Prognostic Value of Liquid-Biopsy-Based Biomarkers in Upper Tract Urothelial Carcinoma.

Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients.

Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern.

The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p < 0.05). After two doses in Rec, levels of total Ig to receptor-binding domain were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (VOCs) Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2-2.8-fold increases. Increasing the interval between SARS-CoV-2 infection and the vaccination with messenger RNA-based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response.

Assessment of liver fibrosis using a 3-dimensional high-resolution late gadolinium enhancement sequence in children and adolescents with Fontan circulation.

OBJECTIVES: To assess abnormal liver enhancement on 15-20 min delayed 3D high-resolution late gadolinium enhancement (3D HR LGE) sequence in patients with Fontan circulation. METHODS: Retrospective study of pediatric Fontan patients (< 18 years old) with combined cardiac-liver MRI from January 2018 to August 2021. Abnormal hepatic enhancement was graded (0-3) for each lobe, summed for a total liver enhancement score (0-6), and compared to repaired tetralogy of Fallot (rTOF) patients. Correlations with other hepatic imaging biomarkers were performed. Temporal relationships of enhancement compared to traditional early portal venous and 5-7-min delayed phase liver imaging were analyzed. RESULTS: The Fontan group (n = 35, 13 ± 3.4 years old, median time from Fontan 10 (9-12) years) had 23/35 (66%) with delayed 3D HR LGE total liver enhancement score > 0 (range 0-5), with greater involvement of the right lobe (1 (0-1) vs 0 (0-1), p < 0.01). The rTOF group (n = 35, 14 ± 2.6 years old) had no abnormal enhancement. In the Fontan group, total liver enhancement was 3 (2-4) in the early portal venous phase, lower at 1 (1-2) in the 5-7-min delayed phase (p < 0.01), and lowest at 1 (0-2) in the 15-20-min delayed phase (p = 0.03). 3D HR LGE enhancement correlated inversely with portal vein flow (rs = - 0.42, p = 0.01) and positively with left lobe stiffness (rs = 0.51, p < 0.01). The enhancement score decreased in 13/35 (37%) between the 5-7- and 15-20-min delayed phases. CONCLUSIONS: Liver fibrosis can be assessed on 3D HR LGE sequences in patients with Fontan circulation, correlates with other imaging biomarkers of Fontan liver disease, and may add information for hepatic surveillance in this population. KEY POINTS: • Abnormal liver enhancement on 3D HR LGE sequences in Fontan patients likely represents liver fibrosis and is seen in up to 66% of children and adolescents with variable distribution and severity. • The degree of 3D HR LGE liver enhancement correlates with decreased portal vein flow and increased left hepatic lobe stiffness.

Tumor-Agnostic Circulating Tumor DNA Testing for Monitoring Muscle-Invasive Bladder Cancer.

Circulating tumor DNA (ctDNA) has recently emerged as a real-time prognostic and predictive biomarker for monitoring cancer patients. Here, we aimed to ascertain whether tumor-agnostic ctDNA testing would be a feasible strategy to monitor disease progression and therapeutic response in muscle-invasive bladder cancer (MIBC) patients after radical cystectomy (RC). Forty-two MIBC patients who underwent RC were prospectively included. Blood samples from these patients were collected at different follow-up time points. Two specific mutations (TERT c.1-124C>T and ATM c.1236-2A>T) were analyzed in the patients' plasma samples by droplet digital PCR to determine their ctDNA status. During a median follow-up of 21 months, 24% of patients progressed in a median of six months. ctDNA status was identified as a prognostic biomarker of tumor progression before RC and 4 and 12 months later (HR 6.774, HR 3.673, and HR 30.865, respectively; p < 0.05). Lastly, dynamic changes in ctDNA status between baseline and four months later were significantly associated with patient outcomes (p = 0.045). In conclusion, longitudinal ctDNA analysis using a tumor-agnostic approach is a potential tool for monitoring MIBC patients after RC. The implementation of this testing in a clinical setting could improve disease management and patients' outcomes.

Zinc Finger E-Box Binding Homeobox 1 Promotes Cholangiocarcinoma Progression Through Tumor Dedifferentiation and Tumor-Stroma Paracrine Signaling.

BACKGROUND AND AIMS: Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that promotes metastatic and stem cell features, which has been associated with poor prognosis in cholangiocarcinoma (CCA), a desmoplastic cancer enriched in cancer-associated fibroblasts (CAFs). We aimed to define ZEB1 regulatory functions in malignant and stromal compartments of CCA. APPROACH AND RESULTS: Bioinformatic and immunohistochemical analyses were performed to determine correlations between ZEB1 and markers of progressiveness in human intrahepatic CCA (iCCA). Gain-of-function and loss-of-function models were generated in CCA cells and liver myofibroblasts as a model of CAFs. Conditioned media (CM) was used to unravel tumor-stroma interplay. In vivo experiments were performed using a xenograft CCA model. ZEB1 expression in tumor cells of human iCCA was associated with undifferentiated tumor and vascular invasion. In vitro, ZEB1 promoted epithelial-mesenchymal transition and stemness in tumor cells, leading to cell migration and spheroid formation. In vivo, ZEB1-overexpressing CCA cells formed larger tumors with more abundant stroma. Expression of cellular communication network factor 2 (CCN2, encoding connective tissue growth factor [CTGF]) was increased in tumor cells from ZEB1-overexpressing xenografts and correlated with ZEB1 expression in human tumors. In vitro, CM from ZEB1-overexpressing tumor cells or recombinant CTGF induced myofibroblast proliferation. ZEB1 was also expressed by CAFs in human CCA, and its expression correlated with CCN2 in myofibroblasts and CCA stroma. In mice, cotransplantation of CCA cells with ZEB1-depleted myofibroblasts reduced CCA progressiveness compared to CCA cells/ZEB1-expressing myofibroblasts. Furthermore, ZEB1 controls the expression of paracrine signals (i.e., HGF and IL6) in tumor cells and myofibroblasts. CONCLUSIONS: ZEB1 plays a key role in CCA progression by regulating tumor cell-CAF crosstalk, leading to tumor dedifferentiation and CAF activation.

Prognostic implication of TERT promoter mutation and circulating tumor cells in muscle-invasive bladder cancer.

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.

Outcomes after 20 years of experience in minimally invasive living-donor nephrectomy.

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.

Effectiveness of a group educational intervention - prolact - in primary care to promote exclusive breastfeeding: a cluster randomized clinical trial.

BACKGROUND: The rates of exclusive breastfeeding at 6 months in Spain are far from recommended by the World Health Organization, which is 50% by 2025. Evidence of the effectiveness of group interventions in late postpartum is limited. The objective of this study was to evaluate the effectiveness of the PROLACT group educational intervention for increasing the proportion of mother-child dyads with exclusive breastfeeding at 6 months compared to the usual practice in primary care. METHOD: Multicentre cluster randomized clinical trial. A total of 434 mother-child dyads who breastfed exclusively in the first 4 weeks of the children's life and agreed to participate were included. The main outcome was exclusive breastfeeding at 6 months. Secondary variables were type of breastfeeding, reasons for abandonment, degree of adherence and satisfaction with the intervention. To study the effectiveness, the difference in the proportions of dyads with exclusive breastfeeding at 6 months was calculated, and the relative risk (RR) and number needed to treat (NNT) were calculated with their 95% CIs. To study the factors associated with the maintenance of exclusive breastfeeding at 6 months, a multilevel logistic regression model was fitted. All analyses were performed to intention to treat. RESULTS: The percentage of dyads with exclusive breastfeeding at 6 months was 22.4% in the intervention group and 8.8% in the control group. PROLACT intervention obtained an RR =2.53 (95% CI: 1.54-4.15) and an NNT = 7 (95%CI: 5-14). The factors associated with exclusive breastfeeding at 6 months were the PROLACT intervention, OR = 3.51 (95%CI: 1.55-7.93); age > 39 years, OR = 2.79 (95%CI: 1.02-7.6); previous breastfeeding experience, OR = 2.61 (95%CI: 1.29-5.29); income between 500 and 833.33 €, OR = 3.52 (95%CI 1.47-8.47).); planning to start work before the infant was 6 months old, OR = 0.35 (0.19-0.63) . CONCLUSIONS: The PROLACT intervention in primary care is more effective than the usual practice for maintaining exclusive breastfeeding at 6 months, and can therefore be considered evidence-based practice for implementation in standard practice. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov under code number NCT01869920 (03/06/2013).

Cell-Free DNA as a Prognostic Biomarker for Monitoring Muscle-Invasive Bladder Cancer.

Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients' clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.

The Role of Fluorescence In Situ Hybridization for Predicting Recurrence after Adjuvant bacillus Calmette-Guérin in Patients with Intermediate and High Risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data.

