Patient satisfaction and outcomes of crisis resolution home treatment for the management of acute psychiatric crises: a study during the COVID-19 pandemic in Madrid.

Background: Crisis Resolution Home Treatment (CRHT) seem to offer comparable results to the traditional hospitalization model, at a lower cost and offering greater flexibility and scope. However, in Madrid, its implementation in Mental Health did not occur until the midst of the COVID-19 pandemic. In this work we analysed the effectiveness of a mental health CRHT unit promoted during the COVID-19 pandemic, as well as the degree of satisfaction of patients and their families. Methods: 90 patients were treated by the CRHT unit in the period between October 2020 and June 2022. All patients met the inclusion criteria: (1) Acute psychopathological decompensation in patients suffering from psychotic disorders, major affective disorder, obsessive compulsive disorder, personality disorder and other severe mental disorders causing functional disability, according to ICD-10 diagnostic criteria; (2) Ages between 18-90 years old; (3) Living in the urban area of Vallecas, Madrid; and (4) Counting with sufficient social and family support. The effectiveness of the intervention was evaluated with the SF-36 health questionnaire, the caregiver burden with the Zarit questionnaire, and patient satisfaction with a survey specifically designed for this work. Results: 55 (61.1%) patients completed the SF-36 at baseline and at the end of hospitalization. Statistically significant improvements were observed in the 8 dimensions of the SF-36 (p < 0.05). However, CRHT did not achieve a statistically significant decrease in caregiver burden. Regarding the satisfaction of the patients with the attention and care received, an average score of 47.72/50 was obtained. Conclusion: The Crisis Resolution Home Treatment intervention resulted in significant improvement in patients' quality of life with high satisfaction scores. However, it did not effectively reduce caregiver burden. Future research should focus on randomized controlled trials with long-term follow-up to assess the effectiveness of CRHT compared to traditional hospitalization and utilize specific assessment scales for different mental disorders.

Impact of the COVID-19 Pandemic on Cancer Diagnosis in Madrid (Spain) Based on the RTMAD Tumor Registry (2019-2021).

The coronavirus disease 2019 (COVID-19) pandemic has caused a significant disruption to cancer diagnosis, treatment and prevention worldwide that could have serious consequences in the near future. We intend to evaluate the weight of this backlog on a community-wide scale in Madrid during the period 2020-2021, and whether a stage shift towards the advanced stage has occurred. Cancer diagnoses in the Madrid tumor registry (RTMAD) from 2019-2021 were evaluated. Absolute and percentage differences in annual volume and observed-to-expected (O/E) volume ratios were calculated. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated using the O/E ratio. The SIR for 2020-2021 compared to 2019 was 94.5% (95% CI 93.8-95.3), with unequal gender-specific cancer diagnosis recovery (88.5% for males and 102.1% for females). Most cancer types were underdiagnosed in 2020. The tendency worsened in 2021 for colorectal and prostate cancers (87.8%), but lung cancer recovered (102.1%) and breast cancer was over-diagnosed (114.4%) compared with reference pre-COVID-19 data. These changes have modified the ranking of the most frequent malignancies diagnosed in Madrid. Breast cancer has overtaken colorectal and prostate cancers, displaced to second and third position, respectively. Not only was colorectal cancer diagnosis affected more as a consequence of the COVID-19 pandemic but diagnosis of this malignancy at the advance stage also increased by 3.6% in 2020 and 4.2% in 2021 compared to the reference period of 2019. In summary, there is a large volume of undetected cancer in Madrid caused by the reduced access to care secondary to the COVID-19 pandemic, especially regarding colorectal and prostate cancer. Strategies are needed to recover the backlog of diagnoses and effectively treat these cases in the future and solve the negative impact that will be caused by the diagnostic delay. Analyzing the impact of new diagnoses suffered by each different malignancy and their recovery will help to understand how the future allocation of resources should look.

