) or without (CON group) a 3-cm small bowel segment reversal, or underwent a sham operation (SHAM group). After surgeries, half of the animals in the REV group were given oral clindamycin plus amoxicillin (50 plus 50 mg/kg/d, ANT group) for 3 weeks., Results: Oral antibiotics administration significantly attenuated the decreases in feeding efficiency (g of body weight/100 kcal diet) and increases in the circulation of white blood cells, serum nitric oxide, and interleukin-6 (1-way ANOVA, p < .05), which are associated with bowel segment reversal. In addition, antibiotics significantly increased serum concentrations of insulin-like growth factor-I, significantly decreased the total numbers of bacteria in the intestine, and tended to reduce the extent of jejunal hyperplasia in rats with bowel segment reversal., Conclusions: Our results suggest that oral antibiotics may be used as an adjuvant to attenuate the inflammatory responses and to enhance the anabolic responses in massively bowel-resected patients with bowel segment reversal.

Background: This paper traces the 29-year survival of Robert Thomas, who received home parenteral nutrition (PN), and contrasts his oral narrative with the clinical history of PN., Methods: Interviews, chart review, review of the literature, and historical analysis., Results: Bobby Thomas was part of an early group of patients scattered throughout the country who, with their medical team, provided the foundation for more successful survival with home PN. They learned together and taught numerous nutrition support clinicians the intricacies of patient management. The importance of the patient to the teaching function of new and experienced practitioners is highly critical. Patients like Robert Thomas gave practitioners firsthand evidence of both the tenacity of the human spirit and the complexity and difficulties of chronic illness and its treatments., Conclusions: While Bobby struggled with the complications and difficulties that came with the disease and the treatment keeping him alive, his own experiences over 29 years, as told to his medical team during his treatment and to informed interviewers before he died, tell a story that is both intersecting and parallel to the medical history. Pioneering patients like Bobby Thomas confirm the possibility of survival. They also, through their own negotiations to maintain a sense of control, can live lives they themselves help define.

"Vanishing bowel" has been rarely reported in the literature. This case and discussion are intended to describe the surgical, medical, and nutrition management of this unusual congenital abnormality. Of 3 reported cases surviving vanishing bowel, one had substantial residual small bowel, another had residual small bowel and bowel-lengthening procedure, and one received an intestinal liver transplant. The patient presented in this case had residual small bowel and lengthening procedure. The patient described is well as of October 2005 (age 3.5 years), still receiving nocturnal parenteral nutrition (PN), but is eating solid foods without significant malabsorption or abdominal distention. He has experienced modest weight gain over the past 2 months.

Intestinal failure is a condition in which inadequate digestion or absorption of fluid, electrolytes, and nutrients leads to dehydration or malnutrition. The most common cause of intestinal failure is short bowel syndrome (SBS) defined as <200 cm of functional small intestine. SBS may result from congenital abnormalities or from surgical resection. For the past 3 decades, patients with severe SBS were managed with home parenteral nutrition (HPN). With the emergence of new therapies, the clinician now has multiple options to treat these patients. These include intestinal rehabilitation regimens whereby patients are treated with specialized oral diets, soluble fiber, oral rehydration solutions (ORS), and trophic factors to enhance absorption. There are also a variety of surgical techniques available to preserve intestinal length. Small bowel and multivisceral transplantation has evolved during the last decade to be a valid therapeutic option for those patients who cannot be rehabilitated or who fail HPN. These are interrelated services designed to offer the patient the best therapeutic options to meet their individual needs. This article reviews the principles associated with the nutrition management of this very complex and diverse group of patients.

Nutrition therapy after small bowel or combined liver/small bowel transplantation is challenging. The objective is to restore enteral autonomy to a patient with a complex past surgical history and equally complex posttransplant immunosuppressive regimen in the context of a newly created surgical anatomy. Improved surgical techniques and immunosuppressive regimens have led to superior outcomes. Accompanying these advances is a range of nutrition issues that require specific management strategies. This review outlines the current clinical practice and decision making used to create individualized nutrition regimens for small bowel or combined liver/small bowel transplant recipients. Successful small bowel transplant outcomes require a coordinated effort from a transplant team to restore nutritional autonomy to transplant recipients and free them from parenteral nutrition.

