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World J Gastroenterol. May 28, 2008; 14(20): 3273–3275.
Published online May 28, 2008. doi:  10.3748/wjg.14.3273
PMCID: PMC2712867

Pneumatosis cystoides intestinalis after fluorouracil chemotherapy for rectal cancer


Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition characterized by intraluminal gas in the gastrointestinal tract. Several chemotherapeutic agents have been reported to be associated with PCI, although fluorouracil-related PCI is extremely rare. We report a case of a 76-year old man who received adjuvant chemotherapy for rectal cancer with fluorouracil (FU) and leucovorin (LV). After 1 cycle of the treatment, he presented with diarrhea and abdominal pain. Abdominal radiogram revealed the presence of free air under the diaphragm and intramural gas in the intestine. Laparotomy was performed, showing a suspected diagnosis of perforation in the gastrointestinal tract. Intraoperative findings revealed pneumatosis of the intestine without evidence of perforation. He was treated supportively and his symptoms improved. In conclusion, we should consider the possibility of PCI occurring in patients with malignancies during chemotherapy treatment.

Keywords: Pneumatosis cystoides intestinalis, Chemotherapy, Fluorouracil, Colorectal cancer


Fluorouracil (FU) is one of the most commonly used chemotherapeutic agents in clinical oncology regimens. With regard to colorectal cancer, treatment involving FU with leucovorin (LV) can improve the survival, tumor response and quality of life[1] of patients. We report a case of pneumatosis cystoides intestinalis (PCI) in a patient who received adjuvant chemotherapy with 5-FU and l-LV[2]. To our knowledge, FU-related or FU-induced PCI has not been reported previously. This case will add to the reported series of patients with FU-induced small bowel toxicity[3,4] and chemotherapy-related PCI[59].


A 76-year-old male underwent anterior resection for stage III rectal cancer. He received an adjuvant chemotherapy protocol comprising intravenous bolus injection of 600 mg/m2 5-FU at 1 h after the initiation of 2 h-long 250 mg/m2 l-LV infusion, once a week for 6 wk, followed by 2 wk of rest[2]. After 1 cycle of this treatment, the patient presented with diarrhea and abdominal pain. Although his abdomen was distended, he did not exhibit any peritoneal signs. He was afebrile and had no neutropenia. His stool culture was negative. An abdominal radiogram revealed the presence of free air under the diaphragm and intramural gas in the entire intestine (Figure (Figure1).1). Abdominal computed tomography (CT) revealed the presence of free air in the intestinal wall, retroperitoneal space (Figure (Figure2A),2A), and falciform ligament (Figure (Figure2B).2B). Since bowel perforation was strongly suspected, an emergency operation was performed. Laparotomy revealed pneumatosis of the intestine (Figure (Figure3)3) and colon, and pneumoretroperitoneum without evidence of perforation. Therefore, gastrostomy was performed to reduce the pressure in the bowel. PCI was disappeared within 2 wk after parenteral nutrition, antibiotic treatment and oxygen therapy. Enema showed no incidence of anastomotic stenosis and he administered oral uracil-ftorafur, and no recurrence of PCI was observed during the 1-year follow-up.

Figure 1
Abdominal radiogram showing intraluminal gases in the entire small intestine and free air under the diaphragm.
Figure 2
Abdominal CT scan showing excessive intraluminal gases in the entire small intestine and free air in the retroperitoneal space (A), and free air in the falciform ligament (B).
Figure 3
Expanded intraluminal air spaces in the small intestine and mesenterium during intra-operation.


PCI is relatively rare condition characterized by multiple intraluminal gases existing in any part of the gastrointestinal tract. The mechanism and etiology of PCI are not fully understood. According to most hypotheses, mechanical and bacterial factors are the predominant causes for PCI[1012]. However, in this present case, no mechanical or bacterial factors, including bowel ischemia, bowel obstruction[13,14], inflammatory bowel disease and infectious colitis, for the gas production in the intestinal wall were observed.

Several chemotherapeutic agents have been reported to be associated with PCI, including cyclophosphamide, cytarabine, vincristine, doxorubicin, daunorubicin, etoposide, docetaxel, irinotecan and cisplatin[59]. Although fluorouracil-related PCI has not been previously described, the cytotoxic effect of chemotherapy on the epithelial bowel can also play a role in the pathogenesis of PCI[7]. Because the intestinal mucosa is highly proliferative, mucosal damage occurs easily during chemotherapy[6]. Moreover, the chemotherapeutic agent might interfere with the mucosal integrity of the intestinal tract, resulting in extensive intramural air[8]. Tamura et al[15] reported that PCI following chemotherapy might be due to depletion of submucosal lymphoid tissue or leukemic infiltrates, such as denuded Peyer’s patches producing mucosal defects, thereby permitting entry of gas into the bowel wall. It was reported that chemotherapy-related PCI occurs due to immunosuppressive treatment for hematological malignancies[5,6]. Neutropenia is an important factor for the development of PCI[59]. However, the current patient did not suffer from neutropenia before or when PCI was diagnosed.

Several studies have reported severe erosion and superficial ulceration in the ileum after chemotherapy comprising 5-FU and LV in colon cancer patients[3,4]. The mechanisms are thought to be multifactorial, including alteration in the local mucosal blood flow and thrombogenic and vasospastic effects of 5-FU on the vascular epithelium[5]. The mechanism underlying 5-FU-induced PCI is thought to be multifactorial, including bowel toxicity caused by 5-FU itself.

In conclusion, although PCI is a rare complication of chemotherapy, the possibility of PCI occurring in patients undergoing chemotherapy should be kept in mind.


The written consent was obtained from the patient for publication of this case report.

Peer reviewer: Damian Casadesus Rodriguez, MD, PhD, Calixto Garcia University Hospital, J and University, Vedado, Havana City, Cuba

S- Editor Li DL L- Editor Wang XL E- Editor Liu Y


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