Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

PURPOSE: To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). METHODS: Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. RESULTS: A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. CONCLUSION: Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Micro-RNA-371a-3p in Germ Cell Testicular Tumors on Diagnosis: A Prospective Case-Control Study in Turkish Population.

PURPOSE: We aimed to evaluate the diagnostic sensitivity and specificity of the miRNA-371a-3p for the primary diagnosis of germ cell tumors (GCT) and to investigate its relationship with pathological factors and clinical stage in the Turkish population. MATERIALS AND METHODS: In this prospective study, a total of 60 patients with GCTs, and 40 healthy male controls were examined for serum levels of miRNA-371a-3p before orchiectomy and again two weeks after surgery. The miRNA-371a-3p, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (bHCG) levels in the preoperative and postoperative periods were compared at different clinical stages. Receiver operating characteristics curve analyses were performed to determine the sensitivity and specificity of miRNA-371a-3p. Clinical and pathological factors such as clinical stage (CS), tumor size, histology, rete testis invasion, and lymphovascular invasion, potentially impacting miRNA-371a-3p expression levels (relative quantity, RQ), were evaluated statistically. RESULTS: The sensitivity of miR-371a-3p in GCT patients was 98.3%, and the specificity was 95% (AUC = 0.997 [95%Cl:0.99-1], p < .001). miR-371a-3p expression was not detected in two patients with teratoma. The median miR-371a-3p RQ was 489 times in GCT and 2.2 times in the Control group (p < .001). In the postoperative period, there was a significant decrease in AFP and bHCG levels in all CS-1 (p = .01) and 30% of the other CS (p = .3). Throughout this time there was a decrease of 19 times at the miR-371a-3p RQ in CS-1(p < .001) and 1.6 times in the other CS (p < .001). The miR-371a-3p RQs were correlated with tumor size and CS. CONCLUSION: The miR-371a-3p seems to have higher diagnostic accuracy than classical serum tumor markers in GCT.

Molecular and histopathological characterization of seminoma patients with highly elevated human chorionic gonadotropin levels in the serum.

Approximately 30% of seminoma (SEM) patients present with moderately elevated human chorionic gonadotropin (hCG) levels at first diagnosis. In case of high hCG serum levels, the presence of a non-SEM component, i.e. choriocarcinoma (CC), may be assumed. To characterize cases described as pure seminoma with high serum hCG levels, tissue samples and DNA were analyzed. Patient files from an international registry were screened for patients with SEM and extraordinarily high hCG serum levels. IHC and qRT-PCR analysis was performed for markers of SEM, embryonal carcinoma (EC) and CC/trophoblast cells. The cell lines TCam-2 (SEM), 2102EP, NCCIT, NT2/D1 (EC) and JAR, JEG3 and BeWo (CC) were included for comparison. Of 1031 SEM patients screened, 39 patients (3.7%) showed hCG serum levels > 1000 U/l. Of these, tumor material for IHC and RNA for qRT-PCR was available from n = 7 patients and n = 3 patients, respectively. Median pre-orchiectomy serum hCG level was 5356 U/l (range: 1224-40909 U/L). Histopathologically, all investigated samples were classified as SEM with syncytiotrophoblast sub-populations. SEM cells were SALL4+ / OCT3/4+ / D2-40+, while syncytiotrophoblast cells were hCG+ / GATA3+ / p63+ and SOX2-/CDX2-. qRT-PCR analysis detected trophoblast stem cell markers CDX2, EOMES and TFAP2C as well as the trophectoderm-specifier TEAD4, but not GATA3. Additionally, SOX17 and PRAME, but not SOX2, were detected, confirming the pure SEM-like gene expression signature of the analyzed samples. In conclusion, excessively increased hCG serum levels can appear in patients with pure SEM. To explain detectable hCG serum levels, it is important to diagnose the subtype of a SEM with syncytiotrophoblasts.

Low-grade inflammation in survivors of childhood cancer and testicular cancer and its association with hypogonadism and metabolic risk factors.

