State of art of robotic prostatectomy: the way we do it in Catalonia, Spain.

INTRODUCTION AND OBJECTIVE: Robotic-assisted laparoscopic prostatectomy (PLAR) seems to improve functional outcomes, however there is not a consensus of a standard procedure. The aim of this study was to identify the PLAR "state of art" in Catalonia, Spain. MATERIAL AND METHODS: This was a cross-sectional survey-based study conducted among urologists across Catalonia, Spain. The survey was distributed through online platforms and the professional urology society. All statistical analyses were performed using Stata software, v20. RESULTS: 59 urologists completed the survey, revealing PLAR as the most commonly used technique (79.7%). Most urologist (70%) create the pneumoperitoneum using a controlled incision with direct access and 78.3% use the Airseal technology. The intraperitoneal approach is performed in >90% of cases. Endopelvic fascia preservation is not routinely performed. 34.5% of the survey not perform the dorsal vein complex suture. All preserves the bladder neck when oncologically safe. Nerve-vascular bundles bleeding control is performed using standard coagulation or suturing. 34% performed posterior reconstruction. Only use hemostatic devices when evident bleeding and 70% does not routinely left a drainage. Multivariable analysis showed that center volume had a significant independent association with dorsal venous complex suturing (OR 0.073, 95%CI 0.07-0.826), nerve-vascular bundles suturing hemostasis (OR 11.67, 95%CI 1.07-127.60) and endopelvic fascia preservation (OR 13.64, 95%CI 1.087-201.27), but there was no correlation with time the bladder catheter or days hospitalized. CONCLUSIONS: The study provides an overview of the state of PLAR in Catalonia, Spain, showing significant variability and reflecting a commitment to advancing surgical technology and patient care.

Systematic review of methods used to improve the efficacy of magnetic resonance in early detection of clinically significant prostate cancer.

BACKGROUND AND OBJECTIVE: Prostate cancer (PC) is the malignant neoplasm with the highest incidence after lung cancer worldwide. The objective of this study is to review the literature on the methods that improve the efficacy of the current strategy for the early diagnosis of clinically significant PC (csPC), based on the performance of magnetic resonance imaging (RM) and targeted biopsies when suspicious lesions are detected, in addition to systematic biopsy. EVIDENCE ACQUISITION: A systematic literature review was performed in PubMed, Web of Science and Cochrane according to the PRISMA criteria (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), using the search terms: multiparametric magnetic resonance imaging, biparametric magnetic resonance imaging, biomarkers in prostate cancer, prostate cancer y early diagnosis. A total of 297 references were identified and, using the PICO selection criteria, 21 publications were finally selected to synthesize the evidence. EVIDENCE SYNTHESIS: With the consolidation of MRI as the test of choice for the diagnosis of prostate cancer, the role of PSA density (PSAD) becomes relevant as a predictive tool included in prediction nomograms, without added cost. PSAD and diagnostic markers, combined with MRI, offer a high diagnostic power with an area under curve (AUC) above 0.7. Only the SHTLM3 model integrates markers in the creation of a nomogram. Prediction models also offer consistent efficacy with an AUC greater than 0.8 when associating MRI. CONCLUSIONS: The efficacy of MRI in clinically significant prostate cancer detection can be improved with different parameters in order to generate predictive models that support decision making.

La resonancia magnética preoperatoria predice la recuperación temprana de la continencia urinaria tras la prostatectomía radical robótica / Preoperative magnetic resonance imaging in predicting early continence recovery after robotic radical prostatectomy

Introducción y objetivos: La incontinencia urinaria es una de las principales complicaciones tras la prostatectomía radical. El objetivo del estudio fue describir las características anatómicas, evaluadas preoperatoriamente mediante resonancia magnética, que permitan predecir la recuperación precoz de la continencia urinaria tras la prostatectomía radical asistida por robot. Material y métodos: Se analizó prospectivamente a 72 pacientes tratados mediante prostatectomía radical asistida por robot. Los resultados funcionales se evaluaron mediante los cuestionarios EPIC (1, 6 y 12 meses) y la fecha de primera continencia autoinformada. La longitud de la uretra membranosa (LUM) y el ángulo entre la LUM y el eje prostático (aLUMP) fueron evaluados preoperatoriamente en imágenes sagitales ponderadas en T2. Resultados: La tasa de continencia fue del 67,2, el 92,6 y el 95,2% a 1, 6 y 12 meses, respectivamente. Los pacientes con valores de aLUMP inferiores alcanzaron continencia urinaria temprana: al mes, los continentes habían tenido una aLUMP media de 107,21° (IC del 95% 90,3-124,6), mientras que entre los que presentaban incontinencia era de 118,5° (IC del 95% 117,7-134); p = 0,014. Hemos encontrado diferencias en el aLUMP entre los grupos según la continencia a los 6 meses: ángulo en continentes de 114,24° (IC del 95% 104,6-123,9), mientras que en los incontinentes había sido 142° (IC del 95% 126,5-157,6), p = 0,015. A los 12 meses, los continentes tenían una LUM preoperatoria significativamente superior a los incontinentes. En el análisis multivariante solamente el aLUMP fue un predictor independiente de continencia urinaria a los 6 meses OR 0,007 (IC del 95% 0,002-0,012), p = 0,012. Conclusiones: La evaluación de parámetros anatómicos preoperatorios previos a la cirugía puede ayudar a definir qué pacientes recuperarán la continencia urinaria precozmente, auxiliando a la toma de decisiones terapéuticas

Introduction and aims: Urinary incontinence is a common complication after radical prostatectomy. The aim of our study was to describe the preoperative anatomical features using magnetic resonance imaging in order to predict early continence recovery after robotic radical prostatectomy. Material and methods: 72 patients who underwent robotic radical prostatectomy were prospectively analysed. EPIC questionnaire (1, 6 and 12 mo) and first self-reported continence were used to assess functional outcomes. Membranous urethral length (MUL) and MUL-prostate axis angle (aMULP) were assessed preoperatively on T2 weighted sagittal images. Results: Continence rate was 67.2%, 92.6% and 95.2% at 1, 6 and 12 months, respectively. Early continence was achieved in patients with the lower aMULP. At 1 month, average aMULP in continent patients was 107.21° (CI 95% 90.3-124.6) vs. 118.5° (CI 95% 117.7-134) in incontinent ones (p = 0.014). At 6 month differences in aMULP among groups were found: 114.24° (CI 95% 104.6-123.9) in continents vs. 142° (CI 95% 126.5-157.6) in incontinents (p = 0.015). At 12 month, continent group showed a significantly higher preoperative aMULP. aMULP was revealed as the only independent predictor of urinary continence at 6 mo in multivariate analysis, OR 0.007 (CI 95% 0.002-0.012), p = 0.012. Conclusions: Preoperative anatomical parameters assessment prior surgery can help to identified those patients will achieve early continence recovery and it supports therapeutic decisions making

Preoperative magnetic resonance imaging in predicting early continence recovery after robotic radical prostatectomy. / La resonancia magnética preoperatoria predice la recuperación temprana de la continencia urinaria tras la prostatectomía radical robótica.

INTRODUCTION AND AIMS: Urinary incontinence is a common complication after radical prostatectomy. The aim of our study was to describe the preoperative anatomical features using magnetic resonance imaging in order to predict early continence recovery after robotic radical prostatectomy. MATERIAL AND METHODS: 72 patients who underwent robotic radical prostatectomy were prospectively analysed. EPIC questionnaire (1, 6 and 12 mo) and first self-reported continence were used to assess functional outcomes. Membranous urethral length (MUL) and MUL-prostate axis angle (aMULP) were assessed preoperatively on T2 weighted sagittal images. RESULTS: Continence rate was 67.2%, 92.6% and 95.2% at 1, 6 and 12 months, respectively. Early continence was achieved in patients with the lower aMULP. At 1 month, average aMULP in continent patients was 107.21° (IC 95% 90.3-124.6) vs. 118.5° (IC 95% 117.7-134) in incontinent ones (P=.014). At 6 month differences in aMULP among groups were found: 114.24° (IC 95% 104.6-123.9) in continents vs. 142° (IC 95% 126.5-157.6) in incontinents (P=0.015). At 12 month, continent group showed a significantly higher preoperative aMULP. aMULP was revealed as the only independent predictor of urinary continence at 6 mo in multivariate analysis, OR 0.007 (IC 95% 0.002-0.012), P=0.012. CONCLUSIONS: Preoperative anatomical parameters assessment prior surgery can help to identified those patients will achieve early continence recovery and it supports therapeutic decisions making.

