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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., (© 2023. The Author(s).)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The aim of our study was to analyze the potential relationship between tumor markers and 18 F-fluorodoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) results in patients affected by seminoma., Material and Methods: 65 18 F-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: 18 F-FDG PET/CT has good accuracy in evaluating patients with relapsed seminoma. HCG levels were significantly correlated with metabolic PET/CT parameters., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

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., (© 2021. The Author(s).)

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., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Purpose: To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker., Material and Methods: Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared., Results: Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10 ± 2.13 to 1.62 ± 0.59 postoperatively (p=0.010)., Conclusions: NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT., Patients and Methods: In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of β-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase., Results: For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p., Conclusion: The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.

Background: Primary malignant mediastinal germ cell tumors (PMMGCTs) including seminomas and nonseminomatous germ cell tumors (NSGCTs) are rare, and sometimes the diagnosis is very difficult., Purpose: The purpose of this study is to compare the clinical characteristics, biomarkers, and imaging findings of seminomas and NSGCTs and to determine whether these features could help distinguish these two types of PMMGCT., Material and Methods: A retrospective study of 24 male patients with histopathologically proven PMMGCT was performed. We collected the information of computed tomography (CT) (the scan area ranged from the apex of lung to the costophrenic angles) and magnetic resonance imaging blood test and histology characteristics of these patients., Results: Twelve of 24 cases were confirmed to be seminomas, whereas the other 12 cases were NSGCTs. Alfa-fetoprotein (AFP) was found to be elevated in all patients with NSGCT, whereas none of the patients with seminomas had elevated AFP level. Beta-human chorionic gonadotropin (β-HCG) level was elevated in all the patients with seminomas (seven/seven), whereas in NSGCT only two of seven patients had elevated β-HCG. Lactate dehydrogenase level was increased in five of the nine patients with seminomas, as well as in the eight patients with NSGCT. CT imaging revealed that 12 masses from the seminoma group were homogeneous, soft tissue opacity and showed minimal contrast enhancement. On the contrary, all 12 NSGCT cases showed cystic and solid masses; on contrast-enhanced CT, heterogeneous enhancement was found on the capsule of the tumor, septum, and solid masses., Conclusion: Seminomas and NSGCT showed different profiles of tumor biomarkers and radiographic features. Evidence from serum test, histopathological analysis, and imaging should be combined to ensure the accurate diagnosis of these two types of PMMGCT., Competing Interests: None

Background: The significance of hilar soft tissue invasion of rete testis in malign germ cell tumors is still controversial on current guidelines., Objectives: We aimed to investigate the importance of hilar soft tissue involvement in germ cell tumors and evaluated the possibility of a risk factor such as rete testis., Method: Totally, 59 radical orchiectomy specimens operated between 2007 and 2015 at our clinics. All records were retrospectively researched. Patients' age, level of tumor markers, tumor size, histological subtype, clinical stage, presence or absence of carcinoma in situ, vascular/lymphatic and/or hilar soft tissue invasion, tumoral necrosis, number, site and diameter of metastasis, type of further treatment (radiotherapy or chemotheraphy) and follow-up period were recorded and evaluated for all patients., Results: Twenty-six of totally 59 malign germ cell tumors were seminomatous and 33 were nonseminomatous (NS). Mean patients age was 38.54 years (range 17-89 years). Mean follow-up duration was 39.84 months (range 3-96). Serum tumor marker levels were found associated with rete testis invasion (p = 0.035). Hilar soft tissue invasion was significantly associated with vascular invasion (p = 0.001). As it was expected, vascular invasion was significantly associated with metastasis (p = 0.024)., Conclusions: We concluded that there is a strong association between hilar soft tissue invasion and vascular invasion. Especially in NS germ cell tumors, hilar soft tissue involvement a risk factor for prognosis and to determine the need for additional treatment. According to our study, hilar soft tissue status should be reported on routine pathology report., (© 2019 S. Karger AG, Basel.)

Background: Clinical practice guidelines recommend the measurement of human chorionic gonadotropin (hCG) and/or hCGβ in serum for management of testicular germ cell tumors (GCTs). These guidelines, however, disregard relevant biochemical information on hCG variants to be detected for oncological application. We set out to provide a critical review of the clinical evidence together with a characterization of the selectivity of currently marketed hCG immunoassays, identifying assays suitable for management of GCTs., Content: Evidence sources in the available literature were critically appraised. Most instances of misdiagnosis and mismanagement of testicular GCTs have been associated with hCG results. According to the clinical evidence, 36% of patients with seminoma show an exclusive hCGβ increase, and 71% of patients with nonseminomatous GCTs (NSGCTs) show an increase of intact hCG and/or hCG + hCGβ, whereas the hCGβ increase in NSGCTs is variable according to the tumor stage and histology., Summary: hCG + hCGβ assays that display an equimolar recognition of hCG and hCGβ, or at least do not overtly underestimate hCGβ, may be employed for management of testicular GCTs. Assays that underestimate hCGβ are not recommended for oncological application. In addition to the hCG + hCGβ assay in service, an additional assay with broader selectivity for other hCG variants should be considered when false-negative or false-positive results are suspected on the basis of clinical data., (© 2017 American Association for Clinical Chemistry.)

