Risk of adhesive obstruction after colorectal surgery: the benefits of the minimally invasive approach may extend well beyond the perioperative period.

BACKGROUND: Risk of adhesive small-bowel obstruction (SBO) is high following open colorectal surgery. Laparoscopic surgery may induce fewer adhesions; however, the translation of this advantage to a reduced rate of bowel obstruction has not been well demonstrated. This study evaluates whether SBO is lower after laparoscopic compared with open colorectal surgery. METHODS: Patients who underwent laparoscopic abdominal colorectal surgery, without any previous history of open surgery, from 1998 to 2010 were identified from a prospective laparoscopic database. Details regarding occurrence of symptoms of SBO (colicky abdominal pain; nausea and/or vomiting; constipation; abdominal distension not due to infection or gastroenteritis), admissions to hospital with radiological findings confirming SBO, and surgery for obstruction after the laparoscopic colectomy were obtained by contacting patients and mailed questionnaires. Patients undergoing open colorectal surgery for similar operations during the same period and without a history of previous open surgery also were contacted and compared with the laparoscopic group for risk of obstruction. RESULTS: Information pertaining to SBO was available for 205 patients who underwent an elective laparoscopic procedure and 205 similar open operations. The two groups had similar age, gender, and sufficiently long duration of follow-up. Despite a significantly longer duration of follow-up for the laparoscopic group, admission to hospital for SBO was similar between groups. Patients who underwent laparoscopic surgery also had significantly lower operative intervention for SBO (8% vs. 2%, p = 0.006). CONCLUSIONS: Although the rate of SBO was similar after laparoscopic and open colorectal surgery, the need for operative intervention for SBO was significantly lower after laparoscopic operations. These findings especially in the context of the longer follow-up for laparoscopic patients suggests that the lower incidence of adhesions expected after laparoscopic surgery likely translates into long-term benefits in terms of reduced SBO.

Indomethacin-induced small intestinal injury is ameliorated by cilostazol, a specific PDE-3 inhibitor.

BACKGROUND: Neutrophil migration, one of the major factors predisposing to nonsteroidal anti-inflammatory drugs (NSAIDs)-induced intestinal lesions, consists of several steps, including interaction with P-selectin from platelets. Cilostazol, a specific phosphodiesterase (PDE)-3 inhibitor, suppresses the expression of P-selectin from platelets and reduces interaction between platelets and leukocytes, leading to inflammatory amelioration in several disease models. We tried to clarify the therapeutic effectiveness of cilostazol for NSAID-induced small intestinal lesions. SUBJECTS AND METHODS: 1) Anti-PSGL-1 antibody (2 mg/kg) or cilostazol (100 mg/kg) was administered to mice one hour before Indomethacin (IND, 2.5 mg/kg) administration for 4 days to evaluate small intestinal lesions. 2) IND-induced migratory behaviors of neutrophils and platelets were evaluated in intestinal vessels by an intravital microscopy. RESULTS: i) IND induced small intestinal lesions with an increase in MPO activity. Anti-PSGL-1 antibody and cilostazol ameliorated intestinal lesions along with suppression of MPO activity. ii) Intravital microscopy revealed that administration of IND increased migration of platelet-bearing neutrophils. Cilostazol treatment ameliorated neutrophil migration by blocking interaction between platelets and neutrophils. CONCLUSION: Our results suggest that enhanced platelets-bearing neutrophil migration is critically involved in the pathogenesis of IND-induced small intestinal lesions and suggest a potential application of cilostazol for prevention of NSAID-induced small intestinal lesions.

Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats.

PURPOSE: High doses of anticancer drugs often damage the intestinal mucosa. The purpose of the present study was to examine the effect of glutamine on mucosal damage induced by cyclophosphamide in a rat model, and to elucidate the mechanisms responsible for its protective effects. METHOD: Rats were randomly assigned to one of the three experimental groups. Group A (control) (n = 8): intraperitoneal injection of saline, group B (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg), group C (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg) and oral glutamine (1.0 g/kg). After 3 days, the ileal segment was removed for morphological and the biochemical analyses. We also evaluated the level of mucosal apoptosis by the TUNEL method and enterocyte proliferation using bromodeoxyuridine (BrdU). RESULTS: Mucosal atrophy was observed in group B but not in groups A or C. The mucosal wet weight, protein and glutathione levels were significantly decreased in group B compared with group A, and were increased significantly in group C compared with group B. While enterocyte proliferation significantly decreased and the apoptotic index significantly increased in group B compared with group A, a significant increase in the enterocyte proliferation and a significant decrease in apoptosis were observed in group C compared with group B. CONCLUSIONS: Glutamine prevented intestinal mucosal injury induced by cyclophosphamide via increased glutathione, decreased apoptosis and increased proliferation of intestinal epithelial cells.

