Early-onset gastrointestinal cancer: An epidemiological reality with great significance and implications.

During the last few years, epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages, the so-called "early-onset cancer". This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms, mainly stomach and in a lesser degree pancreas, and biliary tract. It should be emphasized that data concerning digestive neoplasms, except for those referring to the colon and stomach, could be characterized as rather insufficient. The exact magnitude of the shift in younger ages is expected to become clearer shortly, as long as relevant epidemiological data from many parts of the world would be available. The most important question concerns the etiology of this phenomenon, since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many countries. The existing data support the assumption that a number of environmental factors may play a primary role in influencing carcinogenesis, sometimes from childhood. Changes that have appeared in the last decades related mainly to eating habits, consistency of gut microbiome and an increase of obese people interacting with genetic factors, ultimately favor the process of carcinogenesis. Even these factors however, are not entirely sufficient to explain the age-related changes in the frequency of digestive neoplasms. Studies of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are required. In this article, we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible pathogenesis. Finally, we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

Combination treatment of inflammatory bowel disease: Present status and future perspectives.

The treatment of patients with inflammatory bowel disease (IBD), especially those with severe or refractory disease, represents an important challenge for the clinical gastroenterologist. It seems to be no exaggeration to say that in these patients, not only the scientific background of the gastroenterologist is tested, but also the abundance of "gifts" that he should possess (insight, intuition, determination, ability to take initiative, etc.) for the successful outcome of the treatment. In daily clinical practice, depending on the severity of the attack, IBD is treated with one or a combination of two or more pharmaceutical agents. These combinations include not only the first-line drugs (e.g., mesalazine, corticosteroids, antibiotics, etc) but also second- and third-line drugs (immunosuppressants and biologic agents). It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied. Therefore, a part of these patients are going to surgery. In recent years, several small-size clinical studies, reviews, and case reports have been published combining not only biological agents with other drugs (e.g., immunosuppressants or corticosteroids) but also the combination of two biological agents simultaneously, especially in severe cases. In our opinion, it is at least a strange (and largely unexplained) fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few. As mentioned above, there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations. The appropriate dosage, the duration of the administration, the suitable timing for checking the clinical and laboratory outcome, as well as the treatment side-effects, should be the subject of intense clinical research shortly. In this editorial, we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients. We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Immunotherapy of gastric cancer: Present status and future perspectives.

In this editorial, we comment on the article entitled "Advances and key focus areas in gastric cancer immunotherapy: A comprehensive scientometric and clinical trial review (1999-2023)," which was published in the recent issue of the World Journal of Gastroenterology. We focused on the results of the authors' bibliometric analysis concerning gastric cancer immunotherapy, which they analyzed in depth by compiling the relevant publications of the last 20 years. Before that, we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer (GC) in different countries, attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm. We then briefly discuss the conservative treatment (chemotherapy) of the various forms of this malignant neoplasm. We describe the treatment of resectable tumors, locally advanced neoplasms, and unresectable (advanced) cases. Special attention is given to modern therapeutic approaches with emphasis on immunotherapy, which seems to be the future of GC treatment, especially in combination with chemotherapy. There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications, the countries in which the studies were conducted, the authors, and the scientific centers of origin, as well as the clinical studies in progress. Finally, an attempt is made to draw some con-clusions and to point out possible future directions.

Fibrin glue and coats compromise the integrity of colonic anastomosis: an experimental trial on rats.

Background: Anastomotic leak remains a dreaded complication in colorectal surgery. Identifying optimal techniques that minimize its incidence is an active area of investigation. The aim of this experimental study was to evaluate the effect of commonly used hemostatic products on the integrity of colonic anastomoses. Methods: Male Wistar rats were randomized into 4 groups. In the control group (A), the anastomosis was performed using the standard hand-sewn technique in the ascending colon. In group B the hand-sewn technique was reinforced with a collagen-fibrinogen patch, in group C with fibrin glue, and in group D with a polyethylene glycol (PEG)-coated oxidized cellulose patch. On the 7th postoperative day, anastomotic bursting pressure measurements were obtained. A specimen surrounding the anastomosis was retrieved for histopathologic evaluation. Results: Of the 19 rats, 17 survived and 15 were included in the analysis (5 in each of groups A, B and C). Testing in group D was discontinued following adverse events in the preliminary experiments. The mean bursting pressure of the anastomosis was significantly higher in the control group (A: 221±19.41 mmHg, B: 151±14.42 mmHg, and C: 112±13.57 mmHg; P=0.001). Anastomotic healing parameters were not different between groups. Conclusions: Although experimental data support the use of sealants in defective anastomoses, in this study the reinforcement of colonic anastomosis with fibrin or oxidized cellulose-PEG sealants did not improve either bursting pressure values or anastomotic healing. More data from robust anastomoses of animals and humans are needed before sealing becomes common clinical practice in colorectal surgery.

