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.

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).

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.

[Proposal for a physiologic concept of thought based on the results of stereotaxic psychosurgery]. / Návrh fyziologické koncepce myslení odvozený z výsledku psychostereotaktických operací.

Authors have fifty years long experience with psychostereotactic surgery. On the bases of 209 operations of different types of mentally ill patients, authors built their own physiological conception of the central nervous system function. The new conception is described using block operators of thinking at the level of hypothalamus, limbic system, and neocortex in the hierarchic order. The basic physiological hypothalamic block contains two operators: stimulus evaluation and decision to act. Both operators together form reasonable, objective substantiation of thinking, which is transformed into psychological, subjective description at higher cerebral levels. New operator is added to the block diagram at the level of the limbic system: the choice of response base on experience stored in the high capacity memory. Vast neocortical memory creates a model of the individual world and it enables a new operator to be involved: prediction of the future events. Thinking, originally based on concrete images, is using abstract terms, subjected to the principles of grammar. Physiological basis of thinking enables the convergence of subjective and objective.

Developing strategies for long-term follow up of cancer survivors.

The anticancer treatment has been increasingly successful over the past three decades. With current treatment, over two-thirds of children with cancer and more than half of adult cancer patients can be expected to survive their disease. As a result, there now exists a rapidly growing population of long-term survivors with increased risk of premature morbidity and mortality-induced by therapy. It has become apparent that these patients often face complex of organ damages and psychosocial problems. The awareness of the possible long-term complications of therapy is important for optimal health care for the current survivors and also for modifying future treatment regimens to avoid therapy that is associated with unacceptable morbidity and mortality. ((Tab. 1, Fig. 1, Ref. 17.).

Signal-averaged electrocardiography in survivors of Hodgkin's disease treated with and without dexrazoxane.

Doxorubicin is one of the most effective anticancer drug, but its usefulness is limited by the risk of developing cardiomyopathy, cardiac dysfunction and ventricular arrhythmias. Dexrazoxane is used to protect against doxorubicin cardiotoxicity. It is uncertain whether the dexrazoxane-mediated cardioprotective effect will be reflected in electrophysiological properties of the heart. The aim of the present study was to evaluate the occurrence of frequency-domain signal-averaged electrocardiographic (SAECG) abnormalities of the QRS complex and the initial ST segment in patients treated with and without dexrazoxane. Thirty children and young adults 2 months - 15 years after completion of doxorubicin-containing therapy for Hodgkin's disease were evaluated with SAECG. Patients from group I (n = 13) received combined therapy with doxorubicin and dexrazoxane (DOX/DZX), patients from group II (n = 17) received doxorubicin without dexrazoxane (DOX). Using fast Fourier transformation within the QRS complex and the initial ST segment, area ratio (AR) values 40-100/0-40 Hz were calculated. Significant differences in these frequency parameters in the QRS complex between DOX/DZX group and DOX group (19.45+/-12.72 vs 46.18+/-43.06; p = 0.03) might indicate protective effect of dexrazoxane on electrophysiological myocardial properties.

Signal-averaged ECG in patients after anthracycline therapy for childhood cancer.

Late cardiac complications after anthracycline therapy is an increasingly common problem among survivors of childhood cancer. Routine clinical examination may be normal, but subclinical cardiac abnormalities, which may progress with time, are documented in high percentage of these patients. Microstructural myocardial alterations may result in production of micropotential level signals (late potentials, LP) and altered frequency components of signal-averaged ECGs (SAECG). SAECG abnormalities are valuable in risk stratification of patients with various heart diseases culminating in fatal arrhythmias or heart failure. Forty-five pediatric oncologic patients (mean age 14.4 +/- 4.1 years) were included in the study. SAECG was performed 3 months-12 years (median 5.5 years) following completion of anthracycline therapy. The total cumulative doses of anthracyclines were 90-555 (median 230) mg/m2. The control group consisted of 30 healthy age-matched volunteers. LP were present in six (13.3%) patients after anthracycline therapy at 40 Hz high-pass filter setting. Using frequency-domain analysis within the QRS complex, area ratio 1 (area of 20 to 50 Hz/area of 0 to 20 Hz) and area ratio 2 (area of 40 to 100 Hz/area of 0 to 40 Hz) were calculated. Twenty (44.4%) and fourteen (31.1%) had abnormal values in area ratios 1 and 2, respectively, within the QRS complex. Area ratios 1 and 2 of patients after anthracycline therapy were significantly higher than those in control group (p = 0.0187 and p = 0.0043). Our preliminary results suggest that chemotherapy with anthracyclines, even in low dosage, is associated with increased incidence of SAECG abnormalities. The potential of this simple, noninvasive method to detect subclinical anthracycline-induced myocardial alterations and facilitate prognostic stratification of cancer survivors is promising, however, the clinical value of SAECG remains to be established in a larger and a longer study.