Various microRNAs from the miR-371-3 and miR-302a-d clusters have recently been proposed as markers for testicular germ cell tumours. Upregulation of these miRNAs has been found in both the tissue and serum of testicular cancer patients, but they have never been studied in human seminal plasma. The aim of this study was, therefore, to assess the differences in the expression of miR-371-3 and miR-302a-d between the seminal plasma and serum of testicular cancer patients, and to identify new potential testicular cancer markers in seminal plasma. We investigated the serum and seminal plasma of 28 pre-orchiectomy patients subsequently diagnosed with testicular cancer, the seminal plasma of another 20 patients 30 days post-orchiectomy and a control group consisting of 28 cancer-free subjects attending our centre for an andrological check-up. Serum microRNA expression was analysed using RT-qPCR. TaqMan Array Card 3.0 platform was used for microRNA profiling in the seminal plasma of cancer patients. Results for both miR-371-3 and the miR-302 cluster in the serum of testicular cancer patients were in line with literature reports, while miR-371and miR-372 expression in seminal plasma showed the opposite trend to serum. On array analysis, 37 miRNAs were differentially expressed in the seminal plasma of cancer patients, and the upregulated miR-142 and the downregulated miR-34b were validated using RT-qPCR. Our study investigated the expression of miRNAs in the seminal plasma of patients with testicular cancer for the first time. Unlike in serum, miR-371-3 cannot be considered as markers in seminal plasma, whereas miR-142 levels in seminal plasma may be a potential marker for testicular cancer.

Background: Androgen insensitivity syndrome is an X-linked disorder, and is characterised by a female phenotype in a chromosomally male individual. It usually occurs in puberty with primary amenorrhoea or as an inguinal tumour in a female infant. In recent years, it is often also diagnosed in fertility clinics in adulthood., Objective: The case is presented of a pure seminoma in a woman with the reference diagnosis of inguinal hernia., Clinical Case: A 53 year old woman, who was operated on in 2014 due to a nodule in left groin. Androgen insensitivity syndrome was corroborated, and histopathology reported it as a right testicular seminoma., Discussion: The importance of early diagnosis is discussed, highlighting the consequences of misdiagnosis, and question whether these patients have been adequately treated in the past. The risk of malignant transformation of an undescended testicle increases with age, thus gonadectomy should be performed after puberty, and in some cases hormone replacement therapy., (Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.)

Introduction: MicroRNA (miR)371a-3p was suggested to be a sensitive and specific new serum biomarker of germ cell tumours (GCTs); however, its clinical usefulness remains unproven., Patients, Methods: In 312 consecutive cases with various testicular diseases, serum levels of miR371a-3p were measured. Measurement results became available only after completion of treatment. Five patients with testicular seminoma were selected for review because of unanticipated clinical courses., Results: In each two patients, elevated miR levels heralded undetected primary testicular GCT and metastases despite inconclusive radiological findings. In one case, a normal miR371a-3p level correctly pointed to the absence of metastases contrary to clinical assessment. In all cases, knowledge about the miR371a-3p levels would have altered the clinical management., Conclusions: These cases highlight the exceptional usefulness of the new GCT biomarker. In contrast to classical markers, miR371a-3p can identify primary testicular GCT. The marker can aid in clinical decision making in cases with ambiguous clinical findings., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Background: Pure testicular seminoma does not express alpha fetoprotein (AFP). However, seminoma patients with mildly elevated serum AFP levels are increasingly reported. As this finding may prompt unwarranted treatment measures, we reviewed our experience with AFP levels in seminoma., Patients and Methods: We retrospectively registered AFP levels in 254 consecutive seminoma patients, and in 196 male controls with non-malignant diseases. In those with elevated AFP levels, we re-examined the orchiectomy specimens histologically. We reviewed the clinical course and looked for hepatic disorders., Results: Elevated AFP levels were found in 5 patients (1.97%, 95% CI 0.19-3.68) and in 4 controls (2.04%, 95% CI 0.06-4.02). The elevations were modest and kept elevated throughout the clinical course. No hepatic disorders were recorded. Histologically, pure seminoma was confirmed., Conclusion: Unspecific AFP elevations occur in about 2% of seminoma patients. Care-givers should be aware of this particular subgroup of seminoma patients to avoid unwarranted treatment burden., (© 2017 S. Karger AG, Basel.)

microRNAs (miRs) are short non-coding RNA molecules (≈21 nucleotides) involved in regulation of translation. As such they are crucial for normal cell development and differentiation as well as cellular maintenance. Dysregulation of miRs has been reported in various diseases, including cancer. Interestingly, miRs can be informative as tumor classifiers and disease biomarkers. Recent studies demonstrated the presence of miRs in body fluids like serum, thus providing a putative non-invasive tool to study and monitor disease state. Earlier targeted studies by several independent groups identified specific embryonic miRs as characteristic for germ cell tumors (GCT) (miR-371-2-3 & miR-302/367 clusters). This study reports a high-throughput miR profiling (≈750 miRs) approach on serum from testicular germ cell tumor patients (14 seminoma and 10 non-seminoma) and controls (n = 11), aiming at independent identification of miRs as candidate biomarkers for testicular GCT. A magnetic bead capture system was used to isolate miRs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling. The previously identified miRs 371 and 372 were confirmed to be specifically elevated in serum from germ cell tumor patients. In addition, several novels miRs were identified that were discriminative between germ cell cancer and controls: miR-511, -26b, -769, -23a, -106b, -365, -598, -340, and let-7a. In conclusion, this study validates the power of the embryonic miRs 371 and 372 in detecting malignant GCT (SE and NS) based on serum miR levels and identifies several potential novel miR targets., (© 2014 American Society of Andrology and European Academy of Andrology.)

Objectives: To describe the clinical and pathological characteristics and oncological outcomes of testicular cancer diagnosed in Japan, we report the results of the testicular cancer registration carried out by the Japanese Urological Association., Methods: Testicular cancer survey was conducted by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. The survey included details such as age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, initial treatment and clinical outcomes., Results: We analyzed 1121 cases of testicular primary germ cell tumor among 1157 registered patients. The median age was 37.0 years. Seminomas and non-seminomatous germ cell tumors accounted for 61.9% and 38.1%, respectively. Measurements of tumor markers were documented in 98.6% of the patients; however, there was an unsatisfactory uniform measurement of human chorionic gonadotropin, which made it difficult to evaluate the International Germ Cell Consensus Classification in all patients. The 1- and 3-year overall survival rates from the entire cohort were 98.3% and 96.8%, respectively. According to the International Germ Cell Consensus Classification, 3-year overall survival rates in the good, intermediate, and poor prognosis group were 99.1%, 100% and 79.9%, respectively., Conclusions: The present report is the first large-scale study of the characteristics and survival of testicular cancer patients in Japan based on multi-institutional registry data, and showed a good prognosis even in an advanced stage. The improved survival attributed substantially to accurate diagnosis and effective multimodal treatment., (© 2014 The Japanese Urological Association.)

