Seung-Hun Chon

Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor.

Diagnostic markers are needed for achieving a cure in esophageal cancer, detecting tumor cells earlier. Exosomes are bioactive vesicles secreted by cells into surrounding body fluids. Exosome formation, cargo content, and delivery have major impact in cancer development. This is the first isolation of exosomes from serum of patients with adenocarcinoma of the esophagus and comparison of exosomal miRNA profiles with matching primary tumor and normal tissues. RNA was extracted for miRNA profiling by real-time TaqMan miR arrays. The miR profiles of exosomal cargo, matching tumor, and normal tissue of a subgroup of adenocarcinoma patients have been compared. “Exosomal onco-miRs” such as miR-223-5p, miR-223-3p, miR-483-5p, miR-409-3p, miR-196b-5p, miR-192-5p, miR-146a-5p, and miR-126-5p have been identified as part of exosomal cargo being overexpressed in corresponding tumor compared to normal. Upregulation of miR-223-5p and miR-483-5p in adenocarcinoma (p = 0.034, p = 0.017) has been verified by an independent cohort of 43 patients with T2-3 adeno- and squamous cell carcinoma. In contrast, miR-224-5p, miR-452-5p, miR-23b-5p, miR-203-5p, miR-1201-5p, miR-149-5p, miR-671-3p, miR-944-5p, miR-27b-3p, and miR-22-3p have been identified to be significantly downregulated in adenocarcinoma versus normal and merely or not detectable in exosomes. “Exosomal onco-miRs” are a novel, stable, and noninvasive source for diagnosis and therapy monitoring of esophageal cancer. Oncogenic shuttle miRNAs present in exosomes may contribute to understanding how tumor cells spread their oncogenic potential to the environment. The “exosomal onco-miRs” identified seem to play a major role and may be applied for noninvasive diagnosis and therapy monitoring of adenocarcinoma of the esophagus.

Web-Based Immersive Virtual Patient Simulators: Positive Effect on Clinical Reasoning in Medical Education

Background 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 Objective 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. Methods 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. Results 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. Conclusions 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.

Results of endoscopic vacuum-assisted closure device for treatment of upper GI leaks

BackgroundEsophageal perforations and postoperative leakage of esophagogastrostomies are considered to be life-threatening conditions due to the potential development of mediastinitis and consecutive sepsis. Vacuum-assisted closure (VAC) techniques, a well-established treatment method for superficial infected wounds, are based on a negative pressure applied to the wound via a vacuum-sealed sponge. Endoluminal VAC (E-VAC) therapy as a treatment for GI leakages in the rectum was introduced in 2008. E-VAC therapy is a novel method, and experience regarding esophageal applications is limited. In this retrospective study, the experience of a high-volume center for upper GI surgery with E-VAC therapy in patients with leaks of the upper GI tract is summarized. To our knowledge, this series presents the largest patient cohort worldwide in a single-center study.MethodsBetween October 2010 and January 2017, 77 patients with defects in the upper gastrointestinal tract were treated using the E-VAC application. Six patients had a spontaneous perforation, 12 patients an iatrogenic injury, and 59 patients a postoperative leakage in the upper gastrointestinal tract.ResultsComplete restoration of the esophageal defect was achieved in 60 of 77 patients. The average duration of application was 11.0 days, and a median of 2.75 E-VAC systems were used. For 21 of the 77 patients, E-VAC therapy was combined with the placement of self-expanding metal stents.ConclusionThis study demonstrates that E-VAC therapy provides an additional treatment option for esophageal wall defects. Esophageal defects and mediastinal abscesses can be treated with E-VAC therapy where endoscopic stenting may not be possible. A prospective multi-center study has to be directed to bring evidence to the superiority of E-VAC therapy for patients suffering from upper GI defects.

Gastric cancer treatment in the world: Germany

Epidemiologically, around 15,500 persons per year contract gastric cancer with continuously decreasing incidence and a 5-year survival rate of only 30% to 35%. Contrary to the Asian countries, there are no prevention programs for gastric cancer in Germany, which leads to the disease frequently being diagnosed in locally advanced stages and predominantly being treated with multimodal therapy concepts. Complete (R0) resection is the therapy of choice for resectable gastric cancer. Special forms of gastric cancer that are limited to the mucosa can be endoscopically resected with a curative intent. Systematic D2 lymphadenectomy (LAD) plays a decisive role in the management of local advanced tumors because it significantly contributes to the reduction of tumor-related death and both local and regional relapse rates. Perioperative chemotherapy improves prognosis in the advanced stages, whereas palliative chemotherapy is normally indicated for metastatic diseases. Standardized resection procedures and the use of individualized multimodal therapy concepts have led to improvement in the 5-year survival rate.

