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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.]

Hypertension and nephrology

NOVEMBER 04, 2020

[Hypertension and Covid-19 - part II.]

SZÉKÁCS Béla, KÉKES Ede, NAGY Judit, KOVÁCS Tibor

[The authors review those components and mechanisms in the two major regulatory systems of circulation and inflammation-coagulation whose internal balance and interactions are pathologically altered during SARS-CoV-2 infection, thereby enhancing lung and systemic inflammation threatening to enter into severe clinical condition. They examine the question of how – in addition to potentially promoting the coronavirus cellular entry and penetration – the RAS inhibitor therapy affects these changes and whether can be supposed difference between the anti-/pro-inflammatory influence of ACEi and ARB treatment of old hypertensive patients representing a remarkably high proportion of victims in COVID-19 epidemic. The paper is focussing to the pathomechanical background of inflammation beyond the direct immunological response to the infection: to the significance of immunological alterations characterizing old hypertensive patients also in basic condition, and to the key components as angiotensin II, ACE2, angiotensin1-7, bradykinin, ARB and ACEi. In conclusion a consideration on optimal point of action is offered in RASi treated and SARS-CoV-2 infected (old) hypertensive patients.]

Lege Artis Medicinae

APRIL 18, 2020

[What is worth to know about COVID-19 for (not only) a cardiologist]

HEPP Tamás, CSÉKE Balázs, BENCZÚR Béla

[SARS-CoV-2 virus infection sprang from Wuhan the capital of the Chinese Hubei province, at the end of 2019 and caused a worldwide pandemic with 1.5 million confirmed cases and claimed almost 100 000 victims until the beginning of April, 2020. First analyses of Chinese COVID-patients confirmed that diabetes, hypertension, and cardiovascular diseases were highly prevalent among SARS-CoV2 infected patients, and might be associated with poor outcome. As previously shown for SARS-CoV-1, SARS-CoV-2 similarly utilizes ACE2 as receptor for viral alveolar cell entry. A suspicion has arisen that the widely used ACE-inhibitor/ARB therapy could be potentially harmful for patients suffering from COVID-19 infection as these agents upregulate the ACE2-expressions. From the other point RAAS-blockade might be beneficial due to fact that ACE2 counters the deleterious effects of Angiotensin II. Authors provide a comprehensive over­view of the most recent literature and summarize the link between COVID-19 and car­diovascular disease. It is important to em­phasize that there are no available hu­man evidences confirming if the RAAS-in­hi­bitor therapy were harmful or helpful in pa­tients suffering from COVID-19.]

Lege Artis Medicinae

MARCH 10, 2020

[Recommendations of the European Atherosclerosis Society (EAS) and the European Society of Cardiology (ESC) for dyslipidaemia. Focused on: primary prevention]

BAJNOK László

[In 2019 the European Atherosclerosis So­ciety (EAS) and European Society of Car­dio­logy (ESC) renewed their dyslipidae­mia guidelines. The new version is more progressive than the previous ones. Thus, in the low-risk, not severely hy­per­choles­te­ro­lae­mic population cholesterol-lowering medication is also suggested. Except this low-risk group, atherogenic target values, e.g. for LDL-cholesterol, were reduced by an entire category, in some cases to the lowest one. If these goals cannot be achieved with statin-monotherapy, combined treatment is recommended generally by the cholesterol inhibitor ezetimib, and in some very high-risk cases also by innovative cholesterol lowering so-called PCSK9 inhibitor. ]

Clinical Oncology

APRIL 10, 2019

[CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions]

SPRING M. Laura, WANDER A. Seth, ZANGARDI Mark, BARDIA Aditya

[Purpose of review: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+MBC) as well as current controversies and evolving areas of research. Recent fi ndings: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the fi eld include whether all patients with HR+MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. Summary: The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.]

Clinical Oncology

APRIL 10, 2019

[New perspectives in the treatment of lung cancer]

SZONDY Klára, BOGOS Krisztina

[In recent years, huge research is going on in the fi eld of oncology and as a result, we can see a signifi cantly longer survival in this area of medicine. Lung cancer, which has been taken places in the back for decades, it has not become a curable disease, but begins to belong to the chronic diseases. As a result of brilliant surgical technics and stereotactic radiotherapy, or as a result of changes in drug treatment, 5-year survival is not uncommon in metastatic lung cancer patients, next to relatively long progression free survive. After the third-generation cytotoxic combinations the added growth inhibition (VEGF inhibitor) maintenance therapy or continuous pemetrexed cytotoxic chemotherapy were resulted in high survival benefi ts. The fi rst real breakthrough, long progression-free survival was achieved by targeted treatment, which proved to be effective with known driver mutations. The other great result, especially in squamous cell carcinoma, was the immunotherapy, the inhibition of immune checkpoints, which effi cacy was confi rmed in adenocarcinoma also. Several studies are going on with adjuvant or neoadjuvant immunotherapy, and combined use of immunotherapy (either in combination with radiotherapy or cytotoxic chemotherapy).]

