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Purpose: Intestinal dysmotility (ID) problems are common in patients with pediatric-onset intestinal failure (IF) and short bowel syndrome (SBS), leading to significant morbidity and delays in the advancement of enteral nutrition (EN). We aimed to investigate the clinical features and complications of ID in children with IF and SBS. Methods: Retrospective chart review of all children with IF and/or SBS who required parenteral nutrition (PN) > 6 weeks or small-intestinal resection ≥ 50%. Patients were divided into SBS and non-SBS groups. SBS group was divided into two subgroups: with and without ID. Patients with ID were identified (clinically, radiologically and functionally) and analyzed with regard to demographics, intestinal anatomy, complications and outcomes (short and long term). Results: A total of 42 children with IF were treated in our institution during 2003–2022. In non-SBS group (n = 10), ID was the most common cause of IF (80%). SBS-group included 32 children; 18 children (56%) developed ID. The clinical profile of SBS-ID patients (vs SBS) was: female gender (56%), remaining small bowel length ≤ 55 cm, estimated residual small bowel ≤ 28% (p = 0.045) and absence of ICV (56%). Common symptoms of the SBS-ID group were: food intolerance (61%), abdominal distension (50%), vomiting (44%), malabsorption and severe constipation. Complications included FTT (67%) (p = 0.003), bacterial overgrowth with subsequent bloodstream infection (33%) (p = 0.75), and lactic acidosis (11%). Lengthening procedure (STEP) was performed in 11 SBS-ID patients (61%) (p = 0.002). In all patients, STEP operation "rescued" their dysfunctional intestine. Eight of these patients (73%) were weaned from TPN. Survival rate was 100%; however, one SBS-ID patient is a candidate for combined intestinal and liver transplantation. Conclusions: ID is the most common complication of SBS and is the most common cause of IF in non-SBS patients. ID has a high morbidity rate and various clinical manifestations. Successful treatment of these infants may be achieved with the use of tapering enteroplasty. [ABSTRACT FROM AUTHOR]

Purpose: Many disease processes (necrotizing enterocolitis, caustic esophageal injury, malrotation with volvulus), can result in short-gut syndrome (SGS), where remnant intestinal segments may dilate axially, but rarely elongate longitudinally. Here we mechanically characterize a novel model of a self-expanding mesh prototype intestinal expanding sleeve (IES) for use in SGS. Methods: Gut lengthening was achieved using a proprietary cylindrical layered polyethylene terephthalate IES device with helicoid trusses with isometric ends. The IES is pre-contracted by diametric expansion, deployed into the gut and anchored with bioabsorbable sutures. IES expansion to its equilibrium dimension maintained longitudinal gut tension, which may permit remodeling, increased absorptive surface area while preserving vascular and nervous supplies. We performed mechanical testing to obtain the effective force–displacement characterization achieved on these prototypes and evaluated minimal numbers of sutures needed for its anchoring. Furthermore, we deployed these devices in small and large intestines of New Zealand White rabbits, measured IES length–tension relationships and measured post-implant gut expansion ex vivo. Histology of the gut before and after implantation was also evaluated. Results: Longitudinal tension using IES did not result in suture failure. Maximum IES suture mechanical loading was tested using 4–6 sutures; we found similar failure loads of 2.95 ± 0.64, 4 ± 1.9 and 3.16 ± 0.24 Newtons for 4, 6 and 8 sutures, respectively (n = 3, n.s). Pre-contracted IES tubes were deployed at 67 ± 4% of initial length (i.l.); in the large bowel these expanded significantly to 81.5 ± 3.7% of i.l. (p = 0.014, n = 4). In the small bowel, pre-contracted IES were 61 ± 3.8% of i.l.; these expanded significantly to 82.7 ± 7.4% of i.l. (p = 0.0009, n = 6). This resulted in an immediate 24 ± 7.8% and 36.2 ± 11% increase in gut length when deployed in large and small bowels, respectively, with maintained longitudinal tension. Maintained IES induced tension produced gut wall thinning; gut histopathological evaluation is currently under evaluation. Conclusion: IES is a versatile platform for gaining length in SGS, which may be simply deployed via feeding tubes. Our results need further validation for biocompatibility and mechanical characterization to optimize use in gut expansion. [ABSTRACT FROM AUTHOR]

Purpose: The hedgehog (Hh) signaling pathway is one of the key regulators of gastrointestinal tract development. Recent studies point to the role of hedgehog signaling in regulating adult stem cells involved in maintenance and regeneration of intestinal stem cells. The purpose of this study was to evaluate the role of Hh signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS).Methods: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression analysis was used to determine the Hh signaling gene expression profiling. Hh-related genes and protein expression were determined using Real-Time PCR, Western blotting, and immunohistochemistry.Results: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 13 genes related to Hh signaling were investigated. In jejunum, eight genes were down-regulated, three genes up-regulated, and two genes remained unchanged. In ileum, five genes were down-regulated and six genes were unchanged in SBS vs sham animals. SBS rats also demonstrated a significant three- to fourfold decrease in SMO, GIL, and PTCH mRNA, and protein levels (determined by Real-Time PCR and Western blot) compared to control animals.Conclusion: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by an inhibited Hh signaling pathway. Hh signaling may serve as an important mediator of reciprocal interactions between the epithelium and the underlying mesenchymal stroma during intestinal adaptation following massive bowel resection in a rat. [ABSTRACT FROM AUTHOR]

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass. [ABSTRACT FROM AUTHOR]