BACKGROUND: In childhood (CCS) and testicular cancer (TCS) survivors, low-grade inflammation may represent a link between testosterone deficiency (hypogonadism) and risk of metabolic syndrome. We aimed to study levels of inflammatory markers in CCS and TCS and the association with hypogonadism and future cardio-metabolic risk factors. METHODS: Serum levels of inflammatory markers and testosterone were analyzed in CCS (n = 90), and TCS (n = 64, median time from diagnosis: 20 and 2.0 years, respectively), and in controls (n = 44). Differences in levels between patients and controls were calculated using univariate analysis of variance. T-test and logistic regression were applied to compare levels of cardio-metabolic risk factors and odds ratio (OR) of hypogonadism and metabolic syndrome in low and high inflammatory marker groups after 4-12 years of follow up. Adjustment for age, smoking, and active cancer was made. RESULTS: TCS and CCS, as compared to controls, had 1.44 (95%CI 1.06-1.96) and 1.25 (95 CI 1.02-1.53) times higher levels of IL-8, respectively. High IL-6 levels were associated with hypogonadism at baseline (OR 2.83, 95%CI 1.25-6.43) and the association was stronger for high IL-6 combined with low IL-10 levels (OR 3.10, 95%CI 1.37-7.01). High IL-6 levels were also associated with higher BMI, waist circumference, insulin, and HbA1c at follow up. High TNF-α was associated with higher diastolic blood pressure. No individual inflammatory marker was significantly associated with risk of metabolic syndrome at follow up. High IL-6 combined with low IL-10 levels were associated with risk of metabolic syndrome (OR 3.83, 95%CI 1.07-13.75), however not statistically significantly after adjustment. CONCLUSION: TCS and CCS present with low-grade inflammation. High IL-6 levels were associated with hypogonadism and cardio-metabolic risk factors. Low IL-10 levels might reinforce the IL-6 mediated risk of developing metabolic syndrome.

Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1.

PURPOSE: Lymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels. METHODS: M371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors. RESULTS: Postoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045). CONCLUSION: Postoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation.

Production of 11-Oxygenated Androgens by Testicular Adrenal Rest Tumors.

CONTEXT: Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a direct quantification of steroidogenesis from these tumors has not been yet done. OBJECTIVE: We aimed to define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART. METHODS: Using liquid chromatography-tandem mass spectrometry, steroids were measured in left (n = 7) and right (n = 4) spermatic vein and simultaneously drawn peripheral blood (n = 7) samples from 7 men with 21OHD and TART. For comparison, we also measured the peripheral steroid concentrations in 5 adrenalectomized patients and 12 age- and BMI-matched controls. Additionally, steroids were quantified in TART cell- and adrenal cell-conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation. RESULTS: Compared with peripheral blood from 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11ß-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11ß-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone and lower levels of A4 and 11OHA4 after ACTH stimulation compared with adrenal cells, indicating ACTH-induced production of testosterone in TART. CONCLUSION: In patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic vs peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive.

When is a Seminoma not a Seminoma? The Incidence, Risk Factors and Management of Patients With Testicular Seminoma With Discordant Elevated Serum Alpha-fetoprotein.

OBJECTIVE: To describe the incidence, clinical and demographic factors, and treatment patterns associated with discordant elevated alpha-fetoprotein (AFP) findings in patients with pure seminomatous histology. METHODS: We queried the National Cancer Database to identify patients with testicular germ cell tumors (GCT) diagnosed in 2011-2015. Patients were grouped based on histologic diagnosis and pre-operative serum AFP level. RESULTS: Of 18,616 patients diagnosed with testicular GCT, 53% (N = 9,849) had pure seminomatous histology, of whom 8.3% (N = 821) had an elevated serum AFP pre-operatively. Non-white patients with seminoma were more likely to have a pre-op elevated AFP (OR 1.42; 95% CI: 1.10-1.83); patients treated at higher volume centers were less likely to have a pre-op elevated AFP (0.66, 95% CI: 0.53-0.83). Patients with seminoma with elevated AFP received adjuvant radiation more frequently than those with NSGCT (Stage I: 15% vs 0.2%, P <.01; Stage II: 21.9% vs 0.1%, P <.01) and less frequently underwent retroperitoneal lymph node dissection (RPLND) (Stage 1: 1.9% vs 11.1% P <.01; Stage II: 8.8% vs 17.4%, P <.01). CONCLUSION: The detection of elevated serum alpha-fetoprotein (AFP) in patients with pure seminomatous testicular germ cell tumors (GCT) is a discordant finding that implies the presence of occult non-seminomatous GCT (NSGCT) elements. 8% of patients with pure seminomatous GCTs had diagnostically discordant elevated pre-operative AFP levels. Despite recommendations to manage these patients as NSGCT, patients with seminoma and elevated AFP were managed in a fashion comparable to those with seminoma and normal AFP levels.

Cognitive changes and brain connectomes, endocrine status, and risk genotypes in testicular cancer patients-A prospective controlled study.

OBJECTIVE: Previous research has indicated cognitive decline (CD) among testicular cancer patients (TCPs), even in the absence of chemotherapy, but little is known about the underlying pathophysiology. The present study assessed changes in cognitive functions and structural brain connectomes in TCPs and explored the associations between cognitive changes and endocrine status and hypothesized risk genotypes. METHODS: Thirty-eight newly orchiectomized TCPs and 21 healthy controls (HCs) comparable to TCPs in terms of age and years of education underwent neuropsychological testing, structural MRI, and a biological assessment at baseline and 6 months later. Cognitive change was assessed with a neuropsychological test battery and determined using a standardized regression-based approach, with substantial change defined as z-scores ≤-1.64 or ≥1.64. MRI scans and graph theory were used to evaluate changes in structural brain connectomes. The associations of cognitive changes with testosterone levels, androgen receptor gene (AR) CAG repeat length, and genotypes (APOE, COMT, and BDNF) were explored. RESULTS: Compared with HCs, TCPs showed higher rates of substantial decline on processing speed and visuospatial ability and higher rates of substantial improvement on verbal recall and visuospatial learning (p < 0.05; OR = 8.15-15.84). Brain network analysis indicated bilateral thalamic changes in node degree in HCs, but not in TCPs (p < 0.01). In TCPs, higher baseline testosterone levels predicted decline in verbal memory (p < 0.05). No effects were found for AR CAG repeat length, APOE, COMT, or BDNF. CONCLUSIONS: The present study confirms previous findings of domain-specific CD in TCPs following orchiectomy, but also points to domain-specific improvements. The results do not indicate changes in brain connectomes or endocrine status to be the main drivers of CD. Further studies evaluating the mechanisms underlying CD in TCPs, including the possible role of the dynamics of the hypothalamic-pituitary-gonadal axis, are warranted.

Serum miR371 in testicular germ cell cancer before and after orchiectomy, assessed by digital-droplet PCR in a prospective study.

MicroRNA-371a-3p (miR371) has been suggested as a sensitive biomarker in testicular germ cell cancer (TGCC). We aimed to compare miR371 with the classical biomarkers α-fetoprotein (AFP) and ß-human chorionic gonadotropin (hCGß). Overall, 180 patients were prospectively enrolled in the study, with serum samples collected before and after orchiectomy. We compared the use of digital droplet PCR (RT-ddPCR) with the quantitative PCR used by others for detection of miR371. The novel RT-ddPCR protocol showed high performance in detection of miR371 in serum samples. In the study cohort, miR371 was measured using RT-ddPCR. MiR371 detected CS1 of the seminoma and the non-seminoma sub-types with a sensitivity of 87% and 89%, respectively. The total sensitivity was 89%. After orchiectomy, miR371 levels declined in 154 of 159 TGCC cases. The ratio of miR371 pre- and post-orchiectomy was 20.5 in CS1 compared to 6.5 in systemic disease. AFP and hCGß had sensitivities of 52% and 51% in the non-seminomas. MiR371 is a sensitive marker that performs better than the classical markers in all sub-types and clinical stages. Especially for the seminomas CS1, the high sensitivity of miR371 in detecting TGCC cells may have clinical implications.

Tumor markers and 18F-FDG PET/CT after orchiectomy in seminoma: Is there any correlation?

OBJECTIVE: The aim of our study was to analyze the potential relationship between tumor markers and 18F-fluorodoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) results in patients affected by seminoma. MATERIAL AND METHODS: 65 18F-FDG PET/CT scans of 41 patients with diagnosis of seminoma were analyzed and compared to alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). PET/CT studies were analyzed qualitatively and measuring the maximum and mean standardized uptake value body weight max (SUVbwmax, SUVbwmean), maximum SUV lean body mass (SUVlbm), maximum SUV body surface area (SUVbsa), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of hypermetabolic lesions. All values were compared with serum markers. RESULTS: 31 PET/CT studies were true negative, 28 true positive, 6 false positive and 0 false negative with sensitivity of 100%, specificity of 84%, negative predictive value of 100%, positive predictive value of 82% and accuracy of 91%. No correlation between PET results and tumor marker levels was found and also between AFP and PET/CT semiquantitive parameters. All semiquantitative PET parameters were significantly related to hCG level. CONCLUSIONS: 18F-FDG PET/CT has good accuracy in evaluating patients with relapsed seminoma. HCG levels were significantly correlated with metabolic PET/CT parameters.

Testicular Tumor Markers in the Spermatic Vein - Correlation to Pathology, Stage and Outcome.

