Testicular ultrasonographic features predict future risk for bilateral testicular germ cell tumour: A long-term single centre follow-up study.

BACKGROUND: Bilateral testicular germ cell tumours (B-GCT) are rare, with an incidence of 2-5%, and can be classified as synchronous (sB-GCT) or metachronous (mB-GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB-GCT in a cohort of patients with GCT at a single tertiary referral centre. METHODS: This retrospective case-control study included patients with GCT referred to Policlinico Umberto I-Sapienza University of Rome, from 2005 to 2023. We evaluated clinical history, testicular ultrasound features, hormone levels, semen analysis, histological characteristics, staging, and treatments. mB-GCTs were compared with unilateral GCT patients with a follow-up longer than the median time-to-onset of the second tumour. RESULTS: Of 319 patients, 52 experienced B-GCT, with a median time-to-onset of the second tumour of 62 months (range: 8-229). The mB-GCT group showed higher gonadotropin levels (FSH 13.6mUI/mL vs. 7.4mUI/mL, p < 0.001; LH 6.6mUI/mL vs. 3.9mUI/mL, p = 0.004), lower sperm concentration (27 × 106/ejaculate vs. 78 × 106/ejaculate, p = 0.009), smaller residual testis volume (10.4 mL vs. 16.3 mL, p < 0.001), more inhomogeneous echotexture [57.5% vs. 14%, p < 0.001], and presence of microlithiasis (75% vs. 19.5%, p < 0.001). Kaplan-Meier curves confirmed that ultrasound features of the residual testis increased the cumulative risk of developing a second tumour. Microlithiasis was a strong independent predictor (OR 30.712, 95% CI 3.357-280.942, p = 0.002). CONCLUSIONS: Histological features of the first tumour or its treatment do not influence the onset of a second tumour. However, low residual testis volume, inhomogeneous echotexture, and microlithiasis significantly increase this risk. A comprehensive evaluation of the residual testis at baseline is essential for developing a personalised surveillance programme in GCT survivors, with regular ultrasound follow-up recommended beyond the conventional 5-year limit.

Multiparametric Ultrasound for Diagnosing Testicular Lesions: Everything You Need to Know in Daily Clinical Practice.

BACKGROUND: Ultrasonography (US) represents the gold standard imaging method for the assessment of testicular lesions (TL). The gray-scale (GSUS) and color-Doppler (CDUS) ultrasound examination allow sonographers to investigate the size, margins, echotexture, and vascular features of TLs with the aim to differentiate benign from malignant lesions. Recently, the use of contrast-enhanced US (CEUS) and sonoelastography (SE) has led to further improvements in the differential diagnosis of TL. Although GSUS and CDUS are often sufficient to suggest the benign or malignant nature of the TL, CEUS can be decisive in the differential diagnosis of unclear findings, while SE can help to strengthen the diagnosis. The contemporary combination of GSUS, CDUS, CEUS, and SE has led to a new diagnostic paradigm named multiparametric US (mp-US), which is able to provide a more detailed characterization of TLs than single techniques alone. This narrative and pictorial review aimed to describe the mp-US appearance of several TLs. METHODS: An extensive Medline search was performed to identify studies in the English language focusing on the mp-US evaluation of TLs. RESULTS: A practical mp-US "identity card" and iconographic characterization of several benign and malignant TLs is provided herein. CONCLUSIONS: The mp-US characterization of TL reported herein can be useful in daily clinical practice.

Extra-Gonadal and Non-Canonical Effects of FSH in Males.

Recombinant follicle-stimulating hormone (FSH) is commonly used for the treatment of female infertility and is increasingly being used in males as well, as recommended by notable guidelines. FSH is composed of an α subunit, shared with other hormones, and a ß subunit, which confers specificity of biological action by interacting with its surface receptor (FSHR), predominantly located in granulosa and Sertoli cells. However, FSHRs also exist in extra-gonadal tissues, indicating potential effects beyond male fertility. Emerging evidence suggests that FSH may have extra-gonadal effects, including on bone metabolism, where it appears to stimulate bone resorption by binding to specific receptors on osteoclasts. Additionally, higher FSH levels have been associated with worse metabolic and cardiovascular outcomes, suggesting a possible impact on the cardiovascular system. FSH has also been implicated in immune response modulation, as FSHRs are expressed on immune cells and may influence inflammatory response. Furthermore, there is growing interest in the role of FSH in prostate cancer progression. This paper aims to provide a comprehensive analysis of the literature on the extra-gonadal effects of FSH in men, with a focus on the often-conflicting results reported in this field. Despite the contradictory findings, the potential for future development in this area is substantial, and further research is needed to elucidate the mechanisms underlying these effects and their clinical implications.

cAMP-specific phosphodiesterase 8A and 8B isoforms are differentially expressed in human testis and Leydig cell tumor.

