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.

Iatrogenic rectal perforation due to application of topical treatment in a patient with ulcerative colitis: a rare complication.

Rectal perforations due to topical treatments (enemas or foams) are unusual complications and they have been mostly reported in the use of barium enemas or in elderly patients with constipation. Very little has been reported about perforations secondary to topical treatment in patients with ulcerative colitis. We present the case of a patient with ulcerative colitis who suffered a rectal perforation complicated with a superinfected collection after the application of topical mesalazine foam.

Risk factors and epidemiology of spontaneous intestinal perforation among infants born at 22-24 weeks' gestational age.

OBJECTIVE: To describe the epidemiology, risk factors, and timing of spontaneous intestinal perforation (SIP) among infants born at 22-24 weeks' gestational age (GA). STUDY DESIGN: Observational cohort study among infants born at 22-24 weeks' GA in 446 neonatal intensive care units. RESULTS: We identified 9712 infants, of whom 379 (3.9%) developed SIP. SIP incidence increased with decreasing GA (P < 0.001). Antenatal magnesium (odds ratio (OR) 1.42; 95% confidence interval (CI), 1.09-1.85), antenatal indomethacin (OR 1.40; 95% CI, 1.06-1.85), postnatal indomethacin (OR 1.61; 95% CI, 1.23-2.11), and postnatal hydrocortisone exposure (OR 2.02; 95% CI 1.50-2.73) were associated with SIP. Infants who lost 15-20% (OR 1.77; 95% CI, 1.28-2.44) or >20% (OR 2.04; 95% CI, 1.46-2.85) of birth weight had higher odds of SIP than infants with weight loss <10%. CONCLUSIONS: Antenatal magnesium exposure, antenatal indomethacin exposure, postnatal hydrocortisone exposure, postnatal indomethacin exposure, and weight loss ≥15% were associated with SIP.

Surgical management of spontaneous bowel perforation and fascial dehiscence in a patient on bevacizumab and pembrolizumab in the setting of active Clostridium difficile infection.

Immunotherapy such as bevacizumab and pembrolizumab is used to treat an increasing number of malignancies. These medications have been associated with poor wound healing and several gastrointestinal complications, including intestinal perforations in rare cases. We present a unique case of a patient with metastatic cervical cancer on pembrolizumab and recent bevacizumab therapy, presenting with a colonic perforation requiring urgent exploratory laparotomy, in the setting of active Clostridium difficile infection. She required a second laparotomy shortly after due to fascial dehiscence, where a synthetic absorbable mesh was used for fascial approximation. We review the factors that led to these events and describe the surgical technique used for safe abdominal closure.

Cecal Perforation Following Intraperitoneal Abscess after Anti-tubercular Therapy: A Case Report.

Abdominal tuberculosis is defined as infection of gastrointestinal tract, peritoneum, abdominal solid organs, and/or abdominal lymphatics constituting approximately 12% of extra-pulmonary tuberculosis cases. Intestinal perforation is an acute presentation of abdominal tuberculosis. Intestinal perforation can occur before or at the beginning of anti-tubercular therapy. It is considered to be a paradoxical reaction if it occurs during or after treatment. Intestinal perforation is uncommon but serious and life-threatening as complication-mortality rate secondary to perforation are estimated to be >30%. We present a case of an 18-year-old female who developed cecal perforation following an intraperitoneal abscess after completion of anti-tubercular therapy for intestinal tuberculosis. She was a known case of intestinal tuberculosis. She had undergone pigtail catheterisation for an intraperitoneal abscess and completed 18 months of anti-tubercular therapy after which she developed cecal perforation. A paradoxical response was observed following the completion of anti-tubercular therapy. Early diagnosis and treatment reduce the complications and mortality rates of cecal perforation due to abdominal tuberculosis. Keywords: case reports; cecum; intestinal perforation; tuberculosis.

