RESUMO
OBJECTIVE: To analyse the adverse events (AEs) associated with apalutamide and the impact of a multidisciplinary team (MDT) protocol on its management at a tertiary care hospital in a real-world setting. METHODS: This was an observational, prospective, cohort study based on real-world evidence at the Hospital Clínic de Barcelona. Includes patients diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC) and who started treatment with apalutamide between May 2019 and March 2023 in a real-world clinical setting. RESULTS: Of the 121 patients treated with apalutamide, 52.1% experienced an AE, 19.8% experienced temporarily interruption or a reduction in the dose of apalutamide, and 13.2% discontinued treatment due to AEs. Without MDT protocol (49 patients), 24.5% of patients had to temporarily interrupt or reduce the dose of apalutamide due to AEs, with a median time from the start of treatment of 10.1 months, and 24.5% discontinued apalutamide due to AEs, with a median time from the start of treatment of 3.1 months. Meanwhile, whit MDT protocol (72 patients), 16.7% of patients had to temporarily interrupt or reduce the dose of apalutamide due to AEs, with a median time from the start of treatment of 1.6 months, and 5.6% discontinued apalutamide due to AEs, with a median time from the start of treatment of 4 months. The risk reduction associated with treatment discontinuation was statistically significant (p-value = 0.003). CONCLUSIONS: This study highlights the importance of MDT management of AEs associated with apalutamide to reduce treatment discontinuation.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Tioidantoínas , Humanos , Masculino , Tioidantoínas/efeitos adversos , Tioidantoínas/uso terapêutico , Tioidantoínas/administração & dosagem , Idoso , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Equipe de Assistência ao Paciente , Idoso de 80 Anos ou mais , Estudos de Coortes , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagemRESUMO
PURPOSE: Current clinical prognostic factors are not accurate enough to identify and monitor those muscle-invasive bladder cancer (MIBC) patients at high risk of progression after radical cystectomy (RC). Here, we determined genetic alterations in the tumor and circulating tumor cell (CTC) enumeration to find biomarkers useful for the management of MIBC after RC. METHODS: Thirty-nine MIBC patients undergoing RC were included. Tumoral tissue DNA was analyzed by next generation sequencing. CTCs were isolated from blood collected before RC and one, four and 12 months later. RESULTS: Sixteen (41%) patients progressed in a median time of 8.5 months and 11 (69%) of these patients harbored the TERT c.-124C > T mutation. All progressive patients harboring the TERT c.-124C > T mutation presented a significant increase in CTC number 12 months after RC compared to those without the mutation. Additionally, CTC number at 12 months was identified as an independent prognostic biomarker for tumor progression and cancer specific survival (CSS). Ten (63%) progressive patients showed an increment of CTC number with a median anticipation period of four months compared with imaging techniques. CONCLUSIONS: The TERT c.-124C > T mutation could be considered a biomarker of aggressivity. CTC enumeration is a useful tool for identifying MIBC patients at high risk of progression and CSS after RC and for detecting tumor progression earlier than imaging techniques.
Assuntos
Células Neoplásicas Circulantes , Telomerase , Neoplasias da Bexiga Urinária , Biomarcadores , Cistectomia/métodos , Humanos , Músculos , Mutação , Invasividade Neoplásica , Prognóstico , Regiões Promotoras Genéticas , Telomerase/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
INTRODUCTION: The transperitoneal laparoscopic approach is considered the gold standard technique for living kidney donation. Other accepted laparoscopic techniques include the retroperitoneal approach, natural orifice transluminal endoscopic surgery (NOTES)-assisted, laparo-endoscopic single-site surgery (LESS), with excellent results in the donor and graft. Many studies have compared these techniques with open ones. Our objective is to describe our experience and results in minimally invasive living-donor nephrectomies (MILDN): laparoscopic, NOTES-assisted, and LESS since their introduction in March 2002. MATERIALS AND METHODS: We conducted a retrospective observational study of donors undergoing MILDN between March 2002 and March 2020. RESULTS: A total of 714 MILDNs were performed at our centre. All were completed, except for one, because of recipient death. The conventional laparoscopic approach was used in 541 cases (75.88%), NOTES in 116 (16.9%), LESS in 55 (7.7%), and one mini open (0.14%). Two-thirds of the donors were females (478 cases). The mean donor age was 52.87 years (SD 10.93). Six donors (0.8%) were diagnosed beforehand with a small renal mass, which was removed before transplantation in bench surgery. The right kidney was removed in 17.8% of cases. Warm ischaemia time was higher in the NOTES and LESS groups. We had eight conversions. The global intraoperative and postoperative complication rates were 6.8% and 4.9%, respectively. None of the donors developed renal disease during follow-up (mean 3.68 years). Five-year recipient and graft survival rates were 98.8% and 96.8%, respectively. CONCLUSIONS: MILDN techniques are safe for donors and grafts, with low complication.
Assuntos
Transplante de Rim , Laparoscopia , Feminino , Humanos , Rim , Transplante de Rim/métodos , Laparoscopia/métodos , Doadores Vivos , Pessoa de Meia-Idade , Nefrectomia/métodos , Estudos Retrospectivos , Coleta de Tecidos e ÓrgãosRESUMO
PURPOSE: Few tools are available to predict uretero-lithotripsy outcomes in patients with ureteral stones. Aim of our study was to develop a nomogram predicting the probability of stone free rate in patients undergoing semi-rigid uretero-lithotripsy (ULT) for ureteral stones. METHODS: From January 2014 onwards, patients undergoing semi-rigid Ho: YAG laser uretero-lithotripsy for ureteral stones were prospectively enrolled in two centers. Patients were preoperatively evaluated with accurate clinical history, urinalysis and renal function. Non-contrast CT was used to define number, location and length of the stones and eventually the presence of hydronephrosis. A nomogram was generated based on the logistic regression model used to predict ULT success. RESULTS: Overall, 356 patients with mean age of 54 years (IQR 44/65) were enrolled. 285/356 (80%) patients were stone free at 1 month. On multivariate analysis single stone (OR 1.93, 95% CI 1.05-3.53, p = 0.034), stone size (OR 0.92, 95% CI 0.87-0.97, p = 0.005), distal position (OR 2.12, 95% CI 1.29-3.48, p = 0.003) and the absence of hydronephrosis (OR 2.02, 95% CI 1.08-3.78, p = 0.029) were predictors of success and these were used to develop a nomogram. The nomogram based on the model presented good discrimination (area under the curve [AUC]: 0.75), good calibration (Hosmer-Lemeshow test, p > 0.5) and a net benefit in the range of probabilities between 15 and 65%. Internal validation resulted in an AUC of 0.74. CONCLUSIONS: The implementation of our nomogram could better council patients before treatment and could be used to identify patients at risk of failure. External validation is warranted before its clinical implementation.
Assuntos
Litotripsia a Laser/métodos , Nomogramas , Cálculos Ureterais/cirurgia , Adulto , Idoso , Feminino , Humanos , Litotripsia a Laser/instrumentação , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
TMPRSS2-ERG expression in blood has been correlated with low docetaxel benefit in metastatic castration-resistant prostate cancer (mCRPC). This multicenter study aimed to prospectively asses its role as a taxane-resistance biomarker in blood and retrospectively in tumors, exploring also the impact of prior abiraterone/enzalutamide (A/E) in patients and in vitro. TMPRSS2-ERG was tested by quantitative reverse-transcription PCR. We included 204 patients (137 blood and 124 tumor samples) treated with taxanes. TMPRSS2-ERG expression was correlated with prostate-specific antigen (PSA)-progression-free survival (PFS), radiological-PFS (RX-PFS), and overall survival (OS). Independent association with survival was evaluated by multivariate Cox modeling. In vitro ERG knockdown and combinatorial and sequential experiments with enzalutamide and docetaxel were performed in VCaP cells. Prior A/E (HR 1.8, 95% CI 1.2-2.8) and blood TMPRSS2-ERG detection (HR 2, 95% CI 1.1-3.7) were independently associated to lower PSA-PFS. In patients without prior A/E, blood and tumor TMPRSS2-ERG independently predicted lower PSA-PFS (HR 3.3, 95% CI 1.4-7.9 and HR 1.8, 95% CI 1.02-3.3, respectively) to taxanes. When prior A/E was administered, TMPRSS2-ERG was not associated with outcome. There was a significant interaction between blood TMPRSS2-ERG and prior A/E related to PSA-PFS (p = 0.032) and RX-PFS (p = 0.009). In vitro stable ERG inhibition did not sensitize VCaP cells to docetaxel. Concomitant enzalutamide and taxanes were synergistic, but prior enzalutamide reduced docetaxel cytotoxicity in VCaP cells. Enzalutamide induced the expression of neuroendocrine markers and reduced that of E-cadherin. We conclude that prior hormone-therapy may influence taxanes response and TMPRSS2-ERG prognostic value. Thus, multiple and sequential biomarkers are needed in CRPC follow-up evaluation.
