Comparison of the prognostic value of tumour and patient related factors in patients undergoing potentially curative surgery for colon cancer

<b>Aim</b>: To comprehensively compare the prognostic value of tumour and patient-related factors in patients undergoing curative surgery for colon cancer. <b>Methods</b>: From a database of 287 patients who underwent elective resection between 1997-2005, tumour factors including stage and host factors including systemic inflammatory response (modified Glasgow Prognostic Score (mGPS)) were identified. <b>Results</b>: Median follow-up was 65 months. Over this time period 125 patients died, 80 from cancer. On multivariate analysis of all significant patient and tumour related factors, Dukes stage (P<0.01), vascular invasion (P<0.01), and the mGPS (P<0.01) were independently associated with cancer-survival. Of the patient-related factors, age (P<0.01), haemoglobin (P<0.01), white-cell (P<0.01), neutrophil (P<0.01) and platelet (P<0.01) counts and alkaline phosphatase (P<0.01) were most significantly associated with the mGPS. <b>Conclusion</b>: In addition to tumour-related factors such as Dukes stage and vascular invasion, the pre-operative mGPS should be included to guide prognosis in patients undergoing curative resection for colon cancer

Systemic inflammation, nutritional status and survival in patients with cancer

Systemic inflammation, nutritional status and survival in patients with cance

Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer

BACKGROUND: Advances in the treatment of metastatic colorectal cancer (mCRC) in the last decade have significantly improved survival; however, simple biomarkers to predict response or toxicity have not been identified, which are applicable to all community oncology settings worldwide. The use of inflammatory markers based on differential white-cell counts, such as the neutrophil/ lymphocyte ratio (NLR), may be simple and readily available biomarkers. METHODS: Clinical information and baseline laboratory parameters were available for 349 patients, from two independent cohorts, with unresectable mCRC receiving first-line palliative chemotherapy. Associations between baseline prognostic variables, including inflammatory markers such as the NLR and tumour response, progression and survival were investigated. RESULTS: In the training cohort, combination-agent chemotherapy (P ¼ 0.001) and NLRp5 (P ¼ 0.003) were associated with improved clinical benefit. The ECOG performance status X1 (P ¼ 0.002), NLR45 (P ¼ 0.01), hypoalbuminaemia (P ¼ 0.03) and single-agent chemotherapy (Po0.0001) were associated with increased risk of progression. The ECOG performance status X1 (P ¼ 0.004) and NLR45 (P ¼ 0.002) predicted worse overall survival (OS). The NLR was confirmed to independently predict OS in the validation cohort (Po0.0001). Normalisation of the NLR after one cycle of chemotherapy in a subset of patients resulted in improved progression-free survival (P ¼ 0.012). CONCLUSION: These results have highlighted NLR as a potentially useful clinical biomarker of systemic inflammatory response in predicting clinically meaningful outcomes in two independent cohorts. Results of this study have also confirmed the importance of a chronic systemic inflammatory response influencing clinical outcomes in patients with mCRC

An international multicenter study of protocols for liver transplantation during a pandemic : a case for quadripartite equipoise

Background & Aims: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. Methods: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. Results: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a “sickest-first” approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors – recipient outcome, donor/graft safety, waiting list mortality and healthcare resources – for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. Conclusions: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. Lay summary: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems

A Novel Quantification Method for Determining Previously Undetected Silent Infarcts on MR-perfusion in Patients Following Carotid Endarterectomy

The purpose of this paper is to evaluate the post-operative Magnetic Resonance Perfusion (MRP) scans of patients undergoing carotid endarterectomy (CEA), using a novel image-analysis algorithm, to determine if post-operative neurocognitive decline is associated with cerebral blood flow changes. CEA procedure reduces the risk of stroke in appropriately selected patients with significant carotid artery stenosis. However, 25% of patients experience subtle cognitive deficits after CEA compared to a control group. It was hypothesized that abnormalities in cerebral blood flow (CBF) are responsible for these cognitive deficits. A novel algorithm for analyzing MRperfusion (MRP) scans to identify and quantify the amount of CBF asymmetry in each hemisphere was developed and to quantify the degree of relative difference between three corresponding vascular regions in the ipsilateral and contralateral hemispheres, the Relative Difference Map (RDM). Patients undergoing CEA and spine surgery (controls) were examined preoperatively, and one day postoperatively with a battery of neuropsychometric (NPM) tests, and labeled “injured” patients with significant cognitive deficits, and “normal” if they demonstrated no decline in neurocognitive function. There are apparently significant RDM differences with MRP scans between the two hemispheres in patients with cognitive deficits which can be used to guide expert reviews of the imagery. The proposed methodology aids in the analysis of MRP parameters in patients with cognitive impairment

Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour

Background: Colorectal cancer (CRC) is a major cause of mortality and morbidity. The impact of inflammatory biomarkers (C-reactive protein etc.) on CRC is increasingly studied including systemic neutrophil-to-lymphocyte ratio (NLR) as they seem to predict outcome. Methods: All patients who underwent curative resection for CRC from 2000 to 2004 at Leeds Teaching Hospitals NHS Trust had pre-operative NLR calculated. Demographic, histopathological and survival data were collected. Tissue microarrays were created and stained to determine the mismatch repair (MMR) protein status of each tumour. Local lymphocytic response to the tumour was assessed and graded. Results: About 358 patients were eligible. Of these 88 had an NLR greater than or equal to5, which predicted lower overall survival and greater disease recurrence. A high NLR is associated with higher pT- and pN-stage and a greater incidence of extramural venous invasion. MMR protein status was not associated with NLR. A pronounced lymphocytic reaction at the invasive margin (IM) indicated a better prognosis and was associated with a lower NLR. Conclusion: Neutrophil-to-lymphocyte ratio predicts disease-free and overall survival and is associated with a more aggressive tumour phenotype. The lymphocytic response to tumour at the IM is associated with NLR however dMMR is not. Neutrophil-to-lymphocyte ratio is a cheap, easy-to-access test that predicts outcome in CRC