[High-resolution electrocardiography in monitoring myocardial damage after therapy with anthracyclines in children]. / Vysokorozlisovacia elektrokardiografia v programe sledovania poskodenia myokardu po antracyklínovej liecbe u detí.

BACKGROUND: Anthracycline cytostatics, widely used in oncologic practice, may induce discrete myocardial damage occasionally culminating in life-threatening cardiologic complications. The most serious clinical manifestations of anthracycline cardiotoxicity are dilated cardiomyopathy, heart failure and fatal arrhythmias. OBJECTIVES, STARTING POINT AND MAIN PURPOSE: High-resolution electrocardiography (HRECG) is one of the latest cardiologic methods, which can be promising for early identification of patients at risk of anthracycline cardiotoxicity. The aim of this study is the evaluation of the incidence of HRECG abnormalities in a group of paediatric patients treated with anthracyclines and the usefulness of HRECG for stratification of patients at risk of the clinical cardiotoxicity. PATIENTS AND METHODS: A set of 60 oncologic paediatric patients treated with anthracyclines was divided into two groups. The first group was formed by 15 patients undergoing evaluation during their anthracycline therapy (median after the last administration of antracyclines was 3.2 days). Their average age at the time of examination was 14.7 +/- 4.1 years. The total cumulative dose of antracyclines was 40-300 mg/m2 (median 150 mg/m2). The second group was formed by 45 patients who were evaluated after completing anthracycline therapy. The interval of time from the last administration of antracycline in this subgroup of patients was 3 months-12 years (median 5.5 years). Their average age at the time of HRECG examination was 14 +/- 4.1 years. The total cumulative dose of anthracyclines was 90-440 mg/m2 (median 230 mg/m2). Six patients of this group (13.3%) were treated also with mediastinal radiotherapy (18-40 Gy). 43 patients (95.5%) of second group were in complete remission, two other patients yielded a progression of their malignancy. 10 patients (22%) were examined by HRECG 2-5 times in app. two-month intervals. The control group was formed by 30 randomly selected healthy children and adolescents with normal ECG. Average age was 15.1 +/- 5.8 years. Using HRECG the time- and frequency-domain characteristics of the ECG signal were analyzed. The time-domain analysis was performed at 40-250 Hz filter. The frequency-domain analysis was performed by fast Fourier transformation (FFT), a 120 ms segment starting 20 ms before the end of the QRS complex was analyzed. The altered frequency content was expressed as the ratio of frequency areas (area ratio, AR) 20-50 Hz/0-20Hz. The average level of noise was 0.56 microV in the first group, 0.62 microV in the second group of patients and 0.68 microV in the control group. RESULTS: Abnormalities in the time-domain analysis (ventricular late potentials, VLP) were present in 2 (13.3%) of 15 patients during the anthracycline therapy in the first group and in 4 (8.8%) of 45 patients after completing therapy in the second group. No abnormalities in the time-domain analysis were detected in the control group. Using frequency-domain analysis, abnormalities in AR20-50 Hz/0-20 Hz were found in 8 (53.3%) of 15 patients of the first group, and in 11 (24.4%) of 45 patients of the second group. Significant differences were observed in the frequency parameters of the ECG signal in patients of the first group in comparison to the control group (p = 0.0018) and also when comparing the patients of the second group and the control group (p = 0.045). CONCLUSION: The HRECG results in time- and frequency-domain analyses indicate to high incidence of HRECG abnormalities in patients examined both during and after the antracycline therapy in comparison to the control group. The prognostic use of the HRECG abnormalities must be established in a larger and longer study. (Fig. 4, Tab. 2, Ref. 43.)