Assuntos
Biomarcadores Tumorais/genética , Docetaxel/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Fusão Oncogênica/genética , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Benzamidas , Biomarcadores Tumorais/sangue , Hidrocarbonetos Aromáticos com Pontes , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Intervalo Livre de Doença , Sinergismo Farmacológico , Técnicas de Inativação de Genes , Humanos , Masculino , Nitrilas , Proteínas de Fusão Oncogênica/sangue , Feniltioidantoína/farmacologia , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/genética , Estudos Retrospectivos , Taxoides , Regulador Transcricional ERG/genéticaRESUMO
PURPOSE: To report our initial experience using a patient-specific 3D-printed renal tumor model for the surgical planning of a complex heminephrectomy in a horseshoe kidney. MATERIALS AND METHODS: We selected a clinical case for a complex laparoscopic surgery consisting in a 53 year-old male presenting a local recurrence of a renal tumor in a horseshoe kidney with aberrant vascularisation previously treated with a laparoscopic partial nephrectomy. He is now proposed for a laparoscopic left heminephrectomy. Along with conventional imaging, a real-size 3D-printed renal model was used to plan de surgical approach. The perioperative experience of the surgical team was recorded. RESULTS: The surgical team found the patient-specifi c 3D printed model useful for a better understanding of the anatomy and an easier surgical planning. CONCLUSION: The use of patient-specifi c 3D-printed renal models seem to be helpful for the surgical planning in complex renal tumors.
Assuntos
Carcinoma de Células Renais/cirurgia , Rim Fundido/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Modelos Anatômicos , Impressão Tridimensional , Carcinoma de Células Renais/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Humanos , Imageamento Tridimensional/métodos , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
BACKGROUND: Additional accurate non-invasive biomarkers are needed in the clinical setting to improve prostate cancer (PCa) diagnosis. Here we have developed a new and improved multiplex mRNA urine test to detect prostate cancer (PCa). Furthermore, we have validated the PCA3 urinary transcript and some panels of urinary transcripts previously reported as useful diagnostic biomarkers for PCa in our cohort. METHODS: Post-prostatic massage urine samples were prospectively collected from PCa patients and controls. Expression levels of 42 target genes selected from our previous studies and from the literature were studied in 224 post-prostatic massage urine sediments by quantitative PCR. Univariate logistic regression was used to identify individual PCa predictors. A variable selection method was used to develop a multiplex biomarker model. Discrimination was measured by ROC curve AUC for both, our model and the previously published biomarkers. RESULTS: Seven of the 42 genes evaluated (PCA3, ELF3, HIST1H2BG, MYO6, GALNT3, PHF12 and GDF15) were found to be independent predictors for discriminating patients with PCa from controls. We developed a four-gene expression signature (HIST1H2BG, SPP1, ELF3 and PCA3) with a sensitivity of 77% and a specificity of 67% (AUC = 0.763) for discriminating between tumor and control urines. The accuracy of PCA3 and previously reported panels of biomarkers is roughly maintained in our cohort. CONCLUSIONS: Our four-gene expression signature outperforms PCA3 as well as previously reported panels of biomarkers to predict PCa risk. This study suggests that a urinary biomarker panel could improve PCa detection. However, the accuracy of the panels of urinary transcripts developed to date, including our signature, is not high enough to warrant using them routinely in a clinical setting.
