Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemotherapy: The Implications of Metabolic Nodal Response for Personalized Therapy

INTRODUCTION Only a minority of esophageal cancers demonstrates a pathological tumor response (pTR) to neoadjuvant chemotherapy (NAC). 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is often used for restaging after NAC and to assess response. Increasingly, it is used during therapy to identify unresponsive tumors and predict pTR , using avidity of the primary tumor alone. However, definitions of such metabolic tumor response (mTR) vary. We aimed to comprehensively re-evaluate metabolic response assessment using accepted parameters, as well as novel concepts of metabolic nodal stage (mN) and nodal response (mNR). PATIENTS AND METHODS This was a single-center retrospective UK cohort study. All patients with esophageal cancer staged before NAC with PET-CT and after with CT or PET-CT and undergoing resection from 2006-2014 were identified. pTR was defined as Mandard tumor regression grade 1-3; imaging parameters included metrics of tumor avidity (standardized uptake value [SUV]max/mean/peak), composites of avidity and volume (including metabolic tumor volume), nodal SUVmax, and our new concepts of mN stage and mNR. RESULTS Eighty-two (27.2%) of 301 patients demonstrated pTR. No pre-NAC PET parameters predicted pTR. In 220 patients re-staged by PET-CT, The optimal tumor ΔSUVmax threshold was a 77.8% reduction. This was as sensitive as the current PET Response Criteria in Solid Tumors (PERCIST) 30% reduction, but more specific with a higher negative predictive value (p<0.001). ΔSUVmax and Δlength independently predicted pTR, and composite avidity/spatial metrics outperformed avidity alone. Whilst both mTR and mNR were associated with pTR, in 82 patients with FDG-avid nodes before NAC we observed mNR in 10 (12.2%) not demonstrating mTR. CONCLUSION Current definitions of metabolic response are suboptimal and too simplistic. Composite avidity/volume measures improve prediction. mNR may further improve response assessment, by specifically assessing metastatic tumor sub-populations, likely responsible for disease relapse, and should be urgently assessed when considering aborting therapy on the basis of mTR alone

The Sandwell Project: A controlled evaluation of a programme of targeted screening for prevention of cardiovascular disease in primary care

<p>Abstract</p> <p>Background</p> <p>A pilot cardiovascular disease prevention project was implemented in the inner-city West Midlands. It was evaluated by comparing its effectiveness to a control group where full implementation was delayed by a year.</p> <p>Methods</p> <p>Cardiovascular risk factor data were extracted on all untreated patients 35 to 74 years old from electronic medical databases in six general practices. A best estimate of ten-year CVD risk cardiovascular risk was calculated on all patients using the extracted risk factor data. Default risk-factor values were used for all missing risk factor data. High risk patients were thus identified. In four practices a project nurse systematically invited, assessed and referred high risk patients for treatment. Two control practices were provided with a list of their high risk patients. The outcomes were the proportions of untreated high-risk patients who were assessed, identified as eligible for treatment and treated under two strategies for identifying and treating such patients in primary care.</p> <p>Results</p> <p>Of all high-risk patients suitable for inclusion in the project, 40.6% (95% CI: 36.7 to 45.7%) of patients in intervention practices were started on treatment were started on at least one treatment, compared to 12.7% (95% CI: 9.8% to 16.1%) in control practices.</p> <p>Conclusion</p> <p>A strategy using electronic primary care records to identify high risk patients for CVD prevention works best with a process for acting on information, ensuring patients are invited, assessed and treated.</p

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. © 2013 Zhang et al

Clonal analysis of palmar fibromatosis: a study whether palmar fibromatosis is a real tumor

BACKGROUND: Palmar fibromatosis that arises in the palmar soft tissue is characterized by infiltrative growth with a tendency toward local recurrence but does not metastasize. This study investigated the clonality of this process in twelve female patients, each with a single lesion, by examining the pattern of X-chromosome inactivation. METHODS: Hematoxylin and eosin stained sections of formalin-fixed, paraffin-embedded tissues were microdissected by laser capture microdissection to obtain the proliferative spindle cells. Tumor cells were isolated from the sections of rectum adenocarcinoma, and used for positive control. The genomic DNAs was extracted with phenol-chloroform, digested with a methylation-sensitive restriction endonuclease HpaII, and amplified by polymerase chain reaction (PCR), using primers targeted to a highly polymorphic short tandem repeat (STR) of the human androgen receptor gene (HUMARA). RESULTS: Among the twelve samples, three samples failed amplification, one sample showed homozygosity which was not suitable for further analysis, eight samples were successfully amplified, and showed a random X chromosome inactivation pattern, suggesting polyclonality of these lesions. CONCLUSION: The current findings suggest that palmar fibromatosis is a reactive proliferation rather than a clonal neoplasm

In the absence of cancer registry data, is it sensible to assess incidence using hospital separation records?

