RESUMO
PURPOSE: The aim of this study was to assess the post biopsy infection rate, feasibility and prostate cancer (PCa) detection rate (CDR) by performing transperineal MRI-TRUS fusion biopsy of the prostate (TPBx) under local anesthesia (LA) without antibiotic prophylaxis (AP). METHODS: We prospectively screened 766 men with suspicious lesions on mpMRI, an elevated PSA level or a suspect digital examination undergoing MRI-TRUS-TPBx in LA, from May 2019 to July 2020. Patients with the need for antibiotic prophylaxis or without a PI-RADS target lesion were excluded from final analyses. We reported CDR, perioperative pain (0-10) and postoperative complications. PCa with an ISUP grade ≥ 2 was classified as clinically significant PCa (csPCa). RESULTS: We included 621 patients with a median age of 68 years (IQR 62-74), a PSA of 6.43 ng/mL (IQR 4.72-9.91) and a prostate volume of 45 cc (IQR 32-64). In median, 4 targeted (TB) (IQR 3-4) and 6 (IQR 5-7) systematic biopsies (SB) detected in combination overall 416 (67%) PCa and 324 (52%) csPCa. Overall CDR of TB for PI-RADS 3, 4 and 5 was 26%, 65% and 84%, respectively. Patients reported a median perioperative pain level of 2 (IQR 1-3). Four patients (0.6%) developed a post biopsy infection, one experienced urosepsis. CONCLUSION: Our results demonstrate that transperineal MRI-TRUS fusion-guided prostate biopsy under LA without AP is feasible, safe and well tolerated.
Assuntos
Biópsia Guiada por Imagem/métodos , Neoplasias da Próstata/patologia , Sepse/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecções Urinárias/epidemiologia , Idoso , Anestesia Local , Antibioticoprofilaxia/métodos , Endossonografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica , Períneo , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Estudos RetrospectivosRESUMO
The perineal approach for prostate biopsy (PB) is a sterile alternative to conventional transrectal PB. Targeted local anesthesia allows perineal prostate biopsy (pPB) to be performed without general anesthesia. This paper presents the first results after establishing perineal MRI/ultrasound fusion biopsy (pFB) under local anesthesia without standard perioperative antibiotic prophylaxis. For this purpose, 144 patients were included in the study after pFB at the Vivantes Klinikum am Urban. No peri-interventional antibiotic prophylaxis was applied. Peri- and postoperatively, the pain sensation, measured using an analogue pain scale from 0-10, and complications were recorded. The median patient age was 68 and the median prostate-specific antigen (PSA) value 7.07â¯ng/ml. In all, 49% of the patients received primary PB. The overall detection rate for prostate cancer (PCa) was 71% and for PI-RADS 3, 4 and 5 was 44, 71 and 92%, respectively. The median pain sensation during biopsy was 2. Furthermore, 63% of patients with a transrectal prebiopsy considered this to be more painful and another 20% expressed similar pain levels. Only 1 patient developed a febrile urinary tract infection. The pFB of the prostate under local anesthesia without antibiotic, perioperative prophylaxis is a suitable alternative to the transrectal PB with regard to the detection rate of PCa, the side effect profile and the subjective pain perception of the patients during the intervention.
