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Testicular Cancer

Testicular cancer is most common cancer in men between 15 to 35 years old. There are two broad types: seminoma and nonseminoma histologies. The nonseminoma group of cancers includes embryonal carcinoma, teratoma, yolk sac carcinoma and choriocarcinoma. The two testicles (or testis) produce sperm and male hormones. Men who have an undescended testicle (a testicle that didn't move down into the scrotum) are at higher risk of developing testicular cancer. World-wide about 36,000 men are diagnosed with testicular cancer each year.

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Molecular Biology of Testicular Cancer

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  • PubMed search for publications about Testicular Cancer - Limit search to: [Reviews]

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    MeSH term: Testicular Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Salminen E, Niiniviita H, Järvinen H, Heinävaara S
Cancer Death Risk Related to Radiation Exposure from Computed Tomography Scanning Among Testicular Cancer Patients.
Anticancer Res. 2017; 37(2):831-834 [PubMed] Related Publications
BACKGROUND: A study of the computed tomography (CT) imaging related effective doses and radiation-related cancer death risk.
PATIENTS AND METHODS: Estimate effective doses were computed from CT scans of testicular cancer patients treated and followed-up in Turku University Hospital, South Western Finland. Association between effective doses from follow-up CT scans and radiation-induced cancer death was examined using United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2008 formula.
RESULTS: Mean effective dose per CT abdomen was 9.32 (standard deviation, SD 3.89) mSv and for whole-body CT it was 14.24 (SD 6.84) mSv. During follow-up of 6 years, the patients were estimated to undergo 12 to 14 abdominal/whole-body CTs and the corresponding risk estimates were 0.11 and 1.14, respectively. The risk of estimated radiation-induced cancer deaths (RICD in %) computed for mean effective doses was lower in patients diagnosed at older age, being 0.61 for 10-19 years age and 0.04 for 40-49 years age at the diagnosis.
CONCLUSION: Patient radiation exposure in CT imaging is associated with the type of CT device and imaging protocols, which should be periodically updated and reviewed to minimize individual exposure. Using the UNSCEAR modelling 2 % risk for radiation related cancer death was attributed to diagnostic exposure of study patients. Age at the diagnosis was associated with CT imaging related radiation exposure. The highest exposure was estimated to the youngest patients.

Solinas C, Chanzá NM, Awada A, Scartozzi M
The immune infiltrate in prostate, bladder and testicular tumors: An old friend for new challenges.
Cancer Treat Rev. 2017; 53:138-145 [PubMed] Related Publications
In genito-urinary tumors immunotherapy has been administered for a long time: Calmette-Guèrin Bacillus as adjuvant treatment in high risk patients with non muscle invasive urothelial bladder cancer and interleukin-2 and interferon-α in metastatic kidney cancer. The vaccine Sipuleucel-T has been approved by United States Food and Drug Administration for the treatment of castration resistant prostate cancer patients with asymptomatic or minimally symptomatic disease, given the 22% reduction of mortality risk in this group. Recently immunotherapeutic agents targeting inhibitory immune checkpoint molecules lead to improved outcomes and lasting anti-tumor effects in a variety of hematological and solid malignancies, including urogenital tumors. The benefit from these treatments has been observed only in a proportion of subjects, raising a need in optimizing patients' selection for immune checkpoint blockade. The composition and activity of a pre-existing immune infiltrate may aid in identifying ideal candidates to immunotherapy, with possible implications for the clinical management of neoplastic diseases from earlier to later stages.

Thirunavukkarasu B, Mridha AR, Malhotra N, Chandrashekhara SH
Complete androgen insensitivity syndrome with concomitant seminoma and Sertoli cell adenoma: an unusual combination.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Androgen insensitivity syndrome is a rare disorder of sex development and its clinical manifestations vary from subtle male infertility to an overt complete androgen insensitivity syndrome (CAIS) with a female phenotype. CAIS is often diagnosed at puberty or in adolescence during investigation for primary amenorrhoea. Undiagnosed patients have an increased risk of development of malignancy in the harboured testes. Inguinal hernia is the commonest mode of presentation of CAIS in childhood and various screening methods are available during the initial herniorrhaphy procedure. Controversy exists in the need to screen and the methods of screening in all cases of premenstrual girls with inguinal hernia. Abnormal observation in a suspicious case requires karyotyping for confirmation. We describe a case of CAIS with simultaneous presence of seminoma and a Sertoli cell adenoma in a 17-year-old patient who had a history of surgery for inguinal hernia at age of 5 years.

Marchlewska K, Filipiak E, Walczak-Jedrzejowska R, et al.
Sperm DNA Fragmentation Index and Hyaluronan Binding Ability in Men from Infertile Couples and Men with Testicular Germ Cell Tumor.
Biomed Res Int. 2016; 2016:7893961 [PubMed] Free Access to Full Article Related Publications
Objective. To investigate sperm DNA fragmentation and sperm functional maturity in men from infertile couples (IC) and men with testicular germ cell tumor (TGCT). Materials and Methods. Semen samples were collected from 312 IC men and 23 men with TGCT before unilateral orchiectomy and oncological treatment. The sperm chromatin dispersion test was performed to determine DNA fragmentation index (DFI) and the ability of sperm to bind with hyaluronan (HA) was assessed. Results. In comparison with the IC men, the men with TGCT had a higher percentage of sperm with fragmented DNA (median 28% versus 21%; p < 0.01) and a lower percentage of HA-bound sperm (24% versus 66%; p < 0.001). Normal results of both analyses were observed in 24% of IC men and 4% of men with TGCT. Negative Spearman's correlations were found between DFI and the percentage of HA-bound sperm in the whole group and in IC subjects and those with TGCT analyzed separately. Conclusions. Approximately 76% of IC men and 96% with TGCT awaiting orchiectomy demonstrated DNA fragmentation and/or sperm immaturity. We therefore recommend sperm banking after unilateral orchiectomy, but before irradiation and chemotherapy; the use of such a deposit appears to be a better strategy to obtain functionally efficient sperms.

