Nonsteroidal Anti-inflammatory Drug-induced Small Bowel Research Articles

Nonsteroidal anti-inflammatory drug-induced small bowel strictures (diaphragm disease) – an under-recognized cause of small bowel obstruction

BackgroundSmall bowel obstruction is a major source of morbidity and mortality that carries a significant economic burden. Recurrent small bowel obstruction may be secondary to circumferential strictures (small bowel diaphragm disease), an under-recognized entity secondary to long-term NSAID use. We aim to describe the sensitivity of preoperative CT enterography in patients with surgically treated small bowel diaphragm disease. MethodsWe retrospectively reviewed adult patients who underwent elective small bowel resection for small bowel obstruction performed by a single minimally-invasive surgeon between 2010-2023. Patient history, radiographic, endoscopic, operative, and pathology reports were reviewed for reference to NSAID use, small bowel strictures, diaphragms, and enteropathy. Exclusion criteria were prior radiation, inflammatory bowel disease, malignancy, adhesive disease, and anastomotic strictures. ResultsA total of 225 patients were identified; of those, 22 patients (10%) met inclusion criteria. The mean age was 60.7 years (range 29-78), with 15 women (68%). All patients underwent minimally invasive small bowel resection for obstruction with histopathologic evidence of stricture without evidence of transmural inflammation, granuloma, or dysplasia and confirmed NSAID use (n=22; 100%). Anemia was present in 36% (n=8). Preoperative CT or MR enterography was performed in 18 patients (82%) and stricturing was reported in 13 patients (72%). Intraoperatively, palpation identified strictures in all patients. ConclusionNSAID-induced small bowel injury is an under-recognized condition that, in severe cases, can present as small bowel obstruction. Surgeons should consider diaphragm disease in patients with obstruction and NSAID use, in which preoperative CT or MR enterography may be useful but cannot rule out disease.

Protective effect of the traditional Korean herbal prescription, Bojangunbi-tang, on non-steroidal anti-inflammatory drug-induced small bowel injury

Background: Bojanggunbi-tang (BGT) is a well-known combination of ancient Korean herbal medicines and has been widely used for treating gastrointestinal symptoms. Objectives: This study was aimed at investigating whether BGT protects against non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal injury (NSI), by using a murine model of indomethacin-induced NSI. Materials and Methods: NSI was induced in the mice by subcutaneous injections of 15 mg/kg indomethacin. BGT was administered at doses of 50, 150, and 450 mg/kg, while the positive control received sodium alginate. The treatments were orally administered twice, 30 min before and 6 h after the induction of NSI. The body weight, length of small intestine, macroscopic damages, and histological damages were assessed after 24 h of induction. Results: Gross anatomical analysis revealed that BGT inhibited the shortening of the small intestine and reduced the area of ulceration. Histological analysis revealed that BGT lowered the ulceration and inflammation scores. However, there was no difference between the groups with respect to weight loss. Conclusion: BGT ameliorated NSI via its anti-inflammatory and anti-ulcerative properties. The current study suggests that BGT could be a therapeutic option for NSI.

Efficacy of complementary medicine for nonsteroidal anti-inflammatory drug-induced small intestinal injuries

Nonsteroidal anti-inflammatory drug-induced small bowel injuries (NSIs) have been largely ignored for decades due to the focus on nonsteroidal anti-inflammatory drug gastropathy. With the visualization of the small intestines enabled by video capsule endoscopy, the frequency and severity of NSIs have become more evident. NSIs have a complex pathophysiology, and no effective preventive or treatment options have been proven. Complementary and alternative medicine (CAM) has been used to treat disorders of the small intestine, and more research on its effectiveness for NSIs has been conducted.We reviewed the current evidence and mechanisms of action of CAMs on NSI. Clinical and experimental studies on the effect of CAMs on NSIs were performed using 10 databases.Twenty-two studies (3 clinical and 19 in vivo experimental studies) were included in the final analysis involving 10 kinds of CAMs: bovine colostrum, Orengedokuto (coptis), muscovite, licorice, grape seed, wheat, brown seaweed, Ganoderma lucidum fungus mycelia, Chaenomeles speciosa (sweet) Nakai (muguasantie), and Jinghua Weikang capsule. The mechanisms of CAM include an increase in prostaglandin E2, reparation of the enteric nervous system, inhibition of pro-inflammatory cytokines, reduction of intestinal permeability and enteric bacterial numbers, decrease in oxidative stress, and modulation of small intestinal motility.CAM may be a novel alternative option for treating and preventing NSI, and further studies on human and animal models with relevant comorbidities are warranted.

