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Aims: To report the results and successes of intestinal transplantation (ITx) in the most active European centres, to emphasize that, although it is a difficult procedure, it should remain a therapeutic option for children with total, definitive and complicated intestinal failure when intestinal rehabilitation fails., Methods: We retrospectively collected data about all patients less than 18 receiving an ITx from 2010 to 2022 in 8 centres, and outcomes in July 2022., Results: ITx was performed in 155 patients, median age 6.9 years, in 45% for short bowel syndromes, 22% congenital enteropathies, 25% motility disorders, and 15% re-transplantations. Indications were multiple in most patients, intestinal failure-associated liver disease in half. The graft was in 70% liver-containing. At last follow up 64% were alive, weaned from parenteral nutrition, for 7.9 years; 27% had died and the graft was removed in 8%, mostly early after ITx., Discussion: ITx, despite its difficulties, can give a future to children with complicated intestinal failure. It should be considered among the therapeutic options offered to patients with a predicted survival rate lower than that after ITx. Patients should be early discussed within multidisciplinary teams in ITx centres, to avoid severe complications impacting the results of ITx, or even to avoid ITx., Competing Interests: Declaration of competing interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

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.)

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.

Introduction:  The aims of the study are to systematically assess and critically appraise the evidence concerning two surgical techniques to lengthen the bowel in children with short bowel syndrome (SBS), namely, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP), and to identify patient characteristics associated with a favorable outcome., Materials and Methods:  MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception till December 2019. No language restriction was used., Results:  In all, 2,390 articles were found, of which 40 were included, discussing 782 patients. The median age of the patients at the primary bowel lengthening procedure was 16 months (range: 1-84 months). Meta-analysis could not be performed due to the incomparability of the groups, due to heterogeneous definitions and outcome reporting. After STEP, 46% of patients weaned off parenteral nutrition (PN) versus 52% after LILT. Mortality was 7% for STEP and 26% for LILT. Patient characteristics predictive for success (weaning or survival) were discussed in nine studies showing differing results. Quality of reporting was considered poor to fair., Conclusion:  LILT and STEP are both valuable treatment strategies used in the management of pediatric SBS. However, currently it is not possible to advise surgeons on accurate patient selection and to predict the result of either intervention. Homogenous, prospective, outcome reporting is necessary, for which an international network is needed., Competing Interests: L.M.W. reports other from Shire, outside the submitted work. M.A.B reports other from Shire, Norgine, Tramedico, Allergan, DAnone, Novalac, Friesland Campina, and Abbot, outside the submitted work. M.M.T. reports grants from Baxter Healthcare Company, outside the submitted work. S.H. reports grants and other from Shire/Takeda, outside the submitted work., (Thieme. All rights reserved.)

Background: Short bowel syndrome is a potentially fatal condition with inadequate management options. Tissue-engineered small intestine (TESI) is a promising solution, but confirmation of TESI function will be crucial before human application. We sought to define intestinal epithelial barrier function in human intestinal organoid (HIO)-derived TESI., Materials and Methods: HIOs were generated in vitro from human embryonic stem cells. After 1 mo, HIOs were collected for analysis or transplanted into the kidney capsule of immunocompromised mice. Transplanted HIOs (tHIOs) were harvested for analysis at 4 or 8 wk. Reverse transcription quantitative polymerase chain reaction and immunofluorescent staining were performed for tight junction components: claudin 3 (CLDN3), claudin 15 (CLDN15), occludin (OCLN), and zonula occludens-1, or tight junction protein-1 (TJP1/ZO-1)., Results: Four-week-old tHIOs demonstrated significantly (P < 0.05) higher levels of CLDN15 (6x), OCLN (4x), and TJP1/ZO-1 (3x) normalized to GAPDH than in vitro HIOs. Eight-week-old tHIOs demonstrated significantly (P < 0.05) higher expression levels of CLDN3 (26x), CLDN15 (29x), OCLN (4x), and TJP1/ZO-1 (5x) than in vitro HIOs. There was no significant difference in expression of these tight junction components between 4- and 8-week-old tHIOs. Immunofluorescent staining revealed the presence of claudin 3, claudin 15, occludin, and zonula occludens-1 in both in vitro HIOs and tHIOs; however, the morphology appeared more mature in tHIOs., Conclusions: In vitro HIOs have lower levels of tight junction mRNA, and tight junction proteins appear morphologically immature. Transplantation facilitates maturation of the HIOs and enhances select tight junction gene expression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/purpose: Intraluminal springs have recently been shown to lengthen segments of intestine in a process known as distraction enterogenesis. We hypothesized that biocompatible springs could be used to lengthen defunctionalized murine small intestine and would lead to identifiable intestinal adaptations at the molecular level., Methods: Age and weight matched C57BL/6 mice underwent surgical insertion of nitinol spring-loaded capsules into a Roux limb of jejunum. Segment lengths were measured at initial spring placement and at euthanasia after 14 and 21 days. Histology and gene expression of the Roux limb were evaluated at scarification and compared to untreated control segments., Results: Intestinal segments loaded with compressed springs lengthened an average of 240%, which was significantly longer than control segments loaded with either empty capsules or uncompressed springs. Muscularis thickening was greater in spring-treated mice compared to controls without springs. Crypt depth and Lgr5+ expression was greater in mice that received compressed spring treatments when compared to control groups., Conclusions: Insertion of a compressed nitinol spring into a Roux limb results in significant intestinal lengthening, smooth muscle thickening, and Lgr5+ expression in a mouse model. The ability to increase small bowel length in a defunctionalized murine model may be used to understand the mechanism of distraction enterogenesis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Short bowel syndrome (SBS) has traditionally been regarded as a rapidly fatal medical catastrophe. The advent of pharmacological options directly targeting disease pathophysiology justified this review., Areas Covered: Since the 1970s, home parenteral nutrition has reduced mortality, converting SBS into a chronic and disabling compensated and occasionally curable illness. Off-label antidiarrheal drugs and related products, though having minimal scientific evidence of efficacy, represent the standard-of-care and are here reviewed. Trophic intestinal hormones, including GLP-2 and its analogs, have great promise for alleviating malabsorption, the most important symptom within a nonsurgical, routine outpatient framework. Current indications involve adults with massive intestinal losses (fecal wet weight >1500 g/day). Surgical options such as intestinal lengthening or transplantation are also addressed although these options are considerably more aggressive and have stricter indications., Expert Opinion: GLP-2 analogs are the first candidates from a pioneering pharmacotherapic family within the SBS framework, namely disease-modifying, absorption-restoring agents. This family of drugs, potentially applicable in all contexts of severe intestinal loss, could become the therapeutic benchmark of the near future.