Assuntos
Anestesia Local , Neoplasias da Próstata , Antibioticoprofilaxia , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgiaRESUMO
BACKGROUND: Despite rising incidence rates of colorectal malignancies, only a few prognostic tools have been implemented in proven clinical routine. Cell division and proliferation play a significant role in malignancies. In terms of colorectal cancer, the impact of proliferation associated proteins is controversially debated. The aim of our study was to examine the expression of topoisomerase II α and minichromosome maintenance protein 6 and to correlate these findings with the clinical data. METHODS: Tissue samples of 619 patients in total were stained using the antibodies Ki-S4 and Ki-MCM6 targeting topoisomerase II α as well as minichromosome maintenance protein 6. The median rate of proliferation was correlated with clinical and follow up data. RESULTS: The expression rate of minichromosome maintenance protein 6 is significantly higher than the proportion of topoisomerase II α in tumour cells (p < 0.001). A high expression of both proteins coincides with a beneficial outcome for the patient, indicating a favourable prognostic marker (p < 0.001 and p = 0.008). CONCLUSIONS: We have demonstrated that high expression rates of proliferative markers is linked to a beneficial patient outcome. According to the general opinion, a high expression rate correlates with a poor patient outcome. In this study, we were able to refute this assertion.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , DNA Topoisomerases Tipo II/metabolismo , Componente 6 do Complexo de Manutenção de Minicromossomo/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Idoso , Proliferação de Células , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reto/patologia , Reto/cirurgia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Pylorus-preserving pancreaticoduodenectomy is one of the most complex procedures in general surgery. Laparoscopic pancreaticoduodenectomy was initially described in 1994; however, its worldwide distribution is so far limited to only a few specialist centers. Robotic surgery using the DaVinci® system can overcome many limitations of laparoscopic surgery. The system is a promising tool for a more widespread introduction of minimally invasive surgery for pancreatic diseases. Mortality rates of 0-5% and pancreatic fistula rates of 0-35% are described in the literature; therefore, thorough complication management is crucial in the postoperative course. The video presents a robotic pylorus-preserving pancreaticoduodenectomy for periampullary carcinoma in a female patient.
Assuntos
Adenocarcinoma/cirurgia , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Pancreaticoduodenectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Idoso , Ampola Hepatopancreática/diagnóstico por imagem , Ampola Hepatopancreática/patologia , Colestase Intra-Hepática/diagnóstico por imagem , Colestase Intra-Hepática/cirurgia , Neoplasias do Ducto Colédoco/diagnóstico por imagem , Neoplasias do Ducto Colédoco/patologia , Feminino , Humanos , Jejunostomia/instrumentação , Jejunostomia/métodos , Laparoscopia/instrumentação , Laparoscopia/métodos , Estadiamento de Neoplasias , Pancreaticoduodenectomia/instrumentação , Pancreaticojejunostomia/instrumentação , Pancreaticojejunostomia/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Técnicas de Sutura/instrumentação , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The surgical treatment of pancreatic head tumours is one of the most complex procedures in general surgery. In contrast to colorectal surgery, minimally-invasive techniques are not very commonly applied in pancreatic surgery. Both the delicate dissection along peri- and retropancreatic vessels and the extrahepatic bile ducts and subsequent reconstruction are very demanding with rigid standard laparoscopic instruments. The 4-arm robotic surgery system with angled instruments, unidirectional movement of instruments with adjustable transmission, tremor elimination and a stable, surgeon-controlled 3D-HD view is a promising platform to overcome the limitations of standard laparoscopic surgery regarding precise dissection and reconstruction in pancreatic surgery. INDICATION: Pancreatic head resection for mixed-type IPMN of the pancreatic head. PROCEDURE: Robot-assisted, minimally-invasive pylorus-preserving pancreaticoduodenectomy (Kausch-Whipple procedure). CONCLUSION: The robotic approach is particularly suited for complex procedures such as pylorus-preserving pancreatic head resections. The fully robotic Kausch-Whipple procedure is technically feasible and safe. The advantages of the robotic system are apparent in the delicate dissection near vascular structures, in lymph node dissection, the precise dissection of the uncinate process and, especially, bile duct and pancreatic anastomosis.
Assuntos
Carcinoma Ductal Pancreático/cirurgia , Laparoscopia/instrumentação , Laparoscopia/métodos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/instrumentação , Pancreaticoduodenectomia/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Anastomose Cirúrgica/instrumentação , Anastomose Cirúrgica/métodos , Dissecação/instrumentação , Dissecação/métodos , Estudos de Viabilidade , Feminino , Gastrostomia/instrumentação , Gastrostomia/métodos , Humanos , Jejunostomia/instrumentação , Jejunostomia/métodos , Piloro/cirurgia , Equipamentos Cirúrgicos , Instrumentos CirúrgicosRESUMO
Sertoli cell tumors are a rare malignancy which account for approximately 1.5 % of all testicular tumors. Although malignant Sertoli cell tumors are uncommon, they are associated with a poor prognosis. So far 36 cases of malignant courses of disease have been described. We present a patient with a lymphogenic metastasized Sertoli cell tumor, who 24 months after orchiectomy and extended retroperitoneal lymphadenectomy is relapse-free.