Cyclic adenosine monophosphate/Protein kinase A (cAMP/PKA) signaling pathway is the master regulator of endocrine tissue function. The level, compartmentalization and amplitude of cAMP response are finely regulated by phosphodiesterases (PDEs). PDE8 is responsible of cAMP hydrolysis and its expression has been characterized in all steroidogenic cell types in rodents including adrenal and Leydig cells in rodents however scarce data are currently available in humans. Here we demonstrate that human Leydig cells express both PDE8A and PDE8B isoforms. Interestingly, we found that the expression of PDE8B but not of PDE8A is increased in transformed Leydig cells (Leydig cell tumors-LCTs) compared to non-tumoral cells. Immunofluorescence analyses further reveals that PDE8A is also highly expressed in specific spermatogenic stages. While the protein is not detected in spermatogonia it accumulates nearby the forming acrosome, in the trans-Golgi apparatus of spermatocytes and spermatids and it follows the fate of this organelle in the later stages translocating to the caudal part of the cell. Taken together our findings suggest that 1) a specific pool(s) of cAMP is/are regulated by PDE8A during spermiogenesis pointing out a possible new role of this PDE8 isoform in key events governing the differentiation and maturation of human sperm and 2) PDE8B can be involved in Leydig cell transformation.

Selenium Supplementation in Pregnant Women with Autoimmune Thyroiditis: A Practical Approach.

Selenium (Se) is an essential trace element with antioxidant and anti-inflammatory properties and a pivotal role in thyroid metabolism. Ensuring a sufficient Se supply is possible via a balanced, wholesome diet; however, Se content in foods may be different throughout geographical areas. Se supplementation is expected to improve inflammatory status in patients with autoimmune thyroiditis, especially in those with high activity, and has been demonstrated as effective in reducing the thyroid peroxidase antibodies titer. Se status seems to affect thyroid function in pregnancy, which prompts the potential role of Se supplementation in such patients. Few clinical trials have investigated the effectiveness of Se supplementation in pregnant women with thyroiditis, and their results suggest the safety and effectiveness of this element in reducing autoantibody levels and preventing postpartum thyroiditis development, although limited. Hence, more robust evidence is needed to confirm these data. The current study aims to summarize published data on the relationship between Se and thyroid status in pregnant women with thyroiditis and the potential use of Se. Moreover, an algorithm for Se supplementation is proposed for pregnant women with thyroiditis to help endocrinologists in daily clinical practice to consider Se status.

Diagnostic accuracy of ultrasonographic features in detecting thyroid cancer in the transition age: a meta-analysis.

Context: Significant uncertainty exists about the diagnostic accuracy of ultrasonographic (US) features used to predict the risk of thyroid cancer in the pediatric population. Moreover, there are no specific indications for thyroid nodule evaluation in patients during the transition age. Objective: The meta-analysis aimed to address the following question: which thyroid nodule US features have the highest accuracy in predicting malignancy in the transition age. Methods: We performed a meta-analysis of observational/cohort/diagnostic accuracy studies dealing with thyroid nodule sonography, reporting US features, and using histology as a reference standard for the diagnosis of malignancy and histology or cytology for the diagnosis of benignity in the transition age (mean/median age 12-21 years). Results: The inclusion criteria were met by 14 studies, published between 2005 and 2020, including 1306 thyroid nodules (mean size 17.9 mm) from 1168 subjects. The frequency of thyroid cancer was 36.6%. The US features with the highest diagnostic odds ratio (DOR) for malignancy were the presence of suspicious lymph nodes (DOR: 56.0 (95% CI: 26.0-119.0)), a 'taller than wide' shape of the nodule (6.0 (95% CI: 2.0-16.0)), the presence of microcalcifications (13.0 (95% CI: 6.0-29.0)) and irregular margins (9.0 (95% CI: 5.0-17.0)). Heterogeneity among the studies was substantial. Conclusions: Following the diagnosis of a thyroid nodule in the transition age, a thorough US examination of the neck is warranted. The detection of suspicious lymph nodes and/or thyroid nodules with a 'taller than wide' shape, microcalcifications, and irregular margins is associated with the highest risk of malignancy in the selection of nodules candidates for biopsy.

