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Subspecialist training program in pediatric otorhinolaryngology of UEMS ORL-HNS section
The ORL Section and Board of Otorhinolaryngology-Head and Neck Surgery of the European Union of Medical Specialists (UEMS) developed pediatric ORL subspecialty program. The program was created with support and consultation of the European Society of Pediatric Otorhinolaryngology. It is divided into four sections: Pediatric Otology, Pediatric Rhinology and Facial Plastic Surgery, Pediatric Laryngology and Phoniatrics and Pediatric Head and Neck Surgery. After completion of the program, the trainee is supposed to achieve an advanced level of competency. The aim of the program is to serve as a guideline for training centers, enabling them to meet the European Standard as set out by the European Board of UEMS through competency based assessments
Autofagija i metaboličke promjene u diferencijaciji staničnih linija akutne mijeloične leukemije [Autography and metabolic changes in differentiation of acute myeloid leukemia cell lines]
Pharmacological modulators of metabolism and AMP-dependent kinase (AMPK) inhibit proliferation of tumor cells. Our previous study demonstrated that 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), a compound commonly used as an AMPK-modulator, induced AMPK-independent differentiation of U937 cells. Autophagy has been described as an AMPK-independent effect of AICAR in other cells. Therefore, the aim of this study was to determine the role of autophagy and metabolism in differentiation of U937 cells. The results showed that AICAR-mediated effects were not mimicked by specific AMPK agonist and that AICAR had no significant effects on aerobic glycolysis. Long-term incubation of U937 cells with AICAR and other differentiation agents, all-trans-retinoic acid (ATRA) and phorbol 12-myristate 13-acetate, increased the expression of the autophagy marker LC3B-II. These effects were not observed in response to metformin, an AMPK agonist without differentiative properties. The increase in LC3B-II was due to the increase in autophagy flux and the autophagy inhibitor 3-methyladenine inhibited differentiation in response to all inducers. The effects of AICAR and ATRA on differentiation markers did not depend on Beclin-1, hVps34 and Atg7. These results show that AICAR and other differentiation agents induce autophagy flux in U937 cells and that differentiation does not depend on the classical or canonical autophagy pathway
Elastografske vrijednosti tkiva dojke u žena [Elastographic values of breast tissue in women]
Introduction: Breast elastography is a new ultrasound method for easier BIRADS categorization of the suspect lesions. Aim of this study is to estimate the elasticity of normal breast tissue and to compare it to the estimated mammographic and ultrasound breast density, also to correlate it with some well-known breast cancer risk factors and factors that influence on mammographic density.
Materials and methods: A prospective study with 200 women of different age was performed. All women fulfilled questionary about personal, familiar and reproductive history. A hundred women that had attached mammographic images were placed in one of four groups according to estimated mammographic density. The next step was an ultrasound examination with B-mod and elastography. One of three groups according to ultrasound density was assigned to all women. Elasticity of breast parenchyma and fatty tissue in all breast quadrants was measured. Average elastographic values of breast tissue were calculated and compared to estimated mammographic and ultrasound density, also to personal history factors.
Results: Elasticity of normal breast parenchyma (66,4 kPa) was higher than fatty tissue (26,1 kPa) in all breast quadrants and in both breasts. Lower outer quadrant of breasts had the lowest elasticity values of both parenchyma and fat. A left breast had higher elasticity values of breast tissue, comparing to a right breast. Glandular elasticity positively correlates with mastalgia and number of benign breast lesions. It negatively correlates with age, number of pregnancies and body mass index (BMI). Fat tissue elasticity negatively correlates with age and BMI. Glandular and fat tissue elasticity positively correlates with mammographic and ultrasound estimated breast density.
