PURPOSE Detection of breast cancer at early stage increases patient's survival. Mass spectrometry-based protein analysis of serum samples is a promising approach to obtain biomarker profiles for... Show morePURPOSE Detection of breast cancer at early stage increases patient's survival. Mass spectrometry-based protein analysis of serum samples is a promising approach to obtain biomarker profiles for early detection. A combination of commonly applied solid-phase extraction procedures for clean-up may increase the number of detectable peptides and proteins. In this study, we have evaluated whether the classification performance of breast cancer profiles improves by using two serum workup procedures. METHODS Serum samples from 105 breast cancer patients and 202 healthy volunteers were processed according to a standardized protocol implemented on a high-end liquid-handling robot. Peptide and protein enrichments were carried out using weak-cation exchange (WCX) and reversed-phase (RP) C18 magnetic beads. Profiles were acquired on a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer. In this way, two different biomarker profiles were obtained for each serum sample, yielding a WCX- and RPC18-dataset. RESULTS The profiles were statistically evaluated with double cross-validation. Classification results of WCX- and RPC18-datasets were determined for each set separately and for the combination of both sets. Sensitivity and specificity were 82 and 87 % (WCX) and 73 and 93 % (RPC18) for the individual workup procedures. These values increased up to 84 and 95 %, respectively, upon combining the data. CONCLUSION It was found that MALDI-TOF peptide and protein profiles can be used for classification of breast cancer with high sensitivity and specificity. The classification performance even improved when two workup procedures were applied, since these provide a greater number of features (proteins). Show less
Aims: The aim of the study was to assess which factors contribute to postoperative mortality, especially in elderly patients who undergo emergency colon cancer resections, using a nationwide... Show moreAims: The aim of the study was to assess which factors contribute to postoperative mortality, especially in elderly patients who undergo emergency colon cancer resections, using a nationwide population-based database. Methods: 6,161 patients (1,172 nonelective) who underwent a colon cancer resection in 2010 in the Netherlands were included. Risk factors for postoperative mortality were investigated using a multivariate logistic regression model for different age groups, elective and nonelective patients separately. Results: For both elective and nonelective patients, mortality risk increased with increasing age. For nonelective elderly patients (80+ years), each additional risk factor increased the mortality risk. For a nonelective patient of 80+ years with an American Society of Anesthesiologists score of III+ and a left hemicolectomy or extended resection, postoperative mortality rate was 41% compared with 7% in patients without additional risk factors. Conclusions: For elderly patients with two or more additional risk factors, a nonelective resection should be considered a high-risk procedure with a mortality risk of up to 41%. The results of this study could be used to adequately inform patient and family and should have consequences for composing an operative team. Show less
AIMS: We propose a summarizing measure for outcome indicators, representing the proportion of patients for whom all desired short-term outcomes of care (a 'textbook outcome') is realized. The aim... Show moreAIMS: We propose a summarizing measure for outcome indicators, representing the proportion of patients for whom all desired short-term outcomes of care (a 'textbook outcome') is realized. The aim of this study was to investigate hospital variation in the proportion of patients with a 'textbook outcome' after colon cancer resections in the Netherlands. METHODS: Patients who underwent a colon cancer resection in 2010 in the Netherlands were included in the Dutch Surgical Colorectal Audit. A textbook outcome was defined as hospital survival, radical resection, no reintervention, no ostomy, no adverse outcome and a hospital stay < 14 days. We calculated the number of hospitals with a significantly higher (positive outlier) or lower (negative outlier) Observed/Expected (O/E) textbook outcome than average. As quality measures may be more discriminative in a low-risk population, analyses were repeated for low-risk patients only. RESULTS: A total of 5582 patients, treated in 82 hospitals were included. Average textbook outcome was 49% (range 26-71%). Eight hospitals were identified as negative outliers. In these hospitals a 'textbook outcome' was realized in 35% vs. 52% in average hospitals (p < 0.01). In a sub-analysis for low-risk patients, only one additional negative outlier was identified. CONCLUSIONS: The textbook outcome, representing the proportion of patients with a perfect hospitalization, gives a simple comprehensive summary of hospital performance, while preventing indicator driven practice. Therewith the 'textbook outcome' is meaningful for patients, providers, insurance companies and healthcare inspectorate. Show less
Colorectal cancer is the third most common cancer worldwide with an annual incidence of ~1 million cases and an annual mortality rate of ~655,000 individuals. There is an urgent need for... Show moreColorectal cancer is the third most common cancer worldwide with an annual incidence of ~1 million cases and an annual mortality rate of ~655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers. Show less