Cambios hormonales después del tratamiento de cáncer de próstata localizado. Comparación entre radioterapia de haz externo y prostatectomía radical / Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy

Objetivos: Determinar la influencia de la prostatectomía radical (PR) y de la radioterapia externa (RT) sobre el eje hipotálamo-hipofisario de 120 pacientes con cáncer de próstata clínicamente localizado tratados con PR o RT exclusiva. Material y métodos: Estudiamos 120 pacientes con cáncer de próstata localizado. Noventa y dos pacientes recibieron PR y 28 RT exclusiva. Medimos los niveles séricos de hormona luteinizante, hormona folículo estimulante (FSH), testosterona total (T), testosterona libre y estradiol basalmente y a los 3 y 12 meses tras completar el tratamiento. Resultados: Los pacientes sometidos a PR eran más jóvenes y presentaban mayor volumen prostático (64,3 vs. 71,1 años, p < 0,0001 y 55,1 vs. 36,5 g, p < 0,0001; respectivamente). No encontramos diferencias en los niveles hormonales basales. Los niveles de hormona luteinizante y FSH eran significativamente superiores en los pacientes tratados con RT a los 3 meses (hormona luteinizante 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p < 0,0001) y los niveles de T y testosterona libre significativamente inferiores (T 360,3 vs. 414,83 ng/dl, p 0,039; FT 5,94 vs. 7,5 pg/ml, p 0,018). A los 12 meses los niveles de FSH permanecían significativamente superiores en los pacientes tratados con RT comparado con pacientes tratados con PR (21,01 vs. 8,51 U/l, p < 0,001) y los niveles de T permanecían significativamente inferiores (339,89 vs. 402,39 ng/dl, p 0,03). Conclusiones: El tratamiento del cáncer de próstata influye en el eje hipotálamo-hipofisario. La influencia parece más importante en los pacientes tratados con RT. Necesitamos más estudios que eluciden el papel que la próstata puede jugar como órgano endocrino

Objective: To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. Materials and methods: 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Results: Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p < 0.0001 and 55.1 vs. 36.5 g, p < 0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p < 0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83 ng/dl, p 0,039; free testosterone 5,94 vs. 7,5 pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p < 0,001) while T levels remained significantly lower (339,89 vs. 402,39 ng/dl, p 0,03). Conclusions: Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ

Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy. / Cambios hormonales después del tratamiento de cáncer de próstata localizado. Comparación entre radioterapia de haz externo y prostatectomía radical.

OBJECTIVE: To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. MATERIALS AND METHODS: 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. RESULTS: Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). CONCLUSIONS: Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ.

Extraintestinal spread and replication of a homologous EC rotavirus strain and a heterologous rhesus rotavirus in BALB/c mice.

Although rotavirus infection has generally been felt to be restricted to the gastrointestinal tract, over the last two decades there have been sporadic reports of children with acute or fatal cases of rotavirus gastroenteritis testing positive for rotavirus antigen and/or nucleic acid in various extraintestinal locations such as serum, liver, kidney, bladder, testes, nasal secretions, cerebrospinal fluid, and the central nervous system. Recently, studies in animals and people have demonstrated that rotavirus antigenemia is a common event during natural infection. In this study, we extend these observations and compare the intestinal and extraintestinal spread of wild-type homologous murine rotavirus EC and a heterologous strain, rhesus rotavirus (RRV), in newborn mice. A strand-specific quantitative reverse transcription-PCR (ssQRT-PCR) assay was used to quantify the ability of different rotavirus strains to spread and replicate extraintestinally. Both strain EC and RRV were detected extraintestinally in the mesenteric lymph nodes (MLN), livers, lungs, blood, and kidneys. Extraintestinal replication, as measured by ssQRT-PCR, was most prominent in the MLN and occurred to a lesser degree in the livers, kidneys, and lungs. In the MLN, strain EC and RRV had similar (P < 0.05) RNA copy numbers, although EC was present at a 10,000-fold excess over RRV in the small intestine. Rotavirus nonstructural protein 4 (NSP4) and/or assembled triple-layered particles, indicated by immunostaining with the VP7 conformation-dependent monoclonal antibody 159, were detected in the MLN, lungs, and livers of EC- and RRV-inoculated mice, confirming the ssQRT-PCR findings. Infectious RRV was detected in the MLN in quantities exceeding the amount present in the small intestines or blood. The cells in the MLN that supported rotavirus replication included dendritic cells and potentially B cells and macrophages. These data indicate that extraintestinal spread and replication occurs commonly during homologous and some heterologous rotaviral infections; that the substantial host range restrictions for rhesus rotavirus, a heterologous strain present in the intestine, are not necessarily apparent at systemic sites; that the level and location of extraintestinal replication varies between strains; that replication can occur in several leukocytes subsets; and that extraintestinal replication is likely a part of the normal pathogenic sequence of homologous rotavirus infection.

Entry of rotaviruses is a multistep process.

The infection of epithelial cells by some animal rotavirus strains requires the presence of sialic acid (SA) on the cell surface. Recently, we isolated rhesus rotavirus variants, named nar, whose infectivity, like that of human rotaviruses, is not dependent on SA. In this work, we have determined the binding properties of these SA-dependent and -independent rotavirus strains to MA104 cells. The half-time of attachment of the SA-dependent porcine rotavirus YM and reassortant virus DS1xRRV was found to be about 10 times longer in neuraminidase-treated cells than in untreated cells. On the other hand, human rotaviruses Wa and DS1, and the variant nar3, bound to cells two to three times more rapidly in the absence of SA. To investigate whether the SA-independent cellular structure recognized by the variant and human rotaviruses was the same, we used an infection assay designed to detect competition for cell surface molecules at both attachment and post-attachment steps. In this assay, human rotavirus Wa efficiently competed the infectivity of YM in untreated cells and that of the variant nar3 in untreated, as well as neuraminidase-treated, cells. This competition was nonreciprocal, since YM and nar3 did not compete, but rather increased three- to fivefold the infectivity of Wa. In contrast, a two-direction competition between the variant nar3 and DS1xRRV was found. Similar results were obtained when psoralen-inactivated viruses were used as competitors, indicating that the competition observed was during the early stages of infection. Altogether, these results suggest the existence of multiple interactions between rotaviruses and the cell surface and revealed the existence of common steps during the entry of human and animal rotavirus strains.

A new cysteine in rotavirus VP4 participates in the formation of an alternate disulfide bond.

Most animal rotaviruses bind to a cell surface molecule that contains sialic acid (SA). We have recently isolated variants from simian rotavirus RRV which show an SA-independent phenotype. The VP4 protein of these variants was shown to have three amino acid changes with respect to the wt protein, one of them being Tyr-267 --> Cys. In this work, we have investigated whether the new cysteine could interfere with the disulfide bond (Cys-318/Cys-380) present in the VP5* subunit of the wt protein. Cysteine residues 318 and 380 were mutagenized in gpr8 and RRV VP4 genes, and the wt and mutant genes were transcribed and translated in vitro. The protein products were analysed by electrophoresis under reducing and non-reducing conditions. This approach showed that, in the VP4 protein synthesized in vitro, Cys-267 is capable of forming an alternate disulfide bond with Cys-318. This alternate bond also seems to occur in the VP4 protein present in the variant gpr8 virus particles.

Rotaviruses induce an early membrane permeabilization of MA104 cells and do not require a low intracellular Ca2+ concentration to initiate their replication cycle.

In this work, we found that rotavirus infection induces an early membrane permeabilization of MA104 cells and promotes the coentry of toxins, such as alpha-sarcin, into the cell. This cell permeability was shown to depend on infectious virus and was also shown to be virus dose dependent, with 10 infectious particles per cell being sufficient to achieve maximum permeability; transient, lasting no more than 15 min after virus entry and probably occurring concomitantly with virus penetration; and specific, since cells that are poorly permissive for rotavirus were not permeabilized. The rotavirus-mediated coentry of toxins was not blocked by the endocytosis inhibitors dansylcadaverine and cytochalasin D or by the vacuolar proton-ATPase inhibitor bafilomycin A1, suggesting that neither endocytocis nor an intraendosomal acidic pH or a proton gradient is required for permeabilization of the cells. Compounds that raise the intracellular concentration of calcium ([Ca2+]i) by different mechanisms, such as the calcium ionophores A23187 and ionomycin and the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin, did not block the coentry of alpha-sarcin or affect the onset of viral protein synthesis, suggesting that a low [Ca2+]i is not essential for the initial steps of the virus life cycle. Since the entry of alpha-sarcin correlates with virus penetration in all parameters tested, the assay for permeabilization to toxins might be a useful tool for studying and characterizing the route of entry and the mechanism used by rotaviruses to traverse the cell membrane and initiate a productive replication cycle.