Reactivity to human papillomavirus type 16 Ll virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites

A retrospective seroepidemiologic study was performed to examine the association between human papillomaviruses (HPV) 16 infection and carcinomas of the oropharynx, the oesophagus, penis and vagina. Sera were selected from the serum bank from the Antoni van Leeuwenhoek Hospital (Netherlands Cancer Institute) and the Slotervaart Hospital in Amsterdam, the Netherlands. Presence of HPV 16 specific antibody was assessed using HPV 16 L1 capsids. Sera positive for HPV 16 capsid antibody were further tested for antibody against HPV 16 E7 peptides. Prevalence of antibody against H PV 16 L1 capsids among both the negative control group without cancer and the negative control group with gastric cancer was 18%, while seroprevalence among the control group of patients with HPV-associated cervical squamous cell carcinoma was 47% (P < 0.001). Among the patients with penile squamous cell carcinoma seroprevalence was 38% (P < 0.001), among patients with oropharyngeal carcinoma 33% (P = 0.04) and among patients with oesophageal squamous cell carcinoma 14% (P = 0.7). The serological evidence for association between HPV 16 infection and both oropharyngeal carcinoma and penile carcinoma was established. The conclusion that no association was found between the presence of antibody against HPV 16 L1 capsids and oesophageal squamous cell carcinoma was in accordance with results of other studies carried out in the Netherlands using HPV DNA technology. In the subjects with HPV 16 L1 capsid antibody, no association was found between the antibody against HPV 16 E7 and clinical outcome

Does anti-Mullerian hormone predict change in menopausal symptoms following risk-reducing salpingo-oophorectomy? A prospective observational study

Cervix cance

Impact of risk-reducing salpingo-oophorectomy on lipid determinants, HbA1c and CRP

ObjectiveRisk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c (HbA1c) and C-reactive protein (CRP).MethodsA total of 142 women with increased risk of ovarian cancer were included, 92 premenopausal and 50 postmenopausal. Serum levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and total cholesterol, triglycerides, HbA1c and CRP were determined at three points in time: before (T0) and 6 weeks (T1) and 7 months (T2) following RRSO. The Hot Flush Rating Scale was administered at the same time points.ResultsIn premenopausal women, levels of HDL-cholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within the reference range. In this group, hot flushes increased over time (p < 0.001). In postmenopausal women, no significant changes were observed following RRSO. At T2, serum LDL-cholesterol, triglycerides, HbA1c and CRP were significantly lower in premenopausal women compared to postmenopausal women, whereas HDL was increased.ConclusionsSeven months after RRSO, the lipid profile in premenopausal women had changed, although still staying within the reference range. For postmenopausal women, we did not observe any significant changes. Our results do not suggest a worsening of cardiovascular risk within 7 months of RRSO.Cervix cance

Hot flashes are not predictive for serum concentrations of tamoxifen and its metabolites

Background: Tamoxifen has dramatically reduced the recurrence and mortality rate of estrogen receptor positive breast cancer. However, the efficacy of tamoxifen varies between individuals and 40% of patients will have a recurrence despite adjuvant tamoxifen treatment. Factors that predict tamoxifen efficacy would be helpful for optimizing treatment. Serum concentrations of the active metabolite, endoxifen, may be positively related to treatment outcome. In addition, hot flashes are suggested to be positively associated with tamoxifen treatment outcome. Methods: We investigated in a series of 109 patients whether the frequency and severity of hot flashes were related to concentrations of tamoxifen and its metabolites. A serum sample of all patients was analyzed for the concentration of tamoxifen, N-desmethyltamoxifen, endoxifen and 4-hydroxytamoxifen, as well as for estradiol concentrations and several single nucleotide polymorphisms in CYP2D6. Additionally, these patients completed a questionnaire concerning biometric data and treatment side effects. Results: We found no evidence supporting an association between concentrations of tamoxifen or metabolites and either the frequency or severity of hot flashes in the covariate unadjusted analyses. However, including interactions with menopausal status and pre-treatment hot flash (PTHF) history indicated that post-menopausal women with PTHF experienced an increasing frequency of hot flashes with increasing serum concentrations of tamoxifen and its metabolites. This finding was not altered when adjusting for potential confounding factors (duration of tamoxifen treatment, CYP2D6 phenotype, estradiol serum concentration, age and body mass index). In addition we observed a positive association between body mass index and both hot flash frequency (p = 0.04) and severity (p < 0.0001). We also observed that patients with lower estradiol levels reported more severe hot flashes (p = 0.02). Conclusions: No univariate associations were observed between concentrations of active tamoxifen metabolites and either the frequency or severity of hot flashes during treatment. However, the frequency of hot flashes may be exacerbated by higher serum concentrations of tamoxifen and its metabolites in post-menopausal women with a history of hot flashes prior to tamoxifen treatment

Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial

BackgroundThe gut microbiome plays an important role in immune modulation. Specifically, presence or absence of certain gut bacterial taxa has been associated with better antitumor immune responses. Furthermore, in trials using fecal microbiota transplantation (FMT) to treat melanoma patients unresponsive to immune checkpoint inhibitors (ICI), complete responses (CR), partial responses (PR), and durable stable disease (SD) have been observed. However, the underlying mechanism determining which patients will or will not respond and what the optimal FMT composition is, has not been fully elucidated, and a discrepancy in microbial taxa associated with clinical response has been observed between studies. Furthermore, it is unknown whether a change in the microbiome itself, irrespective of its origin, or FMT from ICI responding donors, is required for reversion of ICI-unresponsiveness. To address this, we will transfer microbiota of either ICI responder or nonresponder metastatic melanoma patients via FMT. MethodsIn this randomized, double-blinded phase Ib/IIa trial, 24 anti-PD1-refractory patients with advanced stage cutaneous melanoma will receive an FMT from either an ICI responding or nonresponding donor, while continuing anti-PD-1 treatment. Donors will be selected from patients with metastatic melanoma treated with anti-PD-1 therapy. Two patients with a good response (& GE; 30% decrease according to RECIST 1.1 within the past 24 months) and two patients with progression (& GE; 20% increase according to RECIST 1.1 within the past 3 months) will be selected as ICI responding or nonresponding donors, respectively. The primary endpoint is clinical benefit (SD, PR or CR) at 12 weeks, confirmed on a CT scan at 16 weeks. The secondary endpoint is safety, defined as the occurrence of grade & GE; 3 toxicity. Exploratory endpoints are progression-free survival and changes in the gut microbiome, metabolome, and immune cells. DiscussionTransplanting fecal microbiota to restore the patients' perturbed microbiome has proven successful in several indications. However, less is known about the potential role of FMT to improve antitumor immune response. In this trial, we aim to investigate whether administration of FMT can reverse resistance to anti-PD-1 treatment in patients with advanced stage melanoma, and whether the ICI-responsiveness of the feces donor is associated with its effectiveness.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Clinical relevance of tumor markers and epidemiology of neuroendocrine tumors

Neuro-endocriene tumoren (NET) ontstaan in neuro-endocriene cellen en kunnen in elk orgaan voorkomen. Specifiek voor de meeste NET is dat ze weinig delen en dat ze hormonen produceren. Tiny Korse maakte een classificatie van NET op basis van groeitempo, van langzaam tot agressief. Ze vond een stijging van de incidentie van NET. Dat komt door de introductie van een nieuwe pathologische benaming: ‘grootcellig neuro-endocrien carcinoom’, een agressief groeiende NET. Dergelijke tumoren werden vroeger als ‘niet nader gespecificeerd’ geregistreerd. Op basis van diverse tumormarkers kan beter beoordeeld worden of een behandeling effectief is en hoe de ziekte verloopt bij een bepaalde patiënt

Somatostatin receptor scintigraphy and chromogranin A assay in staging and follow-up of patients with well-differentiated neuroendocrine tumors

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Serum S100B in elderly patients with and without delirium.

Objective: Elevation of S100B has been shown after various neurologic diseases with cognitive dysfunction. The aim of this study was to compare the serum level of S100B of patients with and without delirium and investigate the possible associations with different subtypes of delirium. Methods: Acutely admitted medical patients aged 65 years or more were included from 2005 through 2008. Delirium was diagnosed by Confusion Assessment Method, delirium subtype by Delirium Symptom Interview and preexistent global cognitive function by the 'Informant Questionnaire on Cognitive Decline-short form'. S100B levels were determined in serum by electrochemiluminescence immunoassay. Results: Samples of 412 patients were included, 91 during delirium, 35 after delirium and 286 of patients without delirium. Patients with delirium (31%) were significantly older, 81.5 versus 76.6 years (p < 0.001) and experienced significantly more often preexistent cognitive and functional impairment (p < 0.001). S100B level differed significantly (p = 0.004) between the three groups: median 0.07 mu g/L (inter-quartile ranges: 0.05-0.14 mu g/L) during delirium, 0.12 mu g/L (0.05-0.29 mu g/L) after delirium and 0.06 mu g/L (0.03-0.10 mu g/L) in patients without delirium. Combining the impact of cognitive impairment, infection and age on S100B, highest S100B was observed in the oldest patients after delirium with preexistent cognitive impaired and infection. Delirium subtype and S100B level were not significantly correlated. Conclusion: Higher S100B levels were found in patients with delirium than in patients without delirium, with highest levels of S100B in samples taken after delirium. Future studies are needed to elucidate the mechanism responsible for the increase of S100B and the possible association with long term cognitive impairment. (aut. ref.

S-100B protein and melanoma inhibitory activity protein in uveal melanoma screening. A comparison with liver function tests.

Item does not contain fulltextAIM: Our purpose was to determine whether S-100B or melanoma inhibitory activity (MIA) concentrations in the serum of patients with large uveal melanomas were better markers for the presentation of metastases than liver function tests. We also investigated whether increased marker levels were related to known clinical and histopathological prognostic parameters. METHODS: Total S-100B (A1B + BB) and MIA concentrations were measured in the sera from 104 patients with uveal melanoma prior to enucleation and in the sera from 50 healthy controls. Concentrations were also determined in the sera from 30 patients with known uveal melanoma metastases. Liaison Sangtec 100, an automated immunoluminometric assay measuring the total S-100B, and Roche MIA ELISA were used to quantify these proteins in serum. Results were compared with liver function tests [alkaline phosphatase, lactate dehydrogenase (LD), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase]. RESULTS: The mean S-100B and MIA concentrations were significantly higher in patients with metastases compared to melanoma patients without metastases. At the time of enucleation, S-100B and MIA were not prognostic for metastases in uveal melanoma, but S-100B and LD were the best tests to predict the occurrence of metastatic disease during the follow-up period. CONCLUSIONS: In our study, the S-100B and MIA serum concentrations were not correlated with any tested established prognostic parameter. S-100B and LD showed better performance in identifying melanoma metastases than gamma-glutamyl transpeptidase and MIA. A prospective follow-up study is needed to evaluate S-100B and MIA in identifying early micrometastasis in uveal melanoma