Mesenchymal Stem Cell Transplantation Has a Regenerative Effect in Ischemic Myocardium: An Experimental Rat Model Evaluated by SPECT-CT Assessment.

Translational perspective: Ischemic heart disease remains a major medical problem with high mortality rates. Beside the great efforts devoted to research worldwide and the use of numerous experimental models, an absolute understanding of myocardial infarction and tissue loss has not yet been achieved. Furthermore, the regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in the medical (and especially cardiovascular) community. In a novel experimental rat model, the beneficial effect of mesenchymal stem cell transplantation (MSCT) in a surgically induced ischemic myocardium was documented. From a clinical perspective, this work supports the surgical administration of MSCT in the infarcted area during coronary artery bypass surgery. AIMS: The regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in cardiovascular research. We developed a novel experimental rat model and used it to examine the effect of mesenchymal stem cell transplantation (MSCT) on myocardial ischemia evaluated by SPECT-CT and immunohistochemistry. METHODS AND RESULTS: An open thoracotomy took place for forty adult female Wistar rats with (n = 30) or without (n = 10) surgical ligation of the left anterior descending coronary artery (LAD) in order to cause myocardial ischemia. Myocardial viability was evaluated via SPECT/CT 7 days before surgery, as well as at 7 and 14 days post-surgery. At day 0, 15 animals received homologous stem cells injected at the ischemic myocardium area. A SPECT/CT evaluation showed decreased activity of the myocardial cells in the left ventricle one week post-infarction. Regeneration of the ischemic myocardium fifteen days post-infarction was recorded only in animals subjected to stem cell transplantation. These findings were also confirmed by histology and immunohistochemical analysis, with the significantly higher expression of GATA4 and Nkx2.5. CONCLUSIONS: The positive effect of mesenchymal stem cell transplantation in the ischemic myocardium was recorded. The application of SPECT-CT allowed a clear evaluation of both the quality and quantity of the living myocardium post-infarction, leading to a new approach in the research of cardiovascular diseases. From a clinical perspective, MSCT may be beneficial when accompanied by myocardial revascularization procedures.

Are Absorbable Plates More Resistant to Infection Than Titanium Implants? An Experimental Pre-Clinical Trial in Rabbits.

Background: Infection of orthopaedic implants after internal fixation of bone fractures remains a major complication with occasionally devastating consequences. Recent studies have reported that the use of absorbable materials, instead of metallic ones, may lead to a lower incidence of postoperative infection. In this experimental pre-clinical animal study, we compared the infection rate between absorbable implants consisting of copolymers composed from trimethylene carbonate, L-polylactic acid, and D, L-polylactic acid monomers, and titanium implants after the inoculation of a pathogenic microorganism. Material and Methods: We used an experimental implant-related infection model in rabbits. Sixty animals were randomly and equally divided into two groups. In all animals, the right femur was exposed via a lateral approach and a 2.5 mm two-hole titanium plate with screws (Group A), or a two-hole absorbable plate and screws (Group B), were applied in the femoral shaft. Afterwards, the implant surface was inoculated with Pseudomonas Aeruginosa at a concentration of 2 × 108 CFU/mL. The primary outcome was the comparison of the incidence of developed infection between the two groups. The wound condition was monitored on a daily basis and radiographies were obtained at 12 weeks postoperatively. Infection-related laboratory markers (white blood cell count, erythrocyte sedimentation rate, and C-reactive protein values) were assessed at 3, 6, and 16 weeks postoperatively. Histologic analysis and cultures of tissue samples were also performed to evaluate the presence of infection. Results: Clinical and laboratory signs of infection were evident in 11 rabbits in Group A (36.7%), and 4 in Group B (13.3%). The difference between the groups was statistically significant (p = 0.04). Five animals in Group B (16.7%) had clinical and histologic signs of a foreign-body reaction with significantly elevated CRP and ESR values but no simultaneous presence of infection was identified (p = 0.04). Bone remodelling with thickening of the periosteum and surrounding sclerosis was demonstrated radiologically in animals developing infection or foreign-body reactions. Conclusions: Absorbable plates and screws show lower susceptibility to infection compared to titanium ones. However, their application is associated with foreign-body reaction and the potential need for a second surgical intervention.

