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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.]

Lege Artis Medicinae

NOVEMBER 15, 2019

[Neuropathic pain: spotligth on amitriptyline]

FEHÉR Gergely, POHL Marietta, KAPUS Krisztián, GOMBOS Katalin, PUSCH Gabriella, MÁK Kornél, KOLTAI Katalin, BANK Gyula, KÓSA Gábor, VARJASI Gábor, TIBOLD Antal

[The management of neuropathic pain is a challenge both for patients and medical professioners. A novel approach is recommended for its management based on the novel neurobiological results of pain research. Multidisciplinary teams and medical consensus are required due to the variety of symptoms and concomittant psychopathology. This approach allows us to avoid extensive diagnostic and trerapeutic workups and appropiate treatment for our patients. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). The aim of our review was to collect articles focusing on the efficacy of the most widely available and cheapest tricyclic agent, amitriptyline in different neuropathic pain conditions. ]

Lege Artis Medicinae

APRIL 18, 2020

[Interrelations between antidepressants and diabetes]

HARGITTAY Csenge, GONDA Xénia, MÁRKUS Bernadett, VÖRÖS Krisztián, TABÁK Gy. Ádám, KALABAY László, RIHMER Zoltán, TORZSA Péter

[Diabetes and depression are frequent comorbidities. They are a heavy burden by themselves, however, as comorbidities increase additionally the number of diabetes-related complications, morbidity, and mortality. In the background of interrelations, there are both well-known and hypothetical mechanisms. The aim of the present review is to outline these interrelations between antidepressants and diabetes and to discuss the effect of medications on carbohydrate metabolism respectively. Anti­depressant treatment on the one hand may improve mood, cognitive function and medication adherence leading to an improved glucose metabolism, on the other hand through their metabolic side effects, they may worsen carbohydrate metabolism. Concerning metabolic side effects, selec­tive serotonin reuptake inhibitors are the sa­fest, while tricyclic antidepressants and mo­noamine oxidase inhibitors should be administered under close monitoring. Se­rotonin and noradrenaline reuptake inhibitors may deteriorate gly­cae­mic control via increased noradre­nergic activation. Novel antidepressants, how­ever, have a neutral or positive impact on gly­caemic measures. Screening for and temporally adjusted treatment of depres­sion may decrease the risk of comorbidities ge­nerated complications. While caring for diabetic patients with depression, one should consider metabolic side effects of antidepressants and close monitoring of carbohydrate metabolism.]

Clinical Neuroscience

JANUARY 30, 2019

[Tension type headache and its treatment possibilities]

ERTSEY Csaba, MAGYAR Máté, GYÜRE Tamás, BALOGH Eszter, BOZSIK György

[Tension type headache, the most common type of primary headaches, affects approximately 80% of the population. Mainly because of its high prevalence, the socio-economic consequences of tension type headache are significant. The pain in tension type headache is usually bilateral, mild to moderate, is of a pressing or tightening quality, and is not accompanied by other symptoms. Patients with frequent or daily occurrence of tension type headache may experience significant distress because of the condition. The two main therapeutic avenues of tension type headache are acute and prophylactic treatment. Simple or combined analgesics are the mainstay of acute treatment. Prophylactic treatment is needed in case of attacks that are frequent and/or difficult to treat. The first drugs of choice as preventatives of tension type headache are tricyclic antidepressants, with a special focus on amitriptyline, the efficacy of which having been documented in multiple double-blind, placebo-controlled studies. Among other antidepressants, the efficacy of mirtazapine and venlafaxine has been documented. There is weaker evidence about the efficacy of gabapentine, topiramate, and tizanidin. Non-pharmacological prophylactic methods of tension type headache with a documented efficacy include certain types of psychotherapy and acupuncture. ]

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

[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

[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

FEBRUARY 20, 2019

[Practical use of meta-analyses in predicting disease risk, outcome, and therapy response in breast cancer]

KAHÁN Zsuzsanna, TARI Gergely, ENYEDI Márton, HARACSKA Lajos

[Germinal BRCA status infl uences patient care both in early and advanced/metastatic breast cancer. Ideally, the patient should make the decision on the type of surgery or the avoidance of radiotherapy being aware of the BRCA status; based on the most recent clinical studies, this knowledge may infl uence the type of chemotherapy in the neoadjuvant, adjuvant, or metastatic setting or may raise the use of emerging targeted therapies. DNA-targeting cytostatic agents, mostly platinum agents and PARP inhibitors that act by inducing synthetic lethality, provide specifi c therapies in BRCA-mutant cases. The optimum place and sequence of these specifi c agents in treatment, however, are not known yet. International guidelines promote BRCA testing for the specifi cation of treatment strategy in all HER2-negative advanced/metastatic breast cancer cases (NCCN) or at least in all cases when, based on certain predictors, the presence of mutations is likely (ESMO). Recently, the methods employed for BRCA testing have improved immensely and are widely available through the services of various providers. For the identifi cation of the mutation, sequencing of the whole genes is needed, which can be achieved faster and more cost-effi ciently using next-generation sequencing (NGS) platforms compared to previous methods. It is the responsibility of the physician to consider the possibility of BRCA mutations and to raise the issue of BRCA testing to the patient if the family history, the age, previous malignant disease(s) of the patient, or the cancer features are suggestive of genetic risk.]

Clinical Neuroscience

JANUARY 30, 2021

Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents

SANLI Arzu, OZTURK Musa, SOYSAL Aysun, DOVENTAS Yasemin, BASOGLU Fulya, GOZUBATIK-CELIK R. Gokcen, BAYBAS Sevim

Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

Clinical Oncology

APRIL 30, 2020

[Tumor induction by chemotherapy]

[Without chemotherapy, the fi ve-year survival rate of detected cancers would be between 0 and 15%, depending on the tumor, and between 17 and 85% with current therapy. Several warnings call attention to the dangers of chemotherapy-induced side effects, most notably the potential for tumor-inducing ability, which can affect 5-10% of patients who have recovered beyond fi ve years. Some systematically applied drugs used in chemotherapy (alkylating agents, etoposide, arsenic trioxide) are able to cause mutations in healthy cells of the patients, increasing the likelihood that the mutated cells will start a later (secondary) tumor formation. In addition to mutagenic effects, some chemotherapeutic agents exert their effects on normal myeloid and epithelial cells of the body, which, by altering the tissue microenvironment, create the potential for malignant transformation. Tumor-associated macrophages (TAMs), which can alter gene expression patterns by tumor cell secreted factors and promote the survival and invasiveness of tumor cells by pro-carcinogenic signals, are very important in this process. It is of utmost importance that doctors, pharmacists, technicians and nurses working with cancer-causing materials do not come into direct contact with dangerous substances and wear appropriate protective equipment.]