Assuntos
Excisão de Linfonodo/métodos , Orquiectomia/métodos , Tumor de Células de Sertoli/secundário , Tumor de Células de Sertoli/cirurgia , Neoplasias Testiculares/secundário , Neoplasias Testiculares/cirurgia , Adulto , Terapia Combinada/métodos , Humanos , Masculino , Tumor de Células de Sertoli/patologia , Neoplasias Testiculares/patologia , Resultado do TratamentoRESUMO
INTRODUCTION: The optimal surgical treatment of patients with a high risk prostate cancer (PCa) in terms of radical prostatectomy (RP) is still controversial: open retropubic RP (RRP), laparoscopic RP (LRP), or robot-assisted (RARP). We aimed to investigate the influence of the different surgical techniques on pathologic outcome and biochemical recurrence. PATIENTS AND METHODS: A total of 805 patients with a high risk PCa (PSA >20 ng/mL, Gleason Score ≥8, or clinical stage ≥cT2c) were included. A comparison of 407 RRP patients with 398 minimally invasive cases (LRP+RARP) revealed significant confounders. Therefore all 110 RARP cases were propensity score (PS) matched 1:1 with LRP and RRP patients. PS included age, clinical stage, preoperative PSA, biopsy Gleason score, surgeon's experience and application of a nerve sparing technique. Comparison of overall survival (OS) and recurrence-free survival (RFS) was done with the log rank test. Predictors of RFS were analyzed by means of Cox regression models. RESULTS: Within the post-matching cohort of 330 patients a pathologic Gleason score < 7, = 7 and > 7 was found in 1.8, 55.5 and 42.7% for RARP, in 8.2, 36.4, 55.5% for LRP and in 0, 60.9 and 39.1% for RRP (p=0.004 for RARP vs. LRP and p=0.398 for RARP vs. RRP). Differences in histopathologic stages were not statistically significant. The overall positive surgical margin rate (PSM) as well as PSM for ≥ pT3 were not different. PSM among patients with pT2 was found in 15.7, 14.0 and 20.0% for RARP, LRP and RRP (statistically not significant). The respective mean 3-year RFS rates were 41.4, 77.9, 54.1% (p<0.0001 for RARP vs. LRP and p=0.686 for RARP vs. RRP). The mean 3-year OS was calculated as 95.4, 98.1 and 100% respectively (statistically not significant). CONCLUSION: RARP for patients with a high risk PCa reveals similar pathologic and oncologic outcomes compared with LRP and RRP.
Assuntos
Laparoscopia/métodos , Pontuação de Propensão , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/etiologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Próstata/patologia , Antígeno Prostático Específico/sangue , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Vomiting is a common complication associated with the use of hydromorphine for pre-emptive analgesia in dogs. The ideal anti-emetic protocol for prevention of this complication has not been established. HYPOTHESIS: Maropitant administered concurrently or before hydromorphone would reduce the incidence of vomiting, signs of nausea, ptyalism, and increased panting compared to administration of acepromazine or a 0.9% saline control. ANIMALS: Sixty mixed-breed female dogs scheduled for ovariohysterectomy. METHODS: Randomized, blinded, placebo-controlled experimental study. Dogs were assigned to 4 experimental groups with 15 dogs per group. All groups received 0.2 mg/kg of hydromorphone IM. Group "Control" received 0.1 mL/kg saline SC 30-45 minutes before hydromorphone, group "Marop1" received 1 mg/kg maropitant SC 30-45 minutes before hydromorphone, group "Ace" received 0.02 mg/kg IM acepromazine 30-45 minutes before hydromorphone, and group "Marop2" received 1 mg/kg SC maropitant concurrently with hydromorphone. A trained and blinded observer documented adverse events from the time hydromorphone was administered until the time dogs were induced for surgery. RESULTS: Marop1 had significantly less vomiting (0%) compared to Control (87%; P < .01) and Ace (53%; P < .01). Marop2 had significantly less vomiting (27%) compared to Control (P < .01). Marop1 had significantly greater incidence of ptyalism (73%) compared to Ace (P < .01; 20%). Ace showed significantly less panting (33%) compared to Marop2 (93%; P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy dogs, maropitant citrate administered before hydromorphone significantly decreases the incidence of vomiting in dogs but does not improve signs of nausea, ptyalism, or increased panting.