Are Markers of Systemic Inflammatory Response Useful in the Management of Patients With Neuroendocrine Neoplasms?

Given the increasing incidence of neuroendocrine neoplasms (NENs) over the past few decades, a more comprehensive knowledge of their pathophysiological bases and the identification of innovative NEN biomarkers represents an urgent unmet need. There is still little advance in the early diagnosis and management of these tumors, due to the lack of sensible and specific markers with prognostic value and ability to early detect the response to treatment. Chronic systemic inflammation is a predisposing factor for multiple cancer hallmarks, as cancer proliferation, progression and immune-evading. Therefore, the relevance of inflammatory biomarkers has been identified as critical in several types of tumours, including NENs. A bidirectional relationship between chronic inflammation and development of NENs has been reported. Neuroendocrine cells can be over-stimulated by chronic inflammation, leading to hyperplasia and neoplastic transformation. As the modulation of inflammatory response represents a therapeutic target, inflammatory markers could represent a promising new key tool to be applied in the diagnosis, the prediction of response to treatment and also as prognostic biomarkers in NENs field. The present review provides an overview of the pre-clinical and clinical data relating the potentially usefulness of circulating inflammatory markers: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), cytokines and tissue inflammatory markers (PD-1/PD-L1), in the management of NENs. (1) NLR and PLR have both demonstrated to be promising and simple to acquire biomarkers in patients with advanced cancer, including NEN. To date, in the context of NENs, the prognostic role of NLR and PLR has been confirmed in 15 and 4 studies, respectively. However, the threshold value, both for NLR and PLR, still remains not defined. (2) Cytokines seem to play a central role in NENs tumorigenesis. In particular, IL-8 levels seems to be a good predictive marker of response to anti-angiogenic treatments. (3) PD-1 and PD-L1 expression on tumour cells and on TILs, have demonstrated to be promising predictive and prognostic biomarkers in NENs. Unfortunately, these two markers have not been validated so far and further studies are needed to establish their indications and utility.

Use of contrast enhanced ultrasound in testicular diseases: A comprehensive review.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a sonographic technique that increases the diagnostic accuracy of ultrasound and color Doppler ultrasound (CDUS) when studying testicular abnormalities. However, its role in clinical practice is still debatable because there are no accepted standards regarding how and when this technique should be used for patients with testicular disease. OBJECTIVES: To perform a nonsystematic review of the current literature to highlight the strength and flaws of performing CEUS and to provide a critical overview of current research evidence on this topic. MATERIALS AND METHODS: A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. RESULTS: Strong enhancement of neoplastic lesions (both benign and malignant) during CEUS aids in differential diagnosis with non-neoplastic lesions, which usually appears either nonenhanced or enhanced in a manner similar to that of the surrounding parenchyma. CEUS enhancement has a high predictive value in the identification of neoplastic lesions, whereas a similar or complete absence of enhancement may be interpreted as strong evidence of benignity, although there are exceptions. Literature on quantitative analysis is still scarce, though promising, particularly in distinguishing benign from malignant neoplasms. Furthermore, CEUS may be useful in many emergency situations, such as acute scrotum, blunt scrotal trauma, and focal infarction of the testis. Finally, CEUS can help increase the probability of sperm recovery in azoospermic males. DISCUSSION AND CONCLUSION: CEUS is a safe, easy-to-perform, and cost-effective diagnostic tool that can provide a more accurate diagnosis in testicular lesions and acute scrotal disease. However, further studies with larger cohorts are required to refine the differential diagnosis between benign and malignant neoplasms. Finally, these preliminary results can instigate the development of innovative research on pre-testicular sperm extraction to increase the chances of sperm recovery.

The role of scrotal ultrasonography from infancy to puberty.

