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Non-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely underdiagnosed and untreated. In this study, we examine the value of pre-screening calcaneal QUS in identifying patients who should be referred for screening for osteoporosis using dual-energy X-Ray absorptiometry (DXA). In a single-center retrospective cross-sectional cohort study, we analysed data on DXA and calcaneal QUS measurements systematically collected between 2011 and 2013 in all non-metastatic PCa patients attending our Uro-Oncological Clinic at the Leiden University Medical Center. Receiver operating characteristic curves were used to assess the positive (PPV) and negative (NPV) predictive values of QUS T-scores of 0, -1.0, and - 1.8 in identifying DXA-diagnosed osteoporosis (T-scores ≤ - 2.5 and ≤ -2) at lumbar spine and/or femoral neck. Complete sets of data were available in 256 patients, median age 70.9 (53.6-89.5) years; 93.0 % had received local treatment, 84.4 % with additional ADT. Prevalence of osteoporosis and osteopenia was respectively 10.5 % and 53 %. Mean QUS T-score was -0.54 ± 1.58. Whereas PPV at any QUS T-score was <25 %, precluding the use of QUS as surrogate for DXA in screening for osteoporosis, QUS T-scores of -1.0 to 0.0 had a NPV of ≥94.5 % for DXA T-scores ≤ 2.5 and ≤ -2 at any site, confidently identifying patients least likely to have osteoporosis, thereby significantly reducing the number of patients requiring DXA screening for diagnosing osteoporosis by up to two-third. Osteoporosis screening is a significant unmet need in non-metastatic prostate cancer patients treated with ADT, and QUS may represent a valuable alternative pre-screening strategy to overcome logistics, time demands, and economic barriers encountered with current strategies for osteoporosis screening in these patients. Summary: Osteoporosis and associated increased fracture risk are common in non-metastatic prostate carcinoma, mainly due to androgen deprivation therapy, but these often remain underdiagnosed and untreated. We demonstrate that QUS is a safe, less costly pre-screen tool that reduces by up to two-third the number of patients requiring referral for DXA for osteoporosis screening.

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Cancer diagnosis and treatment may influence reproductive planning and impact fertility in patients of reproductive age. Although guidelines have been established in the past decade, education, practice, and attitudes of medical oncologists regarding fertility preservation remain undecided. A nationwide survey was performed among members of the Dutch Society for Medical Oncology. Demographics, practice, knowledge, and barriers were measured regarding information provision of fertility preservation towards cancer patients of childbearing age. From 392 members, 120 oncologists completed the questionnaire (30.6%). Majority of oncologists was convinced it is their responsibility to discuss impact of cancer treatment to fertility (93.2%), yet 68.3% discussed the subject often or always (n = 82). Oncologists employed in district general hospitals were less likely to discuss fertility (p = 0.033). On average, 44.6% of reproductive men and 28.9% of reproductive women is referred to fertility specialists. Half of the respondents declared to possess sufficient knowledge regarding fertility preservation (n = 57, 47.5%). Poor prognosis (53%), unlikely survival (43.1%), and high chances on fertility recovery (28.7%) were identified as barriers to discussing fertility preservation. Among oncologists, impact of cancer treatment on fertility is a well-accepted responsibility to counsel. Despite, self-reported knowledge regarding fertility preservation is strongly varying. In practice, fertility is discussed to some extent, influenced by several barriers and depending on prognosis and type of hospital. Patients benefit from knowledge improvement among oncology care providers concerning fertility effects of cancer treatment. Education during medical school, residency, and among practicing oncologists may raise awareness, together with enhancement of referral possibilities.

