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Objectives: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center., Methods: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression., Results: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005)., Conclusions: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Anastomotic ulceration (AU) is a rare but life-threatening complication of pediatric short bowel syndrome (SBS). AUs may be challenging to detect and refractory to treatment. This study aimed to identify features associated with symptomatic bleeding AUs in children with SBS and factors that may impact resolution of bleeding. The relationship between dietary changes and symptomatic anastomotic hemorrhage was also explored., Methods: We conducted a retrospective chart review of 381 patients cared for in the Intestinal Rehabilitation Program at our center from 2013 to 2022. Patients with symptomatic AUs were identified based on at least 1 endoscopic procedure showing AUs and evidence of clinically significant gastrointestinal bleeding. We collected patient demographics, clinical characteristics, dietary history, radiologic imaging, and histopathology. We used descriptive statistics to identify patterns of presentation., Results: AUs were identified in 22 patients who were followed for a median duration of 2.9 years after anastomotic ulcer identification. AUs uniformly evolved years after the initial anastomosis (median 3.2 years). Characteristics included bowel stricture (4/22), small bowel-colon anastomosis (19/22), partial colectomy (17/22), and an increase in whole foods fraction (12/18). Bleeding resolved with operative intervention in the majority with anastomotic stricture (3/4). Recurrent bleeding was common in those without stricture (13/18). In a subset of patients without stricture, whole food reduction was associated with improvement or resolution of bleeding (5/6)., Conclusions: We observed a higher proportion of patients with AUs who responded to surgical intervention in the subset of children with definitive anastomotic strictures versus those without, suggesting that careful characterization of intestinal anatomy may be critical to predicting response to therapy. We also observed that bleeding from AU typically first manifested within 1 year of a shift from elemental or hydrolyzed enteral formula to a whole food-based diet (including commercial blenderized feeds), which may indicate that components of the enteral diet play a role in the pathogenesis of AU. Further studies are needed to validate these hypotheses., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. The first part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose of Review: With the inherent therapeutic limitations of gut transplantation, the concept of surgical gut rehabilitation was introduced to restore nutritional autonomy in pediatric patients. With favorable outcomes in these young patients, there has been increasing interest in the applicability of gut rehabilitative surgery to a growing population of adults with gut failure due to various etiologies. We aim to review the current status of surgical gut rehabilitation for adult gut failure patients in the era of multidisciplinary gut rehabilitation and transplantation., Recent Findings: Indications for surgical gut rehabilitation have been gradually expanding, with gut failure after bariatric surgery recently added. Serial transverse enteroplasty (STEP) has been used with favorable outcomes in adult patients, including those with intrinsic intestinal disease. Autologous gut reconstruction (AGR) is the most frequently used surgical rehabilitative method; its outcome is further improved with conjunctive use of bowel lengthening and enterocyte growth factor as a part of comprehensive gut rehabilitation., Summary: Accumulated experiences have validated the efficacy of gut rehabilitation for survival, nutritional autonomy, and quality of life in adults with gut failure of various etiology. Further progress is expected with growing experience around the world., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The intestinal rehabilitation program (IRP) is a comprehensive treatment strategy that employs various approaches implemented by multidisciplinary teams to treat intestinal failure in children. This program has shown promising results, such as reducing complications and improving prognosis and quality of life (QOL). In this review, we discuss the current status of this program and relevant topics., Recent Findings: IRP includes the prevention and treatment of various complications such as intestinal failure associated liver disease, catheter-related bloodstream infection or sepsis, and venous thromboembolism. In addition, treatment strategies such as glucagon-like peptide-2 analogs, surgical interventions, and intestinal transplantation have evolved over time and have contributed to improved outcomes. In addition, the scope and regions for IRP activities have expanded., Summary: IRP improves the prognosis and QOL of children with intestinal failure. The development of new drugs, surgical methods, and treatment strategies is expected to improve the current and future status of pediatric patients with intestinal failure. Furthermore, international institutions must collaborate, share knowledge, conduct joint research, and establish patient registries to advance IRP progress., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Autologous intestinal reconstructive (AIR) surgery is frequently utilized in the management of pediatric short bowel syndrome (SBS). However, little is known about the long-term sequela of these procedures., Methods: We undertook a retrospective follow-up study addressing parenteral nutrition (PN) dependence, nutritional status, intestinal morbidity, and related complications in SBS patients having undergone AIR surgery (SBS-AIR, n = 19). We compared results with conservatively treated control SBS patients (SBS-C, n = 45). Eligible patients were identified from our institutional intestinal failure registry during 1985-2019., Results: After median 11.4 follow-up years, 42% of SBS-AIR patients received PN in relation to 36% in SBS-C group ( P = 0.6210), and overall PN duration was significantly longer (35.4 vs 10 months, P = 0.0004) in SBS-AIR group. Although symptoms of intestinal dysfunction improved in majority (62%) of patients after AIR surgery, their symptoms remained more frequent and severe at latest follow-up compared to SBS-C group (39% vs 5%, P = 0.0015). Although bacterial overgrowth was more frequent in SBS-AIR group (53% vs 24%, P = 0.0416), latest endoscopy findings and fecal calprotectin levels as well as occurrence of anastomotic/staple line ulcerations were comparable between groups. Histological liver steatosis (50% vs 18%, P = 0.042) and impaired bone health (26% vs 6.7%, P = 0.042) were more frequent in SBS-AIR patients., Conclusions: While AIR surgery improved gastrointestinal symptoms and transition to enteral autonomy in majority of patients, a noteworthy proportion of them continued to suffer from clinically significant intestinal dysfunction and related complications. Close long-term follow-up of pediatric AIR surgery patients is mandatory., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Total colonic aganglionosis involving the small bowel is a rare form of Hirschsprung disease. We aim to analyse the long-term outcomes, digestive autonomy, and complications, to suggest recommendations for prevention and treatment., Methods: All patients born between 2000 and 2015 followed in our centre were retrospectively included. We analysed the length of aganglionosis, surgical procedures, growth, duration of parenteral nutrition (PN), enterocolitis, liver disease, intestinal transplantation., Results: Twenty-five patients were followed for a median of 10.9 years. Fifteen patients had less than 80 cm of ganglionic small bowel (SB) with a median of 20 cm. Ten patients had more than 80 cm of ganglionic sB with a median of 115 cm. The median PN duration was significantly shorter for patients with more than 80 cm: 0.9 versus 7.5 years in those with less than 80 cm (P  < 0.001). No patient with less than 80 cm was weaned off PN, except 1 who underwent intestinal transplantation. Ten patients with less than 80 cm develop enterocolitis on the excluded segment, leading to emergency entero-colectomy in 5. Liver disease was more frequent in patients with less than 80 cm (11 vs 0). Three patients required combined liver-intestine transplantation; 2 underwent an isolated intestinal transplantation., Conclusions: Digestive autonomy was possible in most patients with more than 80 cm of ganglionic SB. The more severe complication was enterocolitis. Liver disease compromised long-term survival without transplantation. Both complications should be prevented by early diversion and enterectomy of the whole aganglionic segment. Follow-up in or together with a multidisciplinary intestinal rehabilitation centre is suggested., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose of Review: Intestinal failure (IF) evolved from being the last recognized organ failure, to become one of the most progressive fields in terms of therapeutic alternatives and results. Short bowel syndrome (SBS) is the main cause of IF in adults and children. The use of surgery allowed patients with unfavorable anatomy type and length to be wean off parenteral nutrition. We aim to evaluate its current impact on intestinal rehabilitation., Recent Findings: Autologous gastro-intestinal reconstructive surgery (AGIRS), including bowel lengthening contributes by converting patient's anatomy to a more favorable one, improving quality of life, and modifying the natural history of the disease, allowing to recover intestinal autonomy in approximately 70% of the adults and 50% of the children's with SBS-IF. The current use of postsurgical medical rehabilitation strategies including the use of enterohormones complement the path to sufficiency, increasing the chances of success in both age group of patients., Summary: The development of AGIRS has changed the outcome of SBS-IF patients, becoming the main surgical procedure prescribed in multidisciplinary units, allowing to enhance the number of patients achieving intestinal autonomy throughout rehabilitation, leaving transplantation as the last surgical alternative., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Intestinal failure secondary to short bowel syndrome is still a very serious condition. Treatment consists of parenteral nutrition to provide nutrients and maintain body weight. During the last decades, intestinal lengthening procedures have become more available. The goal of this review is to discuss the results of the literature on the most commonly performed intestinal lengthening procedures., Recent Findings: Longitudinal Intestinal Lengthening, Serial Transverse Enteroplasty (STEP), and Spiral Intestinal Lengthening and Tailoring (SILT) are currently the most frequently reported intestinal lengthening procedures. The most recent literature of these procedures is described with respect to indication, technical details, complications, short and long-term outcome, and PN independence., Summary: On the basis of indication, surgical complexity, complications, and clinical success, we conclude that the STEP procedure is probably the best choice for most centers., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: This article discusses the current state of the art in artificial intestine generation in the treatment of short bowel syndrome., Recent Findings: Short bowel syndrome defines the condition in which patients lack sufficient intestinal length to allow for adequate absorption of nutrition and fluids, and thus need parenteral support. Advances toward the development of an artificial intestine have improved dramatically since the first attempts in the 1980s, and the last decade has seen significant advances in understanding the intestinal stem cell niche, the growth of complex primary intestinal stem cells in culture, and fabrication of the biomaterials that can support the growth and differentiation of these stem cells. There has also been recent progress in understanding the role of the microbiota and the immune cells on the growth of intestinal cultures on scaffolds in animal models. Despite recent progress, there is much work to be done before the development of a functional artificial intestine for short bowel syndrome is successfully achieved., Summary: Continued concerted efforts by cell biologists, bioengineers, and clinician-scientists will be required for the development of an artificial intestine as a clinical treatment modality for short bowel syndrome.

