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Background: Short bowel syndrome is the most common cause of intestinal failure, with morbidity and mortality linked to remanent small intestine length. There is no current standard for noninvasive bowel length measurement., Materials and Methods: The literature was systematically searched for articles describing measurements of small intestine length from radiographic studies. Inclusion required reporting intestinal length as an outcome and use of diagnostic imaging for length assessment compared to a ground truth. Two reviewers independently screened studies for inclusion, extracted data, and assessed study quality., Results: Eleven studies met the inclusion criteria and reported small intestinal length measurement using four imaging modalities: barium follow-through, ultrasound, computed tomography, and magnetic resonance. Five barium follow-through studies reported variable correlations with intraoperative measurements (r = 0.43-0.93); most (3/5) reported underestimation of length. US studies (n = 2) did not correlate with ground truths. Two computed tomography studies reported moderate-to-strong correlations with pathologic (r = 0.76) and intraoperative measurements (r = 0.99). Five studies of magnetic resonance showed moderate-to-strong correlations with intraoperative or postmortem measurements (r = 0.70-0.90). Vascular imaging software was used in two studies, and a segmentation algorithm was used for measurements in one., Conclusions: Noninvasive measurement of small intestine length is challenging. Three-dimensional imaging modalities reduce the risk of length underestimation, which is common with two-dimensional techniques. However, they also require longer times to perform length measurements. Automated segmentation has been trialed for magnetic resonance enterography, but this method does not translate directly to standard diagnostic imaging. While three-dimensional images are most accurate for length measurement, they are limited in their ability to measure intestinal dysmotility, which is an important functional measure in patients with intestinal failure. Future work should validate automated segmentation and measurement software using standard diagnostic imaging protocols., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Short bowel syndrome is a devastating gastrointestinal disorder in which decreased bowel length results in inadequate absorption causing nutritional deficiencies. Current treatment options are accompanied by significant morbidity. We have proposed spring-mediated distraction enterogenesis as a method to lengthen bowel with success seen in porcine jejunum. We hypothesize that spring-mediated distraction enterogenesis can be demonstrated in porcine ileum with preservation of ileal structure and function., Materials and Methods: Laparotomy was performed on juvenile female mini-Yucatan pigs and a gelatin-encapsulated compressed nitinol spring was inserted into the ileal lumen and affixed proximally and distally. A control segment distal to the spring segment was marked with sutures. Postoperatively, pigs were placed on a liquid diet and euthanized on postoperative day 7. Spring and control segments were measured and processed for immunohistochemistry to evaluate for the presence of vitamin B12-intrinsic factor cotransporter, chromogranin A-producing cells, and 5-HT producing cells., Results: All seven pigs survived to postoperative day 7 with no adverse effects. On average, pigs gained 84.3 ± 66.4 g/d. Spring segments lengthened 1.5 ± 0.7 cm with a relative lengthening by 128% ± 56%, which was statistically significant when compared to control (P < 0.01). The average density of chromogranin-A cells in control compared to spring segments was not significantly changed (2.9 ± 1.1 cells/mm versus 3.2 ± 1.2 cells/mm, P = 0.17). Both vitamin B12-intrinsic factor cotransporter and 5-HT producing cells were present in both control and lengthened ileum., Conclusions: Intraluminal nitinol springs significantly lengthened porcine ileum. The increase in density of enteroendocrine cells may indicate enhanced endocrine function of the lengthened ileum., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Short bowel syndrome (SBS) results from significant intestinal loss and is characterized by insufficient absorption of nutrients and fluids. Preclinical large animal SBS models typically require parenteral nutrition (PN) support and may not be appropriate for studying interventions to improve intestinal absorption or adaptation. Here, we describe the development of a porcine SBS model that does not require PN support., Methods: Eight male Yorkshire piglets underwent either a 75% or 90% jejunoileal resection (n = 5) or no resection (n = 3). Continuous enteral nutrition (EN) was provided via a gastrostomy tube. The final SBS model consisted of a 75% resection and nutrition provided via combination EN (60%) and per oral pig chow (40%). Body weight and concentration of fat-soluble vitamins were assessed on postoperative days (POD) 7, 14, and 21. For assessing fat malabsorption, the coefficient of fat absorption (CFA) was calculated following a 72-h stool collection., Results: Resected animals had decreased weight gain compared to unresected controls (POD21 + 8.3% versus +28.8%, P = 0.048). Vitamin D concentration was significantly lower in resected animals compared to controls on POD 7, POD 14, and POD 21. Serum vitamin E concentration was also lower