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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

[Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond]

MASATOSHI Kudo

[Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since the survival benefi t of a molecular targeted agent, sorafenib, were demonstrated in the SHARP and Asia Pacifi c trials in 2007. Treatment options for patients with advanced HCC increased by sorafenib, and long-term survival for patients with advanced stage HCC has become possible to some extent. However, development of a more potent fi rst-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and lenvatinib) or underway (cabozantinib and ramucirumab). Furthermore, all of 5 clinical trials of combination therapy with transcatheter chemoembolization (TACE) plus a molecular targeted agent failed to date, however, the combination of TACE and sorafenib (TACTICS trials) was reported to be successful and presented at ASCO in 2018. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of HCC in all stages from early, intermediate and advanced stage, is expected to be changed drastically in the very near future.]

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.]

Clinical Neuroscience

NOVEMBER 30, 2020

[New results of neuroscience research – the background of symptomatological and etiological diversity of mental disorders]

OSVÁTH Péter

[Nowadays, the focus of genetic, neurobiological, neuropsychological and psychosocial research is on a more accurate discovery of the etiology of mental illnesses, especially with regard to the role and complex interactions of certain risk factors. It is increasingly challenging to interpret the results of different aspects and methodologies in a coherent theoretical framework, as this can only lead to a more accurate understanding of the complexity and mechanism of the psychiatric disorders. The main aim of this paper to overview recent studies on etiological background of mental disorders and to present the most important aspects of the Research Domain Criteria (RDoC) system. Review of reports from comprehensive studies published in the most important psychiatric journals over the past five years summarizing new findings on the etio­logy of mental disorders. Although current classifications indicate that mental disorders are strictly distinct diagnostic categories, new findings suggest that these marked differences in symptomatic, genetic, and neurobiological backgrounds are not detectable, as many mental disorders have been identified as having common molecular genetic risk factors, which may indicate common neurobiological pathomechanisms. Research results support the need for a rethinking of psychiatric nosology on an etiological basis and represent an important step forward in the more accurate exploration of the neurobiological background factors of mental disorders and thus in the development of more targeted therapeutic approaches. The development of the RDoC system can be a great help in this, as this dimensional approach offers the possibility of integrating the - often diffuse or even contradictory - neuroscientific research findings into a unified theoretical framework for the etiology, nosology and treatment of mental disorders. ]

Clinical Neuroscience

NOVEMBER 30, 2020

Positive airway pressure normalizes glucose metabolism in obstructive sleep apnea independent of diabetes and obesity

KABELOĞLU Vasfiye, SENEL Benbir Gulçin, KARADENIZ Derya

The relationship among obstructive sleep apnea syndrome (OSAS), type 2 diabetes mellitus (DM2) and obesity is very complex and multi-directional. Obesity and increased visceral fat are important perpetuating factors for DM2 in patients with OSAS. On the other hand, OSAS itself leads to obesity by causing both leptin and insulin resistance as a consequence of activation of the sympathetic nervous system. Risk for developing DM2 further increases in patients with OSAS and obesity. Data regarding effects of positive airway pressure (PAP) therapy, gold standard treatment for OSAS, on glycemic control were inconsistent due to variability in duration of and adherence to PAP therapy. In our cohort study we investigated effects of PAP treatment on glucose metabolism in normal-weighted non-diabetic OSAS patients, in obese non-diabetic OSAS patients, and in OSAS patients with DM2. We prospectively analyzed 67 patients diagnosed with OSAS and documented to be effectively treated with PAP therapy for three months. Apnea-hypopnea index was highest in the diabetic group, being significantly higher than in the normal-weighted group (p=0.021). Mean HOMA values were significantly higher in obese (p=0.002) and diabetic group (p=0.001) than normal-weighted group; the differences were still significant after PAP therapy. HbA1c levels were significantly higher in diabetic group compared to those in normal-weighted (p=0.012) and obese (p=0.001) groups. After PAP treatment, decrease in HbA1c levels were significant in normal-weighted (p=0.008), obese (p=0.034), and diabetic (p=0.011) groups. There was no correlation with the change in HbA1c levels and age (p=0.212), BMI (p=0.322), AHI (p=0.098) or oxygen levels (p=0.122). Our study showed that treatment of OSAS by PAP therapy offers beneficial effect on glucose metabolism, not only in diabetic patients, but also in obese and normal-weighted OSAS patients. Although data regarding overall effects of PAP therapy on glycemic control present contradictory results in the literature, it should be emphasized that duration and adherence to PAP therapy were main determinants for beneficial outcome of treatment.

