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7 result(s) for "Vles, Wouter J."
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The fate of research abstracts submitted to a national surgical conference: a cross-sectional study to assess scientific impact
Conference abstracts often lack rigorous peer review, but potentially influence clinical thinking and practice. To evaluate the quality of abstracts submitted to a large surgical conference, presentation and publication rates were investigated to assess scientific impact. A Cross-sectional study of abstracts submitted to Dutch Surgical Society meetings from 2007 to 2012 was conducted. Presentation rates, publication rates in MEDLINE-indexed journals using PubMed Central database, and actuarial times to subsequent publication were investigated. Of 2,174 submitted abstracts, 1,305 (60%) abstracts were accepted for presentation. Actuarial 1, 3, and 5-year publication rates were 22.4%, 62.2%, and 68.6% for presented abstracts, compared with 20.9%, 50.3%, and 57.7% for rejected abstracts, respectively (log-rank x2 23.728, df1, P < .001). Publications resulting from abstracts presented at the conference had a significantly higher mean (±standard error) impact factor (4.4 ± .2 vs 3.4 ± .1, P < .001), compared with publications from previously rejected abstracts. We advocate critical appraisal of the use of findings of scientific abstracts and conference presentations. The 5-year abstract-to-publication ratio is proposed as a novel quality indicator to allow objective comparison between scientific meetings. •Abstract presentation and publication rates were investigated to assess impact.•Two thirds of 2,174 submitted abstracts went on to full publication.•Presented research was published more timely and in journals with higher impact.•Scientific abstracts and conference presentations need critical appraisal.•The 5-year abstract-to-publication ratio is proposed as novel quality indicator.
GSTP1 CpG Island Hypermethylation Is Responsible for the Absence of GSTP1 Expression in Human Prostate Cancer Cells
GSTP1 CpG island hypermethylation is the most common somatic genome alteration described for human prostate cancer (PCA); lack of GSTP1 expression is characteristic of human PCA cells in vivo. We report here that loss of GSTP1 function may have been selected during the pathogenesis of human PCA. Using a variety of techniques to detect GSTP1 CpG island DNA hypermethylation in PCA DNA, we found only hypermethylated GSTP1 alleles in each PCA cell in all but two PCA cases studied. In these two cases, CpG island hypermethylation was present at only one of two GSTP1 alleles in PCA DNA. In one of the cases, DNA hypermethylation at one GSTP1 allele and deletion of the other GSTP1 allele were evident. In the other case, an unmethylated GSTP1 allele was detected, accompanied by abundant GSTP1 expression. GSTP1 CpG island DNA hypermethylation was responsible for lack of GSTP1 expression by LNCaP PCA cells: treatment of the cells with 5-azacytidine (5-aza-C), an inhibitor of DNA methyltransferases, reversed the GSTP1 promoter DNA hypermethylation, activated GSTP1 transcription, and restored GSTP1 expression. GSTP1promoter activity, assessed via transfection of GSTP1 promoter- CAT reporter constructs in LNCaP cells, was inhibited by SssI-catalyzed CpG dinucleotide methylation. Remarkably, although selection for loss of GSTP1 function may be inferred for human PCA, GSTP1 did not act like a tumor suppressor gene, as LNCaP cells expressing GSTP1, either after 5-aza-C treatment or as a consequence of transfection with GSTP1 cDNA, grew well in vitro and in vivo. Perhaps, GSTP1 inactivation may render prostatic cells susceptible to additional genome alterations, caused by electrophilic or oxidant carcinogens, that provide a selective growth advantage.
Confirmation of a metastasis-specific microRNA signature in primary colon cancer
The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding of tumour biology. MicroRNAs have been proposed as markers of the prognosis or treatment response in colorectal cancer. Recently, a 2-microRNA signature ( l et-7i and miR-10b ) was proposed to identify colorectal cancer patients at risk of developing distant metastasis. We assessed the prognostic value of this signature and additional candidate microRNAs in an independent, clinically well-defined, prospectively collected cohort of primary colon cancer patients including stage I-II colon cancer without and stage III colon cancer with adjuvant treatment. The 2-microRNA signature specifically predicted hepatic recurrence in the stage I-II group, but not the overall ability to develop distant metastasis. The addition of miR-30b to the 2-microRNA signature allowed the prediction of both distant metastasis and hepatic recurrence in patients with stage I-II colon cancer who did not receive adjuvant chemotherapy. Available gene expression data allowed us to associate m iR-30b expression with axon guidance and l et-7i expression with cell adhesion, migration, and motility.
Physical activity patterns after diagnosis and survival of prognostic colorectal cancer subgroups
Physical activity (PA) is associated with improved overall survival (OS) among colorectal cancer (CRC) patients, but research on PA changes after diagnosis remains limited. This study examines associations between OS and changes in PA from CRC diagnosis onward, across stage- and treatment-related subgroups. Data were analyzed from patients in two large CRC cohorts (PLCRC and COLON) enrolled between August 2010 and December 2022 (follow-up until February 1st, 2024). This included 3,395 stage I-IIA patients who underwent surgery only, 2,406 stage IIB/C-III patients who received (neo-)adjuvant therapy, and 669 metastatic CRC (mCRC) patients. PA was assessed via the validated SQUASH questionnaire at diagnosis (T0), and at 6, 12, and 24 months post-diagnosis (T6 to T24). Moderate-to-vigorous-intensity recreational activity was quantified by calculating Metabolic Equivalent of Task (MET) hours per week. Associations with OS were examined for change (active [tertile 2 and 3] vs inactive [tertile 1]) between timepoints using multivariable Cox proportional hazards models. Among surgery-only patients, change from inactivity to activity between T0 and T6 was significantly associated with OS (HR 0.58 [95% CI 0.35-0.96]). For (neo-)adjuvantly treated patients, significant associations were observed between T6 and T12 (0.53 [0.31-0.90]). Among mCRC patients, a significant association was observed between T6 and T12 (0.53 [0.29-0.99]). Changing from inactivity to activity is significantly associated with prolonged survival during the early months post-diagnosis for surgery-only CRC patients, and later for those undergoing (neo-)adjuvant therapy or with metastatic disease. Validation is warranted in interventional studies.
