Different outcomes among patients with intermediate-risk metastastic renal cell carcinoma treated with first-line tyrosine-kinase inhibitors.

INTRODUCTION: Systemic therapy of patients with metastatic renal cell carcinoma (mRCC) has improved in the past years, with the advent of new immunotherapy-based combinations as a standard treatment option for first-line therapy. Nevertheless, particularly in good-risk patients by IMDC criteria, tyrosine-kinase inhibitors (TKI) may remain as an option for some patients. We reviewed our experience with TKI as first-line therapy for mRCC patients, trying to identify subgroups of patients that may still benefit from this strategy. MATERIAL AND METHODS: All patients with mRCC treated with first-line TKI, and adequate follow-up, in University Hospital La Paz (Madrid, Spain) between 2007 and 2020 were analyzed. Patients treated inside a clinical trial were excluded from this analysis. RESULTS: A total of 90 patients treated with first-line TKI were included. Regarding IMDC criteria, 33 patients (36.7%) were good-risk, 41 patients (45.5%) intermediate-risk, and 16 patients (17.8%) poor-risk. With a median follow-up of 49 months, the median overall survival (OS) for good, intermediate, and poor-risk patients was 54, 24, and 16 months (p = 0.004). When intermediate-risk was divided into patients with 1 or 2 risk factors, differences in OS were also statistically significant: patients with 1 risk factor had a median OS of 33 months, while patients with 2 risk factors had a median OS of 16 months, the same as poor-risk patients (p = 0.003). In the multivariate analysis, trying to find out which of the IMDC factors had a more remarkable weight in the prognosis of the patients, both ECOG and hemoglobin levels by themselves were significantly associated with OS. CONCLUSION: In our group of patients, survival outcomes were different among patients with intermediate-risk with 1 or 2 risk factors by IMDC criteria. These could help select patients that may benefit from first-line treatment with a TKI, particularly in settings with difficult access to novel therapies, such as immunotherapy-based combinations.

[Laser in prostate cancer. Applicability.] / Láser en cáncer de próstata. Aplicaciones.

OBJECTIVES: In recent years, there has been a rise concerning the research and development of focal prostate cancer therapies as a consequence of the high percentage of low-risk and localized prostate cancers. These focal therapies aim at preserving the gland in selected patients to avoid overtreatment. The application of lasers for focal ablation and photodynamic therapy has shown promising results in exchange for a minimal rate of adverse events compared to radical treatments. MATERIAL AND METHODS: An extensive review of the available literature on focal laser treatments for localized prostate cancer was conducted. A search in PubMed and Embase was carried out by the following keywords: "Localised prostate cancer", "Low-risk prostate cancer", "Focal therapy", "Magnetic Resonance in localized prostate cancer", "Focal laser ablation" , "Photodynamic therapy" and "TOOKAD". RESULTS: Photodynamic therapy with TOOKAD is the only focal therapy evaluated in a phase III clinical trial,showing a lower rate of progression and a longer time to progression compared to active surveillance. Other studies carried out have revealed a percentage up to 80% of negative biopsies 6 months after TOOKAD. Likewise, the quality of life of patients treated using focal laser ablation techniques and photodynamic therapy has been minimally altered, as most adverse effects have been shown to be mild and transient, with dysuria and hematuria being the most frequent. CONCLUSIONS: Despite the fact that focal therapies are still not recommended outside the context of clinical trials and the lack of comparative studies between the different techniques, laser focal therapies seem to havea future within the new approaches for localized prostate cancer.

