Testicular Germ Cell Cancer Patients Research Articles

Quality of life among germ-cell testicular cancer survivors: The effect of time since cancer diagnosis.

IntroductionTesticular cancer is one of the most treatable cancers, with a 10-year survival of more than 95%. Many patients will be long-term survivors and this disease strikes men in an important phase of their lives, therefore the quality of life (QoL) among these patients is an area of particular interest. We aimed to study whether QoL in testicular cancer survivors depends on the time since cancer diagnosis.MethodsData were collected from the EPSAM (Esposizioni postnatali e salute maschile) study, a case-control study on patients with testicular cancer, diagnosed between 1997 and 2008 in the province of Turin, Northern Italy, and interviewed between 2008 and 2010 (response rate among cases 57%). Patients were contacted through their oncologist at the San Giovanni Batista Hospital in Turin or through their general practitioner (GP) in the rest of the Province of Turin. QoL was assessed cross-sectionally using the short form 12 (SF-12) questionnaire, a generic short-form health survey that produces two summary scores, PCS (physical component score) and MCS (mental component score), to evaluate physical and mental health, respectively.ResultsOut of 234 study patients, 125 cases were seminomas and 109 cases were nonseminomas. The mean age at diagnosis was 34.5 years. After adjusting for age, time since diagnosis was not associated with PCS and MCS scores. Among nonseminomas, the median PCS slightly increased (adjusted OR (odds ratio) for 5+ vs < 2 years since cancer diagnosis: 1.78 (1.17–2.73), p = 0.008) and MCS slightly decreased (adjusted OR per 1-year increase since cancer diagnosis: 0.92, 95% CI: 0.82–1.05, p = 0.23) with time. Similar findings of no association between time since diagnosis and PCS and MCS were found when the analyses were restricted to the subgroup of cancer patients contacted through their oncologist, whose response proportion was 82%.ConclusionIn a study of testicular cancer patients interviewed cross-sectionally at 1 to more than 10 years since diagnosis, time since cancer diagnosis was not associated with QoL when we considered all germ-cell testicular cancer patients together. When stratified by histology type, we found certain evidence that nonseminoma cases report higher PCS over time since cancer diagnosis.

Development and validation of prognostic nomogram for germ cell testicular cancer patients.

The purpose of our study was to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with germ cell testicular cancer (GCTC). Patients diagnosed with GCTC between 2004 and 2015 were obtained from the SEER database. Nomograms were constructed using the R software to predict the OS and CSS probabilities and the constructed nomograms were validated and calibrated. A total of 22,165 GCTC patients were enrolled in the study, including the training cohort (15,515 patients) and the validation cohort (6,650 patients). In the training cohort, multivariate Cox regression showed that age, race, AJCC stage, SEER stage and surgery were independent prognostic factors for OS, while age, race, AJCC stage, TM stage, SEER stage and radiotherapy were independent prognostic factors for CSS. Based on the above Cox regression results, we constructed prognostic nomograms of OS and CSS in GCTC patients and found that the OS nomograms had higher C-index and AUC compared to TNM stage in the training and validation cohorts. In addition, in the training and external validation cohorts, the calibration curves showed a good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. The current prognostic nomogram can provide a personalized risk assessment for the survival of GCTC patients.

MiR-371a-3p, miR-373-3p and miR-367-3p as Serum Biomarkers in Metastatic Testicular Germ Cell Cancers Before, During and After Chemotherapy.

Background: LDH (lactate dehydrogenase), AFP (alpha-fetoprotein) and β-HCG (human chorionic gonadotropin) are used in diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. Our aim was to investigate the association between levels of miR-371a-3p, miR-373-3p and miR-367-3p and clinical features in metastatic TGCC. Methods: relative levels of miR-371a-3p, miR-373-3p and miR-367-3p were evaluated in serum of metastatic TGCC patients. A prospectively included and a retrospectively selected cohort were studied (total patient number = 109). Blood samples were drawn at start of chemotherapy and during follow-up. Serum microRNA (miR) levels were determined using the ampTSmiR test. Results: at start of chemotherapy, miR-371a-3p, miR-373-3p and miR-367-3p levels were positively correlated to LDH. The median level of these miRs was higher in patients who developed a relapse after complete biochemical remission (n = 34) than in those who had complete durable remission (n = 60). Higher levels of miR-367-3p were found in patients with refractory disease (n = 15) compared to those who had complete response. miR levels decreased during the first week of chemotherapy in patients with complete response and stayed below threshold after one year of treatment. Conclusion: high miR levels at start of chemotherapy are associated with worse clinical outcome and can assist in early diagnosing of relapses.

