Stage II testicular seminoma: patterns of recurrence and outcome of treatment

OBJECTIVES: To review treatment outcome and patterns of failure for patients with stage II testicular seminoma and to identify prognostic factors for relapse. METHODS: From 1981 to 1999, 126 men with stage II seminoma were treated at Princess Margaret Hospital. Of these, 95 were treated with radiotherapy (RT) and 31 with chemotherapy (ChT). Patient and tumour characteristics were analyzed for prognostic significance for subsequent relapse. RESULTS: At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance. CONCLUSIONS: In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.     

Management of Stage II testicular seminoma over a period of 40 years

ObjectivesTo review the treatment, toxicity, and outcomes in patients with Stage II seminoma after orchidectomy.Materials and methodsA retrospective chart review of all patients with Stage II seminoma referred for initial treatment, from 1965 to 2005, was performed. Treatment approaches, toxicity, and outcomes were analyzed.ResultsA total of 106 patients (83 with Stage IIA, 19 with Stage IIB, and 4 with Stage IIC) were seen between 1965 and 2005. Median age at diagnosis was 36 years (range: 19–71). Median follow-up was 21 years (range: 1.2–42). Eighty-nine patients were treated with adjuvant radiotherapy alone; 13 patients received a combined treatment modality with chemotherapy and radiotherapy after orchidectomy, 4 patients were treated with chemotherapy alone. Generally the treatment was well tolerated, with the main toxicity occurring in patients treated with extended-field radiotherapy. The 5-year disease-specific survival was 96% for the entire group. The 5-year relapse-free survivals for Stages IIA, IIB, and IIC disease were 94%, 72.5%, and 75%, respectively. Fifteen patients developed a relapse and were managed by chemotherapy; 5 of them achieved complete remission and remain free from further recurrence at last follow-up, while 10 died of the disease. Second malignancies were diagnosed in 4 (3.7%) patients during the follow-up.ConclusionsIn Stage IIA seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Radiotherapy or chemotherapy should be offered as an alternative to Stage IIB patients. Chemotherapy remains the treatment of choice for Stage IIC seminoma.     

人类睾丸精原细胞瘤组织中P_（53）基因突变和Rb基因蛋白产物表达的缺失

采用Ｗｅｓｔｅｒｎ印迹和ＤＮＡ聚合酶链反应－单股构造多态性分析法对１７例人睾丸精原细胞瘤组织标本的抗癌基因Ｒｂ表达的蛋白产物和Ｐ_（５３）基因外显子５～８的突变进行检测，发现有３例标本的Ｒｂ基因表达的蛋白产物缺失，有４例标本的Ｐ_（５３）基因有点突变，对照的正常人睾丸组织和视网膜组织均呈Ｒｂ基因蛋白产物表达阳性，对照的正常人睾丸组织中未发现Ｐ_（５３）基因突变。本结果提示人睾丸精原细胞瘤的发生与抗癌基因Ｒｂ蛋白产物表达的缺失和Ｐ_（５３）基因的突变有关。     

多模态超声诊断睾丸精原细胞瘤1例

<正>患者男,24岁,因"右侧睾丸胀痛不适半年余,加重2天"就诊。查体:右侧睾丸轻度增大,下极触及最大径约2.00 cm质硬团块,边界欠清,轻微触痛,未见红肿,皮温正常。二维超声:右侧睾丸约4.51 cm×3.44 cm×2.53 cm,其下极探及约2.00 cm×1.90 cm规则低回声肿块,边界欠清;CDFI于肿块内探及丰富血流信号(图1A),呈动脉样频谱,收缩期峰值流速(peak systolic velocity, PSV)12.00     

Possible mechanism responsible for the acquisition of resistance to cis-diamminedichloroplatinum (II) by cultured human testicular seminoma cells

