Esophageal Magnetic Anastomosis Device (EMAD) to Simplify and Improve Outcome of Thoracoscopic Repair for Esophageal Atresia with Tracheoesophageal Fistula: A Proof of Concept Study.

BACKGROUND: We designed a new Esophageal Magnetic Anastomosis Device (EMAD) for thoracoscopic repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) without the need of handheld suturing or additional gastrostomy. METHODS: Synthetic EA-TEF model: Spherical and tubular shaped rubber balloons and a term infant sized plastic doll were used. Medical students (n = 10) and surgical trainees (n = 10) were asked to perform thoracoscopic repair of an "EA" with a hand sutured anastomosis (HA) and with the EMAD. Euthanized animal model: The esophagus in 5 piglets (3-4 kg) was dissected and a thoracoscopic esophageal magnetic anastomosis (EMA) was performed. Bursting pressure (BP) and pulling force (PF): HA and EMA were created on ex vivo New Zealand white rabbit (2.5-3 kg) esophagi (n = 25 in each test series). BP and PF were measured and compared against each other. RESULTS: Medical students were unable to complete HA, but were successful with the EMAD in 11.1 ± 2.78 min. Surgical trainees completed EMA in 4.6 ± 2.06 min vs. HA 30.8 ± 4.29 min (p<0.001). The BP following a HA (14.1 ± 3.32 cmH2O) was close to the physiological intraluminal pressure reported in a neonatal esophagus (around 20 cmH2O), whereas the BP with the EMAD was extremely high (>90 cmH2O) (p<0.001). The PF of an EMA (1.8 ± 0.30 N) was closer to the safety limits of anastomotic tension reported in the literature (i.e. 0.75 N) compared with the HA (3.6 ± 0.43 N) (p<0.0001). CONCLUSION: The EMAD could simplify, shorten, and potentially improve the outcome of thoracoscopic repair for EA with TEF in the future. A high BS and a relative low PF following EMAD application may lower the risk of postoperative complications such as esophageal leakage and stricture formation.

Paradoxical alteration of indocyanine green concentration in bile and the visibility of the intra-operative fluorescence cholangiography in pigs.

Background: A significant difference exists between the reported optimal timing of indocyanine green (ICG) injection during fluorescence cholangiography and ICG dissipation time from the serum. There are no reports on alterations in ICG concentration in biliary fluid over time. Herein, we measured the concentration of ICG and the fluorescence intensity ratio between the common bile duct (CBD) and liver, which was recognized as a parameter of the visibility of the CBD. Materials and methods: ICG (0.05 mg/kg) was injected intravenously into female pigs (n = 7). Afterwards, the fluorescence of the CBD and liver was detected at 30 min, 2 h, and 4 h. Biliary fluid was collected from cannulated CBD tubes. The fluorescence intensity was measured using captured images and calculated using the ImageJ image-processing program. ICG concentration was measured using spectrophotometry and compared using an analysis of variance test. Results: Biliary ICG concentrations at 30 min, 2 h, and 4 h were 92.07 ± 27.72 µg/mL, 37.14 ± 9.76 µg/mL (p < 0.05 vs. 30 min), and 13.91 ± 5.71 µg/mL (p < 0.05 vs. 30 min), respectively; p < 0.01. The CBD/liver fluorescence intensity ratios at 30 min, 2 h, and 4 h were 1.25 ± 0.72, 2.39 ± 1.28 (p < 0.05 vs. 30 min and 4 h), and 3.38 ± 1.73 (p < 0.05 vs. 30 min and 2 h), respectively. Conclusions: The ICG biliary concentration was highest at 30 min, whereas the CBD/liver fluorescence intensity ratio was highest at 4 h. Decreasing the fluorescence intensity of the liver may be an important approach for improving the visualization of the CBD during fluorescence cholangiography. Institutional protocol number: PE/EA/491-5/2020.

#Erasmus+ ­ or surgical research, development and innovation at the Department of Surgical Research and Techniques at Semmelweis University / #Erasmus+ - avagy sebészeti kutatás-fejlesztés és innováció a Semmelweis Egyetem Kísérletes és Sebészeti Mutéttani Tanszékén

The European Union is earmarking more and more resources each cycle to support research, development and innovation, and the projects set up by the working groups are helping to develop innovative solutions to reflecting societal issues of today. Since 2014, the Department of Surgical Research and Techniques of the Cardiovascular Center at Semmelweis University has been participating in international consortia supported by the Erasmus+ programme, which aim to modernise the teaching methodology of surgical training and to integrate IT technology into the training of surgical residents at pan-European level. This paper briefly summarises the international projects in which the Department has been involved over the last 7 years.

Adhesion stabilization in the early postoperative period in a rat model / Az adhézió stabilizálódásának meghatározása a korai posztoperatív idoszakban patkány modellen

Introduction: Adhesion formation is a complex series of events that results from cellular and molecular processes where, in contrast to the normal case, events that support adhesion genesis dominate over adhesion lysis. Tissue injury, haemorrhage, tissue desiccation and inflammatory processes, among others, play a role in its induction. Since the presence of adhesions can be associated with a number of negative complications, the primary aim is to prevent their development. There are several preventive targets for the process, but in many cases therapy is only provided immediately after the procedure. In this study, we present an experimental rat model of adhesion, where the aim is to understand the stabilization period of adhesion. All animals underwent the same surgical procedure, inducing tissue injury, minor haemorrhage and tissue desiccation, differing only in the timing of reoperations and sampling. On postoperative days 1­7, we assessed macroscopically and histopathologically the type of adhesions formed, the adhesive tissue, the stability of the adhesion. We found that stabilization was a process lasting several days, with unstable and moderately stable adhesions predominating by postoperative day 4. Knowing this allows to broaden the therapeutic window, targeting the most appropriate period in the early postoperative period, possibly combining treatments, to make adhesion prevention even more effective.

Peritoneum, the multifunctional membrane / Peritoneum, a multifunkcionális hártya

Introduction: Not only atraumatic surgical technique, precise bleeding control, removal foreign materials from the abdomen, but also avoiding desiccation or mechanical damage of peritoneal surface at abdominal surgery mean today evidence based expectation. Peritoneum with its extensive surface and special histological structure represents an important factor in normal physiological processes, furthermore as "Guard of abdomen" it has an important role to localise inflammatory reactions, useful as dialysing surface and provides also possibility for hyperthermic abdominal chemotherapy in tumour treatment. Largest part of peritoneal sac covers small intestine and colon. To prevent postoperative complications it is necessary to avoid desiccation of intestinal tract at laparoscopic and at open procedures as well ­ consequently "rehyration" is a routine recommendation today. Desiccation of intestinal tract results postoperative adhesions, furthermore damage of serosa will increase permeability of intestine wall and can result perforation. All the surgical recommendations suggest keeping intestine moist, whereas there are only a few real studies in surgical literature to support or to deny this theory. Our study reviews the pathophysiological and surgical respects of this situation and summarizes the results of latest researches of combined functions of peritoneum.

Early and late effects of absorbable poly(vinyl alcohol) hernia mesh to tissue reconstruction.

Hernia is a defect of the abdominal wall. Treatment is principally surgical mesh implantation. Non-degradable surgical meshes produce numerous complications and side-effects such as inflammatory response, mesh migration and chronic pain. In contrast, the biodegradable, poly (vinyl alcohol) (PVA) based polymers have excellent chemical, mechanical and biological properties and after their degradation no chronic pain can be expected. The toxicology of PVA solution and fibers was investigated with Human dermal fibroblast- Adult cell line. Implantation tests were observed on long-term contact (rat) and large animal (swine) models. To measure the adhesion formation, Diamond and Vandendael score were used. Macroscopical and histological responses were graded from the samples. In vitro examination showed that PVA solution and fibers are biocompatible for the cells. According to the implantation tests, all samples were integrated into the surrounding tissue, and there was no foreign body reaction. The average number of adhesions was found on the non-absorbable suture line. The biocompatibility of the PVA nanofiber mesh was demonstrated. It has a non-adhesive, non-toxic and good quality structure which has the potential to be an alternative solution for the part of the hernia mesh.