Intestinal obstruction by giant Meckel's diverticulum. Case report.

Most cases of Meckel's diverticulum (MD) are asymptomatic and discovered by chance. Management of MD is controversial. The authors describe an exceptional case of intestinal obstruction caused by a giant MD in a patient who had previously undergone appendectomy. A review of the contradictory literature on this subject leads to the conclusion that careful consideration of clinical and morphological data (patient's age, ASA score, the surgical procedure to be performed, morphology and position of the MD, any fibrotic bands) is required before deciding whether or not to resect an asymptomatic MD.

Synergistic Protective Effect of Konjac Mannan Oligosaccharides and Bacillus subtilis on Intestinal Epithelial Barrier Dysfunction in Caco-2 Cell Model and Mice Model of Lipopolysaccharide Stimulation.

As the first line of defense against intestinal bacteria and toxins, intestinal epithelial cells are always exposed to bacteria or lipopolysaccharide (LPS), whereas pathogenic bacteria or LPS can cause intestinal epithelial cell damage. Previous studies have shown that konjac mannan oligosaccharides (KMOS) have a positive effect on maintaining intestinal integrity, and Bacillus subtilis (BS) can promote the barrier effect of the intestine. However, it is still unknown whether KMOS and BS have a synergistic protective effect on the intestines. In this study, we used the LPS-induced Caco-2 cell injury model and mouse intestinal injury model to study the synergistic effects of KMOS and BS. Compared with KMOS or BS alone, co-treatment with KMOS and BS significantly enhanced the activity and antioxidant capacity of Caco-2 cell, protected mouse liver and ileum from LPS-induced oxidative damage, and repaired tight junction and mucus barrier damage by up-regulating the expression of Claudin-1, ZO-1 and MUC-2. Our results demonstrate that the combination of KMOS and BS has a synergistic repair effect on inflammatory and oxidative damage of Caco-2 cells and aIIeviates LPS-induced acute intestinal injury in mice.

Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) causes gastrointestinal dysfunction and increased intestinal permeability. Regulation of the gut barrier may involve the central nervous system. We hypothesize that vagal nerve stimulation prevents an increase in intestinal permeability after TBI. METHODS: Balb/c mice underwent a weight drop TBI. Selected mice had electrical stimulation of the cervical vagus nerve before TBI. Intestinal permeability to 4.4 kDa FITC-Dextran was measured 6 hours after injury. Ileum was harvested and intestinal tumor necrosis factor-alpha and glial fibrillary acidic protein (GFAP), a marker of glial activity, were measured. RESULTS: TBI increased intestinal permeability compared with sham, 6 hours after injury (98.5 microg/mL +/- 12.5 vs. 29.5 microg/mL +/- 5.9 microg/mL; p < 0.01). Vagal stimulation prevented TBI-induced intestinal permeability (55.8 +/- 4.8 microg/mL vs. 98.49 microg/mL +/- 12.5; p < 0.02). TBI animals had an increase in intestinal tumor necrosis factor-alpha 6 hours after injury compared with vagal stimulation + TBI (45.6 +/- 8.6 pg/mL vs. 24.1 +/- 1.4 pg/mL; p < 0.001). TBI increased intestinal GFAP 6.2-fold higher than sham at 2 hours and 11.5-fold higher at 4 hours after injury (p < 0.05). Intestinal GFAP in vagal stimulation + TBI animals was also 6.7-fold higher than sham at 2 hours, however, intestinal GFAP was 18.0-fold higher at 4 hours compared with sham and 1.6-fold higher than TBI alone (p < 0.05). CONCLUSION: In a mouse model of TBI, vagal stimulation prevented TBI-induced intestinal permeability. Furthermore, vagal stimulation increased enteric glial activity and may represent the pathway for central nervous system regulation of intestinal permeability.

Management of ileocutaneous fistulae using TNP after surgery for abdominal malignancy.

Enteric fluids produced by enterocutaneous fistulae can cause severe inflammation in the surrounding skin. By removing these corrosive fluids, topical negative pressure can help maintain skin integrity and promote spontaneous closure.

