Análisis del impacto de la curva de aprendizaje de la cistectomía radical asistida por robot con derivación urinaria intracorpórea sobre los resultados perioperatorios / Evaluating the impact of the learning curve on the perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion

Introducción La cistectomía radical asistida por robot (CRAR) con derivación urinaria intracorpórea (DUIC) es un procedimiento técnicamente complejo. Nuestro objetivo fue analizar el impacto de la curva de aprendizaje (CA) de la CRAR con DUIC sobre los resultados perioperatorios y patológicos.Material y métodos Estudio retrospectivo de 62 pacientes consecutivos intervenidos mediante CRAR con DUIC por tumor vesical entre 2015 y 2020. Se compararon 3 grupos consecutivos de 20 (G1), 20 (G2) y 22 (G3) pacientes para analizar el impacto de la CA. Los casos de G1 fueron intervenidos por un cirujano sénior con experiencia en cirugía robótica y los de G2-G3 por 2cirujanos júnior sin experiencia, pero tutorizados por el sénior.Resultados Los 3grupos tenían características clínico-patológicas similares. A 15 pacientes (24%) se les realizó una neovejiga y a 47 (75%) un conducto ileal. El tiempo medio operatorio descendió 60 min entre G1 y G3 (p=0,001). Ningún paciente precisó conversión a cirugía abierta ni tuvo complicaciones intraoperatorias. No se objetivaron diferencias en la tasa de márgenes positivos (p=0,6) ni en el número de ganglios extraídos (p=0,061) entre los grupos. La tasa de complicaciones postoperatorias fue del 77% y no varió durante la CA (p=0,49). Se objetivó una tendencia en la reducción de tasa de estenosis ureteroileal del 25% en G1 al 9% en G3 (p=0,217).Conclusiones La incorporación de cirujanos júnior a un programa de CRAR con DUIC a partir de los 20 primeros casos no compromete los resultados perioperatorios ni patológicos. Durante la CA se podría reducir el tiempo operatorio y la tasa de estenosis ureteroileal (AU)

Introduction Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is a technically difficult procedure. Our aim was to evaluate the potential impact of the learning curve (LC) on perioperative and pathological outcomes of RARC with ICUD.Material and methods Retrospective study of 62 consecutive patients who underwent RARC with ICUD for bladder cancer between 2015-2020. We compared 3 consecutive groups of 20 (G1), 20 (G2), and 22 (G3) patients to analyze the impact of the LC. G1 cases were performed by a senior surgeon experienced in robotic surgery, while G2-G3 were performed by 2 junior surgeons without experience under the mentorship of the senior surgeon.Results The 3 groups had similar clinical and pathological characteristics. A total of 15 patients (24%) received a neobladder and 47 (75%) an ileal conduit. The mean operative time decreased 60minutes between G1-G3 (P=0.001). No conversions to open approach or intraoperative complications were reported. There were no differences between groups regarding positive margin rates (P=0.6) or the number of lymph nodes removed (P=0.061). The postoperative complication rate was 77% and did not change during the LC (P=0.49). Uretero-enteric stricture rate decreased from 25% in G1 to 9% in G3 (P=0.217).Conclusions The inclusion of júnior surgeons to a RARC with ICUD program after the initial 20 cases does not have an impact on the perioperative and pathological outcomes of the procedure. The operative time and the uretero-enteric stricture rate could be reduced during the LC (AU)

Evaluating the impact of the learning curve on the perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is a technically difficult procedure. Our aim was to evaluate the potential impact of the learning curve (LC) on perioperative and pathological outcomes of RARC with ICUD. MATERIAL AND METHODS: Retrospective study of 62 consecutive patients who underwent RARC with ICUD for bladder cancer between 2015-2020. We compared 3 consecutive groups of 20 (G1), 20 (G2), and 22 (G3) patients to analyze the impact of the LC. G1 cases were performed by a senior surgeon experienced in robotic surgery, while G2-G3 were performed by 2 junior surgeons without experience under the mentorship of the senior surgeon. RESULTS: The 3 groups had similar clinical and pathological characteristics. A total of 15 patients (24%) received a neobladder and 47 (75%) an ileal conduit. The mean operative time decreased 60 min between G1-G3 (p = 0.001). No conversions to open approach or intraoperative complications were reported. There were no differences between groups regarding positive margin rates (p = 0.6) or the number of lymph nodes removed (p = 0.061). The postoperative complication rate was 77% and did not change during the LC (p = 0.49). Uretero-enteric stricture rate decreased from 25% in G1 to 9% in G3 (p = 0.217). CONCLUSIONS: The inclusion of junior surgeons to a RARC with ICUD program after the initial 20 cases does not have an impact on the perioperative and pathological outcomes of the procedure. The operative time and the uretero-enteric stricture rate could be reduced during the LC.