Objective: Management of short bowel syndrome (SBS) has significantly evolved recently. We present our single-center, 25-year experience focusing on the implementation of a refined multidisciplinary SBS care protocol., Methods: This is a retrospective review of the patients with SBS treated at our tertiary center from 1988 to 2014, with either <25% short bowel remaining or duration of parenteral nutrition (PN) >3 months. Patients with primary intestinal motility disorders were excluded. Clinical characteristics, including intestinal anatomy, markers of cholestasis, and catheter-related infections (CRIs), were analyzed. The implementation of a refined modern uniform management protocol in 2009 divided the cohort into 2 subgroups, whose outcomes are compared., Results: Forty-eight patients with SBS were identified (median gestational age 33 weeks). Of them, 22 were born between 2009 and 2014. The main causes of SBS were necrotizing enterocolitis (46%) and midgut volvulus (23%). Median remaining small bowel length was 36 cm. The overall survival was 23 of 26 (88%) before 2009 and 21 of 22 (95%) thereafter, whereas none were transplanted. Duration of PN shortened from a median of 15 to 6 months (P = 0.0015) in the latter cohort, whereas frequency of autologous intestinal reconstruction surgery (31%) remained unchanged. Frequency of neonatal cholestasis was similar in both groups (75%), but cleared in all after 2009. Before 2009, 2 patients died of progressive cholestatic liver failure. The CRI rates decreased from 1.7 to 0.7 per 1000 catheter-days between 2000-2008 and 2009-2014, respectively (P = 0.0178)., Conclusions: Uniform refined multidisciplinary approach decreased the duration of PN and CRI rates with high transplant-free survival and avoidance of liver failure, although the frequency of transient neonatal cholestasis remained unchanged.

