Recent advances in neutropenic enterocolitis: Insights into the role of gut microbiota.

Neutropenic enterocolitis (NE) is a life-threatening complication associated with neutropenia and the main cause of acute abdominal syndrome in neutropenic patients, especially those receiving intensive chemotherapy. This review aims to delineate actual insights into this clinical entity, to emphasize diagnostic and therapeutic management, and to generate hypotheses on pathophysiology to identify avenues for research. Diagnosis is based on the association of neutropenia, fever, abdominal symptoms, and radiologic bowel wall thickening. Main complications are sepsis, perforations, and gastrointestinal bleeding. Several mechanisms may be responsible for mucosal injury: treatment-induced necrosis of the intestinal specific infiltrates, spontaneous intramural hemorrhage, or microvascular thrombosis. The prevailing cause is the direct cytotoxicity of chemotherapy. However, the role of gut dysbiosis in NE remains to be fully elucidated. Therapeutic management includes early multidrug antibiotherapy, transfusion support, hematopoietic growth factor treatment, fluid resuscitation, correction of electrolytes imbalance, and bowel rest. Indication and timing for surgical management are still debated.

Neutropenic Enterocolitis: Case report and literature review.

Typhlitis, is also known as neutropenic enterocolitis, affects the cecum and distal ileum. It was frequently encountered in pediatric patients who were undergoing treatment for leukemia. Nonetheless, it can affect adult patients, regardless of the cause of the immunosuppression. We report the case of a 20-year-old patient who was receiving chemotherapy for Osteosarcoma, who had a 6-day history of nausea and vomiting, fever sensation, diarrhea, and diffuse abdominal pain. Physical examination was relevant for hemodynamic instability, a distended and tender abdomen predominantly in the right iliac fossa. The laboratory workup showed severe neutropenia, thrombocytopenia, and electrolyte disturbances. The image studies evidenced edema of the ascending colon and cecum. Treatment was started with vasopressor support, correction of electrolyte alterations, blood cell and platelet transfusion, G-CSF, hydration, broad spectrum antibiotic therapy, initially with adequate clinical and laboratory response. After a few days, he presented lower gastrointestinal bleeding which was treated by conservative management. In conclusion, typhlitis must be suspected in every patient developing neutropenia as a reaction to chemotherapy and who also presents gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and intense abdominal pain.

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.

Neutropenic colitis is a severe condition usually affecting immunocompromised patients. Its exact pathogenesis is not completely understood. The main elements in disease onset appear to be intestinal mucosal injury together with neutropenia and the weakened immune system of the afflicted patients. These initial conditions lead to intestinal edema, engorged vessels, and a disrupted mucosal surface, which becomes more vulnerable to bacterial intramural invasion. Chemotherapeutic agents can cause direct mucosal injury (mucositis) or can predispose to distension and necrosis, thereby altering intestinal motility. This article aims to review current concepts regarding neutropenic colitis' pathogenesis, diagnosis, and management.

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.

Management of acute colorectal diseases in febrile neutropenic patients / Tratamento das doenças colorretais agudas no paciente neutropênico febril

Patients with hematologic malignancies are susceptible to serious complications due to immunosuppression. Neutropenic-related infection is one of the major causes of morbidity and mortality in this group of diseases. Febrile neutropenia is a common complication of the hematologic neoplasm itself or chemotherapy, and has worse prognosis if prolonged (lasting more than 7 days) or severe (neutrophil count below 500 cells per µL). Among the usual sites of infection, we highlight the neutropenic enterocolitis and perianal infection as gastrointestinal complications of greater interest to the colorectal surgeon. Although most cases respond to conservative treatment, a portion of patients will need surgery for complete recovery. (AU)

Os pacientes com neoplasias hematológicas estão sujeitos a uma séria de complicações devido à imunossupressão. Infecção é umas das principais causas de morbidade e mortalidade nesse grupo de doenças. A neutropenia febril é uma complicação frequente da própria doença onco-hematológica ou da quimioterapia, e apresenta pior prognóstico se prolongada (duração acima de 7 dias) ou severa (contagem de neutrófilos inferior a 500 células por microlitro). Dentre os focos de infecção mais comuns destacamos a enterocolite neutropênica e a infecção perianal como complicações de maior interesse para o cirurgião colorretal. Apesar de grande parte dos casos apresentar boa resposta ao tratamento conservador, uma parcela de pacientes necessitará de cirurgia para completa recuperação.

[Neutropenic enterocolitis after autologous peripheral blood stem cell transplantation in non-Hodgkin's lymphoma - a case report].

Here we report a case of a 59-year-old man who developed neutropenic enterocolitis(NE)after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma in his second complete remission.Four days after transplantation, the patient suffered from diarrhea, abdominal pain, fever, and paralytic ileus.Abdominal computerized tomography scan revealed bowel wall thickening consistent with NE.Owing to his poor performance status, only medical management, including antibiotics and bowel rest, was administered, and the patient died 18 days after transplantation.Although NE after autologous peripheral blood stem cell transplantation is a relatively rare complication, it is important to be aware that this condition can occur as one of the early complications in stem cell transplantation.

