Testicular tumors: Oncologic imaging and diagnosis

The extreme radiosensitivity of testicular seminomas plus recent advances in chemotherapy for nonseminomatous tumors and for advanced seminomas have made long term survival possible in the large majority of patients with testis cancer. Since choice of therapy is determined by tumor histology and extent of disease, accurate clinical staging is critical. Computed tomography (CT) of the abdomen and chest is the imaging procedure of choice for staging testis cancer. Clinical staging accuracy of 80 to 90% can be achieved using CT in combination with radioimmunoassays for β-HCG and AFP. Ultrasonography (US), while less sensitive and specific than CT for determining nodal status, may be useful in thin patients with sparse retroperitoneal fat; in addition US may play an important role in detecting occult testicular neoplasms and in assessing primary tumor extent within the scrotum. Lymphangiography should be reserved for Stage I patients in whom elective treatment of the retroperitoneum is not planned. Follow-up should include serial radioimmunoassays for serum AFP and β-HCG and periodic CT examinations of the abdomen and chest. Technical improvements in CT scanners and further experience with the use of tumor markers should help refine our ability to stage and manage patients with testicular tumors. In addition, nuclear magnetic resonance (NMR) imaging and radionuclide imaging following injection of radioactively labelled antibodies to AFP and β-HCG are new techniques which offer great promise for the future.     

Management of recurrent testicular germ cell tumors

Although front-line chemotherapy cures most men with testicular germ cell tumors, salvage therapy is still important in a small but significant minority. Second-line conventional-dose or high-dose chemotherapy with stem cell rescue may cure 25%-50% of patients. New chemotherapeutic agents, including the taxanes gemcitabine and oxaliplatin, have added to the therapeutic armamentarium. Salvage surgical resection has an important role in selected patients. Cisplatin-refractory patients have a poor prognosis with current therapy, and novel chemotherapeutic and biologic agents need to be discovered for such patients.     

Testicular cancer in androgen insensitivity syndrome in a Mexican population

Male pseudohermaphroditism and androgen insensitivity syndrome cases have an increased risk of developing testicular cancer due to many factors such as mutations, hormonal disturbances involving gonadotropins and cryptorchidism. We describe the clinical features, diagnosis and treatment of two cases with partial androgen insensitivity syndrome and testicular cancer development, which were handled at the National Cancer Institute of Mexico.     

Epidemiological survey of central nervous system germ cell tumors in Canadian children

Objectives To determine the incidence and characteristics of pediatric patients with central nervous system (CNS) germ cell tumors (GCT) in Canada. Method A national retrospective review of hospital charts was done on all patients with CNS GCT diagnosed between 1990 and 2004. Patients had to be under age 18 years at the time of diagnosis of a CNS germ cell tumor and be a resident of Canada. Information extracted included age and year of diagnosis, pathological diagnosis, location of tumor, evidence of disseminated disease at time of diagnosis and biological markers. Results One hundred and twenty-one cases were identified (83 germinoma; 38 non-germinoma germ cell tumor). The mean annual incidence of CNS GCT was 1.06 per million children (0.7 per million for germinoma; 0.3 per million for NGGCT). Though yearly incidences varied, there was no clear trend to increased incidence. Male predominance was noted (2.4:1 for germinoma; 11:1 for NGGCT). The primary locations were the pineal and suprasellar regions. At the time of diagnosis, disseminated disease was not uncommon (22% germinoma; 32% NGGCT). β human gonadotrophin was elevated in the serum, cerebrospinal fluid (CSF) or both in 7% of patients with germinoma and 36% of patients with NGGCT. Elevation of α-fetoprotein in serum, CSF or both was seen in 34% of patients with NGGCT. Conclusion The incidence of CNS germ cell tumors in Canadian children is similar to that observed in other Western countries. All authors are on behalf of the Canadian Pediatric Brain Tumor Consortium     

Novel treatment options for refractory germ cell tumors

Although testicular germ cell tumors (GCTs) are a model for a curable neoplasm, a significant proportion will relapse and require salvage therapy. While currently available conventional and high-dose chemotherapy salvage regimens attain durable complete remissions in a significant proportion of patients, the long-term outcomes are still suboptimal in this young population. Several novel agents are being evaluated for recurrent germ cell tumors, including chemotherapeutic and biologic agents, notably anti-angiogenic agents. A better understanding of biology may lead to enhanced outcomes for cisplatin-refractory patients with germ cell tumors.     