Based on the latest definition, short bowel syndrome is defined as intestinal failure due to the loss of significant small bowel length or function, when the homeostasis and growth can only be maintained with intravenous supplementation of fluid, electrolytes and macronutrients. The natural adaptation of the short bowel can only compensate for the loss up to a certain level. According to this, we differentiate (1) acute, (2) prolonged and (3) chronic types of intestinal failure/short bowel syndrome. The most common causes are necrotising enterocolits, intestinal malrotation and volvulus, gastroschisis and ileal atresia. The management of type 3 short bowel syndrome has evolved significantly during the last decades, due to the multidisciplinary approach, hence the survival and quality of life of the patients have improved and transplantation is rarely necessary. Our aim was to review the most important considerations of intestinal rehabilitation, like management of increased gastrin secretion, high output stoma, decreased transit time, central venous lines, enteral and parenteral nutrition and the enhancement of the natural adaptation. We reviewed the former and the latest options of the autologous intestinal reconstructive surgery (AIRS) like the reversed segment, small bowel interposition, ileocaecal valve replacement, bowel lengthening and tailoring (LILT, STEP and SILT), controlled bowel expansion and the latest results with distraction enterogenesis and tissue engineering. Orv Hetil. 2020; 161(7): 243-251.

Introduction : Short bowel syndrome represents the leading etiology that causes intestinal failure both in children and adults. Total parenteral nutrition support has dramatically improved the prognosis for these patients but, if related irreversible complications occur, the alternative is represented by surgery and/or transplantation. Areas covered : Autologous gastrointestinal reconstructive procedures are a feasible, alternative approach with good long-term outcome data inexperienced surgical centers. Expert opinion : Ongoing innovative efforts have driven the surgical options for successful autologous reconstructive surgery: bowel elongation/tapering techniques (LILT, STEP, and the new SILT) together with the 'reversed bowel segment' procedure are now recognized procedures and all must be tailored to the individual patient needs to obtain the optimal result in terms of enteral autonomy. Background laboratory experimentation with new procedures e.g. options for bowel dilation techniques and distraction-induced enterogenesis, may provide additional management and treatment modalities.

Purpose: To review the effectiveness of the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) operations in a cohort of patients with short bowel syndrome (SBS)., Methods: We conducted a retrospective analysis of children with SBS treated at our institution from 2004 until 2014. Children aged 0 days to 18 years with SBS who underwent autologous intestinal reconstruction were included in the study., Results: Twenty-two SBS patients underwent 31 different lengthening procedures (LP). Seventeen patients underwent their primary lengthening procedures at our institution: 9 (53%) patients underwent a LILT, 7 (41%) underwent a STEP and 1 (6%) had a simultaneous LILT and STEP procedure. 12/22 patients had a second STEP, two had a third STEP and one patient had an intestinal transplantation after the LP. Median intestinal length at the time of surgery was 25 cm (range 12-90 cm). There was no difference in gain of intestinal length after LILT vs. STEP (p = 0.74). Length of stay and initiation of feeds were similar. Serum albumin increased after autologous bowel lengthening (p < 0.001). 50% were weaned off parenteral nutrition (PN) (5/9 of the LILT, 1/7 of the STEP, 1/1 of the combined LILT/STEP). There were no surgical complications or deaths., Conclusion: In patients with SBS, LILT and STEP procedures are effective for autologous intestinal reconstruction and enable intestinal rehabilitation.

Background: There are no in vivo methods to measure adaptation in neonatal short bowel syndrome (SBS). We evaluated citrulline (Cit) levels in neonatal piglet surgical models of SBS., Methods: Piglets underwent 75% mid-intestinal resection with jejunoileal anastomosis (JI), 75% distal resection of ileum with jejunocolic anastomosis (JC) or sham surgery. Jugular and gastric catheters were inserted for parenteral and enteral nutrition. On D7, small intestine length and weight were measured, jejunum collected for histopathology and Cit level determined., Results: JI (n = 5) compared to JC (n = 5) had increased small intestinal length (JC - 17.5 cm; JI +22.0 cm; p = 0.02) and mass (JC 43.1 mg/cm/kg; JI 51.3 mg/cm/kg; p = 0.02), while Cit did not differ (JI 801.0 µM; JC 677.7 µM; p = 0.90). Including non-resected shams (n = 4), Cit correlated with length (R 2  = 0.48; p = 0.006), but not for SBS alone (R 2  = 0.11; p = 0.4), mass (R 2  = 0.05; p = 0.5). A second experiment compared change in Cit levels from baseline to D7. Levels declined in sham (n = 8) and JC (n = 10) (sham - 110.1 µM; JC - 56.6 µM; p = 0.17), regardless of intestinal lengthening (sham 29.9 cm; JC - 10.4 cm; p = 0.002)., Conclusion: Citrulline levels predict large differences in intestinal length and 'identify' SBS. However, citrulline cannot discriminate between adaptation in JI and JC, nor predict intestinal lengthening.

