Preoperative Blood Samples Research Articles

Abstract 2293: Tumor-informed fixed and patient-specific panels for minimal residual disease (MRD) detection in early-stage NSCLC:a head-to-head comparison

Abstract Introduction: Detection of minimal residual disease (MRD) by ctDNA based on tumor-informed or tumor-naive strategy could be used as an effective method to predict the relapse of NSCLC. As for tumor-informed strategy,both fixed panel and patient-specific panel are promising methods in MRD monitoring. Patient-specific panel can be used to monitor tissue specific somatic mutations individually. Besides, fixed panel can make up for the deficiency caused by organizational heterogeneity. In this study, we compared the monitoring effect of novel tumor-informed fixed and patient-specific panels. Methods: 81 patients with stage I-III resected NSCLC were analyzed, including 45 patients (55.6%) with stage I, 15 (18.5%) with stage II and 21 (25.9%) with stage III. Tumor samples were obtained at surgery. Preoperative blood samples (baseline) were analyzed by both tumor-informed fixed and patient-specific panels based on hybrid capture. Tumor-informed fixed panel was performed by using ultra-deep (60000X) next-generation sequencing with 158 gene panel spanning 118 kb of human genome. Patient-specific panel was also performed by using ultra-deep (100000X) next-generation sequencing with customized 40 single nucleotide variants identified using whole-exome sequencing. Results: Tumor-informed fixed panel monitored 212 mutations (median, 3; range, 0-7). Most of them (95.3%) were matched in the corresponding tumor tissues. For patient-specific panels, 91% of patients were customized design 40 mutations, affected by the detection of tissue somatic mutations. Based on fixed or patient-specific panel, ctDNA mutations were detected in 46.9% vs 49.4% (P=0.75) at baseline, respectively (Stage I: 35.6% vs 37.8%, P= 0.83; Stage II: 53.3% vs 60%, P=0.71; Stage III: 66.7% vs 66.7%). Conclusions: Both tumor-informed fixed and patient-specific panel NGS assay can detect the presence of ctDNA in early-stage NSCLC. However, the detection rate of preoperative ctDNA mutations was slightly higher based on patient-specific panel. Citation Format: Pengpeng Zhang, Zetian Gong, Yue Yu, Xiaoxuan Wang, Lei Ye, Xiaoqiang Wang, Xuan Tang, Chao Zhang, Wanglong Deng, Chao Song, Qing Xu, Yansong Li, Wei Wang. Tumor-informed fixed and patient-specific panels for minimal residual disease (MRD) detection in early-stage NSCLC:a head-to-head comparison [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2293.

Is Systemic Inflammatory Response Index (SIRI) a Reliable Tool for Prognosis of Gastric Cancer Patients Without Neoadjuvant Therapy?

The systemic inflammatory response index (SIRI), which depends on peripheral neutrophil, monocyte, and lymphocyte count, was found as an effective prognostic indicator for various malignancies. This study aims to investigate the predictive value of preoperative SIRI in the prognosis of gastric cancer patients without neoadjuvant therapy. The patients who underwent gastric cancer surgery in Marmara University Hospital's General Surgery Department between 2019 and 2021 were analyzed retrospectively. SIRI was calculated from preoperative peripheral blood samples' neutrophil, lymphocyte, and monocyte count. The optimal cut-off value for SIRI was calculated by the receiver operating characteristics (ROC) curve and was found to be 1.35. The clinicopathological outcomes and overall survival (OS) were analyzed under two groups according to the SIRI values lower or higher than 1.35. The number of eligible patients was 199. The median follow-up time was 25 (1-56) months. The higher SIRI was associated with male gender (p = 0.044), lower serum albumin (0.002) level, and Clavien-Dindo (CD) Grade III and higher complications (p = 0.018). However, there was no significant difference between the groups regarded pathological tumor, nodes, and metastases (TNM) stages, histological grade, and Lauren Type. In addition, OS and stage-specific OS were similar between the groups. SIRI may be a valuable and effective predictive indicator for postoperative morbidity. The prognostic performance of SIRI on long-term OS is still controversial. Further investigations are needed into this topic.

