Gastrointestinal Perforation In Patients Research Articles

Risk of gastrointestinal perforation in patients with rheumatic diseases exposed to janus kinase inhibitors versus adalimumab: nationwide cohort study.

To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients initiating a Janus kinase inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases. We conducted a nationwide population-based cohort study of the French national health data system, the exposed group initiating a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic corticosteroids, non-steroidal anti-inflammatory drugs and proton pump inhibitors were time-varying variables. The cohort included 39,758 patients: 12,335 and 27,423 in the JAKi and adalimumab groups (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%). During follow-up, 38 and 42 GIPs occurred in the JAKi and adalimumab groups, incidence rates were 2.1 (95% CI 1.5-2.8) and 1.1 (0.8-1.5) per 1000 person-years respectively. Rates of GIP did not differ between JAKi and adalimumab groups : wHR 1.1 (95% CI 0.7-1.9) (p=0.65). Despite lack of power in some subgroup analyses, results were consistent whatever the JAKi or rheumatic disease subgroup. In this nationwide cohort study, the rates of GIP did not differ between groups of patients initiating JAKi and adalimumab treatment. These results need to be confirmed in other observational studies.

Computed tomographic features of massive pneumoperitoneum in a dog with intestinal lymphoma – a case report

A 6-year-old intact male Jindo dog was presented for reduced appetite, depression, and tympanic abdominal distension. Abdominal radiographs showed severe pneumoperitoneum and an intestinal mass. Computed tomography revealed massive pneumoperitoneum associated with intestinal perforation, with cervical and thoracoabdominal wall emphysema, pneumomediastinum, pneumoretroperitoneum, pneumoscrotum, and peritonitis. Surgery confirmed a ruptured jejunal mass, and histopathologic evaluation of the excised tissues revealed intestinal lymphoma. Clinicians should therefore consider the possibility of gastrointestinal perforation in patients with severe pneumoperitoneum even where there is no history of trauma. Despite clinical stability, intensive monitoring and urgent decompressive intervention should be performed in patients with severe pneumoperitoneum.

Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study

ObjectivesTo compare incidence rates of gastrointestinal (GI) perforations between patients with RA and the general population, and between patients treated with tumour necrosis factor inhibitors (TNFi) and non-TNFi biologics.MethodsIn this...

Bevacizumab-related gastrointestinal perforation in patients with three or more prior chemotherapy regimens: A real-world experience

ObjectiveAssociations between the number of prior chemotherapy (CT) regimens and gastrointestinal (GI) perforation in patients receiving bevacizumab treatment has not been fully investigated. The aim of the study was to investigate the impact of ≥3 prior CT regimens on GI perforation. Materials and methodsWe retrospectively investigated the medical records of 133 patients with gynecological cancer who received bevacizumab-containing treatment. Bevacizumab was intravenously administered at a dose of 15 mg/kg every 4 weeks. Incidence of GI perforation was compared between ≤2 and ≥3 prior CT groups. ResultsTwenty-three (17.3%) patients had a history of ≥3 CT; these patients received bevacizumab at 4-week intervals. The percentage of patients with prior surgery was significantly higher in the ≥3 prior CT group (95.7% vs. 70.0%, P = 0.008), while those with prior bowel resection was significantly higher in the ≥3 prior CT group (30.4% vs. 12.7%, P = 0.034). There was no significant difference in the mean number of bevacizumab cycles between the two groups (10.7 vs. 8.9, P = 0.19). While GI perforation was observed in three (2.7%) patients in the ≤2 prior CT group, no GI perforation was found in the ≥3 prior CT group (P > 0.99). ConclusionA history of ≥3 prior CT did not increase the risk for GI perforation when bevacizumab is administered at a dose of 15 mg/kg every 4 weeks in our cases.

Problems of diagnostics and treatment of gastrointestinal perforations in patients with acute intestinal infections

