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Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer.

ABSTRACT: Ovarian cancer (OVCA) patients with suboptimal residual disease (RD) and advanced stages have poor survival. pGSN is an actin binding protein which protects OVCA cells from cisplatin-induced death. There is an urgent need to discover reliable biomarkers to optimize individualized treatment recommendations. 99 plasma samples with pre-determined CA125 were collected from OVCA patients and pGSN assayed using sandwich-based ELISA. Associations between CA125, pGSN and clinicopathological parameters were examined using Fisher's exact test, T test and Kruskal Wallis Test. Univariate and multivariate Cox proportional hazard models were used to statistically analyze clinical outcomes. At 64?µg/ml, pGSN had sensitivity and specificity of 60% and 60% respectively, for the prediction of RD where as that of CA125 at 576.5?U/mL was 43.5% and 56.5% respectively. Patients with stage 1 tumor had increased levels of pre-operative pGSN compared to those with tumor stage >1 and healthy subjects (P?=?0.005). At the value of 81?µg/mL, pGSN had a sensitivity and specificity of 75% and 78.4%, respectively for the detection of early stage OVCA. At the value of 0.133, the Indicator of Stage 1 OVCA (ISO1) provided a sensitivity of 100% at a specificity of 67% (AUC, 0.89; P?

SUBMITTER: Asare-Werehene M

PROVIDER: S-EPMC6763481 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer.

Asare-Werehene Meshach M Communal Laudine L Carmona Euridice E Le Tien T Provencher Diane D Mes-Masson Anne-Marie AM Tsang Benjamin K BK

Scientific reports 20190926 1

Ovarian cancer (OVCA) patients with suboptimal residual disease (RD) and advanced stages have poor survival. pGSN is an actin binding protein which protects OVCA cells from cisplatin-induced death. There is an urgent need to discover reliable biomarkers to optimize individualized treatment recommendations. 99 plasma samples with pre-determined CA125 were collected from OVCA patients and pGSN assayed using sandwich-based ELISA. Associations between CA125, pGSN and clinicopathological parameters w ...[more]

PMID: 31558772

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Project description:BackgroundResistance to chemotherapy continues to be a challenge when treating epithelial ovarian cancer (EOC), contributing to low patient survival rates. While CA125, the conventional EOC biomarker, has been useful in monitoring patients' response to therapy, there are no biomarkers used to predict treatment response prior to chemotherapy. Previous work in vitro showed that plasma gelsolin (pGSN) is highly expressed in chemoresistant EOC cell lines, where it is secreted in small extracellular vesicles (sEVs). Whether sEVs from tumour cells are secreted into the circulation of EOC patients and could be used to predict patient chemoresponsiveness is yet to be determined. This study aims to identify if sEV-pGSN in the circulation could be a predictive biomarker for chemoresistance in EOC.MethodsSandwich ELISA was used to measure pGSN concentrations from plasma samples of 96 EOC patients (primarily high grade serous EOC). sEVs were isolated using ExoQuick ULTRA and characterized using western blot, nanoparticle tracking analysis, and electron microscopy after which pGSN was measured from the sEVs. Patients were stratified as platinum sensitive or resistant groups based on first progression free interval (PFI) of 6 or 12 months.ResultsTotal circulating pGSN was significantly decreased and sEV-pGSN increased in patients with a PFI ≤ 12 months (chemoresistant) compared to those with a PFI > 12 months (chemosensitive). The ratio of total pGSN to sEV-pGSN further differentiated these groups and was a strong predictive marker for chemoresistance (sensitivity: 73.91%, specificity: 72.46%). Predetermined CA125 was not different between chemosensitive and chemoresistant groups and was not predictive of chemoresponsiveness prior to treatment. When CA125 was combined with the ratio of total pGSN/sEV-pGSN, it was a significant predictor of chemoresponsiveness, but the test performance was not as robust as the total pGSN/sEV-pGSN alone.ConclusionsTotal pGSN/sEV-pGSN was the best predictor of chemoresponsiveness prior to treatment, outperforming the individual biomarkers (CA125, total pGSN, and sEV-pGSN). This multianalyte predictor of chemoresponsiveness could help to inform physicians' treatment and follow up plan at the time of EOC diagnosis, thus improving patients' outcomes.

