Peripheral primitive neuroectodermal tumor (PPNET) is a malignant neoplasm of the peripheral nervous system and soft tissues. Representing the fourth case published we herein report a PPNET arising in the pancreas of a six year old girl. She presented with severe anemia due to ulcerative tumor growth and hemorrhage into the duodenum. From the first biopsy pancreatoblastoma was considered as histological diagnosis. Therefore pancreato-duodenectomy was successfully performed. Immunohistochemically, the tumor cells were positive for cytokeratines and several neuronal markers. Due to focal membranous staining for MIC-2 gene product and rosettes in one lymph node metastasis the diagnosis had to be altered into PPNET. This was confirmed by cytogenetic analysis. We conclude that the interpretation of histologic sample excisions from pediatric pancreatic neoplasms may be difficult and that PPNET should be included in the differential diagnosis.

12E7 Antigen↗

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Pamidronate and calcitonin as therapy of acute cancer-related hypercalcemia in children.

Severe symptomatic hypercalcemia is a rare event in children with malignancies. Up to now there is limited experience treating childhood hypercalcemia with bisphosphonates in addition to calcitonin. We report a 5-year-old boy with acute lymphoblastic lymphoma who presented with malignant hypercalcemia at diagnosis. The maximal serum calcium concentration was 15.2 mg/dl (3.81 mmol/l). Conventional therapy with forced diuresis and furosemide failed. Calcitonin (10 IU/kg/24 h i.v. for 2 days) and pamidronate (1 mg/kg over 2 hours i.v.) were used successfully without adverse effect lowering the serum calcium level within 24 hours to normal values. We recommend the use of calcitonin and pamidronate as first-line therapy together with forced diuresis and furosemide in childhood hypercalcemia secondary to malignancies as it is rapidly effective and has no significant side effects.

Alkaline Phosphatase↗

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Megestrol acetate to correct the nutritional status in an adolescent with growth hormone deficiency: Increase of appetite and body weight but only by increase of body water and fat mass followed by profound cortisol and testosterone depletion.

Megestrol acetate (MA) is a synthetic, orally active derivative of the naturally occurring hormone progesterone. MA is increasingly used to correct loss of appetite and improve the nutritional status. We used MA in an adolescent with growth hormone (GH) deficiency due to former irradiation therapy in order to evaluate if MA can improve the nutritional status. In fact, MA increased appetite and weight dose-dependent. The energy expenditure measured by indirect calorimetry changed from hypo- to normometabolism. However, weight gain was first primarily due to an increase in body water and then in fat mass. The gain of fat mass was much more prominent than the gain of fat free mass. As important side-effect, MA lead to rapid and profound cortisol and testosterone depletion after only 10 days with a long-lasting effect on testosterone depletion. Therefore, MA as a single therapy cannot be recommended to improve the nutritional status. If MA is given, cortisol and testosterone levels have to be monitored and supplemented as needed.

Adipose Tissue↗

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[Results of the German studies (MAHO) for treatment of testicular germ cell tumors in children--an update].

BACKGROUND: The MAHO studies for treatment of testicular germ cell tumors in childhood and adolescence registered between 1982 and 1/2001 260 patients (pts.). Aims of the studies were: 1. Delay of chemotherapy in YST of stage I A. 2. Delay of modified lymphadenectomy for staging in I A tumors. 3. Stepwise reduction of therapy in low stage tumors but increasing therapy in tumors of metastatic pattern. Standard therapy consisted of 4 courses of vinblastine, bleomycin and cisplatin. In stage II C or higher chemotherapy included cisplatin, VP 16 and bleomycin. As salvage therapy VP16, ifosfamide and cisplatin was given. RESULTS: According to histology and stage only 75/260 pts. needed chemotherapy. Out of 140 pts. with YST 139 survived disease free according to a "watch and wait" policy. 16 of these patients (13 %) needed a delayed standard chemotherapy 6 - 60 weeks after orchiectomy. Patients with mature (40 pts.) and immature (19 pts.) teratoma were cured by orchiectomy alone. 59 pts. suffered from other malignant non-seminomatous tumors (EC, chorio, mixed tumors). 20 of these had a clinical stage I including 5 with a pathologic stage I A. 15 received adjuvant chemotherapy and all 20 pts. survived relapse-free. 22 pts. had stage II, 8 of these received salvage therapy in addition to standard chemotherapy, 21 of 22 pts. survived. 17 pts. had stage III or IV, 5 of these died despite receiving salvage therapy, 9 pts. survived in complete remission, 3 pts. had partial remission. Both patients with a seminoma (stage I) survived. In summary, the probability of disease free survival of 260 pts. is 97 % after a median observation time of 60 months. CONCLUSION: In alpha-fetoprotein producing YST tumors of clinical stage I A after semincastratio the "watch and wait" surveillance strategy is found to be optimal. Only about 13 % of these patients had to be treated by chemotherapy at a later time point and thus could be cured. For YST pts. of stages greater than stage I A and all other malignant testicular tumors in childhood effective chemotherapy exists with an overall cure rate of about 95 %. Local irradiation or staging lymphadenectomy is unnecessary.

Adolescent↗

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[Supratentorial primitive neuroectodermal tumor: a single center experience and comparison with the literature].

Supratentorial primitive neuroectodermal tumors (stPNETs) are malignant tumors. We saw within three years six children with stPNETs. In four of the six children radical resection could be achieved. All had craniospinal irradiation and chemotherapy according to the HIT-91 protocol. The two children with incomplete resection died due to tumor progression after 7 and 10 months. Two of the 4 children with complete tumor resection had local relapses 8 months after diagnosis and died after 14 and 18 months. One child had a diffuse meningeal relapse 12 months after diagnosis. Despite (high-dose) systemic chemotherapy and intraventricular mafosfamide, he died 21 months after diagnosis due to tumor although remission could be achieved. Only one child is still in remission 86 months after diagnosis.

Brain Neoplasms↗

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[Therapy of testicular germ cell tumors. Current status of the MAHO studies].

The GPOH-MAHO trials designed in 3/82 and 7/88 for treatment of childhood testicular germ cell tumors registered 3/92 105 pts. In MAHO 82 study 57 pts. and in MAHO 88 study 48 pts. were treated. Histologically 60% of the tumors revealed yolk sac tumors (YST), 22% teratomas (TD) and 18% malignant teratomas (MTI, MTU, MTT). Beside unilateral orchiectomy, according to stage and histology a stratified chemotherapy was administered. Standard chemotherapy consisted of 4 courses VLB, BLM, DDP, after 2 courses standard chemotherapy if vital tumor was suspected: explorative laparatomy. According to laparatomy some patients received salvage chemotherapy of 3 courses VP 16, IFO and DDP. The following results were obtained: YST: 59 pts. with stage I. Of these 10 received adjuvant chemotherapy with VLB, BML, DDP. 49 pts. were followed according to wait and see policy and not treated by adjuvant chemotherapy; 8 pts. had a relapse. 5 were treated with standard chemotherapy and 1 pt. with salvage therapy. 1 pt. had stage II and another stage III. Both received standard chemotherapy. The survival of all 61 pts. is 100%. Median observation time is 4 years. TD: 25 pts. had stage I. No chemotherapy was given. The relapse free survival is 100%. Median observation time is 4 years. Malignant teratomas (MTI, MTU, MTT): 8 pts. had stage I. Of these 3 received adjuvant chemotherapy, 5 lymphadenectomy without chemotherapy. All patients survived without relapse. 8 pts. had stage II and received standard chemotherapy, of these 4 pts. had stage IIc and explorative laparotomy was done. According to the result 2 pts. received salvage therapy. All pts. survived relapse free.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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[BEP/VIP in children and adolescents with malignant non-testicular germ cell tumors. A comparison of the results of treatment of therapy studies MAKEI 83/86 and 89P/89].

The treatment regimen of the ongoing cooperative study for non testicular germ cell tumors (MAKEI 89 of the German Society of Pediatric Oncology and Hematology), was stratified as in MAKEI 83 and 86 according to histology, localisation and stage. In the 1989 study, vinblastine was replaced by etoposide, resulting in a chemotherapeutic regimen of 3 to 4 courses BEP and 3 to 4 courses VIP in patients with stage I to IV. Total chemotherapy was reduced for 25%. In children under 1 year of age, bleomycin was omitted and bleomycin dose was reduced to 50%. In children up to 2 years because of two toxic deaths due to bleomycin who were registered in MAKEI 89 Pilot phase. Until Jan. 31, 1993, 230 patients were registered in the MAKEI 89 pilot study and the MAKEI 89 study, containing 186 protocol and 44 follow-up patients (patients with intracranial tumors are excluded for the review). 78 of the registered patients had a teratoma, 9 of these 78 patients suffered from a relapse. In 7 of 9 patients a lasting second remission has been achieved. 12 patients offered with germinoma. 1 of 12 patients had a recurrence but is in second remission. 47 patients had malignant non germinomatous germ cell tumors with an event free survival of 91 +/- 0.4%. 2 of the 47 patients relapsed and died. Toxicity was mainly hematologic without evidence of long term effects. Bleomycin induced pulmotoxicity (WHO grade IV) was documented in 1 protocol patient (see above). Nephrotoxicity with a grade III (WHO) decrease of creatinine clearance was found in 25% of the documented patients with a fast return to normal values after the end of therapy in most of the children. For the follow-up MAKEI 93 study, different topics are defined. 1. The value of chemotherapy for immature teratoma has to be discussed. 2. In invasive immature teratoma in children over 1 year of age, the effectiveness of chemotherapy should be proved. 3. Germinomas show high platinum sensitivity, therefore a platinum based chemotherapy has to be examined for this risk group. 4. The value of a wait and see strategy similar to the proved regimen in the French germ cell tumor protocol has to be verified in patients with stage I non germinomatous germ cell tumors. 5. An intensification of chemotherapy in patients with malignant stage III and IV non germinomatous germ cell tumors has to be examined as a new therapeutic approach for this risk group.

Adolescent↗

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[Non-testicular germ cell tumors: analysis of the therapy study MAKEI 83/86 anc changes in the protocol for the follow-up study].

205 patients with germ cell tumors were entered into the GPO Cooperative Study MAKEI 83/86 and classified as follows: 97 teratomas, 66 yolk sac tumors, 22 dysgerminomas, 17 embryonal carcinomas and three choriocarcinomas; 20% of all tumors were classified as mixed histology. Predominant primary sites were the ovaries (91 pts), the saccrococcygeal region (74 pts), the mediastinum (12 pts), the peritoneal cavity (10 pts) and other sites (18 pts). The treatment of teratomas was primarily surgery. Localised dysgerminomas received radiotherapy following surgery, in advanced stages (III, IV) four courses of chemotherapy vinblastine 3 mg/m2/day (days 1 + 2), bleomycin 15 mg/m2/day (days 1-3) and cisplatinum 20 mg/m2/day (days 4-8) (VBC) were applied. The other fully malignant tumors received four courses of VBC chemotherapy, in extragonadal primary tumors and advanced stages of all sites additional four courses of VP16 100 mg/m2/day (days 1-3), ifosfamide 1500 mg/m2/day (days 1-5) and cisplatin 20 mg/m2/day (days 1-5) (VPIC) were administered. To avoid mutilating surgery in advanced disease, four courses of VBC chemotherapy were administered prior to resection. The relapse-free survival according to Kaplan-Meier for protocol patients with teratomas is 0.97 +/- 0.01, for dysgerminomas 0.73 +/- 0.09 and for other fully malignant histologic entities 0.81 +/- 0.02 with a median period of observation of 31 months. The toxicity mainly consisted of myelosuppression during VPIC chemotherapy in 39 of 62 pts resulting in twelve incidents of sepsis with lethal outcome in two pts. Impaired renal function was reported in 14 pts, the incidence of neuropathy, ototoxicity and pulmonary toxicity was negligible. For the follow-up study a reduction in chemotherapy seems justified in patients with favourable prognosis. The substitution of VP16 for vinblastine may result in reduced toxicity.

