Adult primary testicular lymphoma: clinical features and survival in a series of patients treated at a high-volume institution in China.

BACKGROUND: To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute. METHODS: From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters. RESULTS: All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit's lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71-71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35-96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8-56.0%) and 53.4% (95%CI, 30.1-76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3-5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients. CONCLUSION: This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients.

Polymetastatic testicular cancer turns out to be secondary syphilis: a case report.

Syphilis is a sexually transmissible infection, with increasing rates of infection worldwide. The differential diagnosis of syphilis should include various diseases, not excluding cancer. Making the right diagnosis can protect the patient against life-threatening complications and the repercussions of a misdiagnosis, as in the present case (orchidectomy).

CXCL12 expression is an adverse predictor for disease recurrence in patients with metastatic non-seminomatous testicular germ cell tumors.

BACKGROUND: To validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT). METHODS: CXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests. RESULTS: CXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease. CONCLUSIONS: CXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.

Impact of hemoglobin levels on hemoglobin-adjusted carbon monoxide diffusion capacity after chemotherapy for testicular cancer.

OBJECTIVES: We aimed to compare the diffusion capacity of carbon monoxide (DLCO), which was adjusted using the two equations the Cotes method and the Dinakara method, to assess bleomycin-induced lung injury in testicular cancer patients preparing for post-chemotherapy surgery. METHODS: Between November 1990 and October 2018, 89 patients with advanced testicular cancer were recruited into the study. All patients received chemotherapy and underwent DLCO measurements using the single-breath technique prior to surgery for residual tumor removal. RESULTS: The mean DLCO adjusted for hemoglobin using the Cotes and Dinakara methods was 69.5% and 86.0%, respectively (P < 0.001). According to the Cotes method, adjusted DLCO was severely diminished to below 65% in 40 patients (45%), whereas this proportion was only 16% according to the Dinakara method. We observed a significant correlation between hemoglobin levels and DLCO adjusted using the Cotes method (P < 0.001), but not using the Dinakara method. Four patients received a clinical diagnosis of bleomycin-induced pneumonitis (BIP), and all patients recovered after oral steroid therapy or observation. The DLCO adjusted by either methods was not well correlated with the development of BIP. No patients had major postoperative respiratory complications. CONCLUSIONS: We found that Cotes-adjusted DLCO may be influenced by anemia. We recommend the addition of Dinakara-adjusted DLCO, along with chest computed tomography, for preoperative risk assessment.

What Is the Significance of Rete Testis Invasion by Malign Germ Cell Tumor and Does Hilum Predict Metastasis?

BACKGROUND: The significance of hilar soft tissue invasion of rete testis in malign germ cell tumors is still controversial on current guidelines. OBJECTIVES: We aimed to investigate the importance of hilar soft tissue involvement in germ cell tumors and evaluated the possibility of a risk factor such as rete testis. METHOD: Totally, 59 radical orchiectomy specimens operated between 2007 and 2015 at our clinics. All records were retrospectively researched. Patients' age, level of tumor markers, tumor size, histological subtype, clinical stage, presence or absence of carcinoma in situ, vascular/lymphatic and/or hilar soft tissue invasion, tumoral necrosis, number, site and diameter of metastasis, type of further treatment (radiotherapy or chemotheraphy) and follow-up period were recorded and evaluated for all patients. RESULTS: Twenty-six of totally 59 malign germ cell tumors were seminomatous and 33 were nonseminomatous (NS). Mean patients age was 38.54 years (range 17-89 years). Mean follow-up duration was 39.84 months (range 3-96). Serum tumor marker levels were found associated with rete testis invasion (p = 0.035). Hilar soft tissue invasion was significantly associated with vascular invasion (p = 0.001). As it was expected, vascular invasion was significantly associated with metastasis (p = 0.024). CONCLUSIONS: We concluded that there is a strong association between hilar soft tissue invasion and vascular invasion. Especially in NS germ cell tumors, hilar soft tissue involvement a risk factor for prognosis and to determine the need for additional treatment. According to our study, hilar soft tissue status should be reported on routine pathology report.

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK.

Bleomycin, a cytotoxic chemotherapy agent, forms a key component of curative regimens for lymphoma and germ cell tumours. It can be associated with severe toxicity, long-term complications and even death in extreme cases. There is a lack of evidence or consensus on how to prevent and monitor bleomycin toxicity. We surveyed 63 germ cell cancer physicians from 32 cancer centres across the UK to understand their approach to using bleomycin. Subsequent guideline development was based upon current practice, best available published evidence and expert consensus. We observed heterogeneity in practice in the following areas: monitoring; route of administration; contraindications to use; baseline and follow-up investigations performed, and advice given to patients. A best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours has been developed and includes recommendations regarding baseline investigations, the use of pulmonary function tests, route of administration, monitoring and patient advice. It is likely that existing heterogeneity in clinical practice of bleomycin prescribing has significant economic, safety and patient experience implications. The development of an evidence-based consensus guideline was supported by 93% of survey participants and aims to address these issues and homogenise practice across the UK.

Effects of high-intensity interval training on fatigue and quality of life in testicular cancer survivors.

BACKGROUND: Testicular cancer survivors (TCS) are at increased risk of cancer-related fatigue (CRF), psychosocial impairment, and poor mental health-related quality of life (HRQoL). Here, we examine the effects of high-intensity interval training (HIIT) on patient-reported outcomes (PROs) in TCS. Secondarily, we explore cardiorespiratory fitness as a mediator of intervention effects and select baseline characteristics as moderators of intervention effects. METHODS: TCS (n = 63) were randomly assigned to 12 weeks of supervised HIIT or usual care (UC). PROs included CRF, depression, anxiety, stress, self-esteem, sleep quality, and HRQoL assessed at baseline, post-intervention, and 3-month follow-up. RESULTS: TCS (median 7 years postdiagnosis) completed 99% of training sessions and achieved 98% of target training intensity. ANCOVA revealed that, compared to UC, HIIT significantly improved post-intervention CRF (p = 0.003), self-esteem (p = 0.029), and multiple HRQoL domains (ps ≤ 0.05). Effects on CRF (p = 0.031) and vitality (p = 0.015) persisted at 3-month follow-up. Cardiorespiratory fitness changes mediated CRF and HRQoL improvements. CRF effects were larger for TCS with an inactive lifestyle, lower fitness, higher testosterone, and clinical fatigue at baseline. CONCLUSIONS: HIIT significantly improves CRF and HRQoL in TCS. Mediation by cardiorespiratory fitness and moderation by clinical characteristics suggests opportunities for targeted exercise interventions to optimise PROs in TCS.

Fertility preservation in testicular cancer - predictors of spermatogenesis.

OBJECTIVES: To determine the frequency of spermatogenesis in patients with testicular cancer and to assess for any predictors of spermatogenesis. PATIENTS AND METHODS: We retrospectively reviewed 103 testicular germ cell tumours (TGCTs) in men who underwent radical orchidectomy conducted at Guy's Hospital, London, between 2011 and 2015. Primary outcome measures included: the presence and characteristics of spermatogenesis (widespread/focal/proximity to tumour). Secondary outcome measures included: the presence of testicular microlithiasis, tumour characteristics (size, stage, and type), and tumour markers. Secondary outcome measures as potential predictors of spermatogenesis were assessed using univariate and multivariate logistic regression analyses. RESULTS: Spermatogenesis was present in 70% (72/103) of the patients; it was widespread in 63% (45/72) and focal in 38% (27/72). Neither tumour type, stage, presence of microcalcification nor tumour markers predicted spermatogenesis. Men with a percentage testis tumour occupation (PTTO) of >50% of their testis were 82% (95% confidence interval 73.2-98.4) less likely to have spermatogenesis than a PTTO of <50%. CONCLUSIONS: Spermatogenesis is present in most testes affected by TGCTs; it is widespread in two-thirds of patients, and located away from the tumour in 94%. These findings can help predict and guide successful surgical sperm retrieval in testes with TGCTs. The finding of focal spermatogenesis in a third of patients would support a microsurgical approach to sperm retrieval at the time of orchidectomy to maximise success.

Are ultrasonographic measurements a reliable parameter to choose non-palpable testicular masses amenable to treatment with sparing surgery?

