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Neutropenic Enteropathy
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     Istanbul University, Istanbul Medical Faculty, Department of Pediatric Surgery, Istanbul, Turkey.

    Abstract:

    Neutropenic enteropathy (NE) is used to describe the inflammation of the bowel in neutropenic patients under aggressive chemotherapy, mainly for Iymphoproliferative and hematologic malignancies .Surgical intervention may be required in patients with the advent of the disease. We report our experience in 7 children with NE who had to be treated surgically. Absolute neutrophil counts were less than 1000/mm3 in all, with positive blood cultures in five patients. Four patients recovered with rapid resolution of neutropenia, while three patients died with persistent neutropenia.

    Key words: Intestinal perforation, Neutropenic enteropathy, Typhlitis.

    Neutropenic enteropathy (NE) is used to describe the inflammation of the bowel (mostly the cecum and the ascending colon) in neutropenic patients under aggressive chemo-therapy, mainly for lymphoproliferative and hematologic malignancies(1,2). Although, the initial treatment of choice is nonoperative treatment with bowel rest, decompression, nutritional support and appropriate antibiotics, operative intervention is needed in patients with the advent of the disease(3,4). We treated 7 such children during last 5 years.

    Case Report

    Table I highlights the clinical details, laboratory findings, intervention and outcome of seven cases of neutropenic enteropathy. All patients were undergoing cancer chemotherapy and required pediatric surgery consultation because of abdominal pain, vomiting and abdominal distension. The neutrophil counts were less than 1000/mm3 in all children at presentation.

    required ileostomy at a second operation due to anastomotic dehiscense

    NHL: NonHodgkin lymphoma, ALL: Acute lymphoblastic leukemia,

    AMI: Acute myeloblastic leukemia, HL: Hodgkin lymphoma.

    All patients were treated with bowel rest, nasogastric decompression, parenteral nutritional support and antibiotics. Plain abdominal radiographs and abdominal ultra-sound revealed dilated, thick walled small bowel loops with air-fluid levels, free intra-peritoneal fluid (n = 6) and free intraperitoneal air (n = l). In two patients, surgery was indicated immediately after suspicion of the intestinal perforation. In others, progressive and/or persistent clinical and radiological findings let us to explore the abdominal cavity, within 3-5 days.

    Free intraperitoneal fluid, hemorrhage, marked edema of the bowel wall, patchy inflammation and localized abscess were the main operative findings. The lesions were mostly localized at terminal ileum and the ascending colon. In one patient, perforation site was the posterior wall of the stomach with diffuse gastrointestinal fungal plaques.

    The histopathological findings were mucosal and transmural hemorrhagic ulceration of the bowel (and stomach), with perforation in 6 patients. In surviving children, neutropenia improved following surgery.

    Discussion

    Cooke was the first to describe submucosal hemorrhage and appendiceal perforation in children with leukemia(5). Later, autopsy reviews demonstrated pathological findings of the bowel in patients who died during induction or consolidation therapy. A disease process, called "typhlitis", "neutropenic enterocolitis" or "ileocecal syndrome" is usually found in the terminal ileum, ascending colon and cecum. Although its exact pathogenesis is not clear, it is thought that chemotherapy may damage the gastro-intestinal tract (whether infiltrated with the primary disease or not) by destroying the rapidly dividing mucosal cells, which when coupled with neutropenia allows bacterial invasion of the bowel wall(2,6). A close relationship between the use of cytosine arabinoside and subsequent perforation has also been reported by several authors(1,4,7). Arabinoside-C was being used in 4 of our patients.

    Recovery of the leucocyte count is fundamentally related with the survival of patients. Prolonged leukopenia may allow continued bacterial invasion of the bowel wall with persistence of the bowel lesion, followed by necrosis and perforation(4,8). We recognized the clinical findings of neutropenic enteropathy on an average of 4 days after the onset of chemotherapy-induced neutropenia. Persistence of neutropenia should also be noted in our patient in whom surgical intervention did not provide regression of the process. The ongoing ileus with impaired vascularity, severe cell mediated immune defect with or without infection with Candida albicans or other opportunistic organisms, would not permit healing of the anastomosis.

    References

    1. Cooke JV. Acute leukemia inchildten, JAMA 1933; 101: 432-435.

    2. Moir DB, Bale PM. Necropsy findings in childhood leukemia. Emphasizing neutropenic enterocolitis and cerebral calcification. Pathology 1976; 8: 247-258.

    3. Schamberger R, Weinstein HJ, Delorey MJ, Levey RB. The medical and surgical management of typhlitis in children with acute. non-lymphocytic (myelogenous) leukemia. Cancer 1986; 57: 603-609.

    4. Wade DS, Nava HR, Douglass HO. Neutropenic enterocolitis: Clinical diagnosis and treatment. Cancer 1992; 69: 17-23.

    5. Baerg J, Murphy JJ, Anderson R, Magee JF. Neutropenic enteropathy: a 10-year review. J Pediatr Surg 1999; 34: 1068-1071.

    6. Stainberg D, Gold J, Brodin A. Necrotizing enterocolitis in leukemia. Arch Intern Med 1973; 131: 538-544.

    7. Slavin RE, Dias MA, Saral R. Cytosine arabinoside-induced gastrointestinal toxic alteration in sequential chemotherapy protocols: A clinicopathologic study of 33 patients. Cancer 1978; 42: 1747-1759.

    8. Wade DS, Douglass HO Jr, Nava HR, Piedmonte M. Abdominal pain in neutropenic patients. Arch Surg 1990; 125: 1119-1127.(G.A. Tireli,H. Ozbey,T. S)