PURPOSE: We established a cis-diamminedichloroplatinum (II) (CDDP) resistant cell line and determined the mechanisms of CDDP resistance. MATERIALS AND METHODS: The CDDP resistant cell line JKT/DDP was established from the highly metastatic human testicular seminoma cell line JKT-HM by long-term intermittent administration of low dose CDDP. Growth curves, CDDP sensitivity and intracellular CDDP concentrations were compared in JKT/DDP, the seminoma cell line JKT-1 and JKT-HM cells. Expression of the mRNA of MDR1, MRP, LRP and GST-pi was also compared. RESULTS: The growth curve and doubling time of JKT/DDP were similar to those of JKT-1 and JKT-HM in culture without CDDP but different with CDDP added to the culture. Morphologically cytoplasm segmentation and chromatin aggregation in JKT-1 and JKT-HM were observed when CDDP was present, while JKT/DDP cells were spindle-shaped and showed cobblestone growth.The IC50 for CDDP determined by the collagen gel drop embedded drug sensitivity test showed that JKT/DDP was more resistant to CDDP than the other 2 cell lines. The expression of MDR1, MRP and GST-pi was higher than in JKT-1 or JKT-HM cells and the intracellular CDDP concentration was lower in JKT/DDP. CONCLUSIONS: The JKT/DDP cell line acquired CDDP resistance by increased cytoplasmic CDDP metabolism.     

Molecular evaluation of CFTR sequence variants in male infertility of testicular origin

Although the involvement of the CFTR gene has been well established in congenital agenesia of vas deferens, its role in non-obstructive (NOb) infertility is still a matter of debate. In order to definitively define the involvement of the CFTR gene in spermatogenic impairment and a potential synergistic contribution to known genetic and clinical factors, genetic variants in the entire coding sequence and the immediately flanking regions of the CFTR gene, along with a thorough clinical evaluation, were analysed in 83 NOb infertile patients and 87 clinically well-defined fertile individuals as controls. The results of our study showed no statistical difference between CFTR carrier frequency in the infertile and fertile population. Specifically, the IVS8-6(5T) allele carrier frequency was similar in NOb infertile patients when compared with fertile men, but it is noteworthy that, when fertile men were classified into having optimal and suboptimal fertility, no 5T allele was found among the 35 men with optimal fertility parameters. In conclusion, extensive CFTR analysis in infertile individuals and fertile population as adequate control definitively excludes the involvement of the CFTR gene variants in sperm production and stresses the importance of carefully identifying those individuals with obstructive defects, in whom CFTR screening will be beneficial.     

Detection of testicular ultrasonographic lesions in severe male infertility

PURPOSE: We retrospectively assessed the number and histology of testicular lesions diagnosed clinically and by ultrasonography in a population of infertile men. MATERIALS AND METHODS: From October 2000 to January 2003, 560 infertile men underwent physical examination, hormonal assessment (follicle-stimulating hormone, luteinizing hormone, testosterone) and scrotal ultrasonography. Eight men were diagnosed with focal testicular ultrasonographic lesions. In 4 cases there was a palpable lesion and in the other 4 cases the lesion was not palpable, diagnosed by ultrasonography (1 was cryptorchid). Only cases of lesions with clear-cut ultrasonographic edges and no history of recent genital infections were considered for explorative surgery through the groin. Microcalcifications were reported if present. The testicle was only preserved when frozen section examination revealed a benign lesion and the margins were negative. RESULTS: Gynecomastia was not present in any patient. No microcalcifications were observed. Follicle-stimulating hormone was high in all patients (range 19.8 to 66.0 mUI/ml, mean 34.4). Luteinizing hormone levels were variable (range 1.32 to 28 mUI/ml, mean 12.3). Testosterone was normal in all cases (range 2.82 to 6.25 ng/ml, mean 4.2). Ultrasonographic features of the lesions were hypoechoic area (6 patients) and mixed hyper-hypoechoic area (2 patients). Histological outcomes of Leydig cell tumor (in 3 patients), focal Leydig cell hyperplasia (1 patient), fibrosis (1 patient), diffuse Leydig cell hyperplasia (1 patient), classic seminoma (1 patient) and embryonal carcinoma (in 1 patient) were observed. CONCLUSIONS: Of 560 infertile patients 8 (1.4%) showed focal testicular lesions, 2 (0.4%) were diagnosed with germ cell tumors and 3 (0.5%) with interstitial cell neoplasms. The malignant tumors were both palpable and in 2 of 3 cases Leydig cell tumors were diagnosed only with ultrasonography.     