BACKGROUND: Within the health literature, a major goal is to understand distribution of service utilisation by social location. Given equivalent access, differential incidence leads to an expectation of differential service utilisation. Cancer incidence is differentially distributed with respect to socioeconomic status. However, not all jurisdictions have incidence registries, and not all registries allow linkage with utilisation records. The British Columbia Linked Health Data resource allows such linkage. Consequently, we examine whether, in the absence of registry data, first hospitalisation can act as a proxy measure for incidence, and therefore as a measure of need for service. METHODS: Data are drawn from the British Columbia Linked Health Data resource, and represent 100% of Vancouver Island Health Authority cancer registry and hospital records, 1990–1999. Hospital separations (discharges) with principal diagnosis ICD-9 codes 140–208 are included, as are registry records with ICDO-2 codes C00-C97. Non-melanoma skin cancer (173/C44) is excluded. Lung, colorectal, female breast, and prostate cancers are examined separately. We compare registry and hospital annual counts and age-sex distributions, and whether the same individuals are represented in both datasets. Sensitivity, specificity and predictive values are calculated, as is the kappa statistic for agreement. The registry is designated the gold standard. RESULTS: For all cancers combined, first hospitalisation counts consistently overestimate registry incidence counts. From 1995–1999, there is no significant difference between registry and hospital counts for lung and colorectal cancer (p = 0.42 and p = 0.56, respectively). Age-sex distribution does not differ for colorectal cancer. Ten-year period sensitivity ranges from 73.0% for prostate cancer to 84.2% for colorectal cancer; ten-year positive predictive values range from 89.5% for female breast cancer to 79.35% for prostate cancer. Kappa values are consistently high. CONCLUSION: Claims and registry databases overlap with an appreciable proportion of the same individuals. First hospital separation may be considered a proxy for incidence with reference to colorectal cancer since 1995. However, to examine equity across cancer health services utilisation, it is optimal to have access to both hospital and registry files

A pilot study comparing two weight loss maintenance interventions among low-income, mid-life women

BACKGROUND: Despite high obesity prevalence rates, few low-income midlife women participate in weight loss maintenance trials. This pilot study aims to assess the effectiveness of two weight loss maintenance interventions in this under-represented population. METHODS: Low-income midlife women who completed a 16-week weight loss intervention and lost ≥ 8 lbs (3.6 kg) were eligible to enroll in one of two 12-month maintenance programs. The programs were similar in content and had the same number of total contacts, but were different in the contact modality (Phone + Face-to-Face vs. Face-to-Face Only). Two criteria were used to assess successful weight loss maintenance at 12 months: (1) retaining a loss of ≥ 5% of body weight from the start of the weight loss phase and (2) a change in body weight of < 3%, from the start to the end of the maintenance program. Outcome measures of changes in physiologic and psychosocial factors, and evaluations of process measures and program acceptability (measured at 12 months) are also reported. For categorical variables, likelihood ratio or Fisher’s Exact (for small samples) tests were used to evaluate statistically significant relationships; for continuous variables, t-tests or their equivalents were used to assess differences between means and also to identify correlates of weight loss maintenance. RESULTS: Overall, during the 12-month maintenance period, 41% (24/58) of participants maintained a loss of ≥ 5% of initial weight and 43% (25/58) had a <3% change in weight. None of the comparisons between the two maintenance programs were statistically significant. However, improvements in blood pressure and dietary behaviors remained significant at the end of the 12-month maintenance period for participants in both programs. Participant attendance and acceptability were high for both programs. CONCLUSIONS: The effectiveness of two pilot 12-month maintenance interventions provides support for further research in weight loss maintenance among high-risk, low-income women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0028830

Feasibility study of portable technology for weight loss and HbA1c control in type 2 diabetes

Background The study investigated the feasibility of conducting a future Randomised Controlled Trial (RCT) of a mobile health (mHealth) intervention for weight loss and HbA1c reduction in Type 2 Diabetes Mellitus (T2DM). Methods The intervention was a small wearable mHealth device used over 12 weeks by overweight people with T2DM with the intent to lose weight and reduce their HbA1c level. A 4 week maintenance period using the device followed. The device records physical activity level and information about food consumption, and provides motivational feedback based on energy balance. Twenty-seven participants were randomised to receive no intervention; intervention alone; or intervention plus weekly motivational support. All participants received advice on diet and exercise at the start of the study. Weight and HbA1c levels were recorded at baseline and weeks 6, 12, and 16. Qualitative interviews were conducted with participants who received the intervention to explore their experiences of using the device and involvement in the study including the training received. Results Overall the device was perceived to be well-liked, acceptable, motivational and easy to use by participants. Some logistical changes were required during the feasibility study, including shortening of the study duration and relaxation of participant inclusion criteria. Descriptive statistics of weight and HbA1c data showed promising trends of weight loss and HbA1c reduction in both intervention groups, although this should be interpreted with caution. Conclusions A number of methodological recommendations for a future RCT emerged from the current feasibility study. The mHealth device was acceptable and promising for helping individuals with T2DM to reduce their HbA1c and lose weight. Devices with similar features should be tested further in larger studies which follow these methodological recommendations

Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips

Introduction In patients with osteoarthritis of the hip (OAH), trochanteric fractures are much more common than femoral neck fractures. One reason may be altered bone composition in the proximal femurs. OAH often leads to a fixed external rotation of the hip, leading to difficulties in positioning during DXA measurements. We compared BMD in OAH-affected legs and healthy legs

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote