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Peer reviewed: True, Funder: Egyptian Cultural and Educational Bureau, The assessment of PD-L1 expression in TNBC is a prerequisite for selecting patients for immunotherapy. The accurate assessment of PD-L1 is pivotal, but the data suggest poor reproducibility. A total of 100 core biopsies were stained using the VENTANA Roche SP142 assay, scanned and scored by 12 pathologists. Absolute agreement, consensus scoring, Cohen's Kappa and intraclass correlation coefficient (ICC) were assessed. A second scoring round after a washout period to assess intra-observer agreement was carried out. Absolute agreement occurred in 52% and 60% of cases in the first and second round, respectively. Overall agreement was substantial (Kappa 0.654-0.655) and higher for expert pathologists, particularly on scoring TNBC (6.00 vs. 0.568 in the second round). The intra-observer agreement was substantial to almost perfect (Kappa: 0.667-0.956), regardless of PD-L1 scoring experience. The expert scorers were more concordant in evaluating staining percentage compared with the non-experienced scorers (R2 = 0.920 vs. 0.890). Discordance predominantly occurred in low-expressing cases around the 1% value. Some technical reasons contributed to the discordance. The study shows reassuringly strong inter- and intra-observer concordance among pathologists in PD-L1 scoring. A proportion of low-expressors remain challenging to assess, and these would benefit from addressing the technical issues, testing a different sample and/or referring for expert opinions.

Addiction and homelessness are closely related outcomes for many Indigenous Canadians who live with extensive intergenerational trauma caused by residential school and the 60s Scoop. In recent years, the rise of opioid addiction along with related overdoses and mortalities in many parts of Canada has led to what is being called an opioid crisis. (Re)connection to Indigenous ways of knowing and practices are frequently seen as a path to healing; therefore, an innovative grassroots program was developed recently in a southern Alberta city to address addictions and homelessness within a largely Blackfoot population. The program increased access to traditional cultural resources and activities in a visible, downtown location to a population who are among the most marginalized in society. A Two-Eyed Seeing framework was used perform a program evaluation and analyze participant and key informant interviews. The results indicated that attendance connected people with their spirits, inspiring strength and hope for the future, and ameliorated spiritual homelessness. The program formed a safe space where relationships were strengthened, people felt respected, and meaningful activity away from substances was available.

Introduction Cancer is likened to a non-healing wound. There is limited evidence on the expression of wound healing tissue inflammatory markers, CD68(pan-macrophage marker), HO-1(tumour cell marker) and FAP(cancer-associated fibroblast marker) in human breast cancer. Method In 201 invasive breast cancer and 58 DCIS patients, CD68+TAM expression, tumour HO-1 and fibroblast FAP expression, quantified by immunohistochemistry(dichotomised: high/present vs low/absent), was correlated with tumour factors (grade, proliferation(Ki67), ER, HER2); demographic factors, behavioural factors (smoking, alcohol) and survival status(DFS, OS) Result High CD68+macrophage expression was increased in invasive breast cancer, compared to DCIS, and normal tissue distant from the tumour(59%,41%and 6% respectively; p Conclusion Tumour inflammation as assessed by CD68+TAM expression shows utility in identifying aggressive breast cancer sub-types. The association reported between CD68+TAM density and alcohol intake suggests a possible mechanism for alcohol as a risk factor for breast cancer. The prognostic value of HO-1 and FAP expression demonstrated here suggests a functional role of these wound healing markers in breast cancer. HO-1:Heme-oxygenase-1; FAP:Fibroblast activation protein; TAM:Tumour associated macrophage; DCIS: Ductal carcinoma in situ Take-home message Wound healing pathways of inflammation may be implicated in early breast cancer development

A 43-year-old woman with a positive family history of breast cancer presented with a painless lump in her left axilla for 2 years. Clinical diagnosis was a left axillary sebaceous cyst as the lump was inseparable from the skin. The lesion was excised under local anaesthesia and reported as breast tissue widely infiltrated by an invasive ductal carcinoma (grade 2). The malignancy was not involving the epidermis but