Prophylactic indomethacin, antenatal betamethasone, and the risk of intestinal perforation in infants <28 weeks' gestation.

OBJECTIVE: To determine if intestinal perforations before 14 days (either spontaneous (SIP) or necrotizing enterocolitis-induced) are increased when infants who received antenatal betamethasone shortly before birth are treated with prophylactic indomethacin (PINDO). STUDY DESIGN: Observational study of 475 infants <28 week's gestation assigned to either a PINDO-protocol (n = 231) or expectant management protocol (n = 244) during consecutive protocol epochs. RESULTS: Intestinal perforations before 14 days occurred in 33/475 (7%). In unadjusted and adjusted models, we found no associations between PINDO-protocol and intestinal perforations. PINDO-protocol did not increase intestinal perforations or SIP-alone even when given to infants who received betamethasone <7 or <2 days before delivery. 213/231 (92%) PINDO-protocol infants actually received indomethacin. The results were unchanged when examined just in those who received indomethacin. CONCLUSION: In our study, early intestinal perforations and SIP-alone were not increased when PINDO was used by protocol in infants who received antenatal betamethasone shortly before birth.

Characteristics, treatment, and outcome of patients with bowel perforation after immune checkpoint inhibitor exposure.

PURPOSE: Exposure to immune checkpoint inhibitors (ICIs) can predispose to immune-related adverse events (irAEs) involving the gastrointestinal tract. The association between ICIs and bowel perforation has not been well studied. We aimed to describe the clinical course, complications, treatment, and outcomes of patients experiencing bowel perforation during or after ICI treatment. METHODS: This retrospective, single-center study included adult cancer patients with bowel perforation that occurred between the first dose of ICI treatment and up to 1 year thereafter between 1/1/2010 and 4/30/2021. Patients' clinical course, imaging, treatment, and outcomes related to bowel perforation were collected and analyzed. RESULTS: Of the 13,991 patients who received ICIs during the study period, 90 (0.6%) met the inclusion criteria. A majority were male (54.4%), the most common cancer type was melanoma (23.3%), and most patients had received PD-1/L1 inhibitor treatment (58.8%). Onset of perforation occurred after a median of four ICI treatment cycles. The most common symptom was abdominal pain (95.5%). The colon was the most common location for the perforation (37.7%). Evidence of diverticulitis, enterocolitis, or appendicitis was seen in 32 (35.6%) patients, and 6 (6.6%) patients had luminal cancer involvement at the time of perforation. The overall hospitalization rate related to perforation was 95.5%, with mortality of 15.5% during the same admission. Antibiotics were given in 95% of our sample; 37.8% of patients also required surgical/interventional radiology intervention. Forty-six patients (51.1%) had perforation-related complications (e.g., sepsis, fistula, abscess), which were associated with a higher mortality rate (30%). CONCLUSION: Our findings suggest a low incidence of bowel perforation after ICI treatment (0.6%), with 40% of patients having coexisting bowel inflammation as a potential contributing factor. Patients with bowel perforation had an aggressive disease course and high rates of hospitalization, complications, and mortality. Early recognition and prompt intervention is critical to improve patient outcomes. Future studies are warranted to further investigate the cause, predictive markers, and optimal treatment for this patient population.

Intestinal perforation after intravitreal low dose ranibizumab injection for the treatment of type 1 retinopathy of prematurity: A case report.

PURPOSE: To report a newborn patient with gastrointestinal (GIS) perforation after intravitreal ranibizumab (RBZ) treatment. CASE REPORT: The patient was born at 31 gestational week and hospitalized with the diagnosis of small for gestational age and prematurity. In the follow up he underwent GIS surgery due to necrotizing enterocolitis (NEC) and was diagnosed with retinopathy of prematurity (ROP). At 43 weeks of postmenstrual age, he developed intestinal perforation after 12 h of the second low-dose RBZ injection. According to our knowledge, this is the first report of GIS perforation due to low-dose intravitreal RBZ treatment in an infant with severe ROP. CONCLUSION: The risk of GIS perforation should be taken into consideration during the application of intravitreal vascular endothelial growth factor antagonist agents, especially in newborns with previous GIS surgery and a history of NEC, and these patients should be carefully monitored for GIS complications.

