Neutropenic Enterocolitis: Clinical Features and Outcomes.

BACKGROUND: Patients undergoing chemotherapy are at risk for mucosal injury and neutropenia, which facilitate colonic mucosal invasion by the bowel flora and subsequent neutropenic enterocolitis, which has a poor prognosis. OBJECTIVE: This study aimed to assess the clinical features and outcomes of neutropenic enterocolitis in patients at a comprehensive cancer center. DESIGN: This is a retrospective cohort study. SETTING: The study was conducted at the University of Texas MD Anderson Cancer Center. PATIENTS: Neutropenic enterocolitis was defined by the presence of an absolute neutrophil count <1000/mm, compatible abdominal symptoms, and either mucosal thickening on abdominal imaging or mucosal injury on colon biopsy. Patients who had been diagnosed between 2010 and 2018 were included. MAIN OUTCOMES: Complication and survival rates were analyzed using logistic regression and Cox regression analyses, respectively. RESULTS: Of the 49,244 patients who had neutropenia during the study period, 134 (2.7%) were included. The median time from neutropenia onset to neutropenic enterocolitis was 2 days (interquartile range, 1-10 days). Neutropenic enterocolitis symptoms lasted for a median of 11 days (interquartile range, 6-22 days). Most patients received antibiotics (88%) and granulocyte colony-stimulating factor (68%). Complications included sepsis (11%), colonic perforation (2%), pneumatosis intestinalis (2%), and abscess formation (2%). The risks associated with complications included immunosuppressive therapy use within 1 month before neutropenic enterocolitis onset (OR, 3.92; 95% CI, 1.04-14.76) and delayed imaging (OR, 1.10; 95% CI, 1.03-1.17). Older age, severe neutropenia, prolonged neutropenia before and after neutropenic enterocolitis diagnosis, and other concomitant systemic infections were associated with lower survival rates. LIMITATIONS: The performance of this study at a single center and its retrospective nature are limitations of the study. CONCLUSION: The prompt diagnosis and management of neutropenic enterocolitis are critical to prevent complications. The use of granulocyte colony-stimulating factor can be beneficial to shorten the duration of neutropenia. See Video Abstract at http://links.lww.com/DCR/B116. ENTEROCOLITIS NEUTROPÉNICA: CARACTERÍSTICAS CLÍNICAS Y RESULTADOS: Los pacientes sometidos a quimioterapia, están en riesgo de lesión de la mucosa y neutropenia, lo que facilita la invasión de la mucosa colónica por la flora intestinal y la subsecuente enterocolitis neutropénica, con un mal pronóstico.Evaluar las características clínicas y los resultados de la enterocolitis neutropénica de pacientes en un centro integral de cáncer.Estudio de cohorte retrospectivo.El estudio se realizó en el MD Anderson Cancer Center de la Universidad de Texas.Se definió la enterocolitis neutropénica, como la presencia de un recuento absoluto de neutrófilos <1000 / mm3, con síntomas compatibles abdominales y engrosamiento de la mucosa en imagen abdominal o lesión de la mucosa en biopsia de colon. Se incluyeron pacientes diagnosticados entre 2010 y 2018.Se analizaron las tasas de complicaciones y supervivencia mediante análisis de regresión logística y regresión de Cox.De 49,244 pacientes que tuvieron neutropenia durante el período de estudio, 134 (2.7%) fueron incluidos. La media del tiempo desde el inicio de la neutropenia hasta la enterocolitis neutropénica, fue de 2 días (RIC, 1-10 días). Los síntomas de enterocolitis neutropénica duraron una media de 11 días (RIC, 6-22 días). La mayoría de los pacientes recibieron antibióticos (88%) y factor estimulante de colonias de granulocitos (68%). Las complicaciones incluyeron sepsis (11%), perforación colónica (2%), neumatosis intestinal (2%) y formación de abscesos (2%). Los riesgos asociados con las complicaciones incluyeron, uso de terapia inmunosupresora dentro de 1 mes antes del inicio de la enterocolitis neutropénica (razón de probabilidades 3.92; intervalo de confianza del 95% 1.04-14.76) y demora en la obtención de imágenes (razón de probabilidades 1.10; intervalo de confianza del 95% 1.03-1.17), edad avanzada, neutropenia grave, neutropenia prolongada antes y después del diagnóstico de enterocolitis neutropénica y de otras infecciones sistémicas concomitantes, se asociaron con bajas tasas de supervivencia.Centro único y estudio retrospectivo.El rápidodiagnóstico y manejo de la enterocolitis neutropénica, es crítico para prevenir complicaciones. El uso del factor estimulante de colonias de granulocitos puede ser beneficioso para acortar la duración de la neutropenia. Consulte Video Resumen en http://links.lww.com/DCR/B116.

