Impact of the anatomical location and the number of metastatic lymph nodes on gastric cancer patient´s survival.

BACKGROUND: The most serious problem in surgical treatment of gastric cancer includes the area of resection and the extent of lymphadenectomy. The extent of gastric resection is determined by the extent of tumor affection. The aim of radical surgical intervention is to achieve microscopically clear resection line, since R0 resection is the main criterion for the patient´s prognosis. Curative surgical resection for gastric cancer includes the lymph nodes dissection. In the treatment of gastric cancer, there are two views on the importance of lymphadenectomy. The Far East considers that operation improves the survival and the Europe considers that surgery is not curative, but it determines the staging and prognosis. There is also a difference in staging systems. The one from East is importance based on the anatomical location of affected lymph nodes, the second from Europe is based on the number of positive lymph nodes. MATERIALS AND METHODS: This work is a retrospective observational study. In the study cohort, comparing the survival of patients according to different classification systems, depending on the N-stage of disease, 119 patients with gastric adenocarcinoma in clinical stage I to III, i.e. without metastasis, who underwent a radical surgical resection with D2 lymphadenectomy, were enrolled. For the evaluation of the survival versus the time after operation, we used Kaplan‒Meier method. To evaluate the correlation between the survival rate and the explanatory variables, Cox regression and Kendall correlation coefficient were used. RESULTS: The median survival, according to different classification systems, depending on the N-stage of the disease, was significantly correlated with the survival for the 6th and 7th editions of TNM classification system for the Japanese classification system, for N-ratio classification system).The new finding was differentiation of patients in groups N1 vs N2 under the 6th TNM classification (HR=0.910249), also a little differentiation in groups N1 vs N2 according to the classification of N-ratio (HR=0.8750926) and equally a poor differentiation in the survival in groups N2 vs N3 according to the 7th TNM classification (HR=0.881797).The strongest correlation reached the Japanese classification system, but not significantly different from the 6th TNM classification system. In the 7th edition of TNM classification system, we then found the weakest correlation with the survival time, but not significantly different from the previous two. CONCLUSION: Our retrospective study confirmed the strongest correlation between the patient´s prognosis and the anatomic localization of the affected lymph nodes. This correlation was not statistically significant compared to the correlation between patient´s prognosis and the number of positive lymph nodes. It leads us to the conclusion that both classification systems are comparable and the difference is statistically insignificant (Tab. 4, Fig. 8, Ref. 16).

Perspectives of 3D printing technology in orthopaedic surgery.

Using most widespread technology of rapid prototyping (RP) in medicine focus on the development of models for diagnosis, for training and planned surgery, as well as the direct manufacture of implants for bone reconstruction. The applications of 3D printing in the field of medicine are giving extraordinary results and tissue and prosthetic 3D printing, medical and engineering research professionals are conducting 3D printing organ bind. Researchers worldwide are pursuing the creation of artificial bone using 3D printers, bones that can be later implanted to humans. In near future, many body parts could be manufactured in a turn and successfully implanted to patients. Although medical advances in 3D printing are used in orthopaedic field, research in 4D printing has already started. Flat objects made with 3D printing, using a regular plastic, combined with smart material, were able to become a hub without an external intervention. In nutshell, the future of additive manufacturing (AM) in trauma and orthopedic surgery is relatively bright with the inclusion of 3D printing in medicine. Bioprinting in this area will be focused on fractures, nonunions, deformities and bone, cartilage and soft tissue reconstruction. CONCLUSION: The innovative technology not only assists the medical staff but is also beneficial for the patients because the medical problems, which were not curable in the past, are now possible with modern technology (Fig. 4, Ref. 52) Keywords: bone defect, tissue engineering, 3D printing, biomaterials, bone, porous scaffold.

Atherosclerosis in cancer patients.

Cancer-related mortality have been declining in the last decades. Approximately half of adults and more than two thirds of children oncological patients live longer than 5 years after diagnosis. However, this optimistic scenario has been counterbalanced by an increasing cardiovascular risk in cancer patients. Atherosclerotic damage has been underestimated in oncology practice for a long time, but recently a significant number of cancer patients with cardiovascular risk factors and serious artery disease during and after anticancer therapy has been reported. Complexity of atherosclerosis in cancer patients is challenging. Herein, we describe cardiovascular risk factors and pathophysiological mechanisms of atherosclerosis induced by selected classic chemotherapeutics, targeted cancer therapies, hormonal agents and radiotherapy and new clinical data regarding atherosclerosis, which received a particular attention in recent years (Tab. 1, Ref. 26). Keywords: cardiovascular disease, atherosclerosis, cardiotoxicity, risk factors, hypertension, hyperlipidemia.