on POD 21. Resected animals developed fat malabsorption with lower CFA (76.5% versus 95.3%, P = 0.014)., Conclusions: We describe the development of a porcine SBS model that does not require PN support. Piglets in this model gain less weight, demonstrate fat malabsorption, and develop fat-soluble vitamin deficiencies. This model will benefit investigations of intestinal absorption or adaptation while potentially decreasing costs and confounding complications related to PN administration., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Murine ileocecal resection (ICR) has been used to investigate intestinal adaptation. The established model often includes the sacrifice of significant length of the proximal colon. Here, we optimized a highly selective vascular approach to the ICR, with primary jejunal-colic anastomosis yielding maximal colonic preservation., Materials and Methods: Forty C57BL/6 mice underwent a highly vascularly selective ICR. The terminal branches of the ileocecal artery are isolated apart from the mesenteric branches supplying the small bowel to be resected. The distal 50% of small bowel and cecum are resected; a primary jejuno-colonic anastomosis is performed. Animals were sacrificed at postoperative weeks 2 (n = 10) and 10 (n = 29). Proximal 50% small bowel resection (SBR) with jejuno-ileal anastomosis was also performed for comparison., Results: The entire colon (with exception of the cecum) was preserved in 100% of animals. Ninety-seven percent of animals survived to postoperative week 10, and all exhibited structural adaptation in the remnant small intestine epithelium. Crypts deepened by 175%, and villi lengthened by 106%, versus 39% and 29% in the proximal SBR cohort, respectively. Colonic proliferation, structural adaptation, and functional adaptation (measured by p-histone 3, luminal-facing apical crypt border size, and sucrase isomaltase, respectively) were increased in ICR compared with proximal SBR., Conclusions: Highly selective isolation of the cecal vasculature allows for greater colon preservation and yields enhanced remnant intestine epithelial adaptation. ICR is also associated with greater colonic adaptation and unique plasticity toward an intestinal phenotype. These findings underscore major differences between resection sites and offer insights into the critical adaptive mechanisms in response to massive intestinal loss., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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

Background: Distraction enterogenesis has been investigated as a novel treatment for short bowel syndrome (SBS). With variable intestinal sizes, it is critical to determine safe, translatable spring characteristics in differently sized animal models before clinical use. Nitinol springs have been shown to lengthen intestines in rats and pigs. Here, we show spring-mediated intestinal lengthening is scalable and feasible in a murine model., Materials and Methods: A 10-mm nitinol spring was compressed to 3 mm and placed in a 5-mm intestinal segment isolated from continuity in mice. A noncompressed spring placed in a similar fashion served as a control. Spring parameters were proportionally extrapolated from previous spring parameters to accommodate the smaller size of murine intestines. After 2-3 wk, the intestinal segments were examined for size and histology., Results: Experimental group with spring constants, k = 0.2-1.4 N/m, showed intestinal lengthening from 5.0 ± 0.6 mm to 9.5 ± 0.8 mm (P < 0.0001), whereas control segments lengthened from 5.3 ± 0.5 mm to 6.4 ± 1.0 mm (P < 0.02). Diameter increased similarly in both groups. Isolated segment perforation was noted when k ≥ 0.8 N/m. Histologically, lengthened segments had increased muscularis thickness and crypt depth in comparison to normal intestine., Conclusions: Nitinol springs with k ≤ 0.4 N/m can safely yield nearly 2-fold distraction enterogenesis in length and diameter in a scalable mouse model. Not only does this study derive the safe ranges and translatable spring characteristics in a scalable murine model for patients with short bowel syndrome, it also demonstrates the feasibility of spring-mediated intestinal lengthening in a mouse, which can be used to study underlying mechanisms in the future., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Small intestinal length has prognostic significance for patients with short bowel syndrome, and accurate measurement of Roux-en-Y limbs is considered important. The flexible elasticity of bowel makes its measurement highly subjective, yet a recommended method for intestinal measurement allowing accurate comparisons between surgeons remains undefined. Measurement of intestinal length has been described, but no comparison of the fidelity of measurement technique has been made. We hypothesized that silk suture and umbilical tape would yield the most consistent measurements., Methods: This institutional review board-approved prospective trial enrolled 12 volunteer surgeons and two Institutional Animal Care and Use Committee-donated rabbits. Participants were asked to measure short, medium, and long segments of small intestine in a euthanized rabbit using common operating room tools: 18-in silk suture, 75-cm umbilical tape, 15-cm straight ruler, laparoscopic Dorsey bowel graspers. Data were analyzed by analysis of variance repeated measures model., Results: Over short segments, intestinal measurements by grasper were significantly shorter than those by