Dutch validation of the low anterior resection syndrome score.

AIM: The aim of this study was to validate the Dutch translation of the low anterior resection syndrome (LARS) score in a population of Dutch rectal cancer patients. METHOD: Patients who underwent surgery for rectal cancer received the LARS score questionnaire, a single quality of life (QoL) category question and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. A subgroup of patients received the LARS score twice to assess the test-retest reliability. RESULTS: A total of 165 patients were included in the analysis, identified in six Dutch centres. The response rate was 62.0%. The percentage of patients who reported 'major LARS' was 59.4%. There was a high proportion of patients with a perfect or moderate fit between the QoL category question and the LARS score, showing a good convergent validity. The LARS score was able to discriminate between patients with or without neoadjuvant radiotherapy (P = 0.003), between total and partial mesorectal excision (P = 0.008) and between age groups (P = 0.039). There was a statistically significant association between a higher LARS score and an impaired function on the global QoL subscale and the physical, role, emotional and social functioning subscales of the EORTC QLQ-C30 questionnaire. The test-retest reliability of the LARS score was good, with an interclass correlation coefficient of 0.79. CONCLUSION: The good psychometric properties of the Dutch version of the LARS score are comparable overall to the earlier validations in other countries. Therefore, the Dutch translation can be considered to be a valid tool for assessing LARS in Dutch rectal cancer patients.

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research.

BACKGROUND: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). METHODS/DESIGN: The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. RESULTS: Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients. CONCLUSION: This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.

[Acute appendicitis or colon cancer? Difference in elderly patients not always clear]. / Acute appendicitis of coloncarcinoom?

Three elderly patients presented with acute abdominal pain in the right lower quadrant and leukocytosis. CT-imaging of the abdomen supported the suspicion of acute appendicitis. The patients underwent appendectomy. After pathological examination, two patients were found to have a colon carcinoma. The third patient had a normal appendix; however, adenocarcinoma of the cecum was found four weeks later. The patients underwent a second operation, a right hemicolectomy, within two months. In patients older than 65 years with symptoms of acute appendicitis, colon cancer should be considered in the differential diagnosis. Distinguishing between appendicitis and colon cancer based on clinical symptoms and imaging is difficult. However, this distinction is important for the prognosis and choice of surgical treatment. If no direct evidence of malignancy is present in elderly patients with symptoms of appendicitis, a colonoscopy should be performed postoperatively to exclude colon cancer.

Mass spectrometry proteomic diagnosis: enacting the double cross-validatory paradigm.

This paper presents an approach to the evaluation and validation of the diagnostic potential of mass spectrometry data in an application on the construction of an "early warning" diagnostic procedure. Our approach is based on a full implementation and application of double cross-validatory calibration and evaluation. It is a key feature of this methodology that we can jointly optimize the classifiers for prediction while simultaneously calculating validated error rates. The methodology leaves the size of the training data nearly intact. We present application to data from a designed experiment in a colon-cancer study. Subsequent to presentation of results from the double cross-validatory analysis, we explore a post-hoc analysis of the calibrated classifiers to identify the markers that drive the classification.

Current status and prospects of clinical proteomics studies on detection of colorectal cancer: hopes and fears.

Colorectal adenocarcinoma (CRC) is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Given the natural history of CRC, early diagnosis appears to be the most appropriate tool to reduce disease-related mortality. A field of recent interest is clinical proteomics, which was reported to lead to high sensitivity and specificities for early detection of several solid tumors. This emerging field uses mass spectrometry-based protein profiles/patterns of easy accessible body fluids to distinguish cancer from non-cancer patients. These discrepancies may be a result of: (1) proteins being abnormally produced or shed and added to the serum proteome, (2) proteins clipped or modified as a consequence of the disease process, or (3) proteins subtracted from the proteome owing to disease-related proteolytic degradation pathways. Therefore, protein pattern diagnostics would provide easy and reliable tools for detection of cancer. This paper focuses on the current status of clinical proteomics research in oncology and in colorectal cancer especially, and will reflect on pitfalls and fears in this relatively new area of clinical medicine, which are reproducibility issues and pre-analytical factors, statistical issues, and identification and nature of discriminating proteins/peptides.

Translational research in prognostic profiling in colorectal cancer.

There is a widening gap between basic research and clinical practice, particularly for colorectal cancer. In recent years, many have expressed concerns regarding the disconnection between the promises of basic science and the delivery of better individual health. In this paper we describe some of our research in serum proteomics, microarrays and minimal residual disease dedicated to this field and discuss some of the roadblocks ahead in translational research. We conclude that translational medicine should be a collective effort for the medical community as a whole with adequate financial support and sound, measurable outcome. Since extensive validation of the above mentioned research fields is necessary, adequate funding is required. This may require some adjustments in the current funding policy because it involves non-innovative studies. Furthermore, the pool of researchers/clinicians capable of performing translational research must be increased. Additionally, there should be an enhanced participation of patients in clinical trials and an optimization of the efficiency of these trials using validated surrogate markers. Only when these conditions are fulfilled will the 'post-genomic; era of biomedical research have unprecedented opportunities to innovate and improve therapy for cancer.