Purpose of Review: Parenteral nutrition enables long-term survival in patients with intestinal failure; however, it is associated with life-threatening complications necessitating alternative techniques of management to enable weaning parenteral nutrition and minimizing parenteral nutrition-associated comorbidities. This review aims at discussing the indications and techniques most commonly utilized for surgical management in a short gut., Recent Findings: Surgical therapy for short gut has evolved and undergone refinement in the past 30-40  years with the older procedures being largely abandoned and replaced by newer and refined techniques. Lengthening surgeries (longitudinal intestinal lengthening and tapering and serial transverse enteroplasty) are the most commonly applied procedures in a dilated bowel with intestinal transplantation option reserved as a last resort for recurrent life-threatening central venous line infections, progressive loss of central venous access, and development of progressive liver disease., Summary: Management of intestinal failure requires a multidisciplinary approach to optimize intestinal rehabilitation and overall patient outcome. Although intestinal transplantation remains an excellent option for patients with severe life-threatening complications, autologous intestinal reconstruction appears to remain the better overall option.

Purpose of Review: The surgical management of short bowel syndrome now includes intestinal (ITx) and multivisceral transplantation (MVTx), which has advanced and is now a sustainable option for the treatment of intestinal failure. Improvements in immunosuppressive therapies, excellence in surgical and medical management and enhanced post-transplant monitoring have all contributed to optimizing this solid organ transplant as a means of supplanting the diseased native bowel and alimentary tract with a functional alternative., Recent Findings: Post-transplant management is a critical and challenging phase of gastrointestinal transplantation, and the transplant pathologist is an essential member of the transplant team who identifies many of the early and late complications after ITx and MVTx. Among the most injurious and common complications of ITx and MVTx is acute rejection and, to a lesser degree, chronic rejection. Both of these broad categories of rejection are principally identified by histopathological changes in the allograft; however, biomarkers and other laboratory analytes are rapidly evolving into critical ancillary tools in identifying and further characterizing the rejection process. Thus, the transplant pathologist must also be able to utilize numerous other laboratory tests and panels of molecular biomarkers that provide supplementary information to accompany the biopsy interpretation and clinical suspicion of rejection., Summary: Using biopsies and an assortment of additional approaches, the transplant pathologist is now able to provide swift and detailed information regarding the rejection process in the gastrointestinal transplant. This enables the clinical team to properly and successfully intercede, contributing to enhanced patient and graft survival.

Purpose of Review: The purpose of this review is to provide an update of recent advances in the areas of short bowel syndrome (SBS) and small bowel transplantation (SBT)., Recent Findings: Recent reports from two of the largest multicenter randomized, controlled trials in patients with SBS support the safety and efficacy of teduglutide as an aid to parenteral nutrition weaning. In well selected SBS patients, outcomes as diverse as survival, macronutrient absorption and parenteral nutrition weaning are improved after autologous gastrointestinal reconstructive surgery. SBT is no longer considered investigational and given improved outcomes noted in recent reports, indications for transplantation are expanding. Although SBT early survival rates are approaching those of other organ allografts, long-term graft survival remains suboptimal., Summary: Recently available trophic factors hold promise as aids in restoring freedom from parenteral nutrition support; however, their long-term benefits, preferred timing of administration in relation to the onset of SBS, optimal patient selection for use, duration of treatment and cost effectiveness require further study. Despite recent evidence of improved early survival after SBT, more dedicated research is needed to design more effective strategies to better tolerize small bowel grafts, prevent rejection and, ultimately, improve long-term outcomes. Reserved for well selected patients, autologous gastrointestinal reconstruction should be considered complementary and not antagonistic to SBT.

Objectives: Intestinal atresia is a common cause of intestinal obstruction in neonates. The predominant cause of late complications in these children is prolonged dependence on parenteral nutrition (PN). Our aims were to analyze the outcomes for patients with intestinal atresia at our institution, and to see how these changed with the implementation of an intestinal rehabilitation program (IRP)., Methods: This is a retrospective cohort study. The patient population is all children with intestinal atresias (118 patients) treated at our institution from July 2000 to June 2010, 20 of whom became PN dependent., Results: Survival to hospital discharge was 95% for all patients, and 100% for those who had isolated atresia. Twenty of 118 patients (17%) were PN dependent beyond initial hospital discharge. At discharge, their median intestinal length was 22.5 cm, and they required PN for a mean of 88.5% of energy needs. Of these 20 patients, 2 died, 2 received transplants, and 2 transferred away for transplantation. The remaining 14 joined the IRP. Their mean energy requirement from PN is presently 10%, down from 87% at IRP enrollment, and 10 patients fully weaned off PN. Eleven of the 14 children had hyperbilirubinemia, with mean direct bilirubin of 7.5 mg/dL. All resolved their cholestasis during an average of 12 weeks., Conclusions: These results compare favorably with those reported in earlier periods. With programs such as the IRP, patients with short bowel secondary to intestinal atresia can show improvement in liver function and nutritional parameters, and discontinue PN, avoiding the need for transplantation.

