Structure-based dual affinity optimization of a SARS-CoV-1/2 cross-reactive single-domain antibody.

The SARS coronavirus 2 (SARS-CoV-2) spike (S) protein binding to the human ACE2 receptor is the molecular event that initiates viral entry into host cells and leads to infection and virus replication. There is a need for agents blocking viral entry into host cells that are cross-reactive with emerging virus variants. VHH-72 is an anti-SARS-CoV-1 single-domain antibody that also exhibits cross-specificity with SARS-CoV-2 but with decreased binding affinity. Here we applied a structure-based approach to affinity-mature VHH-72 for the SARS-CoV-2 spike protein while retaining the original affinity for SARS-CoV-1. This was achieved by employing the computational platform ADAPT in a constrained dual-affinity optimization mode as a means of broadening specificity. Select mutants designed by ADAPT were formatted as fusions with a human IgG1-Fc fragment. These mutants demonstrated improved binding to the SARS-CoV-2 spike protein due to decreased dissociation rates. Functional testing for virus neutralization revealed improvements relative to the parental VHH72-Fc up to 10-fold using a SARS-CoV-2 pseudotyped lentivirus and 20-fold against the SARS-CoV-2 authentic live virus (Wuhan variant). Binding and neutralization improvements were maintained for some other SARS-CoV-2 variants currently in circulation. These improved VHH-72 mutants are predicted to establish novel interactions with the S antigen. They will be useful, alone or as fusions with other functional modules, in the global quest for treatments of COVID-19 infections.

Retroperitoneoscopic adrenalectomy: comparison of retrograde and antegrade approach among a series of 279 cases.

OBJECTIVE: To compare the results of retroperitoneal laparoscopic adrenalectomy using the antegrade and retrograde approach. MATERIALS AND METHODS: We performed an analysis of a single-center series of 279 retroperitoneal laparoscopic adrenalectomies from 1996 to 2010. We compared 172 cases performed with an antegrade approach and 107 with a retrograde approach without dissection of the renal hilum and initial control of the adrenal vein in comparable populations. RESULTS: The operative time was shorter in the group treated with the retrograde technique, 101±51 vs 140±40 minutes, respectively (Student's t test, P<.001). Blood loss was similar in both groups, 85±224 vs 80±126 mL, respectively (P=NS). Hemodynamic instability was defined as the maximal systolic blood pressure minus the minimal systolic blood pressure divided the maximal systolic blood pressure. It was lower in the group who underwent the retrograde technique (32.7 vs 37.6 mL; Student's t test, P=.005) with a lower perioperative consumption of ephedrine (2.2 vs 5.1 mg, P=.004) and atropine (0.09 vs 0.22 mg, P=.026). No difference was found between the 2 groups in the frequency of perioperative complications or postoperative mortality (1 death in each group of causes unrelated to the surgery). CONCLUSION: Retroperitoneal laparoscopic adrenalectomy using a retrograde approach is a safe and reproducible technique. It makes it possible to perform adrenalectomy without dissection of the renal hilum, with a reduction in the operative time. The good hemodynamic stability observed with this technique makes it very attractive for the treatment of pheochromocytoma.

Functional testicular evaluation using PET/CT with 18F-fluorodeoxyglucose.

PURPOSE: PET/CT using (18)F-FDG is a well-established diagnostic examination in oncology, cardiology and neurology. The clinical significance of nontumoral testicular uptake of FDG is unknown. Functional testicular imaging may have important clinical applications in the diagnosis and prognosis of male infertility. The aim of this study was to determine the andrological value of a FDG PET/CT in analysing testicular function, by correlating the PET/CT data with the sperm parameters. METHODS: Retrospective analysis of FDG PET/CT in 20 consecutive cancer patients without testicular pathology in whom two semen samples had been obtained for analysis before any chemotherapy. FDG PET/CT parameters were the mean standardized uptake value (SUVmean), used for measuring the intensity of uptake, and the functional testicular volume (FV). For statistical analysis, a Spearman's rank correlation test and a Mann-Whitney test were used. RESULTS: Of 20 patients (mean age 22 years), 18 had provided two sperm samples for cryopreservation. Sperm concentration was above 20 × 10(6)/ml in 55% of the patients. The intensity of uptake and the FV were correlated with the total sperm count, the sperm concentration and motility (p < 0.05). The difference in SUVmean between the two testes showed an inverse correlation with sperm concentration (p = 0.036). Normospermic and oligospermic men had significant differences in: (1) mean SUVmean, (2) mean FV, and (3) the difference in intensity of uptake between the testes (p < 0.05). CONCLUSION: This is the first report on the andrological value of FDG PET/CT in analysing nontumoral testicular function. This pilot study showed a significant correlation between intensity of uptake of FDG and testicular FV with the main sperm parameters. PET/CT with FDG could become a useful new tool in assisted reproductive technologies and other andrological or urological applications.

