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1.
Minerva Urol Nefrol ; 65(4): 235-48, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24091477

RESUMO

The incidence of muscle-invasive bladder cancer (MIBC) is increasing. Many different and multimodal novel treatment options were brought on the way since the beginning of a new era in the early 1980s, when the neobladder as a common option for urinary diversion had been induced. In addition to open radical cystectomy and urinary diversion, recently, minimal invasive surgery has been implemented in experienced centers and led to promising results in short term follow-up, awaiting confirmation in larger cohorts. Pelvic lymphnode dissection can cure patients with low metastatic load. Expansion of pelvic lymphonodal dissection and its influence on survival was discussed intensively with trends to a moderate enlargement of the standard field. Outcome in nodal positive disease is remaining poor, while 90% of patients with multiple lymphnode metastases will suffer from systemic progress 5 years after diagnosis. In the last decade, treatment regimens based on neoajuvant or adjuvant chemotherapy were published with different results on efficiency. To decide whether to treat with surgery alone, or to offer perioperative systemic cytostatic therapy, is one of the unanswered questions. Furthermore, bladder preserving techniques are still optional for patients with small unifocal lesions or the medically unfit cohort. This review summarizes current data and aims to help guiding through several available recommendations on therapy and management of MIBC.


Assuntos
Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Terapia Combinada , Cistectomia/métodos , Humanos , Excisão de Linfonodo , Procedimentos Cirúrgicos Minimamente Invasivos , Músculo Liso , Invasividade Neoplásica , Tratamentos com Preservação do Órgão , Derivação Urinária
2.
Urologie ; 62(2): 171-175, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36066611

RESUMO

There have been numerous new findings from clinical trials in recent years regarding the treatment of metastatic hormone-sensitive or castration-resistant prostate cancer. The newly approved treatment options make therapy planning and therapy sequencing more challenging. In addition, local therapy of metastatic prostate cancer is becoming increasingly important. In the new German guidelines on prostate cancer (version 6.2, October 2021), new developments in the recommendations for the treatment of mHSPC and mCRPC were implemented, and their most important resulting recommendations for the clinical practice are presented in this review.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/terapia , Guias de Prática Clínica como Assunto
3.
Urologe A ; 47(9): 1133-4, 1136, 2008 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-18679650

RESUMO

CpG-oligodeoxynucleotides (CpG-ODN) are potent stimulators of the innate immune system. They promote a Th1-biased immune response with antineoplastic potential. We recently demonstrated antitumoral effects of CpG-ODN in murine transitional cell carcinoma (TCC) models. The purpose of the present work was to more precisely define the immunological nature of this immunotherapeutic approach to TCC.MB-49 TCC was established in female C57/Bl6 mice by intravesical tumor cell instillation after poly-L-lysine conditioning of the bladder (day 0) as described previously. Three groups of six mice were treated: intravesical instillation of 50 microl PBS on days 1, 3, 5, and 7 (group 1, untreated control); 10 nmol CpG 1668 on days 1, 3, 5, and 7 (group 2); and 10 nmol GpC 1668 on days 1, 3, 5, and 7 (group 3). Six native bladders served as no-treatment/no-tumor controls (group 4). Mice were sacrificed on day 11; bladders and draining lymph nodes were removed, and mRNA was prepared for quantitative real-time polymerase chain reaction. Samples were analyzed on a Bio-Rad iCycler for IL 10, TGF-beta, IL 12, and IFNgamma expression; threshold values were compared to beta-actin as housekeeping gene.Tumor take was 100%. Three animals in group 1 had to be sacrificed in advance due to rapid tumor progression. Relative cytokine expression was comparable in groups 1 and 4. IL-10, IL-12, TGF-beta, and IFNgamma were overexpressed in groups 2 and 3. CpG-ODN treatment of murine TCC results in overexpression of both classic Th1 cytokines (IL 12 and IFNgamma) and the Th2 marker IL 10. TGF-beta expression is increased as well. These phenomena are not induced by the growing TCC but by CpG-ODN therapy. They are accompanied by an objective clinical response, as we were able to show recently. Immunostimulatory DNA holds promise to be a novel therapeutic agent in TCC.