Ischemic injury of the small bowel may recover after revascularization, provided that full-thickness infarction did not occur. Animal studies showed that if the mucosal crypts remain viable, rapid mucosal restitution occurs hours after injury. The treatment of transmucosal infarction that does not extend to full wall thickness, however, was not investigated thoroughly. The patient presented had a mesenteric event leading to resection of about half of his small bowel. The unresected segment had severe ischemic injury, which seemed to cause transmucosal, but not transmural, infarction. Imaging of the remaining small bowel revealed a seromuscular layer denuded of mucosa. The ischemic damage was too deep to allow rapid regeneration, and the patient had short-bowel syndrome. A year later, during operation for stricture complications, new mucosa covered parts of the small-bowel surface, encouraging the surgeon to elect a conservative approach. Sixteen months after the injury, normal mucosa covered the entire small bowel, and enteral feeding resumed successfully. This report shows that infarcted small-bowel mucosa may regenerate even months after injury.

Background: Massive small bowel resection with subsequent short bowel syndrome (SBS) leads to the acute loss of epithelial cell (EC) absorptive function. Keratinocyte growth factor (KGF) has been shown to improve EC growth, although little is known about KGF activity on EC function after SBS. We hypothesized that KGF would improve epithelial function in a mouse SBS model., Methods: Adult C57BL/6J mice were randomized to a 55% mid-small bowel resection (SBS), SBS with KGF administration (SBSKGF), or sham-operated (Control) group, and were killed at 7 days. Ussing chambers were used to study epithelial function. Short circuit current (Isc) was monitored. EC absorption was studied by measuring (1) glucose [3-O-methyl-D-[1-3H]glucose (3-OMG)] absorption; (2) sodium coupled amino acid (alanine) absorption; and (3) changes in Isc by using the absorptive agent D-glucose (stimulated Na+ absorption). Epithelial barrier function was measured with transepithelial resistance (TER) and transmural passage of 3H-mannitol (Papp). ECs were separated along the crypt-villus axis with laser capture microdissection. Epithelial KGF receptor (KGFR) mRNA expression was studied using real time reverse transcriptase-polymerase chain reaction (RT-PCR)., Results: KGF administration increased the basic ion transport activity and net transepithelial absorption of 3-OMG and sodium-coupled alanine absorption. SBS significantly decreased epithelial ion transport, including the Na+ absorption stimulated by D-glucose and L-alanine. KGF administration partially improves Na+ absorption. KGF had no apparent effect on the TER and 3H-mannitol permeability in this study. KGF upregulated EC KGFR mRNA expression, predominately in the crypt and lower portion of the villus., Conclusions: KGF administration improves epithelial absorptive function and stimulates intestinal proliferation after SBS. This suggests that KGF improves intestinal adaptation after SBS and may have clinical applicability.

Background: The choice of treatment options in short bowel syndrome (SBS) is hampered by a lack of comparative studies. This study uses a previously validated juvenile pig model of SBS to compare nontreated controls (C), surgical treatment with either proximal colon interposition (CI) or bowel lengthening (BL), with medical treatment with codeine and cimetidine (M)., Methods: Treatment was initiated 6 weeks after resection of 75% of the small bowel, and animals were followed until sacrifice at week 16. Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment., Results: BL and M treatments resulted in improved rates of weight gain; this improvement was associated with improved absorption of dietary fat. The treatments did not affect carbohydrate or protein absorption in vivo. In vitro fatty acid absorption was not increased in any group. Active uptake of glucose was increased in the colon interposition group, but phlorizin binding (reflecting sodium glucose cotransporter activity) did not differ between groups. Gross serosal and microscopic mucosal surface areas increased in all groups; however, there were no significant differences between the treatment groups., Conclusions: These results demonstrate that bowel lengthening and medical treatment improved the rate of weight gain in this model of SBS. This appeared to be due to improvement in the absorption of dietary fat, which was not caused by alterations in in vitro uptake or mucosal surface area, suggesting these treatments have their affects by altering motility or intraluminal digestion. These findings suggest that these treatments are worthy of further study in treating patients (primary pediatric) with SBS.

