Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 141
Filtrar
1.
J Urol ; : 101097JU0000000000001139, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396409

RESUMO

PURPOSE: Determine if "bag-squeeze" technique decreases pain during flexible cystoscopy in men. METHODS AND MATERIALS: A single center, prospective, double-blinded randomized controlled trial recruiting 200 consenting participants who were ambulatory, outpatient males who had undergone a prior cystoscopy and were not expected to require any secondary procedures. Men with prior urethral stricture or bladder neck contracture were excluded. Once eligibility was assessed and consent obtained, participants were randomized to undergo cystoscopy with the "bag-squeeze" (group A) or the sham bag-squeeze procedure (group B). Following the cystoscopy, participants completed a pain questionnaire: visual analogue scale. Differences in mean pain score between groups were evaluated using a Students T test with two-sided alpha of 0.05. RESULTS: Two hundred patients were randomized and underwent flexible cystoscopy. Ten participants were ineligible because they required secondary procedures. Among the 190 eligible patients, 97 were randomized to bag-squeeze (group A) and 93 to sham bag-squeeze (group B) with mean pain scores of 1.91 and 3.39, respectively. (p<0.005). CONCLUSION: This study demonstrated a clinically meaningful decrease in pain for men undergoing flexible cystoscopy when the irrigation "bag-squeeze" technique was employed versus placebo bag-squeeze. Accordingly, this useful, simple and free method to improve patient comfort during flexible cystoscopy should be adopted by clinicians.Patient Summary:Squeezing the irrigation bag during a flexible cystoscopy improves pain perception by males and we recommend this to be the standard of care.

3.
Urol Oncol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32081560

RESUMO

BACKGROUND: Highly sensitive and specific urinary biomarkers for the early detection of bladder cancer (BC) to improve the performance of urinary cytology are needed. OBJECTIVE: To investigate the usefulness of methylation markers in voided urine to identify BC presence and grade. DESIGN, SETTINGS, AND PARTICIPANTS: Using genome-wide methylation strategies in Toronto, Canada and Liège, Belgium, we have identified differentially methylated genes (TWIST1, RUNX3, GATA4, NID2, and FOXE1) in low-grade vs. high-grade BC tissue and urine. We accrued urine samples from 313 patients using a 2:1 ratio in a case-control setting from Toronto, Canada, Halifax, Canada, and Zurich, Switzerland. We studied the usefulness of these 5 methylated genes to identify BC and discriminate cancer grade in voided urine specimens. Urinary cell sediment DNA was evaluated using qPCR-based MethyLight assay. Multivariable logistic regression prediction models were created. RESULTS AND LIMITATIONS: We included 211 BC patients (180 nonmuscle invasive) and 102 controls. In univariate analyses, all methylated genes significantly predicted BC vs. no BC, and high grade vs. low grade (all P < 0.05). In multivariable analysis, NID2, TWIST1, and age were independent predictors of BC (all P < 0.05). Sensitivity of NID2 and TWIST1 to predict BC and BC grade was 76.2% and 77.6%, respectively, whereas specificity was 83.3% and 61.1%, respectively. Multivariable models predicting BC overall and discriminating between high-grade and low-grade BC reached area under the receiver operating characteristics curves of 0.89 and 0.78, respectively. CONCLUSIONS: This multi-centric study in a real life scenario (different countries, techniques, and pathologists) supports the promise of epigenetic urinary markers in noninvasively detecting BC. With sensitivities and specificities in the range of 80%, the overall performance characteristics of this panel of methylated genes probably does not allow such signature to significantly alter clinical care at this stage but is worth further studying for instance in BC surveillance or screening in high-risk populations.

5.
J Mol Diagn ; 22(1): 30-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605802

RESUMO

After diagnosis of prostate cancer is confirmed by a positive biopsy, the tumor may be surgically removed via radical prostatectomy (RP). However, many prostate cancer patients experience biochemical recurrence after surgery and/or undergo salvage radiotherapy or hormone therapy. Timely treatment is required to prevent the spread of disease in these cases, and biopsy tissue may hold potential for disease prognostication before surgery is ever performed. We previously developed a prognostic multigene methylation panel in RP specimens, including APC, CRIP3, HOXD3, and TGFB2. In the current study, this panel was applied to a cohort of biopsy specimens (n = 86), which were assessed for DNA methylation using the real-time quantitative PCR-based multiplex MethyLight. The biopsy-based methylation panel is significantly associated with biochemical recurrence when combined with the current clinical parameter of prostate-specific antigen (PSA) levels at diagnosis and is able to prognosticate the initiation of salvage radiotherapy, where it outperforms PSA, and/or hormone therapy after RP. In addition, this methylation panel is significantly associated with late recurrence occurring within 5 and 7 years after surgery, when combined with PSA at diagnosis. Combining DNA methylation and clinicopathologic markers at the biopsy stage will not only increase their prognostic ability but will also ensure effective patient management.

