bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver function studies in children with acute lymphocytic leukemia after cessation of therapy
Authors: Bessho Fumio , Kinumaki Hiroshi , Yokota Shunichiro , Hayashi Yasuhide , Kobayashi Miyuki , Kamoshita Shigehiko
Published: February 2007

We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone + vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L‐asparaginase (7 patients). Patients treated with VP regimen short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty‐five patients remained in first complete remission and had completed 3‐year maintenance therapy with methotrexate (MTX) and 6‐mercaptopurine (6‐MP) 1–7 years prior to this study. Twenty‐three patients had transfusions of packed red blood cells or fresh whole blood (1–11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2‐hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids + deoxycholic acids to chenodeoxycholic acids + lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long‐term follow‐up of survivors of ALL treated with hepatotoxic chemotherapy during childhood. © 1994 Wiley‐Liss, Inc.
Cytogenetic abnormalities of small round cell tumours
Authors: Bown N. P. , Reid M. M. , Malcolm A. J. , Davison E. V. , Craft A. W. , Pearson A. D. J.
Published: February 2007

Between 1987 and 1991, cytogenetic studies were carried out on small round cell tumours of 68 patients from the Northern Health Region of England. Clonal chromosome abnormalities were found in 30, comprising 15 neuroblastomas, 7 Ewing's tumours, 7 rhabdomyosarcomas, and 1 granular cell tumour. Characteristic rearrangements were found in five cases of Ewing's tumour [all with translocation t(11;22) (q24;q12)] and in four cases of rhabdomyosarcoma [all with evidence of translocation t(2;13) (q35–37;q14)]. In one case of Ewing's tumour and three of rhabdomyosarcoma, the cytogenetic findings were important in diagnosis. Within the neuroblastomas, examples were found of hyperdiploidy, 1p rearrangements, double minute chromosomes, and homogeneously staining regions, but too few cases were available for prognostic associations to be assessed. Our findings confirm the diagnostic importance of chromosome abnormalities in small round cell tumours and indicate that cytogenetic analysis should be an intrinsic part of the initial investigations of all patients with such tumours. © 1994 Wiley‐Liss, Inc.
Factors contributing to the prognostic significance of bone marrow involvement in childhood non‐Hodgkin lymphoma
Authors: Sandlund J. T. , Ribeiro R. , Lin J.‐S. , Ayers D. , Santana V. M. , Furman W. L. , Mahmoud H. , Berard C. W. , Hutchison R. E. , Crist W. M. , Rafferty M. , Pui C.‐H.
Published: February 2007

To evaluate the clinical characteristics and treatment outcome of childhood non‐Hodgkin lymphoma (NHL) cases with bone marrow involvement, we studied 13 lymphoblastic, 15 small noncleaved cell, and 8 large cell cases with tumor cells in their marrow. They represented 16%, 11%, and 9% of consecutive NHL cases with these respective histologic subtypes. The treatment outcome differed significantly according to histologic subtype—the 5‐year event‐free survivals (EFS ± SE) for large cell NHL, small non‐cleaved cell NHL, and lymphoblastic NHL cases were 11 ± 8%, 40 ± 20%, and 62 ± 15%, respectively. Increased serum lactate dehydrogenase (LDH) levels (>500 U/L) were associated with a poorer EFS (5‐year EFS, 0% vs. 50 ± 10%; P < 0.001). Children ⩽5 years of age had a poorer EFS survival than older children (5‐year EFS, 14 ± 9% vs. 44 ± 10%; P = 0.03). The degree of bone marrow involvement (<5% vs. ⩾5%) and race were not significantly associated with treatment outcome. Although intensive chemotherapy has substantially improved survival for patients with advanced stage lymphoblastic or small noncleaved cell lymphoma, patients with large cell NHL and associated marrow involvement continue to have a dismal outcome and require novel or more intensive therapy. © 1994 Wiley‐Liss, Inc.
Cerebral atrophy in an infant following treatment with ifosfamide
Authors: Bruggers Carol S. , Friedman Henry S. , Tien Robert , Delong Robert
Published: February 2007

Ifosfamide, a nitrogen mustard derived alkylating agent commonly used in the treatment of solid tumors, has been associated with neurotoxicity in 5–33% of treated patients. Encephalopathy most often occurs during or shortly following drug administration, with increased drowsiness or irritability, confusion, hallucinations, visual blurring, extrapyramidal dysfunction, cranial nerve abnormalities, incontinence, generalized muscle twitching, seizures, and coma reported in infants, children, and older adults. While most reported neurologic abnormalities associated with ifosfamide have been reversible, encephalopathy resulting in death has occurred.

We now report an infant who developed ifosfamide‐induced encephalopathy, loss of developmental milestones, progressive brain atrophy, and cessation of cranial growth. This is the first case of cerebral atrophy and loss of developmental milestones that has been reported in a pediatric patient treated with ifosfamide. Given the efficacy of this anti‐neoplastic agent and its increasing use in pediatrics, further investigation is indicated, especially in infants where brain growth is ongoing. © 1994 Wiley‐Liss, Inc.
Treatment of malignant testicular tumors in childhood: Results of the german national study 1982–1992
Authors: Haas Rainer J. , Schmidt Piroska , Göbel Ulrich , Harms Dieter
Published: February 2007

The German Cooperative Protocol for treatment of testicular germ cell tumors in childhood registered 106 patients from January 1982 through February 1992. Sixty‐one patients suffered from yolk sac tumors (YST); 25 patients from differentiated teratomas (TD); 19 patients from malignant teratomas of either intermediate (MTI), undifferentiated (MTU), or trophoblastic type (MTT), and 1 patient from a seminoma.

