Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.

PURPOSE: The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. PATIENTS AND METHODS: Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. RESULTS: The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. CONCLUSION: The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.     

Markers of past infection with simian virus 40 (SV40) and risk of incident non-Hodgkin lymphoma in a Maryland cohort.

Simian virus 40 (SV40) genome sequences have been detected in human non-Hodgkin lymphoma (NHL) tissues, and past infection with SV40 may be a risk factor for NHL. We conducted a population-based nested case-control study to investigate the association between serum antibodies to SV40 and incident NHL. Two research serum banks were established in Washington County, MD, with >45,000 volunteers contributing blood samples collected in 1974 and 1989. Incident cases of NHL diagnosed through 2002 (n = 170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (n = 340) on age, sex, and date of blood draw. Circulating immunoglobulin G antibodies to SV40 were measured using virus-like particle (VLP) ELISA. Positive samples were tested for cross-reactivity with JC virus (JCV) and BK virus (BKV) through competitive inhibition assays. Associations between SV40 antibody seropositivity and NHL were estimated using conditional logistic regression. Whereas SV40 antibodies were detected by VLP ELISA in 15% of cases and 10% of controls [matched odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.03-3.76], the SV40 reactivity of 85% of the SV40 antibody-positive sera was decreased by adsorption with BKV and/or JCV VLPs. Antibodies specific for SV40 (not cross-reactive) were identified in only 1.8% of cases and 1.6% of controls (OR, 1.51; 95% CI, 0.41-5.52). Our findings suggest that past infection with SV40 is not associated with an increased risk of developing NHL.     

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.     

Adolescence as a gateway to adult health outcomes

Adolescence has long been regarded as a transition from childhood to adulthood. More recently it is become a concern of those wishing to avoid adverse health outcomes during middle and late adulthood. Most of this effort has been focused on behavioural risk factors such as tobacco and excessive alcohol use, physical exercise habits, dietary habits, as well as sexual and injury-related behaviours. The concern is that these habits are established during adolescence, continue into adulthood, and come to constitute ongoing risk factors for adverse health outcomes during middle and late adulthood. There is good reason to criticize this approach. These behaviours are themselves shaped by adolescents’ living and working conditions and even then constitute a small proportion of the variance predicting adverse health outcomes during adulthood. More complex models of how adolescence serves as a gateway to adult health outcomes are presented. These are the socio-environmental, public policy, and political economy approaches. The argument is made that adolescence is a period during which public policy plays an especially important role in predicting future health outcomes. Yet, these public policies influence health all across the life span with adolescence providing only one of many important periods during which public policy shapes health prospects during middle and later adulthood. Ultimately one should consider a range of approaches ranging from the behavioural to the political to examine how adolescence serves as a gateway towards future adult prospects. An Adolescent Gateway Towards Adult Health Model is provided to assist in this process.     

Validity of 2D lateral cephalometry in orthodontics: a systematic review

Lateral cephalometric radiography is commonly used as a standard tool in orthodontic assessment and treatment planning. The aim of this study was to evaluate the available scientific literature and existing evidence for the validation of using lateral cephalometric imaging for orthodontic treatment planning. The secondary objective was to determine the accuracy and reliability of this technique. We did not attempt to evaluate the value of this radiographic technique for other purposes. A literature search was performed using specific keywords on electronic databases: Ovid MEDLINE, Scopus and Web of Science. Two reviewers selected relevant articles, corresponding to predetermined inclusion criteria. The electronic search was followed by a hand search of the reference lists of relevant papers. Two reviewers assessed the level of evidence of relevant publications as high, moderate or low. Based on this, the evidence grade for diagnostic efficacy was rated as strong, moderately strong, limited or insufficient. The initial search revealed 784 articles listed in MEDLINE (Ovid), 1,034 in Scopus and 264 articles in the Web of Science. Only 17 articles met the inclusion criteria and were selected for qualitative synthesis. Results showed seven studies on the role of cephalometry in orthodontic treatment planning, eight concerning cephalometric measurements and landmark identification and two on cephalometric analysis. It is surprising that, notwithstanding the 968 articles published in peer-reviewed journals, scientific evidence on the usefulness of this radiographic technique in orthodontics is still lacking, with contradictory results. More rigorous research on a larger study population should be performed to achieve full evidence on this topic.     

High-Frequency Micro-Ultrasound Imaging and Optical Topographic Imaging for Spinal Surgery: Initial Experiences

High frequency micro-ultrasound (µUS) transducers with central frequencies up to 50?MHz facilitate dynamic visualization of patient anatomy with minimal disruption of the surgical work flow. Micro-ultrasound improves spatial resolution over conventional ultrasound imaging from millimeter to micrometer, but compromises depth penetration. This trade-off is sufficient during an open surgery in which the bone is removed and theultrasound probe can be placed into the surgical cavity. By fusing µUS with pre-operative imaging and tracking the ultrasound probe intra-operatively using our optical topographic imaging technology, we can provide dynamic feedback during surgery, thus affecting clinical decision making. We present our initial experience using high-frequency µUS imaging during spinal procedures. Micro-ultrasound images were obtained in five spinal procedures. Medical rationale for use of µUS was provided for each patient. Surgical procedures were performed using the standard clinical practice with bone removal to facilitate real-time ultrasound imaging of the soft tissue. During surgery, the µUS probe was registered to the pre-operative computed tomography and magnetic resonance images. Images obtained comprised five spinal decompression surgeries (four tumor resections, one cystic synovial mass). Micro-ultrasound images obtained during spine surgery delineated exquisite detailing of the spinal anatomy including white matter and gray matter tracts and nerve roots and allowed accurate assessment of the extent of decompression/tumor resection. In conclusion, tracked µUS enables real-time imaging of the surgical cavity, conferring significant qualitative improvement over conventional ultrasound.     

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.