Whole-body computed tomography in trauma patients: optimization of the patient scanning position significantly shortens examination time while maintaining diagnostic image quality

Background The study was conducted to compare examination time and artifact vulnerability of whole-body computed tomographies (wbCTs) for trauma patients using conventional or optimized patient positioning. Patients and methods Examination time was measured in 100 patients scanned with conventional protocol (Group A: arms positioned alongside the body for head and neck imaging and over the head for trunk imaging) and 100 patients scanned with optimized protocol (Group B: arms flexed on a chest pillow without repositioning). Additionally, influence of two different scanning protocols on image quality in the most relevant body regions was assessed by two blinded readers. Results Total wbCT duration was about 35% or 3:46 min shorter in B than in A. Artifacts in aorta (27 vs 6%), liver (40 vs 8%) and spleen (27 vs 5%) occurred significantly more often in B than in A. No incident of non-diagnostic image quality was reported, and no significant differences for lungs and spine were found. Conclusion An optimized wbCT positioning protocol for trauma patients allows a significant reduction of examination time while still maintaining diagnostic image quality.

Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence

Oesophageal cancer (OC) has high mortality. This study aims at determining the feasibility of liquid biopsies for genomic profiling in early stage OC, comparing two different technologies for mutational analysis in circulating cell -free DNA (ccfDNA) and evaluating the clinical impact of these somatic alterations during primary staging. In 25 patients with locally advanced OC, endoscopic tumour biopsies and simultaneous blood samples were taken during primary staging. Genomic DNA from biopsies and ccfDNA were analysed for mutations using a 12 gene panel next-generation sequencing (NGS) assay as well as digital droplet PCR (ddPCR). Genetic data was correlated with patients’ outcome. In 21 of the tested biopsies (84%) at least one somatic mutation was detected by NGS. Mutations detected by NGS were detectable by ddPCR with similar allele frequencies. In three out of the 21 patients with proven mutations, the same mutations were also detectable in ccfDNA using NGS (14%). In contrast, ddPCR detected mutations in ccfDNA of five additional patients (8/21, 38%). Post-surgical outcome analysis was performed for those patients who had received complete tumour resection (n = 16). Five of them suffered from an early relapse within the first year after surgery, including four with detectable somatic mutations in ccfDNA during primary staging. Taken together, we showed a higher sensitivity for ddPCR compared to NGS in detecting mutated ccfDNA in OC. Detection of somatically altered ccfDNA during primary staging seems to be indicative for post-surgical tumour recurrence.

Upregulation of insulin-like growth factor II mRNA-binding protein 3 (IMP3) has negative prognostic impact on early invasive (pT1) adenocarcinoma of the esophagus

PurposeTherapeutic decisions in esophageal adenocarcinomas (EAC) restricted to mucosa (pT1a) or submucosa (pT1b) depend mainly on classic histomorphology-based criteria like tumor grading or lymphovascular invasion with limited success. There is a strong need for reliable pre-therapeutical biomarker-based evaluation also applicable on endoscopically obtained biopsies.MethodsPatients who underwent esophagectomy due to EAC in a high volume center between 1999 and 2016 were included. Tissue microarrays (TMA) were retrospectively established from the formalin-fixed and paraffin-embedded material of the resected specimens and immunohistochemically stained using a monoclonal primary antibody specific for IMP3. IMP3 staining intensity was scored manually according to a 3-tier-scoring system (negative, weak and strong).Results371 EACs were interpretable for analysis. 109 patients (29%) had early invasive (pT1a/pT1b) and 262 patients (71%) locally advanced EAC (> pT2). 259 EACs (70%) revealed positive immunostaining for IMP3 including 167 strongly and 92 weakly positive. Early EAC had significantly lower IMP3 expression compared to advanced tumor stages (p < 0.0001). IMP3 positive pT1 EAC revealed higher levels of lymph node metastases (LNM) (p = 0.0001) and pT1b tumors showed higher rates of IMP3 positivity compared to pT1a (p = 0.007). Subdividing the submucosa in thirds, there was a significant trend for higher IMP3 expression with deeper tumor infiltration from pT1a to pT1b (sm3) (p = 0.0001). There was an association between IMP3 expression and shortened survival in pT1 EAC (p = 0.038).ConclusionsIMP3 expression correlates with depth of tumor infiltration, rate of LNM and is associated with worse outcome. Thus, IMP3 might be useful for therapeutic decisions in early-invasive EAC.