A stratified chemotherapy based on stage and histology was administered in addition to unilateral orchiectomy: Standard chemotherapy consisted of four treatments with vinblastine, bleomycin, and cisplatinum. If viable tumor was suspected after two treatments with standard chemotherapy, a delayed explorative laparotomy was done. There were two options based on the histological findings: In case of complete tumor regression, the standard chemotherapy was continued. In case of incomplete tumor response, patients a salvage chemotherapy consisting of three treatments with VP 16 (etoposide), ifosfamide, and cisplatinum. In addition three injections with VP 16 were given as a maintenance therapy.

The following results were obtained: YST: 59 patients with stage I. Forty‐nine patients were followed according to “wait and see” policy. Eight of these needed a delayed standard chemotherapy. The relapse free survival of all 61 patients in 100%. Median observation time is 49 months.

TD: Twenty‐five patients had stage I. No chemotherapy was given. The relapse free survival is 100%. Median observation time is 48 months.

Malignant teratomas (MTI, MTU, MTT): 8 patients had stage I. Three of these adjuvant chemotherapy and 5 lymphadenectomy without chemotherapy. All patients survived without relapse. Nine patients had stage II and standard chemotherapy. Four of these patients had a delayed explorative laparotomy leading to a salvage therapy in two patients. All patients survived relapse free. Two patients had stage III. Of these 1 standard chemotherapy and is well. One patient suffering from MTU stage IIIA died due to candida septicemia during salvage therapy. Median observation time of the entire group is 60 months. © 1994 Wiley‐Liss, Inc.
Effects of CPT‐11 (a unique DNA topoisomerase I inhibitor) on a highly malignant xeno‐transplanted neuroblastoma
Authors: Komuro Hiroaki , Li Pai , Tsuchida Yoshiaki , Yokomori Kinji , Nakajima Katsuyoshi , Aoyama Takao , Kaneko Michio , Kaneda Norimasa
Published: February 2007

Although many advances have been made in the management of neuroblastoma, the prognosis of patients with advanced neuroblastoma remains poor, and constant efforts are being made to search for newer effective drugs. CPT‐11 is a newly developed derivative of camptothecin and shows a unique anti‐tumor activity by inhibiting DNA topoisomerase I. In this study the effects of CPT‐11 on a human neuroblastoma xenograft, TNB9, were investigated according to the standard Battelle Columbus Laboratories protocol. TNB9 is one of the most malignant strains of neuroblastoma, showing a homogeneously staining resion (HSR) on chromosome 20 and 80‐fold amplification of the N‐myc gene. This study disclosed that CPT‐11 was highly effective against TNB9. Maximum inhibition rate (IR) was 72.5% at a standard dose and 52.8% even at half the dose. No nude mouse used in this study lost weight after an administration of CPT‐11. Plasma pharmacokinetics of CPT‐11 administered in this experimental model were compared to that in clinical patients. Our data suggested that CPT‐11 might be a promising new drug in the treatment of high‐risk neuroblastoma patients and encouraged us to employ CPT‐11 in the protocol of the Study Group of Japan. © 1994 Wiley‐Liss, Inc.
Etiology of neutrophilic granulocytic hypoplasia in a case of large granular lymphocytic leukemia with paraproteinemia
Authors: Friedman Henry D. , Goldberg Jack , Kurec Anthony S. , Davey Frederick R.
Published: February 2007

The association between large granular lymphocytic leukemia (LGLL) and neutropenia is poorly understood. We attempted to assess whether neutropenia in LGLL with paraproteinemia has a different etiology than LGLL without paraproteinemia. We found neither direct serum inhibition of granulocyte/monocyte‐colony forming units in vitro nor increased immunoglobulin binding to granulocytic neutrophils, neutrophil precursors, or granulocyte/monocyte‐colony stimulating factor. Clonogenic assay experiments suggested that suppression of the patient's granulocyte/monocyte‐colony forming units by the neoplastic T‐cells and decreased granulocyte/monocyte‐colony stimulating factor production contributed to the pathogenesis of neutropenia in this particular case. © 1994 Wiley‐Liss, Inc.
Paradoxical response of a pineal immature teratoma to combination chemotherapy
Authors: Lee Anselm C. W. , Chan Godfrey C. F. , Fung C. F. , Leung S. Y. , Lau Y. L.
Published: February 2007

