Venous thromboembolism after esophagectomy for cancer: a systematic review of the literature to evaluate incidence, risk factors, and prophylaxis.

PURPOSE: Although esophagectomy remains the preferred treatment for esophageal cancer, it is still associated with a number of complications, including post-operative venous thromboembolism (VTE). The aim of this study was to summarize the reported incidence of VTE after esophagectomy, its risk factors, and prevention strategies. METHODS: We conducted a systematic search of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Fourteen studies met our inclusion criteria and were selected in the present review. Overall, we identified 9768 patients who underwent esophagectomy, with a post-operative VTE rate of 4% (440 patients). The reported risk factors for VTE included advanced age, American Society of Anesthesiologists (ASA) class III or IV, a history of cardiovascular or pulmonary disease, and the implementation of preoperative chemo-radiotherapy. Postoperative acute respiratory distress syndrome was also associated with VTE. No universally applied prevention strategies for VTE after esophagectomy were identified in the literature. CONCLUSIONS: Despite advances in perioperative care, VTE after esophagectomy still represents a source of morbidity for about 4% of patients. Low molecular weight heparin is suggested as the routine standard prophylactic regimen after esophageal cancer surgery.

Gastrectomy for Cancer: A 15-Year Analysis of Real-World Data from the University of Athens.

Background and Objectives: Encouraging data have been reported from referral centers following gastrointestinal cancer surgery. Our goal was to retrospectively review patient outcomes following gastrectomy for gastric or gastroesophageal junction (GEJ) cancer at a high-volume unit of the University of Athens. Methods: The enrollment period was from June 2003 to September 2018. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were constructed to identify variables independently associated with time-to-event outcomes. Results: A total of 205 patients were analyzed. R0 resection was achieved in 183 (89.3%) patients and was more likely to occur following neoadjuvant chemotherapy (p = 0.008). Recurrence developed in 46.6% of our cohort and the median disease-free survival was 31.2 months. On multivariate analysis, only staging (HR = 2.15; 95% CI: 1.06-4.36) was independently associated with increased risk of recurrence. All-cause mortality was 57.2% and the median time of death was 40.9 months. On multivariate regression, staging (HR: 1.35; 95% CI: 1.11-1.65) and recurrence (HR: 2.87; 95% CI: 1.32-6.22) predicted inferior prognosis. Conclusions: Gastrectomy at the University of Athens has yielded favorable outcomes for patients with GEJ cancer.

Atrial Fibrillation Is Associated with Cognitive Impairment, All-Cause Dementia, Vascular Dementia, and Alzheimer's Disease: a Systematic Review and Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia in patients with stroke history. However, the association between AF and cognitive impairment in broader populations is less clear. OBJECTIVE: To systematically review and quantitatively synthesize the existing evidence regarding the association of AF with cognitive impairment of any severity and etiology and dementia. METHODS: Medline, Scopus, and Cochrane Central were searched in order to identify studies investigating the association between AF and cognitive impairment (or dementia) cross-sectionally and longitudinally. Studies encompassing and analyzing exclusively patients with stroke history were excluded. A random-effects model meta-analysis was conducted. Potential sources of between-study heterogeneity were investigated via subgroup and meta-regression analyses. Sensitivity analyses including only studies reporting data on stroke-free patients, vascular dementia, and Alzheimer's disease were performed. RESULTS: In total, 43 studies were included. In the pooled analysis, AF was significantly associated with dementia (adjusted OR, 1.6; 95% CI, 1.3 to 2.1; I2, 31%) and the combined endpoint of cognitive impairment or dementia (pooled adjusted OR, 1.5; 95% CI, 1.4 to 1.8; I2, 34%). The results were significant, even when studies including only stroke-free patients were pooled together (unadjusted OR, 2.2; 95% CI, 1.4 to 3.5; I2, 96%), but the heterogeneity rates were high. AF was significantly associated with increased risk of both vascular (adjusted OR, 1.7; 95% CI, 1.2 to 2.3; I2, 43%) and Alzheimer's dementia (adjusted HR, 1.4; 95% CI, 1.2 to 1.6; I2, 42%). CONCLUSION: AF increases the risk of cognitive impairment, all-cause dementia, vascular dementia, and Alzheimer's disease. Future studies should employ interventions that may delay or even prevent cognitive decline in AF patients.