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BACKGROUND: Anti-cancer drugs commonly adversely affect fertility and sexual function. Despite this, patients report a lack of counselling of these potential adverse effects. The aim was to determine Dutch oncologists' knowledge about the adverse effects of various cancer drugs on fertility and sexual function. METHODS: A cross-sectional survey was sent to members of the Dutch Society for Medical Oncology (n = 433). The survey questions included various cancer drugs' adverse effects on fertility, ovulation, spermatogenesis, and sexual function. RESULTS: One hundred and five of 392 oncologists responded (26.8%). Oncologists were more aware of the adverse effects on fertility compared to sexual function. Drugs that were mostly believed to negatively affect fertility were cisplatin (n = 81, 80.2%), epirubicin (n = 78, 78.0%) and cyclophosphamide (n = 80, 77.7%). Regarding sexual function, most mentioned drugs were tamoxifen (n = 67, 65.7%), GnRH-agonists (n = 64, 63.4%) and cisplatin (n = 58, 57.4%). Oncologists with expertise in urology possessed more awareness regarding sexuality-related adverse effects (cisplatin p = 0.038, etoposide p = 0.025, ifosfamide p = 0.06, vinblastine p = 0.000). CONCLUSION: Results revealed that oncologists have different beliefs about possible sexual and fertility-related adverse effects concerning medication resources and literature. Based on our results, oncologists do not possess sufficient knowledge to inform patients about sexual and fertility-related adverse effects.

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Sexuality is a significant quality-of-life concern for many cancer patients. Patients may be disadvantaged if they are not informed and not offered sexual health care. We sought to reveal oncologists' current practice and opinions concerning sexual counselling. The aim of this study was to explore the knowledge, attitude and practice patterns of Dutch medical oncologists regarding treatment-related sexual dysfunction. Questionnaires were sent to 433 members of the Dutch Society of Medical Oncology. The majority (81.5%) of the 120 responding medical oncologists (response rate 30.6%) stated they discussed sexual function with fewer than half of their patients. At the same time, 75.8% of the participating oncologists agreed that addressing sexual function is their responsibility. Sexual function was discussed more often with younger patients and patients with a curative treatment intent. Barriers for avoiding discussing sexual function were lack of time (56.1%), training (49.5%) and advanced age of the patient (50.4%). More than half (64.6%) stated they had little knowledge about the subject and the majority (72.9%) wanted to acquire additional training in sexual function counselling. Medical oncologists accept that sexual function counselling falls within their profession, yet they admit to not counselling patients routinely concerning sexual function. Only in a minority of cases do medical oncologists inform their patients about sexual side effects of treatment. Whether they counsel patients is related to how they view patient's prognosis, patient's age, and self-reported knowledge. Findings indicate there is a role for developing education and practical training.

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Cancer and its treatments may result in impaired fertility, which could cause long-term distress to cancer survivors. For eligible patients, fertility preservation (FP) is available to secure future reproductive potential. Many physicians, however, feel inhibited about discussing FP. Oncology nurses may serve as an initiator for discussing the subject and provide additional support. Our aim was to investigate their knowledge about FP, the way they apply this, and possible barriers to discussing FP with patients of reproductive age. A questionnaire was administered via mail, Internet and the Dutch Oncology Nursing Congress. Four hundred and twenty-one oncology nurses participated, a third of whom (31.1%) had "sufficient" knowledge of FP. Twenty-eight per cent of participants reported that they "never/hardly ever" discussed FP; 32.2% "almost always/always." FP discussions were more frequently performed by graduate nurses, academic nurses, experienced nurses and nurses with sufficient knowledge. Reasons for not discussing FP were a "lack of knowledge" (25.2%), "poor prognosis" (16.4%) and "lack of time" (10.5%). In conclusion, several obstacles may result in FP not being routinely discussed, specifically a lack of knowledge. Yet nurses feel responsible for addressing the issue, indicating that assistance with FP discussions should be encouraged. Educational training about FP is recommended.