Assuntos
Biomarcadores Tumorais/urina , Proteínas de Neoplasias/urina , Neoplasias da Próstata/urina , RNA Mensageiro/urina , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/urina , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/urina , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: The aim of this study was to assess the accuracy of Ultrasound (US) and contrast-enhanced ultrasound (CEUS) in the characterization of renal nodules indeterminate on CT by identifying benign cystic lesions not requiring further examination. METHODS: 72 patients with 83 indeterminate renal nodules on CT underwent baseline US and CEUS that classified lesions as benign (Bosniak I, II or IIF cysts) or potentially malignant (Bosniak III or IV cysts, solid nodules). The accuracy of US and CEUS in the differentiation between benign cysts and potentially malignant nodules was analyzed and compared with the final diagnosis obtained by histology or follow-up of at least 23 months with CEUS ± a conclusive CT/MR study. RESULTS: Final diagnoses comprised 50 benign complex cysts, 1 focal nephritis, 1 multilocular cystic nephroma, 3 oncocytomas, 1 transitional cell carcinoma and 27 renal cell carcinomas. Unenhanced US correctly classified 18/50 (36%) benign cysts and 17/33 (51.5%) of the potentially malignant lesions obtaining a sensitivity of 36%, specificity of 51.5%, and overall accuracy of 42.2%. The addition of CEUS allowed a correct diagnosis of 48 /50 (96%) benign cysts and of 31/33 (93.9%) nodules as potentially malignant, with a sensitivity of 96%, specificity of 93.9%, and overall accuracy of 95.2%. CONCLUSION: CEUS is very useful in the differentiation between benign complex cysts and other lesions that require further investigation in non-conclusive renal nodules detected on CT, improving the accuracy of baseline US from 42.2 to 95.2%.
Assuntos
Cistos/diagnóstico por imagem , Nefropatias/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
PURPOSE: We validated the performance of our previously reported test for bladder cancer based on urine gene expression patterns using an independent cohort. We also ascertained whether alternative models could achieve better accuracy. MATERIALS AND METHODS: Gene expression patterns of the previously reported 48 genes, including the 12 + 2 genes of the signature, were analyzed by TaqMan® arrays in an independent set of 207 urine samples. We pooled all samples analyzed to date to obtain a larger training set of 404 and used it to search for putative improved new models. RESULTS: Our 12 + 2 gene expression signature had overall 80% sensitivity with 86% specificity (AUC 0.914) to discriminate between bladder cancer and control samples. It had 75% sensitivity and 75% specificity (AUC 0.83) to predict tumor aggressiveness in the validation set of urine samples. After grouping all samples 3 new signatures for diagnosis containing 2, 5 and 10 genes, respectively, and 1 containing 6 genes for prognosis were designed. Diagnostic performance of the 2, 5, 10 and 12-gene signatures was maintained or improved in the enlarged sample set (AUC 0.913, 0.941, 0.949 and 0.944, respectively). Performance to predict aggressiveness was also improved in the 14 and 6-gene signatures (AUC 0.855 and 0.906, respectively). CONCLUSIONS: This validation study confirms the accuracy of the 12 + 2 gene signature as a noninvasive tool for assessing bladder cancer. We present improved models with fewer genes that must be validated in future studies.
Assuntos
Biomarcadores Tumorais/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Humanos , Prognóstico , Transcriptoma , Neoplasias da Bexiga Urinária/urinaRESUMO
In a context where there is evidence that not every patient with low risk prostate cancer needs to be treated from the start, active treatments are expensive and public health care systems need to save money, studies on cost-effectiveness are a priority. To elaborate this article, we reviewed the publications on cost and cost-effectiveness of localized prostate cancer treatments that include active surveillance. In patients with low risk localized prostate cancer active surveillance is more cost-effective than active treatment. With time active surveillance may be more expensive than brachytherapy or radical prostatectomy. The frequency of prostatic biopsies and the percentage of conversions to active treatment will be determinant in final costs of active surveillance.