Perioperative ctDNA-Based MRD Detection in NSCLC—Response

We appreciate Yu and colleagues for their interest in our study and we would like to give our reply to their concerns.In LUNGCA-1 study, a total of 330 patients with resected tumor tissues and preoperative blood samples available were included in prognostic analysis, and all but one of these 330 patients had at least one available plasma sample at postoperative 3 days and/or 1 month (1). Thus, preoperative circulating tumor DNA (ctDNA) and postoperative ctDNA-based molecular residual disease (MRD) analysis was done for 330 and 329 patients respectively, as reflected in the number of patients in both Fig. 1 and detailed sample information listed in Supplementary Table S5. LUNGCA-1 study was aimed at evaluating the potential of ctDNA-based MRD during perioperative period for predicting disease relapse and identifying patients who may potentially benefit from adjuvant therapy, and throughout the entire article, there was no mentioning of ctDNA testing after adjuvant therapy.We designed two postoperative blood collection timepoints for ctDNA-based MRD detection. We found that the amount of cell-free DNA increased significantly at 3 days after surgery, and then dropped at postoperative 1 month. ctDNA status at postoperative 3 days was significantly associated with recurrence-free survival (P < 0.001), although with lower prognostic value than ctDNA status at postoperative 1 month (HR: 8.6 vs. 14.3). Among 5 patients whose ctDNA was positive at postoperative 3 days but negative at the other two perioperative timepoints, 4 (80.0%) experienced disease relapse, and the only one who remained disease free had received adjuvant therapy and had a relatively short follow-up (437 days) at the time of data lockdown. Therefore, ctDNA at 3 days after surgery proved to be useful in complementing MRD analysis at postoperative 1 month by increasing detection sensitivity without sacrificing specificity.The current LUNGCA-1 study focused on the association of postoperative MRD detection with disease relapse. The clinical relevance of preoperative ctDNA concentration was not a concern of the published paper and therefore not reported. The criteria for determining ctDNA status had been clearly described in the paragraph “Next-generation sequencing and ctDNA analysis” of the Materials and Methods section, as well as the Supplementary Methods. Disease relapse included locoregional recurrence and distant metastases after surgery, which was determined by radiological methods and/or biopsy.See the original Letter to the Editor, p. 1155W. Chen reports other support from Genecast outside the submitted work. No disclosures were reported by the other authors.

Abstract OT3-20-04: SerMa – Seroma formations of the Mammary gland in breast cancer patients after mastectomy and implant-based reconstruction (EUBREAST 5)

Abstract Background Postoperative seroma formations are one of the most common and serious complications after implant-based breast reconstruction and can lead to implant and thus breast loss. The cause hasn`t yet been clarified. Hypothesis generating and thus as a basis for this multicenter study is the suspicion of a connection between immunological-inflammatory processes that promote the development of a seroma. First promising results of the pilot phase (SerMa pilot) have been published and gave the first impulse for this study. Trial design The SerMa (EUBREAST 5) study is a prospective, multicenter, interventional, international study including patients with primary breast cancer and a skin-/nipple-sparing mastectomy combined with an implant-based reconstruction method. Control groups were chosen to work out common group-specific differences. Intra- or directly preoperatively collected blood as well as intraoperatively collected local smear using swabs are preserved specimens. Follow-up includes visits after 2 and 6 weeks as well as after 6 months. In case of a seroma formation fluid aspirations are preserved for laboratory analyses. Eligibility criteria: The study population contains patients with primary diagnosis of breast cancer scheduled for skin-/nipple-sparing mastectomy and implant-based breast reconstruction. The three control groups are: one with simple mastectomy without breast reconstruction as well as healthy persons with implant insert but without breast cancer after bilateral risk reducing mastectomy or last in case of purely cosmetic implant placement. Specific aims: The main objective of the study is to identify a patient subgroup with an increased risk of seroma development for future precision elucidation regarding the prevention of postoperative complications such as implant and thus breast loss. FACS-/Bioplex and microbiome analyses will be applied for the detection of certain immune markers, microbiobes and microbiome diversity using preoperative blood samples, intraoperative local smear collection and in case of later seroma formations also postoperative seroma aspirations. Secondary endpoints include the comparison of these factors and elaborate differences between study and control groups. Furthermore clinico-pathological factors as well as different surgical methods are compared. Statistical methods: A statistical plan for this analysis was specifically developed (Power analyses with Wilcoxon-Mann-Whitney test) and leads to a number of 300 participants per group. Target accrual: Planned start: Q1/2023 Contact: EUBREAST e.V. Citation Format: Nina Ditsch, Nicole Pochert, Udo Jeschke, Mariella Schneider, Melitta Koepke, Maggie Banys-Paluchowski, Claudia Traidl-Hoffmann, Christian Dannecker, Thorsten Kühn. SerMa – Seroma formations of the Mammary gland in breast cancer patients after mastectomy and implant-based reconstruction (EUBREAST 5) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-04.

Clinical significance of the preoperative prognostic nutritional index on age/comorbidity burdens in patients with resectable non-small cell lung cancer.