Testicular cancer is an uncommon cancer and of the estimated 7,920 new cases diagnosed in 2013, 370 will result in death. It is most common in young or middle-aged males and rarely occurs in older males. Ninety-five percent of these cancers originate in sperm-producing germ cells. There are two different subclasses of testicular cancer, namely nonseminoma and seminoma. Nonseminoma testicular cancers, such as embryonal carcinomas, yolk sac carcinomas, choriocarcinomas, and teratomas usually affect younger-aged males, whereas seminoma testicular cancers often occur in older males. It is unclear why testicular cancer is rare in older men, but because it is so unusual in older men, the diagnosis is frequently overlooked when presenting with signs suggestive of testicular carcinoma. A 75-year-old male recently presented with signs and symptoms classically descriptive of testicular cancer. The patient was treated with an orchiectomy. The pathologic evaluation of the excised testicle confirmed the diagnosis of a seminoma. This report is an account of the case from initial visit to treatment and a discussion of its relevance.

Background: Seminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied.The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma., Case Presentation: A 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed "cannon ball" pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively., Conclusion: The association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values.

Background: We aimed to better discriminate metastasized (lymphogen/occult/both combined) from non-metastasized seminoma based on post-transcriptional changes examined in the peripheral blood., Methods: Total RNAs including small RNAs were isolated from the peripheral blood of patients suffering from metastasized testicular tumours (lymphogen, n = 5, clinical stage IIb/c; occult, n = 5, clinical stage I) and non-metastasized patients (n = 5, clinical stage I). Small RNA next generation sequencing (SOLID, Life Technologies) was employed to examine post-transcriptional changes. We searched for small RNAs showing at least 50 reads and a significant  ≥ 2-fold difference using peripheral blood small RNAs of non-metastasized tumours as the reference group. Candidate small RNAs were examined in univariate logistic regression analysis and combinations of two small RNAs were further examined using support vector machines., Results: On average 1.3 x 10(7), 1.2 x 10(7) and 1.2 x 10(7) small RNA reads were detectable in non-metastasized, lymphogen and occult metastasized seminoma, respectively of which 73-76% remained after trimming. From these between 80-82% represented annotated reads and 7.2-7.8% (1.6-1.7 x 10(4)) were annotated small RNA tags. Of them 137 small RNAs showed > 50 reads and a ≥ two-fold difference to the reference. In univariate analysis we detected 33-35 different small RNAs which significantly discriminated lymphogen/occult/combined metastasized from non-metastasized seminoma and among these different comparisons it were the same small RNAs in 44-79%. Many combinations of two of these small RNAs completely discriminated metastasized from non-metastasized seminoma irrespective of the metastasis subtype., Conclusions: Metastasized (either lymphogen or occult) seminoma can be completely discriminated from non-metastasized seminoma with a combination of two small RNAs measured in the peripheral blood.

Purpose: We screened 90 potential parameters as biomarkers of metastatic seminoma to facilitate detection and eliminate unnecessary therapeutic or diagnostic efforts., Materials and Methods: A total of 527 men with pure seminoma (diagnosed 2000 to 2011) were followed during therapy. More than 90 demographic/anamnestic (eg age, height, weight) histopathological parameters (testicular/tumor size, testicular intraepithelial neoplasia) and levels of tumor markers (eg α-fetoprotein, β-human chorionic gonadotropin, lactate dehydrogenase) in peripheral blood and testicular vein were collected for analysis via logistic regression. Previously described risk factors (tumors larger than 4 cm, infiltration of rete testis) were assessed separately., Results: Established parameters such as tumor length (p = 0.0003), involvement of lymphatic (p <0.0001) or vascular channels (p = 0.0009), extent of primary tumor (p <0.0001) and infiltration of the tunica albuginea (p = 0.02) as well as new biomarkers such as absence of testicular intraepithelial neoplasia in tumor bearing testis (p = 0.03), testicular volume (p = 0.04) and tumor volume (p = 0.02) showed a significant association with metastatic disease. This association was also true of lactate dehydrogenase, human chorionic gonadotropin and α-fetoprotein (p <0.0001 at maximum). However, the discriminatory capacity of these biomarkers (concordance or ROC area) did not exceed 65% when examined alone or in combination, and higher values (up to 80%) were detected for enzyme levels. A subset of metastatic seminoma (2% to 27%) was detectable with high accuracy (positive predictive value 92% to 100%) based on enzyme measurements (p <0.0006)., Conclusions: New biomarkers of metastatic seminoma were identified and previously described risk factors were validated. Further prospective studies of these novel parameters are warranted to verify our findings and to explore a potential use for detecting occult metastases., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Primary testicular germ cell tumors typically present with painless testis enlargement and have a propensity to spread to the retroperitoneal lymphatics. Delays in seeking treatment are unfortunately common and may lead to metastatic spread. Pure seminomas are the most commonly seen on histology and are not associated with elevations in serum alpha-fetoprotein. Mild elevations in alpha-fetoprotein in the setting of a pure seminoma may be due to unrecognized nonseminomatous elements and rarely other benign etiologies. We present the case of a 42-year-old man with a large 31 cm stage I pure seminoma and mildly elevated alpha-fetoprotein level at presentation., (Published by Elsevier Inc.)