Adolescent↗

PubMedDate not supplied

[Preoperative chemotherapy of nephroblastoma. Preliminary results of the SIOP-9/GPO therapy study].

The therapeutic strategy of the SIOP-9 study includes pre-operative chemotherapy for all patients with nephroblastoma diagnosed by imaging methods aged between 0.5 and 16 years. By pre-operative chemotherapy the rate of radical resectable tumors should be increased and thereby the intensity of postoperative therapy, in particular of radiotherapy, diminished. Patients with nephroblastoma stage I-III were in case of tumorresponse randomised in either a 4 weeks or 8 weeks arm of pre-operative treatment with ACT D and VCR. The question was, if a prolongation of pre-operative chemotherapy could increase the relative part of stage I. Between 1/1/89 and 6/30/91 from 49 oncologic centres of former western Germany 188 patients were registered in the SIOP-9/GPO. From the stage I-III patients between 0.5 and 16 years 80.1% were pretreated with cytostatic agents. Only 53.9% of the patients with tumorresponse were randomised. The relative frequency of intraoperative ruptures was with 3% lower in the group of pretreated patients than in the primary operated (15.3%). The stage distribution for all Wilms' tumor patients showed a prevalence of stage I with 43.3% (after pre-operative treatment 59%; after primary operation 28%). Abdominal radiotherapy was performed in 22.4%. The event-free survival rate of all nephroblastoma lay at 85% 3 years after diagnosis (stage I standard 96%; unfavorable histology all stages 45%). 7.3% of the patients developed a hepatopathy under treatment and 7.8% even a VOD according to the criteria of McDonald.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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[Hemophagocytic syndrome in childhood].

Disorders of the histiocyte-macrophage system in childhood comprise a manifold variety of clinical entities. The basic immunopathological mechanisms have still not been clarified in detail. We report on a 15 months old Yugoslavian boy of non-consanguineous parents, who developed persistent high temperatures and bloody diarrhoea at the age of 11 months, followed by a rapidly progressive dystrophy, hepatosplenomegaly and peripheral pancytopenia. An extensive virological, bacteriological and protozoal diagnostic program failed to reveal a pathological result. A bone marrow aspiration showed an extremely hypocellular marrow without infiltration of pathological cell populations. In spite of extensive supportive care and systemic steroid therapy, the patient died by bleeding complications due to severe untreatable thrombocytopenia. In post-mortem-biopsies a marked infiltration of RES-organs (lymph nodes, liver and spleen) by mature histiocytes, showing marked hemophagocytosis, was seen.

Disseminated Intravascular Coagulation↗

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[Intracranial germ cell tumors: analysis of the therapy study MAKEI 83/86 and changes in protocol for the follow-up study].

As part of the Cooperative Germ Cell Tumors Studies MAKEI 83/86 of the German Society of Pediatric Oncology, 37 patients with intracranial germ cell tumors were registered. Based on histological criteria and tumor markers, 26 were classified as germinomas, 9 as fully malignant non-germinomatous germ cell tumors (2 yolk sac tumors, 1 embryonal carcinoma, 1 choriocarcinoma, 5 mixed type germ cell tumors), and 2 were mature teratomas. Of 26 patients with germinomas, 14 received radiotherapy only, all patients are surviving disease-free, median period of observation: 2 years, 10 patients were treated with both chemotherapy and radiotherapy, 8 of these patients are surviving disease-free. Of the 2 patients who received chemotherapy only, none is surviving. Of 9 patients with fully malignant non-germinomatous germ cell tumors, 4 are surviving following surgery, cisplatinum-based chemotherapy and radiotherapy more than 2 years following diagnosis, 1 of these 4 patients with stable disease. Of 2 patients with mature teratomas, 1 is surviving disease-free. Based on these data, recommendations for diagnostic evaluation and therapy of intracranial germ cell tumors are outlined.