AC5 Surgical Hemostat™ as an effective hemostatic agent in an anticoagulated rat liver punch biopsy model.

Intra-operative and postoperative bleeding is a major concern in surgical procedures for patients taking anticoagulant medications, or where anticoagulants are used to prevent potential life-threatening embolic complications. Heparin is the anticoagulant used most frequently and has an immediate effect on blood clotting, lasting 4 to 6h. Although synthetic self-assembling peptides have been shown to achieve rapid hemostasis in small animals, none have adequately addressed the potential for hemostasis in the presence of anticoagulant therapy in-vivo. Our goal was to investigate the hemostatic activity of a known synthetic self-assembling peptide in animals treated and untreated with heparin anticoagulation therapy. Using a rat liver puncture model, animals were treated with known synthetic peptide AC5 Surgical Hemostatic Device™, or saline controls. Time-to-hemostasis and coagulation times were recorded in both heparinized and non-heparinized animals. Here we show that AC5™ was able to achieve rapid hemostasis equivalently in both heparinized and non-heparinized animals. FROM THE CLINICAL EDITOR: Intra-operative and postoperative bleeding is a major concern in surgical procedures for patients taking anticoagulant medications. In this work the effective hemostasis was demonstrated both in heparinized and non-heparinized animals using self-assembling peptides.

[Robotic surgery]. / Robotsebészet.

Due to the fast spread of laparoscopic cholecystectomy, surgical procedures have been changed essentially. The new techniques applied for both abdominal and thoracic procedures provided the possibility for minimally invasive access with all its advantages. Robots - originally developed for industrial applications - were retrofitted for laparoscopic procedures. The currently prevailing robot-assisted surgery is ergonomically more advantageous for the surgeon, as well as for the patient through the more precise preparative activity thanks to the regained 3D vision. The gradual decrease of costs of robotic surgical systems and development of new generations of minimally invasive devices may lead to substantial changes in routine surgical procedures.

[Examination of cytoprotective and anti-inflammatory effect of PACAP-38 on small bowel autotransplantation]. / A PACAP-38 citoprotektív és antiinflammatórikus hatásának vizsgálata vékonybél-autotranszplantációs modellben.

INTRODUCTION: The small intestine is one of the most sensitive organs to ischemia-reperfusion injury during transplantation. Cytoprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) is well known. The aim of our study was to measure changes of PACAP-38-like immunoreactivities and cytokine levels in intestinal grafts stored PACAP-38 containing preservation solution. MATERIAL AND METHODS: Small-bowel autotransplantation was performed on male Wistar rats (n = 56). Grafts were stored in University of Wisconsin (UW) solution at 4 °C for 1 (GI), 3 (GII), and 6 hours (GIII); and in PACAP-38 containing UW solution for 1 (GIV), 3 (GV), and 6 hours (GVI). Reperfusion lasted 3 hours in each group. Intestinal PACAP-38 immunoreactivities were measured by radioimmunoassay. To measure cytokine from tissue homogenates we used rat cytokine array and Luminex Multiplex Immunoassay. RESULTS: Levels of PACAP-38-like and PACAP-27-like immunoreactivities decreased by preservation time compared to control. This decrease was significant following 6 hours cold storage (p < 0.05). Values remained significantly higher in grafts stored in PACAP-38 containing UW. Expressions of sICAM-1, L-selectin, tissue inhibitor of metalloproteinase-1 were increased in GIII and were decreased in GVI. CONCLUSION: PACAP-38 increased tissue levels of PACAP-38 and PACAP-27, and decreased cytokine expression. This indicates that PACAP-38 has anti-inflammatory and cytoprotective effects in intestinal autotransplantation model.

[New possibilities in practical education of surgery]. / Új lehetoségek a sebészet gyakorlati oktatásában.

The fast spread of laparoscopic surgery in the surgical community also required introduction of new methods of surgical education of these techniques. Training boxes applied for this reason meant a considerable help. The technique of the virtual reality introduced simulation, which is a new possibility in education. For the first time in the history of surgery we can measure medical students' or residents' dexterity and one can get acquainted with a surgical procedure in the form of "serious games". By application of the up-to-date imaging methods we can plan the movements of the surgeon's hand even before the planned operation, practice and repeating can contribute to the safety of the real procedure. Open surgical procedures can be practiced on plastic phantoms mimicking human anatomy and the use of interactive touch devices and e-learning can also contribute to practical education of surgery.

[The mechanism of adhesion formation and the possibilities of modeling -- a preliminary study]. / Az adhaesioképzodés mechanizmusa és modellezésének lehetoségei -- Elokísérleti modellek.

A huge number of factors play a significant role in the process of adhesion formation, like bleeding, the presence of foreign bodies, tissue injury, tissue destruction, ischemia and hypoxia. Adhesions are present in 95% of the cases following abdominal surgery. As a result of adhesions a large number of postoperative complications can occur, such as abdominal pain, bowel motility disturbances and infertility. Hence, it is important to know the precise mechanism of adhesion formation process and establish a suitable animal model to investigate the underlying mechanisms. Molecules which play a part in the process of adhesion formation were collected from the international literature. Male Wistar rats were used to create the adhesion model. Bleeding, implantation of foreign bodies, creation of ischemic areas and tissue destructions were carried out. Within this experiment the tiny bleeding and ischemic areas did not result in adhesion formation. The adhesion formation due to foreign body implantation depends on the type of the materials. Due to the inhibitory mechanism of adhesion formation there was no adhesion detectable due to tiny peritoneal destruction. The most reliable model was the one when gross tissue destruction of the abdominal wall was applied and the resulting bleeding initiated the adhesion formation process. It is also extremely important to know the key participants in the complex process of adhesion formation. This reliable model can help to work out the proper method of prevention.

A porcine model of complement-mediated infusion reactions to drug carrier nanosystems and other medicines.

Intravenous administration of low (milligram) doses of nanoparticulate materials in pigs can lead to acute cardiopulmonary, hemodynamic, hematological, biochemical and dermatological changes within minutes, mimicking the human infusion (or anaphylactoid) reactions to many state-of-the-art (nano)medicines and biologicals. Because of the causal role of complement (C) activation, the phenomenon was called C activation-related pseudoallergy (CARPA). This review summarizes the available information on porcine CARPA caused by different liposomes and polymers. It provides methodical details of the model and addresses the quantitation, sensitivity, specificity, reproducibility and variability of symptoms caused by different reactogenic drugs. We describe a unique feature of the model: the rise of tachyphylaxis (self-induced tolerance) as a function of structural properties of reactogenic agents. For drugs that cause tachyphylactic CARPA, such as liposomal doxorubicin (Doxil), the review recapitulates a recently reported method of desensitization, which may prevent this, as well as many similar hypersensitivity reactions. In explaining the underlying mechanism of tachyphylactic CARPA, a new theory on "double hit" is outlined, wherein the pulmonary intravascular macrophages (PIM cells) of pigs give aggravated response to simultaneous stimulation of their anaphylatoxin and other surface receptors (e.g., toll-like, PAMP, DAMP or mannose) that recognize vesicle surface molecular patterns. The porcine CARPA model might provide unique advantages in studying the mechanism of severe hypersensitivity reactions in man to i.v. drugs, as well as in identifying drugs and drug carriers that may cause such reactions.