ANZ J. Surg.

2003;

73

: 463–465

CASE REPORT

Case Report

SUCCESSFUL CONSERVATIVE MANAGEMENT OF NEUTROPENIC ENTEROCOLITIS: A REPORT OF TWO CASES AND REVIEW OF

THE LITERATURE

K

EVIN

O’C

ONNOR

, B

IRGIT

D

IJKSTRA

, L

OUISE

K

ELLY

, E

NDA

W. M

C

D

ERMOTT

, A

RNOLD

D. K. H

ILL

AND

N

IALL

O’H

IGGINS

Department of Surgery, St Vincent’s University Hospital, and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

Key words: colitis, neutropenia.

Abbreviations

: GCSF, granulocyte colony stimulating factor; IEV, ifosfamide, etopaside, epirubicin.

INTRODUCTION

Neutropenic enterocolitis is a necrotizing inflammation of thecolon. It is seen with increasing frequency as a complication ofhigh dose chemotherapy for haematological and other malig-nancies including solid tumours; for example, of breast, lung andtestis. Management of this condition has been controversial, withsome advocating emergency surgical intervention,

1

while morerecent studies show that a conservative approach is safe andeffective.

2

The pathogenesis of this condition is multifactorial butdrug induced mucosal injury plays a significant role in the initia-tion of the pathological process. Once the primary mucosaldamage has occurred, a variety of secondary events may follow,the most common of which is sepsis.

3,4

We report two casesof severe neutropenic enterocolitis, presenting after high dosechemotherapy who were treated conservatively.

CASE REPORTS

The first patient is a 53-year-old man with multiple myeloma. Hisinitial treatment consisted of three cycles of low dose continuouschemotherapy consisting of vincristine, adriamycin, dexametha-sone. This regime had little therapeutic effect. He was a suitablecandidate for autologous stem cell transplantation because of hisyoung age. This aggressive treatment prolongs both duration ofremission and overall survival in the younger patient (< 60 years)with myeloma. This protocol consists of collection of peripheralblood stem cells mobilized by granulocyte colony stimulatingfactor (GCSF), followed by high dose therapy with ifosfamide,etopaside, epirubicin (IEV). This is in turn is followed by reinfu-sion of autologous stem cells. On day two after this 4-day cycleof IEV he began to complain of nausea, vomiting and diarrhoea.On examination he was pyrexial with a temperature 39.5

°

C. Hehad abdominal discomfort with localized right iliac fossa tender-ness and diarrhoea. Bowel sounds were reduced. Laboratoryresults revealed a white cell count of 0.9

×

10

9

/L. Plain film of

the abdomen at that time showed no abnormality. A CT scan ofthe abdomen showed marked colitis with bowel wall thicknessmeasuring 2.5 cm (Fig. 1). A diagnosis of neutropenic entero-colitis was made on clinical, haematological and radiologicalgrounds. He was treated conservatively with gastric decompres-sion, replacement of fluids, intravenous antibiotics (piperacillin,gentamicin and metronidazole), GCSF and total parenteral nutri-tion. The patient recovered after three weeks in hospital. A followup computed tomography (CT) scan after 2 weeks revealed thatthe marked colitis had almost completely resolved.

The second patient is a woman aged 43 years with right-sidedbreast cancer for which she had a wide local excision and axillaryclearance. Histology revealed a 4-cm invasive ductal carcinomawith lymphovascular invasion, oestrogen receptor positive andlymph node negative. Metastatic work up was negative. She hadalready completed four sessions of adriamycin and radiotherapybefore starting further chemotherapy. On day five after the secondcycle of cyclophosphamide, methotrexate and 5-flourouracil chemo-therapy (CMF), the patient developed nausea, lower abdominaldiscomfort and diarrhoea. She was pyrexial with a temperature of39

°

C. On examination of the abdomen she had generalized lowerabdominal tenderness. Her full blood count revealed a white cellcount of 0.3

×

10

9

/L. Abdominal X-ray findings were consistentwith toxic megacolon and a CT scan showed an inflammatory

K. O’Connor

MB;

B. Dijkstra

FRACS;

L. Kelly

FRCSI;

E. W. McDer-mott

MCh, FRCSI;

A. D. K. Hill

MCh, FRCSI;

N. O’Higgins

MCh, FRCSI.

Correspondence: Mr Arnold Hill, Department of Surgery, St Vincent’s Uni-versity Hospital, Elm Park, Dublin 4 Ireland.Email: adkhill@ucd.ie

Accepted for publication 14 January 2002.

Fig. 1.

Computed tomography scan of the abdomen showing markedcolitis with a thickened wall of the right colon.

464 O’CONNOR

ET AL

.

pancolitis (Fig. 2). A diagnosis of neutropenic colitis was made.She was treated conservatively with gastric decompression, fluidreplacement, antibiotics (i.v. gentamicin and piperacillin) and totalparenteral nutrition. The patient recovered after 1 week with a cor-responding rise in her white cell count.

DISCUSSION

Typhlitis was first described in 1970 in an autopsy series as aterminal complication of childhood leukaemia.

5

Its definition hassubsequently been broadened to encompass a similar clinical andpathological entity in children and in adults most commonlyinvolving the ileum and proximal colon. It has been referredto alternatively in the literature as necrotizing enteropathy,

3

ileo-caecal syndrome,

6

and neutropenic enterocolitis.

2

The condition has increasingly been recognized and reported.It is thought to be due to proliferation of myelotoxic chemo-therapeutic regimens in adult leukaemias, the use of combinationchemotherapy in solid tumours and also due to patients who areimmuno-compromised because of organ transplantation.

7

Neutropenic enterocolitis has more recently been documentedin patients with breast cancer. It is more commonly associatedwith metastatic breast cancer treated with taxane-based chemo-therapy which results in severe neutropenia and direct toxicity tothe bowel causing neutropenic enterocolitis.

8,9

The pathogenesis of this condition is not fully understood butis thought to be multifactorial. Drug-induced mucosal injuryplays a significant role in the pathological process. Cytotoxicchemotherapy inhibits cellular replication; hence, mucosal prolif-eration may not replace that which is lost by natural desquama-tion and thus mucosal integrity may be lost. The drug-inducedbowel wall mucosal injury is then followed by superinfectionwith colonic and opportunistic organisms. Other factors thatinfluence pathology include relatively poor vascular supply of thecaecum, a breakdown of the normal colonic surface because ofthe absence of neutrophils and the production of endotoxins byenteric organisms particularly

Clostridium septicum

.

3,4,10

The clinical presentation is non-specific, with symptoms suchas nausea, vomiting, abdominal pain and sometimes diarrhoeathat may be bloody. Usually there is pyrexia and right iliac fossatenderness, but even in severe cases physical findings may be

minimal. Differential diagnosis in this setting includes pseu-domembranous colitis, ischaemic colitis, and chemotherapy-induced abdominal pain. A consistent pattern among patients isthe onset of symptoms while their white cell count (wcc) isdeclining during or shortly after the administration of chemo-therapy. Only after the nadir is reached and the wcc is risingwould patients improve.

3,11

Many radiological investigations are useful in making thediagnosis. Of these CT is the most valuable. A plain film of theabdomen may be useful if there are positive physical signs but isgenerally normal or non-specific. It may show a decrease in gasin the right lower quadrant with dilated small bowel loops. It canalso reveal free intraperitoneal air after perforation or localized ordiffuse ‘thumb-printing’. The sonographic findings consistentwith a diagnosis of neutropenic enterocolitis are of a roundedmass with dense central echoes and a wider hyperechoic periph-ery. In general, CT findings are similar to ultrasound, but CT ismore accurate in determining caecal wall thickening and deter-mining the extent of the colitis. Endoscopic investigations areavoided because of the risks of inducing perforation or introduc-ing infection leading to fulminant bowel wall necrosis.

3,12

Management of neutropenic enterocolitis remains contro-versial. Management options range from a conservative approachto early surgical intervention. Conservative management of neu-tropenic enterocolitis includes gastric decompression, fluid andblood product replacement, broad-spectrum antibiotics, GCSFand often parenteral nutritional support.

13

The only definitiveindications for surgery include free intraperitoneal perforation,generalized peritonitis and continued bleeding despite correctionof any coagulopathy.

14

If surgical intervention is necessary,a colectomy with ileostomy and mucous fistula is usuallyperformed, or in a very selected group of patients a primary anas-tomosis may be carried out.

15

In those patients treated con-servatively, close clinical observation combined with repeat CTshould permit the clinician to monitor the progress of treatmentand to detect perforation and other conditions requiring urgentsurgical intervention.

16,17

CONCLUSION

Two cases of neutropenic enterocolitis presenting after chemo-therapy with neutropenic fever, abdominal pain and diarrhoea arereported. The CT scans of the abdomen revealed thickening of thecolonic wall and pericolic oedema. Both clinical and radiologicalfindings supported the diagnosis of neutropenic enterocolitis. Bothpatients were successfully managed without operation. Thesefindings support a trend towards a more conservative approach inthe management of patients with neutropenic enterocolitis.

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Fig. 2.

Computed tomography scan of the abdomen showing aninflammatory pancolitis.

MANAGEMENT OF NEUTROPENIC ENTEROCOLITIS 465

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CASE REPORT