Hammond WJ, Farber BA, Price AP, et al.
Paratesticular rhabdomyosarcoma: Importance of initial therapy.
J Pediatr Surg. 2017; 52(2):304-308 [PubMed] Article available free on PMC after 01/02/2018 Related Publications
PURPOSE: To evaluate factors associated with progression-free and disease-specific survival in patients with paratesticular rhabdomyosarcoma, we performed a cohort study. Also, since many patients present to our institution after initial therapy, we analyzed the effects of salvage therapy for scrotal violation.
PATIENTS AND METHODS: We retrospectively reviewed the records of all consecutive patients with histologically confirmed paratesticular rhabdomyosarcoma treated at our institution between 1978 and 2015. Fifty-one patients were initially identified, but two with incomplete data were excluded from analysis. Variables evaluated for correlation with survival were TNM staging, Children's Oncology Group Soft Tissue Sarcoma pretreatment staging, margins at initial resection, presence of scrotal violation, hemiscrotectomy and/or scrotal radiation. The log-rank test was used to compare survival distributions.
RESULTS: For the analytic cohort of 49 patients, the median age and follow-up were 15.7years (95% CI: 14.2-17.5, range: 0.8-25.1years) and 6.9years (95% CI: 4.4-9.0, range 0.2-37.5years), respectively. The 5-year overall disease-specific survival was 78.7% (95% CI: 67.7%-91.4%) and the progression-free survival was 66.9% (95% CI: 54.8%-81.6%). Median time to recurrence was 0.9years (95% CI: 0.7-0.9, range 0.1-6.2years). Scrotal violation occurred in 41% (n=20) and tripled the risk of recurrence for patients not appropriately treated with either hemiscrotectomy or scrotal radiation therapy (RR=3.0, 95% CI: 1.16-7.73).
CONCLUSIONS: The strongest predictors of disease-specific survival were nodal status and distant metastasis at diagnosis. Scrotal violation remains a problem in paratesticular rhabdomyosarcoma and is a predictor of disease progression unless adequately treated. The risk of progression could be reduced with appropriate initial resection.
LEVEL OF EVIDENCE: Level IV; retrospective study with no comparison group.

Dusaud M, Malavaud B, Bayoud Y, et al.
Post-chemotherapy retroperitoneal teratoma in nonseminomatous germ cell tumors: Do predictive factors exist? Results from a national multicenter study.
J Surg Oncol. 2016; 114(8):992-996 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: To identify predictive preoperative factors of the presence of teratoma in retroperitoneal lymph node dissection specimens.
METHODS: We performed a 20 years multicenter retrospective analysis of all patients who underwent retroperitoneal lymph node dissection for residual masses after chemotherapy (PC-RPLND). Patients had undergone PC-RPLND after chemotherapy for advanced testicular cancer. The histologic components of the primary tumor were compared with those of the residual masses using logistic regression.
RESULTS: A total of 469 NSGCT patients underwent PC-RPLND (complete data available for 211). By PC-RPLND, necrosis was found in 84 cases, teratoma in 102 cases, and viable tumor in 25 cases. The univariate and multivariate analyses showed that teratoma (P = 0.001 and P = 0.002, respectively) and yolk sac tumor (P = 0.009 and P = 0.035, respectively) in orchiectomy specimens were statistically significant predictors of the presence of teratoma in retroperitoneal lymph nodes.
CONCLUSIONS: PC-RPLND is the standard treatment for any supracentimetric residual lesion. This procedure is associated with a high morbidity, and almost half patients are overtreated. The presence of teratoma and yolk sac tumor in the orchiectomy specimen were independent significant predictors of teratoma in retroperitoneal masses. J. Surg. Oncol. 2016;114:992-996. © 2016 Wiley Periodicals, Inc.

Aparicio J, Terrasa J, Durán I, et al.
SEOM clinical guidelines for the management of germ cell testicular cancer (2016).
Clin Transl Oncol. 2016; 18(12):1187-1196 [PubMed] Article available free on PMC after 01/02/2018 Related Publications
Testicular cancer represents the most common malignancy in males aged 15-34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3-4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.