ATOMS (Adjustable Trans-Obturator Male System) in Patients with Post-Prostatectomy Incontinence and Previously Treated Urethral Stricture or Bladder Neck Contracture.

(1) Background: Male stress incontinence in patients with previously treated urethral or bladder neck stricture is a therapeutic challenge. The efficacy and safety of the adjustable trans-obturator male system (ATOMS) in these patients is unknown. (2) Methods: All patients with primary ATOMS implants in our institution between 2014 and 2021 were included. The outcomes of patients with previously treated urethral or bladder neck stricture (≥6 months before ATOMS implant) and stable 16Ch urethral caliber were compared to those without a history of stricture. The primary endpoint was the dry patient rate, defined as the pad test ≤ 20 mL/day, and complication rate, including device removal. The secondary variable was self-perceived satisfaction using the Patient Global Impression of Improvement (PGI-I) scale. Wilcoxon rank sum test, Fisher's exact test and logistic regression were performed. (3) Results: One hundred and forty-nine consecutive patients were included, twenty-one (14%) previously treated for urethral or bladder neck stricture (seven urethroplasty, nine internal urethrotomy and five bladder neck incision). After ATOMS adjustment, 38% of the patients with treated stricture were continent compared to 83% of those without (p < 0.0001). After weighted matched observations using propensity score pairing, the proportion of continent patients without a previous stricture was 56% (p = 0.236). Complications occurred in 29% of the patients with stricture and in 20% of those without (p = 0.34). The severity of the complications was distributed evenly among the groups (p = 0.42). Regarding self-perceived satisfaction with the implant, 90% of the patients with stricture perceived the results satisfactorily (PGI-I 1−3) compared to 97% of the rest (p = 0.167). Stricture was associated with radiotherapy (p < 0.0001) and time from prostatectomy to implantation (p = 0.012). There was a moderate correlation between previous stricture and the severity of incontinence, both evaluated according to the 24-h pad test (Rho = 0.378; p < 0.0001) and the ICIQ-SF questionnaire (Rho = 0.351; p < 0.0001). Multivariate analysis for the factors predictive of failure after ATOMS adjustment revealed previous stricture (OR 4.66; 95% CI 1.2−18.87), baseline 24-h pad test (per 100 mL, OR 1.28; 95% CI 1.09−1.52) and final cushion volume (per mL, OR 1.34; 95% CI 1.19−1.55). This model predicted dryness with an AUC of 92%. After the PSMATCH procedure using a propensity score, the model remained unchanged, with the previous stricture (OR 8.05; 95% CI 1.08−110.83), baseline 24-h pad test (per 100 mL, OR 1.53; 95% CI 1.15−2.26) and final cushion volume (per mL, OR 1.45; 95% CI 1.17−2) being independent predictors and an AUC of 93%. (4) Conclusions: ATOMS can be used to treat male stress incontinence in patients with a history of stricture, although the effectiveness of the device is reduced. On the other hand, the security and perceived satisfaction were equivalent for both groups.

Refined Nomogram Incorporating Standing Cough Test Improves Prediction of Adjustable Trans-Obturator Male System (ATOMS) Success to Treat Post-Prostatectomy Male Stress Incontinence.

