Sema Vural

Brain metastasis in pediatric extracranial solid tumors: survey and literature review

Objectives: Brain is a rare site of metastasis in most extracranial pediatric solid tumors. The aim of this study is to investigate the incidence, treatment, prognosis of brain metastasis in extracranial pediatric malignant tumors in a single institution and to review the literature.Methods: From September 1989 to December 2002, 1100 children ≤16 years of age with extracranial solid tumors including lymphomas were diagnosed and treated in the Division of Pediatric Oncology, Oncology Institute, Istanbul University. Patients with parenchymal metastases in the brain were assessed.Results: Sixteen (10 female, 6 male) of 1100 patients (1.45%) with extracranial solid tumors developed brain metastases. The median age of the patients was 10.5 (1–16) years. The diagnosis was sarcomas in 12 patients: 5 osteosarcomas, 4 Ewing’s sarcoma family tumors, 1 rhabdomyosarcoma, 1 clear cell sarcoma of the soft tissue, 1 alveolar soft part sarcoma. Two patients had Wilms’ tumor and two had germ cell tumors. Four patients (25%) had brain metastasis at diagnosis. Twelve (75%) developed brain metastasis during therapy or relapse at a median duration of 16 (1–70) months from initial diagnosis. All patients had metastases to various sites, mostly lung, at the time the brain metastases were detected. Treatment included surgery, followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 1, S and RT in 1, S in 1, RT and CT in 6, RT in 1, CT in 1 and no treatment in 5. Only one patient with alveolar soft part sarcoma is alive with disease 20 months from diagnosis of brain metastasis. All other patients died at a median time of 2 months (2 days–6 months) from the time of brain metastasis.Conclusions: Children with metastatic cancer who develop headaches or any other neurologic symptom should be investigated for possible brain metastasis. Although, the outcome for these patients is dismal in this series and in the literature; reports of long term survival in a few cases with Wilms’ tumor, osteosarcoma and alveolar soft part sarcoma who had isolated brain metastasis, suggest that a subset of patients may benefit from therapy.

Imipenem-cilastatin versus piperacillin-tazobactam as monotherapy in febrile neutropenia.

Background:  In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem–cilastatin versus piperacillin–tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases.

Comparison of piperacillin tazobactam and cefoperazone sulbactam monotherapy in treatment of febrile neutropenia.

Monotherapy has tended to replace the combination therapy in emprical treatment of febrile neutropenia. There is no reported trial which compares the efficacy of cefoperazone‐sulbactam (CS) and piperacillin‐tazobactam (PIP/TAZO) monotherapies in the treatment of febrile neutropenia. In this prospective randomized study, we aimed to compare the safety and efficacy of CS versus PIP/TAZO as empirical monotherapies in febrile neutropenic children with cancer.

Assessment of hepatitis B immunization status after antineoplastic therapy in children with cancer.

Background and Objectives: Hepatitis B is a disease that is preventable with vaccination. Antibody levels after vaccination may be affected by suppression of the immune system due to cancer therapy. Children with cancer have a high risk of hepatitis B virus (HBV) infection. We aimed to assess the pretreatment immunization status against HBV infection and the rate of continuity of immunization after therapy in children with cancer. Design and Setting:Retrospective case review of patients treated from 2004 to 2008. Patients and Methods: We reviewed the medical records of patients treated in the departments of pediatric hematology and oncology and collected data on immunization history and hepatitis B serology. Anti-HBs antibody titers were compared before and after treatment. Results: This study included 159 (99 males, 60 females) children who had a serologic examination. Antineoplastic therapy had been given for acute leukemia (n=66), non-Hodgkin lymphoma (n=27), Hodgkin lymphoma (n=20), and solid tumors (n=46). Fifty-one patients had not been immunized against HBV prior to the therapy; HBV serology was negative in 49 of these patients and HBsAg was positive in 2 patients. Anti-HBs antibody positivity was present in 99 of 108 patients with an immunization history, whereas no vaccination response was present in 9 patients. The titer of anti-HBs antibody was decreased below the protection level in 33 (33%) patients with positive anti-HBs antibody, whereas the protection level was found to be maintained in 66 (67%) patients. The most significant decrease (63.6%) was observed in leukemia patients. Posttreatment HBsAg and HBV DNA positivity was detected in two of the patients with negative pretreatment serology, whereas no HBV infection developed in the group with positive anti-HBs antibody. Conclusions : This study demonstrated the importance of routine childhood vaccination in reducing the risk of HBV infection in patients with cancer.

Refugee children with cancer in Turkey

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Candida-Related Immune Response Inflammatory Syndrome Treated With Adjuvant Corticosteroids And Review Of The Pediatric Literature.