Han MH, Park SW, Do HJ, et al.
Growth and Differentiation Factor 3 Is Transcriptionally Regulated by OCT4 in Human Embryonic Carcinoma Cells.
Biol Pharm Bull. 2016; 39(11):1802-1808 [PubMed] Related Publications
Growth and differentiation factor 3 (GDF3), a mammalian-specific transforming growth factor β ligand, and OCT4, one of key stem cell transcription factors, are expressed in testicular germ cell tumors (TGCTs) as well as pluripotent stem cells. To understand the molecular mechanism by which OCT4 and GDF3 function in tumorigenesis as well as stemness, we investigated the transcriptional regulation of GDF3 mediated by OCT4 in human embryonic carcinoma (EC) NCCIT cells, which are pluripotent stem cells of TGCTs. GDF3 and OCT4 was highly expressed in undifferentiated NCCIT cells and then significantly decreased upon retinoic acid-induced differentiation in a time-dependent manner. Moreover, GDF3 expression was reduced by short hairpin RNA-mediated knockdown of OCT4 and increased by OCT4 overexpression, suggesting that GDF3 and OCT4 have a functional relationship in pluripotent stem cells. A promoter-reporter assay revealed that the GDF3 promoter (-1721-Luc) activity was significantly activated by OCT4 in a dose-dependent manner. Moreover, the minimal promoter (-183-Luc) was sufficient for OCT4-mediated transcriptional activation and provided a potential binding site for the direct interaction with OCT4. Collectively, this study provides the evidence about the regulatory mechanism of GDF3 mediated by OCT4 in pluripotent EC cells.

Palha A, Cortez L, Tavares AP, Agapito A
Leydig cell tumour and mature ovarian teratoma: rare androgen-secreting ovarian tumours in postmenopausal women.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Androgen-secreting ovarian tumours are extremely rare accounting for <5% of all ovarian neoplasms. They are more frequent in postmenopausal women and should be suspected in the case of a rapid onset of androgenic symptoms. We report 4 cases of postmenopausal women who presented with signs of virilisation. All patients revealed increased serum levels of testosterone, normal dehydroepiandrosterone-sulfate and negative pelvic ultrasound for adnexal masses. An androgen-secreting ovarian tumour was suspected and all of them were submitted to bilateral oophorectomy. Histology confirmed the diagnosis of Leydig cell tumours in 3 patients and mature teratoma in 1. A successful response to surgery, which includes a decline in serum androgen levels and signs of hyperandrogenism, was observed in our patients. This case series demonstrates that androgen-secreting ovarian neoplasms may not be detectable by imaging studies, but should be considered in the differential diagnosis of all postmenopausal women with signs of hyperandrogenism.

Sadeghi M, Ghoncheh M, Mohammadian-Hafshejani A, et al.
Incidence and Mortality of Testicular Cancer and Relationships with Development in Asia.
Asian Pac J Cancer Prev. 2016; 17(9):4251-4257 [PubMed] Related Publications
BACKGROUND: Testicular cancer is one of the most common cancers among young men between ages 20-34 in countries with high or very high levels of the Human Development Index (HDI). This study investigated the incidence and mortality of prostate cancer and the relationship with the HDI and its dimensions in Asia in 2012.
MATERIALS AND METHODS: The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Standardized incidence and mortality rates of testicular cancer were calculated for Asian countries. Correlations between incidence and/ormortality rates, and the HDI and its components were assessed with the use of the correlation test, using SPSS software.
RESULTS: There was a total of 14902 incidences and 5832 death were recorded in Asian countries in 2012. Among the Asian countries, the five countries with the highest standardized incidence rates of testicular cancer were Israel, Georgia, Turkey, Lebanon and Kazakhstan and the five countries with the highest standardized mortality rates were Turkey, Georgia, Jordan, Cambodia and the Syrian Arab Republic. A positive correlation of 0.382 was observed between the standardized incidence rates of testicular cancer and the HDI (p=0.009). Also a negative correlation of 0.298 between the standardized mortality rate of testicular cancer and the Human Development Index was noted although this relation was statistically non-significant (p=0.052).
CONCLUSIONS: There is a positive correlation between HDI and the standardized incidence rate of testicular cancer and negative correlation with standardized mortality rate.

Reekhaye A, Harris A, Nagarajan S, Chadwick D
A giant testicular mixed germ cell tumour.
Ann R Coll Surg Engl. 2016; 98(8):e171-e172 [PubMed] Related Publications
We present a case that we believe to be the largest mixed germ cell testicular tumour reported in the United Kingdom. A 23-year-old male was admitted to our urology department with a large scrotal swelling. The patient was found to have a giant left testicular tumour and a solitary lung metastasis at presentation. He underwent an emergency radical orchidectomy and subsequently received four cycles of bleomycin, etoposide and cisplatin chemotherapy. Four months after starting treatment, the tumour markers had normalised and a repeat staging computed tomography showed no active disease. The tumour reached that size because of the patient's failure to seek medical attention due to fear and embarrassment.

Giunchi F, Vasuri F, Colecchia M, et al.
Frozen section analysis of unusual small testicular tumor masses: report of 3 cases.
Tumori. 2016; 102(Suppl. 2) [PubMed] Related Publications
PURPOSE: Nonpalpable tumors of the testis are generally incidental findings on ultrasound examination. Most of these tumors are benign but some turn out to be germinal tumors at histology. Therefore, intraoperative histopathologic analysis of nonpalpable testicular lesions is pivotal for guiding a testis-sparing surgical approach.
METHODS: We report clinical and pathologic characteristics of 3 small nodules of the testis with challenging histologic features at intraoperative frozen section examination and peculiar histology. One was a known testicular mass, undertreated for 5 years, whose enlargement worried the patient, while the other 2 were incidental findings during clinical testicular examination for non-neoplastic diseases.
CONCLUSIONS: The 3 cases reported are characterized by small size, which limited the accuracy of preoperative ultrasound diagnosis. Intraoperative frozen section examination was able to rule out a diagnosis of germ cell malignancy in all cases, but diagnosis was conclusive only at histology. Knowledge of unexpected rare testicular lesions is of great relevance at the time of frozen section examination in view of conservative surgical strategy.

Sanharawi IE, Correas JM, Glas L, et al.
Non-palpable incidentally found testicular tumors: Differentiation between benign, malignant, and burned-out tumors using dynamic contrast-enhanced MRI.
Eur J Radiol. 2016; 85(11):2072-2082 [PubMed] Related Publications
PURPOSE: To evaluate qualitative, semi-quantitative, and quantitative parameters obtained by dynamic contrast-enhanced (DCE)-MRI for the characterization of histologically proven, non-palpable, incidentally found intratesticular tumors.
MATERIALS AND METHODS: From 2006 to 2014, we included men with non-palpable, incidentally found testicular tumors on ultrasound, normal tumoral marker levels,referred for surgery. DCE-MRI data were analyzed retrospectively and independently by two radiologists blinded to the histological diagnosis. The visual enhancement patterns, time-signal intensity curves, shape of the curves (type 0-3), maximal relative enhancement (Peak), initial enhancement slope (IS), time to peak (TTP), as well as transfer constants Ktrans and Kep were compared between the tumors. The interobserver correlation was evaluated. Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were extracted.
RESULTS: Thirty-one patients (mean age of 37.3 years) were included. Tumor mean size was 1.2±0.77 cm (min=0.3cm, max=2.8cm). Regarding the histology results, three groups were defined: Twelve stromal "benign tumors" (BT) exhibited more type 2 and type 3 curves than 12 "malignant tumors" (MT) and 7 "burned-out tumors" (BOT) (p<0.0001). BT had a higher peak (96 vs. 54 and 17%), shorter TTP (215 vs. 412 and 692 sec), higher IS (73 vs. 12 and 2 arbitrary units), higher Ktrans (255 vs. 88 and 14min(-1)*1000) and higher Kep (554 vs. 159 and 48min(-1)*1000) than MT and BOT, respectively (p<0.0001, p=0.0003, p<0.0001, p<0.0001 and p<0.0001, respectively). The agreement coefficient values and the AUC extracted after gathering MT with BOT varied from 0.83 to 0.96 and from 0.868 to 0.978, respectively.
CONCLUSION: DCE-MRI may assist in differentiating between benign intratesticular stromal tumors,malignant and burned-out tumors.

Yamada Y, Takayama KI, Fujimura T, et al.
A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor.
Cancer Sci. 2017; 108(1):32-41 [PubMed] Article available free on PMC after 01/02/2018 Related Publications
Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM44 overexpression has been observed in various cancers. However, its association with testicular germ cell tumor (TGCT) is unknown. We aimed to investigate the clinical significance of TRIM44 and its function in TGCT. High expression of TRIM44 was significantly associated with α feto-protein levels, clinical stage, nonseminomatous germ cell tumor (NSGCT), and cancer-specific survival (P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariate analysis showed that positive TRIM44 IR was an independent predictor of cancer-specific mortality (P = 0.046). Gain-of-function study revealed that overexpression of TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells. Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA2 cells revealed that tumor suppressor genes such as CADM1, CDK19, and PRKACB were upregulated in TRIM44-knockdown cells compared to control cells. In contrast, oncogenic genes including C3AR1, ST3GAL5, and NT5E were downregulated in those cells. These results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti-apoptosis in TGCT.

Takada H, Iwatsuki S, Itoh Y, et al.
Primary pure carcinoid tumour of the testis: A case report and review of the literature.
Arch Ital Urol Androl. 2016; 88(3):245-246 [PubMed] Related Publications
Primary testicular carcinoid tumours (TCT) are very rare, and a large tumour size and the presence of carcinoid syndrome predict a malignant course. Histologically, it is difficult to differentiate between benign and malignant TCTs. We report a case of a primary pure TCT with an unusual presentation in a 23- year-old man, who had an asymptomatic, enlarged scrotum on the right side for 7 years. On gross examination, the tumour was 9.6 cm in diameter. The Ki-67 labelling index was 19.8%. High inguinal orchidectomy was performed, and 30 months after surgery the patient remains asymptomatic.

Catanzariti F, Servi L, Fabiani A, et al.
Adenomatous hyperplasia of the rete testis: A rare intrascrotal lesion managed with limited testicular excision.
Arch Ital Urol Androl. 2016; 88(3):243-244 [PubMed] Related Publications
INTRODUCTION: Testicular cancer is one of the most frequent in young men and its incidence is increasing in recent years because of incidental finding during routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of the benign and rare pathological types incidentally detected and very few cases are described in the literature.
CASE REPORT: A 40 years old man come to our attention for a balanoposthitis without testicular pain. During andrological examination we performed palpation of the testes and we noticed a palpable nodule of hard consistency in the left testicle. We then performed an ultrasound exam of the testis which highlighted the presence of an intra-didymus neoformation with diameters of 1.2 x 1.6 cm and with the presence of cysts inside. We also performed blood tests to check tumor markers alpha fetoprotein, beta hCG and LDH which resulted inside the normal range. We then conducted a chest and abdomen CT scan that showed no pathological elements. Therefore, as we suspected that this tumor was benign, we performed an enucleation of the neoplasm. The definitive histological examination revealed the presence of dilated ducts lined with epithelial cubic-columnar cells with clear cytoplasm rich in glycogen and the pathologist so concluded that the tumor could be classified as adenomatous hyperplasia of the rete testis. At three months of follow up, the patient doesn't have any recurrent lesion to either testicles.
DISCUSSION: Adenomatous hyperplasia of the rete testis is a very rare intrascrotal lesion. This histological type is the most frequent between benign lesion of the ovary, but few works in literature reported this histological type in the male gonad and, in most of these works, authors described these lesion at epididymis.
CONCLUSION: We believe that a conservative approach must be considered mandatory in case of testicular lesions 1.5 cm in diameter. A radical approach might have alterate fertility of the patient and also have caused psychological trauma more than an enucleation. However a longer follow up is needed to understand if this was the right decision for the oncological point of view.

