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Clinical Oncology

AUGUST 30, 2019

[Electrochemotherapy]

KIS Erika Gabriella

[Tumors with standard electrochemotherapy (ECT) has raised over the past decade from skin cancers to locally advanced or metastatic tumors. The procedure became a reliable alternative of other local tumor ablation methods, because of its patient tolerability, effi cacy across histotypes, and repeatability. ECT is based on the physical phenomenon of reversible electroporation; short electric pulses are applied to tumor nodules to achieve transient cell membrane permeabilization to otherwire poorly permeant chemotherapy drugs, which consequently increases cytotoxicity. At present recognized indications include superfi cial metastases of malignant melanoma, breast cancer, head and neck skin tumors, Kaposi sarcoma, primary and recurrent nonmelanoma skin cancers, and in well-selected patients mucosal oropharyngeal cancers. Emerging applications include skin metastases from visceral or hematological malignancies, vulvar cancer, certain benign skin lesions, and the combination of ECT with systemic immunotherapy. Thanks to the technical developments, the new ECT indications are deep-seated tumors, including bone metastases, liver malignancies, pancreatic and prostate cancers with the use of long needle variable geometry electrodes. Herein we review the present status of ECT from the basic principles to emerging applications, and report the effi cacy of standard ECT across histotypes.]

Lege Artis Medicinae

OCTOBER 21, 2020

[Gene modified immune cells: New weapons not exclusively against cancer]

SZÖŐR Árpád

[The oncological breakthrough of the last decade was the application of CD19-specific CAR T cells in different hematologic diseases. Experience gained by clinical trials, coupled with investments of the private stakeholders and the pharmaceutical industry resulted not only in commercial release to the public of already developed CAR T cell products, but drew the atten­tion of many researchers to the potentials of new type immune cells, and their non-oncological administration. This study aims to present briefly those preclinical applications, which approved successfully the administration of CAR T cells in autoimmune and infectious diseases.]

Hypertension and nephrology

SEPTEMBER 30, 2020

[Post-career development of cardiometabolic changes and hypertension in competitive athletes]

LELBACH Ádám, KÁNTOR Márk, KOLLER Ákos

[Regular physical activity is essential in delaying the aging processes (e.g. arterial remodelling – stiffening, metabolism, bodyweight), the beneficial effects of competitive sports – especially strength sports – according to the recent data of the literature are questionable. The beneficial effects of physical activity on the cardiovascular (CV) system are well known, however less is known regarding the delayed impacts of high intensity competitive sports on the CV system, especially after the sport career is over. This review summarizes the effects of active competitive sport and the post-career period on the cardiometabolic system with special attention to the systemic blood pressure and the development of metabolic syndrome. After sport career, the welldeveloped high performance cardiovascular- and metabolic system suddenly is much less used, but still supported by sport-level diet. It is well known that hypertension is a significant pathogenic factor in the development of cardiovascular diseases, characterized – among others – by reduced elasticity of large- and medium- sized vessels thereby importantly contributing to the development of systolic hypertension. Inflammation and thrombus formation both play an important role in the development of vascular injury and atherosclerosis. The increased tone of microvessels can impair the blood supply of certain organs, including the coronary circulation. It has been ample shown, that regular non-competitive, aerobic exercise activities are important factors in preventing hypertension. Such pathological changes become more evident after the development of post-career obesity, as well as the development of hypertension due to the activation of the renin-angiotensin system through sodium retention and other metabolic changes (increased glucose tolerance, insulin resistance, type II diabetes mellitus). It has been ample shown, that regular non-competitive, dynamic aerobic exercise activities are important factors in preventing hypertension. The frequency, intensity, type, and time (FITT) principle of exercise prescription is the first and common therapeutic approach, which represents the translation of cardiovascular basic science research results into hypertension treatment, thus can provide a personalized physical activity program/therapy according to medical needs not just for the post-career sportspersons, but the wide range of patients.]

