Incidence of bacterial translocation in four different models of experimental short bowel syndrome

The outcome of patients with short bowel syndrome is influenced for factors such as the length of remnant intestine or the presence or absence of ileocecal valve (ICV). Gram-negative sepsis, the main cause of mortality in this group of children, is probably due to bacterial translocation (BT), because after gut resection there are a number of circumstances that favour its occurrence, being the most known intestinal dismotility, bacterial overgrowth, loss of gut-associated lymphoid tissue, total parenteral nutrition (TPN) and fasting related mucosal atrophy. The aim of this experimental controlled study was to test the incidence of BT after four different types of gut resection, in animals fed orally or receiving TPN. Hundred and three adult Wistar rats bred and raised in our facilities according to European Union Regulations were randomly divided in six groups:--Group 1 (n = 26): non-manipulated animals, served as a control.--Group 2 (n = 14): 80% non-lethal small bowel resection, fed orally.--Group 3 (n = 15): same resection as group 2 but including ICV. Rat chow ad libitum.--Group 4 (n = 27): non-resected fasting animals receiving all-in-one TPN solution.--Group 5 (n = 11): same resection as group 2, but fasting and receiving TPN--Group 6 (n = 10): 90% small bowel resection, including cecum and ICV, fasting and TPN. The animals were maintained for 10 days in individual metabolic cages, and, at the end of the experiment, were bled by portal and cardiac puncture. Mesenteric lymph nodes, peripheral and portal blood samples were cultured for BT. Non-manipulated rats (group 1) had lower BT incidence (8%) than resected ones (groups 2, 3, 5 and 6, 93%, 60%, 91%, 60%, p < 0.05) or animals non-resected, receiving TPN (group 4.51%, p < 0.05). When resection included ICV in orally fed rats BT index was also lower (group 3 vs group 2.60% vs 91%, p < 0.05). In TPN resected animals a drop was also found in BT when ICV and cecum were added to small bowel resection (group 6 vs group 5.60% vs 91%, p < 0.05). In conclusion: 1. Gut resection is associated to a high degree of BT, even if the animals are fed orally. 2. Resection including ICV, produced less BT. 3. TPN-related BT was shown in half of the animals non resected. 4. TPN-resected rats had also less BT when ICV and cecum were removed.     

Probiotic supplementation reduces the risk of bacterial translocation in experimental short bowel syndrome

Background/Purpose: Probiotics are live organisms that survive passage through the gastrointestinal tract and have beneficial effects on the host. Lactobacillus and Bifidobacterium have been recommended for cholesterol lowering, acute diarrhea, prevention of cancer, or inflammatory bowel disease. On the other hand, after massive bowel resection, bacterial overgrowth is frequent and favors bacterial translocation (BT). The possible beneficial effects of Bifidobacterium lactis (BL) administration on BT in experimental short bowel syndrome (SBS), have not been investigated. The aim of this study was to test the hypothesis that BL administration decreases BT in SBS in animals fed orally. Methods: One hundred twenty-eight adult Wistar rats fed orally with standard rat chow and tap water [ldquo ]ad libitum[rdquo ] were maintained in individual metabolic cages for 10 days and divided into 3 groups: control group (n = 71): nonmanipulated animals; RES group (n = 39): 80% gut resection from 10 cm beyond the angle of Treitz to 10 cm above the cecum; RES-PRO group (n = 18): same resection and daily 7.8 [times ] 10⁸ CFU B Lactis administration, after orogastric intubation. At the end of the experiment they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal blood specimens were recovered and cultured. Bacterial identification in blood was made by conventional methods, and MLN culture was considered positive with a growth over 100 CFU/g. Results: Bacterial translocation was detected in 6% of control group rats. The incidence of BT in the RES group was 87% (34 of 39), whereas only 50% (9 of 18) of RES-PRO animals had BT (P [lt ] .05). The relative risk reduction (RRR) was 0.43 (95% Cl 0.14 to 0.72), and the number needed to treat (NNT) was 3 (95% Cl 2 to 8). In other words, animals that received BL had the risk of BT reduced by 43% (RRR of 0.43), and of every 3 animals treated, 1 is expected to be free of BT (NNT of 3). Conclusion: Administration of B Lactis reduces the incidence of BT in adult Wistar rats after 80% gut resection.     

