Outcomes of a novel pediatric intestinal rehabilitation program for children with short bowel syndrome: a retrospective cohort study

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M. Cantagalli, Di Mitri, Sofia Chioccioli, Riccardo Coletta, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8279026/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: Pediatric short bowel syndrome (SBS) is a severe cause of intestinal failure, often requiring prolonged parenteral nutrition (PN) and exposing children to sepsis and intestinal failure–associated liver disease (IFALD). In 2018, our institution established a multidisciplinary Pediatric Intestinal Rehabilitation Program (IRP) to optimize medical, nutritional, and surgical care. Methods: We performed a retrospective cohort study of children with anatomic SBS managed within our IRP (Meyer Children’s Hospital, Florence) between 2018 and 2024. SBS was defined as PN dependence for > 60 consecutive days. Data included demographics, SBS etiology and anatomy, major interventions (including autologous bowel lengthening: SILT/LILT/STEP), central line infections, IFALD, survival, enteral autonomy (complete PN discontinuation with adequate growth), and PN volume trends. Results: Forty-nine patients met inclusion criteria; 21 underwent bowel lengthening at our center. In this surgical subgroup, survival was 100% at last follow-up and no patient required intestinal transplantation. Seven of 21 children (33.3%) achieved enteral autonomy during follow-up. PN requirements decreased over time across techniques, with an overall PN volume reduction of 42.3% at 48 months (p < 0.05). SILT and LILT were associated with significant post-operative increases in bowel length and decreases in bowel diameter, whereas STEP showed non-significant length gains. Conclusions: Early outcomes from a newly established IRP show excellent survival, meaningful PN reduction, and no need for transplant in a high-risk pediatric SBS population, supporting the effectiveness and scalability of structured multidisciplinary intestinal rehabilitation. Figures Figure 1 Introduction Short bowel syndrome (SBS) in children represents a severe form of intestinal failure, defined by an inadequate absorptive surface of the remaining intestine to sustain hydration and nutrition, most commonly following extensive bowel resection during infancy. Without specialized care, SBS can be life-threatening or lead to profound malnutrition, as affected patients depend on parenteral nutrition (PN) for survival and growth.​ ( 1 ) Over the past two decades, outcomes for SBS have improved significantly with the introduction of dedicated intestinal rehabilitation programs (IRPs) that integrate medical, nutritional, and surgical management​. ( 2 ) IRPs bring together pediatric surgeons, gastroenterologists, dietitians, nurses, and other specialists to deliver individualized treatment plans aimed to achieve enteral autonomy (independence from PN) and reduce the incidence of life-threatening complications such as sepsis and liver failure​. ( 3 , 4 ) Before the widespread adoption of multidisciplinary care, the prognosis for pediatric SBS was poor, with survival rates of approximately 70% and a high incidence of PN-associated liver disease leading to transplant or death​. ( 5 ) Over time, innovations including novel intravenous lipid emulsions rich in omega-3 fatty acids to prevent intestinal failure–associated liver disease (IFALD), autologous bowel lengthening procedures, and enterotrophic agents such as glucagon-like peptide-2 (GLP-2) analogues (e.g., teduglutide) have markedly improved patient outcomes​. ( 6 , 7 ) These advances have ushered in a “new era” in which intestinal failure in children can often be managed without resorting to intestinal transplantation, which was historically the only option for long-term survival in the most severe cases. In 2018, our institution launched a Novel Paediatric Intestinal Rehabilitation Program with the aim of consolidating and optimizing the care of SBS patients. This report presents the outcomes from the initial years of the program, evaluating survival, achievement of enteral autonomy, and complication rates, and comparing them with published data. We also discuss key insights, including factors influencing success (such as residual bowel length and SBS etiology) and the integration of emerging therapies. We hypothesize that our comprehensive IRP approach improves clinical outcomes for children with short bowel syndrome, reflecting the global trend of better prognosis in this patient population. By sharing our experience, we aim to contribute to the expanding body of evidence supporting multidisciplinary intestinal rehabilitation and to guide further improvements in the care of pediatric SBS. Methods Study Design and Patient Population We conducted a retrospective cohort study including all pediatric patients with SBS managed within Intestinal Rehabilitation Program between 2018 and 2024 at Meyer Children’s Hospital in Florence, a tertiary pediatric referral center. The inclusion criteria were the diagnosis of SBS defined as dependence on PN for more than 60 consecutive days of PN due to intestinal insufficiency. We excluded patients with intestinal failure primarily from motility or mucosal disorders as the study focused on anatomic short bowel syndrome; patients lost to follow-up were also excluded. Intestinal Rehabilitation Program Interventions Our IRP applies a standardized multidisciplinary approach to maximize intestinal adaptation and nutrition management in SBS. Each patient was jointly managed by a pediatric surgeon and a pediatric gastroenterologist as co-directors of care, along with a nutritionist, stoma/wound care nurse, pharmacist, and social worker. Data Collection Patient data were extracted from medical records and managed using REDCap electronic data capture tools hosted at Meyer Children Hospital ( 8 ). We recorded demographic data (age, sex), primary SBS etiology (e.g., NEC, gastroschisis, intestinal atresia, midgut volvulus, etc.), and anatomical data (length of residual small intestine and presence of ileocecal valve and colon). We noted all major interventions: surgical procedures, start, quantity, type and duration of PN and any episodes of sepsis (defined as positive blood culture with systemic infection requiring treatment). The primary outcomes were overall survival and achievement enteral autonomy. Enteral autonomy was defined as complete discontinuation of parenteral nutrition while maintaining of normal growth supported exclusively by enteral or oral nutrition. The time from IRP enrollment to achievement of enteral autonomy was also recorded, when applicable. Secondary outcomes included the incidence of IFALD (cholestasis or liver dysfunction attributed to PN), the numbers of central line-associated bloodstream infections, and the need for intestinal transplantation. For patients who died, the cause of death was recorded. The literature describes three types of Short Bowel Syndrome based on the anatomy of the remaining portion of the intestine, which plays a crucial role in determining the severity and type of malabsorption observed in patients. ( 9 , 10 ) Patients with jejunostomy are those in whom the jejunum, ileum, and colon have been removed. The malabsorption status of these patients often does not improve over time due to the limited capacity for spontaneous intestinal adaptation. ( 9 , 10 ) Patients with jejuno-ileal anastomosis may have undergone jejunal resection and have > 10 cm of the remaining terminal ileum and colon. These patients are relatively few, and they typically do not experience significant clinical problems because, having a residual portion of the ileum, they undergo both structural and functional adaptation. ( 9 ) Patients who have undergone jejuno-colostomy are those in whom the ileum has been removed, often along with the ileocecal valve, and they have a jejuno-jejunocolic anastomosis. These patients have < 10 cm of terminal ileum and are often malnourished, but if the disease is well treated, their conditions may improve with intestinal adaptation. Statistical Analysis Data analysis was primarily descriptive given the sample size. Continuous variables are presented as median with interquartile range (IQR) and categorical variables as counts (percentage). The Kaplan–Meier method was used to estimate survival and freedom from PN (enteral autonomy) over time, with follow-up censored at last contact for those still on PN or alive. We performed subgroup observations to explore factors associated with enteral autonomy: for example, comparing outcomes by SBS etiology (NEC vs non-NEC) and by residual bowel length above or below the median. Due to the limited sample, formal hypothesis testing was only applied to select comparisons; a log-rank