Enterocolitis neutropénica: reporte de un caso en un paciente con SIDA / Neutropenic enterocolitis report of an AIDÆs patient case

La enterocolitis neutropénica es una enteropatía necrotizante en pacientes con neutropenia severa relacionada con tratamientos quimioterápicos. Se presenta el caso de un paciente HIV positivo que desarrolló una enterocolitis neutropénica en el contexto de un tratamiento quimioterápico por Linfoma de Hodgkin. Presentaba leucopenia 400 leucocitos/mm3 y cuadro clínico compatible. La ecografía mostró engrosamiento de las paredes del ciego, del colon ascendente, y del íleon terminal. No hubo aislamiento microbiológico. Recibió tratamiento empírico con cefepime, vancomicina, y metronidazol con buena respuesta clínica y ecográfica. En el paciente con SIDA, diversas entidades pueden presentarse con dolor abdominal y engrosamiento de las paredes intestinales, como por ejemplo Citomegalovirus, Clostridium difficile, tuberculosis, histoplasmosis y linfomas, entre otras. El avance tecnológico, y las características ponderales de estos pacientes (bajo peso) permiten utilizar transductores de alta frecuencia para evaluar el tracto gastrointestinal y detectar mínimas lesiones en otros órganos abdominales, aportando al diagnóstico diferencial.(AU)

Enterocolitis neutropénica: reporte de un caso en un paciente con SIDA / Neutropenic enterocolitis report of an AID’s patient case

La enterocolitis neutropénica es una enteropatía necrotizante en pacientes con neutropenia severa relacionada con tratamientos quimioterápicos. Se presenta el caso de un paciente HIV positivo que desarrolló una enterocolitis neutropénica en el contexto de un tratamiento quimioterápico por Linfoma de Hodgkin. Presentaba leucopenia 400 leucocitos/mm3 y cuadro clínico compatible. La ecografía mostró engrosamiento de las paredes del ciego, del colon ascendente, y del íleon terminal. No hubo aislamiento microbiológico. Recibió tratamiento empírico con cefepime, vancomicina, y metronidazol con buena respuesta clínica y ecográfica. En el paciente con SIDA, diversas entidades pueden presentarse con dolor abdominal y engrosamiento de las paredes intestinales, como por ejemplo Citomegalovirus, Clostridium difficile, tuberculosis, histoplasmosis y linfomas, entre otras. El avance tecnológico, y las características ponderales de estos pacientes (bajo peso) permiten utilizar transductores de alta frecuencia para evaluar el tracto gastrointestinal y detectar mínimas lesiones en otros órganos abdominales, aportando al diagnóstico diferencial.

Neutropenic enterocolitis after high-dose chemotherapy and autologous stem cell transplantation: incidence, risk factors, and outcome.

BACKGROUND: Neutropenic enterocolitis (NE) is a life-threatening complication occurring after intensive chemotherapy; however, no data are available on NE development after hematopoietic stem cell transplantation (SCT). The aim of this study was to determine the incidence, risk factors, and outcome of NE after high-dose chemotherapy and autologous SCT (autoSCT). METHODS: A total of 297 adult patients who qualified for autoSCT with non-Hodgkin's lymphoma (NHL), Hodgkin's disease, multiple myeloma, and acute myeloid leukemia were analyzed. Patients were conditioned with carmustine, etoposide, cytarabine, melphalan (BEAM); melphalan alone; or busulfan and cyclophosphamide (BuCy2), and transplanted with peripheral blood or bone marrow CD34(+) cells. Diagnosis of NE was established in case of neutropenic fever, abdominal pain or diarrhea, and bowel wall thickening >4 mm on abdominal sonography. RESULTS: Neutropenic infections occurred in 262 patients (88%). NE was diagnosed in 32 patients (12%), a median +3 (1-5) days after SCT. Bloodstream infections were present in 18 patients, with gram-negative bacteria in 11 patients. All patients were treated conservatively with carbapenems and total parenteral nutrition with bowel rest. The course of disease was complicated by ileus or septic shock in 9 patients, and was fatal for 3 (9.6%) patients. In univariate analysis, the initial diagnosis of NHL (P = 0.017) and conditioning with BEAM (P = 0.043) had prognostic value. In multivariate analysis, only initial diagnosis of NHL (P = 0.017) had prognostic significance. CONCLUSIONS: NE is a rare but severe complication in patients undergoing autoSCT. Gram-negative bacteria remain the main causative pathogen. Abdominal sonography allows early diagnosis and treatment, effective in most of patients without surgery. In our analysis, NE was seen more often in NHL patients treated with a BEAM regimen.

Recurrent neutropenic enterocolitis in a pediatric patient.

Management of an 8-year-old boy with Hodgkin lymphoma is presented. The patient had several recurrences of neutropenic enterocolitis and eventually required ileocecectomy. A review of the literature on this difficult problem affecting pediatric oncology patients is presented.