Convolutional Neural Networks for Optical Discrimination Between Histological Types of Colorectal Polyps Based on White Light Endoscopic Images.

The objective of this study was to compare different convolutional neural networks (CNNs), as employed in a Python-produced deep learning process, used on white light images of colorectal polyps acquired during the process of a colonoscopy, in order to estimate the accuracy of the optical recognition of particular histologic types of polyps. The TensorFlow framework was used for Inception V3, ResNet50, DenseNet121, and NasNetLarge, which were trained with 924 images, drawn from 86 patients.

A Novel Experimental Rat Model for the In Vivo Assessment of Myocardial Ischemia Based on Single Photon Emission Computed Tomography.

BACKGROUND/AIM: Myocardial infarction, an acute medical situation with a high mortality rate worldwide, has been extensively studied in modern cardiovascular research, using different experimental models. However, a deep understanding of myocardial activity loss has not been fully investigated. We have developed a novel experimental rat model for noninvasive assessment of myocardial ischemia based on single photon emission computed tomography (SPECT/CT), in order to further understand and evaluate myocardial activity before and after surgical induction of myocardial ischemia. MATERIALS AND METHODS: Thirty adult female Wistar rats underwent open thoracotomy with (n=20) or without (n=10) surgical ligation of the left anterior descending coronary artery (LAD). The myocardial ischemia was confirmed with ECG and myocardial viability was evaluated via SPECT/CT at 7 days before as well as at 7 and 14 days post-surgery, after which animals were sacrificed and myocardial ischemic injury was further assessed histologically. RESULTS: All animals were evaluated with anatomical and functional criteria based on the SPECT/CT imaging results. A successful surgical technique causing ischemia and loss of myocardial function in all animals undergoing a LAD ligation was established. Furthermore, evaluation of the viable myocardium with SPECT/CT confirmed the reduction of functional myocardial cells of the left ventricle post-infarction, which was also documented histologically. CONCLUSION: Using our technique, the validity of this animal model to induce and evaluate myocardial ischemia was demonstrated. Our choice to apply SPECT-CT qualitative and quantitative evaluation of myocardial function leads to a new approach in experimentation with an anticipated significant impact in the ongoing cardiovascular laboratory research.

Inhibition of γδ-TcR or IL17a Reduces T-Cell and Neutrophil Infiltration after Ischemia/Reperfusion Injury in Mouse Liver.

Neutrophil and T-cell recruitment contribute to hepatic ischemia/reperfusion injury. The initial inflammatory response is orchestrated by Kupffer cells and liver sinusoid endothelial cells. However, other cell types, including γδ-Τ cells, seem to be key mediators in further inflammatory cell recruitment and proinflammatory cytokine release, including IL17a. In this study, we used an in vivo model of partial hepatic ischemia/reperfusion injury (IRI) to investigate the role of the γδ-Τ-cell receptor (γδTcR) and the role of IL17a in the pathogenesis of liver injury. Forty C57BL6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion (RN 6339/2/2016). Pretreatment with either anti-γδΤcR antibodies or anti-IL17a antibodies resulted in a reduction in histological and biochemical markers of liver injury as well as neutrophil and T-cell infiltration, inflammatory cytokine production and the downregulation of c-Jun and NF-κΒ. Overall, neutralizing either γδTcR or IL17a seems to have a protective role in liver IRI.

Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats.

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.

Combined administration of membrane-permeable and impermeable iron-chelating drugs attenuates ischemia/reperfusion-induced hepatic injury.

