[MOLECULARLY TARGETED BIOLOGICAL THERAPY IN THE TREATMENT OF SOLID TUMOURS]
LÁNG István, HITRE Erika
JANUARY 22, 2008
Lege Artis Medicinae - 2008;18(01)
LÁNG István, HITRE Erika
JANUARY 22, 2008
Lege Artis Medicinae - 2008;18(01)
[In part one of this article we reviewed the modern biological oncotherapy of breast cancer and colorectal cancer. Now we report on the biological therapies that target various kinase inhibitor pathways by monoclonal antibodies or by oral kinase inhibitors in gastrointestinal stromal tumours, pancreatic cancer, head and neck cancer, lung cancer and kidney cancer. Cell surface receptors (e.g., epidermal growth factor receptor in head and neck cancer) and ligands necessary for the growth of metastases (e.g., vascular endothelial growth factor in kidney cancer) can be blocked by specifically developed monoclonal antibodies. Small molecular weight oral kinase inhibitors, e.g., imatinib and sunitinib in gastrointestinal stromal tumour, erlotinib in pancreatic cancer, erlotinib and gefitinib in lung cancer, sunitinib and sorafenib in kidney cancer, sorafenib in hepatocellular cancer block intracellular signal transduction pathways. The mTOR inhibitor temsirolimus can be used in advanced renal cell carcinoma.]
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[INTRODUCTION - The surrounding environment plays an important role in the development of psychosomatic symptoms. This study examines what children think of the consequences of not going outdoors for long periods. METHODS - Data were collected using the “draw-and-write” technique that besides the written answers allows children to express their thoughts in drawings. The questionnaire contained open-ended questions both on sociodemographic data and on the children’s notion of the relationship between environment and health or illness. Questionnaire submission was voluntary and anonymous. The study subjects were 9 to 11-year-old pupils (n=448, 44.6% boys, 55.4% girls) from six primary schools, two in Budapest, and one each in Pest, Jász-Nagykun-Szolnok, Csongrád and Békés counties. The primary schools were selected so as to represent various environmental locations, such as urban, town, suburban residential, area of blocks of flats. RESULTS - We found that all children agreed in that those who don't go outdoors for a long time will, in one way or another, get sick. Illnesses mentioned in the answers were classified in two categories, physical and mental. Physical health problems were further divided into four subcategories: symptoms (e.g., anaemia, pallor, fever, weak joints or bones); diseases; obesity; death. Mental health problems were divided into two subcategories: actual psychiatric diseases (e.g., depression) and symptoms, such as unhappiness, sadness, anger. CONCLUSIONS - We conclude that children in this study sample reckon the close connection between staying indoors for prolonged periods and the development of symptoms and disease.]
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.
Hypertension and nephrology
[This consensus document is intended to provide guidance for the effective and efficient treatment of asymptomatic individuals with high uric acid levels and gout patients.]
[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmelweis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]
Delirium is a syndrome frequently encountered in intensive care and associated with a poor prognosis. Intensive care delirium is mostly based on general and palliative intensive care data in the literature. In this study, we aimed to investigate the incidence of delirium in coronary intensive care unit (CICU), related factors, its relationship with inhospital and follow up prognosis, incidence of age-related delirium and its effect on outcomes. This study was conducted with patients hospitalized in CICU of a tertiary university hospital between 01 August 2017 and 01 August 2018. Files of all patients were examined in details, and demographic, clinic and laboratory parameters were recorded. Patients confirmed with psychiatry consultation were included in the groups of patients who developed delirium. Patients were divided into groups with and without delirium developed, and baseline features, inhospital and follow up prognoses were investigated. In addition, patients were divided into four groups as <65 years old, 65-75 yo, 75-84 yo and> 85 yo, and the incidence of delirium, related factors and prognoses were compared among these groups. A total of 1108 patients (mean age: 64.4 ± 13.9 years; 66% men) who were followed in the intensive care unit with variable indications were included in the study. Of all patients 11.1% developed delirium in the CICU. Patients who developed delirium were older, comorbidities were more frequent, and these patients showed increased inflammation findings, and significant increase in inhospital mortality compared to those who did not develop delirium (p<0.05). At median 9-month follow up period, rehospitalization, reinfarction, cognitive dysfunction, initiation of psychiatric therapy and mortality were significantly higher in the delirium group (p<0.05). When patients who developed delirium were divided into four groups by age and analyzed, incidence of delirium and mortality rate in delirium group were significantly increased by age (p<0.05). Development of delirium in coronary intensive care unit is associated with increased inhospital and follow up morbidity and mortality. Delirium is more commonly seen in geriatric patients and those with comorbidity, and is associated with a poorer prognosis. High-risk patients should be more carefully monitored for the risk of delirium.
Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still unclear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-year-old man with lack of generalised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature.
Clinical NeuroscienceAlexithymia is associated with cognitive impairment in patients with Parkinson’s disease
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