Non-surgical therapies for Peyronie's disease.

BACKGROUND: Peyronie's disease is a condition that results in the development of penile plaques that can lead to penile curvature, pain, and erectile dysfunction, making sexual activity difficult. A number of non-surgical interventions exist to improve this condition, which include topical and injection agents as well as mechanical methods; however, their effectiveness remains uncertain. We performed this review to determine the effects of these non-surgical treatments. OBJECTIVES: To assess the effects of non-surgical therapies compared to placebo or no treatment in individuals with Peyronie's disease. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings, up to 23 September 2022. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included trials in which men with Peyronie's disease were randomized to undergo non-surgical therapies versus placebo or no treatment for penile curvature and sexual function. DATA COLLECTION AND ANALYSIS: Two of four review authors, working in pairs, independently classified studies and abstracted data from the included studies. Primary outcomes were: patient-reported ability to have intercourse, quality of life, and treatment-related adverse effects. Secondary outcomes were: degree of penile curvature, discontinuation from treatment (for any reason), subjective patient-reported change in penile curvature, and improvement in penile pain. We performed statistical analyses using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach. MAIN RESULTS: Our search identified 1288 relevant references of which we included 18 records corresponding to 14 unique randomized controlled trials (RCTs) with 1810 men. These informed 10 distinct comparisons with relevant outcome data that were mostly extracted from single trials. In this abstract, we focus only on the most clinically relevant comparisons for the three primary outcomes and also include the outcome of degree penile curvature. Injectional collagenase (short-term): We found no short-term evidence on injectional collagenase for patients' self-reported ability to have intercourse and treatment-related adverse effects compared to placebo injection. Injectional collagenase may result in little to no difference in quality of life (scale 0 to 20 with lower scores indicating better quality of life; mean difference (MD) 1.8 lower, 95% confidence interval (CI) -3.58 to -0.02; 1 study, 134 participants; low CoE) and there may be little to no effect on the degree of penile curvature (MD 10.90 degrees less, 95% CI -16.24 to -5.56; 1 study, 136 participants; low CoE). Injectional collagenase (long-term): We also found no long-term evidence on injectional collagenase for patients' self-reported ability to have intercourse compared to placebo injection. It likely results in little to no effect on quality of life (MD 1.00 lower, 95% CI -1.60 to -0.40; 1 study, 612 participants; moderate CoE). Treatment-related adverse effects are likely increased (risk ratio (RR) 2.32, 95% CI 1.98 to 2.72; 1 study, 832 participants; moderate CoE). Injectional collagenase likely results in little to no change in the degree of penile curvature (MD 6.90 degrees less, 95% CI -9.64 to -4.14; 1 study, 612 participants; moderate CoE). Injectional verapamil (short-term): We are very uncertain how injectional verapamil may affect patients' self-reported ability to have intercourse compared to placebo injection short-term (RR 7.00, 95% CI 0.43 to 114.70; 1 study, 14 participants; very low CoE). We found no evidence for the outcome of quality of life. We are very uncertain how injectional verapamil may affect treatment-related adverse effects (RR not estimable; 1 study, 14 participants; very low CoE). Similarly, we are very uncertain how injectional verapamil may affect degree of penile curvature (MD -1.86, 95% CI -10.39 to 6.67; 1 study, 14 participants; very low CoE). We found no long-term data for any outcome. Extracorporeal shock wave treatment (ESWT) (short-term): We are very uncertain how ESWT affects patients' self-reported ability to have intercourse short-term (RR 1.60, 95% CI 0.71 to 3.60; 1 study, 26 participants; very low CoE). ESWT may result in little to no difference in quality of life (MD 3.10, 95% CI 1.57 to 4.64; 2 studies, 130 participants; low CoE). We are very uncertain if ESWT has an effect on treatment-related adverse effects (RR 2.73, 95% CI 0.74 to 10.14; 3 studies, 166 participants; very low CoE). ESWT may result in little to no difference in the degree of penile curvature compared to placebo (RR -2.84, 95% -7.35 to 1.67; 3 studies, 166 participants; low CoE). We found no long-term data for any outcome. Penile traction therapy (short-term): We found no evidence for whether penile traction compared to no treatment affects patients' self-reported ability to have intercourse. We are very uncertain how traction therapy may affect quality of life (MD 1.50 lower, 95% CI -3.42 to 0.42; 1 study, 90 participants; very low CoE). We are also very uncertain how traction therapy may affect treatment-related adverse effects (RR not estimable; 1 study, 90 participants; very low CoE) and how it affects the degree of curvature (MD 7.40 degrees less, 95% CI -11.18 to -3.62; 1 study, 89 participants; very low CoE). We found no long-term data for any outcome. AUTHORS' CONCLUSIONS: There is little evidence supporting the effectiveness of most non-surgical treatments for Peyronie's disease. Existing trials are mostly of poor methodological quality and/or fail to address patient-centered outcomes. Injectional collagenase appears to have some effectiveness; however, many individuals may not experience the improvement as clinically relevant, and this comes with the risk of increased adverse events. There is a critical need for better non-surgical treatment options for men with Peyronie's disease.