卵巢恶性生殖细胞肿瘤的治疗(附233例临床分析)

目的探讨改进卵巢恶性生殖细胞肿瘤的治疗方法。方法回顾分析我院收治的２３３例卵巢恶性生殖细胞肿瘤。Ｉ期９４例，Ｉ～ＩＶ期４３例，复发转移９６例。单附件或全宫双附件加大网膜阑尾切除分别为７８例和１５１例，活检４例。单纯手术１７例，手术加放疗和化疗６５例，手术加化疗１５１例。结果全组存活１２７例，Ｉ期存活７８例，Ｉ～ＩＶ期１７例，复发转移３２例。总５年生存率为５５．６％。无性细胞肿瘤预后最好，５年生存率为８４．２％，非无性生殖细胞肿瘤为４４．６％，其中ＰＶＢ、ＢＥＰ方案化疗的生存率较高，为６６．０％和７３．３％。结论卵巢恶性生殖细胞肿瘤对化疗敏感，ＰＶＢ、ＢＥＰ是最有效的化疗方案。早期患者可治愈并保留生育功能；晚期先化疗，肿瘤局限后手术，术后巩固化疗可提高存活率     

Pineal gland tumors: experience from the SEER database

Pineal gland tumors are rare and account for less than 1% of all primary brain tumor diagnoses. They are more commonly seen in pediatric patients than in adults. We analyzed the available SEER data on pineal gland tumors that were diagnosed during the period 1973–2005. The cohort was subdivided into groups on the basis of tumor histology: germ cell tumors, pineal parenchymal tumors, gliomas, and other pineal tumors. Analyses of incidence, survival, factors influencing survival, and treatment modalities are provided. Among the 633 patients with pineal tumors, male sex was predominant, i.e., sex ratio was 3:1 for the whole group and 11.8:1 for those with germ cell tumors. The 5-year overall survival (OS) for the cohort was 65% ± 2.1%. Those with germ cell tumors experienced the best survival (OS = 78.9% ± 2.3%), followed by those with gliomas (OS = 61% ± 9.3%), and those with pineal parenchymal tumors (OS = 47.2% ± 4.2%). Non–germ cell tumors, absence of radiotherapy from treatment regimen, and diagnosis before 1993 were the only factors associated with a negative impact on survival. The extent of surgical tumor resection did not affect survival in any histologic subgroup. We conclude that, although pineal tumors are histologically diverse, they share some similarities due to their unique location. An aggressive surgical approach should be considered with caution in this region. Further studies on different pineal tumors subtypes are needed.     

Testicular cancer: Determinants of cisplatin sensitivity and novel therapeutic opportunities

Testicular cancer (TC) is the most common solid tumor among men aged between 15 and 40 years. TCs are highly aneuploid and the 12p isochromosome is the most frequent chromosomal abnormality. The mutation rate is of TC is low, with recurrent mutations in KIT and KRAS observed only at low frequency in seminomas. Overall cure rates are high, even in a metastatic setting, resulting from excellent cisplatin sensitivity of TCs. Factors contributing to the observed cisplatin sensitivity include defective DNA damage repair and a hypersensitive apoptotic response to DNA damage. Nonetheless, around 10–20% of TC patients with metastatic disease cannot be cured by cisplatin-based chemotherapy. Resistance mechanisms include downregulation of OCT4 and failure to induce PUMA and NOXA, elevated levels of MDM2, and hyperactivity of the PI3K/AKT/mTOR pathway. Several pre-clinical approaches have proven successful in overcoming cisplatin resistance, including specific targeting of PARP, MDM2 or AKT/mTOR combined with cisplatin. Finally, patient-derived xenograft models hold potential for mechanistic studies and pre-clinical validation of novel therapeutic strategies in TC. While clinical trials investigating targeted drugs have been disappointing, pre-clinical successes with chemotherapy and targeted drug combinations fuel the need for further investigation in clinical setting.     

First-line chemotherapy of non-seminomatous germ cell tumors(NSGCTs)

Germ cell tumors (GCTs) account for the majority of testicular cancer cases occurring in men of young age and are divided into two main histologic groups, seminomas and non-seminomas. The introduction of cisplatin in the treatment of germ cell tumors was a breakthrough, classifying them among curable diseases. The identification of 3 subgroups of patients with non-seminomatous tumors (good-risk, intermediate and poor-risk), with different profiles concerning prognosis and response to treatment, supported clinical trials aiming to assess different treatment strategies and recommend the most effective and less toxic regimens. This review describes the toxic effects of therapy and the efforts aiming to overcome toxicity and improve treatment efficacy, focusing on the trials which form the basis of current standard treatment of non-seminomatous germ cell tumors.     

