Spontaneous pneumothorax in children with osteosarcoma: report of three cases and review of the literature.

Spontaneous pneumothorax is a rare manifestation of primary lung cancer or metastasis. It is estimated that < 1% of all cases of spontaneous pneumothorax are tumor-associated and metastatic osteogenic or soft-tissue sarcomas are associated most commonly with pneumothorax especially in the setting of cytotoxic chemotherapy or radiotherapy. In this article, we report three pediatric cases with osteosarcoma that developed spontaneous pneumothorax during chemotherapy with a review of the literature. Two of them had lung metastasis at the time of the detection of pneumothorax and the remaining patient was found to have a bronchopleural fistula. SPx is an emergency situation and early diagnosis and management can improve prognosis and quality of life of the patient however the optimal management has yet to be determined.

Nasopharyngeal carcinoma in children: retrospective review of 50 patients.

PURPOSE: To report a retrospective analysis of epidemiologic, clinical, and therapeutic aspects of 50 children with newly diagnosed nasopharyngeal carcinoma who were treated in a single institution over a period of 18 years. METHODS AND MATERIALS: Thirty-two male and 18 female children ranging from 5 to 16 years, accounted for 7.2% of all nasopharyngeal carcinoma cases and 52% of childhood nasopharyngeal malignancies. Histopathology was World Health Organization Type 3 carcinoma in 45, World Health Organization Type 2 in 4, and World Health Organization Type 1 in one patient. Two of the patients had missing information for staging and treatment evaluation. Disease extent was T1 (n = 4), T2 (n = 9), T3 (n = 21), and T4 (n = 14); N0 (n = 1), N1 (n = 6), N2 (n = 12), and N3 (n = 29). Six patients had base of skull invasion, two had cranial nerve palsies, and six had both. One patient had M1 disease on admission. Twenty-three patients were treated with irradiation only. Thirteen patients received adjuvant, and 12 had neoadjuvant chemotherapy in addition to radiotherapy. Patients received 50-72 Gy to the primary tumor and involved nodes, and 45-50 Gy to uninvolved regions. Chemotherapy consisted of combinations including cisplatin, bleomycin, epirubicin, 5-fluoroucil, and cyclophosphamide. RESULTS: Thirty-eight (79%) patients attained locoregional control. Overall, 22 patients are alive without relapse 6-195 months from diagnosis. Thirteen patients had 21 relapses, at local and/or regional sites (43%), distant sites (48%), or both (9%). The median time for first relapse was 8 months. Overall, the 5-and 10-year survival rates were 52 and 52%, respectively, and the failure-free survival rates were both 53%. The results of three distinct treatments given in subsequent time periods were not statistically different. Three second malignancies occurred 33-156 months following nasopharyngeal carcinoma diagnosis. CONCLUSION: In the current series, nasopharyngeal carcinoma patients under the age of 16 accounted for 7.2% of all nasopharyngeal carcinoma cases. Whereas the impact of chemotherapy on long-term survival remains to be determined by randomized studies, the results suggest that more effective treatment regimens and long-term follow-up are necessary for children with nasopharyngeal carcinoma.

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 Chang's 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.

Clinical and cytogenetic studies of two cases of Klinefelter syndrome with hereditary retinoblastoma and rhabdomyosarcoma.

Two children with Klinefelter syndrome (KS), one associated with bilateral hereditary retinoblastoma (RB) and the other with rhabdomyosarcoma (RMS) are reported. Both were boys and chromosomally mosaic for KS. The hereditary retinoblastoma case yielded 46,XY,del(13)(q12q14.2)/47, XXY(c),del(13)(q12q14.2) in PHA-stimulated lymphocytes. The rhabdomyosarcoma case yielded 46,XY/ 47,XXY(c) in peripheral blood cells whereas tumor revealed trisomy 8, trisomy 7, and t(7;13)(q33;q32) in addition to 46,XY/47,XXyc mosaicism.

De novo germline mutations of the p53 gene in young children with sarcomas.

