Possible case of bortezomib-induced ileus paralytic.

This report describes a case of a patient with active multiple myeloma who was started on bortezomib, cyclophosphamide and dexamethasone and subsequently presented to the emergency department with acute intestinal obstruction one week later. The patient underwent exploratory laparotomy, but no mechanical cause of the obstruction was found. The patient later developed sepsis and eventually died. The possible cause of the intestinal obstruction was attributed to bortezomib, and the paper discusses the potential mechanism of this side effect and its management based on available literature.

Gastrointestinal perforation associated with bevacizumab in metastatic colorectal cancer.

OBJECTIVE: To investigate the risk factors for gastrointestinal perforation in metastatic colorectal cancer patients receiving bevacizumab. METHODS: We retrospectively reviewed 217 patients with metastatic colorectal cancer receiving bevacizumab to investigate the risk factors for gastrointestinal perforation. Three patients occurred intestinal perforation after receiving bevacizumab. We analyzed the clinical characteristics of three patients with intestinal perforation. RESULTS: All patients receiving bevacizumab. Three of 217 patients occurred intestinal perforation after receiving bevacizumab. Patient no. 1 was 70 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation and ultimately died after receiving bevacizumab. Patient no. 2 was 59 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation after receiving bevacizumab, and recovered smoothly after symptomatic treatment. Patient no. 3 was 60 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation and ultimately died after receiving bevacizumab. CONCLUSIONS: Patients with advanced colorectal cancer receiving bevacizumab are at risk of gastrointestinal perforation. The patient's age, gender and history of bowel obstruction may be associated with gastrointestinal perforation.

Anaplastic lymphoma kinase tyrosine kinase inhibitors associated gastrointestinal obstruction, perforation, and ulceration: an analysis of the FDA adverse event reporting system database (FAERS).

BACKGROUND : There have been cases reporting anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and associated serious gastrointestinal (GI) adverse drug reactions (gastrointestinal obstruction, perforation, and ulceration). These adverse drug reactions are not in the drug package inserts, and the drug relationships are not proven in the literature.  AIM: We aimed to examine the potential association between GI obstruction, perforation, and ulceration, and ALK-TKIs by data mining of the US FDA Adverse Event Reporting System (FAERS). METHOD  : We conducted a disproportionality analysis of GI obstruction, perforation, and ulceration by estimating the reporting odds ratios (ROR) and the information component (IC) with 95% confidence intervals. RESULTS : A total of 279 cases of ALK-TKI-associated GI obstruction, perforation, and ulceration from January 1, 2011, to December 31, 2020, were identified. GI obstruction, perforation, and ulceration cause 16% of cases of death. A significantly increased reporting rate for GI obstruction [ROR 1.77 (1.45-2.15); IC 0.82 (0.53-2.03)] and perforation [ROR 1.61 (1.28-2.02); IC 0.68 (0.35-1.92)] was observed for ALK-TKIs as a drug class. The signal of GI ulceration was detected only in crizotinib [ROR 1.23 (1.01-1.50); IC 0.29 (0.01-1.51)]. A statistically significant ROR and IC emerged for the site of the esophagus.  CONCLUSION : Overall, the pharmacovigilance study of the FAERS indicates slightly increased reporting of GI obstruction and perforation, which may cause severe or even fatal outcomes among ALK-TKIs users.

Diaphragm disease in emergency surgery.