Effect of growth hormone, epidermal growth factor, and insulin on bacterial translocation in experimental short bowel syndrome

BACKGROUND/PURPOSE: An adaptive process starts in the remaining intestine after massive resection, and several trophic factors including growth hormone (GH), epidermal growth factor (EGF), and insulin (INS) have been shown to have a positive effect on it. Bacterial translocation (BT) is frequent after extensive small bowel resection, but the effects of GH, EGF, or INS have not been investigated in experimental short bowel syndrome (SBS). This study tests the hypothesis that GH, EGF, or INS decrease BT in SBS in rats with parenteral nutrition (PN). METHODS: Thirty-eight adult Wistar rats underwent central venous cannulation and were assigned randomly to 1 of 4 groups receiving for 10 days 4 treatment regimes: (1) PN group (n = 10): fasting, all-in-one PN solution (300 mL/kg/24 h, 280 kcal/kg/24 h), 80% gut resection including ileo-cecal valve; (2) GH group (n = 9): fasting, same PN regime and resection, GH (1 mg/kg/d, subcutaneously); (3) EGF group (n = 9): fasting, PN, resection, EGF (150 microg/24 h intravenously); (4) INS group (n = 9): fasting, PN, resection, INS (1 UI/100 g/24 h subcutaneously). At the end of the experiment they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal blood samples were recovered and cultured. Several fragments of intestine were taken to determine cell proliferation (PCNA index) and morphometric parameters (villous height, crypt depth). RESULTS: GH, EGF, and INS groups showed a 28%, 29%, and 30% increase in gut mucosal thickness, and PCNA index rose 21%, 20%, and 25%, respectively in comparison with PN controls. Bacterial translocation to peripheral blood was detected in 0% of PN animals and in 44%, 40%, and 28% of GH, EGF, or INS rats, respectively (P < .05). No differences were found in BT in MLN or portal blood among groups. CONCLUSION: Administration of GH, EGF, or INS improves gut mucosal structure in rats with SBS under PN, but, surprisingly, the incidence of BT detected in peripheral blood was increased rather than decreased in animals receiving these treatments.     

Effect of probiotics on intestinal regrowth and bacterial translocation after massive small bowel resection in a rat

Background/Purpose

Because of their ability to inhibit intestinal bacterial overgrowth, probiotics (PROs) have been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of PROs on bacterial translocation and intestinal regrowth after massive small bowel resection in a rat.

Methods

Male Sprague-Dawley rats were divided into 3 experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent 75% small bowel resection, and SBS-PRO rats underwent bowel resection and were treated with a PRO given in drinking water from day 4 through 14. Intestinal structural changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, enterocyte proliferation and enterocyte apoptosis) and bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood, and peripheral blood were determined on day 15 after operation.

Results

Sham rats exhibited a 20% BT to the mesenteric lymph nodes (level I), liver (level II), and blood (level III). Short bowel syndrome rats demonstrated a 100% BT to lymph nodes (level I) and liver (level II) and 40% translocation to peripheral blood (level III). Treatment with PROs resulted in a significant decrease in BT to all 3 target organs and decreased enterocyte apoptosis compared with SBS-untreated animals. Short bowel syndrome rats showed a significant increase (vs sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. Short bowel syndrome rats also had a greater proliferation index and apoptotic index in both jejunum and ileum compared with sham animals. SBS-PRO rats showed a significant increase (vs SBS rats) in crypt depth in ileum and a mild decrease in apoptotic index in jejunum and ileum, compared with SBS-untreated animals.

Conclusions

In a rat model of SBS, PROs decrease BT through mechanisms which maybe dependent on intestinal mucosal integrity.     

Effect of various trophic factors on bacterial translocation in experimental short bowel syndrome