Assuntos
Adjuvantes Imunológicos/farmacologia , Carcinoma de Células de Transição/imunologia , Modelos Animais de Doenças , Oligodesoxirribonucleotídeos/farmacologia , Neoplasias da Bexiga Urinária/imunologia , Administração Intravesical , Animais , Linhagem Celular Tumoral , Citocinas/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias/imunologia
4.
Urologe A ; 47(9): 1182, 1184-6, 2008 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-18679648

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) occurs twice as often in men as in women; however, the influence of gender on stage, grade, subtype and prognosis has not been studied in detail. METHODS: This study included 780 patients treated by (partial) nephrectomy at our institution in Marburg between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS: Of the 780 patients, 486 (62%) were men and 294 (38%) were women. Women were significantly older (mean, 65.3 vs. 62.2 years; p<0.001, t-test), presented at lower T stages (p=0.046, chi(2)) and suffered metastasis less frequently at diagnosis (p=0.026, chi(2)). In addition, women more frequently had clear cell tumours (85.2% vs. 78.3%) and less frequently papillary tumours (11.0% vs. 18.8%) than men (p=0.026, chi(2)). In contrast, men had an increased risk of death from RCC (HR 1.23, CI 0.92-1.63); Kaplan-Meier curves revealed a significant difference in tumour-specific survival between men and women (p=0.033, log rank; 5-year survival 74% vs. 83%). However, unlike tumour stage and tumour grade, gender could not be retained as a significant independent prognostic marker in multivariate analysis. CONCLUSION: In general, RCC in men is characterized by higher tumour stages and more frequent metastasis at diagnosis along with inferior tumour-specific survival. However, as gender failed to qualify as an independent prognostic marker for tumour-specific survival, delayed diagnosis due to insufficient routine medical check-up and/or a more aggressive tumour biology might be be a concurrent cause. Thorough regular medical check-ups for men, also with regard to RCC, are thus mandatory.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores Sexuais
5.
Urologe A ; 47(9): 1137-40, 2008 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-18651122

RESUMO

Up to now markers for transitional cell carcinoma of the bladder (TCC) are missing. Fibronectin (FN) seems to play a key role in progression and invasion of malignant tumors. The aim of this study was to assess the value of cellular FN (cFN), a more specific subform of produced FN, in different stages of TCC.cFN was determined using a highly sensitive immunoassay which we developed. Blood samples were taken of 45 patients with the first diagnosis of TCC before undergoing TUR-B and 6 patients with metastatic TCC before chemotherapy; 70 patients with nonmalignant urological disorders served as a control group.Patients with TCC showed significantly elevated cFN plasma levels compared to controls (p<0.05). Patients with muscle-invasive disease (n=15) showed significantly higher cFN plasma levels compared to the group with superficial TCC. Patients with metastatic TCC showed the highest, but not significantly elevated cFN plasma levels compared to patients with muscle-invasive TCC.The elevated cFN plasma levels in TCC underline the important role of cFN for tumor progression and its potential role as a marker for TCC. Upcoming investigations are necessary to prove the value of the potential marker cFN during follow-up and its impact as a prognostic factor for recurrence and progression of TCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células de Transição/patologia , Fibronectinas/sangue , Neoplasias da Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/cirurgia , Cistoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
6.
HNO ; 56(9): 901-7, 2008 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-18688587

RESUMO

BACKGROUND: The aim of this retrospective study was to evaluate prognostic factors for the development of secondary local lymph node metastases in patients with oral squamous cell carcinoma who had undergone selective neck dissection for primary node-negative disease. PATIENTS AND METHODS: The study included 331 patients with primary squamous cell carcinoma of the oral cavity who underwent 431 selective neck dissections between January 1986 and December 2002 in Germany at the Hannover Medical School's Department of Oral and Maxillofacial Surgery. Several potential prognostic factors were evaluated for their influence on the development of secondary metastases following primary neck dissection. RESULTS: No statistically significant relationship to the appearance of secondary local metastasis following selective neck dissection was detected concerning: patient age or sex, histopathologic tumor stage, primary tumor grade, or adjuvant therapies such as pre- or postoperative radiotherapy and radiochemotherapy. The only study factor with a statistically significant influence was the extent of lymphadenectomy, in which particularly the region of the carotid bifurcation played a decisive role. CONCLUSION: Significantly fewer secondary metastases occurred following neck dissections that included the carotid trigone. In light of these results, we recommend that neck dissection for primary oral squamous cell cancer always include the region of the carotid bifurcation, regardless of the above mentioned associated patient and tumor factors.


Assuntos
Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/cirurgia , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/cirurgia , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
7.
Urologe A ; 56(11): 1440-1444, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-28986618

RESUMO

BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and 223Ra), most of these patients still succumb to prostate cancer. Recently, 177lutetium prostate-specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. OBJECTIVES: Establishment of the current position of 177Lu-PSMA-RLT in mCRPC in 2017. MATERIALS AND METHODS: Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on 177Lu-PSMA-RLT after PubMed-based research. RESULTS: In several larger retrospective studies, 177Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. CONCLUSIONS: Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with 177Lu-PSMA-RLT in the treatment of mCRPC.


Assuntos
Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Ensaios de Uso Compassivo , Dipeptídeos/efeitos adversos , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Humanos , Lutécio , Masculino , Metástase Neoplásica , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos
8.
Urologe A ; 56(12): 1597-1602, 2017 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-28695241

RESUMO

BACKGROUND: Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE: This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS: A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS: In the current treatment of hormone-naïve mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12 months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Taxoides/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Intervenção Médica Precoce , Medicina Baseada em Evidências , Humanos , Masculino , Metástase Neoplásica , Neoplasias da Próstata/mortalidade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Taxoides/efeitos adversos
9.
Urologe A ; 56(7): 910-916, 2017 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-28280863

RESUMO

OBJECTIVES: The German S3 guideline on prostate cancer gives recommendations on early detection of prostate cancer. In this study we analyzed the adherence of urologists in private practice from the administrative district of Münster, Germany to this guideline. METHODS: Data were collected through a semistructured survey of 22 urologists based on the COREQ checklist (Consolidated criteria for reporting qualitative research) in four focus groups consisting of five or six urologists in private practice. We developed 23 questions relating to 12 recommendations of the paragraphs of the S3 guidelines dealing with early detection of prostate cancer and prostate biopsy. The recommendations of the guideline are subdivided in nine "strong", one "optional recommendation" and two "statements". The adherence to the guideline was investigated by using frequency and qualitative content analysis (Mayring) based on a mixed methods design. RESULTS: The urologists follow six of the nine "strong recommendations" of the guideline and deviate from three. Reasons for deviations from "strong recommendations" are the following: information about advantages and disadvantages of early detection for prostate cancer, recommendation of a prostate biopsy in case of PSA level ≥4 ng/ml, and indication for repeat biopsy. CONCLUSION: Most of the "strong recommendations" are followed by the interviewed urologists of the administrative district of Münster. Contextually relevant deviations from "strong recommendations" are justified, e. g., the only limited transferability of the PSA threshold of 4 ng/ml derived from population-based studies of asymptomatic men to men presenting in a urologist's office.


Assuntos
Diagnóstico Precoce , Fidelidade a Diretrizes , Neoplasias da Próstata/diagnóstico , Urologia , Biópsia , Lista de Checagem , Alemanha , Humanos , Masculino , Próstata/patologia , Neoplasias da Próstata/patologia
10.
J Cancer Res Clin Oncol ; 132(3): 137-49, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16308709

RESUMO

OBJECTIVES: Renal cell carcinoma is an aggressive malignancy with a high propensity for both early and metachronous regional and distant metastasis. While surgical resection is the mainstay of therapy for patients with localized disease, the prognosis for patients with distant metastasis is poor with a 5-year survival rate of less than 10%. Response rates to first-line immunotherapy or immunochemotherapy range from 10-35%; responses achieved are predominantly partial remissions of short duration. Until today, there is no standard therapeutic procedure for the growing number of patients who relapse following first-line therapy and desire further active treatment. MATERIALS AND METHODS: This article reviews classic and recent publications about second- and third-line approaches, their potential efficacy and toxicity. RESULTS: Several novel approaches have raised well-founded hope. Especially the application of monoclonal antibodies targeting VEGF signalling as well as different receptor tyrosine kinase inhibitors have the potential to change the face of second-line treatment of patients with metastatic RCC. Both groups of agents are focused in current phase III trials, either as mono- and/or combination therapy. CONCLUSIONS: Until today, second-line treatment of patients with metastatic RCC progressing under therapy with biological response modifiers remains an unresolved issue. The results of ongoing clinical trials evaluating novel targeted approaches can be expected with suspense.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Imunoterapia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
11.
Aktuelle Urol ; 37(6): 429-35; quiz 423-4, 2006 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-17099831

RESUMO

PURPOSE: On the basis of promising first-line data we have evaluated the safety and efficacy of a combination therapy comprising interleukin-2 (IL-2) and thalidomide in patients with metastatic renal cell carcinoma (RCC) refractory to both immuno- and chemotherapy. PATIENTS AND METHODS: 14 patients with progressive metastatic RCC, in whom prior immunochemotherapy had failed but who desired further active therapy, were enrolled in this study. Oral thalidomide was started at 200 mg/d and escalated after two days to 400 mg/d at week 0. IL-2 at 7 MIU/m (2) was given by subcutaneous injection, starting at week 1, days 1 to 5, weeks 1 to 4, with no IL-2 at weeks 5 and 6. The response was assessed every other therapy cycle. RESULTS: 12 patients were evaluable for response. There was no objective response; 4 patients showed stable disease for 21, 15, 13 and 9 months, respectively. Toxicities were predominantly grade 1 - 3 and included somnolence and constipation, as well as flu-like symptoms associated with IL-2. However, one patient developed serious constipation which led to a paralytic ileus and discontinuation of treatment. Another patient left the study after seven weeks due to increasing confusion. 11 patients required IL-2 dose reduction. Time on therapy ranged from 3 - 44 weeks (median, 19 weeks). Median overall survival was 22 months. Up to date, all patients have discontinued treatment. CONCLUSIONS: We conclude that outpatient administration of thalidomide/IL-2 is feasible in patients with heavily pretreated and progressive RCC who desire further active treatment. However, toxicity and costs are considerable and the clinical benefit is uncertain. Therefore thalidomide/IL-2 may not represent a promising therapeutic approach for this subgroup of patients.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Interleucina-2/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Talidomida/administração & dosagem , Administração Oral , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Injeções Subcutâneas , Interleucina-2/efeitos adversos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Projetos Piloto , Talidomida/efeitos adversos
12.
Med Oncol ; 33(7): 80, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27317388

RESUMO

The immunological checkpoints of programmed death 1 and its ligand (PD-L1) are currently in focus as novel therapeutic targets in renal cell carcinoma (RCC). The aim of this study was to evaluate the prognostic association of PD-L1 expression in clear cell (cc) RCC with clinical parameters, tumor aggressiveness and overall survival (OS). Patients who underwent renal surgery due to RCC between 1994 and 2003 were retrospectively evaluated. Tumor specimens were analyzed for PD-L1 expression by immunohistochemistry. One hundred and seventy-seven ccRCC patients were eligible for analysis, in which 140 (79.1 %) were negative and 37 (20.9 %) were positive for PD-L1 expression. PD-L1 positivity was associated with female gender (p = 0.001), lymph node metastasis (p = 0.004), distant metastasis (p = 0.002), higher AJCC stage (p = 0.004), as well as advanced disease (pT3/4 and/or N+ and/or M1) (p < 0.001). Kaplan-Meier analysis revealed a significantly diminished 5- and 10-year overall survival of 46.7 and 28.3 % for PD-L1(+) compared to PD-L1(-) tumors with 66 and 53.4 % (p = 0.005), respectively. Univariate analysis showed a significant negative association of OS with PD-L1 positivity [p = 0.005; HR: 2 (95 % CI 1.2-3.3)], even though PD-L1 positivity only tends to predict independently the OS using multivariate analyses [p = 0.066; HR: 1.6 (95 % CI 0.98-2.7)]. PD-L1 expression in ccRCC is associated with parameters of aggressiveness, as well as with poor OS, even though PD-L1 status was not identified as a significant independent prognostic parameter. However, further studies in larger cohorts are warranted.


Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise Serial de Tecidos
13.
Aktuelle Urol ; 46(1): 52-8, 2015 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-25658231

