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Lege Artis Medicinae

OCTOBER 21, 2020

[Atherosclerosis: an ancient process in a new interpretation]

REIBER István

[The progress of atherosclerosis starts in childhood and lasts until the body dies. Most cardiovascular diseases and deaths can be traced back to atherosclerotic vascular changes. The process is thousands of years old, but its complex pathophysiology becomes recognized and realised only nowadays. Based on the evidence available today, atherosclerosis is such a chronic inflammatory disease of large- and medium-sized arteries, which is characterized by lipoproteins and immune cells transformed through oxidative and other changes and subendothelial accumulation of extracellular matrix. Innate and adaptive immunity provide a complex regulating system of atherogenesis, which while directing specifically the pro-atherogenic inflammatory and atheroprotective anti-inflammatory processes intensify plaque progression or even stabilize them respectively. With our growing knowledge about the pathology of atherogenesis, we can further improve the identification of cardiovascular risk conditions and apply more personalized therapeutic strategies.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[Analysis of factors influencing the efficacy of Hungarian acute cardiac care]

BECKER Dávid, SKODA Réka, BOKOR Laura, BÁRCZI György, VÁGÓ Hajnalka, MERKELY Béla, GAJDÁCSI József, BELICZA Éva, NEMES Attila, DINYA Elek, TÖRŐCSIK Klára

[Despite the modern invasive acute cardiac care available for all, as opposed to short-term mortality, the long-term mortality of Hungarian myocardial infarction patients exceeds significantly those of European patients getting similar treatment. In order to change this situation, it is necessary to assess and analyse exactly the factors behind. While analysing retrospectively the data of Hungarian acute myocardial infarction patients, we identified the influencing factors of short- and long-term mortality. This study processed data from 2003 to the present days from a number of registries (Heart- and Vascular Center of Semmelweis University VMAJOR I and VMAJOR II registry, Stent for Life I and II Programs of the European Society of Cardiology, National Public Health Service’s registry about Cardiac Care in Central Hungary, Budapest Modell database). According to our detailed examination, the proportion of primary per­cutaneous coronary intervention in ST-segment elevation myocardial infarction is at Western-European level, however the invasive treatment of acute coronary attack patients with Non-ST segment myocardial infarction is below the required. The so-cal­led hesitation span of Hungarian pa­tients with ST-segment myocardial infarc­tion is substantially longer than that of neighbouring countries thus the average cardiovascular risk of relevant Hungarian patients is significantly higher than those of the GRACE Register’s population. Based on our results a complex strategy can be developed which may have impact also on strategic health­care decisions in order to reduce the long-term mortality of patients surviving myocardial infarction.]

Lege Artis Medicinae

APRIL 18, 2020

[Digitally-assisted treatment planning in precision oncology]

PETÁK István, VÁLYI-NAGY István

[The progress of molecular information based on personalized precision medicine has reached a new milestone. Actually, about 6 million mutations of 600 genes may be related to the development of cancer, and on average, 3-4 of these “driver” mutations are present in each patient. Due to the progress in molecular diagnostics, we can now routinely identify the molecular profile of tumors in clinical settings. By clinical translation, there are actually available more than 125 targeted pharmaceuticals and hundreds of such therapies are under clinical trial. As a result, we have many first-line and licenced treatment options to be elected by molecular information as the optimal one for every patient. There is an increasing need for complex informatics solutions by medical software. Geneticists, molecular biologists, molecular pathologists, molecular pharmacologists are already using bioinformatics and interpretation software on their daily work. Today, online digital tools of artificial intelligence are also available for physicians for assisted treatment planning. Telemedicine, videoconferencing provide solutions for interdisciplinary virtual molecular tumor boards, which democratizes the access to precision oncology for all doctors and patients. ]

Clinical Oncology

APRIL 10, 2019

[Metals and cancer]

VETLÉNYI Enikő, RÁCZ Gergely

[We often tend to forget about our environment when looking for the origin of a disease. Inhaled air, drinking water and food, substances in contact with the skin all have an effect on the human body. Metals are indispensable parts of our everyday lives, their mining, processing and use cause a continuous exposure to them. Metal exert their effects on the body in various ways. Many of them are essential for maintaining homeostasis, but excessive or harmful metal intake can lead to health damage, including tumour formation through multiple attack points. Metals substitute each other during different transport processes and in the structure of proteins, they cause oxidative stress and bind to DNA, thereby damaging it. Applying them appropriately, the proapoptotic effect of the metal compounds is brought to the fore, thus becoming a therapeutic tool for tumours. Nowadays, platinum(II) compounds are widely used as chemotherapeutic agents and there are many ongoing studies to fi nd metal compounds with an ideal therapeutic and side-effect profi le. The aims of this article were to draw the attention to the dangers of metals in relation to cancer and to highlight their diverse application possibilities in current and future cancer therapy and diagnostics.]

Clinical Oncology

FEBRUARY 28, 2020

[The treatment of the locally advanced and the metastatic gastric cancer]

SIPŐCZ István

[Although signifi cant progress has been made in the treatment of stomach cancer recently, survival results are still quite modest. The purpose of this overview is to take a look into the history of the treatment of locally advanced and metastatic stomach cancer and to present the current treatment standards. It focuses on recent changes in perioperative treatment, as well as the changing of treatment of metastatic patients. The use of multiple line of palliative chemotherapy and the place of the available targeted treatments in metastatic tumours will be analysed in detail. The increasing use and the future possibilities of immunocheckpoint inhibitors will also be discussed. Molecular subtypes of gastric cancer are also mentioned as possible indicators of the choice of therapy. Finally, it intends to give therapeutic proposals to make recommendations to treat the disease taking into account the opportunities in Hungary.]

Clinical Oncology

FEBRUARY 28, 2020

[Treatment sequencing in metastatic colorectal cancer]

MODEST D. P., PANT S., SARTORE-BIANCHI A.

[Metastatic colorectal cancer (mCRC) remains incurable in most cases, but survival has improved with advances in cytotoxic chemotherapy and targeted agents. However, the optimal use and sequencing of these agents across multiple lines of treatment is unclear. Here, we review current treatment approaches and optimal treatment sequencing across the fi rst-, second- and third-line settings in mCRC, including biological aspects affecting sequencing and rechallenge. Effective fi rst-line therapy is a key determinant of treatment outcomes and should be selected after considering both clinical factors and biological markers, notably RAS and BRAF. The second-line regimen choice depends on the systemic therapies given in fi rst-line. Anti-angiogenic agents (e.g. bevacizumab, ramucirumab and afl ibercept) are indicated for most patients, whereas epidermal growth factor receptor (EGFR) inhibitors do not improve survival in the second-line setting. Molecular profi ling is important in thirdline treatment, with options in RAS wild-type patients including EGFR inhibitors (cetuximab or panitumumab), regorafenib and trifl uridine/tipiracil. Immunotherapy with pembrolizumab or nivolumab ± ipilimumab may be considered for patients with high microsatellite instability disease. Targeting HER2/neu amplifi cation shows promise for the subset of CRC tumours displaying this abnormality. Sequencing decisions are complicated by the potential for any treatment break or de-escalation to evoke a distinct clinical progression type. Ongoing trials are investigating the optimal sequencing and timing of therapies for mCRC. Molecular profi ling has established new targets, and increasing knowledge of tumour evolution under drug pressure will possibly impact on sequencing.]

Clinical Oncology

FEBRUARY 28, 2020

[Neoadjuvant and palliative drug therapy for bladder cancer]

MARÁZ Anikó

[The survival of patients with muscle-invasive localized bladder cancer is more favorable if they receive neoadjuvant or adjuvant cisplatin-based chemotherapy before or after cystectomy. Based on the meta-analyses, in case of neoadjuvant cisplatin-based chemotherapy, the 5-year survival benefi t is 5-16%. The outcome is even more favorable in case of patients who respond well to neoadjuvant chemotherapy (pathological complete remission rate 12–50%). More than 3 months delay of cystectomy does not signifi cantly reduce the survival if chemotherapy is performed before the operation. Results of adjuvant phase III studies and meta-analyses are not so unambiguous as neoadjuvant data, but chemotherapy seems to infl uence favorably PD-L1 expression the survival, especially in case of pT3/4 and/or N+ (and high grade or margin positivity) cases. According to the recent publications, outcome data of patients have been effective in case of progression after platinum therapy, in or after second-line and in fi rst-line therapies for cisplatin ineligible, PD-L1 positive patients, respectively. Survival and tumor response data are very promising; in particular stages, they seem to be more effective than the previously administered chemotherapies. Current and ongoing trials are investigating the combinations of new remedies with other immunotherapeutic agents or chemotherapies as well as trying to identify biomarkers in order to further increase effectiveness.]

Clinical Oncology

FEBRUARY 28, 2020

[Non-surgical treatment of ovarian cancer]

PIKÓ Béla, LACZÓ Ibolya,, MARIK László

[The primary surgery with an optimal cytoreduction is an essential step during the treatment of the epithelial ovarian cancer because it determines the effectiveness of other therapeutic options as well. Immediately after the surgery a cytostatic infusion typically 40-42.5 degrees Celsius is pumped directly to the abdomen. During the systemic therapy the main point is the 6 months progression free survival because beyond this time the disease could be considered as platinum sensitive, inside this time as platinum refracter or resistant disease. The cytostatic treatment improved during the years from the alkylating agents through the platinum derivates to the administration of paclitaxel with several combinations of them and with more and more signifi cant results and less side effects. The most signifi cant targeted agents are the angiogenesis inhibitors (mainly the bevacizumab) and the PARP-inhibitors which prevents DNA repairs. In order to a PARP-inhibitor could be administered a platinum sensitivity is required while BRCA mutation not. Recently there are promising clinical researches with immunotherapy as well. The main benefi t of the hormonal therapy is the tolerability. Besides the signifi cant improvement in the systemic agents the role of radiotherapy is more and more decreasing, however the treatment of the whole peritoneal surface – mainly with the modern radiation techniques – could be an alternative solution for the chemotherapy. The palliative irradiation which relieve the symptoms could extend the drug-free period and the combination of radiation and chemotherapy could provide further possibilities.]

Clinical Oncology

DECEMBER 30, 2019

[Treatment of cholangiocellular carcinoma]

ANDRÁS Csilla, ÁRKOSY Péter

[Tumors of the biliary tract are a rare entity, at the time of diagnosis most of the patients are in advanced stage and operation can’t be effectuated. After operation the risk of recurrence is high. The standard adjuvant therapy is capecitabin based on the results of BILCAP study. In advanced stage or in the presence of metastates the standard fi rst line treatment is gemcitabine and cisplatin therapy, there are noninferiority results from a Japan study with gemcitabin and S1 combination therapy. There was no evidence of second line treatment possibilities after gemcitabine and cisplatin therapy until 2019, but based on the results of ABC-06 study mFOLFOX could be the choice in the future. In the case of MSI-H/dMMR tumors immuntherapy should be considered. Personalised medicine with matched molecular targeted therapy is a new option. There are 2 new molecular targets, FGFR and IDH, the preliminary result are very promising.]

Clinical Oncology

DECEMBER 30, 2019

[Prevention and treatment of venous thromboembolism in cancer patients]

[Venous thromboembolism (VTE) is a common and severe complication of cancer. Deep vein thrombosis and pulmonary embolism are the second most common cause of death in cancer patients. Cancer, tumor-related factors as well as patient’s general condition and comorbidities are responsible for the increased risk of VTE. Chemotherapy is one of the most important risk factors for VTE, increasing incidence of VTE by 6.5-fold. In my paper, current guidelines for cancer VTE prevention and treatment are reviewed. Hospitalized patients with active tumor are at higher risk for VTE, and thrombosis prophylaxis is recommended in all cases. Extensive, routine prophylaxis for advanced cancer patients receiving chemotherapy is not recommended, but may be considered in high-risk ambulatory cancer patients (Khorana-score ≥ 3). Risk factors may change during the course of cancer disease, and the score should be continually reviewed and prophylactic treatment changed as necessary. LMWH is the recommended agent for both primary and secondary prophylaxis/treatment. Direct oral anticoagulants (DOACs) are knocking on our door, but results from further clinical trials are pending to determine their exact role.]