Small bowel intramural hematoma caused by warfarin: case report and literature review.

BACKGROUND: Intramural hematoma of the small bowel is a rare yet acute gastrointestinal condition typically linked with impaired coagulation function, often posing diagnostic challenges. It is principally encountered in patients undergoing prolonged anticoagulant therapy, specifically warfarin. CASE PRESENTATION: We reported a case of intramural hematoma associated with warfarin use. The patient was admitted to hospital with abdominal pain and had received anticoagulant therapy with warfarin 2.5 mg/day for 4 years. Laboratory examination showed decreased coagulation function, abdominal CT showed obvious thickening and swelling of part of the jejunal wall, and abdominal puncture found no gastroenteric fluid or purulent fluid. We treated the patient with vitamin K and fresh frozen plasma. The patient was discharged after the recovery of coagulation function. Then we undertaook a comprehensive review of relevant case reports to extract shared clinical features and effective therapeutic strategies. CONCLUSION: Our analysis highlights that hematoma in the small intestinal wall caused by warfarin overdose often presents as sudden and intense abdominal pain, laboratory tests suggest reduced coagulation capacity, and imaging often shows thickening of the intestinal wall. Intravenous vitamin K and plasma supplementation are effective non-surgical strategies. Nevertheless, in instances of severe obstruction and unresponsive hemostasis, surgical resection of necrotic intestinal segments may be necessary. In the cases we reported, we avoided surgery by closely monitoring the coagulation function. Therefore, we suggest that identifying and correcting the impaired coagulation status of patient is essential for timely and appropriate treatment.

Melatonin-Activated Receptor Signaling Pathways Mediate Protective Effects on Surfactant-Induced Increase in Jejunal Mucosal Permeability in Rats.

A well-functional intestinal mucosal barrier can be compromised as a result of various diseases, chemotherapy, radiation, and chemical exposures including surfactants. Currently, there are no approved drugs targeting a dysfunctional intestinal barrier, which emphasizes a significant medical need. One candidate drug reported to regulate intestinal mucosal permeability is melatonin. However, it is still unclear if its effect is primarily receptor mediated or antioxidative, and if it is associated with enteric neural pathways. The aim of this rat intestinal perfusion study was to investigate the mechanisms of melatonin and nicotinic acetylcholine receptors on the increase in intestinal mucosal clearance of 51Cr-labeled ethylenediaminetetraacetate induced by 15 min luminal exposure to the anionic surfactant, sodium dodecyl sulfate. Our results show that melatonin abolished the surfactant-induced increase in intestinal permeability and that this effect was inhibited by luzindole, a melatonin receptor antagonist. In addition, mecamylamine, an antagonist of nicotinic acetylcholine receptors, reduced the surfactant-induced increase in mucosal permeability, using a signaling pathway not influenced by melatonin receptor activation. In conclusion, our results support melatonin as a potentially potent candidate for the oral treatment of a compromised intestinal mucosal barrier, and that its protective effect is primarily receptor-mediated.

Co-exposure to low doses of the food contaminants deoxynivalenol and nivalenol has a synergistic inflammatory effect on intestinal explants.

The global incidence of Fusarium head blight and attendant cereal grains multi-contamination by the trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) are increasing as a possible result of climate change and inadequate agricultural practices. At the molecular level, these mycotoxins bind to the ribosome, activate the mitogen-activated protein kinase and induce a local and systemic inflammation. DON is of public health concern owing to the narrow margin between exposure and tolerable daily intake. The intestinal inflammatory response to DON, NIV and their mixture was analyzed to determine thresholds for their intestinal pro-inflammatory effects and characterize the type and magnitude of their interaction. Fully differentiated three-dimensional porcine jejunal explants were exposed to increasing doses of DON and NIV alone or in combination; the expression levels of IL-1α, IL-1ß, IL-8, IL-17A and IL-22 were measured by RT-PCR. Doses as low as 0.16 µM DON or 0.73 µM NIV significantly increase the intestinal expression levels of the tested inflammation-related genes. These doses are lower than those previously reported for other intestinal toxicity endpoints. The combined pro-inflammatory activity of DON and NIV was synergistic for all the tested genes with combination index value range of 0.23-0.8. Our results indicate that (1) inflammation is a very sensitive endpoint for the intestinal toxicity of the trichothecenes and (2) co-exposure to DON and NIV has a greater inflammatory effect than induced by mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of DON and NIV in the diet.