Is gynecomastia related to the disease characteristics and prognosis in testicular germ cell tumor patients?

We aimed to assess the relationship between gynecomastia and tumor markers, histologic subtypes, and prognosis in patients with testicular germ cell tumors. This study included 73 testicular germ cell cancer patients with pretreatment chest, abdomen and pelvis computed tomography (CT) scans and tumor markers (β-human chorionic gonadotropin [β-hCG], lactate dehydrogenase [LDH], α-fetoprotein [AFP]). The volumetric analysis of the breast glandular tissue, the presence of gynecomastia and metastatic disease were determined using CT scans. Patients were classified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic classification. The association between gynecomastia, breast glandular tissue volume, tumor markers, metastatic disease, and disease prognosis were evaluated. Thirty-four of the patients (46.6%) had gynecomastia. A breast volume cutoff value of 0.78 cm3 to diagnose gynecomastia led to 85% sensitivity and 95% specificity. Serum β-hCG level correlated with the breast glandular tissue volume weakly (r=0.242, P = 0.039). Gynecomastia was more common in patients with elevated β-hCG levels (P = 0.047), and was not associated with pulmonary, nonpulmonary distant, or nodal metastases (P = 0.378, P = 0.884, P = 0.333, respectively). No significant association was found between the disease prognosis and gynecomastia (P = 0.556). Gynecomastia was common among testicular germ cell cancer patients with elevated β-hCG. However, it was not associated with metastatic disease and prognosis.

Outcome Definition Influences the Relationship Between Genetic Polymorphisms of ERCC1, ERCC2, SLC22A2 and Cisplatin Nephrotoxicity in Adult Testicular Cancer Patients.

Although previous research identified candidate genetic polymorphisms associated with cisplatin nephrotoxicity, varying outcome definitions potentially contributed to the variability in the effect size and direction of this relationship. We selected genetic variants that have been significantly associated with cisplatin-induced nephrotoxicity in more than one published study (SLC22A2 rs316019; ERCC1 rs11615 and rs3212986; ERCC2 rs1799793 and rs13181) and performed a replication analysis to confirm associations between these genetic polymorphisms and cisplatin nephrotoxicity using various outcome definitions. We included 282 germ cell testicular cancer patients treated with cisplatin from 2009–2014, aged >17 years recruited by the Canadian Pharmacogenomics Network for Drug Safety. Nephrotoxicity was defined using four grading tools: (1) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for acute kidney injury (AKI) or CTCAE-AKI; (2) adjusted cisplatin-induced AKI; (3) elevation of serum creatinine; and (4) reduction in the estimated glomerular filtration rate (eGFR). Significant associations were only found when using the CTCAE v4.03 definition: genotype CA of the ERCC1 rs3212986 was associated with decreased risk of cisplatin nephrotoxicity (ORadj = 0.24; 95% CI: 0.08–0.70; p = 0.009) compared to genotype CC. In contrast, addition of allele A at SLC22A2 rs316019 was associated with increased risk (ORadj = 4.41; 95% CI: 1.96–9.88; p < 0.001) while genotype AC was associated with a higher risk of cisplatin nephrotoxicity (ORadj = 5.06; 95% CI: 1.69–15.16; p = 0.004) compared to genotype CC. Our study showed that different case definitions led to variability in the genetic risk ascertainment of cisplatin nephrotoxicity. Therefore, consensus on a set of clinically relevant outcome definitions that all such studies should follow is needed.

Re: MicroRNA-371a-3p as Informative Biomarker for the Follow-up of Testicular Germ Cell Cancer Patients.

Re: MicroRNA-371a-3p as Informative Biomarker for the Follow-up of Testicular Germ Cell Cancer Patients.

Evaluation of Serum Biomarkers (FGF-2, HGF, MIF and PTN) in Patients With Testicular Germ Cell Cancer.

