Staging the tumour and staging the host: Pre-treatment combined Neutrophil Lymphocyte Ratio and modified Glasgow Prognostic Score is associated with overall survival in patients with oesophagogastric cancers undergoing treatment with curative intent

Background: This study examined whether an innate systemic inflammatory response (SIR) measured by combination neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) was associated with overall survival (OS) in patients with esophagogastric cancer (EC) undergoing neoadjuvant chemotherapy (NAC) followed by surgery. Methods: Patients diagnosed with EC, managed with NAC prior to surgery at a regional referral center, between January 2010 and December 2015, were included. The mGPS and NLR were calculated within 12 weeks before NAC. Patients were grouped by combined NLR/mGPS score into three groups of increasing SIR: NLR ≤ 3 (n = 152), NLR > 3 + mGPS = 0 (n = 55), and NLR > 3 + mGPS > 0 (n = 32). Univariable and multivariable Cox regression was used to analyse OS. Results: Overall, 337 NAC patients were included, with 301 (89%) proceeding to surgery and 215 (64%) having R0 resection. There were 203 deaths, with a median follow-up of those alive at censor of 69 months (range 44–114). Higher combined NLR/mGPS score (n = 239) was associated with poorer OS independent of clinical stage and performance status (hazard ratio 1.28, 95% confidence interval 1.02–1.61; p = 0.032), higher rate of progression on NAC (7% vs. 7% vs. 19%; p = 0.003), and lower proportion of eventual resection (80% vs. 84% vs. 53%; p = 0.003). Conclusions: The combined NLR/mGPS score was associated with OS and initial treatment outcomes in patients undergoing NAC prior to surgery for EC, stratifying survival in addition to clinical staging and performance status. The host SIR may be a useful adjunct to multidisciplinary decision making

The relationship between computed tomography-derived sarcopenia, cardiopulmonary exercise testing performance, systemic inflammation, and survival in good performance status patients with oesophago-gastric cancer undergoing neoadjuvant treatment

Background: Thought to capture the nutritional and functional reserve of the cancer patient, whether the computed tomography (CT)-derived sarcopenia score (CT-SS) has complimentary prognostic value to commonly utilized pre-treatment host assessments in patients with oesophago-gastric (OG) cancer is unknown. The aim of the present study was to examine if the CT-SS can stratify survival in OG cancer patients with good performance status [Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0/1]. Furthermore, if the CT-SS had complimentary prognostic value to cardiopulmonary exercise testing (CPET) performance and systemic inflammation. Methods: Consecutive patients with confirmed OG cancer and good performance status, who received neoadjuvant chemotherapy (NAC) with a view to surgical resection with curative intent, between 1 January 2010 and 31 December 2015, within NHS Greater Glasgow and Clyde (NHSGGC) and NHS Forth Valley (NHSFV), were identified from a prospectively maintained database. CT-SSs were grouped as 0/1/2. CPET variables recorded included VO2 anaerobic threshold (AT) and peak. Systemic inflammatory response was determined by modified Glasgow prognostic score (mGPS) and neutrophil/lymphocyte ratio (NLR). Associations between categorical variables were examined using χ2 test and binary logistics regression analysis. Results: A total of 232 patients met the inclusion criteria. 75% (n = 174) of patients were male, 54% (n = 126) were 65 years or older, and 60% (n = 139) were overweight [body mass index (BMI) ≥25 kg/m2]; 33% (n = 77) of patients had CT-SS ≥ 1, 36% (n = 83) had a low VO2 AT (≤11 ml/kg/min), and 57% (n = 132) had a low VO2 peak (≤19 ml/kg/min). Of the 200 patients who had pre-NAC bloods facilitating calculation of the mGPS, 28% (n = 55) had mGPS ≥ 1. Of the 211 patients who had pre-NAC bloods facilitating calculation of NLR, 38% (n = 80) had an NLR ≥ 3; 82% (n = 190) and 53% (n = 122) were alive at 1 and 3 years post-NAC, respectively. On univariate analysis, CT-SS was significantly associated with sex (P < 0.05), histological cell type (P < 0.05), low VO2 AT (P < 0.05), low VO2 peak (P < 0.05), BMI (P < 0.05), mGPS (P < 0.05), and 3-year survival (P < 0.05). On multivariate analysis, tumour, node, and metastasis (TNM) stage (P < 0.05) and CT-SS (P < 0.05) remained significantly associated with 3-year survival. CT-SS was significantly associated with 3-year survival in patients who had mGPS 0 (P < 0.05), but not low VO2 AT (P = 0.066) or peak (P = 0.065). Conclusion: The CT-SS would appear to capture the nutritional and functional reserve of the patient and is a useful objective measure for stratifying long-term survival in patients with good performance status undergoing potentially curative treatment for OG cancer

Disequilibrium, adaptation and the Norse settlement of Greenland

This research was supported by the University of Edinburgh ExEDE Doctoral Training Studentship and NSF grant numbers 1202692 and 1140106.There is increasing evidence to suggest that arctic cultures and ecosystems have followed non-linear responses to climate change. Norse Scandinavian farmers introduced agriculture to sub-arctic Greenland in the late tenth century, creating synanthropic landscapes and utilising seasonally abundant marine and terrestrial resources. Using a niche-construction framework and data from recent survey work, studies of diet, and regional-scale climate proxies we examine the potential mismatch between this imported agricultural niche and the constraints of the environment from the tenth to the fifteenth centuries. We argue that landscape modification conformed the Norse to a Scandinavian style of agriculture throughout settlement, structuring and limiting the efficacy of seasonal hunting strategies. Recent climate data provide evidence of sustained cooling from the mid thirteenth century and climate variation from the early fifteenth century. Archaeological evidence suggests that the Norse made incremental adjustments to the changing sub-arctic environment, but were limited by cultural adaptations made in past environments.Publisher PDFPeer reviewe

Endoscopic mucosal resection for gastroesophageal cancer in a U.K. population. Long-term follow-up of a consecutive series

Background: Endoscopic mucosal resection (EMR) of early gastric and esophageal tumors is effective and avoids the morbidity and mortality of surgery. We report the long-term results of a consecutive series of 93 endoscopic resections, during a 7-year period, in a U.K. population.<p></p> Methods: Eighty-eight patients with 93 lesions were included. EMR was performed for 64 and 29 malignant and benign lesions, respectively. Patients with malignant disease were subgrouped into “high risk” or “low risk” for recurrence.<p></p> Results: Of the 35 lesions in the low-risk group, local control was achieved in 31; 29 after 1 EMR session. Two had residual invasive carcinoma, one had treatment ceased due to pancreatic cancer, and one patient did not attend follow-up. Of the 29 lesions in the high-risk group, local control was achieved in 15; 13 after 1 EMR session. Median follow-up was 53 months. Cancer specific survival for the 45 invasive cancers (T1m and T1sm) was 93%; three patients died from their disease.<p></p> Conclusions: This study has shown for the first time in a U.K. population that EMR is effective in controlling disease in patients with local high grade dysplasia (HGD) and early invasive carcinoma, with no mortality and low morbidity.<p></p&gt

Effect of high-dose intravenous vitamin C on inflammation in cancer patients

<p>Abstract</p> <p>Background</p> <p>An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer.</p> <p>Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels.</p> <p>Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients.</p> <p>Methods</p> <p>45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods.</p> <p>CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests.</p> <p>Results</p> <p>According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment.</p> <p>There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein.</p> <p>Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments.</p> <p>Conclusions</p> <p>The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.</p> <p>In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients. Our results suggest that further investigations into the use of IVC to reduce inflammation in diseases where inflammation is relevant are warranted.</p