PURPOSE: To analyze the dimensional characteristics between non-palpable testicular masses detected during ultrasonographic (US) study and their postoperative dimensions reported in definitive histological diagnosis, and evaluate if the sonographic measurements may be a relevant parameter to improve the identification of testicular lesions amenable to treatment with testicular-sparing surgery (TSS). METHODS: A total of 77 patients who underwent radical orchiectomy or TSS for non-palpable testicular masses suspected for malignant neoplasms were included into this study. Preoperative US studies were also carried out in all patients to evaluate the diameter, volume and sonographic characteristics of the testicular lesions and the contralateral testes. All patients underwent inguinal orchiectomy or testicular exploration (for masses ≤1.5 cm) through an inguinal approach. RESULTS: The mean age at the time of diagnosis was 36.5 years. The predominant finding was a hypoechoic mass (71.4%). The vast majority of all malignant masses appeared markedly hypoechoic (89.8%); moreover, this differed significantly from benign lesions (39.3%, p<0.001). Calcified lesions were significantly associated with benign tumors (77.8%, p<0.002). The mean maximum lesion diameter of the affected testicle determined by preoperative US study was 14.1 mm (range 7-21). The mean maximum lesion determined postoperatively by pathology was 13.4 mm (range 5-20). Tumor lesions estimated by US study were more accurate in benign tumors, but the results were not statistically significant (p=0.323). CONCLUSIONS: We demonstrated that the sonographic diameter of the testicular lesions seems to be one of the most important parameter for the indication of an elective TSS and US is an accurate method for detecting and measuring these lesions.

Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis.

Testicular adrenal rest tumors in congenital adrenal hyperplasia-cross-sectional study of 51 Croatian male patients.

Testicular adrenal rest tumors (TARTs) are common cause of infertility in males with congenital adrenal hyperplasia (CAH). We studied the role of genotype and disease regulation on TART development, their impact on gonadal function, and frequency in 47 21-hydroxylase deficiency (21-OHD) and four 11-hydroxylase deficiency (11-OHD) male patients. Testicular ultrasound (TU), genotype, hormonal measurement in 51, and spermiogram in five patients were performed. TARTs were detected in 14 SW21-OHD and one 11-OHD patient: 1/8 patients aged <7 years (1.8 years old is the youngest), 1/8 patients aged <12 years, 5/17 patients aged <18 years, and in 8/18 adults. All 21-OHD TART patients had exclusively severe mutations of CYP21A2 gene. Poor hormonal control in 8/15 patients with and 12/36 patients without TART indicates correlation of tumor development with poor disease control. None of the TART patients fathered a child. Low inhibin-B was found in 7/15 TART patients. Azoospermia was found in four and oligoasthenozoospermia in one patient. CONCLUSION: TART was detected exclusively in patients with severe CYP21A2 mutations. Disease regulation plays a role in development of TART that impairs testicular function and increases the risk of infertility. Screening for TART by TU is indicated from early childhood. What is Known: • Due to improved diagnostic and therapeutic possibilities, majority of the male patients with congenital adrenal hyperplasia nowadays reach adulthood and screening for long-term complications is becoming more important. • Testicular adrenal rest tumors (TARTs) are common cause of infertility and impaired gonadal function in males with CAH. What is New: • A 1.8-year-old boy described in this paper is the youngest reported patient with TART. • Screening for TART by testicular ultrasound from early childhood, especially in patients with severe CYP21A mutations, is recommended.

Bleomycin-Induced Pulmonary Changes on Restaging Computed Tomography Scans in Two Thirds of Testicular Cancer Patients Show No Correlation With Fibrosis Markers.

