Patterns of relapse and treatment outcome after active surveillance or adjuvant carboplatin for stage I seminoma: a retrospective study of the Spanish Germ Cell Cancer Group

Purpose Active surveillance (AS) and adjuvant chemotherapy (AC) with carboplatin are valid alternatives for managing stage I seminoma, and most relapses can be cured with cisplatin-based chemotherapy. However, some reports suggest that AC may modify the classical pattern of recurrences. Methods We analyzed all relapses observed in a series of 879 patients with stage I seminoma included in 4 consecutive studies of the Spanish Germ Cell Cancer Group. After a median follow-up of 67 months, recurrences were detected in 56/467 (12%) low-risk cases on AS and 13/412 (3%) high-risk cases after AC (p < 0.001). The objective was to describe clinical features, treatment and outcome. Univariate comparisons were performed between both groups. Results No significant differences were found between relapses on AS and those after AC in terms of time to relapse (13 vs 17 months), size (26 vs 27 mm), location (retroperitoneum in 88% vs 85%), and method of detection (computed tomography in 77% vs 69%). Treatment consisted of chemotherapy (etoposide + cisplatin ± bleomycin) in 89% and 92%, respectively. Late relapses (after > 3 years) were seen in 11% vs 7.7% (p = NS) and second or successive recurrences in 1.8 vs 23% (p < 0.05). With a median follow-up of 130 moths, two patients died of seminoma-unrelated causes (AS group) and the rest are alive and disease-free. Conclusion In the setting of a risk-adapted treatment of stage I seminoma, the administration of two courses of AC in patients with tumor size > 4 cm and/or rete testis invasion is associated with a higher incidence of second recurrences but does not significantly modify the pattern of relapses or their outcome (AU)

Incidence and clinical pattern of contralateral synchronous and metachronous germ cell testicular cancer.

BACKGROUND: Incidence of a second testicular tumor is higher in patients diagnosed with testicular cancer than in the general population. As incidence of unilateral germ cell cancer is increasing worldwide and most of these patients are cured, a growing number of patients at risk of developing a contralateral testis cancer is expected. OBJECTIVE: To analyze clinical and histological characteristics, as well as the absolute and cumulative incidence of a second testicular cancer in a cohort of 3,834 patients diagnosed with germ cell testicular cancer between I/1994 and I/2018 in 18 referral hospitals of the Spanish Germ Cell Cancer Group. METHODS: Patients were treated according to stage and year of diagnoses. Contralateral testis biopsy was not routinely performed, according to European Association of Urology rules. Follow-up of the contra lateral testis consists of a physical exam only and an annual optional testicular ultrasound for 10 years. RESULTS: Median age of the patients included was 32 years (18-82). With a median follow-up of 61 months (0-240), 67/3,834 patients (1.74%) were diagnosed with a second testicular tumor. The second testicular tumor was synchronic (diagnosed within 6 months of the first orchiectomy) in 19 patients, and metachronous in 48. Pathology of the second tumor was reported as a seminomatous testis tumor in 47 patients and a nonseminomatous cancer in 20. Cumulative incidence of contralateral testicular cancer was 2% at 5 years, and 4% (IC 95% 3%-5%) at 14 years. Younger age was a risk factor for developing a second testicular tumor (P = 0.006), whereas chemotherapy reduced the risk for a metachronous testicular cancer (P = 0.046). Within our cohort, 6 families with testicular cancer aggregation (more than 2 tumors in the same family) were identified. CONCLUSIONS: Incidence of second testicular neoplasm in this cohort of 3,834 patients was similar to that which has been reported in other countries. Metachronous tumors and seminomas are more common. Follow-up of the contralateral testis is mandatory, as well as adequate information for patients to prevent a second neoplasm if feasible, and to detect and treat it as soon as possible.

Patterns of relapse and treatment outcome after active surveillance or adjuvant carboplatin for stage I seminoma: a retrospective study of the Spanish Germ Cell Cancer Group.