TIP方案一线治疗晚期中高危睾丸生殖细胞肿瘤的回顾性分析

目的 回顾性分析紫杉醇、异环磷酰胺联合顺铂（TIP）方案作为一线治疗晚期中高危睾丸生殖细胞肿瘤的疗效和安全性。方法 选取晚期中高危男性睾丸生殖细胞肿瘤患者,一线给予TIP方案进行治疗,评估该方案的客观有效率、2年的无进展生存率（PFS）和总生存率（OS）。结果 共20例患者纳入本研究,平均用药周期为4.25周期,6 例患者获得完全缓解（30%）,7例患者获得部分缓解（35%）, 客观有效率65%。中位随访时间25月,3例患者因肿瘤进展死亡。2年的PFS率为72.9%,OS率为89.1%。血液学毒性为最常见的不良反应 （95%）,其中3~4级中性粒细胞减少的发生率为30%。结论 TIP方案一线治疗晚期中高危睾丸生殖细胞肿瘤较既往报道提高了患者的PFS率和OS率,不良反应可控,确立为一线方案仍需大样本临床研究。     

八聚体结合转录因子4、婆罗双树样基因4在生殖细胞肿瘤中的研究进展

肿瘤标志物是肿瘤学领域的研究热点.既往研究的肿瘤标志物如胎盘碱性磷酸酶、甲胎蛋白（AFP）、干细胞因子受体和CD30等,对于生殖细胞肿瘤（GCT）的早期诊断缺乏足够的敏感性和特异性,最新研究表明八聚体结合转录因子4（OCT4）、人类婆罗双树样基因4（SALL4）可作为GCT的新标志物.文章对OCT4和SALL4的研究进展进行综述,旨在为GCT的早期诊断、肿瘤分型、病情估计、预后判断和靶向治疗提供参考.     

睾丸精原细胞瘤124例临床分析

目的探讨睾丸精原细胞瘤的治疗和预后之间的关系。方法回顾性分析山东省肿瘤防治研究院１９６３年７月～１９９５年１１月收治的精原细胞瘤患者１２４例,其中,Ⅰ期精原细胞瘤患者仅做精索高位结扎睾丸切除加髂－腹主动脉旁淋巴引流区放射治疗;Ⅱ、Ⅲ期精原细胞瘤术后给予放疗及有计划地加用辅助性化疗。结果Ⅰ、Ⅱ、Ⅲ期精原细胞瘤５年生存率分别为９５．９％、７０．４％、和０。结论Ⅰ期精原细胞瘤患者仅做精索高位结扎睾丸切除加髂－腹主动脉旁淋巴引流区放射治疗可以治愈;而对Ⅱ、Ⅲ期病例单用睾丸切除加淋巴引流区放射治疗是不够的,为改善Ⅱ、Ⅲ期精原细胞瘤患者的预后,在预防性／根治性照射后,有计划的加用辅助性化疗是必要的。     

睾丸精原细胞瘤78例临床分析

目的：对78例精原细胞瘤患者的治疗结果及其预后因素加以分析。方法：1983年7月至1992年4月收治78例睾丸精原细胞瘤，均经病理证实为纯精原细胞瘤。78例中74例手术治疗，63例术后放疗，43例联合化疗。结果：中位随访6.6年（随访期5-10年），根据《现代肿瘤学》的分期标准。Ⅰ期44例。Ⅱ期21例。Ⅲ期3例。Ⅳ期10例。全组5，10年生存率分别为；Ⅰ期93.2%,87.0%,Ⅱ期66.7%,60.0%,Ⅲ期33.3%,33.3%,Ⅳ期0，0。结论：临床分期，放疗剂量及联合化疗是影响预后的重要因素。强调高位精索加睾丸切除术及术后预防放疗DT2500cDy为Ⅰ期患者首选治疗方案，Ⅱ期以上患者应术后放疗加联合化疗。     

The Role of Bipedal Lymphangiography in Testicular Seminoma

Determining the extent of intra-abdominal spread of testicular seminoma by radiographic studies is an essential step in planning rational treatment following orchidectomy. CT scanning is generally accepted as being superior to lymphangiography in assessing the retroperitoneal space. We reviewed the relative contribution of these two procedures in a retrospective analysis of 73 consecutive patients with testicular seminoma managed at Westmead Hospital between January 1980 and September 1987. Abdominal CT scans and bipedal lymphangiography (LAG) were carried out in 72 and 51 patients respectively, 50 patients undergoing both procedures. We found concordance between the two techniques to be 88%. Upstaging occurred in 5 patients using CT (10%), 7 patients using LAG (14%), and in 8 patients (16%) when both tests were utilised. Four patients were upstaged by both techniques while the remaining 4 patients were upstaged using one technique alone. Serum ß-HCG was not a reliable screen for residual disease. Residual disease in the few patients with an elevated serum ß-HCG was easily detected by CT scanning. We conclude that there is a continuing role for LAG in assessing patients with clinical Stage I seminoma when the abdominal CT scan is equivocal or normal.     

Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors

High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation has been explored and has played an important role in the management of patients with high-risk germ cell tumors (GCTs) who failed to be cured by conventional chemotherapy. Hematopoietic stem cells (HSCs) collected from the peripheral blood, after appropriate pharmacologic mobilization, have largely replaced bone marrow as the principal source of HSCs in transplants. As it is currently common practice to perform tandem or multiple sequential cycles of HDCT, it is anticipated that collection of large numbers of HSCs from the peripheral blood is a prerequisite for the success of the procedure. Moreover, the CD34+ cell dose/kg of body weight infused after HDCT has proven to be a major determinant of hematopoietic engraftment, with patients who receive > 2 × 10⁶ CD34+ cells/kg having consistent, rapid, and sustained hematopoietic recovery. However, many patients with relapsed/refractory GCTs have been exposed to multiple cycles of myelosuppressive chemotherapy, which compromises the efficacy of HSC mobilization with granulocyte colony-stimulating factor with or without chemotherapy. Therefore, alternative strategies that use novel agents in combination with traditional mobilizing regimens are required. Herein, after an overview of the mechanisms of HSCs mobilization, we review the existing literature regarding studies reporting various HSC mobilization approaches in patients with relapsed/refractory GCTs, and finally report newer experimental mobilization strategies employing novel agents that have been applied in other hematologic or solid malignancies.     

Germ cell tumors in Indian children

The present paper is a retrospective study of one hundred and thirty five germ cell tumors seen in children at the University Hospital, Varanasi during a period of 21 years. These tumors constituted 7.5% of all solid tumors in the pediatric age group. Histologically 89 tumors (65.9%) were benign and 46 (34.1%) were malignant. Eighty percent of ovarian and all the testicular germ cell tumors were malignant. Thirty per cent of the tumors were located in the sacrococcyx. The ovaries were the next common site. There were 80 girls, 53 boys, and 2 cases in which the sex was not recorded. The predominance amongst girls was mainly due to the more frequent involvement of ovaries as compared to the testes. Twenty nine of the children were in the first year of life. The factors probably responsible for the higher incidence of malignancy, the differences in anatomic location, and the sex distribution in comparison to other reports have been examined and discussed.     

Testicular Cancer Biomarkers: A Role for Precision Medicine in Testicular Cancer

Testicular germ cell tumors (TGCTs) represent the most common solid tumors among men aged 15 to 34 years. Fortunately, recent advances have made testicular cancer a highly curable disease. Despite the high cure rates, there are still several areas in testis cancer care where treatment decisions are controversial and guided only with clinical factors and historic serum tumor markers. Unfortunately, unlike other genitourinary malignancies, modern research techniques have not been widely tested or applied to germ cell tumors, perhaps as a result of excellent prognosis in this cohort of young men. Despite this, there remain numerous challenges and pitfalls in testis cancer care that need to be addressed.A reliable set of biomarkers could be extremely useful in helping risk-stratify patients, detect relapse early, guide surgical decision-making, and tailor follow-up.Current tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have low accuracy and low sensitivity when used not only as diagnostic but also as prognostic and predictive markers. In twenty-first century medicine, there is a role for further prognostic stratification and the development of novel biomarkers that offer greater sensitivity and specificity for TGCTs. Despite the initial promising results, the majority of preclinical biomarkers do not, as yet have a proven validated role in clinical practice, and future prospective trials are needed to support and confirm the results of cohort studies.In this narrative review, we aimed to highlight the recent innovations in the development and implementation of novel testicular tumor markers and discuss their clinical applications and limitations in the management of this disease.     

Testicular seminoma: analysis of treatment and failure for stage II disease

Seventy-three patients with seminoma testis stage II have been retrospectively analyzed with regard to prognostic factors and value of prophylactic mediastinal irradiation and chemotherapy. Although survival differences were seen between stage IIa, IIb and IIc, these were not statistically significant. Neither was there a significant difference between IIc patients with tumors greater than 10 cm and less than 10 cm in diameter. The incidence of HCG-producing seminomas in the present series was 16%. No significant difference in survival nor relapse rate was found between HCG-producing and HCG-non-producing seminomas. Prophylactic mediastinal irradiation did not influence the survival nor the relapse rate and may therefore be omitted. In the present series there was no significant improvement neither in relapse rate nor survival in patients receiving pre-irradiation chemotherapy. However, the total number of patients is small and optimal pre-irradiation chemotherapy still have to be defined.