Oral midodrine for prostaglandin e1 induced priapism in spinal cord injured patients.

PURPOSE: We evaluated midodrine as oral treatment for pharmacologically induced priapism in spinal cord injured patients. MATERIALS AND METHODS: From 2004 to 2007 we treated 354 spinal cord injured patients with intracavernous injection of prostaglandin E1 to induce erection. Prolonged erection or priapism occurred in 14 cases (1.3% of intracavernous injections). High blood pressure and bradycardia (autonomic dysreflexia) were noted in 2 tetraplegic cases. Except in 2 patients oral midodrine was used as the only therapeutic approach to this event because of its alpha stimulant properties. RESULTS: All patients returned to the flaccid penile state within 30 to 45 minutes after midodrine administration. Oral midodrine was well tolerated with few side effects and without increasing the incidence of autonomic dysreflexia. At 6 months complete erection could be again induced by intracavernous injection in all treated patients. CONCLUSIONS: Midodrine administered orally is a simple and efficient treatment for the priapism induced by intracavernous injection of prostaglandin E1. It could be the first line therapeutic approach before more aggressive procedures.

Ejaculatory function after permanent 125I prostate brachytherapy for localized prostate cancer.

PURPOSE: Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent (125)I prostate brachytherapy for localized prostate cancer. PATIENTS AND METHODS: Of 270 sexually active men with localized prostate cancer treated with permanent (125)I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. RESULTS: Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). CONCLUSION: Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.

Erectile dysfunction in end-stage liver disease men.

INTRODUCTION: In men, erectile dysfunction (ED) is an important issue. Data concerning ED in men with end-stage liver disease (ESLD) is limited, and the risk factors for ED in this population are still unknown. AIMS: To determine the prevalence, timescale, and risk factors for ED in ESLD patients candidates to liver transplantation. METHODS: Patients candidates for a liver transplantation were asked to participate in a mailed survey about sexual function. Among the 123 eligible men, 98 (84%) agreed to complete the questionnaire. MAIN OUTCOME MEASURES: The quality of erection was evaluated using the five-item International Index of Erectile Function (IIEF-5) score, and satisfaction for sexuality, using the patient-baseline Treatment-Satisfaction Scale (TSS) score. Other questions also focused on patient perception of changes over time. RESULTS: On the overall population, 28 patients (29%) were nonsexually active. Among the 70 patients who were sexually active, 52 patients (74%) had ED. Regarding the development of ED, 50% of the patients perceived that a deterioration of erectile function occurred within the six previous months. The absence of sexual activity was more frequent in hepatitis B or C patients (P = 0.02). The risk factors for ED were alcohol intake (P = 0.03), tobacco use (P = 0.03), and cardiovascular disease (P = 0.004). The significant risk factors for having a low TSS score were having viral hepatitis (P = 0.01), and cardiovascular disease (P = 0.01). CONCLUSION: Population of men with ESLD who are candidates for a liver transplantation is characterized by a high frequency of lack of sexual activity, and by a high prevalence of ED and should be targeted by interventions to improve sexual functioning. These preliminary data need further validation in prospective trial using more comprehensive questionnaires.

Midodrine improves orgasm in spinal cord-injured men: the effects of autonomic stimulation.