BACKGROUND: In metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, bleomycin-induced pneumonitis is a well-known and potentially fatal side effect. We sought to determine the prevalence of lesions as signs of bleomycin-induced pulmonary changes on restaging computed tomography (CT) scans after treatment and to ascertain whether fibrosis markers were predictive of these changes. PATIENTS AND METHODS: This prospective nonrandomized cohort study included metastatic testicular cancer patients, 18-50 years of age, treated with BEP chemotherapy. Restaging CT scans were examined for lesions as signs of bleomycin-induced pulmonary changes by two independent radiologists and graded as minor, moderate, or severe. Plasma samples were collected before, during, and after treatment and were quantified for transforming growth factor-ß1 (TGF-ß1), growth differentiation factor-15 (GDF-15), and high-sensitivity C-reactive protein (hs-CRP). RESULTS: In total, 66 patients were included: forty-five (68%) showed signs of bleomycin-induced pulmonary changes on the restaging CT scan, 37 of which were classified as minor and 8 as moderate. No differences in TGF-ß1, GDF-15, or hs-CRP plasma levels were found between these groups. CONCLUSION: Bleomycin-induced pulmonary changes are common on restaging CT scans after BEP chemotherapy for metastatic testicular cancer. Changes in TGF-ß1, GDF-15, and hs-CRP plasma levels do not differ between patients with and without radiological lesions as signs of bleomycin-induced pulmonary changes and are therefore not helpful as predictive biomarkers. IMPLICATIONS FOR PRACTICE: Bleomycin-induced pneumonitis (BIP) is a well-known and potentially fatal side effect in metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin chemotherapy. Currently, the decision to discontinue bleomycin administration is made during treatment and is based on clinical signs. An upfront or early marker or biomarker that identifies patients likely to develop BIP would be preferable. This study found that bleomycin-induced pulmonary changes are common on restaging computed tomography scans and mostly resolve. No correlation was seen between these changes and fibrosis or inflammation markers (transforming growth factor-ß1, growth differentiation factor-15, and high-sensitivity C-reactive protein).

Metastatic testicular cancer presenting with liver and kidney dysfunction treated with modified BEP chemotherapy combined with continuous hemodiafiltration and rasburicase.

A 25-year-old man was admitted to our hospital complaining of right scrotal pain and upper abdominal pain. A computed tomographic scan indicated a right scrotal mass, a huge liver mass, and multiple lung masses, although there was no enlarged retroperitoneal lymph node swelling. Laboratory tests showed severe liver and kidney dysfunction and high levels of serum α-fetoprotein (11,997 ng/ml). Although needle biopsies of the testicular and liver masses were performed, the tissues were insufficient for a pathological diagnosis. As liver and kidney function worsened, we started chemotherapy with bleomycin, etoposide, and cisplatin (BEP chemotherapy), which was modified because of the liver and renal dysfunction. We also used continuous hemodiafiltration and rasburicase to prevent tumor lysis syndrome. After induction of chemotherapy, the liver and kidney dysfunction improved immediately and the high orchiectomy was performed on day 8 after chemotherapy. The pathological diagnosis was a yolk sac tumor. He underwent four courses of the BEP regimen and five courses of the TIN regimen (paclitaxel, ifosphamide, and nedaplatin), followed by the resection of liver metastases. There was no evidence of viable cells in the resected liver and no recurrence was evident at 1 year postoperatively.

Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors.

BACKGROUND: Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. PATIENTS AND METHODS: Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. RESULTS: Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. CONCLUSIONS: The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important.

Spermatogenesis in tumor-bearing testes in germ cell testicular cancer patients.

STUDY QUESTION: What are the factors that might indicate a greater likelihood of success in oncologic testicular sperm extraction (onco-TESE)? SUMMARY ANSWER: Smaller tumor diameter and greater noncancerous testicular tissue width (NCTW) are positive predictors of spermatogenesis in patients with testicular germ cell tumors (TGCTs). WHAT IS KNOWN ALREADY: Onco-TESE is a key modality for fertility preservation in cases of inadequate pretreatment sperm collection and azoospermic men with testicular cancer. TGCTs are known to reduce sperm quality such that ∼ 10% of these patients are azoospermic, making surgical TESE at the same time as orchiectomy their only means of fertility preservation. STUDY DESIGN, SIZE, DURATION: This study is a retrospective analysis performed in a single university hospital from 2002 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were 102 male patients (104 testes) who underwent inguinal orchiectomy and were diagnosed with a germinoma. In each specimen, the Johnsen Score Count (JSC) in seminiferous tubules at each established distance from the tumor margin (1, 2.5, 5, 7.5, 10 and 12.5 mm) was determined. We analyzed the relations between age, tumor histopathologic type, tumor size (maximum diameter), distance from the tumor, non-tumor tissue width and JSC. MAIN RESULTS AND THE ROLE OF CHANCE: The 104 specimens consisted of 78 seminomas and 26 non-seminomatous TGCTs. The mean ± SD JSC was 4.7 ± 2.4 in seminomas and 3.9 ± 2.5 in non-seminomatous germ cell tumors, with no significant difference between the two subtypes. Single regression analysis showed that tumor diameter was significantly negatively correlated with spermatogenesis (RC = -0.422, P < 0.001). Multiple linear regression analysis also showed that tumor diameter had a negative influence on spermatogenesis (RC = -0.437, P < 0.001). The greater the distance the seminiferous tubules from the tumor, the better the preservation of spermatogenesis. Mature spermatozoa were identified in 93.0% of patients with a NCTW ≥ 7.5 mm and in 41.3% of those with NCTW < 7.5 mm (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Study data were obtained retrospectively, which might have affected the quality of data. We were unable to compare spermatogenesis determined using preoperative seminograms with that determined histopathologically. It was not possible to evaluate spermatogenesis in the total volume of noncancerous testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS: When Onco-TESE is conducted at sites distant from tumors, the rate of sperm extraction is high and contamination by tumor cells can be prevented. By measuring non-testicular cancerous margin before the operation, the possibility of sperm extraction can be predicted and biopsy of the contralateral testis can be considered based on the results.