BACKGROUND: Scrotal ultrasonography is an essential diagnostic tool in daily clinical practice. The availability of new-generation ultrasound machines characterized by clearly improved image quality, low health cost, and higher patient safety, represents only some characteristics of ultrasound investigation. The usefulness of scrotal ultrasonography is particularly evident in the period of life from infancy to puberty, during which males undergo important morphofunctional changes, and several pathological conditions may occur. OBJECTIVES: This pictorial review primarily aimed to investigate the aspects of ultrasonography related to the normal physiological development of the gonads from mini-puberty to pubertal onset. This study also aimed to provide an update on the use of ultrasonography in main andrological pathologies that may occur during this period. The conditions that are discussed in depth are: cryptorchidism, inguinoscrotal hernias, and hydrocele in the neonatal phase; acute scrotum, epididymo-orchitis, and testicular cancers in childhood; and hypogonadism, varicoceles, testicular microlithiasis, and oncohematological pathology in puberty. DISCUSSION: We provided an ultrasound slant for all the above-mentioned pathologies while purposely avoiding excessive deepening of the pathogenetic, clinical, and therapeutic aspects. Studying the ultrasound aspects of the gonads also facilitates differential diagnosis between various conditions and represents a good aid in evaluating therapeutic success (e.g., in hypogonadism or postsurgical evaluation of varicoceles and cryptorchidism). CONCLUSION: Scrotal ultrasonography is now globally recognized as the necessary completion of clinical-laboratory overview in gonads evaluation. This diagnostic procedure is even more indispensable in the infancy-childhood-puberty period for the evaluation of normal gonadal development as well as diagnosis of other possible diseases.

Penile prosthesis and complications: Results from 577 implants.

OBJECTIVE: Penile Prosthetic Surgery is already well characterized but the problems connected with possible complications still need to be evaluated and discussed. MATERIAL AND METHODS: The Authors revaluated their experience in Penile Prosthetic Surgery involving 577 patients (18 - 86 years, mean age 51.3 years) operated by the same surgeon since 1984. We implanted 199 silicone-semi-rigid (Small Carrion, Implantal, Eurogest, Subrini, SSDA GS), 200 malleable (Jonas, Omniphase, Duraphase, AMS600, MentorColoplast Genesis, Vedise) and 178 inflatable (Mentor: Mark II, Alpha I, Titan OTR; AMS: mono-component Hydroflex, Dynaflex; bi-component Ambicor; multicomponent: 700 Ultrex, 700 CX, 700 LGX) prostheses. Operative, postoperative, infectious and malfunctioning complications have been recorded. A total of 156 patients drop out at follow-up and we may not exclude possible late complications treated at different hospitals. RESULTS: The recorded complications and the therapeutic modalities utilized to treat them are examined. Operative complications were recorded in 2 malleable prostheses (MPP) and in one inflatable prosthesis (IPP). Postoperative complications have been recorded in three cases of MPP (1.5%) and in 9 IPP (5.0%) and were strictly connected to general medical co-morbidities as diabetes mellitus (DM), coronary artery dysfunction (CAD), and Peyronie's disease (PD). In three cases of IPP implantation, hematomas were related to the blunt surgical maneuvers utilized to insert the reservoir or the scrotal pumps. Infectious complications were mostly observed in patients with DM: 4 patients with MPP (1.0%) and 15 patients with IPP (8.4%). Malfunction rate of the prostheses in our series was really disappointing considering that 13/17 cases (77%) of mono-component IPP broke while in patients with multicomponent IPP the percentage of malfunction has been of 13/161 (8%) and malfunction was observed in only one case of MPP. We were forced to explant the prostheses in 2 patients with MPP (0.5%) and 40 with IPP (22%). However, after excluding 17 mono-component IPPs, the percentage of explants of multicomponent IPP (23 patients, 4.2%) is in line with other significative experiences. CONCLUSION: The number of complications of PPS are similar to those reported by well qualified urological institutions. In our experience a scrupulous antibiotic therapeutic schedule, avoiding direct contact between the prostheses and the patient's skin, reduced time of surgery with surgeon's experience positively influenced the results.In a limited number of patients medical treatment or minimal surgical acts allowed to solve the complications preserving the prostheses and avoiding the prosthetic explant.

A Novel MAX Gene Mutation Variant in a Patient With Multiple and "Composite" Neuroendocrine-Neuroblastic Tumors.