Dildar Bahar Genç1, Sema Vural1, Nafiye Urgancı2, Tuğçe Kurtaraner3, Nazan Dalgıç4 1Şişli Hamidiye Etfal Training and Research Hospital, Clinic of Pediatric Oncology, İstanbul, Turkey 2Şişli Hamidiye Etfal Training and Research Hospital, Clinic of Pediatric Gastroenterology, İstanbul, Turkey 3Şişli Hamidiye Etfal Training and Research Hospital, Clinic of Pediatrics, İstanbul, Turkey 4Şişli Hamidiye Etfal Training and Research Hospital, Clinic of Pediatric Infectious Disease, İstanbul, Turkey

Wilms Tumor Presenting With Fulminant Hepatic Failure and Successful Initial Treatment With Cyclophosphamide

To the Editor: Right atrium (RA) thrombus extension occurs in 0.5–3% of patients with Wilms tumor (WT).[1,2] The tumor thrombus has no impact on prognosis but complicates the course of disease. A patient with WTand cavoatrial thrombus who recovered from severe liver failure after initial cyclophosphamide chemotherapy is presented here. A 3-year-old patient was referred with loss of consciousness. He had stupor, tachycardia, dyspnea, diminished breath sounds at the right lung, anasarca, ascites, massive hepatomegaly, and poor circulatory status. No mass lesion was palpable. Abnormal laboratory results were: Hemoglobin 8.6 gr/dl, WBC: 17,500/ mm, PLT: 169,000/mm, SGOT: 2,507U/L, SGPT: 1,097U/L, total bilirubin: 0.8mg/dl, prothrombin time: 33 sec, aPTT: 54.3 sec, glucose: 26mg/dl, and severe metabolic acidosis. Mechanical ventilation and other supportive measures were initiated. CT scans showed right-sided pleural effusion, atelectasis, ascites, a 9.7 cm left renal mass lesion with IVC and RA thrombus (Fig. 1), and hepatomegaly without invasion of hepatic veins. Echocardiography demonstrated RA thrombus of 6 cm, protruding into the right ventricle through the tricuspid valve during diastole. The patient was diagnosed with WTwith cavoatrial tumor thrombus, based on imaging. The tumor was clinically staged as NWTS-Stage III as primary nephrectomy was not an option. Cyclophosphamide therapy was initiated at a dose of 14.7mg/kg/day for 3 days. The hepatic dysfunction gradually improved and he was successfully weaned off mechanical ventilation 5 days later. Vincristineþ actinomycin-Dwere initiated at the 8th day of chemotherapy. At the 6th week of chemotherapy, the size of the tumor and persisting RA thrombus regressed to 6 and 2.5 cm, respectively. The tumor was completely resected by nephrectomy, with cardiopulmonary bypass support. The pathology revealed WT with favorable histology. He had radiotherapy and postoperative chemotherapy uneventfully and he has been in remission for 9 months. The frequency of hepatopathy in WT with tumor thrombus ranges between 0.1 and 1.8%.[3–5] However, the real frequency may be underestimated due to lack of documentation of liver function tests. Asymptomatic presentation is common but edema, ascites, varicocele, dilated superficial abdominal veins, cardiac murmur, heart failure, liver dysfunction, dyspnea, encephalopathy, and electrocardiogram changesmay be observed.[1] There are three case reports of severe liver failure with documented liver function tests.[6–8] Two unstable patients were reported to have primary surgery with uneventful postoperative recovery.[6,7] A 6-year-old female with milder liver dysfunction in comparison to previous patients had preoperative conventional chemotherapy and delayed surgery.[8] It is debatable whether urgent primary resection might have been an option for our patient. Severe coagulopathy and poor clinical status were the main obstacles for surgery. Wilms tumor with intraatrial extension is a challenge for the clinician. Preoperative chemotherapy is recommended by SIOP and by NWTS only for cases with tumor extension above the level of hepatic veins due to excessive morbidity of upfront surgery. Vincristine and actinomycin-D are metabolized hepatically and contraindicated in severe liver failure. In our patient, we successfully administered cyclophosphamide, a relatively liversafe drug with proven efficacy against WT,[9] as dose modification was not recommended during hepatic dysfunction.[10] In conclusion, liver failure might be the initial manifestation of WTwith RA extension. Preoperative initial chemotherapy with less hepatotoxic agents like cyclophosphamide might provide urgent relief in such circumstances.

A Rare Cause of Hepatomegaly: Infantile Hepatic Hemangiomendothelioma

Infantile hepatic hemangiomendothelioma, a bening vascular neoplasia derived from endothelial cells, is the most common newborn tumor located in the liver. The tumor has female predominancy. Mostly, it is associated with a good prognosis and may show spontaneous regression by the time the infant is 1 year of age. Although most of the patients are asymptomatic, abdominal mass, hepatomegaly, jaundice, nausea, and vomiting can be encountered among common clinical findings. Herein, a 1.5-month-old boy with abdominal distention was referred to our gastroenterology unit for hepatomegaly. Non-invasive diagnostic modalities revealed infantile hepatic hemangioendothelioma.