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.

[Evaluation of postoperative symptoms after Greenlight™ photovaporization of the prostate through a dedicated questionnaire]. / Évaluation précoce des troubles postopératoires après photovaporisation de la prostate Greenlight™ grâce à un questionnaire dédié.

AIMS: To evaluate postoperative symptoms after Greenlight™ photovaporisation of the prostate (PVP), through a dedicated questionnaire. METHODS: A retrospective study has been conducted between 2008 and 2014. The questionnaire had 5 sections about pain while voiding, hematuria, urgency, incontinence and urinary stream, and was filled at one-month postoperative. The main outcome criterion was pain while voiding. Descriptive statistical analyses were done to identify predictive factors for pain while voiding. RESULTS: Out of 169 patients, 22% had no pain while voiding, 37% had moderate pain, 30% acceptable pain and 11% intense pain. Patients with pain were significantly older, (P=0.012), had more urgency (P=0.01) and more often hematuria (P=0.0001). Only 7% of patients had no symptoms of urgency, and urgency was painful or bothering in 57% of cases. Hematuria was frequent, with clots in 21% of cases. Ninety three percent felt improvement of urinary stream. CONCLUSIONS: Systematic evaluation of symptoms through a dedicated questionnaire one month after PVP has shown that 41% of patients felt pain while voiding, 57% had urgency and 39% significant hematuria. These results should encourage a more accurate patient information and further studies to better understand postoperative healing after PVP.

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.

[The role of simulation in the curriculum of French urologists-in-training: a study by the French Association of Urologists-in-Training (AFUF)]. / Évaluation de l'utilisation de la simulation dans la formation des jeunes urologues français : une enquête de l'association française des urologues en formation (AFUF).

OBJECTIVES: To study the place of simulation in the training curriculum of French urologists-in-training. MATERIALS AND METHODS: An online questionnaire was sent to all residents and fellows members of the AFUF between February and May, 2013. Results are presented as the median (interquartile range). RESULTS: The answers of 125 urologists-in-training were computed (response rate 38%). They were residents in 90 cases (72%), and fellows in 35 cases (28%). Median age was 29 (27-30), male proportion 77%. All French academic urology departments were represented. Ninety of them (72%) had access to a pelvi-trainer and 66 (53%) to animal or cadaveric models, although they never used them or less than once a month in 83 and 97% of cases, respectively. Seventy-two (58%) had used a virtual-reality based simulator at least once and 38 (30%) had regular access to one, but without supervision in 64% of cases. Factors limiting simulation-based training were the lack of available simulators (70%), the lack of time (58%), the absence of incitement (34%) and supervision (20%). If these conditions were met, 86% of urologists-in-training would be ready to spend more than one hour a-week training on a simulator. CONCLUSION: This study revealed among the sample of respondents a limited use of simulation tools for skills aquisition. This was explained by a limited availability of these tools but also by an insufficient use of the tools when available.

[Current state of compensation of on-duty and on-call urologists in France: a study from AFUF]. / État des lieux des rémunérations des gardes et astreintes d'urologie en France: une étude de l'AFUF.

INTRODUCTION: The French Association of Urologists-in-training (AFUF) aimed to assess the current state of remunerations of on-call and on-duty residents, assistants and lecturers in urology in France. MATERIAL AND METHODS: Data were collected from February to May 2013 through a questionnaire sent to all members of the AFUF (327 members). Remunerations were given in gross values. RESULTS: Forty-three residents took part in the study, 16 assistants and 16 lecturers, representing 62 % of the whole centers (54 hospitals out of the 92 centers practicing urology in France). Most of responders were on security or operational on-call. Twenty hospitals were practicing multi-organ removal. Median remunerations of residents were about 59.51€ per on-call when moving at hospital for work and about 119.02€ per onsite duty. Assistants and lecturers were paid a flat fee rate for 37.5 % of them (140€ for assistants [with variability from 40 to 195€] and 130€ for lecturers [42.5-180]) or an hourly rate depending on the hours spent at hospital for the others (62.5 %): first, second move or move<3h were paid 100€ for assistants and 65€ for lecturers, 233.5€ and 236€ respectively for the third one or above 3h, 365€ and 473€ respectively above 8h. Multi-organ removals were paid a flat fee rate (60 %) or an hourly rate (40 %) as well. Beyond a threshold of 2-3hours, the hourly rate was more interesting than the flat fee rate. CONCLUSION: There were disparities in remuneration of on-call and on-duty urologists. Greater variability affected on-call flat fee rate remuneration beyond a certain threshold of hours and remuneration of multi-organ removal. These disparities should be considered in order to get a national harmonization.

[Predictable access to the fellowship of urology in France till 2016: an update of the AFUF]. / Accessibilité prévisible au post-internat d'urologie en France jusqu'en 2016: une mise à jour de l'AFUF.

