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2.
J Pediatr Hematol Oncol ; 36(7): e443-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24072250

RESUMO

Basal ganglia germinomas (BGG) are often associated with delayed diagnosis because of their nonspecific clinical presentation and subtle abnormalities on initial neuroimaging. Despite excellent survival, the prognostic indicators still remained unclear. From our case series, we demonstrated that the MRI classification scheme devised by Phi and colleagues is useful in predicting neurological and cognitive outcomes for patients with unilateral BGG. Subtle lesions with faint or no contrast enhancement are associated with early cerebral atrophy with progressive neurological deficits and poor cognitive outcomes. BGG along with bilateral involvement, regardless of the types of lesion, are also associated with poor neurological and cognitive outcomes.


Assuntos
Gânglios da Base/patologia , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Germinoma/classificação , Germinoma/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Criança , Cognição , Germinoma/terapia , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
3.
J Neurooncol ; 99(2): 227-36, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20087754

RESUMO

Germinoma in the basal ganglia (BG) is notorious for its diagnostic difficulty. Clinical and radiological features of this disease are quite diverse, but have not been well characterized with respect to prognosis. We retrospectively reviewed the clinical course and treatment outcomes of 17 patients with a BG germinoma. The initial magnetic resonance imaging (MRI) features were classified. Clinical features and treatment outcomes were then analyzed with this classification scheme. A Type 1 lesion was defined as a subtle lesion with faint or no contrast enhancement (six patients). Type 2, 3, and 4 lesions were defined as contrast-enhancing lesions and were differentiated by the lesion size and the presence of subependymal seeding (11 patients). Type 1 lesions were distinct from the other lesions. Patients with a Type 1 lesion had a significantly longer time from the initial MRI to diagnosis than patients with Type 2, 3, and 4 lesions (P = 0.012). The actuarial progression-free survival and overall survival of patients 5 years after diagnosis were 66 and 77%, respectively. The presence of a Type 1 lesion (P = 0.004), a longer time delay in the diagnosis (P = 0.038), and radiation therapy without complete ventricular coverage (P = 0.010) were significantly associated with tumor progression. Profound motor deficits at diagnosis were associated with deterioration in motor function after tumor remission (P = 0.035). Early diagnosis of BG germinomas could affect the ability to control a tumor and neurological outcomes. In particular, high clinical suspicion and active diagnostic procedures are recommended. For optimal treatment, radiation fields should include entire ventricles even if there is no subependymal seeding.


Assuntos
Doenças dos Gânglios da Base/diagnóstico , Neoplasias Encefálicas/diagnóstico , Germinoma/diagnóstico , Imageamento por Ressonância Magnética , Adolescente , Adulto , Doenças dos Gânglios da Base/classificação , Doenças dos Gânglios da Base/terapia , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/terapia , Criança , Terapia Combinada , Feminino , Seguimentos , Germinoma/classificação , Germinoma/terapia , Humanos , Masculino , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
J Child Neurol ; 24(11): 1439-45, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19841431

RESUMO

Central nervous system germ cell tumors are neoplasms that affect children and young adults. They are subclassified into germinoma and nongerminomatous germ cell tumors. The latter include teratoma (mature teratoma, immature teratoma, teratoma with malignant transformation), choriocarcinoma, embryonal carcinoma, yolk sac tumors, and mixtures of these entities. Germinoma with syncytiotrophoblastic giant cells is a variant of germinoma. Germinomas respond well to radiation therapy, but late sequelae due to irradiation have been reported. The results of radiation treatment alone for nongerminomatous germ cell tumor are not satisfactory. Combination radiochemotherapy has been applied, and this yields a good outcome with less toxicity for germinomas and better survival of nongerminomatous germ cell tumors. This article also discusses other issues, including the controversy regarding spinal irradiation and the treatment of recurrent disease.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/terapia , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/epidemiologia , Criança , Germinoma/classificação , Germinoma/diagnóstico , Germinoma/epidemiologia , Germinoma/terapia , Humanos , Neoplasias Embrionárias de Células Germinativas/classificação , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias da Medula Espinal/classificação , Neoplasias da Medula Espinal/epidemiologia
5.
J Neurooncol ; 88(2): 161-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18286232

