IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS: The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS: IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS: A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION: Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

No effects of pantoprazole on the pharmacokinetics of rosuvastatin in healthy subjects.

PURPOSE: Rosuvastatin disposition is modulated by the expression and activity of several membrane transporters including BCRP (ABCG2). The objective of our study was to investigate the effects of pantoprazole, a previously proposed BCRP inhibitor, on the disposition of rosuvastatin. METHODS: The impact of pantoprazole (40 mg ID for 2 days) on rosuvastatin pharmacokinetics was evaluated in healthy volunteers (n = 16) who received a single oral dose of rosuvastatin (10 mg) either alone or with pantoprazole. Rosuvastatin, N-desmethylrosuvastatin, and rosuvastatin lactone levels were quantified in plasma while rosuvastatin and N-desmethylrosuvastatin excretion were measured in urine. RESULTS: Ratios and 90 % standard confidence interval of geometric means for C max (1.03 [0.91-1.16]), AUC0-∞ (1.03 [0.89-1.19]) and renal clearance (0.96 [0.85-1.09]) were all within the pre-specified range of 0.8-1.25, indicating a lack of drug-drug interaction between pantoprazole and rosuvastatin. CONCLUSIONS: Concomitant administration of pantoprazole with rosuvastatin did not affect rosuvastatin plasma concentrations. The use of pantoprazole as a BCRP inhibitor should be revisited when characterizing BCRP-mediated transport in humans.

Oncologic outcomes obtained after laparoscopic, robotic and/or single port nephroureterectomy for upper urinary tract tumours.

INTRODUCTION: Open surgery (ONU) is still considered to be the gold standard approach for nephroureterectomy (NU); however, with the introduction of laparoscopic surgery, minimally invasive techniques have been applied to surgical therapy of upper urinary tract tumours (UUT-UC) and they are gaining adepts. However, several concerns still exist about the safety of laparoscopic nephroureterectomy (LNU) in the treatment of UUT-UC, and different authors suggest that, although it could be equivalent to open surgery, this equivalence is not accomplished in all UUT-UC, suggesting that more advanced disease should undergo open surgery. More controversial still is the application of robotic surgery (RALNU) or really novel minimally invasive techniques, such as laparoendoscopic single-site surgery (LESSNU), for the treatment of UUT-UC. Although all these techniques seem feasible, their influence on oncologic results is still a matter of concern. METHODOLOGY: We present a review on the oncologic outcomes of minimally invasive laparoscopic techniques in the treatment of UUT-UC. We focus our analysis on oncologic outcomes and we also analyze the different techniques proposed for the treatment of the distal ureter during minimally invasive surgery for UUT-UC. In the absence of prospective randomized studies with large patient samples, we must base our conclusions on retrospective studies and longer follow-up. CONCLUSION: Given the evidence accumulated so far, LNU has proven to be equivalent or non-inferior, in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS) to ONU. Nevertheless, comparative studies are needed with longer follow-up before determining the equivalence of LNU in advanced tumours.

Indications and histology of 489 orchiectomies analyzed by patient age.

OBJECTIVE: To evaluate the indications and histology of our series of orchiectomies, analysing the results by patient's age. METHODS: We included the orchiectomies realized in our hospital between 2005 and 2020 in patients older than 18 years. We estimated demographic data, indications, histology and effectiveness of testicular ultrasound by three groups of age. RESULTS: We included 489 orchiectomies, which 364 (74%) belonged to Group A (patients between 18-50 years), 59 (12%) to Group B (50-70 years) and 66 (14%) to Group C (older than 70 years). In Group A, 284 (78%) orchiectomies were indicated due to malignancy suspect. In 91.9% cases (261) malign neoplasm was confirmed at final histology and 253 (89%) were germinal cells. Testicular ultrasound had a positive predictive value (PPV) of 90% in this group. In Group B, 34 (57%) orchiectomies were indicated because of malignancy suspect. At final histologic analysis, 25/34 (73.5%) confirmed malign neoplasm. Ultrasound had a PPV of 68%. In Group C, orchiepididymitis was the main cause of testicular removal with 30 cases (45,5%). From the 20 cases (30.3%) with suspicion of malignancy, only 6 had confirmed malign histology. Testicular ultrasound PPV for malignancy was 31%. CONCLUSION: In patients younger than 70 years the main orchiectomy's indication was suspect of malignancy and in older than 70, testicular inflammation. The germinal neoplasm was the predominant histology in younger than 70 years. In older than that, malignancy was infrequent. The positive predictive value of testicular ultrasound for malignancy decreased with patient's age. In patients older than 50 years proper image diagnosis to assess malignancy should be considered before orchiectomy is done.

Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy?

BACKGROUND: Radical nephroureterectomy (RNU) represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. METHODS: This retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with BCG instillations, RNU or distal ureterectomy. Clinicopathological features and outcomes were compared between RNU and BCG groups. RESULTS: A total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via nephrostomy tube in 4 patients, with a single-J ureteral stent in 5, and using a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, and 4 (13.8%) Rus distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. CONCLUSIONS: Although RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment.

[CLINICAL IMPACT OF THE SUSPENSION OF THE ERAS PROTOCOL ON PATIENTS UNDERGOING RADICAL CYSTECTOMY DURING THE COVID-19 PANDEMIC.] / IMPACTO CLÍNICO DE NO APLICAR EL PROTOCOLO ERAS EN LOS PACIENTES SOMETIDOS A CISTECTOMÍA DURANTE LA PANDEMIA COVID-19.

INTRODUCTION: During the beginning of the COVID-19 pandemic in our center, neither prehabilitation nor multimodal rehabilitation could be applied due to the excessive patient load on the health system and to reduce SARS-CoV-2 transmission. The objective of our study was to analyze the evolution, complications, and survival up to one year of patients who underwent radical cystectomy in our hospital from March 1st to May 31st, 2020 (period of the first wave COVID-19 pandemic in Spain). We also compared the results with cystectomized patients outside the pandemic period and with application of the ERAS (Enhanced Recovery After Surgery) protocol. MATERIAL AND METHODS: Single-center, retrospective cohort study of patients scheduled for radical cystectomy from March 1st,2020 to May 31st, 2020. They were matched with previously operated patients using a 1:2 propensity matching score. The matching variables were demographic data, preoperative and intraoperative clinical conditions. RESULTS: A total of 23 radical cystectomies with urinary diversion were performed in the period described. In none of the cases the prehabilitation or the follow-up of our ERAS protocol could be applied, and this was the only difference we found between the 2 groups. Although the minimally invasive approach was more frequent in the pandemic group, the difference was not statistically significant. Three patients were diagnosed with COVID-19 during their admission, presenting severe respiratory complications and high in-hospital mortality. Apart from respiratory complications secondary to SARS-CoV-2, we also found statistically significant differences in other postoperative complications. The hospital stay increased by 3 days in the pandemic group. CONCLUSIONS: Patients who underwent radical cystectomy at our center during the first wave of the COVID-19 pandemic had a higher number and severity of respiratory and non-respiratory complications. Discontinuation of the ERAS protocol was the main difference in treatment between groups.

Clinical impact of the suspension of the ERAS protocol on patients undergoing radical cystectomy during the COVID-19 pandemic.