Purpose of Review: Autologous intestinal reconstructive surgery has evolved over the past 3 decades from rescue to main surgical procedure in the multidisciplinary approach to short bowel syndrome (SBS) patients with intestinal failure. The purpose of this review is to clarify the actual place of intestinal reconstructive surgical techniques in the management of intestinal failure related to SBS and their relationship with intestinal transplantation., Recent Findings: Recent reports from centers of excellence in intestinal rehabilitation underline the efficacy and safety of autologous intestinal reconstructive surgery in patients with SBS. Outcome parameters as survival, parenteral nutrition weaning, and clinical conditions were improved in SBS patients treated by gastrointestinal reconstructive surgery., Summary: Autologous intestinal reconstructive procedures are pivotal to achieve enteral autonomy in patients with intestinal failure related to SBS. They should be considered mutually supportive and not antagonistic to intestinal transplantation.

Objectives: Intestinal failure (IF) is a common consequence of neonatal small bowel pathology. In our experience, bowel dilatation is often responsible for the IF state in patients who fail to adapt despite adequate residual bowel length. The aim of the present study was to investigate the role of surgery to reduce bowel dilatation, and thus favour PN independence, for these children., Methods: Data were collected prospectively for all of the patients referred to our unit for a 7-year period (2004-2011). Eight patients (2 congenital atresia, 2 gastroschisis with atresia, 1 simple gastroschisis, 3 necrotising enterocolitis) with gut dilatation who failed adaptation despite a bowel length >40 cm were identified. Preoperatively, all patients were totally dependent on parenteral nutrition (PN). Patients were managed by longitudinal intestinal lengthening and tailoring (n = 3), serial transverse enteroplasty (n = 2), or tapering enteroplasty (n = 3)., Results: Median age at time of surgery was 273 days (103-1059). Mean gut length increased from 51 (35-75) to 73 cm (45-120) following surgery (P = 0.02). Incidence of sepsis (P = 0.01) and peak serum bilirubin levels (P = 0.005) were reduced postoperatively. PN was discontinued after a median of 110 days (35-537) for 7 patients; 1 patient remains on PN 497 days after surgery., Conclusions: These data indicate that reconstructive surgery to reduce bowel diameter may be an effective technique for treating IF in patients with short bowel syndrome, without sacrificing intestinal length. We suggest that this technique may reduce the need for bowel transplantation in this group of patients.

Purpose of Review: Recent studies have evaluated intestinal physiology following bowel resection; understanding changes in small bowel physiology after intestinal transplantation has received less attention. In this review, we will examine recent studies focused on changes in intestinal physiology following resection and intestinal transplantation., Recent Findings: Absorption, immunity, and motility are fundamental components of small bowel physiology. Absorption after resection or transplantation is mediated by adaptation and enterocyte function. After resection, adaptation results in increased villus height and crypt depth. Hepatocyte growth factor and epidermal growth factors cause enterocyte hypertrophy and hyperplasia, allowing greater peptide uptake. Little is known about intestinal adaptation after transplant, but enteral autonomy is attainable. Immunity in small bowel after transplantation relies on a balance of innate and adaptive immune responses in the presence of the luminal microbiota. Intraepithelial lymphocytes are decreased following small bowel resection. After small bowel transplant, the number and the ratio of intraepithelial lymphocytes to enterocytes, as well as changes in the microbiota, can be used to identify rejection. After intestinal transplant, immune-mediated dysmotility is common. Perioperative infliximab in addition to tacrolimus may decrease the inflammation that contributes to dysmotility., Summary: As intestinal transplantation becomes more successful, understanding how absorption, immunity, and motility changes will allow for optimization of bowel function.

Objectives: The aim of the present study was to investigate the segment- and time-related changes in rat short bowel syndrome and construct a 4-dimensional (4D) geometrical model of intestinal adaptation., Methods: Sprague-Dawley rats were divided into 3 groups: 2-day, 7-day, and 15-day postresection groups in which 75% of the jejunoileum was removed. Histological and morphometrical parameters in the remaining proximal to distal intestinal segments, from the jejunum to the distal colon, were comparatively evaluated in the groups. The data were used to construct a 4D geometric model in which villi were considered as cylinders, and their surface area was expressed as cylinder lateral area., Results: Major adaptive changes were observed in the ileum consisting of an increase in both the diameter of base and the height of villi. A parallel reduction in their number/mm was observed. The resulting ileal architecture was characterized by a limited number of large villi. An opposite pattern was observed in the jejunum whose postresection structure consisted of an increased number of villi. No changes were observed in the colon. Postresection restructuring was early and faster in the ileum than in the jejunum resulting in an increase in absorptive area of 81.5% and 22.5% in the ileum and jejunum, respectively., Conclusions: Postresection adaptation is intestinal segment-specific because all of the major changes occur in the ileum rather than in the jejunum. Sparing ileal segments during resection may improve the outcome of patients undergoing extensive intestinal resection. Our 4D model can be used to test interventions aimed at optimizing postresection intestinal adaptation.

Objectives: In the present study, we evaluated the effect of transforming growth factor-beta 2 (TGF-β2)-enriched diet on enterocyte turnover and correlated it with TGF-β2 receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS)., Methods: CaCo-2 cells were incubated with increasing concentrations of TGF-β2. Alamar Blue reduction test was used for investigation of cell viability and evaluation of cell apoptosis was assessed by flow cytometry. Male rats were divided into 4 groups: Sham rats underwent bowel transection, Sham TGF-β rats were treated with diet enriched with TGF-β2, SBS rats underwent a 75% bowel resection, and SBS TGF-β rats were fed a diet enriched with TGF-β2 after bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at sacrifice. TGF-β2r expression in villus tips, lateral villi and crypts was assessed by immunohistochemistry. The effect of TGF-β2 on enterocyte turnover for each compartment was evaluated in correlation with TGF-β2r expression., Results: Incubation of CaCo-2 cells with TGF-β2 resulted in a significant decrease in cell viability and increased cell apoptosis. TGF-β2r expression in crypts increased in SBS rats (vs sham) and was accompanied by decreased cell proliferation and increased cell apoptosis following TGF-β2 administration. A significant decrease in TGF-β2r expression at villous tips in SBS rats was accompanied by a decreased cell apoptosis in this compartment following exposure to TGF-β2-enriched diet., Conclusions: In a rat model of SBS, the inhibiting effect of TGF-β2 on enterocyte turnover correlates with TGF-β2 receptor expression along the villus-crypt axis.