Serum-derived bovine immunoglobulin/protein isolate in the alleviation of chemotherapy-induced mucositis.

BACKGROUND: Gastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived bovine immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis. METHODS: Animals were gavaged with 250 or 500 mg/kg of SBI twice daily for 4 days, before intraperitoneal administration of 200 mg/kg irinotecan. Twice daily gavaging of SBI continued for 6 days post-irinotecan. Animals were monitored for bodyweight changes and incidence of diarrhoea and clinical symptoms of stress. Tissues and blood samples were collected at necropsy 6 h, and 2, 4 and 6 days post-irinotecan. H&E-stained colon and jejunum were analysed for histological damage. RESULTS: The overall incidence, severity and duration of diarrhoea, and clinical symptoms of mucositis were decreased in irinotecan-treated animals that had received SBI. Animals receiving 500 mg/kg SBI also tended to lose less bodyweight than animals treated only with irinotecan (P > 0.10). SBI-gavaged animals had less pronounced irinotecan-induced changes in neutrophil (P = 0.04959) and lymphocyte (P = 0.0035) levels, and lower tissue damage scores than those receiving irinotecan alone (P < 0.0001). CONCLUSIONS: Twice daily oral gavage of SBI was well-tolerated and reduced the incidence, severity and duration of irinotecan-induced mucositis. SBI was associated with less pronounced changes in inflammatory cell levels and tissue damage to colon and jejunum. Ongoing experiments aim to investigate the mechanisms of SBI-associated gastrointestinal protection.

Jejunitis secondary to Duodopa® probe, a different complication.

Treatment with continuous infusion of intraduodenal (Duodopa®) levodopa / carbidopa is indicated in patients with advanced Parkinson's disease who have not responded to conventional treatment. We present here the case of a patient with this type of probe that debuted jejunitis. A distal phytobezoar was the main causal agent. This rare complication may be favored in cases of intestinal hypomotility. Treatment involves its withdrawal as soon as possible and replacement by a new probe, which results in healing.

Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum.

BACKGROUND AND OBJECTIVE: Although 5-fluorouracil (5-FU) is a widely used as chemotherapy agent, severe mucositis develops in approximately 80% of patients. 5-FU-induced small intestinal mucositis can cause nausea and vomiting. The current study was designed to investigate peripheral alterations due to the 5-FU-induced mucositis of neuronal and non-neuronal 5-HT3 and NK1 receptor expression by immunohistochemical analysis. METHODS: 5-FU was administered by i.p. injection to C57BL/6 mice. After 4 days, segments of the jejunum were removed. The specimens were analyzed by immunohistochemistry, real-time PCR, and enzyme immunoassay. RESULTS: The numbers of 5-HT3 receptor immunopositive cells and nerve fibers in mucosa were increased by 5-FU treatment. The 5-HT3 receptor immunopositive cell bodies were found only in jejunal submucosa and myenteric plexus in the 5-FU-treated mice. The numbers of NK1 receptor cells in mucosa and immunopositive expression of NK1 receptors in deep muscular plexus were dramatically increased in 5-FU-treated mice. Real-time PCR demonstrated that 5-FU treatment significantly increased mRNA levels of 5-HT3A, 5-HT3B, and NK1 receptors. The amounts of 5-HT and substance P increased after 5-FU treatment. The 5-HT3 or NK1 receptor immunopositive cells colocalized with both 5-HT and substance P. Furthermore, 5-HT3 and NK1 receptors colocalized with CD11b. CONCLUSIONS: The 5-HT3 and NK1 immunopositive macrophages and mucosal mast cells in lamina propria release 5-HT and substance P, which in turn activate their corresponding receptors on mucosal cells in autocrine and paracrine manners. It is assumed to result in the release of 5-HT and substance P in mucosa.

[Involvement of endogenous tachykinins in the development of jejunal mucosa injury induced by on-steroidal anti-inflammatory drugs]. / Udzial endogennych tachykinin w powstawaniu uszkodzen blony sluzowej jelita czczego wywolanych niesterydowymi lekami przeciwzapalnymi.