(1) Background: The adjustable transobturator male system (ATOMS) device serves to treat post-prostatectomy incontinence, as it enhances residual urinary sphincteric function by dorsal compression of the bulbar urethra. We investigated the clinical parameters affecting continence recovery using this device and developed a decision aid to predict success. (2) Methods: We reviewed consecutive men treated with first-time ATOMS for post-prostatectomy incontinence from 2014 to 2021 at our institution. Patient demographics, reported pads per day (PPD), 24-h pad-test and Standing Cough Test (SCT), results' grades 1-4, according to Male Stress Incontinence Grading Scale (MSIGS), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaire were assessed. Treatment success was defined as no pads or a single PPD with ≤20-mL 24-h pad-test. Logistic regression was performed using a stepwise model (entry 0.15 and stay criterium 0.1) to evaluate independent variables' determinant of dryness. Receiver-operating characteristic (ROC) curves for predictive variables were evaluated and their area under curve (AUC) was compared. A nomogram was generated and internally validated to predict probability of treatment success. (3) Results: Overall, 149 men (median age 70 years, IQR 7) were evaluated with a median follow-up of 45 months (IQR 26). Twelve patients (8%) had previous devices for incontinence, and 21 (14.1%) had pelvic radiation. Thirty-five men (23.5%) did not achieve continence after ATOMS adjustment (use of no or one security PPD with ≤20-mL 24-h pad-test). In univariate analysis, Charlson comorbidity index (p = 0.0412), previous urethroplasty (p = 0.0187), baseline PPD (p < 0.0001), 24-h pad-test (p < 0.0001), MSIGS (p < 0.0001), and ICIQ-SF questionnaire score (p < 0.0001) predicted ATOMS failure. In a multivariable model, 24-h pad-test (p = 0.0031), MSIGS (p = 0.0244), and radiotherapy (p = 0.0216) were independent variables, with AUC 0.8221. The association of MSIGS and 24-h pad-test was the superior combination (AUC 0.8236). A nomogram to predict the probability of ATOMS failure using the independent variables identified was proposed. (4) Conclusions: Several variables were identified as predictive of success for ATOMS using clinical history, physical examination (MSIGS), and factors that evaluate urine loss severity (PPD, 24-h pad-test, and ICIQ-SF questionnaire). MSIGS adds prognostic value to 24-h pad-test in assessing success of ATOMS device to treat post-prostatectomy incontinence. A nomogram was proposed to calculate the risk of ATOMS failure, which could be of interest to personalize the decision to use this device or not in the individual patient.

(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder.

(Pro)renin receptor (PRR) is being investigated in several malignancies as it activates pathogenic pathways that contribute to cell proliferation, immunosuppressive microenvironments, and acquisition of aggressive neoplastic phenotypes. Its implication in urothelial cancer (UC) has not been evaluated so far. We retrospectively evaluate the prognostic role of PRR expression in a series of patients with invasive UC treated with radical cystectomy and other clinical and histopathological parameters including p53, markers of immune-checkpoint inhibition, and basal and luminal phenotypes evaluated by tissue microarray. Cox regression analyses using stepwise selection evaluated candidate prognostic factors and disease-specific survival. PRR was expressed in 77.3% of the primary tumors and in 70% of positive lymph nodes. PRR expression correlated with age (p = 0.006) and was associated with lower preoperatively hemoglobin levels. No other statistical association was evidenced with clinical and pathological variables (gender, ASA score, Charlson comorbidity index, grade, pT, pN) or immunohistochemical expressions evaluated (CK20, GA-TA3, CK5/6, CD44, PD-L1, PD-1, B7-H3, VISTA, and p53). PRR expression in primary tumors was associated with worse survival (log-rank, p = 0.008). Cox regression revealed that PRR expression (HR 1.85, 95% CI 1.22-2.8), pT (HR 7.02, 95% CI 2.68-18.39), pN (HR 2.3, 95% CI 1.27-4.19), and p53 expression (HR 1.95, 95% CI 1.1-3.45) were independent prognostic factors in this series. In conclusion, we describe PRR protein and its prognostic role in invasive UC for the first time. Likely mechanisms involved are MAPK/ERK activation, Wnt/ß-catenin signaling, and v-ATPAse function.

Multi-Institutional Study of Dorsal Onlay Urethroplasty of the Membranous Urethra after Endoscopic Prostate Procedures: Operative Results, Continence, Erectile Function and Patient Reported Outcomes.