6.
BJU Int ; 125(4): 525-530, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31863617

RESUMO

OBJECTIVES: To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS: A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS: In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS: sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

7.
Urol Oncol ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704141

RESUMO

BACKGROUND: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. OBJECTIVES: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. MATERIALS AND METHODS: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. RESULTS: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. CONCLUSIONS: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.

8.
Can Urol Assoc J ; 13(8): 250-255, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31496491

RESUMO

INTRODUCTION: Active surveillance (AS) is standard of care in low-risk prostate cancer (PCa). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP). METHODS: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years followup. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo/prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival (PFS) curves between TCLo density groups. Test characteristics of TCLo density were explored with receiver operating characteristic (ROC) curves. RESULTS: We included 181 patients who had CBx from 2012-2015 and met inclusion criteria. The mean age of patients was 62.58 years (standard deviation [SD] 7.13) and median followup was 60.9 months (interquartile range [IQR] 23.4). A high TCLo density score (>0.05) was independently associated with time to CP (hazard ratio [HR] 4.70; 95% confidence interval [CI] 2.62-8.42; p<0.001) and GP (HR 3.85; 95% CI 1.91-7.73; p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression. CONCLUSIONS: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PCa.

9.
Urology ; 134: 24-31, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31302137

RESUMO

Lynch Syndrome (LS) entails a defective DNA mismatch repair system, which is the postreplicative proofreading and editing system, ensuring our genome's integrity. LS predisposes to several cancers, most commonly colorectal and endometrial cancers. LS occurs in approximately 1 in 250-1000 people. LS is associated with urological malignancies with upper tract urothelial carcinoma the most common, although still clinically underestimated. Other urologic malignancies possibly associated with LS include bladder, prostate, testis, and renal cell carcinoma. Ascertaining their true prevalence in LS is mandatory for their and their relatives' diagnosis and treatment. Awareness regarding identifying patients at risk for LS through assessment of personal and familial oncologic history is critical among urologists.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Urogenitais , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Reparo de Erro de Pareamento de DNA/genética , Humanos , Administração dos Cuidados ao Paciente , Medição de Risco , Neoplasias Urogenitais/genética , Neoplasias Urogenitais/patologia , Neoplasias Urogenitais/terapia
11.
PLoS One ; 14(4): e0216255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31034504

RESUMO

OBJECTIVES: To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB). RESULTS: The literature search identified 12 eligible studies. Three (all rated as "moderate RoB") out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03-1.88). Four (mainly rated as "serious RoB") out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20-1.59). CONCLUSION: Pooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches.


Assuntos
Cistectomia , Músculos/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Terapia Combinada , Intervalo Livre de Doença , Humanos , Invasividade Neoplásica , Viés de Publicação
12.
J Urol ; 202(2): 319-325, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30865566

RESUMO

PURPOSE: Patients with bladder cancer who undergo intestinal urinary diversion may be at increased risk for bone fractures thought to be secondary to chronic metabolic acidosis and ensuing bone loss. Our main objective was to assess whether patients who undergo intestinal urinary diversion are at increased risk for fracture. MATERIALS AND METHODS: Patients who underwent intestinal urinary diversion between 1994 and 2014 in Ontario, Canada were identified using linked administrative databases. Patients were categorized as undergoing diversion for bladder cancer or nonbladder cancer causes and matched 4:1 to a healthy cohort. We determined incidence rates of the incidence of fractures per 100 person-years. Multivariable Cox proportional hazards models were used to evaluate the impact of intestinal urinary diversion on the risk of fracture. RESULTS: Overall 4,301 patients with and 907 without bladder cancer underwent intestinal urinary diversion. The fracture incidence rate was significantly greater in the bladder cancer and nonbladder cancer cohorts compared to respective matched controls. In the bladder cancer cohort vs matched controls there were 4.41 vs 2.63 fractures per 100 person-years and in the nonbladder cancer cohort vs matched controls there were 5.67 vs 3.51 fractures per 100 person-years (each p <0.001). On multivariable analysis patients who underwent intestinal urinary diversion for bladder cancer or nonbladder cancer reasons had significantly shorter fracture-free survival compared to the respective matched cohorts (HR 1.48, IQR 1.35-1.63, and HR 1.48, IQR 1.31-1.69, respectively). CONCLUSIONS: Our results demonstrated that regardless of age patients with intestinal urinary diversion are at increased risk for bone fractures compared to the general population. Our findings are in line with previous reports and support the need for bone health monitoring.