INTRODUCTION: Orgasm is less frequent in men with spinal cord injury (SCI) than in able-bodied subjects, and is poorly understood. AIM: To assess the effect of autonomic stimulation on orgasm in SCI men using midodrine, an alpha1-adrenergic agonist agent. MATERIALS AND METHODS: Penile vibratory stimulation (PVS) was performed in 158 SCI men on midodrine as part of a treatment for anejaculation, after they failed a baseline PVS. A maximum of four trials were performed, weekly, with increasing doses of midodrine. MAIN OUTCOME MEASURE: The presence and type of ejaculation, orgasm experiences, and cardiovascular data were collected. RESULTS: Ejaculation either antegrade or retrograde was obtained in 102 SCI men (65%). Orgasm without ejaculation was reported by 14 patients (9%) on baseline PVS. Ninety-three patients (59%) experienced orgasm during PVS on midodrine. Orgasm was significantly related to the presence of ejaculation in 86 patients (84%), and more strikingly to antegrade ejaculation (pure or mixed with retrograde), i.e., in 98% of 70 patients. Orgasm was significantly more frequent in patients with upper motor neuron and incomplete lesions who present somatic responses during PVS. There was no effect of the presence of psychogenic erection. There was a significant increase in both systolic and diastolic blood pressure. Sixteen patients, mainly tetraplegics, developed intense autonomic dysreflexia (AD) that required an oral nicardipine chlorhydrate. CONCLUSIONS: Orgasm is the brain's cognitive interpretation of genital sensations and somatic responses, AD, and ejaculation. Intact sacral and T10-L2 cord segments are mandatory, allowing coordination between internal and external sphincters. Autonomic stimulation with midodrine enhances orgasm rate, mainly by creating antegrade ejaculation.

Polyorchidism: presentation of 2 cases, review of the literature and a new management strategy.

OBJECTIVES: To present 2 cases with polyorchidism, to review the literature about polyorchidism, and to propose a rational therapeutic algorithm. METHODS: In our institution, we encountered 2 patients with polyorchidism: The 1st patient had bilateral double testis with testicular torsion, and the 2nd patient presented with an indolent scrotal mass. We also performed a literature search (PubMed) for other reports of polyorchidism. RESULTS: Polyorchidism is a rare congenital anomaly that is not well known by most urologists. So far, as illustrated by our 2 cases, the management of polyorchidism is rarely conservative, and usually the supernumerary testis is removed without any evidence supporting this attitude. Rare cases are complicated by torsion (case 1), cryptorchidism, or testicular neoplasm. In case of torsion, the conservative approach depends on the viability of the twisted testis. In case of cryptorchidism, notably in children or young adults, conservative management should be proposed, if technically feasible. In case of signs of malignancy, orchiectomy must be performed. CONCLUSIONS: Conservative treatment is advised in all uncomplicated cases. Complicated cases need a careful management, but several situations can be managed conservatively. Based on the literature, we propose a simple, rational therapeutic algorithm.

Involvement of Dcr1 in post-transcriptional regulation of gene expression in Schizosaccharomyces pombe.

The ribonuclease III Dicer (Dcr1) has been shown to be required for chromosome segregation and gene silencing in Schizosaccharomyces pombe. These effects are thought to be transcriptional, mediated by formation and maintenance of heterochromatin, and guided by small RNAs derived from Dcr1 along a process known as RNA interference. In order to get further insights into the gene regulatory role of Dcr1, we performed comparative analyses of dcr1 knockout and wild-type fission yeast strains. Analysis of part of the soluble proteomes identified eight cellular proteins whose expression is under Dcr1 control, three of which are integral constituents of the glycolysis pathway. Further correlations with their respective mRNA transcript levels are compatible with the existence of a post-transcriptional gene regulatory mechanism involving Dcr1 or a Dcr1 complex. Experiments designed to identify components of Dcr1 complexes unveiled two novel Dcr1 interactors, namely the zinc finger protein Byr3 and the ribosomal protein L12. Consistently enriched in Dcr1 immune complexes, Byr3 and L12 may link Dcr1 to the transcriptional and translational machineries, respectively, and contribute to post-transcriptional gene regulation in fission yeast.

Impact of diagnostic delay in testis cancer: results of a large population-based study.