BACKGROUND: The underlying pathophysiological mechanisms of hepatic ischemia-reperfusion (I/R) injury have not been completely elucidated. However, it is well known that oxidative stress, caused by a burst of reactive oxygen species (ROS) production during the reperfusion phase, plays a crucial role. A growing body of evidence indicates that the intracellular availability of free iron represents a requirement for ROS-induced adverse effects, as iron catalyzes the generation of highly reactive free radicals. The aim of this study was to examine whether a combination of iron chelators with varying lipophilicity could offer enhanced protection against I/R by diminishing the conversion of weak oxidants, like H2O2, to extremely reactive ones such as hydroxyl radicals (HO.). METHODS: HepG2 cells (hepatocellular carcinoma cell line) were exposed to oxidative stress conditions after pre-treatment with the iron chelators desferrioxamine (DFO) and deferiprone (DFP) alone or in combination. Labile iron pool was estimated using the calcein-acetoxymethyl ester (calcein-AM) method and DNA damage with the comet assay. We subsequently used a rabbit model (male New Zealand white rabbits) of hepatic I/R-induced injury to investigate, by measuring biochemical (ALT, ALT, ALP, γGT) and histological parameters, whether this may be true for in vivo conditions. RESULTS: The combination of a membrane-permeable iron chelator (DFP) with a strong membrane-impermeable one (DFO) raises the level of protection in both hepatic cell lines exposed to oxidative stress conditions and hepatic I/R rabbit model. CONCLUSIONS: Our results show that combinations of iron chelators with selected lipophilicity and iron-binding properties may represent a valuable strategy to protect against tissue damage during reperfusion after a period of ischemia.

Teaching and Assessment of Medical Students During Complex Multifactorial Team-Based Tasks: The "Virtual on Call" Case Study.

Abstract: Although considerable efforts have been made to incorporate simulation-based learning (SBL) in undergraduate medical education, to date, most of the medical school curricula still focus on pure knowledge or individual assessment of objective structured clinical examination skills (OSCE). To this end, we designed a case study named "iG4 (integrated generation 4) virtual on-call (iVOC)". We aimed to simulate an on-call shift in a high-fidelity virtual hospital setting in order to assess delegates' team-based performance on tasks related to patient handovers (prioritisation, team allocation). Methods: A total of 41 clinical year medical students were split into 3 cohorts, each of which included 3 groups of 4 or 5 people. The groups consisted of a structured mix of educational and cultural backgrounds of students to achieve homogeneity. Each performing group received the handover for 5 patients in the virtual hospital and had to identify and deal with the acutely unwell ones within 15 minutes. We used TEAMTM tool to assess team-based performances. Results: The mean handover performance was 5.44/10 ± 2.24 which was the lowest across any performance marker. The overall global performance across any team was 6.64/10 ± 2.11. The first rotating team's global performance for each cycle was 6.44/10 ± 2.01, for the second 7.89/10 ± 2.09 and for the third 6.78/10 ± 1.64 (p = 0.099 between groups). Conclusion: This is one of the first reported, high-fidelity, globally reproducible SBL settings to assess the capacity of students to work as part of a multinational team, highlighting several aspects that need to be addressed during undergraduate studies. Medical schools should consider similar efforts with the aim to incorporate assessment frameworks for individual performances of students as part of a team, which can be a stepping-stone for enhancing safety in clinical practice.

Herbals and Plants in the Treatment of Pancreatic Cancer: A Systematic Review of Experimental and Clinical Studies.

BACKGROUND: Pancreatic cancer represents the most lethal malignancy among all digestive cancers. Despite the therapeutic advances achieved during recent years, the prognosis of this neoplasm remains disappointing. An enormous amount of experimental (mainly) and clinical research has recently emerged referring to the effectiveness of various plants administered either alone or in combination with chemotherapeutic agents. Apart from Asian countries, the use of these plants and herbals in the treatment of digestive cancer is also increasing in a number of Western countries as well. The aim of this study is to review the available literature regarding the efficacy of plants and herbals in pancreatic cancer. METHODS: The authors have reviewed all the experimental and clinical studies published in Medline and Embase, up to June 2021. RESULTS: More than 100 plants and herbals were thoroughly investigated. Favorable effects concerning the inhibition of cancer cell lines in the experimental studies and a favorable clinical outcome after combining various plants with established chemotherapeutic agents were observed. These herbals and plants exerted their activity against pancreatic cancer via a number of mechanisms. The number and severity of side-effects are generally of a mild degree. CONCLUSION: A quite high number of clinical and experimental studies confirmed the beneficial effect of many plants and herbals in pancreatic cancer. More large, double-blind clinical studies assessing these natural products, either alone or in combination with chemotherapeutic agents should be conducted.

Growth of Intestinal Neomucosa on Pedicled Gastric Wall Flap, a Novel Technique in an Animal Model.