OBJECTIVE: To report our findings in patients with determination of testicular tumor markers from the vena spermatica during inguinal orchiectomy. METHODS: In a retrospective setting, data of patients who underwent inguinal orchiectomy between January 2004 and December 2014 were analyzed. Cubital and testicular vein tumor markers were assessed and correlated to histology, clinical stage and outcome. RESULTS: A total of 90 patients (seminomatous: n = 53, non-seminomatous: n = 37) with a median age of 37 years were included. The mean follow-up was 109 months. Overall, 60% (n = 54) of patients had one or more positive tumor marker level in the cubital vein vs 88.9% (n = 80) in the testicular vein. Median tumor marker levels of hCGß in cubital and testicular vein were 1.9 U/l and 30.8U/l; the respective values for AFP were 2.9ng/ml and 2.4ng/ml and for hPLAP 49.9 mU/l and 418.9 mU/l. Differences in cubital vs testicular vein positivity were stage dependant and highest for pT1. Patients with seminomatous tumors had peripheral positivity of 59.3% vs 88.9% in the testicular vein (P = 0.003); in non-seminomatous patients the respective values were 61.1% and 88.9% (P = 0.02). All recurrent cancer patients under active surveillance (n = 5) were positive in the testicular vein. CONCLUSION: Virtually all testicular cancers shed tumor markers in the circulation. Differences in marker positivity (testicular vs testicular vein) were stage dependent (greatest in pT1), largely independent of histology and highest for hCGß. The prognostic value of testicular vein sampling remains speculative.

Liquid Biopsies in the Clinical Management of Germ Cell Tumor Patients: State-of-the-Art and Future Directions.

Liquid biopsies constitute a minimally invasive means of managing cancer patients, entailing early diagnosis, follow-up and prediction of response to therapy. Their use in the germ cell tumor field is invaluable since diagnostic tissue biopsies (which are invasive) are often not performed, and therefore only a presumptive diagnosis can be made, confirmed upon examination of the surgical specimen. Herein, we provide an overall review of the current liquid biopsy-based biomarkers of this disease, including the classical, routinely used serum tumor markers-the promising microRNAs rapidly approaching the introduction into clinical practice-but also cell-free DNA markers (including DNA methylation) and circulating tumor cells. Finally, and importantly, we also explore novel strategies and challenges for liquid biopsy markers and methodologies, providing a critical view of the future directions for liquid biopsy tests in this field, highlighting gaps and unanswered questions.

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

PURPOSE: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. CONCLUSIONS: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Post-treatment persistent alpha-fetoprotein elevation in a patient with testicular cancer.

BACKGROUND: Persistent alpha-fetoprotein elevation in a patient following orchiectomy and chemotherapy for non-seminomatous testicular germ cell tumor is a rare condition when persistence of the tumor and false positivity of tumor marker elevation has to be differentiated. This situation often leads to over-treatment and potential toxicity with adverse events which can be severe. CASE: A case of a patient with the abovementioned disease and course of treatment is presented. As no radiological signs of the disease were present and the level of alpha-fetoprotein was mild and stable, the tumor marker elevation was evaluated as false positive. Possible causes of the tumor marker elevation were identified as other serious diseases are known to cause such a false positivity. The level of alpha-fetoprotein remained unchanged despite alcohol abstinence and hepatoprotective treatment by silymarin. Hepatitis B and C serological tests were negative, and no other malignant tumor was identified. Finding of terminal ileum circular wall thickening and stratification with a reaction of surrounding visceral fat and lymph nodes persisting in CT scans suggests the presence of inflammatory bowel disease, possibly explaining the alpha-fetoprotein elevation. The patient has no evidence of the disease more than 14 months after the end of chemotherapy treatment with no change in the elevation of alpha-fetoprotein. CONCLUSION: After the treatment, when no other indication of testicular cancer than an elevated alpha-fetoprotein level is present, the patient should be managed by ongoing surveillance.

Reliability of Serum Tumor Marker Measurement to Diagnose Recurrence in Patients with Clinical Stage I Nonseminomatous Germ Cell Tumors Undergoing Active Surveillance: A Systematic Review.