Introduction: Pheochromocytomas (PCCs), paragangliomas (PGLs), ganglioneuroblastomas (GNBs), and ganglioneuromas (GNs) are neuroendocrine neoplasms (NENs) that were thought to share a common embryologic origin from neural crest cells. However, they rarely occur concurrently and recurrently. We describe the case of a 40-years-old woman with "composite PCC-GN" and multiple NENs and neuroblastic tumors. Case presentation: The patient was first referred to our department at the age of 15 years for paroxysmal hypertension, headache, sweating, and watery diarrhea. Her personal history included the diagnosis of a pelvic GNB with lumbar-aortic lymph node metastases at 11 months. Her family history was positive for cerebral glioblastoma multiforme (father). An abdominal ultrasound showed a right adrenal mass that histologically was a "composite adrenal PCC-GN." The symptoms disappeared after surgery. At the age of 20 years, the symptoms returned: computed tomography (CT) and 131I-metaiodobenzylguanidine (MIBG) scintigraphy showed an inter-aortocaval mass, found histologically to be an inter-aortocaval PGL. Her symptoms reappeared again at 28 years: CT and magnetic resonance imaging revealed four left adrenal gland nodules, found histologically to be multifocal PCCs with some atypia. Genetic screening for VHL, RET, NF1, Tp53, SDHD, SDHB, SDHC, SDHAF2, SDHAF3, SDHA, and TMEM127 was negative. Mutational analysis of the MAX gene revealed the presence of a novel heterozygous variant, c299G>C (p.Arg100Pro, NM_002382.5) that the bioinformatics prediction programs defined as noxious and causative of pathology. Conclusion: This report represents the first description of a co-occurrence of multiple composite PCC-GN and neuroblastic tumors. The long timeline of the presentation of the NENs/neuroblastic tumors from infancy to adulthood requires a lifelong follow-up for this patient. Moreover, the importance of this case lies in the presence of a novel MAX gene variant deleterious, harmful, and causative of pathology, confirmed by Sanger sequencing and never been associated before with multiple composite PCC-GN. The present case underlines the importance of precision medicine and molecular diagnoses for hereditary pheochromocytomas and paragangliomas, suggesting that when they occur in early childhood, it is necessary to perform an extensive genetic investigation and a lifelong follow-up.

Therapeutic use of pulsed electromagnetic field therapy reduces prostate volume and lower urinary tract symptoms in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) etiology remains poorly understood, but chronic low-grade inflammation plays a role. Pulsed electromagnetic field therapy (PEMF) (1-50 Hz) is effective in reducing tissue inflammation. OBJECTIVES: We designed a pilot study to evaluate the effects of PEMF on prostate volume (PV) in BPH. MATERIALS AND METHODS: This is a prospective interventional trial on 27 naive patients with BPH and lower urinary tract symptoms (LUTS). At baseline (V0 ), all patients had blood tests, transrectal ultrasound, and questionnaires (IPSS, IIEF-15) and received a perineal PEMF device (Magcell® Microcirc, Physiomed Elektromedizin). PEMF was delivered on perineal area 5 minutes twice daily for 28 days, then (V1 ) all baseline evaluations were repeated. Afterward, nine patients continued therapy for 3 more months (PT group) and 15 discontinued (FU group). A 4-month evaluation (V2 ) was performed in both groups. RESULTS: A reduction was observed both at V1 and at V2 in PV: PVV0 44.5 mL (38.0;61.6) vs PVV1 42.1 mL (33.7;61.5, P = .039) vs PVV2 41.7mL (32.7;62.8, P = .045). IPSS was reduced both at V1 and at V2 : IPSSV0 11 (5.7;23.2) vs IPSSV1 10 (6;16, P = .045) vs IPSSV2 9 (6;14, P = .015). Baseline IPSS was related to IPSS reduction both at V1 (rs  = 0.313;P = .003) and at V2 (rs  = 0.664;P < .001). PV reduction in patients without metabolic syndrome (ΔPVV1nMetS -4.7 mL, 95%CI -7.3;-2.0) was greater than in affected patients (ΔPVV1MetS 1.7 mL, 95%CI -2.69;6.1)(P = .017, Relative RiskMetS  = 6). No changes were found in gonadal hormones or sexual function. DISCUSSION: PEMF was able to reduce PV after 28 days of therapy. Symptoms improved in a short time, with high compliance and no effects on hormonal and sexual function or any side effects. Patients with moderate-severe LUTS and without MetS seem to benefit more from this treatment. CONCLUSION: PEMF reduces PV and improves LUTS in a relative short time, in BPH patients. These benefits seem greater in those patients with moderate-severe LUTS but without MetS.

Thyroid disorders in programmed death 1 inhibitor-treated patients: Is previous therapy with tyrosine kinase inhibitors a predisposing factor?