Project description:Importance: Trichiasis surgery programs globally have faced high rates of poor surgical outcomes. Identifying correctable risk factors for improving long-term outcomes is essential for countries targeting elimination of trachoma as a public health problem.Objective: To determine whether the location of trichiatic eyelashes prior to surgery influences development of post-operative trichiasis (PTT) within two years after surgery.Design: Secondary data analysis of four randomized clinical trials evaluating methods to improve trichiasis surgery outcomes. These include the Surgery for Trichiasis, Antibiotics for Recurrence (STAR) trial, Partnership for Rapid Elimination of Trachoma (PRET-Surgery), absorbable versus silk sutures trial, and epilation versus surgery for minor trichiasis trial.Setting: Primary trials were conducted in rural areas of Ethiopia and Tanzania.Interventions or exposures: Trichiasis surgery performed with either the bilamellar tarsal rotation procedure or posterior lamellar rotation procedure.Main outcomes: Prevalence of PTT within two years after surgery, location of trichiatic eyelashes pre-operatively and post-operatively.Results: 6,747 eyelids that underwent first-time trichiasis surgery were included. PTT rates varied by study, ranging from 10-40%. PTT was less severe (based on number of trichiatic eyelashes) than initial trichiasis for 72% of those developing PTT, and only 2% of eyelids were worse at follow up than pre-operatively. Eyelids with central only-trichiasis pre-operatively had lower rates of PTT than eyelids with peripheral only trichiasis in each of the three trials that included severe TT cases. 10% of eyelids with peripheral trichiasis pre-operatively that develop PTT have central TT post-operatively.Conclusions and relevance: Pre-operative central trichiasis is less likely than peripheral trichiasis to be associated with subsequent PTT. Regardless of type of surgery, surgeon skill levels, or pre-operative trichiasis severity, the presence of peripheral trichiasis pre-operatively is associated with higher rates of PTT. Making an incision that extends the length of the eyelid and adequately rotating the nasal and temporal aspects of the eyelid when suturing may help to minimize the chance of developing peripheral PTT.Trial registration: ClinicalTrials.gov PRET: NCT00886015; Suture: NCT005228560; Epilation: NCT00522912.

Project description:BackgroundLimited evidence informs whether pre-operative values of two-point discrimination (2PD) in patients with carpal tunnel syndrome predict response to surgery.Questions/purposesThe primary aim of this study was to determine the predictive value of pre-operative 2PD scores on outcomes following carpal tunnel release (CTR). In particular, we sought to evaluate whether a clinically relevant 2PD threshold exists that can predict symptomatic response after surgery.MethodsPatients who underwent CTR between 2014 and 2018 were retrospectively reviewed. Static 2PD scores in each digit, as well as Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Levine-Katz scores, were collected from pre- and post-operative records. Pearson correlation coefficients assessed the relationship between pre-operative 2PD, early post-operative 2PD, and patient-reported outcome scores. Poor 2PD was defined as 2PD greater than 10 mm.ResultsEighty-nine hands in 73 patients with a mean follow-up of 1.8 years were analyzed. Mean pre- and post-operative 2PD was 7.2 mm and 6.4 mm, respectively, in the most affected digit when measurable. Twenty patients had poor 2PD scores pre-operatively and 14 post-operatively. There was a positive correlation between pre- and early post-operative 2PD scores but no correlation between pre-operative 2PD score and final post-operative functional scores. Only 30% of patients with poor pre-operative 2PD scores demonstrated improvement, compared with 69% of patients with measurable 2PD.ConclusionWe found that greater pre-operative 2PD scores predicted greater early post-operative 2PD scores but did not lead to worse functional outcome scores post-operatively. Patients with poor pre-operative 2PD scores were likely to demonstrate improvement in functional outcomes scores, while having less reliable improvement in 2PD after CTR. Patients with poor 2PD should be counseled that improvement of tactile perception is less predictable.

Dataset Information

Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer.

Publications

Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer.

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