BACKGROUND/AIMS: Diaphragm disease of the small bowel has been described in the literature over the last three decades. The pathognomonic characteristic of multiple circumferential stenosis is noted on gross examination of the bowel. It is a severe form of non-steroidal anti-inflammatory drug-induced enteropathy, often presenting as acute small bowel obstruction. A systematic review was performed to identify risk factors and patient outcomes in histologically-proven diaphragm disease of the small intestine in patients undergoing emergency operation for small bowel obstruction. METHODS: A comprehensive search was performed between January 1975 and March 2019 using relevant MeSH terms. Studies were chosen based on predefined inclusion criteria. Diaphragm disease of the small intestine was defined as macroscopically detected thin diaphragm-like mucosal folding inside the lumen of the bowel. The parameters assessed included patient characteristics, duration of use of non-steroidal anti-inflammatory drugs, type of emergency surgery performed, complications, recurrence, presentation and diagnosis of diaphragm disease. RESULTS: A total of 21 studies were analysed which included 17 case reports, one case series, and three retrospective comparative studies. Overall 29 patients with diaphragm disease of the small bowel were reported following emergency laparotomy for small bowel obstruction. Use of non-steroidal anti-inflammatory drugs was noted in all cases with an average duration of 3-5 years. All patients presented acutely with features of small bowel obstruction and had emergency laparotomy, except one who underwent laparoscopic resection. In the comparative studies patients were more likely to be female and to have been taking non-steroidal anti-inflammatory drugs for more than 7 years. CONCLUSIONS: This is a rare disease, difficult to diagnose and often confirmed by the intra-operative macroscopic appearance of circumferential stenosis of the bowel. Risk factors for developing small bowel diaphragm disease include long-term use of non-steroidal anti-inflammatory drugs, and female gender. Patients with this disease are at increased risk of developing acute small bowel obstruction, so early identification is important.

Nivolumab-induced small bowel obstruction and perforation: a rare but life-threatening side effect of immunotherapy.

We present a case of a 58-year-old female with anti-PD-1 immunotherapy-related small bowel perforation. The patient was on long-term therapy with nivolumab for metastatic non-small cell lung cancer. She presented to the emergency department with acute abdominal pain, in which the CT revealed a short segment of dilated distal ileum proximal to a very short segment of bowel with mural thickening and a perforation near the transition point. The patient underwent subsequent laparotomy, which confirmed the CT findings and revealed a short-segment of friable and dilated loop of distal ileum proximal to a stricture and a small perforation at the transition point. Pathological analysis revealed mural thickening at the site of stricture without evidence of malignancy with focal necrosis and perforation at the transition point. Bowel perforation in the setting of anti-PD-1 immunotherapy is rare, but life-threatening complication, and should be considered in oncology patients on immunotherapy presenting with severe abdominal pain.

Small bowel diaphragm disease from long-term non-steroidal anti-inflammatory use.

Small bowel diaphragm disease (SBDD) is characterised by circumferential lesions of short length (<5 mm), causing intrinsic stenosis of the small bowel lumen. A 63-year-old women with a history of long-term non-steroidal anti-inflammatory use, presented with a 12-month history of intermittent episodes of colicky abdominal pain, nausea and vomiting. Her only past surgery was a laparoscopic hysterectomy. Abdominal CT demonstrated an area of thickening in the mid small bowel, however a diagnostic laparoscopy failed to demonstrate adhesions or any external abnormality. A capsule endoscope did not progress beyond the mid small bowel at the site of a suspected diaphragm. The patient underwent a laparotomy and using the retained capsule as a marker, the area of bowel affected by SBDD was identified. With an ageing population and the widespread use of non-steroidalanti-inflammatory drugs, general surgeons may see an increase in the incidence of SBDD.

Iatrogenic Kaposi sarcoma of the terminal ileum following short-term treatment with immunomodulators for Crohn disease: A case report.

