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Hypertension and nephrology

DECEMBER 19, 2020

[Possibility of ARNI (angiotensin receptor-neprilysin inhibitor) treatment in hypertension]

KÉKES Ede

[The natriuretic peptide (NP) is an important endocrine, autocrine and paracrine system that is in constant interaction with RAAS and the sympathetic nervous system in order to ensure a continuous cardio-renal homeostasis. In abnormal conditions – if the pressure/volume load develops in the heart or there are some disorder in the vascular tone or in sodium-water balance, the NP system triggers the body’s defense mechanism. The neutral endopeptidase (NEP) inactivates the vasodilator NPs, bradykinin and vasoconstrictor angiotensin II and endothelin I as well. From this knowledge, the idea that inhibition of the effect of NEP (NEPg) offers a potentially beneficial option in the treatment of heart failure and hypertension was initiated, only the stimulatory effect of angiotensin II needs to be blocked. After a lengthy search, they arrived at a dualacting molecule with a beneficial effect of NEP inhibition (secubitrile) and the angiotensin II AT1 receptor antagonist valsartan (ARNI). Several clinical studies have shown that ARNI alone and in combination with other antihypertensive agents significantly reduces SBP and DBP in hypertensive patients. Its effect is also present in isolated systolic hypertension and in chronic kidney disease with high risk. Do not administer with an ACE inhibitor. Based on clinical experience to date, there is a logic expectation that ARNI will also be classified as a useful antihypertensive agent in the near future.]

Hypertension and nephrology

DECEMBER 19, 2020

hirdetés

[Arrhythmias in hypertension]

ZÁMOLYI Károly

[Hypertension has been recognized as the principal and most common risk factor and underlies many cardiovascular (CV) conditions, including heart failure, coronary artery disease, stroke, and chronic renal failure. Different cardiac arrhythmias have been recognized as clinical manifestations of hypertensive heart disease, related to structural and functional pathophysiological changes of the myocardium, which may predispose to arrhythmias, most commonly atrial fibrillation. Both supraventricular arrhythmias and ventricular arrhythmias may occur in the hypertensive patients, especially when associated with left ventricular hypertrophy or heart failure.]

Clinical Oncology

APRIL 30, 2020

[Coronavirus pandemic – new challenges in oncotherapy]

MINÁROVITS János

[This review outlines some of the basic observations related to coronaviruses infecting animals and describes – in a nutshell – the characteristics of human coronaviruses causing mild or severe respiratory diseases in infected individuals. A special attention is given to SARS-CoV-2, the causative agent of the current coronavirus disease (Covid-19) pandemic, and to the pathomechanism of severe acute respiratory syndrome (SARS) which is also accompanied with multiorgan failure in a subset of infected patients. Recently discovered unique molecular features of SARS-CoV-2 are described as well. These molecular cues may affect human to human virus transmission whereas they are absent, remarkably, from the other lung-targeting highly pathogenic human coronaviruses (SARS-CoV-1 and MERS-CoV) which did not spread all over the world. The possibilities of active immunization to prevent SARS-CoV-2 infection and the development of selective small molecule inhibitors curbing the replication of the virus are also touched upon. The review closes with a few remarks regarding the Hungarian and international recommendations concerning the treatment of SARSCoV- 2 infected cancer patients.]

Clinical Oncology

APRIL 30, 2020

[Hormone replacement therapy in cancer survivors – Review of the literature]

DELI Tamás, OROSZ Mónika, JAKAB Attila

[Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insuffi ciency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women’s Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude defi nitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Yet, the oncologic risk of HRT is extremely diffi cult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies. We group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: ’HRT is advanageous’ (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); ’HRT is neutral’ (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); ’HRT is relatively contraindicated’ for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); ’HRT is diasadvantageous and thus contraindicated’ (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).]

Lege Artis Medicinae

NOVEMBER 30, 2020

[Lung cancer – a review of thirty years. Thoughts about the past struggles, the present results and promises of the future]

OSTOROS Gyula

[In the past thirty years there was a huge development in the complex treatment of lung cancer. This development is due mostly to the last decade. Nihilism of lung cancer treatment is over and it is a reality that even patients in advanced stage turn out curable by appropriate therapy and their condition may be changed for a chronic disease while using anti-tumour therapy. Thirty years ago, the realistic life expectancy of six to eight months in advanced stage mounted nowadays significantly, and may surpass even five years in a number of cases. It required adequate diagnostic background, which provided the biomarker based treatment. In early stage surgical resection has a fundamental role, coupled with modern complex neoadjuvant and adjuvant treatment, while new surgical techniques also contributed to the improvement of therapeutic results. The same is true for radiation therapy. The same complex strategy is prevailing also in pharmaceutical options, which are dominated by modalities of cytotoxic chemotherapies and targeted immunothe­rapies. Multidisciplinary teams play a significant role in strategic decisions of lung cancer treatment. The future ways are indicating repeated innovations of tar­geted therapies and extended indica­tions of immunotherapy in terms of precision medicine. However, we must keep in mind also the primary and secondary prevention with effective smoking cessation programs and low-dose chest CT scree­ning applied as usual soon in the risk groups. ]

Clinical Oncology

FEBRUARY 28, 2020

[Opportunities and challenges in online support of cancer patients]

B. PAPP László

[The online support of oncological care may increase patients’ adherence, and by this it can contribute to the effectiveness of treatment, the improvement of quality of life and physician-patient communication as well as to a higher sense of control over the disease. With the online support of supportive care, patients and their relatives can get information on what they can do in order to improve their conditions, how they can recognize side effects and alarming symptoms of complications, what kind of changes they need to make in their lifestyle and how they can reduce the level of distress. Though the positive outcomes are feasible in many cases, quite considerable number of reports in the fi eld do not meet the requirements of evidence. The online support of oncological care may offer considerable opportunities, however, it may further increase inequality: the more educated and well-off patients with higher level of health awareness may benefi t more, meanwhile for the ones at the bottom of digital divide, the disadvantages may increase. The Hungarian internet coverage and accessibility make the broader online support technologically possible, however, its effectiveness may be hindered by the lack of human skills. Therefore, it is a real challenge to establish such platforms that can be used by the broadest spectrum of society, they are comprehensible for patients and their relatives with lower education, but also satisfying for patients and their relatives with higher level of literacy and expectations.]

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

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

[Role of infl ammation in the carcinogenesis]

KOPPER László, TÍMÁR József

[Chronic infl ammation is an important promoter of the carcinogenesis of several cancer types and also an important contributor to mutagenicity beside the known carcinogens. Beside the continous regeneration of the affected epithelia chronic infl ammation provide a special microenvironment intra and extracellular environment which support malignant transformation and block emerging immune reactions. On the other hand, cancer is generating chronic infl ammation itself independent from its role in the carcinogenic process. It is due to cancer necrosis as well as to the production of infl ammatory cytokines. Cancer-induced infl ammatory reactions block antitumoral immune responses and continous monitoring of this process provide valuable clinical parameter of cancer progression.]