Expression of Selected miRNAs in Undifferentiated Carcinoma with Osteoclast-like Giant Cells (UCOGC) of the Pancreas: Comparison with Poorly Differentiated Pancreatic Ductal Adenocarcinoma.

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal adenocarcinoma is particularly challenging, with limited prospects for cure. As with many other malignant neoplasms, the exploration of microRNAs (miRNAs, miRs) in regulating the biological characteristics of pancreatic cancer is undergoing extensive investigation to enhance tumor diagnostics and unveil the therapeutic possibilities. Herein, we evaluated the expression of miR-21, -96, -148a, -155, -196a, -210, and -217 in UCOGCs and poorly differentiated (grade 3, G3) PDACs. The expression of miR-21, miR-155, and miR-210 in both UCOGCs and G3 PDACs was significantly upregulated compared to the levels in normal tissue, while the levels of miR-148a and miR-217 were downregulated. We did not find any significant differences between cancerous and normal tissues for the expression of miR-96 and miR-196a in G3 PDACs, whereas miR-196a was slightly, but significantly, downregulated in UCOGCs. On the other hand, we have not observed significant differences in the expression of the majority of miRNAs between UCOGC and G3 PDAC, with the exception of miR-155. UCOGC samples demonstrated lower mean levels of miR-155 in comparison with those in G3 PDACs.

The Efficacy of Fibrin Sealant in Sutureless Deep Sclerectomy - Preliminary Outcomes.

PRCIS: Deep sclerectomy with fibrin adhesive can constitute a safe alternative to the classic procedure using sutures, providing non-allergenic, non-toxic and secure adhesion with no sign of aqueous humor outflow obstruction postoperatively. PURPOSE: To evaluate short- and medium-term postoperative results of deep sclerectomy (DS) with a fibrin sealant. PATIENTS AND METHODS: This prospective, noncomparative, interventional case-series involves 12 eyes of 12 patients with uncontrolled open-angle glaucoma (OAG) who underwent DS with Esnoper (Clip or V2000) implant between February 2021 and March 2022. A novel method of wound closure (sclera, Tenon´s fascia and conjunctiva) employing fibrin glue was used instead of classic sutures. Surgical outcomes assessed include: intraocular pressure (IOP) and glaucoma therapy (GT) reduction, best-corrected visual acuity (BCVA) changes and number of complications registered peri- and postoperatively. All measurements were performed preoperatively, as well as at 1 day, at 1 and 2 weeks, and at 1, 2, 3, 6, 9 and 12 months after surgery. RESULTS: The mean IOP decreased from 24.0±9.1 mmHg to 13.8±6.3 mmHg at one year postoperatively (P<0.001). Kaplan-Meier survival analysis revealed complete and qualified success rates of 83.3% and 91.7%. The mean GT decreased from 3.2±1.1 to 0.8±1.3 drugs 12 months after surgery (P<0.001). Nd:YAG goniopunture was performed in 2 eyes at 1 and 12 months postoperatively. No significant BCVA changes were registered. Perioperatively, we noted a trabeculo-descemet microperforation in one eye, transient hypotony in 5 eyes and mild hyphema in 2 eyes. CONCLUSIONS: Fibrin adhesive provided an effective closure in sutureless DS in the patients included in our study. This modification of classical DS may simplify the surgical technique, ensure secure wound adaptation, optimize healing, and lower the risk of inflammation and fibrosis postoperatively.

Objective Evaluation of Chronic Low-Back Pain Using Serum Lipids: The Role of the Doctor-Patient Relationship.