Human in vivo cellular response to a cross-linked acellular collagen implant.

BACKGROUND: Hernia surgery, in particular parastomal hernia mesh repair and new techniques for hernia prevention, require novel biomaterials that avoid fibrosis and potential bowel erosion, while retaining adequate strength for their intended purpose. The aim was to evaluate the human host response to an acellular porcine-derived cross-linked collagen implant. METHODS: In a prospective pilot study on prevention of parastomal herniation, 15 patients undergoing loop stoma formation had an implant placed within the anterior abdominal wall. Histopathology and immunohistochemistry were performed to analyse the implant qualitatively and, where appropriate, quantitatively for biocompatibility, degradation, cellular infiltration, neo-extracellular matrix (ECM) formation and neovascularization. RESULTS: At a median of 7 (range 1-8) months, 12 of 15 patients had stoma reversal and 11 implant biopsies were obtained. In biopsies from ten of the 11 patients all responses were limited to the periphery of the implant and native pores. There was a minimal inflammatory response and minimal degradation of the implant. Fibroblastic and neovascular infiltration were noted, as was matrix metalloproteinase 1 activity with organized deposition of host collagen, fibronectin and laminin. CONCLUSION: The collagen implant demonstrated excellent biocompatibility and resistance to degradation in most patients. However, fibrovascular in-growth and ECM deposition were limited. This implant has excellent potential for soft tissue reinforcement.

Role of pentoxifylline and iloprost in the prevention of ischemia-reperfusion injury in an experimental model of intestine ischemia-reperfusion in rats.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury can lead to multiple organ failure and death. The aim of this study was to investigate the effects of pentoxifylline and iloprost administered before reperfusion in intestinal ischemia. METHODS: In total, 25 male Wistar Albino rats weighing 250-300 g were divided into five groups each comprising five subjects: control group (n=5), sham group (n=5, no I/R), I/R group (n=5, 45 min ischemia, and 120 min reperfusion), I/R + pentoxifylline group (n=5, 45 min ischemia following intraperitoneal 50 mg/kg pentoxifylline and 120 min reperfusion), and I/R + iloprast group (n=5, 45 min ischemia followed by intraperitoneal 2 mcg /kg iloprost and 120 min reperfusion). At the end of the experiment, ileum specimens were stained using hematoxylin-eosin and histopathologically evaluated using the Chiu score. Isometric contraction-relaxation responses were recorded using organ baths for contraction-relaxation responses. RESULTS: Pentoxifylline provided a significant improvement in response to histopathological and contraction-relaxation responses. Although iloprost provided recovery in reperfusion injury, it was not statistically significant. CONCLUSION: Our findings demonstrate that pentoxifylline may be promising in preventing small bowel ischemia-reperfusion injury. We concluded that further clinical and experimental studies for iloprost are needed.

Laparoscopic Ileocolic Pexy as Preventive Treatment Alternative for Ileocolic Intussusception With Multiple Recurrences in Children.

PURPOSE: Idiopathic intussusception is one of the most common causes of small bowel obstruction in children. To decrease subsequent recurrence and to detect a lead point, an early laparoscopy was performed for children with multiple recurrent ileocolic intussusception. MATERIALS AND METHODS: Between January 2014 and July 2017, a total of 2561 consecutive children with intussusception were treated and followed. There were 110 patients with multiple recurrences, 61 were treated with ileocolic pexy and 49 were not and the results were compared. Using a 5-mm laparoscope and 2 additional transabdominal wall stab incisions, an appendectomy and an ileocolic pexy with nonabsorbable sutures were performed simultaneously for the children after the last successful enema reduction. RESULTS: The mean operative time was 59.4±13.1 minutes (range, 45 to 85 min). No cases required conversion to an open surgery, blood loss was minimal. There was no operative morbidity. Two patients were found with a Meckel's diverticulum, and were removed by slightly enlarged transumbilical incision. The 61 cases were followed up for 4 to 42 months (mean, 19.3±1.1 mo). In the ileocolic pexy group, 2 of 61 (3.2%) got 2 episodes of recurrences. Among the 25 patients with 3 recurrences without undergoing ileocolic pexy, 18 (72%) had 22 episodes of recurrence. Of the 16 patients with 4 recurrences and without ileocolic pexy, 14 (87.5%) had 17 episodes of recurrence. There was statistical difference in recurrent rate among the 3 groups (ileocolonic pexy group vs. 3 recurrences group, P<0.01; ileocolic pexy group vs. 4 recurrences group, P<0.01). CONCLUSIONS: Early preventive laparoscopic ileocolic pexy should be undertaken for the patients with multiple recurrences after the last nonsurgical reduction had been attempted successfully.