Massive bowel resection triggers an adaptive process in the remaining intestine in spite of which, bacterial translocation (BT) is frequent under these conditions. Several trophic factors, including growth hormone (GH), epidermal growth factor (EGF) and insuline (INS) are involved in the process of adaptation in short bowel syndrome (SBS). However, the effect of GH, EGF or INS on BT has not been investigated experimentally. The aim of the study was to test the hypothesis that GH, EGF or INS administration prevents BT in rats with SBS receiving only parenteral nutrition (PN). Thirty-seven adult Wistar rats underwent central venous cannulation and were randomly assigned to one of two groups receiving for ten days four treatment regimes: PN group (N = 10) fasting, all-in-one PN solution (300 mL/kg/24 h, 280 kcal/kg/24 h), 80% gut resection including ileo-cecal valve. GH group (N = 9) fasting, same PN regime and resection plus GH (1 mg/kg/d, s.c.). EGF group (N = 9): same PN regime and resection plus EGF (150 microgr/24 h, e.v.) INS group(N = 9): same PN regime and resection plus INS (1 U.I./100 g/24 h s.c.) At the end of the experiment the rats were exanguinated and mesenteric lymph nodes and samples of systemic and portal blood were obtained and cultured. Several samples of full-thickness jejunal wall were taken for measuring cell proliferation index (PCNA) and mucosal thickness. Jejunal mucosal thickness increased by 30%, 28% and 29% and PCNA index by 21%, 20% and 25% in GH, EGF and INS, treated rats respectively in comparison with those treated with PN alone. However, contrary to our expectations, BT expressed by positive culture of intestinal germs in systemic blood was demonstrated respectively in 44%, 40% and 28% of GH, EGF and INS animals, respectively, and in 0% of PN-only rats. Although exogenous GH, EGF or INS improves gut mucosal structure in rats with SBS treated with PN, it seems to increase rather than decrease mucosal permeability to intestinal germs in them.     

Pediatric short bowel syndrome: redefining predictors of success

OBJECTIVE: To determine predictors of survival and of weaning off parenteral nutrition (PN) in pediatric short bowel syndrome (SBS) patients. SUMMARY BACKGROUND DATA: Pediatric SBS carries extensive morbidity and high mortality, but factors believed to predict survival or weaning from PN have been based on limited studies. This study reviews outcomes of a large number of SBS infants and identifies predictors of success. METHODS: Multivariate Cox proportional hazards analysis was conducted on 80 pediatric SBS patients. Primary outcome was survival; secondary outcome was ability to wean off PN. Nonsignificant covariates were eliminated. P < 0.05 was considered significant. RESULTS: Over a mean of 5.1 years of follow-up, survival was 58 of 80 (72.5%) and 51 weaned off PN (63.8%). Cholestasis (conjugated bilirubin > or =2.5 mg/dL) was the strongest predictor of mortality (relative risk [RR] 22.7, P = 0.005). Although absolute small bowel length was only slightly predictive, percentage of normal bowel length (for a given infant's gestational age) was strongly predictive of mortality (if <10% of normal length, RR of death was 5.7, P = 0.003) and of weaning PN (if > or =10% of normal, RR of weaning PN was 11.8, P = 0.001). Presence of the ileocecal valve (ICV) also strongly predicted weaning PN (RR 3.9, P < 0.0005); however, ICV was not predictive of survival. CONCLUSIONS: Cholestasis and age-adjusted small bowel length are the major predictors of mortality in pediatric SBS. Age-adjusted small bowel length and ICV are the major predictors of weaning from PN. These data permit better prediction of outcomes of pediatric SBS, which may help to direct future management of these challenging patients.     

Short bowel syndrome in the research setting: 15 years' experience

The fight against infection and liver disease associated with parenteral nutrition (PN) are surely two of the most problematic aspects in the management of paediatric patients with short bowel syndrome (SBS). In the Research Unit of Donostia Hospital, we have spent the past 15 years investigating different ways of reducing these complications in an experimental model of short bowel in the Wistar rat (resection of 80% of the small bowel, with and without PN). All the experiments had a duration of 10 days and 323 animals reached the end of the study period. Nine groups were established in which some type of intervention was performed, and there were 8 control groups. The interventions were: 3 dietary (minimal enteral nutrition [MEN] with low or high dose probiotics); 5 pharmacological (administration of growth hormone [GH], epidermal growth factor [EGF], insulin, cholecystokinin [CCK], and selective intestinal decontamination [SID]); and 1 surgical (resection of the ileocaecal valve). Infection due to bacterial translocation (BT) was detected by culture of mesenteric lymph nodes, portal blood and peripheral blood, and liver damage by the levels of proinflammatory cytokines (IL-1 and TNF-alpha). In summary, our results are: Probiotics, MEN and SID reduce BT. Liver damage was milder in the groups with MEN, SID and CCK. The groups receiving GH, EGF or insulin presented a higher incidence of BT. BT was lower after resection of the ileocaecal valve. In conclusion, the probiotics, MEN and CCK could be useful in the management of children with SBS. These data confirm the utility of this experimental model of short bowel for the investigation of different aspects of SBS.     

Outcome and intestinal adaptation in neonatal short-bowel syndrome.

We reviewed 52 consecutive patients with short-bowel syndrome (SBS) treated with long-term parenteral nutrition (PN) from 1978 through 1990. The SBS etiologies included necrotizing enterocolitis (NEC) in 26 patients (50%), abdominal wall defects in 11 (22%), jejunoileal atresia in 6 (12%), midgut volvulus in 4 (8%), Hirschsprung's disease in 3 (6%), and segmental volvulus and cloacal exstrophy in 1 (2%) each. The average initial small bowel length was 48.1 cm, and only 31% of the patients retained an ileocecal valve (ICV). The mean duration of PN therapy was 16.6 months, and 39 patients (75%) were successfully weaned from it. Forty-three patients (83%) survived. Significant differences between the initial 20 patients treated from 1978 through 1984 and the next 32 from 1985 through 1990 were duration of PN therapy (25.1 v 11.4 months; P = .04), incidence of PN-associated jaundice (80% v 31%; P = .001), and survival (65% v 94%; P = .02). NEC patients had a significantly lower mean birthweight than those with other etiologies (mean, 1,367 v 2,544 g; P less than .0001) but did not differ in initial small bowel length, ICV retention rate, duration of PN treatment, incidence of successful PN weaning, or outcome. The presence of an ICV did not correlate with successful PN weaning but did affect the mean duration of PN therapy (7.2 months with ICV v 21.6 months without; P = .03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of sex and sex hormones on structural intestinal adaptation after massive small bowel resection in rats

Purpose

The gonadal steroids play a major role in the regulation of many functions. The purpose of the current study was to evaluate the effect of sex and sex hormones on intestinal adaptation in a rat model of short bowel syndrome (SBS).

Methods

In the first experiment, male and female Sprague-Dawley rats underwent bowel transection and re-anastomosis (sham group) or 75% small bowel resection and anastomosis (SBS group). Relative changes in parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) were measured on day 15 and were compared with respect to sex. In the second experiment, male rats were divided into 4 experimental groups: SBS rats, SBS castrated rats, SBS castrated rats treated with testosterone, and SBS castrated rats treated with estradiol. Parameters of intestinal adaptation were compared with respect to hormonal treatment. Statistical significance was determined by Student's t test and analysis of variance with P < .05 considered significant.

Results

Sex had minimal effects on intestinal adaptation. Both male and female rats showed a comparable increase in all parameters of intestinal adaptation. In the second experiment, castration led to significant decrease in bowel and mucosal weight, mucosal DNA and protein in both jejunum and ileum compared with SBS animals. Castrated rats also had lower jejunal villus height and crypt depth compared with SBS animals. Testosterone attenuated this negative effect of castration on bowel regrowth. Rats treated with testosterone showed a significant increase in bowel and mucosal weight, mucosal protein in both jejunum and ileum, mucosal DNA, villus height, and crypt depth in jejunum compared with castrated nontreated animals. Treatment with estradiol after resection and castration had minimal effect on bowel regrowth.

Conclusions

Bowel regrowth after massive small bowel resection is not sex-related. Depletion of androgens by castration inhibited intestinal adaptation. Testosterone has shown a strong stimulating effect on bowel regrowth.     

Novel effect of leptin on small intestine adaptation

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.     

The Importance of the ileocecal valve and colon in achieving intestinal independence in infants with short bowel syndrome

PurposeInfants with short bowel syndrome (SBS) wean from parenteral nutrition (PN) support at variable rates. Small bowel length is a predictor, but the importance of the ileocecal valve (ICV) and colon are unclear. We aim to determine if the ICV and/or colon predict enteral autonomy.MethodsInfants from a single intestinal rehabilitation program were retrospectively reviewed. Etiology of SBS, intestinal anatomy, and duration of nutritional support were collected for three years. The primary outcome was time to full enteral nutrition. ANCOVA and Cox proportional hazards model were used, with p < 0.05 significant.Results55 infants with SBS were included. After accounting for the effect of small bowel, PN duration was shorter for infants with the ICV compared to those without (mean 218 vs. 538 days, p = 0.003), and had a more significant effect on infants with ≤50% of small bowel. Increased small bowel length was a positive predictor of weaning. Patients with ≤50% of colon spent less time on PN with the ICV, compared to without (mean 220 vs 715 days, p = 0.009).ConclusionsPreservation of the ICV was associated with shorter duration of PN support, while colon was not. Small bowel length is a positive predictor of enteral autonomy.Level of EvidenceLevel III retrospective comparative studyType of StudyRetrospective review     

