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Short bowel syndrome / intestinal failure (SBS/IF) is a rare and debilitating disease process that mandates a multidisciplinary approach in its management. Inflammatory bowel disease (IBD), in particular Crohn's disease (CD), predisposes patients to development of SBS/IF. This review discusses SBS/IF from the perspective of IBD, with an emphasis on prevention and treatment in the setting of CD. The aims of this review are to emphasize the unique treatment goals of the newly diagnosed SBS/IF patient, and highlight the role of both medical and surgical therapies in the management of IBD-related SBS/IF, including intestinal transplantation.

Fibrotic strictures are one of the most severe complications of Crohn’s Disease (CD). They occur in about 50% of patients at five years and in 70% at ten years of the diagnosis. The only treatment available for symptomatic fibrotic strictures is surgical resection and endoscopic dilation. Both strategies are associated with a high rate of recurrence, and with multiple surgical resections, which pose the threat of surgical morbidity and short bowel syndrome. Therefore, it is crucial to identify, early, the patients more prone to develop intestinal fibrosis to intensify follow-ups, switch to more aggressive treatments, and suggest lifestyle modifications. Scarce data are available concerning biomarkers and genetic determinants to predict which patient will develop intestinal fibrosis. Biologic or clinical markers would be useful to determine this subgroup of CD patients and to predict the onset of intestinal fibrosis and, ideally, its severity. Furthermore, the identification of environmental risk factors may suggest lifestyle changes aimed at modifying the natural course, thus decreasing the risk of complicated CD. In this review, we will critically revise clinical, environmental, genetic, and serologic factors that have been associated with a complicated CD course with a particular focus on the fibrostenosing phenotype and their possible implications as predictive factors of intestinal fibrosis.

Crohn's disease is a chronic and progressive inflammatory disorder of the gastrointestinal tract. Despite the availability of powerful immunosuppressants, many patients with Crohn's disease still require one or more intestinal resections throughout the course of their disease. Multiple resections and a progressive reduction in bowel length can lead to the development of short bowel syndrome, a form of intestinal failure that compromises fluid, electrolyte, and nutrient absorption. The pathophysiology of short bowel syndrome involves a reduction in intestinal surface area, alteration in the enteric hormonal feedback, dysmotility, and related comorbidities. Most patients will initially require parenteral nutrition as a primary or supplemental source of nutrition, although several patients may eventually wean off nutrition support depending on the residual gut anatomy and adherence to medical and nutritional interventions. Available surgical treatments focus on reducing motility, lengthening the native small bowel, or small bowel transplantation. Care of these complex patients with short bowel syndrome requires a multidisciplinary approach of physicians, dietitians, and nurses to provide optimal intestinal rehabilitation, nutritional support, and improvement in quality of life.

Introduction: Crohn’s disease (CD) has an annual incidence per 100.000 person-year of 20.2 in North America and 12.7 in Europe, and the purpose of this review is to evaluate its medical management, from diagnosis to transplant. Pharmacologic manipulation with nutritional care aims to achieve and maintain remission, but more than half of patients will undergo an intestinal resection, very often repeated over time. They could experience short bowel syndrome (SBS) requiring total parenteral nutrition (TPN). Intestinal transplantation (ITx) represents an alternative in case of irreversible intestinal failure (IF) with life-threatening TPN complications. Patient survival after ITx is 79%, 53% and 43% at 1, 3 and 5 years respectively, with no differences among ITx for other disorders. Areas covered: The research discussed medical therapy with nutritional support, evaluating the role of endoscopy, surgery and transplant in CD. A systematic literature review was conducted using the PubMed search engine up to May 31th, 2017 without restriction of the language. The decision on paper’s eligibility was reached by consensus between the 3 screening authors. Expert commentary: CD treatment is mainly medical, leaving endoscopy and surgery for a complex course. ITx represents a therapeutic option if TPN complications with IF arise. Fil: Lauro, Augusto. Universidad de Bologna; Italia Fil: D'Amico, Francesco. Azienda Ospedaliera Di Padova; Italia Fil: Gondolesi, Gabriel Eduardo. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina

Many patients with Crohn’s disease (CD) require surgery. Indications for surgery include failure of medical treatment, bowel obstruction, fistula or abscess formation. The most common surgical procedure is resection. In jejunoileal CD, strictureplasty is an accepted surgical technique that relieves the obstructive symptoms, while preserving intestinal length and avoiding the development of short bowel syndrome. However, the role of strictureplasty in duodenal and colonic diseases remains controversial. In extensive colitis, after total colectomy with ileorectal anastomosis (IRA), the recurrence rates and functional outcomes are reasonable. For patients with extensive colitis and rectal involvement, total colectomy and end-ileostomy is safe and effective; however, a few patients can have subsequent IRA, and half of the patients will require proctectomy later. Proctocolectomy is associated with a high incidence of delayed perineal wound healing, but it carries a low recurrence rate. Patients undergoing proctocolectomy with ileal pouch-anal anastomosis had poor functional outcomes and high failure rates. Laparoscopic surgery has been introduced as a minimal invasive procedure. Patients who undergo laparoscopic surgery have a more rapid recovery of bowel function and a shorter hospital stay. The morbidity also is lower, and the rate of disease recurrence is similar compared with open procedures.

Crohn’s disease (CD) is a chronic condition with an unpredictable course that is frequently characterized by a high rate of recurrence and in most patients a need for surgical treatment. Approximately 60% to 70% of patients require at least one surgical treatment, 1 often for bowel obstruction. In the past, wide resections have proved to be ineffective in preventing relapses, and repeated resective surgery can lead to malabsorption and short bowel syndrome in many instances. 2–5 During the past decade, strictureplasty and new bowel-sparing techniques have therefore been proposed for the conservative treatment of intestinal strictures. 4,6–9 The early postoperative results show that these techniques are effective and safe in terms of complications and death; further, long-term clinical and surgical recurrence rates are comparable with those observed after conventional resective surgery. 10–12 However, despite these encouraging results, the clinical course of CD and the behavior of the diseased intestinal walls after conservative surgery have so far been little investigated. Ultrasonography has recently been proposed as an accurate means of evaluating bowel walls in patients with CD. 13–18 Several studies have shown that transabdominal ultrasound can detect transmural changes and the degree of thickness of intestinal bowel wall, 19–21 and this technique is as accurate as barium radiology or scintigraphy in assessing the presence, location, and extent of inflammatory bowel disease, 15,18,21 particularly in bowel segments such as the ileum that are not easily to assess by endoscopy. It has also been shown that ultrasound can detect recurrences after “radical” surgical resections 22,23 and the intestinal complications of CD. 24,25 No study has yet evaluated the behavior of the thickness of diseased intestinal wall after conservative surgery in CD, or whether the presurgical ultrasound characteristics and postsurgical behavior of bowel wall thickness (BWT) have prognostic implications on clinical and surgical recurrences. The aims of this study were to evaluate in patients with CD using transabdominal ultrasound the morphologic characteristics of the diseased bowel wall before and after conservative surgery and to assess whether these characteristics and their postoperative behavior are useful prognostic factors for clinical and surgical recurrence after conservative surgery.

Summary Background & aims Short bowel syndrome (SBS) and intestinal failure (IF) are multi-factorial conditions which in adults result from extensive intestinal resection. NOD2 is an intracellular pattern recognition receptor associated with CD. An unexpected high frequency of NOD2 mutations has been found in patients undergoing intestinal transplantation (35%). The role of NOD2 in a cohort with SBS/IF not specifically requiring intestinal transplantation has not been studied yet. Methods The course of 85 patients with non-malignant SBS/IF was characterized. The major NOD2 mutations, as well as ATG16L1 and IL23R were determined. The allele frequencies were compared to the published frequencies of CD patients and controls. Results In non-CD patients (72%) allele frequencies of NOD2 mutations were statistically more frequent than in controls (14% vs 6%, p = 0.006). In CD patients (28%) allele frequencies were not different between SBS and controls (29% vs 22%, p = 0.23). NOD2 mutations were neither associated with parameters potentially heralding the need for transplantation nor with an earlier time to the indication for intestinal transplantation. Conclusions NOD2 mutations are associated with the development of SBS/IF in the absence of CD, but not with specific complications. NOD2 mutations may increase the risk for more extensive intestinal resection or may impair intestinal adaptation.

Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, as reported for GLP-1 in diabetes therapy and insulinoma diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal actions translated into preliminary clinical studies using the GLP-2 analogue teduglutide for treatment of short bowel syndrome and Crohn's disease, remains poorly characterized in terms of expression of its receptor in tissues of interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and 148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2 receptor expression was present in 68% of gastrointestinal stromal tumors (GIST). Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus, with significant up-regulation in active Crohn's disease. The GLP-2 receptors in GIST may be used for clinical applications like in vivo targeting with radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over-expressed GLP-2 receptor in the myenteric plexus may represent the morphological correlate of the clinical target of teduglutide in Crohn's disease.