test was used for Kaplan–Meier curve comparisons, considering p < 0.05 as significant. Results Patient Characteristics Forty-nine patients met inclusion criteria, with baseline characteristics detailed in Table 1 . In summary, 26 (53% of the total) were male and 23 (47%) females demonstrating a substantial gender balance. The mean gestational age is just over 33 gestational weeks, with an average birth weight of 2,00 Kg. Anthropological analysis of the sample has shown a prevalence of individuals of white race (40 out of a total of 49 patients analyzed), as well as a majority of Hispanic, Latino, or Spanish origin patients (31 in total). The prevalent primary diagnosis of Intestinal Failure is intestinal volvulus, with a total of 16 patients diagnosed (31.4% of the database). Following this, necrotizing enterocolitis is identified in 11 analyzed patients. Notably, Intestinal Atresia assumes significant importance as a primary diagnosis of Intestinal Failure, with a total of 7 patients affected by this congenital condition. Within this subgroup of 7 patients, 1 case involved duodenal atresia, 3 cases of jejunal atresia, and an additional 3 cases of ileal atresia. Other pathologies identified as primary diagnoses of Intestinal Failure include Hirschsprung's disease (3 cases), gastroschisis (3 cases), congenital enteropathy (2 cases), and meconium ileus (1 case). A secondary diagnosis contributing to the outcome of Intestinal Failure was identified in 10 patients within the analyzed cohort. The primary pathology in question is intestinal atresia, particularly ileal, found in 2 patients as a secondary diagnosis. Another aspect explored in studying these patients is the presence of non-intestinal comorbidities. The existence of 19 patients with this type of condition has been demonstrated, with the most prevalent comorbidities being of cardiac (4 patients), neurological (5 patients), genitourinary (5 patients), endocrine (3 patients), and pulmonary (2 patients) nature. This aspect carries significant importance as it adds to the primary pathology, i.e., Intestinal Failure, imposing a greater burden on both the patient and the family. At the time of writing this article, out of the total 49 patients analyzed, 10 cases presented with the presence of a stoma, including 1 jejunal case, 7 ileal cases, and 2 colon cases. Finally, attention was focused on the more specifically surgical aspect of these patients. Out of the total 49 patients diagnosed with Short Bowel Syndrome, 46 have undergone at least one intestinal resection during their lifetime, with a resulting mean measurement of residual small intestine less than 38.5 cm. Additionally, 21 patients underwent a bowel lengthening procedure as a therapeutic surgical intervention for Short Bowel Syndrome. Among these, the most represented techniques were: Serial Transverse Enteroplasty Procedure (STEP), with a total of 5 patients undergoing this procedure. Spiral Intestinal Lengthening and Tailoring (SILT), with a total of 9 patients. Longitudinal Intestinal Lengthening and Tailoring (LILT), with a total of 3 patients. The overall mean measurement of small intestine pre-procedure was 42 cm, compared to a post-procedure mean length of 58 cm. Additionally, to gather data supporting the argument for the importance of addressing Short Bowel Syndrome in specialized Centers, such as the newly established Intestinal Rehabilitation Centre at Meyer Children Hospital, founded in 2018, we analyzed the data narrowing the focus to patients who underwent intestinal lengthening procedures at our Centre. Over a 5-year period, a total of 21 patients underwent intestinal lengthening at our Centre. Of these 21, 12 were females (57%) and 9 were males (43%). The focus of our study has been on intestinal lengthening techniques that have revolutionized the field of autologous intestinal regeneration. We discuss the Serial Transverse Enteroplasty (STEP), Longitudinal Intestinal Lengthening and Tailoring (LILT), and Spiral Intestinal Lengthening and Tailoring (SILT). Below are graphs illustrating the impact of surgical interventions on intestinal lengthening and diameter reduction in patients undergoing SILT, LILT, and STEP procedures. These visual representations highlight the differential outcomes associated with each surgical technique, providing a clear comparison of their efficacy in terms of both intestinal elongation and diameter normalization. The p-values displayed under each graph indicate the statistical significance of the observed changes, thereby supporting the reliability of the findings. The data demonstrates a statistically significant increase in intestinal length following both the SILT and LILT procedures. Specifically, the SILT intervention resulted in a mean increase in length with a p-value of 0.0011, while the LILT procedure demonstrated a similar positive outcome with a p-value of 0.000466. These results indicate a robust improvement in intestinal length, confirming the efficacy of these surgical techniques. Conversely, the STEP procedure, primarily aimed at intestinal remodeling rather than lengthening, did not achieve statistically significant results in terms of length increase, as indicated by a p-value of 0.093193. In addition to lengthening, the study also assessed the reduction in intestinal diameter post-procedure. Both SILT and LILT interventions showed a significant reduction, with p-values of 0.00785 and 0.001025, respectively, highlighting the procedures' effectiveness in achieving a more favorable intestinal morphology. In summary, SILT and LILT procedures have proven to be significantly effective in increasing intestinal length and reducing diameter, while the STEP intervention did not show significant length improvement but may still play a role in intestinal remodeling. Survival Outcomes By the end of follow-up, 21 of 21 patients were alive, yielding an overall survival rate of 100%. Our survival outcomes exceed historically reported survival in SBS children managed with multidisciplinary care. ( 11 , 12 )) For example, a recent large Nordic study (208 infants with SBS-IF from 2010–2019) reported 96% overall survival with IRP management. ( 13 ) While our cohort is smaller, the high survival rate (100%) underscores the effectiveness of dedicated multidisciplinary management even in a nascent program. Enteral Autonomy and Weaning off PN Achieving enteral autonomy was a primary goal of the IRP. Out of 21 patients, 7 (33,3%) successfully weaned off parenteral nutrition during the follow-up period. The figure below depicts the reduction of Parenteral Nutrition by surgical technique. By 24 months of follow-up, 100% of patients had reduce the quantity (volume expressed in mg/Kg/die) of PN, and by 48 months, the overall reduction of PN volume was 42,28% (p < 0.05). Fourteen patients remained PN-dependent at last follow-up; they are all still actively in the program with ongoing gradual progress in enteral feeding. No patients in our series have required an intestinal transplant to date. Even the child with only 10 cm of small bowel has been maintained on PN with manageable complications and is considered for possible future transplant only if life-threatening issues arise. The avoidance of transplant in all cases highlights the program’s success in managing even the most severe SBS with non-transplant therapies, echoing findings from other contemporary series where intestinal transplantation has become a rare necessity when IRP care is optimized. ( 14 ) Discussion The establishment of our novel Paediatric Intestinal Rehabilitation Program has initiated a new era in the management of short bowel syndrome at our institution, yielding outcomes that affirm the benefits of specialized multidisciplinary care. The high survival rate (100%), enteral autonomy rate (33% at 48 months follow-up) and PN volume reduction (42,28% at 48 months follow-up) observed in our cohort are encouraging and in line with, if not exceeding, the improvements reported by other established IRPs​. ( 15 , 16 ) In this discussion, we will contextualize our findings with respect to current literature, explore the factors contributing to patient outcomes, and highlight the innovations and remaining challenges in pediatric intestinal rehabilitation. Improved Survival in the IRP Era Our program’s 100% survival is substantially better than historical outcomes for pediatric SBS and reflects the general trend of improved survival in the IRP era​. ( 17 ) In earlier decades, infants with severe SBS often faced mortality rates of 30–50% due to sepsis or liver failure while on prolonged PN. The advent of multidisciplinary IR teams has changed this prognosis. A systematic review and meta-analysis by Stanger et al. demonstrated that the introduction of multidisciplinary IR programs significantly increased survival and