PURPOSE: Active surveillance (AS) and adjuvant chemotherapy (AC) with carboplatin are valid alternatives for managing stage I seminoma, and most relapses can be cured with cisplatin-based chemotherapy. However, some reports suggest that AC may modify the classical pattern of recurrences. METHODS: We analyzed all relapses observed in a series of 879 patients with stage I seminoma included in 4 consecutive studies of the Spanish Germ Cell Cancer Group. After a median follow-up of 67 months, recurrences were detected in 56/467 (12%) low-risk cases on AS and 13/412 (3%) high-risk cases after AC (p < 0.001). The objective was to describe clinical features, treatment and outcome. Univariate comparisons were performed between both groups. RESULTS: No significant differences were found between relapses on AS and those after AC in terms of time to relapse (13 vs 17 months), size (26 vs 27 mm), location (retroperitoneum in 88% vs 85%), and method of detection (computed tomography in 77% vs 69%). Treatment consisted of chemotherapy (etoposide + cisplatin ± bleomycin) in 89% and 92%, respectively. Late relapses (after > 3 years) were seen in 11% vs 7.7% (p = NS) and second or successive recurrences in 1.8 vs 23% (p < 0.05). With a median follow-up of 130 moths, two patients died of seminoma-unrelated causes (AS group) and the rest are alive and disease-free. CONCLUSION: In the setting of a risk-adapted treatment of stage I seminoma, the administration of two courses of AC in patients with tumor size > 4 cm and/or rete testis invasion is associated with a higher incidence of second recurrences but does not significantly modify the pattern of relapses or their outcome.

Treatment and Outcome of Patients with Stage IS Testicular Cancer: A Retrospective Study from the Spanish Germ Cell Cancer Group.

PURPOSE: Stage IS testicular cancer is defined by the persistence of elevated serum tumor markers, including α-fetoprotein and/or ß-human chorionic gonadotropin, after orchiectomy without radiological evidence of metastatic disease. Current treatment recommendations include cisplatin based chemotherapy up front but the recommendations are based on limited single center series. MATERIALS AND METHODS: We retrospectively analyzed clinical and pathological characteristics, and long-term outcomes in 110 patients uniformly treated with primary chemotherapy between 1994 and 2016. The primary objective was to evaluate long-term disease-free survival. We also explored factors associated with the need for additional treatment. RESULTS: The elevated prechemotherapy tumor markers were α-fetoprotein in 48% of cases, ß-human chorionic gonadotropin in 14%, and α-fetoprotein and ß-human chorionic gonadotropin in 38%. Median α-fetoprotein and ß-human chorionic gonadotropin values were 71 ng/ml and 80 mIU/ml, respectively. The IGCCCG (International Germ Cell Cancer Collaborative Group) prognostic classification was good in 94% of cases. Mixed nonseminomatous germ cell tumor was found in 78% of cases. Of the patients 103 achieved a complete response to chemotherapy. In 6 patients radiological signs of progressive disease developed during chemotherapy, while 8 experienced relapse after an initial complete response. At a median followup of 108 months 108 patients were alive and disease-free. Five and 10-year disease-free survival rates were 87% and 85%, respectively. The predominance of embryonal carcinoma in the primary tumor was the only factor associated with the probability of needing additional therapy. CONCLUSIONS: Stage IS testicular cancer is more commonly associated with elevated α-fetoprotein, an IGCCCG good prognosis and mixed nonseminomatous germ cell tumor. Treatment with cisplatin based chemotherapy leads to cure in most cases. However, a proportion of patients require the integration of additional therapies, including more frequently when embryonal carcinoma is not predominant.

SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018)

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents

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SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018).

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

Long-term toxicity of the treatment for germ cell-cancer. A review.

Testicular germ-cell cancer (GCC) is a curable disease. Stage I patients are mostly cured by surgery alone. For those with good prognosis advanced disease, radiotherapy in some patients with stage II Seminoma and chemotherapy for all other patients, are responsible for 95% of long-term survivors. Unfortunately, despite this high level of curability, overall survival has been reported lower for those patients receiving either radiotherapy or chemotherapy versus patients treated by surgery alone. Long-term survivors face a higher incidence of second neoplasms, and a higher risk of cardiovascular disease and metabolic syndrome than expected. Other non-life-threatening toxicities such as ototoxicity, neurotoxicity and fertility problems are common. This paper reviews the potential causes of the higher mortality among long-term survivors of testicular tumors, the incidence of them and some recommendations for the diagnoses and prevention of long-term sequelae in patients with GCC.

HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma.

BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. OBJECTIVE: To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. METHODS: This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan-Meier method was applied to measure progression-free survival (PFS) and overall survival. RESULTS: Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4-13.5 months), median overall survival was 21.8 months (95% CI: 14.7-29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI: 1.03-6.80, P=0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P=0.263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome. CONCLUSION: These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials.

Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

SEOM clinical guidelines for the management of germ cell testicular cancer (2016)

Testicular cancer represents the most common malignancy in males aged 15-34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3-4 courses of cisplatin based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease (AU)

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SEOM clinical guidelines for the management of germ cell testicular cancer (2016).

Testicular cancer represents the most common malignancy in males aged 15-34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3-4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.

New advances in genitourinary cancer: evidence gathered in 2014.

This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed.

¿Existe un límite para el abordaje laparoscópico de la masa residual retroperitoneal posquimioterapia? / Is there a limit for the laparoscopic approach of a retroperitoneal residual mass postchemotherapy?

Objetivos: La linfadenectomía de rescate en el cáncer de testículo es una cirugía compleja, con un elevado número de complicaciones. El abordaje laparoscópico parece ofrecer una recuperación más temprana y mejorar la calidad de vida respecto a la cirugía abierta. El objetivo de nuestro estudio es describir nuestra experiencia, y a partir de esta definir si existe algún límite (oncológico, anatómico o técnico) para el manejo laparoscópico. Material y métodos: Estudio retrospectivo de 15 pacientes sometidos a linfadenectomía retroperitoneal laparoscópica tras quimioterapia. Analizamos además de variables epidemiológicas y oncológicas el tiempo quirúrgico medio, las complicaciones intra y postoperatorias, la mediana de días de ingreso y el tiempo medio de seguimiento. Resultados: El tiempo quirúrgico medio fue de 294 min (180-240). Hubo 4 lesiones vasculares de grandes vasos, tratándose en todos los casos de masas retroperitoneales de gran volumen, diámetro > 7 cm. La tasa de complicaciones postoperatorias fue del 33%, solo un caso de Clavien > III. La estancia hospitalaria media fue de 5,38 días (2-9) y el seguimiento medio de los pacientes de 28,9 meses (1-79), no observándose recidiva en ningún caso. Conclusiones: El abordaje laparoscópico es una opción oncológicamente segura para el tratamiento de rescate del cáncer de testículo. La localización compleja de estas masas conlleva a que aparezcan complicaciones intraoperatorias graves. Hemos observado una clara relación entre las complicaciones vasculares y las masas de gran tamaño > 7 cm, por lo que creemos que sería conveniente establecer un límite de tamaño para el tratamiento laparoscópico

Objectives: Rescue lymphadenectomy for testicular cancer is a complex surgery, with a high number of complications. The laparoscopic approach appears to offer faster recovery and improved quality of life compared with open surgery. The aim of our study is to report on our experience and to define whether there is a limit (oncological, anatomical or technical) for laparoscopic management. Material and methods: A retrospective study was conducted of 15 patients who underwent laparoscopic retroperitoneal lymphadenectomy after chemotherapy. In addition to epidemiological and oncologic variables, we analyzed the mean surgical time, intraoperative and postoperative complications, the mean hospital stay and the mean follow-up time. Results: The mean surgical time was 294 minutes (range, 180-240). There were 4 large-vessel vascular lesions, all of which were large-volume retroperitoneal masses, with diameters > 7 cm. The rate of postoperative complications was 33%; there was only 1 case of Clavien >III. The mean hospital stay was 5.38 days (range, 2-9), and the mean patient follow-up was 28.9 months (range, 1-79). There was no recurrence in any of the cases. Conclusions: The laparoscopic approach is an oncologically safe option for the rescue treatment of testicular cancer. The complex location of these masses entails the onset of severe intraoperative complications. We have observed a clear relationship between vascular complications and large masses (> 7 cm). We therefore believe that it would be appropriate to establish a limit on the size for laparoscopic treatment

Is there a limit for the laparoscopic approach of a retroperitoneal residual mass postchemotherapy?

OBJECTIVES: Rescue lymphadenectomy for testicular cancer is a complex surgery, with a high number of complications. The laparoscopic approach appears to offer faster recovery and improved quality of life compared with open surgery. The aim of our study is to report on our experience and to define whether there is a limit (oncological, anatomical or technical) for laparoscopic management. MATERIAL AND METHODS: A retrospective study was conducted of 15 patients who underwent laparoscopic retroperitoneal lymphadenectomy after chemotherapy. In addition to epidemiological and oncologic variables, we analyzed the mean surgical time, intraoperative and postoperative complications, the mean hospital stay and the mean follow-up time. RESULTS: The mean surgical time was 294 minutes (range, 180-240). There were 4 large-vessel vascular lesions, all of which were large-volume retroperitoneal masses, with diameters >7 cm. The rate of postoperative complications was 33%; there was only 1 case of Clavien >III. The mean hospital stay was 5.38 days (range, 2-9), and the mean patient follow-up was 28.9 months (range, 1-79). There was no recurrence in any of the cases. CONCLUSIONS: The laparoscopic approach is an oncologically safe option for the rescue treatment of testicular cancer. The complex location of these masses entails the onset of severe intraoperative complications. We have observed a clear relationship between vascular complications and large masses (>7 cm). We therefore believe that it would be appropriate to establish a limit on the size for laparoscopic treatment.

Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive, risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG).

BACKGROUND: We aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both groups. PATIENTS AND METHODS: From 1994 to 2008, 744 patients were included in three consecutive, prospective risk-adapted studies by the Spanish Germ Cell Cancer Group. Low-risk patients were managed by surveillance and high-risk patients were given two courses of adjuvant carboplatin. Relapses were treated mainly with chemotherapy. Patient age, tumor size, histological variant, pT staging, rete testis invasion, and preoperative serum BHCG levels were assessed for prediction of disease-free survival (DFS). RESULTS: After a median follow-up of 80 months, 63 patients (11.1%) have relapsed: 51/396 (14.8%) on surveillance and 12/348 (3.2%) following adjuvant carboplatin. Actuarial overall 5-year DFS was 92.3% (88.3% for surveillance versus 96.8% for chemotherapy, P = 0.0001). Median time to relapse was 14 months. Most recurrences were located at retroperitoneum (86%), with a median tumor size of 26 mm. All patients were rendered disease-free with chemotherapy (92%), radiotherapy (5%), or surgery followed by chemotherapy (3%). A nomogram was developed from surveillance patients that includes two independent, predictive factors for relapse: rete testis invasion and tumor size (as a continuous variable). CONCLUSION: Long-term follow-up confirms the risk-adapted approach as an effective option for patients with stage I seminoma. The pattern of relapses after adjuvant chemotherapy is similar to that observed following surveillance. A new nomogram for prediction of DFS among patients on surveillance is proposed. Rete testis invasion and tumor size should be taken into account when considering the administration of adjuvant carboplatin. Prospective validation is warranted.

Tratamiento de la fisura anal crónica con diltiazem gel 2% seis años de experiencia / Treatment of chronic anal fissure with diltiazem gel 2% six-years experience

Introducción: En la actualidad existe consenso que el tratamiento médico de la fisura anal crónica, es el de elección, como consecuencia de la morbilidad asociada a la esfinterotomía quirúrgica. Objetivo: Valorar la eficacia, seguridad y recidiva del diltiazem tópico en el tratamiento de la fisura anal crónica. Pacientes y Método: Se estudian los pacientes diagnosticados de fisura anal crónica en nuestro hospital, durante el periodo comprendido entre el uno de enero de 2008 y el 31 de diciembre de 2013 (6 años). Criterios de inclusión: edad mayor de 18 años y menor de 65 años, ausencia de otra patología anorrectal asociada, manometría con hipertonía del esfínter anal interno y consentimiento informado firmado. Criterios de exclusión: cirugía anorrectal previa, enfermedad inflamatoria intestinal, hipotensión arterial, intolerancia o alergia a calcio-antagonistas, deterioro cognitivo y bloqueo auriculo- ventricular. Se empleó una fórmula magistral de gel de diltiazem al 2%, en 3 aplicaciones diarias con una duración máxima de 8 semanas. Se realizaron controles clínicos y medida del dolor mediante escala analógica visual (EAV) al final de la cuarta, sexta y octava semanas. Se compararon los grupos con y sin respuesta al diltiazem mediante las pruebas de la -2 y t de Student. Resultados: Se analizaron 265 pacientes (137 mujeres), con una media de edad de 46,7 (18-65) años. Localización de la fisura: posterior en el 96%, anterior 3% y lateral en el 1%. Todos tenían dolor; 231 sangrado y 198, prurito. Al final de las 8 semanas de tratamiento se curó el 65,7% (174 pacientes), con una morbilidad del 11,7%, de los que el 2,6% abandonó el tratamiento por reacciones adversas. De los 174 pacientes que mejoraron con el tratamiento, 142 (81,6%), lo hicieron a las cuatro semanas de iniciado el tratamiento, 27 (15,5%) a las 6 semanas y tan sólo 5 pacientes (2,9 %) mejoraron a la octava semana, con una diferencia estadísticamente significativa (p<0,05) entre los pacientes respondedores a las 4 semanas, con respecto a la sexta y octava semanas de iniciado el tratamiento. No hubo diferencias significativas (p<0,05) entre los grupos con y sin respuesta al diltiazem en relación a la edad, el sexo, la localización, el sangrado o el prurito. Después de una media de seguimiento de 31 (3-72) meses, se detectaron 43 (16,2%) recidivas. El tiempo medio de recidiva tras finalizar el tratamiento con éxito, fue de 5,7 (2,5-32) meses. Conclusiones: El diltiazem gel 2%, es un medicamento eficaz en el tratamiento de la fisura anal crónica, en casos bien seleccionados. Carece de efectos secundarios importantes con un aceptable cumplimiento del tratamiento, evitando la morbilidad que conlleva la esfinterotomía quirúrgica. Aunque las recidivas son relativamente frecuentes, suelen responder a un nuevo tratamiento con diltiazem