Development of next generation medical countermeasures to nerve agent poisoning.

Medical countermeasures provide a key role in the UK integrated approach to chemical defence and are aimed at preventing or mitigating the effects of exposure to nerve agents. It is UK policy that medical countermeasures will be licensed products. Demonstration of efficacy relies on extrapolation of animal-derived data to man which means that species selection is extremely important. For the foreseeable future it is likely that a combination of pretreatment and therapy will be required to provide protection against nerve agent poisoning. There is a longer-term aspiration to develop a post poisoning-therapy which would reduce the reliance on pretreatment, prevent or mitigate the effects of exposure to all nerve agents and decrease the requirement for three autoinjectors. Immediate therapy comprising physostigmine (0.2mg/kg), hyoscine hydrobromide (4mg/kg) and HI-6 (93.6mg/kg) protected all animals against the lethal effects of a supralethal dose of GD, when given 1min after nerve agent poisoning in the absence of any pretreatment. In contrast when hyoscine hydrobromide was replaced with hyoscine methyl nitrate most of the animals died within 24h, whereas when an equal mixture of hyoscine hydrobromide and hyoscine methyl nitrate was used all the animals survived. None of these animals had an intussusception. It would not be possible to deliver these doses of HI-6 to a human from a single autoinjector device. Recent studies have shown that a lower dose of HI-6 (7mg/kg) which can be delivered via an autoinjector, in combination with physostigmine and hyoscine hydrobromide provides good protection against the lethal effects of a supralethal dose of GD. A number of animals died between 6 and 24h and had an intussusception. The surviving animals did not begin to regain weight until 48h after poisoning. In contrast when a mixture of hyoscine hydrobromide and hyoscine methyl nitrate was used, one animal died within 15min, the other animals all survived, regained weight from 24h and did not have an intussusception. These studies will now be extended to include other agents and will be taken forward to studies in non-human primates where the incidence of intussusception will be closely monitored.

N-hexacosanol prevents diabetes-induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system.

We evaluated the effects of N-hexacosanol, a cyclohexenonic long-chain fatty alcohol, on muscarinic receptors in diabetic rat ileal dysfunction. Eight-week-old male SD rats were divided into four groups. After induction of diabetes (streptozotocin 50 mg/kg, i.p.), three groups were maintained for eight weeks with treatment by N-hexacosanol (0, 2 or 8 mg/kg, s.c. every day). Ileum function was investigated by organ bath studies using carbachol and KCl, and the expression levels of muscarinic M(2) and M(3) receptors were investigated by real-time polymerase chain reaction. Various concentrations of subtype-selective muscarinic antagonists, i.e., atropine (non-selective), pirenzepine (M(1) selective), methoctramine (M(2) selective), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M(1)/M(3) selective), were used in this study. In the presence and absence of these antagonists, contractile response curves to increasing concentrations of carbachol were investigated. Treatment with N-hexacosanol did not alter the diabetic status of the rats, but did significantly prevent the carbachol-induced hypercontractility in diabetic rat ileum. Estimation of the pA(2) values for atropine, pirenzepine, methoctramine, and 4-DAMP indicated that the carbacholinduced contractile response in the ileum is mainly mediated through the muscarinic M(3) receptor subtype in all groups. Furthermore, N-hexacosanol significantly prevented the diabetes-induced up-regulation of intestinal muscarinic M(2) and M(3) receptor mRNAs in streptozotocin-diabetic rats. Our data indicated that N-hexacosanol exerts preventive effects with respect to carbachol-induced hypercontractility in the diabetic rat ileum without qualitative alteration of the muscarinic receptor system.

Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast.