RESUMO

BACKGROUND: After radical prostatectomy (RP) the pre-RP PSA value, Gleason Score, pT-stage, state of seminal vesicles and state of surgical margins are key indicators for the risk of biochemical or clinical recurrence. Depending on the tumour stage, 50-70% of the high-risk patients suffer biochemical progression. The treatment options in these circumstances are adjuvant radiotherapy (ART, for an undetectable PSA) or salvage radiotherapy (SRT, for persisting PSA or PSA re-rising above detection limits). Data from ongoing randomised trials that compare ART and SRT directly have not yet been published. METHOD: A search in PubMed for ART and SRT after RP for prostate cancer was undertaken to compare the results of the 2 treatment approaches. RESULTS: 3 randomised phase-III studies have shown a nearly 20% advantage in terms of biochemical progression after ART (60-64 Gy) compared with a wait-and-see strategy. The largest effect was seen in patients with pT3 prostate cancer with positive surgical margins. According to the German S3-guidelines, SRT with at least 66 Gy can be offered to patients with a post-RP persisting PSA or a PSA re-rising above detection limits. 30-70% of these patients re-achieve an undetectable PSA. Thus, there is a second option for curative treatment. Due to the lower total dose, ART seems to be connected with fewer late complications than SRT. SRT, on the other hand, reduces the risk of potential interactions with post-RP complications and of overtreatment. There is a controversial discussion about the inclusion of the pelvic lymph nodes in the treatment volume, the additional application of anti-androgens and the total dose of both ART and SRT. CONCLUSIONS: The comparison of SRT after PSA progression with ART at a PSA below the detection limits cannot yet be judged conclusively. The indication for ART depends on the associated risk factors. However, regarding freedom from biochemical progression, it is backed up by high level evidence. If SRT is applied for biochemical progression, then it should be initiated early, i. e., at the lowest PSA possible.


Assuntos
Prostatectomia , Neoplasias da Próstata/terapia , Radioterapia Adjuvante/métodos , Terapia de Salvação/métodos , Antagonistas de Androgênios/uso terapêutico , Terapia Combinada , Progressão da Doença , Humanos , Metástase Linfática/patologia , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Melanoma Res ; 10(4): 355-62, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10985670

RESUMO

The presence or absence of melanoma cells in human peripheral blood has recently been shown to be associated with disease prognosis, including overall survival. The detection of tyrosinase mRNA-positive circulating melanoma cells by reverse transcription-polymerase chain reaction (RT-PCR) has been limited to disseminated tumours expressing measurable amounts of this melanocyte-specific enzyme. To biologically classify both melanotic and amelanotic melanomas and to evaluate the clinical and prognostic relevance of tumour cell microcontamination, we examined autologous peripheral blood stem cell (PBSC) harvests from patients with advanced malignant melanoma prior to dose-escalated chemotherapy. To assay heterogeneous melanoma cell antigen expression, we developed a highly sensitive RT-PCR using four melanoma- and one tumour-associated antigen as molecular markers. Expression of the melanocyte-associated transcripts of tyrosinase, MART1/Melan-A, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) as well as the tumour-specific transcript of MAGE-3 was analysed by RT-PCR in PBSC harvests from 31 patients. Seven of the 31 PBSC harvests tested positive for one or more molecular markers: two patients for tyrosinase only, and one patient for MAGE-3 only, one patient for tyrosinase and MAGE-3, one for tyrosinase and MART1/Melan-A, and two patients for tyrosinase, MART1/Melan-A, TRP-2 and MAGE-3. mRNA-positive patients exhibited a significantly impaired overall survival (P = 0.0032), with a median survival of 3 months as opposed to 10 months in PBSC mRNA-negative patients. In conclusion, the use of this multiple-marker microcontamination assay allowed for molecular and prognostic classification of advanced malignant melanoma.


Assuntos
Antígenos de Neoplasias , Biomarcadores Tumorais/análise , Células-Tronco Hematopoéticas/química , Melanoma Amelanótico/classificação , Melanoma/classificação , Células Neoplásicas Circulantes/classificação , Adulto , Feminino , Humanos , Imuno-Histoquímica , Interferon Tipo I/genética , Oxirredutases Intramoleculares/genética , Antígeno MART-1 , Masculino , Melanoma/sangue , Melanoma/diagnóstico , Melanoma Amelanótico/sangue , Melanoma Amelanótico/diagnóstico , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes/química , Proteínas da Gravidez/genética , Prognóstico , RNA Mensageiro/análise , RNA Neoplásico/análise , Sensibilidade e Especificidade , Células Tumorais Cultivadas
15.
Anticancer Res ; 20(5B): 3619-24, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11131671

RESUMO

The value of tyrosinase messenger RNA (mRNA) detection by reverse-transcriptase polymerase chain reaction (RT-PCR) as a marker for circulating melanoma cells remains controversial. However, it has been suggested that detection of melanoma cell mRNA may be used to evaluate prognosis and disease progression in patients with advanced malignant melanoma. We used a highly sensitive tyrosinase RT-PCR detection assay to test peripheral blood specimens of 80 patients with metastatic malignant melanoma. Moreover, we developed a multiple marker RT-PCR assay detecting a variety of additional melanocyte/tumour specific markers addressing the potential heterogeneity of gene expression of circulating melanoma cells. Thus subgroups of 32 and 12 out of all the 80 patients were also analysed for multimarker gene expression in their peripheral blood and bone marrow specimens, respectively. Altogether, 15 out of 80 patients tested positive for one or more molecular markers with heterogeneous melanocyte/tumour gene expression patterns. All RT-PCR positive patients presented with progressive and widely disseminated disease. We concluded that the detection of melanoma cell mRNA occurs in a stage of massive tumour progression and may predict poor clinical outcome in advanced malignant melanoma patients (p < 0.001). In addition, the multiple marker RT-PCR analysis was more reliable and sensitive than a single molecular marker assay for the detection of melanoma cells.


Assuntos
Melanoma/secundário , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Medula Óssea/enzimologia , Medula Óssea/metabolismo , Feminino , Humanos , Masculino , Melanoma/sangue , Melanoma/enzimologia , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/biossíntese , Monofenol Mono-Oxigenase/sangue , Monofenol Mono-Oxigenase/genética , Células Neoplásicas Circulantes/patologia , Prognóstico , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue , RNA Mensageiro/genética , Sensibilidade e Especificidade , Análise de Sobrevida
16.
Cancer Biother Radiopharm ; 16(5): 401-9, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11776757

RESUMO

BACKGROUND: The natural history of malignancies, the response to cytokine-based therapy and survival of patients may be partly determined by the human leukocyte antigen (HLA) phenotype. Here, we investigated in a retrospective analysis the correlation of the HLA phenotype of 73 prognostic favored patients with advanced renal cell carcinoma to (a) the expected HLA distribution in Caucasians, (b) the susceptibility or resistance to metastatic sites, (c) response to cytokine-based therapy and (d) sustained cytokine-induced effective tumor control. METHODS: We retrospectively determined the MHC class I and II antigens in patients with metastatic renal cell carcinoma selected by survival. Antigens were serologically typed by standard lymphocytotoxicity techniques. For statistical analysis, we calculated the probability of the presented HLA antigens in correlation to the expected Caucasian HLA phenotypes. An independent confirmation was performed by using the chi-square and two-tailed Fisher's exact test. RESULTS: Various HLA antigens deviated significantly from the normal distribution in the Caucasian population. HLA.B44 was the only antigen associated (p < 0.01) with the absence of lung and presence of bone metastases, while it did not impact on overall survival or response to therapy. A1 (p < 0.0001, p < 0.002) and B8 (p < 0.009, p < 0.04) alleles were more frequently expressed in responding patients than expected from the normal distribution in Caucasians and that observed in non-responding patients, respectively. The HLA analysis of patients achieving a durable complete remission showed a significantly higher frequency of expression of the A1 and B8 antigens and furthermore of the B14 antigen (p < 0.05). CONCLUSIONS: Our data underline the pivotal role of the MHC complex in controlling and regulating the cellular immune response in renal cell cancer. We could identify HLA antigens, which correlate with response to cytokine-treatment, with a long-lasting effective tumor control and prolonged overall survival.


Assuntos
Antígenos de Neoplasias/análise , Carcinoma de Células Renais/tratamento farmacológico , Antígenos HLA/análise , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Frequência do Gene , Antígenos HLA/genética , Humanos , Fatores Imunológicos/administração & dosagem , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Tábuas de Vida , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Proteínas Recombinantes , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , População Branca
17.
Aktuelle Urol ; 45(1): 21-32, 2014 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-24500957

RESUMO

What is new in urooncology in the year 2013? This review gives a brief but comprehensive overview of new developments in diagnosis and treatment of localized as well as advanced prostate, bladder and kidney cancer which have been presented on the occasion of the annual meetings of the European and American urologic and oncological associations in 2013. Attention is particularly directed to those data and results from trials which might be of direct or indirect clinical relevance.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias da Próstata , Sociedades Médicas , Neoplasias da Bexiga Urinária , Europa (Continente) , Humanos , Masculino , Estados Unidos
18.
Urologe A ; 53(9): 1302-9, 2014 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-25142787