tape (P = 0.002) and ruler (P = 0.039). Over medium lengths of bowel, measurements by grasper were significantly shorter than those by suture (P = 0.032) and tape (P = 0.046), and measurements by ruler also were significantly shorter than those by suture (P = 0.008). Over the long intestinal segment, measurements by ruler resulted in the greatest variability, and comparison of variance across all possible pairs of groups found significant difference by method of measurement (P = 0.049). There was a significant difference in measurements taken along the mesenteric border compared with those taken along the antimesenteric border (P = 0.001)., Conclusions: Measurement technique along short segments matters less; however, rigid tools underestimate length, and smaller variances in measurement by silk suture and umbilical tape suggest that these methods are more reliable across longer distances., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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

Background: Small intestinal submucosa (SIS) is a porcine-derived, acellular, collagen-based matrix that has been tested without seeded smooth muscle cells (SMCs) for intestinal tissue engineering. We examined the expression patterns of contractile proteins of SIS with SMCs implanted in an in vivo rodent model., Materials and Methods: Intestinal SMCs were isolated from Lewis rat pups. Four-ply tubular SMCs-seeded SIS or blank SIS scaffolds were implanted in an adult rat jejunal interposition model. Recipients were sacrificed at 2, 4, and 8 wk following the implantation. The retrieved specimens were examined using antibodies against contractile proteins of SMCs., Results: Cultured intestinal SMCs expressed α-smooth muscle actin (α-SMA), calponin, and less smooth muscle myosin heavy chain (SM-MHC) in vitro. Cell-seeded SIS scaffolds contracted significantly over 8 wk of implantation but were comparable to SIS scaffolds without cell seeding. Implanted cell-seeded SIS scaffolds at 2 wk expressed extensive α-SMA, some calponin, and minimal SM-MHC. At 4 wk, α-SMA-expressing cells decreased significantly, whereas calponin or SM-MHC expressing cells were rarely detected. A small number of α-SMA-expressing cells were present at 8 wk, whereas more calponin or SM-MHC expressing cells emerged in proximity with the anastomotic interface., Conclusions: Cell-seeded SIS contracted significantly after implantation, but the expressions of contractile proteins were present at the site of SIS interposition. No organized smooth muscle was formed at the site of implantation. A better scaffold design is needed to produce structured smooth muscle., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: We tested the coupling portion of a prototype intraluminal distraction enterogenesis device to allow flow-through of simulated enteric contents (SEC) in both pig and human jejunum., Materials and Methods: SEC was made using 80% corn syrup. Ten-cm pig and human intestinal segments had a spoke-shaped 2.2 cm coupling adaptor sutured in place, intraluminally. The adaptor had a flow-through area of 33.6 mm(2). SEC was pumped into the proximal part of the intestinal segment at 0.083 mL/s. The times to first passage of SEC through the coupler (first drop), 10 mL, and 20 mL of SEC eluted from the distal end were recorded., Results: Mean time to first drop elution was 155 ± 38 s with pig, and 149 ± 22 s with human bowel (P = 0.8). This corresponded to a hydrostatic pressure of 37.5 mmHg before the initial drop passed through. Mean flow rates were 0.094 mL/s in pig bowel and 0.084 mL/s in human bowel (P = 0.09). To account for occlusion from luminal debris, a 75% occlusion of coupler holes was studied in the smaller pig bowel to investigate if reductions in flow-through area could be tolerated. Mean time to first drop increased slightly to 171 ± 15 s, but the elution rate stayed the same (P = 0.5)., Conclusions: After a physiologic level of initial pressure buildup allowing the first drop of SEC to pass the coupling adaptor, our prototype intestinal coupling adaptor did not obstruct flow-through of SEC, even after a 75% decrease in flow-through area. This type of attachment represents a viable approach to placing a device in-continuity without obstructing flow of enteric contents., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Biodegradable scaffolds have been used for regenerating the small intestine. The aim of this study was to evaluate the feasibility of small intestinal submucosa (SIS) as scaffolds for intestinal regeneration in a rat model., Materials and Methods: A tubular one-ply or four-ply SIS was interposed between isolated jejunal segments in rats. The scaffolds were harvested at 2, 4, and 8 weeks after implantation, and the specimens were examined grossly and histologically., Results: Significant contractions were observed in SIS scaffolds after implantation. The one-ply SIS contracted to 44% of its initial length at 2 weeks and continued to contract to 6% of its initial length at 8 weeks. The contraction of four-ply SIS scaffolds was less than that of the one-ply SIS, reaching 29% of its initial length at 8 weeks. Minimal epithelial and smooth muscular regeneration was observed in the SIS scaffolds after implantation., Conclusions: A significant shrinkage was observed in the SIS scaffolds after implantation. Although the four-ply SIS contracted less than the one-ply SIS, neither scaffold supported significant amount of intestinal regeneration.