Conclusions: There is good correlation between breast elasticity and breast density. It means that the women could be classified in one of the groups with lower or higher breast cancer risk without ionizing radiation, also with the method which is fast and cheap. This study could contribute to widen indications for elastography in routine clinical practice
Praćenje onkoloških bolesnika – kliničke preporuke Hrvatskog društva za internističku onkologiju HLZ-a IV. Dio: planocelularni rak glave i vrata, rak jednjaka, rak želuca, rak debelog i završnog crijeva [Cancer patients follow-up – Croatian society for medical oncology clinicalguidelines Part IV: planoceular head and neck cancer, oesophageal cancer, gastric cancer, colorectal cancer]
Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert’s opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures’ algorithm in follow–up of oncological patients after primary treatment, in patients with planocellular head and neck cancer, oesophageal cancer, gastric cancer and colorectal cancer
Smjernice za genetičko savjetovanje i testiranje na nasljedni rak dojke i jajnika [Guidelines for genetic counselling and testing for hereditary breast and ovarian cancer]
The last few decades have witnessed a great progress in feasibility and clinical utilization of genetic testing for hereditary cancers. Hereditary breast and ovarian cancers are most often the result of BRCA1 and BRCA2 gene mutations. In these guidelines we have covered: the criteria for referral of patients to genetic counselling and testing; the criteria for referral of healthy family members to predictive testing in the event when there is no possibility of testing the patient; the process of genetic counselling before and after testing; test results, their categories and risk levels; recommendations for monitoring of individuals with an increased risk; chemoprevention and prophylactic surgery for carriers of BRCA1 and BRCA2 gene mutations; preservation of reproductive function in women with breast cancer and in carriers of BRCA mutations; and informed consent for genetic testing. The guidelines are intended for all specialists who are in any way involved in the care of patients with hereditary breast and ovarian cancer, and are compiled by the working group according to the data from the relevant medical literature and from clinical experience of the members of the working group
Diameters and bone thickness at the margin of the foramen magnum in dry skulls from pediatric population: a cross-sectional anatomical study
PURPOSE:
The purpose of the study was to estimate the size and bone thickness at the margin of the foramen magnum in a pediatric population. -----
METHODS:
Sixty occipital bone specimens from the collection of macerated skulls at the Department of Anatomy, University of Zagreb, were examined and measured using a vernier scale/caliper. For the purpose of analysis, specimens were divided into two age groups: 1-6 years and 7-18 years of age (before and after the fusion of ossification centers in the occipital bone). We measured the following: antero-posterior and transverse diameters of the foramen magnum, bone thicknesses at the basion, opisthion, two paramedial points on the anterior and posterior margins, and at the occipito-squamous junction. -----
RESULTS:
Data presented in this study show that diameters of the foramen magnum increase with age, whereas bone thickness shows variable behavior depending on the measured area. -----
CONCLUSIONS:
Increases in diameters in specimens from the younger age group and their absence in specimens from older subjects reflect the growth pattern of the basilar part of occipital bone. Variability of bone thickness at the margin of the foramen magnum and lack of its association with age of the subjects may be attributed to various factors and may potentially affect the clinical presentation of compression syndromes at the level of foramen magnum
Lack of CD4+ T cell percent decrease in alemtuzumab-treated multiple sclerosis patients with persistent relapses
Alemtuzumab, a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), induces lymphopenia especially of CD4+ T cells. Here, we report the atypical CD4+ T population behaviour of two patients with persistent disease activity despite repeated alemtuzumab treatments. Whereas lymphocytes count decreased and fluctuated accordingly to alemtuzumab administration, their CD4+ cell percentage was not or just mildly affected and was slightly below the lowest normal limit already before alemtuzumab. These cases anticipate further studies aimed to investigate whether the evaluation of the CD4+ cell percentage could represent a helpful tool to address the individual clinical response to alemtuzumab
Klinički značaj izraženosti gena BORIS i MYC u karcinomu pločastih stanica hipofarinksa [Clinical significance of BORIS and MYC expression in hypopharyngeal squamous cell carcinoma]
Hypopharyngeal squamous cell carcinoma belongs to malignant
diseases with dismal prognosis. The most prominent risk factors for this type of
cancer are known to cause global DNA hypomethylation and activate cancer-related
genes. BORIS is often aberrantly activated in cancer and is involved in activation of
MYC transcription.