Patients with Crohn's disease are at high risk for recurrent disease and often undergo multiple operations. Our aims were to evaluate surgical management and outcome of patients with Crohn's disease who develop short bowel syndrome (SBS) and to identify factors leading to this complication. We reviewed the records of 170 adult patients with SBS evaluated over a 20-year period. Thirty (18%) had Crohn's disease. SBS was defined as an intestinal remnant less than 180 cm with associated malabsorption. There were 20 women and 10 men ranging in age from 18 to 62 years. Eighteen (60%) presented initially with ileocolonic disease, seven (23%) with colonic disease, and five (17%) with small intestinal disease. The interval from initial diagnosis to development of SBS ranged from 2 to 32 years, with 21 patients (71%) having an interval greater than 15 years. The number of resections leading to SBS varied from 2 to 12 with 24 patients (80%) having four or fewer resections. Nineteen patients (63%) had an ostomy. Small intestinal remnant length was less than 60 cm in 10 patients, 60 to 120 cm in six patients, and greater than 120 cm in 14 patients. Only one patient underwent stricturoplasty before developing SBS. Five patients were initially diagnosed as having ulcerative colitis and underwent a pouch procedure, which was subsequently resected. Twenty patients (67%) required parenteral nutrition. Three patients have undergone reversed intestinal segment to slow intestinal transit. Two patients underwent intestinal transplantation. Two patients have died: one from parenteral nutrition-related liver failure and the other after intestinal transplantation. Crohn's disease remains a common cause of SBS. Aggressive resectional therapy, surgical complications, and errors in initial diagnosis contribute to development of SBS in these patients. Selected patients are candidates for surgical therapy for SBS.

Evidence is presented that many of the enteric and systemic manifestations after jejunoileal bypass can be related to an inflammatory process within the bypassed small bowel rather than to the surgically induced sequelae of a short bowel syndrome with malabsorption. Invasion of the excluded segment by fecal flora was associated with a histologically demonstrable inflammatory response of the mucosa. The disorder was of variable severity and duration and occurred in the majority of 28 bypass patients. Progression to a clinical syndrome resembling an acute abdomen occurred in about 15% of the patients. Small bowel ileus and, in some patients, obstruction of the colon were suggested by physical signs and x-ray findings. Surgical exploration in such instances demonstrated an inflammaotry process of the excluded small bowel loops with severe distention of this segment and of the colon, but not organic obstruction. Pneumatosis cystoides intestinalis was a sequal in two patients. Exudative protein loss was documented in the severe cases. Most of the systemic sequelae are comparable to those seen with inflammatory diseases of the bowel such as Crohn's disease. Fever, excessive weight and lean tissue loss, and the involvement of skin, blood vessels, joints and possibly, the liver suggest an immune response as a common factor in the pathogenesis. The clinical improvement with antibiotics such as metronidazole or with restitution of normal bowel continuity indicates that the bacterial flora in the excluded small bowel segment or its byproducts are causally related to the systemic complications. Hyperoxaluria may be primarily the sequela of steatorrhea and not of the inflammatory process.

The authors have investigated intestinal absorption of folic acid by jejunal perfusion with a triple lumen tube in five subjects with regional enteritis. The subjects' intestinal disabilities ranged from terminal ileitis to short bowel syndrome. Two had steatorrhea and two had low serum folate levels. Absorption of pteroylglutamic acid was normal in all five. This suggests that folic acid deficiency, common in this disorder, is largely caused by malnutrition, not malabsorption.

Total parenteral nutrition now permits long-term survival in patients after massive intestinal resection. Surgical therapy for the short-bowel syndrome is still largely experimental and cannot be recommended routinely. Thus, prevention of intestinal resection and conservation of intestinal length, when resection is necessary, should be emphasized. Strategies are presented that can be employed to preserve intestinal length when surgery is required in patients with a shortened bowel. These include strictureplasty, minimal resection, serosal patching, and intestinal tapering. In suitable candidates strictureplasty can relieve obstruction from strictures while avoiding resection. Minimal resection of involved intestine can be performed safely in selected patients with radiation injury or Crohn's disease. Serosal patching is an alternative to resection for the treatment of perforation or strictures of the intestine. Intestinal tapering can improve the function of dilated intestinal segments and eliminate the need for resection in intestinal atresia. The judicious use of these procedures can preserve intestinal length and obviate the need for long-term parenteral nutrition in patients after massive intestinal resection.