Assuntos
Acepromazina/uso terapêutico , Analgésicos Opioides/efeitos adversos , Antieméticos/uso terapêutico , Doenças do Cão/induzido quimicamente , Hidromorfona/efeitos adversos , Náusea e Vômito Pós-Operatórios/veterinária , Quinuclidinas/uso terapêutico , Animais , Doenças do Cão/prevenção & controle , Cães , Feminino , Histerectomia/efeitos adversos , Histerectomia/veterinária , Incidência , Ovariectomia/efeitos adversos , Ovariectomia/veterinária , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Náusea e Vômito Pós-Operatórios/prevenção & controleRESUMO
The introduction of prostate cancer treatment centers according to the criteria of the German Cancer Society ("Deutsche Krebsgesellschaft", DKG) aims at improving the quality of care for patients with prostate cancer. Systematic analyses of the effects and costs are lacking as yet. Three years after certification of the Interdisciplinary Prostate Cancer Center at the Charité Hospital Berlin we observed a decrease in the rate of positive surgical margins (tumor stage pT2), but other parameters of treatment quality including patient satisfaction remained unchanged. A survey among urologists of the region showed a high acceptance of prostate cancer centers in general. The majority of participating urologists appreciated the work of the Charité center, in particular the treatment recommendations given by the center were mostly followed and the majority of urologists regularly use educational activities of the center. However, only 30% of the participating urologists confirmed short-term improvements in the quality of patient care. Yearly additional costs for the Charité prostate cancer center are estimated at 205,000 euro (precertification phase and certification) and 138,000 euro (monitoring phase), despite the initial drop in mean treatment costs per case (radical prostatectomy). The introduction of prostate cancer treatment centers certified by the DKG is cost intensive, increases in treatment efficiency notwithstanding. Short-term improvements in quality of care cannot be unequivocally demonstrated. Prostate cancer centers serve an important role in counseling and medical education and may thus help disseminate evidence-based treatment strategies.
Assuntos
Acreditação , Institutos de Câncer , Comportamento Cooperativo , Comunicação Interdisciplinar , Neoplasias da Próstata/cirurgia , Sociedades Médicas , Instituições Filantrópicas de Saúde , Acreditação/economia , Institutos de Câncer/economia , Análise Custo-Benefício , Coleta de Dados , Alemanha , Humanos , Laparoscopia/economia , Masculino , Programas Nacionais de Saúde/economia , Estadiamento de Neoplasias , Satisfação do Paciente/economia , Prostatectomia/economia , Neoplasias da Próstata/economia , Neoplasias da Próstata/patologia , Garantia da Qualidade dos Cuidados de Saúde/economia , Encaminhamento e Consulta/economia , Reoperação/economia , Sociedades Médicas/economia , Instituições Filantrópicas de Saúde/economiaRESUMO
INTRODUCTION: For more than 50 years vasectomy reversal is a routinely performed procedure in the field of urology. However, there is no scientific agreement about morphological changes of the testes caused by vasectomy. The existing evidence for reduced fertility rates following vasectomy reversal demands a clear statement regarding potential histological changes and impaired spermatogenesis following vasectomy. Thus far there is little knowledge about potential histological changes of the testis caused by vasectomy. MATERIAL AND METHODS: 330 consecutive patients who underwent vasectomy reversal had bilateral testicular biopsies which were evaluated utilising semi-thin sections. The number of mature spermatids per seminiferous tubule was considered the variable of interest as it represents an objective and reproducible parameter of spermatogenesis. The number of mature spermatids per tubule was correlated with patient age, obstructive interval and the presence or absence of sperm granulomas via the chi-square test. RESULTS: Overall, 570 sections of 285 patients were eligible for evaluation. The mean patient age was 41.2 years (range 27-63 years, SD +/- 6.5 years) with a mean obstructive interval of 105.9 months (range 12-328, SD +/- 66.1). 56 patients (19.6 %) had a sperm granuloma on the right and 22 (11.6 %) on the left ductus deferens. There was no statistically significant correlation between the presence of a sperm granuloma with the number of mature spermatids per tubule (p = 0.717). Furthermore, there was neither an association of obstructive interval (p = 0.144) nor patient age (p = 0.168) with spermatogenesis. CONCLUSION: Regular spermatogenetic activity in all examined samples with development of mature spermatids was shown. Furthermore, for the first time we were able to demonstrate in a large cohort of patients that neither patient age nor obstructive interval nor sperm granuloma have a significant impact on spermatogenesis.