Clinical Oncology

AUGUST 30, 2019

[Role of calcium metabolism in malignant diseases]

MÉSZÁROS Szilvia, TAKÁCS István

[Calcium plays a key role in a wide range of biologic functions. It is involved in skeletal mineralization, muscle functions, nerve transmission, and hormonal secretion and modulate various cellular functions too. Lines of research, on possible association of calcium metabolism regulation with tumorigenesis have been extensively studied in the recent decades. Implying disruptions and/or alterations of known regulatory and molecular pathways can lead to severe, sometimes life-threatening complications. The shift in physiological regulation and pathological factors also affect bone metastases and hypercalcaemia in cancer patients. For this reason, it is important to know about the changes in calcium metabolism and its treatment options in cancerous diseases.]

Clinical Oncology

AUGUST 30, 2019

[Beyond second line therapy in patients with metastatic colorectal cancer: a systematic review]

D. Arnold, G. W. Prager, A. Quintela, A. Stein, S. Moreno Vera, J. Taieb

[Background: The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the effi cacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes. Results: The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefi t for trifl uridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in effi cacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy. Conclusions: These fi ndings support the introduction of an approved agent such as trifl uridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second line treatment.]

Clinical Oncology

AUGUST 30, 2019

[Prevention of drug-related neuropathy in the clinical practice]

VAJDICS Tímea

[There was a revolution of oncological treatments in the last fi ve years caused by introduction of immuncheckpoint inhibitors. Platinum and taxane based chemotherapies are the standard of care of the most frequent malignancies such as colon and breast cancer. Signifi cant improvement was achieved concerning side effects of chemotherapy in the few past decades. Preventive treatment of vomiting, neutropenia, aneamia are now based on clinical evidences. Meanwhile, there remained side effects (including chemotherapy induced neuropathy) which are diffi cult to treat. This article provides overwiev of the pharmacological therapies, vitamins and non-pharmacological procedures aimed to prevent chemotherapy induced neuropathy. Unfortunately still there are no drugs that are highly effective of preventing of chemotherapy induced periferial neuropathy validated in randomized clinical trials.]

Hypertension and nephrology

NOVEMBER 04, 2020

[The role of stress management in the care of hypertension and the treatment of cardiovascular disease]

SOMOGYI Éva, KISS Zoltán, STAUDER Adrienne

[The aim of this paper is to give an overview of the relationship between stress and hypertension and cardiovascular diseases, furthermore to introduce an evidence based stress management intervention available in Hungary. The correlation between cardiovascular disease and psychosocial factors (including concomitant mental disorders as well as personality traits or the effect of social environment) has been established in numerous studies aimed at investigating pathogenesis or various clinical endpoints. The 2016 Guidelines of the European Society of Cardiology include the assessment and the management of psychosocial problems with behavioral medicine interventions as a I.A level recommendation. The implementation of these guidelines in everyday clinical practice is crucial to decrease cardiovascular risk. This involves the training of health care professionals, the facilitation of multidisciplinary collaboration and the integration of behavioral intervention into everyday care. The Williams Life Skills (WLS) program is an evidence based behavioral medicine intervention aiming to improve stress management and communication skills which implemented internationally and also available all over Hungary. It involves the learning of simple coping strategies that facilitate the successful management of every day psychosocial stress situations and the self-conscious reduction of bodily and psychological tensions. In cardiovascular disease, this improves quality of life and survival. The WLS program is especially recommended for healthcare workers to decrease the negative health consequences of their high stress load and to prevent burnout. Stress may affect both doctors and patients during their interactions. Bálint groups have a positive impact on the physician-patient collaboration and help to reduce burnout by improving the understanding of the diseases from a more complex approach.]