ANTECEDENTES: La enfermedad de Peyronie es una afección que da lugar al desarrollo de placas en el pene que pueden provocar curvatura peneana, dolor y disfunción eréctil, dificultando la actividad sexual. Existen varias intervenciones no quirúrgicas para mejorar esta afección, que incluyen agentes tópicos e inyectables, así como métodos mecánicos; sin embargo, su eficacia aún es incierta. Esta revisión se realizó para determinar los efectos de estos tratamientos no quirúrgicos. OBJETIVOS: Evaluar los efectos de los tratamientos no quirúrgicos en comparación con placebo o ningún tratamiento en individuos con enfermedad de Peyronie. MÉTODOS DE BÚSQUEDA: Se realizó una búsqueda exhaustiva en múltiples bases de datos (la Biblioteca Cochrane, MEDLINE, Embase, Scopus, Google Scholar y Web of Science), en registros de ensayos, otras fuentes de literatura gris y resúmenes de congresos, hasta el 23 de septiembre de 2022. No se impusieron restricciones respecto al idioma ni el estado de publicación. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos en los que se asignó al azar a hombres con enfermedad de Peyronie a someterse a tratamientos no quirúrgicos versus placebo o ningún tratamiento para la curvatura del pene y la función sexual. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos de los cuatro autores de la revisión, trabajando en pareja, clasificaron de forma independiente los estudios y resumieron los datos de los estudios incluidos. Los desenlaces principales fueron: capacidad para mantener relaciones sexuales autoinformada por el paciente, calidad de vida y efectos adversos relacionados con el tratamiento. Los desenlaces secundarios fueron: grado de curvatura del pene, interrupción del tratamiento (por cualquier motivo), cambio subjetivo de la curvatura del pene autoinformado por el paciente y mejoría del dolor del pene. Se realizaron análisis estadísticos con un modelo de efectos aleatorios. La certeza de la evidencia se calificó según el método GRADE. RESULTADOS PRINCIPALES: La búsqueda identificó 1288 referencias pertinentes, de las cuales se incluyeron 18 registros correspondientes a 14 ensayos controlados aleatorizados (ECA) individuales con 1810 hombres. Éstos informaron 10 comparaciones distintas con datos de desenlaces relevantes que se extrajeron en su mayoría de ensayos individuales. Este resumen se centra solo en las comparaciones clínicamente más relevantes para los tres desenlaces principales y también se incluye el desenlace de grado de curvatura peneana. Colagenasa inyectable (a corto plazo): No se encontró evidencia a corto plazo de la colagenasa inyectable, en comparación con la inyección placebo, en la capacidad autoinformada por los pacientes de tener relaciones sexuales ni en los efectos adversos relacionados con el tratamiento. La colagenasa inyectable podría dar lugar a poca o ninguna diferencia en la calidad de vida (escala de 0 a 20 con puntuaciones más bajas que indican mejor calidad de vida; diferencia de medias [DM] 1,8 menor; intervalo de confianza [IC] del 95%: ­3,58 a ­0,02; un estudio, 134 participantes; evidencia de certeza baja) y podría haber poco o ningún efecto en el grado de curvatura del pene (DM 10,90 grados menos; IC del 95%: ­16,24 a ­5,56; un estudio, 136 participantes; evidencia de certeza baja). Colagenasa inyectable (a largo plazo): Tampoco se encontró evidencia a largo plazo sobre la colagenasa inyectable en la capacidad autoinformada por los pacientes de tener relaciones sexuales en comparación con la inyección placebo. Es probable que tenga un efecto escaso o nulo sobre la calidad de vida (DM 1,00 inferior; IC del 95%: ­1,60 a ­0,40; un estudio, 612 participantes; evidencia de certeza moderada). Es probable que aumenten los efectos adversos relacionados con el tratamiento (razón de riesgos [RR] 2,32; IC del 95%: 1,98 a 2,72; un estudio, 832 participantes; evidencia de certeza moderada). La colagenasa inyectable probablemente provoca poco o ningún cambio en el grado de curvatura del pene (DM 6,90 grados menos; IC del 95%: ­9,64 a ­4,14; un estudio, 612 participantes; evidencia de certeza moderada). Verapamilo inyectable (a corto plazo): No está muy claro cómo el verapamilo inyectable podría afectar la capacidad autoinformada por los pacientes de tener relaciones sexuales en comparación con la inyección placebo a corto plazo (RR 7,00; IC del 95%: 0,43 a 114,70; un estudio, 14 participantes; evidencia de certeza muy baja). No se encontró evidencia del desenlace de calidad de vida. No se sabe con certeza cómo podría afectar el verapamilo inyectable los efectos adversos relacionados con el tratamiento (RR no estimable; un estudio, 14 participantes; evidencia de certeza muy baja). Del mismo modo, es muy incierto cómo el verapamilo inyectable podría afectar el grado de curvatura peneana (DM ­1,86; IC del 95%: ­10,39 a 6,67; un estudio, 14 participantes; evidencia de certeza muy baja). No se encontraron datos a largo plazo para ningún desenlace. Tratamiento con ondas de choque extracorpóreas (OCE) (a corto plazo): No está muy claro cómo el tratamiento con OCE afecta la capacidad autoinformada por los pacientes de mantener relaciones sexuales a corto plazo (RR 1,60; IC del 95%: 0,71 a 3,60; un estudio, 26 participantes; evidencia de certeza muy baja). El tratamiento con OCE podría dar lugar a poca o ninguna diferencia en la calidad de vida (DM 3,10; IC del 95%: 1,57 a 4,64; dos estudios, 130 participantes; evidencia de certeza baja). No está muy claro si el tratamiento con OCE influye en los efectos adversos relacionados con el tratamiento (RR 2,73; IC del 95%: 0,74 a 10,14; tres estudios, 166 participantes; evidencia de certeza muy baja). El tratamiento con OCE podría dar lugar a poca o ninguna diferencia en el grado de curvatura peneana en comparación con el placebo (RR ­2,84; 95%: ­7,35 a 1,67; tres estudios, 166 participantes; evidencia de certeza baja). No se encontraron datos a largo plazo para ningún desenlace. Terapia de tracción peneana (a corto plazo): No se encontró evidencia de si la tracción peneana comparada con ningún tratamiento afecta la capacidad autoinformada por los pacientes de tener relaciones sexuales. No se sabe con certeza cómo podría afectar la terapia de tracción la calidad de vida (DM 1,50 inferior; IC del 95%: ­3,42 a 0,42; un estudio, 90 participantes; evidencia de certeza muy baja). Tampoco se sabe con certeza cómo podría afectar la terapia de tracción los efectos adversos relacionados con el tratamiento (RR no estimable; un estudio, 90 participantes; evidencia de certeza muy baja) ni cómo afecta el grado de curvatura (DM 7,40 grados menos; IC del 95%: ­11,18 a ­3,62; un estudio, 89 participantes; evidencia de certeza muy baja). No se encontraron datos a largo plazo para ningún desenlace. CONCLUSIONES DE LOS AUTORES: Existe poca evidencia que respalde la eficacia de la mayoría de los tratamientos no quirúrgicos para la enfermedad de Peyronie. Los ensayos existentes son en su mayoría de baja calidad metodológica y no abordan los desenlaces centrados en el paciente. La colagenasa inyectable parece tener cierta eficacia; sin embargo, es posible que muchas personas no experimenten una mejoría clínicamente relevante, lo que conlleva el riesgo de un aumento de los eventos adversos. Existe una necesidad imperiosa de mejores opciones terapéuticas no quirúrgicas para los hombres con enfermedad de Peyronie.