GVHD as a complication of SOT presents both a diagnostic and therapeutic challenge. Typically affecting the skin, gastrointestinal tract, and liver, GVHD occurs when donor lymphocytes engrafted in recipient tissues are activated by host antigen-presenting cells resulting in cytokine release and donor cell-mediated cytotoxicity to host tissue. Here, we describe a 5-year-old girl who developed fatal, refractory GVHD after isolated intestinal transplantation when recipient immune cells failed to repopulate the allograft in the setting of CMV viremia. Persistence of the donor immune cells in the allograft mucosa, rather than engraftment in the recipient bone marrow, likely perpetuated this refractory GVHD. Early diagnosis and intervention are critical to reduce morbidity and mortality. Thus, periodic monitoring of peripheral blood and allograft mucosal chimerism with sensitive detection methods may allow early detection and potentially curative enterectomy in similar cases of refractory GVHD., (© 2019 Wiley Periodicals, Inc.)

Introduction: Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved. Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results. Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.

Background: Short bowel syndrome is a debilitating condition with few effective treatments. Spring-mediated distraction enterogenesis can be used to lengthen intestine. The purpose of this study is to determine whether multiple springs in series can safely increase the total amount of lengthening., Methods: Juvenile mini-Yucatan pigs each received three nitinol springs placed within their jejunum. Plication was used to narrow the intestine around each spring to secure them. Compressed springs were used in the experimental group, while uncompressed springs were used in the control group. The intestine was examined 3 weeks later for lengthening and histologic changes., Results: All pigs tolerated diets postoperatively with continued weight gain, and no dilation or obstruction of the intestine was observed. Segments of intestine that contained compressed springs had a significant increase in length from 2.5 cm to 3.9 ± 0.2 cm per spring, compared to segments containing control springs that showed no change (p < 0.001)., Conclusions: Intestinal plication can be safely used to secure multiple springs in series to achieve intestinal lengthening without compromising intestinal function. Using several springs at once allows for a greater amount of total lengthening. This is a promising model that has potential in the treatment of short bowel syndrome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Intestinal transplantation (ITx) is a treatment for refractory intestinal failure (IF). However, the indications for and timing of ITx are still controversial because the course of IF is unknown. We performed a prospective multi-institutional cohort study to identify the prognostic factors for referral to an ITx facility. Patients under 18 years of age in Japan who suffered from IF and had received parenteral nutrition for longer than 6 months were enrolled in this study. They were followed up for 3 years. Seventy-two patients were followed. The mean age at the beginning of the study was 7.0 years. Diagnoses were short gut syndrome (n = 25), motility disorder (n = 45), and other (n = 2). The overall 3-year survival rate was 95%. The 3-year survival rate was 86% in patients with intestinal-failure-associated liver disease (IFALD) (n = 6) compared to 97% in those without IFALD (n = 66) (P = .0003). Furthermore, the 3-year survival rates of patients who did and did not meet the criteria for ITx were 82% (n = 11) and 97% (n = 62), respectively (P = .034). Six (44%) of 14 patients whose performance status (PS) was ≥3 at enrollment were dead or still had a PS ≥ 3 at 3 years. This study indicates that IFALD is a poor prognostic factor in pediatric patients with IF. Our indication for ITx, namely the presence of IFALD or loss of more than 2 parenteral nutrition access sites, seems to be applicable., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Transplantation of the intestine in children has presented significant challenges even as it has become a standard to treat nutritional failure due to short gut syndrome. These challenges have been addressed in part by significant improvements in short and long-term care. Noteworthy enhancements include reduced need for intestine transplantation, drug-sparing immunosuppressive regimens, immune monitoring, and improved surveillance and management of PTLD and non-adherence., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

The management of short bowel syndrome has mainly been focused on intestinal rehabilitation as part of multidisciplinary team approach in specialized centers. While some patients go through a process of bowel adaptation that allows them to reach enteral autonomy, others reach a plateau before this and require prolonged parenteral nutrition and/or intestinal transplantation. Various autologous intestinal reconstruction procedures centered on bowel tapering have been described to increase functional intestinal area and help gain enteral autonomy. This review discusses the surgical techniques, advantages, limitations, and general outcomes of each procedure., (Copyright © 2018. Published by Elsevier Inc.)

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.)

Introduction:  Short bowel syndrome (SBS) is the main cause of intestinal failure (IF) in the pediatric population. To promote the standardization of care of these patients, the registry of Pediatric Intestinal Rehabilitation and Transplantation (PIRAT) has been established. The aim of this study is to describe patients with IF using PIRAT database., Materials and Methods:  Data from two tertiary care European referral Centers registered in PIRAT (https://www.studeon.eu/pirat) were analyzed (1994-2015). Neonatal SBS-related IF was defined as need for parenteral nutrition (PN) to sustain life and growth for more than 75 days, after extensive bowel resection during neonatal period. Data included patient demographics, disease at birth, residual small intestine, and intestinal autonomy (PN on/off)., Results:  In this study, 114 children with SBS-related IF were identified (male 60%). Median gestational age was 35.3 weeks (interquartile range [IQR]: 33.0-38.0); median birth weight was 2,440 g (IQR: 1,700-2,990). The main causes of SBS were intestinal atresia in 31 (27%), midgut volvulus in 29 (25%), necrotizing enterocolitis in 23 (20%), and gastroschisis in 12 (11%). Nine (7.9%) patients died on PN (six sepsis, two IF-associated liver disease, and one multiorgan failure). Median residual small bowel length was 46 cm (IQR: 13.0-92.5). Ileocecal valve was resected in 48 patients (42%). Intestinal autonomy was achieved in 68% patients., Conclusion:  We present the web-based registry PIRAT and the first results of patients with IF registered from two European Centers. PIRAT could give the opportunity to create a dedicated international network (IF-net) to standardize, improve, and spread the therapeutic paths for the rare and heterogeneous condition of SBS-related IF., Competing Interests: Conflict of Interest: None., (Georg Thieme Verlag KG Stuttgart · New York.)

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.)

Aim of the Study: To report the current activity of intestinal transplantation in Europe (EU) and Unites States of America (USA), underlining outcomes in the last 5 years and discussing possible trends., Patients and Methods: Data review of results was performed through analysis of ITR and UNOS registries, Eurotransplant and newsletter transplant reports, congress abstracts, international published literature, personal communications and hospital web sites., Results: The absence in Europe of a sole organization collecting donors and the presence of many low-volume centers (less than 5 cases/year) makes the difference with USA: in the last 5 years (2010-2014), 222 intestinal/multivisceral transplants have been performed in EU countries (most of them in the UK), while in USA, the number of transplants achieved 634 procedures in the same period of time. Waiting list mortality remains unacceptable in both continents. Improved short-term results, with over 80% survival at 1 year, have been achieved in the busiest transplant centers likely due to immune-induction agents, more recently to innovative cross match strategies and optimizing organ allocation, but long term outcomes are still inferior to other organ transplants. Most long-term survivors were reintegrated to society with self-sustained socioeconomic status. The economic burden for the society is high and related costs are different between USA and EU (and inside Europe between member state's health-care systems), but cost-effectiveness for intestinal transplantation still needs to be proved., Conclusion: Overall intestinal transplantation continues to develop in EU and USA together with surgical and medical rehabilitation of patients affected by short gut syndrome., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome-editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease-causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large-animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans. Stem Cells Translational Medicine 2017;6:666-676., (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Abdominal wall transplantation (AWTX) has revolutionized difficult abdominal closure after intestinal transplantation (ITX). More important, the skin of the transplanted abdominal wall (AW) may serve as an immunological tool for differential diagnosis of bowel dysfunction after transplant. Between August 2008 and October 2014, 29 small bowel transplantations were performed in 28 patients (16 male, 12 female; aged 41 ± 13 years). Two groups were identified: the solid organ transplant (SOT) group (n = 15; 12 ITX and 3 modified multivisceral transplantation [MMVTX]) and the SOT-AWTX group (n = 14; 12 ITX and 2 MMVTX), with the latter including one ITX-AWTX retransplantation. Two doses of alemtuzumab were used for induction (30 mg, 6 and 24 h after reperfusion), and tacrolimus (trough levels 8-12 ng/mL) was used for maintenance immunosuppression. Patient survival was similar in both groups (67% vs. 61%); however, the SOT-AWTX group showed faster posttransplant recovery, better intestinal graft survival (79% vs. 60%), a lower intestinal rejection rate (7% vs. 27%) and a lower rate of misdiagnoses in which viral infection was mistaken and treated as rejection (14% vs. 33%). The skin component of the AW may serve as an immune modulator and sentinel marker for immunological activity in the host. This can be a vital tool for timely prevention of intestinal graft rejection and, more important, avoidance of overimmunosuppression in cases of bowel dysfunction not related to graft rejection., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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.

Background: A joint adult and pediatric intestinal transplant (ITx) program for Australia was developed in 2009 to provide life-saving ITx to patients with irreversible intestinal failure (IF). We aimed to analyze the outcomes of patients treated by our service over the past 5 years., Methods: A retrospective medical record review was conducted on all IF patients referred to our service. Patient demographics, underlying disease, nutrition support, TPN complications, and current transplant program status were evaluated., Results: Fifty-seven patients (35 adults, 40.4 ± 12.4 years; 22 children, 6.3 ± 4.3 years) throughout Australia and New Zealand have been referred. Leading causes of IF were short bowel syndrome followed by pseudo-obstruction. Forty patients (70%) exhibited at least 1 life-threatening complication of PN at referral: liver failure, impending loss of venous access, and/or recurrent line sepsis. Three patients have undergone ITx with 100% survival (median follow-up, 1161 days). Four patients (8%) are listed for transplant, 6 patients (12%) are awaiting transplant assessment, and 4 patients (8%) have died (2 while awaiting transplantation, 2 during assessment period). Causes of death included sepsis and intracranial bleed. Two-thirds of all referred patients (n = 40) were deferred or rejected from wait-listing., Conclusions: After 5 years of establishing the first dedicated ITx program in Australia and New Zealand, early results indicate that ITx is an available and life-saving option for IF patients in these countries. Current barriers to ITx in Australia include a shortage of appropriate donors and a high rate of donor-specific antibodies among potential recipients. Growing awareness of the service and early referral to assist appropriate patient selection will aid in the program's success., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Background: Intestinal failure (IF) patients received parenteral nutrition (PN) as the only available therapy until intestinal transplantation (ITx) evolved as an accepted treatment. The aim of this article is to report the long-term outcomes of a series of ITx performed in pediatric and adult patients at a single center 9 years after its creation., Patients and Methods: This is a retrospective analysis of the ITx performed between May 2006 and January 2015. Diagnoses, pre-ITx mean time on PN, indications for ITx, time on the waiting list for types of ITx, mean total ischemia time, and warm ischemia time, time until PN discontinuation, incidence of acute and chronic rejection, and 5-year actuarial patient survival are reported., Results: A total of 42 patients received ITx; 80% had short gut syndrome (SG); the mean time on PN was 1620 days. The main indication for ITx was lack of central venous access followed by intestinal failure-associated liver disease (IFALD) and catheter-related infectious complications. The mean time on the waiting list was 188 days (standard deviation, ±183 days). ITx were performed in 26 children and 14 adults. In all, 32 procedures were isolated ITx (IITX); 10 were multiorgan Tx (MOT; 3 combined, 7 multivisceral Tx (MVTx), 1 modified MVTx and 2 with kidney); 2 (4.7 %) were retransplantations: 1 IITx, 1 MVTx, and 5 including the right colon. Thirteen patients (31%) received abdominal rectus fascia. All procedures were performed by the same surgical team. Total ischemia time was 7:53 ± 2:04 hours, and warm ischemia time was 40.2 ± 10.5 minutes. The mean length of implanted intestine was 325 ± 63 cm. Bishop-Koop ileostomy was performed in 67% of cases. In all, 16 of 42 Tx required early reoperations. The overall mean follow-up time was 41 ± 35.6 months. The mean time to PN discontinuation after Tx was 68 days (P = .001). The total number of acute cellular rejection (ACR) episodes until the last follow-up was 83; the total number of grafts lost due to ACR was 4; and the total graft lost due to chronic rejection was 3. At the time of writing, the overall 5-year patient survival is 55% (65% for IITx vs 22% for MOT; P = .0001); 60% for pediatric recipients vs 47% for adults (P = NS); 64% when the indication for ITx was SG vs 25% for non-SG (P = .002)., Conclusions: At this center, candidates with SG, in the absence of IFALD requiring IITx, showed the best long-term outcomes, independent of recipient age. A multidisciplinary approach is mandatory for the care of intestinal failure patients, to sustain a rehabilitation and transplantation program over time., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The spiral intestinal lengthening and tailoring (SILT) procedure is a new surgical technique for autologous intestinal reconstruction in patients with short bowel syndrome. The aim of this work is to present a first description of a modified SILT technique by which the mucosal layer is left intact to possibly reduce the severe postoperative complications of intestinal leakage and abdominal abscess formation., Materials and Methods: The modified SILT technique was performed on a 10-cm-long intestinal segment in 2 pigs to determine the technical feasibility. Thereafter, the short-term clinical feasibility was monitored clinically in 2 dogs by gastrointestinal X-ray series at postoperative day 4 and by relaparotomy postoperative day 10., Results: It was technically feasible to lengthen the intestinal segment from 10 cm to 20 cm and tailoring it from 3 cm to 1.7 cm in diameter, while leaving the intestinal mucosal layer intact. The postoperative course was uneventful for both dogs. The gastrointestinal X-ray series showed an inconspicuous intestinal transit time without any signs of stricture, perforation, or leakage. In the relaparotomy, the initially achieved lengthening and tailoring extents were preserved and the operated intestinal segment was well perfused with no early signs of necrosis, stenosis, or leakage., Conclusions: Leaving the mucosal layer intact during SILT is technically and clinically feasible in the short term in a large animal model. Further studies are needed to fully assess the impact of this technical modification on the long-term outcome of larger series., (© The Author(s) 2015.)

Background: When total parenteral nutrition (TPN) is not an option, intestinal transplantation is the sole treatment for patients with end-stage intestinal failure to increase the chance of long-term survival. However, in 20-33% of patients, abdominal wall-related complications occur after isolated intestinal transplantation., Case Description: The patient is a 24-year-old woman with ultra-short bowel syndrome, caused by a severely complicated history of Crohn's disease. After 5 years of TPN, the patient was referred for intestinal transplantation. In addition, an abdominal wall transplant was required due to an abdominal wall defect, extensive scarring of the abdominal wall and lack of free space within the abdomen. Therefore, a combined intestinal and abdominal wall transplantation was performed. Six months after transplantation the patient has a sufficient abdominal wall, a normal body mass index and no longer requires any feeding lines., Conclusion: This case report describes the first combined intestinal and abdominal wall transplantation in the Netherlands and in the Eurotransplant region in a patient with end-stage intestinal failure and loss of abdominal domain.