BACKGROUND: Programmed death 1 (PD-1) inhibitors are frequently associated with thyroid-related adverse events (TAEs), but many aspects remain unclear. This study aims to evaluate the incidence and characteristics of such events and to find any predictive factor for its development. METHODS: We retrospectively analysed data from patients with advanced solid tumours (non-small-cell lung carcinoma, renal cell carcinoma, metastatic melanoma) treated with PD-1 inhibitors (nivolumab, pembrolizumab) in Oncology Unit B, Policlinico Umberto I of Rome, from June 2015 to December 2018. All patients underwent baseline thyroid function evaluations repeated monthly. RESULTS: The cohort consisted of 126 patients (66.7% male, mean age 66.4 ± 9.7 years). One hundred and seven received nivolumab and 19 pembrolizumab. Twenty-three per cent of patients experienced TAEs (mainly CTCAE grade 1), with hypothyroidism in 15.1% (subclinical: 11.9%, overt: 3.2%) and hyperthyroidism in 8.0% (subclinical: 4.8%, overt: 3.2%). Median time to TAE onset was 8.7 ± 6.8 weeks (10.4 ± 7.6 weeks for hypothyroidism, 5.4 ± 3.0 weeks for hyperthyroidism). Most TAEs (89.7%) appeared within the first 3 months, none after 8 months. Most hypothyroid patients (63.2%) had previously been treated with a tyrosine kinase inhibitor (TKI). Logistic regression analysis showed that pretreatment with a TKI was a major predisposing factor for the development of hypothyroidism (OR 9.2, 95% CI: 1.4-59.9, P = .020). CONCLUSIONS: TAEs are common during anti-PD-1 therapy and usually occur within the first 3 months of treatment. This is the first study evaluating the impact of previous oncologic therapies on TAEs, identifying TKI as a major risk factor for the development of hypothyroidism in patients treated with anti-PD-1.

Clinical presentation, management and follow-up of 83 patients with Leydig cell tumors of the testis: a prospective case-cohort study.

STUDY QUESTION: When should 'not so rare' Leydig cell tumors (LCTs) of the testis be suspected, diagnosed, and treated? SUMMARY ANSWER: LCTs are more frequent than generally believed, are associated with male infertility, cryptorchidism and gynecomastia, and should be treated conservatively (in compliant patients) with active surveillance, which appears to be a safe alternative to surgical enucleation. WHAT IS KNOWN ALREADY: Increasing referrals for testicular imaging have led to an increase in findings of LCTs. The features and natural history of these tumors remain largely unknown, as the available studies are small and heterogeneous. LCTs were previously treated aggressively and follow-up data are lacking. STUDY DESIGN, SIZE, DURATION: A case-cohort study of consecutive patients diagnosed with LCTs over a 10-year period was prospectively enrolled from 2009 to 2018 and compared to matched cohorts of patients with seminomas or no testicular lesions screened in the same timeframe. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 9949 inpatients and outpatients referred for scrotal ultrasound, a total of 83 men with LCTs were included. Enrolled subjects underwent medical history and clinical examination and were asked to undergo routine blood tests, hormone investigations (FSH, LH, total testosterone, estradiol, inhibin B, sex hormone-binding globulin (SHBG), prolactin), and semen analysis. Patients who consented also underwent contrast-enhanced ultrasound, elastography, gadolinium-enhanced scrotal magnetic resonance imaging, and hCG stimulation test (5000 IU i.m.) with serum total testosterone and estradiol measured at 0, 24, 48, and 72 hours. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 83 patients diagnosed with LCTs were compared against 90 patients diagnosed with seminoma and 2683 patients without testicular lesions (NoL). LCTs were diagnosed by enucleation (48.2%), orchiectomy (13.3%), or clinical surveillance (38.5%). Testicular volume, sperm concentration, and morphology were lower (P = 0.001, P = 0.001, and P < 0.001, respectively) in patients with LCTs than in the NoL group. FSH, LH, and SHBG were higher and the testosterone/LH ratio was lower in LCTs than in the NoL group (P < 0.001). The LCT group showed higher SHBG (P = 0.018), lower sperm concentration (P = 0.029), and lower motility (P = 0.049) than the seminoma group. Risk factors for LCTs were cryptorchidism (χ2 = 28.27, P < 0.001), gynecomastia (χ2 = 54.22, P < 0.001), and low testicular volume (χ2 = 11.13, P = 0.001). Five cases were recurrences or bilateral lesions; none developed metastases during follow-up (median, 66 months). LIMITATIONS, REASONS FOR CAUTION: This study has some limitations. First, hCG and second-line diagnostic investigations were not available for all tumor patients. Second, ours is a referral center for infertility, thus a selection bias may have altered the baseline features of the LCT population. However, given that the comparison cohorts were also from the same center and had been managed with a similar protocol, we do not expect a significant effect. WIDER IMPLICATIONS OF THE FINDINGS: LCTs are strongly associated with male infertility, cryptorchidism, and gynecomastia, supporting the hypothesis that testicular dysgenesis syndrome plays a role in their development. Patients with LCTs are at a greater risk of endocrine and spermatogenesis abnormalities even when the tumor is resected, and thus require long-term follow-up and prompt efforts to preserve fertility after diagnosis.LCTs have a good oncological prognosis when recognized early, as tissue-sparing enucleation is curative and should replace orchiectomy. Conservative surgery and, in compliant patients, active surveillance through clinical and radiological follow-up are safe options, but require monitoring of testicular failure and recurrence. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Ministry of University and Research Grant MIUR 2015ZTT5KB. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: ALCeP trial (ClinicalTrials.gov Identifier: NCT01206270).