Statistical data show that pain intensity in patients with low back pain is associated with a higher BMI, total serum cholesterol, and triacylglycerol levels. The objective of our study was to evaluate how these associations are dependent on the nature of the patient-doctor relationship. Eighty-nine patients hospitalized with chronic low-back pain (50 women, 39 men; average age: 64.5 ± 12.7 years) were assessed over a 3-year period. A serum lipid analysis was conducted (LDL-C, HDL-C, and total cholesterols) at admission in parallel with a subjective evaluation of pain intensity, which was assessed using a numeric rating scale. The participating physician assigned, based on their personal interaction with the patient, an attribute of affinity (positive, neutral, and negative) towards them. Current serum lipid levels and pain intensity were correlated relative to these attributes. Pain intensity did not differ between the groups assigned positive or negative attributes of affinity. In patients belonging to the "positive" group, pain intensity correlated positively with total cholesterol (p=0.01) and LDL cholesterol (p=0.007). No correlations were found in the "negative" group or when the patient-doctor relationship was ignored. We found a significant association between subjectively assessed low back pain intensity and serum levels of total and LDL cholesterol in patients with whom the physician had a positive affinity. A positive affinity with the patients having chronic pain and the patient's trust in their physicians may ultimately mean that the patient's statement about pain is more credible, which may retroactively affect the outcome of therapy.

Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma.

Therapy for pancreatic ductal adenocarcinoma remains challenging, and the chances of a complete cure are very limited. As in other types of cancer, the expression and role of miRNAs in controlling the biological properties of this type of tumor have been extensively studied. A better insight into miRNA biology seems critical to refining diagnostics and improving their therapeutic potential. In this study, we focused on the expression of miR-21, -96, -196a, -210, and -217 in normal fibroblasts, cancer-associated fibroblasts prepared from a ductal adenocarcinoma of the pancreas, and pancreatic carcinoma cell lines. We compared these data with miRNAs in homogenates of paraffin-embedded sections from normal pancreatic tissues. In cancer-associated fibroblasts and cancer cell lines, miRNAs differed significantly from the normal tissue. In detail, miR-21 and -210 were significantly upregulated, while miR-217 was downregulated. Similar transcription profiles were earlier reported in cancer-associated fibroblasts exposed to hypoxia. However, the cells in our study were cultured under normoxic conditions. We also noted a relation to IL-6 production. In conclusion, cultured cancer-associated fibroblasts and carcinoma cells reflect miR-21 and -210 expression similarly to the cancer tissue samples harvested from the patients.

Effect of neurofeedback therapy on neurological post-COVID-19 complications (A pilot study).

OBJECTIVE: Anxiety, fatigue and depression are common neurological manifestations after COVID-19. So far, post-COVID complications were treated by rehabilitation, oxygen therapy and immunotherapy. Effects of neurofeedback on post-COVID complications and their potential interrelatedness have not been studied yet. In this pilot study, we investigated the effectiveness of neurofeedback (Othmer method) for treatment of fatigue, anxiety, and depression after COVID-19. METHODS: 10 participants met inclusion criteria for having positive anamnesis of at least one of the following complications following COVID-19: fatigue, anxiety, and depression which were measured by questionnaires. ANOVA was used for calculating differences in questionnaire score before and after neurofeedback. Pearson's correlation coefficient was used to calculate correlations between anxiety, depression and fatigue. RESULTS: After five neurofeedback sessions, there came to significant reduction of severity of post-COVID anxiety and depression persisting for at least one month. Effect of neurofeedback on fatigue was insignificant. Severity of anxiety, fatigue and depression as well as reductions in depression and fatigue were positively correlated with each other. CONCLUSION: These findings showed effectiveness neurofeedback for reducing anxiety and depression after COVID-19 and for studying correlations between neurological complications after COVID-19. However, since our pilot clinical trial was open-label, it is hard to differentiate between neurofeedback-specific and unspecific effects on our participants. Future randomized controlled trials with more robust sample are necessary to investigate feasibility of neurofeedback for post-COVID neurological complications. The study has identification number trial ID ISRCTN49037874 in ISRCTN register of clinical trials (Retrospectively registered).

The size and shape of the human pelvis: a comparative study of modern and medieval age populations.