FGF-2, HGF, MIF and PTN have been suggested as biomarkers for testicular germ cell cancer patients in earlier studies. Our study was designed to validate these potential novel tumor markers. Serum FGF-2, HGF, MIF and PTN levels were analysed using an ELISA technique in a screening cohort of 20 testicular germ cell cancer patients and 10 healthy men. MIF levels were measured in a validation cohort of 84 patients with testicular cancer, 24 with non-malignant testicular tumors and 64 healthy men. Serum FGF-2, HGF and PTN levels did not differ in cancer patients and healthy males within the screening cohort, whereas MIF was significantly increased among cancer patients. Within the validation cohort, a modest but insignificant increase of serum MIF was observed in TGCT patients compared to healthy men. MIF levels were not correlated with adverse clinical-pathological parameters. FGF-2, HGF, MIF and PTN are not suitable as non-invasive biomarkers for testicular germ cell cancer patients.

MicroRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients

Purposeα-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up.MethodsWe investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers.ResultsAt primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma.ConclusionsThe ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.

Accurate primary germ cell cancer diagnosis using serum based microRNA detection (ampTSmiR test).

Multiple studies, including various methods and overall limited numbers of mostly heterogeneous cases, indicate that the level of embryonic stem cell microRNAs (miRs) (e.g. 371a-3p, 372-3p, 373-3p, and 367-3p) are increased in serum at primary diagnosis of almost all testicular germ cell cancer (TGCC).Here we determine the status of three of these miRs in serum samples of 250 TGCC patients, collected at time of primary diagnosis, compared with 60 non-TGCC patients and 104 male healthy donors. The levels of miRs were measured by the robust ampTSmiR test, including magnetic bead-based miR isolation and target specific pre-amplification followed by real-time quantitative PCR (RT-qPCR) detection. Calibration is performed based on the non-human spike-in ath-miR-159a, and normalization on the endogenous control miR-30b-5p.The serum levels of miR-371a-3p, 373-3p, and 367-3p are informative to accurately detect TGCC patients, both seminomas and non-seminomas, at the time of primary diagnosis (p< 0.000). Receiver Operating Characteristic (ROC) analysis demonstrate that the Area Under the Curve (AUC) for miR-371a-3p is 0.951 (being 0.888 for miR-373-3p and 0.861 for miR-367-3p), with a sensitivity of 90%, and a specificity of 86% (positive predictive value of 94% and negative predictive value of 79%). Inclusion of miR-373-3p and 367-3p resulted in a AUC of 0.962, with a 90% sensitivity and 91% specificity. Similar results were obtained using the raw Ct data. Importantly, the results demonstrate that ampTSmiR is not suitable to detect pure teratoma as well as the precursor of TGCC, i.e., Germ Cell Neoplasia In Situ (GCNIS).The largest series evaluated so far, demonstrate that detection of the embryonic stem cell miR-371a-3p, 373-3p and 367-3p is highly informative to diagnose patients with a primary TGCC.

Spermatogenesis in tumor-bearing testes in germ cell testicular cancer patients.

What are the factors that might indicate a greater likelihood of success in oncologic testicular sperm extraction (onco-TESE)? Smaller tumor diameter and greater noncancerous testicular tissue width (NCTW) are positive predictors of spermatogenesis in patients with testicular germ cell tumors (TGCTs). Onco-TESE is a key modality for fertility preservation in cases of inadequate pretreatment sperm collection and azoospermic men with testicular cancer. TGCTs are known to reduce sperm quality such that ∼ 10% of these patients are azoospermic, making surgical TESE at the same time as orchiectomy their only means of fertility preservation. This study is a retrospective analysis performed in a single university hospital from 2002 to 2014. Participants were 102 male patients (104 testes) who underwent inguinal orchiectomy and were diagnosed with a germinoma. In each specimen, the Johnsen Score Count (JSC) in seminiferous tubules at each established distance from the tumor margin (1, 2.5, 5, 7.5, 10 and 12.5 mm) was determined. We analyzed the relations between age, tumor histopathologic type, tumor size (maximum diameter), distance from the tumor, non-tumor tissue width and JSC. The 104 specimens consisted of 78 seminomas and 26 non-seminomatous TGCTs. The mean ± SD JSC was 4.7 ± 2.4 in seminomas and 3.9 ± 2.5 in non-seminomatous germ cell tumors, with no significant difference between the two subtypes. Single regression analysis showed that tumor diameter was significantly negatively correlated with spermatogenesis (RC = -0.422, P < 0.001). Multiple linear regression analysis also showed that tumor diameter had a negative influence on spermatogenesis (RC = -0.437, P < 0.001). The greater the distance the seminiferous tubules from the tumor, the better the preservation of spermatogenesis. Mature spermatozoa were identified in 93.0% of patients with a NCTW ≥ 7.5 mm and in 41.3% of those with NCTW < 7.5 mm (P < 0.001). Study data were obtained retrospectively, which might have affected the quality of data. We were unable to compare spermatogenesis determined using preoperative seminograms with that determined histopathologically. It was not possible to evaluate spermatogenesis in the total volume of noncancerous testicular tissue. When Onco-TESE is conducted at sites distant from tumors, the rate of sperm extraction is high and contamination by tumor cells can be prevented. By measuring non-testicular cancerous margin before the operation, the possibility of sperm extraction can be predicted and biopsy of the contralateral testis can be considered based on the results.