Background & Aims: Chronic intestinal failure (CIF) requires long term parenteral nutrition (PN) and, in some patients, intestinal transplantation (ITx). Indications and timing for ITx remain poorly defined. In the present study we aimed to analyze causes and outcome of children with CIF., Methods: 118 consecutive patients referred to our institution were assessed by a multidisciplinary team and four different categories were defined retrospectively based on their clinical course: Group 1: patients with reversible intestinal failure; group 2: patients unsuitable for ITx, group 3: patients listed for ITx; group 4: patients stable under PN. Analysis involved comparison between groups for nutritional status, central venous catheter (CVC) related complications, liver disease, and outcome after transplantation by using non parametric tests, Mann-Whitney tests, Kruskal-Wallis, Wilcoxon signed rank tests and chi square distribution for percentage., Results: 118 children (72 boys) with a median age of 15 months at referral (2 months-16 years) were assessed. Etiology of IF was short bowel syndrome [n = 47], intractable diarrhea of infancy [n = 37], total intestinal aganglionosis [n = 18], and chronic intestinal pseudoobstruction [n = 17]. Most patients (89.8%) were totally PN dependent, with 48 children (40.7%) on home-PN prior to admission. Nutritional status was poor with a median body weight at -1.5 z-score (ranges: -5 to +2.5) and median length at -2.0 z-score (ranges: -5.5 to +2.3). The mean number of CVC inserted per patient was 5.2 (range 1-20) and the mean number of CRS per patient was 5.5 (median: 5; range 0-12) Fifty-five patients (46.6%) had thrombosis of ≥2 main venous axis. At admission 34.7% of patients had elevated bilirubin (≥50 μmol/l), and 19.5% had platelets <100,000/ml, and 15% had both. Liver biopsy performed in 79 children was normal (n = 4), or showed F1 or F2 fibrosis (n = 29), bridging fibrosis F3 (n = 20), or cirrhosis (n = 26). Group 1 included 10 children finally weaned from PN (7-years survival: 100%). Group 2 included 12 children with severe liver disease and associated disorders unsuitable for transplantation (7-years survival: 16.6%). Group 3 included 66 patients (56%) who were listed for small bowel or liver-small bowel transplantation, 62/66 have been transplanted (7 years survival: 74.6%). Factors influencing outcome after liver-ITx were body weight (p < .004), length (p < .001), pre-Tx bilirubin plasma level (p < .001) and thrombosis (p < .01) for isolated ITx, Group 4 included 30 children (25.4%) with irreversible IF considered as potential candidates for isolated ITx. Four children were lost from follow up and 3 died within 2 years (survival 88.5%). Among potential candidates, the following parameters improved significantly during the first 12 months of follow up: Body weight (p.0001), length (p < .0001) and bilirubin (p < .0001)., Conclusions: many patients had a poor nutritional status with severe complications especially liver disease. PN related complications were the most relevant indication for ITx, but also a negative predictor for outcome. Early patient referral for Tx-assessment might help to identify and separate children with irreversible IF from children with transient IF or uncomplicated long-term PN, allowing to adapt a patient-based treatment strategy including or not ITx., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Treatment of short bowel syndrome (SBS) remains difficult, entailing severe morbidity and mortality. Accepted surgical treatment modalities for SBS are the Bianchi intestinal lengthening procedure and reversed-segment procedure. We seek to investigate the short-term effects regarding growth, nutrition, and microscopic and functional adaptation after the intestinal lengthening and RS procedures in a piglet SBS-model., Material and Methods: Twenty-four piglets (Sus scrofa, ±30 kg) were divided into four groups (n = 6 each) as follows: sham, SBS, Bianchi lengthening procedure (BIA), and reversed-segment (RS). At day one either sham laparotomy (sham) or 75% small bowel resection (SBS, BIA, and RS) was performed. After 2 wk sham laparotomy (sham and SBS), BIA, or RS procedure was performed. After 8 wk all animals were terminated. During the experimental time course, the following parameters were assessed: body weight, intestinal length, diameter, and weight, fat absorption, and biochemical parameters from serum and urine. Citrulline was used as a marker of absorptive enteral mass to demonstrate massive functional bowel loss. Intestinal biopsies were obtained for histologic analysis and electrophysiological measurements to analyze glucose absorptive capacity., Results: Eight weeks after bowel resection, piglet growth was reduced in SBS, BIA, and RS piglets as demonstrated by reduced weight (51 ± 4 kg, 47 ± 2 kg, and 53 ± 1 kg, respectively) compared with sham (69 ± 3 kg; P < 0.01), with no demonstrable difference between SBS and treatment groups. Malabsorption and malnutrition occurred in SBS, BIA, and RS piglets reflected by increased fecal fat loss per 24 h (35 ± 4%, 30 ± 2%, and 32 ± 4%, respectively versus 18 ± 1% in sham; P < 0.01) and reduced serum albumin levels (24 ± 1 g/L, 22 ± 1 g/L, and 24 ± 1 g/L, respectively versus sham 33 ± 1 g/L; P < 0.01), but there was no significant difference between SBS and treatment groups. Serum citrulline levels reflected massive functional bowel loss (SBS 36 ± 7 μmol/L, BIA 23 ± 1 μmol/L, and RS 24 ± 2 μmol/L) compared with sham (64 ± 5 μmol/L; P < 0.01). Electrophysiological measurements demonstrated reduced glucose absorption after intestinal resection, which did not return to base levels within the experimental time course. However, the intestine of BIA and RS piglets adapted more profoundly than SBS piglets, as reflected by a greater crypt depth (490 ± 25 μm and 492 ± 21 μm versus 388 ± 20 μm; P < 0.01); and BIA piglets showed greater villus length (884 ± 58 μm) than RS or SBS piglets (715 ± 30 μm and 737 ± 64 μm, respectively; P < 0.01) after 8 wk., Conclusions: Despite increased histologic intestinal adaptation, neither intestinal lengthening nor RS procedure demonstrated significantly improved absorption, nutrition, or weight gain for the treatment of SBS during the study period. Reduced glucose uptake on electrophysiology measurements and persistent low levels of citrulline may indicate reduced small bowel enterocyte functioning during the initial phase of intestinal adaptation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the 1990s, the introduction of visceral transplantation fuelled interest in other innovative therapeutic modalities for gut rehabilitation. Ethanol lock and omega-3 lipid formulations were introduced to reduce the risks associated with total parenteral nutrition (TPN). Autologous surgical reconstruction and bowel lengthening have been increasingly utilized for patients with complex abdominal pathology and short-bowel syndrome. Glucagon-like peptide 2 analogue, along with growth hormone, are available to enhance gut adaptation and achieve nutritional autonomy. Intestinal transplantation continues to be limited to a rescue therapy for patients with TPN failure. Nonetheless, survival outcomes have substantially improved with advances in surgical techniques, immunosuppressive strategies and postoperative management. Furthermore, both nutritional autonomy and quality of life can be restored for more than two decades in most survivors, with social support and inclusion of the liver being favourable predictors of long-term outcome. One of the current challenges is the discovery of biomarkers to diagnose early rejection and further improve liver-free allograft survival. Currently, chronic rejection with persistence of preformed and development of de novo donor-specific antibodies is a major barrier to long-term graft function; this issue might be overcome with innovative immunological and tolerogenic strategies. This Review discusses advances in the field of gut rehabilitation, including intestinal transplantation, and highlights future challenges. With the growing interest in individualized medicine and the value of health care, a novel management algorithm is proposed to optimize patient care through an integrated multidisciplinary team approach.