Objective: This study aimed to assess the results of segmental reversal of the small bowel (SRSB) in patients with short bowel syndrome (SBS) who were "permanently" dependent on parenteral nutrition (PN) and to identify possible prognostic factors for weaning., Summary Background Data: SRSB is a nontransplant surgical option for patients with SBS who require long-term PN. Few studies have reported outcomes in humans., Methods: : All patients who were permanently dependent on PN and underwent a SRSB between 1985 and 2010 for SBS were included. The data were retrospectively retrieved., Results: Thirty-eight patients underwent SRSB. The median age was 55.5 years (range, 18-76). The median length of the small bowel remnant was 49 cm (20-140), including a reversed segment of 10 cm (6-15). The median follow-up was 57.7 months (1-304). At the 5-year follow-up, 17 patients had been weaned from PN (45%). In the remaining patients, PN dependency had decreased from 7 ± 1 to 4 ± 1 days per week. The survival rate was 84%. The prognostic factors for weaning were a short time between subtotal enterectomy and SRSB (P = 0.036), a longer than typical stay in the nutrition unit (P = 0.035), and an SRSB longer than 10 cm (P = 0.024)., Conclusions: SRSB has a role as a conservative alternative to small bowel transplantation in patients with SBS permanently dependent on PN. With a segmental reversal of 10 to 12 cm, almost half of the patients can be expected to be weaned from PN.

Background: Intestinal transplantation is a relatively new form of therapy for short gut syndrome. Pregnancy after intestinal transplantation is rare., Case: A 26-year-old small bowel transplant recipient presented for prenatal care. She previously had undergone bariatric surgery and later experienced small bowel necrosis and resection. The resulting short gut syndrome was treated with an isolated small bowel transplant. Medications during this pregnancy included prednisone, esomeprazole, diphenoxylate-atropine, ascorbic acid, tacrolimus, and magnesium supplementation. Throughout her pregnancy, her creatinine level was elevated. Labor was induced at 39 3/7 weeks and resulted in a spontaneous vaginal delivery of a healthy female neonate. Twelve weeks after delivery, the mother was admitted for a rejection reaction that was treated successfully., Conclusion: A successful pregnancy in an intestinal transplant recipient resulted in delivery of a healthy term newborn.

Purpose of Review: Intestinal transplantation (ITx) and multivisceral transplantation (MVTx) has evolved into a viable treatment option for short bowel syndrome and intestinal failure due to a variety of factors including improved immunosuppressive regimens, superior surgical and medical management, and enhanced posttransplant monitoring., Recent Findings: The transplant pathologist is a central member of the transplant team in all phases of solid organ transplantation and as such, plays an important role in the evaluation of early and late complications after ITx and MVTx. Central among the tools for the pathologist is the mucosal biopsy, used for discerning histopathological changes in the allograft. The principal complications seen in the late posttransplant phase are acute rejection, chronic rejection, infections, and a variety of other inflammatory conditions. In order to more precisely characterize these conditions, the transplant pathologist must also be able to utilize numerous other laboratory tests and panels of molecular biomarkers that serve as ancillary information to complement the biopsy impression., Summary: Using this array of tools, the transplant pathologist is now able to provide rapid and precise information regarding the gastrointestinal (GI) transplant complications, a function that allows the clinical team to appropriately and successfully intervene and that helps contribute to the observed improvement in patient and graft survival.

Background and Aim: Short bowel syndrome poses a great challenge to pediatric teams. Several innovative techniques in the management of total parenteral nutrition (TPN) and bowel reconstructive surgery have improved the outcomes of these children. The authors present their experience during the last decade as a specialist unit using improved techniques and multidisciplinary approaches in the management of this condition., Methods: All of the children presenting with short bowel syndrome between 2000 and 2009 were identified. Diagnosis, length of residual gut, age at definitive surgery, length of gut prelengthening, length of gut postlengthening, TPN status, and survival were recorded. Median values were calculated., Results: Twenty-seven children were identified (14 boys, 13 girls). Overall survival was 92%. Two children died. Nineteen children required bowel lengthening and 8 children had simple bowel reconstruction while on our protocol. Overall median age at definitive surgery was 12 months. Overall median residual gut length for these was 35.5 cm, whereas the median residual gut length for patients undergoing bowel lengthening was 25 cm. Postbowel lengthening, the median gut length was 90 cm. TPN data were unavailable for 2 patients. Overall, excluding the 2 patients who died and the 2 we have no TPN data on, of 23 patients, 21 (91%) are now off TPN., Conclusions: Our series shows improved results not only with survival but also in the number of patients that are off TPN. Multidisciplinary approach consisting of both medical and surgical expertise is necessary in the management of these patients. The authors advocate centralisation of short gut services to experienced centers with multidisciplinary expertise.

