Small Bowel Transection Research Articles

Small-bowel transection after peroral motorized spiral enteroscopy

Small-bowel transection after peroral motorized spiral enteroscopy

Muscle hypertrophy and neuroplasticity in the small bowel in short bowel syndrome

Short bowel syndrome (SBS) is a severe, life-threatening condition and one of the leading causes of intestinal failure in children. Here we were interested in changes in muscle layers and especially in the myenteric plexus of the enteric nervous system (ENS) of the small bowel in the context of intestinal adaptation. Twelve rats underwent a massive resection of the small intestine to induce SBS. Sham laparotomy without small bowel transection was performed in 10 rats. Two weeks after surgery, the remaining jejunum and ileum were harvested and studied. Samples of human small bowel were obtained from patients who underwent resection of small bowel segments due to a medical indication. Morphological changes in the muscle layers and the expression of nestin, a marker for neuronal plasticity, were studied. Following SBS, muscle tissue increases significantly in both parts of the small bowel, i.e., jejunum and ileum. The leading pathophysiological mechanism of these changes is hypertrophy. Additionally, we observed an increased nestin expression in the myenteric plexus in the remaining bowel with SBS. Our human data also showed that in patients with SBS, the proportion of stem cells in the myenteric plexus had risen by more than twofold. Our findings suggest that the ENS is tightly connected to changes in intestinal muscle layers and is critically involved in the process of intestinal adaptation to SBS.

A CASE SERIES OF 5 RARE ABDOMINAL EMERGENCIES

Gastrointestinal perforation is a common cause of acute abdomen due to peritonitis. The etiology and pathophysiology of gastrointestinal perforations is varied and can range from a small prepyloric perforation that is relatively clean to transection of small or large bowel with spillage of contents in peritoneum with gross contamination. Some of these are more common than others. Here we present 6 cases of rare perforations presenting to us in the casualty, their management and postoperative course in hospital. Methods: We will be assessing the cases of patients, their history, clinical presentation, radiological imaging who presented with acute abdomen secondary to bowel perforation and were intraoperatively diagnosed to have a rare pathology and assess the management and postoperative outcomes. Results: In this case series, 5 rare cases of GI perforations are highlighted including rare cases of posterior gastric perforation, DJ transection, jejunal transection, jejunal perforation, large mesenteric tear and sigmoid colon perforation. All these cases required a different approach in managing intraoperatively. Conclusion: Gastrointestinal perforation is a common cause of acute abdomen and requires emergency surgical intervention. CT imaging has become a fundamental part of the preoperative evaluation and can determine site and cause of perforation.Gastrointestinal tract perforations can occur due to various causes, and most of these perforations are emergency conditions that require early recognition and timely surgical treatment the mainstay of treatment for bowel perforation is surgery. Atypical presentation of perforation can be a challenge to surgeons andshould be prepared to deal with it.

LigaSure Vessel Sealing System for Small Bowel Transection During Roux Limb Construction.

Roux limb construction is an essential part of several major reconstructive hepatobiliary and upper gastrointestinal surgeries. This can be achieved with a stapling device or suturing. For over two decades, the LigaSure vessel sealing systems (Medtronic, MN, USA) have been in use for omental division, mesenteric transection, and sealing of vessels. We used the LigaSure vessel sealing system with a ForceTriad energy platform (Medtronic) for transection of the bowel during the formation of the Roux limb for a Roux-en-Y reconstruction. Between July 2019 and December 2020, patients who had Roux limb construction as part of a pancreato-enteric anastomosis in surgery for chronic pancreatitis were analysed. The data was reviewed from a prospectively maintained database. Fifteen patients had undergone surgery for chronic pancreatitis. The mentioned technique takes approximately eight minutes to construct a Roux limb. There was no bleeding from the gut ends that had been transected. There was no breach in the bowel’s seal. The field was free of enteric contamination. In the post-operative course of these individuals, there was no Roux limb-related morbidity. This procedure is useful because it is cost-effective, time-saving, dependable, and prevents contamination and blood loss. It is also simple to learn and apply.