The use of European Randomized study of Screening for Prostate Cancer calculator as a diagnostic tool for prostate biopsy indication.

BACKGROUND: It is a well-known fact, that too many men are having prostate biopsy performed with negative biopsy results. The decision to undertake prostate biopsy is usually based on prostate specific antigen (PSA) level and digital rectal examination (DRE). A risk-based strategy may reduce the numbers of unnecessary prostate biopsies. METHODS: Retrospective statistical analysis of data from 195 men undergoing their initial prostate biopsy from 1.1.2015 to 31.12.2015 based on elevated PSA ≥ 4.0 ng/ml and/or abnormal DRE were included. Subsequent risk stratification using the European Randomized study of Screening for Prostate Cancer calculator (ERSPC) was used with the intent to calculate the accuracy of ERSPC with the aim to avoid unnecessary (negative) prostate biopsies. RESULTS: The specific values of sensitivity and specificity in this cohort were 94.34 % and 24.72 %. In direct comparison of PSA and ERSPC calculator, the differences between sensitivity, specificity, negative predictive value and false omission rate as negative were statistically insignificant, but the positive predictive value was on the edge of statistical significance (p = 0.054), slightly in favor for ERSPC calculator. CONCLUSION: PSA still remains the single most predictive factor for identifying men with an increased risk of prostate cancer to be detected on prostate biopsy, but using other risk factors included in ERSPC can considerably reduce the numbers of unnecessary biopsies on initial screening (Tab. 4, Fig. 2, Ref. 23).

New principles of cancer therapy give new hope for oncological patients.

The Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation". A number of therapeutic approaches are available for cancer treatment, including surgery, radiation, and other strategies, some of which have been awarded previous Nobel Prizes. These include methods for hormone treatment for prostate cancer (Huggins, 1966), chemotherapy (Elion and Hitchins, 1988), and bone marrow transplantation for leukemia (Thomas, 1990). Many scientists engaged in intense basic research and uncovered fundamental mechanisms regulating immunity and also showed how the immune system can recognize cancer cells. T-cells were shown to have receptors that bind to structures recognized as non-self and such interactions trigger the immune system to engage in defense. However, additional proteins acting as T-cell accelerators are also required to trigger a full-blown immune response. Many scientists contributed to this important basic research and identified other proteins that function as brakes on the T-cells, inhibiting immune activation. This intricate balance between the accelerators and inhibitors is essential for a tight control. New strategy was developed into a therapy for humans. Promising results soon emerged from several groups, and in 2010 an important clinical study showed striking effects in patients with advanced melanoma. In several patients, signs of remaining cancer disappeared. The results were dramatic, leading to long-term remission and possible cure in several patients with metastatic cancer, a condition that had previously been considered essentially untreatable. Such remarkable results had never been seen in this patient group before (Fig. 2, Ref. 12). Keywords: Nobel Prize, physiology, medicine, immune system, inhibition, cancer therapy.

The future of spinal cord stereotaxy.

The spinal cord is an integral part of central nervous system, therefore it can be expected that spinal cord has the same properties as the brain. Movement activity is realized by the activation of individual motoneurons of various spinal cord segments under the influence of analytical function of the spinal cord. When a hypothesis is accepted that the mentioned large volume of spinal cord white matter represents the entire length of neuronal network, an idea can be established that the activated motoneurons project through their reticular processes to this connecting network forming a synthetic picture of this movement and after fluent continuity the entire act of movement. Therefore, neuronal network plays the role of dynamic memory.The perspective of spinal cord stereotaxy in functional neurosurgery hypothetically enables a recognition and understanding of how brain and spinal cord communicate in movement performance (Fig. 2, Ref. 6).

Targeting angiogenesis for cancer (gene) therapy.

Suppression of development of new blood vessels in solid tumors provides a clear therapeutic benefit both in experimental animals and human patients. Molecules targeting multiple pathways with VEGF pathway being one of the best described are currently under consideration to reach use in clinical settings. Even though some success has been observed using traditional protein-based inhibitors, alternative strategies and new approaches to inhibit excessive tumor angiogenesis are being developed and tested. Gene therapy represents a powerful tool for therapeutic intervention to angiogenesis. Delivery of genes encoding endogenous angiogenesis inhibitors and decoy receptors for proangiogenic factors may bear an advantage over classic non-gene therapy in terms of specific targeting, cost-effectiveness and safety. Modern approaches focused on gene targeting such as RNA interference and microRNA will show the future direction in the field of angiogenesis inhibition for cancer treatment (Ref. 68).

