Delayed anastomotic leakage during treatment with ramucirumab: a case report

While adverse gastrointestinal events related to chemotherapy are known to occur, delayed anastomotic leakage during chemotherapy with concurrent ramucirumab treatment has never been reported.We describe the clinical course of a patient who experienced delayed anastomotic leakage during 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) and ramucirumab treatments, which was ultimately fatal.The patient was a 78-year-old man who underwent laparoscopic right hemicolectomy with regional lymphadenectomy for advanced ascending colon cancer that was symptomatic and accompanied by unresectable and multiple liver metastases.Anastomosis was performed using a stapler (a functional end-to-end anastomosis technique); the postoperative course was uneventful.One-month post-surgery, the patient received five courses of chemotherapy, which included 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) with bevacizumab as the first-line treatment and FOLFIRI with ramucirumab as the second-line treatment due to the progression of liver metastases observed on contrast-enhanced computed tomography.During the sixth course of ramucirumab and FOLFIRI, the patient reported right lower abdominal pain.Butylscopolamine was administered because the abdominal pain was considered a side effect of irinotecan, and his symptoms slightly improved.That night, he presented to our emergency room with sustained abdominal pain.Abdominal computed tomography showed intra-abdominal free air and anastomotic leakage at the ileo-colonic anastomosis from his previous surgery, without any peritoneal dissemination or local recurrence.Emergency surgery including resection of the leaked anastomosis and ileostomy was performed.Postoperative ileus was observed, and leucopenia (neutropenia) occurred from postoperative day 7. Severe pneumonia and respiratory failure also occurred.The patient died on postoperative day 11.We believe that our patient's delayed anastomotic leakage (6 months post-initial surgery) was a novel adverse event related to ramucirumab use.Although abdominal pain may occur after irinotecan administration, clinicians should be aware of this potentially fatal side effect of ramucirumab to facilitate rapid treatment.