Small Intestinal Perforation Caused by Enteric-coated Low-dose Aspirin.

A 77-year-old man presented with abdominal pain for 1 week. He was taking enteric-coated low-dose aspirin (LDA) to prevent secondary cardiovascular events and a proton pump inhibitor (PPI). Computed tomography indicated a small intestinal perforation; thus, small intestine resection was performed. Two months after surgery, he experienced a recurrence of the perforation. Since his repeated perforation was suspected to be due to LDA, LDA was discontinued. He has experienced no further recurrence since then. This is the first case of small intestinal perforation caused by enteric-coated LDA. Enteric-coated LDA may cause small intestinal perforation in patients with severe atherosclerosis under PPI administration.

A case of HCC successfully treated with infliximab-steroid sequential therapy for small bowel perforation due to atezolizumab/bevacizumab combination therapy.

BACKGROUND: Although reports of gastrointestinal perforation after immune-related adverse events (irAE) enteritis are rare, the anti- vascular endothelial growth factor (VEGF) effect of bevacizumab may be involved in gastrointestinal perforation. We report a rare case of gastrointestinal perforation in a patient with hepatocellular carcinoma treated with atezolizumab/bevacizumab combination therapy and infliximab before steroid use. CASE: A 72-year-old man, who received seven courses of atezolizumab/bevacizumab for hepatocellular carcinoma due to hepatitis B, was admitted to our department with idiopathic abdominal pain and diarrhea (grade 2 [G2]). Computed tomography (CT) and colonoscopy confirmed edema in the gastrointestinal tract. Perforation of the jejunum was observed in a CT performed on the third day and an emergency operation was performed. Intraoperative findings showed severe edema of the jejunum and leakage of feces into the abdominal cavity. The patient was diagnosed with irAE enteritis comprehensively with severe wall thickening on CT and colonoscopy, negative stool culture, and pathological findings of CD8-positive cells. Infliximab was administered before initiating steroids, to prevent reperforation. The enteritis improved by the 22nd day; however, CT performed on the 35th day of illness showed relapse of gastrointestinal wall thickening and G2 diarrhea symptoms; therefore, prednisolone (PSL) 60 mg/day was started on the 36th day of illness. After introducing PSL, enteritis did not reoccur, and the patient was discharged on the 63rd day of illness after admission. CONCLUSION: There are no reports of gastrointestinal perforation by atezolizumab/bevacizumab for hepatocellular carcinoma, and prior administration of infliximab. We therefore report the clinical course and management.

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.

Metastatic osteosarcoma bowel perforation secondary to chemotherapy-induced tumour necrosis.

Osteosarcoma is the most common paediatric and adolescent primary bone malignancy and is highly chemosensitive. Gastrointestinal metastases from osteosarcomas are rare. Bowel perforation secondary to chemotherapy is a potential serious complication reported in ovarian, colorectal and haematological malignancies. We report the first documented case of chemotherapy-mediated bowel perforation in an osteosarcoma patient with gastrointestinal metastases. A man in his 20s, with a history of resected osteosarcoma in remission, presented with abdominal pain. A computed tomography (CT) scan demonstrated a large calcified intrabdominal mass (15×13×9 cm) consistent with new peritoneal disease. After one cycle of palliative ifosfamide and etoposide chemotherapy, he developed a large bowel perforation and neutropenic sepsis consequently requiring resection of the perforated mass. Chemotherapy-induced bowel perforation is a rare but serious complication that should be considered in patients with osteosarcoma, and other chemosensitive malignancies, with intra-abdominal metastases. Recommencement of systemic therapies after bowel complications must be assessed cautiously on a case-by-case basis.