RESUMO

Complete remission can be achieved soon after irradiation in patients with intracranial germinoma. This study aimed to analyze the follow-up outcome of intracranial germinoma patients. About 39 intracranial germinoma patients (29 males and 10 females; average age, 15 years; range, 7-27 years) treated at Kyoto University Hospital from 1978 to 2004 were included in the study group. Six patients had multifocal disease at initial diagnosis, and 10 had human chorionic gonadotropin (HCG)-producing tumors. Thirteen patients were treated with craniospinal axis irradiation, 6 with whole-brain irradiation, 17 with whole-ventricle irradiation, and 3 with local field irradiation. Since 1997, 15 patients were treated with reduced-dose whole-ventricle irradiation (median, 23.4 Gy; range, 20.4-27 Gy) followed by a local boost (median, 40.8 Gy; range, 36-54 Gy) combined with chemotherapy. The median follow-up was 94 months (18 months to 25 years). The 5- and 10-year overall survival (OS) rates of the entire group were 97 and 90%, respectively. The 5- and 10-year progression-free survival (PFS) rates of the entire group were 91 and 87%, respectively. The 8-year OS and PFS in 15 patients treated by whole-ventricle irradiation combined with chemotherapy were 100% and 92%, respectively. Four patients had recurrences within a median period of 59.5 months (51-85 months). All relapses occurred outside the radiation fields. Tumor site, tumor size, HCG production, multifocal disease and radiation dose to the primary site or whole ventricle did not significantly affect PFS. All initial recurrences of intracranial germinoma occurred at the distant site out of the radiation field. Our data suggested that reduced doses to the whole ventricle, combined with chemotherapy, should be sufficiently effective in patients with intracranial germinoma.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Tratamento Farmacológico/métodos , Germinoma/tratamento farmacológico , Germinoma/radioterapia , Adolescente , Adulto , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Criança , Intervalo Livre de Doença , Feminino , Germinoma/classificação , Germinoma/patologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
6.
BMC Med Inform Decis Mak ; 7: 27, 2007 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-17877822

RESUMO

BACKGROUND: Numerous methods for classifying brain tumours based on magnetic resonance spectra and imaging have been presented in the last 15 years. Generally, these methods use supervised machine learning to develop a classifier from a database of cases for which the diagnosis is already known. However, little has been published on developing classifiers based on mixed modalities, e.g. combining imaging information with spectroscopy. In this work a method of generating probabilities of tumour class from anatomical location is presented. METHODS: The method of "belief networks" is introduced as a means of generating probabilities that a tumour is any given type. The belief networks are constructed using a database of paediatric tumour cases consisting of data collected over five decades; the problems associated with using this data are discussed. To verify the usefulness of the networks, an application of the method is presented in which prior probabilities were generated and combined with a classification of tumours based solely on MRS data. RESULTS: Belief networks were constructed from a database of over 1300 cases. These can be used to generate a probability that a tumour is any given type. Networks are presented for astrocytoma grades I and II, astrocytoma grades III and IV, ependymoma, pineoblastoma, primitive neuroectodermal tumour (PNET), germinoma, medulloblastoma, craniopharyngioma and a group representing rare tumours, "other". Using the network to generate prior probabilities for classification improves the accuracy when compared with generating prior probabilities based on class prevalence. CONCLUSION: Bayesian belief networks are a simple way of using discrete clinical information to generate probabilities usable in classification. The belief network method can be robust to incomplete datasets. Inclusion of a priori knowledge is an effective way of improving classification of brain tumours by non-invasive methods.


Assuntos
Teorema de Bayes , Neoplasias Encefálicas/classificação , Técnicas de Apoio para a Decisão , Diagnóstico por Computador , Germinoma/classificação , Tumores Neuroectodérmicos/classificação , Neoplasias Encefálicas/diagnóstico , Criança , Bases de Dados Factuais , Diagnóstico Diferencial , Germinoma/diagnóstico , Humanos , Espectroscopia de Ressonância Magnética , Estadiamento de Neoplasias , Tumores Neuroectodérmicos/diagnóstico , Probabilidade
7.
Fertil Steril ; 88(5): 1377-81, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17544417

RESUMO

OBJECTIVE: To assess the quality and activity of spermatogenesis in the contralateral healthy testicle at the time of orchiectomy and to assess whether any tumor-related factor such as tumor type or vascular invasion is a risk factor for impaired spermatogenesis. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Seventy-six patients undergoing orchiectomy for seminoma or nonseminomatous germ cell tumor (NSGCT). INTERVENTION(S): Open biopsy of contralateral healthy testicle at the time of orchiectomy. MAIN OUTCOME MEASURE(S): Quality of spermatogenesis using median and highest Johnsen score in correlation with histopathologic tumor type, vascular invasion, and serum tumor markers and hormone levels. RESULT(S): Contralateral spermatogenesis is reduced in seminomas and in NSGCTs, with median Johnsen scores of 8.9 and 8.6, respectively. Similar results were seen in tumors with vascular invasion (median Johnsen score 8.8 [range 8.2-9.5]) and without vascular invasion (median Johnsen score 8.8 [range 8.1-9.2]). Areas with good-quality spermatogenesis were found in 88.9% of seminoma and 92.5% of NSGCT biopsies. CONCLUSION(S): Testicular cancer is associated with impaired spermatogenesis, but neither the histopathologic tumor type nor the presence of vascular invasion correlated with significantly reduced spermatogenesis.


Assuntos
Germinoma/patologia , Espermatogênese , Neoplasias Testiculares/patologia , Neoplasias Vasculares/patologia , Adulto , Estudos de Coortes , Germinoma/classificação , Humanos , Masculino , Invasividade Neoplásica , Estudos Retrospectivos , Espermatogênese/fisiologia , Neoplasias Testiculares/classificação , Neoplasias Vasculares/classificação
8.
Med. infant ; 14(2): 134-140, jun. 2007. graf, tab
Artigo em Espanhol | LILACS, BINACIS, UNISALUD | ID: lil-510157

RESUMO

Objetivos: Evaluación de las características clínicas y los resultados terapéuticos de los tumores germinales malignos (TGM) extra cerebrales tratados según los lineamientos del protocolo TGM 95 de la Sociedad Francesa de Oncología Pediátrica (SFOP) en una sola institución. Pacientes y Métodos: Entre septiembre de 1995 y septiembre de 2005, 110 pacientes (pts) nuevos consecutivos con tumores germinales extra cerebrales fueron registrados en nuestra institución, 62 de los cuales eran malignos, todos ellos fueron evaluados. El primer gesto diagnóstico terapéutico fue la gonadectomía inicial o la detección de niveles elevados de marcadores tumorales. Los pacientes fueron tratados según los lineamientos del Protocolo TGM 95 de la SFOP. Para la enfermedad estadio I-II completamente resecada y con marcadores positivos, se utilizó una estrategia de expectación y seguimiento. Para los casos avanzados de diseminación hemátogena o niveles de alfa fetoproteína superiores a 15.000 ng/ml se empleó el régimen "VIP" (Etopósido, ifosfamida y cisplatino) 4-6 ciclos. El resto de los casos fue tratado con el regimén VBP (vinblastina, bleomicina y cisplatino) 3-5 ciclos. Resultados: La mediana edad para el grupo fue 12.1 (r: 0-17) años. Varones: 30; mujeres:32 (V/M: 0.94). La signo sintomatología clínica varió según la localización y la extensión tumoral. Hubo 13 (21) pacientes en estadio I y 9 (14,5) en estadio II (35,5). En estadio III y 18 (29) en estadío IV. Ocho (12,9) fueron tumores puros del saco vitelino. Cincuenta (80.6) fueron TGM mixtos con variadas combinaciones de componentes malignos teratomatosos. Dos (3,2) fueron teratomas inmaduros de alto grado. Veintiseis (41,9) fueron de origen ovárico, 25 (40,3) testiculares., 6 (9,7) sacrococcigeos, 3 (4,8) mediastinales y 2 (3,2) de otra localización. Catorce pacientes en estadio I-II y enfermedad inicialmente resecada en forma completa, no recibieron quimioterapia luego del a cirugía.


Assuntos
Criança , Adolescente , Germinoma/classificação , Germinoma/diagnóstico , Germinoma/terapia , Protocolos Antineoplásicos , Protocolos Clínicos
9.
Genes Chromosomes Cancer ; 45(11): 995-1006, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16897744

RESUMO

Previous studies on childhood germ cell tumors (GCTs) report highly variable frequencies of losses at chromosome arm 1p. Since deletions at 1p portend a poor prognosis in other embryonal tumors, this study aims to clarify the question of the frequency of true allelic loss at 1p and whether it constitutes a prognostic parameter. We analyzed 13 GCTs from different gonadal and extragonadal sites of children (4 teratomas, 9 malignant GCTs) and 18 GCTs of adolescents and adults (3 teratomas; 15 malignant GCTs) using automated microsatellite analysis with 23 polymorphic markers and chromosomal "high resolution" comparative genomic hybridization (HR-CGH). With this combined approach, we detected loss of heterozygosity (LOH) at 1p in 8/9 childhood malignant GCTs with concordant data from HR-CGH and microsatellite analyses. In contrast, LOH at 1p was not detected in childhood teratomas (0/4) and constituted a rare event in GCTs of adolescence and adulthood (3/18). The commonly deleted region was located at distal 1p36-pter, with a proximal boundary between the markers D1S450 and D1S2870. These data unequivocally demonstrate that deletion at 1p is common in childhood GCTs and results in allelic loss. This observation argues for the presence of a classical tumor suppressor at distal 1p. Considering the high frequency of LOH at 1p and the overall favorable prognosis of childhood GCTs, a prognostic impact of LOH at 1p in childhood GCTs appears unlikely. However, since two postpubertal tumors with LOH at 1p progressed, a prognostic relevance in this age group seems possible, warranting a prospective evaluation.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 1/genética , DNA de Neoplasias/análise , Germinoma/genética , Perda de Heterozigosidade , Repetições de Microssatélites , Hibridização de Ácido Nucleico , Adolescente , Adulto , Criança , Pré-Escolar , Análise Citogenética , Feminino , Germinoma/classificação , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias do Mediastino/genética , Hibridização de Ácido Nucleico/métodos , Neoplasias Ovarianas/genética , Neoplasias Testiculares/genética
10.
Pathologe ; 25(6): 469-73, 2004 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-15549315

RESUMO

Today the treatment of gonadal germ cell tumors is standardized. The cisplatin containing chemotherapy and the multi-modal therapy strategies have increased the rate of successful treatment enormously. Germ cell tumors are almost always treated surgically. Following the rare, primary chemotherapy, the residual tumor must be classified according to the WHO as accurately as possible. A binding system for the documentation of tumor regression does not exist. The diagnostic retroperitoneal lymphadenectomy is also rare. Here as well, the classification is performed according to the WHO and the TNM classification. The examination of the tissue samples from a retroperitoneal lymphadenectomy after chemotherapy is problematic. The morphology is often bizarre, preparatory and terminological standards do not exist. Is there still vital tumor present then it can most often be diagnosed as a teratoma. In that case a classification takes place as to whether it is "mature" or "immature". If a tissue sample contains other differentiations, the classification is performed in detail according to the WHO classification of germ cell tumors. Sarcomas or carcinomas must be reliably distinguished and classified, as they lead to different therapeutic consequences. The terminology must be defined in a binding manner between both the pathology and the clinic, due to the lack of global definitions.


Assuntos
Germinoma/tratamento farmacológico , Germinoma/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Diferenciação Celular , Feminino , Germinoma/classificação , Humanos , Masculino , Neoplasia Residual , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/patologia , Neoplasias da Próstata/classificação , Neoplasias da Próstata/patologia
11.
J Neurooncol ; 68(2): 153-9, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15218952

RESUMO

There is little literature to guide therapy in children and young adults with intracranial germ cell tumors. We present 17 consecutively diagnosed intracranial germ cell tumors at The Children's Hospital, Denver, from 1995 to 2001. Of 17 patients, 3 had considerable delay in diagnosis. Two with suprasellar tumors presented with dementia, blindness and pan-hypopituitarism and another with recurrent subarachnoid hemorrhage. Seven had germinoma, three were metastatic at diagnosis. Ten had non-germinomatous germ cell tumors (NGGCT), 5/10 were alpha feto-protein (AFP) positive only, one beta-human chorionic growth (betaHCG) factor positive only, 3 positive for AFP and betaHCG, and 1 malignant teratoma. Therapy for metastatic patients consisted of chemotherapy followed by craniospinal radiation (CSI). Patients with localized disease received chemotherapy followed by focal radiation. Two patients received chemotherapy only, one because she died of sepsis while receiving chemotherapy and one because of neurologic injury incurred during surgery parents elected for no therapy. Three patients have died, one of tumor recurrence, one from a remote complication of surgery and one of sepsis. Twelve patients are alive without evidence of disease from 10 to 68 months (median 31.5 months). All five children with only AFP positivity, treated with chemotherapy and focal radiation are alive without evidence of disease at 10, 16, 22, 41 and 41 months. Thus, there is little evidence that CSI is necessary in non-metastatic germinomas and AFP positive NGGCTs when combined chemotherapy and radiation therapy is used. However, complications of delayed diagnosis, surgery and chemotherapy are important causes of mortality, with only one patient dying of tumor.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Germinoma/patologia , Adulto , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Criança , Terapia Combinada , Germinoma/classificação , Germinoma/tratamento farmacológico , Humanos , Estudos Retrospectivos
12.
BMC Cancer ; 4: 10, 2004 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-15113444

RESUMO

BACKGROUND: Traditionally, tumors have been classified by their morphologic appearances. Unfortunately, tumors with similar histologic features often follow different clinical courses or respond differently to chemotherapy. Limitations in the clinical utility of morphology-based tumor classifications have prompted a search for a new tumor classification based on molecular analysis. Gene expression array data and proteomic data from tumor samples will provide complex data that is unobtainable from morphologic examination alone. The growing question facing cancer researchers is, "How can we successfully integrate the molecular, morphologic and clinical characteristics of human cancer to produce a helpful tumor classification?" DISCUSSION: Current efforts to classify cancers based on molecular features ignore lessons learned from millennia of experience in biological classification. A tumor classification must include every type of tumor and must provide a unique place for each tumor within the classification. Groups within a classification inherit the properties of their ancestors and impart properties to their descendants. A classification was prepared grouping tumors according to their histogenetic development. The classification is simple (reducing the complexity of information received from the molecular analysis of tumors), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. The clinical and research value of this historical approach to tumor classification is discussed. SUMMARY: This manuscript reviews tumor classification and provides a new and comprehensive classification for neoplasia that preserves traditional nomenclature while incorporating information derived from the molecular analysis of tumors. The classification is provided as an open access XML document that can be used by cancer researchers to relate tumor classes with heterogeneous experimental and clinical tumor databases.


Assuntos
Neoplasias/classificação , Vocabulário Controlado , Germinoma/classificação , Humanos , Neoplasias/genética , Neoplasias/patologia
13.
Radiographics ; 24(2): 387-404, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15026588

RESUMO

Germ cell tumors (GCTs) occur most frequently in the gonads and are relatively rare in other sites, such as the pineal gland, neurohypophysis, mediastinum, and retroperitoneum. GCTs are thought to originate from primordial germ cells, which migrate to the primitive gonadal glands in the urogenital ridge. Extragonadal GCTs might also originate from these cells when the cells are sequestered during their migration. Pathologic subtypes of GCTs vary, and the prevalence of mixed tumors is high. These factors produce a diversity of radiologic findings and make prospective radiologic diagnosis difficult in many cases. However, similar radiologic findings have been observed in pathologically equivalent tumors in varying sites. Seminomas appear as uniformly solid, lobulated masses with fibrovascular septa that enhance intensely. Nonseminomatous GCTs appear as heterogeneous masses with areas of necrosis, hemorrhage, or cystic degeneration. Fat and calcifications are hallmarks of teratomas, most of which are benign. In immature teratomas, scattered fat and calcification within larger solid components are occasionally seen. These imaging characteristics reflect the pathologic features of each tumor, and histologically similar GCTs at varying sites have similar radiologic features. Knowledge of the pathologic appearances of GCTs and their corresponding radiologic appearances will allow radiologists to diagnose these tumors correctly.


Assuntos
Germinoma , Adulto , Movimento Celular , Criança , Pré-Escolar , Feminino , Germinoma/classificação , Germinoma/diagnóstico por imagem , Germinoma/embriologia , Germinoma/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/embriologia , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/embriologia , Neoplasias Ovarianas/patologia , Pinealoma/diagnóstico por imagem , Pinealoma/embriologia , Pinealoma/patologia , Radiografia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/embriologia , Neoplasias Testiculares/patologia , Ultrassonografia
14.
Br J Cancer ; 90(6): 1176-83, 2004 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-15026798

RESUMO

The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility. We aimed to examine the extent of any loss in discrimination within the IGCC classification in comparison with alternative modelling by formal weighing of the risk factors. We analysed survival of 3048 NSGCT patients with Cox regression and recursive partitioning for alternative classifications. Good, intermediate and poor prognosis groups were based on predicted 5-year survival. Classifications were further refined by subgrouping within the poor prognosis group. Performance was measured primarily by a bootstrap corrected c-statistic to indicate discriminative ability for future patients. The weights of the risk factors in the alternative classifications differed slightly from the implicit weights in the IGCC classification. Discriminative ability, however, did not increase clearly (IGCC classification, c=0.732; Cox classification, c=0.730; Recursive partitioning classification, c=0.709). Three subgroups could be identified within the poor prognosis groups, resulting in classifications with five prognostic groups and slightly better discriminative ability (c=0.740). In conclusion, the IGCC classification in three prognostic groups is largely supported by Cox regression and recursive partitioning. Cox regression was the most promising tool to define a more refined classification. British Journal of Cancer (2004) 90, 1176-1183. doi:10.1038/sj.bjc.6601665 www.bjcancer.com Published online 24 February 2004


Assuntos
Biomarcadores Tumorais/análise , Germinoma/classificação , Germinoma/patologia , Estadiamento de Neoplasias/métodos , Neoplasias Testiculares/classificação , Neoplasias Testiculares/patologia , Humanos , Masculino , Metástase Neoplásica , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
15.
Crit Rev Clin Lab Sci ; 40(4): 377-427, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14582602

RESUMO

The International Germ Cell Consensus Classification (IGCCC) of testicular germ cell tumors (TGCT) in 1997 included three serum tumor markers, serum lactate dehydrogenase catalytic concentration (S-LD), serum alpha fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG). The recommendation should be implemented for all patients with TGCT and is also useful for patients with ovarian and extragonadal germ cell tumors. A fourth serum tumor marker for TGCT, S-LD isoenzyme 1 (S-LD-1), is also relevant for TGCT. Patients with seminoma have a raised S-LD-1 more often than a raised S-AFP and S-hCG, whereas patients with nonseminoma have a raised S-AFP more often than a raised S-LD-1 and S-hCG. A new model combining IGCCC and S-LD-1 predicts survival better than previous staging systems. LD-1 is related to a characteristic chromosomal abnormality in all types of TGCT, a high copy number of chromosome 12p. In contrast, AFP and hCG are found mainly in nonseminomatous germ cell tumors and they related to the histologic differentiation of the tumors. The different biologic background for the serum tumor markers may contribute to the difference in their clinical behavior.


Assuntos
Biomarcadores/sangue , Germinoma/sangue , Gonadotropina Coriônica/sangue , Gonadotropina Coriônica/genética , Disgerminoma/sangue , Disgerminoma/enzimologia , Feminino , Regulação Neoplásica da Expressão Gênica , Germinoma/classificação , Germinoma/patologia , Humanos , Isoenzimas/sangue , Isoenzimas/metabolismo , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Estadiamento de Neoplasias/normas , Prognóstico , Recidiva , Seminoma/sangue , Seminoma/classificação , Seminoma/enzimologia , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/genética
17.
Cancer ; 97(8): 1869-75, 2003 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-12673712

RESUMO

BACKGROUND: Various staging systems have been proposed for disseminated germ cell neoplasms. The Indiana University staging system was based on clinical and radiographic findings only, whereas the newly created International Germ Cell Cancer Collaborative Group (IGCCCG) staging system also utilized serum markers as a prognostic factor. This study updated the intergroup trial that compared the standard therapy of bleomycin, etoposide, and cisplatin (BEP) with etoposide, ifosfamide, and cisplatin (VIP) in advanced germ cell tumors and reanalyzed the results using the IGCCCG staging system. METHODS: From October 1987 to April 1992, 304 patients with advanced-stage germ cell tumors (using the Indiana University staging system) were randomized to receive four cycles of BEP or VIP. Two hundred and eighty-six patients were eligible and fully evaluable. With a median follow-up of 7.3 years, 283 of the 286 evaluable patients from the Eastern Cooperative Oncology Group protocol, E3887, were reclassified using the IGCCCG staging system. Progression-free survival (PFS), overall survival (OS), and toxicity were assessed for the treatment arms. RESULTS: With a longer follow-up of 7.3 years and using the Indiana University staging system, the PFS rates were 64% versus 58% and the OS rates were 69% versus 67% in the VIP and BEP arms, respectively. For patients reclassified with the IGCCCG staging system, the PFS rates were 81%, 72%, and 54% and the OS rates were 89%, 81%, and 60% for good, intermediate, and poor-risk patients, respectively. Differences in OS (VIP, 62%; BEP, 57%) and PFS (VIP, 56%; BEP, 49%) for the subset of patients reclassified as poor risk by the IGCCCG staging system were not significantly different. More toxicity, primarily hematologic toxicity, occurred on the VIP arm. CONCLUSIONS: With a median follow-up of 7.3 years and with a reclassification based on the IGCCCG, OS and PFS rates were comparable between BEP and VIP. Toxicity, primarily hematologic, was modestly greater with the ifosfamide-containing arm. The VIP regimen may be considered a treatment alternative for patients with underlying pulmonary disease. In most patients with poor and intermediate-risk germ cell tumors, four cycles of BEP remain the standard therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Germinoma/tratamento farmacológico , Ifosfamida/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Cisplatino/efeitos adversos , Etoposídeo/efeitos adversos , Seguimentos , Germinoma/classificação , Germinoma/patologia , Humanos , Ifosfamida/efeitos adversos , Masculino , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Chest Surg Clin N Am ; 12(4): 769-89, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12471877