Factors associated with emergent colectomy in patients with neutropenic enterocolitis.

PURPOSE: Neutropenic enterocolitis (NEC) is a severe complication of neutropenia. NEC is characterized by segmental ulceration, intramural inflammation, and necrosis. Factors present in patients who underwent colectomy have never been studied. The present study aimed to describe the clinical factors present in patients who underwent emergent colectomy for the treatment of neutropenic enterocolitis. METHODS: Patients admitted with neutropenic enterocolitis from November 2009 to May 2018 were retrospectively analyzed. Logistic regression analysis was used to determine clinical factors associated with emergent colectomy. RESULTS: Thirty-nine patients with NEC were identified. All patients had a hematological disorder. Medical treatment was the only management in 30 (76.9%) patients, and 9 (23.1%) patients underwent colectomy. No differences were found between the treatment groups regarding sex, age, or comorbidities. Patients were more likely to undergo colectomy if they developed abdominal distention (OR = 12, p = 0.027), hemodynamic failure (OR = 6, p = 0.042), respiratory failure (OR = 17.5, p = 0.002), multi-organic failure (OR = 9.6, p = 0.012), and if they required ICU admission (OR = 11.5, p = 0.007). Respiratory failure was the only independent risk factor for colectomy in multivariable analysis. In-hospital mortality for the medical and surgical treatment groups was 13.3% (n = 4) and 44.4% (n = 4), respectively (p = 0.043). CONCLUSIONS: In our study, most NEC patients were treated conservatively. Patients were more likely to undergo colectomy if they developed organ failures or required ICU admission. Early surgical consultation is suggested in all patients with NEC.

Neutropenic Enterocolitis in Critically Ill Patients: Spectrum of the Disease and Risk of Invasive Fungal Disease.

OBJECTIVES: Neutropenic enterocolitis occurs in about 5.3% of patients hospitalized for hematologic malignancies receiving chemotherapy. Data from critically ill patients with neutropenic enterocolitis are scarce. Our objectives were to describe the population of patients with neutropenic enterocolitis admitted to an ICU and to investigate the risk factors of invasive fungal disease. DESIGN: A multicentric retrospective cohort study between January 2010 and August 2017. SETTING: Six French ICUs members of the Groupe de Recherche Respiratoire en Onco-Hématologie research network. PATIENTS: Adult neutropenic patients hospitalized in the ICU with a diagnosis of enteritis and/or colitis. Patients with differential diagnosis (Clostridium difficile colitis, viral colitis, inflammatory enterocolitis, mesenteric ischemia, radiation-induced gastrointestinal toxicity, and Graft vs Host Disease) were excluded. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 134 patients (median Sequential Organ Failure Assessment 10 [8-12]), with 38.8% hospital mortality and 32.1% ICU mortality rates. The main underlying malignancies were acute leukemia (n = 65, 48.5%), lymphoma (n = 49, 36.6%), solid tumor (n = 14, 10.4%), and myeloma (n = 4, 3.0%). Patients were neutropenic during a median of 14 days (9-22 d). Infection was documented in 81 patients (60.4%), including an isolated bacterial infection in 64 patients (47.8%), an isolated fungal infection in nine patients (6.7%), and a coinfection with both pathogens in eight patients (5.0%). Radiologically assessed enteritis (odds ratio, 2.60; 95% CI, 1.32-7.56; p = 0.015) and HIV infection (odds ratio, 2.03; 95% CI, 1.21-3.31; p = 0.016) were independently associated with invasive fungal disease. CONCLUSIONS: The rate of invasive fungal disease reaches 20% in patients with neutropenic enterocolitis when enteritis is considered. To avoid treatment delay, antifungal therapy might be systematically discussed in ICU patients admitted for neutropenic enterocolitis with radiologically assessed enteritis.

Gastrointestinal emergencies in critically ill cancer patients.