Background: The purpose of this study was to regenerate a larger size of small intestinal tissue than that of our previous study and to evaluate the regeneration of the endocrine cells (ECC) and nerve system of autologous tissue-engineered small intestine. The effect of implantation of large numbers of smooth muscle cells (SMC) for the regeneration of small intestine was also investigated., Methods: Two types of scaffolds with different cell densities were fabricated: low density (LD) of SMC in the scaffold and high density (HD) of SMC in the scaffold. Both scaffolds were implanted into defects of isolated ileum in a canine model. Animals were sacrificed at 8, 12, 18, and 24 weeks., Results: The area of engineered small intestine in the HD group was four times larger than that in the LD group, although that was smaller in size than the original size of the defect. There were no significant changes in the thickness of regenerated smooth muscle layer (SML) in the LD and HD groups. The numbers of endocrine cells gradually increased after implantation. At 18 weeks of regeneration, the number of ECC reached levels comparable to that of normal mucosa. The nerve fibers extended to the center of the graft area and were observed in regenerated SML and regenerated villi at 24 weeks., Conclusions: The ECC and nerve fibers were regenerated in autologous in situ tissue-engineered small intestine. Seeding a large number of SMC was not sufficient for the regeneration of the small intestine in a tubular configuration.

Background: Infectious complications are associated with high morbidity in patients with short bowel syndrome and after small bowel transplantation. Bacterial translocation from the intestine is probably an essential factor in the genesis of these infections. In a model for bacterial translocation in the rat we examined the consequence of mesenteric lymphadenectomy and the depletion of Kupffer cells., Materials and Methods: The effect of mesenteric lymphadenectomy was studied in two different models; in rats where a Thiry-Vella loop had been created from small bowel and in rats that had received a syngeneic small bowel transplant. To study the role of the Kupffer cells, rats with Thiry-Vella loops were treated intravenously with the Kupffer cell inhibitor gadolinium chloride. All animals were sacrificed on Day 3 postoperatively and the bacterial translocation to the mesenteric lymph nodes, liver, spleen, lung, and blood was evaluated., Results: Removal of the mesenteric lymph nodes did not result in any increased bacterial translocation in animals with a Thiry-Vella loop. However, the inactivation of Kupffer cells with gadolinium chloride produced a more severe translocation to the liver, spleen, and lungs. After small bowel transplantation the bacterial translocation to the spleen was increased in animals without mesenteric lymph nodes., Conclusions: In the model of bacterial translocation from a defunctionalized loop of small bowel the inhibition of Kupffer cells will promote the systemic spread of the translocating bacteria. This indicates an important protective function of the Kupffer cells against translocating microbes., ((c)2001 Elsevier Science.)

Background: Small intestinal submucosa (SIS) is an extracellular matrix used in tissue engineering studies to create de novo abdominal wall, urinary bladder, tendons, blood vessels, and dura mater. The purpose of this study is to evaluate the feasibility of using SIS as a scaffold for small bowel regeneration in an in situ xenograft model., Materials and Methods: Twenty-three dogs had a partial defect created on the small bowel wall which was repaired with a SIS patch. Four dogs underwent small bowel resection with placement of an interposed tube of SIS. The animals were followed 2 weeks to 1 year., Results: Three of the 23 dogs with SIS placed as a patch died shortly after surgery due to leakage from the site. The other 20 dogs survived up to time of elective necropsy with no evidence of intestinal dysfunction. At necropsy, the bowel circumference in the patched area had no stenosis. Histological evaluation showed the presence of a mucosal epithelial layer, varying amount of smooth muscle, sheets of collagen, and a serosal covering. Architecturally, the layers were not well organized in the submucosal region. An abundance of inflammatory cells was present in the early postoperative period but receded with time. All 4 dogs with a tubular segment of SIS interposed had significant problems. One had partial obstruction at 1 month, and 3 died in the early postoperative period due to leakage., Conclusions: This preliminary study suggests that SIS patches can be used for small bowel regeneration. Tubular segmental replacement is not feasible at this time., (Copyright 2001 Academic Press.)

Background: Leptin is a 16-kDa peptide produced by adipocytes that plays an important role in the regulation of body fat and satiety. We have previously shown that leptin is a growth factor for normal rat small intestine. This study was designed to examine the effect of systemic leptin administration on small bowel absorptive function after massive small bowel resection (MSBR)., Materials and Methods: Twenty-one adult male Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days following resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic minipump and were divided into three groups based on the content of each minipump: Group 1 (n = 7) 0.1% bovine serum albumin; Group 2 (n = 7) leptin 2 microg/kg/day; and Group 3 (n = 7) leptin 4 microg/kg/day. Following a 14-day infusion period, [(14)C]galactose absorption was measured using a closed-recirculation technique. Mucosal DNA content was determined for all groups using a standard DNA purification kit. Mucosal RNA was extracted and RT-PCR was performed using the following primers: sodium/glucose cotransporter (SGLT-1), fructose transporter (GLUT-5), and glyceraldehyde-3-phosphate dehydrogenase, an internal standard. PCR products were separated on a 4% agarose gel and relative band intensities were measured. Statistical analysis was performed using ANOVA and expressed as means +/- SEM., Results: Group 2 showed a 44% increase in galactose absorption (P < 0.01) and a 14% increase in GLUT-5 band intensity (P < 0.05), but no change in DNA content or SGLT band intensity., Conclusions: This study demonstrates for the first time that leptin enhances small intestine carbohydrate absorption beyond the normal adaptive response following MSBR. Leptin may be clinically useful in patients with inadequate intestinal function., (Copyright 2001 Academic Press.)

Background: Following massive small bowel resection (SBR), the expression of bax and bcl-w is associated with increased enterocyte apoptosis. Epidermal growth factor (EGF) has been shown to enhance enterocyte proliferation and retard apoptosis in the adapting bowel. This study examined the effect of EGF on the expression of these bcl-2 family members during adaptation., Materials and Methods: Mice (C57Bl/6; n = 38) underwent a 50% SBR or sham operation and then were randomized to receive twice-daily orogastric saline or EGF (50 microg/kg/day). After 3 days, the remnant ileum was removed, apoptotic index (No. apoptotic bodies/crypt) calculated, and expression of mRNA and protein for bax and bcl-w quantified., Results: EGF prevented the expected increase in the apoptotic index after SBR and altered the ratio of bax to bcl-w in favor of cell survival., Conclusion: Following massive small bowel resection, EGF retards rates of enterocyte apoptosis and modifies the expression of bcl-2 family members. By decreasing bax and increasing bcl-w expression, the balance between pro- and anti-apoptotic genes is shifted in favor of cell survival. Alteration of bcl-2 family member expression may be an important mechanism by which EGF reduces the increased enterocyte apoptosis that occurs after massive small bowel resection., (Copyright 2000 Academic Press.)

Despite numerous investigations short bowel syndrome (SBS) is still an unsolved clinical problem. The purpose of this study was to develop a new surgical approach that combines both intestinal lengthening and growing neomucosa. The operative principle is based on a longitudinal division of an intestinal segment antimesenterically and a formation of two intestinal tubes out of bowel halves anastomosing one cutting edge to the incised mucosal midline and the other to the antimesenteric side of the constructed first intestinal tube, so that a common wall between the two hemiloops was created which leads to grow neomucosa. This procedure was applied to 11 rabbits. The hemiloops and neomucosa were investigated for its feasibility and morphologic characteristics. Gross and microscopic examinations at 8 weeks revealed that all the intestinal tubes were viable and patent. No anastomotic leakage was present. In all animals, the serosal surfaces of the common walls were covered with neomucosa that resembles the mucosa of the existing intestine morphologically; there was no significant difference in villus height, villus width at base, crypt depth, number of villi per unit serosal length, villus surface, and villus surface per unit serosa. The growth of neomucosa was completely a result of epithelialization without any evidence of contraction. The quantity and rate of neomucosal growth seems unaffected by intestinal segment length. Finally a two times increase in intestinal length, whereas the diameter halved and a statistically significant increase (P < 0.001) in total villus surface via growing neomucosa was obtained. This model might be useful in the management of SBS when supported by clinical and functional investigations.