Catanzariti F, Polito B, Polito M
Testicular prosthesis: Patient satisfaction and sexual dysfunctions in testis cancer survivors.
Arch Ital Urol Androl. 2016; 88(3):186-188 [PubMed] Related Publications
PURPOSE: We studied patient satisfaction about sexual activity after prosthesis implantation using validated questionnaires with the aim to discover if testicular prosthesis could be responsible of sexual dysfunctions (erectile dysfunction or premature ejaculation).
MATERIALS AND METHODS: We evaluated a total of 67 men who underwent radical orchiectomy for testicular cancer and a silicon testicular prosthesis implantation from January 2008 to June 2014 at our Hospital. These patients completed 5 validated questionnaires the day before orchiectomy and 6 months after surgery: the International Index of Erectile Function 5 (IIEF5), the Premature Ejaculation Diagnostic Tool (PEDT), the Body Exposure during Sexual Activities Questionnaire (BESAQ), the Body-Esteem Scale and the Rosenberg Self- Esteem Scale. We also evaluated 6 months after surgery any defects of the prosthesis complained by the patients.
RESULTS: The questionnaires completed by patients didn't show statistically significant changes for erectile dysfunction (p > 0.05) and premature ejaculation (p > 0.05). On the contrary the psychological questionnaires showed statistically significant change for the BESAQ (p < 0.001) and the Body Esteem Scale (p < 0.001), but not for the Rosenberg Self-Esteem Scale (p > 0,05). A total of 15 patients (22.37%) were dissatisfied about the prosthesis: the most frequent complaint (8 patients; 11.94%) was that the prosthesis was firmer than the normal testis.
CONCLUSIONS: Testicular prosthesis implantation is a safe surgical procedure that should be always proposed before orchiectomy for cancer of the testis. The defects complained by patients with testicular prosthesis are few, they don't influence sexual activity and they aren't able to cause erectile dysfunction or premature ejaculation.

Mesa H, Gilles S, Datta MW, et al.
Immunophenotypic differences between neoplastic and non-neoplastic androgen-producing cells containing and lacking Reinke crystals.
Virchows Arch. 2016; 469(6):679-686 [PubMed] Related Publications
We performed a detailed morphologic, immunophenotypic, and endocrine characterization of neoplastic and non-neoplastic lesions of androgen-producing cells known to harbor or lack Reinke crystals (RCs) with an aim to provide further insight into the nature of these cells and crystals. Study cases were selected from the files of participating hospitals and subclassified according to current classifications: 20 with Leydig cell tumors (LCTs), 2 with testicular adrenal rest tumors (TARTs), 2 with testicular tumors of adrenogenital syndrome (TTAGS), and 2 with androgen insensitivity syndrome (AIS). An extensive immunophenotypic panel including markers used in sex cord-stromal cell tumors, androgen hormones, enzymes, and receptors was applied to the cases and 10 non-tumoral adrenal glands. Non-tumoral tissues were scored separately. RCs were present in 90 % of LCT cases and all cases with normal Leydig cells; RCs stained specifically with calretinin and 3β-hydroxysteroid dehydrogenase (3BHSD) and were present only in cells with high concomitant expression of both proteins, a phenotype unique to Leydig cells and LCTs. Leydig cells from AIS cases lack RCs due to decreased expression of 3BHSD. Calretinin is decreased in testicular adrenal-like tumors and absent in normal adrenocortical cells, which explain why they lack RCs. Calretinin expression in androgen-producing cells is independent from androgen receptors and androgen synthesis. RCs represent for the most part, if not exclusively, crystallized forms of a 3BHSD/calretinin complex. Androgen-producing cells containing and lacking RCs differ mainly in the level of expression of these proteins and androgen receptors.

Sakr H, Cruise M, Chahal P, et al.
Anaplastic lymphoma kinase positive large B-cell lymphoma: Literature review and report of an endoscopic fine needle aspiration case with tigroid backgrounds mimicking seminoma.
Diagn Cytopathol. 2017; 45(2):148-155 [PubMed] Related Publications
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare distinct type of non-Hodgkin's lymphoma that arises in association with alterations of the ALK gene. This distinct disease entity is typically associated with an aggressive clinical course and appears in light microscopic preparations as a monomorphic population of large, immunoblast-like cells. In this report, we describe a case of ALK+ LBCL diagnosed by transgastric endoscopic ultrasound-guided fine needle aspiration (EUS FNA) of splenic hilar lymph nodes. Modified Giemsa stained direct smears from the FNA sample demonstrated large lesional cells with foamy cytoplasm and macronucleoli admixed with small lymphocytes in tigroid backgrounds, mimicking the cytologic appearance of seminoma. Ancillary immunohistochemical studies subsequently confirmed the diagnosis of ALK+ LBCL with the lesional cells being immunoreactive for CD138, VS38c, MUM1, ALK1, and lambda light chain. The cohesiveness of the cells, the cellular morphology, and the tigroid backgrounds were all pitfalls for accurate diagnosis of this rare specific type of lymphoid malignancy by cytology. To our knowledge this is the first case report detailing the diagnosis of ALK+ LBCL by EUS FNA and the first report describing a glycogen-rich tigroid background in direct FNA smears. Establishing a refined diagnosis in cases of this rare form of LBCL is necessary, as therapies targeting ALK may be of value in clinical management. Diagn. Cytopathol. 2017;45:148-155. © 2016 Wiley Periodicals, Inc.