Esophageal cancer surgery in Greece during the era of the financial crisis.

The aim of this study is to describe outcomes of esophageal cancer surgery in a quaternary upper gastrointestinal (GI) center in Athens during the era of the Greek financial crisis. We performed a retrospective analysis of patients that underwent esophagectomy for esophageal or gastroesophageal junction (GEJ) cancer at an upper GI unit of the University of Athens, during the period January 2004-June 2019. Time-to-event analyses were performed to explore trends in survival and recurrence. A total of 146 patients were identified. Nearly half of the patients (49.3%) underwent surgery during the last 4 years of the financial crisis (2015-2018). Mean age at the time of surgery was 62.3 ± 10.3 years, and patients did not present at older ages during the recession (P = 0.50). Most patients were stage III at the time of surgery both prior to the recession (35%) and during the financial crisis (39.8%, P = 0.17). Ivor-Lewis was the most commonly performed procedure (67.1%) across all eras (P = 0.06). Gastric conduit was the most common form of GI reconstruction (95.9%) following all types of surgery (P < 0.001). Pre-recession anastomoses were usually performed using a circular stapler (65%). Both during (88.1%) and following the recession (100%), the vast majority of anastomoses were hand-sewn. R0 resection was achieved in 142 (97.9%) patients. Anastomosis technique did not affect postoperative leak (P = 0.3) or morbidity rates (P = 0.1). Morbidity rates were not significantly different prior to (25%), during (46.9%), and after (62.5%) the financial crisis, P = 0.16. Utilization of neoadjuvant chemotherapy (26.9%, P = 0.90) or radiation (8.4%, P = 0.44) as well as adjuvant chemotherapy (54.8%, P = 0.85) and irradiation (13.7%, P = 0.49) was the same across all eras. Disease-free survival (DFS) and all-cause mortality rates were 41.2 and 47.3%, respectively. Median DFS and observed survival (OS) were 11.3 and 22.7 months, respectively. The financial crisis did not influence relapse (P = 0.17) and survival rates (P = 0.91). The establishment of capital controls also had no impact on recurrence (P = 0.18) and survival (P = 0.94). Austerity measures during the Greek financial crisis did not influence long-term esophageal cancer outcomes. Therefore, achieving international standards in esophagectomy may be possible in resource-limited countries when centralizing care.

Association Between Atrial Fibrillation and Cognitive Impairment in Individuals With Prior Stroke: A Meta-Analysis and Meta-Regression Analysis.

Background and Purpose- Atrial fibrillation (AF) is the most common chronic arrhythmia. Dementia and cognitive impairment (CI) are major burdens to public health. The prevalence of all 3 entities is projected to increase due to population aging. Previous reports have linked AF with a higher risk of CI and dementia in patients without prior stroke. Stroke is known to increase the risk for dementia and CI. It is unclear if AF in patients with history of stroke can further increase the risk for dementia or CI. Our purpose was to evaluate the impact of AF on risk for dementia or CI among patients with history of stroke. Methods- Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Pubmed, Scopus, and Cochrane central were searched. The outcomes of interest were dementia, CI, and the composite end point of dementia or CI. A random-effect model meta-analysis was performed. Meta-regression analysis was also performed. Publication bias was assessed with the Egger test and with funnel plots. Results- Fourteen studies and 14 360 patients (1363 with AF) were included in the meta-analysis. In the meta-analysis of adjusted odds ratio, AF was associated with increased risk of CI (odds ratio, 1.60 [95% CI, 1.20-2.14]), dementia (odds ratio, 3.11 [95% CI, 2.05-4.73]), and the composite end point of CI or dementia (odds ratio, 2.26 [95% CI, 1.61-3.19]). The heterogeneity for the composite end point of dementia or CI was moderate (adjusted analysis). The heterogeneity for the analysis of the end point of CI only was substantial in the unadjusted analysis and moderate in the adjusted analysis. The heterogeneity for the end point of dementia only was moderate in the unadjusted analysis and zero in the adjusted analysis. Conclusions- Our results indicate that an association between AF and CI or dementia is patients with prior strokes is possible given the persistent positive associations we noticed in the unadjusted and adjusted analyses. The heterogeneity levels limit the certainty of our findings.