enteral weaning rates in children with intestinal failure compared to prior standard care​. ( 18 ) Subsequent reports have consistently shown survival well above 85–90% in experienced centers​. For instance, the multi-center Nordic study (2010–2019) documented 96% 5-year survival with comprehensive IR management​, and the Hong Kong single-center experience reported 89% survival over two decades​. ( 19 , 20 , 21 , 22 ) Our results are congruent with these findings, underscoring that even a newly established program can rapidly achieve excellent survival outcomes when adhering to modern best practices. Achieving Enteral Autonomy – Predictors and Strategies Achieving enteral autonomy is a central goal for quality of life and long-term health in SBS patients. We observed a 61.8%% (p-value < 0.000001) reduction in PN total volume enteral autonomy rate, with a 33.3% of Parenteral autonomy, which is notable given the severity of cases (many NEC and Volvolus with short residual lengths). This result is comparable to published rates; for example, Quiros-Tejeira et al. historically reported around 50% autonomy in SBS children, but more recent cohorts in IRPs show 60–80% reaching full enteral nutrition depending on follow-up duration and patient mix​. ( 12 ) The Nordic study had 76% enteral autonomy by ~ 4.4 years median follow-up​ ( 13 ), very similar to our 69.6% at 4 years follow-up, based on patient-specific linear regression. Our findings reaffirm known predictors of enteral autonomy while also providing some nuanced insights: Parenteral Volume Reduction based on Surgical Interventions: Across all follow-up times, a progressive reduction in parenteral volume is observed for each technique, indicating sustained improvement in enteral autonomy over the years. At 6 months, all techniques achieve some degree of reduction, with STEP showing the highest mean decrease, followed by SILT and LILT. However, variability is substantial, as reflected by the wide error bars. By 12 months, SILT surpasses both LILT and STEP in mean reduction, suggesting a faster improvement trajectory. This trend continues at 24 and 48 months, where SILT achieves the greatest percentage reduction (around 72% at 48 months), while LILT and STEP reach more moderate but still clinically relevant improvements. Notably, the magnitude of reduction for LILT and STEP appears to plateau after 24 months, whereas SILT maintains a sharper upward trajectory. Despite these trends, the substantial overlap in error bars across groups and time points indicates considerable interpatient variability and limits definitive conclusions about the superiority of one technique over another. Nevertheless, the data suggest that while all three procedures can substantially decrease dependence on parenteral nutrition, SILT may offer a greater long-term reduction, potentially reflecting differences in preserved bowel function, absorptive capacity, or postoperative adaptation. Study Limitations While our results are promising, we acknowledge the limitations of this study. Foremost, the sample size is relatively small (n = 21) and from a single center, reflecting the rarity of pediatric SBS. The follow-up duration, with a median around 3 years, is relatively short to assess very long-term outcomes such as sustained autonomy into adulthood or late complications. Continued follow-up of this cohort will be important to ensure that autonomy is maintained and to monitor for any late sequelae (for example, renal issues, bone density concerns, or liver fibrosis that might not have been apparent yet). Our retrospective design also carries inherent biases, though the data were collected prospectively as part of program quality improvement, which improves accuracy. We did not have a concurrent or historical control group (e.g., SBS patients managed before the IRP initiation) for formal comparison. However, given the extensive evidence in the literature of outcome improvements over time, and the ethical imperative to provide the best known care, a control group without IRP was neither feasible nor desirable. Instead, we compared our outcomes to published benchmarks. Another limitation is that surgical decisions were individualized and not randomized, which could introduce selection bias (surgeons might choose to operate on those deemed to have better chances, etc.). These factors mean our results must be interpreted in context and with caution regarding generalizability. Clinical Impact and Future Directions Despite these limitations, our findings have important clinical implications. They provide further evidence that establishing an IRP leads to tangible improvements in survival and independence from PN for children with SBS. For centers that have not yet organized a formal intestinal rehabilitation team, our experience can serve as a model. Key components like early referral to the IRP, standardized protocols for PN and enteral advancement, and continuous team communication were crucial to our success and can be replicated. The learning curve in our first years was steep, but by drawing on expertise from established programs (via literature and expertise from previous founded programs), we rapidly implemented an effective system. As we move forward, our program will continue to evolve. We plan to integrate new therapies as evidence emerges – for instance, emerging data on hormonal therapies or modified diets that may promote adaptation. Research is ongoing into areas such as gut microbiota manipulation and novel trophic factors (e.g., GLP-1, ghrelin analogues). We are also participating in multi-center collaborations to contribute our data to larger analyses, which will help overcome the limitation of small sample size and allow more robust conclusions. One particular area of interest is neurodevelopmental outcomes and quality of life for SBS survivors. While beyond the scope of this report, we intend to systematically evaluate cognitive and developmental outcomes in our patients, as prolonged illness in early life can have subtle effects. Ensuring that children not only survive and wean off PN, but also reach their full developmental potential, will be the next horizon of care. This may require incorporating early intervention services and neurodevelopmental experts into the IRP framework. In conclusion, our novel pediatric IRP for short bowel syndrome has demonstrated outcomes on par with leading international centers, validating our multidisciplinary approach. Through comprehensive management, we achieved high survival, a strong rate of enteral autonomy, and low complication rates in a historically high-risk population. These results highlight the clinical impact of modern intestinal rehabilitation – turning SBS from a frequently fatal condition into one where most children can survive and eventually thrive without transplant. The insights gained will help us further refine care and can inform best practices for other programs. By continuing to share experiences and innovations across IRPs, we can collectively initiate a new era in which pediatric intestinal failure is a manageable chronic condition with ever-improving outcomes. Conclusions In this study, we report the successful implementation of a novel multidisciplinary intestinal rehabilitation program for children with Short Bowel Syndrome and Intestinal Failure. The program’s outcomes mark a significant improvement over historical expectations for these patients. The key findings include a 100% survival rate and 33.3% enteral autonomy within a median of 48 months, achieved without any need for intestinal transplantation in our cohort. These results underscore that comprehensive, team-based management can markedly improve the prognosis of pediatric SBS, transforming it from a condition with high mortality and transplant reliance into one that is compatible with long-term survival and improved enteral nutrition for the majority of patients. Our experience highlights several critical components driving this success: early and aggressive nutritional management (including the use of advanced PN formulations to prevent liver disease) and timely surgical interventions to maximize absorptive anatomy. Clinically, these findings reinforce the importance of establishing specialized intestinal rehabilitation teams for the care of children with intestinal failure. For healthcare providers and hospital administrators, our results provide evidence that investing in an IRP yields tangible benefits in patient outcomes. For families of children with SBS, this study offers hope and a clearer expectation that with modern care, their children have a strong chance not only to survive but to eventually grow without lifelong dependence on parenteral nutrition. In conclusion, the initiation of our IRP represents a new era in regional SBS management, aligning with global