PURPOSE: The objective of this study was to assess the value of fluorescence in situ hybridization to predict early recurrence in patients with nonmuscle invasive bladder cancer at intermediate and high risk treated with bacillus Calmette-Guérin. MATERIALS AND METHODS: We performed a systematic review using MEDLINE®, Embase® and the Cochrane Library. Individual patient data from prospective observational studies of fluorescence in situ hybridization in patients treated with bacillus Calmette-Guérin were included. A 2-stage individual patient data meta-analysis was done to assess the value of fluorescence in situ hybridization to predict tumor recurrence after bacillus Calmette-Guérin induction therapy. RESULTS: From a total of 4 studies we obtained individual data on 422 patients, of whom 408 with a median followup of 18.8 months were included in the final analysis. When fluorescence in situ hybridization was positive, the recurrence HR was 1.20 (95% CI 0.81-1.79) before bacillus Calmette-Guérin (time 0), 2.23 (95% CI 1.31-3.62) at 6 weeks (time 1), 3.70 (95% CI 2.34-5.83) at 3 months (time 2) and 23.44 (95% CI 5.26-104.49) at 6 months (time 3). CONCLUSIONS: A positive fluorescence in situ hybridization test after bacillus Calmette-Guérin correlated with higher risk of recurrent tumor. Fluorescence in situ hybridization could aid urologists in risk stratifying and counseling patients. Based on the HR and the narrowest CI the preferred timing of fluorescence in situ hybridization is 3 months after transurethral resection of bladder tumor. This is also in time for patients in whom induction therapy fails to enter clinical trials or change the treatment strategy.

Pain relief after triamcinolone infiltration in patients with bladder pain syndrome with Hunner's ulcers.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is a chronic condition with severe implications in the patient's quality of life with no definitive treatment. Our objective was to assess pain relief after triamcinolone injection in patients with BPS with Hunner's ulcers (HU). METHODS: Retrospective study of 20 consecutive patients with BPS treated at the Hospital Clinic of Barcelona with triamcinolone injection with flexible cystoscope between 2015 and 2016. Pain was assessed according to the visual analog scale (VAS) (0-10) before and after treatment. Outcomes were compared using Student's t test for paired samples. RESULTS: Twenty-seven procedures were performed in 20 patients, who were followed up for a median of 7 months (range 1-15). Median age was 75 years (52-86), and median time from diagnosis to treatment was 4.5 years (1-7). Fifteen (75 %) patients had received treatment with corticoid injection for BPS before entering the study. Pre- and postreatment VAS was 8 and 2.5 (p < 0.001), respectively. Pre -and postreatment VAS in those with muscular pain was 8 and 5 (p = 0.012), respectively and in those without muscular pain was 8 and 2 (p < 0.001), respectively. Three (15 %) patients required retreatment due to nonresponse and 5 (25 %) patients for pain recurrence after 4 months (3.5-8). Four of them (50 %) were performed with triamcinolone injection again. Seven of ten patients (70 %) followed for ≥8 months required at least one retreatment. CONCLUSION: Triamcinolone injection for HU in patients with BPS is associated with significant pain reduction. However, most patients will require retreatment.

Lianas suppress seedling growth and survival of 14 tree species in a Panamanian tropical forest.

Lianas are a common plant growth form in tropical forests, where they compete intensely with trees, decreasing tree recruitment, growth, and survival. If the detrimental effects of lianas vary significantly with tree species identity, as is often assumed, then lianas may influence tree species diversity and community composition. Furthermore, recent studies have shown that liana abundance and biomass are increasing relative to trees in neotropical forests, which will likely magnify the detrimental effects of lianas and may ultimately alter tree species diversity, relative abundances, and community composition. Few studies, however, have tested the responses of multiple tree species to the presence of lianas in robust, well-replicated experiments. We tested the hypotheses that lianas reduce tree seedling growth and survival, and that the effect of lianas varies with tree species identity. We used a large-scale liana removal experiment in Central Panama in which we planted 14 replicate seedlings of 14 different tree species that varied in shade tolerance in each of 16 80 x 80 m plots (eight liana-removal and eight unmanipulated controls; 3136 total seedlings). Over a nearly two-yr period, we found that tree seedlings survived 75% more, grew 300% taller, and had twice the aboveground biomass in liana-removal plots than seedlings in control plots, consistent with strong competition between lianas and tree seedlings. There were no significant differences in the response of tree species to liana competition (i.e., there was no species by treatment interaction), indicating that lianas had a similar negative effect on all 14 tree species. Furthermore, the effect of lianas did not vary with tree species shade tolerance classification, suggesting that the liana effect was not solely based on light. Based on these findings, recently observed increases in liana abundance in neotropical forests will substantially reduce tree regeneration, but will not significantly alter tropical tree species diversity, relative abundance, or community composition.

Using gene expression from urine sediment to diagnose prostate cancer: development of a new multiplex mRNA urine test and validation of current biomarkers.

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.

The role of cystectomy in elderly patients - a multicentre analysis.

INTRODUCTION: Life expectancy in developed countries is continuously increasing. Hence elderly patients are becoming more common in our clinical practice. Currently, one of the greatest challenges of medicine is balancing the life expectancy of elderly patients against aggressive treatments that carry significant risks. OBJECTIVE: To outline the complications and survival in surgical patients 80 years and over undergoing radical cystectomy for bladder cancer. PATIENTS AND METHODS: A review of a radical cystectomy in elderly recorded in four different institutional prospective databases during the period between 1991 and 2014. Clinical and pathologic features, complications and survival were evaluated. RESULTS: A total of 111 patients were available. Median (range) age 82.2 (80-89) years. Seventeen women and 94 men. Regarding the ASA score, 6 patients were ASA I, 47 patients were ASA II, 49 patients ASA III and 9 ASA IV. Prior to surgery, 48 patients had hydronephrosis. The median (range) creatinine series was 1.1 (0.71-11.1) ng/dL. In 88 cases an ileal conduit was performed, 17 a cutaneous ureterostomy diversion, 5 neobladders and 1 ureterosigmoidostomy case. The median (range) operative time was 230 (120-420) min and a total of 97 patients required blood transfusion. The median (range) hospital stay was 14 (7-126) days. The early and late complication rates were 50.4% and 32%, respectively. A total of 14 patients (12.6%) required surgical reintervention. Eight patients (7.2%) died in the immediate postoperative period. The readmission rate of the series was 27.2%. The mean follow-up of the series was 18 (0.27-134.73) months. During this period 66 patients died, 52 of them due to the tumor. Twelve month tumour progression free survival was 83.9% for ≤pT1, 70.2% for pT2 and 36% for ≥pT3, respectively. Twelve month cancer specific survival was 85.6% for ≤pT1, 75.1% for pT2 and 42.5% for ≥pT3, respectively. CONCLUSION: Radical cystectomy in elderly population is an aggressive surgical treatment with a significant complication rate, hospital readmission and perioperative mortality rate. Careful selection of patients is essential in order to minimize the complications of this surgery and balance benefits against risks in the elderly population. Tumour progression and cancer specific survival are poor for patients with ≥pT3 disease. Alternatives such as tri-modality therapy need to be considered within a multi-disciplinary approach. More data is required to determine which sub-groups of elderly patients would benefit from a complication, survival and quality of life perspective.

Prognostic value of microRNA expression pattern in upper tract urothelial carcinoma.

OBJECTIVE: To examine the microRNA (miRNA) expression pattern in tumour samples from patients with progressing and non-progressing upper tract urothelial carcinoma (UTUC) in order to identify putative miRNAs that may be used as prognostic markers. PATIENTS AND METHODS: We conducted a multicentre, retrospective study of formalin-fixed paraffin-embedded tissue samples from 150 patients with UTUC who had undergone radical nephroureterectomy. Global miRNA expression patterns were analysed in 18 selected samples from patients with UTUC using TaqMan arrays. The differential expression of five key miRNAs was validated by quantitative polymerase chain reaction in an independent cohort of 132 samples from patients with UTUC. Models to predict tumour progression and cancer-specific survival that included miRNA expression patterns were developed by Cox regression analysis. RESULTS: Twenty-six miRNAs were found to be aberrantly expressed between samples from patients with progressing and non-progressing UTUC and five of these were selected for subsequent studies. The regression analysis identified tumour stage and miR-31 and miR-149 expression as independently associated with tumour progression and tumour stage and miR-149 expression as independently associated with cancer-specific survival. The risk scores derived from these miRNA models were able to discriminate two groups with a highly significantly different probability of tumour progression (hazard ratio [HR] 4.78; P < 0.001) and death (HR 276; P = 0.004). CONCLUSIONS: There is a differential miRNA expression pattern between patients with progressing and non-progressing UTUC. The identification of new miRNAs associated with a high probability of tumour recurrence and cancer-specific survival in patients with UTUC and their combination in a robust, easy-to-use and reliable algorithm may help tailor treatment and surveillance strategies in these patients.

Health-related quality of life in patients with urostomies.

