Explore the vast range of titles available.

Background: miRNAs are small noncoding RNA molecules that can be released into body fluids. Germ cell tumours (GCTs) overexpress miRNAs of the miR-371-3 cluster. Thus, serum levels of these miRNAs may correlate with tumour load. Methods: miRNAs of the miR-371-3 cluster were quantified in cubital vein blood samples of 20 GCT patients with clinical stage 1, and of 4 patients with advanced stages before and after treatment. In six patients testicular vein blood (TVB) was examined additionally. Seventeen healthy males served as controls. Likewise, expression of miRNAs in 15 matching tumour specimens was measured. Results: In all patients, serum levels of miRNAs 371-3 were much higher than in controls. In stage 1, levels decreased postoperatively 336.7-fold, 7.4-fold, and 7.7-fold for miRNAs 371a-3p, 372, and 373-3p, respectively ( P <0.01). Also, in those cases with advanced disease levels dropped to the normal range after completion of treatment. miR-371-3 levels in TVB exceeded those in peripheral blood in all cases. Expression of miR-371a-3p was also documented in tumour tissue. However, no correlation was found regarding the extent of miRNA expression in tissue and the values measured in matching serum. Conclusion: Thus, miR-371a-3p serum level appears to be a useful biomarker in GCTs.

Background The microRNA-371a-3p (M371) is a sensitive novel serum biomarker of testicular germ cell tumours (GCTs) and a certified test is available for consistent clinical testing. In view of the well-known biological analogies of GCTs and embryogenesis, we hypothesized that the marker substance M371 is also present in serum of pregnant women. The goal of this report was to analyse maternal serum for M371. Materials and methods M371 serum levels were measured in 36 third-trimester pregnant women. Control groups consisted of 12 non-pregnant young women, 12 healthy young males, and 12 patients with GCTs. M371 levels were measured by quantitative real time PCR using the certified M371 test with the standard cutoff of RQ = 5. Statistical methods involved receiver operating characteristics (ROC) analysis with Youden index analysis, and statistical comparisons of median serum levels of patients with those of controls as well as for comparisons of subgroups of patients according to age and infant sex. Results All pregnant women had measurable M371 levels, with 83.3% of the patients having elevated levels above the cutoff, while traces below cutoff were detected in the remainder. Healthy female and male controls were both below cutoff. ROC analysis revealed a 100% sensitivity and 100% specificity of the test when the cutoff of RQ = 0.4 defined by Youden index analysis was employed. The median level in pregnant women was significantly lower than that in GCT patients (10.8 [interquartile range 6.1–20.3] versus RQ = 139.5 [IQR 54.9–630.3], p  < 0.001). Individual M371 levels were not associated with patient age and with infant sex. Conclusions The evidence for elevated levels of microRNA-371a-p in maternal serum is a novel finding. This result accords with the various analogies between GCTs and embryogenesis documented previously. The finding supports the view that cells involved in human reproduction share epigenetic features with human embryonic stem cells. Further studies are required to explore if this finding could be utilized clinically.

Clinical epidemiology is sometimes called the basic science of clinical medicine. In terms of the pathogenesis of testicular germ cell tumors (GCTs), clinical epidemiology analyzes suspected risk factors. The present review highlights the risk factors established so far and briefly summarizes those factors currently under investigation. In analogy to the methods of evidence based medicine, this review attributes levels of evidence to each of the putative risk factors. Level I represents highest quality of evidence while level V denotes the lowest level. So far, undescended testis (UDT), contralateral testicular GCT and familial testis cancer are established risk factors attaining high levels of evidence (levels I-III a). In a meta-analysis of 21 studies exploring the association of UDT with GCT risk, an over-all relative risk (RR) of 4.8 (95% confidence interval 4.0-5.7) was found. Contralateral testicular GCT involves a roughly 25-fold increased RR of GCT, while familial testis cancer constitutes a RR of 3-10. Infertility, testicular atrophy, and twin-ship represent risk factors with lesser levels of evidence (level III a). There is also some evidence for HIV infection being a predisposing factor for GCT (level IV a). Scrotal trauma is probably not associated with GCT risk. The estrogen excess theory implies high estrogen levels during the first trimester of pregnancy. As a consequence, primordial germ cells lose track of the normal developmental line and transform into premalignant cells that later become testicular intraepithelial neoplasia (TIN), the precursor of full-blown testicular GCT. Surrogate parameters for high gestational estrogen levels are investigated in case control studies. Such factors are maternal age >30 years, first-born, low birth weight, maternal breast cancer, high sex-ratio of siblings. So far, the sum of evidence is promising but still conflicting (especially for level III b). Another novel theory is the childhood nutrition hypothesis. This concept postulates a modulating or \"catalyzing\" effect by high dietary intake during childhood on the pathogenesis of testicular GCT. A surrogate parameter of early childhood nutrition is adult height. So far, 12 controlled studies have looked to the possible association of attained height and GCT risk of which six demonstrated a significant association. Thus, the sum of evidence corresponds to level III b. This concept is appealing because it would explain several hitherto unexplained epidemiological features of GCT.