Selective intestinal decontamination and parenteral nutrition related liver disease. Experimental study

Selective intestinal decontamination (SID) has been useful restraining Bacterial translocation (BT) in both animal models and human clinics. The not well known parenteral nutrition-related liver disease is a serious problem associated to short bowel and long-term parenteral nutrition (PN) use, and BT is also frequent in those patients. Germs reach liver through portal vein and activate Kupffer cells, which release cytokines as IL-1 or TNF-alpha. The aim of this study was to test the use of SID restraining BT in a PN undergoing experimental short bowel model, and its possible favourable consequences on hepatic injury determined by IL-1 and TNF-alpha levels. Twenty-five 240-280 g Wistar rats were divided into two groups and maintained in individual metabolic cages for ten days: Resection-PN group (n=15): animals with a bowel resection of the 80% and a continuous PN infusion. Resection-PN-SID (n=10) group: similar to previous group and a daily oral administration of Tobramycine (20mg/kg/day) and Polymyxine-E (25mg/kg/day). Animals were sacrificed and mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered for TB determination in bacterial culture. Determination of both IL-l and TNF-alpha seric levels were carried out by ELISA. Bacterial translocation incidence was higher in RES-NPT group (66.6%) than RES-NPT-SID group (30%) (P>0,05). The relative risk was 2.22 (IC 95% 0,81-6,11) and the number needed to treat was 3 (IC 95% 2-235). Seric levels of IL-1 and TNF-alpha were also higher in RES-NPT group (7,537 and 5,399 pg/ml, respectively) than in RES-NPT-SID group (6,397 and 5,032 pg/ml respectively) (p<0,001). 1. SID reduces TB in a PN undergoing experimental short bowel resection murine model. 2. Parenteral nutrition-related liver disease decreases in DIS receiving animals.     

The ontogeny of the gut-associated lymphoid tissue in short bowel syndrome

Newborns suffering from short bowel syndrome (SBS) after massive intestinal resection have numerous infectious complications, which may be due to immunoincompetence from the loss of gut-associated lymphoid tissue (GALT). This study examines the ontogeny of GALT in the rat with SBS. A total of 36 3-week-old rats were divided into two groups: I, sham operated (C, n = 16); and II (SBS, n = 20), with a 50% resection of small intestine with jejunoileostomy. At 4, 5, 6, and 10 weeks of age the animals were sacrificed and the GALT was assessed by video analysis and immunoperoxidase monoclonal antibodies, OX8 (CD8), W-3/25 (CD4), and MARA-2 (IgA). The data were expressed as positive staining lymphocytes per 10(4) microns2 (mean +/- SD). table; see text In the sham group there was an increase in all lymphocyte subsets over time. In the SBS group there was a rapid fall in OX8 and W-3/25 T-lymphocytes by 10 weeks, with no increase in IgA plasma cells at 6 and 10 weeks. This study demonstrates that in the massive bowel resection in the suckling rat decreases the T- and B-lymphocyte populations in the GALT. This lack of development may underlie the associated infectious complications and malabsorption in SBS.     

Induction of short gut syndrome and transplantation in a porcine model

Experimental models in small animals have been described for nutritional studies after small bowel transplantation for extensive resection. Herein, we compared the outcome of transplanted pigs that underwent transplantation after total small bowel resection (SBR) with controls without transplantation. METHODS: Twenty-one Landrace pigs (mean weight 30 kg) were assigned to 1 of 3 groups: group 1 (n = 6) underwent 80% SBR; group 2 (n = 9), total bowel resection; and group 3 (n = 6) total resection plus small bowel transplantation. Postoperative evaluation included biochemical analyses, weights, and evaluation of clinical status. Conventional endoscopies with graft biopsies were obtained every 4 days to assess rejection. RESULTS: Group 1 showed increased body weight after 3 weeks due to bowel adaptation, whereas groups 2 and 3 lost weight, an observation that correlated with biochemical analyses. Median survival in group 3 was 10 +/- 2 days; all hosts died of sepsis related to severe acute rejection. DISCUSSION: Short gut syndrome appeared in group 2 but not in group 1, where intestinal adaptation was observed by 4 weeks after the resection. Rejection was confirmed in group 3 using conventional endoscopy plus biopsies and at necropsy. CONCLUSION: Total bowel resection is an adequate model for short gut syndrome in pigs, rejection can be readily identified by using conventional endoscopy.     

Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.     

Compromised duodenal mucosal integrity in children with short bowel syndrome after adaptation to enteral autonomy

BackgroundIntestinal adaptation has been extensively studied experimentally, but very limited data is available on human subjects. In this study we assessed intestinal adaption in humans with short bowel syndrome (SBS).MethodsWe comparatively evaluated mucosal hyperplasia, inflammation, barrier function and nutrient transport using histology, immunohistochemistry and qPCR for selected 52 key genes in duodenal biopsies obtained from children with SBS after weaning off parenteral nutrition (n = 33), and matched controls without intestinal pathology (n = 12). Small bowel dilatation was assessed from contrast small bowel series.ResultsDuodenal mucosa of SBS children showed increased histologic inflammation of lamina propria (p = 0.033) and mucosal mRNA expression of tumor necrosis factor (p = 0.027), transforming growth factor (TGF)-β2 (p = 0.006) and caveolin-1 (CAV1; p = 0.001). Villus height, crypt depth, enterocyte proliferation, apoptosis and expression of proliferation and nutrient transport genes remained unchanged. Pathologic small bowel dilatation reduced crypt depth (p = 0.045) and downregulated mRNA expression of interleukin (IL)-6 by three-fold (p = 0.008), while correlating negatively with IL6 (r = -0.609, p = 0.004). Loss of ileocecal valve (ICV) upregulated mRNA expression of toll-like receptor 4 (TLR4), TGF-β1, CAV1, several apoptosis regulating genes, and mRNA expression of zonulin (p < 0.05 for all).ConclusionsDespite successful adaptation to enteral autonomy, duodenal mucosa of SBS children displayed histologic and molecular signs of abnormal inflammation and regulation of epithelial permeability, whereas no structural or molecular signs of adaptive hyperplasia or enhanced nutrient transport were observed. Excessive dilatation of the remaining small bowel paralleled impaired duodenal crypt homeostasis, while absence of ICV modified regulation of mucosal inflammation, regeneration and permeability.Level of evidenceII     

The role of antibiotic prophylaxis with sodium ceftriaxone to prevent bacterial translocation associated with hypovolemic shock: an experimental study in rats.

One of the measures adopted to reduce or prevent intestinal bacterial translocation (BT) in patients who are in hemorrhagic shock consists of prophylactic antibiotics. This study attempted to assess the effectiveness of administering systemic antibiotic to suppress BT in rats submitted to hemorrhagic shock. Sixty-eight male Wistar rats were divided into two experiments. In experiment 1 (n = 28), the animals were randomly divided into three groups: group I (n = 7), sham operation; group II (n = 11), constituted by animals that were submitted to hemorrhagic shock by removing 40% of the volemia, and were resuscitated after 40 min of sustained shock, replacing the previously removed blood; and group III (n = 10), animals that, besides hemorrhagic shock and volemic replacement, received 50 mg/kg of sodium ceftriaxone intravenous 1 min after blood readministration. Mesenteric lymph nodes (MLN) for culture tests and segments of the small bowel were removed for histopathological studies 1 day after the operation in the three groups. In experiment 2, the same procedures were performed, except the laparotomy for removing MLN and segments of jejunal and ileal bowel, but the animals were followed during 7 days, in order to evaluate the mortality rate. In the control group (group I), the bacteriological assessment of the MLN was negative in all cases. Only 40% of the animals treated with antibiotics after hypovolemic shock (group III) presented positive bacteriological exams of the MLN, and this rate was 90% in the group of animals that did not receive this substance (group II) (p < .05). Escherichia coli was the bacteria identified most frequently in culture tests (92.8%). The villosities atrophy and inflammatory infiltrate of the lamina propria were the most common histological changes in the bowel, although the intensity was similar in groups II and III (p > .05), but more intense that in group I (p < .05). The mortality rates in groups I, II, and III 7 days after hypovolemic shock were 0%, 20%, and 20%, respectively. Prophylactic antibiotics significantly reduced the presence of bacteria in the MLN in situations of hypovolemic shock, in rats. This was probably related to a lower BT. However, this aspect did not modify the mortality rate of the animals. Also, the possibility that BT may not have a significant influence in this outcome should be considered.     