advances. The program has become a model of care in which multidisciplinary collaboration and innovation directly translated into improved patient survival, nutrition, and quality of life. Ongoing efforts will focus on sustaining these outcomes, further reducing complications, and sharing our insights to help other centers optimize intestinal rehabilitation. Our findings add to the growing body of evidence that comprehensive intestinal rehabilitation is an effective, life-changing approach for pediatric short bowel syndrome, fundamentally altering its clinical trajectory in a positive way. Declarations Ethical Considerations This study was conducted in accordance with the Declaration of Helsinki. Given the retrospective nature of the study, the IRB granted a waiver of informed consent. Patient confidentiality was maintained by de-identifying data; only aggregate results are reported. No interventions outside standard care were performed for the purposes of this study. The novel aspects of the intestinal rehabilitation program were part of established or compassionate-use protocols and were administered with appropriate regulatory approvals and parental consent when required. There were no financial incentives or external influences on patient treatment decisions. Author Contributions Study Conception and Design: Cantagalli M.M. and Coletta R. conceived the study and established the rehabilitation program framework. Data Collection: Cantagalli M.M. and Coletta R. collected patient data and maintained the program database. Data Analysis: Cantagalli M.M. and Di Mitri M. performed the data analysis and interpretation with input from Coletta R. Surgical Management: Morabito A., Coletta R. and Cantagalli M.M. led the surgical care of patients and contributed to surgical data interpretation. Manuscript Writing: Cantagalli M.M. drafted the initial manuscript. Manuscript Review & Editing: Morabito A., Coletta R. and Di Mitri M. critically revised the manuscript for important intellectual content. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work. Acknowledgments The authors thank the entire Intestinal Rehabilitation Team at Meyer Children Hosptial, including our pediatric intensive care unit staff, nutrition support pharmacists, and nursing staff, for their unwavering dedication to our patients and for making this program possible. We also extend our gratitude to the patients and their families, whose resilience and cooperation have been integral to the success of the program. Special thanks to Dr. Lacitignola L. for her advice on implementing the feeding protocols, and to the surgical fellows who assisted in the operative care of these children. We also acknowledge the valuable feedback from the reviewers, which significantly improved the quality of this manuscript. Funding Declaration This study was supported in part by funds from the ‘Current Research Annual Funding’ of the Italian Ministry of Health. Competing Interest The authors declare no conflicts of interest related to this work. References Chiba M, Masumoto K, Kaji T, Matsuura T, Morii M, Fagbemi A et al (2023) Efficacy and safety of teduglutide in infants and children with short bowel syndrome dependent on parenteral support. 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Gut 44(6):844–852 Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research Electronic Data Capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf 42(2):377–381. 10.1016/j.jbi.2008.08.010 Nightingale JMD (2001) The Short Bowel. In: Nightingale J (ed) Intestinal Failure. Greenwich Medical Media, London, England, pp 177–198 Buchman AL, Scolapio J, Fryer J (2003) AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterology 124(4):1111–1134 Belza C, Wales PW (2017) Impact of multidisciplinary teams for management of intestinal failure in children. Curr Opin Pediatr 29(3):334–339 Tsang JT, Fung AC, Lau SC, Wong KK (2025) Outcomes of children with short bowel syndrome: experiences in a multidisciplinary intestinal rehabilitation unit over two decades. J Pediatr Surg 60(2):161646 Mutanen A, Engstrand Lilja H, Wester T, Norrby H, Borg H, Persson S et al (2023) A Nordic multicenter study on contemporary outcomes of pediatric short bowel syndrome in 208 patients. Clin Nutr 42(7):1095–1103 Dore M et al (2017) Ultrashort bowel syndrome outcome in children treated in a multidisciplinary intestinal rehabilitation unit. Eur J Pediatr Surg 27(2):116–120 Jeppesen PB et al (2005) Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut 54(9):1224–1231 Nagelkerke SCJ et al (2022) Bowel lengthening procedures in children with short bowel syndrome: a systematic review. Eur J Pediatr Surg 32(4):301–309 Reyes J et al (2001) Intestinal transplantation for children with short bowel syndrome. Semin Pediatr Surg 10(2):99–104 Jo SC et al (2019) Outcomes of children with chronic intestinal failure: experience over 2 decades at a tertiary paediatric hospital. J Pediatr Gastroenterol Nutr 69(6):e79–e87 Khan FA et al (2015) Predictors of enteral autonomy in children with intestinal failure: a multicenter cohort study. J Pediatr 167(1):29–34e1 DiBaise JK, Young RJ, Vanderhoof JA (2004) Intestinal rehabilitation and the short bowel syndrome: part 1. Am J Gastroenterol 99(7):1386–1395 Colomb V et al (2007) Long-term outcome of children receiving home parenteral nutrition: a 20-year single-center experience in 302 patients. J Pediatr Gastroenterol Nutr 44(3):347–353 Goulet O et al (2004) Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 38(3):250–269 Tables Tables 1 to 8 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8279026","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":559982425,"identity":"e50ca6d6-3a00-49d6-bc73-5ef004eddd94","order_by":0,"name":"M. M. Cantagalli","email":"data:image/png;base64,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","orcid":"","institution":"University of Florence","correspondingAuthor":true,"prefix":"","firstName":"M.","middleName":"M.","lastName":"Cantagalli","suffix":""},{"id":559982426,"identity":"6a900433-33f6-42c9-9cd5-0ea282865f5e","order_by":1,"name":"Di Mitri","email":"","orcid":"","institution":"Meyer Children's 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12:25:59","extension":"html","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92300,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8279026/v1/62efbb78989f63b0c6ba57dc.html"},{"id":98779039,"identity":"71280d10-eef5-4dc8-bb8f-68995548bcc8","added_by":"auto","created_at":"2025-12-22 12:29:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":677506,"visible":true,"origin":"","legend":"\u003cp\u003eClassification of Short Bowel Syndrome\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8279026/v1/4b6c3af750da2cac1d63479f.png"},{"id":98783630,"identity":"70b6b5a4-083c-4a5f-8f1a-a5dbb31bf4ec","added_by":"auto","created_at":"2025-12-22 12:42:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1323322,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8279026/v1/9a9a7029-3b45-47cc-ac8c-3e39610b1e9f.pdf"},{"id":98748904,"identity":"a3007123-e2fc-4d03-879d-22a46f958c00","added_by":"auto","created_at":"2025-12-22 08:58:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":314133,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8279026/v1/3723d462d4ae9464424a43f7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Outcomes of a novel pediatric intestinal rehabilitation program for children with short bowel syndrome: a retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eShort bowel syndrome (SBS) in children represents a severe form of intestinal failure, defined by an inadequate absorptive surface of the remaining intestine to sustain hydration and nutrition, most commonly following extensive bowel resection during infancy. Without specialized care, SBS can be life-threatening or lead to profound malnutrition, as affected patients depend on parenteral nutrition (PN) for survival and growth.​ (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOver the past two decades, outcomes for SBS have improved significantly with the introduction of dedicated intestinal rehabilitation programs (IRPs) that integrate medical, nutritional, and surgical management​. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIRPs bring together pediatric surgeons, gastroenterologists, dietitians, nurses, and other specialists to deliver individualized treatment plans aimed to achieve enteral autonomy (independence from PN) and reduce the incidence of life-threatening complications such as sepsis and liver failure​. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eBefore the widespread adoption of multidisciplinary care, the prognosis for pediatric SBS was poor, with survival rates of approximately 70% and a high incidence of PN-associated liver disease leading to transplant or death​. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOver time, innovations including novel intravenous lipid emulsions rich in omega-3 fatty acids to prevent intestinal failure\u0026ndash;associated liver disease (IFALD), autologous bowel lengthening procedures, and enterotrophic agents such as glucagon-like peptide-2 (GLP-2) analogues (e.g., teduglutide) have markedly improved patient outcomes​. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThese advances have ushered in a \u0026ldquo;new era\u0026rdquo; in which intestinal failure in children can often be managed without resorting to intestinal transplantation, which was historically the only option for long-term survival in the most severe cases.\u003c/p\u003e \u003cp\u003eIn 2018, our institution launched a Novel Paediatric Intestinal Rehabilitation Program with the aim of consolidating and optimizing the care of SBS patients. This report presents the outcomes from the initial years of the program, evaluating survival, achievement of enteral autonomy, and complication rates, and comparing them with published data. We also discuss key insights, including factors influencing success (such as residual bowel length and SBS etiology) and the integration of emerging therapies. We hypothesize that our comprehensive IRP approach improves clinical outcomes for children with short bowel syndrome, reflecting the global trend of better prognosis in this patient population. By sharing our experience, we aim to contribute to the expanding body of evidence supporting multidisciplinary intestinal rehabilitation and to guide further improvements in the care of pediatric SBS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Patient Population\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study including all pediatric patients with SBS managed within Intestinal Rehabilitation Program between 2018 and 2024 at Meyer Children\u0026rsquo;s Hospital in Florence, a tertiary pediatric referral center. The inclusion criteria were the diagnosis of SBS defined as dependence on PN for more than 60 consecutive days of PN due to intestinal insufficiency. We excluded patients with intestinal failure primarily from motility or mucosal disorders as the study focused on anatomic short bowel syndrome; patients lost to follow-up were also excluded.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIntestinal Rehabilitation Program Interventions\u003c/h3\u003e\n\u003cp\u003eOur IRP applies a standardized multidisciplinary approach to maximize intestinal adaptation and nutrition management in SBS. Each patient was jointly managed by a pediatric surgeon and a pediatric gastroenterologist as co-directors of care, along with a nutritionist, stoma/wound care nurse, pharmacist, and social worker.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003ePatient data were extracted from medical records and managed using REDCap electronic data capture tools hosted at Meyer Children Hospital (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). We recorded demographic data (age, sex), primary SBS etiology (e.g., NEC, gastroschisis, intestinal atresia, midgut volvulus, etc.), and anatomical data (length of residual small intestine and presence of ileocecal valve and colon). We noted all major interventions: surgical procedures, start, quantity, type and duration of PN and any episodes of sepsis (defined as positive blood culture with systemic infection requiring treatment).\u003c/p\u003e \u003cp\u003eThe primary outcomes were overall survival and achievement enteral autonomy. Enteral autonomy was defined as complete discontinuation of parenteral nutrition while maintaining of normal growth supported exclusively by enteral or oral nutrition. The time from IRP enrollment to achievement of enteral autonomy was also recorded, when applicable. Secondary outcomes included the incidence of IFALD (cholestasis or liver dysfunction attributed to PN), the numbers of central line-associated bloodstream infections, and the need for intestinal transplantation. For patients who died, the cause of death was recorded.\u003c/p\u003e \u003cp\u003eThe literature describes three types of Short Bowel Syndrome based on the anatomy of the remaining portion of the intestine, which plays a crucial role in determining the severity and type of malabsorption observed in patients. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePatients with jejunostomy are those in whom the jejunum, ileum, and colon have been removed. The malabsorption status of these patients often does not improve over time due to the limited capacity for spontaneous intestinal adaptation. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with jejuno-ileal anastomosis may have undergone jejunal resection and have \u0026gt;\u0026thinsp;10 cm of the remaining terminal ileum and colon. These patients are relatively few, and they typically do not experience significant clinical problems because, having a residual portion of the ileum, they undergo both structural and functional adaptation. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients who have undergone jejuno-colostomy are those in whom the ileum has been removed, often along with the ileocecal valve, and they have a jejuno-jejunocolic anastomosis. These patients have \u0026lt;\u0026thinsp;10 cm of terminal ileum and are often malnourished, but if the disease is well treated, their conditions may improve with intestinal adaptation.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData analysis was primarily descriptive given the sample size. Continuous variables are presented as median with interquartile range (IQR) and categorical variables as counts (percentage). The Kaplan\u0026ndash;Meier method was used to estimate survival and freedom from PN (enteral autonomy) over time, with follow-up censored at last contact for those still on PN or alive. We performed subgroup observations to explore factors associated with enteral autonomy: for example, comparing outcomes by SBS etiology (NEC vs non-NEC) and by residual bowel length above or below the median. Due to the limited sample, formal hypothesis testing was only applied to select comparisons; a log-rank test was used for Kaplan\u0026ndash;Meier curve comparisons, considering p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 as significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient Characteristics\u003c/h2\u003e\n \u003cp\u003eForty-nine patients met inclusion criteria, with baseline characteristics detailed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eIn summary, 26 (53% of the total) were male and 23 (47%) females demonstrating a substantial gender balance. The mean gestational age is just over 33 gestational weeks, with an average birth weight of 2,00 Kg.\u003c/p\u003e\n \u003cp\u003eAnthropological analysis of the sample has shown a prevalence of individuals of white race (40 out of a total of 49 patients analyzed), as well as a majority of Hispanic, Latino, or Spanish origin patients (31 in total).\u003c/p\u003e\n \u003cp\u003eThe prevalent primary diagnosis of Intestinal Failure is intestinal volvulus, with a total of 16 patients diagnosed (31.4% of the database). Following this, necrotizing enterocolitis is identified in 11 analyzed patients. Notably, Intestinal Atresia assumes significant importance as a primary diagnosis of Intestinal Failure, with a total of 7 patients affected by this congenital condition. Within this subgroup of 7 patients, 1 case involved duodenal atresia, 3 cases of jejunal atresia, and an additional 3 cases of ileal atresia. Other pathologies identified as primary diagnoses of Intestinal Failure include Hirschsprung\u0026apos;s disease (3 cases), gastroschisis (3 cases), congenital enteropathy (2 cases), and meconium ileus (1 case).\u003c/p\u003e\n \u003cp\u003eA secondary diagnosis contributing to the outcome of Intestinal Failure was identified in 10 patients within the analyzed cohort. The primary pathology in question is intestinal atresia, particularly ileal, found in 2 patients as a secondary diagnosis. Another aspect explored in studying these patients is the presence of non-intestinal comorbidities. The existence of 19 patients with this type of condition has been demonstrated, with the most prevalent comorbidities being of cardiac (4 patients), neurological (5 patients), genitourinary (5 patients), endocrine (3 patients), and pulmonary (2 patients) nature. This aspect carries significant importance as it adds to the primary pathology, i.e., Intestinal Failure, imposing a greater burden on both the patient and the family.\u003c/p\u003e\n \u003cp\u003eAt the time of writing this article, out of the total 49 patients analyzed, 10 cases presented with the presence of a stoma, including 1 jejunal case, 7 ileal cases, and 2 colon cases.