Diagnosing Prostate Cancer: The Role of Intravesical Prostatic Gland Protrusion on Accuracy of Prostate Biopsies.

PURPOSE: We evaluated the association between intravesical prostate protrusion (IPP) and the detection rate of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TB). MATERIALS AND METHODS: A total of 538 consecutive men who underwent MRI-TRUS fusion TB and concomitant systematic biopsy were evaluated. IPP on MRI was independently measured by 4 blinded reviewers. The primary outcome was per-lesion detection of csPCa on TB. We assessed the association between IPP and csPCa detection on TB, controlling for age, prostate specific antigen, Prostate Imaging Reporting and Data System® (PI-RADS®) score, prostate volume, targeted cores sampled and previous biopsy experience. RESULTS: A total of 847 PI-RADS 3 or greater lesions were targeted across 570 biopsies. Intra- and interrater reliability for measuring IPP was strong. A total of 81 (14.2%), 127 (22.3%), 237 (41.6%) and 125 (21.9%) men had 0, small, medium and large IPP, respectively. A total of 230, 392 and 196 lesions were PI-RADS 3, 4 and 5, respectively. Of the lesions 198 (34.7%) had csPCa on TB. The overall relationship between IPP size and csPCa found on TB was not significant; however, large IPP is associated with a significantly lower rate of csPCa detection than 0 IPP (p=0.007). Every mm increase in IPP is associated with a 5.6% decrease in the odds of csPCa detection on TB (p=0.004) and a 66.5% decrease in odds of detection in large IPP compared to 0 IPP (p=0.003). CONCLUSIONS: As the size of the IPP and volume increase, there is a decrease in the detection rate of csPCa on MRI-guided TB. These findings may be driven by poor MRI-TRUS co-registration and prostate asymmetry.

Posterior musculofascial reconstruction in robot-assisted laparoscopic prostatectomy for the treatment of clinically localised prostate cancer: a Cochrane Review.

OBJECTIVES: To assess the effects of posterior musculofascial reconstruction robot-assisted laparoscopic prostatectomy (PR-RALP) compared to no PR during standard RALP (S-RALP) for the treatment of clinically localised prostate cancer. PATIENTS AND METHODS: We performed a systematic search with no restrictions including randomised controlled trials (RCTs) comparing variations of PR-RALP vs S-RALP for clinically localised prostate cancer. The quality of evidence was assessed on outcome basis according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Our search identified 13 records of eight unique RCTs, of which six were published studies, and two were abstract proceedings. There were 1085 randomised patients, of whom 963 completed the trials. All patients had either cT1c or cT2 or cT3a disease. RESULTS: A PR-RALP may improve urinary continence 1 week after catheter removal compared to no PR (risk ratio [RR] 1.25, 95% confidence interval [CI] 0.90-1.73; I2 = 42%, five studies, 498 patients, low certainty of evidence [CoE]). A PR-RALP may have little to no effect on urinary continence 3 months after surgery compared to no PR (RR 0.98, 95% CI 0.84-1.14; I2 = 67%, six studies, 842 patients, low CoE). A PR-RALP probably results in little to no difference in serious adverse events compared to no PR (RR 0.75, 95% CI 0.29-1.92; I2 = 0%, six studies, 835 patients, moderate CoE). CONCLUSIONS: This review found evidence that PR-RALP may improve early continence 1 week after catheter removal but not thereafter. Meanwhile, adverse event rates are probably not impacted and positive surgical margin rates are likely similar. There was no difference in our subgroup analysis for all outcomes with anterior reconstruction technique when combined with PR vs only PR.

Retzius-sparing versus standard robot-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

OBJECTIVES: To assess the effects of Retzius-sparing (RS) robotic-assisted laparoscopic prostatectomy (RALP) compared to standard RALP for the treatment of clinically localized prostate cancer. METHODS: We performed a systematic search of multiple databases and the grey literature with no restrictions on the language of publication or publication status, up until June 2020. We included randomized controlled trials (RCTs) comparing RS-RALP with standard RALP. We performed a meta-analysis using a random-effect model. The quality of evidence was assessed on an outcome basis according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Our search identified six records of five unique RCTs, of which two were published studies, one was in press, and two were abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. The mean age of participants was 64.6 years and the mean prostate-specific antigen level was 6.9 ng/mL. Approximately 54.2% of participants had cT1c disease, 38.6% had cT2a-b disease, and 7.1% had cT2c disease. RS-RALP probably improves continence within 1 week after catheter removal (risk ratio [RR] 1.74, 95% confidence interval [CI] 1.41-2.14; I2 = 0%; studies = 4; participants = 410; moderate-certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery. RS-RALP may increase continence at 3 months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06-1.68; I2 = 86%; studies = 5; participants = 526; low-certainty evidence). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery. We are very uncertain about the effects of RS-RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47-4.17; studies = 2; participants = 230; very low-certainty evidence). CONCLUSIONS: The findings of this review indicate that RS-RALP may result in better continence outcomes than standard RALP up to 6 months after surgery. Continence outcomes at 12 months may be similar. The disadvantages of RS-RALP may be higher positive surgical margin rates. We are very uncertain about the effect on biochemical recurrence-free survival and potency outcomes. Longer-term oncological and functional outcomes are lacking, and no preplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade-offs and the limitations of the evidence with their patients when considering this approach.

Posterior musculofascial reconstruction in robotic-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

BACKGROUND: Delayed recovery of urinary continence is a major adverse effect of robotic-assisted laparoscopic prostatectomy (RALP) in men undergoing prostate cancer treatment. To address this issue, a number of surgical techniques have been designed to reconstruct the posterior aspect of the rhabdosphincter, which is responsible for urinary continence after removal of the prostate; however, it is unclear how well they work.  OBJECTIVES: To assess the effects of posterior musculofascial reconstruction RALP compared to no posterior reconstruction during RALP for the treatment of clinically localized prostate cancer. SEARCH METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to 12 March 2021. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which participants were randomized to undergo variations of posterior musculofascial reconstruction RALP versus no posterior reconstruction during RALP for clinically localized prostate cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery at six and twelve months after surgery, potency recovery twelve months after surgery, positive surgical margins (PSM), and biochemical recurrence-free survival (BCRFS). We performed statistical analyses using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach. MAIN RESULTS: Our search identified 13 records of eight unique RCTs, of which six were published studies and two were abstract proceedings. We included 1085 randomized participants, of whom 963 completed the trials (88.8%). All participants had either cT1c or cT2 or cT3a disease, with a mean prostate-specific antigen level of 8.15 ng/mL. Primary outcomes Posterior reconstruction RALP (PR-RALP) may improve urinary continence one week after catheter removal compared to no posterior reconstruction during RALP (risk ratio (RR) 1.25, 95% confidence interval (CI) 0.90 to 1.73; I2 = 42%; studies = 5, participants = 498; low CoE) although the CI also includes the possibility of no effect. Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 84 more men per 1000 (33 fewer to 244 more) reporting urinary continence recovery.  Posterior reconstruction may have little to no effect on urinary continence three months after surgery compared to no posterior reconstruction during RALP (RR 0.98, 95% CI 0.84 to 1.14; I2 = 67%; studies = 6, participants = 842; low CoE). Assuming 701 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 14 fewer men per 1000 (112 fewer to 98 more) reporting urinary continence after three months. PR-RALP probably results in little to no difference in serious adverse events compared to no posterior reconstruction during RALP (RR 0.75, 95% CI 0.29 to 1.92; I2 = 0%; studies = 6, participants = 835; moderate CoE). Assuming 25 per 1000 men undergoing standard RALP experience a serious adverse event at this time point, this corresponds to six fewer men per 1000 (17 fewer to 23 more) reporting serious adverse events.  Secondary outcomes PR-RALP may result in little to no difference in recovery of continence 12 months after surgery compared to no posterior reconstruction during RALP (RR 1.02, 95% CI 0.98 to 1.07; I2 = 25%; studies = 3, participants = 602; low CoE). Assuming 918 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 18 more men per 1000 (18 fewer to 64 more) reporting urinary continence recovery.  We are very uncertain about the effects of PR-RALP on recovery of potency 12 months after surgery compared to no posterior reconstruction during RALP (RR 1.02, 95% CI 0.82 to 1.26; I2 = 3%; studies = 2, participants = 308; very low CoE). Assuming 433 per 1000 men undergoing standard RALP are potent at this time point, this corresponds to nine more men per 1000 (78 fewer to 113 more) reporting potency recovery.  PR-RALP may result in little to no difference in positive surgical margins compared to no posterior reconstruction during RALP (RR 1.24, 95% CI 0.65 to 2.33; I2 = 50%; studies = 3, participants = 517; low CoE). Assuming 130 per 1000 men undergoing standard RALP have a positive surgical margin, this corresponds to 31 more men per 1000 (46 fewer to 173 more) reporting positive surgical margins.  PR-RALP may result in little to no difference in biochemical recurrence compared to no posterior reconstruction during RALP (RR 1.36, 95% CI 0.74 to 2.52; I2 = 0%; studies = 2, participants = 468; low CoE). Assuming 70 per 1000 men undergoing standard RALP have experienced biochemical recurrence at this time point, this corresponds to 25 more men per 1000 (18 fewer to 107 more) reporting biochemical recurrence.  AUTHORS' CONCLUSIONS: This review found evidence that PR-RALP may improve early continence one week after catheter removal but not thereafter. Meanwhile, adverse event rates are probably not impacted and surgical margins rates are likely similar. This review was unable to determine if or how these findings may be impacted by the person's age, nerve-sparing status, or clinical stage. Study limitations, imprecision, and inconsistency lowered the certainty of evidence for the outcomes assessed.

Retzius-sparing robot-assisted radical prostatectomy improves early recovery of urinary continence: a randomized, controlled, single-blind trial with a 1-year follow-up.

OBJECTIVE: To evaluate the impact of Retzius-sparing robot-assisted radical prostatectomy (posterior approach) on early recovery of urinary continence (UC) compared to the conventional approach (anterior approach) for the treatment of clinically localized prostate cancer (PCa). METHODS: A total of 110 consecutive patients with clinically localized PCa were prospectively randomized in a 1:1 ratio to an anterior group (n = 55) or a posterior group (n = 55). The primary outcome was immediate UC, defined as freedom from any pad use within 1 week after removal of the urinary catheter. The UC rate following surgery was also calculated with Kaplan-Meier curves, and the log-rank test was used for statistical comparison. Intra-operative outcomes, pathological data and oncological outcomes, including positive surgical margin (PSM) status and biochemical recurrence-free survival (BCRFS), were also compared between the two groups. The comparison of the two approaches was also analysed in subgroups after risk stratification. RESULTS: Of the patients who underwent the posterior approach, 69.1% achieved immediate UC compared with 30.9% in the anterior group (relative risk 2.24, 95% confidence interval [CI] 1.48-3.51; P = 0.000). The relative Kaplan-Meier curves for UC during the 12-month follow-up revealed statistically better recovery in the posterior group when compared with the anterior group (hazard ratio [HR] 1.51, 95% CI 1.01-2.24; log-rank P = 0.007). No statistically significant differences were observed between the groups regarding complications (P = 0.399), PSM status (P = 0.225) or BCRFS (HR 4.80, 95% CI 0.97-23.78; log-rank P = 0.111). In sub-analyses, no significant difference between the two approaches with regard to UC recovery in patients with high-risk PCa was observed (HR 1.26, 95% CI 0.63-2.51; log-rank P = 0.415). CONCLUSIONS: The Retzius-sparing approach significantly improved early recovery of UC compared to the conventional approach. Further prospective studies are needed to confirm the benefits of the Retzius-sparing approach for clinically localized PCa, especially for high-risk cases.

Retzius-sparing versus standard robotic-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

BACKGROUND: Robotic-assisted laparoscopic prostatectomy (RALP) is widely used to surgically treat clinically localized prostate cancer. It is typically performed using an approach (standard RALP) that mimics open retropubic prostatectomy by dissecting the so-called space of Retzius anterior to the bladder. An alternative, Retzius-sparing (or posterior approach) RALP (RS-RALP) has been described, which is reported to have better continence outcomes but may be associated with a higher risk of incomplete resection and positive surgical margins (PSM). OBJECTIVES: To assess the effects of RS-RALP compared to standard RALP for the treatment of clinically localized prostate cancer. SEARCH METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to June 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included trials where participants were randomized to RS-RALP or standard RALP for clinically localized prostate cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery six and 12 months after surgery, potency recovery 12 months after surgery, positive surgical margins (PSM), biochemical recurrence-free survival (BCRFS), and urinary and sexual function quality of life. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: Our search identified six records of five unique randomized controlled trials, of which two were published studies, one was in press, and two were abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. Mean age of participants was 64.6 years and mean prostate-specific antigen was 6.9 ng/mL. About 54.2% of participants had cT1c disease, 38.6% had cT2a-b disease, and 7.1 % had cT2c disease. Primary outcomes RS-RALP probably improves continence within one week after catheter removal (risk ratio (RR) 1.74, 95% confidence interval (CI) 1.41 to 2.14; I2 = 0%; studies = 4; participants = 410; moderate-certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery. RS-RALP may increase continence at three months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06 to 1.68; I2 = 86%; studies = 5; participants = 526; low-certainty evidence). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery. We are very uncertain about the effects of RS-RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47 to 4.17; studies = 2; participants = 230; very low-certainty evidence). Secondary outcomes There is probably little to no difference in continence recovery at 12 months after surgery (RR 1.01, 95% CI 0.97 to 1.04; I2 = 0%; studies = 2; participants = 222; moderate-certainty evidence). Assuming 982 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 10 more men per 1000 (29 fewer to 39 more) reporting continence recovery.  We are very uncertain about the effect of RS-RALP on potency recovery 12 months after surgery (RR 0.98, 95% CI 0.54 to 1.80; studies = 1; participants = 55; very low-certainty evidence).  RS-RALP may increase PSMs (RR 1.95, 95% CI 1.19 to 3.20; I2 = 0%; studies = 3; participants = 308; low-certainty evidence) indicating a higher risk for prostate cancer recurrence. Assuming 129 per 1000 men undergoing standard RALP have positive margins, this corresponds to 123 more men per 1000 (25 more to 284 more) with PSMs. We are very uncertain about the effect of RS-RALP on BCRFS compared to standard RALP (hazard ratio (HR) 0.45, 95% CI 0.13 to 1.60; I2 = 32%; studies = 2; participants = 218; very low-certainty evidence). AUTHORS' CONCLUSIONS: Findings of this review indicate that RS-RALP may result in better continence outcomes than standard RALP up to six months after surgery. Continence outcomes at 12 months may be similar. Downsides of RS-RALP may be higher positive margin rates. We are very uncertain about the effect on BCRFS and potency outcomes. Longer-term oncologic and functional outcomes are lacking, and no preplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade-offs and the limitations of the evidence with their patients when considering this approach.

Prediction of Arteriovenous Fistula Dysfunction: Can it be Taught?

Physical examination (PE) is an excellent means of predicting arteriovenous fistula (AVF) dysfunction. Although quick and inexpensive, PE is seldom used as a tool to assess stenosis by general nephrologists, dialysis nurses, and dialysis technicians. Previous studies have demonstrated that PE can be taught to interventional specialists, but the perception remains that it is too complex to be performed by other health care professionals. We hypothesized that the physical exam can be taught to a nonmedical professional, and that, with time, it would be comparable to the physical exam performed by a full-time interventional specialist. An undergraduate student and an interventional specialist (MD) examined AVF for dysfunction in a tertiary care hospital over a 6-month period. PE was performed on patients who were suspected of having dialysis access dysfunction and were referred for angiography and intervention (n = 49). Physical exam findings were categorized blindly by each examiner into four categories of lesion location: inflow, outflow, both, or neither. Data were privately recorded and compared to the gold standard of angiographic results. Potential confounding variables, including age, gender, diabetic status, and location of AVF were recorded. Weighted Cohen's kappa value was used as a measurement of the level of agreement beyond chance between the diagnoses made by physical exam and angiography. The full-time interventional specialist demonstrated correct prediction of lesion location of 89.8% (kappa = 0.850), while the undergraduate student had a correct prediction of 77.6% (kappa = 0.625). The student's performance, however, differed significantly over time. The student correctly predicted the location of the lesion in 6 (42.9%) of the first 14 patients (kappa = 0.082), compared to 32 (91.4%) of the last 35 patients (kappa = 0.855). We suggest that physical exam of AVF can be taught to a nonmedical professional in a short duration of time and the predictive value of the exam can be similar to that of an interventional specialist.

Review: Failure of current digoxin monitoring for toxicity: new monitoring recommendations to maintain therapeutic levels for efficacy.

The current recommendations for monitoring digoxin, a narrow therapeutic index drug, are limited to confirming medication use or investigating suspicion of toxicity and fail our oath to do no harm. Numerous meta-analyses evaluating digoxin use consistently recommend frequent monitoring to maintain the level of 0.5 to ≤1.0 ng/ml because higher levels lead to increased morbidity and mortality without benefit. Data from the United States National Poison Control Center (2012-2020) show annual deaths due to digoxin of 18-36 compared to lithium's 1-7, and warfarin's 0-2 respectively. The latter drugs also have narrow therapeutic indexes like digoxin yet are more carefully monitored. Recognition of digoxin toxicity is impaired as levels are not being routinely checked after medications are added to a patient's regimen. In addition, providers may be using ranges to guide treatment that are no longer appropriate. It is imperative that monitoring guidelines and laboratory therapeutic levels are revised to reduce morbidity and mortality due to digoxin. In this review, we provide a comprehensive literature review of digoxin monitoring guidelines, digoxin toxicity, and evidence to support revising the ranges for serum digoxin monitoring.

The Evolution of Retzius-Sparing Robot-Assisted Laparoscopic Prostatectomy: An Idea, Development, Evolution, Assessment, and Long-Term Study Perspective.

Purpose: The Retzius-sparing (RS) approach represents an important surgical innovation in how robot-assisted laparoscopic prostatectomy (RALP) is performed. The aim of this study was to examine to what extent its development has followed the idea, development, evolution, assessment, and long-term study (IDEAL) recommendations. Materials and Methods: We conducted a comprehensive literature search for studies up to the 18th of March 2021. Abstracted data points included authorship, year of publication, study design, reported endpoints, and length of follow-up. We mapped each study to the five IDEAL stages of surgical innovation using published criteria. Results: Of 415 references, 118 were included in our analysis. Five academic centers authored >50% of all study reports, with the groups from Seoul (24; 20.3%), Milan (15; 12.7%), and Ninjang (10; 8.5%) being the main contributors. Approximately 40% of studies (50/118) were reported as full-text publications. Most of the reports mapped to retrospective studies (97/118; 82.2%) with approximately one-third (31/97; 32.0%) reporting the use of prospectively collected data. Cumulatively, 17,974 were reported on RS-RALP. Of those, 13,929 were unique cases. Approximately 23% of cases were reported in multiple publications (4045/17,974). We mapped 2, 12, and 3 studies to the idea, assessment, and long-term study stages, respectively, and no study to the development and evaluation stages. Conclusions: Few reported studies followed the IDEAL stages for surgical innovation; none addressed the stages of development and evaluation. Future systematic prospectively planned assessments would be helpful to refine the approach and address issues related to the surgical learning curve.

Impact of protruded median lobe on perioperative, urinary continence and oncological outcomes of Retzius-sparing robot-assisted radical prostatectomy.

BACKGROUND: To investigate the effect of protruded median lobe (PML) on the perioperative, oncological, and urinary continence (UC) outcomes among patients underwent Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). METHODS: 231 consecutive patients who had undergone RS-RARP were collected and analyzed. Patients were divided into three groups based on the PML degree: PML<5 mm (n=99); 5≤ PML <10 mm (n=91); PML ≥10 mm (n=41). The perioperative outcomes, short-term oncological, and UC outcomes were compared among the three groups. Those outcomes were also compared in patients with significant PML (>10 mm) who underwent the traditional or Retzius-sparing RARP. RESULTS: The median PML was significantly associated age (P<0.001) and prostate volume (P<0.001). Perioperative characteristics including console time, estimated blood loss (EBL), intraoperative transfusion rate, and complications were not statistically different among the three groups (P=0.647, 0.574, 0.231, 0.661, respectively). The rate of positive surgical margin (PSM) were not significantly different in the three groups (P=0.065). No significant difference regarding UC and biochemical recurrence (BCR) at 12-month follow-up was observed in the three groups (P>0.05). Comparison between the two approaches in men with significant PML showed better recovery of UC (HR =1.83, 95% CI: 1.117-3.01, log-rank P=0.002) and similar BCR (log-rank P=0.072) after RS-RARP. CONCLUSIONS: RS-RARP is an oncologically and functionally equivalent approach for patients with PML. Compared with the traditional approach, RS-RARP offers benefits regarding UC for cases with significant PML.

Automatic Segmentation of Kidneys and Kidney Tumors: The KiTS19 International Challenge.

Purpose: Clinicians rely on imaging features to calculate complexity of renal masses based on validated scoring systems. These scoring methods are labor-intensive and are subjected to interobserver variability. Artificial intelligence has been increasingly utilized by the medical community to solve such issues. However, developing reliable algorithms is usually time-consuming and costly. We created an international community-driven competition (KiTS19) to develop and identify the best system for automatic segmentation of kidneys and kidney tumors in contrast CT and report the results. Methods: A training and test set of CT scans that was manually annotated by trained individuals were generated from consecutive patients undergoing renal surgery for whom demographic, clinical and outcome data were available. The KiTS19 Challenge was a machine learning competition hosted on grand-challenge.org in conjunction with an international conference. Teams were given 3 months to develop their algorithm using a full-annotated training set of images and an unannotated test set was released for 2 weeks from which average Sørensen-Dice coefficient between kidney and tumor regions were calculated across all 90 test cases. Results: There were 100 valid submissions that were based on deep neural networks but there were differences in pre-processing strategies, architectural details, and training procedures. The winning team scored a 0.974 kidney Dice and a 0.851 tumor Dice resulting in 0.912 composite score. Automatic segmentation of the kidney by the participating teams performed comparably to expert manual segmentation but was less reliable when segmenting the tumor. Conclusion: Rapid advancement in automated semantic segmentation of kidney lesions is possible with relatively high accuracy when the data is released publicly, and participation is incentivized. We hope that our findings will encourage further research that would enable the potential of adopting AI into the medical field.

The state of the art in kidney and kidney tumor segmentation in contrast-enhanced CT imaging: Results of the KiTS19 challenge.

There is a large body of literature linking anatomic and geometric characteristics of kidney tumors to perioperative and oncologic outcomes. Semantic segmentation of these tumors and their host kidneys is a promising tool for quantitatively characterizing these lesions, but its adoption is limited due to the manual effort required to produce high-quality 3D segmentations of these structures. Recently, methods based on deep learning have shown excellent results in automatic 3D segmentation, but they require large datasets for training, and there remains little consensus on which methods perform best. The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was a competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) which sought to address these issues and stimulate progress on this automatic segmentation problem. A training set of 210 cross sectional CT images with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated systems to predict the true segmentation masks on a test set of 90 CT images for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between the kidney and tumor across all 90 cases. The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an "open leaderboard" phase where it serves as a challenging benchmark in 3D semantic segmentation.

Five New Cases of Primary Renal Carcinoid Tumor: Case Reports and Literature Review.

Carcinoid tumors, a slow-growing NET, most commonly arise in the gastrointestinal tract (73.7%), followed by the bronchopulmonary system (25.1%), and least commonly in the genitourinary system (<1%). Primary carcinoid tumors of the kidney-with approximately 100 cases reported in the literature since the first described case in 1966-are thought to be so rare because neuroendocrine cells are not typically found in the renal parenchyma. Here we present a series of five cases at our institution with primary carcinoid tumors of the kidney followed by a literature review. In the literature we describe the diagnostic stains used to determine renal carcinoid tumors. We also describe why partial nephrectomies are the gold standard treatment in these cases, while radical nephrectomy can be used in certain circumstances. Limited research on treatment of metastasis of these tumors exists, but we summarize the results of existing treatments. Major prognostic factors and survival of patients with these tumors is described as well as the increased prevalence of this tumors in patients with horseshoe kidneys. This study presents five new cases of primary renal carcinoid tumors and a comprehensive review of the previously published cases. We are able to make limited prognostic predictions from currently published literature, but we will continue to learn from our patients' long-term courses to draw conclusions about biological behavior, treatment outcomes, and recurrence of rare disease.