A case of primary intracranial germ cell tumour is reported in a 5‐year‐old Chinese boy who presented with symptoms and signs of increased intracranial pressure. Computed tomography (CT) scan of the brain revealed a multicystic tumour over the pineal region. Stereotactic biopsy yielded enteric epithelium and isolated cells with hyperchromatic nuclei and high nuclear‐to‐cytoplasmic ratio, suggesting the diagnosis of an immature teratoma. Grossly elevated serum and cerebrospinal fluid (CSF) levels of α‐fetoprotein and mildly elevated levels of β human chorionic gonadotrophin suggested the simultaneous presence of embryonal tissues. Combination chemotherapy with cisplatin, etoposide, and bleomycin resulted in a gradual but complete normalisation of the serum and CSF tumour markers. Paradoxically, the patient's consciousness deteriorated and repeat CT scan after 3 months of treatment showed that the tumour was actually increasing in size. Complete surgical removal was attempted and histologic sections of the specimen revealed only mature teratomatous tissues. The child is now well and remains disease‐free with minimal left hemiparesis 12 months after completion of treatment. This case illustrates the importance of combined neoadjuvant chemotherapy and surgery in the management of intracranial non‐germinomatous germ cell tumour harbouring both germ cell and teratomatous components, while monitoring of both biochemical and radiological parameters are necessary in assessing the clinical behaviour of mixed germ cell tumours. © 1995 Wiley‐Liss, Inc.
Prolonged survival following multiple thoracotomies for metastatic hepatoblastoma
Authors: Passmore S. Jane , Noblett Helen R. , Wisheart James D. , Mott Martin G.
Published: February 2007

A 14‐month‐old boy presented with hepatoblastoma, which was completely excised. He had pulmonary metastases, diagnosed 1 year later, treated with chemotherapy followed by resection at age 2 1/2 years. At the age of 3 1/2 years a further metastasis was shown on CT scan and this was resected. Two further metastses were resected at ages 4 1/2 and 5 1/2 years. At age 9 1/2 he had a further isolated pulmonary metastasis resected and is again disease‐free more than 30 months from the last thoracotomy. Prolonged survival following metastatic hepatoblastoma can be achieved with repeated thoracotomies, especially if the first recurrence is more than 6 months from diagnosis and the number of metastases is small. Follow‐up examinations should be both radiological and with serum alpha fetaprotein (SαFP). © 1995 Wiley‐Liss, Inc.
Treatment of osteosarcoma with ifosfamide: Comparison of response in pediatric patients with recurrent disease versus patients previously untreated: A pediatric oncology group study
Authors: Harris Michael B. , Cantor Alan B. , Goorin Allen M. , Shochat Stephen J. , Ayala Alberto G. , Ferguson William S. , Holbrook Tate , Link Michael P.
Published: February 2007

This study was designed to test if the activity of a phase II agent, ifosfamide, would have been underestimated if it was tested exclusively in a population of children and young adults with recurrent osteosarcoma. The response rate to ifosfamide was compared in patients younger than 30 years of age with previously untreated osteosarcoma with metastases at diagnosis and/or unresectable primary tumors (stratum 1) with that of patients with recurrent osteosarcoma following adjuvant chemotherapy who were not previously exposed to ifosfamide (stratum 2). Evaluation of response was conducted 3 weeks after two courses of ifosfamide (2400 mg/m2 × 5 days) were administered 3 weeks apart.

Nine of 33 (27%) evaluable patients in stratum 1 responded (1 complete and 8 partial responses) to ifosfamide. Among 30 evaluable patients in stratum 2, only 3 (10%) responded (1 complete and 2 partial responses; P = .04) Both groups of patients received equal doses of ifosfamide and experienced comparable toxicities.

Results from this study suggest that the activity of new agents will be underestimated if tested in a population of heavily pretreated patients with recurrent disease. When possible, new chemotherapeutic agents should be tested in patients with a poor prognosis who have not been exposed to chemotherapy. © 1995 Wiley‐Liss, Inc.
Acute urticaria and hepatitis complicating high‐dose methotrexate therapy
Authors: Al‐Lamki Zakiya , Thomas Eileen , El‐Banna Nagwa , Jaffe Norman
Published: February 2007

We report an unusual case of anaphylaxis and hepatitic dysfunction in a child with the administration of the twenty‐third course of high‐dose methotrexate. The latter had been used as an adjuvant to prevent pulmonary metastases and the prior 22 courses had been well tolerated. An attempt to reinstate methotrexate after the twenty‐third course was again followed by a similar reaction. © 1995 Wiley‐Liss, Inc.
Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma
Authors: Caron Huib
Published: February 2007

In neuroblastoma, N‐myc amplification and loss of heterozygosity for the short arm of chromosome 1 (LOH 1p) are common genetic abnormalities. We have recently shown that the presence of additional material of the long arm of chromosome 17 (add.17q) also occurs relatively frequently. In the present study, we analyzed a series of 55 tumors for LOH 1p, N‐myc amplification and add.17q, using Southern blot analysis with polymorphic DNA probes of pairs of tumor and constitutional DNA. We determined the correlation of these parameters with clinical variables, such as age, stage, serum lactate dehydrogenase (LDH) and ferritin and also with outcome. LOH 1p occurred in 20 out of 55 cases (36%) and was found more often in stage III/IV tumors and in the older age group, although both correlations were not statistically significant. N‐myc amplification was only demonstrated in 12 tumors with concomitant LOH 1p and was not present in the 35 cases without LOH 1p. Add.17q was found in 20/53 (38%) informative cases. LOH 1p was shown to be the most significant predictor of a poor outcome (P < 0.00001), independent of age and stage. LOH 1p is also of prognostic value in those cases without N‐myc amplification, indicating a stronger prognostic value for LOH 1p. Add.17q was also associated with an unfavourable prognosis, although this was less significantly then with LOH 1p (P = 0.00004). © 1995 Wi1ey‐Liss Inc.
Diabetes insipidus in langerhans cell histiocytosi: Results from the DAL‐HX 83 study
Authors: Grois N. , Flucher‐Wolfram B. , Heitger A. , Mostbeck G. H. , Hofmann J. , Gadner H.
Published: February 2007

Diabetes insipidus (DI) in Langerhans cell histiocytosis (LCH) is a common complication of unclear etiology. The incidence varies among different publications from 15% to 50%. In the prospective DAL‐HX 83 study, 19 out of 199 patients (9.5%) registered with newly diagnosed LCH were diagnosed to have DI. All patients were stratified according to uniform criteria. One hundred and six patients with disseminated disease were treated with standardized polychemotherapy promptly after diagnosis. At the time of diagnosis of LCH, DI was already established in 8 out of 199 patients (4%). After diagnosis, DI occurred in only one out of the remaining 91 patients with localized disease (1%) and in 10 out of 100 remaining patients with disseminated disease (10%). In 8 patients, the onset of DI was associated with other signs of active LCH. The cumulative risk to develop DI after a median observation time of 5 years 3 months was 11%. Retrospective analysis of clinical features revealed multisystem involvement, skull and orbital lesions, and in particular intracranial extension from osseous lesions to constitute risk factors for DI. Magnetic resonance imaging studies (MRI) were available in 12 patients and showed abnormalities of the pituitary region in 10 children. In none of the patients with established DI was it reversed or ameliorated by any treatment. However, the rapid institution of systemic chemotherapy for disseminated disease seems to prevent the occurrence of DI and may be responsible for the low frequency of DI in the DAL‐HX 83 study. © 1995 Wi1ey‐Liss Inc.
Preoperative chemotherapy for mesoblastic nephroma
Authors: Chan K. L. , Chan K. W. , Lee C. W. , Saing Htut
Published: February 2007

A neonate with extensive stage III mesoblastic nephroma was confirmed at operation to have a tumor that was too infiltrative and too advanced for primary excision. The abdomen was closed after multiple biopsies. Vincristine (1.1 mg/m2) was given intravenously once a week for a total of eight doses. Repeat CT scan confirmed shrinkage of the tumor and a nephrectomy could be performed safely and the tumor removed at the second laparotomy. CT scan repeated 1 year later showed no recurrence. This case illustrates the effective use of a single drug pre‐excision chemotherapy which allowed a nephrectomy for extensive stage III mesoblastic nephroma to be carried out safely. © 1995 Wi1ey‐Liss Inc.
The Role of Surgery in the Management of Stage IV Neuroblastoma: A Single Institution Study
Authors: Shorter Nicholas A. , Davidoff Andrew M. , Evans Audrey E. , Ross Arthur J. , Zeigler Moritz M. , O'Neill James A.
Published: February 2007

The role of surgery in the management of Stage IV neuroblastoma is still far from clear. Seventy‐nine patients with this diagnosis presented to the Children's Hospital of Philadelphia during the 10‐year period, 1977 to 1986. Four‐year survival was 23%. A major resection of the primary tumor was undertaken in 54 patients. The timing of the procedure (at presentation or delayed) had no effect on survival. The patients were divided into three groups based on the extent of surgical resection: Group 1, no surgery or biopsy only (25); Group 2, complete gross resection (34); Group 3, incomplete resection with residual gross disease (20). Four‐year survival was 16, 15, and 45%, respectively. The patients were then classified as favorable or unfavorable, on the basis of biological prognostic factors at presentation. When this analysis was combined with the extent of surgery it was discovered that Group 3 contained a higher proportion of favorable patients, accounting for the better survival. Within each group survival correlated with the expected prognosis. The outcome for a patient with Stage IV neuroblastoma depends on the biological characteristics of the tumor, and there is currently no evidence that these can be favorably altered by the timing or extent of surgical resection. Defining the appropriate role of surgery in the management of these patients will require a prospective randomized study which takes into account the inherent biological variability of the disease. © 1995 Wi1ey‐Liss, Inc.
Prognostic Value of Proliferating Cell Nuclear Antigen (PCNA) Immunostaining in Neuroblastoma
Authors: Kawasaki Hirohide , Mukai Kiyoshi , Yajima Shuhei , Tanaka Ryuhei , Takayama Jun , Takasaki Yoshinari , Ohira Mutsuro
Published: February 2007

Immunostaining for proliferating cell nuclear antigen (PCNA), a marker of cell proliferation, is being increasingly used to study the proliferative activity of tumors, and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms. Formalin‐fixed, paraffin‐embedded tissue specimens of 24 primary neuroblastomas were immunostained using an anti‐PCNA monoclonal antibody and the PCNA index was calculated. Then the relationship between the PCNA index, prognosis, and various other factors was assessed, retrospectively. The mean PCNA index was 11.0%. Patients having tumors with a high PCNA index (⩾11.0%) showed a significantly lower survival rate than those possessing tumors with a low PCNA index (P < 0.001). Moreover, the tumors showing N‐myc amplification had a high mean PCNA index of 15.6%, while those without N‐myc amplification had a low mean index of 1.7% (P < 0.01). The PCNA index was closely related to the prognosis of neuroblastoma and to N‐myc amplification. It has the potential to be a useful prognostic indicator of the patients with neuroblastoma. © 1995 Wi1ey‐Liss, Inc.
Recovery of Natural Killer Cells After Chemotherapy for Childhood Acute Lymphoblastic Leukemia and Solid Tumors
Authors: Alanko Soile , Salmi Toivo T. , Pelliniemi Tarja‐Terttu
Published: February 2007

Recovery of natural killer (NK) cells after cessation of chemotherapy for childhood acute lymphoblastic leukemia (ALL) and solid tumors was investigated in 25 children aged 3 to 18 years. The numbers of CD3‐CD56+, CD16+, and CD8‐CD57+ cells in peripheral blood were analyzed with monoclonal antibodies and flow cytometry at 0, 1, 3, 6, 9, and 12 months after discontinuation of therapy. The CD3‐CD56+ and CD16+ cell counts of ALL patients (n = 14) were below the mean ‐1SD values of controls at cessation but normalized within one month due to a rapid 2.1 and 4.5 fold increase, respectively. The CD8‐CD57+ cell count of ALL patients was normal compared to controls at cessation. In solid tumor patients (n = 11), the counts of all NK cell phenotypes studied were of normal amount compared to controls at cessation and no vigorous increase occurred after the therapy.