\u003c/p\u003e\n \u003cp\u003eFinally, attention was focused on the more specifically surgical aspect of these patients. Out of the total 49 patients diagnosed with Short Bowel Syndrome, 46 have undergone at least one intestinal resection during their lifetime, with a resulting mean measurement of residual small intestine less than 38.5 cm. Additionally, 21 patients underwent a bowel lengthening procedure as a therapeutic surgical intervention for Short Bowel Syndrome.\u003c/p\u003e\n \u003cp\u003eAmong these, the most represented techniques were:\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eSerial Transverse Enteroplasty Procedure (STEP), with a total of 5 patients undergoing this procedure.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eSpiral Intestinal Lengthening and Tailoring (SILT), with a total of 9 patients.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eLongitudinal Intestinal Lengthening and Tailoring (LILT), with a total of 3 patients.\u003c/p\u003e\n \u003c/li\u003e\n \u003c/ul\u003e\n \u003cp\u003eThe overall mean measurement of small intestine pre-procedure was 42 cm, compared to a post-procedure mean length of 58 cm.\u003c/p\u003e\n \u003cp\u003eAdditionally, to gather data supporting the argument for the importance of addressing Short Bowel Syndrome in specialized Centers, such as the newly established Intestinal Rehabilitation Centre at Meyer Children Hospital, founded in 2018, we analyzed the data narrowing the focus to patients who underwent intestinal lengthening procedures at our Centre.\u003c/p\u003e\n \u003cp\u003eOver a 5-year period, a total of 21 patients underwent intestinal lengthening at our Centre. Of these 21, 12 were females (57%) and 9 were males (43%).\u003c/p\u003e\n \u003cp\u003eThe focus of our study has been on intestinal lengthening techniques that have revolutionized the field of autologous intestinal regeneration. We discuss the Serial Transverse Enteroplasty (STEP), Longitudinal Intestinal Lengthening and Tailoring (LILT), and Spiral Intestinal Lengthening and Tailoring (SILT).\u003c/p\u003e\n \u003cp\u003eBelow are graphs illustrating the impact of surgical interventions on intestinal lengthening and diameter reduction in patients undergoing SILT, LILT, and STEP procedures.\u003c/p\u003e\n \u003cp\u003eThese visual representations highlight the differential outcomes associated with each surgical technique, providing a clear comparison of their efficacy in terms of both intestinal elongation and diameter normalization.\u003c/p\u003e\n \u003cp\u003eThe p-values displayed under each graph indicate the statistical significance of the observed changes, thereby supporting the reliability of the findings.\u003c/p\u003e\n \u003cp\u003eThe data demonstrates a statistically significant increase in intestinal length following both the SILT and LILT procedures. Specifically, the SILT intervention resulted in a mean increase in length with a p-value of 0.0011, while the LILT procedure demonstrated a similar positive outcome with a p-value of 0.000466. These results indicate a robust improvement in intestinal length, confirming the efficacy of these surgical techniques.\u003c/p\u003e\n \u003cp\u003eConversely, the STEP procedure, primarily aimed at intestinal remodeling rather than lengthening, did not achieve statistically significant results in terms of length increase, as indicated by a p-value of 0.093193.\u003c/p\u003e\n \u003cp\u003eIn addition to lengthening, the study also assessed the reduction in intestinal diameter post-procedure. Both SILT and LILT interventions showed a significant reduction, with p-values of 0.00785 and 0.001025, respectively, highlighting the procedures\u0026apos; effectiveness in achieving a more favorable intestinal morphology.\u003c/p\u003e\n \u003cp\u003eIn summary, SILT and LILT procedures have proven to be significantly effective in increasing intestinal length and reducing diameter, while the STEP intervention did not show significant length improvement but may still play a role in intestinal remodeling.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eSurvival Outcomes\u003c/h3\u003e\n\u003cp\u003eBy the end of follow-up, 21 of 21 patients were alive, yielding an overall survival rate of 100%. Our survival outcomes exceed historically reported survival in SBS children managed with multidisciplinary care. (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e))\u003c/p\u003e\n\u003cp\u003eFor example, a recent large Nordic study (208 infants with SBS-IF from 2010\u0026ndash;2019) reported 96% overall survival with IRP management. (\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eWhile our cohort is smaller, the high survival rate (100%) underscores the effectiveness of dedicated multidisciplinary management even in a nascent program.\u003c/p\u003e\n\u003ch3\u003eEnteral Autonomy and Weaning off PN\u003c/h3\u003e\n\u003cp\u003eAchieving enteral autonomy was a primary goal of the IRP. Out of 21 patients, 7 (33,3%) successfully weaned off parenteral nutrition during the follow-up period. The figure below depicts the reduction of Parenteral Nutrition by surgical technique. By 24 months of follow-up, 100% of patients had reduce the quantity (volume expressed in mg/Kg/die) of PN, and by 48 months, the overall reduction of PN volume was 42,28% (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Fourteen patients remained PN-dependent at last follow-up; they are all still actively in the program with ongoing gradual progress in enteral feeding.\u003c/p\u003e\n\u003cp\u003eNo patients in our series have required an intestinal transplant to date. Even the child with only 10 cm of small bowel has been maintained on PN with manageable complications and is considered for possible future transplant only if life-threatening issues arise. The avoidance of transplant in all cases highlights the program\u0026rsquo;s success in managing even the most severe SBS with non-transplant therapies, echoing findings from other contemporary series where intestinal transplantation has become a rare necessity when IRP care is optimized. (\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe establishment of our novel Paediatric Intestinal Rehabilitation Program has initiated a new era in the management of short bowel syndrome at our institution, yielding outcomes that affirm the benefits of specialized multidisciplinary care. The high survival rate (100%), enteral autonomy rate (33% at 48 months follow-up) and PN volume reduction (42,28% at 48 months follow-up) observed in our cohort are encouraging and in line with, if not exceeding, the improvements reported by other established IRPs​. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn this discussion, we will contextualize our findings with respect to current literature, explore the factors contributing to patient outcomes, and highlight the innovations and remaining challenges in pediatric intestinal rehabilitation.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eImproved Survival in the IRP Era\u003c/h2\u003e \u003cp\u003eOur program\u0026rsquo;s 100% survival is substantially better than historical outcomes for pediatric SBS and reflects the general trend of improved survival in the IRP era​. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn earlier decades, infants with severe SBS often faced mortality rates of 30\u0026ndash;50% due to sepsis or liver failure while on prolonged PN. The advent of multidisciplinary IR teams has changed this prognosis. A systematic review and meta-analysis by Stanger et al. demonstrated that the introduction of multidisciplinary IR programs significantly increased survival and enteral weaning rates in children with intestinal failure compared to prior standard care​. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eSubsequent reports have consistently shown survival well above 85\u0026ndash;90% in experienced centers​. For instance, the multi-center Nordic study (2010\u0026ndash;2019) documented 96% 5-year survival with comprehensive IR management​, and the Hong Kong single-center experience reported 89% survival over two decades​. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOur results are congruent with these findings, underscoring that even a newly established program can rapidly achieve excellent survival outcomes when adhering to modern best practices.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eAchieving Enteral Autonomy \u0026ndash; Predictors and Strategies\u003c/h2\u003e \u003cp\u003eAchieving enteral autonomy is a central goal for quality of life and long-term health in SBS patients. We observed a 61.8%% (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.000001) reduction in PN total volume enteral autonomy rate, with a 33.3% of Parenteral autonomy, which is notable given the severity of cases (many NEC and Volvolus with short residual lengths). This result is comparable to published rates; for example, Quiros-Tejeira et al. historically reported around 50% autonomy in SBS children, but more recent cohorts in IRPs show 60\u0026ndash;80% reaching full enteral nutrition depending on follow-up duration and patient mix​. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe Nordic study had 76% enteral autonomy by ~\u0026thinsp;4.4 years median follow-up​ (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), very similar to our 69.6% at 4 years follow-up, based on patient-specific linear regression.\u003c/p\u003e \u003cp\u003eOur findings reaffirm known predictors of enteral autonomy while also providing some nuanced insights:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eParenteral Volume Reduction based on Surgical Interventions:\u003c/h2\u003e \u003cp\u003eAcross all follow-up times, a progressive reduction in parenteral volume is observed for each technique, indicating sustained improvement in enteral autonomy over the years. At 6 months, all techniques achieve some degree of reduction, with STEP showing the highest mean decrease, followed by SILT and LILT. However, variability is substantial, as reflected by the wide error bars. By 12 months, SILT surpasses both LILT and STEP in mean reduction, suggesting a faster improvement trajectory. This trend continues at 24 and 48 months, where SILT achieves the greatest percentage reduction (around 72% at 48 months), while LILT and STEP reach more moderate but still clinically relevant improvements. Notably, the magnitude of reduction for LILT and STEP appears to plateau after 24 months, whereas SILT maintains a sharper upward trajectory. Despite these trends, the substantial overlap in error bars across groups and time points indicates considerable interpatient variability and limits definitive conclusions about the superiority of one technique over another. Nevertheless, the data suggest that while all three procedures can substantially decrease dependence on parenteral nutrition, SILT may offer a greater long-term reduction, potentially reflecting differences in preserved bowel function, absorptive capacity, or postoperative adaptation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eStudy Limitations\u003c/h2\u003e \u003cp\u003eWhile our results are promising, we acknowledge the limitations of this study. Foremost, the sample size is relatively small (n\u0026thinsp;=\u0026thinsp;21) and from a single center, reflecting the rarity of pediatric SBS. The follow-up duration, with a median around 3 years, is relatively short to assess very long-term outcomes such as sustained autonomy into adulthood or late complications. Continued follow-up of this cohort will be important to ensure that autonomy is maintained and to monitor for any late sequelae (for example, renal issues, bone density concerns, or liver fibrosis that might not have been apparent yet). Our retrospective design also carries inherent biases, though the data were collected prospectively as part of program quality improvement, which improves accuracy.\u003c/p\u003e \u003cp\u003eWe did not have a concurrent or historical control group (e.g., SBS patients managed before the IRP initiation) for formal comparison. However, given the extensive evidence in the literature of outcome improvements over time, and the ethical imperative to provide the best known care, a control group without IRP was neither feasible nor desirable. Instead, we compared our outcomes to published benchmarks.\u003c/p\u003e \u003cp\u003eAnother limitation is that surgical decisions were individualized and not randomized, which could introduce selection bias (surgeons might choose to operate on those deemed to have better chances, etc.). These factors mean our results must be interpreted in context and with caution regarding generalizability.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eClinical Impact and Future Directions\u003c/h2\u003e \u003cp\u003eDespite these limitations, our findings have important clinical implications. They provide further evidence that establishing an IRP leads to tangible improvements in survival and independence from PN for children with SBS. For centers that have not yet organized a formal intestinal rehabilitation team, our experience can serve as a model. Key components like early referral to the IRP, standardized protocols for PN and enteral advancement, and continuous team communication were crucial to our success and can be replicated. The learning curve in our first years was steep, but by drawing on expertise from established programs (via literature and expertise from previous founded programs), we rapidly implemented an effective system.\u003c/p\u003e \u003cp\u003eAs we move forward, our program will continue to evolve. We plan to integrate new therapies as evidence emerges \u0026ndash; for instance, emerging data on hormonal therapies or modified diets that may promote adaptation. Research is ongoing into areas such as gut microbiota manipulation and novel trophic factors (e.g., GLP-1, ghrelin analogues). We are also participating in multi-center collaborations to contribute our data to larger analyses, which will help overcome the limitation of small sample size and allow more robust conclusions.\u003c/p\u003e \u003cp\u003eOne particular area of interest is neurodevelopmental outcomes and quality of life for SBS survivors. While beyond the scope of this report, we intend to systematically evaluate cognitive and developmental outcomes in our patients, as prolonged illness in early life can have subtle effects. Ensuring that children not only survive and wean off PN, but also reach their full developmental potential, will be the next horizon of care. This may require incorporating early intervention services and neurodevelopmental experts into the IRP framework.\u003c/p\u003e \u003cp\u003eIn conclusion, our novel pediatric IRP for short bowel syndrome has demonstrated outcomes on par with leading international centers, validating our multidisciplinary approach. Through comprehensive management, we achieved high survival, a strong rate of enteral autonomy, and low complication rates in a historically high-risk population. These results highlight the clinical impact of modern intestinal rehabilitation \u0026ndash; turning SBS from a frequently fatal condition into one where most children can survive and eventually thrive without transplant. The insights gained will help us further refine care and can inform best practices for other programs. By continuing to share experiences and innovations across IRPs, we can collectively initiate a new era in which pediatric intestinal failure is a manageable chronic condition with ever-improving outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this study, we report the successful implementation of a novel multidisciplinary intestinal rehabilitation program for children with Short Bowel Syndrome and Intestinal Failure. The program\u0026rsquo;s outcomes mark a significant improvement over historical expectations for these patients. The key findings include a 100% survival rate and 33.3% enteral autonomy within a median of 48 months, achieved without any need for intestinal transplantation in our cohort. These results underscore that comprehensive, team-based management can markedly improve the prognosis of pediatric SBS, transforming it from a condition with high mortality and transplant reliance into one that is compatible with long-term survival and improved enteral nutrition for the majority of patients.\u003c/p\u003e \u003cp\u003eOur experience highlights several critical components driving this success: early and aggressive nutritional management (including the use of advanced PN formulations to prevent liver disease) and timely surgical interventions to maximize absorptive anatomy.\u003c/p\u003e \u003cp\u003eClinically, these findings reinforce the importance of establishing specialized intestinal rehabilitation teams for the care of children with intestinal failure. For healthcare providers and hospital administrators, our results provide evidence that investing in an IRP yields tangible benefits in patient outcomes. For families of children with SBS, this study offers hope and a clearer expectation that with modern care, their children have a strong chance not only to survive but to eventually grow without lifelong dependence on parenteral nutrition.\u003c/p\u003e \u003cp\u003eIn conclusion, the initiation of our IRP represents a new era in regional SBS management, aligning with global advances. The program has become a model of care in which multidisciplinary collaboration and innovation directly translated into improved patient survival, nutrition, and quality of life. Ongoing efforts will focus on sustaining these outcomes, further reducing complications, and sharing our insights to help other centers optimize intestinal rehabilitation. Our findings add to the growing body of evidence that comprehensive intestinal rehabilitation is an effective, life-changing approach for pediatric short bowel syndrome, fundamentally altering its clinical trajectory in a positive way.