Germline p53 mutations are associated with cancer predisposition in Li-Fraumeni families as well as in individuals with component tumors of the syndrome. In the majority of cases these mutations have been shown to be inherited rather than de novo. We screened 59 children with primary bone or soft tissue sarcomas. Germline p53 mutations were identified in 2 patients. Interestingly, analysis revealed that both mutations were de novo. Although the frequency of germline p53 mutations in primary pediatric sarcoma patients is low, there is evidence for the importance of considering pediatric patients for testing for de novo mutations.

P53 overexpression in normal oral mucosa of heavy smokers.

The observation that p53 alterations are early events in the tumorigenesis of head and neck cancer and the association with cigarette smoking have prompted us to search for p53 overexpression in the oral mucosa of heavy smokers who have no overt precancerous or cancerous lesions. Formalin-fixed paraffin embedded tissue sections, obtained from oral mucosa of 30 otherwise healthy heavy smokers, were evaluated for tobacco related changes, and immunostained with a mouse monoclonal antibody p53-DO7 for p53 immunoreactivity. Histopathological evaluation revealed hyperplastic changes in twenty eight samples (93%), eight of which also demonstrated dysplastic changes. Positive immunoreaction for p53 was detected in six (20%) of the tissue samples. The study provided significant information about the frequency of hyperplasia, dysplasia, and p53 overexpression in individuals who were heavy smokers. It is suggested, also, that chemoprevention might have some impact in this particular group of individuals.

Renal dysfunctions secondary to ifosfamide treatment in children.

With the increasing use of ifosfamide in pediatric tumors, nephrotoxicity became the point of interest since it may cause chronic morbidity. In this study, the renal glomerular and tubular functions of 25 cases with solid tumors aged between 2-17 years (median 9) who were treated with ifosfamide, were investigated. For this purpose, routine blood urea, creatinine, calcium, phosphorus, electrolytes, urinary creatinine, phosphorus, glucose, protein and urinary retinol binding protein as well as microglobulin were evaluated. Except for two patients who had hypophosphatemia, phosphaturia, and proteinuria, all the cases had normal blood biochemistry, creatinine clearance, tubular phosphate reabsorption; and none had proteinuria, hematuria, or glycosuria. In spite of these findings, urine beta 2 microglobulin and retinol binding protein were found to be high in 11 patients and this elevation persisted during the following one year in 8 cases whose treatments were stopped and their levels increased in three patients who continued to receive fosfamide therapy. In correlation with the increasing cumulative dose of ifosfamide (32-126 g/m2), urinary retinol binding protein or beta 2 microglobulin of patients who are treated with ifosfamide may predict the existence of renal toxicity even if other routine renal function tests are normal. Thus, the periodic evaluation of urinary beta 2 microglobulin and retinol binding protein in patients receiving chemotherapy containing ifosfamide is recommended.

Germline mutations of the p53 gene in children with malignant solid tumors.

Although somatic mutations of p53 are the most common genetic changes observed to date, the frequency of germline p53 mutations is found to be very low in sporadic malignant tumors. It has been postulated that de novo germline p53 mutations may occur in a substantial population of patients in pediatric age group, who die of their disease and do not propagate the mutation. To determine the frequency and type of p53 germline mutations in pediatric patients, we screened 65 children who were consecutively admitted with primary malignant solid tumors.

Extracranial neuroblastomas and neurological complications.

Between October 1989 and March 1997, 25 pediatric inpatients were treated for primary extracranial neuroblastoma (NB; n=20) or ganglioneuroblastoma (GNB; n=5) at the University of Istanbul, Institute of Pediatric Oncology, and these children were the subjects of this retrospective study. Seventeen (68%) of these patients experienced 19 neurological complications during the course of their disease. Fourteen had nervous system metastases or invasion. Nonmetastatic complications, including CNS infections (n=3) and new onset of seizures (n=2) secondary to metabolic encephalopathy were seen in 5 cases. By the time of the final analysis of the results, 8 of the 17 patients with neurological complications had died, 7 had either been lost to follow-up (n=4) or were in the terminal stage of their disease (n=3), and 2 were in remission. Both of the patients who were in remission had dumbbell neuroblastoma (DNB), and 1 of them, with congenital DNB, also had neurological sequelae, characterized by paraplegia and neurogenic bladder. Neurological complications occurred in 68% of NB and GNB cases. Metastatic complications were more common than nonmetastatic complications and had a poor prognosis. Neurological complications were the primary cause of mortality in this study, mortality being related to neurological complications in 63% of cases, and the final outcome was worse than expected. However, regardless of any differences in social, economic and geographic factors and different treatment protocols for NB in different pediatric oncology institutions, neurological complication rates in pediatric NB are similar in all.