NK cell function was determined by killing K 562 target cells in five patients. In the two standard risk ALL patients tested, the activity was still low at 5 months after therapy. In contrast, the function was normal at 1 month (Wilms' tumor), 3 months (Mb Hodgkin's) and 6 months (Burkitt lymphoma).

In conclusion, NK cell counts were decreased compared to controls during therapy for ALL, but recovered rapidly afterwards. In spite of normal counts, NK cell function may be impaired for several months. The number and function of NK cells is less affected in solid tumor patients. These differences may reflect the milder immunosuppressive effect of interval cytostatic medication in solid tumor patients when compared to the more intensive continuous therapy in ALL patients. © 1995 Wi1ey‐Liss, Inc.
Response of untreated stage IV Wilms' tumor to single dose carboplatin assessed by “up front” window therapy
Authors: Zoubek Andreas , Kajtar Paul , Flucher‐Wolfram Burgi , Holzinger Beatrix , Mostbeck Gerhard , Thun‐Hohenstein Leonhardt , Fink Franz Martin , Urban Christian , Mutz Ingomar , Schuler Deszö , Gadner Helmut
Published: February 2007

A total of nine children with previously untreated stage IV Wilms' tumor of favorable histology were treated according to the Austrian/Hungarian Wilms' Tumor Protocol 89 and received a preoperative single dose of carboplatin as an “up front” window therapy. The treatment consisted of carboplatin as a single‐dose of 600 mg/m2 over 30 minutes on day 1. Response evaluation by chest X‐ray, serial CT scans, and sonography was performed on day 22. Investigation of the abdominal tumors revealed seven partial responses (78%), one nonresponse, and one progressive disease with a median tumor volume reduction of 62%. Response of metastases evaluated by CT scans was as follows: four complete remission, four partial response, and one nonresponse.

Thrombocytopenia (WHO grade III 1, grade II 2, grade I 2) and leukocytopenia (WHO grade II 1, grade I 5) were the main side effects. No renal or liver toxicity were observed.

The overall response rate after a preoperative single‐dose of 600 mg/m2 carboplatin in untreated patients with stage IV Wilms' tumor is encouraging and the toxicity acceptable. This data indicate that carboplatin seems to be an additional effective drug in patients with previously untreated Wilms' tumor of favorable histology. © 1995 Wiley‐Liss, Inc.
Does chemotherapy have a role in low‐grade astrocytoma management? a report of 13 cases
Authors: Castello M. A. , Schiavetti A. , Padula A. , Varrasso G. , Properzi E. , Trasimeni G. , Operamolla P. , Gualdi G. F. , Clerico A.
Published: February 2007

Surgery is the treatment of choice for low‐grade astrocytoma while radiotherapy is carried out only when total resection is not possible. This study assessed the effectiveness of chemotherapy in nonresectable cases. Thirteen children with nonresectable astrocytoma were treated with carboplatin and etoposide and after four cycles the response to treatment was evaluated according to radiologic criteria. The results were: one with complete response (CR), three with minor response (MR), six with stable disease (SD), and three with progressive disease (PD). Moreover, in 77% there was an improvement in the neurologic picture. In particular, two cases with hypothalamic astrocytoma showed a regression of the diencephalic syndrome following chemotherapy. In six cases chemotherapy was carried out, at reduced dosage, after the first four cycles either because there was clinical improvement or because it was necessary to postpone radiotherapy in very young patients. After a follow‐up period ranging between 11 and 63 months (average: 30 months), nine of the 13 patients are alive (69%) while four died of disease progression. Further studies would be useful to evaluate the role of chemotherapy in the management of low‐grade astrocytoma. © 1995 Wiley‐Liss, Inc.
Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy
Authors: Fink Franz‐Martin , Genser Norbert , Fink Christoph , Falk Markus , Mair Johannes , Maurer‐Dengg Kathrin , Hammerer Ignaz , Puschendorf Bernd
Published: February 2007

Anthracyclines (doxorubicin, daunorubicin, and derivatives) are among the most effective antineoplastic drugs for pediatric cancer with dose‐limiting acute and longterm cardiotoxicity. The exact mechanism of the development of cardiomyopathy is still not clear. Anthracyclines may induce subclinical acute myocardial injury leading to lysis of a limited number of myocytes. Alternatively, myocytes may experience a transient loss of cytoplasmic membrane integrity. Both conditions may lead to a transient efflux of small amounts of cytoplasmic enzymes and other proteins specific to the heart muscle fibers.

To test these hypotheses we assayed plasma creatine kinase (CK) MB mass and cardiac specific troponin T (TnT). CKMB may be released even in case of reversible cell membrane injury, while prolonged elevation of TnT is the most sensitive and specific marker of limited myocardial necrosis.