Portomesenteric vein gas and pneumatosis intestinalis--a rare complication after neoadjuvant radiochemotherapy in oesophageal cancer.

Portomesenteric vein gas and pneumatosis intestinalis is most commonly caused by mesenteric ischemia and bowel necrosis but may have a variety of other causes. The etiology is multifactorial and the clinical presentation is variable. The diagnosis is based on a combination of clinical suspicion and radiographic findings. The finding of hepatic portal venous gas alone is not an indication for emergent exploration. We report portomesenteric venous gas as a rare complication after neoadjuvant radiochemotherapy of the oesophageal cancer (Fig. 3, Ref. 12).

MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects.

Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 -2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41).

[ECG markers in patients with hypertrophic cardiomyopathy]. / Elektrokardiografické markery u pacientov s hypertrofickou kardiomyopatiou.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited disease of the heart muscle whose main characteristic is unexplained hypertrophy of the left ventricle and/or right ventricle. It is considered to be the most common genetically determined cardiovascular disease with the prevalence in the population approximately 1 to 500 inhabitants. The disease is associated with severe complications such as heart failure, arrhythmias and sudden cardiac death (SCD). Nowadays the aim of intensive clinical research is to judge the contribution of noninvasive methods in the risk stratification of HCM patients. Abnormal electrocardiogram occurs in 75-95% and it often presents the first point for HCM suspicion although it is nonspecific. AIM: The aim of our study was to evaluate the electrocardiographic (standard 12-lead) and certain echocardiographic markers in patients with recurrent syncope of unknown origin in comparison with patients without these episodes. PATIENTS AND METHODS: 42 patients (17 men a 25 women) with verified HCM diagnosis underwent extensive clinical, standard 12-lead electrocardiographic and echocardiographic testing to compare these parameters in the subgroup of patients with syncope (n = 17) of unknown origin and patients without syncope (n = 23). RESULTS: As for the electrocardiographic signs we found that more than one half of patients had positive Sokolow-Lyon index (55.6%), prolonged QTc interval (63.2%). Depression of ST segment was present in 60.5%. We also found positive correlation between prolonged QTc interval and maximal left ventricle thickness. We observed that patients with syncope had statistically significantly left ventricle end-diasotlic diameter in comparison with patients without syncope. CONCLUSION: Standard electrocardiography represents a "gold standard" in the diagnostics of HCM patients. We found positive correlation between prolonged QTc interval and maximal left ventricle thickness. Patients with syncope had statistically significantly smaller left ventricle end-diastolic diameter in comparison with patients without syncope.

The physiological conception of thinking based on the results of psychostereotactic operations.

The authors have gained their experience in psychostereotactic operations during the past 50 years. The operations were indicated in psychiatric patients on the basis of their clinical pictures. The results gained in operations of the hypothalamus, limbic system and neocortical structures of the brain were logically analysed and served as the basis for physiological conception of the function of the nervous system in the area of thinking. The elemental thinking of the hypothalamus resides in relatively simple memory that contains standard values of the internal environment of the body. The immense memory on the highest neocortical level of the human brain grew to become an independent degree of development independent of the objective reality. The entrance of physiological thinking into psychology enables to clarify the aspects of human psychology that are still liable to subjective view, such as emotions, motivation or consciousnesses (Fig. 1, Ref. 9). Full Text (Free, PDF) www.bmj.sk.

The MCP-1 -2518 (A/G) single nucleotide polymorphism is associated with ischemic heart disease and myocardial infarction in men in the Slovak population.

We investigated the MCP-1 -2518 (A/G) single nucleotide polymorphism (SNP) in Slovak cohort of patients with ischemic heart disease (IHD). Our study comprised 270 patients with IHD, out of them 92 with myocardial infarction (MI). We found that the frequencies of the mutant GG genotype in Slovak patients with IHD (10.7%; p=0.019) and MI (12.0%; p=0.046) were significantly higher than those in the control subjects (5.8%). After subdividing the groups according to the sex, statistically significant difference was found only in men (IHD: p=0.013, MI: p=0.009). We also found a higher rate of GG homozygous genotype in patients with early (< or =50 years of age) MI (18.4%; p=0.004)--statistically significant again only in men (23.1%; p=0.002). The frequencies of G alleles in IHD male patients (30.3%, p=0.046) and in early MI male patients (38.5%, p=0.019) were also statistically significantly higher than in control group. Our results confirm that IHD and MI are linked to MCP-1 -2518 (A/G) single nucleotide polymorphism (Tab. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.

