Project description:Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) but also up to one year after the intervention by using untargeted metabolomics. 132 serum samples taken from 44 patients before surgery, after hospital discharge (1–3 weeks after surgery) and at a 1-year follow-up during a prospective study (NCT01271062) performed at two study centers (Austria and Switzerland). The samples included 24 patients with type 2 diabetes at baseline, thereof 9 with diabetes remission after one year. The samples were analyzed by using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS, HILIC-QExactive). Raw data was processed with XCMS and drift-corrected through quantile regression based on quality controls. 177 relevant metabolic features were selected through Random Forests and univariate testing and 36 metabolites were identified. Identified metabolites included trimethylamine-N-oxide, alanine, phenylalanine and indoxyl-sulfate which are known markers for cardiovascular risk. In addition we found a significant decrease in alanine after one year in the group of patients with diabetes remission relative to non-remission. Our analysis highlights the importance of assessing multiple points in time in subjects undergoing bariatric surgery to enable the identification of biomarkers for treatment response, cardiovascular benefit and diabetes remission. Key-findings include different trend pattern over time for various metabolites and demonstrated that short term changes should not necessarily be used to identify important long term effects of bariatric surgery.
Project description:Background. Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. Methods. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Results. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. Conclusions. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome.
Project description:Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis, with a 5-year survival rate of 100%. However, early invasive adenocarcinoma (EIA) often has a fatal outcome. In this study, we compared the expression profiles of AIS with those of EIA showing a fatal outcome, and screened the differentially expressed genes by cDNA microarray.
Project description:Interventions: Lap group:laparoscopic radical resection of colorectal cancer;TV-NOSE group:laparoscopic radical resection of colorectal cancer with transvaginal specimen extraction
Primary outcome(s): Sexual function (After);5 year disease free survival;5 year disease free survival;postoperative length of stay;postoperative length of stay;rate of short-term complication
Study Design: Factorial
Project description:Interventions: study group, control group:incomplete ERAS
Primary outcome(s): 5-year Disease free survival and overall survival
Study Design: Cohort study
Project description:Purpose: The objective of this study was to evaluate the impact of operation duration on short- and long-term outcomes of colorectal cancer patients following surgical resection. Methods: 6224 consecutive patients who underwent radical colorectal surgery were retrospectively assessed and were divided into short operation duration group (SOD) and long operation duration group (LOD) according to the operation duration cutoff value of 110 minutes. Results: Compared with patients in LOD group, patients in SOD group had significantly lower total costs in hospital, reduced expenses for drugs and antibiotics, shorter length of stay (LOS) in hospital and in the ICU. Moreover, 5-year overall survival (OS) and disease-free survival (DFS) for patients in the SOD group were markedly higher than for patients in the LOD group. Mutivariate regression analysis indicated that longer operation duration was associated with poor prognosis, with a hazard ratio of 1.004 (1.003, 1.005) for OS and 1.005 (1.003, 1.006) for DFS. Finally, surgeons' qualifications had meaningful correlation with operation duration (r= 0.450). Conclusions: Operation duration is an independent risk factor for patients' short-term and long-term outcome after radical colorectal surgery. Improve the surgical skills of the surgeon may shorten the operation duration, and further improve the outcome for patients.
Project description:Acute Myeloid Leukaemia (AML) carries a 5 year survival rate of just 24%. Toxic chemotherapy regimens remain the backbone of standard of care for AML. The KIT tyrosine kinase is a recognised AML oncogene, associated with poor outcome. We recently identified DNA-PK as a novel therapeutic target in FLT3 mutant AML. The similarity between KIT and FLT3 regulated signalling pathways led us to investigate DNA-PK in KIT-mutant AML.
Project description:This study aimed to identify the genetic signatures associated with disease prognosis in bladder cancer. We used 165 primary bladder cancer samples, 23 recurrent non-muscle invasive tumor tissues, 58 normal looking bladder mucosae surrounding cancer and 10 normal bladder mucosae for microarray analysis. Hierarchical clustering was used to stratify the prognosis-related gene classifiers. For validation, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of top-ranked 14 genes was performed. On unsupervised hierarchical clustering using prognosis related gene-classifier, tumors were divided into 2 groups. The high risk gene signatures had significantly poor prognosis compared to low risk gene signatures (P<0.001 by the log-rank test, respectively). The prognosis-related gene classifiers correlated significantly with recurrence of non-muscle invasive bladder cancer (hazard ratio, 4.09; 95% confidence interval [CI], 1.94 to 8.64; P<0.001), and progression (hazard ratio, 23.68; 95% confidence interval [CI], 4.91 to 114.30; P<0.001), cancer-specific survival (hazard ratio, 29.25; 95% confidence interval [CI], 3.47 to 246.98; P=0.002) and overall survival (hazard ratio, 23.33; 95% confidence interval [CI], 4.97 to 109.50; P<0.001) of muscle invasive bladder cancer (p < 0.001, respectively). No patient with non-muscle invasive bladder cancer experienced cancer progression in low risk gene signature group. Prognosis-related gene classifiers validated by RT- PCR showed identical results. Prognosis related gene-classifiers provided strong predictive value for disease outcome. These gene classifiers could assist in selecting patients who might benefit from more aggressive therapeutic intervention or surveillance. Keywords: Gene expression, Bladder cancer, Prognosis