Assuntos
Fraturas Ósseas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Derivação Urinária , Idoso , Estudos de Coortes , Humanos , Intestinos/cirurgia , Ontário , Estudos Retrospectivos , Medição de Risco , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos
13.
Ecancermedicalscience ; 13: 905, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915163

RESUMO

The high recurrence and progression rates of non-muscle invasive bladder cancer (NMIBC) have led investigators to study the use of intravesical therapy in order to prevent them. Bacillus Calmette-Guérin (BCG) has been successfully used for this indication to treat NMIBC for more than four decades. BCG is the only intravesical agent shown to reduce the risk of progression of NMIBC to muscle-invasive disease. Despite over 40 years of clinical use, the precise mechanism of action for what has often been considered the most successful cancer immunotherapy in humans remains largely unknown. Unfortunately, BCG therapy is not a universal panacea and it still fails in up to 40% of patients. Many of these patients, especially in the high-risk category (T1 high-grade disease, carcinoma in situ) will require aggressive therapy like cystectomy or in selected cases, bladder-sparing options like chemo-radiation. Indeed, there is no gold standard intravesical treatment after BCG failure.

14.
Clin Epigenetics ; 11(1): 54, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917865

RESUMO

BACKGROUND: Global DNA methylation alterations are hallmarks of cancer. The tumor-suppressive TET enzymes, which are involved in DNA demethylation, are decreased in prostate cancer (PCa); in particular, TET2 is specifically targeted by androgen-dependent mechanisms of repression in PCa and may play a central role in carcinogenesis. Thus, the identification of key genes targeted by TET2 dysregulation may provide further insight into cancer biology. RESULTS: Using a CRISPR/Cas9-derived TET2-knockout prostate cell line, and through whole-transcriptome and whole-methylome sequencing, we identified seven candidate genes-ASB2, ETNK2, MEIS2, NRG1, NTN1, NUDT10, and SRPX-exhibiting reduced expression and increased promoter methylation, a pattern characteristic of tumor suppressors. Decreased expression of these genes significantly discriminates between recurrent and non-recurrent prostate tumors from the Cancer Genome Atlas (TCGA) cohort (n = 423), and ASB2, NUDT10, and SRPX were significantly correlated with lower recurrence-free survival in patients by Kaplan-Meier analysis. ASB2, MEIS2, and SRPX also showed significantly lower expression in high-risk Gleason score 8 tumors as compared to low or intermediate risk tumors, suggesting that these genes may be particularly useful as indicators of PCa progression. Furthermore, methylation array probes in the TCGA dataset, which were proximal to the highly conserved, differentially methylated sites identified in our TET2-knockout cells, were able to significantly distinguish between matched prostate tumor and normal prostate tissues (n = 50 pairs). Except ASB2, all genes exhibited significantly increased methylation at these probes, and methylation status of at least one probe for each of these genes showed association with measures of PCa progression such as recurrence, stage, or Gleason score. Since ASB2 did not have any probes within the TET2-knockout differentially methylated region, we validated ASB2 methylation in an independent series of matched tumor-normal samples (n = 19) by methylation-specific qPCR, which revealed concordant and significant increases in promoter methylation within the TET2-knockout site. CONCLUSIONS: Our study identifies seven genes governed by TET2 loss in PCa which exhibit an association between their methylation and expression status and measures of PCa progression. As differential methylation profiles and TET2 expression are associated with advanced PCa, further investigation of these specialized TET2 targets may provide important insights into patterns of carcinogenic gene dysregulation.


Assuntos
Metilação de DNA , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas/genética , Linhagem Celular Tumoral , Reprogramação Celular , Progressão da Doença , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Masculino , Gradação de Tumores , Regiões Promotoras Genéticas , Neoplasias da Próstata/patologia , Análise de Sequência de RNA , Análise de Sobrevida , Sequenciamento Completo do Exoma
16.
Int J Radiat Oncol Biol Phys ; 104(1): 61-66, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625410