The results of treatment of 97 patients with perforations of the hollow organs of the gastrointestinal tract were analyzed, 31 acute intestinal infections of which were verified. Clinical features of perforation of hollow organs on the background of acute intestinal infection have been revealed. A comparative analysis of clinical and instrumental methods for diagnosing perforations in patients with intestinal infections and without them was carried out. The most sensitive in identifying perforations of hollow organs in patients with acute intestinal infections instrumental methods of investigation were diagnostic laparoscopy (100%) and radiography of abdominal organs (80%). It was established that the combination of the two diseases contributes to the growth of diagnostic errors, increase in the number of common forms of peritonitis and development of the syndrome of mutual aggravation. Analysis of surgical interventions showed that in patients with confirmed diagnosis of acute intestinal infection the primary surgical interventions in most patients resulted in the formation of laparostoma with programmed relaparotomy, in connection with the presence of contraindications for the formation of a primary interintestinal anastomosis. Postoperative complications in the study groups developed in 61,3; 41.7 and 23,8% of cases, respectively. In patients with confirmed diagnosis of acute intestinal infection, lethality was 32,3%, in patients with atypical flow of perforations of hollow organs, simulating the symptoms of acute intestinal infection - 16,7 and 14,3% - in patients with perforations of hollow organs without concomitant acute intestinal infection. The results of the research testify to the relevance of the problem under study and the need to optimize therapeutic-diagnostic algorithm for this category of patients.

Risk of gastrointestinal perforation in patients taking oral fluoroquinolone therapy: An analysis of nationally representative cohort.

BackgroundFluoroquinolone is a commonly prescribed antimicrobial agent, and up to 20% of its users registers adverse gastroenterological symptoms. We aimed to evaluate the association between use of fluoroquinolone and gastrointestinal tract perforation.MethodsWe conducted a nested case-control study on a national health insurance claims database between 1998 and 2011. The use of fluoroquinolones was classified into current (< 60 days), past (61–365 days prior to the index date) and any prior year use of fluoroquinolones. We used the conditional logistic regression model to estimate rate ratios (RRs), adjusting or matching by a disease risk score (DRS).ResultsWe identified a cohort of 17,510 individuals diagnosed with gastrointestinal perforation and matched them to 1,751,000 controls. Current use of fluoroquinolone was associated with the greatest increase in risk of gastrointestinal perforations after DRS score adjustment (RR, 1.90; 95% CI, 1.62–2.22). The risk of gastrointestinal perforation was attenuated for past (RR, 1.33; 95% CI, 1.20–1.47) and any prior year use (RR, 1.46; 95% CI, 1.34–1.59). To gain insights into whether the observed association can be explained by unmeasured confounder, we compared the risk of gastrointestinal perforation between fluoroquinolone and macrolide. Use of macrolide, an active comparator, was not associated with a significant increased risk of gastrointestinal perforation (RR, 1.11, 95%CI, 0.15–7.99). Sensitivity analysis focusing on perforation requiring in-hospital procedures also demonstrated an increased risk associated with current use. To mitigate selection bias, we have also excluded people who have never used fluoroquinolone before or people with infectious colitis, enteritis or gastroenteritis. In both of the analysis, a higher risk of gastrointestinal perforation was still associated with the use of fluoroquinolone.ConclusionsWe found that use of fluoroquinolones was associated with a non-negligible increased risk of gastrointestinal perforation, and physicians should be aware of this possible association.

Incidence of Gastrointestinal Perforations in Patients with Rheumatoid Arthritis Treated with Tocilizumab from Clinical Trial, Postmarketing, and Real-World Data Sources.

IntroductionThe aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA).MethodsReporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept.ResultsThe clinical trial, global postmarketing, and healthcare claims populations provided 17,906, 382,621, and 3268 patient-years (PYs) of TCZ exposure, respectively. GIP incidence rates [95% confidence interval (CI)] were 1.9 (1.3–2.7), 1.2 (1.1–1.3), and 1.8 (0.7–4.0; specific definition) to 2.8 (1.3–5.2; sensitive definition) per 1000 PYs for the clinical trial, postmarketing, and healthcare claims populations, respectively. The GIP incidence rate (95% CI) for the comparator aTNF healthcare claims population ranged from 0.6 (0.3–1.2) to 0.9 (0.5–1.5) per 1000 PYs, for an absolute rate difference between TCZ and aTNFs of 1.2 (−0.3 to 2.5) to 1.9 (0.0–3.7) per 1000 PYs, corresponding to a number needed to harm between 533 and 828.ConclusionThe TCZ GIP event rates from multiple data sources were consistent with previously reported rates, did not increase over time, and were significantly associated with the number of prior biologics. Comparison of GIP incidence rates among patients with prior biologic exposure suggests that, for every 1000 patients treated with TCZ per year, an additional 1–2 GIP events might occur compared with patients treated with aTNFs.FundingRoche.