Objective nutritional scoring systems using preoperative blood samples have shown the potential to predict the postoperative outcomes of patients with non-small cell lung cancer (NSCLC). However, it remains unclear whether the prognostic impact depends on age and comorbid burdens. We conducted this study to validate the impact of preoperative nutritional status, stratified with age and comorbidity. We reviewed the preoperative prognostic nutritional index (PNI) and postoperative outcomes of 713 consecutive patients with completely resected NSCLC. We identified the optimal cutoff values of the PNI as 46. Significantly higher postoperative complication rates and worse survival rates were observed in the low PNI (≤ 46) group, regardless of age/comorbidity burdens. Multivariate analysis showed that a low PNI (≤ 46) was an independent prognostic factor for poor overall survival (hazard ratio: 2.5). A matched-pair analysis gave consistent results, showing that a low PNI (≤ 46) was an independent prognostic factor for poor overall survival (OS; hazard ratio: 1.8) and recurrence-free survival (RFS; hazard ratio: 1.6). Nutritional status, indexed by the PNI, is a strong prognostic factor for the postoperative outcomes of patients undergoing curative resection for NSCL, regardless of age/comorbidity burdens.

Plasma Lipoprotein Lipase Is Associated with Risk of Future Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy

Carotid plaque intraplaque haemorrhage (IPH) is associated with future cardiovascular events. It was hypothesised that plasma proteins associated with carotid plaque IPH are also likely to be associated with major adverse cardiovascular events (MACE) after carotid endarterectomy (CEA). In pre-operative blood samples from patients undergoing CEA within the Athero-Express biobank, proteins involved in cardiovascular disease were measured using three OLINK proteomics immunoassays. The association of proteins with IPH was analysed using logistic regression analyses. Subsequently, the association of the IPH associated plasma proteins with the three year post-operative risk of MACE (including stroke, myocardial infarction, or cardiovascular death) was analysed. Within the three year follow up, 130 patients (18.9%) out of 688 symptomatic and asymptomatic patients undergoing CEA developed MACE. Six out of 276 plasma proteins were found to be significantly associated with IPH, from which only lipoprotein lipase (LPL) was associated with the post-operative risk of MACE undergoing CEA. Within the 30 day peri-operative period, high plasma LPL was independently associated with an increased risk for MACE (adjusted hazard ratio [HR] per standard deviation [SD] 1.60, 1.10 - 2.30), p = .014). From 30 days up to three years, however, high LPL was associated with a lower risk for MACE (adjusted HR per SD 0.80, 0.65 - 0.99, p = .036). High LPL concentrations were found to be associated with a higher risk for MACE in the first 30 post-operative days but associated with a lower risk MACE in the time period from 30 days to three years, meaning that LPL has different hazards at different time points.

Evaluation of Afamin Level after Bariatric Surgery in Patient with Obesity.

The aim of this study is to evaluate afamin levels after weight loss in obese patients who underwent laparoscopic sleeve gastrectomy (LSG) and to investigate the relationship between them. In addition, after bariatric surgery, thyroid stimulating hormone (TSH), thyroxine (T4), low-density lipoprotein (LDL), very low-density protein (VLDL), total cholesterol, triglyceride (TG), high-density lipoprotein (HDL), insulin, and hemoglobin A1c (HgbA1c) levels were evaluated. Preoperative and postoperative 6th month venous blood samples were obtained from 43 patients included in this study. The preoperative and postoperative 6th month body mass index (BMI), TG, total cholesterol, VLDL, HDL, insulin, HgbA1c, TSH, T4, and afamin levels of the patients who underwent bariatric surgery with obesity were compared. Serum afamin levels of patients decreased at 6 months postoperatively; however, it was not statistically significant. We observed a statistically significant decrease in patients' BMI, HDL, VLDL, TG, total cholesterol, TSH, T4, HgbA1c, and insulin values (p < 0.05). There were significant increases in HDL and T4 values. The change in LDL value was statistically insignificant. Recent studies have shown that there may be a cause-effect relationship between afamin and obesity. In our study, we observed a decrease in serum afamin levels after weight loss following bariatric surgery. In addition, we think that afamin may be used as a potential marker of metabolic syndrome in the future and may lead to improvements in the medical treatment of obesity.