Thirty‐five anthracycline‐containing chemotherapy courses in 22 children with cancer were analyzed. CKMB mass and TnT concentrations were within the normal range in all children before anthracycline therapy. Within 72 hours from anthracycline therapy no increment of one of these two marker proteins was detected (ANOVA for repeated measures, P = 0.94 [TnT] and 0.25 [CKMB]).

We conclude that only minimal if any acute necroses of cardiac myocytes occur after anthracycline therapy. Even membrane integrity appears to be maintained within the first 3 days after anthracycline therapy, in the absence of electrocardiographic or echocardiographic signs of acute cardiotoxicity. © 1995 Wiley‐Liss, Inc.
Health insurance access to young adult survivors of childhood cancer in North Carolina
Authors: Vann Julie C. Jacobson , Biddle Andrea K. , Daeschner Charles W. , Chaffee Sara , Gold Stuart H.
Published: February 2007

Historically, there has been evidence to support the hypothesis that survivors of childhood cancer have been discriminated against in the private health insurance market in some areas of the United States. Results of previous studies have been inconsistent and have generally focused on a limited number of outcome variables. A retrospective cohort study of young adult survivors of childhood cancer and their siblings was performed to determine the risk of health insurance access problems of childhood cancer survivors in North Carolina. Mailed questionnaires were completed by 182 cancer survivors from three institutions who were diagnosed between 1976 and 1988, and by 101 of their siblings for a response of 62.1%. Using logistic regression in SAS, cancer survivors were found to be more likely to be denied health insurance than their siblings, with an adjusted odds ratio of 15.1. Childhood cancer survivors also had health insurance policies that excluded care for pre‐existing medical conditions more often than their siblings (OR = 5.5). In addition, cancer survivors reported problems obtaining health insurance coverage more frequently than their siblings with an adjusted odds ratio of 22.8. In general, survivors of childhood cancer who were diagnosed in North Carolina have had decreased access to health insurance coverage when compared to their siblings of similar age. North Carolina health insurance regulations permit health insurance firms to discriminate against cancer survivors because of their history of illness, often decreasing their access to needed follow‐up care. © 1995 Wiley‐Liss, Inc.
SIOP working committee on psychosocial issues in pediatric oncology: Guidelines for school/education
Authors: Masera Giuseppe , Jankovic Momcilo , Deasy‐Spinetta Pat , Adamoli Luigia , Ben Arush Myriam W. , Challinor Julia , Chesler Mark , Colegrove Robert , van Dongen‐Melman Jeanette , McDowell Heather , Eden Tim , Epelman Claudia , Kingma Annette , Jones Patricia Morris , Nesbit Mark E. , Reynolds Heidi , Schuler Dezso , Stevens Michael , Vasankari‐Vayrynen Leena , Wilbur Jordan R. , Spinetta John J.
Published: February 2007

This is the second official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology constituted in 1991. It develops one of the topics enclosed in the first document approved by the SIOP Board. The topic, “School/Education,” is addressed to the Pediatric Oncology Community as guidelines to follow for considering this issue in a more appropriate way. © 1995 Wiley‐Liss, Inc.
p53 gene mutations in pediatric brain tumors
Authors: Felix Carolyn A. , Slavc Irene , Dunn Michael , Strauss Eric A. , Phillips Peter C. , Rorke Lucy B. , Sutton Leslie , Bunin Greta R. , Biegel Jaclyn A.
Published: February 2007

We investigated the frequency of p53 mutations in 47 pediatric brain tumors of various histologic subtypes that were collected over a period of 5 years. The specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed glial tumor, eight ependymomas, one choroid plexus carcinoma, and one gangliocytoma/ganglioneuroma. Mutations were identified by single strand conformation polymorphism analysis of exons 4–8 and verified by sequencing. Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC to AGC transition (gly to ser) at codon 245 with loss of the wild‐type allele. A second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with loss of the wildtype allele, but normal tissue was not available for comparison. In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in other histologic subtypes and in two cases with multiple primary cancers. These data are consistent with earlier findings that p53 mutations are rare in PNETs, which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in pediatric low grade astrocytomas suggests not only histological differences, but also a different molecular pathogenesis in adult and pediatric patients. © 1995 Wiley‐Liss, Inc.
Pleuro‐pulmonary blastoma: A case report and review of the literature
Authors: Schmaltz Cornelius , Sauter Siegfried , Opitz Oliver , Harms Dieter , Kremens Bernhard , Lohner Michael , Metz Klaus , Brandis Matthias , Niemeyer Charlotte
Published: February 2007

Pleuro‐pulmonary blastoma is a rare malignant lung tumor in children and distinct from ordinary pulmonary blastoma of adulthood. Combination chemotherapy plays an important role in the treatment of this tumor, but so far no attempt of high dose chemotherapy with subsequent bone marrow or blood stem cell transplantation has been published. The case is reported of a 2‐year‐old boy with pleuro‐pulmonary blastoma who achieved partial remission with conventional chemotherapy and surgery. Subsequent administration of high dose melphalan, etoposide, and carboplatin, followed by autologous blood stem cell transplantation resulted in a 3‐month disease‐free interval but did not prevent eventual local recurrence, leading to death within a few weeks. Clinical presentation, pathology, management, and prognosis are discussed and the literature reviewed. © 1995 Wiley‐Liss, Inc.
Prostatic crystalloids: Association with adenocarcinoma
Authors: Jensen Peter E. , Gardner William A. , Piserchia Philip V.
Published: February 2007