Purpose Diagnosing germ cell neoplasia in situ (GCNis) can detect germ cell tumours (GCTs) at the pre-invasive stage. To date, testicular biopsy with the potential of surgical complications is the only way of safely diagnosing GCNis. Recently, microRNAs (miRs) 371-3, and miR 367 were shown to be valuable serum biomarkers of GCTs. We explored the usefulness of these candidate miRs as a marker for GCNis. Methods 27 patients with GCNis and no concomitant GCT were enrolled. All patients underwent measuring serum levels of miR-371a-3p and miR-367-3p before treatment, 11 had repeat measurement after treatment, 2 also had testicular vein blood examinations. Serum levels were measured by quantitative PCR. In addition, four orchiectomy specimens of patients with GCT were examined immunohistochemically and by in situ hybridization (ISH) with a probe specific for miR-371a-3p to look for the presence of this miR in GCNis cells. Results The median serum level of miR-371a-3p was significantly higher in patients with GCNis than in controls, miR-367 levels were not elevated. Overall, 14 patients (51.9%) had elevated serum levels of miR-371a-3p. The highest levels were found in patients with bilateral GCNis. Levels in testicular vein serum were elevated in both of the cases. After treatment, all elevated levels dropped to normal. In two orchiectomy specimens, miR-371a-3p was detected by ISH in GCNis cells. Conclusions Measuring miR-371a-3p serum levels can replace control biopsies after treatment of GCNis. In addition, the test can guide clinical decision making regarding the need of testicular biopsy in cases suspicious of GCNis.

Background Primary retroperitoneal lymph node dissection (RPLND) ultimately lost its role as the standard management of clinical stage (CS) 1 nonseminomatous (NS) testicular germ cell tumours (GCTs) in Europe when the European Germ Cell Cancer Consensus Group released their recommendations in 2008. Current guide-lines recommend surgery only for selected patients but reasons for selection remain rather ill-defined. We evaluated the practice patterns of the management of CS1 patients and looked specifically to the role of RPLND among other standard treatment options. Methods We retrospectively evaluated the treatment modalities of 75 consecutive patients treated for CS1 NS at one centre during 2008–2017. The patients undergoing RPLND were selected for a closer review. Particular reasons for surgery, clinical features of patients, and therapeutic outcome were analyzed using descriptive statistical methods. Results Twelve patients (16%) underwent nerve-sparing RPLND, nine surveillance, 54 had various regimens of adjuvant chemotherapy. Particular reasons for surgery involved illnesses precluding chemotherapy ( n  = 2), patients´ choice ( n  = 4), and teratomatous histology of the primary associated with equivocal radiologic findings ( n  = 6). Five patients had lymph node metastases, two received additional chemotherapy. Antegrade ejaculation was preserved in all cases. One patient had a grade 2 complication that was managed conservatively. All RPLND-patients remained disease-free. Conclusions Primary RPLND is a useful option in distinct CS1 patients, notably those with concurrent health problems precluding chemotherapy, and those with high proportions of teratoma in the primary associated with equivocal radiological findings. Informed patient’s preference represents another acceptable reason for the procedure. RPLND properly suits the needs of well-selected patients with CS1 nonseminoma and deserves consideration upon clinical decision-making.

