M. Tezer Kutluk

Childhood cancer and hypercalcemia: Report of a case treated with pamidronate

Hypercalcemia in a 4-year-old boy with non-Hodgkin lymphoma treated with pamidronate is presented. The child had relapsed disease with bone metastasis. Hypercalcemia is rare in children, and bisphosphonates are relatively new agents for the treatment of hypercalcemia. Information concerning their use in the treatment of hypercalcemia in childhood is limited. We found that pamidronate is effective and has no significant side effects in a child.

MANAGEMENT OF CUTANEOUS HEMANGIOMAS: A RETROSPECTIVE ANALYSIS OF 1109 CASES AND COMPARISON OF CONVENTIONAL DOSE PREDNISOLONE WITH HIGH-DOSE METHYLPREDNISOLONE THERAPY

The effectiveness of the different pharmacological agents and different doses of systemic cortico steroids was analyzed. A total of 1109 patients (median age 8 months; F/M: 2.3) with hemangioma, followed up in our unit for 23 years, were evaluated retrospectively. Forty-five of them received systemic corticosteroids. Two different pharmacological agents, prednisolone (in 26 patients) and methyl prednisolone (in 19 patients), had been used in three different regimens. Groups were compared according to the final results and rebound regrowth. Response was considered good or excellent in 16 patients (36%). There were no differences in response to therapy among the three regimens. No difference was found in response to therapy between prednisolone and methylprednisolone and the two different doses of the methylprednisolone. Rebound regrowth was significantly higher in methyl prednisolone than in the prednisolone group (p = .045). In multivariate analysis the dimension of the lesion (p = .0065) and age at initiation of treatment (p = .0041) were the most important factors affecting the response. In conclusion, the systemic corticosteroids are effective in 36% of patients, independent of dosage and pharmacological agents and duration of the therapy. The dimension of the lesion and age at initiation of treatment are the most important factors affecting the response to treatment.

Second malignant neoplasms following the treatment of brain tumors in children.

We investigated retrospectively 992 children with central nervous system tumors who were treated at our center between 1970 and 2004. All of the patients were treated by surgery, chemotherapy, and/or radiotherapy. Six patients developed second malignant neoplasms, and their clinical and histopathologic characteristics are reviewed in this article. The second malignant neoplasms were diagnosed as non-Hodgkin lymphoma, myelodysplastic syndrome, basal cell carcinoma, malignant melanoma, Kaposi sarcoma, and high-grade neuroectodermal tumor. The initial diagnoses were ependymoblastoma in one, medulloblastoma in three, and low-grade astrocytoma in two patients. The median latency time was 3.03 years (range 0.39—22.93 years). The outcome varied according to the histopathologic type of the second tumor. The patients who developed non-Hodgkin lymphoma and myelodysplastic syndrome died of progressive disease. The patients with second skin neoplasms are alive as of the time of this writing. The patient with Kaposi sarcoma developed one of the rare reported second malignant neoplasms following a primary brain tumor in childhood. A wide spectrum of second malignant neoplasms was detected after treatment of primary brain tumors with surgery, radiotherapy, and chemotherapy. Long-term follow-up is therefore necessary for the child who has survived a primary central nervous system tumor. (J Child Neurol2006;21:433—436; DOI 10.2310/7010.2006.00108.

Intracranial involvement in Hodgkin's disease.

The authors report 3 cases of Hodgkins disease with intracranial involvement. The patients were 4, 12, and 15 years old (male/female = 1/2). Initially, they were treated with ABVD or COPP chemotherapies and low-dose involved field radiotherapy. Intracranial recurrences occurred 27, 40, and 42 months after initial diagnosis, respectively. Two patients experienced convulsions and the other complained of diplopia. The metastatic lesions were located supratentorially with CT or MRI. Despite initial response achieved following systemic chemotherapy and external irradiation to cranial lesions, all patients died with disseminated disease. In patients with intracranial involvement of Hodgkins disease, prolonged disease-free survival may be achieved by combined modality treatment.

Treatment results and prognostic factors in Ewing sarcoma.

Files of 133 children with Ewing sarcoma (median age 10 years) were reviewed. Frequent primary sites were extremities, trunk, pelvis, and cranium. Half of 43 patients with metastases had disease in the lungs. Ten-year overall and event-free survival rates were 31% and 19%, respectively. Five-year overall survival rates were 42% in localized and 15% in metastatic disease (p <. 0001); 66% in cases with primary tumors < 8 cm and 29% in larger tumors (p =. 013). VAC (vincristine, actinomycine D, and cyclophosphamide) regimens with anthracyclines resulted in better survival. Presence of distant metastases, large primary tumors, and pelvic localization were related to poor prognosis. Novel therapeutic approaches are needed to produce better results, especially in high-risk patients.

Neuroblastoma in Turkish children: experience of a single center.

Objective and Method The survival of the patients with neuroblastoma has improved in last few decades. But still it depends on various clinical and biological factors. To assess the clinical features and trends in survival, the data for 500 newly diagnosed patients between January 1972 and December 2004 from a single center were retrospectively analyzed. Results Histopathologic subtypes were neuroblastoma (NBL) in 462 patients (92.4%) and ganglioneuroblastoma in 38 patients (7.6%). The median age was 2.9 years and Male/Female ratio was 1.3/1. Primary tumor sites were abdomen, thorax, pelvis, neck, and others with the frequency of 72.2%, 14.9%, 3.8%, 3.2%, and 5.9%, respectively. There were 30, 49, 133, 257, 31 patients with stage 1, 2, 3, 4, 4S disease and their 10-year survival rates were 100%, 75.8%, 34.1%, 6.5%, and 59.4%, respectively. The outcome has significantly improved according to 10-year periods. The 5-year overall survival rates were 14%, 26.1%, 39.2%, and 52.4% for the years of 1970s, 1980s, 1990s, and after 2000. Surgical procedure involving total or near total tumor removal improved the survival (P=0.002). Both 5-year overall survival and event free survival rates were higher when partial resection was performed, especially in stage 3 disease (P=0.002 and P=0.02). In multivariate analysis, age above 18 months at diagnosis (P=0.01), stage 4 disease (P<0.001), abdominal primary tumor site (P<0.001), NBL subtype in histopathology (P=0.001), responsiveness to chemotherapy (P<0.001) positive or high Vanillyl mandelic acid levels (P=0.02) and male sex (P=0.008) were the determinants of poor prognosis. Conclusions The survival rates in children with local disease are comparable with the results of developed countries; however, the results in children with advanced disease are still not satisfactory. To improve the outcome, especially in children with advanced disease, more effective chemotherapy regimens and molecular therapies should be investigated. Sharing the knowledge and capacity building to improve the treatment results in NBL are also critical for developing countries.

FIBROLAMELLAR HEPATOCELLULAR CARCINOMA WITH SKELETAL METASTASES

Skeletal metastases is relatively rare in hepatocellular carcinoma and accounts for 4-16% of extrahepatic metastases. The authors report a 13-year-old girl with fibrolamellar hepatocellular carcinoma, who rejected further systemic chemotherapy following hepatic lobectomy and experienced sternal and vertebral painful metastases nearly 5 years after the operation. The sternal metastatic lesion was removed surgically, whereas external irradiation was delivered to the lumbar vertebral lesion. The patient received no systemic treatment following metastases and died with widespread disease. Despite metastatic disease, the patient survived 6.5 years following the initial diagnosis.

Testicular Germ Cell Tumors in Childhood: Treatment Results of 52 Patients

We analysed the treatment results of 52 children with testicular germ cell tumors. Histopathological diagnoses were endodermal sinus tumor (63.4%), embryonal carcinoma (28.8%), teratocarcinoma (5.7%), and mixed tumors (2.1%). Radical inguinal orchiectomy was performed in 42 patients and retroperitoneal lymph node dissection in 10 (3/10 positive). Overall survival rates were: whole group: 71.2%; stage I: 89.7%; II: 68.5%; III: 31.2%; IV: 30% (p =. 001). Five-year overall survival rates were 85.8% and 100% for stage I patients who received chemotherapy or not (p =. 27); BEP regimen: 85.7%; classical VAC: 67.9%; vinblastine + bleomycin: 63.6%. Chemotherapy is not required in stage I. BEP regimen is effective in testicular germ cell tumors.

GLUTATHIONE S-TRANSFERASE AND P-GLYCOPROTEIN EXPRESSIONS IN NEUROBLASTOMA

This study was planned to evaluate the prognostic role of glutathione S-transferase pi (GST-pi) and P-glycoprotein (P-gp) expressions in children with neuroblastoma. Sections from formalin-fixed paraffin-embedded tumor blocks from 52 neuroblastoma cases (17 with localized, 35 with advanced disease) were subjected to immunohistochemistry for P-gp and GST-pi expressions. The overall number of tumors positive for P-gp and GST-pi were 19 (36.5%) and 21 (40.4%), respectively. Twenty-two tumors were negative for both GST-pi and P-gp expressions, whereas 10 expressed both proteins. The distribution of staining status of samples in the groups of both proteins showed no significant difference. No relation between the expressions of both proteins and the clinical characteristics of the patients was demonstrable. The differences between the survival rates of patients with positive and negative staining for P-gp expression were not statistically significant. Although 2 common mechanisms of multiple drug resistance, P-gp and GST-pi, might be responsible for drug resistance in neuroblastoma, this complex mechanism has no direct significant impact on prognosis. Multiple mechanisms at cellular levels are responsible for the resistance against antineoplastic therapies in neuroblastoma.

CEREBROSPINAL FLUID SOLUBLE CD27 LEVELS IN CHILDREN WITH NON-HODGKIN LYMPHOMAS

The authors investigated the diagnostic value of cerebrospinal fluid (CSF) soluble CD27 (sCD27) for leptomeningeal involvement of non-Hodgkin lymphomas (NHL). Cytospin slides were prepared from CSF samples of 64 children treated for NHL. sCD27 levels were determined by sandwich ELISA method using two CD27 monoclonal antibodies. 8/194 (4.1%) samples were considered tumor-positive by cytology. Mean sCD27 values were 5.8 and 13.8 U/mL in tumor-negative and tumor-positive samples, respectively (p =.18). 26/194 samples were false positive and 2/194 false negative (cutoff: 7 U/mL) (sensitivity, 75%; specificity, 86%; positive predictive value, 18.8%; negative predictive value, 98.8%; accuracy, 85.6%). With these results, the value of adding sCD27 determination to the cytological CSF examination remains questionable.