Evaluating the impact of the learning curve on the perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion. / Análisis del impacto de la curva de aprendizaje de la cistectomía radical asistida por robot con derivación urinaria intracorpórea sobre los resultados perioperatorios.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is a technically difficult procedure. Our aim was to evaluate the potential impact of the learning curve (LC) on perioperative and pathological outcomes of RARC with ICUD. MATERIAL AND METHODS: Retrospective study of 62 consecutive patients who underwent RARC with ICUD for bladder cancer between 2015-2020. We compared 3 consecutive groups of 20 (G1), 20 (G2), and 22 (G3) patients to analyze the impact of the LC. G1 cases were performed by a senior surgeon experienced in robotic surgery, while G2-G3 were performed by 2 junior surgeons without experience under the mentorship of the senior surgeon. RESULTS: The 3 groups had similar clinical and pathological characteristics. A total of 15 patients (24%) received a neobladder and 47 (75%) an ileal conduit. The mean operative time decreased 60minutes between G1-G3 (P=0.001). No conversions to open approach or intraoperative complications were reported. There were no differences between groups regarding positive margin rates (P=0.6) or the number of lymph nodes removed (P=0.061). The postoperative complication rate was 77% and did not change during the LC (P=0.49). Uretero-enteric stricture rate decreased from 25% in G1 to 9% in G3 (P=0.217). CONCLUSIONS: The inclusion of júnior surgeons to a RARC with ICUD program after the initial 20 cases does not have an impact on the perioperative and pathological outcomes of the procedure. The operative time and the uretero-enteric stricture rate could be reduced during the LC.

Current status of genetic urinary biomarkers for surveillance of non-muscle invasive bladder cancer: a systematic review.

BACKGROUND: Genetic biomarkers are a promising and growing field in the management of bladder cancer in all stages. The aim of this paper is to understand the role of genetic urinary biomarkers in the follow up of patients with non muscle invasive bladder cancer where there is increasing evidence that they can play a role in avoiding invasive techniques. METHODS: Following PRISMA criteria, we have performed a systematic review. The search yielded 164 unique articles, of which 21 articles were included involving a total of 7261 patients. Sixteen of the articles were DNA based biomarkers, analyzing different methylations, microsatellite aberrations and gene mutations. Five articles studied the role of RNA based biomarkers, based on measuring levels of different combinations of mRNA. QUADAS2 critical evaluation of each paper has been reported. RESULTS: There are not randomized control trials comparing any biomarker with the gold standard follow-up, and the level of evidence is 2B in almost all the studies. Negative predictive value varies between 55 and 98.5%, being superior in RNA based biomarkers. CONCLUSIONS: Although cystoscopy and cytology are the gold standard for non muscle invasive bladder cancer surveillance, genetic urinary biomarkers are a promising tool to avoid invasive explorations to the patients with a safe profile of similar sensitivity and negative predictive value. The accuracy that genetic biomarkers can offer should be taken into account to modify the paradigm of surveillance in non muscle invasive bladder cancer patients, especially in high-risk ones where many invasive explorations are recommended and biomarkers experiment better results.

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

Objetivos: Comparar los resultados oncológicos de dos técnicas quirúrgicas abiertas y dos endoscópicas para el manejo del uréter distal durante nefroureterectomía laparoscópica (NUL). Material y métodos: Revisión retrospectiva de 152 pacientes sometidos a NUL por tumor del tramo urinario superior entre 2007 y 2014. Se analizó el potencial impacto de distintas técnicas de desinserción abierta (extravesical vs. intravesical) y endoscópica (resección meato con evacuación de fragmentos vs. rodete perimeático) sobre el desarrollo de recidiva vesical, extraurotelial y supervivencia cáncer-específica (SCE). Resultados: Un total de 152 pacientes con edad media de 69,9 años (±10,1) fueron sometidos a NUL. Se reportaron 62 pTa-T1 (41%), 35 pT2 (23%) y 55 pT3-4 (36%). Treinta y dos fueron bajo grado (21,1%) y 120 alto grado (78,9%). Se realizó desinserción endoscópica en 89 casos (58,5%), 32 con resección (36%) y 57 con rodete (64%), y abierta en 63 (41,5%), 42 intravesical (66,7%) y 21 extravesical (33,3%). Con mediana de seguimiento de 32 meses (3-120), 38 pacientes (25%) desarrollaron recidiva vesical, 42 extraurotelial (27,6%) y 34 murieron por tumor (22,4%). En el análisis univariante, el tipo de técnica endoscópica no se relacionó con recidiva vesical (p = 0,961), extraurotelial (p = 0,955) ni SCE (p = 0,802). El abordaje abierto extravesical no se relacionó con recidiva vesical (p = 0,12) pero sí con aumento de recidiva extraurotelial (p = 0,045) y menor SCE (p = 0,034) respecto al intravesical. Conclusiones: El subtipo de desinserción endoscópica no influye en los resultados de la NUL. La desinserción abierta extravesical es una técnica más compleja que la intravesical y podría empeorar los resultados oncológicos

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

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.

Comparación de los resultados perioperatorios de la cistectomía radical asistida por robot con derivación urinaria extracorpórea vs. Intracorpórea / Comparison of perioperative outcomes and complications of robot assisted radical cystectomy with extracorporeal vs intracorporeal urinary diversion

Objetivos: Comparar los resultados perioperatorios y las complicaciones de la cistectomía radical asistida por robot (CRAR) con derivación urinaria extracorpórea (DUEC) vs. intracorpórea (DUIC). Material y métodos: Revisión retrospectiva de 43 pacientes sometidos a CRAR por tumor vesical entre 2015-2018 con seguimiento mínimo de 3 meses. Se analizó la serie inicial de CRAR realizada por un cirujano con amplia experiencia en cistectomía radical abierta. Resultados: Cuarenta y tres pacientes, 40 hombres (93%) y 3 mujeres (7%), con mediana de edad de 65 años (44-83) y seguimiento medio de 27,7 meses (± 20,1) fueron sometidos a CRAR. Se realizó DUEC en 22 casos (51%), 10 conductos ileales (45,5%) y 12 neovejigas (54,5%), y DUIC en 21 (49%), 14 conductos ileales (66,7%) y 7 neovejigas (33,3%). Las características clínicas y preoperatorias fueron comparables entre grupos. La mediana de tiempo operatorio fue 360minutos (240-540) y de estancia hospitalaria 12 días (7-73). Treinta y cinco pacientes (81%) presentaron complicaciones postoperatorias, de las cuales 10 (23%) fueron mayores. No se encontraron diferencias en tiempo operatorio, complicaciones perioperatorias, estadificación patológica, márgenes y número de ganglios extirpados entre DUEC y DUIC. Los pacientes sometidos a DUEC presentaron mayor tasa de estenosis uretero-ileal en comparación con la DUIC (45,5% vs. 14,3%, p = 0,026). En las neovejigas la DUEC presentó mayor tasa de estenosis uretroneovesical que la DUIC (33% vs. 0%, p = 0,044). Conclusiones: La CRAR con derivación urinaria intracorpórea ofrece resultados perioperatorios y complicaciones comparables a la extracorpórea. La derivación intracorpórea podría reducir el riesgo de desarrollar estenosis ureteroileal y uretroneovesical

Objectives: To compare perioperative outcomes and complications of robot assisted radical cystectomy (RARC) with extracorporeal (ECUD) vs. intracorporeal urinary diversion (ICUD) for bladder cancer. Material and methods: Retrospective revision of 43 patients who underwent RARC for bladder cancer between 2015 and 2018 with at least 3 months of follow-up. The analysis included the initial series of RARC performed by one surgeon with extensive experience in open radical cystectomy. Results: Forty-three patients, 40 men (93%) and 3 women (7%), with a median age of 65 years (44-83) and mean follow-up of 27.7 months (±20.1) underwent RARC. A ECUD was performed in 22 cases (51%), of whom 10 were ileal conduits (45.5%) and 12 neobladders (54.5), and ICUD in 21 cases (49%), of whom 14 were ileal conduits (66.7%) and 7 neobladders (33.3%). Clinical and preoperative characteristics were similar in both groups. The median operative time was 360 min (240-540) and length of hospital stay was 12 days (7-73). Thirty-five patients (81%) had postoperative complications, of whom 10 (23%) were major. Operative time, peroperative complications, pathological stage, positive margins, and number of lymph nodes removed did not significantly differ among groups. Patients who underwent ECUD had a higher rate of uretero-ileal strictures than those with ICUD (45.5% vs. 14.3%, p = 0.026). Among the neobladders, the ECUD developed a higher rate of urethro-neobladder stricture than the ICUD (33% vs. 0%, p = 0.044). Conclusions: RARC with ICUD achieved peroperative outcomes and complication rates comparable than those with ECUD. The ICUD could reduce the risk of developing uretero-ileal and urethro-neobladder strictures

Comparison of perioperative outcomes and complications of robot assisted radical cystectomy with extracorporeal vs intracorporeal urinary diversion. / Comparación de los resultados perioperatorios de la cistectomía radical asistida por robot con derivación urinaria extracorpórea vs. intracorpórea.

OBJECTIVES: To compare perioperative outcomes and complications of robot assisted radical cystectomy (RARC) with extracorporeal (ECUD) vs. intracorporeal urinary diversion (ICUD) for bladder cancer. MATERIAL AND METHODS: Retrospective revision of 43 patients who underwent RARC for bladder cancer between 2015-2018 with at least 3 months of follow-up. The analysis included the initial series of RARC performed by one surgeon with extensive experience in open radical cystectomy. RESULTS: Forty-three patients, 40 men (93%) and 3 women (7%), with a median age of 65 years (44-83) and mean follow-up of 27.7 months (±20.1) underwent RARC. A ECUD was performed in 22 cases (51%), of whom 10 were ileal conduits (45.5%) and 12 neobladders (54.5), and ICUD in 21 cases (49%), of whom 14 were ileal conduits (66.7%) and 7 neobladders (33.3%). Clinical and preoperative characteristics were similar in both groups. The median operative time was 360 minutes (240-540) and length of hospital stay was 12 days (7-73). Thirty-five patients (81%) had postoperative complications, of whom 10 (23%) were major. Operative time, peroperative complications, pathological stage, positive margins, and number of lymph nodes removed did not significantly differ among groups. Patients who underwent ECUD had a higher rate of uretero-ileal strictures than those with ICUD (45.5% vs. 14.3%, P=.026). Among the neobladders, the ECUD developed a higher rate of urethro-neobladder stricture than the ICUD (33% vs. 0%, P=.044). CONCLUSIONS: RARC with ICUD achieved peroperative outcomes and complication rates comparable than those with ECUD. The ICUD could reduce the risk of developing uretero-ileal and urethro-neobladder strictures.

Estado actual de la ingeniería tisular aplicada a la reconstrucción vesical en humanos / Current status of tissue engineering applied to bladder reconstruction in humans

Contexto y objetivo: La reconstrucción vesical es el procedimiento para sustituir o ampliar la vejiga, siendo el intestino el tejido utilizado en la práctica clínica habitual. Las complicaciones de su uso van desde las propias de una resección intestinal hasta las resultantes del contacto continuo de la orina con un tejido no preparado para ello. En este artículo se describen y clasifican los diferentes biomateriales y cultivos celulares utilizados en la ingeniería tisular vesical y se revisan los estudios realizados en humanos. Adquisición de la evidencia: Se ha realizado una revisión de la literatura publicada en la base Pubmed entre 1950 y 2017, siguiendo los principios de la declaración PRISMA. Síntesis de la evidencia: Se han realizado múltiples estudios in vitro y en modelo animal, pero solo se han realizado 18 experimentos en humanos, con un total de 169 pacientes. La pruebas actuales indican que utilizar una matriz acelular o bien un polímero sintético y adherirle in vitro células uroteliales y musculares lisas autógenas, o bien células madre, sería la aproximación más realista para realizar una reconstrucción vesical experimental. Conclusiones: La sustitución o ampliación vesical sin utilizar intestino continúa siendo hoy un reto, a pesar del progreso en la fabricación de biomateriales y del desarrollo de la terapia celular. Para plantear una traslación clínica efectiva será necesario en el futuro realizar estudios bien diseñados, con mayor número de pacientes y tiempo de seguimiento, además de estandarizar las pruebas funcionales de control

Context and objective: Bladder reconstruction is performed to replace or expand the bladder. The intestine is used in standard clinical practice for tissue in this procedure. The complications of bladder reconstruction range from those of intestinal resection to those resulting from the continuous contact of urine with tissue not prepared for this contact. In this article, we describe and classify the various biomaterials and cell cultures used in bladder tissue engineering and reviews the studies performed with humans. Acquisition of evidence: We conducted a review of literature published in the PubMed database between 1950 and 2017, following the principles of the PRISM declaration. Synthesis of the evidence: Numerous in vitro and animal model studies have been conducted, but only 18 experiments have been performed with humans, with a total of 169 patients. The current evidence suggests that an acellular matrix, a synthetic polymer with urothelial and autologous smooth muscle cells attached in vitro or stem cells would be the most practical approach for experimental bladder reconstruction. Conclusions: Bladder replacement or expansion without using intestinal tissue is still a challenge, despite progress in the manufacture of biomaterials and the development of cell therapy. Well-designed studies with large numbers of patients and long follow-up times are needed to establish an effective clinical translation and standardisation of the check-up functional tests

Current status of tissue engineering applied to bladder reconstruction in humans. / Estado actual de la ingeniería tisular aplicada a la reconstrucción vesical en humanos.

CONTEXT AND OBJECTIVE: Bladder reconstruction is performed to replace or expand the bladder. The intestine is used in standard clinical practice for tissue in this procedure. The complications of bladder reconstruction range from those of intestinal resection to those resulting from the continuous contact of urine with tissue not prepared for this contact. In this article, we describe and classify the various biomaterials and cell cultures used in bladder tissue engineering and reviews the studies performed with humans. ACQUISITION OF EVIDENCE: We conducted a review of literature published in the PubMed database between 1950 and 2017, following the principles of the PRISM declaration. SYNTHESIS OF THE EVIDENCE: Numerous in vitro and animal model studies have been conducted, but only 18 experiments have been performed with humans, with a total of 169 patients. The current evidence suggests that an acellular matrix, a synthetic polymer with urothelial and autologous smooth muscle cells attached in vitro or stem cells would be the most practical approach for experimental bladder reconstruction. CONCLUSIONS: Bladder replacement or expansion without using intestinal tissue is still a challenge, despite progress in the manufacture of biomaterials and the development of cell therapy. Well-designed studies with large numbers of patients and long follow-up times are needed to establish an effective clinical translation and standardisation of the check-up functional tests.

An antisense oligonucleotide targeting TGF-ß2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages.

BACKGROUND: The transforming growth factor (TGF)-ß pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-ß pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-ß isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-ß2. MATERIALS AND METHODS: We have studied the anticancer response to ISTH0047 using gymnotic delivery in tumor cell cultures and in in vivo preclinical orthotopic mouse models for primary tumors (breast and kidney tumors) and lung metastasis. RESULTS: We observed that ISTH0047 is able to significantly reduce TGF-ß2 mRNA and protein levels without altering the levels of TGF-ß1 and TGF-ß3. ISTH0047 prevented lung metastasis in syngeneic orthotopic renal cell carcinoma (RENCA) and breast cancer (4T1) tumor models. In addition, using an orthotopic xenograft model of a lung cancer cell line (CRL5807) that mainly expresses TGF-ß2, we observed that ISTH0047 had an important effect on the lung microenvironment inhibiting the growth of lung lesions. ISTH0047 treatment re-educated macrophages in the lung parenchyma to express the tumor-suppressive factor, CD86. CONCLUSION: Overall, our data point to TGF-ß2 as a therapeutic target and ISTH0047 as a novel anticancer drug to prevent lung metastasis by impacting on the tumor niche, in part, through the induction of CD86 in tumor-associated macrophages.

Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients.

BACKGROUND: Management of high-grade T1 (HGT1) bladder cancer represents a major challenge. We studied a treatment strategy according to substaging by depth of lamina propria invasion. METHODS: In this prospective observational cohort study, patients received initial transurethral resection (TUR), mitomycin-C, and BCG. Subjects with shallower lamina propria invasion (HGT1a) were followed without further surgery, whereas subjects with HGT1b received a second TUR. Association of clinical and histological features with outcomes (primary: progression; secondary: recurrence and cancer-specific survival) was assessed using Cox regression. RESULTS: Median age was 71 years; 89.5% were males, with 89 (44.5%) cases T1a and 111 (55.5%) T1b. At median follow-up of 71 months, disease progression was observed in 31 (15.5%) and in univariate analysis, substaging, carcinoma in situ, tumour size, and tumour pattern predicted progression. On multivariate analysis only substaging, associated carcinoma in situ, and tumour size remained significant for progression. CONCLUSIONS: In HGT1 bladder cancer, the strategy of performing a second TUR only in T1b cases results in a global low progression rate of 15.5%. Tumours deeply invading the lamina propria (HGT1b) showed a three-fold increase in risk of progression. Substaging should be routinely evaluated, with HGT1b cases being thoroughly evaluated for cystectomy. Inclusion in the TNM system should also be carefully considered.

Impacto de la supresión androgénica sobre el perfil lipídico y el riesgo aterogénico en pacientes con cáncer de próstata / Impact of Androgen Deprivation on the Lipid Profile and Atherogenic Risk in Prostate Cancer Patients

Objetivo: Analizar los cambios observados en el perfil lipídico y el riesgo aterogénico en pacientes con cáncer de próstata sometidos a supresión androgénica. Material y métodos: Los niveles séricos de lipoproteínas (colesterol total, colesterol HDL, colesterol LDL y triglicéridos) fueron determinados en 636 pacientes entre 2001 y 2008. De estos, 120 fueron tratados con bloqueo androgénico máximo y 177 fueron tratados únicamente con análogo de LHRH. El grupo control estaba formado por 339 pacientes sometidos a biopsia prostática (212 con cáncer de próstata y 127 sin cáncer de próstata). El riesgo aterogénico fue calculado según la fórmula de Castelli (colesterol total/HDL). Resultados: El riesgo aterogénico medio en el grupo control fue de 4,2 y de 4 en el grupo sometido a supresión androgénica (p>0,05). El riesgo aterogénico medio en los pacientes sometidos a monoterapia con análogos de LHRH fue de 4,1, mientras que en los pacientes en tratamiento con bloqueo androgénico máximo fue de 3,9 (p=0,02). No se observaron diferencias significativas del valor del riesgo aterogénico en función de la duración del tratamiento. El análisis multivariante confirmó que la modalidad de tratamiento fue la única variable significativa respecto al riesgo aterogénico. Conclusiones: Este estudio demuestra que la supresión androgénica no incrementa el riesgo aterogénico en pacientes con cáncer de próstata. Este riesgo tampoco se incrementa a lo largo del tratamiento. La asociación de la bicalutamida al análogo de LHRH parece ejercer un efecto protector sobre el riesgo aterogénico (AU)

Objective: This study has aimed to analyze the changes observed in the lipid profile and atherogenic risk in prostate cancer patients subjected to androgen deprivation. Material and methods: Between 2001 and 2008, serum lipoproteins (total cholesterol, HDL, LDL and triglycerides) were determined in 636 patients. Of these, 129 were treated with maximum androgen blockade and 177 patients were only treated with LHRH analogue. The control group was formed by 339 subjected to prostate biopsy (212 with prostate cancer and 127 without prostate cancer). The atherogenic risk was calculated using the Castelli formula (total cholesterol/HDL). Results: Mean atherogenic risk was 4.2 in the control group and 4 in the group of patients subjected to androgenic deprivation, p>0.05. The mean atherogenic risk in those subjected to monotherapy with LHRH analogues was 4.1 while it was 3.9 in patients subjected to maximal androgen blockade, p=0.02. We did not found significant differences for atherogenic risk according to length of treatment, p>0.05. The multivariate analysis confirmed that the treatment modality was the only significant variable influencing atherogenic risk. Conclusions: This study demonstrates that continuous androgen deprivation does not increase atherogenic risk in patients with prostate cancer. This risk also did not increase during the treatment. The association of bicalutamide to the LHRH analogue seems to have a protective effect on atherogenic risk (AU)

[Impact of androgen deprivation on the lipid profile and atherogenic risk in prostate cancer patients]. / Impacto de la supresión androgénica sobre el perfil lipídico y el riesgo aterogénico en pacientes con cáncer de próstata.

OBJECTIVE: This study has aimed to analyze the changes observed in the lipid profile and atherogenic risk in prostate cancer patients subjected to androgen deprivation. MATERIAL AND METHODS: Between 2001 and 2008, serum lipoproteins (total cholesterol, HDL, LDL and triglycerides) were determined in 636 patients. Of these, 129 were treated with maximum androgen blockade and 177 patients were only treated with LHRH analogue. The control group was formed by 339 subjected to prostate biopsy (212 with prostate cancer and 127 without prostate cancer). The atherogenic risk was calculated using the Castelli formula (total cholesterol/HDL). RESULTS: Mean atherogenic risk was 4.2 in the control group and 4 in the group of patients subjected to androgenic deprivation, p>0.05. The mean atherogenic risk in those subjected to monotherapy with LHRH analogues was 4.1 while it was 3.9 in patients subjected to maximal androgen blockade, p=0.02. We did not found significant differences for atherogenic risk according to length of treatment, p>0.05. The multivariate analysis confirmed that the treatment modality was the only significant variable influencing atherogenic risk. CONCLUSIONS: This study demonstrates that continuous androgen deprivation does not increase atherogenic risk in patients with prostate cancer. This risk also did not increase during the treatment. The association of bicalutamide to the LHRH analogue seems to have a protective effect on atherogenic risk.

[Benign retroperitoneal schwannoma, laparoscopic ressection]. / Schwanoma retroperitoneal benigno, exéresis por laparoscopia.

Schwannomas are tumors rarely localized in the retroperitoneum, generally appear in craneal as well as periferic nerves. Seldom cases the diagnosis is preoperatively made just because imaging is very poor in this field. MRI is proven to be the diagnostic method. Radical surgical ressection is standarized treatment. We document a case of a benign retroperitoneal schwannoma where we explain the laparoscopic ressection of this kind of tumors for first time.

Schwanoma retroperitoneal benigno, exéresis por laparoscopia / Benigne retroperitoneal schwannoma, laparoscopic ressection

Los Schwanomas son tumores raramente localizados en el retroperitoneo, ya que habitualmente se encuentran en nervios craneales o periféricos. Raramente se diagnostican preoperatoriamente ya que ninguna de las técnicas de imagen es capaz de determinarlos con certeza. La RMN parece la prueba de elección. La exéresis quirúrgica completa es el tratamiento estándar. El caso que presentamos corresponde aun schwanoma retroperitoneal benigno como hallazgo a partir de dolor lumbar, en el describimos por primera vez la resección laparoscópica de este tipo de tumors (AU)

Schwannomas are tumors rarely localized in the retroperitoneum, generally appear in craneal as well as periferic nerves. Seldom cases the diagnosis is preoperatively made just because imaging is very poor in this field. MRI is proven to be the diagnostic method. Radical surgical ressection is standarized treatment. We document a case of a benign retroperitoneal schwannoma where we explain the laparoscopic resection of this kind of tumors for first time (AU)

Carcinoma urotelial de vejiga estadio T1: subestadiaje, patrones morfológicos de invasión y su significado pronóstico / Bladder urothelial carcinoma stage T1: substaging, invasion morphological patterns and its prognosis significance

Desde 1990 en que se publicaron las primeras series sobre subestadiaje, han aparecido numerosas publicaciones sobre el subnivel de invasión de los carcinomas de alto grado T1. La invasión profunda conlleva un elevado riesgo de progresión (alrededor del 30-35% de casos progresan) frente a los casos de invasión superficial por encima de la muscularis mucosae, en los que la progresión se encuentra alrededor del 10%, por lo que para la mayoría de autores vale la pena tener en cuenta los subT1, en el manejo del paciente. En esta revisión se presentan las series más exhaustivas que han valorado el subestadiaje y se valoran los diferentes métodos de efectuar esta estadificación teniendo en cuenta la dificultad inherente a las muestras que proceden de resección transuretral (RTU)

Since 1990 when the first series on substaging were published, they have published numerous publications on the invasion sublevel of high degree T1 carcinomas. The deep invasion entails a high risk of progression (around 30-35% of cases progress) as opposed to the cases of superficial invasion over “muscularis mucosae”, in which the progression is around 10%, reason why most authors consider subT1, in patient management. In this revision the more exhaustive series that have evaluated substaging are shown and also the different methods to carry out this staging considering the inherent difficulty to the samples that come from transurethral resection (RTU)

[Bladder urothelial carcinoma stage T1: substaging, invasion morphological patterns and its prognosis significance]. / Carcinoma urotelial de vejiga estadio T1: subestadiaje, patrones morfológicos de invasión y su significado pronóstico.

Since 1990 when the first series on substaging were published, they have published numerous publications on the invasion sublevel of high degree T1 carcinomas. The deep invasion entails a high risk of progression (around 30-35% of cases progress) as opposed to the cases of superficial invasion over "muscularis mucosae", in which the progression is around 10%, reason why most authors consider subT1, in patient management. In this revision the more exhaustive series that have evaluated substaging are shown and also the different methods to carry out this staging considering the inherent difficulty to the samples that come from transurethral resection (RTU).

Correlation between the biopsies in marginal donor kidneys for transplantation: is it necessary to biopsy both kidneys?

OBJECTIVES: The objective of this study was to analyze the correlation between histological findings in both transplanted kidneys from marginal donors. METHODS: We retrospectively reviewed the histological information on 92 kidneys obtained between January 2001 and January 2004, corresponding to 46 marginal donors. Criteria for biopsy were age greater than 55 years, hypertension, diabetes, and proteinuria. Scores were established by the pathologist including glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. The score for each lesion was classified as 0 if absent; 1 if <20%; 2 if >20% and <50%; and 3 if >50%. Finally, we defined an index of renal severity damage (RSD) in order to classify the kidneys for single transplantation (0), double transplantation (1), and unsuitable for transplantation (2). RESULTS: Of the kidneys studied, 82.6% of both kidneys showed similar degrees of glomerulosclerosis (<20% in 71.7% and >20% in 10.9%), while 17.4% showed discrepancies (> vs <20%; P=.008). On the other hand, RSD correlated in 82.6% of both kidneys (in 69.6% RSD=0; in 8.7% RSD=1; and in 4.3% RSD=2), while 17.4% showed discrepancies (P=.001). In one case (2.2%), a great discrepancy was observed; one kidney was valid for single transplantation, and the other one not valid for any transplantation, single or double. CONCLUSIONS: This study demonstrated a correlation between the biopsy findings in both kidneys in 82.6% of marginal organ donors. However, in 17.4% of cases we observed discrepancies. The degree of glomerulosclerosis seemed to be a powerful parameter to define renal severity damage. According to these results we would recommend biopsy of both kidneys.

Urinary retention secondary to presacral myelolipoma; first reported case diagnosed by prostate TUR and requiring a cystectomy.

Obstructive voiding symptoms may exceptionally be caused by extrinsic compression. We herein present a singular case of a 68-year-old male that presented with urinary retention and underwent prostate trans-urethral resection (TUR) with histology showing benign prostatic hyperplasia admixed with large amounts of myelolipoma tissue. To the best of our knowledge this is the first reported presacral myelolipoma diagnosed at prostate trans-urethral resection (TUR). Computed tomography revealed a 13 x 9 cm presacral mass displacing the rectum. Even though myelolipomas are regarded as benign, this case behaved aggressively since compressive effect evolved to severe constipation and eventually required a cystectomy.