Management of neutropenic enterocolitis in children with cancer.

AIM: To describe the symptoms, clinical management and short-term outcome in a series of paediatric oncology patients with severe typhlitis following conservative treatment. METHODS: Twelve episodes of severe typhlitis in 11 children with cancer treated at the paediatric oncology ward at Queen Silvias Children's Hospital between 1995 and 2006 were analysed retrospectively. Data on symptoms, radiological findings, laboratory status and treatment as well as outcome were collected and analysed. RESULTS: In all episodes, the classical signs of neutropenia, fever, abdominal pain and thickening of the bowel wall were present. All were successfully treated with bowel rest, broadspectrum antibiotics and supportive care. After recovery from typhlitis, three patients needed surgical intervention because of complications. CONCLUSION: A high clinical suspicion combined with radiological imaging aids early diagnosis. Predisposing factors for developing typhlitis were haematologic malignancy and treatment with chemotherapy within 3 weeks of onset. Supportive care, bowel rest including parenteral nutrition, correction of cytopenias and aggressive antimicrobial treatment is essential. Measurements of C-reactive protein in blood may be of benefit when assessing the clinical course.

Gastrointestinal manifestations of leukemia.

Gastrointestinal (GI) manifestations of leukemia occur in up to 25% of patients at autopsy, generally during relapse. Its presence varies with the type of leukemia and has been decreasing over time due to improved chemotherapy. Gross leukemic lesions are most common in the stomach, ileum, and proximal colon. Leukemia in the esophagus and stomach includes hemorrhagic lesions from petechiae to ulcers, leukemic infiltrates, pseudomembranous esophagitis, and fungal esophagitis. Lesions in the small and large bowel are usually hemorrhagic or infiltrative. Infiltration of lymphoreticular organs, mainly spleen, liver, and lymph nodes, is more prominent in chronic than acute leukemia. Neutropenic enterocolitis, a necrotizing process involving the cecum, ascending colon, and terminal ileum, is increasing in incidence due to greater intensity of chemotherapy. Distension of bowel leads to mucosal breaches, permitting entry of organisms that grow profusely in the absence of neutrophils. Ischemic necrosis follows, leading to perforation and/or peritonitis. Patients present with fever, abdominal pain, diarrhea, nausea, vomiting, abdominal distension and tenderness. Ultrasound and computed tomography scans show thickening of the bowel wall. Treatment is supportive with surgery for necrosis and perforation. The main GI causes of death in leukemia are hemorrhage, infection, and necrotizing enterocolitis.

[Treatment of neutropenic enterocolitis]. / Behandling av nøytropen enterokolitt.

BACKGROUND: Neutropenic enterocolitis is a life-threatening complication that usually occurs in connection with chemotherapy for acute leukemias. Our experience with diagnosis and treatment of these patients is presented. MATERIAL AND METHODS: Medical records from patients treated for neutropenic enterocolitis at Ullevaal University Hospital in the period 2000-2008 were retrospectively reviewed. RESULTS: 16 patients with median age 33 years were treated for neutropenic enterocolitis. Induction chemotherapy was given for acute myelogenic (n = 9) or lymphatic (n = 4) leukemia, myelomatosis (n = 2) or lymphoma (n = 1). The patients developed aplasia five days (median) after start of chemotherapy. All patients were first treated conservatively with broad-spectrum antibiotics, fluids and electrolyte supplementation; nine of them recovered without complications. Four underwent surgery for perforation or ileus and these had the longest period with aplasia (median 31 days). Surgery for perforation is mainly limited resection and construction of ileostomy reservoirs (one or two). Three patients died. These were only treated conservatively; aplasia occurred quicker in these patients (after median two days) and they had the largest number of affected bowel segments (median nine). INTERPRETATION: Neutropenic enterocolitis is a heterogeneous condition and the treatment is mainly conservative. Surgical intervention is mandatory in patients with free intraabdominal air, ileus and intractable intestinal bleeding. The prognosis seems to worsen when aplasia develops after a short time and when there is a large number of affected bowel segments.

Gastrointestinal bleeding in the cancer patient.

Gastrointestinal bleeding is a common occurrence in patients with cancer and is a frequent indicator of a gastrointestinal malignancy. Rapid evaluation and treatment is key for the hemodynamically unstable patient. Endoscopy remains the cornerstone of diagnosis and management for cancer patients with gastrointestinal bleeding. The emergency physician should also be aware of other diagnostic and treatment modalities that may be needed to take care of these patients.

Neutropenic enterocolitis.

Neutropenic enterocolitis, also known as typhlitis or ileocecal syndrome, is a rare but important complication of neutropenia associated with malignancy. It occurs as a result of chemotherapeutic damage to the intestinal mucosa in the context of an absolute neutropenia, and can rapidly progress to intestinal perforation, multisystem organ failure, and sepsis. Presenting signs and symptoms may include fever, abdominal pain, nausea, vomiting, and diarrhea. Rapid identification by emergency physicians and timely, aggressive medical and/or surgical intervention are the cornerstones of survival for these patients.