The effect of parental age on NF1 patients in Turkey.

Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder worldwide, and its clinical presentations are highly variable. NF1 is caused by mutations in the NF1 gene, and 50% of NF1 cases are sporadic, which occur in the absence of a family history of the disease and usually result from a new mutation in the germline of a parent. Advanced paternal age may increase the risk for germinal NF1 mutations; however, some dominant conditions, including neurofibromatosis, have shown a lesser association with paternal age, although there are conflicting reports in the literature. We investigated the effects of paternal and maternal age in 241 NF1 patients (121 sporadic and 120 familial cases) who were seen in Hacettepe hospital, a reference center for genetic diseases in Turkey. For statistical analysis, Spearman's and Chi-square tests were used. In this study, we evaluated paternal and maternal age at birth in sporadic and familial cases of NF1. We also compared the effect of parental age on the appearance and coexistence of various NF1 symptoms. There were no significant statistical differences between paternal age and coexistence of the NF1 symptoms. However, a slightly negative correlation was observed between paternal age and the coexistence of NF1 symptoms in familial cases (p < 0.05). We did not find strong evidence for the effect of parental age on the clinical severity of NF1.

Risk factors for hospitalisation and associated costs among patients with hepatitis A associated with imported pomegranate arils, United States, 2013.

OBJECTIVES: To assess hospitalisation risk factors and economic effects associated with a multistate hepatitis A outbreak in 2013. STUDY DESIGN: Retrospective case series. METHODS: Eligible outbreak-related cases confirmed by September 1, 2013, were defined as acute hepatitis symptoms and positive IgM anti-hepatitis A during March 15-August 12 among patients who consumed the food vehicle or had the outbreak genotype. We reviewed medical records, comparing demographic and clinical characteristics among hospitalized and non-hospitalized patients; we used logistic regression analysis to identify factors associated with hospitalization. We interviewed patients regarding symptom duration and healthcare usage and estimated per-patient and total costs. Health departments reported outbreak-related personnel hours. RESULTS: Medical records were reviewed for 147/159 (92%) eligible patients; median age was 48 (range: 1-84) years, and 64 (44%) patients were hospitalized. Having any chronic medical condition was independently associated with hospitalisation (odds ratio, 3.80; 95% confidence interval, 1.68-8.62). Interviews were completed for 114 (72%) eligible patients; estimated per-patient cost of healthcare and productivity loss was $13,467 for hospitalized and $2138 for non-hospitalized patients and $1,304,648 for all 165 outbreak-related cases. State and local public health personnel expenditures included 82 h and $3221/outbreak-related case. CONCLUSIONS: Hospitalisations in this outbreak were associated with chronic medical conditions and resulted in substantial healthcare usage and lost productivity. These data can be used to inform future evaluation of expansion of hepatitis A vaccination recommendations to include adults with chronic medical conditions.

Neurofibromatosis type 1 and malignancy in childhood.

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary neurocutaneous syndrome characterized by multi-system involvement and an increased incidence of both benign and malignant tumors. In this study, we evaluated the clinical presentation and prognosis of NF1 and malignancy. Between 1975 and 2013, 26 (5%) of the 473 patients with NF1 at our center developed non-neurofibroma neoplasms. The patient files of 26 subjects with tumors, other than optic glioma, were analyzed retrospectively to evaluate clinical features and treatment results. The age at diagnosis of NF1 ranged from 3 months to 16 years (median 5.5 years). The age range at tumor diagnosis was 1.5-33 years (median 8 years) in these 26 patients. The tumor histological subtypes included the following: 12 soft-tissue tumors (6 malignant peripheral nerve sheath tumors (MPNST), 5 rhabdomyosarcomas (RMS) and 1 malignant fibrous histiocytoma), 11 brain tumors (6 low-grade gliomas, 3 high-grade gliomas, and 2 medulloblastoma), 2 neuroblastomas and 1 non-Hodgkin's lymphoma. Twelve of 26 patients were alive at the time of the study. Although benign brain tumors with NF1 are more common, high-grade brain tumors also occur. Thus, careful and regular follow-up is crucial for early detection of malignancy in NF1 patients.

Maxillofacial osteosarcoma successfully treated with surgery and adjuvant chemotherapy in a child.