High mRNA expression of splice variant SYK short correlates with hepatic disease progression in chemonaive lymph node negative colon cancer patients
Overall and splice specific expression of Spleen Tyrosine Kinase (SYK) has been posed as a marker predicting both poor and favorable outcome in various epithelial malignancies. However, its role in colorectal cancer is largely unknown. The aim of this study was to explore the prognostic role of SYK in three cohorts of colon cancer patients. Total messenger RNA (mRNA) expression of SYK, SYK(T), and mRNA expression of its two splice variants SYK short (S) and SYK long (L) were measured using quantitative reverse transcriptase (RT-qPCR) in 240 primary colon cancer patients (n = 160 patients with chemonaive lymph node negative [LNN] and n = 80 patients with adjuvant treated lymph node positive [LNP] colon cancer) and related to microsatellite instability (MSI), known colorectal cancer mutations, and disease-free (DFS), hepatic metastasis-free (HFS) and overall survival (OS). Two independent cohorts of patients with respectively 48 and 118 chemonaive LNN colon cancer were used for validation. Expression of SYK and its splice variants was significantly lower in tumors with MSI, and in KRAS wild type, BRAF mutant and PTEN mutant tumors. In a multivariate Cox regression analysis, as a continuous variable, increasing SYK(S) mRNA expression was associated with worse HFS (Hazard Ratio[HR] = 1.83; 95% Confidence Interval[CI] = 1.08-3.12; p = 0.026) in the LNN group, indicating a prognostic role for SYK(S) mRNA in patients with chemonaive LNN colon cancer. However, only a non-significant trend between SYK(S) and HFS in one of the two validation cohorts was observed (HR = 4.68; 95%CI = 0.75-29.15; p = 0.098). In our cohort, we discovered SYK(S) as a significant prognostic marker for HFS for patients with untreated LNN colon cancer. This association could however not be confirmed in two independent smaller cohorts, suggesting that further extensive validation is needed to confirm the prognostic value of SYK(S) expression in chemonaive LNN colon cancer.
Multicenter fresh frozen tissue sampling in colorectal cancer: does the quality meet the standards for state of the art biomarker research?
The growing interest in the molecular subclassification of colorectal cancers is increasingly facilitated by large multicenter biobanking initiatives. The quality of tissue sampling is pivotal for successful translational research. This study shows the quality of fresh frozen tissue sampling within a multicenter cohort study for colorectal cancer (CRC) patients. Each of the seven participating hospitals randomly contributed ten tissue samples, which were collected following Standard Operating Procedures (SOP) using established techniques. To indicate if the amount of intact RNA is sufficient for molecular discovery research and prove SOP compliance, the RNA integrity number (RIN) was determined. Samples with a RIN < 6 were measured a second time and when consistently low a third time. The highest RIN was used for further analysis. 91% of the tissue samples had a RIN ≥ 6 (91%). The remaining six samples had a RIN between 5 and 6 (4.5%) or lower than 5 (4.5%). The median overall RIN was 7.3 (range 2.9–9.0). The median RIN of samples in the university hospital homing the biobank was 7.7 and the median RIN for the teaching hospitals was 7.3, ranging from 6.5 to 7.8. No differences were found in the outcome of different hospitals ( p  = 0.39). This study shows that the collection of high quality fresh frozen samples of colorectal cancers is feasible in a multicenter design with complete SOP adherence. Thus, using basic sampling techniques large patient cohorts can be organized for predictive and prognostic (bio)marker research for CRC.
Operative management of isolated posterior cruciate ligament injuries improves stability and reduces the incidence of secondary osteoarthritis: a systematic review
Purpose To evaluate the evidence for operative and non-operative management of isolated posterior cruciate ligament (PCL) injuries. Methods Using Pubmed, EMBASE and Cochrane databases, a systematic review was conducted of studies investigating the treatment of isolated PCL injuries published until July 2020. Quality assessment was performed with the Cochrane risk of bias tool (level I), the Newcastle–Ottowa Scale (level II–III) and the National Institute of Health quality assessment tool (level IV). Clinical outcome measures included residual laxity, return to sports, patient-reported outcome measures, subsequent articular degeneration and complications. Results Twenty-seven studies [23 case series, 2 case–control, 1 cohort study and 1 randomized controlled trial (RCT)] including 5197 patients (5199 knees) with a mean age of 29.5 ± 3.6 years (range 15–68) fulfilled the study requirements. Significantly less residual laxity was found after posterior cruciate ligament reconstruction (PCLR) compared to non-operative management (3.43 vs. 5.47 mm, CI: 1.84–2.23, p  < 0.001). Both treatment modalities yielded satisfying functional outcomes and a high return to sports (64–77%, mean: 70.3, CI: 67.8–72.2). Osteoarthritis (OA) occurred less frequently following PCLR (21.5 vs. 44.1%, p  < 0.001). Conclusion In the absence of level I RCTs, this systematic review suggests that surgical management for selected isolated PCL injuries is a reasonable option to consider, especially when the surgeon aims at minimizing residual laxity and presumably secondary osteoarthritis. Level of evidence IV.