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. Given the retrospective nature of the study, the IRB granted a waiver of informed consent. Patient confidentiality was maintained by de-identifying data; only aggregate results are reported. No interventions outside standard care were performed for the purposes of this study. The novel aspects of the intestinal rehabilitation program were part of established or compassionate-use protocols and were administered with appropriate regulatory approvals and parental consent when required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere were no financial incentives or external influences on patient treatment decisions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Conception and Design:\u003c/strong\u003e Cantagalli M.M. and Coletta R. conceived the study and established the rehabilitation program framework. \u003cstrong\u003eData Collection:\u003c/strong\u003e Cantagalli M.M. and Coletta R. collected patient data and maintained the program database. \u003cstrong\u003eData Analysis:\u003c/strong\u003e Cantagalli M.M. and Di Mitri M. performed the data analysis and interpretation with input from Coletta R. \u003cstrong\u003eSurgical Management:\u003c/strong\u003e Morabito A., Coletta R. and Cantagalli M.M. led the surgical care of patients and contributed to surgical data interpretation. \u003cstrong\u003eManuscript Writing:\u003c/strong\u003e Cantagalli M.M. drafted the initial manuscript. \u003cstrong\u003eManuscript Review \u0026amp; Editing:\u003c/strong\u003e Morabito A., Coletta R. and Di Mitri M. critically revised the manuscript for important intellectual content.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors approved the final version of the manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the entire Intestinal Rehabilitation Team at Meyer Children Hosptial, including our pediatric intensive care unit staff, nutrition support pharmacists, and nursing staff, for their unwavering dedication to our patients and for making this program possible. We also extend our gratitude to the patients and their families, whose resilience and cooperation have been integral to the success of the program. Special thanks to Dr. Lacitignola L. for her advice on implementing the feeding protocols, and to the surgical fellows who assisted in the operative care of these children.\u003c/p\u003e\n\u003cp\u003eWe also acknowledge the valuable feedback from the reviewers, which significantly improved the quality of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported in part by funds from the ‘Current Research Annual Funding’ of the Italian\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMinistry of Health.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest related to this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChiba M, Masumoto K, Kaji T, Matsuura T, Morii M, Fagbemi A et al (2023) Efficacy and safety of teduglutide in infants and children with short bowel syndrome dependent on parenteral support. 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Eur J Pediatr Surg 27(2):116\u0026ndash;120\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeppesen PB et al (2005) Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut 54(9):1224\u0026ndash;1231\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNagelkerke SCJ et al (2022) Bowel lengthening procedures in children with short bowel syndrome: a systematic review. Eur J Pediatr Surg 32(4):301\u0026ndash;309\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReyes J et al (2001) Intestinal transplantation for children with short bowel syndrome. Semin Pediatr Surg 10(2):99\u0026ndash;104\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJo SC et al (2019) Outcomes of children with chronic intestinal failure: experience over 2 decades at a tertiary paediatric hospital. J Pediatr Gastroenterol Nutr 69(6):e79\u0026ndash;e87\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan FA et al (2015) Predictors of enteral autonomy in children with intestinal failure: a multicenter cohort study. J Pediatr 167(1):29\u0026ndash;34e1\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiBaise JK, Young RJ, Vanderhoof JA (2004) Intestinal rehabilitation and the short bowel syndrome: part 1. Am J Gastroenterol 99(7):1386\u0026ndash;1395\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColomb V et al (2007) Long-term outcome of children receiving home parenteral nutrition: a 20-year single-center experience in 302 patients. J Pediatr Gastroenterol Nutr 44(3):347\u0026ndash;353\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoulet O et al (2004) Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 38(3):250\u0026ndash;269\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 8 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8279026/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8279026/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003ePediatric short bowel syndrome (SBS) is a severe cause of intestinal failure, often requiring prolonged parenteral nutrition (PN) and exposing children to sepsis and intestinal failure\u0026ndash;associated liver disease (IFALD). In 2018, our institution established a multidisciplinary Pediatric Intestinal Rehabilitation Program (IRP) to optimize medical, nutritional, and surgical care.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eWe performed a retrospective cohort study of children with anatomic SBS managed within our IRP (Meyer Children\u0026rsquo;s Hospital, Florence) between 2018 and 2024. SBS was defined as PN dependence for \u0026gt;\u0026thinsp;60 consecutive days. Data included demographics, SBS etiology and anatomy, major interventions (including autologous bowel lengthening: SILT/LILT/STEP), central line infections, IFALD, survival, enteral autonomy (complete PN discontinuation with adequate growth), and PN volume trends.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eForty-nine patients met inclusion criteria; 21 underwent bowel lengthening at our center. In this surgical subgroup, survival was 100% at last follow-up and no patient required intestinal transplantation. Seven of 21 children (33.3%) achieved enteral autonomy during follow-up. PN requirements decreased over time across techniques, with an overall PN volume reduction of 42.3% at 48 months (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). SILT and LILT were associated with significant post-operative increases in bowel length and decreases in bowel diameter, whereas STEP showed non-significant length gains.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eEarly outcomes from a newly established IRP show excellent survival, meaningful PN reduction, and no need for transplant in a high-risk pediatric SBS population, supporting the effectiveness and scalability of structured multidisciplinary intestinal rehabilitation.\u003c/p\u003e","manuscriptTitle":"Outcomes of a novel pediatric intestinal rehabilitation program for children with short bowel syndrome: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-22 08:58:27","doi":"10.21203/rs.3.rs-8279026/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-17T23:56:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"302212563827727204202586423222385093738","date":"2026-01-19T13:14:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"85357211156020284960831663165832128372","date":"2026-01-15T01:44:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"156670671693200755576662496286307015497","date":"2026-01-14T10:20:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-12T06:52:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-11T23:21:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Colorectal Disease","date":"2025-12-10T21:40:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-colorectal-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcd","sideBox":"Learn more about [International Journal of Colorectal Disease](http://link.springer.com/journal/384)","snPcode":"384","submissionUrl":"https://submission.nature.com/new-submission/384/3","title":"International Journal of Colorectal Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7fb2778c-8d09-468e-8f6a-b15e4d337868","owner":[],"postedDate":"December 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T08:58:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-22 08:58:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8279026","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8279026","identity":"rs-8279026","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}