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BackgroundThe International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus.Materials and methodsWe identified mSGCT and mNSGCT patients within the SEER database (2004–2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan–Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates.ResultsOf 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups.ConclusionsOur findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

Background Poly(ADP-ribose)polymerase (PARP) inhibitors represent a new class of promising drugs in anticancer therapy. Aims To evaluate PARP expression in testicular germ cell tumours (GCTs) and to correlate expression patterns with clinicopathological variables. Methods In this translational study, tumour specimens from 124 patients with GCTs (114 patients with testicular primary tumours and 10 with extragonadal GCTs) were identified. PARP expression was detected by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method and compared to PARP expression in normal testicular tissue. Results We observed higher expression of PARP in testicular tumours compared to normal testicular tissue (mean QS=10.04 vs 3.31, p<0.0000001). Mean QS±SD for each histological subtype was as follows: intratubular germ cell neoplasia unclassified (IGCNU)=18.00±0.00, embryonal carcinoma=9.62±5.64, seminoma=9.74±6.51, yolk sac tumour=7.8±7.20, teratoma=5.87±5.34, and choriocarcinoma=4.50±8.33. The PARP overexpression (QS>9) was most often detected in IGCNU (100% of specimen with PARP overexpression), seminona (52.6%), embryonal carcinoma (47.0%), yolk sac tumour (33.3%), teratoma (26.7%) and choriocarcinoma (25.0%), compared to 1.9% of normal testicular tissue specimens. There was no association between PARP expression and clinical variables. Conclusions In this pilot study, we showed for the first time, that PARP is overexpressed in testicular germ cell tumours compared to normal testis.

Less than 5% of germ cell tumours arise from an extragonadal primary site, such as the retroperitoneum or mediastinum. 4 Germ cell cancers are more common in men who have had a germ cell cancer of the contralateral testis, men with a first degree relative who has had testicular germ cell cancer, and those with a history of testicular maldescent. 5 The testicular lump is usually noticed by the patient.Because of the lack of pain, medical consultation is often delayed, typically for several months. 6 Delay can influence the stage of the cancer and survival in men with non-seminomas.[...]line chemotherapy, often with surgery, can salvage about half of recurrences. 27 The chance of cure depends on the extent of disease at relapse and initial sensitivity of the disease.There was clear evidence for continued recovery beyond one year; the probability of spermatogenesis increased to 48% by two years and 80% by five. 34 These concerns have led to studies aimed at maintaining cure rate with less toxicity. 35 A large prospective trial showed that for metastatic disease with a good prognosis, three cycles of bleomycin, etoposide, and cisplatinum are as effective as four. 36 For men who present with advanced disease and a poor prognosis, more intensive chemotherapy schedules have been evaluated, 37 38 although high dose treatments have not been proved to be beneficial. 39 What are the long term health consequences in testicular cancer survivors?A review of reports on problems encountered by survivors of testicular cancer found overall quality of life scores similar to those in the general population, but that anxiety associated with fear of recurrence, economic worries, alcohol misuse, and sexual difficulties were more common in survivors. 46 Tips for non-specialists Refer patients with testicular lumps to a urologist under the two week suspected cancer referral pathway Patients may present with gynaecomastia owing to the production of human chorionic gonadotrophin, or with backache or chest symptoms from metastases Assessment of a germ cell cancer includes histological review; computed tomography of the thorax, abdomen, and pelvis; and monitoring of serum tumour markers Cure rates are more than 90% even in those with metastases, but treatment can be less intensive when disease is diagnosed at an earlier stage Ongoing research Germ cell cancers are more common in first degree relatives of affected men and genetic studies are trying to identify predisposing genes Because surveillance for stage I seminoma seems to be a safe and practicable option, an ongoing Medical Research Council (MRC) trial, TRISST, is investigating the optimal radiological techniques and schedule There is limited evidence that a single cycle of bleomycin, etoposide, and cisplatinum is sufficient in the adjuvant setting to prevent recurrence in stage I non-seminoma, and further supportive evidence will come from the current MRC prospective 111 trial The risks of cardiac events and second cancers were increased in patients given curative treatment before 1990, and we need to determine whether newer chemotherapy and radiotherapy regimens have reduced these risks.