With review of 393 consecutive cases of previously documented prostatic adenocarcinoma, the coexistence of intraglandular crystalloids was confirmed. The various morphologic appearances of these structures are described. Unequivocal crystalloids were identified in 10% of cases. They were most often located in the acini of malignant glands but occasionally were observed in benign glands adjacent to carcinoma. Of available clinical and demographic parameters analyzed, several unexplained statistical relationships were observed, but none of the variables could be used to characterize the patients with crystalloids. This paper suggests that these structures may be useful in the diagnosis of prostatic adenocarcinoma when only inadequate or equivocal biopsy material is available.
Extended field radiation therapy for prostate cancer: Influence of positive lymph nodes on prognosis
Authors: Sause William T. , Roland Thomas A. , Plenk Henry P.
Published: February 2007

One hundred forty‐eight patients with prostate cancer, treated with curative intent at the LDS Hospital from 1969 to 1977, were analyzed. Local control and survival were excellent in patients with negative lymph node evaluations. Eighty‐six percent (24/28) were without evidence of disease at the time of this report. Patients with tumor in pelvic lymph nodes had a poor five‐year disease‐free survival, despite regional radiation therapy. At five years, 17% (3/18) were disease free. External beam radiation is excellent therapy for localized cancer of the prostate gland. The value of regional radiation in the presence of positive adenopathy remains to be defined.
Immunohistological approaches to human prostatic epithelial cells
Authors: Choe B. K. , Pontes J. E. , Lillehoj H. S. , Rose N. R.
Published: February 2007

Specific anti‐acid phosphatase antisera were prepared by the use of purified prostatic acid phosphatase (PAP) from prostatic tissue and lysosomal acid phosphatase (L‐AcP) from diploid fibroblast (WI‐38) as antigen. Since the antigenic difference between the PAP and L‐AcP was established, distribution of these enzymes among various tissues and tissue culture cells was investigated by the indirect immunofluorescence method and the unlabeled antibody method [14]. The L‐AcP has been detected as granules localized in a perinuclear portion of all of the epithelial cells, fibroblasts, and peripheral blood cells except erythrocytes. Presence of the PAP was limited to the prostatic epithelial cells. It is also noted that the biosynthesis of the PAP is strikingly diminished in the long‐term culture of prostatic epithelial cells. However, because of the antigenic difference between the PAP and L‐AcP, and because of the high concentration of PAP in the cytoplasm of prostatic epithelial cells, it is feasible to apply the anti‐PAP immunofluorescence method to the identification of metastatic prostatic carcinoma cells in the biopsy materials.
Fundamental biochemical and immunological aspects of prostatic acid phosphatase
Authors: Lin M. F. , Lee C. L. , Wojcieszyn J. W. , Wang M. C. , Valenzuela L. A. , Murphy G. P. , Chu T. M.
Published: February 2007

Prostatic acid phosphatase (PAP) was purified from human malignant prostate tissue by means of ammonium sulfate fractionation followed by sequential chromatographies of ion exchange, affinity column, and gel filtration. PAP has a molecular weight of 100,000 and consists of two subunits of 50,000. Owing, in part, to sialic acid contents in the molecule, PAP has multiple isoelectric points (pIs) at 4.2‐5.5. In 0.2 M citrate, PAP has the highest affinity (Km 9.2 × 10−5 M) in hydrolyzing α‐naphthyl phosphate among the phosphomonoesters. Tartrate and heat at 37†C for 2 hours almost completely inhibit PAP enzymic activity. By immunoprecipitate technique, anti‐PAP heteroantiserum exhibited a distinct immunologic characteristics. Further, PAP possessed different antibody‐binding site from enzyme hydrolytic site.
The zonal anatomy of the prostate
Authors: McNeal John E.
Published: February 2007

Earlier morphologic studies of the prostate, though often extensive, have never systematically delineated its complete structure. Recent comprehensive analysis of 500 prostates has more precisely defined its anatomic composition, identifying previously undetected features and unsuspected complexities. Using a three‐dimensional model, these structures and relationships are demonstrated. Four basic anatomic regions are described. The relationship of each to the urethra provides a central anatomic reference point.

The peripheral zone constitutes over 70% of the glandular prostate. It forms a disc of tissue whose ducts radiate laterally from the urethra lateral and distal to the verumontanum. Almost all carcinomas arise here.

The central zone constitutes 25% of the glandular prostate. Its ducts arise close to the ejaculatory duct orifices and follow these ducts proximally, branching laterally near the prostate base. Its lateral border fuses with the proximal peripheral zone border, completing in continuity with the peripheral zone, a full disc of secretory tissue oriented in a coronal plane. Marked histologic differences between central and peripheral zones suggest important biologic differences.

Preprostatic region. The urethral segment proximal to the verumontanum is kinked anteriorly at a 35‐degree angle to the distal segment. No major ducts arise in the proximal segment, but the lateral rows of peripheral zone orifices continue. Duct development is aborted here, producing only a small transition zone and several tinier periurethral ducts. The development of these small ducts is possibly determined and limited by their intimate relationship to a periurethral smooth muscle sphincter that exists only proximal to the verumontanum. These small ducts in a restricted area are the exclusive site of nodular hyperplasia (BPH) origin.