BACKGROUND: Tumour associated macrophages (TAMs) are prognostic markers in breast cancer, however the influence of patient demographic and behavioural factors on these inflammatory markers has not been fully appreciated. METHODS: In 201 invasive breast cancer and 58 ductal carcinoma in-situ (DCIS) patients, TAM density (percentage % CD68 [IHC-immunohistochemistry] positive cells) was correlated with tumour factors (grade, proliferation (Ki67), ER, HER2); demographic factors (age, menopausal status, breast density, BMI, diabetes) and behavioural factors (smoking, alcohol). RESULTS: TAM density was increased in invasive breast cancer, compared to DCIS, and normal tissue distant from the tumour (59%, 41% and 6% respectively; p In terms of demographic factors, TAM density did not correlate with age, menopausal status, breast density (BIRADs), BMI or history of diabetes. TAM density was not increased in patients who smoked; however, it was increased in patients who self-reported alcohol intake (non-drinker 43% vs. drinker 62%; p=0.01). CONCLUSION: TAM density shows utility in identifying aggressive breast cancer sub-types. The association reported between TAM density and alcohol intake suggests a possible mechanism for alcohol as a risk factor for breast cancer. Citation Format: Urvashi Singh, John Castle, Sophie Greenhalgh, Umar Hussain, Tine Descamps, Sarah Nash, Mary Wilson, Roger Hunt, Cliona C Kirwan. The relationship between tumour associated macrophage markers and tumour, demographic & behavioural factors in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-27.

Background: This research investigated whether bioimpedance spectroscopy (BIS) has the potential to improve prognostication in an outpatient clinic for patients with cancer receiving palliative care. Methods: Survival time, and BIS measures of basal metabolic rate and 11 body composition parameters (extracellular fluid [ECF], intracellular fluid [ICF], ratio of ECF to ICF, fluid in trunk and each arm and leg, protein mass, mineral mass, and percent body fat) were recorded for 84 oncology patients. Results: None of the BIS measures showed a linear association with survival time. However, threshold values associated with short survival were identified for basal metabolic rate and 6 of the body composition measures related to fluid (ECF, ratio of ECF to ICF, fluid in right and left arms, and right and left legs). In addition, almost all patients who died within 6 weeks of assessment reached the threshold values for ECF and/or ECF:ICF ratio. Conclusion: Results confirm that elevated metabolic rate and accumulation of body fluid are indicators of a poor prognosis in patients with cancer receiving palliative care. Because BIS is simple for clinicians to use, is noninvasive,and allows early detection of these parameters, it has the potential to improve prognostication. Refereed/Peer-reviewed

Distributions of scatter-to-primary and signal-to-noise ratios per pixel in digital chest imaging The aim of this work was to calculate distributions of scatter- to-primary ratios (epsilon(s)/epsilon(p)) and signal-to-noise ratios per pixel (SNRp) in chest images. Such distributions may provide useful information on how physical image quality (contrast, SNR) is distributed over the posterior/anterior (PA) chest image. A Monte Carlo computer program was used for the calculations, including a model of both the patient (voxel phantom) and the imaging system (X-ray tube, anti-scatter grid and image detector). The calculations were performed for three PA thicknesses 20, 24 and 28 cm. For a 24 cm patient, the epsilon(s)/epsilon(p) varies between 0.5 in the lung to 2.5 behind the spine and heart. The corresponding variation of the SNRp is a factor of 3, with the highest values in the lung. Increasing the patient thickness from 20 to 28 cm increases the epsilon(s)/epsilon(p) by a factor of 2.2 behind the spine and heart.

A novel method of noise reduction has been tested for mammography using computer-simulated images for which the truth is known exactly. This method is based on comparing two images. The images are compared at different scales, using a cross-correlation function as a measure of similarity to define the image modifications in the wavelet domain. The computer-simulated images were calculated for noise-free primary radiation using a quasi-realistic voxel phantom. Two images corresponding to slightly different geometry were produced. Gaussian noise was added with certain properties to simulate quantum noise. The added noise could be reduced by >70% using the proposed method without any noticeable corruption of the structures. It is possible to save 50% dose in mammography by producing two images (each 25% of the dose for a standard mammogram). Additionally, a reduction of the anatomical noise and, therefore, better detection rates of breast cancer in mammography are possible.