Two male patients, aged 55 and 75 years, were referred to the ENT and haematology team respectively, with an asymptomatic left supraclavicular neck mass. Investigations revealed metastatic primary testicular seminoma. CT contrast study of the thorax, abdomen and pelvis demonstrated an additional left para-aortic nodal mass in both cases. The initial presentation of a solitary left neck lump from a metastatic testicular seminoma is extremely unusual, especially in an older age group. The pattern of metastatic spread to the supraclavicular neck nodes from a single para-aortic lymph node is also an interesting finding. Although the majority of seminomas present in younger patients in the early stages when confined to the testis, seminoma can also occur in older patients and can present in an atypical manner. The ability to recognise an atypical presentation in an older patient is invaluable for prompt diagnosis, treatment and follow-up of disease. This case also highlights the importance of a multisystematic structured and an open-minded approach to investigating and diagnosing a neck mass.

AimsFirst, to determine the frequency of intravascular granulomas (IVGs) in seminomas and assess for the presence of entrapped seminoma cells. Second, to identify the relationship of this unusual form of vascular space invasion with tumour relapse and/or dissemination.Methods86 cases of seminoma were reviewed to identify IVGs. Immunostaining for OCT3/4 and CD68 was performed. Pathological stage, presence of conventional vascular and rete testis invasion, parenchymal granulomas and follow-up were recorded. Multivariable analysis incorporating tumour size, vascular invasion (conventional granulomas and IVGs) and rete testis invasion was performed.ResultsIVGs were identified in 13 cases (13/86). CD68 confirmed histiocytes in all cases. OCT3/4 identified tumour cells in 9/13 seminomas. 27 patients had disease progression with either dissemination at presentation (n=11) or relapse (n=16). Of these 27 patients, 8 had IVG (29.6%). By comparison, 6 of 57 clinical stage 1 seminomas that did not relapse had IVG (10.53%). Multivariable analysis revealed that no single parameter was statistically significant at predicting tumour relapse and/or dissemination (size: HR 1.65; CI 0.71 to 3.82, p=0.24, rete testis invasion: HR 1.04; CI 0.48 to 2.26, p=0.92, lymphovascular space invasion/IVG: HR 1.62; CI 0.65 to 4.01, p=0.30).ConclusionsIVGs may represent a previously unrecognised form of vascular space invasion in seminomas. Studies on larger cohorts are needed to demonstrate its clinical value.

Background: We aimed to better discriminate (occult) metastasised from non-metastasised seminoma based on transcriptional changes of small RNAs in the primary tumour. Methods: Total RNAs including small RNAs were isolated from five testicular tumours of each, lymphogenic, occult and non-metastasised patients. Next-generation sequencing (SOLID, Life Technologies) was used to examine transcriptional changes. Small RNAs showing ⩾50 reads and a significant ⩾2-fold difference using non-metastasised tumours as the reference group 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 × 10 7 , 1.4 × 10 7 and 1.7 × 10 7 small RNA reads were detectable in non-metastasised, occult and lymphogenic metastasised seminoma, respectively, of which 30–32% remained after trimming. Between 59 and 68% represented annotated reads and between 8.6 and 11% were annotated small RNA tags. Of them, 137 small RNAs showed>50 reads and a two-fold difference to the reference. In univariate analysis, 32–38 small RNAs significantly discriminated lymphogenic/occult from non-metastasised seminoma, and among these different comparisons, it were the same small RNAs in 51–88%. Many combinations of two of these small RNAs allowed a complete discrimination of metastasised from non-metastasised seminoma irrespective of the metastasis subtype. Conclusions: Metastasised and non-metastasised seminoma can be completely discriminated with a combination of two small RNAs.