Background Testicular epidermoid cysts (TECs) are rare benign testicular neoplasms. As TECs are rarely associated with germ cell tumours (GCTs), the understanding of biological behaviour and clinical management of TEC is unresolved. Methods We retrospectively searched the files of patients treated for testicular neoplasms and germ cell cancer in the time from 2000 to 2017. Those with TEC were subjected to closer review looking to clinical and histological features, and to results from imaging with ultrasonography (US), contrast enhanced sonography (CEUS) and magnetic resonance imaging (MRI). Results Among 589 patients undergoing surgery for testicular tumour, nine simple TECs were identified (1.5, 95% confidence intervals 0.53–2.50%). Median age was 26 years. Imaging revealed sharply demarcated roundish lesions with avascular central areas. Eight patients underwent testis-sparing excision with no recurrence ensuing. One had orchiectomy because of large size of the mass. Histologically, TECs consisted of cornifying squamous cell epithelium and no accompanying germ cell neoplasia in situ. Two additional cases (0.3% of all) required orchiectomy because these TECs were associated with ipsilateral GCT. Conclusions TEC is usually a benign lesion that can safely be diagnosed with US, CEUS and MRI due to its roundish shape and its avascular centre. Histologically, this TEC corresponds to the prepubertal-type teratoma unrelated to germ cell neoplasia in situ of the 2016 WHO classification. The other subtype of TEC that is associated with invasive GCT represents a teratoma of postpubertal-type. From a clinical point of view it could be easier to differentiate between a “simple TEC” which is benign (prepubertal type) and a “complex TEC” which is malignant because of its association with invasive GCT.

PurposeClinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS.MethodsData from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher’s exact and Chi-square test.ResultsOut of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death.ConclusionAround 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

Purpose: Second malignancies in patients with pure testicular seminoma were studied in order to look for adverse late effects of treatment and to study the significance of second malignancies during follow-up. Patients, Methods: In a multicentric investigation, 839 consecutive patients with pure testicular seminoma were observed for a median follow-up of 3.9 years. Thirty-seven patients had been excluded from the study because they already had had either a contralateral testicular germ cell tumor or another malignancy. 758 patients received radiotherapy, 76 underwent chemotherapy, 5 had surveillance only. The expected rate of second cancers was calculated according to the data of the cancer registry of Saarland, Germany. Results: Twenty-two second cancers (13 contralateral testicular tumors, 9 extratesticular malignancies) were recorded. The overall risk of having a second cancer was RR = 4.8 (95% CI 3.0–7.3). The risk of having a subsequent testicular tumor is RR = 44.8 (95% Cl 23.9–76.7). 1.1% of the patients developed a nontesticular second tumor. The risk of having a nontesticular second cancer is RR = 2.1 (95% CI 1.0–4.0). A significantly increased risk was observed for renal cell cancer as well (RR = 12.5; 95% Cl: 1.5–45.1). Increased RR without reaching statistical significance were found for rectal cancer (RR = 5.0; 95% Cl: 0.1–27.9) and non-Hodgkin lymphoma (RR = 6.7; 95% CI 0.2–37.1). None of the second cancers were directly located within the radiation field; 5 neoplasms arose at the border of the radiation field. Conclusions: This study confirmed the increased risk of having a second testicular germ cell cancer. There is also a small but definitely increased overall risk of having a nontesticular second cancer. Treatment-unrelated factors – possibly genetic predisposition – must be considered for a substantial number of these second tumors, since in the present study the follow-up was rather short and most of the second cancers were located outside of the radiation fields. In particular, the association of renal cancer with testicular cancer appears to be a more than chance occurrence. Second cancer is a real hazard following treatment of testicular cancers and should always be considered during follow-up.

The pathogenesis of testicular germ cell tumours (GCTs) is potentially influenced by high-energy nutrition during infancy. As adult height is a proxy for childhood nutrition, we investigated the role of nutrition in GCT pathogenesis by comparing stature of patients with healthy men. In a matched case–control study, 6415 patients with GCT were compared with healthy army conscripts (1:6 matching modus) with regard to height (cm) and body mass index (BMI; kg/m 2 ). Statistical analysis involved tabulation of descriptive height measures and BMI. Conditional logistic regression models were used to quantify the association of GCT with height, with odds ratios (OR) adjusted for BMI. The literature was searched for studies on stature in GCT patients. Body size is significantly associated with risk of GCT, very tall men (>195 cm) having a GCT risk of OR=3.35 (95% confidence intervals (CI): 2.88–3.90; adjusted). Short stature is protective (OR=0.798; 95% CI: 0.68–0.93). Both histologic subgroups are associated with tallness. Of 16 previous reports, 7 were confirmative, 5 had null and 4 equivocal results. The association of stature with GCT risk accords with the nutrition hypothesis of GCT. This study expands the current view of GCT tumorigenesis by suggesting that high-calorie intake in childhood promotes GCT precursors originating in utero .