Pneumatosis Intestinalis Induced by Anticancer Treatment: A Systematic Review

Abstract

Pneumatosis intestinalis (PI) is a rare condition due to the presence of gas within the bowel wall; it is mainly caused by endoscopic procedures, infections and other gastrointestinal diseases. Oncological therapies have been reported to be a cause of PI as well, but their role is not clearly defined. This systematic review investigates the concurrency of PI and antitumor therapy in cancer patients, considering both solid tumors and onco-hematological ones. We performed a literature review of PubMed, Embase and the Web of Science up to September 2021 according to the PRISMA guidelines. A total of 62 papers reporting 88 different episodes were included. PI was mainly reported with targeted therapies (sunitinib and bevacizumab above all) within the first 12 weeks of treatment. This adverse event mostly occurred in the metastatic setting, but in 10 cases, it also occurred also in the neoadjuvant and adjuvant setting. PI was mostly localized in the large intestine, being fatal in 11 cases, while in the remaining cases, symptoms were usually mild, or even absent. A significant risk of PI reoccurrence after drug reintroduction was also reported (6/18 patients), with no fatal outcomes. Potential pharmacological mechanisms underlying PI pathogenesis are also discussed. In conclusion, although uncommonly, PI can occur during oncological therapies and may lead to life-threatening complications; therefore, consideration of its occurrence among other adverse events is warranted in the presence of clinical suspicion.

Pneumatosis Intestinalis Induced by Alpha-Glucosidase Inhibitors in Patients with Diabetes Mellitus

“…The number of patients with other comorbidities was 1.9 times the number of patients without comorbidities. The exact pathophysiological mechanism of PI is unclear, but there are three theories: “mechanical theory” (the air penetrates the bowel wall), “bacterial theory” (gas-forming bacteria penetrate the submucosa), and “biochemical theory” (luminal carbohydrates are fermented, increasing intraluminal pressure) [ 2 , 36 ]. Based on those theories, the authors propose that multiple factors contribute to the development of αGIs-induced PI: increased production of intestinal gas, the hypomotility of the gastrointestinal tract, weakened intestinal mucosa and wall, and/or air carried from the lungs.…”

“…Prednisone and immunosuppressants could deplete lymphocytes and shrink Peyer’s patches, facilitating gas entry into the intestinal wall [ 41 ]. Mizoribine and methotrexate are cytotoxic and may cause mucosa and epithelial cell damage directly [ 2 ]. In our case series, the patient with dermatomyositis treated with prednisolone and methotrexate was the only one developing subcutaneous air in the cervical area, along with pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and PI [ 25 ].…”

“…Pneumatosis intestinalis (PI) is a condition in which gas is present within the walls of the intestines [ 1 ]. It is characterized by gas and free air in the mucosa, submucosa, and subserosa, and it can present in linear and/or cystic forms [ 2 ]. It is also called pneumatosis cystoides intestinalis.…”

“…The incidence of PI is 2/6553 (0.03%) in autopsies [ 3 ]. There are two subtypes of PI: primary/idiopathic and secondary; secondary PI consists of up to 85% of all PI cases in adults [ 1 , 2 ].…”

“…While uncommon, some drugs are suspected of causing PI [ 8 ]. In particular, PI has been described in patients receiving corticosteroids, immunosuppressants, anticancer drugs, alpha-glucosidase inhibitors (αGIs), lactulose, and sorbitol [ 2 , 8 , 10 ]. In a multicenter study in Japan, out of 167 PI patients, 31 (19%) cases were related to diabetes.…”