The expression of BORIS and MYC was investigated in retrospective
study of 59 hypopharyngeal carcinoma samples. BORIS and MYC expression was
analyzed regarding to conventional prognostic factors: tumor size, lymph node
involvement and the degree of tumor differentiation. The influence of BORIS and
MYC expression on five-year survival rate was analyzed.
Two detected BORIS transcript variants, BORISd and BORISk, were
expressed in 33.9% and 76.3% of tumor analyzed tumors. The expression of both
BORIS transcript variants significantly influenced the five-year survival rate (BORISd,
p=0,001; BORISk, p=0,011). BORIS protein was detected in 42.4% of tumor samples
and its expression had no impact on patients survival rate. The expression of MYC,
regardless of its subcellular localization had no influence on patients survival.
Multivariate analysis by recursive partitioning profiled BORISd expression as most
powerful prognostic factor in this type of cancer
Immunoglobulin G glycosylation in patients with colorectal cancer
INTRODUCTION: Colorectal cancer (CRC) is a malignant neoplasm of the colon and the rectum. CRC is still associated with poor prognosis, low survival rate and usually relatively late diagnosis.
MATERIALS AND METHODS: We analysed IgG glycome composition in 1229 patients with CRC and 538 matching controls. Effects of surgery were evaluated in 28 patients sampled before and three times after surgery. Furthermore, IgG glycome composition was analysed in 39 plasma samples collected before initial diagnosis of CRC.
RESULTS: Clinical algorithms showed good prediction of all cause and CRC mortality. The inclusion of IgG glycan data in regression models did not lead to any statistically significant improvements in overall prediction of survival (Harrell’s C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). However, the inclusion of IgG glycan data substantially improved the prediction of rapid progressors over clinical models in AJCC stage 4 patients (AUC 0.53 vs. 0.75, IDI 0.21). When analysing clinical characteristics among 760 patients and 538 matching controls it was found that CRC associates with decrease in IgG galactosylation, IgG sialylation and increase in core-fucosylation of neutral glycans with concurrent decrease of core fucosylation of sialylated glycans.
COCLUSION: The glycan differences among CRC patients are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. Considering the functional relevance of IgG glycosylation for both tumor immunosurveilance and clinical efficacy of therapy with monoclonal antibodies, individual variation in IgG glycosylation may turn out to be important for prediction of disease course or the choice of therapy
Ekspresija i prognostička vrijednost imunohistokemijskih biljega matičnih stanica raka u bolesnika s melanomom srednje očne ovojnice [Expression and prognostic value of cancer stem cell markers in patients with uveal melanoma]
Uveal melanoma is a rare ocular malignancy with intrinsic resistance to conventional systemic chemoterapy. This study investigated paraffin embedded samples of 31 patient with primary choroidal and ciliary body melanoma in order to determine the presence of tumor cells that express putative cancer stem cell markers CD133, CD117 (c-kit), CD34, CD20 and CD15 and their possible impact on survival.
Immunohistochemical expression of CD133 was observed in 16 of 22 samples with AEC chromogen. CD117 expression was observed in 12 of the 31 samples when AEC chromogen was used and in 14 of 26 samples when DAB was used. CD15 positivity was seen in 3 out of 30 samples with AEC and in 6 out of 26 samples with DAB. CD20 and CD34 exhibited no positivity in the tested samples.
During the average follow-up time of 8.7 years, more than half of the patients died due to metastatic disease. The Kaplan-Meier plots showed a significantly shorter overall and disease-free survival in CD117-positive patients when AEC chromogen was used. CD133 and CD15 expression had no impact on patients’ survival. In multivariate analysis, patients expressing CD117 AEC had 4 times higher risk of lethal outcome in comparison with CD117 AEC negative patients