Everolimus/polmacoxib

Abstract

Colon perforation with multiple transmural ulcers: case report A 66-year-old woman developed colon perforation with multiple transmural ulcers during treatment with everolimus for metastatic breast cancer and polmacoxib for seronegative rheumatoid arthritis [not all dosage stated]. The woman, who had been hospitalised in the orthopaedic department, developed acute-onset whole abdominal pain following haematochezia. Her surgical history included a modified radical mastectomy with axillary lymph node dissection for right breast cancer (pT2N1M0, stage IIB) 5 years previously. A month after breast surgery, she had received adjuvant chemotherapy with cyclophosphamide, methotrexate and fluorouracil. Four years after surgery, bone metastasis was detected on the T8 vertebra. Three months later, the chemotherapy regimen was changed to oral everolimus 10 mg/day along with an unspecified aromatase inhibitor. Seven months later, she received an arthrotomy of the left wrist due to seronegative rheumatoid arthritis, and she started receiving oral polmacoxib. After seventeen days from the initiation of polmacoxib, she complained of acute-onset whole-abdominal pain following haematochezia (current presentation). Physical examination showed that she was acutely ill. Body temperature was 37.5°C, pulse rate was 87 beats/minute and blood pressure was 111/68mm Hg. Her abdomen was rigid, and exhibited wholeabdomen tenderness and rebound tenderness. The left upper quadrant showed a maximal point of tenderness. Rectal examination revealed no active bleeding or rectal mass. Laboratory investigation results were as follows: leukocyte count 12.44 × 103/mm3, haemoglobin count 9.9 g/dL, haematocrit level 29.8%, platelet count 332 × 103/mm3, prothrombin time 14.5s and INR ratio 1.36s. An abdominopelvic CT revealed multiple wall defects in the descending colon with perilesional fat infiltration and pneumoperitoneum, suggesting multiple perforations of the descending colon. Emergency laparoscopic exploration revealed diffuse inflammation and multiple abscess pockets in the mesocolon, severely inflamed left colon and a gross perforation in the proximal descending colon measuring 2cm that was connected to the largest abscess pocket. The woman underwent a left hemicolectomy using hand-assisted laparoscopy with abscess drainage and irrigation of the peritoneal cavity. The severely inflamed left colon and perforation site were resected, and a transverse sigmoid anastomosis was created. The specimen obtained during the operation revealed multiple transmural ulcerations adjacent to the gross perforation site. There was no evidence of underlying gastrointestinal disease such as diverticulitis or inflammatory bowel disease. Pathological evaluation of the specimen demonstrated chronic active transmural inflammation, vascular congestion and acute serositis. Everolimus and polmacoxib were considered as risk factors for colon perforation with multiple transmural ulcers. Post operation, she was treated with IV antibiotics for peritonitis. All previous oral medications including everolimus and polmacoxib were discontinued. On postoperative day 1, there was an improvement in abdominal pain. However, on postoperative day 3, fresh red blood haematochezia without abdominal pain started. Under the suspicion of intraluminal bleeding at the anastomosis site an emergency sigmoidoscopy was performed, which showed that the anastomosis was clean and patent, and multiple geographic ulcers existed in the remnant colon wall. As there were no signs of additional perforation, a decision was made to not operate on her immediately. Considering a possibility of total colectomy, she was monitored closely. On postoperative day 5, the haematochezia stopped spontaneously after conservative management. On postoperative day 8, follow-up abdominopelvic CT revealed diffuse oedematous wall thickening from the distal transverse colon to the rectosigmoid colon. Loculated fluid appeared in the lower abdomen and percutaneous drainage was performed. There was no evidence of newly developed colon perforation. On postoperative day 13, she started an oral diet. On postoperative day 34, she was discharged from the hospital. After 6 months from the operation, colonoscopy showed that the colon ulceration had self-resolved and the remainder of the colon was normal.