Venous Thromboembolism Following Major Abdominal Surgery for Cancer: A Guide for the Surgical Intern.

BACKGROUND: Venous thromboembolism (VTE) is a term used to compositely describe deep vein thrombosis (DVT) and pulmonary embolism (PE). Overall, the incidence of VTE after major abdominal and pelvic surgery has been reported to be between 10% and 40%. OBJECTIVE: The aim of this study is to estimate the incidence of post-operative VTE in patients undergoing major abdominal surgery for cancer, to identify risk factors associated with VTE, and to assess available thromboprophylaxis tools. METHODS: A Medline and Cochrane literature search from database inception until February 1st, 2021 was performed according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. RESULTS: Thirty-one studies met our eligibility criteria and were included in the current review. In total, 435,492 patients were identified and the overall incidence of VTE was 2.19% (95% CI: 1.82-2.38). Τhe following risk factors were associated with VTE: smoking, advanced age (>70 years), a history of diabetes mellitus, American Society of Anesthesiologists' (ASA) classification of Physical Health class III or IV, a history of cardiovascular or pulmonary disease, a history of DVT or PE, elevated plasma fibrinogen level, c-reactive protein (CRP) level, cancer stage III or IV, postoperative acute respiratory distress syndrome (ARDS), prolonged postoperative hospital stay, previous steroid use, history of Inflammatory Bowel Disease (IBD), heart failure and neoadjuvant and adjuvant chemotherapy. CONCLUSION: VTE remains an important complication after major abdominal surgery for cancer and seems to increase mortality rates.

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19.

Comprehensive review of hemolysis in ventricular assist devices.

Ventricular assist devices (VADs) have played an important role in altering the natural history of end-stage heart failure. Low-grade hemolysis has been traditionally described in patients with VADs, indicating effective device functionality. However, clinically significant hemolysis could be crucial in terms of prognosis, calling for prompt therapeutic actions. The absence of solid and widely approved diagnostic criteria for clinically significant hemolysis, render the utilization of hemolysis laboratory markers challenging. Hemolysis incidence varies (5%-18%) depending on definition and among different VAD generations, being slightly higher in continuous-flow devices than in pulsatile devices. Increased shear stress of red blood cells and underlying device thrombosis appear to be the main pathogenetic pathways. No certain algorithm is available for the management of hemolysis in patients with VADs, while close clinical and laboratory monitoring remains the cornerstone of management. Imaging examinations such as echocardiography ramp test or computed tomography scan could play a role in revealing the underlying cause. Treatment should be strictly personalized, including either pharmacological (antithrombotic treatment) or surgical interventions.

Perioperative Management of Antiplatelet Therapy in Patients With History of Coronary Artery Disease Undergoing Surgery for Esophageal Cancer: A Single-center Experience.

AIM: To present the experience of the upper Gastrointestinal Unit of the Surgical Department of National and Kapodistrian University of Athens in order to inform surgeons of the exact harms and benefits associated with their decisions concerning management of antiplatelet therapy. MATERIALS AND METHODS: This was a single-center study of patients who underwent surgery for esophageal cancer and had concomitant coronary artery disease from 1/1/2005 to 31/7/2017. Patients were divided into two cohorts based on when their antiplatelet therapy was stopped (<7 vs. ≥7 days). Esophageal cancer was classified as esophageal only or as Siewert type I, II, or III based on tumor location at the gastroesophageal junction. A univariate logistic regression model was developed to assess the relationship between baseline variables and myocardial infraction, mortality, bleeding and stroke after the operation. For all tests, differences with a value of p<0.05 were considered significant. RESULTS: During the study period, 135 esophagectomies were performed for esophageal cancer. Almost 17% of them had concomitant coronary artery disease medically managed with antiplatelet therapy. No difference was found in terms of myocardial infarction, stroke or severe bleeding events between patients that stopped antiplatelet therapy for more or less than 7 days before esophagectomy. CONCLUSION: It is a reasonable approach to discontinue antiplatelet therapy for more than 7 days before surgery, especially in such a population of patients with esophageal cancer that require complex operations with high bleeding risk.

