Inter- and Intra-Observer Agreement of PD-L1 SP142 Scoring in Breast Carcinoma-A Large Multi-Institutional International Study.

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.

Lidocaine Continuous Subcutaneous Infusion for Neuropathic Pain in Hospice Patients: Safety and Efficacy.

Lidocaine continuous subcutaneous infusion (L-CSCI) for neuropathic pain in hospice patients has limited evidence for its safety and efficacy, and guidelines are lacking. This study assesses a series of patients admitted to a hospice over a six-month period that had neuropathic pain and received L-CSCI. The primary outcome was improvement in patient-rated distress from pain following L-CSCI titration. Also assessed were changes in oral morphine equivalent dose (OME), frequency of breakthrough medication, functional status, adverse effects and perception of response. Fifteen patients received L-CSCI for an average of 6.7 days (range 1-92). Average pain distress score decreased by 2 or more in six patients. Positive responses to L-CSCI were documented in the clinical notes of 10 patients. Opioid down-titration occurred in four patients. Lidocaine levels were performed in 3 patients but did not change management. Five patients experienced adverse effects attributable to lidocaine and all responded to simple measures. In conclusion, L-CSCI can help manage neuropathic pain in hospice patients, particularly in those who cannot swallow oral medications. Further systematic research is warranted to establish efficacy and tolerability, and to inform guideline development.

Ectopic breast carcinoma presenting as sebaceous cyst left axilla.

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 <1 mm away from deeper margins. Re-excision of the deeper tissue with an axillary sentinel lymph nodes biopsy was performed and deep margins were reported to be tumour-free with no nodal involvement.

Where Patients With Cancer Die: A Population-Based Study, 1990 to 2012.

AIMS: To describe changes in the place of death of patients with cancer from 1990 to 2012, and to identify issues for their end-of-life care. MATERIALS AND METHODS: Population-based descriptive study, with analyses of place of death patterns, using the South Australian Cancer Registry records of 86 257 patients with cancer who died from 1990 to 2012. RESULTS: From 1990 to 2012, the proportion of cancer deaths in hospital decreased from 63.4% to 50.9%, and in nursing homes increased from 8.2% to 22.5%. After the year 2000, the proportions in hospices and at home were both below 15%. Multivariate analyses showed that young patients with cancer were more likely to die in a hospice or at home, compared to elderly patients with cancer who were more likely to die in a nursing home; the likelihood of dying in a hospice increased with socioeconomic status; patients with a short survival time or a hematological malignancy were more likely to die in a metropolitan hospital. CONCLUSIONS: Compared to most other countries, the proportion of cancer deaths at home was low, and many patients would not have died at their preferred place. The trend for more cancer deaths to occur in nursing homes is likely to continue, but nursing homes generally lack the resources and skilled staff to provide quality palliative care. Models of palliative care delivery should take account of patient preferences, the growth of terminal cancer care in nursing homes, and apparent inequities.

Documenting the process of developing the Victorian voluntary assisted dying legislation.

Many countries across the world have legislated for their constituents to have control over their death. Commonalities and differences can be found in the regulations surrounding the shape and practices of voluntary assisted dying (VAD) and euthanasia, including an individual's eligibility and access, role of health professions and the reporting. In Australia there have been perennial debates across the country to attempt legislative change in assisting a terminally ill person to control the ending of their life. In 2017, Victoria became the first state to successfully legislate for VAD. In describing the Victorian process that led to the passage of legislation for VAD, this paper examines the social change process. The particular focus of the paper is on the vital role played by a multidisciplinary ministerial advisory panel to develop recommendations for the successful legislation, and is written from their perspective.

Delivery strategies to optimize resource utilization and performance status for patients with advanced life-limiting illness: results from the "palliative care trial" [ISRCTN 81117481].

CONTEXT: Evidence-based approaches are needed to improve the delivery of specialized palliative care. OBJECTIVES: The aim of this trial was to improve on current models of service provision. 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. 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 <70), case conferencing and patient/caregiver education better maintained performance status (AKPS case conferences 55.0 [SE 2.1] vs. control 46.5 [SE 2.9], P=0.0143; patient/caregiver education 54.7 [SE 2.8] vs. control 46.8 [SE 2.1], P=0.0206). Pain was unchanged. GP education did not change outcomes. 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.

Estimating survival in patients with cancer receiving palliative care: is analysis of body composition using bioimpedance helpful?

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.

Adenocarcinoma of the caecum metastatic to the bladder: an unusual cause of haematuria.

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.

Factors predictive of preferred place of death in the general population of South Australia.

In a population survey, 2652 respondents aged 15+ years reported their preferred place of death, if dying of 'a terminal illness such as cancer or emphysema', to be home (70%), a hospital (19%), hospice (10%), or nursing home (<1%). The majority of respondents in all socio-demographic categories reported a preference for dying at home, with the greatest majorities occurring in younger age groups. After weighting to the age-sex distribution of all South Australian cancer deaths, 58% in our survey declared a preference to die at home, which is much higher than the 14% of cancer deaths that actually occurred at home in South Australia in 2000-2002. Multivariable analyses indicate that predictors of preferred home death include younger age, male, born in the UK/Ireland or Italy/Greece, better physical health, poorer mental health, and fewer concerns about dying at home. Predictors of preference for death in a hospice rather than hospital include older age, female, single, metropolitan residence, having higher educational and income levels, paid employment, awareness of advanced directives, and interpreting 'dying with dignity' as death without pain or suffering. Investigating the differences between preferred and actual places of death may assist service providers to meet end-of-life wishes.

Towards optimization in digital chest radiography using Monte Carlo modelling.

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.

A pragmatic 2 x 2 x 2 factorial cluster randomized controlled trial of educational outreach visiting and case conferencing in palliative care-methodology of the Palliative Care Trial [ISRCTN 81117481].

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 x 2 x 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.

Evaluation of a novel method of noise reduction using computer-simulated mammograms.

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 (SNR(I)), 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 measures of physical image quality (contrast, SNR(I)) 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 investigated. The DR system provides both lower doses and better image quality compared with the CR system. The SNR(I)2/E is approximately 2.9 times higher for the DR system compared with the CR system.

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.