We reviewed 12 pediatric and 18 adult patients with short bowel syndrome (SBS) from Osaka University Hospital and compared clinical characteristics between them. The length of the residual small intestine ranged from 0 to 75 cm (mean 47 cm) in pediatric patients and from 0 to 150 cm (mean 47 cm) in adult patients. In all cases, total parenteral nutrition (TPN) was started immediately after surgery and was gradually replaced by enteral nutrition. Eight pediatric patients (67%) and 4 adult patients (22%) were weaned from TPN. Residual intestinal length in these patients ranged from 27 to 75 cm (mean 57 cm) in pediatric patients and 57 to 150 cm (mean 96 cm) in adult patients. Pediatric patients with residual small intestinal lengths of 0, 16, 25, and 45 cm were not weaned from TPN. None of the adult patients with residual small intestinal length less than 40 cm could achieve complete intestinal adaptation. Five adult patients died due to liver failure (2 cases), heart failure (2 cases), or pneumonia (1 case), whereas all pediatric patients survived. The average life span of indwelling central venous catheters was 511 days and 780 days, and the rate of catheter-related sepsis per 1000 catheter days was 0.73 and 0.48 in pediatric and adult patients, respectively. Plasma levels of arginine and citrulline in patients receiving TPN were significantly decreased compared with those in patients receiving TPN without SBS both in pediatric and adult patients (p < .01). These results indicate that pediatric and adult patients with SBS can survive with TPN and enteral nutrition. The minimum remaining intestinal length necessary for complete bowel adaptation is shorter for pediatric patients than adults, suggesting better bowel adaptation in pediatric patients.

From November 1994 to November 1998, 20 children (2.5 to 14 years) received a jejunoileal graft alone (SBTx; n = 10) or in combination with the liver (SBLTx; n = 10 and/or the right colon (5 SBTx). Indications were intractable diarrhea of infancy (n = 8), short bowel syndrome (n = 6), extensive Hirschsprung disease (n = 4), and chronic intestinal pseudoobstruction (n = 2). Immunosuppression included tacrolimus, methylprednisolone, and azathioprine. Current follow-up ranges from 6 to 54 months. Five patients died (3 SBTx) within the first 2 months. Acute liver rejection occurred in 5 patients during the first 2 months. Sixteen episodes of intestinal rejection during the first 3 months in 11 patients (8 in 4 SBTx) were successfully treated in all but 3 by increasing tacrolimus dose and/or a 3-day methyprednisolone bolus or required antilymphoglobulins in 3 cases. Surgical complications occurred 8 times after SBLTx and 3 after SBTx. Infectious complications were more frequent in SBLTx recipients. Reversible Epstein-Barr virus-related posttransplant lymphoproliferative disease occurred in 3 recipients. Five presented cytomegalovirus infection. The SB graft was removed in 5 recipients (3 chronic rejection). All patients were started with oral and/or enteral feeding from the 7th postoperative day by using either normal food or protein hydrolysate diet. Currently, 10 of 11 children (8 SBLTx) achieved digestive autonomy after 5 to 30 weeks. All recipients gained weight; however, growth velocity remained reduced during the first 6 months because of the steroid therapy. Overall graft and patient survival is higher after SBLTx. Intestinal transplantation is indicated for patients with permanent intestinal failure. However, because parenteral nutrition is generally well tolerated, even for long periods, each indication for transplantation must be weighed carefully in terms of risk and quality of life.

Small bowel transplantation (SBT) presents a formidable challenge to perioperative nurses. Patients who survive these procedures have difficult postoperative courses with lengthy intensive care stays. They also are at significant risk for graft rejection and long-term immunosuppression complications. The option for SBT is reserved for patients who otherwise face the prospect of life-long total parenteral nutrition (TPN). Advances in donor and recipient surgical techniques and improvements in immunosuppressive therapies have raised hopes that patients with intestinal failures who undergo SBT procedures will be allowed to resume full oral nutrition and independence from TPN.

Short bowel syndrome is the clinical manifestation of a fundamental reduction in the functional intestinal absorptive surface area and malabsorption. The development of total parenteral nutrition has improved the natural course of this disease. Home parenteral nutrition-related complications continue to generate significant morbidity and mortality for these patients. Small-bowel transplantation is an alternative to home parenteral nutrition. There are significant risks of graft rejection and the potential complications of long-term immunosuppression. Small-bowel transplantation is an option, but it should be reserved for patients no longer considered candidates for continued home parenteral nutrition.