Background and Aims: Short bowel syndrome (SBS) describes the malabsorptive state seen following extensive bowel resection. Management aims to optimise nutritional intake, promote intestinal adaptation, and prevent the development of complications. Surgical options such as autologous gastrointestinal reconstruction (AGIR) attempt to restore enteral autonomy to the patient. Although the literature focuses on the objective measurements of success following AGIR techniques, subjective assessment of its effect on the quality of life (QoL) should also be sought. Because children with SBS are reliant on caregivers, caregivers' satisfaction with surgery and their perception of the effect of AGIR on their daily lives should be assessed. This is the first report of caregiver satisfaction following AGIR in children., Methods: All children with SBS who had AGIR between January 1999 and June 2010 were identified. A questionnaire was developed. Caregivers were asked to complete the questionnaire to rate their satisfaction with surgery and the pre- and postoperative daily care, medical needs, and subjective interpretation of QoL for their child. Data were analysed using SPSS version 18, using the Friedman nonparametric test and 2-way analysis of variance by rank. Statistical significance was set at ≤0.05., Results: Thirty-two children were identified. Seven assessments were done outside our centre (5 outside the UK) and were not included in the study. One patient moved to another city and was not contacted. Two children died. Twenty patients were contactable and were included in the present study. Parents were satisfied with the AGIR and saw improvements in their child's physical condition, bowel habit, and subjective interpretation of QoL postoperatively. Parents perceived significant improvements in the ease of caring and in aspects of their relationship with their child, including the quality of time spent, their enjoyment, and the level of their frustration with them., Conclusions: The present study found that AGIR improved the physical well-being of the child and gave the impression of improvements on specific QoL aspects for both the child and the parents.

Background: Significant bowel lengthening can occur in an isolated intestinal segment with the use of linearly directed distractive forces, resulting in increased surface area and epithelial cell proliferation. We hypothesized that reimplantation of this lengthened intestine into normal jejunum would preserve this gain in intestinal length and function similar to normal jejunum., Methods: An intestinal lengthening device was inserted into isolated jejunal segments in pigs, and fully expanded over 8 days. Lengthened segments were then reimplanted into normal intestinal continuity. Pigs were studied after another 28 days. Function was assessed by motility, mucosal enzyme activity, barrier function, and intestinal ion transport., Results: Lengthened segments were significantly longer than control segments and had nearly 2-fold greater surface area. Bowel lengthening was maintained 4 weeks after reimplantation. Motility after reimplantation was similar to nonoperated pigs. Barrier function, mucosal disaccharidase levels, and electrophysiologic measures declined immediately after lengthening but returned to nearly normal levels 28 days after reimplantation., Conclusion: Bowel lengthening results in a transient decline in mucosal absorptive function and smooth muscle contractility. However, function approaches that of normal bowel after reimplantation into enteric flow. These data may support the use of this technique as a potential new option for the treatment of patients with short bowel syndrome.

A 33-year-old Chinese man with short bowel syndrome received intestinal rehabilitation therapy. We observed microscopically morphologic changes of remnant small intestine by magnifying endoscopy and histopathologic examination before and after 3 courses of treatment. The results revealed that the 2 methods have a fairly good correlativity, and magnifying endoscopy examination of intestinal adaptation in patients with short bowel syndrome possesses great applicative value.

Objectives: Short bowel syndrome occurring after surgery for acquired or congenital intestinal abnormalities causes considerable neonatal morbidity and mortality. Animal models are a valuable research tool for this problem; however, few successful neonatal models have been developed and most do not include distal intestinal resection as seen commonly in human babies. We report novel piglet models addressing these gaps., Subjects and Methods: Neonatal piglets (1-6 days) underwent venous and gastric catheter insertion and 75% intestinal resection. Group 1 (n = 6) had midintestinal resection with jejunoileal anastomosis; group 2 (n = 5) had distal intestinal resection with jejunocolic anastomosis; group 3 (n = 5) were sham controls; and group 4 (n = 5) were sow reared. Postoperatively, groups 1 to 3 piglets commenced parenteral nutrition (PN), and enteral nutrition was introduced and advanced using a standard regimen. Data collection included days on PN, weight gain, fat absorption, small intestine lengthening, and bowel/liver histology., Results: Group 2 piglets had more days on PN (P = 0.008), less weight gain (P = 0.027), and greater malabsorption (P = 0.012). They did not show small intestine lengthening and had more cholestatic liver disease. Group 1 piglets had histological evident intestinal adaptation and 1.5-fold intestinal lengthening (P = 0.001)., Conclusions: These novel piglet models of short bowel syndrome are the first to represent the full clinical spectrum of intestinal failure as observed in human neonates. By considering the impact of different short bowel anatomy on potential for adaptation and growth, these animal models are a significant advance. They permit evaluation of new therapies to promote intestinal adaptation and reduce complications, such as cholestasis.

Intestinal failure (IF), typically due to short bowel syndrome in adults and congenital disorders in pediatric patients, is universally managed with parenteral nutrition (PN). When patients fail PN due to recurrent infection, loss of central venous access or PN-induced liver disease, intestinal transplant (ITx) is indicated. ITx consists of transplant of the small bowel, small bowel plus liver, or intestine plus multiple abdominal viscera. ITx allows for freedom from PN but is complicated by rejection and infection. Early referral of patients with IF to centers with experience in intestinal rehabilitation and transplantation is essential to improve patient outcome.

Purpose of Review: Medical management of children with intestinal failure has gained increased relevance in recent years, in part owing to the growth of small bowel transplantation as a therapeutic option. The capacity of a patient to attain enteral autonomy through intestinal adaptation is critical in the decision process of whether or not transplantation is beneficial. This article reviews several important advances in the field of intestinal rehabilitation, focusing on enhancing adaptation and briefly mentioning recent insights into the morbidity of intestinal failure., Recent Findings: The field of intestinal rehabilitation has developed into a multidisciplinary venture with many facets. From a medical standpoint, intestinal adaptation efforts have come to focus upon identifying objective prognostic factors and therapies geared to increase functional gut mass. However, the stalwart of adaptive therapy remains the provision of enteral feeds, which must be balanced with nutritional goals. Although the common complications of parenteral nutrition therapy continue to affect outcomes, new therapies offer promise with regard to prevention of morbidity in this population., Summary: Medical intestinal rehabilitative therapy has progressed from the solitary concept of providing sufficient calories for growth to the promotion of enteral autonomy via intestinal adaptation. As strategies evolve with enhancing adaptation and minimizing morbidity, a clearer perspective will be gained regarding the difficult choice of rehabilitation versus transplantation as optimal therapy.

Purpose of Review: Multidisciplinary management of intestinal failure has progressed over the past 30 years, facilitating the transition to enteral autonomy in many pediatric patients. However, there remains a select group of patients who reach a plateau in advancement of their enteral nutrition. Numerous surgical options have been pursued to attempt to slow intestinal transit, taper dilated bowel, and promote intestinal adaptation. This review highlights the current literature on autologous intestinal reconstruction surgery, focusing on the two most commonly performed procedures, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP)., Recent Findings: LILT and STEP remain viable options to treat medically refractory short bowel syndrome. There is over 20 years of experience with the LILT procedure in the literature, with one large series showing that 67% of patients eventually transitioned to full enteral nutrition. The International STEP Data Registry reported a weaning rate of 34% after median follow-up of 12.6 months. Repeat STEP has been described as a possible treatment for the redilation that occurs after both LILT and STEP., Summary: LILT and STEP may facilitate enteral feeding advancement in patients with medically refractory short bowel syndrome.

Purpose of Review: To analyze the current status of living donor intestinal transplantation (LDIT) as a treatment option for intestinal failure., Recent Findings: Long-term outcomes from LDIT and combined living donor intestinal/liver transplantation (CLDILT) are comparable with those from transplantation using deceased donors. In certain life-threatening situations, especially in pediatric patients, this strategy may offer potential advantages., Summary: According United Network for Organ Sharing (UNOS) data children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list compared with all candidates for solid organ transplantation. Elective nature of CLDILT offers multiple advantages for this patient population. LDIT also could be life-saving option for patients with intestinal failure who run out of venous access. Optimal timing, short ischemia time and good human leukocyte antigen (HLA) matching may contribute to lower postoperative complications. Current literature suggests that living intestinal donors experience very low morbidity and high level of satisfaction.

Purpose of Review: Immune monitoring is needed in small bowel transplantation (SBTx) because of a high incidence of rejection and graft loss, and life-threatening complications of high-dose prophylactic immunosuppression., Recent Findings: Clinical tests relevant to SBTx include methods to detect antidonor human leukocyte antigen antibodies, among which those which use known purified human leukocyte antigen peptides as substrates correlate best with graft loss; enumerate peripheral lymphocyte subsets to determine the efficacy of lymphocyte-depleting antibodies; estimate general immune function based on ATP production by mitogen-stimulated T-helper cells. Research tests that show clinical utility in SBTx recipients include following markers. First, flow cytometric mixed leukocyte responses, which detect donor-induced proliferation of recipient T-cytotoxic cells by dilution of the intravital dye carboxyfluorescein succinimidyl ester, or donor-induced CD154 expression in recipient T-cytotoxic memory cells. Among such tests, CD154 T-cytotoxic memory cells achieve the highest known sensitivity and specificity of at least 90% for the detection of acute cellular rejection. Second, elevated fecal calprotectin, an early screening marker for intestinal inflammation, which can indicate the need for a SBTx biopsy, especially after ileostomy stoma closure. Third, single-nucleotide polymorphisms associated with inflammatory bowel diseases, for example, nucleotide-binding oligomerization protein, macrophage stimulating 1, and so on. These single-nucleotide polymorphisms may be used to select the rejection-prone SBTx recipient for more potent immunosuppression, if additional studies confirm their associations with outcomes., Summary: The final approach to monitor the SBTx recipient will likely involve using the method(s) with the best sensitivity and specificity for detecting acute cellular rejection or graft loss during time periods when such events are most likely.

Objective: Few infant animal models have been used to study infantile short bowel syndrome (SBS). Most SBS models involve removal of the proximal small bowel followed by jejunoileal anastomosis, which has unclear clinical relevance to human infantile SBS that often results from surgical treatment for necrotizing enterocolitis and involves removal of the ileum, ileocecal valve, and part of or the entire colon. Our objective was to develop a more appropriate SBS model in developing rats., Materials and Methods: Twenty-day-old weanling rats were divided into 2 surgery groups, ileocecal resection (ICR) and sham groups, and a control group that did not undergo surgery. All were fed a liquid diet ad libitum for 7 days after surgery or for 7 days in the controls, and body weight, food intake, and stool changes were recorded daily. The rats were then euthanized and intestinal lengths and weights were recorded. Samples of intestine from the distal jejunum and proximal colon were collected for histology. Mucosal samples from the middle, distal jejunum, and colon were collected for measurements of mucosal weights, DNA, RNA, and protein levels. Maltase activity was determined in the small intestine., Results: Eighty-five percent of rats survived the ICR with subsequent development of diarrhea, hyperphagia, and poor growth. Adaptive responses to ICR, as compared with sham, were evidenced by increased intestinal and mucosal weights, DNA, RNA, and protein levels, increased maltase activity and villous thickness in distal jejunum, and increased mucosal thickness in the colon., Conclusions: This ICR model in weanling rats is appropriate for studying human infantile SBS.

