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Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer?

ABSTRACT: BACKGROUND:Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer. METHODS:Retrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ?20ms or RMSSD ?19ms). Primary endpoints were overall and cancer free survival. RESULTS:A total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ?20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607-1.493), p = 0.829; RMSSD <19ms vs RMSSD ?19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802-2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ?20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599-1.592), p = 0.924; RMSSD <19ms vs ?19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706-2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications. CONCLUSIONS:Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.

SUBMITTER: Strous MTA

PROVIDER: S-EPMC7440652 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer?

Strous M T A MTA Daniels A M AM Zimmermann F M FM van Erning F N FN Gidron Y Y Vogelaar F J FJ

PloS one 20200820 8

<h4>Background</h4>Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer.<h4>Methods</h4>Retrosp ...[more]

PMID: 32817663

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Project description:The Hippo pathway restricts the activity of transcriptional coactivators TAZ (WWTR1) and YAP. TAZ and YAP are reported to be overexpressed in various cancers, however, their prognostic significance in colorectal cancers remains unstudied. The expression levels of TAZ and YAP, and their downstream transcriptional targets, AXL and CTGF, were extracted from two independent colon cancer patient datasets available in the Gene Expression Omnibus database, totaling 522 patients. We found that mRNA expressions of both TAZ and YAP were positively correlated with those of AXL and CTGF (p<0.05). High level mRNA expression of TAZ, AXL or CTGF significantly correlated with shorter survival. Importantly, patients co-overexpressing all 3 genes had a significantly shorter survival time, and combinatorial expression of these 3 genes was an independent predictor for survival. The downstream target genes for TAZ-AXL-CTGF overexpression were identified by Java application MyStats. Interestingly, genes that are associated with colon cancer progression (ANTXR1, EFEMP2, SULF1, TAGLN, VCAN, ZEB1 and ZEB2) were upregulated in patients co-overexpressing TAZ-AXL-CTGF. This TAZ-AXL-CTGF gene expression signature (GES) was then applied to Connectivity Map to identify small molecules that could potentially be utilized to reverse this GES. Of the top 20 small molecules identified by connectivity map, amiloride (a potassium sparing diuretic), and tretinoin (all-trans retinoic acid) have shown therapeutic promise in inhibition of colon cancer cell growth. Using MyStats, we found that low level expression of either ANO1 or SQLE were associated with a better prognosis in patients who co-overexpressed TAZ-AXL-CTGF, and that ANO1 was an independent predictor of survival together with TAZ-AXL-CTGF. Finally, we confirmed that TAZ regulates Axl, and plays an important role in clonogenicity and non-adherent growth in vitro and tumor formation in vivo. These data suggest that TAZ could be a therapeutic target for the treatment of colon cancer.

Project description:BackgroundVenous thromboembolism (VTE) is the most common preventable cause of 30-day post-operative mortality, with many events occurring after hospital discharge. High-level evidence supports post-discharge VTE chemoprophylaxis following abdominal/pelvic cancer resection; however, some studies support a more tailored approach. Our objectives were to (1) identify risk factors associated with post-discharge VTE in a large cohort of patients undergoing colorectal cancer resection and (2) develop a post-discharge VTE risk calculator.MethodsPatients who underwent colorectal cancer resection from 2012 to 2016 were identified from ACS NSQIP colectomy and proctectomy procedure-targeted modules. Multivariable logistic regression was used to identify factors associated with post-discharge VTE. Incorporating pre-operative, intra-operative, and post-operative variables, a post-discharge VTE risk calculator was constructed and validated.ResultsOf 51,139 patients, 387 (0.76%) developed post-discharge VTE. Pre-operative factors associated with post-discharge VTE included BMI (e.g., morbidly obese OR 2.27, 95% CI 1.65-3.12 vs. normal BMI), and thrombocytosis (OR 1.41, 95% CI 1.03-1.92). Intra-operative factors included operative time (4-6 h OR 1.56, 95% CI 1.12-2.17; > 6 h, OR 1.85, 95% CI 1.21-2.84, vs. < 2 h), and type of operation (e.g., open partial colectomy OR 1.67, 95% CI 1.30-2.16 vs. laparoscopic partial colectomy). Post-operative factors included anastomotic leak (OR 2.05, 95% CI 1.31-3.21) and post-operative ileus (OR 1.39, 95% CI 1.07-1.79). Using the risk calculator, the predicted probability of post-discharge VTE ranged from 0.04 to 10.29%. On a 10-fold cross validation, the calculator's mean C-Statistic was 0.65.ConclusionsPatient-specific factors are associated with varying rates of post-discharge VTE. We present the first post-discharge VTE risk calculator designed for use at the time of discharge following colorectal cancer resection.

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Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer?

Publications

Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer?

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