INTRODUCTION: During the beginning of the COVID-19 pandemic in our center, neither prehabilitation nor multimodal rehabilitation could be applied due to the excessive patient load on the health system and to reduce SARS-CoV-2 transmission. The objective of our study was to analyze the evolution, complications, and survival up to one year of patients who underwent radical cystectomy in our hospital from March 1st to May 31st, 2020 (period of the first wave COVID-19 pandemic in Spain). We also compared the results with cystectomized patients outside the pandemic period and with application of the ERAS (Enhanced Recovery After Surgery) protocol. MATERIAL AND METHODS: Single-center, retrospective cohort study of patients scheduled for radical cystectomy from March 1st, 2020 to May 31st, 2020. They were matched with previously operated patients using a 1:2 propensity matching score. The matching variables were demographic data, preoperative and intraoperative clinical conditions. RESULTS: A total of 23 radical cystectomies with urinary diversion were performed in the period described. In none of the cases the prehabilitation or the follow-up of our ERAS protocol could be applied, and this was the only difference we found between the 2 groups. Although the minimally invasive approach was more frequent in the pandemic group, the difference was not statistically significant. Three patients were diagnosed with COVID-19 during their admission, presenting severe respiratory complications and high in-hospital mortality. Apart from respiratory complications secondary to SARS-CoV-2, we also found statistically significant differences in other postoperative complications. The hospital stay increased by 3 days in the pandemic group. CONCLUSIONS: Patients who underwent radical cystectomy at our center during the first wave of the COVID-19 pandemic had a higher number and severity of respiratory and non-respiratory complications. Discontinuation of the ERAS protocol was the main difference in treatment between groups.

Reduced- vs full-dose BCG in bladder cancer: A systematic review and meta-analysis.

OBJECTIVE: To assess the oncologic outcomes and the safety profile of a reduced-dose versus full-dose BCG regimen in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS: We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed, Embase, and Web of Science databases were searched in January 2022 for studies that analyzed oncological outcomes and compared between reduced- and full-dose BCG regimens. RESULTS: Seventeen studies including 3757 patients met our inclusion criteria. Patients who received reduced-dose BCG had significantly higher recurrence rates (OR 1.19; 95%CI, 1.03-1.36; p = 0.02). The risks of progression to muscle-invasive BC (OR 1.04; 95%CI, 0.83-1.32; p = 0.71), metastasis (OR 0.82; 95%CI, 0.55-1.22; p = 0.32), death from BC (OR 0.80; 95%CI, 0.57-1.14; p = 0.22), and all-cause death (OR 0.82; 95%CI, 0.53-1.27; p = 0.37) were not statistically different. When restricting the analyses to randomized controlled trials, we found similar results. In subgroup analysis, reduced dose was associated with a higher rate of BC recurrence in studies that used only an induction regimen (OR 1.70; 95%CI, 1.19-2.42; p = 0.004), but not when a maintenance regimen was used (OR 1.07; 95%CI, 0.96-1.29; p = 0.17). Regarding side effects, the reduced-dose BCG regimen was associated with fewer episodes of fever (p = 0.003), and therapy discontinuation (p = 0.03). CONCLUSION: This review found no association between BCG dose and BC progression, metastasis, and mortality. There was an association between reduced dose and BC recurrence, which was no longer significant when a maintenance regimen was used. In times of BCG shortage, reduced-dose regimens could be offered to BC patients.

Robot-assisted vs. open radical cystectomy: systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Several randomized controlled trials (RCTs) have been launched in the last decade to examine the surgical safety and oncological efficacy of robot-assisted (RARC) vs open radical cystectomy (ORC) for patients with bladder cancer. The aim of the study was to perform a systematic review and meta-analysis of RCTs to compare the perioperative and oncological outcomes of RARC vs ORC. METHODS: A literature search was conducted through July 2022 using PubMed/Medline, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The outcomes were intraoperative, postoperative, and oncological outcomes of RARC vs ORC. RESULTS: A total of eight RCTs comprising 1,024 patients met our inclusion criteria. RARC was associated with longer operative time (mean 92.34min, 95% CI 83.83-100.84, p<0.001) and lower blood transfusion rate (Odds ratio [OR] 0.43, 95% CI 0.30-0.61, p<0.001). No differences emerged in terms of 90-day overall (p=0.28) and major (p=0.57) complications, length of stay (p=0.18), bowel recovery (p=0.67), health-related quality of life (p=0.86), disease recurrence (p=0.77) and progression (p=0.49) between the two approaches. The main limitation is represented by the low number of patients included in half of RCTs included. CONCLUSIONS: This study supports that RARC is not inferior to ORC in terms of surgical safety and oncological outcomes. The benefit of RARC in terms of lower blood transfusion rate need to be balanced with the cost related to the procedure.