The introduction of total parenteral nutrition has resulted in more patients surviving massive intestinal resection. Long-term parenteral nutrition is expensive, has potential complications, and causes inconvenience for the patient. Therefore, interest persists in surgical therapy for the short bowel syndrome. The goals of surgical therapy in the short bowel syndrome are to slow intestinal transit, increase the area of absorption, and reduce gastric hyperacidity. Patients with sufficient absorptive area, but rapid intestinal transit, benefit from antiperistaltic segments or colon interposition. Intestinal valves yield inconsistent results. Recirculating loops are associated with prohibitive morbidity and mortality. Experience with intestinal pacing is limited. Patients with dilated bowel segments may benefit from intestinal tapering or lengthening. Growing neomucosa holds promise but has not been evaluated clinically. Recent improvement in the results of intestinal transplantation in animals may warrant clinical trials. The efficacy of H2 receptor antagonists makes procedures for reducing gastric hyperacidity less necessary. None of the operations to treat the short bowel syndrome are sufficiently safe and effective to recommend their routine use. Operations should be performed only on selected patients to achieve specific goals. Although investigation continues, our emphasis should continue to be conservation of as much of the intestine as possible when massive resection is necessary.

Growing intestinal neomucosa in patched intestinal defects has been investigated as a means of permanently increasing the absorptive capacity in the short bowel syndrome. Several factors, including luminal contents, appear to affect the growth and function of the neomucosa. The purpose of this study was to compare function and rate of growth of neomucosa in patched defects of the jejunum and ileum. In both the jejunum and ileum of 11 New Zealand white male rabbits 2 X 5-cm patched intestinal defects were created using the serosal surface of adjacent colon. The animals were sacrificed at 4 weeks (n = 6) and 8 weeks (n = 5) after operation. Grossly there was more complete coverage of the defect by neomucosa in the ileum at both 4 and 8 weeks (99.1 +/- 1.1% vs 92.6 +/- 6.3% overall P less than 0.005). Villous height of the ileal neomucosa was similar to normal mucosa at 8 weeks (209 +/- 21 vs 244 +/- 18 m) but was significantly less in the jejunum (209 +/- 16 vs 273 +/- 16 m, P less than 0.005). Glucose uptake by neomucosa was greater in the ileum than the jejunum (3.34 +/- .84 vs 2.39 +/- .46 nmole/min/mg, P less than 0.05) but was similar to normal mucosa at both sites. Disaccharidase activity (lactase, sucrase, and maltase) was similar in both jejunum and ileum but was significantly less in ileal neomucosa than in normal mucosa (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Segmental intestinal transplantation was studied in a rat model of severe short gut syndrome across major histoincompatibility barriers. Lewis (RT1l) recipient rats whose entire small bowel (approximately 80 cm), ileocecal valve, and cecum were resected and who had no transplant, uniformly died of malabsorption on Day 9.8 +/- 0.4 (n = 11). Without cyclosporine, allograft recipients (n = 2), died of rejection on Days 8 and 10. Recipient animals with 20-cm jejunum and 40-cm jejunal transplants from Buffalo (RT1b) rats and treated daily with cyclosporine (5 mg/kg/day) intramuscularly (Days 0-28) and vitamin B12 (every other week) enjoyed significantly prolonged survival to Day 58.2 +/- 13.7, P less than 0.003, n = 10, and Day 129.1 +/- 7.4, P less than 0.001, n = 10, respectively. While 7 of 10 rats in the 20-cm jejunal transplant group died of malabsorption between Days 14 and 58, none of 10 animals in the 40-cm jejunal transplant group died of this complication. Four of 10 rats in the 40-cm jejunal transplant group thrived at 150 days after the operation, at which time they were sacrificed. Morphologically, the grafts demonstrated hypertrophic changes. The data from this study suggest that intestinal allografts have pronounced intestinal adaptative characteristics. Using segmental jejunal grafts, intestinal transplantation is an effective surgical modality for the short gut syndrome in the rat.