scholarly journals Insights from animal models for growing intestinal neomucosa with serosal patching - a still untapped technique for the treatment of short bowel syndrome

2001 ◽  
Vol 35 (2) ◽  
pp. 180-187 ◽  
Author(s):  
E. Freud ◽  
R. Eshet

The aim of surgical treatment of short bowel syndrome is to increase the intestinal absorptive capacity by increasing the area of absorption or by slowing intestinal transit. The use of serosal patching to grow new intestinal mucosa is a technique for enlarging the intestinal surface. The regenerated intestine develops by lateral ingrowth from the neighbouring mucosa and is functionally similar to normal intestinal mucosa. The present review summarizes the main contributions of the rabbit, the rat and the canine models used to date for growing neomucosa using the serosal patch technique, as well as examining the influence of some growth factors on the development of neomucosa.

2007 ◽  
Vol 22 (6) ◽  
pp. 430-435 ◽  
Author(s):  
Dâmaso de Araújo Chacon ◽  
Irami Araújo-Filho ◽  
Arthur Villarim-Neto ◽  
Amália Cínthia Meneses Rêgo ◽  
Ítalo Medeiros Azevedo ◽  
...  

PURPOSE: To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. METHODS: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as significant. RESULTS: There were no significant differences in %ATI/g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was significantly greater than that of C and sham rats (p<0.05). CONCLUSION: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated.


2003 ◽  
Vol 62 (3) ◽  
pp. 711-718 ◽  
Author(s):  
G. L. Carlson

Surgery plays a key role in the management of both acute and, less frequently, chronic intestinal failure. Acute intestinal failure frequently requires surgical treatment when it arises as a consequence of intestinal fistulation or obstruction. In specialised clinical practice approximately 50% of acute intestinal failure is associated with intestinal fistulas and in approximately 50% of patients, this condition arises as part of the natural history or complicating treatment for Crohn's disease. A considerable proportion of such patients have abdominal infection and present complex nutritional and metabolic problems. The most important aspect of the surgical management of patients with acute intestinal failure associated with intra-abdominal infection is management of sepsis, since recovery is unlikely in the presence of active infection. Moreover, effective nutritional support and restoration of body composition is not possible if sepsis remains unresolved. Surgical strategies to deal with intra-abdominal infection may involve percutaneous drainage, laparotomy and resection of fistulating segments of intestine and, when infection is persistent and contamination extensive, laparostomy (a technique in which the abdomen is left open and allowed to heal by secondary intention). Surgical treatment should not only be timely and effective, but also aimed at preventing secondary damage to the small intestine, in order to minimise the risk of short bowel syndrome. In some cases a proximal defunctioning stoma may be required, with prolonged nutritional support, using either home total parenteral nutrition or feeding via the defunctioned distal gut (fistuloclysis), pending restoration of intestinal continuity. The role of surgical treatment for patients with short bowel syndrome is less clear. While surgery is frequently required for the management of complications of short bowel syndrome (including gallstones and possibly peptic ulcer disease), the role of intestinal lengthening and tapering procedures (to increase functional intestinal length), and artificial valves, reversed segments and colonic interposition (to reduce intestinal transit) remains controversial. For some patients with short bowel syndrome and, in particular, those with combined intestinal and hepatic failure, intestinal transplantation may become the treatment of choice as long-term results continue to improve.


2014 ◽  
Vol 307 (12) ◽  
pp. G1147-G1168 ◽  
Author(s):  
Per T. Sangild ◽  
Denise M. Ney ◽  
David L. Sigalet ◽  
Andreas Vegge ◽  
Douglas Burrin

Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing enterocolitis, atresia, gastroschisis, volvulus, and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the choice of SBS model for each clinical or basic research question.


1997 ◽  
Vol 32 (11) ◽  
pp. 1652-1655 ◽  
Author(s):  
Jeffrey Lukish ◽  
Marshall Z Schwartz ◽  
Jeanne M Rushin ◽  
G.Patrick Riordan

2017 ◽  
Vol 312 (4) ◽  
pp. G390-G404 ◽  
Author(s):  
David W. Lim ◽  
Crystal L. Levesque ◽  
Donna F. Vine ◽  
Mitsuru Muto ◽  
Jacob R. Koepke ◽  
...  

Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet models of short bowel syndrome (SBS). Neonatal Landrace-Large White piglets were block randomized to 75% midintestinal [jejunoileal (JI) group] or distal intestinal [jejunocolic (JC) group] resection or sham control, with 7-day infusion of saline (control), intravenous human GLP-2 (11 nmol·kg−1·day−1) alone, enteral EGF-cm (80 μg·kg−1·day−1) alone, or GLP-2 and EGF-cm in combination. Adaptation was assessed by intestinal length, histopathology, Üssing chamber analysis, and real-time quantitative PCR of intestinal growth factors. Combined EGF-cm and GLP-2 treatment increased intestinal length in all three surgical models ( P < 0.01). EGF-cm alone selectively increased bowel weight per length and jejunal villus height in the JI group only. The JC group demonstrated increased intestinal weight and villus height ( P < 0.01) when given either GLP-2 alone or in combination with EGF-cm, with no effect of EGF-cm alone. Jejunal permeability of mannitol and polyethylene glycol decreased with combination therapy in both SBS groups ( P < 0.05). No difference was observed in fat absorption or body weight gain. IGF-1 mRNA was differentially expressed in JI vs. JC piglets with treatment. Combined treatment with GLP-2 and EGF-cm induced intestinal lengthening and decreased permeability, in addition to the trophic effects of GLP-2 alone. Our findings demonstrate the benefits of novel combination GLP-2 and EGF treatment for neonatal SBS, especially in the JC model representing most human infants with SBS. NEW & NOTEWORTHY Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) are intestinotrophic, with demonstrated benefit in both animal models and human studies of short bowel syndrome (SBS). The current research shows that over and above known trophic effects, the combination of GLP-2 and EGF synergistically lengthens the bowel in neonatal piglet models of SBS. Most notable benefit occurred with resection of the terminal ileum, the common clinical anatomy seen in neonatal SBS and associated with least de novo lengthening postsurgery.


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