The effect of pre-resection obesity on post-resection body composition after 75% small bowel resection in rats

In patients with short bowel syndrome, an elevated pre-resection Body Mass Index may be protective of post-resection body composition. We hypothesized that rats with diet-induced obesity would lose less lean body mass after undergoing massive small bowel resection compared to non-obese rats. Rats (CD IGS; age = 2 mo; N = 80) were randomly assigned to either a high-fat (obese rats) or a low-fat diet (non-obese rats), and fed ad lib for six months. Each diet group then was randomized to either underwent a 75% distal small bowel resection (massive resection) or small bowel transection with re-anastomosis (sham resection). All rats then were fed ad lib with an intermediate-fat diet (25% of total calories) for two months. Body weight and quantitative magnetic resonance-determined body composition were monitored. Preoperative body weight was 884 ± 95 versus 741 ± 75 g, and preoperative percent body fat was 35.8 ± 3.9 versus 24.9 ± 4.6%; high-fat vs. low fat diet, respectively (p < 0.0001); preoperative diet type had no effect on lean mass. Regarding total body weight, massive resection produced an 18% versus 5% decrease in high-fat versus low-fat rats respectively, while sham resection produced a 2% decrease vs. a 7% increase, respectively (p < 0.0001, preoperative vs. necropsy data). Sham resection had no effect on lean mass; after massive resection, both high-fat and low-fat rats lost lean mass, but these changes were not different between the latter two rat groups. The high-fat diet and low-fat diet induced obesity and marginal obesity, respectively. The massive resection produced greater weight loss in high-fat rats compared to low-fat rats. The type of dietary preconditioning had no effect on lean mass loss after massive resection. A protective effect of pre-existing obesity on lean mass after massive intestinal resection was not demonstrated.

Modified Antimesenteric Tapering Enteroplasty: An Alternative Technique for the Treatment of Dysfunctional Anastomosis in Patients With Short Bowel.

Several techniques have been described to taper the dilated small bowel to improve intestinal motility and decrease complications related to overdilated small bowel, including longitudinal intestinal lengthening and tapering, serial transverse enteroplasty, and spiral intestinal lengthening and tailoring. We propose an alternative technique designed to optimize bowel function and minimize the effects of recurrent small-bowel bacterial overgrowth in patients with short or ultra-short gut syndrome and dysfunctional anastomosis with maintenance of the actual absorptive surface. The dilated side-to-side anastomosis is identified, and the mesentery leaves from both the proximal and distal small-bowel loops are separated by using blunt dissection. The previous anastomosis is divided longitudinally with a GI stapler. Once the small-bowel transection is completed, 2 separate blind loops of intestine are created, each one with half the circumference of the dilated side-to-side anastomosis. The antimesenteric stapled line is then reinforced with an outer layer of running suture. The blind loops of the tapered small bowel are then trimmed and anastomosed in an end-to-end isoperistaltic fashion in 2 layers. There were no postoperative complications. The length of the tapering ranged from 10 to 23 cm, corresponding to approximately 16% (range, 13%-20%) of the remaining small-bowel length. Three of 4 patients presented significant improvement of their symptoms and were able to have their parenteral support discontinued. Modified antimesenteric tapering enteroplasty is an alternative technique to improve intestinal motility and treat patients with short-bowel syndrome and dysfunctional side-to-side anastomosis without the need for further small-bowel resection. This bowel-sparing technique represents a valuable option in the armamentarium of the surgeon who manages patients with intestinal failure.

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

BackgroundShort bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood.AimsThe aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation.MethodsMale C57BL6/J mice underwent 40% ICR and were followed for 7 or 14 days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded.ResultsUnlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased.Conclusions40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss.