ENDOCRINOLOGY AND ADOLESCENCE: Dealing with transition in young patients with pituitary disorders.

INTRODUCTION: The transition age is the period between childhood to adulthood; it refers to a broad set of physical, cognitive and sociocultural modifications, arbitrarily defined as starting in late puberty and ending with full adult maturation. Pituitary disorders in adolescence represent a challenge that requires careful management during the transition to adult care. METHODS: Given the complexity of care of pituitary disorders in the transition age, we have reviewed the relevant medical literature focusing on aetiology, clinical manifestations, treatment strategies of GH deficiency (GHD), hypogonadotrophic hypogonadism (HH) in male and female adolescents, central hypothyroidism (CH), central adrenal insufficiency (CAI) and cranial diabetes insipidus (CDI) at this time. The objective of the present review is to provide an up-to-date evaluation of the transition period to evaluate the specific needs of adolescents with chronic pituitary disease in order to optimise their management. RESULTS: We provide an overview of current clinical management of GHD, HH, CH, CAI and CDI in the transition age. CONCLUSIONS: Specific changes occur in pituitary function during the transition period. A holistic approach including discussion of patients' concerns and emotional support should constitute a key component of managing pituitary disorders in adolescence. Special transition clinics where paediatric and adult endocrinologists work together, should be increasingly created and strengthened to bridge care, to promote continuity and adherence to treatment and to limit potential negative development, metabolic, skeletal and cardiovascular sequelae of discontinuity of care among adolescents with pituitary disorders.

MANAGEMENT OF ENDOCRINE DISEASE: Precision medicine in neuroendocrine neoplasms: an update on current management and future perspectives.

Neuroendocrine neoplasms (NENs) are traditionally considered as a single group of rare malignancies that originate from the highly spread neuroendocrine system. The clinical management is complex due to the high heterogeneity of these neoplasms in terms of clinical aggressiveness and response to the therapy. Indeed, a multidisciplinary approach is required to reach a personalization of the therapy, including cancer rehabilitation. In this review, we discuss the possibility to adopt a precision medicine (PM) approach in the management of NENs. To this purpose, we summarize current knowledge and future perspectives about biomarkers and preclinical in vitro and in vivo platforms, potentially useful to inform clinicians about the prognosis and for tailoring therapy in patients with NENs. This approach may represent a breakthrough in the therapy and tertiary prevention of these tumors.

Smoke, alcohol and drug addiction and male fertility.

In recent decades, the decline in human fertility has become increasingly more worrying: while therapeutic interventions might help, they are vexing for the couple and often burdened with high failure rates and costs. Prevention is the most successful approach to fertility disorders in males and females alike. We performed a literature review on three of the most common unhealthy habits - tobacco, alcohol and drug addiction - and their reported effects on male fertility. Tobacco smoking is remarkably common in most first-world countries; despite a progressive decline in the US, recent reports suggest a prevalence of more than 30% in subjects of reproductive age - a disturbing perspective, given the well-known ill-effects on reproductive and sexual function as well as general health. Alcohol consumption is often considered socially acceptable, but its negative effects on gonadal function have been consistently reported in the last 30 years. Several studies have reported a variety of negative effects on male fertility following drug abuse - a worrying phenomenon, as illicit drug consumption is on the rise, most notably in younger subjects. While evidence in these regards is still far from solid, mostly as a result of several confounding factors, it is safe to assume that cessation of tobacco smoking, alcohol consumption and recreational drug addiction might represent the best course of action for any couple trying to achieve pregnancy.