OBJECTIVE: Testis cancer is the most common cancer in young men, and its incidence continues to rise. Even if prognosis is considered as good, a group with bad prognosis still remains. Diagnostic delay (DD), defined as the time elapsing from the onset of tumour symptoms to the day of diagnosis, is a way to evaluate the rapidity of diagnosis. We assessed the relationship between DD, disease stage, and survival rate. METHODS: A series of 542 patients diagnosed with a germ cell tumour between 1983 and 2002 at health facilities in the Midi-Pyrenees region, southwest France, were asked about DD. We analysed DD together with data regarding the disease (histologic type, stage), its treatments, and prognosis (impact on survival). RESULTS: Mean DD was longer in seminoma (4.9+/-6.1 mo) than in non-seminomatous germ cell tumour (NSGCT; 2.8+/-4.0 mo). DD was correlated with disease stage for the whole population (p=0.014) and for NSGCT (p=0.0009), but not for seminoma. DD had a significant impact on the 5-yr survival rate in the overall population (p=0.001) and in the NSGCT group (p=0.001), but not in the seminoma group. Global trends in mean DD did not change over the 20-yr study period, but we observed a slight decrease during the last decade. CONCLUSIONS: DD is highly correlated with stage and survival in NSGCT. Urologists should promote programmes to enhance awareness and knowledge of testis cancer, so the diagnosis can be made more rapidly.

Lethal posttraumatic rupture of a pheochromocytoma: lesson from a postmortem diagnosis.

Pheochromocytoma is challenging to diagnose, and a life-threatening situation may occur if pheochromocytoma is incorrectly diagnosed and treated. We report the first case of a lethal posttraumatic rupture of an undiagnosed pheochromocytoma in a 46-year-old man who presented with peripheral vasoconstriction and signs of peritoneal irritation after being kicked by a horse. Computed tomography, arteriography, and two exploratory laparotomies were performed. The patient died of multiorgan failure 8 h after the trauma. The diagnosis of ruptured pheochromocytoma of the left adrenal gland was made during the postmortem examination. Pheochromocytoma should be considered in cases of blunt abdominal trauma associated with unstable blood pressure, peripheral vasoconstriction and adrenal hematoma.

Azoospermic HIV-1 infected patients wishing to have children: proposed strategy to reduce HIV-1 transmission risk during sperm retrieval and intracytoplasmic sperm injection: Case Report.

BACKGROUND: To date, assisted reproductive technology (ART) with sperm washing is offered to serodiscordant couples with an human immunodeficiency virus-1 (HIV-1) infected male partner in order to have a child while reducing the risk of transmission to the woman. However, ART programmes are not possible if the man is azoospermic. We report here the first birth following intracytoplasmic sperm injection (ICSI) using frozen epididymal spermatozoa obtained after surgical sperm retrieval in a HIV-1 infected man with obstructive azoospermia. METHODS; Sperm obtained by micro-epididymal sperm aspiration was frozen after density gradient preparation and tested for HIV-RNA and DNA. ICSI with frozen sperm was performed. RESULTS: A twin pregnancy was obtained following ICSI. Two healthy girls were born. Maternal HIV-1 RNA and HIV-1 serology were negative during pregnancy and at delivery. CONCLUSIONS: This case report demonstrates that ART is possible in azoospermic HIV-1 infected men. On the basis of current knowledge, we propose a strategy to reduce HIV-1 transmission risk during sperm retrieval and ICSI in couples where the man is HIV-1 infected and azoospermic.

[Vasectomy and vas deferens contraceptive surgery: legal and technical aspects]. / Vasectomie et chirurgies contraceptives déférentielles: aspects légaux et techniques.

OBJECTIVES: To analyse technical innovations, their results and the changing legislation in France concerning sterilizing or contraceptive vas deferens surgery. MATERIAL AND METHODS: A review of the literature was performed using the key words: male/contraception/vas deferens. From the 332 research articles obtained from PUBMED, we selected 54 articles for their methodological quality and the importance of their results. RESULTS: Vasectomy remains the only validated vas deferens surgical technique. Although microsurgical reconstructive techniques have improved the vas deferens restoration rate, vasectomy must be considered to be a definitive method of sterilization. The other contraceptive (reversible) vas deferens surgical techniques have not demonstrated sufficient efficacy to be used outside of the context of clinical trials. However the encouraging results ofsome ofthese studies could allow their development in the intermediate term. From a legal point of view, since the reform of sterilizing surgery in Article L2123-1 of the French Public Health Act, vasectomy is now authorized in a regulatory framework. CONCLUSION: The urology community must take into account progress in the field of contraceptive vas deferens surgical techniques.

