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

Blood Transcript Profiling for the Detection of Neuroendocrine Tumors: Results of a Large Independent Validation Study

Background: Available neuroendocrine biomarkers are considered to have insufficient accuracy to discriminate patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) from healthy controls. Recent studies have demonstrated a potential role for circulating neuroendocrine specific transcripts analysis—the NETest—as a more accurate biomarker for NETs compared to available biomarkers. This study was initiated to independently validate the discriminative value of the NETest as well as the association between tumor characteristics and NETest score.Methods: Whole blood samples from 140 consecutive GEP-NET patients and 113 healthy volunteers were collected. Laboratory investigators were blinded to the origin of the samples. NETest results and chromogranin A (CgA) levels were compared with clinical information including radiological imaging to evaluate the association with tumor characteristics.Results: The median NETest score in NET patients was 33 vs. 13% in controls (p &lt; 0.0001). The NETest did not correlate with age, gender, tumor location, grade, load, or stage. Using the cut-off of 14% NETest sensitivity and specificity were 93 and 56%, respectively, with an AUC of 0.87. The optimal cut-off for the NETest in our population was 20%, with sensitivity 89% and specificity 72%. The upper limit of normal for CgA was established as 100 μg/l. Sensitivity and specificity of CgA were 56 and 83% with an AUC of 0.76. CgA correlated with age (rs = 0.388, p &lt; 0.001) and tumor load (rs = 0.458, p &lt; 0.001).Conclusions: The low specificity of the NETest precludes its use as a screening test for GEP-NETs. The superior sensitivity of the NETest over CgA (93 vs. 56%; p &lt; 0.001), irrespective of the stage of the disease, emphasize its potential as a marker of disease presence in follow up as well as an indicator for residual disease after surgery

Markers of cerebral damage during delirium in elderly patients with hip fracture

BACKGROUND: S100B protein and Neuron Specific Enolase (NSE) can increase due to brain cell damage and/or increased permeability of the blood-brain-barrier. Elevation of these proteins has been shown after various neurological diseases with cognitive dysfunction. Delirium is characterized by temporal cognitive deficits and is an important risk factor for dementia. The aim of this study was to compare the level of S100B and NSE of patients before, during and after delirium with patients without delirium and investigate the possible associations with different subtypes of delirium. METHODS: The study population were patients aged 65 years or more acutely admitted after hip fracture. Delirium was diagnosed by the Confusion Assessment Method and the subtype by Delirium Symptom interview. In maximal four serum samples per patient S100B and NSE levels were determined by electrochemiluminescence immunoassay. RESULTS: Of 120 included patients with mean age 83.9 years, 62 experienced delirium. Delirious patients had more frequently pre-existing cognitive impairment (67% vs. 18%, p<0.001). Comparing the first samples during delirium to samples of non-delirious patients, a difference was observed in S100B (median 0.16 versus 0.10 ug/L, p=<0.001), but not in NSE (median 11.7 versus 11.7 ng/L, p=0.97). Delirious state (before, during, after) (p<0.001), day of blood withdrawal (p<0.001), pre- or postoperative status (p=0.001) and type of fracture (p=0.036) were all associated with S100B level. The highest S100B levels were found 'during' delirium. S100B levels 'before' and 'after' delirium were still higher than those from 'non-delirious' patients. No significant difference in S100B (p=0.43) or NSE levels (p=0.41) was seen between the hyperactive, hypoactive and mixed subtype of delirium. CONCLUSIONS: Delirium was associated with increased level of S100B which could indicate cerebral damage either due to delirium or leading to delirium. The possible association between higher levels of S100B during delirium and the higher risk of developing dementia after delirium is an interesting field for future research. More studies are needed to elucidate the role of S100B proteins in the pathophysiological pathway leading to delirium and to investigate its possibility as biomarker for deliriu

