Using established biorepositories for emerging research questions: a feasibility study

Background: Proteomics and metabolomics offer substantial potential for advancing kidney transplant research by providing versatile opportunities for gaining insights into the biomolecular processes occurring in donors, recipients, and grafts. To achieve this, adequate quality and numbers of biological samples are required. Whilst access to donor samples is facilitated by initiatives such as the QUOD biobank, an adequately powered biobank allowing exploration of recipient-related aspects in long-term transplant outcomes is missing. Rich, yet unverified resources of recipient material are the serum repositories present in the immunological laboratories of kidney transplant centers that prospectively collect recipient sera for immunological monitoring. However, it is yet unsure whether these samples are also suitable for -omics applications, since such clinical samples are collected and stored by individual centers using non-uniform protocols and undergo an undocumented number of freeze–thaw cycles. Whilst these handling and storage aspects may affect individual proteins and metabolites, it was reasoned that incidental handling/storage artifacts will have a limited effect on a theoretical network (pathway) analysis. To test the potential of such long-term stored clinical serum samples for pathway profiling, we submitted these samples to discovery proteomics and metabolomics. Methods: A mass spectrometry-based shotgun discovery approach was used to obtain an overview of proteins and metabolites in clinical serum samples from the immunological laboratories of the Dutch PROCARE consortium. Parallel analyses were performed with material from the strictly protocolized QUOD biobank. Results: Following metabolomics, more than 800 compounds could be identified in both sample groups, of which 163 endogenous metabolites were found in samples from both biorepositories. Proteomics yielded more than 600 proteins in both groups. Despite the higher prevalence of fragments in the clinical, non-uniformly collected samples compared to the biobanked ones (42.5% vs 26.5% of their proteomes, respectively), these fragments could still be connected to their parent proteins. Next, the proteomic and metabolomic profiles were successfully mapped onto theoretical pathways through integrated pathway analysis, which showed significant enrichment of 79 pathways. Conclusions: This feasibility study demonstrated that long-term stored serum samples from clinical biorepositories can be used for qualitative proteomic and metabolomic pathway analysis, a notion with far-reaching implications for all biomedical, long-term outcome-dependent research questions and studies focusing on rare events

On the role of radiologists in the Belgian PROject on CAncer of the REctum, PROCARE.

Radiologists are involved at all stages of the treatment of patients with rectum cancer: in the preoperative staging, in the diagnosis of postoperative complications, in the detection of recurrent or metastatic disease during follow-up, in the monitoring of the therapeutic effect of palliative therapy. PROCARE is a Belgian national project to improve outcome in all patients with rectum cancer. Guidelines were made by a multidisciplinary workgroup and are available on the web. Decentralised implementation of guidelines is organised by the scientific and professional organisations. It is planned that a central review committee of radiologists, delegated by the Royal Belgian Society of Radiology, will survey the quality of preoperative staging. Overall quality of care will be assured by registration in a specific national database starting in 2006. Participating teams will receive annual feedback. Radiologists should provide data on cTNM staging and cCRM. Differentiation between cT2 and cT3, cN0 and cN+, and measurement of the cCRM in mm are crucial as they have a relevant impact on treatment strategy. While spiral abdominal CT is adequate for cM staging, high-resolution MRI is highly recommended and, in fact, a necessity for locoregional staging because its adequacy is superior to that of CT-scan and EUS. However, EUS is mandatory when local excision is considered, i.e. for cT1N0 lesions

Scoring the quality of total mesorectal excision for the prediction of cancer-specific outcome.

AIM: A three-grade system for macroscopic evaluation of the resection plane is used to describe the quality of total mesorectal excision (TME). In several studies, two of the three grades have been combined when analysing the outcome. The aim of our study was to compare the predictive value of the three-graded with that of a two-graded TME score. METHOD: The quality of TME in 1382 patients who underwent elective resection for mid or low rectal adenocarcinoma was registered by 65 hospitals in PROCARE, a Belgian multidisciplinary improvement project. Prediction of outcome based on the classic three-grade score was compared with a two-grade scoring system in which intramesorectal resection (IMR) was combined with mesorectal (MRR) or with muscularis propria resection (MPR). End-points included the local recurrence rate, distant metastasis rate (DMR), disease-free survival (DFS) and overall survival (OS). RESULTS: Among the 1382 resections, 63% were MRR, 27% IMR and 9% MPR. No significant differences were found in local recurrence between the different grades of TME. A two-grade score distinguishing MRR from the others was found to predict DMR, DFS and OS as well as the three-grade score. CONCLUSION: The discriminatory and predictive value of a two-grade score, differentiating MRR from the combined IMR and MPR, was as good as the classic three-grade score

Scoring the quality of total mesorectal excision for the prediction of cancer specific outcome

A three grade system for macroscopic evaluation of the resection plane is used to describe the quality of total mesorectal excision (TME). In several studies, two of the three grades have been combined when analysing the outcome. The aim of the study was to compare the predictive value of the three-graded with that of a two-graded TME score .status: publishe

Quantitative contribution of prognosticators to oncologic outcome after rectal cancer resection.