切除不能進行再発大腸癌に対するBevacizumab併用化学療法における消化管穿孔危険因子の検討

目的：Bevacizumab併用化学療法を行った切除不能進行再発大腸癌症例を対象に，消化管穿孔の危険因子を検討する．方法：2007年7月から2012年12月までに当院でBevacizumab併用化学療法を開始した切除不能進行再発大腸癌症例195例をレトロスペクティブに解析した．消化管穿孔の危険因子を単変量，多変量ロジスティック回帰分析により検索した．結果：消化管穿孔は7例（3.6%）に認めた．単変量解析では，直腸癌（オッズ比4.933，95%信頼区間1.061～22.947），放射線照射既往（オッズ比39.120，95%信頼区間4.518～338.691）の二つの因子が統計学的有意（P<0.05）に消化管穿孔の発生と関連していた．多変量解析では，放射線照射既往のみが独立して有意な因子であり，照射既往ありの調整オッズ比は34.831（95%信頼区間3.566～340.204）であった．結語：放射線照射症例に対するBevacizumab投与は慎重に行われるべきであると考えられた．

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab.

To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease. We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups. Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.

FRI0146 The risk of gastrointestinal perforations in patients with rheumatoid arthritis treated with anti-TNF therapy - results from the british society for rheumatology biologics register (BSRBR)

ObjectivesTo evaluate the risk of gastrointestinal perforation (GIP) in subjects with RA treated with anti-TNF therapy compared to non-biological disease-modifying antirheumatic drugs (nbDMARDs).MethodsThe analysis was conducted in the British Society...

The risk of gastrointestinal perforations in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the BSRBR-RA

ObjectivesTo evaluate the risk of gastrointestinal perforation (GIP) in subjects with rheumatoid arthritis (RA) treated with antitumour necrosis factor (anti-TNF) therapy compared with non-biological disease-modifying antirheumatic drugs (nbDMARDs).MethodsUsing data from...

Bevacizumab関連消化管穿孔の外科治療に関する検討

Bevacizumab関連消化管穿孔の外科治療に関する検討

Risk of gastrointestinal perforation in patients with metastatic breast cancer treated with bevacizumab: A meta-analysis.

1091 Background: Bevacizumab, a vascular endothelial growth factor inhibitor, has shown to be active in patients with metastatic breast cancer (MBC) as first or second line therapy. In some tumor types, the addition of bevacizumab to chemotherapy increase the risk of gastrointestinal (GI) perforation compared with controls. The aim of this systematic review and meta-analysis of randomized trials was to assess the overall risk of GI perforation associated with bevacizumab in MBC. Methods: We selected all randomized trials which compared chemotherapy with or without bevacizumab in MBC. For the analysis, we used a fixed-effects and random effects models to calculate the pooled event-based relative risk ratios (RR) with 95% confidence interval (CI). The Cochran's Q statistic and I2 statistics were first calculated to assess the heterogeneity among the proportions of the included trials. For this study, we collected all events as reported in these trials. We did not consider differences in grade or outcomes. Results: Five trials were included in the meta-analysis: E2100, AVADO, RIBBON-1, RIBBON-2, and AVF-2119g. In total, 2,368 patients received bevacizumab-based therapy and 1,416 chemotherapy alone. GI perforation was reported in 9 and 3 patients, respectively. There was no statistical heterogeneity (p=0.532) considering all trials, so the fixed-effects model was used. Patients treated with bevacizumab-containing regimens had a RR for GI perforation, of 1.172 (95% CI, 0.342-4.016; p=0.801). Conclusions: GI perforation is an uncommon finding in patients with MBC treated with chemotherapy in the first or second line. According to this meta-analysis, the addition of bevacizumab to chemotherapy was not associated with a significant increase risk of GI perforation in this population. No significant financial relationships to disclose.

Incidence and management of bevacizumab-associated gastrointestinal perforations in patients with recurrent ovarian carcinoma