Lege Artis Medicinae

OCTOBER 20, 2019

[Medical therapy of peripherial artery disease]

BENCZÚR Béla

[Care of PAD (peripherial arterial disease) is one of the most negligent area of cardiovascular diseases: on one hand patients suffering from PAD are the most uncared, less educated and health-minded population (it’s enough to keep in mind the high rate of smoking and alcohol-abuse among them) in addition the number of angiologists is insufficient for the treatment of PAD. Although detection of PAD would be easy as a widely applicable, cheap screening method, the ankle-brachial index is available which is an obligatory screening investigation in general care. Therapeutic options are better and better since cilostazol was launched we have an evidence-based treatment which can solve the symptoms, slower the progression which is strongly recommended (IA recommendation) in both American and Hungarian guidelines. Cilostazol, a PDE3-inhibitor has complex pharmacological effect but contraindicated in several clinical conditions as pentoxiphylline is not totally excluded from the therapeutic arsenal of PAD. The place of antiplatelet agents is well-defined in the most recent European guidelines in the treatment of PAD. The jumping development of interventional radiology beyond medical therapy contributed a lot to prevent limb amputations in the case of early detection of PAD. ]

Hypertension and nephrology

MAY 10, 2019

[One-year persistence of fixed-dose combinations of angiotensin-converting enzyme inhibitor and calcium channel blocker in hypertensive patients]

SIMONYI Gábor, FERENCI Tamás, FINTA Ervin, IGAZ Iván, BALOGH Sándor, GASPARICS Roland, MEDVEGY Mihály

[Introduction: The most recent European guidelines for the treatment of hypertension suggest the use of renin-angiotensin-aldosterone system antagonists (RAAS inhibitors) and calcium channel blockers (CCBs) or diuretics fixed-dose combinations (FDCs) as the first therapeutic option. In antihypertensive therapy, the patient’s adherence is one of the most important factors in reducing unwanted cardiovascular events. Aim: Our aim was to assess the one-year persistence of angiotensin-converting enzyme inhibitor (ACEI) and CCB FDCs in hypertensive patients. Method: Authors have analysed the prescription database of the National Health Insurance Fund in Hungary on pharmacy claims between October 1, 2012 and September 30, 2013. Those patients were identified who filled prescriptions for FDCs of ACEI and CCBs prescribed for the first time for hypertensive patients and who had not re ceived similar drugs during the year before. Apparatus of survival analysis was used, where ‘survival’ was the time to abandon the medication. Results: 124,388 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinua tion in patients with ramipril/amlodipine FDC was 54% (HR = 1.00, reference), perindopril/amlodipine 47% (HR = 1.30, p<0.0001), lisinopril/amlodipine 36% (HR = 1.79, p<0.0001), ramipril/felodipine 26% (HR = 2.28, p<0.0001) and trandolapril/verapamil 12% (HR = 4.13, p<0.0001). The average survival time of drug limited to 360 days was 270.2 days for ramipril/amlodipine FDC, 242.7 days for perindopril/amlodipine FDC, 211.2 days for lisinopril/amlodipine FDC, 186.3 days for ramipril/felodipine FDC and 125.7 days for trandolapril/verapamil FDC. Conclusions: The authors demonstrated that the one-year persistence of ACEI/CCB FDCs was significantly different in hypertensive patients. Ramipril/amlodipine FDC was more advantageous for patient adherence.]

Clinical Oncology

MAY 10, 2018

[Immunotherapy of lungcancer – an update]

OSTOROS Gyula

[Ten years ago the median survival of small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC) was less than one year. In the case of SCLC the situation did not change. There are revolutionary new possibilities in the treatment of NSCLC (histology based cytotoxic chemotherapy, molecular targeted therapy etc.). Unfortunately there is no signifi cant development in treatment strategy of SCLC in the last 30 years. Nowadays in NSCLC immune check point inhibitor therapy is a novel treatment method in the clinical praxis as well. The integration of the PD axis and the CTLA4 inhibitors in the complex therapy of the management of NSCLC is a new challenge. The pembrolizumab monotherapy in fi rst line setting is a new standard of care with high PDL1 expression. In second line setting the pembrolizumab, nivolumab and atezolizumab widely used in clinical praxis as well. In locally advanced disease of NSCLC after radiochemotherapy the durvalumab maintenance monotherapy showed a signifi cant progression free survival benefi t, comparing to placebo. We have got new treatment possibilities in the treatment of SCLC as well. The results of clinical trials with antibody conjugate therapy are promising. The nivolumab monotherapy and the combination treatment of nivolumab + ipilimumab gave promising results as well. In the treatment of SCLC and NSCLC there is a need for biomarker selected therapy (tumor mutational burden [TMB], DLL3, cMyc etc.). Based on the new positive results of the clinical trials there is a possibility to transform lung cancer from a subacute disease to a chronic illness.]