RESUMO

This article has reviewed recent advances in understanding the molecular mechanisms of germ cell transformation, germ cell tumor differentiation, and germ cell tumor chemotherapy sensitivity and resistance. Future developments should include the following: The use of high-throughput techniques to assess tumor biology and evaluate new markers will allow more sophisticated assessment of prognosis. Future therapy will use oligonucleotide chips, perhaps specific to germ cell tumors or gene products associated with drug resistance, to assign treatment (radiation, RPLND, chemotherapy). The pathways associated with metastases and resistance will either replace or amplify the current risk algorithms and the clinician's ability to select therapy. The same high-throughput techniques will identify critical molecules and pathways, providing new specific treatment targets. Cell cycle-specific targets are an ideal focus of study, because genes abrogating normal cell cycle control and promoting germ cell tumorigenesis are increasingly identified. In germ cell tumors, CCND2 and KIT are open to study. Molecular and genetic markers of differentiation are additional resistance markers and should be a focus of study. In this context, the treatment of malignant transformation and the prediction of teratoma at metastatic sites will take on a greater importance. Over the past 2 decades, the treatment of germ cell tumors has become well-defined. Further improvement requires that investigators find new markers corresponding to tumor phenotype. This achievement will prevent unnecessary treatment in patients destined to have a favorable outcome, and will target biologically unfavorable or resistant disease for new therapy developed specifically to target the molecular or genetic defects that disrupt normal cell cycle control.


Assuntos
Germinoma/diagnóstico , Germinoma/terapia , Teratoma/diagnóstico , Teratoma/terapia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Previsões , Germinoma/classificação , Germinoma/epidemiologia , Humanos , Masculino , Biologia Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Teratoma/classificação , Teratoma/epidemiologia , Neoplasias Testiculares/classificação , Neoplasias Testiculares/epidemiologia , Resultado do Tratamento
19.
Cancer Genet Cytogenet ; 135(1): 57-62, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12072204

RESUMO

Most adult testicular germ cell tumors have a characteristic chromosomal abnormality that is an isochromosome 12p [i(12p)]. Furthermore, these tumors are characterized by a chromosome number in the triploid range and gains and losses of (parts of) specific chromosomes. Cytogenetic investigation of three cases of infantile testicular germ cell tumors, all diagnosed as yolk sac tumors, revealed highly abnormal karyotypes. We found one case to be diploid; the other two cases were in the hypertriploid/hypotetraploid range. Structural abnormalities of chromosomes 1, 3, and 6 were recurrent and no i(12p) was found. Our results, together with data from the literature, suggest that infantile and adult testicular germ cell tumors have a different origin and pathogenetic pathway. Aberrations of chromosomes 1, 3, and 6 may play an important role in the pathogenesis of infantile testicular yolk sac tumors.


Assuntos
Cromossomos Humanos Par 12/genética , Cromossomos Humanos/genética , Tumor do Seio Endodérmico/genética , Germinoma/classificação , Neoplasias Testiculares/classificação , Adulto , Fatores Etários , Aneuploidia , Pré-Escolar , Aberrações Cromossômicas , Cromossomos Humanos/ultraestrutura , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 1/ultraestrutura , Cromossomos Humanos Par 12/ultraestrutura , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 3/ultraestrutura , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 6/ultraestrutura , Tumor do Seio Endodérmico/patologia , Germinoma/genética , Germinoma/patologia , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia
20.
J Korean Med Sci ; 17(2): 287-91, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11961322

RESUMO

A rare case of intraventricular germinoma in the third ventricle, which occurred 30 months after total removal of mature teratoma on the same location in a 29- yr-old man is presented. Recurrence is supposed to represent an acceleration of localized dysplastic processes of totipotent germ cells present in the midline neuraxis or a growth of unidentified microscopic residue of germinoma component in mature teratoma. Although the radiation therapy after total removal of mature teratoma is still controversial, careful follow-up is warranted for evaluating a possible recurrence of other germ cell tumors.


Assuntos
Neoplasias do Ventrículo Cerebral/diagnóstico por imagem , Germinoma/diagnóstico por imagem , Segunda Neoplasia Primária/diagnóstico por imagem , Teratoma/cirurgia , Adulto , Neoplasias do Ventrículo Cerebral/classificação , Neoplasias do Ventrículo Cerebral/patologia , Neoplasias do Ventrículo Cerebral/cirurgia , Germinoma/classificação , Germinoma/patologia , Germinoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Segunda Neoplasia Primária/classificação , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Teratoma/complicações , Tomografia Computadorizada por Raios X , Derivação Ventriculoperitoneal
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