Objective The objective of this study was to examine the incidence and management of bevacizumab-associated gastrointestinal (GI) perforations in patients with recurrent ovarian carcinoma. Methods We identified all patients who received bevacizumab off protocol from August 2004–August 2008. We examined their medical records for reports of confirmed GI perforation, associated clinicopathological factors, treatment, and outcomes. Results Six (4%) of 160 patients with ovarian carcinoma who had been treated with bevacizumab developed GI perforations, with a median of 4 (range, 2–8) previous cytotoxic regimens. The median serum CA-125 at the start of treatment was 228 U/mL (range, 50–3106 U/mL). The median number of bevacizumab cycles prior to perforation was 10.5 (range, 2–20). The median time from the last bevacizumab dose to diagnosis of GI perforation was 13 days (range, 1–28 days). Four (67%) patients underwent an exploratory surgery. At laparotomy, one had a gastric perforation and one had an appendiceal perforation; the site of perforation could not be identified in the other 2 Two patients (33%) were managed conservatively—one with a PEG tube and the other with supportive care. The median time of death from the date of diagnosis of GI perforation was 27 days (range, 4–326 days). Only two patients—one with a gastric and the other with an appendiceal perforation—survived > 65 days. The 30-day mortality rate following a bevacizumab-associated GI perforation was 50%. Conclusion Bevacizumab-associated GI perforations in patients with recurrent ovarian carcinoma occurred in 4% of our patients. The prognosis of patients diagnosed with bevacizumab-associated GI perforations in this study was poor, and treatment should be individualized.

Bevacizumab-associated gastrointestinal perforation

Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysisThe addition of bevacizumab to cancer therapy significantly increased the risk of gastrointestinal perforation compared with controls. The risk may vary with bevacizumab dose and tumour type. Further studies are recommended to investigate the use of bevacizumab in selected patients who have recovered from gastrointestinal perforation. Full-Text PDF

Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis

Gastrointestinal perforation is a serious adverse event associated with bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF) widely used in current cancer treatment. The association is highlighted by a black-box warning issued by the US Food and Drug Administration, recommending that bevacizumab be permanently discontinued in patients with gastrointestinal perforation. However, no significant association has yet been established between bevacizumab and gastrointestinal perforation in randomised controlled trials. We did a systematic review and meta-analysis of published randomised controlled trials to assess the overall risk of gastrointestinal perforation associated with bevacizumab treatment. We searched PubMed and Web of Science for articles published between January, 1966, and July, 2008. Additionally, abstracts presented at American Society of Clinical Oncology conferences held between January, 2000, and July, 2008, were searched to identify relevant clinical trials. Eligible studies included prospective randomised controlled trials in which bevacizumab was compared with controls in combination with standard anti-neoplastic therapy. Summary incidence rates, relative risks, and 95% CIs were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. 12,294 patients with a variety of solid tumours from 17 randomised controlled trials were included in our analysis. The incidence of gastrointestinal perforation was 0.9% (95% CI 0.7-1.2) among patients receiving bevacizumab, with a mortality of 21.7% (11.5-37.0). Patients treated with bevacizumab had a significantly increased risk of gastrointestinal perforation compared with patients treated with control medication, with a relative risk of 2.14 (95% CI 1.19-3.85; p=0.011). Risk varied with bevacizumab dose and tumour type. Relative risks for patients receiving bevacizumab at 5 and 2.5 mg/kg per week were 2.67 (95% CI 1.14-6.26) and 1.61 (0.76-3.38), respectively. Higher risks were observed in patients with colorectal carcinoma (relative risk 3.10, 95% CI 1.26-7.63) and renal cell cancer (relative risk 5.67, 0.66-48.42). The addition of bevacizumab to cancer therapy significantly increased the risk of gastrointestinal perforation compared with controls. The risk may vary with bevacizumab dose and tumour type. Further studies are recommended to investigate the use of bevacizumab in selected patients who have recovered from gastrointestinal perforation. Stony Brook University Research Foundation.

Risk of bevacizumab-associated gastrointestinal perforation in patients with colorectal cancer and noncolorectal cancer

9622 Background: Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor. It is a widely used angiogenesis inhibitor in the treatment of colorectal cancer (CRC) and other solid tumors. Gastrointestinal (GI) perforation is a potentially fatal adverse event associated with bevacizumab, but the risk unclear. This study was conducted to determine the risk of developing GI perforation among CRC and non-CRC patients receiving bevacizumab. Methods: Databases from PUBMED and the Web Science from January 1966 until July 2008 and abstracts presented at the American Society of Clinical Oncology conferences from January 2000 to through July 2008 were searched to identify relevant studies. Eligible studies included prospective phase III clinical trials in which standard anti-neoplastic therapy was administered with and without the use of bevacizumab with available data for GI perforation. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated using fixed or random effect models based upon the heterogeneity of the included studies. Results: A total of 12084 patients with various solid tumors from 14 phase III trials were included for analysis. Among patients receiving bevacizumab, the incidence of GI perforation was 0.8% (95% CI: 0.6–1.1%), and RR was 2.0 (95% CI: 1.1–3.8, p = 0.028) in compared with controls. The risk of GI perforation was significantly increased in patients receiving bevacizumab at 5 mg/kg/week (RR 2.6, 95% CI: 1.0–6.6, p=0.04), but not at 2.5 mg/kg/week (RR=1.5, 95%CI: 0.7–3.3, p=0.3). Among 2151 patients with CRC, the incidence of GI perforation was 0.8% (95% CI: 0.5–1.6%); while for 2.999 patients with non-CRC malignancies, the incidence of GI perforation was 0.7% (95% CI: 0.5–1.1%); The relative risk of GI perforation varied with tumor type, with significantly increased risk observed in patients with CRC (RR = 3.1, 95% CI: 1.2–8.2, p&lt;0.023), but not non-CRC (RR=1.5, 95% CI: 0.67–3.4, p=0.3). Conclusions: There is a significant difference in the risk of developing GI perforation in CRC and non-CRC patients receiving bevacizumab with a higher relative risk in patients with CRC. Further investigation into the etiology of this difference is recommended. No significant financial relationships to disclose.

