Clinical Oncology

[Cardiovascular Side Effects of Anti-Cancer Therapies]

LANDHERR László1, NAGY András Csaba2, NAGYKÁLNAI Tamás3

DECEMBER 05, 2014

Clinical Oncology - 2014;1(04)


  1. Uzsoki utcai Kórház, Budapest, Onkoradiológiai Központ
  2. Uzsoki utcai Kórház, Budapest, I. Belgyógyászat-Kardiológia
  3. Budapest, XV. ker. Szakrendelő, Onkológia, Budapest



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[Current management of GIST]


[Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs are generally resistant to chemotherapy and radiotherapy. The understanding of pathology at molecular level promised the development of novel treatment modalities. KIT and PDGFRA gene mutations play an important role in the pathogenesis of GIST. IMutational analysis should be considered as standard practice during the diagnostic work-up, since it has a predictive value for sensitivity to molecular-targeted therapy and also has prognostic value. The aim of this review is to summarize recent knowledge about diagnosis, treatment and follow up of GIST.]

Clinical Oncology

[Bone metastases - Current treatment strategy]

BOÉR Katalin, NÉMETH Zsuzsanna

[Bone is the most common site of metastatic disease in many solid tumours, mainly in breast, prostate and lung cancer. Patients with bone metastases are at risk for skeletal-related events such as bone pain, pathological fractures requiring surgery and/or radiation to bone lesions, hypercalcemia, and spinal cord compression. Skeletal-related events are major source of morbidity for cancer patients and may be associated with negative impact on quality of life and survival. Bisphosphonates inhibit osteoclast function and are widely used in the treatment of malignant bone disease, as preventive therapy against skeletal-related events. Recently, the NF-κappa B-ligand (RANKL)-mediated osteoclast activity and this pathway in bone metabolism became a prime target for the treatment of bone metastases. The fi rst drug targeting the RANK-RANKL pathway is denosumab, a fully monoclonal human antibody which binds to RANKL and inhibits osteoclast activity. Nowadays optimal treatment of bone metastases requires multidisciplinary management of patients including the administration of bone-modifying agents such bisphosphonates or denosumab. The use of bone-targeted agents is a valuable additional treatment in the fi ght against bone metastases and multiple, randomised trials have demonstrated the effectivity of these drugs in reducing skeletal morbidity caused by advanced cancer.]

Clinical Oncology

[Immuno(onco)therapy – road to the future]

DANK Magdolna, SZENTMÁRTONI Gyöngyvér, OROSZ Zsuzsanna, TÓTH Andrea, TŐKÉS Tímea

[Our immune system fi ghts effectively against infections, but the same activity exists against invading cancer cells, as well. However, malignant tumors are able to escape from these mechanisms; therefore tumor cells become unrecognizable for the immune system. Immuno-oncology is a novel and innovative discipline, focusing on a long-term purpose: to enhance the immune-response against malignancies. The main goal is to stimulate the immune system to properly recognize and destroy malignant tumor cells. This approach is comprehensive, includes the initiation of antitumor immune-response and enhancing its controlling mechanisms, moreover, provides active, anti-tumor effector cells. Recent results of anticancer research highlighted a new era of oncology, which is based on targeted, personalized medicine over cytotoxic therapies, and mainly focusing on the rapidly evolving discipline of immuno-oncology.]

Clinical Oncology

[Tyrosine-kinase inhibitors and bisphosphonates in the treatment of metastases from renal cell carcinoma]

EDUARD Vrdoljak, TOMISLAV Omrčen

[Bone metastases (BMs) are common in patients with renal cell carcinoma (RCC) and approximately in 30% of patients with metastatic RCC (mRCC) will develop. Inhibition of vascular endothelial growth factor (VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear cell RCC (mRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and axitinib, became the therapy of choice for patients with mRCC. Apart from the undisputed effi cacy of TKI in treatment of mRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of BMs in m-RCC patients has a signifi cant and clinically-relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, common practice in the treatment of such patients is bonedirected therapy with BPs. Recent evidence shows a potentially synergistic effect on effi cacy but also a potential impact on increased toxicity of combining TKIs and BPs. This review highlights the importance of this subject and aims to facilitate further research and optimize the treatment of this important and common group of RCC patients.]

Clinical Oncology

[Clinical role of multigenic prognostic tests in breast cancer therapy]


[Current clinical practice for breast cancer originates in “evidence based medicine”. In this, each tumor receives a therapy optimal for a given patient population - which might not be optimal for each individual patient. Multigenic tests determining expression of a set of genes can provide additional support in this decision process. Two such tests (MammaPrint and Prosigna) have already received FDA clearance. A number of additional test are commercially available (IHC4, Oncotype DX, EndoPredict, BCI). A common property of these assays is their utility in estrogen receptor positive early breast cancer. The main clinical problem answered by them is the necessity of adjuvant chemotherapy. To date, no reliable algorithm has been identifi ed capable to pinpoint the most effective chemotherapy combination for a given patient. Furthermore, there is no trustworthy test for triple negative breast cancer. The assays utilize different technologies (immunohistochemistry, gene chips, RT-PCR) and a discrepant list of genes - these result in discordance of the predictions for the individual patient. Despite these shortcomings, multigenic tests quickly gained foothold in breast cancer therapy decision process. Their utility is supported by the cost reduction for the health care providers by lowering the number of patients eligible for chemotherapy.]

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Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Electrophysiological investigation for autonomic dysfunction in patients with myasthenia gravis: A prospective study


Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.

Clinical Neuroscience

Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study

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We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients. This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine. Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05–1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27–3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16–0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding. Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

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[The rapidly spreading SARS-CoV2 respiratory virus has evoked an epidemic with serious aftermath around the world. In addition to the health effects, the global economic damage is actually unpredictable. At the same time, the pandemic has launched a series of unprecedented collaborative scientific research, including the development of vaccines. This study summarizes up-to-date information on vaccines, immune memory, and some emerging clinical effects.]

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[Risk of nonsteroidal antiinflammatory drugs. Focus on aceclofenac]


[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]