Background: The aim of this study was to assess fluctuations in normal serum alpha-fetoprotein (AFP) levels in patients with germ cell cancer. Marked variations occur after serum AFP levels normalize, creating anxiety among patients and physicians during surveillance., Patients and Methods: We conducted a retrospective review of patients with germ cell tumors in clinical remission, who had normal AFP levels and were followed at our center from 1991 to 2009. 72 patients, with a median follow-up of 50 months, were identified., Results: Of the 72 patients, 57 (79%) had a non-seminomatous germ cell histology, and 15 (21%) had seminomas. Seminomas were included as controls as serum AFP levels do not increase in this group. 68 patients underwent orchiectomy, and 50 patients received systemic chemotherapy. The majority of patients (93%) demonstrated fluctuations in serum AFP. There was no difference in the mean AFP values between patients with seminona (2.95 ng/ml) and those with non-seminomatous germ cell tumors (3.3 ng/ml) (standard deviation 1.01 ng/ml)., Conclusion: Marked variations occur after serum AFP levels normalize in patients undergoing surveillance. Fluctuating AFP levels within normal limits did not result in relapse in our cohort of patients with extended follow-up., (Copyright © 2012 S. Karger AG, Basel.)

Objectives: To report the retroperitoneal histologic findings from a contemporary series of patients with pure seminoma at orchiectomy with an elevated serum α-fetoprotein (AFP) level. These patients underwent treatment on the assumption that the lesion was nonseminomatous germ cell tumor (NSGCT)., Methods: We identified 22 patients from 1989 to 2009 with pure seminoma diagnosed at orchiectomy with an elevated serum AFP level (>15 ng/mL) either before or after orchiectomy. The retroperitoneal histologic and relapse data are reported., Results: The median preorchiectomy and prechemotherapy serum AFP level was 248 ng/mL (interquartile range 48-4693) and 279 ng/mL (interquartile range 66-5311), respectively. The percentage of patients with clinical Stage I, II, and III disease was 5%, 50%, and 45%, respectively. The percentage of patients with a good, intermediate, and poor risk status according to the International Germ Cell Cancer Collaborative Group was 32%, 32%, and 36%, respectively. Of the 22 patients, 21 underwent induction chemotherapy followed by retroperitoneal lymph node dissection. Overall, 67% of patients had NSGCT elements in the retroperitoneum. The histologic findings were pure teratoma in 38%, malignant transformation in 14%, and viable NSGCT in 14%. Also, 59% had some component of teratoma in the retroperitoneum. Only 1 patient (5%) had any seminoma in the retroperitoneum, but this patient also had retroperitoneal teratoma. Of the 22 patients, 7 developed a relapse and received salvage chemotherapy. The actuarial relapse-free survival rate at 5 and 10 years was 76% and 61%, respectively, reflecting the high percentage of patients with Stage II-III disease., Conclusions: Pure seminoma at orchiectomy with an elevated serum AFP level portends a high likelihood of NSGCT elements in the retroperitoneum., (Copyright © 2011. Published by Elsevier Inc.)

Background: Testicular cancer is the most frequent cancer in patients between 20 and 40 years of age. Cure rates are very high due to standardised operative treatment as well as additional chemotherapy and radiotherapy according to -histological subtype and tumour stage. Histological subtypes are seminoma, non-seminoma and mixed tumours (partly seminoma and partly non-seminoma). The aim of this study was to determine the value of different tumour markers in the primary diagnosis of testicular cancer., Material and Methods: In a retrospective study we investigated 152 consecutive patients with testicular cancer as well as 75 patients with benign scrotal conditions. In all patients the tumour markers human alkaline phosphatase (hPLAP), alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and the enzyme lactate dehydrogenase (LDH) were measured. Statistical analyses included descriptive analysis, boxplots, fourfold table, receiver operating characteristic (ROC), calculation of confidence intervals and analysis of variance (ANOVA)., Results: 145 patients with a mean age of 34.3 years were eligible. There were 72 seminomas, 33 non-seminomas and 40 mixed tumours with 69% of patients being in Lugano stage I, 19% in stage II and 11% in stage III. hPLAP, AFP and hCG were statistically significantly higher in patients with testicular cancer compared to patients with benign scrotal conditions (p < 0.005). hPLAP showed the best sensitivity/specificity (51.1%/84.0%) followed by AFP (35.7%/97.1%), hCG (32.6%/98.6%) and LDH (31.4%/97.8%). ROC analysis demonstrated no difference between hPLAP, AFP and hCG in the specificity range of 80-100%. However, a combination of hPLAP, AFP and hCG provided statistically significantly better results than single markers (p < 0.001)., Conclusion: hPLAP is the most often elevated marker in the serum of patients with testicular cancer and potentially demonstrates a significant benefit for therapy monitoring. In our opinion there is a need to debate the consideration of hPLAP in the usual guide-lines of the cancer societies. The unspecific elevation in smokers must be considered. In this regard, reference values of hPLAP depending on smoking habits could be a solution, but valid data are not yet available., (© Georg Thieme Verlag Kg Stuttgart ˙ New York.)

Purpose: Surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) allows rapid protein profiling of complex biological mixtures. We analyzed testicular germ cell cancer serum samples to differentiate between cancer and controls with a special focus on beta-hCG-negative seminomas., Methods: Proteomic spectra were generated by the ProteinChip system and analyzed by the proteomic platform "proteomic.net". For statistical analysis, an artificial intelligence learning algorithm was used., Results: The classification algorithm correctly identified the pattern in 90.4% of the patients. Decision trees predicted seminomas with 91.5% sensitivity and 89.4% specificity. Seminoma patients with normal beta-hCG serum level were correctly predicted with 80% sensitivity and 70% specificity., Conclusions: Our study demonstrates protein profiles of testicular germ cell cancer patients that differ in a highly significant degree from normal controls. Validation of these findings may enable proteomic profiling to become a valuable tool, especially for aftercare.