Successful treatment of angioinvasive aspergillosis causing diaphragmatic rupture with bowel perforation and cerebral aspergillosis in a patient with FLT3-mutated acute myeloid leukemia: A case report.

RATIONALE: Throughout the clinical course of acute myeloid leukemia (AML), aspergillosis infection remains a significant determinant of treatment outcomes and survival. To emphasize the importance of early diagnosis and appropriate application of integrated therapeutic approaches, we present a case of AML patient who survived through angioinvasive aspergillosis infection causing diaphragmatic rupture with bowel perforation and cerebral aspergillosis during active AML treatment. PATIENT CONCERNS: A 39-year old male with FLT3-mutated AML was transferred to our hospital due to persistent fever after induction therapy. DIAGNOSIS AND INTERVENTIONS: During voriconazole treatment for his invasive pulmonary aspergillosis, the patient was diagnosed with colon perforation at splenic flexure and suspected perforation of left diaphragm with communication with left pleural space. Although pancytopenic, emergency laparotomy was performed with granulocyte transfusion. Also, dual antifungal therapy with voriconazole and micafungin was applied. With supportive care, he was able to successfully complete 3 cycles of consolidation using tyrosine kinase inhibitor. However, 80 days after the last chemotherapy, the patient experienced seizure caused by a single 1.5 cm sized enhancing mass in the right occipital lobe. Diagnostic and therapeutic mass removal was carried out, and pathology-confirmed cerebral aspergillosis was diagnosed. OUTCOMES: The patient's neurologic symptoms are resolved and he is leukemia free, but remains on voriconazole for his cerebral aspergillosis till this day. CONCLUSIONS: Our case highlights the importance of timely integrated intervention and adequate underlying disease control in treatment of invasive aspergillosis in immunocompromised patients. Such rigorous efforts can save even the most seemingly dismal case.

Colonic perforation in 4 dogs following treatment with meloxicam.

OBJECTIVE: To describe the clinical findings and treatment of 4 dogs that developed colonic perforation shortly after meloxicam administration. SERIES SUMMARY: Three cases were treated with meloxicam for variable nonspecific signs including lethargy and pyrexia. Hemorrhagic diarrhea developed following meloxicam administration in 2 cases. Gastrointestinal perforation was suspected on diagnostic imaging leading to exploratory celiotomy in all 3 cases. Partial colectomy was performed in 2 cases and suture repair with serosal patching in 1 followed by broad spectrum antimicrobials. All 3 dogs recovered from surgery well. One dog that had undergone perineal herniorrhaphy and received meloxicam perioperatively collapsed and died 7 days postsurgery. Postmortem examination revealed ulceration and perforation of the ascending colon with resultant generalized septic peritonitis. Histopathologic findings in all cases showed full thickness infiltration of the colonic wall with inflammatory cells along with ulceration and perforation. Thrombosis of vessels underlying the ulcerated areas was also noted. NEW OR UNIQUE INFORMATION PROVIDED: This report suggests that colonic perforation may be a complication of nonsteroidal anti-inflammatory drug use in some cases. To the authors' knowledge, this has not previously been described in dogs. Colonic perforation associated with NSAIDs administration may be more commonly identified in dogs with concurrent morbidities. Caution may be warranted when using NSAIDs in dogs with colonic pathology or possible risk factors to develop such pathology. Prompt diagnosis and treatment is essential for a positive outcome.

[Patient with Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma with Small Intestinal Perforation Development during Chemotherapy].

Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is classified under type Ⅱ enteropathy-associated T-cell lymphoma(EATL). It is a rare disease with a low incidence rate. This study reports a case of a patient with MEITL who developed small intestinal perforation during chemotherapy. The patient was a 55-year-old woman who presented to a previous clinic with epigastric pain. Enteroscopy results showed a map-like ulcer in the jejunum. Examination of the tissue specimen collected from this site suggested T-cell lymphoma. The patient was referred to our hospital for chemotherapy. Seven days following the initiation of chemotherapy, an abdominal computed tomography(CT)revealed free air, leading to a diagnosis of gastrointestinal perforation. Emergency surgery was performed. Intraoperatively, bowel perforation and a degenerative ulcer were observed at 95 cm and 80 to 115 cm from the Treitz' ligament, respectively. In addition, all-layer intestinal necrosis was noted 150 and 90 cm from the terminal ileum. Total resection and anastomosis were performed. Postoperatively, the patient developed sepsis due to chemotherapy-related pancytopenia but recovered. She was discharged on postoperative day 24. Subsequently, positron emission tomography(PET)-CT revealed residual intestinal tumor cells and peritoneal dissemination. Chemotherapy was initiated, but there was no response. The patient died after 6.5 months. A radical treatment for MEITL has not yet been established. More case reports are needed to improve the prognosis of this disease.

COVID 19 and the risk of gastro-intestinal perforation: A case series and literature review.

BACKGROUND: COVID19 is a viral disease with pneumonia as its most common presentation. Many presentations and complications have been reported, but gastro-intestinal perforation has not received much attention. METHODS: three cases from our hospital are presented, and the current literature was reviewed. RESULTS, CASES: All three patients were admitted to the ICU with respiratory failure due to COVID19 pneumonia and intubated. Our first patient was treated with steroids, and subsequently diagnosed with rectal perforation on day 34 of his hospital admission. The second patient was treated with steroids and tocilizumab, and diagnosed with colonic perforation 1 day after neostigmine administration, on day 14 of his hospital admission. Our third patient was treated with steroids and tocilizumab, and diagnosed colonic perforation 4 days after neostigmine administration, on day 14 of his hospital admission. RESULTS, LITERATURE: 25 more cases were found in current literature, both upper GI and lower GI perforations, either as a presenting symptom or during the course of hospitalization. These were often associated with treatment with steroids, interleukin 6 inhibitors, or both. CONCLUSIONS: Gastro-intestinal perforation is a rare but dangerous complication of COVID19. Treatment with tocilizumab and steroids may both increase the risk of this complication, and hamper diagnosis.

Reduction of ileocolic intussusception under sedation or anaesthesia: a systematic review of complications.

BACKGROUND: Despite the increased use of sedation in children undergoing stressful procedures, reduction of ileocolic intussusception (RII) is usually performed on awake children without any form of sedation. OBJECTIVE: To evaluate the incidence of severe complications of RII under sedation or anaesthesia. DESIGN: A systematic review including English language original articles of any date. PATIENTS: Children undergoing RII (pneumatic or hydrostatic) under sedation or anaesthesia. DATA SOURCES: Ovid Embase, Scopus, PubMed, the Cochrane Database of Systematic Reviews and the internet search engine Google Scholar. DATA EXTRACTION: Three authors independently reviewed each article for eligibility. The Newcastle-Ottawa Scale was used to assess the quality of included studies. MAIN OUTCOME MEASURES: The primary outcome was the incidence of intestinal perforation during RII. The secondary outcomes were the incidence of sentinel adverse events defined as death, cardiopulmonary resuscitation, permanent neurological deficit and pulmonary aspiration syndrome. RESULTS: The search yielded 368 articles. Nine studies with 1391 cases were included in the analysis. Of the nine studies, six had a score of ≤6 stars in the Newcastle-Ottawa Scale assessment, indicating low-to-moderate quality. Propofol-based sedation was used in 849 (59.2%) cases; 5 (0.6%) had intestinal perforation. Intestinal perforation was not reported in patients who were sedated with other sedatives. One patient had pulmonary aspiration syndrome. CONCLUSIONS: Although caution remains warranted, current data suggest that the incidence of severe complications due to RII under sedation or anaesthesia is low. Due to the lack of prospective data, it is difficult to ascertain the exact incidence of severe complications.