BACKGROUND: Sepsis is a generalized inflammatory response, which involves organ systems remote from the locus of the initial infectious insult, involves the release of cytokines and the subsequent formation of reactive oxygen and nitrogen species. OBJECTIVE: The aim of this study was to investigate the possible protective effect of montelukast, a leukotriene receptor blocker, against oxidative damage in the liver and ileum of septic rats. METHODS: Sepsis was induced by cecal ligation and puncture method in female Wistar albino rats. Sepsis and sham operated (control) groups received either saline or montelukast (10 mg/kg, ip) immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, glutathione (GSH) levels--a key antioxidant, myeloperoxidase (MPO) activity--an index of neutrophil infiltration, and collagen contents were determined in the liver and ileum. Formation of reactive oxygen species in liver and ileal tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Both tissues were also analyzed histologically. Serum lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) level were assessed in trunk blood. RESULTS: Sepsis resulted in decreased GSH levels, and increased MDA levels, MPO activity, CL levels and collagen contents in both the liver and the ileum (P < 0.05-P < 0.001) indicating the presence of the oxidative damage. Similarly, serum TNF-alpha and LDH were elevated in the sepsis group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by sepsis. CONCLUSION: Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on sepsis-induced hepatic and intestinal damage and protects against oxidative injury by a neutrophil-dependent mechanism.

Effect of bifidobacterium on defensin-5 expression in intestinal injury of preweaning rats.

AIM: To investigate the protective effect of bifidobacterium in endotoxin-induced intestinal injury in preweaning rats. METHODS: Preweaning rats were randomly divided into three groups (n = 40 for each): a control group (group C), a model group (group E) and a treatment group (group T). Both groups E and T were intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 5 mg/kg (5 mg/L in normal saline), and group T was intragastrically administrated with bifidobacterium suspension (2.0 × 10(9) CFU/mL, 0.5 mL each time, twice a day, until the end of the experiment) 7 d before LPS administration. Group C was intraperitoneally injected with normal saline. After intraperitoneal injection and intragastric administration, the rats were placed back to the initial cage to receive breast feeding. The rats were killed at 2, 6, 12, 24 or 72 h, respectively, after endotoxin or physiological saline injection to collect serum and ileal tissue samples. Myeloperoxidase (MPO) contents in serum and ileum were detected at different times, and expression of ileal defensin-5 mRNA was evaluated by reverse transcription-polymerase chain reaction. RESULTS: Serum and ileal MPO contents in group E were significantly higher than those in group C (serum contents: 107.50 ± 17.70 vs 157.14 ± 24.67, P < 0.05; ileal contents: 1.03 ± 0.21 vs 1.57 ± 0.33, P < 0.05), which peaked at 12 h and 6 h, respectively. MPO contents in group T were significantly lower than those in group E (serum contents: 114.38 ± 24.56 vs 145.25 ± 23.62, P < 0.05; ileal contents: 1.25 ± 0.24 vs 1.57 ± 0.33, P < 0.05). The expression of defensin-5 mRNA in group E was significantly higher than that in group C (0.953 ± 0.238 vs 0.631 ± 0.146, P < 0.05), which peaked at 2 h, and then decreased gradually. The expression of defensin-5 mRNA in group T was significantly lower than that in group E (0.487 ± 0.149 vs 0.758 ± 0.160, P < 0.05) apparently in 24 h. The expression of defensin-5 mRNA at 2 h in group T was significantly higher than that in group C (0.824 ± 0.158 vs 0.631 ± 0.146, P < 0.05). CONCLUSION: MPO and defensin-5 mRNA increase in preweaning rats with LPS-induced intestinal injury. Bifidobacterium protects the gut by inhibiting MPO activity, not by increasing defensin-5 secretion.

Postoperative ileus: progress towards effective management.

The pathogenesis of postoperative ileus (PI) is multifactorial, and includes activation of inhibitory reflexes, inflammatory mediators and opioids (endogenous and exogenous). Accordingly, various strategies have been employed to prevent PI. As single-modality treatment, continuous postoperative epidural analgesia including local anaesthetics has been most effective in the prevention of PI. Choice of anaesthetic technique has no major impact on PI. Minimally invasive surgery reduces PI, in accordance with the sustained reduction in the inflammatory responses, while the effects of early institution of oral nutrition on PI per se are minor. Several pharmacological agents have been employed to resolve PI (propranolol, dihydroergotamine, neostigmine, erythromycin, cisapride, metoclopramide, cholecystokinin, ceruletide and vasopressin), most with either limited effect or limited applicability because of adverse effects. The development of new peripheral selective opioid antagonists is promising and has been demonstrated to shorten PI significantly. A multi-modal rehabilitation programme including continuous epidural analgesia with local anaesthetics, enforced nutrition and mobilisation may reduce PI to 1-2 days after colonic surgery.