Objectives: To investigate the association between androgen deficiency symptoms and sexual function, serum testosterone, and therapy in testicular cancer survivors (TCS)., Methods: A total of 83 patients treated for testicular cancer were investigated. All patients completed the International Index of Erectile Function-15 and the Aging Males Symptoms scale. Age, months of follow-up, treatment modality, and serum testosterone levels were measured. Scores for the erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction subdomains of the International Index of Erectile Function-15 were calculated., Results: Overall, almost half (47.0%) of TCS experienced clinical symptoms of androgen deficiency, 28.9% had erectile dysfunction, and 25.3% had laboratory-proven hypogonadism. TCS with clinical symptoms of androgen deficiency were significantly older (median age 45.0 vs 37.5 years, P = .001) and had a longer follow-up (median follow-up 48.0 vs 39.5 months, P = .985, respectively) than TCS without symptoms. TCS with clinical symptoms had significantly lower scores for erectile function (P = .004), orgasmic function (P = .05), sexual desire (P = .001), intercourse satisfaction (P = .005), and overall satisfaction (P = .001) than those without symptoms. The aging males' symptoms correlated significantly with erectile dysfunction (r = -0.410, P = .001). In TCS with symptoms, age (r = -0.457, P = .003), but not treatment modalities (r = 0.223, P = .173) or testosterone levels (r = 0.205, P = .210), correlated with sexual function., Conclusions: Clinical symptoms of androgen deficiency were associated with sexual problems and increasing age, but not with serum testosterone or treatment.

Objective: Human chorionic gonadotrophin (HCG) is secreted by 10 to 20% of seminomas. The authors evaluated variations of serum total HCG levels in patients with normal baseline levels for the surveillance of treated testicular seminomas in order to determine the value of assay of this tumour marker in the follow-up of testicular seminoma., Patients and Methods: Retrospective study from January 1988 to March 2007, including 95 cases of operated testicular cancer, including 28 seminomas, 25 of which did not secrete HCG (baseline total HCG less than 15 IU/L). Patients were reviewed periodically: every three months for one year, every six months during the second year, then annually, comprising of clinical examination, CT examination and assay of tumour markers (HCG, LDH and AFP)., Results: Mean follow-up was 77.5 months (range: 6-120). Twenty-five patients had a total HCG level less than 15 IU/L three months after orchidectomy. Serum HCG remained stable at less than 15 IU/L in all patients with a follow-up of more than three years. Two patients developed non-regional lymph node recurrence with no modification of the serum HCG level., Conclusion: All treated non-HCG-secreting seminomas with or without recurrence had stable and normal HCG levels throughout follow-up, which raises the question of the value of HCG assay in the follow-up of these patients following histological confirmation of the diagnosis.

Background: We studied whether measurement of the free beta subunit of human chorionic gonadotropin (hCGbeta) in serum offers additional diagnostic information compared to determination of intact hCG alone in testicular cancer., Methods: We determined hCG and hCGbeta with ultrasensitive assays in 94 serum samples obtained preoperatively, 22 samples obtained during relapse, and 3687 samples obtained during routine follow-up of 351 patients with testicular tumors., Results: In preoperative samples, isolated increases of hCGbeta were seen in 40% of the samples from seminoma patients (n = 42) and in 8% of those from patients with nonseminomatous testicular cancer (NSGCT) (n = 51). Both markers were increased in 12% of the seminoma and 71% of the NSGCT patients and were within reference intervals in 43% of the seminoma and 20% of the NSGCT patients. Specific determination of hCGbeta increased the frequency of marker-positive seminomas from 17% to 57% and of marker-positive relapses from 32% to 59% (n = 22). Theoretically, about 40% of marker-positive seminomas and relapses would have been missed with an assay measuring hCG and hCGbeta together. Preoperative hCG and hCGbeta concentrations correlated with stage, tumor histology, and disease-related mortality. Additionally, hCGbeta correlated with tumor size., Conclusions: hCGbeta is a diagnostically sensitive marker for testicular cancer. In patients with seminomatous testicular cancer, hCGbeta is superior to hCG, and in some NSGCT patients it provides additional information.

Background: We report the case of a patient with treated Stage Ia seminoma who was found to have an elevated beta human chorionic gonadotrophin (hCG) on routine follow - up. This instigated restaging and could have lead to commencement of chemotherapy., Case Presentation: The patient was a bodybuilder, and following a negative metastatic work - up, admitted to injecting exogenous beta hCG. This was done to reduce withdrawal symptoms from androgen abuse. The patient remains well eight years post diagnosis., Conclusion: This case highlights the need for surgical oncologists to conduct vigilant screening of young male patients with a history of testicular germ cell tumours and who may indulge in steroid abuse.

The authors report a case of stage N3 pure testicular seminoma associated with paradoxical elevation of alphafoetoprotein (AFP). Despite the absence of histological arguments after review of the slides, this lesion was considered to be a stage pT1 N3 M0 S3 non seminomatous germ cell tumour with a poor prognosis. Simple surveillance was proposed following normalization of tumour markers, regression of retroperitoneal masses and negative PET scan. Laboratory and then clinical relapse at three months was treated by salvage chemotherapy followed by retroperitoneal lymph node dissection. The presence of embryonic carcinoma in one of the residual masses led to a revision of the initial histological diagnosis. The rare data of the literature indicate a variable approach according to alphafoetoprotein levels.

Approximately 30% of patients with pure seminoma of the testis have mild elevation of human chorionic gonadotropin (hCG) due to the presence of syncytiotrophoblastic giant cells. Levels are usually less than 500 IU/L; however, the occurrence of higher levels is rare. We report a case of a man with a stage I histologically pure seminoma, copious syncytiotrophoblast cells, and a serum beta human chorionic gonadotropin (beta-hCG) of 4497 IU/L. To our knowledge this is the third highest value of beta-hCG reported with a stage I pure seminoma. The patient underwent an orchiectomy and chemotherapy. His beta-hCG level was undetectable by postoperative day 13, and he remains disease free at 30 months.