INTRODUCTION: Great variability in shape and size of the bony pelvis can be observed in the current population, but there is not enough data on how long the historical period must elapse to gain changes in pelvic shape and size. The aim of the study was to identify morphological changes in bony pelvis in males and females after a developmentally short period of approximately one thousand years. MATERIAL AND METHODS: Seventeen defined external dimensions of pelvic bone from 120 adult individuals (two craniocaudal, two ventrodorsal, six mediolateral, three acetabular dimensions, and four dimension of the auricular surface) were measured. The medieval sample of 60 pelvic bones (30 male and 30 female) was obtained from the Great Moravian site of Mikulcice-Valy (9th-10th century), while the modern collection of 60 pelvic bones (30 male and 30 female) dates from the late 19th and first half of the 20th centuries. Obtained results were evaluated using the independent t-test at a 5% level of significance. RESULTS: A comparison of male and female pelvic dimensions within a single population yielded expected results: the mean male values were greater. In modern population, male pelvis mean values were greater in 15 of defined parameters, while in medieval population, male dimensions were larger in 16 variables. A comparison of modern and medieval female pelvic bones found 11 variables to be greater in medieval sample (one determining the craniocaudal dimension, five the mediolateral, all three the acetabular, and two determining the auricular surface dimensions), but only two were significant (two dimensions determining the mediolateral dimensions). In modern female samples, there were five variables greater (one determining the craniocaudal dimension, one the ventrodorsal, one the mediolateral, and two determining the auricular surface dimensions), but only two were significant as well (one determining the craniocaudal and one the ventrodorsal dimensions). A comparison of male pelvic bones found 13 variables to be greater in medieval pelvis (one determining the craniocaudal dimension, all six the mediolateral, one the ventrodorsal, all three the acetabular, and two determining the auricular surface dimensions), but only four were significant as well (all determining the mediolateral dimensions). In modern male sample, there were only four variables greater (one determining the craniocaudal dimension, one the ventrodorsal, and two determining the auricular surface dimensions), but only one was significant (determining the craniocaudal dimension). CONCLUSION: Unexpectedly, our study did not find the early medieval population to have a smaller pelvis compared to the modern population. While pelvic bones of the former were somewhat lower, but wider, those of the latter population were a bit higher and narrower. The study allows a very careful statement that one millennium is a time period long enough for measurable morphological deviations of the pelvic bones shape and size to occur.

Importance of breath tests for the evaluation liver function in patients with chronic kidney disease.

Breath tests for the evaluation liver metabolic function are a non-invasive diagnostic method with high sensitivity and specificity. Up today, the issue of liver damage in patients with chronic kidney disease has not been investigated sufficiently, although it might have significant clinical consequences. The following article describes the principles of breath tests, experiences with breath tests in patients with chronic kidney disease (CKD) and the results of our pilot study with methacetin breath tests in patients with CKD and in regular peritoneal dialysis treatment.

Vascular supply of the anterior interventricular epicardial nerves and ventricular Purkinje fibers in the porcine hearts.

The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well-developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves.

Role of biomarkers of cardiac remodeling, myofibrosis, and inflammation in assessment of disease severity in euvolemic patients with chronic stable heart failure.

OBJECTIVE: This study aimed to determine the importance of biomarkers of chronic heart failure (CHF) for assessing disease severity in euvolemic stable patients. PATIENTS AND METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, galectin-3, cystatin-C, soluble suppression of tumorigenicity 2 (sST2), tissue type inhibitor of matrix metalloproteinase (TIMP)-1, and ceruloplasmin levels were measured in euvolemic patients with stable CHF. Severity of CHF was defined by echocardiographic and biochemical parameters. RESULTS: In 160 patients (123 men and 37 women, mean age: 65.8±12.2 years), we found strong associations between NT-proBNP and bilirubin levels (r = 0.434) and the estimated glomerular filtration rate (r = -0.321). GDF-15 and cystatin-C levels were significantly correlated with parameters of kidney function. In multivariable regression analysis, NT-proBNP levels were associated with the left ventricular ejection fraction and left ventricular end-systolic volume (coefficient of determination R2 = 0.777). Additionally, GDF-15 levels were correlated with urea levels (R2 = 0.742), and cystatin C levels were correlated with urea and bilirubin levels (R2 = 0.732). CONCLUSION: Besides NT-proBNP, GDF-15 and cystatin C are promising biomarkers for establishing the severity of disease in euvolemic patients with stable CHF.