Mucoprotective drugs can prevent and treat nonsteroidal anti-inflammatory drug-induced small bowel enteropathy: a systematic review and meta-analysis of randomized controlled trials.

Background:Small bowel enteropathy (SBE) is a complication of nonsteroidal anti-inflammatory drug (NSAID) therapy occurring in 71% of NSAID users. We aimed to analyse the efficacy and safety of medications to prevent and treat NSAID-induced SBE in randomized controlled trials (RCTs).Methods:This review was registered on PROSPERO (CRD42021223371). We systematically searched four databases until 20 October for comparing mucoprotective (MP), antibiotic and probiotic treatments to placebo, proton-pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists in NSAID-associated small intestinal injuries. The main outcomes were mucosal integrity, mucosal breaks after treatment, mucosal injury improvement and complete healing of mucosal breaks. Meta-analytical calculations for weighted mean differences (WMDs) and odds ratios (ORs) were performed with the random-effects model and interpreted with 95% confidence intervals (CIs).Results:A total of 18 RCTs were included in the quantitative synthesis. MP medications administered preventively reduced the number of mucosal erosions (WMD = −1.24, CI: −2.15 to −0.34) and lead to a significantly lower chance of developing mucosal breaks after treatment (OR = 0.38, CI: 0.16–0.93). MP therapy was associated with a higher rate of complete healing of mucosal breaks (OR = 5.39, CI: 2.79–10.42). In the qualitative synthesis, there were tendencies for a lower increase in the mean number of mucosal breaks and reddened lesions with prophylactic and a higher decrease in mucosal breaks with therapeutic MP drug administration.Conclusion:MP treatment administered with NSAIDs can prevent and reduce small intestinal mucosal lesions.

Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Stricture in Rheumatoid Arthritis.

Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Stricture in Rheumatoid Arthritis.

Can Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-inflammatory Drug-induced Small Bowel Injury?

교신저자: 전성란, 04401, 서울시 용산구 대사관로 59, 순천향대학교 의과대학 내과학교실 소화기병센터 소화기연구소 Correspondence to: Seong Ran Jeon, Digestive Disease Center, Institute for Digestive Research, Department of Internal Medicine, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea. Tel: +82-2-709-9202, Fax: +82-2-709-9696, E-mail: 94jsr@hanmail.net Financial support: None. Conflict of interest: None. 요약: 최근 비스테로이드성 항염증제(NSAIDs)와 양성자펌 프억제제(proton pump inhibitor)를 함께 복용 중인 환자에 서의 소장 점막 손상을 60-80% 정도로 높게 보고하고 있다. 이에 Washio 등은 양성자펌프억제제가 비스테로이드성 항 염증제 유발성 소장 점막 손상을 악화시키는지에 대해 전향적 무작위대조연구를 진행하였다. 이 연구에서는 다양한 비스테 로이드성 항염증제 중 상부위장관에 대한 부작용을 최소화하 고 위약군에서 위산 분비 억제제 사용을 중단하기 위해 cyclooxygenase-2 (COX-2) 억제제인 celecoxib를 사용하였다. 57명의 건강 지원자를 celecoxib (200 mg, 하루 2회)와 위약 을 복용시킨 군(30명)과 celecoxib와 양성자펌프억제제인 rabeprozole (20 mg, 하루 1회)을 복용시킨 군(27명)으로 무작 위 배정하여 2주 동안 복용토록 하였다. 대상자는 모두 연구 시작 시점과 약제 복용을 종료한 2주 시점에 캡슐 내시경 검 사를 받았고, 이를 통해 두 군에서 소장 점막 손상(궤양과 미 란)의 개수와 발생률을 비교하고자 하였다. 미란의 개수는 COX-2+양성자펌프억제제군이 COX-2+위약군보다 더 많았 지만(p=0.02), 궤양의 개수는 두 군 간에 차이를 보이지 않았 다. COX-2+양성자펌프억제제군의 26%에서 공장에 점막 손 상이 발생하였으나 COX-2+위약군에서는 공장에 점막 손상 이 관찰되지 않았고(p=0.003), 이러한 경향은 회장에서는 관 찰되지 않았다. COX-2+양성자펌프억제제군이 COX-2+위 약군에 비해 소장 점막 손상(44.4% vs. 16.7%, p=0.04)과 소 장 손상의 위험도(상대위험도, 2.67; 95% CI, 1.08-6.58) 모두 의미 있게 높았다.

Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury: ARandomized, Placebo-Controlled Trial.