Spermatogenesis of tumor-bearing testes in germ cell testicular cancer patients.

e15569 Background: Oncologic testicular sperm extraction (onco-TESE) is a key modality for fertility preservation in cases of inadequate pretreatment sperm collection and azoospermic men with testi...

Novel tumor markers in the serum of testicular germ cell cancer patients: a review

Novel tumor markers in the serum of testicular germ cell cancer patients: a review

High-dose chemotherapy and autologous stem cell transplantation in refractory/metastatic nonseminomatous germ cell-tumors: A retrospective study of the Turkish Oncology Association.

e15623 Background: Testicular cancer is a chemosensitive tumor that may be curable even in relapsed disease. Those patients who do not respond to standard combination chemotherapy or relaps may be treated with high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) as salvage therapy. Methods: Eighty five patients that received HDC and ASCT between Feb 1993 - Dec 2012 in different university clinics of Turkey were retrospectively reviewed and evaluated. Results: Median age of the patients was 24 (range: 11-54 years) and 63 patients (74,1%) had stage III, 21 (24,7%) had stage II disease at initial diagnosis. The primary tumor location was testis in 71 patients (83,5%), and 14 patients (16,5%) had extragonadal region origin. Evaluation of metastatic focuses before HDC and ASCT was as follows: Liver metastasis (n = 23, 27.05%), lung involvement (n = 23, 27.05%) and multiorgan involvement (n =14, 16.47%) and other metastatic involvements (n=4, 4.7%). ICE (ifosfamide, carboplatin, etoposide) regimen was performed as HDC in all patients. Median follow-up was 59 (range: 8-218) months. Pre-ASCT patients’ condition was complete remission (n=28, 32.9%), partial remission (n=36, 42.4%) and never in CR (n=21, 24.7%) respectively. 32 patients (37.6%) relapsed or progressed within 1 year after HDC and ASCT median relaps was time 3 months (range: 0.3 - 36.13). Transplant related mortality was %3.5 and 3 patients died within the engraftment period after HDC. Five-year overall survival rate was 59.7%. Conclusions: HDC and ASCT is an effective and safe approach for patients with metastatic and refractory germ cell testicular cancer patients that do not respond to standard combination chemotherapy.

Survival after a diagnosis of testicular germ cell cancers in Germany and the United States, 2002–2006: A high resolution study by histology and age

Introduction: The aim of this study was to provide detailed age-specific (5-year age groups) and histology-specific (histologic subtypes of seminoma and nonseminoma) relative survival estimates of testicular germ cell cancer patients in Germany and the United States (U.S.) for the years 2002–2006 and to compare these estimates between countries. Methods: We pooled data from 11 cancer registries of Germany and used data from the U.S. (SEER-13 database) including 11,508 and 10,774 newly diagnosed cases (1997–2006) in Germany and the U.S., respectively. We estimated 5-year relative survival (5-year-RS) by histology and age based on period analysis. Results: 5-year-RS for testicular germ cell tumors was 96.7% and 96.3% in Germany and the U.S., respectively. 5-Year-RS for spermatocytic seminoma was close to 100% in both countries. 5-Year-RS for nonseminoma was lower than for classical seminoma in Germany (93.3% versus 97.6%) and the U.S. (91.0% versus 98.2%). Among nonseminomas, choriocarcinomas provided the lowest 5-year-RS in both countries (Germany 80.1%, U.S. 79.6%). Age-specific 5-year-RS for seminoma showed only little variation by age. 5-Year-RS for nonseminomas tended to be lower at higher ages, especially for malignant teratoma. Discussion: This is the first study that provides up-to-date survival estimates for testicular cancer by histology and age in Germany and the U.S. Survival after a diagnosis of testicular cancer is very comparable between Germany and the U.S. 5-Year-RS for spermatocytic seminoma was close to 100% and the lowest 5-year-RS occurred among choriocarcinoma. Higher age at diagnosis is associated with a poorer prognosis among nonseminoma patients.