Background: Radical inguinal orchiectomy followed by adjuvant para-aortic radiotherapy has been the standard treatment in stage I seminoma. We have reviewed our experience with reduced total doses (less than 26 Gy) in stage I seminoma to investigate if patients with an elevated beta-human chorionic gonadotropin (beta-hCG) level before orchiectomy possibly require higher total doses of adjuvant radiotherapy (RT)., Patients and Methods: Two hundred and sixty-seven consecutive patients, with newly diagnosed pure seminoma of the testis, were treated with adjuvant RT between 1992 and 2000. All patients had stage I disease. Serum AFP and beta-hCG levels were analyzed prior to and after orchiectomy in case of an elevated beta-hCG level. The measurements were repeated after RT in routine follow-up at regular intervals. Serum beta-hCG was considered as elevated if the values exceeded the normal range (up to 5 U/L). A median total dose of 25.2 Gy (range, 19.8 to 26.0 Gy) was applied to the para-aortic region., Results: Fourteen patients were excluded from this analysis because beta-hCG measurement was not available. Nineteen of the remaining 253 patients (7.5%) had an elevated serum beta-hCG, which returned to normal post-operatively by the start of adjuvant radiotherapy. Median serum beta-hCG level before orchiectomy was 27.7 U/L (range, 5.1 to 420 U/L) in the group of patients with initial elevation of serum beta-hCG. This did not correlate with tumor size or rete testis invasion. After a median follow-up of 6.1 years (range, 3.0 to 11.2 years), 11 out of 267 (4.1%) patients had developed lymph node recurrence, resulting in an actuarial 5-year relapse-free survival of 96%. Median time to relapse was 19 months (range, 11 to 47 months) after RT. Only one relapsing patient initially had an elevated serum beta-hCG level of 34.1 U/L. This patient had nodal relapse within the mediastinum without renewed elevation of the serum beta-hCG level., Conclusion: An elevated pre-treatment beta-hCG level appears to have neither importance nor a predictive value in stage I seminoma. Therefore, we recommend the current adjuvant standard treatment without any modification for all beta-hCG-positive stage I seminoma.

A male 8-year-old Yorkshire Terrier dog with unilateral cryptorchism was presented for investigation of reduced appetite and multifocal alopecia. Abdominal sonography and radiography demonstrated abnormal enlargement of left testicle in abdominal cavity. Both of the retroperitoneal cryptorchid testicle and the other contralateral testicle were removed surgically. The concentrations of testosterone and estradiol in blood collected from the jugular vein and the two spermatic veins were evaluated and the results revealed high estradiol concentration. The retroperitoneal cryptorchid testicle was enlarged, firm, bulging sphere mass. The cut surface revealed homogeneous white color and lobulation by septa. The contralateral testicle in scrotum showed atrophic testicle and enlarged epididymis. Histopathologically, the retroperitoneal cryptorchid testicle was diagnosed as seminoma. We thought that hyperesterogenemia and alopecia in this case was probably related with his seminoma, although high correlations between Sertoli cell tumor and alopecia have been reported. To our knowledge, this report may be a rare case of seminoma with hyperesterogenemia and alopecia.

A 45-year-old man was referred to our hospital because of polycythemia. A physical examination revealed a large tumor in his scrotum enlarged to the size of 13 x 10 cm. A laboratory examination revealed severe erythrocytosis with a red blood cell count of 6,820 x 10(9)/L, a hemoglobin concentration of 21.2 g/dL, and a hematocrit of 59.8%. The total red cell volume was increased. A right radical orchidectomy was done with minimum bleeding, and he was diagnosed as having pure seminoma. After the operation, polycythemia improved spontaneously. Polycythemia is a rare complication of seminoma and only two cases have been reported previously. The precise mechanism of polycythemia in our patient could not be clearly evaluated, but clinical course did indicate a close relationship between two distinct disorders.

Aim of the Study: We report the results of a retrospective study in 96 patients with advanced seminoma, who received first line chemotherapy at the centre Léon-Bérard from 1980 to 2000., Patients and Methods: The primary site of disease was gonadonal in 88 patients and extragonadal in 8 others. Among the 96 patients, 8 patients had an atypic seminoma and 88 a classical seminoma. Extranodal metastases were present in 25 patients, metastatic site was unique in 69 patients. Except 9 patients, all had a good prognosis according to the IGCCCG. All patients had normal serum AFP level at diagnosis. Ten and 38 patients had elevated hCG and LDH serum marker level respectively., Results: After first line chemotherapy, 18 patients achieved a complete response (CR) and 73 a marker negative partial response (PR-). Two presented a marker positive partial response (PR+), and two others, a progressive disease (PD). One toxic death occurred after first cycle of chemotherapy. Seventy-seven patients had residual masses. Resection was performed in 27 patients with PR- and led to 18 CR. Only two of the 27 residual mass contained active tumor. After chemotherapy and additional treatment as surgery or radiotherapy, a residual mass was still present in 55 patients but disappeared spontaneously for 23 of them. Relapse occurred in 18 patients, 16 of whom received salvage chemotherapy. A favourable response was observed in 9 patients with 6 complete responses. Despite this treatment, 14 patients eventually died. No adverse prognostic factor such as primary extragonodal site, prior radiotherapy, number of metastastic sites, international classification, serum markers levels (hCG, LDH) was found. The 5-years overall survival rate was 78%., Conclusion: This study show the poor outcome of patients with advanced seminoma after relapse. Renewed efforts are required to identify specific markers in seminoma in order to optimize treatment at initial presentation. Spontaneous regression of residual mass is frequent, thus an observation can be proposed without indication of immediate additional treatment, as surgery.