Web-Based Immersive Patient Simulator as a Curricular Tool for Objective Structured Clinical Examination Preparation in Surgery: Development and Evaluation

Background Objective Structured Clinical Examination is a standard method of testing declarative and process knowledge in clinical core competencies. It is desirable that students undergo Objective Structured Clinical Examination training before participating in the exam. However, establishing Objective Structured Clinical Examination training is resource intensive and therefore there is often limited practice time. Web-based immersive patient simulators such as ALICE (Artificial Learning Interface of Clinical Education) can possibly fill this gap as they allow for the training of complex medical procedures at the user’s individual pace and with an adaptable number of repetitions at home. ALICE has previously been shown to positively influence knowledge gain and motivation. Objective Therefore, the aim of this study was to develop a Web-based curriculum that teaches declarative and process knowledge and prepares students for a real Objective Structured Clinical Examination station. Furthermore, we wanted to test the influence of ALICE on knowledge gain and student motivation. Methods A specific curriculum was developed in order to implement the relevant medical content of 2 surgical Objective Structured Clinical Examination stations into the ALICE simulator framework. A total of 160 medical students were included in the study, where 100 students had access to ALICE and their performance was compared to 60 students in a control group. The simulator performance was validated on different levels and students’ knowledge gain and motivation were tested at different points during the study. Results The curriculum was developed according to the Kern cycle. Four virtual clinical cases were implemented with different teaching methods (structured feedback, keynote speech, group discussion, and debriefing by a real instructor) in order to consolidate declarative and process knowledge. Working with ALICE had significant impact on declarative knowledge gain and Objective Structured Clinical Examination performance. Simulator validation was positive for face, content, construct, and predictive validity. Students showed high levels of motivation and enjoyed working with ALICE. Conclusions ALICE offers Web-based training for Objective Structured Clinical Examination preparation and can be used as a selective didactic intervention as it has positive effect on knowledge gain and student motivation.

Medical students' attitude towards artificial intelligence: a multicentre survey

ObjectivesTo assess undergraduate medical students’ attitudes towards artificial intelligence (AI) in radiology and medicine.Materials and methodsA web-based questionnaire was designed using SurveyMonkey, and was sent out to students at three major medical schools. It consisted of various sections aiming to evaluate the students’ prior knowledge of AI in radiology and beyond, as well as their attitude towards AI in radiology specifically and in medicine in general. Respondents’ anonymity was ensured.ResultsA total of 263 students (166 female, 94 male, median age 23 years) responded to the questionnaire. Around 52% were aware of the ongoing discussion about AI in radiology and 68% stated that they were unaware of the technologies involved. Respondents agreed that AI could potentially detect pathologies in radiological examinations (83%) but felt that AI would not be able to establish a definite diagnosis (56%). The majority agreed that AI will revolutionise and improve radiology (77% and 86%), while disagreeing with statements that human radiologists will be replaced (83%). Over two-thirds agreed on the need for AI to be included in medical training (71%). In sub-group analyses male and tech-savvy respondents were more confident on the benefits of AI and less fearful of these technologies.ConclusionContrary to anecdotes published in the media, undergraduate medical students do not worry that AI will replace human radiologists, and are aware of the potential applications and implications of AI on radiology and medicine. Radiology should take the lead in educating students about these emerging technologies.Key Points• Medical students are aware of the potential applications and implications of AI in radiology and medicine in general.• Medical students do not worry that the human radiologist or physician will be replaced.• Artificial intelligence should be included in medical training.

Successful closure of a gastropulmonary fistula after esophagectomy using the Apollo Overstitch and endoscopic vacuum therapy

Gastropulmonary fistulas following transthoracic en bloc esophagectomy and intrathoracic gastric reconstruction (Ivor Lewis esophagectomy) are rare but life-threatening complications. Surgical management of these is difficult and associated with significant instances of morbidity andmortality [1]. One possible treatment for leaks after upper gastrointestinal surgery is endoluminal vacuum therapy (EVT) [2]. A newer treatment option is the endoscopic suturing system Apollo Overstitch [3–5]. The Overstitch is a single-use device that is placed on top of a double-channel therapeutic endoscope, which facilitates full-thickness surgical suturing in single or running technique. To our knowledge, the case presented below constitutes the first successful clinical application of a combination of Overstitch and EVT to close a gastropulmonary fistula after Ivor Lewis esophagectomy. We present the case of a 58-year-old man who underwent neoadjuvant chemoradiation (CROSS protocol) followed by Ivor Lewis esophagectomy for esophageal adenocarcinoma (histopathology: ypT3, ypN2 (3/45), L1, V0, Pn0, R0). About 3 months after the initial surgery, the patient was admitted to our hospital with recurring episodes of pneumonia. Computed tomography (CT) scanning with oral contrast and endoscopy showed a fistula between the pull-up gastric interponate and the right lung parenchyma (▶Fig. 1 and ▶Fig. 2). We applied the Overstitch system to close the fistula endoscopically. After two attempts, we were able to close the fistula using the single-suturing technique (▶Fig. 3; ▶Video1). A triple-lumen diverted nasal tube (e. g. Freka Trelumina; Fresenius Kabi, Germany) was then inserted to allow the patient to receive enteral feeding. Furthermore, to evacuate any biliary reflux and to reduce the pressure on the suturing line, we placed a polyurethane foam drainage tube (e. g. EsoSponge; Braun, Germany) with negative pressure (–125mmHg, continuous; VivanoTec; Hartmann AG, Germany). During the 31 days of this EVT, the foam drainage was changed seven times. E-Videos