RATIONALE: Kaposi sarcoma (KS) is a mesenchymal neoplasm associated with human herpes virus-8. It is often found in patients with primary or secondary immunodeficiency. An iatrogenic form of KS is detectable in patients who have received immunosuppressive therapy. To date, there are few reported cases of patients with KS treated with immunosuppressants for inflammatory bowel disease. PATIENT CONCERNS: We report the case of a 45-year-old young woman with abdominal pain, episodic diarrhea and a mild weight loss. The patient was treated with immunosuppressive therapy for a parietal thickening of the terminal ileum, wrongly diagnosed as Crohn disease. After 9 months after the beginning of antitumor necrosis factor-α, the patient was admitted for obstructive symptoms. A computed tomography suspected neoplasia of ileocecal region. The patient underwent an uneventful ileocecal surgical resection. DIAGNOSES: The histopathology showed endometriosis of the ileal wall and an irrefutable diagnosis of KS by immunohistochemistry-positive staining for human herpes virus-8. INTERVENTIONS AND OUTCOMES: The patient underwent surgical resection and is disease free at 6 years follow-up. LESSONS: This case underlines the interaction of immunosuppressive therapy with the possible consequent development of visceral KS.

Anti-TNF biologic therapy does not increase postoperative morbidity in pediatric Crohn's patients.

INTRODUCTION: Limited knowledge exists as to what impact preoperative biologic therapy has on postoperative complications in pediatric patients undergoing abdominal surgery for Crohn's disease (CD). Therefore, we sought to determine the 30-day postoperative infectious complication rate among pediatric CD patients who received biologic therapy within 12 weeks of an abdominal operation. METHODS: A retrospective chart review was performed on pediatric (<18 years of age) CD patients who underwent an abdominal operation between 1/1/2008 and 12/31/2017. Patients were grouped according to whether they received an anti-TNF (infliximab, adalimumab, certolizumab pegol) or no biologic therapy within 12 weeks prior to the operation. The primary outcome was the overall 30-day postoperative infectious complication rate. Secondary outcomes included 30-day readmission rate and return to the operating room (ROR). RESULTS: A total of 69 pediatric CD patients met inclusion criteria (n = 54 anti-TNF therapy, n = 15 received no biologic therapy). There were no differences between the anti-TNF and no biologic cohorts with respect to demographics or CD characteristics. No significant differences in overall 30-day postoperative infectious complications existed between patients exposed to anti-TNF agents and those with no preoperative exposure, or in its subcategories of surgical infectious complications and nonsurgical infectious complications. There was also no difference in the rate of ileus, readmission, or ROR. CONCLUSIONS: Preoperative exposure to anti-TNF biologic therapy does not add to overall or infectious 30-day postoperative morbidity in pediatric CD patients. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Retrospective review.

Postoperative complications of pediatric patients with inflammatory bowel disease treated with vedolizumab.

BACKGROUND: Vedolizumab is a biologic, which inhibits leukocyte adhesion in the gut and is used to treat ulcerative colitis (UC) and Crohn's disease (CD). Little is known of the surgical outcomes in patients treated with vedolizumab. We reviewed the postoperative complications in a cohort of pediatric UC and CD patients treated with vedolizumab. METHODS: We identified pediatric UC and CD patients treated with vedolizumab at our institution from 2014 to 2016. We compared postoperative outcomes in the vedolizumab exposed group to a cohort of vedolizumab naïve patients who required diverting ileostomy. RESULTS: Of the 31 patients who were treated with vedolizumab, 13 patients required surgery. Eight of 13 (62%) vedolizumab exposed patients had a postoperative complication, including mucocutaneous separation at the stoma (3), readmission for pain/dehydration (2), bowel obstruction at the ostomy, and intraoperative colonic perforation. In comparison, four of 16 (25%) vedolizumab naive patients had a postoperative complication, including readmission for ileus and for high stoma output with mucocutaneous separation. p=0.07. CONCLUSIONS: At our institution, patients treated with vedolizumab prior to surgery have a high prevalence of postoperative complications, notably mucocutaneous separation of the stoma. A prospective, multicenter study is needed to determine if these observed complications are attributable to vedolizumab. LEVEL OF EVIDENCE: Level III.

Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon.

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.

Treatment of Intestinal Fibrosis in Experimental Inflammatory Bowel Disease by the Pleiotropic Actions of a Local Rho Kinase Inhibitor.