(1) Background: To critically evaluate dorsal onlay buccal mucosal graft urethroplasty (DOBMGU) for posterior urethral stenosis repair following transurethral resection and other endoscopic prostate procedures. (2) Methods: A retrospective multi-institutional review of patients with membranous or bulbomembranous urethral stenosis for whom treatment with DOBMGU was conducted after receipt of prostate endoscopic procedures. Baseline data, peri-operative care, post-operative care and patient-reported outcomes were analyzed. The primary outcomes were procedural failure and development of de novo stress urinary incontinence (SUI). The secondary outcomes were changes in voiding, sexual function and patient satisfaction. (3) Results: A total of 107 men with a mean age of 69 ± 9.5 years and stenosis length of 3.5 ± 1.8 cm were included. Prior endoscopic procedures among participants were 47 patients (44%) with monopolar TURP, 33 (30.8%) with bipolar TURP, 16 (15%) with Greenlight laser, 9 (8.4%) with Holmium laser enucleation and 2 (1.9%) with bladder neck incision. At a mean follow-up time of 59.3 ± 45.1 months, stenosis recurred in 10 patients (9.35%). Multivariate analysis confirmed that postoperative complications (OR 12.5; p = 0.009), history of radiation (OR 8.3; p = 0.016) and ≥2 dilatations before urethroplasty (OR 8.3; p = 0.032) were independent predictors of recurrence. Only one patient (0.9%) developed de novo SUI. Patients experienced significant improvement in PVR (128 to 60 cc; p = 0.001), Uroflow (6.2 to 16.8 cc/s; p = 0.001), SHIM (11.5 to 11.7; p = 0.028), IPSS (20 to 7.7; p < 0.001) and QoL (4.4 to 1.7; p < 0.001), and 87 cases (81.3%) reported a GRA of + 2 or better. (4) Conclusions: DOBMGU is an effective and safe option for patients with posterior urethral stenosis following TURP and other prostate endoscopic procedures. This non-transecting approach minimizes external urinary sphincter manipulation, thus limiting postoperative risk of SUI or erectile dysfunction.

ATOMS (Adjustable Transobturator Male System) Is an Effective and Safe Second-Line Treatment Option for Recurrent Urinary Incontinence after Implantation of an AdVance/AdVance XP Fixed Male Sling? A Multicenter Cohort Analysis.

(1) Background: This study examined outcomes of second-line ATOMS implantation after failure of the fixed male sling (FMS) AdVance/AdVance XP. (2) Methods: A retrospective multicenter cohort analysis was carried out in men implanted with an ATOMS between 2011 and 2020 after failure of an AdVance/AdVance XP. Success was assessed on the basis of objective (dryness, 0-1 pad/24 h or >20 g/24 h pad test) and subjective results (PGI-I). We performed the Wilcoxon rank sum test, Fisher's exact test, logistic regression, and multivariate analysis. (3) Results: The study included 88 patients from 9 centers with a mean age of 71.3 years. No Clavien-Dindo > II complications occurred within the first 3 months after ATOMS implantation. A total of 10 cases (9%) required revision in the ensuing clinical course. After a mean follow-up of 42.5 months, 76.1% achieved social continence, and 56.8% used no pads at all. Mean urine leakage/24 h dropped from 422 g (3.9 pads) to 38 g (0.69 pads) and the mean ICIQ-SF decreased from 16.25 to 5.3 (p < 0.0001). PROMs (patient-reported outcome measures) showed improvement in 98.9% of cases, and 63.6% gave a "very much better" PGI-I rating. Multivariate analysis identified a lower probability of achieving maximum satisfaction for the following factors: the AdVance XP as first-line therapy (OR 0.35), a lower ICIQ-SF question 1 (OR 0.26), status post-irradiation (OR 0.14), and more severe pain prior to ATOMS implantation (OR 0.51). (4) Conclusions: Implantation of an ATOMS is an effective and safe second-line treatment option for recurrent urinary incontinence after implantation of an AdVance/AdVance XP sling. High patient satisfaction was demonstrated in a long-term follow-up.

Outcomes of a Series of Patients with Post-Prostatectomy Incontinence Treated with an Adjustable Transobturator Male System or Artificial Urinary Sphincter.

