Filip Zavada

Molecular biology of pancreatic cancer

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

Training on an ex vivo animal model improves endoscopic skills: a randomized, single-blind study

BACKGROUND Animal models are used for training of different endoscopic procedures. Whether this really improves endoscopic skills remains controversial. OBJECTIVE To assess the effectiveness of training by using an ex vivo animal gastric model on the performance of two therapeutic procedures-hemostasis and treatment of perforation. DESIGN A randomized, single-blind study. SETTING An experimental endoscopy center in a university hospital. PARTICIPANTS Thirty-one gastroenterology fellows with comparable endoscopic experience. METHODS Participants were randomized into two groups: with (T, n = 16) and without (S, n = 15) training. All fellows continued with standard endoscopic practice. Baseline skills were assessed at enrollment. All physicians in group T underwent 2 full days of a hands-on course over a 3-month period, in addition to their standard endoscopic practice. Both groups then underwent a blinded, final evaluation. Endoscopic skills were scored from 1 (best) to 5 (poorest) by two expert, blinded tutors. Outcomes of clinical hemostatic procedures also were analyzed. MAIN OUTCOME MEASUREMENTS Successful hemostasis and successful perforation closure. RESULTS Thirty physicians completed the study. Hemostasis results (n = 15): The number of physicians who carried out a successful hemostasis procedure increased significantly in the group with training (27% vs 73%; P = .009) but did not change in the group without training (20% vs 20%). The mean scores of injection and clipping technique improved significantly only after training. The number of clips used decreased significantly only in the group with training; the time of clipping did not change significantly in either group. Perforation results (n = 15): The number of physicians with a successful and complete perforation closure increased nearly significantly in the group with training (40% vs 73%, P = .06) as opposed to the group without training (27% vs 47%; P = .27). The procedure time decreased significantly in the group with training only. In clinical practice, fellows in group T had a significantly higher success rate with respect to hemostatic procedures (83.2%, range 67-100 vs 63.6%, range 25-100; P = .0447). The majority of participants (93%) agreed that such courses should be compulsory in gastroenterological credentials. LIMITATIONS A retrospective analysis of clinical outcomes. Clinical outcome data were based on self-reporting of the participants. CONCLUSION Hands-on training by using an animal ex vivo model improves endoscopic skills in both hemostasis and perforation closure. In clinical practice, the training improves the outcome of hemostatic procedures.

Training of Different Endoscopic Skills on Ex-vivo Animal Model

Introduction Virtual reality simulator and ex vivo animal models are used for training of both basic and advanced endoscopic techniques. The aim of this study was to assess whether hands-on training on ex vivo animal model improves endoscopic skills. Four different endoscopic techniques were practiced: endoscopic resection, endoscopic stenting, application of the over-the-scope (OVESCO) clip, and endoscopic submucosal dissection (ESD). Methods Except for 2 participants, all trainees participated in a 1-day course. Two remaining participants took part in 7 ESD courses. All training courses consisted of theoretical introduction and a 6-hour training on Erlangen Active Training Simulator. The endoscopic skills were assessed before and after the training session by 2 independent assessors. Each assessor evaluated the skills by using a score on a scale of 1 to 5, where 1 stands for excellent and 5 for insufficient. Each assessor also assessed whether the procedure was successfully completed. The main outcome measurement was the percentage of participants who successfully completed the procedure during the test. Results For endoscopic resection, endoscopists (n = 15) improved their skills (median [10th and 90th percentiles] score before training, 3.5 [2.7–4.2]; after training 1.5 [1–2.3], P < 0.001). Seven procedures were assessed as successful before the course (47%); after the training, 13 procedures were assessed as successful (87%) (P = 0.02). For stenting, participants (n = 15) significantly improved their abilities to place both self-expandible metallic and plastic stents. For OVESCO clip (n = 10), participants (n = 10) improved their skills to prepare and apply the clip (given the score of 4.5 [3.9–5] before and 2.0 [1.2–2.8] after, P < 0.01). Before the training, only 1 clip application had been successful (10%), whereas the number rose to 9 after the course (90%). For endoscopic submucosal dissection (n = 10), eight participants of the 1-day course did not improve their competences (with scores of 4.2 [3.8–5] before and 4.0 [3.1–4.8] after, nonsignificant). Two participants who had undertaken 7 ESD courses improved their skills (with scores of 4 before and 1.6 after); given the small number of participants, this finding is statistically insignificant. Limitation The effect of training on clinical outcome was not investigated. There was a lack of pretraining versus posttraining tests blinding. Conclusions A 1-day training course on ex vivo animal model improves general endoscopic competence on simulator in endoscopic resection, insertion of stents, and application of OVESCO clips. In contrast, 1-day course does not improve skills for ESD that requires a higher number of training courses.