Assessment of immunological mechanism in infertility of the rat after experimental testicular torsion

Summary A necrotic torted testis left in the scrotum affects the contralateral testis, resulting in depressed fertility. It was suggested that testicular torsion provoked a systemic response of an immunologic nature. In order to prove this theory, 56 rats were operated. Ten had a sham operation, in 17 a testis was torted and excised after 24 h, and in 29 a testis was torted and excised after 24 h, and in 29 a testis was torted but left in situ till the sacrifice. Antisperm-antibodies were not found in any phase of the experiment in the sham group. Using indirect immunofluorescence, antisperm-antibodies were found in the sera of 8/17 rats of the orchiectomy group and in 24/29 of the detorted group. In the direct immunofluorescence study, all the antibodies were localized in the tail of the spermatozoid. The antisperm-antibodies dissappeared after 3 to 6 months.     

Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis

PURPOSE: We determined the standardized incidence ratio of testicular cancer in infertile men presenting with an abnormal semen analysis compared to the general population. MATERIALS AND METHODS: The charts from more than 3,800 men presenting with infertility and abnormal semen analysis during a 10-year period were retrospectively reviewed. The incidence of testicular tumors diagnosed in this group was compared to that of race and age matched controls during the same period from the general population (as reported by the Surveillance, Epidemiology and End Results [SEER] database). RESULTS: Of 3,847 men 10 (0.3%) with infertility and abnormal semen analysis were diagnosed with testicular tumors. Mean patient age was 32.6 years (range 25 to 52) and all 10 men were diagnosed with a seminomatous germ cell tumor. Two men had a history of cryptorchidism while the remaining 8 had no identifiable risk factors for testicular cancer. The SEER database reported an incidence of 10.6 cases of testicular cancer (95% CI 10.3-10.8) per 100,000 men of similar age group and racial composition during the same period. The standardized incidence ratio of testicular cancer was 22.9 (95% CI 22.4-23.5) when comparing our infertile group to the control population. Exclusion from analysis of the 2 patients with a history of cryptorchidism decreased the standardized incidence ratio to 18.3 (95% CI 18.0-18.8). CONCLUSIONS: Infertile men with abnormal semen analyses have a 20-fold greater incidence of testicular cancer compared to the general population. Patients and physicians should be aware that one of the causes of infertility could be cancer, particularly testicular cancer.     

Patterns of care in the management of seminoma stage I: results from a European survey

Study Type – Therapy (practise pattern survey) Level of Evidence 3b What's known on the subject? and What does the study add? The uncertainties about differences in relapse and rates of other late events such as second malignancy and cardiovascular events for the three post‐orchidectomy strategies in seminoma stage I patients has led to debates about whether the three strategies are equally effective and safe. The differences in interpretation of the data as well as the debates are likely to result in differences in treatment after orchidectomy in seminoma stage I patient management. Current care patterns after orchidectomy are, however, unknown. We assessed patterns of care for seminoma stage I patients after orchidectomy by distributing a survey among doctors treating such patients across Europe. The 969 respondents showed large differences in care strategies between specialties and countries that indicate the need for research into long‐term relapse rates and long‐term adverse effects to standardize and optimize care for seminoma stage I patients.

OBJECTIVE

• ? To assess precise patterns of care after orchidectomy in Europe for stage I seminoma patients, we aimed to perform a survey among doctors in the various European countries.

PATIENTS AND METHODS

• ? We distributed a survey in 2009 and 2010 among American Society of Clinical Oncology and European Association of Urology members.

RESULTS

• ? In total, 969 questionnaires were included in the analysis. More than half of the 969 physicians (58%) currently offer only one post‐surgical treatment: 18% only surveillance, 19% only radiotherapy and 21% only chemotherapy. Thirteen percent of the 969 physicians currently offer all three strategies, 25% offer surveillance and adjuvant radiotherapy or chemotherapy, and 5% offer either adjuvant radiotherapy or chemotherapy without surveillance.
• ? We found large differences in care patterns between specialties and countries. Even within countries, care after orchidectomy was not standardized.
• ? Before 2005, 73% of the physicians offered only one treatment and of those 51% gave adjuvant radiotherapy.

CONCLUSIONS

• ? Large differences in pattern of care after orchidectomy for stage I seminoma patients exist between specialties and countries within Europe.
• ? More information on long‐term relapse rates and long‐term adverse effects of the three strategies is needed to standardize and optimize care after orchidectomy.

     

Preservation of testicular tissue before fixation: Die Aufbewahrung von Hodengewebe vor einer Fixierung

An optimum evaluation of testicular tissue for diagnostic purposes is only possible by means of the semithin-section-technique, which implies fixation in glutaraldehyde/OsO4 followed by embedding in Epon. Since in clinical departments adequate fixatives are not always available, various storage conditions until further processing were tested. Testicular tissues from 5 men, who underwent orchidectomy, were stored for different periods in solutions of Ringer, 0.9% NaCl, Macrodex, Dextran, 1640 Medium or in a humid chamber either at room temperature or at 4 degrees C, subsequently fixed and then studied by means of light and electron microscopy. Under most conditions, primary spermatocytes and Leydig cells disintegrated rather quickly, while spermatogonia, spermatids and Sertoli cells without fixation were relatively well preserved up to 5 hrs. For optimum preservation the storage of testicular tissue in a humid chamber at 4 degrees C is recommended.     

Stage IIA and IIB testicular seminoma treated post-orchiectomy with radiation therapy versus other approaches: a population-based analysis of 241 patients

Objectives

To evaluate post-orchiectomy utilization of radiation therapy (RT) versus other management approaches in stage IIA and IIB testicular seminoma patients.

Materials and Methods

Two hundred and forty-one patients with stage IIA and IIB testicular seminoma were identified between 1988 and 2003 using the Surveillance, Epidemiology, and End Results (SEER) database.

Results

Median follow-up was 10 years. Patients with stage IIA disease underwent RT more frequently than those with stage IIB disease (72% vs. 46%, respectively; P<0.001). There was no significant change in RT utilization for stage IIA or IIB disease between 1988 and 2003 (P = 0.89).

Conclusions

Between 1988 and 2003, stage IIA patients underwent RT more often than stage IIB patients in the United States. There was no significant change in RT utilization for stage IIA or IIB disease during this time period. Based on reports describing excellent progression-free survival with cisplatin-based chemotherapy, this approach has increased in popularity since 2003 and may eventually become the most popular treatment approach for both stage IIA and IIB testicular seminoma.     

Serum lactate dehydrogenase isoenzyme 1 as predictor of tumour-associated death in patients with testicular germ cell tumours

Summary. Serum lactate dehydrogenase isoenzyme 1 (S-LD-1) was determined in 24 patients with testicular germ cell tumours who died during follow-up. Serum samples were obtained at the start of chemotherapy or late into the clinical course for those without evidence of a tumour. Seven of the eight patients with tumour-associated death had S-LD-1 > 150 U 1⁻¹ (median 260 U 1⁻¹ range 90–905 U 1⁻¹, as did two of the six who died without evidence of a tumour (median 134 U 1⁻¹ range 89–128 U 1⁻¹) ( P =0.03, Mann-Whitney U-test, two-tailed). The remaining 10 patients had previously been reported as to prediction of S-LD-1 for the prognosis, and were evaluated only as to the reproducibility of the S-LD-1 determination. S-LD-1 was determined in two serum samples obtained concomitantly from eight of these 10 patients: the difference between the two S-LD-1 determinations was median 6% of the average of the two S-LD-1 determinations (25–75% range 3–17%). Our study showed an unforeseeable high level of imprecision of the assay system. Nevertheless, S-LD-1 determinations in the regular monitoring of patients with testicular germ cell tumours may be useful for predicting tumour-associated deaths.     

The association between variants in the CFTR gene and nonobstructive male infertility: A meta-analysis

The association of genetic variants and congenital bilateral absence of the vas deferens (CBAVD) has been well acknowledged. By contrast, the link between nonobstructive azoospermia (NOA) or oligospermia and alterations in the cystic fibrosis transmembrane conductive regulator (CFTR) remains inconclusive. To clarify the problem, a meta-analysis was performed out after systematically searching Pubmed, Web of Science, Embase and the Chinese national knowledge infrastructure (CNKI) database. As we know, the ∆F508 and IVS8-5T gene mutations are the most studied genetic variants in CFTR gene. We reviewed the data from male patients who underwent the aforementioned genetic test. Our study revealed that the IVS8-5T mutation may be positively associated with the risk of nonobstructive male infertility (odds ratio (OR) 1.69; 95% CI: 1.12–2.55). This association strengthened when concerning NOA (OR: 2.62; 95% CI: 1.49–4.61). However, the ∆F508 mutation seemed to be a smaller contributing factor to this risk (OR: 1.63; 95% CI: 0.86–3.08). Our study aims to clarify the association between the ∆F508 and IVS8-5T gene mutations and nonobstructive male infertility. Therefore, screening for the IVS8-5T mutation in the CFTR gene may be recommended for men with NOA or severe oligozoospermia seeking assisted reproductive technology (ART).     

脂肪细胞因子导致不孕症的相关生殖内分泌机制研究进展

脂肪组织是机体内重要的内分泌和旁分泌器官,可分泌多种生物活性肽,称为脂肪细胞因子,其中瘦素(LEP)、脂联素(ADPN)、抵抗素(resistin)等因子水平与肥胖症密切相关,可作用于机体局部和系统水平,影响女性生殖内分泌系统,甚至导致不孕症。本文通过整理和分析相关研究,进一步揭示脂肪细胞因子与生殖内分泌系统功能的相关性,及其导致女性不孕症的作用机制。     

Laparoscopic excision of a large prostatic utricle revealed by haematuria: 1-year follow-up

Prostatic utricles revealed by the presentation of haematuria are very rare. Only limited experience with laparoscopic surgery of prostatic utricle has been reported to date. Herein we report a 20-year-old male with frequently terminal haematuria and oligozoospermia who underwent successful laparoscopic excision of a large prostatic utricle. Haematuria disappeared and semen quality improved during 1-year follow-up.     

Effect of α-chlorohydrin on metabolism and testosterone secretion by rat testicular interstitial cells

The direct effect of alpha-chlorochydrin (alpha-CH) on basic metabolism (glucose utilization and oxygen consumption) and testosterone secretion by isolated rat interstitial cells (I-cells) has been studied. In the range of concentrations between 5 and 100 microliter/ml, only the highest doses of alpha-CH decreased cell vitality and their histochemical stain for 3 beta-HSD. Oxygen consumption of I-cells was depressed at all doses higher than 10 microliter/ml and this effect was reversible only with doses lower than 50 microliter/ml. glucose utilization by I-cells was depressed significantly by alpha-CH and this effect was particularly dramatic with doses higher than 50 microliter/ml. alpha-CH decreased testosterone secretion by I-cells, with maximal effects at 100 microliter/ml. I-cells responded to hCG challenge by increasing testosterone secretion, and hCG prevented the toxic effect of alpha-CH at the lowest dose (10 microliter/ml) of alpha-CH, but failed to overcome the effects of a high dose (100 microliter/ml).     

Radical inguinal orchidectomy: the gold standard for initial management of testicular cancer

Radical inguinal orchidectomy with division of the spermatic cord at the internal inguinal ring is the gold standard for diagnosis and local treatment of testicular malignancies. The technique is well established and described in detail in this paper, collating methods from various surgical textbooks and articles. We also discuss pre-operative considerations including fertility counselling and potential testicular prosthesis at time of orchidectomy, and the importance of contemplating differential diagnoses such as para-testicular sarcoma and primary testicular lymphoma (PTL) prior to performing radical orchidectomy (RO). The evidence and indications for new surgical techniques to treat local testicular malignancies are also described, including testis sparing surgery (TSS) and spermatic cord sparing orchidectomy.