The incidence of testicular germ cell cancer, which is the most common cancer among young male adults, is increasing. The aetiology remains unknown, although a virus has been proposed. A previous study has shown a high prevalence of human parvovirus B19 (B19) DNA in the testes of patients with testicular germ cell tumours (85%) and suggested that B19 may play a role in tumour development. To address this question of causality, seroreactivity to B19 was studied among cases (n=80) and controls (n=241) using serum samples drawn before the onset of disease, in addition to an elucidation of the frequency of virus DNA in a retrospectively collected 2-year testicular carcinoma series. No association was found between B19 seropositivity and the risk of testicular cancer (odds ratio=1.03; 95% confidence interval=0.60-1.77) nor was there any dose-response relation (P for trend=0.53). This study did, however, confirm the observation that B19 DNA can be detected in testicular carcinoma tissue, as 4 of 24 cases were found to be positive, while no B19 DNA could be detected in the control cases. It is speculated that this finding may be due to susceptibility of the carcinoma cells to B19 virus owing to high-level expression of the viral receptor glycosphingolipid (Gb4) and possible other putative cellular factors resulting in a localized persistence initiated after the development of cancer.

Objectives: To measure the expression levels of Fas and Fas ligand (FasL) in testicular germ cell tumor (TGCT) and to determine whether the serum level of soluble FasL (sFasL) could be used as a marker for patients with TGCT., Methods: The expression of Fas and FasL in 51 specimens obtained from patients with TGCT was examined by reverse transcriptase-polymerase chain reaction, and the results were confirmed by Western blot analysis. The serum levels of sFasL in 24 patients with TGCT were measured using an enzyme-linked immunosorbent assay system., Results: Of 33 TGCT specimens that included seminomatous elements, Fas and FasL was expressed in 24 (73%) and 24 (73%), respectively. On the other hand, 10 (56%) and 2 (11%) specimens expressed Fas and FasL, respectively, in 18 TGCT specimens without seminomatous elements. Moreover, the serum levels of sFasL were significantly higher in patients with TGCT with a seminomatous element than in those without it., Conclusions: These results indicate that FasL is strongly expressed in tumor tissue and is present at high levels in the serum of patients with TGCT with a seminomatous element compared with those without it and that the serum levels of sFasL could be used as a novel diagnostic marker for TGCT with seminomatous elements.

Background: Simultaneous determinations of human chorionic gonadotropin hormone (hCG) and hCG-beta frequently produce discrepancies, that is when hCG or hCG-beta is normal, the other is elevated. Accordingly, we examined the significance of simultaneous determination of serum hCG and hCG-beta in testicular tumors., Methods: Simultaneous determination of hCG and hCG-beta was performed in 54 patients with testicular seminoma and 74 with non-seminomatous testicular tumors., Results: For detection of seminoma patients, hCG-beta was more effective than hCG because hCG-beta was positive in 83% (45/54) of the patients and hCG was positive in 50% (27/54). In non-seminomatous testicular tumor cases, hCG-beta was positive in 74% (55/74) and hCG was positive in 82% (61/74). The cases of hCG<1.0 mIU/mL and HCG-beta>0.1 ng/mL were significantly more frequently seen in patients with seminoma than in those with non-seminomatous testicular tumor (P < 0.001). Fourteen patients had recurrent tumor. At recurrence, only hCG was elevated in nine cases, only hCG-beta was elevated in two cases and both in one case. For diagnosis of falsely positive hCG, testosterone administration was effective because after testosterone administration, serum hCG levels became undetectable (< 1.0 mIU/mL) within one week in three examined cases., Conclusion: Human chorionic gonadotropin-beta was a better marker of seminoma than hCG. For earlier detection of recurrence, both markers should be examined. For diagnosis of falsely positive hCG, testosterone administration was effective.

Objective: In a prospective multicenter trial, it was our intention to elucidate clinical prognostic factors of seminomas with special reference to the importance of human chorionic gonadotropin (HCG) elevations in histologically pure seminomas., Methods: Together with 96 participating urological departments in Germany, Austria, and Switzerland, we recruited 803 seminoma patients between 1986 and 1991. Out of 726 evaluable cases, 378 had elevated, while 348 had normal HCG values in the cubital vein. Histology was reviewed by two reference pathologists. HCG levels were determined in local laboratories and in a study laboratory. Standard therapy was defined as radiotherapy in stages I (30 Gy) and IIA/B (36 Gy) to the paraaortal and the ispilateral (stage I) and bilateral (stage IIA/B) iliac lymph nodes; higher stages received polychemotherapy and surgery in case of residual tumor masses. Statistics included chi-square tests, linear Cox regression, and log-rank test., Results: The HCG elevation is associated with a larger tumor mass (primary tumor and/or metastases). HCG-positive and HCG-negative seminomas had no different prognostic outcome after standard therapy. The overall relapse rate of 6% and the survival rate of 98% after 36 months (median) indicate an excellent prognosis. The calculation of the relative risk of developing a relapse discovered only stage of the disease and elevation of the lactate dehydrogenase concentration and its prolonged marker decay as independent prognostic factors for seminomas. A more detailed analysis of the prognostic significance of the stage revealed that the high relapse rate in stage IIB seminomas after radiotherapy (24%) is responsible for this result., Conclusions: We conclude that HCG-positive seminomas do not represent a special entity. Provided standard therapy is applied, HCG has no influence on the prognosis. Patients with stage IIB disease should be treated with chemotherapy because of the demonstrated higher relapse rate outside the retroperitoneum., (Copyright 1999 S. Karger AG, Basel.)

Background: A case of testicular typical seminoma associated with bilateral undescended testes in Down's syndrome is reported. A 42-year-old institutionalized male patient developed left testicular seminoma with retroperitoneal metastasis., Methods/results: Neither adjuvant chemotherapy nor radiotherapy were performed due to his severe mental retardation. He died as a result of the cancer 2 years after a left radical orchiectomy and an autopsy was carried out., Discussion: Recently an increase in the incidence of the association of testicular tumors and Down's syndrome has been repeatedly documented. Thirty-six cases of testicular tumors associated with Down's syndrome have been reported and of these 17.1% had cryptorchidism. This is a much lower percentage considering the high risk of cryptorchidism in males with Down's syndrome. The relationship between testicular germ cell tumors associated with cryptorchidism and Down's syndrome is discussed.