Introduction: In recent years, the medical treatment of chronic anal fissure has consolidated as the choice as a result of the morbidity associated to surgical sphincterotomy. Objective: To evaluate the efficacy, safety and recurrence of topical diltiazem in the treatment of chronic anal fissure Patients and Method: We studied patients diagnosed of chronic anal fissure in our hospital during the period January 2008 to December 2013 (6 years). Inclusion criteria: age greater 18 and less than 65 years, manometry with hypertensive internal anal sphincter and signed informed consent. Exclusion criteria: previous anorrectal surgery, inflammatory bowel disease, intolerance or allergy to calcium antagonists, cognitive impairment, immune suppression, hypotension, and atrioventricular block. We used a formulation of diltiazem gel 2% in 3 daily applications for 8 weeks. There was a clinical and an extent of pain evaluation by visual analog scale (VAS) at the end of the fourth, sixth and eighth weeks. We compared the groups with and without response to diltiazem by the -2 and the Student test. Results: 46 patients were excluded, because they could'nt be contacted the follow-up (lost patients). We analyzed 265 patients (137 woman) with a mean age of 46, 7 (18 to 65) years. Localization of the fissure: Posterior 96%, anterior 3% and side 1%. All had pain, 231 bleeding and 198 itching. At the end of 8 weeks of treatment 65.7% (174 patients) were cured, with a morbidity of 11, 7%, of which the 2,6% discontinued the treatment due to adverse effects. Of the 174 patients who improved with treatment, 142 (81,6%) improved after four weeks of treatment, 27 (15,5%) after 6 weeks and only 5 (2, 9%) patients, after the eighth week, with a statistically significant difference (p <0.005) among responders at four weeks, compared to sixth and eighth week of initiation of treatment. There were no significant differences (p< 0,05) between groups with and without response to diltiazem related to age, sex, location, bleeding or itching. After a mean follow up of 31 (7 to72) months, 43 recurrences were detected (16,2%). The median time to recurrence after successful completion of treatment was 5.7 (2.5 to 32) months Conclusions: Diltiazem 2% gel is an effective drug in the treatment of chronic anal fissure, in selected cases. No major side effects were observed with an acceptable compliance, avoiding the morbidity associated to surgical sphincterotomy. Although recurrences are relatively common, they often respond to repeated treatment with diltiazem

Predictive factors for impaired renal function following nephroureterectomy in upper urinary tract urothelial cell carcinoma.

OBJECTIVES: Despite the uncertain value of adjuvant chemotherapy after radical nephroureterectomy (RNU) it is clear that impaired renal function represents a contraindication to its administration. The objective of this study was to identify possible predictive clinical factors for impaired renal function following RNU in patients with upper urinary tract urothelial cell carcinoma (UUT-UCC). PATIENTS AND METHODS: A retrospective analysis was conducted of 546 patients who underwent RNU between 1992 and 2008 at our institution. Data of interest for this study included estimated glomerular filtration rate (eGFR), age, pathological stage and preoperative hydronephrosis (HN). The predictive value of HN, age and pathological stage for impaired renal function after RNU was calculated by multivariate linear regression analysis. RESULTS: In total, 138 patients met the criteria for inclusion, including 108 men (78%). Mean age at surgery was 67 ± 10 years. There was a significant correlation (p < 0.001) between pre- and postoperative eGFR (decrease of 21% after NU). Preoperative HN was present in 51 patients (37%). On linear regression analysis, preoperative eGFR ≤60 ml/min (p = 0.012; OR = 4.60) and HN (p = 0.027; OR = 10.34) were confirmed to be predictive factors for a postoperative eGFR ≤60 ml/min. When postoperative eGFR ≤45 ml/min was used as the criterion for impaired renal function, predictive factors proved to be preoperative eGFR ≤45 ml/min (p < 0.0001; OR = 18.53), HN (p = 0.038; OR = 0.380) and age ≥70 years (p < 0.0001; OR = 0.169). CONCLUSIONS: Preoperative HN, older age and preoperative eGFR <60 ml/min were proven to be predictive factors for impaired renal function after RNU. In these settings, neoadjuvant chemotherapy may be considered.