Heart transplantation versus left ventricular assist devices as destination therapy or bridge to transplantation for 1-year mortality: a systematic review and meta-analysis.

BACKGROUND: The optimal treatment for advanced heart failure (HF) patients with regards to mortality remains unknown. Heart transplantation (HTx) and left ventricular assist devices (LVAD) used either as a bridge to transplant (BTT) or destination therapy (DT) have been compared in a number of studies, without definite conclusions with regards to mortality benefit. We sought to systematically review the pertinent literature and perform a meta-analysis of all the available studies presenting head-to-head comparisons between HTx and LVAD BTT or LVAD DT for late (>6 months) all-cause mortality. METHODS: We performed a systematic search of Medline and Cochrane Central databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a meta-analysis of late mortality comparing HTx vs. BTT LVAD and HTx vs. DT LVAD using a random effects model. RESULTS: Eight studies were included in our meta-analysis, reporting data on 7,957 patients in total. Although the available studies are of high quality [8 stars in Newcastle-Ottawa Scale (NOS) on average], there is paucity of mortality data. Specifically, seven studies compared HTx with BTT and five studies compared HTx with DT for 1-year mortality. Our pooled estimates showed that there was no difference in late mortality among these strategies. CONCLUSIONS: Our meta-analysis highlights the small number and the heterogeneity of available studies referring to the optimal invasive management of advanced HF, and shows that there are no differences between HTx and LVAD for these patients with regards to late mortality.

The predictive value of baseline pulmonary hypertension in early and long term cardiac and all-cause mortality after transcatheter aortic valve implantation for patients with severe aortic valve stenosis: A systematic review and meta-analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a safe and effective alternative to surgical aortic valve replacement (SAVR) for the treatment of severe aortic valve stenosis (AS). The impact of concomitant baseline elevated pulmonary artery pressures on outcomes after TAVI has not been established, since different studies used different definitions of pulmonary hypertension (PH). OBJECTIVE: To determine the association of PH with early and late cardiac and all-cause mortality after TAVI. METHODS: We performed a meta-analysis of studies comparing patients with elevated pulmonary artery pressures (defined as pulmonary hypertension or not) versus patients without elevated pulmonary artery pressures undergoing TAVI. We first performed stratified analyses based on the different PH cut-off values utilized by the included studies and subsequently pooled the studies irrespective of their cut-off values. We used a random effects model for the meta-analysis and assessed heterogeneity with I-square. Separate meta-analyses were performed for studies reporting outcomes as hazards ratios (HRs) and relative risks (RRs). Subgroup analyses were performed for studies published before and after 2013. Meta-regression analysis in order to assess the effect of chronic obstructive pulmonary disease and mitral regurgitation were performed. RESULTS: In total 22 studies were included in this systematic review. Among studies presenting results as HR, PH was associated with increased late cardiac mortality (HR: 1.8. 95% CI: 1.3-2.3) and late all-cause mortality (HR: 1.56; 95% CI: 1.1-2). The PH cut-off value that was most likely to be associated with worst outcomes among the different endpoints was pulmonary artery systolic pressure of 60 mm Hg (HR: 1.8; 95% CI: 1.3-2.3; I2 = 0, for late cardiac mortality and HR: 1.52; 95% CI: 1-2.1; I2 = 85% for late all-cause mortality). CONCLUSION: This systematic review and meta-analysis emphasizes the importance of baseline PH in predicting mortality outcomes after TAVI. Additional studies are needed to clarify the association between elevated baseline pulmonary artery pressures and outcomes after TAVI.