The Evaluation of Dynamic Thiol/Disulfide Homeostasis in Papillary Thyroid Carcinoma

Objectives: Aim of this study is to analyze the correlation between thiol/disulfide homeostasis (TDH) and papillary thyroid carcinoma (PTCA) and to reveal the possible impact of TDH on the development of PTCA. Material and Methods: Preoperative venous blood sampling was obtained from the patients having applied to our hospital due to euthyroid nodular goiter and detected with suspected malignancy or malignant cytology in FNAB, according to the BETHESDA system. Those whose postoperative histopathological results proved the presence of PTCA were involved in this study. Healthy volunteers who were without any thyroid nodules and thyroid dysfunction. Results: The number of participants in the patient and control groups was 34 and 101, respectively. Compared to the control group, native thiol (μmol/L), total thiol (μmol/L), and native thiol/total thiol × 100 values were ascertained to be lower in the patient group with PTCA; however, these values were not statistically significant. Disulfide, disulfide/native thiol × 100, and disulfide/total thiol × 100 values were detected to be lower in the patient group with PTCA, but not statistically significant. When the patients with PTCA were assessed within themselves, TDH parameters were not associated with the PTCA subtype, the number of foci, the presence of lymphovascular invasion, and the presence of metastatic lap. Conclusion: Considering the parameters of PTCA and TDH, the results were not statistically significant. And besides postoperative histopathological findings such as the PTCA subtype, the number of foci, the presence of lymphovascular invasion, and presence of metastatic lap were not correlated with THD parameters.

PS-C28-6: HIGH TESTOSTERONE AND LOW ESTRADIOL SERA LEVELS ARE ASSOCIATED WITH UNSTABLE PLAQUE COMPOSITION IN MEN WITH SEVERE CAROTID ATHEROSCLEROSIS

Background and Objectives: Ischemic strokes caused by the rupture of unstable atherosclerotic plaques in the carotid arteries, are leading causes of mortality and disability worldwide. Sex differences exist in plaque composition, where men are more likely to develop unstable plaques than women. Sex hormones affect vascular reactivity and inflammation, but it remains unclear if they are involved in plaque instability and how their role differs in men and women. Herein, we investigated the association between circulating endogenous sex hormone levels and plaque composition/instability in men and women with severe carotid atherosclerosis. Design and method: Pre-operative fasting blood samples and plaque specimens were collected from post-menopausal women and men greater than 55 years old with severe carotid atherosclerosis who underwent a carotid endarterectomy at McGill-affiliated hospitals in Montreal, Canada. Plaque composition and stability were examined by experienced vascular pathologists according to gold-standard histological classifications. Liquid chromatography-tandem mass spectrometry-based methods were developed to quantify endogenous sex hormones, 17ß-estradiol (E2), testosterone, androstenedione, and dehydroepiandrosterone, in sera samples. Results: Subjects (n = 460) had a mean age of 71.0 ± 9.0, were 68.9% male, and had various comorbidities (hypercholesterolemia [82.6%], hypertension [84.6%], type 2 diabetes [34.5%]). Clinical characteristics were similar among post-menopausal women (n = 143) and men (n = 317) with stable versus unstable plaques. Men had a significantly greater proportion of unstable versus stable plaques compared to women (men unstable: 61.5%, women unstable: 41.3%; P &lt; 0.001), characterized predominantly by a large lipid-rich core, hemorrhage, and high presence of inflammatory cell infiltration. Men with unstable plaques had significantly higher levels of testosterone than men with stable plaques (P = 0.004). In men, testosterone levels were inversely associated with fibrosis (P &lt; 0.05), while directly associated with unstable plaque features, including greater lipid core size (P &lt; 0.05), and a greater presence of foam cells (P &lt; 0.05), neovascularization (P &lt; 0.01), and plaque (P &lt; 0.01) and cap inflammation (P &lt; 0.05). No associations were observed between testosterone levels and plaque features in women. Endogenous E2 levels were inversely associated with neovascularization (P &lt; 0.05) and plaque and cap inflammation (P &lt; 0.001) in men, while inversely associated with fibrosis levels in women (P &lt; 0.05). Conclusion: Our findings suggest that higher testosterone and lower E2 levels are associated with unstable plaque composition in men with carotid atherosclerotic disease and may partly explain the higher proportion of unstable plaques observed among men than women of similar age and comorbidity status. Instead, in women, estradiol appears to play a detrimental role in plaque instability by inversely affecting fibrous tissue levels (a key stabilizing feature of plaques).

Hematological and Biochemical Responses of Newly Formulated Primary Root Canal Obturating Material: An In Vivo Study.