Assuntos
Granuloma/patologia , Complicações Pós-Operatórias/patologia , Espermátides/patologia , Espermatogênese/fisiologia , Testículo/patologia , Vasovasostomia/métodos , Adulto , Fatores Etários , Biópsia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Túbulos Seminíferos/patologia , Contagem de Espermatozoides , Ducto Deferente/patologiaRESUMO
BACKGROUND: Guidelines are developed to improve the quality of patient care. The effect of German urologic guidelines has not been evaluated so far. Therefore, we aimed to systematically investigate the acceptance, use, and quality of the published guidelines from a user's perspective. METHODS: A link to an online questionnaire concerning use and barriers to the application of guidelines was distributed via e-mail by the German Society of Urology (DGU). German urologists' opinions on differences in national guideline quality were evaluated regarding prostate cancer (PCA), bladder cancer, germ cell tumors (GCT), renal cell carcinomas, and erectile dysfunction. RESULTS: Four hundred sixty-seven German urologists participated. More than 90% of the participants considered guidelines to be helpful. The Internet as the main tool for guideline distribution was favored by 28.4%, followed by publication in Urologe A. The main barrier to guideline usage was attributed to the lack of up-to date clinical data. Guidelines for GCT scored best in all quality categories and reached the highest level of use (65.8%), and 40.5% of participating urologists considered the additional establishment of comprehensive care centers for GCT as more effective for quality improvement than guideline development alone. For the other urologic tumors, especially PCA, guideline development was favored as a tool for quality improvement. CONCLUSION: More than 90% of participating urologists accept clinical guidelines as useful instruments in clinical practice and for therapeutic decisions. Our results should be integrated into guideline dissemination and implementation strategies in order to achieve a higher degree of treatment conformation to guidelines.
Assuntos
Atitude do Pessoal de Saúde , Fidelidade a Diretrizes/estatística & dados numéricos , Médicos/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Urologia/estatística & dados numéricos , Urologia/normas , AlemanhaRESUMO
The objective of this study was to determine the effect of the obstructive interval and the presence of a sperm granuloma on vas patency and pregnancy rate following vasectomy reversal. We identified 334 patients with complete follow-up who met the inclusion criteria. There were significant associations between the obstructive interval and procedure performed as well as with patient age. Patients with longer obstructive intervals were more often older (p < 0.001) and more likely to have a vaseoepididymostomy performed (p < 0.001). There was no association between the presence of a sperm granuloma or the length of the obstructive interval with post-operative vas patency and pregnancy rates. The only independent predictor of post-operative fertility was age of the female partner (p = 0.015). Our data clearly demonstrates that when state of the art surgical techniques are used, neither the presence of a sperm granuloma nor the obstructive interval serve as prognosticators of post-operative vas patency and pregnancy rates. However, when counselling patients and their female partners, it is of utmost importance to stress that the age of the female partner is an independent predictor of successful vasectomy reversal.