Lohiya NK, Balasubramanian K, Ansari AS
Indian folklore medicine in managing men's health and wellness.
Andrologia. 2016; 48(8):894-907 [PubMed] Related Publications
India is a home for a large variety of plants with remarkable medicinal and pharmacological value. Traditional medicine in the form of Ayurveda, Siddha and Unani has used many of these plants since ancient days for treating and curing various ailments of the body. When it comes to issues related to reproductive health, people still hesitate to discuss and/or accept it openly and hence look for alternate and natural remedies. The various tribal populations distributed across different parts of the country still use these plant extracts in various formulations for maintenance of good health. The medical utilities of several of these plants have been documented; however, there are many more, whose potential is yet to be explored. This review discusses the role of various plants grown in the Indian subcontinent that have been widely used in maintaining various aspects of reproductive health in men such as infertility, aphrodisiac, contraception, libido, sexually transmitted infections and reproductive tract cancers as well as in treating chronic disorders.

Ong WL, Nazareth L, Hindson B, et al.
Long-term outcomes following post-operative radiotherapy for Stage I/II testicular seminoma - an Australasian single-institution experience.
J Med Radiat Sci. 2016; 63(3):161-9 [PubMed] Article available free on PMC after 01/02/2018 Related Publications
INTRODUCTION: The aim of the study is to review the long-term oncological outcomes and adverse effects of post-operative radiotherapy (PORT) for Stage I/II seminoma patients in an Australian radiation treatment centre.
METHODS: This is a retrospective study of 125 patients with Stage I/II seminoma treated with PORT at the Alfred Health Radiation Oncology Service between 1992 and 2013. Patients were linked to the Victorian Cancer Registry to enable confirmation of survival and diagnosis of secondary malignancies (SM). The relapse-free survival (RFS), testicular-cancer-specific survival (TCSS), overall survival (OS) and SM-free survival (SMFS) were estimated with Kaplan-Meier methods.
RESULTS: The median age at diagnosis was 36 (range 20-62). The median time between diagnosis and PORT was 1.6 months (range: 0.5-4.5). Fifty patients (40%) had PORT to the para-aortic (PA) target alone, while the remaining had PORT to PA and ipsilateral or bilateral iliac lymph nodes. There were no acute adverse effects requiring admission. The median follow-up after PORT was 7.8 years (range = 0.1-19.1). There were two relapses, both of which occurred within 1 year of PORT (estimated 10-year RFS = 98.4%). Five deaths were reported, none of which were testicular cancer-related death (estimated 10-year TCSS = 100%, 10-year OS = 97.3%). There were seven SM (one lower lip cancer, one upper shoulder melanoma, one mesothelioma, two prostate cancer, one acute myeloid leukaemia and one contralateral testicular seminoma) reported in six patients, with estimated 10-year SMFS of 92.9%.
CONCLUSION: Our series confirms excellent oncological outcomes among patients with Stage I/II seminoma treated with PORT, with uncommon occurrence of SM.

Rades D, Dziggel L, Veninga T, et al.
Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.
Anticancer Res. 2016; 36(9):4817-9 [PubMed] Related Publications
BACKGROUND/AIM: To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer.
PATIENTS AND METHODS: Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients.
RESULTS: KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively.
CONCLUSION: A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided.

Fabijanovic D, Zunic I, Martic TN, et al.
The expression of SFRP1, SFRP3, DVL1, and DVL2 proteins in testicular germ cell tumors.
APMIS. 2016; 124(11):942-949 [PubMed] Related Publications
Germ cell tumors of the testis are a heterogeneous group of neoplasms that affect male adolescents and young adults. Wnt signaling pathway components have been shown to be actively involved in normal and malignant germ cell differentiation and progression. In this study, we aimed to explore the expression patterns of the secreted frizzled-related protein (SFRP) and Disheveled protein family (DVL) in a subset of testicular germ cell tumors. Eighty-five formalin-fixed, paraffin-embedded tissue samples of the primary germ cell tumors of the testis were stained against SFRP1, SFRP3, DVL1, and DVL2 proteins using immunohistochemistry. SFRP1 and SFRP3 exhibited lower expression in both seminomas and mixed/non-seminomatous tumors, compared with atrophic/benign tissue (p < 0.001). SFRP3 expression was lower than SFRP1 expression within the seminoma group (p = 0.004), but not within the mixed/non-seminomatous group (p = 0.409). The majority of the tested cases (27/28, 96%) exhibited low DVL1 protein expression (median 0%, range 0-90%). In contrast, 20 out of 22 tested cases (91%) exhibited strong expression of DVL2 protein (median 80%, range 0-100%). No significant difference in DVL1 and DVL2 protein expression was observed between seminomas and mixed/non-seminomatous tumors (p = 0.68 and 0.29). The secreted frizzled-related protein and disheveled protein family members appear to be actively involved in the pathogenesis of primary testicular germ cell tumors.