PURPOSE: To evaluate the predictable accessibility to the fellowship of urology for residents expecting to accomplish their residentship from November 2013 to November 2016. MATERIAL: Between September and November 2013, the representants of the residents ongoing for the residentship of urology in each region of France were reached to participate to the study. A questionnaire was given in aim at reporting all the local residents expecting to accomplish their residentship between November 2013 and 2016, and the number and the expected availability of fellow and specialist assistant posts in the region during the same period. RESULTS: In November 2013, our study listed 334 junior urologists (197 residents, 81 fellows, 56 assistants). Fifty-five residents were ending their internship by November 2013, whereas 67, 50, 77 residents were expecting to accomplish their residentship from November 2014 to 2016 respectively. The predictable accessibility to the fellowship of urology was 96.4%, 82.1%, 90.0%, 74.0% respectively for the residents accomplishing their residentship from November 2013 to November 2016. The predictable deficit of fellow and assistant posts were -2, -12, -5, -20 posts from November 2013 to November 2016 respectively. CONCLUSION: The predictable number of fellow and assistant post in Urology remains insufficiently available for the 2013-2016 period. By reason of the unstable number of residents accomplishing their residentship from 2014 to 2016, the fellowship accessibility was measured at 82.1%, 90.0%, 74.0% from 2014 to 2016 respectively.

[Research fellowship in the curriculum of French urologists-in-training: a study by the French Association of Urologists-in-training (AFUF)]. / Place du Master 2 recherche dans la formation des jeunes urologues français : une étude de l'AFUF.

OBJECTIVES: To assess motivations, the practical organization and the funding of a research fellowship in the training curriculum of French urologists-in-training. MATERIALS AND METHODS: An online questionnaire was sent to members of the AFUF and to participants of a research training seminar "Graines et Sol" organised by the AFU, between July and September 2013. Results are presented as the median (interquartile range). RESULTS: Sixty answers out of 115 research fellows (response rate 52%) were computed. Median age was 29 years (28-30) during the research year and male proportion 75%. The AFU grant was obtained by 57.4% of applicants, 56.4% for various grants and 47.6% for the research fellowship university grant. The annual gross amount was 29,870€ (22,710-30,195), without any significant difference between residency subdivisions. Financial supplements were obtained by being on-duty (26.2%), on-call (28.6%) and replacements (25%). The research fellowship year was done between 4th and 5th years of residency (53%), for a one-year length (96.7%) and in France (86.6%). Urologic cancerology was the thematic the most studied (60%). The research fellowship was done in view of an academic career (31.7%) or was done to wait for a post-residency position (20.8%). About a quarter was being proposed a chief-residency position before the beginning of the research year. During this year, 76.7% published. About 63% were interested in pursuing with a PhD. CONCLUSION: This study confirmed the interest for a research fellowship by French urologists-in-training. Financial support thanks to grants facilitated the conduct of a research fellowship in the aim of an academic career for most of them.

[A majority of useless call of an on-call urology resident: a study of the AFUF]. / Une majorité d'appels évitables au cours des astreintes d'urologie en CHU : l'étude de l'AFUF.

GOAL: To assess the workload of an on-call urology resident at a French University Hospital. MATERIAL: A prospective study was performed during 15 days in February 2012. The data recorded in our database regarded the resident (sex, age, time to go to work), the call (emergency, type and reason) and the person who called (grade, department). RESULTS: Seven centres including 18 residents participated. On average five calls were received per day [0-17]. After midnight, the resident was called less than twice (1.6). There was an actual emergency in 64% of cases [0-13]. The urology-related call motives (73%) mainly consisted in acute urine retention (AUR) and catheter problems (73), renal colic (RC) (49), acute pyelonephritis (23), and hematuria (22). Residents had to go to the hospital in 55% of AUR and catheter problems, 30% of acute pyelonephritis, 17% of RC and 14% of hematuria. The emergency department (ED) called the urology resident in 39% of cases but only 18% required the presence of the resident. A call made by a senior was more likely to be an emergency (67%) than by a resident or a nurse (51%, P=0.02). CONCLUSION: The urology resident when on-call is mainly asked for an advice by the ED. Among urology-related advice, bladder catheterization problems were the most frequent. RC was the second call motive but most of the time was not an actual emergency.

[Alert on the predictable accessibility of the fellowship of urology until 2013: a study of the AFUF]. / Alerte sur l'accessibilité prévisible du postinternat d'urologie jusqu'en 2013: une étude de l'AFUF.