UNLABELLED: Previous studies have shown that tachykinins, the largest family of neuropeptides, affect the development of mucosal damage in the stomach and colon. The aim of the study was to assess the influence of tachykinins receptors antagonists on the development of the mucosa injury in the proximal and distal jejunum. MATERIAL AND METHODS: Mucosal damage was induced by administration of non-steroidal anti inflammatory drugs (NSAIDs), indomethacin, celecoxib or combination of indomethacin plus celecoxib given intragastrically. NK-1 receptor antagonist (SR 140333), NK-2 receptor antagonist (SR 48968) and NK-3 receptor antagonist (SR 142801) were administered intraperitoneally twice, 30 min before treatment with NSAID and again 24 h later, 30 min before the end of the experiment. RESULTS: Administration of indomethacin, a relatively selective inhibitor for cyclooxygenase-1 (COX-1), induced mucosal lesions in the jejunum. Lesions area in the distal jejunum was 8-fold bigger than in the proximal jejunum. This effect was associated with a significant reduction in mucosal blood flow and an increase in mucosal concentration of pro-inflammatory interleukin-1beta (IL-1beta). Celecoxib, selective inhibitor for COX-2 failed to induce mucosal lesions and did not affect the mucosal blood flow and IL-1beta concentration in the proximal and distal jejunum. In rats treated with a combination of indomethacin plus celecoxib, ulcers reached maximal area. This effect was associated with the highest concentration of mucosal IL-1beta and maximal reduction in mucosal blood flow. Administration of NK-1 receptor antagonist, SR 140333 reduced jejunal damage induced by indomethacin given alone or in combination with celecoxib. This effect was associated with significant reduction in mucosal concentration of IL-1beta. Effect of SR 140333 on mucosal blood flow was statistically insignificant. Neither NK-2 nor NK-3 receptor inhibitor affected mucosal blood flow, IL-1beta concentration area of NSAIDs-induced mucosal damage in the jejunum. CONCLUSIONS: Blockade of NK-1 receptor protects the jejunum against NSAIDs-induced mucosal injury and reduces local inflammation. This observation indicates the involvement of endogenous tachykinins in deleterious effects of NSAID.

Systematic review of small bowel diaphragm disease requiring surgery.

AIM: To perform a systematic review of all cases of small bowel diaphragm disease requiring surgery. Small bowel diaphragm disease is a rare complication of small bowel enteropathy secondary to the use of non-steroidal anti-inflammatory drugs (NSAIDs). The objective was to determine the presenting symptoms, duration of NSAID use, mode of diagnosis and type of surgery associated with cases of small bowel diaphragm disease requiring surgery. METHOD: A comprehensive search of the world literature between January 1980 and December 2010 was undertaken. The search terms 'diaphragm disease' and 'mucosal diaphragm disease' in combination with the terms 'surgery', 'intestine' or 'small bowel' were used. All cases of small bowel diaphragm disease requiring surgery in adult patients within the the last 30 years were included. Data including age, gender, mode of presentation, NSAID use, mode of diagnosis, form of surgery, affected area of small bowel and mortality were recorded and analysed. RESULTS: There were 55 cases of small bowel diaphragm disease requiring surgery (31F:18M) with a median age of 69 years. NSAID use occurred in 44 cases and the mean duration of NSAID use was 7 years. The most common presentation was with anaemia in combination with obstructive symptoms. The diagnosis was established by a laparotomy in 51% of cases followed by capsule endoscopy in 25% of cases. Operations performed included small bowel resection (56), combined resection and strictureplasty (three), strictureplasty (one) and hemicolectomy (two). There was only one death. CONCLUSION: Small bowel diaphragm disease presenting as a surgical emergency is likely to become more common due to the increased use of NSAIDs. A history of NSAID use in patients with iron deficiency anaemia or obstructive symptoms should lead to a high index of suspicion for this condition and should be preoperatively investigated.

[Intramural intestinal hematoma--a complication of the oral anticoagulant therapy]. / Hematom intestinal intramural, complicatie a tratamentului anticoagulant oral.