Randomized comparison of cefepime versus ceftazidime monotherapy for fever and neutropenia in children with solid tumors.

BACKGROUND: With the availability of new broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations, especially beta-lactam antibiotics plus aminoglycosides, in the management of febrile neutropenic cancer patients. PROCEDURE: Since January 1994, monotherapy has been used for empiric initial treatment at our center. The aim of this prospective randomized study is to compare the efficacy of cefepime (CFP), a new fourth-generation cephalosporin, and ceftazidime (CFZ) as empirical monotherapy of febrile neutropenic patients with solid tumors. From January 1998 to November 1998, 63 episodes of fever and neutropenia occurring in 33 children with solid tumors including lymphomas, were randomized to receive treatment with either CFP or CFZ. The patients were analyzed for leukocyte count and absolute neutrophil count (ANC) at entry, days in fever, neutropenia and hospitalization, and side effects of drugs. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. RESULTS: In our study group, with a median age of 7 [(1/12)-14] years, CFP was administered in 32, and CFZ in 31 episodes. An infection was documented microbiologically in eight episodes (25%) in the CFP arm and in nine episodes (29%) in the CFZ arm. The success rate with initial empiric monotherapy was 62.5% in the CFP arm and 61.3% in the CFZ arm respectively (P > 0.05). The total success rate (success with or without modification) was 100% in both arms. No major adverse effects were observed in either groups. CONCLUSION: CFP is as effective and safe as CFZ for the empirical treatment of febrile episodes in neutropenic patients with solid tumors.

Intraspinal hemorrhage in a child with factor XIII deficiency.

The rarity of spinal cord injuries and hemorrhages and of fibrin-stabilizing factor XIII deficiency during childhood has induced us to report the case of this two-year-old boy with factor XIII deficiency who presented with cervical intraspinal hemorrhage between the C4 and C7 levels as well as paraplegia presumably following a minor trauma. The findings in this patient, who was brought in two weeks after the appearance of the first symptoms, indicate the importance of early diagnosis and early intervention to minimize the extent of the damage from the injury in such cases. The case also points to the need for close follow-up of patients with factor XIII deficiency for CNS bleeding.

Non-resective management of pineoblastoma.

The results of a non-resective treatment approach for pineoblastoma comprising stereotactic biopsy, cerebrospinal fluid diversion, and fractionated radiotherapy in six patients over a period of six years are presented. There were three male and three female patients, with a median age at diagnosis of 20 years. Magnetic resonance imaging of the spine, ventricular cerebrospinal fluid cytology, and tumour markers in cerebrospinal fluid were negative. Tumour response to initial radiotherapy was complete in three patients and partial in three patients. Recurrences were treated with interstitial irradiation with iodine-125 seeds in four instances, repeat radiotherapy when time elapsed was more than five years in one instance, with surgical resection in two instances, and chemotherapy in two instances. The diagnostic and therapeutic effectiveness of this management strategy is assessed. There were no complications related to surgical procedures. The median follow-up time was 48 months (range 14-70 months). Five patients were alive at 14, 45, 51, 57, and 70 months of follow-up. One patient died of disease at 28 months following diagnosis. The overall survival rate was 80 % +/- 17.89 % at 28 months. The results of this study suggest that this non-resective treatment approach is acceptable as an initial treatment alternative to radical surgical resection of pineoblastomas.

Granulocyte colony-stimulating factor in neutropenic, pediatric solid tumor patients following chemotherapy.