Purpose of Review: Intestinal transplantation is a treatment for patients with short bowel syndrome and associated severe complications. The intestine has long been seen as a 'forbidden' organ to transplant. This fact is because the first attempts at intestinal transplantation were rapidly defeated by rejection and sepsis., Recent Findings: Several factors have contributed to improve the results: tacrolimus-based immunosuppression, induction therapy (independent of the type), introduction of ganciclovir and rituximab and subsequent better control of cytomegalovirus and posttransplant lymphoma, better differential diagnosis between rejection versus infection and ischemia (avoiding unnecessary overimmunosuppression), better patient follow-up. Center experience is more important than a particular immunosuppressive protocol. M-TOR inhibitors, infliximab have been used. Mycophenolate mofetil is less frequently used because of its potential gastrointestinal toxicity. Of note, no significant improvement in short-term and long-term (>1 year) survival was observed since 2000 and 1985, respectively., Summary: Intestinal transplantation remains a formidable clinical/immunological challenge. With newer immunosuppression and accumulated experience, intestinal transplantation results have improved and the procedure represents a life-saving option in patients with short bowel syndrome-related complications. Before intestinal transplantation becomes a 'quality of life-improving' procedure (offered to patients who are free of short bowel syndrome-related complications), new strategies focusing on facilitating graft acceptance and reducing the need for immunosuppression will have to be developed.

Purpose of Review: Although intestinal transplantation is uniquely suited for the treatment of patients with intestinal failure suffering from life-threatening complications, patient survival at 5 years remains suboptimal at approximately 50-60%., Recent Findings: The introduction of effective medications to improve intestinal absorption, alternate intravenous lipid preparations that may reduce cholestasis and a technically easier nontransplant intestinal lengthening procedure have largely changed the available options for nontransplant interventions. Multidisciplinary teams created to manage the complexities of this population have shown improved outcomes and the ability to prevent or slow progression of life-threatening complications that would otherwise lead to intestinal transplantation in a large number of patients with short bowel syndrome., Summary: Here, we review the historical options, recent advances and cutting-edge research that will likely provide the basis for further advances in the treatment of patients with short bowel syndrome as the cause of their intestinal failure.

Colon is a crucial partner for small intestinal adaptation and function in patients who underwent extensive small intestinal resection or transplantation. This short review deals with the different properties and roles of the colon in these settings, involving fluid and electrolytes absorption, absorption of medium-chain triglycerides, and production of short-chain fatty acids for malabsorbed energy salvage. The colon may adapt after small intestinal resection, whereas it hosts the most important part of the intestinal microbiota, which plays a crucial role in intestinal function and health. Also, colon may be responsible for D-lactic acidosis as well, as it can be injured by noninfectious colitis. Finally, the relevance of a simultaneous colon grafting is discussed as it is occasionally considered in specific patients requiring intestinal transplantation.

Objective: Selected infants with short bowel syndrome (SBS) and progressive intestinal failure associated liver disease (IFALD) may benefit from isolated liver transplantation (iLTx). The aim of the study is to identify risk factors for unfavourable outcome in iLTx., Patients and Methods: A retrospective review of medical records from 1998 to 2005 was undertaken. Risk factors were assessed by comparing long-term survivors with those who died after iLTx., Results: Fifteen iLTx were performed in 14 infants with IFALD. All were parenteral nutrition (PN) dependent, but had tolerated enterally 54% (38-100) of energy intake before iLTx. Median residual bowel was 60 cm (30-200). Eight out of 14 had intact ileocaecal valve (ICV). Median bilirubin was 298 micromol/L (87-715) and all had portal hypertension. Eight out of 9 survivors were weaned from PN after median 15 months. In 4 out of 9 children, nontransplant surgery after iLTx facilitated intestinal adaptation. Growth velocity had improved at 3 years after iLTx (P=0.001). Five children who died had poor enteral tolerance following iLTx (P<0.002), which correlated with pretransplant dysmotility seen in 4 out of 5 children shown by contrast studies (P=0.02)and increased frequency of line infections before (>6/year P<0.04) and after (P<0.001) iLTx., Conclusions: Isolated liver transplantation is a lifesaving option for selected children with SBS and IFALD. Revised criteria are proposed: progressive IFALD; 50 cm functional bowel in absence of ICV or 30 cm with ICV; 50% daily energy intake tolerated enterally for 4 weeks with satisfactory growth; and children with dysmotile bowel should be assessed for combined liver/bowel transplant unless the dysmotility is resolved and associated with minimal line infections.

Objectives: Longitudinal intestinal lengthening and tailoring (LILT) is a well-established surgical treatment for short bowel syndrome. It has been shown to enhance peristalsis, decrease bacterial overgrowth, and extend mucosal contact time for nutrients. We present the results of a long-term follow-up of patients who underwent LILT and define prognostic parameters for the survival of these patients., Patients and Methods: Between 1987 and 2006, 53 patients underwent LILT in our institution. The main diagnoses were gastroschisis, intestinal volvulus, intestinal atresias, and necrotizing enterocolitis. LILT was performed at a mean age of 24 months (range 4144 months). The follow-up time was 79.76 months (range 6234 months)., Results: After LILT, 41 of 53 patients survived, and 36 of 41 surviving patients were successfully weaned from parenteral nutrition (PN). In long-term follow-up 79% stayed free of PN. The overall survival rate was 77.36%. Weight gain occurred in 58% of the patients after LILT. The quality of life after LILT is on a high level, with most patients having normal physical strength and participating in normal social life and education. Prognostic factors for survival after LILT in short bowel syndrome are length of small intestine (0.06582 + 0.0131 x bowel cm), length of large bowel (P = 0.039), preoperative liver function, and successful weaning from PN within 18 months postoperatively (P = 0.0032)., Conclusions: Patients undergoing LILT in short bowel syndrome have a high survival rate, weight gain, and a high quality of life. Autologous gastrointestinal reconstruction remains therefore the first choice in the treatment of patients with short bowel syndrome.