Background and objective Any drug or medicinal agent, when implanted into the body, gets biotransformed by various organ systems and the toxic byproducts of this process alter the normal physiological process. In this experimental study, we aimed to quantify the safety of newly formulated primary root canal obturating material by investigating the hematological and biochemical parameters related to liver function. Methodology Forty-eight Wistar rats (weighing 250-350 grams) were classified into three groups (n=16) through random allocation. Preoperative blood samples were collected by puncturing the orbital venous plexus, the values of which were used as control. Zinc oxide eugenol (ZOE), calcium hydroxide iodoform paste (Metapex), and newly formulated triple antibiotic obturating paste (TAOP) were implanted (100 µg) into dorsal connective tissues. Blood samples on the seventh, 15th, and 30th postoperative days were evaluated respectively by analyzing hematological, hepatic, and, renal function tests for acute and chronic inflammatory responses. Results The intra-group and inter-group comparisons among all the test materials after seven days exhibited high significance in terms of hemoglobin (Hb), mean corpuscular volume (MCV), neutrophils, andserum glutamic-oxaloacetic transaminase (SGOT) (p<0.001), while others showed mixed responses (p<0.05 to p>0.05). After 15 days, the comparisons showed high significance with respect to packed cell volume(PCV), mean cell volume (MCV), and serum creatinine (p<0.001), while others showed significant to nonsignificant differences (p<0.05 to p>0.05). At the end of 30 days, all the parameters showed mixed responses (p<0.001 to p>0.05). Conclusion The newly formulated obturating material TAOP showed lower adverse hematological, hepatic, and renal effects in experimental animals compared to other test materials, with most parameters reverting to normal after 30 days.

Systemic Metal Ion Concentrations in Patients With Hip and Knee Megaprostheses: A Prospective Cohort Study.

Local tissue and serum metal ions have been shown to be elevated in some metal-on-metal and metal-on-polyethylene joint replacements. Local elevations have been linked to adverse local tissue reactions in some patients, and systemic elevation has been less commonly implicated cardiac and neurologic issues. Using a prospective study design, we aimed to identify the changes in serum metal ion levels after hip or knee megaprosthesis reconstruction. Furthermore, we will evaluate the occurrence of adverse effects and complications, possibly linked to metal ion elevation. Fourteen consecutive patients receiving a Modular Universal Tumor Revision System megaprosthesis were enrolled. Blood samples were collected preoperatively and postoperatively to determine the serum ion concentrations of aluminum, chromium, cobalt, and silver. To evaluate the safety of the megaprostheses and the subsequently possible related (elevated) serum metal ion concentrations, all adverse effects and complications were registered until last outpatient clinic visit at the time of this study. Compared to the preoperative median serum concentrations, the postoperative median serum concentrations of chromium, silver, and cobalt increased 11-fold, 62-fold, and 64-fold, respectively. The median serum concentration of aluminum increased with 16%. Elevations were primarily noted in patients with knee prostheses. Eight patients had no adverse effects or complications during the period between preoperative and postoperative blood sampling. One adverse effect directly related to the serum metal ion concentrations, namely argyria, was observed. This study documents significantly elevated concentrations of the metal ions, but only one adverse effect directly related to the metal ion concentrations was observed. Future studies are needed to further assess the impact of elevated metal ion levels after megaprostheses, specifically knee implants, which are metal-on-metal.

Prognostic impact of postoperative circulating tumor DNA as a molecular minimal residual disease marker in patients with pancreatic cancer undergoing surgical resection.

We aimed to clarify the prognostic impact of postoperative circulating tumor DNA (ctDNA) shortly after pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC). Preoperative and paired postoperative blood samples were obtained from 66 patients in patients with PDAC. Cell-free DNA was extracted from the plasma, and KRAS mutations, as a benchmark of ctDNA, were examined using droplet digital PCR. Disease-free survival (DFS) and overall survival (OS) were compared between patients with presence and absence of ctDNA. In univariate analysis, patients with detectable postoperative ctDNA showed worse survival than those with undetectable in both DFS (P=.034) and OS (P=.022). Multivariate analysis also revealed that the presence of postoperative ctDNA was an independent risk factor for recurrence (hazard ratio: 2.677, P=.011). In contrast, preoperative ctDNA detection did not affect long-term outcomes. These trends persisted in 34 patients with resectable PDAC who underwent resection after neoadjuvant chemotherapy. Patients with detectable postoperative ctDNA were more prone to developing hepatic recurrence than those with undetectable postoperative ctDNA (P=.039). Postoperative ctDNA, as a minimal residual marker, can be useful for predicting the risk of recurrence in patients with PDAC even after curative resection.

Longitudinal profiling in patients undergoing cardiac surgery reveals postoperative changes in DNA methylation

BackgroundCardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant pulmonary, cardiovascular, and neurologic complications. Commensurate with the immune and inflammatory response are changes in the heart and vasculature itself, which together drive postoperative complications through mechanisms that are poorly understood. Longitudinal DNA methylation profiling has the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass.ResultsWhile the vast majority of DNA methylation is unchanged by surgery after accounting for changes in cell-type composition, we identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. Paired statistical analysis, use of FACS data to support sufficient control of cell-type heterogeneity, and measurement of IL6 levels in a subset of patients add rigor to this analysis, allowing us to distinguish cell-type variability from actual changes in methylation.ConclusionsThis study identifies significant changes in DNA methylation that occur immediately after cardiac surgery and demonstrates that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications. This research also establishes methods for controlling for cell-type variability in a large human cohort that may be useful to deploy in other longitudinal studies of epigenetic marks in the setting of acute and chronic disease.

Combining prostate health index and multiparametric magnetic resonance imaging may better predict extraprostatic extension after radical prostatectomy.

In patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), preoperative prediction of extraprostatic extension (EPE) can facilitate patient selection for nerve-sparing procedures. Since both multiparametric magnetic resonance imaging (mpMRI) and prostate health index (PHI) have shown promise for the diagnosis and prognostication of PCa, we investigated whether a combination of mpMRI and PHI evaluations can improve the prediction of EPE after RP. Patients diagnosed with PCa and treated with RP were prospectively enrolled between February 2017 and July 2019. Preoperative blood samples were analyzed for PHI (defined as [p2PSA/fPSA] × √tPSA), and mpMRI examinations were performed and interpreted by a single experienced uroradiologist retrospectively. The area under the receiver operating characteristic curve (ROC) was used to determine the performance of mpMRI, PHI, and their combination in predicting EPE after RP. A total of 163 patients were included for analysis. The pathological T stage was T3a or more in 59.5%. Overall staging accuracy of mpMRI for EPE was 72.4% (sensitivity and specificity: 73.2% and 71.2%, respectively). The area under the ROC of the combination of mpMRI and PHI in predicting EPE (0.785) was higher than those of mpMRI alone (0.717; p = 0.0007) and PHI alone (0.722; p = 0.0236). mpMRI showed false-negative non-EPE results in 26 patients (16%), and a PHI threshold of >40 could avoid undiagnosed EPE before RP in 21 of these 26 patients. The combination of PHI and mpMRI may better predict the EPE preoperatively, facilitating preoperative counseling and tailoring the need for nerve-sparing RP.

Preoperative Fibrinogen-to-Albumin Ratio as Potential Predictor of Bladder Cancer: A Monocentric Retrospective Study.

Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal–Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004–1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378–3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors.

Simultaneous metabolomics analysis of atrial tissue, pericardial fluid and blood reveal novel metabolite signatures of the pathophysiology and biomarkers related to permanent atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is the most common, complex, and clinically relevant arrhythmia [1]. It is a growing medical condition associated with significant morbidity and mortality, but its pathophysiology has remained widely unknown [2]. Aims We aim to unravel the complex pathophysiological mechanisms of AF and identify clinically relevant AF-related metabolites. We aim to identify targets for therapeutical interventions and biomarkers for AF diagnostics. Our study material is unique as we can safely study human heart and pericardial fluid in addition to blood, that has been mainly examined in previous studies. Material and methods Patients recruited were undergoing cardiac surgery due to valve defects at the University Hospital. For our research, we collected preoperative blood samples and intraoperative right atrial appendage biopsy and pericardial fluid. For our metabolomics study on AF patients, we selected 16 patients with permanent AF and 17 age, gender and underlying disease matched control patients (Fig. 1). Liquid chromatography mass spectrometry (LC-MS) was used to identify molecules and metabolites related to AF. We integrated targeted assays for absolute quantification of specific metabolites with untargeted metabolomics to discover novel compounds and metabolites. Results Untargeted mass spectrometry (MS) metabolite analysis identified altogether 15751 molecular features and metabolites divided unequally between the sample types (Fig. 2). Altogether, we found 1041 (p&amp;lt;0.05) metabolites from the heart tissue, 774 from the pericardial fluid and 382 from the blood. There were 61 metabolites associated with permanent AF that were found in all three sample types. The approach and our research set-up also allowed us to distinguish metabolites that entered directly from heart tissue to blood and those that remained in heart tissue and pericardial fluid. According to the identified metabolites in the heart tissue, permanent AF was associated with a clear metabolite signature including signs of dysregulated energy -, histidine -, glutathione -, purine -, sugar -, and lipid metabolism and antioxidant defense. Altogether we identified altered, circulating AF-related biomarkers including novel carnitines and acylcarnitines, aminoacids, metabolites from immune response and lipid metabolism. Among the highest statistical significance with qualifiable difference (multivariate α-level 0.0007) we found two novel circulating molecules with known MS spectrum and molecular weight. Conclusions We identified totally new pathophysiological processes and novel potential metabolites related to permanent AF to be used as AF biomarkers. Permanent AF is associated with dysreculation of multiple biologically relevant metabolic pathways. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Academy of FinlandThe Finnish Foundation for Cardiovascular Research