PURPOSE: Men with nonseminomatous germ cell tumors of the testicle without evidence of residual disease after radical orchiectomy (clinical stage I) are increasingly managed with active surveillance. The guideline-recommended cornerstones of surveillance are conventional serum tumor markers and computerized tomography. The reliability of serum tumor markers as a tool to diagnose early recurrence of clinical stage I nonseminomatous germ cell tumors is unclear. The study objective was to conduct a systematic review of the currently available evidence assessing the reliability of serum tumor markers as a test to diagnose recurrence in patients with clinical stage I nonseminomatous germ cell tumors under active surveillance. MATERIALS AND METHODS: A systematic review was conducted in accordance with PRISMA guidelines, with no language or date restrictions. Studies were included that readily identified the tumor marker status of patients with clinical stage I nonseminomatous germ cell tumors who had a recurrence on active surveillance. The primary outcome was marker positivity at the time of recurrence. Risk of bias assessment was undertaken. RESULTS: A total of 2,157 studies were identified and independently screened by 2 reviewers, with 37 studies ultimately being included. A relatively high risk of bias was identified among the studies, with the vast majority being retrospective series. The total population for the included studies was 8,545 patients with clinical stage I nonseminomatous germ cell tumors managed by active surveillance, and 2,254 ultimately relapsed. Serum tumor markers were elevated in 28% to 75% of patients at the time of recurrence and were the only indication of recurrence in 4% to 39%. The unavailability of patient-level data is the major limitation to the present findings. CONCLUSIONS: In patients with clinical stage I nonseminomatous germ cell tumors managed by active surveillance, the use of serum tumor markers cannot obviate the need for computerized tomography. More reliable serum markers are needed in order to limit radiation exposure for these patients.

[Leydig Cell Tumor in a Patient with Contralateral Cryptorchidism: A Rare Association]. / Tumor de Células de Leydig num Doente com Criptorquidia Contralateral: Uma Associação Rara.

Gynecomastia is a frequent sign that may be physiological or caused by various benign or malignant diseases. In rare cases, it may be caused by testicular tumors. We describe a case of progressive gynecomastia at age 20 due to a Leydig cell tumor of the right testicle in a patient with a previous history of left-sided cryptorchidism. The patient underwent orchidectomy and testicular prosthesis placement, with subsequent improvement of gynecomastia and normalization of estrogen. Our case, in addition to demonstrating that gynecomastia may regress if the underlying cause is treated in a timely manner, shows that cryptorchidism may be related with the development of Leydig cell tumors in the same way as it is in other testicular tumors.

A ginecomastia é um sinal frequente que pode ser fisiológica ou causada por várias doenças benignas ou malignas. Em casos raros pode ser originada por tumores testiculares. Nós descrevemos um caso de ginecomastia de início rapidamente progressivo aos 20 anos por um tumor de células de Leydig do testículo direito em doente com história pregressa de criptorquidia esquerda. O doente foi submetido a orquidectomia e colocação de prótese testicular assistindo-se a melhoria da ginecomastia e normalização dos valores de estrogénio. O nosso caso, além de demonstrar que a ginecomastia pode regredir se a causa subjacente for tratada atempadamente, mostra que a criptorquidia poderá estar associada ao aparecimento de tumores de células de Leydig à semelhança do que acontece com outros tumores testiculares.

Impact of circulating microRNA test (miRNA-371a-3p) on appropriateness of treatment and cost outcomes in patients with Stage I non-seminomatous germ cell tumours.

OBJECTIVES: To determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost-effectiveness for patients with Stage I non-seminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: A decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2-4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA-based approach using the standard model + post-orchidectomy serum miR-371a-3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer. RESULTS: Utilising the miRNA marker-based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision-making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA-based approach remained cost-effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease. CONCLUSION: A miRNA-based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost-effective manner. Identification of residual teratoma-only remains an issue. Prospective studies are necessary to validate these findings.

Real-World Application of Pre-Orchiectomy miR-371a-3p Test in Testicular Germ Cell Tumor Management.

PURPOSE: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy. MATERIALS AND METHODS: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoprotein/ß-human chorionic gonadotropin/lactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis. RESULTS: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test. CONCLUSIONS: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.

Comparison of inflammation-based prognostic scores as predictors of survival outcomes in patients with germ cell tumors.

PURPOSE: The aim of this study was to compare the prognostic value of pretreatment inflammation-based scoring systems in terms of overall survival (OS) and progression-free survival (PFS) in patients with germ cell tumors (GCTs) receiving bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: We evaluated 63 patients with GCTs retrospectively. The Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio, prognostic index, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index, and albumin-to-globulin ratio (AGR) were measured in all patients before chemotherapy. To assess the predictive ability of each scoring system, areas under the receiver operating characteristic curve were calculated, and multivariate analysis was performed to identify associations between the predictive scores and OS. RESULTS: Of all the inflammation-based scoring systems, the GPS had the greatest area under the curve (0.847) for predicting OS, followed by the PNI (0.829) and AGR (0.810). Kaplan-Meier analyses revealed that the GPS, PNI, and AGR were significantly associated with OS, whereas the GPS, PLR, and PNI were significantly associated with PFS. In the multivariate analysis, the GPS was an independent predictor of OS and PFS. CONCLUSIONS: We demonstrated that the GPS was the most valuable biomarker of OS and PFS in patients with GCTs.