OBJETIVO: En los últimos años, se ha visto un auge en la investigación y el desarrollo de las terapias focales del cáncer de próstata como consecuencia del alto porcentaje de cánceres localizados y de bajo riesgo diagnosticados. Estas terapias focales tienen como objetivo la preservación de la glándula en pacientes seleccionados para evitar un sobretratamiento. La aplicación de los láseres para la ablación focal y la terapia fotodinámica ha demostrado resultados prometedores a cambio de una mínima tasa de complicaciones comparado con los tratamientos radicales clásicos.MATERIAL Y MÉTODOS: Se realizó una revisión extensa de la literatura disponible sobre tratamientos focales con láser para el cáncer de próstata localizado. Se llevó a cabo una búsqueda bibliográfica en PubMed y Embase incluyendo las siguientes palabras clave: "Localised prostate cancer", "Low-risk prostate cancer", "Focaltherapy", "Magnetic Resonance in localised prostate cancer", "Focal laser ablation", "Photodynamic therapy" y "TOOKAD". RESULTADOS: La terapia fotodinámica con TOOKAD es la única terapia focal evaluada en un ensayo clínico fase III, habiendo demostrado una menor tasa de progresión y un mayor tiempo hasta la progresión comparado con la vigilancia activa. En otros de los estudios llevados a cabo, se ha objetivado un porcentaje de biopsias negativas a los 6 meses del tratamiento de hasta el 80%. Igualmente, la calidad de vida de los pacientes tratados mediante las técnicas de ablación focal con láser y terapia fotodinámica se ha visto mínimamente alterada al haberse demostrado que la mayoría de los efectos adversos son leves y transitorios, siendo los más frecuentes la disuria y la hematuria. CONCLUSIONES: A pesar de que las terapias focales siguen sin ser recomendadas fuera del contexto de los ensayos clínicos y de la falta de estudios comparativos entre las diferentes técnicas, las terapias focales con láser parecen tener un futuro dentro de los nuevos abordajes para el cáncer de próstata localizado.

Retroperitoneal fibrosis: A literature review. / Fibrosis retroperitoneal. Revisión de la literatura.

OBJECTIVES: Retroperitoneal fibrosis (RPF) is an uncommon disease due an inflammatory condition and deposit of fibrotic tissue that involves the retroperitoneal area over the lower four lumbar vertebrae. Very few epidemiologic studies exist that accurately characterize the incidence and prevalence of the disease. MATERIALS AND METHODS: A review of the English language literature was performed using the MEDLINE combining the keywords: "retroperitoneal fibrosis", "Ormond´ disease", "IG4 related disease". Additionally, hand search of bibliographies of included studies and previous reviews was also performed to include additional information. RESULTS: RPF develops insidiously, because the initial symptoms are non-specific. Pain is the most common presenting symptom. Various radiological diagnostic methods are used in the diagnosis of retroperitoneal fibrosis. Contrast-enhanced computerized tomography (CT) is a useful method for diagnosing retroperitoneal pathologies. Magnetic resonance imaging (MRI) is an important radiological method especially in the diagnosis of fibrotic tissue and in the examination of the retroperitoneal organ relation with fibrous tissue. Nuclear imaging is also a method used in renal function evaluation and patient follow-up. Various medical and surgical treatments would be used in the treatment of retroperitoneal fibrosis. In general, immunosuppressive agents such as corticosteroids, tamoxifen, azothiopurine, cyclophosphamide, cyclosporine, progesterone, mycophenolate mofetil are used in medical treatment. Surgical treatment methods are recommended in cases where medical treatment is not efficient. CONCLUSION: Unfortunately, despite a recent surge in the number of publications on this topic, a few progress has been made in our understanding of the classification, pathophysiology, and, most importantly, the most appropriate treatment for this disease.