Cáncer de próstata resistente a castración: ¿hacia dónde vamos? / Castration-Resistant Prostate Cancer: Where are We Going?

Contexto: El tratamiento hormonal permite un control eficaz de los síntomas relacionados con el cáncer de próstata metastásico; sin embargo, la práctica totalidad de estos pacientes sufrirán progresión de su enfermedad cuando esta se hace resistente a la supresión androgénica. La aparición de nuevos fármacos permite abrir nuevas expectativas en el tratamiento de esta enfermedad. Objetivo: Elaborar un documento de revisión sobre la situación actual del cáncer de próstata resistente a castración y compartir las grandes expectativas que se muestran con los nuevos tratamientos. Adquisición de la evidencia: Reuniones multidisciplinares con la participación de urólogos y oncólogos, donde se pusieron en común el análisis bibliográfico de artículos originales y se definió el contenido del artículo. Síntesis de la evidencia: Tras el fracaso de la hormonoterapia, la quimioterapia con docetaxel supuso un punto de inflexión en el cáncer de próstata resistente a castración, consiguiendo por primera vez beneficio en la supervivencia sobre mitoxantrone y prednisona. La combinación de docetaxel y prednisona es el tratamiento de elección en primera línea. Cuando progresa no hay alternativa clara, aunque nuevos agentes están generando expectativas en el tratamiento de esta enfermedad. Conclusiones: El horizonte terapéutico del cáncer de próstata resistente a la castración se abre de forma espectacular con la llegada de nuevos fármacos. Por el momento, cabazitaxel y en el futuro próximo abiraterona se han mostrado como fármacos eficaces en el tratamiento de segunda línea tras la progresión a docetaxel, añadiendo más de 2-4 meses de supervivencia y reduciendo un 30-35% el riesgo de muerte (AU)

Context: Hormonal therapy allows effective control of cancer-related symptoms in advanced stages. However, the disease will progress in almost all these metastatic prostate cancer patient until becoming resistant to androgen suppression. The emergence of new drugs will most probably have open up new expectations regarding the treatment of this cancer. Objective: The aim of the present review has been to provide an overview of the current status of castration-resistant prostate cancer and to share the high expectations created with the new treatments. Evidence Acquisition: Evidence was obtained from multidisciplinary meetings with the participation of urologists and oncologists, where they pooled the analysis of original articles in the literature and defined the content of the article. Evidence Synthesis: Chemotherapy with docetaxel was a turning point in castration-resistant prostate cancer after the failure of hormonal therapy failure. For the first time, it achieved increased survival time in comparison with mitoxantrone and prednisone. Combination therapy with docetaxel and prednisone is the first-line choice treatment. Once the cancer has progressed, there is no clear alternative, although some novel agents have created expectations for the treatment of this type of cancer. Conclusions: The range of therapeutic options for castration-resistant prostate cancer has increased dramatically with the arrival of new drugs. At present, cabazitaxel, and in the near future, abiraterone, have been found to be effective drugs in second-line treatment after progression to docetaxel, increasing survival by 2-4 months and reducing risk of death by 30-35% (AU)

Castration-resistant metastatic prostate cancer: current status and treatment possibilities

Prostate cancer (PCa) is the most common cancer in the male population in Western countries, second to skin cancer. Hormonal therapy allows long-lasting and effective control of cancer-related symptoms in advanced stages; however, in almost all patients with metastatic PCa the disease will progress when it becomes castration-resistant (CRPC). Chemotherapy with docetaxel was a turning point in CRPC, as, for the first time, it resulted in an increased survival time in comparison with mitoxantrone and prednisone. Combination therapy with docetaxel and prednisone is the first-line treatment of choice. Once the cancer has progressed, there is no clear alternative, although some new agents have shown promise in the treatment of this type of cancer. This review will provide an overview of the current status of CRPC, including clinical status, prognosis, firstline treatment and new second-line treatment options (AU)