Solution blow spun polymer: A novel preclinical surgical sealant for bowel anastomoses

BackgroundSolution blow spinning is a technique for depositing polymer fibers with promising potential use as a surgical sealant. This study assessed the feasibility and efficacy of solution blow spun polymer (BSP) for sealing bowel perforations in a mouse model of partial cecal transection. We then evaluated its use for reinforcing a surgical anastomosis in a preclinical piglet model. MethodsThree commercially available surgical sealants (fibrin glue, polyethylene glycol (PEG) hydrogel, and cyanoacrylate) were compared to BSP in the ability to seal partially transected cecum in mice. For anastomosis feasibility testing in a piglet model, piglets were subjected to small bowel transection with sutured anastomosis reinforced with BSP application. Outcome measures included anastomotic burst pressure, anastomotic leak rate, 14-day survival, and complication rate. ResultsFor the mouse model, the survival rates for the sealants were 30% for fibrin glue, 20% for PEG hydrogel, 78% for cyanoacrylate, and 67% for BSP. Three of 9 mice died after BSP administration because of perforation leak, failure to thrive with partial obstruction at the perforation site, and unknown causes. All other mice died of perforation leak. The mean burst pressure at 24h was significantly higher for BSP (81mm Hg) when compared to fibrin glue (6mm Hg, p=0.047) or PEG hydrogel (10mm Hg, p=0.047), and comparable to cyanoacrylate (64mm Hg, p=0.91). For piglets, 4 of 4 animals survived at 14days. Mean burst pressures at time of surgery were 37±5mm Hg for BSP and 11±9mm Hg for suture-only controls (p=0.09). ConclusionsSolution blow spinning may be an effective technique as an adjunct for sealing of gastrointestinal anastomosis. Further preclinical testing is warranted to better understand BSP properties and alternative surgical applications.

Small Bowel Transection as a Rare Complication of Lumbar Disc Surgery: Report of a Case.

Small bowel injury resulting from the perforation of anterior longitudinal ligament during lumbar disc surgery is very rare, with prompt diagnosis being difficult. In the present study, we present a case of intestinal transection and discuss technical methods to prevent this complication with a review of literature. A 34-year-old woman, who had a history of lumbar disc surgery one day before, presented with abdominal pain. On physical examination, rebound tenderness and muscular rigidity were obtained, with emergency abdominal computed tomography confirming the diagnosis of perforation by showing free air and free fluid. The patient underwent laparoscopic exploration; the small bowel was found transected 60 cm proximally to the ileocecal valve. Since there were no signs of generalized peritonitis, the abdomen was irrigated with sterile saline, and side-to-side ileal anastomosis was performed. Her postoperative course was uneventful and she was discharged on the postoperative fifth day. Although bowel perforation after discectomy rarely occurs, it might be very fatal unless a prompt diagnosis is achieved. Especially, an early postoperative course can mask the symptoms and signs. Therefore, general surgeons should be aware of such a complication after lumbar disc surgery, and spine surgeons must be more cautious while they are using retractors in the intervertebral space.

Coughing-induced bowel transection in a patient with an incarcerated inguinal hernia: a case report

IntroductionAlthough blunt trauma to a hernia-containing bowel is known to cause bowel perforation, this report documents the first incident of a small bowel transection following a non-traumatic event.Case presentationWe report the case of a 49-year-old African American man with a chronic incarcerated inguinal hernia awaiting elective repair. He presented to the Emergency Department with abdominal pain following an episode of coughing. On examination, he was found to have peritonitis. He underwent exploratory laparotomy, and had a complete small bowel transection. A bowel resection with primary anastomosis was performed, as well an inguinal hernia repair.ConclusionChronic hernia incarceration can lead to weakening and ischemia of the bowel, and minimal trauma can lead to perforation of the weakened segment. In such presentations, bowel resection and repair of the defect with a biological material is safe and feasible.