Genetic screening of patients with hypertrophic cardiomyopathy--a new diagnostic strategy for risk stratification?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited disease of the heart muscle and its main characteristic is unexplained hypertrophy of the left and/or the right ventricle. HCM is the most common genetically determined cardiovascular disease and is prevalent in approximately in 1 of 500 of the population. The most serious complication of HCM is sudden cardiac death (SCD) which can be the first manifestation of the disease. However, there are other forms of benign prognosis which do not jeopardize patient's health or life. The clinical symptoms of HCM are partly dependent on mutations in affected sarcomere genes. Different mutations in the same gene can present as malign with a high risk of SCD, while other mutations can be benign. The clinical symptomatology can also be influenced by other factors such as the presence of polymorphisms in other genes. Nowadays the aim of intensive clinical research is to access the contribution of molecular genetic methods in HCM diagnostics as well as in risk stratification of SCD. It is expected that genetic analyses will have an important consequence in the screening the relatives of HCM patients and also in the prenatal diagnostics and genetic counseling (Tab. 2, Fig. 1, Ref. 45). Full Text (Free, PDF) www.bmj.sk.

C-reactive protein, cytokines and inflammation in cardiovascular diseases.

Inflammation of vascular cell wall is the key problem and proinflammatory cytokines and chemokines play a great role in it. These molecules, togheter with C-reactive protein (CRP) can predict risk of coronary events. It is questionable to what extend are CRP and pro-inflammatory cytokines purely acute phase markers and to what extend are they active inflammatory participants. Besides inflammation, other prominent mechanism in the pathogenesis of atherosclerosis and atherothrombosis--underlying causes of coronary events, is genetics. Gene polymorphisms including polymorphisms of inflammatory markers are studied and one of them, polymorphism of monocyte chemoattractant protein (MCP-1/CCL2) and its receptor CCR2 (key components of atherosclerosis) belong to most studied one. MCP-1/CCL2 and CCR2 polymorphisms have been implicated as susceptibility factors for chronic stable angina pectoris and myocardial infarction by several independent investigators. It seems that CCL2/CCR2 axis plays an important role both in post-ischemic and post-reperfusion inflammation and could become a new therapeutic goal in selected cardiovascular diseases as well as in stroke in future. Inhibition of this axis disrupts ischemic-reperfusion injury by decreasing edema, leucocyte infiltration and expression of inflammatory mediators. One can suppose that identifying genes influencing inflammatory biomarkers might improve understanding of genetic determinants of cardiovascular disease our management and prevention (Tab. 2, Fig. 1, Ref. 105). Full Text (Free, PDF) www.bmj.sk.

Enterovesical fistulas in Crohn's disease.

BACKGROUND: Crohn's disease is a chronic inflammatory disease of the bowel, that may affects the urinary system. Although fistula formation has been reported in up to 35% patients suffering from Crohn's disease, urinary fistulas affect only 2 to 8% patients. PATIENTS AND METHODS: Authors have done a retrospective study with the aim to investigate the incidence of enterovesical fistulas in patients admitted due to Crohn's disease to the IInd Department of Surgery of the Comenius University Medical School and Department of Surgery of University Hospital Nitra during 10 years long period. RESULTS: The overall incidence of enterovesical fistulas in our clinical material was 6.83%. All patiens underwent elective surgery. There were no serious postoperative complication. A two stage approach was necessary due to severe inflammation in one patient. Severity of inflammation decreased later on, after treatment with anti TNF *, which allowed subsequent elective surgery. CONCLUSION: Authors consider elective surgery as a treatment of choice in the managenet of enterovesical fistulas in Crohn's disease. Surgery is effective and safe (Fig. 2, Ref. 3). Full Text (Free, PDF) www.bmj.sk.

Considerations on physiological mechanisms of spinal cord movement performance according to cerebral stimuli.