Background: Short bowel syndrome (SBS) remains an unsolved issue in modern medicine. Numerous experimental surgical techniques have been proposed in the attempt to increase the intestinal absorptive capacity.Materials and Methods: Ten female Landrace pigs, divided in two groups of 5 (A and B), were explored through a midline incision. A spindle-shaped vascularized full-thickness gastric wall flap (GWF) consisting of part of the major curvature with the gastroepiploic arch preserved was de-epithelialized and then placed as a "patch" to cover an antimesenteric border defect of either a nonfunctional blind intestinal loop (group A) or a functional intestinal loop of the gastrointestinal tract (group B). A spindle-shaped curved, rigid, low density polyethylene (LDPE) splint was sutured on the external surface of the patch in order to prevent shrinkage of GWF and collapse of the intestinal wall in group A.Results: There was a decrease of both dimensions of the patch. Microscopically a thin layer of columnar epithelial cells covered the center of the patch, evolving in shorter, blunt, poorly developed villi with increasing maturation laterally. The patch surface was covered by nearly 90%. In the three animals that died prematurely the coverage of GWF was negligent or suboptimal directly dependent on the length of survival.Conclusions: The hereby-described patching technique demonstrated the growth of intestinal neomucosa on the GWF. The capability of the stomach to provide large flaps and the advantages of the use of native tissues render this animal model valuable for the future research in the field.

Description of a Recovery Model in Rabbits for the Study of the Late Phase of Liver Ischemia-Reperfusion Injury.

AIM: Description of an anesthetic recovery model with endotracheal intubation in rabbits which provides metabolic stability for the study of the late phase of liver ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Two groups of New Zealand rabbits, n=7 in each, were used: Ischemia/reperfusion (I/R) group (45 min of partial liver ischemia/reperfusion) and no intervention (sham) group. Blood alanine aminotransferase, lactate, pH values, mean arterial pressure and pCO2 were calculated at baseline, and at 2 and 24 h post reperfusion. Tissue samples from left (ischemic) and right (non-ischemic) liver lobes were examined at 2 and 24 h after reperfusion. RESULTS: The I/R group presented significantly higher levels of alanine aminotransferase (p=0.001) at 2 and 24 h, and of lactate (p=0.016) at 2 h post reperfusion. No differences were documented for pH, mean arterial pressure and pCO2 Histological exanimation revealed significant injury at 24 h post reperfusion for the I/R group. CONCLUSION: This anesthetic recovery model permitted avoidance of hypoxia and respiratory acidosis, allowing the study of the late phase of I/R injury.

Beneficiary Effect of Fibrin Glue on Healing of Ileoileal Anastomoses in Rats.

BACKGROUND/AIM: Intestinal anastomosis' integrity is crucial in surgery. This study aimed to investigate whether fibrin glue (FG) (a fibrin sealant containing human factor XII and fibrinogen) has a positive effect on the healing and the integrity of the ileoileal anastomosis in rats. MATERIALS AND METHODS: Twenty Wistar rats underwent enterotomy, ileoileal anastomosis and divided into four groups (A: complete anastomosis-no FG, B: complete anastomosis-FG, C: incomplete anastomosis-no FG, D: incomplete anastomosis-FG). Data included leak, adhesions, bursting pressure of the anastomosis, neoangiogenesis, and hydroxyproline levels. RESULTS: Angiogenesis was significantly higher in group B compared to group A (p=0.019). There were no significant differences between groups A and B regarding adhesions, hydroxyproline, and bursting pressure (p=0.500, p=0.158 and p=0.829, respectively). Hydroxyproline levels were higher in group D compared to C, but did not reach significance (p=0.098). CONCLUSION: Fibrin glue has a positive effect on ileoileal anastomoses. It is not entirely clear whether this effect is due to mechanical support or to the facilitation of the healing process or both. Further research is needed before FG can be applied to humans.

Mentoring Medical Students Towards Oncology: Results from a Pilot Multi-institutional Mentorship Programme.

The mounting global cancer burden has generated an increasing demand for oncologists to join the workforce. Yet, students report limited oncology exposure in undergraduate medical curricula, while undergraduate oncology mentorships remain underutilised. We established an undergraduate oncology society-led mentorship programme aimed at medical students across several UK universities to increase medical student oncology exposure. We electronically recruited and paired oncologist mentors and medical student mentees and distributed a dedicated questionnaire (pre- and post-mentorship) to compare mentees' self-reported cancer specialty knowledge and oncology career motivation after undertaking a 6-week mentorship. We also determined students' interest across specialties and subspecialties and measured mentor availability via percentage programme uptake. Statistical analysis included univariate inferential tests on SPSS software. Twentynine (23.4%) of 124 oncology specialists agreed to become mentors. The mentorship was completed by 30 students across three medical schools: 16 (53.3%) Barts, 10 (33.3%) Birmingham, and 4 (13.3%) King's; 11 (36.7%) mentored by medical oncologists, 10 (33.3%) by clinical/radiation oncologists, and 9 (30%) by surgical oncologists. The mentorship generated a statically significant increase in students' knowledge of the multidisciplinary team and all oncology-related specialties including academia/research but not interest towards a career in oncology. Undergraduate oncology mentoring is an effective educational, networking and motivational tool for medical students. Student societies are a valuable asset in cultivating medical student oncology interest by connecting students to faculty and increasing mentor accessibility. Further research should focus on developing an optimal mentorship structure and evaluating long-term outcomes of such educational initiatives.