OBJETIVO: La fibrosis retroperitoneal (FPR) es una enfermedad poco común debido a una afección inflamatoria y depósito de tejido fibrótico que afecta el área retroperitoneal sobre las cuatro vértebras lumbares inferiores. Existen muy pocos estudios epidemiológicos que caractericen con precisión la incidencia y la prevalencia de la enfermedad. El objetivo de esta revisión es ofrecer una visión general de las características clínicas, los métodos de diagnóstico, los tratamientos y su eficacia en los pacientes con FPR.MATERIALES Y MÉTODOS: Se realizó una revisión de la literatura en idioma inglés utilizando las bases de datos MEDLINE, combinando las palabras clave: "fibrosis retroperitoneal", "enfermedad de Ormond", "enfermedad relacionada con IG4". Además, la búsqueda manual de bibliografías de estudios incluidos y revisiones anteriores también se realizó para incluir información adicional. RESULTADOS: La FRP se desarrolla insidiosamente, ya que los síntomas iniciales son inespecíficos. El dolor es el síntoma de presentación más común. Varios métodos de diagnóstico radiológico se utilizan en el diagnóstico de la fibrosis retroperitoneal. La tomografía computarizada (TC) con contraste es un método útil para diagnosticar patologías retroperitoneales. La resonancia magnética (RM) es un método radiológico importante, especialmente en el diagnóstico de tejido fibrótico y en la valoración de la relación del órgano retroperitoneal con el tejido fibroso. La imagen nuclear también es un método utilizado en la evaluación de la función renal y el seguimiento de los pacientes. Varios tratamientos médicos y quirúrgicos se usarían en el tratamiento de la fibrosis retroperitoneal. En general, los agentes inmunosupresores como los corticosteroides, el tamoxifeno, la azatioprina, la ciclofosfamida, la ciclosporina, la progesterona y el micofenolato mofetilo se usan en el tratamiento médico. Los métodos de tratamiento quirúrgico se recomiendan en casos donde el tratamiento médico no es eficiente.CONCLUSIÓN: Desafortunadamente, a pesar de un aumento reciente en el número de publicaciones sobre este tema, se ha avanzado poco en nuestra comprensión de la clasificación, la fisiopatología y, lo que es más importante, el tratamiento más adecuado para esta enfermedad.

Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project).

PURPOSE: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor. PATIENTS AND METHODS: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM). RESULTS: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis. CONCLUSIONS: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Ureteral injury during abdominal and pelvic surgery: immediate versus deferred repair.

INTRODUCTION: The incidence of ureteral damage during abdominal surgery is <1%. Repair of these lesions can be performed immediately when the injury is detected or deferred when it has been missed. MATERIAL AND METHODS: We retrospectively reviewed ureteral injuries that required surgical repair and were made during gynaecological and general surgery procedures between the years 2004 and 2016. We compared the clinical and functional outcomes between immediate and deferred repair. RESULTS: We registered 84 lesions after 4000 abdominal procedures (2.1%). A total of 20 injuries were noted during general surgery interventions (24%) and 64 during gynaecological procedures (76%). The approach was laparoscopic in 66 of these cases and open in the other 18. Mean time of follow-up was 24 months. Immediate repair was accomplished in 35 cases (41%) and deferred in 49 (59%), with a median time to repair of 5.7 months. The laparoscopic approach was more frequent in deferred repairs (76% vs. 16%), while the open approach was more common in immediate repairs (54% vs. 40%). Procedures used for ureteral repair included 62 ureteral reimplantations using a psoas hitch technique, 8 end-to-end ureteral anastomoses, 6 ureterorraphies and 6 ureteral catheterisations. Two nephrectomies were also performed. Success rates and complications were similar for both immediate and deferred procedures (68% vs. 73% and 26% vs. 23% respectively, both p >0.05). CONCLUSIONS: The occurrence of ureteral injury during abdominal surgery is low. Immediate repair is preferred when feasible, but delayed recognition of the injury is more common. We found no difference between immediate and deferred repair in terms of success rates.

[Evolution of radical prostatectomy in the Autonomous Community of Madrid.] / Evolución de la prostatectomía radical en el tratamiento del cáncer de próstata en la Comunidad de Madrid.

