Potential Receptors for Targeted Imaging of Lymph Node Metastases in Penile Cancer

Imaging modalities using tumor-directed monoclonal antibodies may be of value to improve the pre- and intraoperative detection and resection of lymph node (LN) metastatic disease in penile squamous cell carcinoma (PSCC). We investigated the expression of prostate-specific membrane antigen (PSMA), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) to analyze their potency for diagnostic applications. Antigen expression was determined in primary tumors and LNs with and without metastases of 22 patients with PSCC. The total immunostaining score (TIS, 0-12) was determined as the product of a proportion score (PS, 0-4) and an intensity score (IS, 0-3). EGFR and VEGF expression were high in primary tumor (median TIS 8) and LN metastases (median TIS 6 and 8, respectively). No EGFR expression was seen in LNs without metastases. However, LNs without metastases did show VEGF expression (median TIS 6). No EpCAM or PSMA expression was seen in PSCC. This study shows that VEGF and EGFR expression is moderate to high in LN metastases of PSCC. Both VEGF and EGFR warrant further clinical evaluation to determine their value as a target for pre- and intraoperative imaging modalities in the detection of LN metastases in PSCC

Relevance of the JAK2V617F mutation in patients with deep vein thrombosis of the leg

Venous thromboembolism (VTE) can be the first presenting symptom in myeloproliferative neoplasms (MPN). Studies have demonstrated a high prevalence of the JAK2V617F mutation in patients with splanchnic vein thrombosis. Fewer studies have been done in patients with thrombosis outside the splanchnic area, showing a lower prevalence although the clinical relevance of the mutation in these patients, e.g., progression to overt MPN, remains unknown. The objective of this study was to determine the effect size of JAK2V617F in prospectively collected DNA samples of patients objectively diagnosed with deep vein thrombosis (DVT) of the leg and controls without DVT, with follow-up on JAK2V617F-positive patients to assess clinical relevance. Presence of JAK2V617F was determined in DNA samples from 187 patients with DVT and 201 controls, using quantitative RT-PCR. Hematological parameters were also analyzed. All initially JAK2V617F-positive patients were reassessed. Of 187 patients with DVT, 178 were analyzed for JAK2V617F, and in four (2.3%; 95% CI 0.1–4.4), JAK2V617F was present. Of 201 controls, 198 were analyzed; one was JAK2V617F positive (0.5%; 95% CI −0.5–1.5, OR 4.5; 95% CI 0.5–40.9). None had MPN features, nor upon reassessment after a median follow-up of 68.5 months. Four JAK2V617F-positive patients with DVT and one control without DVT did not develop overt MPN after a median follow-up of nearly 6 years. Thus, in patients with non-splanchnic venous thrombosis, JAK2V617F appears not to be clinically relevant

Using an equity-based framework for evaluating publicly funded health insurance programmes as an instrument of UHC in Chhattisgarh State, India

Universal health coverage (UHC) has provided the impetus for the introduction of publicly funded health insurance (PFHI) schemes in the mixed health systems of India and many other low- and middle-income countries. There is a need for a holistic understanding of the pathways of impact of PFHI schemes, including their role in promoting equity of access. Methods: This paper applies an equity-oriented evaluation framework to assess the impacts of PFHI schemes in Chhattisgarh State by synthesising literature from various sources and highlighting knowledge gaps. Data were collected from an extensive review of publications on PFHI schemes in Chhattisgarh since 2009, including empirical studies from the first author's PhD and grey literature such as programme evaluation reports, media articles and civil society campaign documents. The framework was constructed using concepts and frameworks from the health policy and systems research literature on UHC, access and health system building blocks, and is underpinned by the values of equity, human rights and the right to health

What happened to the popularity of the Polder Model? Emergence and disappearance of a political fashion

This article studies the rise and fall of the popular Polder Model concept from a fashion perspective. By applying both the epistemological and methodological tools developed to study management fashions, the authors focus on the events connected to this political fashion. First, a description of the content of the Polder Model is provided in which it is suggested that the concept contains two different meanings, one rooted in the Dutch decision-making style (neocorporatism) and one in a specific policy mix (i.e. problem solving) concerning labour and social welfare policies. Second, an analysis is given of the genesis of the concept and its popularity over time. Third, attention paid in other countries to the model is discussed and also criticism of the model. The article concludes with a discussion on the similarities and differences between fashions in the discourses of management and of politics

What is the effect of high-dose radiation on bone in patients with sacral chordoma? A CT study

Background Effects of high-dose radiation using protons and photons on bone are relatively unexplored, but high rates of insufficiency fractures are reported, and the causes of this are incompletely understood. Imaging studies with pre- and postradiation scans can help one understand the effect of radiation on bone. Questions/purposes The purpose of this study was to assess the effects of high-dose radiation on the trabecular density of bone in the sacrum using CT-derived Hounsfield units (HU). Methods Between 2009 and 2015, we treated 57 patients (older then 18 years) with sacral chordoma. Fourteen (25%) of them were treated with radiation only. The general indication for this approach is inoperability resulting from tumor size. Forty-two (74%) patients were treated with transverse sacral resections and high-dose radiotherapy (using either protons or photons or a combination) before surgery and after surgery. During this time period, our indication for this approach generally was symptomatic sacral chordoma in which resection would prevent further growth and reasonable sacrifice of nerve roots was possible. Of those patients, 21 (50%) had CT scans both before and after radiation treatment. We used HU as a surrogate for bone density. CT uses HU to derive information on tissue and bone quantity. A recent study presented reference HU values for normal (mean 133 6 38 HU), osteoporotic (101 6 25 HU), and osteopenic bone (79 6 32 HU). To adjust for scanning protocol-induced changes in HU, we calculated the ratio between bone inside and outside the radiation field rather than using absolute values. To assess the effect of radiation, we tested whether there was a difference in ratio (sacrum/L1) before and after radiation. A control measurement was performed (L2/L1) and also tested for a difference before and after radiation. Statistical analyses were performed using the paired t-test. Results The effects of radiation appeared confined to the intended field, because the bone density outside the treated field was not observed to decrease. The ratio of HU (a surrogate for bone density) in L2 relative to L1 did not change after radiotherapy (preradiation mean: 0.979 6 0.009, postradiation mean: 0.980 6 0.009, mean difference outside the radiation field: -0.001, 95% confidence interval [CI], -0.009 to 0.007, p = 0.799). The ratio of HU within the radiation field relative to L1 decreased after radiotherapy (preradiation mean: 0.895 6 0.050, postradiation mean: 0.658 6 0.050, mean difference inside the radiation field: 0.237, 95% CI, 0.187-0.287, p < 0.001), suggesting the bone density stayed the same outside the radiation field but decreased inside the radiation field. Conclusions Trabecular bone density decreased after high-dose radiation therapy in a small group of patients with sacral chordoma. High-dose radiation is increasingly gaining acceptance for treating sacral malignancies; further long-term prospective studies using calibrated CT scanners and preferably bone biopsies are needed. Level of Evidence Level IV, therapeutic study