Study of total serum amylase, its salivary and pancreatic fraction and the pancreatic to salivary amylase ratio in testicular tumours.

Serum levels of total amylase, its pancreatic fraction (P), salivary fraction (S), and the ratio of pancreatic to salivary fraction (P/S) were determined in 52 cases of histologically proved testicular germ cell tumours and 33 healthy controls. Total serum amylase remained unchanged, but the salivary fraction had a lower mean value. P/S ratio and the pancreatic fraction were significantly elevated in both seminomatous and non- seminomatous tumours. The ratio was more frequently raised in non-seminomatous (100%) as compared to seminomatous (66.67%) tumors. Following treatment there was no appreciable fall in P/S ratio in non-seminomatous tumors whereas in seminomas there was a slight increase in the ratio. The pancreatic fraction showed a transient fall in seminomatous but not in non-seminomatous tumors following treatment. The pancreatic fraction of amylase and the P/S ratio may help in the diagnosis of testicular germ cell tumor but does not appear to be of use in assessment of prognosis or monitoring the course of the disease during treatment.     

Positive expressions of N-acetylglucosaminyltransferase-V (GnT-V) and beta1-6 branching N-linked oligosaccharides in human testicular germ cells diminish during malignant transformation and progression

N-acetylglucosaminyltransferase-V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagines (N)-linked oligosaccharides of cell proteins. We examined the implication of GnT-V and beta1-6 branching N-linked oligosaccharide expression in human testicular germ cells during malignant transformation and cancer progression. We analyzed immuhistochemically orchiectomy specimens of 130 patients with testicular germ cell tumors (TGCT) using anti-GnT-V monoclonal antibody, and compared GnT-V expression with clinicopathological features. N-linked oligosaccharide structural analysis was also performed to confirm the oligosaccharide profile produced by GnT-V. GnT-V was positive in all normal testis samples. This positive incidence declined in TGCT according to clinical stage; 16/71 (22.5%) in stage I, and 3/59 (5.1%) in stage II/III (p=0.015, chi(2) test). When divided into pathological subtypes, GnT-V positive incidences in stage I seminoma, stage II/III seminoma, stage I non-seminomatous germ cell tumor (NSGCT), and stage II/III NSGCT were 3/43 (7%), 0/22 (0%), 13/28 (46.4%), and 3/37 (8.1%), respectively. In stage I NSGCT, patients with GnT-V-negative tumor samples were at a significantly higher risk of recurrence than those with GnT-V-positive tumors (p=0.015, log-rank test). N-linked oligosaccharide structural analysis revealed that a normal testis has three kinds of beta1-6 branching N-linked oligosaccharides, all of which are downregulated in TGCT tissues. These results suggest that GnT-V and beta1-6 branching N-linked oligosaccharide expressions are downregulated during carcinogenesis and progression of human TGCT. GnT-V may be a promising recurrence predictor for stage I NSGCT.     

Serum lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase and ratio of alpha-hydroxybutyrate dehydrogenase to lactate dehydrogenase in testicular tumours

Serum levels of Lactate Dehydrogenase (LDH), alpha-Hydroxybutyrate Dehydrogenase (HBDH) and the relative ratio of alpha-Hydroxybutyrate Dehydrogenase to Lactate Dehydrogenase (HBDH/LDH) were determined in 51 cases of histologically proved testicular germ cell tumors and 40 healthy controls. Serum LDH and HBDH levels were found to be raised in both seminomatous and non-seminomatous germ cell tumors. The ratio of HBDH/LDH was found to be statistically significant in seminomas and insignificant in non-seminomatous germ cell tumors. Furthermore, the levels of LDH and HBDH showed a fall, following treatment indicating response to therapy. Serum LDH and HBDH could both be used as tumor markers in the diagnosis of testicular germ cell tumors as well as prognostic indicators in monitoring therapy, HBDH, being more specific in monitoring therapy as compared to serum LDH.     

Characteristics of Incident Testicular Cancer in Lebanon - 1990-2015 Single Institutional Experience

Background: Despite the fact that testicular cancer is a major health issue with its increasing incidence, very few studies have described its characteristics in the Middle East, particularly in Lebanon. Materials and Methods: We report in this paper a retrospective pilot study of the characteristics of testicular cancer in Lebanon. The demographic, epidemiologic and survival characteristics of 178 patients diagnosed between 1990 and 2015 at an oncology clinic affiliated to Hotel Dieu de France Hospital were analyzed. Results: The mean age at diagnosis was 32 10 years. The most prevalent testicular tumor was the germ cell type (GCT) (95.2%) of which non-seminomatous tumors (NST) were the commonest (64.7%). Most of our patients were diagnosed at an early stage. Lymph node spread affected most commonly the retroperitoneal region and distant visceral metastases occurred in 14.6%. All patients underwent orchiectomy with 67% receiving adjuvant treatment, mainly chemotherapy. After a median follow up of 2,248 days (75.9 months) 16 patients were reported dead. Two, five and ten-year overall survival rates were 96%, 94% and 89% respectively. The median overall survival rate was not reached. Conclusions: Despite being part of the developing world, demographic, epidemiologic and survival analyses of testicular cancer reported in our study are in line with those reported from developed countries and would allow us to extrapolate management plans from these populations.     

睾丸生殖细胞肿瘤综合治疗的长期疗效

目的 分析睾丸生殖细胞肿瘤(TGCTs)患者的临床特征、综合治疗疗效、生存率以及与预后有关的因素。方法 对107例行高位睾丸切除 精索静脉结扎术、术后均行化疗的TGCTs患者进行回顾性分析。近期疗效比较采用χ^2检验;生存率的计算采用Kaplan-Meiel生存曲线;生存率的比较采用Log rank检验。结果 107例患者中位年龄32岁。精原细胞瘤33例(30．8％),其中Ⅰ期14例,占42．4％;非精原细胞瘤74例(69．2％),其中I期21例,占28．4％。临床分期和病理类型是影响患者预后的主要因素。患者总的3,5,10年生存率分别为75．8％、73．5％和73．5％。精原细胞瘤患者3,5,10年生存率分别为100％、96．8％和96．8％;非精原细胞瘤患者3,5,10年生存率分别为63、5％、61．7％和61．7％。64例患者可评价疗效,单用化疗的患者中,17例(26,6％)达CR,另有8例(12．5％)化疗加放疗或解救手术后达CR。获CR与未获CR者5年生存率分别为91．7％和26．2％。结论 Ⅰ期TGCTs预后好。采用以化疗为主的综合治疗可明显提高转移性TGCTs患者的疗效和生存率。     

Clinicopathological Features and Survival of Young Turkish Patients with Testicular Germ Cell Tumors

Background: Testicular germ cell tumors (TGCTs) are a relatively common malignancy in young men. Theaim of this study was to investigate the clinicopathological features and survival of young Turkish patientswith TGCT. Materials and Methods: In this retrospective study, the clinical and pathological characteristics ofyoung Turkish patients with TGCT who were monitored by the Department of Medical Oncology of a militaryhospital between 2008 and 2013 were investigated. Overall survival data were analyzed. Results: Ninety-sixpatients were included in the study. The mean age was 26.4 years. Among the patients, 17.7% had seminomaand 43.8% had mixed non-seminomatous germ cell tumors. Some 46.9% were Stage I, 30.2% were Stage II, and22.9 were Stage III. Of the patients, 83.3% received chemotherapy, 25% underwent retroperitoneal lymph nodedissection (RPLND), 3.1% received radiotherapy, and 12.5% were followed-up without treatment. In addition,18.8% of the patients were administered salvage chemotherapy due to relapse or progression. The 5-year overallsurvival rate was 90.2% for all patients. The 2-year overall survival rate was 100% for Stage I patients, 94%for Stage II patients, and 70.2% for Stage III patients. The difference between the survival curves of stages wasstatistically significant (p=0.029). Conclusions: In young Turkish patients with TGCT, good results were obtainedwith appropriate treatment, most receiving chemotherapy. The prognosis of the disease was good even in theadvanced stage.     

Lactate dehydrogenase isoenzyme 1 is the most important LD isoenzyme in patients with testicular germ cell tumor

We examined the clinical utility of serum lactate dehydrogenase (LD) isoenzyme catalytic concentrations in 58 patients with testicular germ cell tumors (TGCT) (13 with seminoma and 45 with non-seminomatous tumors). Twenty-one patients with no evidence of disease (NED) all had serum LD isoenzyme 1 catalytic concentrations (LD-1) and LD-1/LD fractions below the upper limit of the reference values (ULR). LD-1 and the LD-1/LD fraction discriminated significantly between evidence of disease (ED) and NED (p=0.00009 and p     

Exome Sequencing of Bilateral Testicular Germ Cell Tumors Suggests Independent Development Lineages

Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients.     

Expression of HER-2/neu in testicular tumors

BACKGROUND: Although the overexpression of the Epidermal Growth Factor Receptor 2 (EGFR-2, HER-2/neu, c-erbB-2) in malignancies might predict chemoresistance and poor prognosis, its clinical relevance has not been widely studied and determined in testicular tumors. PATIENTS AND METHODS: Since teratomas are relatively chemoresistant tumors, we evaluated the HER-2/neu receptor status of 28 primary testicular tumors (7 pure teratomas, 21 mixed germ cell tumors containing teratomatous components) using a standardized immunohistochemical method (HercepTest Kit). RESULTS: Seven (25%) out of 28 non-seminomatous germ cell tumors showed HER-2/neu positivity. The teratomatous components of mixed GCTs showed HER-2/neu overexpression in 5 cases. Three of the 5 choriocarcinoma components of mixed tumors overexpressed HER-2/neu. In one case (teratoma + choriocarcinoma) both components showed HER-2/neu overexpression. No HER-2/neu overexpression was detected in other, less differentiated histological subtypes. Among the HER-2/neu-positive cases, 3 patients are in complete remission, 3 patients are in partial remission and one patient died after primary chemotherapy. CONCLUSION: Twenty-five percent of the non-seminomatous germ cell tumors which contain teratomatous components overexpress HER-2/neu protein. The overexpression is restricted to the more differentiated histotypes. Further molecular investigations and clinicopathological studies are necessary to determine the correlation between HER-2/neu overexpression and clinical resistance of testicular tumors.     

Bilateral testicular germ cell tumors: twenty-year experience at M. D. Anderson Cancer Center

BACKGROUND: The incidence of testicular carcinoma in the United States has increased significantly over the last two decades. Germ cell tumors form the majority of malignant testicular tumors. With advances in diagnosis and therapeutic approaches, germ cell tumors are now highly sensitive to treatment, providing long-term survival. It has been speculated that the incidence of bilateral germ cell tumors may increase due to the improved survival of patients with unilateral germ cell tumors. In this report, the authors present a study of bilateral germ cell tumors of the testis in men who were treated at The University of Texas M. D. Anderson Cancer Center over a 20-year period with emphasis on their incidence, histologic features, and clinical features. METHODS: Between 1978 and 1999, 2431 patients with testicular germ cell tumors were treated at The University of Texas M. D. Anderson Cancer Center. Among these, 24 patients with bilateral germ cell tumors were identified. Clinical records and all available pathology slides of the tumors were reviewed. RESULTS: The overall incidence of bilateral germ cell tumors in the patients with testicular germ cell tumors was 1% (24 of 2431 patients). The incidence was 1.8% (14 of 776 patients) in patients with seminoma and 0.6% (10 of 1655 patients) in patients with nonseminomatous germ cell tumors. Patients with seminoma who were age 相似文献   

Testicular neoplasms. Evaluation of the experience during 25 years in a military hospital

Introduction Testicular tumors are frequent in young adults, coinciding with incorporation to military service. The present study evaluates the tumor characteristics, time course and results obtained with the treatments used in our center for this type of neoplasms. Material and methods A retrospective longitudinal study was conducted in a cohort of 98 patients with an average age of 28.6 years, subjected to orchiectomy for testicular tumors in our center between 1979 and 2004. Data were collected relating to patient age, tumor characteristics, the outcome of treatment, and the course of the disease. Results The right testicle was affected in 61% (with significant differences versus the left side). The most common histological type corresponded to non-seminomatous germ cell tumors (NSGCTs) (65.3%), followed by pure seminomas (27.6%) and non-germinal cell tumors (NGCs) (7.1%). NSGCT was diagnosed at a significantly younger average age (23.2 years) than the other two tumor types. Stage I was the most frequent presentation (58%). Seminomas presented in stage I significantly more often (80%) than the others tumors. The data collected over the 25-year study period showed no significant variations in tumor characteristics. Thelog-rank test showed a significant difference in terms of patient survival according to the tumor cell line (p=0.000) and stage (p=0.000), except between stages I and II, where no significant differences were observed in terms of survival. Conclusions Non-seminomatous germ cell tumors (NSGCTs) are the most frequent testicular tumors in young adults. Most neoplasms are diagnosed in early stages, the prognosis being better in the case of seminomas and tumor stages I and II.     

