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OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.
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Metabolómica , Humanos , Metabolómica/métodos , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/metabolismo , Neoplasias Gástricas/sangre , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/diagnóstico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Neoplasias Gastrointestinales/sangre , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/diagnóstico , Metaboloma/fisiología , Estudios de Casos y Controles , Unión Esofagogástrica/patología , Unión Esofagogástrica/metabolismoRESUMEN
PURPOSE: Beside many advantages, disadvantages such as reduced degrees of freedom and poorer depth perception are still apparent in laparoscopic surgery. 3D visualization and the development of complex instruments are intended to counteract the disadvantages. We want to find out whether the use of complex instruments and 3D visualization has an influence on the performance of novices. METHODS: 48 medical students with no experience in laparoscopic surgery or simulator-based laparoscopy training were included. They were randomized in four groups according to a stratification assessment. During a structured training period they completed the FLS-Tasks "PEG Transfer", "Pattern Cut" and "Intracorporeal Suture" and a transfer task based on these three. Two groups used conventional laparoscopic instruments with 3D or 2D visualization, two groups used complex curved instruments. The groups were compared in terms of their performance. RESULTS: In 2D laparoscopy there was a better performance with straight instruments vs. curved instruments in PEG Transfer and Intracorporeal Suture. In the transfer task, fewer errors were made with straight instruments. In 2D vs. 3D laparoscopy when using complex curved instruments there was an advantage in Intracorporeal Suture and PEG Transfer for 3D visualization. Regarding the transfer exercise, a better performance was observed and fewer errors were made in 3D group. CONCLUSION: We could show that learning laparoscopic techniques with complex curved instruments is more difficult with standard 2D visualization and can be overcome using 3D optics. The use of curved instruments under 3D vision seems to be advantageous when working on more difficult tasks.
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Laparoscopía , Entrenamiento Simulado , Humanos , Competencia Clínica , Imagenología Tridimensional/métodos , Laparoscopía/métodos , Curva de Aprendizaje , Entrenamiento Simulado/métodosRESUMEN
RATIONALE: Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far. MATERIAL AND METHODS: Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison. RESULTS: We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFß pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFß pathway. CONCLUSION: Our results suggest the TGFß pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFß pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFß pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.