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PURPOSE: In most types of cancer, the disease and its treatment can result in altered sexual function (SF). Oncology nurses are strategically placed to address SF since they have frequent patient interaction. Our aim was to establish their knowledge about and attitudes to SF in oncology care and identify their perceived barriers to addressing the subject. METHODS: A 37-item questionnaire was administered during the 2012 Dutch Oncology Nursing Congress and mailed to 241 Dutch oncology nursing departments. RESULTS: The majority of 477 nurses (87.6%) agreed that discussing SF is their responsibility. Discussing SF routinely is performed by 33.4% of these nurses, consultations mainly consisted of mentioning treatment side-effects affecting SF (71.3%). There were significant differences depending on experience, knowledge, age, academic degree and department policy. Nurses ≤44 years old (p < 0.001), with <10 years oncology experience (p = 0.001), insufficient knowledge (p < 0.001), no academic degree (p < 0.001), and in whose department policy was lacking or inadequate (p < 0.001), were less comfortable discussing SF. Barriers included lack of training, presence of a third party and no angle or motive for initiating discussion. CONCLUSIONS: Findings suggest oncology nurses consider counselling on sexual issues to be an important responsibility, in line with discussing other side-effects caused by the disease or its treatment. Nevertheless, cancer patients may not routinely be receiving a sexual health evaluation by oncology nurses. Results emphasize the potential benefit of providing knowledge, including practical training and a complete department protocol.

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CONTEXT: Patients with germ cell tumors (GCTs) have an excellent prognosis but are at risk for silent fractures. Data on bone mineral density (BMD) after anticancer treatment are scarce. OBJECTIVE: The objective of the study was BMD monitoring in GCT patients treated with or without chemotherapy. DESIGN: We prospectively studied 63 newly diagnosed GCT patients with a median age of 33 years (range 16-70 y) within 3 months of unilateral orchidectomy. Twenty-seven patients (42.9%) had no metastases. Thirty-six patients (57.1%) with metastatic disease received combination chemotherapy. SETTING: This study was conducted at the outpatient clinic of a single academic institution. INTERVENTIONS: We performed dual-energy X-ray absorptiometry scans and collected blood samples on a yearly basis, before and up to 5 years after anticancer treatment. MAIN OUTCOME MEASURES: Changes in total hip and lumbar spine BMD, serum concentrations of gonadal hormones, and bone turnover markers were measured. RESULTS: BMD remained normal in stage I patients. In patients with metastatic disease, a significant decrease in lumbar spine BMD (-1.52%; P = .004) and total hip BMD (-2.05%; P < .0001) was observed 1 year after chemotherapy and remained stable thereafter for up to 5 years. There was no significant relationship between the observed decrease in BMD and gonadal status, vitamin D status, or cumulative dose of cisplatin or (antiemetic) corticosteroids. CONCLUSIONS: Metastatic GCT survivors demonstrate significant bone loss within the first year after curative combination chemotherapy, with no recovery up to 5 years after anticancer treatment. Whether this bone loss is associated with increased fracture risk and whether this could be prevented by bone modifying treatment remains to be established.

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BACKGROUND: After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore acute effects of chemotherapy on cardiac function in patients treated for TC. METHODS: Fourteen TC patients (age 34.6 ± 12.3 years) were studied before and 3 months after start with cisplatin-based chemotherapy. Cardiac function was assessed with magnetic resonance imaging. Fasting glucose and insulin levels were measured and insulin sensitivity, reflected by the quantitative insulin sensitivity index (Quicki index), was calculated. RESULTS: Left ventricular (LV) end-diastolic volume and LV stroke volume (SV) significantly decreased from 192 ± 27 to 175 ± 26 ml (P<0.05) and 109 ± 18 to 95 ± 16 ml (P<0.05), respectively. The ratio of early and atrial filling velocities across the mitral valve, a parameter of diastolic heart function, decreased after chemotherapy from 1.87 ± 0.43 to 1.64 ± 0.45 (P<0.01). Metabolic parameters were unfavourably changed, reflected by a decreased Quicki index, which reduced from 0.39 ± 0.05 to 0.36 ± 0.05 (P<0.05). CONCLUSION: Chemotherapy for TC induces acute alterations in diastolic heart function, paralleled by unfavourable metabolic changes. Therefore, early after chemotherapy, metabolic treatment may be indicated to possibly reduce long-term cardiovascular complications.