Maxillofacial osteosarcoma constitutes a minor percentage of all the head and neck tumors. We describe a 10 year-old girl presenting with swelling and pain in left maxillary region and diagnosed as low grade osteosarcoma. The patient was operated and given a chemotherapy protocol consisted of Cisplatin and Doxorubicin. After six courses of chemotherapy the patient was in complete remission and she is well with no evidence of disease for five years. Since high local recurrence rates have been reported in craniofacial osteoarcoma and we know the deleterious side effects of radiation therapy in children, we believe that best management strategy for osteosarcomas in maxillofacial region in children is radical surgical excision and postoperative chemotherapy (Fig. 3, Ref. 11).

Primitive neuroectodermal tumors of the central nervous system associated with genetic and metabolic defects.

AIM: To evaluate the genetic, congenital and metabolic disorders which were detected concurrently with primitive neuroectodermal tumors (PNET) of the central nervous system in children. METHODS: Medical records of 1030 children who were admitted to our department with diagnosis of brain tumor between 1975 and 2005 were reviewed retrospectively. Medulloblastoma and supratentorial PNETs were detected in 289 patients. They were reviewed for associated metabolic conditions, genetic and congenital defects. RESULTS: One of the following conditions were detected in 10 patients with medulloblastoma and supratentorial PNETs: Neurofibromatosis type 1, Gorlin syndrome, juvenile polyposis coli, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, bilateral retinoblastoma, L-2-hydroxyglutaric aciduria, Gilbert syndrome, gray platelet syndrome, cleft lip-palate and left renal agenesis. In the patients with multiple malignant diseases, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, Gorlin syndrome and juvenile polyposis coli were diagnosed after diagnosis of the malignant tumors. Medulloblastoma was the first manifestation in the case with Gorlin syndrome. In case with retinoblastoma, pineal PNET was detected 2 months after diagnosis of retinoblastoma. Cleft lip-palate and L-2-Hydroxyglutaric aciduria were detected previously in the patients before their brain tumors whereas Gray platelet, Gilbert syndrome and left renal agenesis were diagnosed during treatment of medulloblastoma. CONCLUSION: Associated genetic, metabolic and congenital conditions were detected in 3.5% of the cases. Thus the patients with PNET should be followed for these defects.

Clinical value of cystatin c determination in children with lymphoma.

Cystatin, a proteinase inhibitor, is involved in the intracellular catabolism of proteins. We investigated the change in concentration of serum Cystatin C (CysC) in children with lymphomas and its diagnostic utility. Twenty-eight newly diagnosed patients with lymphoma were included in this study. The male/female ratio was 20/8, with a median age of 8.5 years (range 3-17 years). Thirteen patients had Hodgkin's lymphoma (HL) and 15 had non-Hodgkin's lymphoma (NHL). Cystatin C concentration was determined at the time of diagnosis and during remission. In the entire group, CysC concentrations at diagnosis and during remission were 0.87+/-0.29 mg/L and 0.86+/-0.21 mg/L, respectively (p=0.93). In the NHL group, CysC concentrations at diagnosis and remission were 0.89+/-0.32 mg/L and 0.85+/-0.23 mg/L, respectively (p=0.73). The CysC concentrations in the HL group at diagnosis and remission were 0.88+/-0.36 mg/L and 0.88+/-0.18 mg/L, respectively (p=0.73). No significant difference was observed between CysC concentrations in the HL (0.88+/-0.36 mg/L) and NHL (0.89+/-0.32 mg/L) groups. Cystatin C concentrations in all the patients with localized versus those with advanced disease were 0.91+/-0.41 mg/L and 0.88+/-0.3 mg/L, respectively (p=0.83). Cystatin C concentrations of the patients with localized and advanced HL were 0.95+/-0.45 mg/L and 0.77+/-0.14 mg/L, respectively, (p=0.41). Cystatin C level was higher in patients with localized disease, in those without B symptoms, and, at diagnosis, in those with an unfavorable response (Tab. 2, Ref. 20). Full Text in free PDF www.bmj.sk.

Pineal region tumors in children: a single center experience.

