The Consequences of Surgical Trauma on Intra-Peritoneal Tumour Recurrence and/or Adhesion Formation

Peritoneal carcinomatosis and postoperative intra-abdominal adhesion formation still are genuine problems after potentially curative intra-abdominal surgery. The inflammatory reaction triggered by surgical trauma to the peritoneum not only promotes adhesion formation but also stimulates tumour recurrence. Implicating a common denominator. The exact mechanisms involved are only partly clarified. To be able to prevent or reduce these surgical “complications” a thorough knowledge of the underlying process is necessary. Animal experimental models as well as cell culture models were used to unravel this process. For tumour recurrence this thesis showed that the (post) surgical intra-peritoneal microenvironment enhances successful implantation of spilled tumour cells, whereas growth of adhered tumour cell cl

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm

Background: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. Methods: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Results: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of −0.092 (−0.148, −0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: −0.128 (−0.212, −0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). Conclusion: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD. ClinicalTrials.gov Identifier: NCT03703947.</p

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning

Background and aims: Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans. Methods: Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines. Results: 271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)). Conclusions: Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising.</p

Survival After Uncomplicated EVAR in Octogenarians is Similar to the General Population of Octogenarians Without an Abdominal Aortic Aneurysm

Objective: Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians. Methods: Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately. Results: The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84–1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p < .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.