25-gauge vitrectomy and gas for the management of rhegmatogenous retinal detachment.

AIMS: To evaluate the anatomical and functional results in patients with rhegmatogenous retinal detachment (RRD) who underwent 25-gauge pars plana vitrectomy (PPV) with gas tamponade. MATERIALS AND METHODS: A retrospective evaluation of 126 eyes of 126 patients (79 men, 47 women) with RRD who underwent 25-gauge PPV with gas tamponade (13% C3F8 in 87 eyes, 20% SF6 in 39 eyes). 113 patients (89.7%), were operated on under local anaesthesia, 13 patients (10.3%) under general anaesthesia. Macula was detached in 85 eyes (67.5%). 53 eyes had pseudophakic RRD, 73 eyes were phakic. Anatomical success of the primary intervention, change in best corrected visual acuity (BCVA) and incidence of complications were assessed. An average follow-up period is 7.2 months (6-15). RESULTS: With single operation, retinal attachment was achieved in 125 eyes (99.2%); the final anatomical success was 100%. The initial mean BCVA was 0.89 logMar (2.00 to 0.00); at the end of the follow-up period, it improved to 0.23logMAR (1.00 to -0.10), P < 0,0001. During the first post-intervention day, hypotony of the eye below 10 mmHg was observed in 1 patient (0.8%); on the contrary, intraocular pressure was temporarily increased to 25 mmHg and more in 36 patients (28.6%). CONCLUSION: The surgical treatment of RRD using 25-gauge PPV with expansive gas tamponade renders excellent anatomical results and improvement in BCVA. The incidence of complications and necessity of sclerotomy suturing are low.

Deep Sclerectomy with Nonabsorbable Implant (T-Flux) in Patients with Pseudoexfoliation Glaucoma.

Purpose. To evaluate the effectiveness of deep sclerectomy with T-flux implant (DS T-flux) in patients with pseudoexfoliation glaucoma (PExG). Methods. 20 eyes of 18 patients with medically uncontrolled PExG have undergone DS T-flux implantation. Postoperatively we evaluated the IOP values and the frequency of complications. The minimum follow-up time was 12 months (20 eyes) and the maximum 24 months (10 eyes). Results. The mean preoperative IOP was 36.8 ± 8.7 mmHg. The IOP significantly decreased throughout all postoperative periods (P < 0.05) and reached 1 day after surgery 11.45 ± 6.6 mmHg; 3 months 13.45 ± 3.6 mmHg; 12 months 14 ± 2.8 mmHg; and 24 months 14.80 ± 2.4 mmHg. Complete success rate, defined as IOP ≤ 18 mmHg without medication, was 85% (17/20 eyes) at 12 months. Qualified success rate, defined as IOP ≤ 18 mmHg with or without medication, was 100% (20/20 eyes). The most frequent postoperative complications were mild hyphaema (9 patients, 45%), choroidal detachment (3 patients, 15%), and hypotony-IOP < 5 mmHg (2 patients, 10%). Conclusions. DS with T-flux implant is a safe and effective surgical treatment method for medically uncontrolled PExG. The number of complications is low.

Fabrication of biodegradable textile scaffold based on hydrophobized hyaluronic acid.

In this work, we report on the preparation of a novel biodegradable textile scaffold made of palmitoyl-hyaluronan (palHA). Monofilament fibres of palHA with a diameter of 120µm were prepared by wet spinning. The wet-spun fibres were subsequently processed into a warp-knitted textile. To find a compromise between swelling in water and degradability of the final textile scaffold, a series of palHA derivatives with different degrees of substitution of the palmitoyl chain was synthesized. Freeze-drying not only provided shape fixation, but also speeded up scaffold degradation in vitro. Fibronectin, fibrinogen, laminin and collagen IV were physically adsorbed on the textile surface to enhance cell adhesion on the material. The highest amount of adsorbed cell-adhesive proteins was achieved with fibronectin (89%), followed by fibrinogen (81%). Finally, textiles modified with fibronectin or fibrinogen both supported the adhesion and proliferation of normal human fibroblasts in vitro, proving to be a useful cellular scaffold for tissue engineering.