Clinical Profile,Treatment and Survival Outcome of Testicular Tumors: A Pakistani Perspective

Background: Testicular cancer management is considered a marvel of modern science with excellenttreatment results. Pakistan has a distinct ethnic variation and geographic distribution but data regardingclinical presentation of testicular tumors and their management is under reported. The objective of this studywas to determine clinical profile, treatment modalities and survival outcome of testicular tumors in the Pakistanipopulation. Materials and Methods: A retrospective review of patients who received treatment for testicularcancer at Shaukat Khanum Cancer Hospital from January 2009 to December 2012 was performed. Patientdemographics, clinical features at presentation and treatment modalities were assessed. For categorical variableschi square test was used. Survival was calculated using Kaplan Meier survival curves and Log rank test wasemployed to determine significance. Results: The most common tumor was mixed germ cell tumor in 49%patients. For all tumor variants except seminoma, stage III was the most common clinical stage at presentation.Majority of patients with non seminomatous germ cell tumors presented in the15-30 year age group as comparedto seminoma which was most prevalent in the 30-40 year age group. Orchiectomy followed by chemotherapywas the most common treatment modality in 80% patients. Expected 5 year survival for seminomas and nonseminomatousgerm cell tumors was 96% and 90% respectively which was not significantly different (p=0.2).Conclusions: Despite a distinct clinical profile of testicular tumors in Pakistani population, survival is comparablewith published reports.     

Methylation profile of DNA repetitive elements in human testicular germ cell tumor

Testicular germ cell tumors (TGCTs) have a unique epigenetic profile distinct from that of other types of cancer. To further evaluate epigenetics of TGCTs, this study examines DNA methylation patterns of DNA repetitive elements in TGCTs. Bisulfite genomic sequencing and combined bisulfite restriction analysis (COBRA) were used to analyze the methylation patterns of DNA repetitive elements (LINE1 and Alu repeats) in embryonal carcinoma (EC) derived cell lines, primary TGCT tissues, noncancerous testicular tissues adjacent to TGCTs and cancer cells derived from somatic tissues (testicular malignant lymphoma tissues and renal cell carcinoma cell lines). Through both bisulfite genomic sequencing and COBRA, LINE1 was extensively hypomethylated in both seminomatous and nonseminomatous TGCT tissues as well as EC cell lines. We studied two Alu repeats locating in the 5' end of E-cadherin and XIST by bisulfite genomic sequencing. These two Alu elements were extensively hypomethylated in seminomatous TGCTs, but methylated in nonseminomatous TGCTs, including two EC derived cell lines. This increased unmethylated profile in seminomatous TGCTs was observed also by COBRA for Alu repeats. Although partial demethylation of DNA repetitive elements was observed in cancer cells of somatic tissue origin, the degree of demethylation was more pronounced in TGCTs than in cancer cells of somatic tissue origin. We observed abnormal demethylation of DNA repetitive elements in some of the tissues adjacent to TGCTs. The results indicate that the underlying mechanisms to undergo or maintain demethylation of DNA repetitive sequences differ between TGCTs and cancer cells of somatic tissue origin.     

Distinct epigenetic phenotypes in seminomatous and nonseminomatous testicular germ cell tumors

The genetic nature of testicular germ cell tumors and the molecular mechanisms underlying the morphological and clinical differences between the two subtypes, seminomas and nonseminomas, remains unclear. Genetic studies show that both subtypes exhibit many of the same regional genomic disruptions, although the frequencies vary and few clear differences are found. We demonstrate significant epigenetic differences between seminomas and nonseminomas by restriction landmark genomic scanning. Seminomas show almost no CpG island methylation, in contrast to nonseminomas that show CpG island methylation at a level similar to other solid tumors. We find an average of 1.11% of CpG islands methylation in nonseminomas, but only 0.08% methylated in seminomas. Furthermore, we demonstrate that seminomas are more highly hypomethylated than nonseminomas throughout their genome. Since both subtypes are thought to arise from primordial germ cells, the epigenetic differences seen between these subtypes may reflect the normal developmental switch in primordial germ cells from an undermethylated genome to a normally methylated genome. We discuss these findings in relation to different developmental models for seminomatous and nonseminomatous testicular germ cell tumors.     