Semiparametric regression in testicular germ cell data

It is possible to approach regression analysis with random covariates from a semiparametric perspective where information is combined from multiple multivariate sources. The approach assumes a semiparametric density ratio model where multivariate distributions are "regressed" on a reference distribution. A kernel density estimator can be constructed from many data sources in conjunction with the semiparametric model. The estimator is shown to be more efficient than the traditional single-sample kernel density estimator, and its optimal bandwidth is discussed in some detail. Each multivariate distribution and the corresponding conditional expectation (regression) of interest are estimated from the combined data using all sources. Graphical and quantitative diagnostic tools are suggested to assess model validity. The method is applied in quantifying the effect of height and age on weight of germ cell testicular cancer patients. Comparisons are made with multiple regression, generalized additive models (GAM) and nonparametric kernel regression.

Interdisciplinary Evidence-Based Recommendations for the Follow-Up of Early Stage Seminomatous Testicular Germ Cell Cancer Patients

To provide guidance regarding follow-up procedures after initial treatment of early stage testicular seminoma (clinical stages (CS) I-II A/B) based on current published evidence complemented by expert opinion. An interdisciplinary, multinational working group consisting of urologists, medical oncologists, and radiation oncologists analyzed the published evidence regarding follow-up procedures in various stages of seminomatous and nonseminomatous testicular cancers. Focusing on radiooncological aspects, the recommendations contained herein are restricted to early stage seminoma (with radiotherapy being a standard treatment option). In particular, extent, frequency, and duration of imaging at follow-up were analyzed concerning relapse patterns, risk factors, and mode of relapse detection. Active surveillance, adjuvant carboplatin or radiotherapy are equally accepted options for CS I seminoma but they result in different relapse rates and patterns. Usually relapses occur within the first 2(-6) years. Routinely performed follow-up using computerized tomography (CT) after adjuvant treatment yield only low detection rates of recurrences. Therefore, there is no evidence to maintain routine examinations every 3-4 months. After treatment of stage IIA/B, detection rates of relapses or progression identified solely by routinely performed CT during follow-up are low. Considering lifelong cure rates of up to 99% for patients treated for seminoma CS I-IIA/B, the negative impact of unnecessary ionizing radiation exposure has to be considered. The presented recommendations for various follow-up scenarios for early stage seminoma strongly promote the restrictive use of imaging procedures that utilize ionizing radiation (especially CT), due to its potential to induce secondary malignancies.

Interdisciplinary Evidence-Based Recommendations for the Follow-Up of Testicular Germ Cell Cancer Patients

Over the last years, clear treatment recommendations for patients with testicular cancer have been published. This has led to significant improvements in outcome and survival. Moreover, active surveillance has become a cornerstone in the management of clinical stage I seminomatous and non-seminomatous germ cell tumors. On the other hand, the existing recommendations for the follow-up of testis cancer patients are unclear and differ widely. Follow-up recommendations in this young patient population have to be as evidence based as possible, feasible in order to ensure adherence, and must not be harmful. Therefore, attention has to be paid to the negative impact of unnecessary radiation exposure. Recently, new evidence became available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging at follow-up, and the risks of excessive radiation due to imaging, and in particular that of computed tomography (CT) scans. This article summarizes the recommendations for follow-up of testicular cancer patients of an interdisciplinary multinational working group consisting of urologists, medical oncologists, and radiation oncologists.