Nachulewicz P, Golonka A, Żądkowski T, et al.
Closure of the thoracic duct from the left-side access: A case report.
Medicine (Baltimore). 2016; 95(35):e4552 [PubMed] Article available free on PMC after 01/02/2018 Related Publications
BACKGROUND: We report a 16-year-old patient with a massive left-sided chylothorax after chemotherapy due to mixed germinal tumor of the testis with massive metastases located in the retroperitoneal space and posterior mediastinum. Chemotherapy resolved the metastases in the mediastinum but evoked a huge pleural effusion in the left pleural cavity, requiring surgical intervention.Left-sided access was used. The 5-mm camera and 3 5-mm working ports were inserted. The parietal pleura was incised and the esophagus located and protected. Behind the esophagus, the thoracic duct and concomitant tissue were clipped with titanium clips, and additionally, thrombin glue was used. Stopping of the lymph leakage was observed during surgery. A local argon pleurodesis was used to finish the procedure. The thoracic tube was removed on the third postoperative day.
CONCLUSION: Left-side access may be a good alternative in the left-sided chylothorax, but the crucial points are location and protection of the esophagus during the procedure, which is also the landmark that allows for locating the thoracic duct.

Ligia Cebotaru C, Zenovia Antone N, Diana Olteanu E, et al.
A phase II single institution single arm prospective study with paclitaxel, ifosfamide and cisplatin (TIP) as first-line chemotherapy in high-risk germ cell tumor patients with more than ten years follow-up and retrospective correlation with ERCC1, Topoisomerase 1, 2A, p53 and HER-2 expression.
J BUON. 2016 May-Jun; 21(3):698-708 [PubMed] Related Publications
PURPOSE: One half of high-risk germ cell tumor (HRGCT) patients relapse after standard chemotherapy. This phase II study evaluated prospectively the toxicity and efficacy in first-line of the paclitaxel-ifosfamide-cisplatin combination (TIP) in HRGCT patients and tried to identify biomarkers that may allow patient-tailored treatments.
METHODS: Between October 1997- September 2000, 28 chemo-naive HRGCT patients were enrolled. Patients received 4 cycles of TIP (paclitaxel 175 mg/m(2) day 1/; ifosfamide 1.2 g/m(2)/day, days 1-5; Mesna 1.2 g/m(2)/day, days 1-5; and cisplatin 20 mg/m(2)/day, days 1-5 every 3 weeks). A non-randomized comparison was made between HRGCT patients treated in the same period with first-line TIP and bleomycin-etoposide-cisplatin (BEP) (28 patients vs 20). In 17 HRGCT patients treated between 1998-2006, ERCC1, Topoisomerase 1 and 2A, p53 and HER-2 expression was retrospectively analysed by immunohistochemistry (IHC) (7 patients with TIP, 10 with BEP), and correlations were made with response to chemotherapy and survival.
RESULTS: With a median follow-up of 72 months [range 48+...89+], 5-year disease free survival (DFS) was 55%, with 95% CI 36-72, and the overall survival (OS) was 63%, with 95% CI 44-78. In June 2015, with a median follow-up of 196.47 months (range 177.30-209.27) (>15 years), 12 [%?] patients were alive and disease-free, and 16 [%?] had died (12 specific causes). There was no significant correlation between the expression of ERCC1, Topoisomerase 1 and 2A, HER-2 and p53 and response to treatment.
CONCLUSION: Long-term follow-up showed no difference in OS between TIP vs BEP as first-line therapy. Both regimens had mild toxicity.

Friend J, Barker A, Khosa J, Samnakay N
Benign scrotal masses in children - some new lessons learned.
J Pediatr Surg. 2016; 51(10):1737-42 [PubMed] Related Publications
INTRODUCTION: A preponderance of benign intratesticular masses in pre-pubertal males encourages testicular-sparing surgery (TSS).
OBJECTIVE: To review outcome of benign testicular lumps in children managed at a tertiary pediatric center more than 7.5years.
METHODS: A retrospective review of pediatric benign testicular lesions from January 2008 to June 2015 was performed.
RESULTS: There were twelve benign intratesticular tumors. Of these, 11 were in pre-pubertal males; comprising four teratomas, two epidermoid cysts, one dermoid cyst, two cases of Leydig cell hyperplasia, one cystic dysplasia of the rete testis and one large simple intratesticular cyst. We illustrate a case of Leydig cell hyperplasia presenting with precocious puberty limited to the ipsilateral hemi-scrotum. TSS was attempted in all 11 pre-pubertal cases, but successfully performed in seven. TSS was possible for a large testicular cyst seemingly replacing the entire testis, with evidence that the testis reconstituted itself after surgery. Recurrence of an epidermoid cysts reported.
CONCLUSION: For the first time in the literature, this series reports Leydig cell hyperplasia presenting with ipsilateral hemi-scrotal changes of precocious puberty; shows evidence that the testis reconstitutes itself after TSS for a large cyst; and reports recurrence of an epidermoid cyst after TSS.