Pineal region tumors are a relatively uncommon, deep-seated heterogeneous group of mass lesions of the brain. Their management is much more complicated in children with cancer, both in terms of survival and sequelae, due to primary location of the tumor and treatment modality. The goal of this retrospective study was to report the presentation, treatment, and outcome of tumors that arose from this region in 24 children treated at our institution between March 1975 and May 2006. In all, 15 (62.5%) of the 24 children were initially treated with partial or complete resection, adjuvant radiotherapy was given to 18 (75%) patients, and chemotherapy was given to 15 (62.5%) of the patients. Overall survival was 44.5%. Although statistically insignificant, the most favorable outcome were obtained in patients with grossly resected tumors (66%) and in children >10 years of age (80%). Long-term sequelae occurred at a high rate in this study due to the primary location of the tumors and treatment modalities, which warrants further investigation.

Varicella vaccination in children with lymphoma and solid tumours.

BACKGROUND: Varicella infection can be a severe disease, especially in immunosuppressed patients. Here, experience with live varicella vaccine to prevent varicella infection is reported in children who were undergoing treatment for lymphoma and solid tumours. METHODS: 40 children, aged between 12 months and 15 years with no clinical history of varicella, were vaccinated with live varicella vaccine. All received two doses of the vaccine subcutaneously 4 weeks apart. Serum samples were taken before the first dose and 6 weeks after the second dose of vaccine. RESULTS: Before vaccination, 32 patients were seronegative for varicella and eight were seropositive. Seroconversion was observed 6 weeks after the second dose in 24 of the 32 (75%) seronegative children. In 4 of 8 previously seropositive patients, antibody titres increased after immunisation. Zoster infection occurred 5 weeks after the second dose of vaccine in only one previously seronegative child. 7 children, who had responded to the vaccine, have been exposed to varicella in their families or in school without contracting clinical disease. CONCLUSION: Although the small number of patients in our group prevents us from drawing definitive conclusions, the varicella vaccine seems to be well tolerated and can be administered to children with lymphoma and solid tumours undergoing treatment.

Primary lacrimal sac non-Hodgkin's lymphoma in a child.

Primary lacrimal sac lymphoma is extremely rare in children. To our knowledge, only two previous cases have been reported in the literature. Here, we report the case of a 9-year-old girl with primary lacrimal sac lymphoma who has recurrent mass.

Urticaria pigmentosa associated with Wilms tumor.

Urticaria pigmentosa is the most common manifestation of mastocytosis, with the majority of cases undergoing spontaneous resolution, especially in children. Several reports have documented hematologic malignancies developing in patients with urticaria pigmentosa. We present a 4.5-year-old boy with urticaria pigmentosa who developed Wilms tumor. To our knowledge, coexisting urticaria pigmentosa and Wilms tumor have not previously been described.

Extraneural metastasis in a child with atypical teratoid rhabdoid tumor of the central nervous system.

Atypical teratoid rhabdoid tumor is a distinctive brain tumor appearing in infancy and early childhood. Leptomeningeal dissemination is common, both at presentation and relapse. Extracranial metastases of the central nervous system tumors are rarely seen. To our knowledge there is only one report with an atypical teratoid rhabdoid tumor metastasizing via a ventriculoperitoneal shunt. We describe the first case of atypical teratoid rhabdoid tumor of the central nervous system who developed lung metastasis without the presence of a shunt.

Malignant ovarian tumors in children: 22 years of experience at a single institution.

PURPOSE: Malignant ovarian tumors of childhood are relatively rare and thus, management is still unclear. We reviewed our experience with these tumors to evaluate their histopathologic characteristics, treatment, and outcome. PATIENTS AND METHODS: From January 1975 to December 1997, 56 patients had their malignant ovarian tumors diagnosed, treated, and followed-up in our institution. All tumors were completely excised when possible; otherwise, biopsy was performed. Staging was made according to Federation Internationale de Gynecologie Oncologique classification. Chemotherapy was recommended for all patients. Twelve cases were treated with vincristine, actinomycin, cyclophosphamide (VAC) before 1986; 12 with cisplatin, vinblastine, and bleomycin (PVB) from 1986 to 1989; and 23 with the bleomycin, etoposide, and cisplatin (BEP) regimen from 1989 to present. The Kaplan-Meier survival method was used to calculate the survival. The log-rank test was used to compare groups with respect to survival. RESULTS: Age range was 0 to 16 years (median 11 yrs; average 9.8 yrs). Only two patients were younger than 1 year. The most common presenting symptom was abdominal pain, occurring in 27 patients (48.2%). Thirty-three patients (60%) had total one-sided salpingo-oophorectomy and three patients had bilateral salpingo-oophorectomy. Nineteen patients had stage I, 15 had stage II, 19 had stage III, and 3 had stage IV disease. Dysgerminoma was the most common type. Overall survival (OAS) and event-free survival were 68% (median follow-up time: 71 mos) and 57%, respectively, after 22 years. Histopathology was not correlated with survival. Two important predictors for survival are age (P < 0.0001) and treatment protocol (P = 0.013). The BEP protocol was superior to the other regimens. The OAS was 74.6% in BEP, 55% in PVB, and 63.6% in VAC regimens. CONCLUSION: Although age at diagnosis and treatment with BEP regimen have major roles in determining prognosis of the ovarian tumors in childhood, for patients with advanced ovarian germ cell tumors, intensification of chemotherapy or the development of new approaches is necessary.