Spontaneous rupture of incisional hernia with transection and perforation of small bowel: A case report

Spontaneous rupture of an abdominal hernia is rare and usually occurs in incisional or recurrent groin hernia. The hernial contents can be covered primarily by mesh repair if the general condition of the patient and local condition of the operative site allows it or it can be covered by skin followed by delayed mesh repair. We report a case of spontaneous rupture of incisional hernia with transection of small bowel and perforation in a 60-year-old woman who had developed hernia following a cesarean operation and was managed by resection and end-to-end anastomosis and herniorrhaphy.

Seat Belt Injuries of the Abdominal Aorta in Adults—Case Report and Literature Review

Blunt abdominal trauma with major vascular involvement is found to be rare. Although few series have been reported in the literature, the true incidence of blunt abdominal aortic injury is unknown. Different modalities of blunt trauma may occur among civilians with steering wheel and seat belt injury secondary to motor vehicle accident the most frequent. Mechanical forces produce variable patterns of injury; therefore, the onset of signs and symptoms can be different. Dissection and thrombosis of the abdominal aorta have been frequently described among seat-belted adult patients with major vascular involvement. The associated abdominal viscus and/or vertebral lesions must always be taken into account. Prompt diagnosis allows adequate surgical treatment. We present the case of a 66-year-old woman, restrained front passenger involved in a motor vehicle collision, who had small bowel transection, vertebral fractures, and aortic partial occlusion below inferior mesenteric artery with bilateral iliac artery involvement. Along with the case reported, the purpose of this study is to highlight and compare features and management of the previous cases described in the English literature.

Dietary Sulfur Amino Acid Supplementation Reduces Small Bowel Thiol/Disulfide Redox State and Stimulates Ileal Mucosal Growth after Massive Small Bowel Resection in Rats

Following massive small bowel resection in animal models, the remnant intestine undergoes a dynamic growth response termed intestinal adaptation. Cell growth and proliferation are intimately linked to cellular and extracellular thiol/disulfide redox states, as determined by glutathione (GSH) and GSH disulfide (GSSG) (the major cellular redox system in tissues), and cysteine (Cys) and its disulfide cystine (CySS) (the major redox system in plasma), respectively. The study was designed to determine whether dietary supplementation with sulfur amino acids (SAA) leads to a greater reduction in thiol/disulfide redox state in plasma and small bowel and colonic mucosa and alters gut mucosal growth in an established rat model of short bowel syndrome (SBS). Adult rats underwent 80% jejunal-ileal resection (RX) or small bowel transection (surgical control) and were pair-fed either isonitrogenous, isocaloric SAA-adequate (control) or SAA-supplemented diets (218% increase vs. control diet). Plasma and gut mucosal samples were obtained after 7 d and analyzed for Cys, CySS, GSH, and GSSG concentrations by HPLC. Redox status (Eh) of the Cys/CySS and GSH/GSSG couples were calculated using the Nernst equation. SAA supplementation led to a greater reduction in Eh GSH/GSSG in jejunal and ileal mucosa of resected rats compared with controls. Resected SAA-supplemented rats showed increased ileal adaptation (increased full-thickness wet weight, DNA, and protein content compared with RX control-fed rats; increased mucosal crypt depth and villus height compared with all other study groups). These data suggest that SAA supplementation has a trophic effect on ileal adaptation after massive small bowel resection in rats. This finding may have translational relevance as a therapeutic strategy in human SBS.

Local glutathione redox status does not regulate ileal mucosal growth after massive small bowel resection in rats.