Assuntos
Granuloma/patologia , Taxa de Gravidez , Espermatozoides/patologia , Ducto Deferente/cirurgia , Vasovasostomia/métodos , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The polycomb group (PCG) proteins are epigenetic transcriptional repressors involved in the control of cellular proliferation and oncogenesis. This study aimed at examining whether mRNA tumor levels of the PCG family members BMI1, SUZ12, RING1, and CBX7 relate to histopathological parameters in urothelial carcinomas of the bladder and whether they may provide prognostic information following tumor resection. METHODS: The relative gene expression of BMI1, SUZ12, RING1, and CBX7 was analyzed by real-time RT-PCR in tumor tissue obtained from 93 patients with urothelial carcinoma of the bladder undergoing surgical treatment. Expression data was correlated with pathological variables and outcome. RESULTS: PCG family members BMI1, SUZ12, RING1, and CBX7 are commonly expressed in urothelial carcinomas of the bladder. The relative CBX7 mRNA expression levels gradually decreased from superficial (pTa) to invasive (pT1) and finally to muscle-invasive (> or =pT2) tumors (p = 0.008). Furthermore, CBX7 expression was statistically significantly correlated with tumor grade (p = 0.04). No correlation of mRNA levels with histopathological tumor features or tumor recurrence was observed for the other PCG components investigated. CONCLUSION: Expression levels of CBX7 inversely correlate with the progression of tumor stage and grade in urothelial carcinomas of the bladder, suggesting that downregulation of CBX7 indicates aggressive urothelial carcinoma phenotype.
Assuntos
Proteínas de Transporte/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Musculares/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Invasividade Neoplásica , Proteínas de Neoplasias , Estadiamento de Neoplasias , Complexo Repressor Polycomb 1 , Complexo Repressor Polycomb 2 , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Fatores de Transcrição , Neoplasias da Bexiga Urinária/patologiaRESUMO
This article offers a review about the current facts of chemotherapy in testicular cancer. Besides a short presentation of the guideline-standard therapy the authors deal with the question as to why testicular cancer shows an extraordinarily high chemosensibility compared to other tumours. Furthermore, the current data on alternative chemotherapies as well as of molecular, molecular-genetic and pharmacogenetic therapeutic concepts are explored. Data were obtained from researches in Medline of the Pubmed database.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Cisplatino/administração & dosagem , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Cisteína Endopeptidases/genética , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/genética , Endonucleases/genética , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Polimorfismo Genético/genética , Guias de Prática Clínica como Assunto , Taxa de Sobrevida , Neoplasias Testiculares/genética , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
PURPOSE: Down-regulation of the IAP antagonistis XAF1, Smac/DIABLO and HtrA2, has been related to the onset and progression of various malignancies. We examined the mRNA-expression of these pro-apoptotic parameters in testicular germ cell tumors (TGCT) and normal testicular tissue and correlated their expression levels to clinicopathological tumour features. MATERIAL AND METHODS: Real-time RT-PCR was used to quantify the mRNA-expression of XAF1, Smac/DIABLO and HtrA2 in normal testicular tissue (n = 18), carcinoma in situ (n = 4), seminomas (n = 64), and non-seminomatous germ cell tumors (n = 35). RESULTS: Compared to normal testicular tissue, the expression levels of XAF1 were increased in TGCT (p < 0.001), whereas those of Smac/DIABLO and HtrA2 were decreased (p < 0.001 and p < 0.001). Smac/DIABLO expression levels showed a significant trend towards a gradual decrease from normal testicular tissue to CIS and seminomas and finally to NSGCT (p < 0.001). Moreover, XAF1 and HtrA2 expression levels gradually increased with progression of clinical tumour stage in seminoma patients (p = 0.001 and p = 0.018), their expression levels being strongly intercorrelated (Spearman rho correlation coefficient: 0.674; p < 0.001). CONCLUSION: These data suggest that a down-regulation of Smac/DIABLO and HtrA2 is implicated in the development and progression of TGCT, whereas overexpression of XAF1 in TGCT might contribute to their extraordinary sensitivity to chemotherapy. Regarding the additional correlation of XAF1 and HtrA2 expression with clinical tumour stage in seminoma patients, it appears reasonable to further evaluate these three IAP antagonists as molecular parameters for the prediction of treatment response and prognosis of TGCT patients.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/genética , Neoplasias Embrionárias de Células Germinativas/genética , Serina Endopeptidases/genética , Neoplasias Testiculares/genética , Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Biópsia , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Embrionário/genética , Carcinoma Embrionário/patologia , Progressão da Doença , Regulação para Baixo/genética , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Seminoma/genética , Seminoma/patologia , Teratocarcinoma/genética , Teratocarcinoma/patologia , Neoplasias Testiculares/patologia , Testículo/patologiaRESUMO
INTRODUCTION: PSA is still the most important parameter in the diagnosis and follow-up of prostate cancer. We searched for single nucleotide polymorphisms (SNP) in four different parts of the PSA promoter, which harbour binding sites for major transcriptional regulators using PCR-based combined SSCP and sequence analysis. MATERIALS AND METHODS: Lymphocyte DNA samples from 279 prostate cancer patients and 55 age-matched controls were subjected to SSCP analysis after PCR amplification of four approximately 200-bp fragments selected to contain the known AREs I-III or the transcriptional start site, respectively. Conspicuous PCR fragments with variant SSCP patterns were subsequently cloned and sequenced. Computer-assisted comparison with published sequences of the promoter region was performed to reveal polymorphic sites. RESULTS: In 66.6 % of the carcinoma cases DNA displayed polymorphisms in ARE I-, whereas the benign cases showed this SNP only in 14.5 %. This difference was highly significant (p < 0.0001). In addition, we found novel SNPs with lower frequency at positions - 179, - 230, - 233 (ARE I) and - 356 (ARE II). CONCLUSION: The present study confirmed that the otherwise already described polymorphism in the position - 158 is highly significantly more frequent in prostate cancer patients than in the control group. There is no significant correlation to the clinical stage of the disease. Furthermore we described for the first time four rare, previously unknown polymorphisms.
Assuntos
Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples/genética , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologiaRESUMO
PURPOSE: We determined the relation between promoter methylation and mRNA expression of the p53 target genes APAF-1 and DAPK-1 in 55 consecutive tumor and corresponding normal tissue samples. MATERIALS AND METHODS: Tissue was taken from nonmetastatic clear cell renal cell carcinoma at a median followup of 75 months. Quantitative methylation specific real-time polymerase chain reaction and quantitative real-time reverse transcriptase-polymerase chain reaction were used. RESULTS: The mRNA expression levels of APAF-1 and DAPK-1 were significantly higher in tumor vs nontumor tissue from the same kidney (p = 0.003 and 0.0001, respectively). Expression levels of the 2 genes did not correlate with tumor stage but they were significantly lower in high grade (G3) tumors (p = 0.018 and 0.05, respectively). In patients with positive lymph node staging mRNA expression of APAF-1 and DAPK-1 was significantly lower. On matched pair analysis of tumor tissue the methylation level of the APAF-1 gene correlated inversely with the mRNA expression level (p = 0.02). In tumor and normal kidney tissue from patients with lesions 4 cm or greater mRNA expression levels of DAPK-1 were significantly lower in those who later had metastatic disease (p = 0.04 and 0.02, respectively). CONCLUSIONS: These data demonstrate decreased tumor suppressor gene expression in more aggressive subtypes of clear cell renal cell carcinoma. The lower mRNA level of the DAPK-1 gene in tumor and normal tissue from patients with an unfavorable clinical outcome suggests the organ specific loss of tumor suppressor gene expression, predisposing to metastatic tumor disease and shorter overall survival.
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Proteínas Reguladoras de Apoptose/genética , Fator Apoptótico 1 Ativador de Proteases/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Carcinoma de Células Renais/genética , Metilação de DNA , Neoplasias Renais/genética , Adulto , Idoso , Biópsia por Agulha , Carcinoma de Células Renais/patologia , Proteínas Quinases Associadas com Morte Celular , Feminino , Secções Congeladas , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro/genética , Estudos de Amostragem , Sensibilidade e Especificidade , Estatísticas não ParamétricasRESUMO
The EZH2 gene controls methylation of various EZH2 target promoters. The APAF-1, DAPK-1 und IGFBP-3 genes are frequently methylated in bladder cancer, and methylation of these genes is found in more aggressive tumor types. The aim of our study was to investigate a potential link between EZH2 mRNA expression and the extent of APAF-1, DAPK-1 and IGFBP-3 methylation in urothelial transitional cell carcinoma (TCC) and to correlate the data with histopathological parameters and follow-up data. EZH2 mRNA expression was measured by real-time reverse transcription polymerase chain reaction, and the methylation analysis was performed using methylation-specific real-time polymerase chain reaction. Tissue specimens were obtained from 35 patients with TCC. EZH2 mRNA expression was detected in all tumor specimens investigated. The EZH2 expression levels correlated well with the differentiation grade of the tumor specimens (p = 0.03), and the APAF-1 methylation correlated with tumor stage (p = 0.0001) and grade (p = 0.004). Matched pair analysis demonstrated a statistically significant correlation between elevated EZH2 mRNA expression and higher methylation levels of APAF-1 in superficial (p = 0.024) and well- differentiated (p = 0.04) TCC. In patients with recurrent TCC, APAF-1 and IGFBP-3 methylation levels were significantly higher (p = 0.03 and p = 0.01, respectively), which was not observed when EZH2 mRNA expression or DAPK-1 methylation levels were related to the clinical outcome. In conclusion, our data show that EZH2 expression and APAF-1 methylation are related to tumor progression and invasiveness. Moreover, these data present first evidence that APAF-1 methylation is related to transcriptional activity of EZH2 expression in early-stage tumor disease of the bladder.
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Fator Apoptótico 1 Ativador de Proteases/genética , Carcinoma de Células de Transição/genética , Proteínas de Ligação a DNA/genética , RNA Mensageiro/genética , Fatores de Transcrição/genética , Neoplasias da Bexiga Urinária/genética , Carcinoma de Células de Transição/patologia , Linhagem Celular Tumoral , Metilação de DNA , Primers do DNA , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias Musculares/patologia , Neoplasias Musculares/secundário , Invasividade Neoplásica , Estadiamento de Neoplasias , Complexo Repressor Polycomb 2 , Regiões Promotoras Genéticas , Neoplasias da Bexiga Urinária/patologiaRESUMO
AIMS: To analyze prognostic factors influencing survival and tumour recurrence after resection of gastrointestinal stromal tumours. METHODS: Forty patients who underwent surgery for a GIST at our institution were reviewed. Patients were classified on the basis of tumour size, mitotic rate and CD117 positivity. The overall survival and disease free survival were calculated using Kaplan-Meier method considering the extent of surgery comparing local tumour excisions with segmental organ resections. RESULTS: Tumours were localized in the oesophagus, stomach, duodenum, small bowel and large bowel and rectum. Sixty-five percent of the patients had an intermediate or high risk GIST according to tumour size and mitotic count. In 26/40 patients tumour resection was performed using segmental organ resection, in all other patients local tumour excision was carried out. The mean overall survival was 73 months. Disease free survival was significantly better after local tumour excision compared to segmental organ resection (73 months versus 53 months; p=0.05). Large tumour size (p=0.07) and high mitotic count (p=0.14) were negative prognostic factors for disease free survival, although statistical significance was not reached yet. CONCLUSION: Primary surgery remains the cornerstone in the treatment of primary and recurrent GIST. Risk adapted surgery is the most important factor to avoid early tumour recurrence. In case of small tumour size segmental organ resections can be avoided favouring local tumour excisions with a low risk of tumour recurrence.
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Tumores do Estroma Gastrointestinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Tumores do Estroma Gastrointestinal/classificação , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Recidiva Local de Neoplasia , Prognóstico , Análise de Sobrevida , Taxa de SobrevidaRESUMO
Operative approaches to solve severe urinary incontinence following radical prostatectomy include artificial urinary sphincters, bulking agents, urethral sling procedures, and the ProACT device (Uromedica Inc.). Previously reported complications of the ProACT procedure comprise ruptures and dislocations of balloons as well as erosions and perforations of the bladder or urethra. We report the case of a rectal perforation as a late complication of the ProACT procedure after prostatectomy and adjuvant radiotherapy. To the best of our knowledge this complication has not been described before.