INTRODUCTION: A prospective evaluation of outcomes in a series of patients with post-prostatectomy incontinence (PPI) treated with two different devices is presented. METHODS: Consecutive patients with PPI underwent interventions with an adjustable transobturator male system (ATOMS) or artificial urinary sphincter (AUS). Decisions were based on patient preference after physician counselling. Patient characteristics and operative and postoperative parameters including dryness, satisfaction, complications, revision and device durability were evaluated. RESULTS: One hundred twenty-nine patients were included: 102 (79.1%) received ATOMS and 27 (20.9%) AUS. Mean follow-up was 34.9 ± 15.9 months. No difference was observed between patient age (p = 0.56), ASA score (p = 0.13), Charlson index (p = 0.57) and radiation (p = 0.3). BMI was higher for AUS (27.1 vs. 29.7; p = 0.003) and also baseline incontinence severity (7.9% mild, 44.1% moderate and 48% severe for ATOMS vs. 11.1% moderate and 88.9% severe for AUS; p = 0.0007). Differential pad test was higher for AUS (- 470 vs. - 1000 ml; p < 0.0001) and so was ICIQ-SF (15.62 vs. 18.3; p < 0.001), but total dryness (76.5 vs. 66.7%; p = 0.33), social continence (90.2 vs. 85.2%; p = 0.49) and satisfaction (92.2 vs. 88.9%; p = 0.69) were equivalent. The postoperative complication rate was similar (22.6 vs. 29.6%; p = 0.4). The surgical revision rate was higher for AUS (6.9 vs. 22.2%; p = 0.029) and also the explant rate but did not reach statistical significance (4.9 vs. 14.8%; p = 0.09). Time to explant was shorter for AUS (log-rank p = 0.021). Regression analysis revealed radiation (p = 0.003) and incontinence severity (p = 0.029) predict total dryness, while complications (p < 0.005) and type of device (p = 0.039) independently predict surgical revision. CONCLUSIONS: Both ATOMS and AUS are effective devices. Pad test change for AUS exceeds that of ATOMS. The revision rate is higher for AUS, and durability is superior for ATOMS. The satisfaction rate is equivalent. Larger series and longer follow-up are needed to compare both devices more appropriately. According to our experience, the AUS is not the only gold standard for PPI.

Prediction of infection caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: development of a clinical decision-making nomogram.

OBJECTIVE: This study aimed to assess the population at risk of infection by extended-spectrum beta-lactamase (ESBL)-producing organisms, using clinical criteria. MATERIALS AND METHODS: All urine cultures positive for Enterobacteriaceae in a Spanish hospital department from January 2010 to 2014 were reviewed. All isolates with ESBL-positive strains were collected, and isolates received during the first week of each month with ESBL-negative strains from symptomatic patients hospitalized or admitted to the emergency room. Multivariate analysis of the factors involved was undertaken and a nomogram developed to predict the probability of infection by ESBL-producing microorganisms. RESULTS: The study included 1524 patients with urinary tract infection (UTI): 416 ESBL-positive and 1108 ESBL-negative. In univariate analysis, risk factors were: male gender (p = 0.036), age (p < 0.0001), nursing home (p < 0.0001), previous antimicrobial therapy (p < 0.0001) or hospitalization (p < 0.0001), diabetes (p < 0.0001), chronic renal insufficiency (p < 0.0001), severe underlying disease (p < 0.0001), neoplasia (p = 0.0005), urological (p < 0.0001) and non-urological invasive procedure (p = 0.0003), recurrent UTI (p < 0.0001), urological (p < 0.0001) or abdominal surgery (p < 0.0001) and permanent urethral catheter (p < 0.0001). In multivariate analysis, the data set was split into a development cohort of 1067 patients and a validation cohort of 457 cases. A nomogram was developed to predict the probability of infection by ESBL-producing bacteria, which included seven variables: age (p < 0.0001), gender (p = 0.004), nursing home (p < 0.0001), previous antimicrobial therapy (p = 0.04) or hospitalization (p < 0.0001), recurrent UTI (p < 0.0001) and non-urological invasive procedure (p = 0.005). The discriminative accuracy was 0.79 (95% confidence interval 0.77-0.83). CONCLUSIONS: A nomogram was developed that predicts the risk of infection by ESBL-producing Enterobacteriaceae with reasonable accuracy. It could improve clinical decision making and enable more efficient empirical treatment.