Seminomas account for 50% of testicular germ-cell tumors, and more than 90% of these are classic seminomas. When patients with a histologically pure testicular seminoma show an elevated level of serum á-fetoprotein (AFP), it is generally assumed that an undetected focus of yolk sac tumor (YST) is present and the patient is managed with a treatment regimen for non-seminomatous tumor. We studied 10 cases of histologically pure seminoma with elevated levels of serum AFP in an attempt to identify any distinctive clinical, histopathologic, or immunohistochemical features. The patients ranged in age from 27 to 48 years (mean, 31 years). Eight patients had primary tumors of the testis, and two presented with supraclavicular and ileal tumors. The clinical stage at presentation varied: four tumors were stage I, four were stage II, and two were stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to 16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary tumors and metastases when present exhibited classic seminoma histology without other germ-cell components. The tumor cells expressed keratin in seven cases. The pattern of keratin immunoreactivity ranged from focal staining in five cases to moderate staining in two cases. All cases were negative for AFP, and the nine cases in which staining for CD30 (Ki-1) was performed were also negative. All four patients with stage I tumors underwent the conventional therapy for pure seminoma, i.e., orchiectomy and subsequent radiation therapy. Five patients received treatment for non-seminomatous tumors, i.e., chemotherapy after orchiectomy. Extensive work-up failed to detect the primary tumor in one patient, and he was treated for a non-seminomatous tumor, undergoing chemotherapy and irradiation. All patients are alive and well, and none has developed evidence of YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one patient who presented with an ileal metastasis recently developed a second primary extragonadal mediastinal mixed germ-cell tumor with YST and embryonal carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10-year disease-free follow-up. This study strongly suggests that minor elevations (

Natural killer (NK) and lymphokine-activated killer (LAK) activities in patients with seminoma were determined, and the timing of effective NK cell collection was evaluated, compared to autologous peripheral blood stem cell (PBSC) collection. After chemotherapy, patients were injected with granulocyte-colony stimulating factor (G-CSF). CD56 cells decreased in parallel with white blood cells and then were restored. After discontinuing the G-CSF, the CD56 cells increased and reached peak 3-5 days after PBSC collection. The peak showed higher levels than those at premedication. Recovery-peripheral blood lymphocytes (PBL) which were obtained 4 days after PBSC collection showed higher NK and LAK activities than the PBL obtained before chemotherapy (Before-PBL). They exhibited a high expression of CD2, CD18, CD29, and CD49d. Furthermore, the LAK cells generated from the Recovery-PBL could acquire 9.6 folds of killer unit compared with the Before-PBL-LAK. These results suggest that, in order to obtain large numbers of NK cells, Recovery-PBL collection may be more advantageous than PBL collection in no relation with the chemotherapy.

Objectives: During the past 25 years, radiotherapy has been considered the standard adjuvant treatment for clinical Stage I seminoma after orchiectomy. However, the late effects of this treatment have prompted a re-examination of the alternatives, including surveillance and adjuvant administration of carboplatin. To our knowledge, the present clinical study is the first to report the effects of two adjuvant courses of single-agent carboplatin on the pituitary-testicular axis and on sperm analysis., Methods: Twenty-two patients with clinical Stage I seminoma participated in a prospective investigation of gonadal function before and after carboplatin therapy. After orchiectomy but before chemotherapy, blood samples for determination of follicle-stimulating hormone (FSH) serum levels were obtained from all 22 patients. Seventeen patients provided a semen sample at the same time, but 5 were unable to do so. At the end of chemotherapy, all 22 patients provided repeated semen samples starting 1 year after the termination of treatment and continuing at intervals of 12 months. FSH serum levels were determined at the same time. The study period was 48 months., Results: Before chemotherapy, 2 patients (12%) had azoospermia, 9 (53%) had oligospermia, and 6 (35%) had normospermia. During the study period, sperm counts continued to increase in all patients. After 4 years, 7 patients (32%) had oligospermia and 15 (68%) normospermia. The mean prechemotherapy FSH level (15.5 IU/L) was increased in accordance with subnormal spermatogenesis, but a constant trend toward normalization was observed thereafter., Conclusions: Our results show recovery of spermatogenesis after adjuvant single-agent carboplatin for clinical Stage I seminoma in a remarkably high percentage of patients.

Purpose: We evaluate the use of pretreatment follicle-stimulating hormone (FSH) in patients with germ cell tumors as a prognostic serum marker of spermatogenesis after standard treatment. Additionally, Leydig cell function was investigated by estimation of luteinizing hormone (LH) and testosterone (T), and calculation of the T/LH ratio., Materials and Methods: Serum FSH, LH and T were determined radioimmunologically associated with semen analyses in 20 patients with seminoma (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24 months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were performed in 18 patients with nonseminomatous germ cell tumor (pathological stages IIA to C) before and up to 36 months after standard cisplatin based chemotherapy., Results: Seminoma patients undergoing radiotherapy were divided into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8 with elevated FSH reflecting spermatogenesis deficits even before treatment. Six months after irradiation a significant increase in FSH (p <0.01) associated with a decrease in sperm density was observed in both groups and 24 months after radiotherapy patients with initially normal FSH had significantly lower serum FSH (p <0.01) associated with higher sperm density than those with initially elevated FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable results were observed in chemotherapy treated germ cell tumor patients with initially normal (11) and elevated serum FSH (7), respectively, and 36 months after chemotherapy patients with initially normal FSH had significantly lower FSH concentrations than those with initially elevated FSH (p <0.01). Compensated impairment of Leydig cell function reflected by a subnormal T/LH ratio was evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma patients showed a subnormal ratio reflecting less damage to the Leydig cells caused by irradiation., Conclusions: Pretreatment FSH is a prognostic serum marker of spermatogenesis status of germ cell tumor patients receiving standard radiotherapy or chemotherapy. In contrast to seminoma patients after radiotherapy, impairment of Leydig cell function was evident in germ cell tumor patients after cisplatin based chemotherapy.