The process of communication between brain and spinal cord remains unclear. Therefore an attempt supported by spinal cord stereotaxy was made to disclose the physiological mechanisms underlying the cooperation between the brain and spine as generated by the spinal cord. The initializing stimulus was the discovery of motoneuron location in all spinal cord segments providing an organic substrate for spinal cord stereotaxy. What remains to be clarified are the anatomical structures of spinal cord, participating in the feedback between brain and spinal cord. Therefore two possible hypotheses were proposed by the authors. One of them is closely related to the analytical synthetical mechanism of real objects and thoughts depiction in the memory of the brain and in form of concrete ideas it forms the basis for concrete thinking. In case of spinal cord another more probable mechanism should be considered: the process of analysis and synthesis between the participating spinal motoneurons. The mutual neuronal spinal cord connections are capable of depicting the movement pattern, and the movement is transferred by means of the described spinal cord pathways to the memory of the brain as a concrete movement idea. From here the ideas are transferred according to the individual needs backwards by means of another described spinal cord pathway back to the spinal cord, and the spinal cord is the final effector. The process of thinking is the physiological correlation of technical software, but in form of abstract thinking it is transferred to the form of abstract thinking. (Fig. 3, Ref 7). Full Text (Free, PDF) www.bmj.sk.

Realisation of Bologna Declaration at the Slovak medical schools.

Implementation of Bologna Declaration should result in development and facilitating of the education system. Following tasks need to be done: (1) Establish committees of expert, at the level of institutes, schools and universities, which would compare and harmonize syllabus and credits of individual courses with the aim to maximally support students' and teachers' mobility. (2) It is necessary to re-evaluate the transformation of medical education in Slovakia in the near future, so as key identical courses within Slovak schools of medicine have similar syllabus, number of hours and number of given credits. Then medical study at the School of Medicine Comenius University Bratislava will be comparable to study at Slovak, Czech and other European schools of medicine. (3) Harmonize academic titles within European Union. (4) Finish all syllabi of new study programs according the programs of European Union. (5) Evaluate the prerequisites and consider the variability of some study programs. (6) Maintain flexibility of theory and practice in relation 1:2 in theoretical and practical study. (7) Determine possible forms of thesis, their content and forms, technical equipment considering experience in student's research activity. (8) Develop conditions for an adequate teachers input. (9) Objectively validate and evaluate students' gained knowledge regarding their use in practice. (10) Solve transparent conditions of support and economic guarantee of higher education for universities, teachers and students by Ministry of Education of Slovak Republic (Ref. 18). Full Text (Free, PDF) www.bmj.sk.

Asserting Bologna Declaration in restructuring of school system at Comenius University Medical School Bratislava.

Asserting Bologna Declaration into university education is a long-term and challenging process. New features have to be asserted sensitively in order to develop school system and to strengthen the baseline for Declaration. Slovakia has started the restructuring of university system and study programs undergoing the process of accreditation, however marked support (or reform) for covering the costs of university education is missing (expressed as % of gross domestic product, Slovakia is still not comparable to other EU countries). At present, not satisfactory economic conditions prevent from reaching the content, personal and equipment preconditions at universities (Ref. 7).

Long-term monitoring of the changes in signal-averaged ECG after coronary artery occlusion and intracoronary endothelin-1 injection in dogs.

Myocardium undergoes functional changes in the infarcted region primarily due to ischemia. Following myocyte functional alterations of the noninfarcted myocardium are caused by remodelling and hypertrophy. We have monitored and compared changes in the electrocardiographical (ECG) image after coronary artery occlusion (CAO, n=5) and intracoronary endothelin-1 (ET-1, n=3) administration during a 6-month period. In 3 dogs, the CAO was repeated 6 months after the first occlusion. Signal-averaged ECG (SA ECG) was recorded before the operation and 10 days, 1 month, 3 months and 6 months after myocardial infarction (MI). The modified Wigner distribution was used for spectrotemporal analysis of the SA ECG. Eight-hour Holter monitoring was performed in each dog before and after experimental MI. Spectrotemporal representations of the QRS complex were stabilized after the first 1-month period in the group of dogs after CAO. The same results were also observed after the repeated CAO. No arrhythmias were recorded 9 days after CAO. The spectrotemporal representations of the QRS complex after intracoronary ET-1 administration were not stabilized during the whole observed period. Very few arrhythmic events were recorded by Holter monitoring already 3 days after intracoronary ET-1 injection. Experimental MI induced by CAO caused a changed ECG image, which was stable from 1 month after MI induction till the end of the monitoring. However, the ECG image after ET-1 administration was not stable during the whole observed period. No arrhythmic events were recorded in either group 3 months postoperatively that could be caused by healthy myocardial status before the experimental MI induction. In clinical practice, however, ischemic heart disease usually precedes the MI. Arrhythmogenic substrate could thus be a consequence of combination of healthy status of the myocardium before MI and MI itself.