BACKGROUND: Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFß-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium (DSS) and adoptive T-cell transfer. The in vitro and ex vivo effects of AMA0825 were studied in different cell types and in CD biopsy cultures. RESULTS: ROCK is expressed in fibroblastic, epithelial, endothelial, and muscle cells of the human intestinal tract and is activated in inflamed and fibrotic tissue. Prophylactic treatment with AMA0825 inhibited myofibroblast accumulation, expression of pro-fibrotic factors, and accumulation of fibrotic tissue without affecting clinical disease activity and histologic inflammation in 2 models of fibrosis. ROCK inhibition reversed established fibrosis in a chronic DSS model and impeded ex vivo pro-fibrotic protein secretion from stenotic CD biopsies. AMA0825 reduced TGFß1-induced activation of myocardin-related transcription factor (MRTF) and p38 mitogen-activated protein kinase (MAPK), down-regulating matrix metalloproteinases, collagen, and IL6 secretion from fibroblasts. In these cells, ROCK inhibition potentiated autophagy, which was required for the observed reduction in collagen and IL6 production. AMA0825 did not affect pro-inflammatory cytokine secretion from other ROCK-positive cell types, corroborating the selective in vivo effect on fibrosis. CONCLUSIONS: Local ROCK inhibition prevents and reverses intestinal fibrosis by diminishing MRTF and p38 MAPK activation and increasing autophagy in fibroblasts. Overall, our results show that local ROCK inhibition is promising for counteracting fibrosis as an add-on therapy for CD.

[A Case of Malignant Lymphoma of the Jejunum That Developed Stenosis and Perforation after a Complete Response to Chemotherapy].

A 57-year-old woman was admitted owing to epigastric pain.Abdominal computed tomography demonstrated a tumor in the origin of the jejunum.After an endoscopic biopsy, we diagnosed diffuse large B-cell lymphoma.We treated her with CHOP chemotherapy because pancreaticoduodenectomy is highly invasive.After 1 course of chemotherapy, the tumor was reduced.However, she developed a jejunal stenosis; therefore, we performed laparoscopic gastrojejunostomy.Furthermore, she developed perforated peritonitis on the sixth day after the surgery, and therefore, an emergency partial jejunum resection was performed.Histopathologically, viable lymphoma cells were not found in the resected intestine.She had a complete response 10 months after the surgery.Chemotherapy may cause intestinal stenosis and perforation requiring surgery; therefore, decisions about surgical procedures must be made carefully.

COX-2 inhibitory NSAID-induced multiple stenosis in the small intestine diagnosed by double-balloon endoscopy.

The patient was a 72 year old man who had been given non-steroidal anti-inflammatory drug (NSAID) for two years. He repeatedly developed small intestinal ileus; therefore, he underwent several imaging examinations, but the cause was not identified. He subsequently underwent a double-balloon endoscopy (DBE). The membranous stenoses were detected in the jejunum, and the biopsy specimens were taken during the DBE. The membranous stenoses in the gastrointestinal tract were characteristic of NSAID-induced enteropathy, and he was endoscopically and histopathologically diagnosed with NSAID-induced small intestinal disorder. NSAID administration was withdrawn, and the balloon dilation was conducted for small intestinal stenosis. After that, no small intestinal ileus developed again. Some studies were conducted on the mechanism of NSAID-induced small intestinal dysfunction, but the drug that was administered to the patient was a highly selective NSAID for cyclooxygenase (COX)-2, and there are few studies that reported a dysfunctional mechanism induced by this drug. In the tissue sampled by DBE, apoptotic bodies were found; therefore, it was suggested that the stenoses in this case were caused by the COX-2 inhibitor from the relationship between COX-2 inhibition and apoptosis. Further studies are necessary to investigate the mechanism of NSAID enteropathy.

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

BACKGROUND: The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. OBJECTIVES: The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. METHODS: Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. RESULTS: Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. CONCLUSIONS: Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921).

Gliptins, exenatide, liraglutide: "intestinal obstruction".

Reduced gastrointestinal motility exposes to potentially serious consequences.