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

Purpose: We sought to test a novel, extraluminal method of intestinal lengthening that precludes violation of the intestinal wall., Methods: Sprague-Dawley rats (n=45) with size-matched bowel segments isolated by Roux-en-Y reconstruction were divided into three groups. Group 1 (n=14) had no further manipulations. In Groups 2 (n=12) and 3 (n=19), the isolated segment was wrapped around a length-matched device in a helicoidal fashion. In Group 2, the device consisted of plain polyurethane tubing. In Group 3, it consisted of a gradually expanding hygroscopic hydrogel (12.5mm final diameter). Euthanasia was performed at 8-21 days. Statistical analysis was by two-way ANOVA (P<0.05)., Results: Overall survival was 87% (39/45). There was a statistically significant increase in bowel length in Group 3 compared to the other two groups (P<0.001). This increase correlated with the number of helicoidal coils (P=0.018), but not with post-operative time (P>0.50). There were no significant differences in total DNA/protein ratio across the groups (P=0.65). Histologically, there was an apparent increase in the goblet cell density in Group 3., Conclusions: Measured extraluminal helicoidal stretch (Helixtretch) is tolerated by the intestine. Helixtretch induces bowel lengthening in a rodent model. Further analysis of this novel, minimally invasive alternative for intestinal augmentation is warranted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Kidney function usually deteriorates after intestinal transplant, with prevalence of renal failure almost 20% after 5 years. We report our results on adults from single institution over >10 years., Methods: Forty-six patients were transplanted with 22 survivors; we divided them in 2 groups: Group 1, recipients with creatinine>1.2 mg/dL (normal, 0.50-1.2) and Group 2, normal creatinine. Group 1 included 12 patients (9 males) with a mean age of 42.8 years; all lived at home, with normal creatinine at transplant (apart from 1 patient with a creatinine of 1.6 mg/dL), and were mainly transplanted for short bowel syndrome. One underwent retransplantation. Immunosuppression was based on alemtuzumab (8 recipients) plus tacrolimus (FK). Group 2 included 10 patients (6 males) with a mean age of 34.7 years; all lived at home, had normal creatinine at transplantation, and were mainly transplanted for short bowel syndrome. Immunosuppression was mainly based on alemtuzumab (8 recipients) plus FK., Results: There were no relevant differences between the 2 groups regarding number of recipients, sex, baseline creatinine at transplant, reason for transplantation, retransplantation, immunosuppression, antifungal or antiviral therapy, hospitalization, total parenteral nutrition (or fluids), or stoma. The only relevant difference was age (P=.04); patients with deteriorated kidney function or altered creatinine were found to be older., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Intestinal transplantation is a well-accepted treatment for SBS. However, patients with SBS often have decreased abdominal capacity, which makes size-matching of donor organs more difficult, thus decreasing organ availability. Reported approaches for addressing this problem include surgically reducing the graft size, leaving an open abdomen for a prolonged period, and cotransplanting rectus fascia as a non-vascularized allograft. Each approach has significant disadvantages. There has been one previous report of tissue expanders used intra-abdominally and two reports of subcutaneous use to increase intra-abdominal capacity prior to transplantation. We report the first use of bi-planar expander placement for this purpose. In our case, a two-yr-old male child with SBS due to malrotation was treated with tissue expanders 10 months prior to intestinal transplantation, thus allowing transplantation of a larger graft with the ability to close the abdomen safely. There were no complications, and the patient is now doing well and tolerating diet off PN. The use of tissue expanders prior to intestinal transplantation is a promising approach for such patients and avoids the morbidity associated with other approaches. This approach requires a multidisciplinary effort by gastroenterology, transplant surgery, and plastic surgery teams., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Advances in the medical and surgical treatments of intestinal failure have led to a decrease in the number of transplants over the past decade. In 2012, 152 candidates were added to the intestinal transplant waiting list, a new low. Of these, 64 were listed for intestine-liver transplant and 88 for intestinal transplant alone or with an organ other than liver. Historically, the most common organ transplanted with the intestine was the liver; this practice decreased substantially from a peak of 52.9% in 2007 to 30.0% in 2012. Short-gut syndrome, which encompasses a large group of diagnoses, is the most common etiology of intestinal failure. The pretransplant mortality rate decreased dramatically over time for all age groups, from 51.0 per 100 wait-list years in 1998-1999 to 6.7 for patients listed in 2010-2012. Numbers of intestinal and intestine-liver transplants steadily decreased from 198 in 2007 to 106 in 2012. By age, intestinal transplant recipients have changed substantially; the number of adult recipients now approximately equals the number of pediatric recipients. Graft survival has improved over the past decade. Graft failure in the first 90 days after transplant occurred in 15.7% of 2011-2012 intestinal transplant recipients, compared with 21% in 2001-2002., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Intestinal transplantation is gaining worldwide acceptance as the main option for patients with irreversible intestinal failure and complicated total parenteral nutrition course. In adults, the main cause is still represented by short bowel syndrome, but tumors (Gardner syndrome) and dismotility disorders (chronic intestinal pseudo-obstruction [CIPO]) have been treated increasingly by this kind of transplantation procedure. We reviewed our series from the disease point of view: although SBS confirmed results achieved in previous years, CIPO is nowadays demonstrating an excellent outcome similar to other transplantation series. Our results showed indeed that recipients affected by Gardner syndrome must be carefully selected before the disease is to advanced to take advantage of the transplantation procedure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