PURPOSE: To evaluate the accessibility of the fellowship for the residents of Urology expecting to accomplish their residentship between November 2010 and 2013. PATIENTS: Between November 2010 and January 2011, all the residents ongoing for the residentship of Urology in France were reached by an electronic mailing using the AFUF register. A questionnaire reported all the residents expecting to accomplish their residentship between November 2010 and 2013, and the number and the expected availability of fellow and specialist assistant posts during the same period. RESULTS: Our study counted 306 urologists on training (190 residents, 76 fellows, 30 assistants, 10 on other posts). On November 2010, 56 residents accomplished their residentship, while 68 and 79 residents expected to accomplish their residentship on November 2011 and 2012, respectively. One hundred and six posts validated the fellowship of Urology on November 2010 (76 fellows, 30 assistants), among 54 posts were available. Over the residents expecting to accomplish their residentship on November 2011 and 2012, 22 and 54 residents may not find a fellow post available. CONCLUSION: The number of residents expecting to accomplish the residentship of Urology between November 2010 and 2013 was increasing, showing a greater interest for this speciality and a lack of regulation for its accessibility. By reason of a discrepancy of fellow and specialist assistant posts, only 67.6 and 31.6% of the residents expecting to accomplish their residentship on November 2011 and 2012 may be able to find a post available.

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.

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.

Terminal cancer. duration and prediction of survival time.

The duration of the terminal period of cancer allows us to determine its prevalence, which is necessary to plan palliative care services. Clinical prediction of survival influences access to palliative care and the healthcare approach to be adopted. The objective of this study was to determine the duration of the terminal period, the prognostic ability of healthcare professionals to predict this terminal period and the factors that can improve the prognostic accuracy. In the island of Mallorca, Spain, we followed 200 cancer patients at the inception of the terminal period. Twenty-one symptoms, quality of life, prognosis and duration of survival were measured. Using a Cox regression model, a predictive survival model was built. Median duration was 59 days; 95% confidence interval (CI)=49-69 days, mean=99 days. The oncologists were accurate in their predictions (+/-1/3 duration) in 25.7% of cases, the nurses in 21.5% of cases and the family physicians in 21.7% of cases. Errors of overestimation occurred 2.86-4.14 times more frequently than underestimation. In the final model, in addition to clinical prognosis (P=0.0094), asthenia (P=0.0257) and the Hebrew Rehabilitation Centre for Aged Quality of Life (HRCA-QL) Index (P=0.0002) were shown to be independent predictors of survival. In this study, the estimated duration of the terminal period was greater than that reported in a series of palliative care programmes, and survival was overestimated. Oncologists could estimate prognosis more accurately if they also take into account asthenia and HRCA-QL Index.

GABA receptors mediate cerebral vasodilation in the unanesthetized goat.

The effects of gamma-aminobutyric acid (GABA) and muscimol upon cerebral blood flow were evaluated in the unanesthetized goat. Cerebral blood flow was continuously measured by means of an electromagnetic flow probe chronically implanted on the internal maxillary artery after occlusion and thrombosis of the distal extracerebral vessels. Administration of GABA (1-100 micrograms) directly into the cerebral circulation produced dose-dependent increases in cerebral blood flow, without accompanying systemic effects. Muscimol mimicked the effects of GABA at doses 10 times lower. Administration of picrotoxin (1-3 mg) into the internal maxillary artery did not significantly change cerebral blood flow, but inhibited in a dose-dependent manner the vasodilation induced by GABA. Selective blockade of beta-adrenergic or muscarinic cholinergic receptors by propranolol or atropine, respectively, did not modify the cerebrovascular response to the GABAergic agonists. These results indicate that GABA increases total cerebral blood flow, acting on specific receptor sites in the cerebral blood vessels. The absence of influence of picrotoxin on resting cerebral blood flow suggests that the GABAergic receptors are not tonically activated under physiological conditions.

P1-purinoceptors in the cerebrovascular bed of the goat in vivo.

The possible existence and function of specific P1-purinoceptors in the cerebrovascular bed of the unanesthetized goat have been investigated. Blood flow to one cerebral hemisphere (cerebral blood flow) was measured by means of an electromagnetic flow probe previously implanted around the ipsilateral internal maxillary artery. The injection of adenosine, AMP, ADP and ATP (3-30 micrograms) directly into the internal maxillary artery increased cerebral blood flow and decreased cerebrovascular resistance in a dose-dependent manner. Continuous infusion of 8-phenyltheophylline (8-PT), 100 micrograms/min, into the internal maxillary artery did not alter the resting cerebral blood flow or the cerebrovascular resistance, but significantly inhibited the cerebral vasodilation induced by adenosine, AMP, ADP and, to a lesser degree, ATP. The acetylcholine- and histamine-induced cerebral vasodilation was unaffected by 8-PT. These results indicate that adenosine, AMP, ADP and, at least in part, ATP increase cerebral blood flow by acting on specific P1-purinoceptors located in the cerebrovascular wall. These P1-purinoceptors do not appear to be tonically activated under physiological conditions.