Primary urethral carcinoma: Results from a single center experience.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN+ with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

Improving signal/noise resolution in single-molecule experiments using molecular constructs with short handles.

We investigate unfolding/folding force kinetics in DNA hairpins exhibiting two and three states with newly designed short dsDNA handles (29 bp) using optical tweezers. We show how the higher stiffness of the molecular setup moderately enhances the signal/noise ratio (SNR) in hopping experiments as compared to conventional long-handled constructs (≅700 bp). The shorter construct results in a signal of higher SNR and slower folding/unfolding kinetics, thereby facilitating the detection of otherwise fast structural transitions. A novel analysis, as far as we are aware, of the elastic properties of the molecular setup, based on high-bandwidth measurements of force fluctuations along the folded branch, reveals that the highest SNR that can be achieved with short handles is potentially limited by the marked reduction of the effective persistence length and stretch modulus of the short linker complex.

Primary urethral carcinoma: Results from a single center experience. / Carcinoma uretral primario: resultados de la experiencia de un único centro.

INTRODUCTION AND AIM OF THE STUDY: Primary urethral carcinoma (PUC) is a rare neoplastic disease arising in the urethra, without any evidence of a previous or synchronous carcinoma of the entire urinary tract. Since rare diseases are often incorrectly diagnosed and managed, the aim of this study was to analyze the experience of a single urology center in the treatment of PUC, focusing on neoplasms arising from the male anterior urethra. MATERIALS AND METHODS: Medical records of patients with neoplasms at the level of the penile and bulbar urethra who presented at our tertiary referral center between January 1988 and December 2018 were retrospectively reviewed. Patients with carcinoma of the prostatic urethra were excluded. The diagnosis was obtained with the aid of urethroscopy and lesion biopsy. Local staging was performed by means of contrast-enhanced MRI in selected patients. Staging was achieved by clinical examination, ultrasonography, and CT scan. Radical surgery (radical cystectomy + total penectomy + bilateral inguinal lymphadenectomy) was proposed to patients with ≥T2 tumors or cN + with a good performance status, proximal tumor and without severe comorbidities. In case of nodal involvement, neoadjuvant chemotherapy was additionally offered. Patients with localized disease (

History of urological malignancies before kidney transplantation, oncological outcome on the long term. / Antecedentes de neoplasias urológicas previos al trasplante renal. Resultados oncológicos a largo plazo.

INTRODUCTION: We aimed to report the oncological outcomes of ESRD patients with histories of urological malignancies who were subsequently submitted to kidney transplantation (KT). MATERIAL AND METHOD: Retrospective study lead in the Puigvert Foundation (Barcelona) registry of 1,200 KT performed from 1988 to 2018. Eighty-five urological malignancies that were treated before KT in 81 patients were identified: 15 (18%) prostate cancers, 49 (58%) RCC, 19 (22%) urothelial carcinomas and 2 (2%) testicular cancers. Baseline characteristics, cancer staging, treatment and follow-up were registered as well as the chronology of the start of dialysis, inscription on the waiting list and kidney transplantation. Endpoints included were cancer recurrence, metastatic progression, cancer-specific death and overall survival. RESULTS: In a median follow-up of 13.1 years (2.2-32), 16/85 (19%) cancer recurrences were reported, with 3 (4%) who progressed to metastasis and died of cancer. Median overall survival after cancer treatment was 25.3 years and cancer-specific survival was 95% at 25 years. Median time from cancer treatment to kidney transplantation was 4.8 years: 3.7 years in prostate cancer, 3.9 years in RCC and 8.8 years in bladder cancer. The median time from start of dialysis to kidney transplantation was 1.8 years in patients with histories of urological malignancy versus 0.5 year in the total cohort of 1,200 renal transplanted over the same period. CONCLUSIONS: Well-selected patients with histories of urological malignancies greatly benefit from kidney transplantation with infrequent and late cancer recurrence. Waiting time could be optimized in low-risk prostate cancer and RCC, but more robust data are needed.

History of urological malignancies before kidney transplantation, oncological outcome on the long term.

INTRODUCTION: We aimed to report the oncological outcomes of ESRD patients with histories of urological malignancies who were subsequently submitted to kidney transplantation (KT). MATERIAL AND METHOD: Retrospective study lead in the Puigvert Foundation (Barcelona) registry of 1,200 KT performed from 1988 to 2018. Eighty-five urological malignancies that were treated before KT in 81 patients were identified: 15 (18%) prostate cancers, 49 (58%) RCC, 19 (22%) urothelial carcinomas and 2 (2%) testicular cancers. Baseline characteristics, cancer staging, treatment and follow-up were registered as well as the chronology of the start of dialysis, inscription on the waiting list and kidney transplantation. Endpoints included were cancer recurrence, metastatic progression, cancer-specific death and overall survival. RESULTS: In a median follow-up of 13.1 years (2.2-32), 16/85 (19%) cancer recurrences were reported, with 3 (4%) who progressed to metastasis and died of cancer. Median overall survival after cancer treatment was 25.3 years and cancer-specific survival was 95% at 25 years. Median time from cancer treatment to kidney transplantation was 4.8 years: 3.7 years in prostate cancer, 3.9 years in RCC and 8.8 years in bladder cancer. The median time from start of dialysis to kidney transplantation was 1.8 years in patients with histories of urological malignancy versus 0.5 year in the total cohort of 1,200 renal transplanted over the same period. CONCLUSIONS: Well-selected patients with histories of urological malignancies greatly benefit from kidney transplantation with infrequent and late cancer recurrence. Waiting time could be optimized in low-risk prostate cancer and RCC, but more robust data are needed.

Whole and hemi-gland cryoablation for primary localized prostate cancer: Short and medium-term oncological and functional outcomes. / Crioablación total o hemiglandular para el cáncer de próstata primario localizado: resultados oncológicos y funcionales a corto y medio plazo.

INTRODUCTION: To compare oncological, functional and post-operative outcomes of hemi (HC) vs. whole gland (WGC) cryoablation as first line treatment of localized prostate cancer. MATERIAL AND METHOD: Sixty-six consecutive patients undertaking whole-gland cryoablation (WGC=40) or hemi-cryoablation (HC=26) in a tertiary referral centre between 2010 and 2018 were included. All patients had a low-intermediate risk prostate cancer according to D'Amico risk classification. Hemi-ablation was proposed in case of biopsy and prostate MRI proven unilateral prostate cancer. Primary endpoint was Cryotherapy Failure for which 3 definitions were considered and compared: 1) biochemical failure (> PSA nadir+≥ 2 ng/mL), 2) positive prostate re-biopsy with Gleason score ≥ 7, 3) initiation of further prostate cancer treatment. RESULTS: Median patients age at treatment was 74 [42-81] vs. 76 [71-80] years in WGC vs. HC group, respectively (p=.08). Low and intermediate D'Amico risk group were 15% and 85% vs. 23% and 77% (p=.75), respectively. Median follow- up time was 41 [1.5-99.0] vs. 27 [0.9-93] months (p=.03). Four-years cryotherapy failure free survival in WGC vs. HC were 69% vs. 53% with definition 1 (p=.24), 82% vs. 80% with definition 2 (p=.95), 83% vs. 77% with definition 3 (p=.73). Early and 1-year urinary continence were 60% and 83% in WGC vs. 72% and 83% in HC (p=.26). De novo impotency after cryotherapy was 75% vs. 46% (p=.33) in WGC vs. HC. CONCLUSIONS: In our cohort of highly selected patients with unilateral low/intermediate risk PCa, hemi-cryoablation may provide similar oncological outcomes and less early complications compared to whole-gland cryoablation.