Testosterone deficiency in testicular germ-cell cancer patients is not influenced by oncological treatment

The aim of the study was to investigate prospectively the prevalence of testosterone deficiency (TD) in patients with testicular germ-cell cancer (TGCC) using longitudinal data. A total of 376 TGCC patients were evaluated for serum testosterone levels before, during and after the following therapies: cisplatin-based polychemotherapy, carboplatin monotherapy, radiotherapy or surgery only. Complete serial hormone analyses were performed on 160 patients (age: 33.8±9.1years, mean±SD). All patients received treatment according to the guidelines of the 'German Testicular Cancer Study Group' and the 'European Germ Cell Cancer Consensus Group' or within studies performed by the 'European Organisation for Research and Treatment of Cancer' and the 'Deutsche Krebsgesellschaft'. Main outcome measurements were sexual hormone profiles over time. Statistical analysis of 1831 testosterone serum levels over time revealed a persistent TD in 23.9% of seminoma and 26.2% of non-seminoma patients. TD was associated with subnormal residual testicular volumes (<12mL). In conclusion, TD rates are high in testis cancer patients. This is present at primary diagnosis and most likely related to testicular dysgenesis or atrophy. Our longitudinal evaluation indicates that treatment modalities have minor influence and effect on the persistently high rates of TD in TGCC patients.

Myocardial infarction and other major vascular events during chemotherapy for testicular cancer

BackgroundChronic vascular morbidity resulting from chemotherapy for testicular germ-cell cancer (TGCC) is recognized. Cardiovascular events (CVEs) occurring early during chemotherapy are less understood. We evaluated the incidence and clinical features of CVEs associated with chemotherapy of TGCC. Patients and methodsA questionnaire was sent to 355 institutions in Germany to explore for early CVEs occurring during 1996–2008. To assess the relative incidence of CVEs, the number of events was put into relation to the total number of patients treated during the time span (n = 8233, calculated from national database). The response rate was 79%. ResultsTwenty cases with myocardial infarction (MI), 3 with cerebral stroke, and 2 with arterial thrombosis were recorded. The estimated incidence of MI and of all CVEs during chemotherapy is 0.24% [95% confidence intervals (CIs) 0.137% to 0.349%] and 0.30% (95% CI 0.188% to 0.423%), respectively. This estimate represents a minimum figure because the calculation is on the basis of simplifications. Six MI patients had no risk factors. Coronary angiography was indicative of thromboembolic rather than atherosclerotic origin of MI. ConclusionsThere is a small but definite risk of major early CVE associated with chemotherapy of TGCC. Physicians caring for TGCC patients must be aware of this hazard.

Familial Coaggregation of Cryptorchidism, Hypospadias, and Testicular Germ Cell Cancer: A Nationwide Cohort Study

Cryptorchidism, hypospadias, and testicular germ cell cancer (TGCC) may be symptoms of a testicular dysgenesis syndrome that manifests during fetal life. To address the inheritability of this syndrome, we examined whether family history of cryptorchidism or hypospadias is associated with an increased risk of TGCC. A total of 2,159,883 men born since 1953, identified through Danish health registers, were followed from April 2, 1968, through May 31, 2008. First-, second-, and third-degree relatives were identified in the Danish Family Relations Database; cryptorchidism and hypospadias patients were identified in the Danish Hospital Discharge Register; and TGCC patients were identified in the Danish Cancer Register. Poisson regression was used to calculate the risk ratio for TGCC by family history of cryptorchidism or hypospadias. A total of 5441 patients developed TGCC. A personal history of cryptorchidism or hypospadias was associated with an increased relative risk (RR) of developing TGCC (RR = 3.71, 95% confidence interval [CI] = 3.29 to 4.19; and RR = 2.13, 95% CI = 1.26 to 3.61, respectively). For example, in men in their thirties, the overall rate per 100 000 is 25.1 in the cohort, but 88.6 and 55.4 in men born with cryptorchidism or hypospadias, respectively. In contrast, relatives of a hypospadias patient did not have a statistically significantly increased risk of TGCC nor did the first- and second-degree relatives of cryptorchidism patients. However, we found a small increased risk of TGCC for third-degree relatives of patients with cryptorchidism. Having hypospadias or cryptorchidism was associated with an increased risk of developing TGCC. However, our finding that family history of hypospadias or cryptorchidism generally was not associated with increased risk of developing TGCC does not support the hypothesis of shared inheritability of cryptorchidism, hypospadias, and TGCC.