Clinical Neuroscience

SEPTEMBER 30, 2020

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Neuroscience

SEPTEMBER 30, 2020

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Frequency and risk factors of “de novo” tumors after kidney transplantation ]

BORDA Bernadett, HÓDI Zoltán, SZEDERKÉNYI Edit, OTTLAKÁN Aurél, SEREGÉLY Edit, LÁZÁR György, KERESZTES Csilla, VIRÁG Katalin

[After kidney transplantation, the administration of immunosuppressive therapy not only renders the patient susceptible to infections, but it may also damage the function of tumor cell recognition and elimination. Our study was performed at the Department of Surgery, University of Szeged. After establishing the inclusion criteria, 570 patients were involved in the study. We examined the age, sex, immunosuppressive therapy of the patients, and searched for the rela­tionship between the different immunosuppressive agents and the type of the tumor. In 81 cases, de novo cancer was diagnosed. Among patients treated with cyclosporin and tacrolimus there was no significant difference in the mean age (p = 0.734) and body mass index (p = 0.543). There was no significant difference in graft function between the two groups of patients (Tac vs Cyc; 44 vs 20). Related to the time passed since the trans­plantation to diagnosing the tumors the earliest were prostate and cervix cancers however without significant difference. Skin cancers are the most frequent followed by post-transplant lym­pho­prolife­ra­tive diseases. The increasing risk of developing tumors is mainly due to immunosuppressive therapy. ]

Lege Artis Medicinae

JULY 01, 2020

[Persisting Hashimoto’s thyroiditis converting to Graves’ disease]

TÓTH Géza

[Graves’disease and Hashimoto’s thyroiditis are the two most important types of autoimmune thyroid dis­eases. Autoimmune hyperthyroidism commonly leads later on to hypothyroidism. The conversion from persisting Hashimoto-thyroiditis to hyperthyroidism is rare in the literature. The author presents the cases of two patients, whose Hashimoto’s thyroiditis treated with thyroxin for years, changed into Graves’ hyperthyroidism sponta­neously. CASE REPORT – The patients had been diagnosed with autoimmune hypothyroidism since several years. The clinical symp­­toms, the low peripheral hormone le­vels, the high level of antithyroid antibo­dies and the ultrasound imaging confirmed the hypertrophic form of Hashimoto’s thy­roiditis. After several years of high dose le­vothyroxin treatment, clinical symptoms of hyperthyroidism have appeared. After omit­ting the substitution, the thyroid hormone levelled off at high values and the level of anti-TSH receptor antibodies raised too. The diffuse, obviously increased blood flow of the thyroid glands, and in one of the patients the thyroid scan, confirmed the Graves’ disease. During the thyreostatic treatment, the symptoms of the patients disappeared, they became euthyreoid and the antibody levels decreased as well. The Graves’ disease and the Hashimoto’s thyroiditis have many common features. These immunological, ge­netic and other common features enable the mutual transition of these two diseases.]

Lege Artis Medicinae

JULY 01, 2020

[Sarcopenia – muscle loss – pathomechanism, clinical presentation and metabolic comorbidities]

VERECKEI Edit, HODINKA László

[Sarcopenia, or the age-related involution of muscle strength and muscle mass, is a serious public health concern, due to the growing number of elderly population caused by nowadays demographic changes i.e. prolonged life expectancy. By ageing, the muscle tissue is shrinking gradually, leading to the loss of muscle strength and masses. This condition is called sarcopenia. Sar­co­penia is the simultaneous decrease of muscle mass, muscle strength and functional independence. In parallel the physical performance deteriorates (weakness, slowness and poor physical balancing). Fatigue, el­derly behaviour and weight loss are the consequences of these accumulating deficits, which associate with cognitive decline and result in increasing social isolation. The primary form of sarcopenia is the decrease of the energy production of muscle cells and then the death of muscle cells. Se­con­dary, endocrine dysfunctions, diseases of the nervous system, decreased physical activity, malnutrition or malabsorption, chronic infection accelerate the process and aggravate the patient’s condition. Complex genetic, biochemical and endocrine mechanisms take part in the development of sarcopenia. This involution is due to the impaired balance of restoring and depleting processes of muscles. A questionnaire and algorithm have been developed to recognize, screen and diagnose the risks of sarcopenic condition; these separate the sarcopenic and non-sarcopenic patients with specific cut-off values. Sar­co­penia can be diagnosed based on walking speed, decreased handgrip strength and measured or calculated muscle mass in persons over 65. Sarcopenia can be considered as a phenomenon of “physiological” aging, however, it becomes a disease when diagnostic cut-offs are exceeded and the patient experiences functional disability and declining quality of life. Prevention and treatment of sarcopenia and reducing the risk of falling are based on regular active resistance and coordination exercises. Options for pharmaceutical treatments are limited since despite of identified molecular targets there are no convincingly effective innovative therapy on the horizon. Nevertheless, there are some weak evidence for efficacy of the application of amino acids stimulating muscle cell differentiation, such as leucine or the analogue of beta-hydoxy-methylbutyrate beside exercise therapy.]

Hypertension and nephrology

JUNE 24, 2020

[Covid-19 and the kidney]

PATÓ Éva, DEÁK György

[Covid-19 pandemy has emerged from Wuhan, China in December 2019. The infection affects not only the lung but other organs such as the kidney, as well. The relation between Covid-19 infection and the kidney is bidirectional. On one hand, Covid-19 infection may cause kidney damage in 50-75% of the cases resulting in proteinuria, haematuria and acute kidney injury (AKI). The etiology of AKI is multifactorial. Main pathogenic mechanisms are direct proximal tubular cell damage, sepsis-related haemodinamic derangement, citokine storm and hypercoagulability. The virus enters proximal tubular cells and podocytes via the ACE2 receptor followed by multiplication in the lysomes and consequential cell lesion. Histopathology shows acute tubular necrosis and acute tubulointerstitial nephritis. AKI is a strong predictor of mortality in critically ill patients. On the other hand, the risk of Covid-19 infection and mortality is substantially increased in patients with chronic kidney disease – especially in those with a kidney transplant or on dialysis – due to their immunocompromised status. Among haemodialysis patients, infection may spread very easily due to the possibility of getting contacted in the ambulance car or at the dialysis unit. The mortality rate of patients on renal replacement therapy with Covid-19 infection is 20-35%. In order to avoid mass infection it is obligatory to employ preventive measures and implement restricions along with (cohors) isolation of infected patients. In Hungary, every dialysis or kidney transplant patient with Covid-19 infection should be admitted to dedicated Covid-19 wards.]

Hypertension and nephrology

JUNE 24, 2020

[Hypertension and Covid-19 – Part I. Significance of age, underlying diseases, and ACEI/ARB therapy in hypertension and co-morbidities during SARS-Cov2 infection]

KÉKES Ede, SZÉKÁCS Béla, NAGY Judit, KOVÁCS Tibor

[The appearance of the Covid-19 epidemic in different continents shows specific clinical features. Confirmed infected patients are detectable from approximately 30 years, with a maximum between 40 and 70 years of age. At the same time, however, a significant proportion of those who die from the infection come from patients over 65 years. The prevalence and mortality rates of the hypertensive population show a very similar formation. Based on the data collected, it is not surprising that hypertension as the underlying disease in the Covid- 19 epidemic is the first in all analysis. A more precise analysis clarified that it is not hypertension per se, but co-morbidities and complications of hypertension that play a primary role behind large-scale mortality in old age, such as diabetes, coronary heart disease, stroke, heart failure, and chronic kidney disease. Data from China, North America, and Italy suggest that hypertension and diabetes – and in North America, pathological obesity – in infected patients actually only reflect the prevalence of these diseases in a given population. The presence of comorbidities (coronary artery disease, stroke, heart failure, arrhythmia, chronic kidney disease) – based on multivariate logistic regression analysis – presents a more risk for severe clinical course and mortality. Some recent analyses have provided strong evidence that ACEI/ARB treatment does not pose a higher risk for the course or outcome of infection. Their administration is constantly needed in hypertension and comorbidities due to their organ protective and slowing the progression of diseases.]