AIM: The presentation of a rare complication of oral anticoagulant treatment involving abdominal surgery. MATERIAL AND METHOD: A 59 years old patient who received oral anticoagulant treatment with Warfarine for repeated episodes of thrombosis of the lower limbs, suddenly develops an occlusive abdominal simptoms, which did not submit under conservative treatment. Biologically the clotting times were modified and the abdominal CT showed lesions of the first jejunal loop. RESULTS: During surgery an amount of blood was found in abdominal cavity and a large haematoma of the first jejunal loop which required resection. The postoperative evolution was simple with discharge in the 12th day, surgically cured. CONCLUSIONS: 1. Intramural intestinal haematoma is a rare, but possible complication of the oral anticoagulant treatment. 2. Precise diagnosis is possible, avoiding unnecessary surgical intervention because the complication is treatable using conservative therapy. 3. Surgical intervention is required in case of a sudden onset, imprecise diagnosis and unfavorable evolution which could point associated intraabdominal lesions.

TNF-alpha modulates iNOS expression in an experimental rat model of indomethacin-induced jejunoileitis.

Multiple mucosal immune factors, such as TNF-alpha and IL-1beta, are thought to be key mediators involved in inflammatory bowel disease. We evaluated the role of the pro-inflammatory cytokine TNF-alpha on nitric oxide synthase (NOS) expression in indomethacin-induced jejunoileitis in rats. Jejunoileitis was induced in rats with subcutaneous injections of indomethacin (7.5 mg/kg) 24 h apart for two consecutive days, and animals were randomized into four groups. Group 1 received only indomethacin. Group 2 was treated with a daily dose of phosphodiesterase (PDE) inhibitor (theophylline or pentoxifylline) by oral gavage for 2 days before and 4 days after indomethacin. Group 3 received a single dose of anti-TNF-alpha monoclonal antibody (TNF-Ab, IP) 30 min before indomethacin. Group 4 was treated with 1 h hyperbaric oxygenation (HBO(2)) for 5 days after indomethacin. Rats were sacrificed at 12 h or 4 days after final indomethacin injection. PDE inhibitor, TNF-Ab, or HBO(2) treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-alpha and nitrate/nitrite (NOx) concentrations above control values at 12 h, inducible NOS (iNOS) expression was detected only at day 4. Serum IL-1beta levels did not change at 12 h but increased 4-fold after 4 days. Indomethacin had no effect on constitutive NOS. Treatment with PDE inhibitor, TNF-Ab, or HBO(2) significantly reduced serum/tissue TNF-alpha, IL-1beta, NOx, and iNOS expression. Our data show TNF-alpha plays an early pro-inflammatory role in indomethacin-induced jejunoileitis. Additionally, down-regulation of NOx by PDE inhibitors, TNF-Ab, or HBO(2) suggests that TNF-alpha modulates iNOS expression.

[Spontaneous intramural hematoma of the small bowel due to use of oral anticoagulants: case report and review of the literature]. / Hematoma intramural espontáneo de intestino delgado debido al uso de anticoagulantes orales: reporte de caso y revisión de la literatura.

We describe a case of 78 year-old woman under anticoagulant therapy who presented abdominal pain, nausea, vomiting and an elevated prothrombin time levels (INR = 9.03). The ultrasound and abdominal CT showed a thickened small bowel wall mainly involving duodenum and jejunum. The endoscopy showed an ecchymotic aspect of duodenum and jejunum. The patient received conservative medical treatment and her symptoms spontaneously subsided.

[Non-traumatic spontaneous intramural hematoma of the small bowel: an infrequent complication of anticoagulation therapy]. / Hematoma intramural espontáneo no traumático del intestino delgado: una complicación poco habitual de los anticoagulantes.

Intramural hematoma of the small bowel is an infrequent complication of the use of oral anticoagulants. Diagnosis can only be performed when these symptoms are associated with a history of oral anticoagulant use and radiological tests. We report the case of a patient admitted for epigastric pain associated with oral anticoagulation therapy with warfarin and a 48-h history of retention vomiting. Ultrasound and abdominal computed tomography scans revealed a jejunal loop with diffuse parietal thickening, suggesting an intramural hematoma. Conservative therapy was provided with symptomatic regression on the second day and reabsorption of the jejunal intramural hematoma. Anticoagulation therapy was reintroduced with no recurrences.