Some studies have reported a high incidence of small bowel injuries in 60%-80% of subjects who take nonselective nonsteroidal anti-inflammatory drugs and PPIs simultaneously. We performed a randomized, double-blind, controlled study to determine whether proton pump inhibitors (PPIs) exacerbate nonsteroidal anti-inflammatory drug-induced small bowel injury. Fifty-seven healthy subjects were randomly assigned groups given the cyclooxygenase (COX) 2inhibitor celecoxib (200 mg, twice daily) plus placebo for 2 weeks (COX-2+ placebo group, n= 30), or celecoxib plus the PPI rabeprazole (20 mg, once daily) for 2 weeks (COX-2+ PPI group, n= 27). The study was performed from October 2012 through September 2013 at a tertiary medical center in Japan. All subjects were evaluated by capsule endoscopy at the start of the study and then after 2 weeks administration of celecoxib with rabeprazole or placebo. The incidence rates and the numbers of small bowel injuries (ulcers and erosions) that were observed under capsule endoscopy were compared between groups. The primary endpoint was the incidence of mucosal injuries at the second capsule endoscopy examination. A significantly higher proportion of subjects in the COX-2+ PPI group developed small bowel injury (12 of 27 subjects; 44.4%) than in the COX-2+ placebo group (5 of 30 subjects; 16.7%; P= .04). Subjects in the COX-2+ PPI group had a significant increase in risk of small bowel injury compared with the COX-2+ placebo group (relative risk, 2.67; 95% confidence interval, 1.08-6.58). The number of erosions in each member of the COX-2+ PPI group was greater thanin each member of the COX-2+ placebo group (P= .02). The number of ulcers did not differ between groups. Twenty-six percent of subjects in the COX-2+ PPI group developed mucosal injury in the jejunum, compared with none of the subjects in the COX-2+ placebo group (P= .003); no such trend was found in the ileum. In a randomized, controlled trial, PPIs increased the risk of short-term nonsteroidal anti-inflammatory drug-induced small bowel injury. UMIN clinical trial registry number: UMIN000008883.

Small bowel capsule endoscopy: Where are we after almost 15 years of use?

The development of capsule endoscopy (CE) in 2001 has given gastroenterologists the opportunity to investigate the small bowel in a non-invasive way. CE is most commonly performed for obscure gastrointestinal bleeding, but other indications include diagnosis or follow-up of Crohn's disease, suspicion of a small bowel tumor, diagnosis and surveillance of hereditary polyposis syndromes, Nonsteroidal anti-inflammatory drug-induced small bowel lesions and celiac disease. Almost fifteen years have passed since the release of the small bowel capsule. The purpose of this review is to offer the reader a brief but complete overview on small bowel CE anno 2014, including the technical and procedural aspects, the possible complications and the most important indications. We will end with some future perspectives of CE.

Muscovite is protective against non-steroidal anti-inflammatory drug-induced small bowel injury.

To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs). We recruited and screened thirty-two healthy volunteers who were randomly allocated equally into two groups: an NSAID control group, who received 75 mg slow-release diclofenac, twice daily for 14 d; and an NSAID-muscovite group, who received 3 g of muscovite in addition to the 75 mg of slow-release diclofenac, twice daily for 14 d. For gastroprotection, both groups were administered 20 mg/d of the proton pump inhibitor omeprazole. All eligible subjects underwent video capsule endoscopy (CE) prior to and 14 d after treatment. Thirty subjects (NSAID-muscovite group, n =16; NSAID control group, n =14) finally completed the whole trail. At the baseline CE examination, no statistically significant differences between the two groups have been observed. However, after 14 d of drug treatment, a significant difference was observed in the percentage of subjects with mucosal breaks when comparing the NSAID-muscovite group with the NSAID control group. While 71.4% (10/14) of subjects in the NSAID control group had at least one mucosal break, co-administration of muscovite in the NSAID-muscovite group reduced the rate to 31.3% (5/16) (P = 0.028). Moreover, higher number of mucosal breaks was found in the NSAID control group vs that in the NSAID-muscovite group (P < 0.05). Muscovite co-therapy reduced the incidence of small intestinal injury after 14 d of diclofenac administration.

Anti-tumour necrosis factor agents reduce non-steroidal anti-inflammatory drug-induced small bowel injury in rheumatoid arthritis patients

ObjectiveThe role of tumour necrosis factor α (TNFα) in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage remains unclear. We evaluated the preventive effect of anti-TNF therapy against...