Serum soluble CD27, but not thymidine kinase, is an independent prognostic factor for outcome in indolent non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) forms a heterogeneous group of diseases. Tumor markers may help to identify high-risk patients who might benefit from more aggressive therapy. Serum soluble CD27 (sCD27) and thymidine kinase (TK) are potentially valuable markers, since sCD27 has previously been shown to be related to tumor load and TK to proliferation of malignant cells. We determined serum sCD27, TK, beta-2-microglobulin (beta(2)M) and lactic dehydrogenase (LD) levels at diagnosis in 79 lymphoma patients and correlated these parameters with the stage of disease, the International Prognostic Index (IPI) score and survival. Receiver operator characteristic (ROC) curve analysis showed an excellent ability for sCD27 to discriminate between low- and high-stage disease (p <0.001), especially in indolent lymphomas. No discriminative value for TK, beta(2)M or LD was found. For aggressive NHL, sCD27, TK, beta(2)M and LD did predict survival in the univariate analyses. However, LD was found to be the most independent prognostic factor in a multivariate Cox regression model. In indolent lymphomas, sCD27 proved to be a powerful marker to predict progression-free survival (p = 0.008). Taken together, the results of the ROC curve and survival analysis suggest that substitution of LD by sCD27 in the IPI may be considered for indolent lymphomas to enhance the prognostic value. A study in a larger cohort of patients is required to validate this approac

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

A Randomized Phase II Study Adding Axitinib to Pemetrexed-Cisplatin in Patients with Malignant Pleural Mesothelioma: A Single-Center Trial Combining Clinical and Translational Outcomes

Mesothelioma often presents with a high vessel count and increased vascular growth factors levels. Interference with angiogenesis may therefore improve outcome. This study reports on clinical and translational parameters in patients treated with the small molecule tyrosine kinase inhibitor axitinib and chemotherapy. Chemonaive patients with mesothelioma were eligible. Patients received pemetrexed (500 mg/m(2) every 3 weeks) and cisplatin (75 mg/m(2) every 3 weeks) and were randomized to receive axitinib daily (two 5-mg tablets on days 2-19) or observation. Before treatment and after three cycles of chemotherapy, a thoracoscopy was performed to evaluate vascular changes. Twenty-five patients were randomized after a successful lead-in with six patients who received axitinib. Median follow-up was 45 months. In all but one patient, it was feasible to perform a second thoracoscopy. However, there was more grade 3 or 4 neutropenia leading to pneumonia in the axitinib group. The rates of partial response and stable disease in the axitinib arm were 36% and 43% compared with 18% and 73% in the chemotherapy-only arm. Median progression-free survival and overall survival (5.8 and 18.9 months versus 8.3 and 18.5 months) were not different between the two groups. Axitinib reduced vessel number and vessel immaturation. Yet, the mRNA levels of a number of vascular growth factors, their receptors, serum VEGF levels, and activation of tissue vascular endothelial growth factor receptor 2 were increased. Gene expression of platelet-derived growth factor receptor beta, fms-related tyrosine kinase 1, and fms-related tyrosine kinase 4 even correlated with outcome. Axitinib was well tolerated in combination with cisplatin and pemetrexed. Despite the lack of a clinical benefit, axitinib reduced angiogenesis. Whether changes in differentially expressed growth factors in tissue and serum may serve as a biomarker needs further investigatio

Markers of cerebral damage during delirium in elderly patients with hip fracture

Abstract Background S100B protein and Neuron Specific Enolase (NSE) can increase due to brain cell damage and/or increased permeability of the blood-brain-barrier. Elevation of these proteins has been shown after various neurological diseases with cognitive dysfunction. Delirium is characterized by temporal cognitive deficits and is an important risk factor for dementia. The aim of this study was to compare the level of S100B and NSE of patients before, during and after delirium with patients without delirium and investigate the possible associations with different subtypes of delirium. Methods The study population were patients aged 65 years or more acutely admitted after hip fracture. Delirium was diagnosed by the Confusion Assessment Method and the subtype by Delirium Symptom interview. In maximal four serum samples per patient S100B and NSE levels were determined by electrochemiluminescence immunoassay. Results Of 120 included patients with mean age 83.9 years, 62 experienced delirium. Delirious patients had more frequently pre-existing cognitive impairment (67% vs. 18%, p Conclusion Delirium was associated with increased level of S100B which could indicate cerebral damage either due to delirium or leading to delirium. The possible association between higher levels of S100B during delirium and the higher risk of developing dementia after delirium is an interesting field for future research. More studies are needed to elucidate the role of S100B proteins in the pathophysiological pathway leading to delirium and to investigate its possibility as biomarker for delirium.</p