The influence of patient thickness and imaging system on patient dose and physical image quality in digital chest imaging The aim of this work was to study the influence of patient thickness, tube voltage and image detector on patient dose, contrast and ideal observer signal-to-noise ratio (SNRI), for pathological details positioned at different regions in the Image in posterior-anterior (PA) chest radiology. A Monte Carlo computational model was used to compute measure,. of physical image quality (contrast, SNRI) and patient effective dose, E. Two metastasis-like details positioned in the central right lung and right lung near the spine, respectively, were studied. The tube voltage was varied between 100 and 150 kV and the patient thickness between 20 and 28 cm. Both, a computed radiography (CR) system and a direct radiography (DR) system. were 2 investigated. The DR system provides both lower doses and better image quality compared with the CR system. The SNRI2/E is similar to 2.9 times higher for the DR system compared with the CR system.

Abstract Using immunolocalization techniques, we have shown that paraoxonase (Pon), clusterin, and apolipoprotein (apo) A-I accumulate in the artery wall during the development of atherosclerosis. In normal aortas (n=6) there were low levels of extracellular Pon, clusterin, and apoA-I immunoreactivity. The cytoplasm of smooth muscle cells in the media showed granular positivity for both Pon and apoA-I, indicating that these proteins were undergoing lysosomal degradation. This activity was also indicated by the presence of both intact and degradation products of Pon in smooth muscle cells as shown by Western blotting. With the progression of disease from fatty streaks (n=3) to advanced atherosclerosis (n=8) there was an increase in Pon, apoA-I, and clusterin immunoreactivity, indicating the increasing presence of these proteins with disease progression. These proteins are the components of a specific HDL subspecies that has been implicated in the prevention of peroxidative damage to phospholipids in LDL and membranes. The increase in Pon, clusterin, and apoA-I during the development of atherosclerosis may therefore represent a protective response to the oxidative stress associated with the development of atherosclerosis.

Context: Evidence-based approaches are needed to improve the delivery of specialized palliative care. Conclusion: A single case conference added to current specialized community-based palliative care reduced hospitalizations and better maintained performance status. Comparatively, patient/caregiver education was less effective; GP education was not effective. Methods: This 2 × 2 × 2 factorial cluster randomized controlled trial was conducted at an Australian community-based palliative care service, allowing three simultaneous comparative effectiveness studies. Participating patients were newly referred adults, experiencing pain, and who were expected to live >48 hours. Patients enrolled with their general practitioners (GPs) and were randomized three times: 1) individualized interdisciplinary case conference including their GP vs. control, 2) educational outreach visiting for GPs about pain management vs. control, and 3) structured educational visiting for patients/caregivers about pain management vs. control. The control condition was current palliative care. Outcomes included Australia-modified Karnofsky Performance Status (AKPS) and pain from 60 days after randomization and hospitalizations. Objectives: The aim of this trial was to improve on current models of service provision. Results: There were 461 participants: mean age 71 years, 50% male, 91% with cancer, median survival 179 days, and median baseline AKPS 60. Only 47% of individuals randomized to the case conferencing intervention received it; based on a priori-defined analyses, 32% of participants were included in final analyses. Case conferencing reduced hospitalizations by 26% (least squares means hospitalizations per patient: case conference 1.26 [SE 0.10] vs. control 1.70 [SE 0.13], P = 0.0069) and better maintained performance status (AKPS case conferences 57.3 [SE 1.5] vs. control 51.7 [SE 2.3], P = 0.0368). Among patients with declining function (AKPS

Background Primary malignancies of colorectal origin can metastasise to the bladder. Reports are however extremely rare, particularly from the caecum. Case report The report describes the case of a 45-year old male with Duke's B caecal carcinoma treated with a laparoscopically-assisted right hemicolectomy and adjuvant 5-Fluorouracil chemotherapy. Subsequently, a metastatic lesion to the bladder was demonstrated and successfully excised by partial cystectomy. Conclusion In order that optimal therapeutic options can be determined, it is important for clinicians to distinguish between primary disease of the bladder and other causes of haematuria. Various immunohistochemical techniques attempt to differentiate primary adenocarcinoma of the bladder from secondary colorectal adenocarcinoma. Suspicion of metastatic disease must be raised when histologically unusual bladder tumours are identified.

