Estradiol and Testosterone Levels Are Lower after Oophorectomy than after Natural Menopause

Objective: The aim of this study was to compare hormone levels between women who became postmenopausal after a prophylactic bilateral salpingo-oophorectomy, and women who became postmenopausal in a natural way. Methods: In this cross-sectional study, we investigated estradiol, testosterone, SHBG, IGF-1 and IGFBP-3 levels in 35 surgically and 40 naturally postmenopausal women. Results: Serum samples were drawn at a mean age of 45.9 years for women with surgical menopause and at 56.5 years for women with natural menopause. Mean estradiol levels declined 1.4 pmol/l per year in both menopausal groups, however, at an 11.1 pmol/l lower level for women with surgical menopause. Testosterone levels of naturally postmenopausal women remained stable at a level of 0.89 nmol/l, while testosterone levels of the surgically postmenopausal women declined 0.04 nmol/l per year. Conclusions: For IGF-1, IGFBP-3 and SHBG, no differences were found between surgically and naturally postmenopausal women. Lower estradiol levels of surgically as compared to naturally postmenopausal women seem to be fully explained by the earlier onset of menopause in combination with the same age-related decrease. However, a decrease in testosterone levels seems to occur in oophorectomized women only, suggesting postmenopausal activity of ovaries in situ. Copyright (C) 2009 S. Karger AG, Base

Significance of serum S-100B in melanoma patients before and after sentinel node biopsy

BACKGROUND AND OBJECTIVES: The clinical utility of the tumor marker serum S-100B has been described in determining prognosis, for early diagnosis of recurrence and for disease monitoring in melanoma patients. Sentinel node biopsy is increasingly used as staging procedure for patients with clinically localized melanoma. The aim of this study was to determine the value of serum S-100B in melanoma patients before and after sentinel lymph node biopsy. METHODS: S-100B values were measured prior to sentinel node biopsy in 89 patients and during follow-up (median 41 months; range 7-73 months) in 88 patients. The detection limit is < or =0.08 microg/L. In our laboratory levels of 0.16 microg/L and above are classified as increased. RESULTS: Twenty-four patients had tumor-positive sentinel nodes, 65 had tumor-free sentinel nodes. The median S-100B value prior to the operation was < or =0.08 microg/L for all patients. Sensitivity and specificity of S-100B to predict the tumor-status of the sentinel node were 13% and 98%, respectively. Eighteen patients developed a melanoma-related recurrence. Sensitivity for early diagnosis of recurrence was 55% and 33%, respectively for patients with a positive versus a negative sentinel node. Specificity was 100% in both patient groups. CONCLUSIONS: S-100B is not useful in predicting the tumor-status of the sentinel node, and questionable for early diagnosis of recurrence afterwards. Elevation of serum S-100B is highly specific for melanoma recurrenc

Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma

PURPOSE: Human papillomavirus (HPV) infections are suggested to be involved in the development of penile squamous cell carcinoma (SCC), but comprehensive studies to define the association are limited. Therefore, we performed molecular and serologic analyses for a broad spectrum of HPV types on a large series of 83 penile SCCs, and we compared serological findings to those of age-matched male controls (N = 83). METHODS: Penile SCCs were subjected to detection and typing assays for mucosal and cutaneous HPVs and to subsequent, type-specific viral load and viral gene expression assays. Sera of patients and of controls were analyzed for type-specific mucosal and cutaneous HPV L1, E6, and/or E7 antibodies using bead-based, multiplex serology. RESULTS: HPV DNA of mucosal and/or cutaneous types was found in 46 of 83 (55%) penile SCCs. HPV16 was the predominant type, appearing in 24 (52%) of 46 of penile SCCs. The majority of HPV16 DNA-positive SCCs (18 of 24; 75%) demonstrated E6 transcriptional activity and a high viral load. Additionally, HPV16 molecular findings were strongly associated with HPV16 L1-, E6-, and E7-antibody seropositivity. Furthermore, serologic case-control analyses demonstrated that, in addition to the association of HPV16 with penile SCC, seropositivity against any HPV type was significantly more common in patients compared with in controls. HPV18 and HPV6 seropositivity were associated with HPV16-negative SCCs but were not correlated to molecular findings. CONCLUSION: HPV16 is the main HPV type etiologically involved in the development of penile SCC. Although individuals who develop penile SCC show a greater prior exposure to a broad spectrum of HPV types, insufficient evidence was found to claim a role for HPV types other than HPV16 in penile carcinogenesis

Design of tumor biomarker-monitoring trials: a proposal by the European Group on Tumor Markers

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs. In phase I, biomarker kinetics and correlation with tumor burden are assessed. Phase II evaluates the ability of the biomarker to identify, exclude, and/or predict a change in disease status. In phase III, the effectiveness of tumor biomarker-guided intervention is assessed by measuring patient outcome in randomized trials. Phase IV consists of an audit of the long-term effects after biomarker monitoring has been included into standard patient care. Systematic well-designed evaluations of biomarkers for monitoring may provide a stronger evidence base that might enable their earlier use in evaluating responses to cancer therap

Socioeconomic differences in participation and diagnostic yield within the Dutch national colorectal cancer screening programme with faecal immunochemical testing

Background CRC mortality rates are higher for individuals with a lower socioeconomic status (SES). Screening could influence health inequalities. We therefore aimed to investigate SES differences in participation and diagnostic yield of FIT screening. Methods All invitees in 2014 and 2015 in the Dutch national CRC screening programme were included in the analyses. We used area SES as a measure for SES and divided invitees into quintiles, with Quintile 1 being the highest SES. Logistic regression analysis was used to compare the participation rate, positivity rate, colonoscopy uptake, positive predictive value (PPV) and detection rate across the SES groups. Results Participation to FIT screening was significantly lower for Quintile 5 (67.0%) compared to the other Quintiles (73.0% to 75.1%; adjusted OR quintile 5 versus quintile 1: 0.73, 95%CI: 0.72–0.74), as well as colonoscopy uptake after a positive FIT (adjusted OR 0.73, 95%CI: 0.69–0.77). The detection rate per FIT participant for advanced neoplasia gradually increased from 3.3% in Quintile 1 to 4.0% in Quintile 5 (adjusted OR 1.20%, 95%CI 1.16–1.24). As a result of lower participation, the yield per invitee was similar for Quintile 5 (2.04%) and Quintile 1 (2.00%), both being lower than Quintiles 2 to 4 (2.20%-2.28%). Conclusions Screening has the potential to reduce health inequalities in CRC mortality, because of a higher detection in participants with a lower SES. However, in the Dutch screening programme, this is currently offset by the lower participation in this group

Quality monitoring of a fit-based colorectal cancer screening program

BACKGROUND: Quality assessment is crucial for consistent program performance of colorectal cancer (CRC) screening programs using fecal immunochemical test for hemoglobin (FIT). However, literature on the consistency of FIT performance in laboratory medicine was lacking. This study examined the consistency of FIT in testing positive or detecting advanced neoplasia (AN) for different specimen collection devices, lot reagents, and laboratories. METHODS: All participants with a FIT sample with a cutoff concentration of 47 g Hb/g feces in the Dutch CRC screening program in 2014 and 2015 were included in the analyses. Multivariable logistic regression analyses were performed to estimate the odds ratios of collection devices, reagents, and laboratories on testing positive or detecting AN and positive predictive value (PPV). RESULTS: In total, 87 519 (6.4%) of the 1 371 169 participants tested positive. Positivity rates and detection rates of AN differed between collection devices and reagents (all P 0.01). In contrast, PPVs were not found to vary between collection devices, reagents, or laboratories (all P 0.05). Positivity rates showed a small difference for laboratories (P 0.004) but not for detection rates of AN. Size of the population affected by the deviating positivity rates was small (0.1% of the total tested population). CONCLUSIONS: Variations were observed in positivity and detection rates between collection devices and reagents, but there was no detected variation in PPV. Although the overall population effect of these variations on the screened population is expected to be modest, there is room for improvement