623. A NEW PROGNOSTIC EVALUATION OF POSTOPERATIVE ESOPHAGEAL CANCER: LONG-TERM FLAIL INVESTIGATION

Abstract Recurrence-free survival and 5-year survival rates are still commonly used as prognostic indicators for gastrointestinal cancer. We believe that there is a need to find an appropriate index to evaluate changes in health status over time in postoperative patients. We evaluated changes in "frailty" after esophageal cancer surgery using the Kihon Checklist (KCL) developed by the Japanese Ministry of Health, Labour and Welfare, and examined risk factors for worsening health status after surgery. Twenty-four patients (21 thoracoscopic sub-total esophagectomy, 1 mediastinoscopic sub-total esophagectomy, and 2 total laryngopharyngoesophagectomy) who underwent esophageal cancer surgery in our department from December 2019 to April 2021 were included. Patients were asked to write down their KCL before surgery and one year after surgery at an outpatient clinic, and changes over time were checked. We compared the background factors in the "maintain" group (M group) and the "worsened" group (W group), and investigated the risk factors for pre-frail and frail states one year after the surgery. 8 patients worsened from robust to pre-frail to frail and pre-frail to frail, and 16 patients maintained their condition, with 33% of them worsening. Age (M/W: 70/72, p=0.296), male (M/W: 0.88/1.0, p=0.536), BMI (M/W: 22.4/19.6, p=0.142), pStage≥3 (M/W: 0.38/0.38, p=1.0), preoperative chemotherapy (M/W: 0.69/0.63, p=1.0), operative time (M/W: 566/610 minutes, p=0.327), blood loss (M/W: 103/151 ml, p=0.342), postoperative pneumonia (M/W: 0.25/0.25, p=1.0), and cancer recurrence (M/W: 0.19/0.50, p=0.167). The preoperative blood samples were Alb (M/W: 4.3/3.8 g/dl, p=0.046), Hb (M/W: 14.2/12.8 g/dl, p=0.015) and Cre (M/W: 0.85/0.79 mg/dl, p=0.713). At 1 year after esophageal cancer surgery, health worsened and 33% of patients were in a pre-frail or frail state. Risk factors for worsening health were low Alb and low Hb, which were not related to stage or actual age. Further study is needed to clarify risk factors for frailty.

A Delay in Adjuvant Therapy Is Associated With Worse Prognosis Only in Patients With Transitional Circulating Tumor Cells After Resection of Pancreatic Ductal Adenocarcinoma.

The aim of the study was to assess the association of circulating tumor cells (CTCs) with survival as a biomarker in pancreatic ductal adenocarcinoma (PDAC) within the context of a delay in the initiation of adjuvant therapy. Outcomes in patients with PDAC remain poor and are driven by aggressive systemic disease. Although systemic therapies improve survival in resected patients, factors such as a delay in the initiation of adjuvant therapy are associated with worse outcomes. CTCs have previously been shown to be predictive of survival. A retrospective study was performed on PDAC patients enrolled in the prospective CircuLating tUmor cellS in pancreaTic cancER trial (NCT02974764) on CTC-dynamics at the Johns Hopkins Hospital. CTCs were isolated based on size (isolation by size of epithelial tumor cells; Rarecells) and counted and characterized by subtype using immunofluorescence. The preoperative and postoperative blood samples were used to identify 2 CTC types: epithelial CTCs (eCTCs), expressing pancytokeratin, and transitional CTCs (trCTCs), expressing both pancytokeratin and vimentin. Patients who received adjuvant therapy were compared with those who did not. A delay in the receipt of adjuvant therapy was defined as the initiation of therapy ≥8 weeks after surgical resection. Clinicopathologic features, CTCs characteristics, and outcomes were analyzed. Of 101 patients included in the study, 43 (42.5%) experienced a delay in initiation and 20 (19.8%) did not receive adjuvant therapy. On multivariable analysis, the presence of trCTCs ( P =0.002) and the absence of adjuvant therapy ( P =0.032) were associated with worse recurrence-free survival (RFS). Postoperative trCTC were associated with poorer RFS, both in patients with a delay in initiation (12.4 vs 17.9mo, P =0.004) or no administration of adjuvant chemotherapy (3.4 vs NR, P =0.016). However, it was not associated with RFS in patients with timely initiation of adjuvant chemotherapy ( P =0.293). Postoperative trCTCs positivity is associated with poorer RFS only in patients who either experience a delay in initiation or no receipt of adjuvant therapy. This study suggests that a delay in the initiation of adjuvant therapy could potentially provide residual systemic disease (trCTCs) a window of opportunity to recover from the surgical insult. Future studies are required to validate these findings and explore the underlying mechanisms involved.

