[Neutropenic enterocolitis in the pediatric cancer patient]. / Enterocolitis neutropénica en el paciente oncológico pediátrico.

Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.

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.

Enterocolitis neutropénica en el paciente oncológico pediátrico / Neutropenic enterocolitis in the pediatric cancer patient

Resumen La enterocolitis neutropénica (ECN) es una enfermedad heterogénea de foco digestivo, pero afectación sistémica, que corresponde a una condición clínica grave que amenaza la vida de pacientes inmunocomprometidos, particularmente oncológicos pediátricos. De patogenia aún poco definida y aunque de causa multifactorial, la ECN se asocia a los efectos citotóxicos de la quimioterapia empleada y se caracteriza por la triada clásica que incluye fiebre, neutropenia y dolor abdominal, donde la principal injuria se localiza en la mucosa intestinal, provocando su alteración como barrera y facilitando la invasión bacteriana intramural. La ECN constituye un reto diagnóstico para el equipo tratante, que requiere ser oportuno y contar con apoyo de un óptimo laboratorio general e imagenológico, para iniciar un completo manejo multidisciplinario en unidades y centros de alta complejidad. Se presenta una revisión actualizada del tema incorporando aspectos epidemiológicos, factores de riesgo, elementos de apoyo diagnóstico, consideraciones terapéuticas y medidas de prevención a fin de aportar en el conocimiento de esta patología, y reducir morbimortalidad en estos pacientes.

Abstract Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.

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.

Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature.

BACKGROUND: Bacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis. CASE PRESENTATION: We report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention. CONCLUSION: Mucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.

Neutropaenic enterocolitis: A medical/surgical oncological dilemma.

Neutropaenic enterocolitis (NE) is a life-threatening condition characterised by an inflammation of the colon and/or the small bowel in the background of chemotherapy-induced neutropaenia. A 16-year-old girl with acute myeloblastic leukaemia (AML) developed fever, right-sided abdominal pain and tenderness with severe neutropaenia. Initial ultrasound findings suggested acute appendicitis for which she had surgery. She developed recurrent symptoms 3 weeks later. Abdominal computed tomography (CT) scan showed features of NE, but she succumbed to the illness. Another 17-year-old boy with AML developed fever and severe right-sided lower abdominal pain and tenderness, following completion of induction chemotherapy. He was neutropaenic and abdominal CT was typical of NE. He was managed nonoperatively and symptoms resolved. The diagnosis of NE can be a dilemma. A high index of suspicion is needed to avoid a misdiagnosis of acute appendicitis.

Neutropenic Enterocolitis and Sepsis: Towards the Definition of a Pathologic Profile.

Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.

Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis.

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.

Neutropenic enterocolitis (typhlitis) in a pediatric renal transplant patient. A case report and review of the literature.

NE (typhlitis) is a potentially life-threatening disease process characterized by bowel wall edema, ulceration, and hemorrhage in an immunosuppressed patient. We report a 15-year-old boy status post deceased donor renal transplantation who presented with fever, abdominal pain, and diarrhea. Laboratory studies revealed neutropenia 5 days prior to admission, and abdominal computed tomography revealed bowel wall thickening in the cecum consistent with NE. He was treated with piperacillin-tazobactam and gentamicin and recovered. To our knowledge, this is the first report of a case of NE in a pediatric kidney transplant recipient.

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.

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.

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.

[19-year old male with Crohn's disease complicated by retroperitoneal abscesses and coxarthritis dexter]. / Choroba Lesniowskiego-Crohna u 19-letniego mezczyzny powiklana ropniami zaotrzewnowymi i zapaleniem stawu biodrowego prawego.

The article presents the case of a patient with Crohn's disease in whom an infection of the complex ileo-caecal be spread into the retroperitoneal space and the right hip.

Infection of the right iliac fossa.

Febrile pain in the right iliac fossa is one of the most common reasons for consulting at an emergency service. Within this framework, the main diagnosis that is considered is appendicitis, the main complication of which is perforation. However, a certain number of other conditions can be responsible for this clinical picture, primarily including digestive tract and mesentery disorders including mesenteric lymphadenitis, Crohn's disease, infectious enterocolitis, small intestine or colonic diverticulitis, ischaemic colitis or cancer of the caecum. This article illustrates the imaging semiology of the various right colonic, iliac, mesenteric and appendicular conditions that could potentially cause an infection of the right iliac fossa. It specifies the indications of ultrasound and CT scans, respectively, which depend on the age of the patient and the clinical signs and symptoms. Though the CT scan is commonly used in abdominal emergencies in general, and particularly in clinical pictures of infection of the right iliac fossa, ultrasound remains recommended as first line imaging when confronted with suspected appendicitis or lymphadenitis in a young subject or in the monitoring of Crohn's disease.

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.