Background:Rurality and distance from cancer treatment centres have been shown to negatively impact cancer outcomes, but the mechanisms remain obscure.Methods:We analysed the impact of travel time to key healthcare facilities and mainland/island residency on the cancer diagnostic pathway (treatment within 62 days of referral, and within 31 days of diagnosis) and 1-year mortality using a data-linkage study with 12 339 patients.Results:After controlling for important confounders, mainland patients with more than 60 min of travelling time to their cancer treatment centre ((OR 1.42; 95% CI 1.25–1.61) and island dwellers (OR 1.32; 95% CI 1.09–1.59) were more likely to commence cancer treatment within 62 days of general practitioner (GP) referral and within 31 days of their cancer diagnosis compared with those living within 15 min. Island-dweller patients were more likely to have their diagnosis and treatment started on the same or next day (OR 1.72; 95% CI 1.31–2.25). Increased travelling time to a cancer treatment centre was associated with increased mortality to 1 year (30–59 min (HR 1.21; 95% CI 1.05–1.41), >60 min (HR 1.18; 95% CI 1.03–1.36), island dweller (HR 1.17; 95% CI 0.97–1.41).Conclusions:Island dwelling and greater mainland travel burden was associated with more rapid cancer diagnosis and treatment following GP referral even after adjustment for advanced disease; however, these patients also experienced a survival disadvantage compared with those living nearer. Cancer services may need to be better configured to suit the different needs of dispersed populations.
BackgroundResistance to chemotherapy is common in gastroesophageal cancer. Mechanisms of resistance are incompletely characterised and there are no predictive biomarkers in clinical practice for cytotoxic drugs. We used new cell line models to characterise novel chemotherapy resistance mechanisms and validated them in tumour specimens to identify new targets and biomarkers for gastroesophageal cancer.MethodsCell lines were selected for resistance to oxaliplatin, cisplatin and docetaxel and gene expression examined using Affymetrix Exon 1.0 ST arrays. Leads were validated by qRT-PCR and HPLC of tumour metabolites. Protein expression and pharmacological inhibition of lead target SPHK1 was evaluated in independent cell lines, and by immunohistochemistry in gastroesophageal cancer patients.ResultsGenes with differential expression in drug resistant cell lines compared to the parental cell line they were derived from, were identified for each drug resistant cell line. Biological pathway analysis of these gene lists, identified over-represented pathways, and only 3 pathways - lysosome, sphingolipid metabolism and p53 signalling- were identified as over-represented in these lists for all three cytotoxic drugs investigated. The majority of genes differentially expressed in chemoresistant cell lines from these pathways, were involved in metabolism of glycosphingolipids and sphingolipids in lysosomal compartments suggesting that sphingolipids might be important mediators of cytotoxic drug resistance in gastroeosphageal cancers . On further investigation, we found that drug resistance (IC50) was correlated with increased sphingosine kinase 1(SPHK1) mRNA and also with decreased sphingosine-1-phosphate lysase 1(SGPL1) mRNA. SPHK1 and SGPL1 gene expression were inversely correlated. SPHK1:SGPL1 ratio correlated with increased cellular sphingosine-1-phosphate (S1P), and S1P correlated with drug resistance (IC50). High SPHK1 protein correlated with resistance to cisplatin (IC50) in an independent gastric cancer cell line panel and with survival of patients treated with chemotherapy prior to surgery but not in patients treated with surgery alone. Safingol a SPHK1 inhibitor, was cytotoxic as a single agent and acted synergistically with cisplatin in gastric cancer cell lines.ConclusionAgents that inhibit SPHK1 or S1P could overcome cytotoxic drug resistance in gastroesophageal cancer. There are several agents in early phase human trials including Safingol that could be combined with chemotherapy or used in patients progressing after chemotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1718-7) contains supplementary material, which is available to authorized users.
Purpose: To investigate the outcomes of cataract surgery in eyes with pseudoexfoliation syndrome in a real-world National Health Service setting. Setting: Prince Charles Eye Unit, Windsor, United Kingdom. Design: Single-center retrospective cohort study. Methods: All eyes that underwent phacoemulsification cataract surgery from January 2010 to December 2019 were included. Eyes with combined intraocular surgery or with a history of ocular trauma were excluded. Eyes were classified as pseudoexfoliation (n = 280 [1.2%]) or no pseudoexfoliation (n = 23 049). The primary outcome was mean change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA). Secondary outcomes included intraoperative and postoperative complications. Results: The study comprised 23 329 eyes of 15 257 patients. Eyes in the pseudoexfoliation group were older and more likely to have multiple co-pathologies. Intraoperatively, they were more likely to experience zonular dialysis and dropped nucleus. Postoperatively, they had significantly higher rates of corneal edema, elevated intraocular pressure, postoperative uveitis, and intraocular lens subluxation and were more likely to require a second operation within 90 days. Although the pseudoexfoliation group had worse preoperative and postoperative logMAR VA, logistic regression analysis confirmed that mean VA improvement was comparable to reference group (mean ± standard deviation −0.49 ± 0.52 vs −0.55 ± 0.66, adjusted mean difference 0.02 [95% CI, −0.01 to 0.06]). Conclusions: Although patients with pseudoexfoliation had a significantly higher risk of some complications, they achieved similar VA improvements with cataract surgery compared to the nonpseudoexfoliation group. These findings will help inform the consent process and management of patient expectations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.