Widefield imaging of upconverting nanoparticles on epifluorescence microscopes adapted for laser illumination with top-hat profile.

We describe a modification of epifluorescence microscopes that allows quantitative widefield imaging of samples labeled by upconverting nanoparticles (UCNP). A top-hat illumination profile on the sample was achieved with a 980-nm laser diode by using tandem microlens arrays, a moving diffuser and a telescope, which adjusts the top-hat area to the field of view. Illumination homogeneity is a critical factor for imaging of UCNP since the intensity of their luminescence typically scales with the second power of the excitation intensity. Our illuminator is combined with the epifluorescence attachment of the microscope, allowing easy switching between observation of UCNP and traditional fluorescent dyes. Illumination profile homogeneity of about 98% was measured for objectives with magnification from 4× to 100×, and the top-hat profile was also obtained with phase contrast objectives. We demonstrate capability of the illuminator by evaluating in vitro uptake of UCNP encapsulated in oleyl-hyaluronan micelles into breast cancer cells. Micelles bearing the targeting peptide were about an order of magnitude more efficient than nontargeted micelles.

Comparison of quality of facial scars after single low-level laser therapy and combined low-level with high-level (PDL 595 nm) laser therapy.

The main goal of our study was to compare the quality of resulting facials scar 12 weeks after single and combined laser therapy. Forty-one children from age 1.5 to 5 years with facial scars after injury participated in the study. Thirty-one underwent laser therapy, 14 were treated using single low-level laser therapy (670 nm, fluence 3-5 J/cm(-2) ), and 17 underwent combined high-level laser therapy with non-ablative pulsed dye laser (PDL; 595 nm, spot size 7 mm, delay 0.45 ms or 1.5 ms, fluence 9-11 J/cm(-2) , cryogen spray/delay 20/30 ms) and low-level laser therapy. The control group consisted of 10 untreated children. Before treatment and at week 4, 8, and, 12 the scars were evaluated using the POSAS questionnaire. A statistically significant improvement in scars (between ratings before treatment and 4 weeks after therapy, before treatment and 8 weeks after therapy and before treatment and 12 weeks after therapy) was observed in all parameters in both treatment groups (p < 0.0001). For the HLLT+LLLT group the most significant enhancement in the quality of scars was found for all items and at all evaluations, except pigmentation and pliability. There was no improvement observed in quality of facial scars in the control group.

Role of duodenal iron transporters and hepcidin in patients with alcoholic liver disease.

Patients with alcoholic liver disease (ALD) often display disturbed iron indices. Hepcidin, a key regulator of iron metabolism, has been shown to be down-regulated by alcohol in cell lines and animal models. This down-regulation led to increased duodenal iron transport and absorption in animals. In this study, we investigated gene expression of duodenal iron transport molecules and hepcidin in three groups of patients with ALD (with anaemia, with iron overload and without iron overload) and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in duodenal biopsies by using real-time PCR and Western blot. Serum hepcidin levels were measured by using ELISA. Serum hepcidin was decreased in patients with ALD. At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly increased in ALD. This pattern was even more pronounced in the subgroups of patients without iron overload and with anaemia. Protein expression of FPN1 paralleled the increase at the mRNA level in the group of patients with ALD. Serum ferritin was negatively correlated with DMT1 mRNA. The down-regulation of hepcidin expression leading to up-regulation of iron transporters expression in the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol consumption very probably causes suppression of hepcidin expression in patients with ALD.

Assessment of left ventricular diastolic function by radionuclide ventriculography in patients with chronic heart failure and reduced ejection fraction.