Should extragonadal germ cell tumors be included in studies of families with testicular germ cell tumors?

Background

Family history is among the few established risk factors for testicular germ cell tumor (TGCT). Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to six fold and eight- to tenfold increase in TGCT risk, respectively. In twins of men with TGCT the relative risk of testicular cancer is 37.5 (12.3-115.6). Nevertheless, information about the occurrence of TGCT in relatives of patients with extragonadal germ cell tumor is limited.

Case report

A 24 year-old male patient was diagnosed with a mediastinum tumor and was submitted to image-guided biopsy, which revealed a seminoma. Two months later, his non-identical asymptomatic twin brother was submitted to an elective ultrasound of the testes, which showed a left testicular mass of 4.2 cm. This patient underwent orchiectomy revealing a seminoma of the left testis. There are no other cases of seminoma or other types of cancers reported in first-degree relatives in this family.

Conclusions

Although familial aggregations of TGCT have been well described, to the best of our knowledge, no data concerning the association of gonadal and extragonadal germ cell tumor in relatives has been previously reported. Further investigation on this association is warranted and may help in improving our knowledge of familial pattern inheritance.     

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.     

机器人辅助腹腔镜下行睾丸恶性肿瘤腹膜后淋巴结清扫术的疗效及安全性

目的:探讨机器人辅助腹腔镜下腹膜后淋巴结清扫术（RA-RPLND）治疗早期睾丸恶性肿瘤的手术技术及治疗效果。方法:2013年9月至2017年3月,3例原发性睾丸非精原细胞肿瘤根治性睾丸切除术后行RA-RPLND治疗。其中左侧1例,右侧2例,根治性睾丸切除术后病理证实为恶性混合型生殖细胞瘤1例,胚胎癌1例,胚胎性横纹肌肉瘤1例。记录手术时间、术中出血量、围手术期并发症、肠功能恢复时间、住院时间,并监测肿瘤标志物,进行手术后随访。结果:3例手术均成功完成。手术时间（144±17）min,术中出血量（110±29）ml,术后肠功能恢复时间（52±15）h,总住院时间（6.0±0.8）d。未出现肠管损伤、大血管损伤和淋巴瘘;无中转开放。2例术前临床分期为Ⅰa期,1例术前为Ⅰb期;其中1例术后病理分期为IIb 期。术后随访3～18个月未见肿瘤复发及转移,无死亡病例,术后无逆向射精。其中胚胎性横纹肌肉瘤者术后行常规全身化疗,随访18个月无复发。结论:RA-RPLND治疗早期睾丸肿瘤是安全可行的,在保留正常射精、减少副损伤方面有明显的优势。     

Frequent epigenetic inactivation of p53 target genes in seminomatous and nonseminomatous germ cell tumors

Hypermethylation of tumor-suppressor genes has been implicated in the pathogenesis of human cancers. This study was designed to examine the methylation profiles of a selected group of p53 target genes (APAF-1, CASP-8, DAPK-1, IGFBP-3) and to correlate the findings with the histopathological characterization of testicular germ cell tumors (TGCT). Promoter methylation status was analysed by highly sensitive real-time methylation-specific PCR in 46 primary TGCTs (26 seminomas and 20 nonseminomas) and 15 normal testicular tissue samples. APAF-1 methylation was detected in all of the seminomatous and nonseminomatous TGCTs as well as in 60% of normal testicular tissue. Methylation of DAPK-1 was frequent in seminomas (50%) and nonseminomas (20%), but not in normal testicular tissue (6%). The degree of DAPK-1 methylation correlated with the clinical stage of the disease (P=0.05) and was useful in differentiating seminomatous from nonseminomatous, and malignant from nonmalignant testicular tissue (P=0.04 and 0.02, respectively). The APAF-1 methylation index achieved a highly significant differentiation between seminomatous or nonseminomatous tissue and nonmalignant testicular tissue (P=0.0001). In testicular tumorigenesis, promoter methylation of specific p53 target genes occurs at early stage but to varying degrees. Methylation also occurs in normal testicular tissue, which is in contrast to findings in other urogenital malignancies. Further studies will be necessary to determine whether the methylation level may be used as marker for risk estimation, especially in clinical stage I disease.