The trend view of nonsteroidal anti-inflammatory drug-induced small bowel injury

The trend view of nonsteroidal anti-inflammatory drug-induced small bowel injury

Nonsteroidal antiinflammatory drugs and the small intestine

The small intestine may be a more common site for nonsteroidal antiinflammatory drug toxicity than the gastroduodenal mucosa. Two-thirds of regular nonsteroidal antiinflammatory drug users develop subclinical small bowel enteropathy. This review highlights this emerging issue in patients requiring antiinflammatory drugs. Nonsteroidal antiinflammatory drug enteropathy is a stepwise process involving direct mucosal toxicity, mitochondrial damage, breakdown of intercellular integrity, enterohepatic recirculation and neutrophil activation by luminal contents including bacteria. Unlike upper gastrointestinal toxicity, cyclooxygenase-mediated mechanisms are probably less important. Newer imaging modalities such as capsule endoscopy studies demonstrate nonsteroidal antiinflammatory drug-induced small bowel erosions, but the clinical implications are unclear. Nonsteroidal antiinflammatory drug toxicity to the small intestine is common. Useful research tools have been developed to indirectly measure intestinal inflammation and permeability, but these are not generally available to the clinician, although enteroscopy and capsule endoscopy can be illuminating. Anaemia or hypoalbuminaemia are useful indications of nonsteroidal antiinflammatory drug enteropathy. Cessation of the drug would be the preferred option, alternatively there are experimental data to support the use of sulphasalazine and metronidazole. Animal models are unravelling new mechanisms for mucosal toxicity beyond the cyclooxygenase model, including mucosal oxidative injury and nitric oxide mediated pathways.

Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by double-balloon endoscopy

To clarify clinical features of the NSAID-induced small bowel lesions using a new method of endoscopy. This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone double-balloon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at Jichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient. Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively. The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug. NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon.

Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration.

The association between nonsteroidal antiinflammatory drug (NSAID) intake and gastroduodenal peptic ulceration is well recognized. Recent experimental data implicate NSAIDs in the development of a similar spectrum of pathologic lesions of the small bowel. However, clinically significant NSAID-induced small bowel ulcerations have been reported infrequently. This study sought to examine small bowel complications of NSAID use requiring surgical intervention. A retrospective study of all patients (n = 283) who underwent small bowel resection on the general surgery services at the University of Texas Southwestern Medical Center during a 3-year period from 1991 to 1994 was conducted. Patients who had a history of chronic NSAID use, no other predisposing risk factors for gastrointestinal bleeding, and pathologically confirmed small bowel ulcerations complicated by hemorrhage, perforation, or obstruction were included in this study. Eleven patients with 12 surgical complications of NSAID-induced small bowel ulcerations were identified. These 11 patients all underwent emergent laparotomies with small bowel resection (one patient had two separate operations, 8 months apart). Small bowel ulcerations were noted to occur in the jejunum (4) and the ileum (8) and were multiple in half of the cases. Complications included bleeding (50%), perforation (33%), and obstruction (17%). This report is the first examining a series of surgical complications of NSAID-associated small bowel ulcerations. Our data suggest that small bowel complications of NSAID use requiring surgical intervention may occur more frequently than is currently recognized and, like peptic ulcer disease attributed to NSAIDs, result in significant morbidity and mortality.

Surgical complications of nonsteroidal antiinflammatory drug-induced small bowel ulceration

Background: The association between nonsteroidal antiinflammatory drug (NSAID) intake and gastroduodenal peptic ulceration is well recognized. Recent experimental data implicate NSAIDs in the development of a similar spectrum of pathologic lesions of the small bowel. However, clinically significant NSAID-induced small bowel ulcerations have been reported infrequently. This study sought to examine small bowel complications of NSAID use requiring surgical intervention. Study Design: A retrospective study of all patients (n = 283) who underwent small bowel resection on the general surgery services at the University of Texas Southwestern Medical Center during a 3-year period from 1991 to 1994 was conducted. Patients who had a history of chronic NSAID use, no other predisposing risk factors for gastrointestinal bleeding, and pathologically confirmed small bowel ulcerations complicated by hemorrhage, perforation, or obstruction were included in this study. Results: Eleven patients with 12 surgical complications of NSAID-induced small bowel ulcerations were identified. These 11 patients all underwent emergent laparotomies with small bowel resection (one patient had two separate operations, 8 months apart). Small bowel ulcerations were noted to occur in the jejunum 4 and the ileum 8 and were multiple in half of the cases. Complications included bleeding (50%), perforation (33%), and obstruction (17%). Conclusions: This report is the first examining a series of surgical complications of NSAID-associated small bowel ulcerations. Our data suggest that small bowel complications of NSAID use requiring surgical intervention may occur more frequently than is currently recognized and, like peptic ulcer disease attributed to NSAIDs, result in significant morbidity and mortality.