A Monte Carlo based computer model of the x-ray imaging system was used to investigate how various image quality parameters of interest in chest PA radiography and the effective dose E vary with tube voltage (90-150 kV), additional copper filtration (0-0.5 mm), anti-scatter method (grid ratios 8-16 and air gap lengths 20-40 cm) and patient thickness (20-28 cm) in a computed radiography (CR) system. Calculated quantities were normalized to a fixed value of air kerma (5.0 microGy) at the automatic exposure control chambers. Soft-tissue nodules were positioned at different locations in the anatomy and calcifications in the apical region. The signal-to-noise ratio, SNR, of the nodules and the nodule contrast relative to the contrast of bone (C/C(B)) as well as relative to the dynamic range in the image (C(rel)) were used as image quality measures. In all anatomical regions, except in the densest regions in the thickest patients, the air gap technique provides higher SNR and contrast ratios than the grid technique and at a lower effective dose E. Choice of tube voltage depends on whether quantum noise (SNR) or the contrast ratios are most relevant for the diagnostic task. SNR increases with decreasing tube voltage while C/C(B) increases with increasing tube voltage.

Calculation of the properties of digital mammograms using a computer simulation A Monte Carlo computer model of mammography has been developed to study and optimise the performance of digital mammographic systems. The program uses high-resolution voxel phantoms to model the breast, which simulate the adipose and fibroglandular tissues, Cooper's ligaments, ducts and skin in three dimensions. The model calculates the dose to each tissue, and also the quantities such as energy imparted to image pixels, noise per image pixel and scatter-to-primary (SIP) ratios. It allows studies of the dependence of image properties on breast structure and on position within the image. The program has been calibrated by calculating and measuring the pixel values and noise for a digital maminographic system. The thicknesses of two components of this system were unknown, and were adjusted to obtain a good agreement between measurement and calculation. The utility of the program is demonstrated with the calculations of the variation of the SIP ratio with and without a grid, and of the image contrast across the image of a 50-mm-thick breast phantom.

A test phantom, including a wide range of mammographic tissue equivalent materials and test details, was imaged on a digital mammographic system. In order to quantify the effect of scatter on the contrast obtained for the test details, calculations of the scatter-to-primary ratio (S/P) have been made using a Monte Carlo simulation of the digital mammographic imaging chain, grid and test phantom. The results show that the S/P values corresponding to the imaging conditions used were in the range 0.084-0.126. Calculated and measured pixel values in different regions of the image were compared as a validation of the model and showed excellent agreement. The results indicate the potential of Monte Carlo methods in the image quality-patient dose process optimisation, especially in the assessment of imaging conditions not available on standard mammographic units.

A computer model of X-ray mammography has been developed, which uses quasi-realistic high-resolution voxel phantoms to simulate the breast. The phantoms have 400 microm voxels and simulate the three-dimensional distributions of adipose and fibro-glandular tissues, Cooper's ligaments, ducts and skin and allow the estimation of dose to individual tissues. Calculations of the incident air kerma to mean glandular dose conversion factor, g, were made using a Mo/Mo spectrum at 28 kV for eight phantoms in the thickness range 40-80 mm and of varying glandularity. The values differed from standard tabulations used for breast dosimetry by up to 43%, because of the different spatial distribution of glandular tissue within the breast. To study this further, additional voxel phantoms were constructed, which gave variations of between 9 and 59% compared with standard values. For accurate breast dosimetry, it is therefore very important to take the distribution of glandular tissues into account.

A wavelet based method of noise reduction has been tested for mammography using computer-simulated images for which the truth is known exactly. This method is based on comparing two images at different scales, using a cross-correlation-function as a measure of similarity to define the image modifications in the wavelet domain. The computer-simulated images were calculated for noise-free primary radiation using a quasi-realistic voxel phantom. Two images corresponding to slightly different geometry were produced. Gaussian noise was added with a mean value of zero and a standard deviation equal to 0.25% to 10% of the actual pixel value to simulate quantum noise with a certain level. The added noise could be reduced by more than 70% using the proposed method without any noticeable corruption of the structures for 4% added noise. The results indicate that it is possible to save 50% dose in mammography by producing two images (each 25% of the dose for a standard mammogram). Additionally, a reduction or even a removal of the anatomical noise might be possible and therefore better detection rates of breast cancer in mammography might be achievable.

The demand for palliative care is increasing, yet there are few data on the best models of care nor well-validated interventions that translate current evidence into clinical practice. Supporting multidisciplinary patient-centered palliative care while successfully conducting a large clinical trial is a challenge. The Palliative Care Trial (PCT) is a pragmatic 2 × 2 × 2 factorial cluster randomized controlled trial that tests the ability of educational outreach visiting and case conferencing to improve patient-based outcomes such as performance status and pain intensity. Four hundred sixty-one consenting patients and their general practitioners (GPs) were randomized to the following: (1) GP educational outreach visiting versus usual care, (2) Structured patient and caregiver educational outreach visiting versus usual care and (3) A coordinated palliative care model of case conferencing versus the standard model of palliative care in Adelaide, South Australia (3:1 randomization). Main outcome measures included patient functional status over time, pain intensity, and resource utilization. Participants were followed longitudinally until death or November 30, 2004. The interventions are aimed at translating current evidence into clinical practice and there was particular attention in the trial's design to addressing common pitfalls for clinical studies in palliative care. Given the need for evidence about optimal interventions and service delivery models that improve the care of people with life-limiting illness, the results of this rigorous, high quality clinical trial will inform practice. Initial results are expected in mid 2005.

We investigated how the thickness of a mass lesion at the observer detection threshold varied with lesion location in the breast. A digital mammography system was used to acquire radiographs of an anthropomorphic breast phantom. Mammograms were acquired with and without mass lesions, thereby permitting a difference image to be generated corresponding to the lesion alone. This isolated lesion was added at a reduced intensity to a non-lesion digital mammogram during a 4-Alternate Forced-Choice (4-AFC) experiment. The lesion intensity that corresponded to a 92% correct performance level in the 4-AFC experiments was determined (I 92% ). Values of I 92% were obtained at different locations in the anthropomorphic phantom, thereby permitting the importance of breast thickness and structured background on lesion detection to be investigated. Lesion detection (I 92% ) was found to be best in high signal intensity regions (black) and ~25% lower in the low signal regions (white). Lesion detection also appeared to depend on the characteristics of the structured background. The experimental results showed a good correlation with a computation that used a convolution of the lesion and the local background region in the mammogram.

UI - 21670817DA - 20020128IS - 0147-5185LA - engPT - LetterPT - ReviewPT - Review, TutorialSB - IM

Holly Bekarma and colleagues outline their model for advising foundation doctors on their career paths

8517 Background: Evidence-based palliative care service delivery models are needed. General practitioner (GP) and patient-centered case conferences may increase multidisciplinary interaction and enhance patient care. Educational outreach visiting in pain management may empower learners and improve care. Methods: Three interventions were tested against a routine care control in a 2×2×2 cluster factorial randomized controlled trial. Interventions were case conferencing, educational visiting for GPs, and educational visiting for patients. Subjects were adult patients referred to palliative care services in southern Adelaide, Australia, with any pain in the preceding 3 months. Participants were followed longitudinally until death. Main outcomes included performance status (Australian-modified Karnofsky Performance Status (AKPS)) and hospitalization rates. Longitudinal intention-to-treat analyses using cluster-specific methods were conducted. The sample goal was 460. Results: 461 participants were enrolled from 4/02–6/04. Mean age was 71 yrs, 50% were male, 91% had cancer. Mean and median survival was 146 and 87 days; median baseline AKPS was 60%. When participants had AKPS No significant financial relationships to disclose.