Assuntos
Neoplasias da Próstata/economia , Neoplasias da Próstata/terapia , Conduta Expectante/economia , Biópsia/economia , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/cirurgiaRESUMO
Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (P< 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P= 0.001 and 16.3, 95% CI = 1.8-2151.5; P= 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.
RESUMO
Current standard methods used to detect and monitor bladder urothelial cell carcinoma (UCC) are invasive or have low sensitivity. The incorporation into clinical practice of a non-invasive tool for UCC assessment would enormously improve patients' quality of life and outcome. This study aimed to examine the microRNA (miRNA) expression profiles in urines of UCC patients in order to develop a non-invasive accurate and reliable tool to diagnose and provide information on the aggressiveness of the tumor. We performed a global miRNA expression profiling analysis of the urinary cells from 40 UCC patients and controls using TaqMan Human MicroRNA Array followed by validation of 22 selected potentially diagnostic and prognostic miRNAs in a separate cohort of 277 samples using a miRCURY LNA qPCR system. miRNA-based signatures were developed by multivariate logistic regression analysis and internally cross-validated. In the initial cohort of patients, we identified 40 and 30 aberrantly expressed miRNA in UCC compared with control urines and in high compared with low grade tumors, respectively. Quantification of 22 key miRNAs in an independent cohort resulted in the identification of a six miRNA diagnostic signature with a sensitivity of 84.8% and specificity of 86.5% (AUC = 0.92) and a two miRNA prognostic model with a sensitivity of 84.95% and a specificity of 74.14% (AUC = 0.83). Internal cross-validation analysis confirmed the accuracy rates of both models, reinforcing the strength of our findings. Although the data needs to be externally validated, miRNA analysis in urine appears to be a valuable tool for the non-invasive assessment of UCC.
Assuntos
Biomarcadores Tumorais/urina , Regulação Neoplásica da Expressão Gênica , MicroRNAs/urina , Neoplasias da Bexiga Urinária/urina , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/classificação , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologiaRESUMO
Bladder cancer represents a very important entity in the field of urologic oncology. At the time of diagnosis 70% of them are non muscle-invasive tumors with a very variable risk of recurrence and progression. These patients will require a periodic follow up, at least for 5 years, performing multiple cystoscopies and urine cytologies throughout their lifes. These diagnostic tests are either invasive or have a low sensitivity, a fact that has stimulated the search of non-invasive markers with high sensitivity for the diagnosis of bladder cancer. The great advantage in this neoplasia is the availability of a biologic sample such as urine, which being in close contact with the urothelium collects exfoliated cells, representing a valuable non invasive tool for the diagnosis and follow up of this neoplasias. In this article we try to perform a review of those markers for bladder cancer already marketed and under development, as well as future diagnostic perspectives.
Assuntos
Biomarcadores/análise , Neoplasias da Bexiga Urinária/diagnóstico , Animais , Antígenos de Neoplasias/análise , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Proteínas NuclearesRESUMO
Over the last 20 years surgery has suffered a dramatic change. We saw how open surgery was almost replaced by laparoscopic surgery and this latter has evolved to minimally invasive surgical techniques such as LaparoEndoscopic Single-site Surgery (LESS) and NOTES ((Natural Orifice Transluminal Endoscopic Surgery). These minimally invasive operations try to maximally reduce the size and number of abdominal scars in order to minimize morbidity, reducing surgical aggression and therefore the need for analgesia during the postoperative period, and they offer excellent cosmetic results. LESS surgery implies the performance of intra-abdominal surgery through a single 3-4 cm incision, through which laparoscopic instruments are introduced. This may be considered the next step in the evolution of laparoscopic surgery advancing to the ideal of scarless surgery. This modality is having great acceptance, since it allows the insertion of an extra trocar at any time transforming it in conventional laparoscopic surgery. Furthermore, when performing the incision within the umbilical scar, it enables concealing the incision in it at the end of the operation, achieving very good cosmetic results. NOTES surgery would be another step forward. Pure NOTES techniques in the field of Urology are very complex to perform today with the available equipment. Hybrid NOTES and assisted NOTES are variations described which have demonstrated they are viable and offer very good cosmetic results and lower morbidity. Regarding this, the vaginal approach offers a good working channel that can also be used for specimen extraction. Recent published studies confirm the feasibility and reproducibility of both techniques in urologic surgery, specifically in the treatment of renal cancer, with comparable results to conventional laparoscopic surgery.
Assuntos
Rim/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Humanos , Neoplasias Renais/cirurgia , Laparoscopia/métodosRESUMO
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. PATIENT SUMMARY: It is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.
Assuntos
Cisplatino , Neoplasias da Bexiga Urinária , Humanos , Terapia Neoadjuvante , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais/genética , Cistectomia , Genômica , Invasividade Neoplásica , Proteína Grupo D do Xeroderma PigmentosoRESUMO
UNLABELLED: What's known on the subject? and What does the study add? Prostate growth is ruled by testosterone. Nevertheless, the paradigm that high testosterone levels induce prostate cancer development or lead to a poor prognosis in prostate cancer is not supported by evidence. A growing number of studies suggest that, on the contrary, low testosterone levels are related to poor prognosis features in prostate cancer such as higher prostate-specific antigen or higher Gleason score. Our experience shows that testosterone levels are related to risk of progression of prostate cancer - those men with lower testosterone levels are at higher risk of progression of their prostate cancer after treatment delivery. OBJECTIVES: ⢠Low testosterone levels have been related to a higher diagnosis of prostate cancer (PCa). Hormonal levels have been related to poor prognosis factors in men with PCa, mainly after radical prostatectomy. ⢠Our aim was to determine the relationship between hormonal levels and PCa prognosis factors in men with PCa prior to the onset of treatment. PATIENTS AND METHODS: ⢠We prospectively analysed 137 males diagnosed in our centre with PCa with 5+5 core prostate biopsies from February 2007 to December 2009. ⢠As part of our clinical protocol, we performed hormonal determination (testosterone and sex hormone binding globulin) following International Society of Andrology, International Society for the Study of the Aging Male and European Association of Urology recommendations. ⢠Free testosterone and bioavailable testosterone were calculated using Vermeulen's formula. ⢠Age, prostate-specific antigen (PSA), free to total PSA, PSA density, number of previous biopsies, digital rectal examination staging, Gleason score, percentage of tumour in the biopsy sample, bilaterality of the tumour and risk of progression group were prospectively recorded. RESULTS: ⢠Higher testosterone levels were related to lower digital rectal examination staging (P= 0.02) and lower PSA level (P= 0.05). Higher testosterone was not related to lower Gleason score (P= 0.08). ⢠Testosterone was inversely related to PCa bilaterality (P < 0.01) and percentage of tumour in the biopsy (P < 0.01). ⢠High testosterone levels were found in patients allocated to the low risk of progression group and inversely (P= 0.03). ⢠In multivariate analysis, higher age and lower testosterone were related to higher D'Amico risk of progression. CONCLUSION: ⢠Patients with PCa and lower testosterone levels have poor prognosis factors and higher tumour burden before treatment onset. These findings reinforce the idea that low testosterone levels pretreatment are related to a poor prognosis in PCa.
Assuntos
Próstata/patologia , Neoplasias da Próstata/sangue , Testosterona/sangue , Idoso , Biomarcadores Tumorais/sangue , Biópsia , Terapia Combinada , Progressão da Doença , Seguimentos , Humanos , Masculino , Gradação de Tumores , Prognóstico , Estudos Prospectivos , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Fatores de RiscoRESUMO
UNLABELLED: What's known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia (HGPIN) is a risk factor for prostate cancer (PCa), but only multifocality is an indication for early rebiopsy. Other risk factors for PCa development from HGPIN remain unknown. PCa is related to testosterone. Testosterone has been proven to be linked to PCa detection and poor prognosis PCa. This study shows that low free and bioavailable testosterone levels are associated with an increased risk of PCa in a rebiopsy after HGPIN diagnosis. Men with low testosterone levels and HGPIN could therefore be considered a high-risk cohort for developing PCa. OBJECTIVE: To determine the relevance of the hormonal profile of patients with high grade prostatic intraepithelial neoplasia (HGPIN) and its relationship to prostate cancer (PCa) in rebiopsy. PATIENTS AND METHODS: We prospectively analysed 82 consecutive patients with a diagnosis of HGPIN without PCa in a prostate biopsy between September 2007 and December 2009. Of these 82 patients, 45 underwent rebiopsy and their hormonal profile was determined (testosterone and sex hormone-binding globulin [SHBG]) as part of our clinical protocol. Patient age, PSA level, prostate volume, PSA density, testosterone, free testosterone, bioavailable testosterone and SHBG were recorded prospectively. A comparative study between those patients with a positive rebiopsy and those with a negative rebiopsy was performed. RESULTS: We found that free testosterone (P = 0.04), bioavailable testosterone (P = 0.04) and SHBG (P = 0.02) were significantly associated with a positive rebiopsy. Other variables such as age (P = 0.745), PSA level (P = 0.630), prostate volume (P = 0.690), PSA density (P = 0.950), testosterone (P = 0.981) and prostatic intraepithelial neoplasia multifocality (P = 0.777) were not associated with the presence of adenocarcinoma in the rebiopsy. CONCLUSIONS: Patients with adenocarcinoma of the prostate after a diagnosis of HGPIN have higher SHBG levels and lower calculated free testosterone levels than patients with a negative rebiopsy. Testosterone levels might be a useful indication for rebiopsy after HGPIN diagnosis.
Assuntos
Neoplasia Prostática Intraepitelial/sangue , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Testosterona/sangue , Idoso , Biópsia/estatística & dados numéricos , Humanos , Masculino , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Muscle invasive bladder cancer has a mortality rate at 5 years of 50%, despite radical therapy, as a result of tumour progression and dissemination. This suggests that half of patients have disseminated disease at the time of diagnosis, which is not detected by the staging techniques currently used. The prognostic factors (histological grade and tumour stage) and current staging techniques do not discriminate between those patients who will be cured with surgical treatment and those who will die from metastatic spread. New diagnostic and prognostic tools that complement the existing methods and provide a proper assessment of carcinoma invading bladder muscle are therefore essential. Molecular staging techniques using specific biomarkers have been applied in various solid tumours to determine the presence of missed tumour cells in lymph nodes (LNs) during routine pathological examination. These techniques could identify patients with LN micrometastases who may potentially benefit from early treatment with chemotherapy. This study compares the performance of conventional histological analysis and molecular biomarkers in detecting bladder cancer LN micrometastases and predicting patient's clinical outcome. The study found that, even though a clear trend to a worse outcome was shown in those patients who became node-positive after molecular analysis, no statistical differences were found in cancer-specific and recurrence-free survival analysis between those patients who were negative by histology but positive by molecular analysis and those who were negative by both techniques. We concluded that molecular analysis of LN spreading in bladder cancer has a better detection rate than conventional histological examination. OBJECTIVE: ⢠To improve the sensitivity of histological examination in detecting occult lymph node (LN) dissemination of bladder cancer using gene expression analysis. PATIENTS AND METHODS: ⢠We carried out a retrospective study that included 504 formalin-fixed paraffin-embedded LNs from 90 patients with muscle invasive bladder cancer and 35 controls. ⢠Gene expression values of two molecular biomarkers (FXYD3 and KRT20) were analysed using reverse transcription real-time quantitative PCR (RT-qPCR). ⢠Molecular results were compared with histological status and patients' clinical outcomes. RESULTS: ⢠Of the 90 patients analysed, 16 were positive and 74 were negative by histological analysis. Of these 74, 19 were classified as positive using RT-qPCR. ⢠Significant differences in cancer-specific (P= 0.011) and recurrence-free (P= 0.009) survival were found between the three patient groups (patients positive by both techniques, patients negative by both techniques, and patients negative by histological but positive by molecular analysis). ⢠A significant difference was not found between histologically negative but molecularly positive patients and patients who were negative by both techniques, but a clear trend to a worse outcome was found in those patients who became node-positive after molecular analysis. CONCLUSIONS: ⢠The analysis of FXYD3 and KRT20 could improve current pathological examination for the detection of micrometastases in LNs. ⢠Further and more extensive studies will determine the real prognostic value of such LN micrometastases.