PURPOSE: To assess health-related quality of life in patients with urothelial (bladder) cancer 6 months following radical cystectomy with construction of a urostomy. SUBJECTS: The target sample was 54 patients with urothelial cancer who underwent radical cystectomy with Bricker-type incontinent urinary diversion between December 2008 and December 2009; 37 out of 54 (68%) of potential respondents agreed to participate. Seven potential subjects died within the 6-month period and we were unable to locate 10 potential respondents. INSTRUMENT: The Stoma-Quality of Life was developed to be valid for measurement of 20 items that query the impact of the ostomy on the health-related quality of life and its impact on daily life. Scores were categorized as 70% to 100% (indicating good quality of life), 30% to 69% (indicating moderate quality of life), and 0 to 29% (indicating poor quality of life). METHODS: Subjects responded to the Stoma-Quality of Life questionnaire by telephone 6 months after urostomy surgery. RESULTS: Thirty-five were ranked as having a good quality of life. The remaining 2 subjects had scores indicating moderate quality of life; no respondent was ranked as having a poor quality of life. CONCLUSIONS: Health-related quality of life was ranked as good in 95% of a group of patients managed by radical cystectomy and Bricker ileal conduit construction and moderate in 5%. Based on these findings, we conclude that the Bricker-type incontinent urinary diversion remains a viable treatment option for bladder cancer that allows an acceptable health-related quality of life.

Recent advances of natural orifice transluminal endoscopic surgery in urological surgery.

Natural orifice transluminal endoscopic surgery designates a surgical procedure that utilizes one or more patent natural orifices of the body with the intention to puncture a hollow viscera in order to enter the abdominal cavity. First carried out at the beginning of the 2000s in experimental models, it can be considered the natural evolution of laparoscopy towards the ideal of scarless surgery, as the avoidance of a large abdominal scar is associated with better cosmetic results and better recovery. However, the technology currently available does not allow the performance of complete pure natural orifice transluminal endoscopic surgery procedures. The surgical tools used are not specially designed for this approach, so difficulties in retracting organs, bleeding control and clashing of instruments are the main obstacle surgeons face. For this reason, the current available technique is the so-called hybrid approach, where a natural orifice approach is combined with some abdominal trocars, using the natural orifice as the exit door for the specimen removal. As not many comparative studies have been published evaluating the advantages of natural orifice transluminal endoscopic surgery in front of traditional laparoscopic surgery, a review of the history of natural orifice transluminal endoscopic surgery, and an assessment of the available evidence of this technique regarding renal and urological pelvic surgery are performed in this article.

Impact of a nurse-run clinic on prevalence of urinary incontinence and everyday life in men undergoing radical prostatectomy.

PURPOSE: To determine the prevalence of urinary incontinence (UI) in patients undergoing prostatectomy and to evaluate the impact of UI on the everyday life in order to select the patients eligible to enter a pelvic floor rehabilitation program. SUBJECTS AND SETTINGS: The sample comprised 114 consecutive men undergoing laparoscopic or open radical prostatectomy between April 2007 and April 2008. Participants' mean age was 59 years (range, 46-67 years). The research setting was a hospital-based clinic in Barcelona, Spain. Patients who required an indwelling urinary catheter due to other factors were excluded from the trial. During admission, nursing staff explained the study and obtained informed consent from patients willing to participate in the trial. METHODS: The impact of UI on daily living was evaluated via administration of the International Consultation on Incontinence Questionnaire-Short Form. Impact of UI was evaluated before surgery, and after 1 and 12 months following indwelling catheter removal. RESULTS: A total of 95.5% patients developed UI 1 month following bladder catheter removal. Slightly less than 1 in 4 patients (24.8%) indicated that UI had no effect on activities of daily living. In contrast, 27.5% indicated that UI had a moderate impact and 47.7% indicated a severe impact. Ninety-one patients reported performing pelvic floor muscle exercises to improve UI, but only 45% were found to be performing them correctly. When evaluated at 1 year following catheter removal, 52.64% of the patients continued to experience UI. The majority (79.8%) indicated that UI did not impact their daily lives, 8.8% indicated a moderate impact, and 20.4% reported that UI had a severe impact on daily life. Seventy patients (61.4%) continued to perform pelvic floor muscle exercises; after 1 year, 93% were deemed to be correctly identifying, contracting, and relaxing their pelvic floor muscles. CONCLUSIONS: Urinary incontinence remains prevalent as long as 12 months following catheter removal. Incontinence exerts a moderate to severe impact on daily life in 27.5% to 20.4% of respondents. In order to minimize the negative impact as much as possible, we advocate a pelvic floor muscle training program overseen by RNs.