Interpersonal Sensitivity and Sexual Functioning in Young Men with Testicular Cancer: the Moderating Role of Coping.

BACKGROUND: Interpersonal sensitivity is characterized by the predisposition to perceive and elicit criticism, rejection, and negative social evaluation. It may be linked to poorer physical or functional health outcomes, particularly in the interpersonal context (cancer-related sexual dysfunction). PURPOSE: This study tested the association of interpersonal sensitivity with sexual functioning following testicular cancer in young men and whether this association is moderated by coping processes. METHOD: Men ages 18 to 29 (N = 171; M age = 25.2, SD = 3.32) with a history of testicular cancer were recruited via the California State Cancer Registry and completed questionnaire measures including assessments of interpersonal sensitivity, sexual functioning, and approach and avoidance coping. RESULTS: Regression analysis controlling for education, age, partner status, ethnic status, and time since diagnosis revealed that higher interpersonal sensitivity was significantly related to lower sexual functioning (ß = -0.18, p < 0.05). Cancer-related approach-oriented coping was associated with better sexual functioning (ß = 0.19, p < 0.05). No significant association was observed for avoidance coping (ß = -0.08, ns). Approach-oriented coping, but not avoidance, moderated the relationship with sexual functioning (ß = 0.19, p < 0.05), such that higher interpersonal sensitivity was more strongly associated with lower functioning among men with relatively low use of approach coping. CONCLUSION: Interpersonal sensitivity may be an important individual difference in vulnerability to sexual dysfunction after testicular cancer. Enhancement of coping skills may be a useful direction for intervention development for interpersonally sensitive young men with cancer.

[THREE CASE REPORTS OF METACHRONOUS BILATERAL TESTICULAR TUMOR: INVESTIGATION OF SEXUAL FUNCTION AND FERTILITY].

The sexual dysfunction and infertility after treatment of bilateral germ cell tumors (GCT) becomes the serious problem. Therefore andrological aspects as well as cancer curability should be considered in planning of bilateral GCT treatment. Here we report 3 cases of metachronous bilateral GCT treated with different regimens, and discuss from the viewpoint of preservation of sexual function. Case presentations: (1) A 38-year-old man underwent right-sided orchitectomy for a right testicular tumor at the age of 26 years. Pathological diagnosis was seminoma and clinical stage was T1N0M0S2. 12 years later, contralateral testicular tumor developed. Left-sided orchitectomy was performed. Pathological diagnosis was seminoma and clinical stage was T1N0M0S2. He has been followed up for 4 years after the second operation without any evidence of tumor recurrence. Endocrinological examination show low testosterone level, and high LH and FSH levels. Erection and ejaculation are impossible but he does not request androgen replacement therapy. (2) A 21-year-old man underwent right-sided orchitectomy for a right testicular seminoma at the age of 20 years (T1 N0M0S0). 1 year later, contralateral seminoma (T1N0M0S0) developed and left-sided organ-preserving operation was performed. Histologic specimens showed seminoma and intratubular malignant germ cells (ITMGC) in surrounding seminiferous tubules. 2 cycles of BEP was added after the operation. He has been followed up for 5 years without any evidence of tumor recurrence. Endocrinological examination shows normal levels of testosterone and LH, but FSH is slightly high. Erection and ejaculation are possible. (3) A 36-year-old man underwent right-sided orchitectomy for a right testicular embryonal carcinoma at the age of 30 years. Clinical T1N0M0S1 was confirmed. 6 years later, he noticed the induration at his left testis. The result of fine needle aspiration cytology was embryonal carcinoma. At first, organ-preserving operation after chemotherapy was planned. However, he refused the operation considering the possibility of erectile dysfunction and infertility. As a result, he received only chemotherapy (3 cycles of BEP), and has been free of the disease for 11 years after chemotherapy. The level of testosterone, LH, and FSH are all normal. Erection and ejaculation are possible.

[Fertility in testicular cancer patients].

Testicular cancer(TC)is the most common and curable cancer affecting men of reproductive age. Successful treatment approaches have resulted in longer life expectancy in TC survivors. The most frequently used treatment for TC is a combination of inguinal orchiectomy, and either radiotherapy or cisplatin-based chemotherapy. In many TC patients, sperm quality is already abnormal and there may even be a lack of viable spermatozoa at the time of diagnosis. Therefore, the effect of cancer treatment on fertility is a potentially significant issue. Fertility preservation in these men has become essential and needs to be discussed prior to the start of cancer treatment. The only currently established fertility preservation method is the cryopreservation of sperm before therapy. For most patients seeking cryopreservation, the semen sample is collected via masturbation. If the patient is unable to ejaculate for any reason, other techniques such as vibratory stimulation and electroejaculation can be performed. In azoospermic or severely oligozoospermic patients, testicular sperm extraction at the time of the inguinal orchiectomy is a useful technique for obtaining spermatozoa before cytotoxic therapy. We herein present an overview of the current topics on fertility in TC patients, including the effects of surgery, chemotherapy, and radiation therapy. We also describe the strategy for fertility preservation in these patients.

Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: a randomized controlled trial.

BACKGROUND: Bleomycin-etoposid-cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. METHODS: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks of BEP therapy. Resistance training consisted of thrice weekly sessions of four exercises, 3-4 sets/exercise of 10-15 repetitions at 12-15 repetition maximum load. The primary endpoint was muscle fibre size, assessed in muscle biopsies from musculus vastus lateralis. Secondary endpoints were fibre phenotype composition, body composition, strength, blood biochemistry and patient-reported endpoints. Healthy age-matched subjects (REF, n=19) performed the same RT-programme for comparison purposes. RESULTS: Muscle fibre size decreased by -322 µm(2) (95% confidence interval (CI): -899 to 255; P=0.473) in the CON-group and increased by +206 µm(2) (95% CI: -384 to 796; P=0.257) in the INT-group (adjusted mean difference (AMD), +625 µm(2), 95% CI: -253 to 1503, P=0.149). Mean differences in type II fibre size (AMD, +823 µm(2), P=0.09) and lean mass (AMD, +1.49 kg, P=0.07) in favour of the INT-group approached significance. The REF-group improved all muscular endpoints and had significantly superior changes compared with the INT-group (P<0.05). CONCLUSIONS: BEP was associated with significant reduction in lean mass and strength and trends toward unfavourable changes in muscle fibre size and phenotype composition. Resistance training was safe and attenuated dysfunction in selected endpoints, but BEP blunted several positive adaptations observed in healthy controls. Thus, our study does not support the general application of resistance training in this setting but larger-scaled trials are required to confirm this finding.

Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.

BACKGROUND: Seminoma stage I is the most frequent testis cancer and single-dose carboplatin (AUC7) is an effective and widely used adjuvant treatment. Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial. The gold standard of GFR measurement with a radiolabelled isotope is expensive and not readily available. In many institutions, it is replaced by GFR estimation with the Cockcroft-Gault formula, which might lead to significant carboplatin underdosing and potentially inferior clinical outcome. METHODS: Retrospective analysis of all patients with stage I seminoma treated with adjuvant carboplatin between 1999 and 2012. All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias, precision, rates of under- and overdosing of GFR estimates were compared with measured GFR. Bland-Altman plots were done. RESULTS: A total of 426 consecutive Caucasian male patients were included: median age 39 years (range 19-60 years), median measured GFR 118 ml/min (51-209), median administered carboplatin dose 1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% using CKD-EPI. The flat dosing strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean percentage error of +1.9, +0.4 and +2.1, respectively. CONCLUSIONS: Using Cockcroft-Gault or any other formula for GFR estimation leads to underdosing of adjuvant carboplatin in a relevant number of patients with Seminoma stage I and should not be regarded as standard of care.