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BACKGROUND: Testicular cancer patients have an increased risk for cardiovascular disease (CVD), which might be related to the increased prevalence of the metabolic syndrome (MetS) in this group of patients. METHODS: We assessed the prevalence of MetS and calculated the 10-year CVD risk in a cohort of 255 testicular germ cell tumour survivors (median age, 38.7 years; interquartile range, 31-48) at a mean of 7.8 years after anti-cancer treatment, and compared these with data obtained from 360 healthy men. RESULTS: Survivors had an age-adjusted increased risk for MetS of 1.9 compared with that of healthy controls. The risk for MetS was highest in survivors treated with combination chemotherapy (CT) 2.3 (Adult Treatment Panel of the National Cholesterol Education Program classification) and 2.2 (International Diabetes Federation classification). The risk of MetS was especially increased in survivors with testosterone levels in the lowest quartile (OR, 2.5). Ten-year cardiovascular risk as assessed by the Framingham Risk Score (3.0%) and Systemic Coronary Risk Evaluation (1.7%) algorithms was low, independent of treatment, and was comparable to controls. CONCLUSION: Testicular germ cell tumour survivors have an increased prevalence of MetS, with hypogonadism and CT treatment being clear risk factors for the development of the syndrome. The increased prevalence of MetS was not associated with an increased 10-year cardiovascular risk.

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Microparticles, also known as microvesicles, found in blood plasma, urine, and most other body fluids, may serve as valuable biomarkers of diseases such as cardiovascular diseases, systemic inflammatory disease, thrombosis, and cancer. Unfortunately, the detection and quantification of microparticles are hampered by the microscopic size of these particles and their relatively low abundance in blood plasma. The use of a combination of microfluidics and atomic force microscopy to detect microparticles in blood plasma circumvents both problems. In this study, capture of a specific subset of microparticles directly from blood plasma on antibody-coated mica surface is demonstrated. The described method excludes isolation and washing steps to prepare microparticles, improves the detection sensitivity, and yields the size distribution of the captured particles. The majority of the captured particles have a size ranging from 30 to 90 nm, which is in good agreement with prior results obtained with microparticles immediately isolated from fresh plasma. Furthermore, the qualitative shape of the size distribution of microparticles is shown not to be affected by high-speed centrifugation or the use of the microfluidic circuit, demonstrating the relative stable nature of microparticles ex vivo.

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G-protein-coupled receptors (GPCRs) have been implicated in the tumorigenesis and metastasis of human cancers and are considered amongst the most desirable targets for drug development. Utilizing a robust quantitative PCR array, we quantified expression of 94 human GPCRs, including 75 orphan GPCRs and 19 chemokine receptors, and 36 chemokine ligands, in 40 melanoma metastases from different individuals and benign nevi. Inter-metastatic site comparison revealed that orphan GPR174 and CCL28 are statistically significantly overexpressed in subcutaneous metastases, while P2RY5 is overexpressed in brain metastases. Comparison between metastases (all three metastatic sites) and benign nevi revealed that 16 genes, including six orphan receptors (GPR18, GPR34, GPR119, GPR160, GPR183 and P2RY10) and chemokine receptors CCR5, CXCR4, and CXCR6, were statistically significantly differentially expressed. Subsequent functional experiments in yeast and melanoma cells indicate that GPR18, the most abundantly overexpressed orphan GPCR in all melanoma metastases, is constitutively active and inhibits apoptosis, indicating an important role for GPR18 in tumor cell survival. GPR18 and five other orphan GPCRs with yet unknown biological function may be considered potential novel anticancer targets in metastatic melanoma.

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INTRODUCTION: Microparticles (MPs) carrying active tissue factor (TF) have been detected in the plasma of cancer patients in particular in those presenting with acute deep vein thrombosis (DVT) or pulmonary embolism (PE). Experimental studies in mice have revealed that circulating MPs carrying TF contribute to thrombus formation. AIM: To study whether unselected patients with an acute confirmed PE have elevated TF activity in the MP fraction (MP-TF activity). MATERIALS AND METHODS: Plasma MP-TF activity was measured in 159 non-selected patients with clinically suspected PE and in 48 healthy controls as previously described. Blood was collected at time of inclusion. The diagnosis of acute PE was confirmed in 54 patients and excluded in 105 patients. RESULTS: Median MP-TF activity in 159 patients with clinically suspected PE was 72 fM Xa/min [range 32-6657] fM Xa/min and higher than in healthy controls (66 [range 28-183] fM Xa/min; P<0.05). There was no significant difference (P=0.169) in MP-TF activity between patients with confirmed PE (median 84.5 fM Xa/min [range 36-2149]) and patients without PE (72 fM Xa/min [range 32-6657]) fM Xa/min). In the 159 patients with clinically suspected PE we observed in an exploratory analysis higher MP-TF activity levels in patients with active cancer (median 137 fM Xa/min [range 36-6657]) and cardiovascular disease (median 131.5 fM Xa/min [range 45-2149]) than in patients without these disorders (P=0.0004 and P=0.014, respectively). CONCLUSION: In patients presenting with clinically suspected PE plasma MP-TF activity was not associated with confirmed PE.