Antineoplastic Combined Chemotherapy Protocols↗

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[Malignant testicular tumors in children. Concept of the cooperative therapy study MAHO 88 based on MAHO 82].

The German society of Pediatric Oncology (GPO) designed in 1982 a cooperative study to improve the outlook of patients with malignant testicular germ cell tumors (MAHO 82). So far the combined modality therapy was effective to increase the relapse free survival (Haas et al. 1988). From the data the MAHO 88 protocoll was outlined as follows: Yolk sac tumor: Unilateral orchiectomy; Stage I A - wait and see. Stage I B/C-IV 4 courses standard chemotherapy. If alpha-feto-protein after 2 courses is still positive explorative laparatomy has to be performed. Malignant teratoma (MTI, MTU, MTT), seminoma: Unilateral orchiectomy. Stage I: 4 courses standard chemotherapy. Stage II-IV: 2 courses standard chemotherapy, explorative laparatomy. During explorative laparatomy 3 different approaches are recommended: Modified lymphadenectomy, radical lymphadenectomy or removal of "bulky disease". In case of presence of vital tumor cells patients with teratoma receive "salvage therapy", patients with seminoma receive instead x-irradiation. If only differentiated teratoma cells are found in addition 2 courses of standard chemotherapy are administered. Standard chemotherapy consists of Vinblastine, Bleomycine and Cis-platinum, salvage therapy of VP 16, Ifosfamide and Cis-platinum.

Adolescent↗

PubMedDate not supplied

[The COALL-85 cooperative study for risk patients with acute lymphatic leukemia: initial results].

A frequent change of non-crossresistant drug combinations might obviate the problem of multiple resistant cell lines in malignant diseases and thus increase cure rates. In a multicenter cooperative study for childhood acute lymphoblastic leukemia (ALL) 109 high-risk patients were randomized to receive 5-6 different drug combinations either in slow rotation (change of drugs every 4-6 weeks) or in rapid rotation (change of drugs every 2-3 weeks) for early intensive treatment. Both groups received the same total amount of drugs within the same period of time. 108/109 patients achieved complete remission. One child failed to enter remission and one was lost in remission due to viral infection. Patients in the rapid rotation arm required 2-3 weeks less time to complete the intensive therapy due to fewer episodes of prolonged myelosuppression. Toxic side effects and infectious complications were comparable in both groups. 9/109 patients relapsed, 6 in the bone marrow and 3 in the central nervous system. As yet none of the 31 patients with an initial white blood count of greater than or equal to 100/nl has relapsed. The probability of relapse-free survival is 88% in the rapid rotation arm and 86% in the slow rotation arm at 2 1/2 years. The results compare favourably with other protocols for high-risk patients but have still to be considered as preliminary because of the short median observation time of 18 months.

Adolescent↗

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[Myeloablative chemo- and radiotherapy with autologous and allogenic bone marrow reconstitution in children with metastatic neuroblastoma].

22 children with metastatic neuroblastoma received myeloablative chemoradiotherapy followed by bone marrow transplantation (BMT). The duration of preceding chemotherapy was 4-30 months and included treatment of recurrences in 10 children. At BMT 12 patients were in CR, 9 in PR and one had tumor progression. 10/15 of autologous bone marrows were purged using immunomagnetic bead method of Kemshead and 2/15 using 4 hydroperoxycyclophosphamide. Myeloablative therapy consisted of melphalan and total body irradiation (TBI) in 13 patients (three each supplemented by vincristine or adriamycin/etoposide), in one child of melphalan and mIBG and in 3 children of melphalan alone. 3 children received double autograft and 2 cyclophosphamide (and TBI). 10 patients survived 0-32 months from BMT and 5-48 months from diagnosis, respectively. 12 patients died including 7/12 of tumor progression and 5/12 of toxicity (venoocclusive disease, gut toxicity, septicemia, pneumonia). We conclude that at this point BMT after conventional high dose chemotherapy may provide the only real chance of survival for a significant number of children with metastatic neuroblastoma.

Abdominal Neoplasms↗