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Membrana/metabolismo , Micrometástase de Neoplasia/diagnóstico , Proteínas de Neoplasias/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , DNA Complementar/metabolismo , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Queratina-20/genética , Queratina-20/metabolismo , Metástase Linfática , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , RNA Neoplásico/metabolismo , Radioterapia Adjuvante , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapiaRESUMO
INTRODUCTION: Relationship between prostate cancer (PCa) and testosterone (T) is controversial. Conflicting evidence has been published about T levels and development of PCa. AIM: (1) To determine the relationship between hormone levels and the diagnosis of PCa. (2) To specifically focus on the relationship between PCa and T in men classified as biochemically hypogonadal. MATERIALS AND METHODS: Prospective analysis of 1,000 transrectal ultrasound guided prostate biopsies (5 + 5 cores biopsies) between September 2007 and January 2010 in one center. Indication for prostate biopsy was suspicion of PCa on the basis of elevated prostate-specific antigen (PSA) and/or digital rectal examination (DRE). Serum testosterone and sex hormones binding globulin (SHBG) were determined in these patients. Of 557 men, the data were sufficient for further analysis. Age, body mass index (BMI), smoking/drinking habits, PSA, free PSA, PSA density, prostate volume, number of previous biopsies, DRE, and hormone levels were prospectively recorded. RESULTS: No relationship was found between T and PCa (449 ± 167 ng/dL in PCa versus 437 ± 169 ng/dL in non-PCa). SHBG was significantly higher in patients with PCa (51 ± 27 ng/dL in PCa vs. 44 ± 18 ng/dL in non-PCa). In hypogonadal men, T levels correlated with the PCa (235 ± 95 ng/dL in men with PCa versus 270 ± 58 ng/dL in men without PCa, P = 0.004). CONCLUSIONS: T levels were comparable in men with and without PCa, but SHBG levels were significantly higher in men with PCa. In men with low T, the men with PCa had a lower serum T levels and a lower prostate volume than the men without PCa.
Assuntos
Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Testosterona/sangue , Idoso , Biópsia por Agulha , Estudos de Coortes , Exame Retal Digital , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Globulina de Ligação a Hormônio Sexual/metabolismo , Ultrassom Focalizado Transretal de Alta IntensidadeRESUMO
BACKGROUND: This study aims to evaluate the feasibility and usefulness of an ovine model in order to perform natural orifice translumenal endoscopic surgery (NOTES) approach and laparoscopic nephrectomy for research and training purposes. METHODS: Ten healthy female sheep were used to perform transvaginal NOTES-assisted right laparoscopic nephrectomy using a flexible 12-mm gastroscope through a vaginal access and two additional 5- and 10-mm trocars placed in the abdomen. The renal artery, the renal vein, and the ureter were dissected, and ligation was accomplished by using laparoscopic clips. The right kidney was retrieved transvaginally after enlarging the vaginal trocar incision. All data related with the surgical procedure, perioperative, and postoperative outcomes were recorded. The animals were monitored after surgery for a 30-day period with daily clinical follow-up. RESULTS: We established a useful animal model of transvaginal NOTES-assisted laparoscopic nephrectomy, performing the transvaginal approach and the abdomen exploration with no complications in any animals. The renal artery, the renal vein, and the ureter were identified, clipped, and transected combining the 5-mm laparoscopic access and the endoscopic vision in the whole group. Mean operative time was 86 ± 14.49 min, estimated blood loss was less than 20 ml in all cases, and there was no bleeding or laceration of adjacent organs. The animals recovered successfully in all cases postoperatively. After 1 month, exploratory laparotomy did not show alterations in abdominal cavity, and the vaginotomy incision healed completely in every animal. CONCLUSIONS: This experiment shows that transvaginal NOTES-assisted laparoscopic nephrectomy in ovine model is feasible and reproducible while offering an innovative possibility to help surgeons with this recent technology in the treatment of renal cancer. Well-managed experimental studies need to be carried out to determine the safety and efficacy of NOTES in the treatment of renal cancer.