Granulocyte colony-stimulating factor (G-CSF) has been used to reduce the duration and/or degree of neutropenia of different etiologies in recent years. In this study, experience with the use of G-CSF (Neupogen, Roche) after 123 courses of highly myelosuppressive chemotherapy administered to 31 (20 female, 11 male) patients with pediatric solid tumors is reported. G-CSF was initiated at a white blood cell (WBC) count of 918 +/- 452/microL (100-2000), at a dose of 7.6 +/- 2.3 micrograms/kg/d (5-14) subcutaneously for 5.2 +/- 2.4 days (2-18). G-CSF was given for afebrile neutropenia after 82 and for febrile neutropenia after 41 courses. Only in two episodes where G-CSF was given for afebrile neutropenia, fever developed. The average hospitalization period for febrile neutropenia was 9.8 +/- 3.3 days (5-20). Chemotherapy could be given on scheduled time and dosage in 90% of the courses in which G-CSF was used for afebrile neutropenia. G-CSF was well tolerated. Bone pain was observed in two patients and urticaria in one patient. In conclusion, G-CSF increased the WBC count effectively, there were only two febrile episodes in 82 courses in children receiving G-CSF for afebrile neutropenia, it was well tolerated, and it was found to be feasible for use in a developing country.

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.

Primary spinal column sarcomas.

Five cases of primary spinal column sarcomas are presented. Sarcomas primarily originating from paravertebral soft tissues were excluded. Patients' age ranged from 1 to 14 years (mean 8.4 years). The male:female ration was 2:3. Two patients had Ewing's sarcoma (ES) originating from L5-S1 and L4-5 pedicles, respectively; two patients had mesenchymal chondrosarcoma (MCS) originating from L1-2 pedicles and L5 body, respectively; and one patient had osteogenic sarcoma (OS) of C4 body. All patients clinically presented with pain and progressive weakness of the extremities. The time that elapsed between the onset of symptoms and diagnoses ranged from one to five months. All cases were treated with chemotherapy, radiotherapy and subtotal tumour resection with spinal canal decompression. Two cases received posterior spinal fusion operations. Three patients were alive 10 to 98 months following diagnosis. Only the case with ES of L5-S1 pedicles was in complete remission and off therapy at the 98th postoperative month. The two MCS cases were in partial remission, and were receiving chemotherapy at the time of analysis. These tumours caused similar clinical findings and prognoses, and required combined treatment, which consisted of surgery, radiotherapy and chemotherapy; histologically three different types of malignant tumours are presented in the same category. We preferred surgical decompression and stabilization procedures especially for neurologically symptomatic patients, even if they had extensive tumours with high grades. By spinal canal decompression and stabilisation, we did not intend to cure the disease; however, we intended to provide neurological improvement, spinal stabilisation, improved quality of life, early mobilisation of the patient, and cytoreduction by means of surgical tumour ablation, which could render the chemotherapy more effective.

Epidural metastasis in Wilms' tumor: a case report and review of the literature.

Spinal canal involvement is not a common pattern of metastasis in Wilms' tumor. Although early detection and treatment can achieve improvement of neurological deficit, mortality remains high. We present a 5-year-old girl who had an epidural metastasis while she was receiving chemotherapy for stage IV Wilms' tumor. Within 2 months following laminectomy, total removal of tumor, radiotherapy, and adjuvant chemotherapy some of the neurological signs improved.

Seroprevalence of hepatitis B, hepatitis C, and human immunodeficiency virus infections in children with cancer at diagnosis and following therapy in Turkey.

BACKGROUND: Children with cancer receiving intensive chemotherapy require multiple transfusions and are at increased risk for blood transmittable diseases such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections. PROCEDURE: Sera from 50 children (24 female, 26 male) admitted between January, 1994, and December, 1995, with solid tumors receiving intensive chemotherapy and multiple transfusions were investigated for HBsAg, anti-HBs, anti-HBc, anti-HCV, and anti-HIV by ELISA at diagnosis and at the end of therapy. RESULTS: HBsAg, HBV, HCV, and HIV seropositivities were 0%, 4%, 2% and 0% at diagnosis and 10%, 20%, 14% and 0% at the end of therapy, respectively. CONCLUSIONS: The high seroprevalence of HCV may be due to the lack of anti-HCV screening of blood products in the blood banks during the study period. Although the HBV seroprevalance of 20% found in this study is much lower than the value of 56% found in a previous study conducted during 1986-1989 in a similar patient population and a similar setting, it is still high. Children infected with HBV during immunosuppressive therapy are at greater risk of becoming chronic carriers and precautions must be taken for immunization of these children.