Descriptive features of Turkish pathological gamblers.

This study investigated the descriptive features of Turkish pathological gamblers. Participants were 31 male pathological gamblers and 42 "regular gamblers" who acted as controls. The subjects were diagnosed on the basis of DSM-IV pathological gambling criteria and completed the Turkish Version of South Oaks Gambling Screen (SOGS). The nonpathological group was quite comparable with the pathological gambling group with respect to types and frequency of gambling and socio-demographic features. The data on the variables that defined and discriminated pathological gamblers from regular gamblers were collected through administration of a 68-item questionnaire, prepared by the authors. Compared to the non pathological gamblers, the pathological gamblers gambled more to recover their losses, experienced craving for gambling more often, gambled more often to obtain relief from disturbing emotions, harboured more irrational and unrealistic cognitions to rationalize their gambling behavior and suffered more emotionally, financially and socially as a result of their involvement in gambling. The results of the study suggested that Turkish pathological gamblers are very much like their counterparts in Western countries.

Hypertrophic osteoarthropathy in a child with nasopharyngeal carcinoma.

We report a 13-year-old boy with nasopharyngeal carcinoma, skull metastases and hypertrophic osteoarthropathy. Although the metastases and the primary tumour responded well to chemotherapy, hypertrophic osteoarthropathy persisted during follow-up.

Serum CA 125 levels in children with non-Hodgkin's lymphoma.

To evaluate the role of serum CA 125 levels for the diagnosis, follow-up, and prognosis in childhood non-Hodgkin's lymphomas (NHL), 44 children (35 newly diagnosed patients and 9 patients with relapsed or progressive disease, median age 6.5 years, M/F ratio 2.1) with NHL were included in this study. CA 125 levels in serum and/or ascites and effusions were measured by radioimmunoassay. The upper limit of normal was 35 IU/mL. The correlation of CA 125 levels with tumoral location and treatment results were investigated. A total of 27 (61.4%) patients had increased and 17 patients had normal serum CA 125 levels. Fifteen patients with increased CA 125 levels had malignant ascites, pleural effusion, or both, although none with normal CA 125 levels had any serous membrane involvement. The mean CA 125 levels were 72.5 IU/mL in patients with no serosal involvement (ascites or effusion) and, 144.0, 273.7, 324.3 IU/mL in patients with pleural effusion, ascites, and ascites + effusion, respectively. The mean CA 125 levels in ascites and pleural effusion were 202.1 and 156.2 IU/mL, respectively, and were similar to the corresponding serum levels. The increased CA 125 levels returned to normal in 18 patients whose diseases were in remission during the follow-up. One-year survival rate for newly diagnosed patients was 80.2 and 87.5% in patients with increased and normal serum CA 125 levels, respectively. In conclusion, CA 125 levels were significantly higher in patients with serous membrane involvement and there was a correlation between treatment response and marker levels. Little is known about the expression of CA 125 in NHLs. This is the first report suggesting that serum CA 125 levels can be a useful marker for the follow-up of childhood NHL. CA 125 seems to be a promising tumor marker in the assessment of prognosis and therapeutic response in non-Hodgkin's lymphomas.

Prognostic importance of magnetic resonance imaging in bone marrow involvement of Hodgkin disease.