As of September 19, 2014, 2441 cases of intestinal transplantation have been performed in 46 centers (2400 deceased, 41 living). Eight centers did more than 100 transplants. Annual case numbers peaked in 2007 (N = 198) and steadily decreased to 109 cases in 2013. Short gut syndrome (68%) and functional bowel problems (15%) are two major indications for intestinal transplantation. The 3 major types of transplants involving the intestine include: isolated intestine transplant (I); simultaneous intestine, liver, and pancreas transplant (I+L+P); and, combined intestine and liver (I+L) transplant. Graft survival has significantly improved in recent years, mainly due to improved first year graft survival. The 1-, 5-, and 10-year graft survivals were: 74%, 42%,and 26%, respectively (I); 70%, 50%, and 40%, respectively (I+L+P); and 61%, 46%, and 40%, respectively (I+L). The longest graft survivals for I, l+L+P, and l+L were 19 years, 16 years, and 23 years, respectively. Steroids, Thymoglobulin, and rituximab are 3 major induction agents used in recent years. Prograf, steroids, and Cellcept are 3 major maintenance agents. Induction recipients (68% of all patients) had a significantly lower acute rejection rate than nonrecipients before discharge (60% versus 75%, p < 0.001). Most of the patients received 2 (53%) or 3 (25%) maintenance immunosuppressants. Acute rejection episodes were usually treated with one (60%) or two agents (27%). Steroids were most commonly used (50-60%). OKT3 has been replaced with antithymocyte globulin (since 1999) and rituximab (since 2006). During 1990-2000, 94% (N = 445) of patients received ABO identical intestinal transplants, while 6% (N = 29) received ABO compatible transplants. ABO identical transplant recipients had a significantly higher 5-year graft survival rate than ABO compatible recipients (39% versus 21%, p < 0.0001). In recent years (2001- 2012), more patients received ABO compatible (N = 188, 11%) than in the early decade (p < 0.01). 5-year graft survival rates of ABO compatible transplants were lower than those of ABO identical transplants. However, the difference did not reach statistical significance (46% versus 49%, p = 0.07). The effect of ABO compatibility on graft outcome was further confirmed by Cox Analysis. ABO incompatible transplants are still rarely performed (N = 4) in intestine. In conclusion, annual case numbers of intestinal transplants have been decreasing, regardless of improved graft survival. ABO compatible intestinal transplants previously had a significantly lower graft survival rate than ABO identical transplants. However, the graft survival difference became less significant in recent years, possibly due to, or at least partly due to the use of new immunosuppressive agents.

Intestinal transplantation has continued to evolve over the past decade. Fewer patients have received intestine transplants in the past 5 years, perhaps due to efforts in intestine rehabilitation. Despite improvement in earlier outcomes, long-term survival has remained steady over the past decade. This is potentially due to the complications of immunosuppression, as well as inherent poor graft half-life due to chronic rejection. Improvements in outcome will require multidisciplinary efforts to understand the long-term mechanisms of intestine graft acceptance and to properly optimize and individualize immunosuppression for the transplant recipient.

Liver and small bowel transplant is an established treatment for infants with IFALD. Despite organ reduction techniques, mortality on the waiting list remains high due to shortage of size-matched pediatric donors. Small abdominal cavity volume due to previous intestinal resection poses a significant challenge to achieve abdominal closure post-transplant. Seven children underwent tissue expansion of abdominal skin prior to multiorgan transplant. In total, 17 tissue expanders were placed subcutaneously in seven children. All seven subjects underwent re-exploration to deal with complications: hematoma, extrusion, infection, or port related. Three expanders had to be removed. Four children went on to have successful combined liver and small bowel transplant. Two children died on the waiting list of causes not related to the expander and one child died from sepsis attributed to an infected expander. Tissue expansion can generate skin to facilitate closure of abdomen post-transplant, thus allowing infants with small abdominal volumes to be considered for transplant surgery. Tissue expansion in children with end-stage liver disease and portal hypertension is associated with a very high complication rate and needs to be closely monitored during the expansion process., (© 2013 John Wiley & Sons A/S.)

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.

Background: It has been thirty years since Bianchi introduced the technique that made intestinal lengthening possible. The last three decades have seen lengthening procedures established as vital components of intestinal rehabilitation programs. The goal of the present study was to use a systematic literature review to determine patient outcomes for the two most commonly used lengthening procedures, the Bianchi procedure and the serial transverse enteroplasty procedure (STEP)., Methods: Pubmed and Embase were searched using the terms "intestinal lengthening" and "bowel lengthening." Patient outcomes were extracted from each relevant journal article on the basis of a set proforma. The results were combined to create overall mean outcomes. Mean outcomes were also calculated separately for the Bianchi procedure and STEP. Significance was tested with the independent t-test., Results: Overall survival for the last thirty years is 83%. However, survival for the last fifteen years has been 89%, with no significant difference between the two procedures. The Bianchi procedure has a higher rate of weaning patients who were static on parenteral nutrition with conservative measures: 55% versus 48%. In addition, the Bianchi procedure was associated with a higher rate of patients receiving transplants: 10% versus 6%. The STEP has a higher rate of complication. Length of follow-up is significantly longer for the Bianchi procedure: 76 versus 22 months. The impact that this differential could have had on our results must be considered., Conclusions: Outcomes for intestinal lengthening procedures are very good, and increasingly so. However, further analysis is required in order to fully understand the relative strengths and weaknesses of each procedure.