Public Perceptions of Artificial Intelligence and Robotics in Medicine.

Objective: To understand better the public perception and comprehension of medical technology such as artificial intelligence (AI) and robotic surgery. In addition to this, to identify sensitivity to their use to ensure acceptability and quality of counseling. Subjects and Methods: A survey was conducted on a convenience sample of visitors to the MN Minnesota State Fair (n = 264). Participants were randomized to receive one of two similar surveys. In the first, a diagnosis was made by a physician and in the second by an AI application to compare confidence in human and computer-based diagnosis. Results: The median age of participants was 45 (interquartile range 28-59), 58% were female (n = 154) vs 42% male (n = 110), 69% had completed at least a bachelor's degree, 88% were Caucasian (n = 233) vs 12% ethnic minorities (n = 31) and were from 12 states, mostly from the Upper Midwest. Participants had nearly equal trust in AI vs physician diagnoses. However, they were significantly more likely to trust an AI diagnosis of cancer over a doctor's diagnosis when responding to the version of the survey that suggested that an AI could make medical diagnoses (p = 9.32e-06). Though 55% of respondents (n = 145) reported that they were uncomfortable with automated robotic surgery, the majority of the individuals surveyed (88%) mistakenly believed that partially autonomous surgery was already happening. Almost all (94%, n = 249) stated that they would be willing to pay for a review of medical imaging by an AI if available. Conclusion: Most participants express confidence in AI providing medical diagnoses, sometimes even over human physicians. Participants generally express concern with surgical AI, but they mistakenly believe that it is already being performed. As AI applications increase in medical practice, health care providers should be cognizant of the potential amount of misinformation and sensitivity that patients have to how such technology is represented.

Markers of mineral metabolism and vascular access complications: The Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study.

INTRODUCTION: Vascular access dysfunction is a major cause of morbidity in patients with end-stage renal disease (ESRD) on chronic hemodialysis. The effects of abnormalities in mineral metabolism on vascular access are unclear. In this study, we evaluated the association of mineral metabolites, including 25-hydroxy vitamin D (25(OH)D) and fibroblast growth factor-23 (FGF-23), with vascular access complications. METHODS: We included participants from the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study who were using an arteriovenous fistula (AVF; n = 103) or arteriovenous graft (AVG; n = 116). Serum levels of 25(OH)D, FGF-23, parathyroid hormone (PTH), calcium, phosphorus, C-reactive protein (CRP) and interleukin-6 (IL-6) were assessed from stored samples. Participants were followed for up to 1 year or until a vascular access intervention or replacement. FINDINGS: A total of 24 participants using an AVF and 43 participants using an AVG experienced access intervention. Those with 25(OH)D level in the lowest tertile (<11 ng/mL) had an increased risk of AVF intervention compared to those with higher 25(OH)D levels (adjusted relative hazard [aHR] = 3.28; 95% confidence interval [CI]: 1.31, 8.20). The highest tertile of FGF-23 (>3750 RU/mL) was associated with greater risk of AVF intervention (aHR = 2.56; 95% CI: 1.06, 6.18). Higher PTH was associated with higher risk of AVF intervention (aHR = 1.64 per SD of log(PTH); 95% CI: 1.02, 2.62). These associations were not observed in participants using an AVG. None of the other analytes were significantly associated with AVF or AVG intervention. DISCUSSION: Low levels of 25(OH)D and high levels of FGF-23 and PTH are associated with increased risk of AVF intervention. Abnormalities in mineral metabolism are risk factors for vascular access dysfunction and potential therapeutic targets to improve outcomes.

The association of mineral metabolism with vascular access patency.

BACKGROUND: Declining kidney function leads to progressively dysregulated mineral homeostasis and contributes to vascular calcification and a pro-inflammatory milieu, both of which play a critical role in loss of dialysis vascular access patency. We designed this study to examine the relationship between markers of bone and mineral metabolism, vitamin D replacement medications, and vascular access outcomes. We hypothesized that higher levels of calcium, phosphorous, parathyroid hormone (PTH), and albumin are independently associated with vascular access patency and that vitamin D supplementation is associated with lower risk of access failure. METHODOLOGY: We abstracted data on 204 consecutive patients referred for angiographic evaluation of their permanent arteriovenous access over a 25-month period. We followed patients from the time of access salvage until subsequent referral for access failure. RESULTS: The incidence of vascular access failure did not differ by serum phosphorus, PTH, calcium, calcium-phosphorus product or albumin level. Patients receiving any vitamin D replacement therapy, however, had a lower incidence of access failure compared to those receiving no therapy. Those receiving vitamin D3 therapy with or without paricalcitol (Zemplar, Abbot Laboratories, Abbot Park, IL) or calcitriol had an adjusted HR = 0.18 compared to those receiving no vitamin D therapy. CONCLUSIONS: This study suggests a relationship between vitamin D3 usage and better vascular access patency, independent of the effect of vitamin D on PTH. Though this relationship needs more rigorous investigation prior to clinical application, the known differences in the pro- and anti-inflammatory effects of various vitamin D metabolites provide a potential mechanism for these clinical observations.