BACKGROUND: Determination of bone marrow involvement is important in staging Hodgkin disease (HD), so we compared the effectiveness of magnetic resonance imaging (MRI) with bone marrow biopsy in diagnosing bone marrow involvement in HD patients. PROCEDURE: Twenty-six patients with the diagnosis of HD were included in this study. The ages of the patients were between 4 and 24 years, with a median of 12. Eleven of them had stage III or IV disease and 15 had been previously diagnosed as having HD and were in relapse. They were evaluated by bone marrow biopsy and MRI of lumbar vertebrae. The biopsies were taken from the anterosuperior iliac spine with an age-appropriate Jamshidi biopsy needle. Within 14 days following biopsy, MRI of lumbar vertebrae was carried out. RESULTS: MRI revealed decreased signal intensity in T1-weighted images in 7 of 26 patients. On the other hand, bone marrow biopsies showed HD involvement in three out of seven patients. The remaining 19 patients who had normal bone MRI were negative for HD in their bone marrow biopsies. The patients with positive MRIs and negative biopsy for HD had bone pain. One of them had a femoral periosteal reaction on bone survey; the other two had height loss in their lumbar vertebral bodies. There was a statistically significant difference in the disease-free survival rates between MRI-positive and -negative patients in the following 24 months period (P < 0.0001). CONCLUSIONS: This study suggests that MRI is a useful method for diagnosing bone marrow involvement in HD, in that our MRI-positive patients had a higher relapse rate in the 24 months follow-up period than the MRI-negative patients.

Recombinant human erythropoietin treatment for chemotherapy-related anemia in children.

OBJECTIVE: The efficacy and safety of recombinant human erythropoietin (rHuEPO) treatment in chemotherapy-induced anemia in children were investigated. rHuEPO is used to treat chemotherapy-induced anemia. Several studies recommend 150 to 300 IU/kg rHuEPO for 2 to 8 months. There are only a few controlled trials in children and no precise data about the optimal dose and duration of rHuEPO treatment is available. PATIENTS AND METHODS: Thirty-four patients receiving chemotherapy for treatment of their solid tumors between October 1996 and June 1997 were included in this study. Patients were randomly selected for each group. The male/female ratio was 20/14, and the median age was 5 years (range, 1-16 years). They had normal hemoglobin levels at the time of diagnosis. When hemoglobin levels decreased to levels lower than 10 g/dL, rHuEPO (150 IU/kg/d, 3 times a week, subcutaneously) was given to 17 patients for 2 months. Their renal, liver, and pulmonary functions were normal. None of the patients had hematologic disease. We did not use any other drugs such as iron or granulocyte colony-stimulating factor. There were 17 patients in the control group. Fifteen patients got chemotherapy regimens including cisplatin (CDDP), but 19 were treated with regimens without CDDP. At the end of rHuEPO treatment, all patients were examined in terms of transfusion requirements and rate of change in hemoglobin levels. RESULTS: One patient in the study group needed a blood transfusion, whereas 8 patients needed a transfusion in the control group. Patients in the study group had less transfusion requirements compared with the control group. The mean hemoglobin levels before and after the study were 8.48 +/- 0.98 g/dL and 8.41 +/- 1.65 g/dL in the control group and 8.50 +/- 0.85 g/dL and 10.21 +/- 2.14 g/dL in the rHuEPO group, respectively. Optimal hemoglobin increments began in 4 weeks and continued during treatment. CDDP-receiving and CDDP-nonreceiving groups did not have any difference in pretreatment serum erythropoietin levels. rHuEPO treatment was more effective in patients treated with non-CDDP regimens. Mean hemoglobin level increased from 8.68 +/- 0.73 g/dL to 10.26 +/- 1.84 g/dL in 9 patients treated with non-CDDP chemotherapy regimens in the erythropoietin group, although it increased from 8.28 +/- 0.97 g/dL to 10.15 +/- 2.5 g/dL in 8 patients treated with CDDP-containing regimens in the erythropoietin group. rHuEPO caused high blood pressure in only 1 patient that resolved spontaneously after cessation of erythropoietin treatment for a week. CONCLUSION: rHuEPO treatment (150 IU/kg/d 3 times a week) is effective and safe in children with chemotherapy-induced anemia. It decreases blood transfusion requirements in solid tumor patients. Our results show that the response to rHuEPO in CDDP-induced anemia is less than the response in non-CDDP receiving patients. Higher doses may be necessary in patients using CDDP.