BACKGROUND: Prognostication is an important aspect of medical practice. It relies on statistical modeling testing the correlation of variables with the outcome of interest. OBJECTIVE: In contrast with the classic approach of predictive modeling, this study aimed to estimate the unique, individual, and relative contributions. This includes the quantitative contributions of patient-, tumor-, and treatment-related factors to oncologic outcome after rectal cancer resection. DESIGN: This was a retrospective analysis of prospectively registered data. SETTINGS: The study included 65 hospitals participating on a voluntary basis in the Project on Cancer of the Rectum, a Belgian multidisciplinary improvement project of rectal cancer care. PATIENTS: A total of 1470 patients presenting midrectal or low-rectal adenocarcinoma without distant metastasis were included. INTERVENTION: The study intervention was total mesorectal excision with or without sphincter preservation. MAIN OUTCOME MEASURES: The unique, individual, and relative contributions of a set of covariables to the statistical variability of the distant metastasis rate and overall survival have been calculated. RESULTS: The 5-year distant metastasis rate was 21% and overall survival 76%. A large amount of the variability of the outcomes (ie, 83.6% to 84.2%) could not be predicted by the prognostic factors. Unique contributions of the predictors ranged from 0.1% to 3.1%. The 3 risk factors with the highest unique contribution for distant metastasis were lymph node ratio, pathologic tumor stage, and total mesorectal quality; for overall survival they were age, lymph node ratio, and ASA score. LIMITATIONS: The main weakness of this study was incomplete participation and registration in the Project on Cancer of the Rectum. CONCLUSIONS: Several factors influence oncologic outcomes and are present in prediction models. However, the models predict relatively little of outcome variation

Effect of hospital volume on quality of care and outcome after rectal cancer surgery

BACKGROUND: Research on the relationship between hospital volume and quality of care in the treatment of rectal cancer is limited. METHODS: Process and outcome indicators were assessed in patients with rectal adenocarcinoma who underwent total mesorectal excision, registered on a voluntary basis in the PROCARE clinical database. Volume was derived from an administrative database and analysed as a continuous variable. Sphincter preservation, 30-day mortality and survival rates were cross-checked against population-based data. RESULTS: A total of 1469 patients registered in PROCARE between 2006 and 2011 were included in this study. A volume effect was observed regarding neoadjuvant therapy for stage II-III disease, reporting of the circumferential resection margin, R0 resection rate, sphincter preservation rate, and number of nodes examined after chemoradiotherapy. The global estimate of quality of care was highly variable, but surgery was the single domain in which quality correlated with volume. No volume effect was observed for recurrence and overall survival rates. In the population-based data set (5869 patients), volume was associated with 30-day mortality adjusted for age (odds ratio 0·99, 95 per cent confidence interval (c.i.) 0·98 to 1·00; P = 0·014) and adjusted overall survival (HR 0·99 (95 per cent c.i. 0·99 to 1·00) per additional procedure; P = 0·001), but not with the sphincter preservation rate. Because of incomplete and biased registration on a voluntary basis, results from a clinical database could not be extrapolated to the population. CONCLUSION: Some volume effects were observed, but their effect size was limited

Outcome following laparoscopic and open total mesorectal excision for rectal cancer.

There are few reports on the oncological quality of resection and outcome after laparoscopic versus open total mesorectal excision (TME) for rectal cancer in everyday surgical practice.Comparative StudyEvaluation StudiesJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tFLWINSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Defunctioning stoma and anastomotic leak rate after total mesorectal excision with coloanal anastomosis in the context of PROCARE.

BACKGROUND: Anastomotic leakage (AL) after total mesorectal excision is a major adverse event. Construction of a defunctioning stoma (DS) reduces the morbidity of AL. This study aims to illustrate the AL rate and its related morbidity with and without primary stoma formation in the context of a Belgian project, PROCARE. METHODS: Between January 2006 and March 2011, 1912 patients who underwent elective TME with colo-anal anastomosis for invasive rectal adenocarcinoma up to 15 cm above the anal verge were registered. A primary DS was constructed in 1183 patients (62%). Early clinical AL rate, AL-related re-operation rate, length of stay (LoS), in-hospital mortality were analysed. RESULTS: In patients without leak, mortality was 1.1% and the mean LoS was 14.7 days. AL occurred in 6.5%, varying from 0%-25% between participating centres. In patients with AL, mortality was 4.8% (p < 0.001). In the presence of a primary DS, AL rate was 4.3%, requiring re-operation under narcosis in 78% with no mortality, resulting in a mean LoS of 30.4 days. In the absence of a primary DS, AL rate was 10.2%, requiring re-operation under narcosis in 93% with a mortality of 8.1% and a mean LoS of 33.4 days. Analysis per centre showed a weak relation between percentage of DS construction and AL rate. CONCLUSION: Construction of a primary DS significantly reduced the incidence of early AL, re-operation rate, and mortality. Although technical aspects of colo-anal anastomosis are of paramount importance, construction of a DS at primary surgery has to be considered by those teams with high early AL rate and/or high AL related mortality

Prognostic impact of quality control of total mesorectal excision specimen evaluation.

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Risk adjusted benchmarking of abdominoperineal excision for rectal adenocarcinoma in the context of the Belgian PROCARE improvement project.

The abdominoperineal excision (APE) rate, a quality of care indicator in rectal cancer surgery, has been criticised if not adjusted for confounding factors. This study evaluates variability in APE rate between centres participating in PROCARE, a Belgian improvement initiative, before and after risk adjustment. It also explores the effect of merging the Hartmann resections (HR) rate with that of APE on benchmarking.0Journal ArticlePROCARESCOPUS: ar.jinfo:eu-repo/semantics/publishe