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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 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.

Lege Artis Medicinae

APRIL 18, 2020

[The relationship of traumatic experiences and eating disorders – therapeutical options]


[In the etiology of eating disorders (espe­cially bulimia nervosa and binge eating) traumatic experiences (sexual, physical, emo­tional abuse, neglect) play an important role. Traumatization can have a serious impact, which is influenced by the parameters of the traumatization, risk and protective factors, and the resiliency of the traumatized patient. The consequences may lead to the development of specific psychiatric and somatic disorders, and may cause lifetime revictimization. The exploration of data related to the traumatization is essential in eating disorders as well. If traumatic expericences can be detected in the back­ground of eating disorders, the targeted therapy of eating disorders while applying its specific elements should also follow the guide­lines of the general trauma-therapy. Providing safety in therapeutical relation­ship is fundamental. The therapeutic options are extensive. Along with psychodynamically oriented therapies, the newer methods based on cognitive-behavioral therapy (e.g., dialectic behavior therapy, integrative cognitive analytic therapy) are also proposed. Hyp­no­therapy can also be useful. ]

Clinical Oncology

DECEMBER 30, 2019

[Treatment of cholangiocellular carcinoma]


[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

MAY 10, 2018

[Immunotherapy of lungcancer – an update]


[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.]

Lege Artis Medicinae

OCTOBER 20, 2018

[Gene modified T cells against cancer]


[Chimeric antigen receptor modified (CAR) T cells are hailed as a revolutionary breakthrough in the field of oncology. CAR T cells were first applied, with outstanding success, in the treatment of various leukaemias, yielding unprecedented antitumor activity and long periods of disease free survival. Following the success of CAR T cell therapy in leukaemias, solid tumors should now be targeted. These are more complex targets, therefore CAR T cell therapy needs to be further optimized for this purpose. Also, some unfortunate side effects, including the potentially deadly global inflammation called cytokine storm have to be minimized and possibly even eradicated. The next decade will be an exciting time to define whether this therapy which is yet exclusively used for cancer patients is also successful in the treatment of other diseases. In a recent study, T cells reengineered with CAR derived chimeric autoantibody receptors (CAAR) efficiently prevented disease progression in pre-clinical animal models simulating the serious autoimmune disorder, pemphigus vulgaris. Therapy was based on CAAR constructs which have the unique ability to selectively recognize and eliminate the B-cell clones secreting autoantibodies against a self-protein, thus playing a key role in disease pathogenesis and progression. In this review, we would like to give an overview about the history of the CAR T-cell concept, summarize briefly the currently running clinical trials, and discuss the challenges and future prospects of CAR T-cell therapy.]

Lege Artis Medicinae

JUNE 07, 2021

[Lipid lowering therapy during COVID-19 pandemic]

MÁRK László

[The COVID-19 pandemic posed significant challenges to all healthcare systems of the world as created a new situations above the large number of people infected, solutions of which were lacking any previous patterns. Former experiences were specifically needed among physicians who practised usually with therapies supported by evidence based clinical experiences thus they were working along the principles of Evidence-Based Medicine. The new observations and recommendations for treating infected patients increased gradually, however they were not always well-founded by the general urgency. In this situation, physicians faced often problems of the patient’s former medications since they had to focus on the therapy of the prevalent life-threatening condition. In such cases, therapy as lipid lowering, which is inherently inimically and lightly taken, may be omitted even more often. Basic drugs of lipid lowering are statins. They are used to reduce cholesterol levels and the risk of cardiovascular events, but they have also been described as having beneficial effect on the new viral infection. In this effect, the statins beyond the well-known anti-inflammatory impact and increasing the expression of angiotensin-converting enzyme-2 further mechanisms can take part as well. These may include among others the promoted breakdown of lipid rafts, which directly inhibits the entry of coronavirus into the cell through the S protein by decreasing the level of cholesterol required for this proceeding. In a group of more than 1200 statin treated and SARS-COV-2 infected patients the overall mortality rate by the 28th day was 48% lower than among the non-statin-users. According to a meta-analysis of nearly nine thousand COVID-19-infected statin users, they had 30% lower mortality rate or serious complications. Up to date observational studies suggest that statin therapy and the administration of other lipid lowering drugs should be continued or initiated according to the guidelines also during the COVID-19 infection.]

Clinical Oncology

AUGUST 28, 2020

[The hormonal therapy of breast cancer]


[Breast cancer will be diagnosed in 12% of women in well-developed countries over the course of their lifetimes. This review focus on current approaches and strategies of systemic endocrine therapy of breast cancer. Breast cancer can be divided into three main subgroups based on the presence and absence of molecular markers (ER, PR, HER2 receptors). For patients without metastases the therapeutic goals are preventing the locoregional and distant recurrence. The length of adjuvant hormonal treatment is an important question in the everyday oncological practice. For patients with metastatic breast cancer the goal of the therapy is prolonging life, keep quality of life and palliating cancer symptoms. Patients with hormone receptor positive (HR+) tumours receive endocrine therapy, in monotherapy or in combination. As the result of new therapeutic approaches and of international drug development, HR+ breast cancer patients have more and more therapeutic options in case of early breast cancer as well as in metastatic settings.]

Journal of Nursing Theory and Practice

APRIL 30, 2020

[Survey of Medication Habits in Hypertensive Adults]

VARGA Bernadett, FUSZ Katalin, CSIMA Melinda, LUKÁCS-HORVÁTH Marianna, DEÁK András, STROMAJER-RÁCZ Tímea

[Hypertension is the best known risk factor in development of cardiovascular diseases and stroke. Survey has assessed –in hypertensive patients over 40, - the illness representation, lifestyle and medicine taking habits. Quantitative, cross-section descriptive research was conducted in 2017 with online questionnaire among hypertensive people over 40 (n=267) using shortened version of Brief Illness Perception Questionnaire, Morisky Medication Adherence Scale (8-item) and our questionnaire. Therapy adherence is typical for older individuals in surveyed population. (r= 0,26; p<0,001). Who were advised by general practitioners (GP) to implement lifestyle changes show more inclination following therapy. (p=0,032). Those with higher blood pressure (r-0,18; p=0,003) has harder time living with hypertension. (r=0,15; p=0,014). Quality of living with hypertonia and therapy adherence can be influenced by health behaviour and the information provided by general practitioners (GP). Beside the, general practitioners (GP) advanced practice nurse can have significant role in increasing the level of health behaviour and therapy adherence. ]

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.]