Bacterial translocation after cirrhotic liver resection: a clinical investigation of 181 patients

BACKGROUND: Cirrhotic patients are usually associated with a high susceptibility to infection. Although bacterial translocation from gut mucosa to mesenteric lymph node (MLN) and systemic circulation is a well-known phenomenon after hepatectomy, its role in cirrhotic patients remains unclear. MATERIALS AND METHODS: MLN was harvested for bacterial culture before and after liver resection in 181 cirrhotic patients. The characteristics and postoperative courses of patients with positive and negative bacterial culture for MLN after hepatectomy were compared. Postoperative systemic antibiotics were administered if infectious complications occurred. RESULTS: No bacteria were cultured in MLN before hepatectomy. Bacterial translocation (BT) to MLN after hepatectomy occurred in 36 patients (BT group). After multivariate analysis, intraoperative blood transfusion was the only independent factor that influenced bacterial translocation rates after cirrhotic liver resection. BT group patients also had higher infectious and overall complication rates, with a longer postoperative hospital stay. Among the cultured bacteriae from infected sites in BT group patients with infectious complications, only 2 patients (12.5%) had totally different bacterial species to those cultured from MLNs. CONCLUSIONS: Bacterial translocation more often occurred after liver resection in cirrhotic patients who received intraoperative blood transfusion. Such patients had higher postoperative infectious and overall complication rates. Thus, avoidance of intraoperative blood transfusion is mandatory for cirrhotic liver resection.     

Short bowel syndrome after trauma

PURPOSE: Traumatic injury to the intestine and its vasculature is a potential cause of short bowel syndrome (SBS). Our aim was to determine the incidence and mechanisms of traumatic injury to the bowel resulting in massive resection. METHODS: We reviewed the records of 196 adult patients evaluated with SBS over a 23-year period. RESULTS: Sixteen (8%) patients had SBS secondary to traumatic injury. Injury to the intestinal blood supply accounted for 81% (n = 13), and direct injury to the bowel wall accounted for the remaining 19% (n = 3). Nineteen associated injuries were present in 11 (67%) patients. CONCLUSION: Traumatic injury to the abdomen accounts for a small proportion of patients with SBS. These patients often have other associated injuries which might influence their outcome. Early diagnosis of vascular injury, use of second look procedures, appropriate resuscitation, and avoidance of all unnecessary resections may aid in prevention of this serious complication.     

Intrinsic myenteric denervation: a new model to increase the intestinal absorptive surface in short-bowel syndrome.

INTRODUCTION: Short-bowel syndrome (SBS) is caused by resection of massive portions of the small intestine and is characterized by symptoms related to malabsorption, of which severe weight loss is the most apparent. Surgical treatments for SBS are not yet satisfactory. In rats, the myenteric denervation by benzalkonium chloride (BAC) leads to development of megaileum with visceral dilatation and mucosal hyperplasia and increases the intestinal transit time. Such operation in the remaining intestinal segment after massive small bowel resection could increase the duration of contact between luminal nutrients and ileal mucosal epithelium, and furthermore, it could increase the superficial area of the mucosa. Thus, our aim in this study was to evaluate the epithelial morphology and body weight changes of animals after intrinsic ileal denervation associated with extensive small intestine resection. MATERIAL AND METHODS: Wistar rats were submitted to resection of 80% of small intestinal length (Group R). Another group (B) of animals also received topical serosal application of BAC 0.3%. Control animals were submitted to simulated surgery (Group C). Animals were weighed weekly and sacrificed after 90 days. Intestinal walls were collected for histological procedure and morphometry. RESULTS: At the end of the experimental period all groups showed weight increase, which was reduced in the R group (P < 0.01). Interestingly, the denervated Group B showed a marked increase in weight, similar to the control animals. Morphometric analysis of the mucosal layer area showed a major increase in mucosal surface area, mainly in Group B. CONCLUSIONS: Our results showed that the ileal intrinsic denervation associated with massive intestinal resection induced an increase in the superficial absorptive area and was able to improve the postsurgical conditions for the animals, with accentuated weight increase. This procedure may be a useful model for further studies related to the role of the enteric nervous system on intestinal adaptations after extensive resections and may provide a new approach for the surgical treatment of short-bowel syndrome.