Relationship between platelet mass index and postoperative atrial fibrillation after elective coronary artery bypass surgery: aretrospective study.

Atrial fibrillation (AF) is the most common complication after cardiac surgery. The pathogenesis of postoperative atrial fibrillation (POAF) is multifactorial and one of the known factors is inflammation. Platelet mass index (PMI) is an indicator of platelet activation and abetter inflammatory marker than mean platelet volume (MPV). In this retrospective study, we investigated the relationship between POAF and PMI. The study included 848 consecutive patients (655male and 193female) who had elective isolated coronary artery by-pass grafting (CABG) or combined CABG and valvular surgery. Platelet count and MPV were measured from preoperative blood samples to calculate PMI. Post-operative atrial fibrillation was defined as irregular and fibrillatory Pwaves occurring 48-96 h after cardiac surgery and lasting at least 30 s. The PMI values in patients who developed POAF were compared with those in patients who did not develop POAF. Patients who developed POAF had higher PMI values (2549.3 ± 1077.1) when compared with patients in sinus rhythm (2248.1 ± 683.4; p < 0.01). In multivariate regression analysis, age (OR: 1.05; 95%CI: 1.02-1.09; p = 0.01), left atrial diameter (OR: 1.05; 95% CI: 1.03-1.09; p = 0.02), hs-CRP (OR: 1.09; 95%CI: 1.05-1.13; p < 0.01), EuroSCOREII (OR: 1.27; 95% CI: 1.14-1.41; p < 0.01), and PMI (OR: 1.01; 95% CI: 1.001-1.02; p < 0.01) were independent predictors of POAF. In ROC analysis, PMI ≥ 2286 predicted POAF development with asensitivity of 69% and aspecificity of 58% (AUC: 0.66; p < 0.01) CONCLUSION: Asignificant relationship was found between preoperatively calculated PMI and POAF. We showed that PMI may be used to predict patients who are at high risk of developing POAF.

Multivariate logistic regression analysis of the correlation between five biomarkers and ovarian cancer in patients with intermediate-risk: A prospective cross-sectional study.

Objective: To find potential diagnostic biomarkers for ovarian cancer (OC), a prospective analysis of the expression of five biomarkers in patients with intermediate-risk and their correlation with the occurrence of OC was conducted. Method: A prospective observational study was carried out, patients who underwent surgical treatment with benign or malignant ovarian tumors in our hospital from January 2020 to February 2021 were included in this study, and a total of 263 patients were enrolled. Based on the postoperative pathological results, enrolled patients were divided into ovarian cancer group and benign tumor group (n = 135). The ovarian cancer group was further divided into a mid-stage group (n = 46) and an advanced-stage group (n = 82). The basic information of the three groups of patients was collected, the preoperative imaging data of the patients were collected to assess the lymph node metastasis, the preoperative blood samples were collected to examine cancer antigen 125 (CA125), carbohydrate antigen 19–9 (CA19–9), Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and the postoperative pathological data were sorted and summarized. Result: The average during of disease in the advanced ovarian cancer group was 0.55 ± 0.18 years higher than the benign tumor group (0.43 ± 0.14 years), p < 0.001. In the advanced ovarian cancer group, the ratio of patients with the tumor, node, metastasis (TNM) stage IV (64.63%), with tumor Grade stage II and III (93.90%), and without lymph node metastasis (64.63%) was respectively more than that in the mid-stage group (accordingly 0.00, 36.96, 23.91%) (p < 0.001); The ratio of patients with TNM grade III in the mid-stage group (73.91%) was more than that in the advanced group (35.37%) (p < 0.001). The levels of the five biomarkers: CA19-9, CA125, NLR, PLR, and BDNF were different among the three groups (p < 0.001). Conclusion: CA19-9, CA125, NLR, PLR, BDNF are five biomarkers related to the occurrence of ovarian cancer and are risk factors for it. These five biomarkers and their Combined-Value may be suitable to apply in the diagnosis and the identification of ovarian cancer in patients with intermediate-risk.