Early Diagnosis of Neutropenic Enterocolitis by Ultrasound Sonography.
Authors: Benedetti Edoardo , Simonetti Federico , Caracciolo Francesco , Papineschi Federico , Bruno Benedetto , Pelosini Matteo , Focosi Daniele , Galimberti Sara , Petrini Mario 
Published: October 2019

Abstract
Abstract 4742

Introduction
Neutropenic enterocolitis (NEC) is a life threatening complication of chemotherapy in leukemic and solid tumor patients with an incidence ranging from 2.6% to 33%. It is a necrotizing inflammatory disease that most commonly involves the ileo-cecal region. The cecum is almost invariably affected likely due to its distensibility and limited blood supply. Macroscopically the involved bowel segments show oedematous and thickened walls, with varying degrees of ulceration and haemorrhage. Perforation occurs in 5%-10% of cases. Early diagnosis is crucial to start conservative medical treatment which appears the optimal strategy. Criteria for prompt surgical treatment have also been proposed (Shamberger RC et al, 1986) so that a careful clinical evaluation by both the physician and the surgeon is mandatory (Davila ML et al, 2004). NEC should be always suspected in neutropenic patients with abdominal pain, fever and diarrhea. Ultrasound (US) has been used to evaluate bowel-wall thickening (BWT). One study correlated BWT with clinical outcome: 60% of patients with BWT > 10 mm died from NEC as compared with 4.2% of those with BWT < 10 mm (Cartoni C. et al, 2001). Overall, despite aggressive treatment, mortality rate is up to 21-48% and patients may die within hours from the onset of acute symptoms. Because of the risk of early death, a swift diagnosis is imperative. We investigated if US could detect early signs of NEC and lead to prompt treatment. We analyzed two patients cohorts (A and B). In cohort A US was performed later in the course of the disease whereas, in cohort B US was immediately performed at the onset of a single symptom (diarrhea and/or abdominal pain whichever occurred first with/without fever). Underlying haematological diagnoses were Hodgkin Disease (N=10), acute leukemias (N=9), multiple myeloma (N=3) and non-Hodgkin lymphomas (N=10). Treatments consisted of standard chemotherapy (N=10), myeloablative allografting after busulfan/cytoxan (N=1) and cytoxan/total body irradiation (N=1); autografting after busulfan/cytoxan (N=1), BEAM (N=16) and melphalan (N=3).

Results
All 32 patients showed grade 4 neutropenia at the onset of symptoms. Thirty-one/32 (97%) complained of abdominal pain whereas diarrhea was present in 30/32 (94%). Positive stool (for Clostridium Difficilis and Escherichia Coli) and blood cultures (62% Gram negative and 38% Gram positive bacteria) were found in 4/32 (12.5%) and 8/32 (25%) respectively. Trans-abdominal real-time US scanning of the bowel was performed using a 3.5-5 MHz convex probe and a 7 MHz linear transducer. A portable sonographer (Esaote model My Lab 25) was used for bed-side US. Both trans-abdominal axial and transverse US scans were performed on the colon. US signs of NEC were defined as thickening or dilation of small and/or large intestine. The intestinal involved areas were ileum, 21%, last terminal ileum, 21%, cecum 7%, ascending colon, 16%, transverse colon, 16%, descending colon, 14% and jejunum, 4%. US revealed signs of NEC in 8/14 in cohort A and 18/18 in cohort B. In cohort B, early US detected signs of NEC in 7 patients with abdominal pain and diarrhea without fever. Complete response to prompt medical treatment occurred in 6. Three/7 patients developed fever 48 hours after the US-guided diagnosis of NEC. Two patients, at risk of wall rupture by US imaging (confirmed by CT scans), underwent successful colon surgery within 12 hours from diagnosis. Except for these 2, all patients received medical treatment (broad spectrum antibiotics for gram-negative, gram-positive and anaerobic coverage, and antifungal drugs, granulocyte transfusions, bowel rest and granulocyte colony stimulating factor as per internal protocol). Overall 3/32 patients died.

Conclusions
Early bed-side intestinal US in neutropenic patients performed at the onset of a single symptom suggestive of NEC led to timely and successful treatment of this life threatening complication even before the development of fever.

Disclosures:
No relevant conflicts of interest to declare.