Dynamic contrast-enhanced and diffusion-weighted MR imaging in the characterisation of small, non-palpable solid testicular tumours.

OBJECTIVES: To explore the role of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), using semiquantitative and quantitative parameters, and diffusion-weighted (DW) MRI in differentiating benign from malignant small, non-palpable solid testicular tumours. METHODS: We calculated the following DCE-MRI parameters of 47 small, non-palpable solid testicular tumours: peak enhancement (PE), time to peak (TTP), percentage of peak enhancement (Epeak), wash-in-rate (WIR), signal enhancement ratio (SER), volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space volume fraction (Ve) and initial area under the curve (iAUC). DWI signal intensity and apparent diffusion coefficient (ADC) values were evaluated. RESULTS: Epeak, WIR, Ktrans , Kep and iAUC were higher and TTP shorter in benign compared to malignant lesions (p < 0.05). All tumours had similar ADC values (p > 0.07). Subgroup analysis limited to the most frequent histologies - Leydig cell tumours (LCTs) and seminomas - replicated the findings of the entire set. Best diagnostic cutoff value for identification of seminomas: Ktrans ≤0.135 min-1, Kep ≤0.45 min-1, iAUC ≤10.96, WIR ≤1.11, Epeak ≤96.72, TTP >99 s. CONCLUSIONS: DCE-MRI parameters are valuable in differentiating between benign and malignant small, non-palpable testicular tumours, especially when characterising LCTs and seminomas. KEY POINTS: • DCE-MRI may be used to differentiate benign from malignant non-palpable testicular tumours. • Seminomas show lower Ktrans, Kep and iAUC values. • ADC values are not valuable in differentiating seminomas from LCTs. • Semiquantitative DCE-MRI may be used to characterise small, solid testicular tumours.

Extrathyroidal Calcitonin Secreting Tumors: Pancreatic Neuroendocrine Tumors in Patients With Multinodular Goiter: Two Case Reports.

Calcitonin is the hallmark of medullary thyroid carcinoma. However, extrathyroidal neuroendocrine tumors can also release calcitonin.We report 2 cases of calcitonin-secreting pancreatic tumors found in asymptomatic patients with thyroid nodules referred to our center within 11 months.Case 1: A man initially referred for thyroid nodule characterization was found to have hypercalcitoninemia (>200 pg/mL) during non-neoplastic fine-needle aspiration.Case 2: A woman evaluated for liver metastasis was found to have hypercalcitoninemia and multinodular goiter.Our research emphasizes that marked hypercalcitoninemia in the presence of thyroid nodules is not necessarily due to medullary thyroid carcinoma; awareness of this could avoid unnecessary thyroidectomy. The lack of specific symptoms related to hypercalcitoninemia may be the reason that the prevalence of calcitonin-secreting pancreatic tumors is underestimated.

500 penile prostheses implanted by a surgeon in Italy in the last 30 years.

OBJECTIVES: The aim of our study was to report our experience with patients affected by Erectile Dysfunction (ED) and undergoing penile prosthetic implantation (PPI) in a single center by a single surgeon. MATERIAL AND METHODS: We retrospectively evaluated the clinical outcome of 500 patients (mean age: 51.5 years, range: 20-86 years) affected by ED and referred to our private andrological center from January 1984 to December 2013 who underwent penile prosthesis implantation, including the reported level of patient satisfaction. RESULTS: 182 silicone, 180 malleable, 18 monocomponent hydraulic and 120 multicomponents hydraulic prostheses were implanted by the same experienced surgeon. All patients were hospitalized for the procedure. All patients were evaluated immediately, 1 month (496 patients) and, for the great majority, every year after implantation. One hundred twenty five patients were lost to follow-up. Twenty two patients underwent revision surgery for complications in the postoperative period. The most serious postoperative complications were mechanical problems (45 patients, 9.0%) and infection (15 patients, 3%). Forty two (8.4%) prostheses were explanted. Overall, 80% (400/500) of patients were able to have sexual intercourse and were fully satisfied with the results. CONCLUSIONS: In our experience prosthetic surgery should be considered a good solution for men affected by ED and not responsive to other therapeutic solutions. Prosthetic surgery can be performed not only in large public hospitals but also in smaller private facilities.