• Neutropenic enterocolitis
• Pediatric cancer
• Primary anastomosis
• Side-to-side isoperistaltic anastomosis
• Stoma
• Typhlitis

• Electronic Health Records
• Humans
• Software
• Neoplasms/epidemiology
• Child
• Data Curation/methods
• Medical Oncology/methods

• U24 CA055727 NCI NIH HHS

• Complications
• Hematologic
• Intestinal barrier
• Oncologic
• Pathogenesis

• Adolescent
• Adult
• Algorithms
• Anti-Bacterial Agents
• Child
• Child, Preschool
• Electronic Health Records
• Humans
• Infant
• Infant, Newborn
• Predictive Value of Tests
• Typhlitis
• Young Adult

• U10 CA180886 NCI NIH HHS
• U10 CA180899 NCI NIH HHS

Hematolymphoid malignancies are common neoplasms in childhood. The involvement of the gastrointestinal (GI) tract, liver, biliary system, pancreas, and peritoneum are closely interlinked and commonly encountered. In leukemias, lymphomas, and Langerhans cell histiocytosis (LCH), the manifestations result from infiltration, compression, overwhelmed immune system, and chemotherapy-induced drug toxicities. In acute leukemias, major manifestations are infiltrative hepatitis, drug induced gastritis, neutropenic typhlitis and chemotherapy related pancreatitis. Chronic leukemias are rare. Additional presentation in lymphomas is cholestasis due to infiltration or biliary obstruction by lymph nodal masses. Presence of ascites needs a thorough workup for the underlying pathophysiology that may modify the therapy and affect the outcome. Uncommon hematolymphoid malignancies are primary hepatic, hepatosplenic, and GI lymphomas which have strict definitions. In advanced diseases with extensive spread, it may be impossible to distinguish these diseases from the primary site of origin. LCH produces biliary strictures that mimic as sclerosing cholangitis. Liver infiltration is associated with poor liver recovery even after chemotherapy. The heterogeneity of gut and liver manifestations in hematolymphoid malignancies has a clinical impact on their management. Though chemotherapy is the mainstay of therapy in all hematolymphoid malignancies, debulking surgery and radiotherapy have an adjuvant role in specific clinical scenarios. Rare situations presenting as liver failure or end-stage liver disease require liver transplantation. At their initial presentation to a primary care physician, given the ambiguity in clinical manifestations and the prognostic difference with time-bound management, it is vital to recognize them early for optimal outcomes. Pooled data from robust registries across the world is required for better understanding of these complications.

• Leukemia
• Lymphoma
• Langerhans cell histiocytosis
• Gastrointestinal
• Hepatobiliary

• Neutropenic enterocolitis
• Shock Index Pediatric Age-Adjusted
• Typhlitis

• Abscess
• Neutropenia
• Pneumoperitoneum

• Appendicitis
• Emergencies
• Humans
• Immunocompromised Host
• Neutropenia/etiology
• Retrospective Studies

• T32 CA009599 NCI NIH HHS

• Appendicitis
• chemotherapy
• neutropaenia
• neutropaenic enterocolitis
• typhlitis

Acute appendicitis is a rare gastrointestinal complication of anti-cancer chemotherapy and hematopoietic stem cell transplantation. Among a cohort of 2341 hemato-oncologic patients at a pediatric tertiary care cancer center, we identified 21 patients (0.9%) with 23 episodes of acute appendicitis, based on pathological imaging of the appendix and clinical findings. Median age at diagnosis was 10.21 years. Types of underlying disease included acute leukemias (n = 15), solid tumors (n = 4), and aplastic anemia (n = 2). Clinical symptoms seen in > 1 case were recorded for all 23 episodes as follows: abdominal pain, n = 22; abdominal tenderness, n = 4; fever, n = 7; nausea, n = 2; emesis; n = 2; diarrhea, n = 5; and constipation, n = 2. Median leukocyte count at diagnosis was 0.5 × 10⁹/L, with a median of 0.1 × 10⁹/L for the absolute neutrophil count (ANC). All patients received broad-spectrum antibiotics and 18/23 (78%) patients underwent uneventful appendectomy after a median of 5 days and with a median ANC of 0.7 × 10⁹/L. Median duration until continuation of chemotherapy was 17 days for the 20 cases of appendicitis occurring during the patients’ disease course. Overall, 5/21 (19%) patients died including one related to the appendicitis itself which progressed to a typhlitis and was due to a fungal infection. The other fatalities were transplant- (n = 2) and leukemia-related (n = 2). Acute appendicitis is a rare and usually not life-threatening event in pediatric hemato-oncologic patients, which, if managed by prompt administration of broad-spectrum antibiotics (and antimycotics), can be safely followed by an elective (delayed) appendectomy, even before complete recovery of the neutrophils is achieved.

• Acute leukemia
• Induction chemotherapy
• Intestinal complication
• Neutropenic enterocolitis
• Pediatric oncology

• Typhlitis
• enterocolitis
• epidemiology
• febrile neutropenia
• treatment

• Bacteria, Anaerobic/classification
• Bacteria, Anaerobic/isolation & purification
• Bacterial Infections/diagnosis
• Bacterial Infections/drug therapy
• Bacterial Infections/epidemiology
• Bacterial Infections/pathology
• Bacteriological Techniques/methods
• Disease Susceptibility
• Humans
• Immunocompromised Host

AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.

METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: “gastrointestinal infection AND antineoplastic chemotherapy AND children”, “gastrointestinal infection AND oncology AND children”, “liver infection AND antineoplastic chemotherapy AND children”, “liver abscess AND chemotherapy AND child”, “neutropenic enterocolitis AND chemotherapy AND children”, “thyphlitis AND chemotherapy AND children”, “infectious diarrhea AND children AND oncology”, “abdominal pain AND infection AND children AND oncology”, “perianal sepsis AND children AND oncology”, “colonic pseudo-obstruction AND oncology AND child AND chemotherapy”, “microflora AND children AND malignancy”, “microbiota AND children AND malignancy”, “fungal flora AND children AND malignancy”. We also analysed evidence from several articles and book references.

RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infection in those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available.

CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented (also by further studies on new biomarkers) for a prompt and individualized therapy.

• Gastrointestinal tract
• Liver
• Microflora
• Infection
• Oncology
• Chemotherapy
• Children

• Adolescent
• Antineoplastic Agents/adverse effects
• Child
• Colonic Pseudo-Obstruction/etiology
• Colonic Pseudo-Obstruction/immunology
• Diarrhea/etiology
• Diarrhea/immunology
• Dysbiosis/etiology
• Dysbiosis/immunology
• Enterocolitis, Neutropenic/etiology
• Enterocolitis, Neutropenic/immunology
• Gastroenteritis/etiology
• Gastroenteritis/immunology
• Gastrointestinal Microbiome
• Hepatitis, Viral, Human/etiology
• Hepatitis, Viral, Human/immunology
• Humans
• Immunocompromised Host
• Liver Abscess/etiology
• Liver Abscess/immunology
• Liver Diseases/etiology
• Liver Diseases/immunology
• Mycoses/etiology
• Mycoses/immunology
• Neoplasms/drug therapy
• Sepsis/etiology
• Sepsis/immunology

• Acute appendicitis
• Acute leukemia
• Decitabine
• Management