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

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

Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non-palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non-palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non-palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non-neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6-97.0) and 85.5% specificity (95% CI 75.0-92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9-98.5) and 87.1% specificity (95% CI 70.2-96.4) in discriminating neoplasms from non-neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non-neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non-neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2 = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8-92.0) and 79.1% specific (95% CI 68.3-88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7-69.9) and 100% specific (95% CI 88.8-100) in discriminating non-neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non-neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven

Performance of the ForenSeqTM DNA Signature Prep kit on highly degraded samples

Next generation sequencing (NGS) is the emerging technology in forensic genomics laboratories. It offers higher resolution to address most problems of human identification, greater efficiency and potential ability to interrogate very challenging forensic casework samples. In this study, a trial set of DNA samples was artificially degraded by progressive aqueous hydrolysis, and analyzed together with the corresponding unmodified DNA sample and control sample 2800 M, to test the performance and reliability of the ForenSeqTM DNA Signature Prep kit using the MiSeq Sequencer (Illumina). The results of replicate tests performed on the unmodified sample (1.0 ng) and on scalar dilutions (1.0, 0.5 and 0.1 ng) of the reference sample 2800 M showed the robustness and the reliability of the NGS approach even from sub-optimal amounts of high quality DNA. The degraded samples showed a very limited number of reads/sample, from 2.9\u201310.2 folds lower than the ones reported for the less concentrated 2800 M DNA dilution (0.1 ng). In addition, it was impossible to assign up to 78.2% of the genotypes in the degraded samples as the software identified the corresponding loci as \u201clow coverage\u201d ( 50x). Amplification artifacts such as allelic imbalances, allele drop outs and a single allele drop in were also scored in the degraded samples. However, the ForenSeqTM DNA Sequencing kit, on the Illumina MiSeq, was able to generate data which led to the correct typing of 5.1\u201344.8% and 10.9\u201358.7% of 58 of the STRs and 92 SNPs, respectively. In all trial samples, the SNP markers showed higher chances to be typed correctly compared to the STRs. This NGS approach showed very promising results in terms of ability to recover genetic information from heavily degraded DNA samples for which the conventional PCR/CE approach gave no results. The frequency of genetic mistyping was very low, reaching the value of 1.4% for only one of the degraded samples. However, these results suggest that further validation studies and a definition of interpretation criteria for NGS data are needed before implementation of this technique in forensic genetics

Monitoring the quality of laboraties and the prevalence of resistance to antituberculosis drugs: Italy, 1998-2000

In 1998 a network of 20 regional tuberculosis (TB) laboratories (the Italian Multicentre Study on Resistance to Antituberculosis drugs (SMIRA) network) was established in Italy to implement proficiency testing and to monitor the prevalence of drug resistance nationwide. The network managed 30% of all TB cases reported in Italy each year. The aim of the present report is to describe: 1) the accuracy of drug-susceptibility testing in the network; 2) the prevalence of drug resistance for the period 1998-2000. Data were collected from the network laboratories. Sensitivity to streptomycin and ethambutol increased from the first survey (1998-1999) to the second survey (2000) from 87.7 to 91.9%. Specificity, predictive values for resistance and susceptibility, efficiency and reproducibility were consistent in both surveys. In previously untreated cases, the prevalence of multidrug-resistance was the same in both surveys (1.2%), while a slight decrease from the first to the second survey was observed for monoresistance to rifampicin (from 0.8 to 0.4%) and isoniazid (from 2.9 to 2%,). The significant association found between isoniazid resistance and immigration is a useful indicator for both clinicians managing individual tuberculosis cases and public health services planning control strategies

MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

https://pos.sissa.it/395/815/pdfPublished versio

Studio in doppio cieco, cross-over, controllato con placebo sugli effetti della somministrazione acuta di testosterone transdermico sulla funzione endoteliale in pazienti affetti da ipogonadismo grave

Introduzione Il tema riguardante la possibilità che il testosterone (T) possa avere effetti dannosi sul sistema cardiovascolare sta ricevendo una crescente attenzione da parte della comunità scientifica. Non vi sono studi che documentano l’effetto acuto della somministrazione di T transdermico sulla funzione endoteliale in soggetti affetti da ipogonadismo grave. In questo studio abbiamo indagato gli effetti acuti del T sulla funzione vascolare di uomini affetti da ipogonadismo grave. Materiali e metodi Sono stati arruolati 10 uomini (età 18-40 anni) affetti da ipogonadismo grave di diversa origine (valori medi di T = 0.6 ng/mL ± 0.3 DS) dopo un periodo di wash-out di 4 settimane. Lo studio, in doppio cieco, crossover controllato con placebo, con dose fissa di 80 mg di T transdermico gel, ha una durata di 4 giorni. Gli end-points primari sono le variazioni dell’RHI (Reactive Hyperemia Index) e dell’AI (Augmentation Index) determinate mediante tonometria arteriosa periferica (metodica Endopat 2000). Risultati 4 e 96 ore dopo la somministrazione transdermica di T in formulazione gel (Tostrex©), i livelli sierici di T totale sono fortemente incrementati, raggiungendo concentrazioni medie di 4 ± 2.1 ng/mL (p<0.0001) e di 2 ± 1.48 ng/mL (p<0.001) rispettivamente. Non sono state rilevate variazioni significative dei livelli circolanti di 17β-estradiolo e di SHBG. L’RHI è migliorato significativamente al tempo 4 ore (p<0.05), mentre l’AI è migliorato ai tempi 4 e 96 ore (p<0.01 e p<0.001, rispettivamente). In modo interessante è stata trovata una relazione diretta tra Δ-T totale e Δ-RHI (p<0.01 r=0.37). Conformemente è stata trovata una relazione inversa tra Δ-T totale e Δ-AI (p<0.01 r=0.35), anche dopo aggiustamento per la frequenza cardiaca (Δ-AI@75 p<0.01 r=-0.38). Non sono stati riportati eventi avversi. Conclusioni La somministrazione di dosi fisse di T transdermico causa una vasodilatazione acuta ed un miglioramento della rigidità arteriosa probabilmente dovuta ad azioni non-genomiche del T. La risposta endoteliale è stata quanto più pronunciata quanto più elevati i livelli di T ottenuti