Öztürk A, Aktaş Z, Yılmaz A
Endobronchial metastasis of mixed germ cell tumors: two cases.
Tuberk Toraks. 2016; 64(2):175-8 [PubMed] Related Publications
Lung metastases from extrapulmonary malignancies are common however endobronchial metastases (EBM) from nonpulmonary neoplasms are rare. A variety of extrathoracic tumors have a tendency to EBM especially breast, colon, and renal carcinomas are most frequent reported tumors however EBM of germ cell tumors are extremely rare. A 39-year-old and a 27-year-old male patient were admitted to our hospital with hemoptysis and dyspnea at different times. Both of them had a history of left orchiectomy due to mixed germ cell tumor two years and one year ago, respectively. On chest X-Ray and thorax computed tomography, first had a right upper lobe atelectasis and second had right total atelectasis. Fiberoptic bronchoscopy (FOB) performed and a vascularized endobronchial lesion (EBL) which tended to bleed was seen in the orifis of right upper lobe in the first case and right main bronchus was totally obstructed by EBL also in the second. Interventional bronchoscopy was performed via rigid bronchoscopy for biopsy and palliative treatment (argon plasma coagulation and debulking) in both two patients because of tendency to bleeding. A partial aperture was achieved at right upper lobe bronchus in the first case and total atelectasis resolved in the second case. Immunohistochemically, histopathological examinations of both patients biopsies confirmed EBM of mixed germ cell tumors. In conclusion, EBM of the germ cell tumors especially with total or partial atelectasis are extremely rare. We want to present these cases to emphasize the importance of distinguishing EBM from primary lung carcinoma which treatment and survival could be different.

Burnik Papler T, Frković Grazio S, Kobal B
Sertoli - Leydig cell tumor with retiform areas and overgrowth of rhabdomyosarcomatous elements: case report and literature review.
J Ovarian Res. 2016; 9(1):46 [PubMed] Article available free on PMC after 01/02/2018 Related Publications
BACKGROUND: Sertoli - Leydig cell tumors (SLCTs) are sex-cord stromal tumors that account less than 0.5 % of primary ovarian neoplasms. They are mostly benign and occur in reproductive age women. Variants with heterologous mesenchymal elements are exceptionaly rare. The usual presentation of SLCTs is with signs of androgen excess as majority of them produce androgens.
CASE PRESENTATION: We present a case of a SLCT occurring in a 70 year old woman. Her presenting complaint was abdominal distension and pain. She had no signs of androgen or estrogen excess. Transvaginal ultrasound (TVUS) and CT scan showed a multilocular adnexal tumor and level of CA 125 was raised. A complete cytoreduction was achieved with surgical procedure. Histopathological examination revealed moderately differentiated SLCT with retiform areas and owergrowth of heterologous component in form of embrional rhabdomyosarcoma (RMS). She returned 7 months after the surgery with a large abdominal mass, ascites, right- sided hydronephrosis and massive pulmonary embolism. Due to the widespread disease and her poor general condition, she received only palliative care. She died 15 days after the admission. No autopsy was performed.
CONCLUSIONS: Due to the rarity of SLCTs, especially those with retiform areas and heterologous elements, their management remains challenging. There is no firm evidence that adjuvant chemotherapy is effective in improving survival in SLCTs with malignant heterologous elements. Further studies with a higher number of cases and a longer follow-up are needed to better predicting the prognosis and determine the role of chemotherapy in such cases.

Gerwing M, Jacobsen C, Dyshlovoy S, et al.
Cabazitaxel overcomes cisplatin resistance in germ cell tumour cells.
J Cancer Res Clin Oncol. 2016; 142(9):1979-94 [PubMed] Related Publications
BACKGROUND: Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines.
METHODS: In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array.
RESULTS: Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT.
CONCLUSION: Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.

Sadow CA, Maurer AN, Prevedello LM, et al.
CT restaging of testicular germ cell tumors: The incidence of isolated pelvic metastases.
Eur J Radiol. 2016; 85(8):1439-44 [PubMed] Related Publications
PURPOSE: We determined the incidence of isolated pelvic metastases at restaging computed tomography (CT) in patients with testicular germ cell tumors to consider if imaging the pelvis could be omitted.
METHODS: After receiving IRB approval for this HIPAA-compliant retrospective study, medical records of 560 men (mean age 32.8) with 583 testicular germ cell tumors who underwent 3683 restaging CT scans of the abdomen and pelvis were reviewed to determine the proportion of patients with metastatic disease in the pelvis alone, as verified by histology or by resolution after therapy. Chi-square statistical analysis tested the association between factors currently thought to predispose patients to pelvic metastases. Patients were also categorized by clinical stage, tumor histology, and initial treatment.
RESULTS: Isolated pelvic metastases were detected in nine (1.6%) of 560 men. Neither bulky abdominal disease (p=0.85) nor extratesticular invasion by the primary tumor (p=0.37) were statistically significant in predicting which patients were more likely to have isolated pelvic metastases. Among the nine patients with isolated pelvic recurrence, only three (0.7%) of 408 men with no known pelvic disease at initial staging and no tumor marker elevation at restaging had isolated pelvic metastases. Isolated pelvic recurrence was not statistically different when analyzed by initial stage and treatment.
CONCLUSION: The incidence of isolated pelvic metastases in testicular germ cell tumors at restaging CT is low, but no group of patients was found to be without risk. Therefore, given the small, if any, risk of radiation-induced harm, the decision about whether to include routine pelvic CT in surveillance protocols should be individualized.

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