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CONTEXT: The prognosis of testicular germ cell tumors (GCT) is excellent, and survival of GCT patients has significantly increased. However, skeletal morbidity may potentially be increased in these patients due to chemotherapy-associated hypogonadism. OBJECTIVE: Our objective was assessment of skeletal fragility in testicular GCT patients. DESIGN AND SETTING: We conducted a cross-sectional study in long-term survivors and newly diagnosed patients at a single center with recruitment over a 2-yr period. PATIENTS AND METHODS: We studied 199 cured long-term survivors of GCT, a mean of 7.4 yr after unilateral orchidectomy, and 45 newly diagnosed patients within 3 months of unilateral orchidectomy but before anticancer treatment. Bone mineral density (BMD) measurements were performed, and the presence of vertebral fractures (VF) was assessed in lateral thoracolumbar x-rays of the spine using the Genant's semiquantitative method. RESULTS: Sixty-three patients (25.8%) had Z-scores between -1 and -2 sd, and 12 patients (5.7%) had Z-scores below -2 sd. Moderate and severe VF (grade 2 or higher) were observed in 13.6% of cured long-term survivors and in 15.6% of newly diagnosed patients. Including mild (grade 1) VF, the prevalence was 40.2 and 31.1%, respectively. There was no relationship between severity or number of VF and age, tumor type, staging, previous chemotherapy, gonadal status, vitamin D levels, or BMD values. CONCLUSION: We identify a relatively high prevalence of mild to moderate VF independently of BMD or previous chemotherapy in long-term survivors and in newly diagnosed patients with GCT. Although the pathogenesis of these fractures remains unclear, their presence represents a potential cause of skeletal morbidity in otherwise healthy survivors of testicular GCT.

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BACKGROUND: Microparticles (MPs) are small vesicles released from cells of different origin, bearing surface antigens from parental cells. Elevated numbers of blood MPs have been reported in (cardio)vascular disorders and cancer. Most of these MPs are derived from platelets. OBJECTIVES: To investigate whether atomic force microscopy (AFM) can be used to detect platelet-derived MPs and to define their size distribution. METHODS: Blood MPs isolated from seven blood donors and three cancer patients were immobilized on a modified mica surface coated with an antibody against CD41 prior to AFM imaging. AFM was performed in liquid-tapping mode to detect CD41-positive MPs. In parallel, numbers of CD41-positive MPs were measured using flow cytometry. Mouse IgG1 isotype control was used as a negative control. RESULTS: AFM topography measurements of the number of CD41-positive MPs were reproducible (coefficient of variation=16%). Assuming a spherical shape of unbound MPs, the calculated diameter of CD41-positive MPs (dsph) ranged from 10 to 475 nm (mean: 67.5+/-26.5 nm) and from 5 to 204 nm (mean: 51.4+/-14.9 nm) in blood donors and cancer patients, respectively. Numbers of CD41-positive MPs were 1000-fold higher than those measured by flow cytometry (3-702x10(9) L(-1) plasma vs. 11-626x10(6) L(-1) plasma). After filtration of isolated MPs through a 0.22-microm filter, CD41-positive MPs were still detectable in the filtrate by AFM (mean dsph: 37.2+/-11.6 nm), but not by flow cytometry. CONCLUSIONS: AFM provides a novel method for the sensitive detection of defined subsets of MPs in the nanosize range, far below the lower limit of what can be measured by conventional flow cytometry.

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