Risk of Immediate and Delayed Gastrointestinal Perforation in Patients Receiving Bevacizumab (Avastin) with Endoluminal Stents in Place

Background: Endoluminal stenting for malignant bowel obstruction has a reported perforation rate of approximately 4%. Bevacizumab is a humanized monoclonal neutralizing antibody against the vascular endothelial growth factor receptor. It is a first line angiogenesis inhibitor used to treat variety of malignancies including several gastrointestinal cancers which are frequently associated with malignant bowel obstruction. Gastrointestinal perforation is a known complication of Bevacizumab. The aim of this study is to review all patients who had endoluminal stents and received Bevacizumab within sixty days of stent placement to determine the rate of immediate and delayed perforation.

Predictors of Vascular and Gastrointestinal Complications in Severe Acute Pancreatitis

Aim: To determine prognostic factors for arterial injury and gastrointestinal perforation in patients with severe acute pancreatitis (AP). Methods: A prospective cohort study was performed in 39 patients with AP whose Ranson scores were ≥3. The following parameters were assessed: Ranson score, APACHE II score, C-reactive protein (CRP) concentration on admission and on day 7, and contrast-enhanced computed tomography (CT) scans on admission (first CT) and between days 6 and 8 (second CT). The Balthazar CT severity index was calculated. Results: Six patients developed seven vascular and/or gastrointestinal complications (duodenal perforations in 3 and arterial pseudoaneurysm in 4). CRP on day 7 and the CT severity indices at the second CT were significantly higher in the complication group than in the noncomplication group. A stepwise logistic regression analysis demonstrated that CRP ≥15 mg/dl on day 7 and CT severity index ≥7 at the second CT were independent risk factors (p = 0.02 and 0.04, respectively). The odds ratio for CRP ≥15 mg/dl was 23.0 and 15.7 for a CT severity index of ≥7. Conclusion: A persistent elevation of the CRP concentration and a high CT severity index are independent riskfactors for local complications associated with AP. Copyright © 2008 S. Karger AG, Basel and IAP

Gastrointestinal Perforation Due to Bevacizumab in Colorectal Cancer

Bevacizumab is the first U.S. Food and Drug Association-approved vascular endothelial growth factor-targeted agent that greatly increases progression-free and overall survival in combination with standard chemotherapy regimens in patients with metastatic colorectal cancer. Although bevacizumab is generally well tolerated, some serious adverse events have occurred in some patients in clinical trials, including arterial thromboembolism and gastrointestinal (GI) perforation. GI perforation was first observed in the pivotal phase 3 trial, in which six events occurred in bevacizumab group (1.5%), compared with no events in the control group. Since then, similar rates of GI perforation have been observed in other large trials. Typical presentation was abdominal pain associated with constipation and vomiting. Such events occurred throughout treatment and were not correlated with duration of exposure. No difference in rate of GI perforations was found in patients who did and did not have a baseline history of peptic ulcer disease, diverticulosis, and history of chronic use of nonsteroidal anti-inflammatory drugs. However, the incidence of GI perforation seemed to be higher in patients with primary tumor intact, recent history of sigmoidoscopy or colonoscopy, or previous adjuvant radiotherapy, but it is necessary to confirm these preliminary findings by multivariate analyses. The mechanism responsible for causing GI perforation is not known and may be multifactorial. Bevacizumab should be permanently discontinued in patients who develop GI perforation. This article reviews the incidence, presentation, pathogenesis, risk factors, and management of GI perforation in patients with colorectal cancer who are treated with bevacizumab.