Glutathione (GSH) concentration affects cell proliferation and apoptosis in intestinal and other cell lines in vitro. However, in vivo data on gut mucosal GSH redox status and cell turnover are limited. We investigated the effect of altered GSH redox status on the ileal mucosa in a rat model of short bowel syndrome following massive small bowel resection (SBR). Rats underwent 80% mid-jejunoileal resection (RX) or small bowel transection (TX; as operative controls), with administration of either saline or D, L-buthionine-sulfoximine (BSO), a specific inhibitor of cellular GSH synthesis. Ileal mucosal redox, morphology, and indices of cell proliferation and apoptosis were determined at different days after surgery. Ileal GSH redox status was assessed by GSH and GSH disulfide (GSSG) concentrations and the redox potential of GSH/GSSG (Eh). Ileal lipid peroxidation [free malondialdehyde (MDA)] was measured as an index of lipid peroxidation. BSO markedly decreased ileal mucosal GSH, oxidized GSH/GSSG Eh, and increased MDA content without inducing morphological damage as assessed by light or electron microscopy. As expected, SBR stimulated adaptive growth of ileal villus height and total mucosal height at 7 d after surgery, but this response was unaffected by BSO treatment despite a modest increase in crypt cell apoptosis. Ileal cell proliferation (crypt cell bromodeoxyuridine incorporation) increased at 2 d after SBR but was unaffected by BSO. Collectively, our in vivo data show that marked depletion of ileal GSH and oxidation of the GSH redox pool does not alter indices of ileal epithelial proliferation or SBR-induced ileal mucosal adaptive growth.

Stimulation of colonic mucosal growth associated with oxidized redox status in rats

Limited data in animal models suggest that colonic mucosa undergoes adaptive growth following massive small bowel resection (SBR). In vitro data suggest that intestinal cell growth is regulated by reactive oxygen species and redox couples [e.g., glutathione (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) redox]. We investigated the effects of SBR and alterations in redox on colonic growth indexes in rats after either small bowel transection (TX) or 80% midjejunoileal resection (RX). Rats were pair fed +/- blockade of endogenous GSH synthesis with buthionine sulfoximine (BSO). Indexes of colonic growth, proliferation, and apoptosis and GSH/GSSG and Cys/CySS redox potentials (E(h)) were determined. RX significantly increased colonic crypt depth, number of cells per crypt, and epithelial cell proliferation [crypt cell bromodeoxyuridine (BrdU) incorporation]. Administration of BSO markedly decreased colonic mucosal GSH, GSSG, and Cys concentrations in both TX and RX groups, with a resultant oxidation of GSH/GSSG and Cys/CySS E(h). BSO did not alter colonic crypt cell apoptosis but significantly increased all colonic mucosal growth indexes (crypt depth, cells/crypt, and BrdU incorporation) in both TX and RX groups in a time- and dose-dependent manner. BSO significantly decreased plasma GSH and GSSG, oxidized GSH/GSSG E(h), and increased plasma Cys and CySS concentrations. Collectively, these data provide in vivo evidence indicating that oxidized colonic mucosal redox status stimulates colonic mucosal growth in rats. The data also suggest that GSH is required to maintain normal colonic and plasma Cys/CySS homeostasis in these animal models.

Dietary glutamine increases secretory IgA and may suppress gram‐negative bacterial translocation in a rat model of short bowel syndrome (SBS)

Background Normal gut barrier function is dependent upon mucosal gut-associated lymphoid tissue and anatomic factors (e.g. tight junctions). Previous studies in animal models of SBS after massive small bowel resection (SBR) show that increased translocation of luminal bacteria (BT) may occur, signifying abnormal gut barrier function. In this study, we investigated BT, fecal levels of secretory IgA (sIgA) and responses to dietary glutamine (GLN) and oral antibiotic therapy in a rat model of combined small-bowel-colonic resection. Methods Adult Sprague-Dawley rats underwent resection of 60% of distal small bowel and proximal colon (RX) or small bowel transection (TX; control). Rats were pair-fed diets ± L-glutamine (GLN; 4% of diet) for 3 weeks after intestinal surgery. Oral antibiotics [neomycin, metronidazole, and polymyxin; (Abx)] were given in one RX group. At sacrifice, mesentery lymph nodes (MLN) were cultured for gram-negative bacteria as an index of BT. Fecal sIgA was determined on days 1, 6, 13 and 21 by ELISA. Results RX significantly increased bacterial positivity in MLN (1/9 TX rats vs 7/9 RX rats; P<0.02), concomitant with a marked increase in fecal sIgA over time (15-fold increase RX vs TX day 21; P<0.001). Oral Abx eliminated RX-induced BT and decreased fecal sIgA (P<0.02). Dietary GLN after RX markedly increased sIgA (P<0.001 vs all other groups) and blunted BT (2/6; NS). Conclusion RX-induced BT occurs despite an increase in sIgA. Dietary GLN augments the sIgA response, which may play a role in protection against BT in this model. Supported by DK55850.

