Rejin Kebudi

Paediatric cancer in low-income and middle-income countries

Patterns of cancer incidence across the world have undergone substantial changes as a result of industrialisation and economic development. However, the economies of most countries remain at an early or intermediate stage of development-these stages are characterised by poverty, too few health-care providers, weak health systems, and poor access to education, modern technology, and health care because of scattered rural populations. Low-income and middle-income countries also have younger populations and therefore a larger proportion of children with cancer than high-income countries. Most of these children die from the disease. Chronic infections, which remain the most common causes of disease-related death in all except high-income countries, can also be major risk factors for childhood cancer in poorer regions. We discuss childhood cancer in relation to global development and propose strategies that could result in improved survival. Education of the public, more and better-trained health professionals, strengthened cancer services, locally relevant research, regional hospital networks, international collaboration, and health insurance are all essential components of an enhanced model of care.

Survival of retinoblastoma in less-developed countries impact of socioeconomic and health-related indicators

Background The survival of retinoblastoma in less-developed countries (LDCs) and the impact of socioeconomic variables on survival are not widely available in the literature. Methods A systematic review of publications from LDCs was performed. Articles were from multiple databases and written in seven languages. Results were correlated with socioeconomic indicators. Lower-income countries (LICs) and middle-income countries (MICs) were included in our analyses. Results An analysis of 164 publications including 14 800 patients from 48 LDCs was performed. Twenty-six per cent of the papers were written in languages other than English. Estimated survival in LICs was 40% (range, 23–70%); in lower MICs, 77% (range, 60–92%) and in upper MICs, 79% (range, 54–93%; p=0.001).Significant differences were also found in the occurrence of metastasis: in LICs, 32% (range, 12–45); in lower MICs, 12% (range, 3–31) and in upper MICs, 9.5% (range, 3–24; p=0.04). On multivariate analysis, physician density and human development index were significantly associated with survival and metastasis. Maternal mortality rate and per capita health expenditure were significantly associated with treatment refusal. Conclusions Important information from LDCs is not always available in English or in major databases. Indicators of socioeconomic development and maternal and infant health were related with outcome.

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.

Ependymal tumors in childhood

Ependymal tumors are classified as ependymoma (benign or low grade) versus anaplastic ependymoma (malignant or high grade). Ependymomas represent 5–10% of intracranial neoplasm in children. In this study, demographic data and the treatment results of pediatric patients with ependymal tumors, treated in a single institute, is reported.

Yolk sac tumours of the ovary: Evaluation of clinicopathological features and prognostic factors

OBJECTIVE To evaluate the clinicopathological prognostic features, factors and outcomes of chemotherapy in ovarian yolk sac tumours (YST). STUDY DESIGN We reviewed the medical records of 32 women with ovarian YST treated from 1990 to 2006 at two centres. RESULTS The median follow-up was 36 months. The median age was 22 (range, 9-68). Two patients were postmenopausal. The most common symptoms at diagnosis included abdominal swelling or mass (72%) and abdominopelvic pain (62%). The location of the tumour was bilateral in 2 cases. Eight patients were in stage I, 4 patients in stage II, 17 patients in stage III, and 3 patients in stage IV. Eighteen patients underwent unilateral salpingo-oophorectomy, two bilateral salpingo-oophorectomy and two cystectomy, while 10 patients had total abdominal hysterectomy and two bilateral salpingo-oophorectomy. Of 32 patients who received postoperative chemotherapy, 27 were treated with a bleomycin/etoposide/cisplatin (BEP) regimen. Seventy-two percent of patients were alive at the last follow-up visit. Ten (31%) patients suffered from a recurrence of the disease with a median time to recurrence of 8 months (range, 6-28 months). The most common site of recurrence was the intra-abdominal space, with 8 patients. Only one patient who had recurrence could be salvaged. Fertility-sparing surgery was found at least as effective as radical surgery. While age, histology (mixed vs. pure), stage, tumour size, ascites, and marker levels were not found as prognostic factors, the presence of residual tumour (P=0.014) and BEP chemotherapy (P=0.016) were significant prognostic factors in univariate analysis. CONCLUSIONS In patients with ovarian YST, fertility-sparing surgery is as effective as radical surgery. Optimal cytoreductive surgery and standard BEP regimen are the most decisive prognostic factors. In these tumours, adjunctive therapeutic modalities to eradicate intra-abdominal disease and effective salvage therapy strategies are needed.

Immunohistochemical detection of p53 protein in rhabdomyosarcoma: association with clinicopathological features and outcome.

PURPOSE Alteration in the p53 tumor suppressor gene is the most common tumor specific genetic change identified in most major cancer types including rhabdomyosarcomas. To investigate the overexpression of p53 and its relation to clinical features and outcome in patients with rhabdomyosarcoma (RMS), an immunocytochemical study was performed. METHODS Formalin-fixed paraffin embedded tissue sections obtained from 42 cases of RMS were immunostained with a mouse monoclonal antibody p53-D07. Staining was assessed by evaluating the percentage of p53 immunopositive cancer cell nuclei. RESULTS Nuclear accumulation of p53 protein was detected in 8 of 42 (19%) samples. Clinical analyses of patients demonstrated no correlation between positive staining and age, sex, histological subtype, stage and overall survival. This analysis, however, was limited by the small number of patients who demonstrated p53 immunostaining. Nonetheless, a statistically significant association was observed between p53 expression and adverse outcome. Nuclear p53 expression was associated with disease progression or recurrence (p <0.001) and with a worse event free survival (p = 0.0015). CONCLUSION The nuclear p53 immunoreaction rate is low in RMS, but p53 expression appears to correlate with poor prognosis.

Potential risks associated with traditional herbal medicine use in cancer care: A study of Middle Eastern oncology health care professionals.

The authors assessed the use of herbal medicine by Middle Eastern patients with cancer, as reported by their oncology health care professionals (HCPs). Herbal products identified by the study HCPs were evaluated for potential negative effects.

Hypertrophic osteoarthropathy and intrathoracic Hodgkin disease of childhood.

BACKGROUND Hypertrophic osteoarthropathy (HOA), well known in adults, is rarely encountered in children. The clinical features include clubbing of the fingers and toes, arthritis, and painful periosteal new bone formation of the tubular bones. The association of malignant disorders with HOA is more common in adults than in children. CASE In this paper, a 12-year-old boy with intrathoracic Hodgkin disease and HOA is presented and four other children with HOA and Hodgkin disease in the literature reviewed. DISCUSSION The presence of HOA has been thought to be a bad prognostic sign, but complete remission of Hodgkin disease and regression of clinical signs and symptoms of HOA were attained in our patient after chemotherapy and radiotherapy, and continue during 9 months post-therapy follow-up. CONCLUSIONS HOA accompanying a malignant tumor in children is very rare. Only 5 cases have been associated with Hodgkin disease, including the present boy. It is important that patients with symptoms of HOA and an intrathoracic mass be examined carefully to rule out a malignancy.

MICROSCOPIC LOCAL LEPTOMENINGEAL INVASION AT DIAGNOSIS OF MEDULLOBLASTOMA

PURPOSE To document the incidence and outcome of patients with microscopic local leptomeningeal invasion at presentation, children with medulloblastoma were reviewed. METHODS AND MATERIALS Nineteen patients (1-12 years of age), who had surgical resection (14 total, 5 subtotal) and were diagnosed as medulloblastoma, were evaluated for disease extent by pre- and postoperative computerized tomography/magnetic resonance imaging, histopathologic evaluation of leptomeninges adjacent to the resected tumor tissue, myelography/magnetic resonance of the entire spine, and analysis of cerebrospinal fluid cytology. Patients were also reviewed for disease outcome. RESULTS Staging revealed one T2, nine T3a, eight T3b, and one T4 disease. There were 10 M0, 2 M1, 2 M2, 2 M3, and 3 Mx patients according to Changs classification. Ten out of 19 patients (52.6%) demonstrated microscopic local leptomeningeal invasion. When only the 10 patients with M0 disease were considered, three out of five patients with microscopic local leptomeningeal invasion was found to have one or more relapses. The five other M0 patients without microscopic local invasion were in complete remission at the time of analysis. CONCLUSION The incidence of microscopic local leptomeningeal invasion in patients with medulloblastoma is high. Whereas the impact on survival remains to be determined in larger series, data suggests prognostic role for isolated microscopic local leptomeningeal invasion, thus validity for inclusion in the future staging system.

Polyostotic Monosystemic Calvarial and Spinal Langerhans’ Cell Histiocytosis Treated by Surgery and Chemotherapy

There are several treatment modalities for Langerhans’ cell histiocytosis (LCH) of bone, formerly usually referred to as eosinophilic granuloma, including surgery, radiotherapy and chemotherapy. In spinal lesions, surgery is not recommended generally, because of the potential for reconstitution of vertebral height. We report a case of multifocal monosystemic LCH treated by surgery and chemotherapy for calvarial and spinal lesions. A 7-year-old boy was initially operated for an occipital monostotic LCH of bone. Then, he was treated by surgery for cervical and thoracic lesions, and by chemotherapy with vinblastine. The patient had no complaints at the 24-month follow-up. Although surgery is not recommended for spinal lesions in children with LCH of bone, short segmental fusion and internal fixation may be a suitable choice for selected cases, especially in children who are not likely to comply with activity restrictions and in those who it is difficult to follow up. The treatment must be planned according to the characteristics of the patient.