The anterior fibromuscular stroma forms the entire anterior surface of the prostate as a thick, nonglandular apron, shielding from view the anterior surface of the three glandular regions. Its inseparable fusion to the glandular prostate has probably delayed recognition of the anatomic features described here.
The immunocytochemical detection of protein hormones in human prostatic tissues
Authors: Sibley P. E. C. , Harper M. E. , Joyce B. G. , Griffiths K. , Peeling W. B.
Published: February 2007

The immunocytochemical detection of four pituitary protein hormones in tissue from 13 patients with benign prostatic hyperplasia has been described. There have been marked differences in the distribution and intensity of reaction product attributable to the various hormonal antisera. The intracellular presence of endogenous prolactin and FSH in the epithelial cytoplasm has been suggested together with the stromal localization of growth hormone and prolactin. Minimal diffuse staining over most cellular components was observed with the LH antiserum. This technique has provided an invaluable means of studying the potential involvement of pituitary protein hormones in the control of prostatic function and disease.
Effect of estrogen on the mixed lymphocyte reaction in normal individuals and prostatic cancer patients
Authors: Herr Harry W.
Published: February 2007

Lack of initial response or relapse to hormones in advanced prostatic cancer may be due to an adverse effect of estrogen on host immune function. This study investigated the effect of dieth‐ylstilbestrol diphosphate (DES‐P) on the normal mixed lymphocyte reaction (MLR) and on the MLR in prostatic cancer patients before and during treatment with DES‐P. These data showed that the normal MLR was suppressed by high concentrations of estrogen in vitro, but physiologic levels of DES‐P were not suppressive. Therapeutic doses of DES‐P did not suppress the spontaneous MLR of prostatic cancer patients compared with previous treatment. Estrogens did not significantly impair the immunologic responsiveness of normal individuals or prostatic cancer patients.
Effect of a new 5α‐reductase inhibitor on size, histologic characteristics, and androgen concentrations of the canine prostate
Authors: Brooks J. R. , Berman D. , Glitzer M. S. , Gordon Lea R. , Primka R. L. , Reynolds G. F. , Rasmusson G. H.
Published: February 2007

Mature male beagles were used in studies designed to determine the effect of the steroidal 5α‐reductase inhibitor 17β‐N,N‐diethylcarbamoyl‐4‐aza‐4‐methyl‐5α‐androstan‐3‐one (4‐MA) on size, histology, and androgen concentration of the prostate. Subcutaneous administration of 3 or 15 mg/kg/day for 43 days caused a sharp decline in prostate volume, flattening of prostatic epithelial cells, vacuolization of the cytoplasm and pycnosis of the nuclei. Whereas serum testosterone levels remained normal in dogs injected with 3 mg/kg/day, they were lower in those that received 15 mg/kg/day. Concentrations of both testosterone and 5α‐dihydrotestosterone were reduced in the prostates of dogs that had received either 3 or 15 mg/kg/day of 4‐MA. The 15 mg/kg/day level also appeared to adversely affect spermatogenesis.

In a 43‐day study, 4‐MA given orally once each day at levels of 0.1, 0.3, or 1 mg/kg failed to cause a significant decrease in prostate volume. However, daily divided oral doses totaling 1 or 3 mg/kg were given in a 42‐day test and both treatment levels produced significant reductions in prostate size.
Cancer of the prostate and aging: An autopsy study in black men from Washington, DC, and selected African cities
Authors: Kovi Joseph , Jackson Marvin A. , Rao M. S. , Heshmat Martin Y. , Akberzie M. E. , Williams A. O. , Christian E. C.
Published: February 2007

Age‐related changes of arteries, veins, glands, and stroma in the prostate of black men from Washington, DC, and from Ibadan, Nigeria, and Accra, Ghana, West Africa, were studied in a total of 795 consecutive, unselected prostate specimens removed at autopsy during a 7‐year period (1973–1980). Except for age group 80 and over, aging changes in the prostate were more severe in all age groups in black men from Washington, DC, than in black men from Ibadan and Accra (P < 0.01). However, when the intensity of age‐dependent alterations was compared in either US or African black men with carcinoma and with no carcinoma, no significant differences were found. These findings do not support the idea that the aging process per se increases susceptibility to cancer.
Plasma androgen levels after subcapsular orchiectomy or estrogen treatment for prostatic carcinoma
Authors: Vermeulen A. , Schelfhout W. , De Sy W.
Published: February 2007

In this study evolution of plasma androgen levels in patients with advanced prostatic carcinoma, treated by either subtotal bilateral orchiectomy or estrogens, was studied in order to determine whether subcapsular orchiectomy results in complete elimination of testicular testosterone secretion and whether in subsequent months there occurs any reactivation of eventually remaining Leydig or increased adrenal androgen secretion. This study, performed on 40 patients having undergone bilateral subcapsular orchiectomy for prostatic carcinoma, shows that this intervention results in testosterone levels in the female range and that during the year following subcapsular orchiectomy there is no evidence for reactivation of Leydig cells or for increased adrenal androgen secretion as evaluated from plasma testosterone, androstenedione, and dehydroepian‐drosterone sulphate levels. In patients treated with estrogens we found no evidence for stimulation of adrenal androgen secretion, whereas in neither group of patients with prostatic carcinoma we found evidence for increased androgen levels at the time of recurrence of the carcinoma.