RESUMO

PURPOSE: Neoadjuvant radiation therapy (RT) improves disease control in various cancers and has become an established oncologic treatment strategy. During 2001 to 2004, we conducted a phase 1 pilot study assessing the role of short-course preoperative RT (PreORT) for men with unfavorable intermediate- and high-risk localized prostate cancer. Herein, we present long-term follow-up toxicity and oncologic outcomes. METHODS AND MATERIALS: Eligible patients had histologically proven prostate cancer, cT1-T2N0M0 disease, prostate-specific antigen >15 to 35 ng/mL regardless of Gleason score, or prostate-specific antigen 10 to 15 ng/mL with Gleason score ≥7. Patients received 25 Gy in 5 consecutive daily fractions (5 Gy per fraction) to the prostate only, followed by radical prostatectomy within 14 days after RT completion. Primary outcomes were intraoperative morbidity and late genitourinary (GU) and gastrointestinal toxicities. RESULTS: In total, 15 patients were enrolled; 14 patients completed PreORT followed by radical prostatectomy, which also included bilateral lymph node dissections in 13 cases. Median follow-up was 12.2 years (range, 6.7-16.3). Late GU toxicity was common, with 2 patients (13.3%) experiencing G2 toxicity and 6 patients (40%) G3 toxicity. There were no patients with G4 to G5 late GU toxicity. Late gastrointestinal toxicity was infrequent, with only 1 patient (6.7%) experiencing transient G2 proctitis. At last follow-up, 8 (53.3%) and 6 (40%) patients experienced biochemical and metastatic disease recurrence, respectively. CONCLUSIONS: The use of PreORT in men with high-risk prostate cancer is associated with unexpected high rates of late GU toxicity. Future studies examining the role of RT preradical prostatectomy must cautiously select RT technique and dose schedule. Importantly, long-term follow-up data are essential to fully determine the therapeutic index of PreORT in the management of localized disease.


Assuntos
Neoplasias da Próstata/radioterapia , Idoso , Fracionamento da Dose de Radiação , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Projetos Piloto , Cuidados Pré-Operatórios , Proctite/etiologia , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Conformacional , Fatores de Tempo , Resultado do Tratamento , Sistema Urogenital/efeitos da radiação
18.
Clin Genitourin Cancer ; 17(1): 38-45, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30686350

RESUMO

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) before cystectomy improves survival in muscle-invasive urothelial bladder cancer (MIBC). The use of NAC before chemoradiation (CRT) has been limited, as these patients are often elderly, frail, and ineligible for cisplatin. However, the role of NAC in fit, cisplatin-eligible patients who opt for bladder preservation warrants further evaluation. PATIENTS AND METHODS: Patients with MIBC treated with NAC followed by CRT at the Princess Margaret and Durham Regional cancer centers from 2008 to 2017 were retrospectively reviewed. Gemcitabine-cisplatin NAC was given for 2 to 4 cycles, followed by reassessment for CRT. External-beam radiotherapy (60-66 Gy) over 6 weeks was given with concurrent weekly cisplatin at 40 mg/m2. Kaplan-Meier method was used for survival analyses. RESULTS: We identified 57 consecutive patients. Median age was 72 (range 45-87), and all had an Eastern Cooperative Oncology Group performance status of 0 (60%) or 1 (40%). Stage II disease (65%), stage III disease (25%), and regional nodal metastases (11%) were included. Most completed planned NAC (95%). All patients completed external-beam radiotherapy, and 84% completed at least 60% of the planned concurrent weekly cisplatin doses. Median (range) follow-up was 19.3 (4.8-96.1) months. Median overall survival (OS) was not reached. Two-year OS and disease-specific survival rates were 74% (95% confidence interval, 57.7-84.9) and 88% (95% confidence interval, 78.5-98.1), respectively. Two-year bladder-intact disease-free survival was 64%. Salvage cystectomy was performed in 14%. Distant relapse occurred in 11%, and 9% died of metastatic disease. OS was associated with baseline hydronephrosis and with bladder-intact disease-free survival with residual disease on cystoscopy. CONCLUSION: NAC followed by CRT can result in encouraging outcomes and tolerability in cisplatin-eligible patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Cistectomia/mortalidade , Neoplasias Musculares/mortalidade , Terapia Neoadjuvante/mortalidade , Tratamentos com Preservação do Órgão/mortalidade , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Neoplasias Musculares/terapia , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
19.
Int J Cancer ; 144(7): 1676-1684, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30350309

RESUMO

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut ) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher-risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh /TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer.


Assuntos
Metilação de DNA , Mutação , Telomerase/genética , Neoplasias da Bexiga Urinária/genética , Progressão da Doença , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Regiões Promotoras Genéticas , Análise de Sequência de RNA , Regulação para Cima
20.
Curr Probl Diagn Radiol ; 48(2): 161-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29655890

RESUMO

Urinary diversions are surgical procedures that reconstruct the lower urinary tract following cystectomy. The 2 common surgical approaches are based on the continence status of the urinary tract. Incontinent diversions have continuous urine drainage through a cutaneous stoma, whereas continent diversions offer the patient the ability to self-void either via stoma catheterization or with the patient's own urethra. Given the large number of diversion procedures available, postsurgical anatomy may be complex. Multiple imaging modalities can be used to assess the postprocedural anatomy, potential complications, and for on-going oncologic monitoring. The purpose of this review is to describe the common surgical techniques and associated complications.


Assuntos
Cistectomia , Complicações Pós-Operatórias/diagnóstico por imagem , Derivação Urinária/métodos , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA