G.A. Tireli
H. Ozbey
T. Salman
From Istanbul University, Istanbul Medical Faculty,
Department of Pediatric Surgery, Istanbul, Turkey.
Correspondence to: Dr. Gulay A. Tireli, Zuhuratabab
Sarsilmaz sok, Ugur ap. No. 6/1, 34740, Bakirkoy, Istanbul, Turkey.
E-mail: [email protected]
Manuscript received: October 23, 2003; Initial
review completed: January 23, 2004; Revision accepted: September 27,
2004.
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.
Table I
Details of Children with Neutropenic Enteropathy.
Case |
Age at
diagnosis |
Sex |
Primary
disease |
Neutrophil
count/mm3 |
Blood
culture |
Operative
findings |
Operation |
Course |
1
|
6yrs
|
M
|
NHL
|
800
|
+
|
Multiple
ileal
perforations
|
ileostomy
|
died
|
2.
|
9 mo
|
F
|
NHL
|
600
|
+
|
Multiple
ileal
perforations
|
anastomosis
|
died
|
3.
|
5 yrs
|
F
|
ALL
|
100
|
+
|
ileal
performation
|
ileostomy
|
alive
|
4.
|
1 yrs
|
F
|
AML
|
300
|
-
|
segmental
necrosis
jejunum
|
anastomosis*
|
died
|
5.
|
8 yrs
|
M
|
NHL
|
6400
|
-
|
perforation
of terminal
ileum
|
ileostomy
|
alive
|
6.
|
6 yrs
|
F
|
HL
|
3200
|
+
|
gastric
perforation
|
primary
repair
|
alive
|
7.
|
16 yrs
|
M
|
AML
|
1900
|
+
|
patchy
inflammation
of terminal
ileum
|
appendectomy
|
alive
|
* 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.
|
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