Search results

Clinical Oncology

DECEMBER 30, 2019

[Sequential therapy of metastatic renal cell carcinoma]

TORDAY László

[The incidence of renal carcinoma is on the rise in developed countries, with the tumor being among the 10 most common malignancies. However, the survival of patients with irresecable renal carcinoma has improved signifi cantly in recent years, mainly due to signifi cant advances in oncology treatment. The use of agents acting on the VEGF and mTOR signaling pathways is widespread and has become a standard clinical practice in fi rst and later line therapy. Recent clinical trials have provided many new drugs with new targets (cMET and AXL, FGFR, PD-1/PD-L1, CTLA-4) and combinations thereof, and have completely redrawn the treatment landscape of metastatic renal carcinoma and signifi cantly improved clinical results. This report reviews data on targeted drug therapy of renal cell carcinoma and discusses the therapeutic position of various drugs and combinations to our knowledge.]

Clinical Oncology

DECEMBER 30, 2019

[Cell death]

KOPPER László, TÍMÁR József

[Cell proliferation and cell death (mainly apoptosis) have programs forming a network to maintain the functional integrity of the organism. Apoptosis has an external and internal units with ligands, signalling pathways and targets. Besides, some other participants (e.g. p53) are involved in the regulation of cell death. Although, apoptosis is a multitargeted process, there is no useful therapy, if it is needed, to correct accumulation of unwanted cells.]

Clinical Oncology

DECEMBER 30, 2019

[Chemicals and tumors]

MARCSEK Zoltán

[Tumorigenesis is driven usually by non-lethal genetic alterations such as malfunctioning regulatory systems; mainly by inactivating suppressor genes or activating proto-oncogenes or malfunctioning of apoptatic system or decresed activity of the DNA repair system. Several chemicals induces mutations in the regulatory genes forces the cell for continous divisions increasing the chance of accumulation of further mutations. Chemicals, inducing mutations (mutagens) increase the rate of tumor occurrence, are carcinogens.]

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.]

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

[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.]