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.

Neutropenic enterocolitis in patients with FLT3 mutated acute myeloid leukemia undergoing induction chemotherapy with midostaurin.

Neutropenic enterocolitis mostly affects patients with acute myeloid leukemia (AML) who get treated with intensive chemotherapy which is associated with prolonged neutropenia; its pathogenesis is not well understood and the main factors in this life-threatening condition appear to be neutropenia, mucosal injury and a weakened immune system as a consequence of intensive chemotherapeutic agents. Midostaurin in combination with chemotherapy became the standard of care for FLT3 mutant AML since its approval by the United States Food and Drug Administration (FDA) in April 2017. Anecdotally in our institution, we noticed the common occurrence of neutropenic colitis in three out of three patients who were treated with midostaurin as part of induction chemotherapy for AML.

Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia.

Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset.

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.

Diagnosis and outcome of neutropenic enterocolitis: experience in a single tertiary pediatric surgical center in China.

BACKGROUND/PURPOSE: Neutropenic enterocolitis (NE) is clinically defined by the triad of neutropenia, abdominal pain and fever. This retrospective study is to review 24 cases of NE in a single Chinese tertiary center, to elucidate clinical feature, treatments and outcome for this dangerous gastrointestinal complication of neutropenia. PATIENTS AND METHODS: The medical records of pediatric patients who were diagnosed with neutropenic enterocolitis from 2000 to 2009 were reviewed. RESULTS: Of 24 cases, the ratio of male to female was 2:1, the mean age was 7.2 years. There were eight cases of acute lymphocytic leukemia, eight cases of acute non-lymphocytic leukemia, four cases of non-Hodgkin's lymphoma, one case of severe aplastic anemia, one case of neuroblastoma and two cases of simple neutropenia without underlying cause. The hematologic malignancy was significantly associated with the occurrence of NE (OR = 19.4). Seventeen cases developed NE during anticancer chemotherapy (chemo group), four cases presented with leukemia and one case presented with aplastic anemia before the initiation of chemotherapy and their presenting event leading to diagnosis. Two cases simply presented with NE without definitive reasons (no chemo group). All the patients had the typical clinical presentation, six cases had disseminated peritonitis, toxic shock, and assisted ventilations were necessary in three of these six cases. CT or ultrasound demonstrated bowel wall thickness, paucity of air in the cecum and/or right colon, pneumatosis or pneumoperitoneum. There was no difference in the nadir neutrophil count in patients, who received chemotherapy versus those who did not (P = 0.001), but the recovering time from NE in chemo group (9.3 ± 1.9) was shorter than non-chemo group (10.7 ± 5.3, P = 0.034). Sixteen (88.8%) cases have been successfully managed medically, using aggressive hemodynamic support, bowel rest, and broad-spectrum antibiotic therapy with surgical intervention reversed only for the more severe six cases (25%). Two cases died. CONCLUSION: NE is a life-threatening gastrointestinal complication of neutropenia. Physicians might remain vigilant and consider NE in any neutropenic patient rather than only in oncologic patients. It has typical clinical presentation and CT can provide clear delineation for diagnosis. Early recognition and progressed management have reduced mortality. Most children with NE may be treated without surgery with favorable outcome.

[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%.

Enterocolitis neutropénica en el niño con cáncer: nuestra casuistica y revisión de la literatura / Neutropenic enterocolitis in the child with cancer: our casuistics and review of the literature

Introducción: La enterocolitis neutropénica o tiflitis es una alteración de la región ileocecal con ausencia de infiltrado inflamatorio o tumoral y diferentes grados de afectación de la pared intestinal, típica de pacientes con tumores hematológicos afectos de neutropenia grave o prolongada secundaria a la quimioterapia. Objetivos: Revisar los casos de enterocolitis neutropénica diagnosticados en niños con cáncer del Hospital Universitario de Canarias (HUC) durante los últimos 6 años y medio y realizar una revisión actualizada de la literatura sobre el tema. Pacientes y métodos: Revisión retrospectiva de historias clínicas de los niños que padecieron tiflitis. Se analizaron las siguientes variables: edad, sexo, tipo de neoplasia, protocolo de quimioterapia, y al diagnóstico de la tiflitis; número de días desde el último ciclo de quimioterapia (quimioterápicos recibidos), días de neutropenia, síntomas, método diagnóstico (grosor máximo de la pared intestinal), tratamiento y evolución. Resultados: De los 41 casos de tumores malignos tratados con quimioterapia, el 7,3% (n = 3) presentaron uno o más episodios de enterocolitis neutropénica (todos afectos de leucemia aguda; dos mieloblásticas y una linfoblástica).Todos eran varones, con una edad media de 11 años y medio. La clínica predominante fue dolor abdominal en el contexto de una neutropenia febril postquimioterapia. La confirmación diagnóstica se realizó mediante ecografía abdominal en dos casos y tomografía computarizada (TC) en los otros dos (media del grosor intestinal máximo: 11,5 mm). El tratamiento instaurado en todos los casos fue conservador, logrando una recuperación clínico-radiológica en el 100% de los pacientes. Conclusión: En todo niño con cáncer en tratamiento quimioterápico, especialmente en afectos de leucemia aguda, con neutropenia febril que además refiera dolor abdominal persistente, vómitos y/o diarrea, se debe sospechar una enterocolitis neutropénica, solicitar una ecografía y/o una TC abdominal urgente para confirmarla, e instaurar lo antes posible el tratamiento recomendado, logrando, así, una reducción significativa de la morbimortalidad que conlleva esta grave complicación (AU)

Background: Neutropenic enterocolitis or thyphlitis is a lesion of the ileocecal arca with lack of inflammatory or tumoral infiltration and different degrees of affection on the bowel wall. It is typical in patients with hematologic malignancies with prolonged or severe neutropema alter intensive chemotherapy. Objectives: Revise all neutropenic enterocolitis diagnosed at Hospital Universitario de Canarias (HUC) in the last six and a half years in children with cancer, and carry out an up today literature review. Patients and methods: Retrospective review of the medical histories to the children who had thyplitis. We analyzed the following data: age, sex, cancer type and chemotherapy protocol, and when thyplitis was diagnosed; days from the last cytotoxic chemotherapy cycle (anticancer drugs used), days of neutropenia, symptoms, diagnosis method used (maximum thickness on the bowel wall), treatment and evolution. Results: Forty one cases of malignant neoplasms were treated with chemotherapy and 7,3% (n = 3) had one or more episodes of neutropenic enterocolitis (all of them with acute leukemia, two myelogenus and one lymphoblastic). All of them were male, with an average age of 11 years and 6 months. The symptom more frequently seen was abdominal pain in a child with a febrile neutropenia alter intensive chemotherapy. The diagnosis confirmation was with abdominal ultrasonography (US) in two cases, and computed tomography (CT) in the other two ones (average thickness on the bowel wall was 11,5 mm). All the children recovered without problems with medical treatment. Conclusion: Any child with cancer treated with chemotherapy, especially with acute leukaemia, and febrile neutropenia associated with persistent abdominal pain, vomiting and/or diarrhea, we must suspect neutropenic enterocolitis, ask for an urgent abdominal US and/or CT to confirm the diagnosis, and start as far as possible the recommended treatment, achieving as that a significative morbimortality reduction so common in this severe complication (AU)

Sonographic signs of neutropenic enterocolitis.

AIM: To investigate the sonographic features at time of diagnosis and follow-up in patients with neutropenic enterocolitis. METHODS: The sonographic findings in 14 patients with neutropenic enterocolitis were described and evaluated regarding symptoms and clinical outcome. RESULTS: In all patients with neutropenic enterocolitis, the ileocoecal region was involved with wall thickening >10 mm. A transmural inflammatory pattern, hypervascularity of the thickened bowel wall and free abdominal fluid were the common findings. The sonographically revealed thickness of the bowel wall was associated with lethal outcome (P<0.03). In the 11 surviving patients,the improvement of clinical symptoms was accompanied by progressive reduction of intestinal wall thickness. CONCLUSION: High-end sonography of the bowel is a helpful tool for diagnosis,assessment of prognosis and follow-up of patients with neutropenic enterocolitis.The ultrasonographically revealed bowel thickness reflects the severity and the course of the disease, and seems to be predictive for the clinical outcome.