[Fertility before and after treatment of patients with Leydig cell tumour]. / Fertilité avant et après traitement des patients présentant une tumeur à cellule de Leydig.

OBJECTIVE: To determine the long-term fertility status of patients treated for Leydig cell testicular tumour. MATERIAL AND METHODS: [corrected] In a series of 506 testicular tumours observed in the Midi-Pyrenées region between 1980 and 1998, 17 were Leydig cell tumours (3.3%) and constituted the study population. Andrological records were available for all patients. Information concerning fertility before and after orchidectomy was obtained by validated letter questionnaire. All patients completed the questionnaire. RESULTS: The mean follow-up was 84 months (range: 36-173). The mean age at diagnosis was 32 years (range: 24-51). The presenting symptom was gynaecomastia in 9 cases (53%), enlarged testis in 4 cases (24%), scrotal pain in 2 cases (12%) and male infertility in 2 cases (12%). Before onset of their disease, 13/17 (76.5%) patients had tried to have a child and 6 (46.2%) had successfully fathered a child. After treatment of their Leydig cell tumour, 10/17 (58.8%) had tried to have a child and 7 (70%) were successful. CONCLUSION: The population of men with Leydig cell tumour of the testis is a population with decreased fertility before treatment of the tumour. Resection of the tumour improves this situation, but 3 out of 10 patients remain infertile, indicating the need for semen storage measures in this population.

Synchronous epidermoid cyst and mature teratoma of the testis: an unusual association.

We describe here the first case of a synchronous epidermoid cyst and mature teratoma of the testis occurring in a young man presenting a with bilateral testicular tumor. After a clinical, biological and ultrasound evaluation, testis-sparing surgery was performed on the left testis and a total orchiectomy on the right side in accordance with oncological principles. Histopathological examination revealed a simple epidermoid cyst on the left side and a mature teratoma on the right side, following Price's criteria. No metastasis was detected, and the patient was closely followed. The patient remains disease-free and has normal postoperative testosterone levels 3 years after the surgery.

[Non-deferential male contraception: review of the literature]. / Contraceptions masculines non déférentielles: revue de la littérature.

OBJECTIVES: To review the state of progress of the various male contraceptive methods (with the exception of deferential methods). MATERIAL AND METHODS: A review of the literature was performed by using the key words: male/contraception, limiting the search to original articles in English and French. Articles on vasectomy and the other deferential methods of contraception are not considered in the present review. RESULTS: Three methods of male contraception are widely used at the present time: withdrawal, male condom and vasectomy, although other types of male contraception have been shown to be effective, including hormonal contraception, which appears to be the most promising technique and the subject of the majority of research. Other contraceptive methods (immunological, thermal...) could constitute possible alternatives. CONCLUSION: Male contraception remains under-used, as only male condoms are commonly used (apart from withdrawal and vasectomy). Consequently, new research protocols in the field of male contraception must be strongly encouraged.

Gonadal impact of target of rapamycin inhibitors (sirolimus and everolimus) in male patients: an overview.

The immunosuppressive agents target of rapamycin inhibitors (TOR-I) (sirolimus, and everolimus) have been widely used in kidney transplantation for >10 years. Up to 40% of men receiving a kidney transplant are younger than 50, and fertility as well as erectile function are major concerns. In this review, we provide a synopsis of past studies focusing on gonadal function in men treated with TOR-I, mainly sirolimus, to establish what impact they have on male gonads, and which pathophysiological pathways are involved. A PubMed search for the years 1990-2006 selected articles that focused on the gonadal impact of TOR-I. Primary outcome measures were testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels. Secondary outcome measures were sexual function, fertility status and sperm parameters. Treatment with TOR-I results in a decrease in testosterone level, and an opposite increase in LH. Moreover, spermatogenesis seems to be disrupted by TOR-I and FSH levels are increased. Sirolimus and everolimus inhibit the activity of mammalian targets of rapamycin, a serine/threonine kinase involved in numerous cell-growth processes. Molecular mechanisms of action of TOR-I on the testis involve inhibition of a stem cell factor/c-kit-dependant process in spermatogonia. Preliminary results appear to show that TOR-I treatment has deleterious actions on the testis and impairs gonadal function after renal transplantation, but the impact of these effects are unknown.

[Partial nephrectomy by selective renal parenchymal clamping using a new clamp]. / Néphrectomie partielle par clampage parenchymateux sélectif utilisant un nouveau clamp.

OBJECTIVE: To study the results of open partial nephrectomy by selective renal parenchymal clamping using a new renal parenchyma clamp, the Réniclamp. MATERIAL AND METHODS: Partial nephrectomy was performed in 37 patients using the Réniclamp for an imperative indication in 7 patients (solitary kidneys) and an elective indication in 30 patients. The tumour was situated in a pole in 22 cases and on the lateral border of the kidney in 15 cases. The mean tumour diameter was 29 mm (range: 10 - 60 mm). RESULTS: The mean operating time was 147 minutes and the mean clamping time was 25 minutes. Mean blood loss was 191 cc (range : 50-450 cc) and no patient required blood transfusion. No cases of slipping of the clamp or renal parenchymal lesion due to the clamp were observed. COMPLICATIONS: A urinary fistula treated by endoscopy and obstructive clot of the upper urinary tract, which required endoscopic treatment and selective embolisation. The surgical margins were negative in every case. CONCLUSION: Partial nephrectomy by selective renal parenchymal clamping is an alternative to the pedicle clamping technique in almost every case of renal tumour except for central renal lesions. Réniclamp distributes the pressure homogeneously, avoiding damage to the parenchyma due to excess pressure on the proximal part of the clamp and bleeding due to insufficient pressure on the distal part of the clamp.

[Retroperitoneal laparoscopic surgery for phaeochromocytoma: analysis of morbidity and haemodynamic instability]. / Chirurgie du phéochromocytome par laparoscopie rétropéritonéale: analyse de la morbidité et de l'instabilité hémodynamique.

OBJECTIVE: To study the morbidity and haemodynamic parameters on a consecutive series of adrenalectomies performed Jbr phaeochromocytoma by retroperitoneal laparoscopy. MATERIAL AND METHODS: The study population comprised 23 phaeochromocytomas in 20 patients treated by controlled retroperitoneal laparoscopic surgery. The following parameters were studied: intraoperatively: operating time, blood loss, blood pressure, heart rate, and postoperatively: infectious, haemorrhagic and thromboembolic complications. RESULTS: The mean operating time was 156 minutes (range: 105-224). Mean blood loss was 58 ml (range: 0-300). Intraoperatively, 1500 of patients presented a peak SBP >220 mmHg and 70% presented a peak SBP >200 mmHg. In contrast, 200 of patients presented a nadir SBP <60 mmHg, but no patient presented a nadir SBP less than 40 mmHg. One case of intraoperative haemorrhage was observed (4.3%). Three postoperative complications (1 case of respiratory distress, 1 case of haemorrhagic shock, and 1 abscess) were observed (13%). CONCLUSION: Laparoscopic surgery for phaeochromocytoma is associated with a risk of haemodynamic instability. Phaeochromocytoma surgery should therejbre continue to be performed in specialized centres (surgical, anaesthetic and endocrinological).

Testicular cancer variations in time and space in Europe.

OBJECTIVES: Testicular cancer (TC) is the most common malignancy in young men. A review of all published articles on TC incidence revealed an increased incidence in Northern and Central Europe. We extended the analysis to the whole of Europe by using all data available, notably from registries. METHODS: We performed a PubMed search and selected articles dealing with TC incidence. We obtained additional information from data of European registries through the eight volumes of the Cancer Incidence in Five Continents, IARC Scientific Publications. RESULTS: Since the Second World War, TC incidence has been increasing in nearly all European countries. It has doubled in several countries, including France, since 1970. We observed that the increase followed a gradient: the highest rate is centred in Denmark and Germany, and decreases progressively in a centrifugal manner. CONCLUSIONS: TC incidence is increasing throughout Europe, but wide discrepancies exist between the different countries. The reasons for such a phenomenon are still unclear although environmental factors are strongly suspected, which could have an impact on male fertility. From a public health perspective, further research using cases collected through national and regional population-based registers and case-control studies must be strongly encouraged.