[Prevalence and characterization of overactive bladder detected in a population in Madrid with self-administered OAB-V3 questionnaire in Primary Care]. / Prevalencia y caracterización de la vejiga hiperactiva detectada en una población de Madrid con el cuestionario OAB-V3 autoadministrado en atención primaria.

OBJECTIVE: Determining the prevalence of symptoms suggestive of overactive bladder (OAB) in a Spanish population and evaluate the impact of these symptoms on well-being and labour productivity in this population. DESIGN: Transversal study. LOCATION: Primary health care, Madrid, Spain. PARTICIPANTS: Males and females >30 years. INTERVENTIONS: Classification by primary care physicians with the Overactive Bladder Awareness Tool abbreviated version (OAB-V3). Subjects with score ≥3 and a similarly balanced control population with score <3 were clinically investigated. PRINCIPAL MEASUREMENTS: History, physical examination, urinalysis, sonography, general well-being scale and the questionnaires PPBC, OAB-q y WPAI-SHP. RESULTS: A total 923 subjects were screened, of which 209 (22.6%), 35% males and 65% females, had probable OAB. Age distribution increased from 11.1% in 4th decade to 44.4% in 9th decade. Kappa coefficient between suspected OAB and definite diagnosis was .83. The area under ROC curve for diagnosis based on OAB-V3 questionnaire and the presence of perceived bother and coping strategies was 92%. Subjects classified by score ≥3 had worse well-being, higher PPBC score and worse parameters on total OAB-q and transformed scores for each OAB-q subscale (P<.0001). In these subjects labour productivity was not affected (P=.14) but the capacity to perform regular activities was (P<.0001). CONCLUSIONS: OAB-V3 is a simple questionnaire to screen OAB with good predictive accuracy in a primary care setting and reveals important implications on health related quality of life issues.

Outcome Measures of Adjustable Transobturator Male System with Pre-attached Scrotal Port for Male Stress Urinary Incontinence After Radical Prostatectomy: A Prospective Study.

INTRODUCTION: The objective of this study was to report outcome measures with third-generation pre-attached scrotal port adjustable transobturator male system (ATOMS) for male stress urinary incontinence (SUI) after radical prostatectomy. METHODS: A prospective open study was conducted on consecutive patients. Evaluation included cough test, urethroscopy, filling and voiding cystometry, 24-h pad count and pad test, patient-reported outcomes (ICIQ-SF, IIQ-7, PGI, GRA, and VAS), complications according to the Clavien-Dindo system, operative results, number of adjustments, and filling of the system. RESULTS: Thirty-four patients with median pad test 510 (170-1225) ml were operated on. Preoperative SUI was mild (5.9%), moderate (17.6%), and severe (76.5%). At median 18.5 (12-26) months follow-up distribution of SUI was none (85.3%), mild (8.8%), and moderate (5.9%). Median intraoperative filling was 14 (8-17) ml, number of adjustments 1 (0-5), and total filling 17.5 (11-33.5) ml. At 3 months, median ICIQ-SF (p = 0.0001) and IIQ-7 (p < 0.0001) decreased. At 12 months, 24-h pad count and pad test decreased (both p < 0.0001), residual volume slightly increased (p = 0.018), PGI-I was 1 (1-3), GRA 6 (3-6), and 97% were satisfied with treatment. Continence (p = 0.016) and satisfaction (p = 0.09) were worse in irradiated patients. Median operative time was 67 (35-120) min, hospital stay 1 (1-3) days, and VAS for pain on postoperative day 1 was 0 (0-2). Complications presented in 14.7% (8.8% grade I and 5.9% grade III). CONCLUSION: Treatment of severe male SUI after radical prostatectomy with pre-attached scrotal port ATOMS is safe and very effective in the short term. A positive cough test before implant and intraoperative overfilling of the system may optimize patient selection and results.