Systematic review of case reports concerning adults suffering from neutropenic enterocolitis

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Introduction. Neutropenic enterocolitis (NEC) is awell recognised clinical-pathological and life-threateningcomplication in patients suffering from severalconditions, including solid and haematologicalmalignancies or aplastic anaemia.Objective. This review was aimed at evaluatingoverall NEC mortality rate, describing clinical diagnosticfindings and therapeutical interventions reportedin the literature and generating a hypothesisregarding factors influencing mortality and surgicalintervention.Materials and methods. An advanced search wasmade in Medline, Embase, Lilacs and Google. Additionalstrategies included manual search of specificjournals. Reports were considered if they describedcase definition, inclusion and exclusion criteria.Results. 275 cases were selected; 109 were from individualdata and 40 from grouped data. Comparingdata between case reports and case series revealedno significant differences related to mortality, surgicalintervention, sex or age. Higher mortality (÷2 =7.51 p = 0.006) was found in women (50%) comparedto men (28%). No significant difference wasfound between antibiotic combinations and mortality(÷2 = 12.85 df 13 p = 0.45).Mortality (÷2 = 3.89 df 1, p = 0.049), surgical intervention(÷2 = 7.64 df 1, p = 0.006) and duration of diarrhoea(÷2 = 4.71 df 1, p = 0.043) were significantly differentin 26.4% of individuals using antifungal agents;death occurred in 81% of patients! who did not receivesuch medication compared to 19% individualsreported as being treated with antifungal agents.Conclusion. The current evidence suggests that antifungalagents should be used early in patients sufferingfrom NEC. However, this hypothesis must beevaluated in multi-centric, randomised controlledtrials

Neutropenic enterocolitis.

PURPOSE OF REVIEW: This review will cover the recent literature pertaining to the pathogenesis, diagnosis, and management of patients with neutropenic enterocolitis. RECENT FINDINGS: Neutropenic enterocolitis, also referred to as typhlitis, is a life-threatening gastrointestinal complication of chemotherapy, most often associated with leukemia or lymphoma. Recently, a larger number of reports have been published of individuals presenting with this syndrome after being treated with newer chemotherapeutic agents for solid tumors such as non-small cell lung, ovarian, and peritoneal cancer, as well as following autologous stem cell transplantation. Recent studies have also better characterized computed tomographic and ultrasonographic features of this entity that can help differentiate neutropenic enterocolitis from other gastrointestinal complications. A newly published systematic analysis of the literature, which included 145 articles, defines appropriate diagnostic criteria and treatment recommendations. SUMMARY: Neutropenic enterocolitis is a serious, potentially lethal complication of anticancer therapy. The studies discussed in this review will help the practitioner make an appropriate, early diagnosis and implement a therapeutic program that would improve the outcome of these patients.

[Clinical and microbiological characteristics of neutropenic enterocolitis in adults with blood cancer in the National Cancer Institute of Bogota D.C. (Colombia)]. / Características clínicas y microbiológicas de la colitis neutropénica en adultos con neoplasias hematológicas del Instituto Nacional de Cancerología de Bogotá D.C. (Colombia).

OBJECTIVES: This study describes the clinical, epidemiological and microbiological characteristics of adult patients with blood cancer and neutropenic enterocolitis treated in the Instituto Nacional de Cancerologia (National Cancer Institute) in Bogota, Colombia. METHODS: The clinical histories of 692 adult patients hospitalized in the Instituto Nacional de Cancerologia between 1997 and 2001 with a diagnosis of leukemia or lymphoma were reviewed. Thirty-five of these cases met the criteria for probable or confirmed neutropenic enterocolitis. RESULTS: Twenty-two cases were confirmed and the remaining 13 were probable neutropenic enterocolitis. All patients were undergoing chemotherapy and all presented watery diarrhea and abdominal pain. In addition, 17% had melena and 25% severe vomiting. Eight of 26 stool cultures (30%) and 17 of 32 (58%) blood cultures were positive for potentially pathogenic microorganisms, particularly gram-negative bacilli. Three patients with probable neutropenic enterocolitis and ten confirmed cases died (37%); mortality was higher among patients who were managed surgically. CONCLUSION: Neutropenic colitis presents as a multifactorial syndrome in patients with blood cancer undergoing cytotoxic therapy with agents such as cytosine arabinoside, etoposide, vincristine, cyclophosphamide and corticoids. This highly lethal complication is partly due to infections caused by gram-negative bacilli.

Pseudomembranous and neutropenic enterocolitis in pediatric oncology patients.

Neutropenic enterocolitis in oncological patients represents a wide spectrum of clinicopathological pictures each with its own entity. Early diagnosis of enterocolitis can lead to improved supportive care and therefore better outcome. We present two cases--patient A, a child with pseudomembranous colitis caused by Clostridium difficile, and patient B, a child with neutropenic enterocolitis, where no organism was found. By allowing an insight into the pathology, immunology and culture results, we demonstrated that early diagnosis leads to improved management and therefore improved outcome.