Statistical properties of metastable intermediates in DNA unzipping.

We unzip DNA molecules using optical tweezers and determine the sizes of the cooperatively unzipping and zipping regions separating consecutive metastable intermediates along the unzipping pathway. Sizes are found to be distributed following a power law, ranging from one base pair up to more than a hundred base pairs. We find that a large fraction of unzipping regions smaller than 10 bp are seldom detected because of the high compliance of the released single stranded DNA. We show how the compliance of a single nucleotide sets a limit value around 0.1 N/m for the stiffness of any local force probe aiming to discriminate one base pair at a time in DNA unzipping experiments.

Endoscopic pneumatic balloon dilation in primary achalasia: predictive factors, complications, and long-term follow-up.

Pneumatic dilation (PD) has been widely used in the treatment of idiopathic achalasia with a 70-90% response. The aim of this study was to evaluate the effectiveness of PD and its predictive factors by means of clinical assessment. In addition, we evaluated its safety and the need for subsequent surgical intervention. Fifty-six patients were treated with a Witzel dilator. The response was evaluated at medium (1-5 years) and long term (>5 years). Diverse possible predictive factors to response were analyzed. After the first PD, 85.7% of the 56 patients improved and passed from clinical stage II-III to clinical stage 0-I (P < 0.005). After the second dilation, 84.6% of the patients (13) passed to clinical stage 0-I (P < 0.05). Only patients who were not young (>40 years) avoided a second dilation and/or surgery (P < 0.001). During the first 5 years of follow-up, 80% of patients maintained their response; this percentage decreased to 58% after 10 years. PD therapy of achalasia is a safe technique, with few adverse effects (4% perforations and 10% gastroesophageal reflux). It offers a medium-term response of 80% and long-term response of around 60%. Age was the only predictive response factor.

A comparative study of different surgical techniques for the management of distal ureter during laparoscopic radical nephroureterectomy. / Estudio comparativo de diferentes técnicas quirúrgicas para el manejo del uréter distal durante la nefroureterectomía laparoscópica.

OBJECTIVES: To compare the oncological outcomes between two open surgical techniques and two endoscopic approaches for the management of the distal ureter during laparoscopic radical nephroureterectomy (LRNU). MATERIAL AND METHODS: Retrospective review of 152 patients submitted to LRNU for the management of upper urinary tract tumors between 2007-2014. We analyzed the potential impact of two different open surgical (extravesical vs intravesical) and two endoscopic (resection of ureteral orifice and fragment removal vs endoscopic bladder cuff) techniques on the development of bladder recurrence, distant/local recurrence and cancer-specific survival (CSS). RESULTS: A total of 152 patients with a mean age of 69.9 years (±10.1) underwent LRNU. We reported 62 pTa-T1 (41%), 35 pT2 (23%) and 55 pT3-4 (36%). Thirty-two were low grade (21.1%) and 120 high grade (78.9%). An endoscopic approach was performed in 89 cases (58.5%), 32 with resection (36%) and 57 with bladder cuff (64%), and open approach in 63 (41.5%), 42 intravesical (66.7%) and 21 extravesical (33.3%). Within a median follow-up of 32 months (3-120), 38 patients (25%) developed bladder recurrence, 42 distant/local recurrence (27.6%) and 34 died of tumor (22.4%). In the univariate analysis, the type of endoscopic technique was not related to bladder recurrence (P=.961), distant/local recurrence (P=.955) nor CSS (P=.802). The open extravesical approach was not related to bladder recurrence (P=.12) but increased distant/local recurrence (P=.045) and decreased CSS (P=.034) compared to intravesical approach. CONCLUSIONS: LRNU outcomes are not dependant on the type of endoscopic approach performed. The open extravesical approach is a more difficult technique and could worsen the oncological outcomes when compared to the intravesical.