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy.

PURPOSE: Detection of DNA hypermethylation is emerging as a novel molecular biomarker for different malignancies. We intend to define whether a hypermethylation profile of patients with prostate cancer (PCa) predicts biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIAL AND METHODS: Genome-wide methylation analysis was performed using the GoldenGate Methylation Cancer Panel-I (Illumina, Inc.) on 10 normal prostate tissues and 58 tumor samples from patients treated by RP followed for prostate-specific antigen (PSA) failure (>0.4 ng/ml) and disease progression. Patients were classified on the basis of D'Amico criteria according to clinical staging, PSA at diagnosis and Gleason score after pathologist review. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Hierarchical clustering analysis was performed and relationships with outcome were investigated using log-rank analysis and Cox regression model. RESULTS: We found 28 genes significantly hypermethylated in >20% of the tumors analyzed. Four clusters of patients were characterized by their DNA methylation profile, one at higher risk to develop BCR (p = 0.005). Multivariate analysis revealed patients in this cluster (HR 2.56), and high-risk patients (HR 4.34) according to D'Amico classification were independent predictors of BCR after prostatectomy. From the selected genes MT1A, ALOX12, GSTM2, APC, MYCL2 and RARB hypermethylation predicted BCR and GSTM2 (HR 3.78) and MYCL2 hypermethylation (HR 2.71) did so independently. CONCLUSION: Epigenetic silencing of GSTM2 and MYCL2 comprise novel molecular markers to predict BCR after surgery for medium- and high-risk localized PCa undergoing surgical treatment and hypermethylation of these genes could be incorporated to the clinical and pathological factors defining the patient at higher risk of PSA failure after prostatectomy. The limitation of the study is that no independent validation cohort is analysed.

Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study.

PURPOSE: To determine the recommended dose, cardiac safety, and antitumor activity of nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and the anti-HER-2 monoclonal antibody trastuzumab in patients with HER-2-overexpressing locally advanced nonoperable breast cancer (LABC) and metastatic breast cancer (MBC). EXPERIMENTAL DESIGN: Women with measurable, previously untreated, HER-2-overexpressing LABC and MBC with a baseline left ventricular ejection fraction (LVEF) >50% received weekly trastuzumab in combination with escalating doses of weekly paclitaxel and TLC-D99 every 3 weeks for 6 cycles. LVEF monitoring was done every 3 weeks for the first 18 weeks and every 8 weeks thereafter. RESULTS: Sixty-nine patients participated, 15 in the dose escalating part and 54 at the recommended phase II dose (28 patients with LABC and 26 patients with MBC). The recommended doses of TLC-D99 and paclitaxel were 50 mg/m(2) every 3 weeks and 80 mg/m(2)/wk, respectively. Twelve (17%) patients developed asymptomatic declines in LVEF. In 8 of these patients, LVEF recovered to >or=50% after a median time of 9 weeks (range, 3-38 weeks). In the rest of patients, LVEF ranged from 44% to 49%. No patients developed symptomatic cardiac heart failure. The overall response rate was 98.1% (95% confidence interval, 90.1-99.9) with a median time to progression not reached in LABC and of 22.1 months (95% confidence interval, 16.4-46.3) in MBC patients. CONCLUSIONS: Nonpegylated doxorubicin, paclitaxel, and trastuzumab combination is safe, does not result in clinically manifest cardiac toxicity, and has a high rate of durable responses in HER-2-overexpressing breast cancer patients. Further exploration of this combination is warranted.