OBJECTIVES: To analyze the implantation of laparoscopic radical prostatectomy (LRP) in the Public Health System in the Autonomous Community of Madrid (CAM) and to investigate the different results between laparoscopic and open radical prostatectomy. METHODS: We performed a retrospective analysis over a database containing data from 25 hospitals in CAM. We chose 8225 patients treated by radical prostatectomy (open or laparoscopic). Data were collected using a questionnaire including hospital, length of stay, readmissions and mortality. Values are shown in number, percentage and rank. Statistical significance is shown with p<0.05. RESULTS: Increase of LRP is shown in the period of study, representing only a 11.9% of the radical prostatectomies in 2004 and reaching 56.8% in 2012. There were no significant statistical differences in age, severity or readmissions when stratified by hospital or by technique. We found a 1.05 days increase in length of stay in long-standing hospitals compared to newer hospitals. We also found a decrease in length of stay in LRP group compared to open retropubic prostatectomy (ORP): 4.84 days vs 6.79 days, (p<0.001). CONCLUSIONS: RP is consolidated as a therapy in CAM. LRP has been successfully implemented in CAM, offering advantage over ORP in terms of hospital stay. We observed statistically significant difference in length of stay in advantage of recent hospitals regarding longstanding.

[Oncological results in high grade prostate cancer treated surgically]. / Resultados oncológicos en el cáncer de próstata de alto riesgo tratado quirúrgicamente.

OBJECTIVES: Prostate cancer is considered a tumour with a long natural history. However, its high-risk variants exhibit variable behaviour. We analyse the factors that affect BR and CSS (multivariate, Kaplan Meier). METHODS: From 1997 to 2013, 657 patients were operated of a high-grade prostate cancer (pT2b 7.2%, pT3a 73%, pT3b 18.3%, pT4 1.5%). Gleason score was ≥8 in 23% of cases. Percentage of PSMs was 46.1%. Mean follow-up was 113 months (24-192). RESULTS: BR occurred in 36.5%. Patients with Gleason score <8, 31.7% had BR, Gleason ≥8 had BR in 48% (p<0.05). PSMs recurrence occurred in 48.9%, whereas 26.1% in NSM (p<0.05). If lymphadenectomy, BR occurred in 48.7%, if not 30.9% (p<0,05). In multivariate analysis, stage, Gleason≥8 and PSMs were independent factors for BR. Treatment of BR was 36.5% radiotherapy, 24.1% HT, and 21.2% both simultaneously. Active surveillance was performed in 13.3%. Disease progression (biochemical or radiological) occurred in 23.5%. CSS was 98.93%, pT4 was the stage with the greatest mortality (10%), followed by pT3b (3.4%), p<0.05. Patients with a Gleason score ≥8 accounted for 71% CSM (p<0,05). PSMs and lymphadenectomy didn't have repercussions for survival. In multivariate analysis, Gleason≥8 was independent factor for CSM. CONCLUSIONS: Radical prostatectomy plays an important role in multi-modal approach with good oncological control at medium follow up. Gleason score ≥8 was the factor with the greatest effect on CSM. Lymphadenectomy didn't affect CSS.

Biochemical recurrence risk factors in surgically treated high and very high-risk prostate tumors.

INTRODUCTION: High and very high-risk prostate cancers are tumors that display great variation in their progression, making their behaviour and consequent prognosis difficult to predict. We analyse preoperative and postoperative risk factors that could influence biochemical recurrence of these tumors. MATERIAL AND METHODS: We carried out univariate and multivariate analyses in an attempt to establish statistically significant preoperative (age, rectal examination, PSA, biopsy Gleason score, uni/bilateral tumor, affected cylinder percentage) and postoperative (pT stage, pN lymph node affectation, Gleason score, positive surgical margins, percentage of tumor affectation, perineural infiltration) risk factors, as well as their relationship with biochemical recurrence (PSA >0.2 ng/mL). RESULTS: We analysed 276 patients with high and very high-risk prostate cancer that were treated with laparoscopic radical prostatectomy (LRP) between 2003-2007, with a mean follow-up of 84 months. Incidence of biochemical recurrence is 37.3%. Preoperative factors with the greatest impact on recurrence are suspicious rectal exam (OR 2.2) and the bilateralism of the tumor in the biopsy (OR 1.8). Among the postoperative factors, the presence of a LRP positive surgical margins (OR 3.4) showed the greatest impact, followed by the first grade of the Gleason score (OR 3.3). CONCLUSIONS: The factor with the greatest influence on biochemical recurrence when it comes to surgery and high and very high-risk prostate cancer is the presence of a positive margin, followed by the Gleason score. Preoperative factors (PSA, biopsy Gleason score, rectal examination, number of affected cylinders) offered no guidance concerning the incidence of BCR.

Laparoscopy in elderly patients.

OBJECTIVES: Aging of the current population is an evident fact, and the surgical treatment of these patients is something we find in our daily practice. In this sense, all doubts that may arise when it comes to carrying out this technique in patients with important comorbidities appear to be cleared, as even patients with prior respiratory or heart disease benefit from the laparoscopic approach. METHODS: An analysis was carried out on a total of 99 patients over 70 years of age who underwent renal laparoscopic surgery, compared, on one hand, to 173 patients under 70 years of age undergoing the same procedure, and on the other, to 95 patients over 70 years of age who underwent open surgery We collected and compared all complications described intraoperatively and in the immediate postoperative period, as well as hospital stay. RESULTS: Patients over 70 years of age have a greater comorbidity compared to patients under 70 (ICH 1.46 vs. 0.89 p<0.05), but there are no statistical differences in terms of intraoperative or postoperative complications, or mean hospital stay. When compared to patients over 70 years of age with a similar comorbidity who underwent classic surgery, (ICH 1.46 vs. 1.45), we found a lower rate of complications (12.2 vs. 28.4% transfusion, 1.4 vs. 4.0% fever, p<0.05) and a shorter hospital stay (4.9 vs. 7.1%p<0.002). CONCLUSION: Patient age does not seem to have a determining effect on complications or on the postoperative period of kidney disease when laparoscopy is used, which is why this method of treatment seems adequate in such cases.

Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery.

BACKGROUND: The occurrence of positive surgical margins (PSMs) after partial nephrectomy (PN) is rare, and little is known about their natural history. OBJECTIVE: To identify predictive factors of cancer recurrence and related death in patients having a PSM following PN. DESIGN, SETTING, AND PARTICIPANTS: Some 111 patients with a PSM were identified from a multicentre retrospective survey and were compared with 664 negative surgical margin (NSM) patients. A second cohort of NSM patients was created by matching NSM to PSM for indication, tumour size, and tumour grade. MEASUREMENTS: PSM and NSM patients were compared using student t tests and chi-square tests on independent samples. A Cox proportional hazards regression model was used to test the independent effects of clinical and pathologic variables on survival. RESULTS AND LIMITATIONS: Mean age at diagnosis was 61+/-12.5 yr. Mean tumour size was 3.5+/-2 cm. Imperative indications accounted for 39% (43 of 111) of the cases. Some 18 patients (16%) underwent a second surgery (partial or total nephrectomy). With a mean follow-up of 37 mo, 11 patients (10%) had recurrences and 12 patients (11%) died, including 6 patients (5.4%) who died of cancer progression. Some 91% (10 of 11) of the patients who had recurrences and 83% of the patients (10 of 12) who died belonged to the group with imperative surgical indications. Rates of recurrence-free survival, of cancer-specific survival, and of overall survival were the same among NSM patients and PSM patients. The multivariable Cox model showed that the two variables that could predict recurrence were the indication (p=0.017) and tumour location (p=0.02). No other variable, including PSM status, had any effect on recurrence. None of the studied parameters had any effect on the rate of cancer-specific survival. CONCLUSIONS: PSM status occurs more frequently in cases in which surgery is imperative and is associated with an increased risk of recurrence, but PSM status does not appear to influence cancer-specific survival. Additional follow-up is needed.

Testicular albuginea neurofibroma: findings at ultrasonography and magnetic resonance imaging with pathological correlation.

OBJECTIVES: To report the second case of solitary neurofibroma arising from the tunica albuginea in the literature and to show its imaging findings. METHODS/RESULTS: We present a case of neurofibroma arising from the tunica albuginea in an adult patient not affected by neurofibromatosis. We describe the ultrasonographic and magnetic resonance imaging (MRI) features and the histopathological characteristics along with a brief bibliographic review. CONCLUSION: MRI may be useful to characterize paratesticular lesions. Neurofibroma should be included in the differential diagnosis when MRI depicts a well-circunscribed tumour with high-signal intensity on T2 and marked enhancement after gadolinium administration.

Open and laparoscopic nephroureterectomy for urothelial tumors of the upper urinary tract: initial experience.

OBJECTIVE: Advances in urological laparoscopy have increased the oncological safety of this approach for managing upper urinary tract tumours, although the open surgical route remains the method of choice. This article describes our experience of the laparoscopic approach over the past four years compared to open surgery. MATERIALS AND METHODS: Between 1995 and 2009 a total of 95 nephroureterectomies were carried out to remove tumours: 70 by open surgery and 25 by laparoscopy. Lumbotomy with endoscopic detachment of the ureter was the most common approach in open surgery, while transperitoneal access was used for laparoscopy in all cases, with laparoscopic bladder cuff resection in most patients (56%). RESULTS: The mean procedure time for open nephroureterectomies was 205 min (130-300), with a mean blood loss of 525 ml (100-1,800) involving 17 (24.2%) transfusions. The mean hospital stay was 8.4 days (3-30). The mean procedure time for the laparoscopic nephroureterectomies was 189 min (120-270), with a mean blood loss of 130 ml (100-400) and 4 (16%) transfusions. The mean hospital stay was 4.5 (2-28) days. CONCLUSIONS: The patients who underwent the laparoscopic procedure had a lower transfusion rate and shorter hospital stay. Oncological control was similar for both approaches, although laparoscopy requires greater monitoring and a larger caseload.

In situ kidney insonation with microbubble contrast agents does not cause renal tissue damage in a porcine model.

OBJECTIVE: Knowledge and quantification of the microcirculation are very important for estimating the status of an organ. Real-time contrast-enhanced sonography assesses microvascular tissue perfusion. This technique has been proposed as innocuous; however, data from experimental animals (rats) have shown renal interstitial microhemorrhage after the procedure. Therefore, we developed a porcine model to explore potential renal damage that in situ exposure might cause. METHODS: Kidneys from 8 anesthetized pigs were surgically exposed. An ultrasound contrast agent (sulfur hexafluoride) was infused through the femoral vein in a continuous perfusion. Destructive ultrasonic flashes were applied with a high mechanical index over only 1 kidney (the contralateral kidney was used as a control). Blinded histologic and laboratory analyses were performed to reveal any lesions. RESULTS: Histologic analysis of the kidney samples showed no evidence of renal damage. Biochemical parameters that could represent renal tissue damage and hemoglobin levels did not change after the microbubble-ultrasound interaction. CONCLUSIONS: The ultrasound contrast agent-ultrasound interaction in anesthetized pig kidneys under the output level for the imaging visualization and microbubble destruction used did not cause tissue damage. Our results suggest that this procedure could be used in humans for regular analysis of the kidney microcirculation with minimal risk of tissue damage.

Human recombinant erythropoietin does not promote cancer growth in presence of functional receptors expressed in cancer cells.

Human recombinant erythropoietin (hrEPO) therapy might be associated with tumor progression and death. This effect has been suggested to be secondary to rhEPO binding to its receptor (EPOR) expressed on cancer cells. However, there are several concerns about EPOR functionality when expressed on cancer cells. In this paper we have provided evidence that EPOR expressed in cancer cells could be implicated in proliferation events because a transfection of EPOR siRNA to EPOR-expressing bladder cancer cells resulted in a marked reduction in cell growth. However, these cell lines do not grow in the presence of hrEPO. Furthermore, bladder cancer patients that expressed EPOR in tumor samples had a reduced survival in absence of rhEPO treatment. Therefore, EPOR is implicated in bladder cancer growth but this effect appears to be independent from rhEPO supplementation. Reports which suggest that rhEPO promotes cancer growth due to the expression of EPOR in cancer cells must be observed with caution since in the presence of functional EPOR rhEPO does not promote growth.