Proteasome gene upregulation: a possible mechanism for intestinal adaptation

Background/Purpose The mechanisms that control intestinal adaptation remain unknown. To better understand the adaptive process, microarray technology was used to analyze gene expression in a rat model of intestinal adaptation. Methods Adult male Sprague-Dawley rats underwent either a massive small bowel resection (70%) with anastomosis or a sham operation with small bowel transection and reanastomosis. After 21 days, ileal mucosa RNA was extracted. Individual RNA samples (n = 5 per group) were labeled and hybridized to 10 separate RAE 230A rat GeneChips. The signal values were calculated and the 2 groups were compared using a t test with the multiple testing correction of Benjamini and Hochberg (false discovery rate of 10%). Probe sets were analyzed for overrepresented physiologic pathways using Expression Analysis Systematic Explorer (EASE). Results Of the 15,866 probe sets on the RAE 230A GeneChip, 5437 probe sets were unexpressed and excluded. Of the remaining 10,429 probe sets, several overrepresented pathways (EASE score <0.01 after Bonferroni correction) were identified. Further analysis revealed that 13 probe sets related to proteasome degradation (an enzyme complex implicated in the regulation of cell proliferation) were significantly upregulated in the intestinal adaptation group compared to the sham group. Conclusions Proteasomes may play a critical role in regulating the proliferation of intestinal mucosa during intestinal adaptation.

Impaired Intestinal Cell Proliferation and Cell Death in Leptin-Deficient Obese Mice

After massive small-bowel resection and loss of absorptive capacity, residual intestine has compensatory ability to adapt by cellular hyperplasia and increased absorptive function. Growth factors have been shown to enhance intestinal adaptation, but the mechanisms involved are not well defined. Leptin has been shown to function as a trophic factor in the intestine and enhances carbohydrate absorption after small-bowel resection. Therefore, we hypothesized that leptin deficiency may impair the adaptive response by modulating cellular proliferation or cell death after small-bowel resection. Twelve-week-old male lean control (C57BL/6J, n = 28) and leptin-deficient (Lep(ob), n = 24) obese mice underwent sham laparotomy, intestinal transection, or 50% proximal small-bowel resection. Mice were killed at 48 hours postresection, and remnant intestine was harvested. Phenotypic analysis to assess adaptation included characterization of cell proliferation (percentage BrdU incorporation), apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling assay), and morphometric response (villus height, crypt depth). The percentage S-bromodeoxyuridine (BrdU) incorporation and apoptotic indices of obese transected mice were significantly lower than lean transected mice (7.3 vs 21.9% and 0.70 vs 1.53% respectively, p < .05). In resected animals, the percentage BrdU incorporation and apoptotic indices of obese resected mice were significantly lower than for lean resected (6.1 vs 22.0% and 0.93 vs 1.80% respectively, p < .05). No differences between groups, regardless of surgery, were identified in villus height or crypt depth. Therefore, we conclude that leptin deficiency impairs both cell proliferation and cell death in the early adaptive period after either small-bowel transection or resection.

Comparative Effects of Glucagon‐Like Peptide‐2 (GLP‐2), Growth Hormone (GH), and Keratinocyte Growth Factor (KGF) on Markers of Gut Adaptation After Massive Small Bowel Resection in Rats

Administration of specific growth factors exert gut-trophic effects in animal models of massive small bowel resection (SBR); however, little comparative data are available. Our aim was to compare effects of a human glucagon-like peptide-2 (GLP-2) analog, recombinant growth hormone (GH) and recombinant keratinocyte growth factor (KGF) on jejunal, ileal, and colonic growth and functional indices after 80% SBR in rats. Thirty-seven male rats underwent small bowel transection (sham operation) with s.c. saline administration (control; Tx-S; n = 7) or 80% midjejuno-ileal resection (Rx) and treatment with either s.c. saline (Rx-S, n = 7), GLP-2 at 0.2 mg/kg/d (Rx-GLP-2; n = 8), GH at 3.0 mg/kg/d (Rx-GH; n = 8), or KGF at 3.0 mg/kg/d (Rx-KGF; n = 7) for 7 days. All groups were pair-fed to intake of Rx-S rats. Gut mucosal cell growth indices (wet weight, DNA and protein content, villus height, crypt depth, and total mucosal height) were measured. Expression of the cytoprotective trefoil peptide TFF3 was determined by Western blot. Gut mucosal concentrations of the tripeptide glutathione (L-glutamyl-L-cysteinyl-glycine) and glutathione disulfide (GSSG) were measured by high-performance liquid chromatography and the glutathione/GSSG ratio calculated. SBR increased adaptive growth indices in jejunal, ileal, and colonic mucosa. GLP-2 treatment increased jejunal villus height and jejunal total mucosal height compared with effects of resection alone or resection with GH or KGF treatment. Both GH and KGF modestly increased colonic crypt depth after SBR. SBR did not affect small bowel or colonic goblet cell number or TFF3 expression; however, goblet cell number and TFF3 expression in both small bowel and colon were markedly up-regulated by KGF treatment and unaffected by GLP-2 and GH. SBR oxidized the ileal and colonic mucosal glutathione/GSSG redox pools. GLP-2 treatment after SBR increased the glutathione/GSSG ratio in jejunum, whereas KGF had an intermediate effect. In addition, GLP-2 (but not GH or KGF) prevented the SBR-induced oxidation of the glutathione/GSSG pools in both ileum and colon. GLP-2 exerts superior trophic effects on jejunal growth and also improves mucosal glutathione redox status throughout the bowel after massive SBR in rats. Both GH and KGF increase colonic mucosal growth in this model. KGF alone potently increases gut mucosal goblet cell number and expression of the cytoprotective trefoil peptide TFF3. The differential effects of GLP-2, GH and KGF administration in this model of short bowel syndrome suggest that individual therapy with these growth factors may not be an adequate strategy to maximally improve adaptive gut mucosal growth and cytoprotection after massive small intestinal resection. Future research should address the use of these agents in combination in short bowel syndrome.

IGF-I augments resection-induced mucosal hyperplasia by altering enterocyte kinetics.

Our objective was to determine if exogenous insulin-like growth factor-I (IGF-I) augments the adaptive growth response to mid small bowel resection in association with changes in enterocyte kinetics. We determined structural adaptation and concomitant changes in enterocyte proliferation, apoptosis, and migration of the jejunum in growing, parenterally fed rats after mid small bowel resection or small bowel transection, and treatment with IGF-I or vehicle. IGF-I treatment in resected rats significantly increased jejunal mucosal mass by 20% and mucosal concentrations of protein and DNA by 36 and 33%, respectively, above the response to resection alone. The enhancement of resection-induced adaptive growth and cellularity by IGF-I reflected an increase in enterocyte proliferation, an expansion of the proliferative compartment in the crypt, and no further decrease in enterocyte apoptosis or increase in enterocyte migration beyond the effects of resection. The ability of IGF-I to augment the mucosal hyperplasia stimulated by the endogenous response to resection substantiates the role of IGF-I as an intestinal mitogen that promotes tissue regeneration.