PURPOSE: To describe gastrointestinal emergencies in cancer patients. METHODS: All cancer patients admitted to the medical ICU of Saint-Louis Hospital for an acute abdominal syndrome during the study period (1997-2011) were included. RESULTS: A total of 164 patients were included. The most common diagnoses were: neutropenic enterocolitis (NE) (n=54, 33%), infectious colitis and peritonitis (n=51, 31%), bowel infiltration by malignancy (n=14, 9%), and mucosal toxicity of chemotherapy (n=12, 7%). Microbiologically documented infections were reported in 82 patients (50%), including 12 fungal infections. Twenty-seven patients (16%) underwent urgent surgery. The hospital mortality rate was 35%. Five factors were independently associated with hospital mortality: the Simplified Acute Physiology Score II (SAPS II) score on day 1 (OR 1.03/SAPS II point, 95% CI 1.01 to 1.05), microbiological documentation (OR 0.27, 95% CI 0.11 to 0.64), neutropenia (OR 0.42, 95% CI 0.19 to 0.95), allogenic hematopoietic stem-cell transplantation (HSCT) (OR 5.13, 95% CI 1.71 to 15.4), and mechanical ventilation (OR 3.42, 95% CI 1.37 to 8.51). CONCLUSIONS: Gastrointestinal emergencies in cancer patients are associated with significant mortality. Mortality correlated both with the severity of organ failure upon ICU admission and the underlying diagnosis. Interestingly, patients admitted to the ICU with neutropenia had better survival.

Neutropenic Enterocolitis: New Insights Into a Deadly Entity.

Neutropenic enterocolitis (NE) is a deadly ileocecal-based disease seen in patients with a recent history of chemotherapy. As histology is not included in the current diagnostic criteria, the pathologic features of NE are poorly understood. We undertook a multi-institutional study of NE, and report helpful clinical clues, such as immunosuppression (n=20/20), recent chemotherapy (n=17/18), neutropenia (n=16/18) gastrointestinal symptoms (n=19/19), abnormal imaging studies of the cecum/right colon (n=11/14), and positive microbiological studies (n=13/15). Fever (n=9/15) and sepsis (n=8/16) were also common. Pathologically, the cecum/right colon was always involved (n=17/17), but findings were identified in other bowel segments as well. NE lesions consisted of patchy necrosis (n=18/20), infiltrating organisms (n=17/20), hemorrhage (n=15/20), ulcer (n=15/19), edema (n=15/20), and depletion of inflammatory cells (n=15/20). Seventy-nine percent (n=15/19) of patients with histologically confirmed NE died: 47% (n=7/15) of these deaths were attributed to NE and the remainder to the patients' underlying conditions. Importantly, we observed a clinical diagnostic discordancy rate of 35% (n=9/26): 15% (n=3/20) of histologically confirmed NE were clinically unsuspected, and 26% (n=6/23) of clinically suspected NE represented a different disease process. Alternative diagnoses included unspecified colitis, infection, graft-versus-host disease, relapsed malignancy, mycophenolate injury, appendicitis, and ischemia. The causes of death in patients with NE mimics included unrecognized appendicitis and unrecognized graft-versus-host disease. To improve diagnostic accuracy, we propose that histology be required for a diagnosis of "definitive NE," with other clinically suspicious cases reported as "suspicious for NE" until all other possible diagnoses have been reasonably excluded.

Supervivencia en pacientes afectados de enterocolitis neutropénica con sepsis y sus diferentes estadios / Survival of patients with neutropenic enterocolitis and different stage of sepsis

Objetivo: Determinar la supervivencia de los pacientes con enterocolitis neutropénica (ECN) con sepsis y sus diferentes estadios, ingresados en una unidad de cuidados intensivos pediátricos (UCIP). Métodos: Se realizó un estudio de cohortes en pacientes con diagnóstico de ECN, definida en sujetos con quimioterapia reciente, un recuento de neutrófilos totales <500 células/cm3, abdomen agudo y estudio de imagen compatible, que ingresaron en una UCIP. Se clasificó la sepsis de acuerdo con los criterios del «Consenso internacional de sepsis en pediatría», y se realizó a los pacientes un seguimiento hasta el séptimo día de estancia intrahospitalaria, registrándose las defunciones. Análisis estadístico: Se procedió al análisis de la supervivencia según el método de Kaplan-Meier, así como al cálculo de la tasa de riesgo. Resultados: Se seleccionó una muestra total de 64 pacientes, y se registraron 28 (43%) defunciones. La supervivencia registrada al séptimo día de seguimiento fue del 100% en la sepsis, del 92% en la sepsis grave, del 25% en el choque séptico y del 9% en la disfunción orgánica múltiple (p <0,0001). Conclusiones: La sepsis y sus distintos grados repercuten negativamente sobre la mortalidad de los pacientes pediátricos con ECN (AU)

Objective: To determine the survival of oncologic patients with neutropenic enterocolitis (NEC) and different stages of sepsis. Methods: A cohort study was performed in patients with the diagnosis of NEC defined in patients with recent chemotherapy, total neutrophils under 500 cells/cm3, acute abdomen and image compatible cabinet, admitted in a pediatric intensive care unit. Sepsis was classified according to the criteria of the "International pediatric sepsis consensus" were classified and were followed for up to seven days of hospital stay, registering deaths. Statistical analysis: Analysis of survival by Kaplan-Meier estimate of hazard ratio. Results: Total population of 64 patients, presenting 28 (43%) deaths. Survival on the seventh day follow-up was as follows: 100% sepsis, severe sepsis 92%, septic shock 25%, and multiple organ dysfunction 9% (p <0.0001). Conclusions: Sepsis in its different stages has a negative impact on mortality in pediatric patients with NEC (AU)

Neutropenic enterocolitis in children and young adults with cancer: prognostic value of clinical and image findings.

Intensive chemotherapy regimens can result in severe toxicities, particularly those that involve the digestive systems, leading to morbidity and mortality in this group of patients. Acute enterocolitis can be a frequent complication. The authors performed a retrospective review or patients treated at their institution to ascertain the prognostic value of the clinical symptoms and signs of acute enterocolitis, the corresponding abdominal ultrasonographic findings, and the impact of previous chemotherapy. Amongst 1159 patients with cancer treated at the Centro Infantil Boldrini from 2003 to 2007, 188 (16.2%) patients had 1 or more episode of enterocolitis. An intestinal wall thickness of >or=3 mm on ultrasound was considered diagnostic of enterocolitis. There were 231 episodes of enterocolitis with a death rate of 11.7%. Previous therapy with cytarabine and the presence of abdominal distention affected survival. An intestinal wall thickness of >or=10 mm in the ultrasonographic examination was associated with greater mortality. In multivariate analysis, age, gender, tumor type, degree of neutropenia, intestinal wall thickness, and number of intestinal segments were not statistically significant difference. In children and young adults with cancer and enterocolitis, the clinical findings of 4 or more symptoms and presence of abdominal distention were associated with higher risk of death. Use of cytarabine and an intestinal wall thickness of >or=10 mm were associated with a higher death rate.

[Prevalence of neutropenic enterocolitis in adults with severe neutropenia and associated mortality.]. / Prevalencia de enterocolitis neutropénica en adultos con neutropenia grave y mortalidad asociada.

BACKGROUND: Neutropenic enterocolitis (NEC) is characterized by inflammatory damage and necrosis of the intestinal mucosa, mainly of the terminal ileum and the cecum. It is more frequent in patients with leukemia and/or undergoing antineoplastic chemotherapy, and the main risk factor is neutropenia <1000/mm3. OBJECTIVE: To know the prevalence of NEC and the mortality associated with it in adults with hematologic conditions and neutropenia <1000/mm3. MATERIAL AND METHODS: All adult patients who were hospitalized for malignant hematologic conditions with neutropenia <1000/mm3 were enrolled in the study; those with neutropenia >1000/mm3 were excluded. The diagnosis of NEC was based on the clinical data and imaging tests (abdominal plain X-rays and CT scan). Demographics of all patients were collected, as well as the data related with the course and treatment of the underlying hematologic condition and the NEC. RESULTS: 117 patients were enrolled in the study; 75.2% of them with some type of acute leukemia. The diagnosis of NEC was made in 8 patients (6.8%). NEC occurred in 10.5% of the patients with acute myeloid leukemia and in 8.0% of those with acute lymphocytic leukemia. Three patients died, which resulted in a 37.5% mortality rate. No association was found between the severity of neutropenia and the onset of NEC or NEC-related mortality. CONCLUSIONS: The prevalence of NEC in patients with hematologic conditions admitted for severe neutropenia is 6.8% and the mortality rate associated with this complication is 37.5%.

[Neutropenic enterocolitis in adult patients with acute leukemia or stem cell transplant recipients: study of 7 cases]. / Enterocolitis neutropénica en adultos con leucemia aguda o receptores de un trasplante de progenitores hematopoyéticos: estudio de 7 casos.

BACKGROUND AND OBJECTIVE: Neutropenic enterocolitis (NE) is a complication arising in neutropenic patients with acute leukemia or solid tumours while treated with intensive chemotherapy. The optimal therapeutic procedures have not been well established. PATIENTS AND METHOD: Seven cases of NE diagnosed and treated in a tertiary hospital between 2000 and 2007 are described. Their clinico-biological characteristics, therapeutic procedures and evolution were analysed retrospectively. RESULTS: Five of the patients were males, their median age was 39 years. Acute myeloblastic leukemia was the most frequent diagnosis (5 cases). Two other patients had received an stem cell transplantation. Abdominal pain was present in all patients, diarrhoea in 6, and fever in 5. Microorganisms were isolated from blood cultures in 4 cases (Clostridium septicum, Escherichia coli, Pseudomonas aeruginosa and Aeromonas hydrophila). Abnormal mural thickening of the caecum was observed in the 6 cases in which a computed tomography scan could be performed. The median mural thickness at its maximum section was 11 mm (range: 8-16). All patients first received medical treatment with wide spectrum antibiotics and intestinal rest, and abdominal surgery was indicated in 6 cases after a median time from first symptom of 4 days (range: 0-12). NE was confirmed histologically in all 6 patients. Five patients required admission in Intensive Care Unit and 2 (29%) died as a result of NE. CONCLUSIONS: NE is a severe complication of patients with hematologic malignancies submitted to intensive chemotherapy or receiving stem cell transplantation. Abdominal computed tomography scan is the most valuable diagnostic tool. Prompt surgical intervention may improve the prognosis in patients with NE.

Systematic review of case reports concerning adults suffering from neutropenic enterocolitis.

INTRODUCTION: Neutropenic enterocolitis (NEC) is a well recognised clinical-pathological and life-threatening complication in patients suffering from several conditions, including solid and haematological malignancies or aplastic anaemia. OBJECTIVE: This review was aimed at evaluating overall NEC mortality rate, describing clinical diagnostic findings and therapeutical interventions reported in the literature and generating a hypothesis regarding factors influencing mortality and surgical intervention. MATERIALS AND METHODS: An advanced search was made in Medline, Embase, Lilacs and Google. Additional strategies included manual search of specific journals. Reports were considered if they described case definition, inclusion and exclusion criteria. RESULTS: 275 cases were selected; 109 were from individual data and 40 from grouped data. Comparing data between case reports and case series revealed no significant differences related to mortality, surgical intervention, sex or age. Higher mortality (chi2 = 7.51 p = 0.006) was found in women (50%) compared to men (28%). No significant difference was found between antibiotic combinations and mortality (chi(2) = 12.85 df 13 p = 0.45). Mortality (chi2 = 3.89 df 1, p = 0.049), surgical intervention (chi2 = 7.64 df 1, p = 0.006) and duration of diarrhoea (chi2 = 4.71 df 1, p = 0.043) were significantly different in 26.4% of individuals using antifungal agents; death occurred in 81% of patients! who did not receive such medication compared to 19% individuals reported as being treated with antifungal agents. CONCLUSION: The current evidence suggests that antifungal agents should be used early in patients suffering from NEC. However, this hypothesis must be evaluated in multi-centric, randomised controlled trials.

ED presentation of neutropenic enterocolitis in adult patients with acute leukemia.

The purpose of this study was to investigate the initial clinical features and subsequent outcomes in patients with adult leukemia with typhlitis or neutropenic enterocolitis. A retrospective review of 10 episodes of neutropenic enterocolitis in nine patients (age range, 21-71 years) with acute leukemia from March 1, 1990, through February 28, 2002, was conducted. In clinical presentations, fever appears in all patients, followed by abdominal pain or tenderness (90%) and diarrhea (60%), respectively. In particular, three cases were coincidentally diagnosed as leukemia before any chemotherapy. The most common diagnostic modality used for the diagnosis of neutropenic enterocolitis was computed tomography (CT) scan (seven episodes). Medical treatments, including broad-spectrum antibiotics, bowel rest, and total parenteral nutrition, were applied to seven patients. Laparotomy with bowel resection was performed on two patients with bowel necrosis and severe peritonitis. Of all nine cases, six were fatal as a result of sepsis, a common complication of neutropenic enterocolitis. As the incidence of neutropenic enterocolitis increases in patients with acute leukemia, EPs should be alert and make an early diagnosis of this rapidly deteriorated and life-threatening disease.