Dantrolene Induces Mitigation of Myocardial Ischemia-Reperfusion Injury by Ryanodine Receptor Inhibition.

The impairment of intracellular calcium homeostasis plays an essential role during ischemia-reperfusion injury. Calcium release from sarcoplasmic reticulum which is triggered by myocardial ischemia is mainly mediated by ryanodine receptors. Dantrolene sodium is a ryanodine receptor antagonist. The objective of the present study was to evaluate the in-vivo impact of dantrolene sodium on myocardial ischemia-reperfusion injury in swine models. An in vivo, experimental trial comparing 10 experimental animals which received dantrolene sodium with 9 control swine models was conducted. Their left anterior descending coronary artery was temporarily occluded for 75 minutes via a vessel tourniquet, which was then released. Myocardial reperfusion was allowed for 24 hours. Dantrolene was administered at the onset of the reperfusion period and levels of troponin, creatine phosphokinase and creatine kinase myocardial band between the two groups were compared. Additionally, various other hemodynamic parameters and left ventricular morphology and function were examined. There were significantly lower values of troponin, creatine phosphokinase and creatine kinase myocardial band in the dantrolene group indicating less ischemia-reperfusion injury. Moreover, the postischemic cardiac index was also greater in the dantrolene group, whereas viable myocardium was also better preserved. In conclusion, the in vivo cardioprotective role of dantrolene sodium against ischemia-reperfusion injury in swine models was indicated in this study. Therefore, dantrolene sodium administration could be a promising treatment against ischemia-reperfusion injury in humans. However, large randomized clinical studies should be firstly carried out to prove this hypothesis.

Ventilation With or Without Endotracheal Tube Leak in Prolonged Neonatal Asphyxia.

Background Severe and prolonged asphyxia can result in either intrauterine fetal death and stillbirth or multiorgan failure in surviving neonates. Establishing effective ventilation is the primary aim of resuscitation in newborns with asphyxia. The objective of this study was to compare the outcome of resuscitation by applying an endotracheal tube (ETT) with less, an ETT with moderate, and an ETT with high leakage during mechanical ventilation in swine neonates after prolonged perinatal asphyxia. Materials and methods A prospective, randomized controlled laboratory study was performed. Thirty Landrace/large white pigs, aged one to four days and weighted 1.754±218 gr, were randomly allocated into three groups depending on the ETT size: Group C (less leak: ETT no 4.0, n=10); Group A (high leak: ETT no 3.0, n=10); and Group B (moderate leak: ETT no 3.5, n=10). Mechanical asphyxia was performed until their heart rate was less than 60 bpm or their mean arterial pressure was below 15 mmHg. All animals with return of spontaneous circulation (ROSC) were monitored for four hours for their hemodynamic parameters, arterial oxygen saturation, and lactate acid levels. Results We demonstrate that 70% of the surviving animals were ventilated with an ETT with a leak (no. 3.5 and 3). A statistically significant difference was noted in PO2 (p=0.032) between Group B (126.4±53.4 mmHg) compared to Group A (72.28±29.18 mmHg) and Group C (94.28±20.46 mmHg) as well as in the right atrial pressure (p<0.001) between Group C (4.5 mmHg) vs Groups A (2 mmHg) and B (2 mmHg) during ROSC time. Lactate levels were statistically significantly lower (p=0.035) in Group C (mean=0.92 ± 0.07mmol/L) as compared to Group A (mean=1.13 ± 0.1 mmol/L) and Group B (mean= 1.08 ± 0.07 mmol /L; p = 0.034) at 4h post-ROSC. Conclusion We provide preliminary evidence that ventilation with ETT with moderate leakage improves survival after 2h of ROSC, along with oxygenation and hemodynamic parameters, in a porcine model of neonatal asphyxia and resuscitation, compared to less leakage ETT.