PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988 ) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.
1 January 2020 in International Journal of Biological Sciences
As one of the most common malignant tumors worldwide, hepatocellular carcinoma (HCC) is known for its poor prognosis due to diagnosis only in advanced stages. Nearly 50% of the patients with the first diagnosis of HCC die within a year. Currently, the advancements in the integration of omics information have begun to transform the clinical management of cancer patients. Molecular profiling for HCC patients is in general obtained from resected tumor materials or biopsies. However, the resected tumor tissue is limited and can only be obtained through surgery, so that dynamic monitoring of patients cannot be performed. Compared to invasive procedures, circulating tumor DNA (ctDNA) has been proposed as an alternative source to perform molecular profiling of tumor DNA in cancer patients. The detection of abnormal forms of circulating cell-free DNA (cfDNA) that originate from cancer cells (ctDNA) provides a novel tool for cancer detection and disease monitoring. This may also be an opportunity to optimize the early diagnosis of HCC. In this review, we summarized the updated methods, materials, storage of sampling, detection techniques for ctDNA and the comparison of the applications among different biomarkers in HCC patients. In particular, we analyzed ctDNA studies dealing with copy number variations, gene integrity, mutations (RAS, TERT, CTNNB1, TP53 and so on), DNA methylation alterations (DBX2, THY1, TGR5 and so on) for the potential utility of ctDNA in the diagnosis and management of HCC. The biological functions and correlated signaling pathways of ctDNA associated genes (including MAPK/RAS pathway, p53 signaling pathway and Wnt-β catenin pathway) are also discussed and highlighted. Thus, exploration of ctDNA/cfDNA as potential biomarkers may provide a great opportunity in future liquid biopsy applications for HCC.
17 November 2015 in Journal of Medical Internet Research
Clinical reasoning is based on the declarative and procedural knowledge of workflows in clinical medicine. Educational approaches such as problem-based learning or mannequin simulators support learning of procedural knowledge. Immersive patient simulators (IPSs) go one step further as they allow an illusionary immersion into a synthetic world. Students can freely navigate an avatar through a three-dimensional environment, interact with the virtual surroundings, and treat virtual patients. By playful learning with IPS, medical workflows can be repetitively trained and internalized. As there are only a few university-driven IPS with a profound amount of medical knowledge available, we developed a university-based IPS framework. Our simulator is free to use and combines a high degree of immersion with in-depth medical content. By adding disease-specific content modules, the simulator framework can be expanded depending on the curricular demands. However, these new educational tools compete with the traditional teaching It was our aim to develop an educational content module that teaches clinical and therapeutic workflows in surgical oncology. Furthermore, we wanted to examine how the use of this module affects student performance. The new module was based on the declarative and procedural learning targets of the official German medical examination regulations. The module was added to our custom-made IPS named ALICE (Artificial Learning Interface for Clinical Education). ALICE was evaluated on 62 third-year students. Students showed a high degree of motivation when using the simulator as most of them had fun using it. ALICE showed positive impact on clinical reasoning as there was a significant improvement in determining the correct therapy after using the simulator. ALICE positively impacted the rise in declarative knowledge as there was improvement in answering multiple-choice questions before and after simulator use. ALICE has a positive effect on knowledge gain and raises students' motivation. It is a suitable tool for supporting clinical education in the blended learning context.
Background Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Methods Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. Results The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm3, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, −7.7% to 8.6%; MELV vs MAG3 0.4%, −8.9% to 9.7%; RCV vs MAG3 0.8%, −9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Conclusions Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.
8 April 2015 in Journal of Medical Internet Research
Background: Immersive patient simulators (IPSs) combine the simulation of virtual patients with a three-dimensional (3D) environment and, thus, allow an illusionary immersion into a synthetic world, similar to computer games. Playful learning in a 3D environment is motivating and allows repetitive training and internalization of medical workflows (ie, procedural knowledge) without compromising real patients. The impact of this innovative educational concept on learning success requires review of feasibility and validity. Objective: It was the aim of this paper to conduct a survey of all immersive patient simulators currently available. In addition, we address the question of whether the use of these simulators has an impact on knowledge gain by summarizing the existing validation studies. Methods: A systematic literature search via PubMed was performed using predefined inclusion criteria (ie, virtual worlds, focus on education of medical students, validation testing) to identify all available simulators. Validation testing was defined as the primary end point. Results: There are currently 13 immersive patient simulators available. Of these, 9 are Web-based simulators and represent feasibility studies. None of these simulators are used routinely for student education. The workstation-based simulators are commercially driven and show a higher quality in terms of graphical quality and/or data content. Out of the studies, 1 showed a positive correlation between simulated content and real content (ie, content validity). There was a positive correlation between the outcome of simulator training and alternative training methods (ie, concordance validity), and a positive coherence between measured outcome and future professional attitude and performance (ie, predictive validity). Conclusions: IPSs can promote learning and consolidation of procedural knowledge. The use of immersive patient simulators is still marginal, and technical and educational approaches are heterogeneous. Academic-driven IPSs could possibly enhance the content quality, improve the validity level, and make this educational concept accessible to all medical students. [J Med Internet Res 2015;17(4):e91]
Objective: To evaluate if “state-of-the-art” 3D- versus 4K-display techniques could influence surgical performance. Background: High quality minimally invasive surgery is challenging. Therefore excellent vision is crucial. 3D display technique (3D) and 2D-4K technique (4K) are designed to facilitate surgical performance, either due to spatial resolution (3D) or due to very high resolution (4K). Methods: In randomized cross-over trial the surgical performance of medical students (MS), non-board certified surgeons (NBC), and board certified surgeons (BC) was compared using 3D versus 4K display technique at a minimally invasive training Parkour. Results: One hundred twenty-eight participants were included (February 2018 through October 2019, 49 MS, 39 NBC, 40 BC). The overall Parkour time (s) 3D versus 4K was 712.5 s ± 17.5 s versus 999.5 s ± 25.1 s (P < 0.001) for all levels of experience. It was (3D vs 4K) for MS (30 tasks) 555.4 s ± 28.9 s versus 858.7 s ± 41.6 s, (P < 0.0001), for NBC (42 tasks) 935.9 s ± 31.5 s versus 1274.1 s ± 45.1 s (P =< 0.001) and for BC (42 task) 646.3 s ± 30.9 s versus 865.7 s ± 43.7 s (P < 0.001). The overall number of mistakes was (3D vs 4K) 10.0 ± 0.5 versus 13.3 ± 0.7 (P < 0.001), for MS 8.9 ± 0.9 versus 13.1 ± 1.1 (P < 0.001), for NBC 12.45 ± 1.0 versus 16.7 ± 1.2 (P < 0.001) and for BC 8.8 ± 1.0 versus 10.0 ± 1.2 (P = 0.18). MS, BC, and NBC showed shorter performance time in 100% of the task with 3D (significantly in 6/7 tasks). For number of mistakes the effect was less pronounced for more experienced surgeons. The National Aeronautics and Space Administration-task load index was lower with 3D. Conclusion: 3D laparoscopic display technique optimizes surgical performance compared to the 4K technique. Surgeons benefit from the improved visualization regardless of their individual surgical expertise.