Experimentally induced ileal ulcers in rats. Formula diet is a preventive factor.

We recently described an experimental model in the rat to create recurring chronic ileal inflammation including ulceration. This model is dependent on an "in vivo culture" of normal intestinal contents. In the present experimental study we examined the effect of a polymeric and a hydrolyzed formula diet on the formation of ulcerating lesions using our rat model. Two groups of rats (twenty in each group) were fed either one of these formula diets eight weeks prior to the experimental procedure and this diet was continued until sacrifice eight weeks later. Twenty control rats also underwent the experimental procedure but were fed standard rat pellets for the same time periods. At sacrifice 60% of the control rats had developed ileal ulcers. None of the rats fed the formula diets developed macroscopic ileal inflammation or ulceration. The effectiveness of formula diets in inducing remission in Crohn's disease in humans may be linked to alterations in the intestinal microflora. We hypothesize that the formula diets in this experiment exerted a protective effect against ileal ulceration by altering the ileal microflora. Preliminary studies support this hypothesis but need to be expanded.

Formula diet is a preventive factor in experimentally induced ideal ulcers in rats. A bacteriological study.

We earlier described an experimental model to create recurring chronic ileal inflammation with ulceration in the rat. A 2 cm segment of the distal ileum is excised but left attached to its intact mesentery; the ileum is reanastomosed. The ileal segment will seal off its open ends and a cyst-like structure of varying size will be formed, containing mucus, cell debris and bacteria. Approximately two thirds of the animals develop chronic inflammation with ulceration proximal to the ileal anastomosis. The ileal cyst and the surgical procedure on the distal ileum were shown to be prerequisites of the rat model for the development of lesions. We recently described that, in contrast to rats fed a standard diet, rats fed a hydrolyzed formula diet never developed inflammation or ulceration when subjected to the experimental procedure. In the present study we confirmed these observations and showed that the normal ileal flora (NIF) and the ileal cyst flora (ICF) were significantly influenced by the diets. The bacterial counts of both the aerobic and anaerobic NIF were 2 10log lower, i.e. > or = 99%, in rat fed the formula diet as compared to in those fed standard rat pellets. The NIF of the former group was represented by more aerobic species than the NIF of rats on the standard diet. Compared to the NIF there was a parallel increase in the bacterial counts of the ICF by approximately 2 10log CFU values in both groups of rats. The mean number of anaerobic species, mainly Gram-negative rods of the ICF, increased by approximately 70% in the rats on the standard diet that developed ileal ulceration, whereas identified aerobic species of the ICF decreased by 61% in rats on the formula diet and by 46% in those on the standard diet that did not develop ileal ulceration. The number of anaerobes in those groups of rats remained unchanged. The significant bacteriological differences between the rats that developed ileal ulcers and those which did not indicate that bacteria may be involved, directly or indirectly, in the development of chronic ileal ulceration.

Placebo-controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).

OBJECTIVE: Endoscopic postoperative recurrences occur early after 'curative' surgery for Crohn's disease. Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn's disease. The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after 'curative' resection for ileal, colonic or ileocolonic Crohn's disease. We conducted a multicentre double-blind controlled trial comparing Claversal (1g tid) with placebo, starting within 15 days after surgery. The macroscopic normality of the two anastomotic segments was assessed at surgery. Patients were clinically and biologically evaluated twice (6-week interval), and colonoscopy was performed at 12 weeks. Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four-grade score. RESULTS: Between May 1989 and May 1991 12 centres included 126 patients, 70 women and 56 men, aged 33 +/- 12 years (range 16-70) in the study. Disease locations were ileal, colonic and ileocolonic in 45, 6 and 49%, respectively. Claversal and placebo groups were similar at inclusion, except for ESR (37 +/- 26 vs. 27 +/- 23 mm/h in the Claversal and placebo groups, respectively; P < 0.05). Nine patients were withdrawn from the study. Adverse reactions occurred only in six patients. Five patients were excluded for protocol violation. Finally, 106 patients could be evaluated at 12 weeks (55 Claversal and 51 placebo). An endoscopic relapse was observed in 50% and 63% of the Claversal and placebo groups, respectively (P = 0.16), with a similar grade distribution. Claversal was well tolerated. CONCLUSIONS: Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn's disease. There was a slight trend towards greater efficacy of Claversal; it could be worthwhile trying higher dosages and/or 5-ASA compounds with different intestinal release profiles.