RESUMO

BACKGROUND: The therapy of malignant testicular neoplasms has always been characterized by a high degree of radicality. Thanks to a number of medical achievements the cure rate of testicular cancer has notably increased through the last decades. In the meanwhile the main focus is on reducing therapy load, scrutinizing radical orchiectomy as the only adequate therapy for the primary tumour. OBJECTIVES: This article discusses the question, if and under which conditions an organ-sparing approach can be used appropriately in clinical practice. MATERIALS AND METHODS: A selective literature search was performed in PubMed. RESULTS: A set of data suggest that endocrine and exocrine function of the testis can be preserved using an organ-sparing approach and many patients could benefit regarding their quality of life, e.g., preserving the ability to father a child at least temporarily and avoiding the need for hormone substitution. Different from kidney tumors, precancerous lesions (testicular intraepithelia neoplasia, TIN) can almost inevitably be found in the surrounding tissue of testicular tumors. This has to be considered when making a decision in favor of an organ-sparing approach, because radiation therapy on the affected testis has to be performed after tumor resection. Despite the absence of prospective data, organ-sparing surgical tumor resection can be recommended in carefully selected patients. CONCLUSION: After careful selection of patients, particularly young men can profit from an organ-sparing therapy regimen. Therefore, organ preservation should always be considered in the surgical treatment of testicular masses.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/cirurgia , Recuperação de Função Fisiológica , Neoplasias Testiculares/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Humanos , Masculino , Neoplasias Testiculares/diagnóstico
19.
Aktuelle Urol ; 45(6): 454-6, 2014 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-25514778

RESUMO

The second opinion network for testicular cancer is an internet-based platform addressed to physicians treating testicular cancer patients. They are offered a second opinion before determining further therapy after orchiectomy and completion of staging procedures. The platform has been used in more than 3,000 cases of testicular cancer to date. The rate of discrepancies between first and second opinions is higher than 30%. This suggests a deficit in the implementation of published therapy guidelines. According to our present interim analysis, the second opinion platform helps in avoiding overtreatment of testicular cancer. The high acceptance of the project and the encouraging results of this interim analysis open the door for expansion of the second opinion model to other diseases, e. g., penile carcinoma.


Assuntos
Redes de Comunicação de Computadores , Comportamento Cooperativo , Medicina Baseada em Evidências , Comunicação Interdisciplinar , Internet , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Encaminhamento e Consulta/organização & administração , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Terapia Combinada , Alemanha , Humanos , Masculino , Uso Excessivo dos Serviços de Saúde/prevenção & controle , Orquiectomia , Guias de Prática Clínica como Assunto
20.
Urologe A ; 53(11): 1656-60, 2014 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-25123561

RESUMO

BACKGROUND: Due to a worldwide rise of incidence, urolithiasis presents an increasing strain on the health system. Ureterorenoscopy (URS) is a standard treatment to extract stones in case of ureteral calculi. To increase the success rate of URS and to minimize complications, preoperative ureteral stenting (prestenting) has previously been described as suitable. However, published data are still conflicting. This article describes our single-center experience on the influence of prestenting on the outcome of ureterorenoscopic stone therapy. METHODS: A total of 442 patients who had undergone ureterorenoscopic stone extraction at the Wolfsburg Clinic between 2010 and 2011 were retrospectively evaluated regarding peri- and postoperative results. The Fisher's exact, the χ(2), and the Mann-Whitney U test were used to compare the group of patients with and without prestenting. RESULTS: Even though patients with prestenting suffered from stones with larger diameter that were more frequently located in the proximal ureter, the rates for postoperative stenting, perioperative complications, and retreatment were much lower then in the group of patients without prestenting (p<0.001). Furthermore, patients who had received prestenting had a significantly shorter hospital stay (median, 3 vs. 2 days, p<0.001) and higher rates of stone clearance (83.0 vs. 69.7%, p=0.001). CONCLUSION: According to our retrospective monocentric analysis, prestenting may significantly reduce the risk of complications as well as intra-/post-URS restenting and can increase the rate of complete stone clearance.


Assuntos
Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Stents/estatística & dados numéricos , Cálculos Ureterais/epidemiologia , Cálculos Ureterais/cirurgia , Ureteroscopia/estatística & dados numéricos , Adulto , Idoso , Terapia Combinada/instrumentação , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Ureterais/patologia
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