Wedge resection versus lobectomy in T1 lung cancer patients: a propensity matched analysis

Objectives: Performing wedge resection rather than lobectomy for primary lung cancer remains controversial. Recent studies demonstrate no survival advantage for non-anatomical resection compared to lobectomy in patients with early-stage lung cancer. The objective of this study was to investigate whether in patients with T1 tumours, non-anatomical wedge resection is associated with equivalent survival to lobectomy. Methods: This was a retrospective cohort study of patients who underwent lung resection at the Lancashire Cardiac Centre between April 2005 and April 2018. Patients were subjected to multidisciplinary team discussion. The extent of resection was decided by the team based on British Thoracic Society guidelines. The primary outcome was overall survival. Propensity matching of patients with T1 tumours was also performed to determine whether differences in survival rates exist in a subset of these patients with balanced pre-operative characteristics. Results: There were 187 patients who underwent non-anatomical wedge resection and 431 patients who underwent lobectomy. Cox modelling demonstrated no survival difference between groups for the first 1.6 years then a risk of death 3-fold higher for wedge resection group after 1.6 years (HR 3.14, CI 1.98–4.79). Propensity matching yielded 152 pairs for which 5-year survival was 66.2% for the lobectomy group and 38.5% for the non-anatomical wedge group (SMD = 0.58, p = 0.003). Conclusions: Non-anatomical wedge resection was associated with significantly reduced 5-year survival compared to lobectomy in matched patients. Lobectomy should remain the standard of care for patients with early-stage lung cancer who are fit enough to undergo surgical resection

Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer

From MDPI via Jisc Publications RouterHistory: accepted 2021-12-02, pub-electronic 2021-12-07Publication status: PublishedFunder: This research was funded by the Rosemere Cancer Foundation, Hasen Alhebshi was funded by the Libyan government.; Grant(s): No grant number available.Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment

Long-term survival in patients who had CABG with or without prior coronary artery stenting

Objective To conduct a large-scale, single-centre retrospective cohort study to understand the impact of prior percutaneous coronary intervention (PCI) on long-term survival of patients who then undergo coronary artery bypass graft (CABG). Methods Between 1999 and 2017, a total of 11 332 patients underwent CABG at a hospital in the UK. The patients were stratified into those who received PCI (n=1090) or no PCI (n=10 242) prior to CABG. A total of 1058 patients from each group were matched using propensity score matching. Kaplan-Meier estimates were used to assess risk-adjusted survival in patients with prior PCI. Cox proportional hazards (CoxPH) model was then used to assess the effect of prior PCI and other variables in patients undergoing CABG. Results The immediate postoperative outcome showed no difference in number of grafts per patients, blood transfusion, hospital stay or 30 days mortality between the groups. There was no significant difference in 5 years (90.8% vs 87.9), 10-year (76.5% vs 74.6%) and 15-year (64.4% vs 64.7%) survival between the non-PCI versus PCI groups. The Cox proportional hazards model further supports the null hypothesis as the PCI variable was found to be non-significant (CoxPH=1.03, p=0.75, CI=0.87–1.22) implying there was no difference in hazard of death for CABG patients with or without previous PCI. However, the model did yield information on the covariates that do affect the hazard of death. Conclusion There is no difference in 5-year, 10-year and 15-year survival between patients undergoing CABG with or without prior PCI. However, certain patient, preoperative and intraoperative risk factors were identified with high hazard of death which needs to be investigated further

Evaluation of the role of p53 tumor suppressor post-translational modifications and TTC5 cofactor in lung cancer

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment