Clinical Oncology

[Pancreas cancer: Therapeutic trials in metastatic disease]

SMITHY W. James 1, O’REILLY M. Eileen 1

NOVEMBER 30, 2021

Clinical Oncology - 2021;8(4)

AFFILIATIONS

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA

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[New systemic treatment possibilities in non-small cell lung cancer]

OSTOROS Gyula, BOGOS Krisztina

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[Gastrointestinal cancers: role of biomarkers and based on driven treatment of gastrointestinal cancers]

PAJKOS Gábor

[Remarkable advancements in techniques of genomic profiling and bioinformatics have led to the precision medicine in oncology approach, targeted therapy and immune checkpoint inhibitors achieved radically change in treatment efficacy based on accumulation of knowledge on the genomic profiles of gastrointestinal tract cancer (GI). Advanced or disseminated poor risk GI cancer patients have had a better chance for that progression free and/or overall survival. Highly effective treatment needs to incorporate numerous molecular characteristic into clinics – expression of PD-L1, MSI (micro satellite instability)/dMMR (defective mismatch repair), TMB (tumor mutation burden), resistance mutation, insertions/deletions and other genomic alterations. This review aims to summarize predictive and prognostic biomarkers might suggested for precision oncology treatment of GI cancers.]

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[Microbiome and cancer]

MIKÓ Edit, BAI Péter

[Most compartments and organs of the human body are not sterile, bacterial DNA and RNA can be detected using next generation sequencing techniques. All bacterial DNA in a compartment is called the metagenome, all bacterial transcripts are termed metatranscriptome, while all bacterial species is coined the microbiome. The microbiome transforms in neoplastic diseases that is called the oncobiome. Most tumors are colonized by bacteria that supports tumor growth and development. Microbiome compartments distant to the tumors (as the microbiome of the gastrointestinal tract) can also undergo oncobiotic transformation. The metabolic capacity of the oncobiotic microbiome in the gastrointestinal tract is suppressed and the production of a large set of cytostatic and antimetastatic bacterial metabolites is blunted supporting cancer cells proliferation and metastasis. The microbiome of the gastrointestinal tract has pivotal role in setting the tolerance of the immune system against cancer cells, therefore, has prime importance in tumor immunity. Oncobiosis, by itself, cannot induce tumors, but can support tumor growth and metastasis formation. Bacteria have key role in the success of cytostatic therapy and in setting the side effect profile.]

Clinical Oncology

[Mechanisms of metastasis formation as potential therapeutic targets]

TÍMÁR József, SEBESTYÉN Anna, KOPPER László

[The end-stage of the tumor progression is the development of the metastatic disease. The biological basis of this progression is well known, however the exact molecular background of it is not. In this process the metastatic cancer cells develop maximal adaptation to extreme environmental clues and collaborative potential with wide array of host cells, accordingly the metastatization takes place in an organ specific manner. The metastases are different from the primary tumor but from each other as well, and this true for their genetic background as well. The ultrasensitive monitoring of this process is possible with the use of liquid biopsy and molecular tests. Till we don’t have organ metastasis specific therapeutic modalities similarly to bone metastases, the available modalities must be fine-tuned for metastatic disease and not for the primary tumor. ]

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[The concept and use of placebo and nocebo in oncology]

VÉGH Éva, BAKI Márta

[Placebo and nocebo effects recognised through all of the history of medicine, and these effects can be found also in the field of oncology research and clinical practice. Placebo effect are more than the effects of an inert substance. Placebo benefits the health status because of the person’s belief and nocebo worsens the health status of the patient. Several psychological mechanisms are involved in placebo/nocebo effects; expectation, learning processes (classical conditioning and observational learning), reinforced expectations, personality traits of the patient and the health care provider. At the same time placebo effects rely on neurobiologic mechanism (neurotransmitters like dopamine, cholecystokinin, opioids and activation of specific brain areas). The use of placebo is an important methodological tool in oncological research and drug development. Inert substance can be associated with positive (placebo) and negative (nocebo) adverse event profiles also can modify the measured therapeutic effects in randomized clinical trials.]

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

NÉMETH Klára Zsófia, SZÛCS Anna , VITRAI József , JUHÁSZ Dóra , NÉMETH Pál János , HOLLÓ András

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.

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.

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Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

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[Diagnosis and treatment of microvascular coronary heart disease. Specialities of conditions in Hungary]

SZAUDER Ipoly

[Invasive investigations show that in two-thirds of patients the myocardial ischaemia persists without obstructive coronary disease and any other heart conditions (INOCA). The underlying cause may be microvascular dysfunction (CMD) with consecutive microvascular coronary disease (MVD) and microvascular or epicardial vasospastic angina (MVA). The modern practice of clinical cardiology while using the developed non-invasive cardiac imaging permits exact measuring of the coronary flow with its characteristic indices. All of these improve the diagnosing of CMD-induced myocardial ischemia and provide opportunity to determine primary MVD cases. Since the recognition and treatment of MVD is significantly underrep­resented in the Hungarian medical care, the primary stable microvascular angina (MVA) is described in detail below with its modern invasive and non-invasive differential diagnosis and treatment, concerning especially its frequency provoked by high blood pressure and female coronary heart diseases. There are highlighted all recommended diagnostic procedures available under domestic conditions.]

Clinical Neuroscience

Atypical presentation of late-onset Sandhoff disease: a case report

SALAMON András , SZPISJAK László , ZÁDORI Dénes, LÉNÁRT István, MARÓTI Zoltán, KALMÁR Tibor , BRIERLEY M. H. Charlotte, DEEGAN B. Patrick , KLIVÉNYI Péter

Sandhoff disease is a rare type of hereditary (autosomal recessive) GM2-gangliosidosis, which is caused by mutation of the HEXB gene. Disruption of the β subunit of the hexosaminidase (Hex) enzyme affects the function of both the Hex-A and Hex-B isoforms. The severity and the age of onset of the disease (infantile or classic; juvenile; adult) depends on the residual activity of the enzyme. The late-onset form is characterized by diverse symptomatology, comprising motor neuron disease, ataxia, tremor, dystonia, psychiatric symptoms and neuropathy. A 36-year-old female patient has been presenting progressive, symmetrical lower limb weakness for 9 years. Detailed neurological examination revealed mild symmetrical weakness in the hip flexors without the involvement of other muscle groups. The patellar reflex was decreased on both sides. Laboratory tests showed no relevant alteration and routine electroencephalography and brain MRI were normal. Nerve conduction studies and electromyography revealed alterations corresponding to sensory neuropathy. Muscle biopsy demonstrated signs of mild neurogenic lesion. Her younger brother (32-year-old) was observed with similar symptoms. Detailed genetic study detected a known pathogenic missense mutation and a 15,088 base pair long known pathogenic deletion in the HEXB gene (NM_000521.4:c.1417G>A; NM_000521:c.-376-5836_669+1473del; double heterozygous state). Segregation analysis and hexosaminidase enzyme assay of the family further confirmed the diagnosis of late-onset Sandhoff disease. The purpose of this case report is to draw attention to the significance of late-onset Sandhoff disease amongst disorders presenting with proximal predominant symmetric lower limb muscle weakness in adulthood.