STUDY OBJECTIVE: To compare parameters of diastolic function as assessed by radionuclide ventriculography (RNVG) and Doppler echocardiography (ECHO) in the patients with chronic heart failure and reduced ejection fraction (HF REF). PATIENTS AND METHODS: RNVG and ECHO were performed on the same day in 40 patients with systolic chronic HF, NYHA II and III, with LV EF < 50 % and sinus rhythm, followed at tertiary HF clinic. Diastolic function was assessed by RNVG using parameters: PFR (peak filling rate [% SV/sec]), TFR - time to peak filling rate (ms), and by ECHO using pulse Doppler parameters: the peak Doppler velocities of early (E) and late diastolic flow (A), the E/A ratio, the calculated mean of the early (E´) diastolic velocity of septal and lateral mitral annulus measured by tissue Doppler imaging, and the E/E´ ratio. RESULTS: The mean PFR was 421.7 (median 371.0) % SV/sec and TPF was 198.7 ms (median 169.5), the mean E/A ratio was 1.21 (median 0.85) and the E/E´ ratio was 9.0 (median 8.40). TPF correlated significantly (inverse correlation) with the E/A ratio (r = -0.34, p = 0.030), and not significantly with E´ (r = -0.27, p = 0.082), the PFR/age ratio correlated with the E/E´ ratio (r = -0.31, p = 0.05). CONCLUSION: Significant correlations of parame-ters of diastolic function as assessed by radionuclide and Doppler studies were identified in the HF REF patients.

Comprehensive treatment of temporomandibular joint disorders.

AIMS: Changing lifestyles, decreasing physical activity, which is increasing the number of degenerative joint diseases of various etiology, and certain dental procedures are increasing the number of patients complaining of pain in their temporomandibular joints. The aim of the study was to assess the benefits of comprehensive physiotherapy sessions in order to decrease the number of temporomandibular joint problems, thereby improving the patient's quality of life. METHODOLOGY: An examination by a dentist determined each patient's treatment plan, which consisted of a medical exam, physical therapy and education. Each form of treatment was applied 10 times at intervals of 7-14 days. The main goal of the therapeutic physical education was to redress the muscle imbalance in the mandibular joint. This was achieved by restoring balance between the masticatory muscles, along with releasing the spastic shrouds found in the masticatory muscles. The aim of education was to teach the patient exercises focused on the temporomandibular joint and masticatory muscles. The intensity of the exercises and their composition were individually adjusted and adapted to their current state. Physical therapy consisted of the application of pulsed magnetic therapy, laser therapy, and non-invasive positive thermotherapy. RESULTS: The above procedure was conducted on a therapeutic group of 24 patients (3 men and 20 women). In the course of therapy, there were no complications, and all patients adhered to the prescribed regime. None reported any side effects. The mean treatment duration was 123 +/- 66 days. The outcome of the therapy was evaluated as described in the methodology, the degree of pain affecting the joint, and the opening ability of the mouth. In both parameters, there was a significant decline in patient pain. CONCLUSIONS: In a study devoted to tactics of rehabilitation treatment for temporomandibular joint disorders, the need for comprehensive long-term therapy, involving education, and learning proper chewing habits was made apparent for recovery and pain reduction. A priority in physical therapy, and combinations of pulsed magnetic therapy and hyperthermia-positive peloids, are also beneficial.

Malignant melanoma in the Czech Republic: incidence and mortality according to sex, age and disease stage.

BACKGROUND: The Czech Republic has reported one of the highest incidence rates of cutaneous melanoma (CM) in Europe and the rate continues to rise. Our study undertook a detailed investigation of the incidence and mortality of melanoma relative to sex, age and disease stage. The main goals were to elucidate the causes of the rising trends and explain the differences in development relative to sex, age and disease stage. METHODS AND RESULTS: The estimated annual percentage change (EAPC) using the Joinpoint Regression Model was calculated separately for men and women for all age categories and for all T stages of TNM classification. The EAPC for women was slightly higher than for men. This was only found in melanomas thinner than 1 mm (T1). For all other stages (T2, T3 and T4) the situation was worse in men. A higher incidence rate of CM and the higher value of EAPC were found for women in younger age categories (up to 49 years). In the next age category, from 50 to 59 years, the incidence of CM was comparable in both sexes as well as the EAPC. In the older age categories, i.e. 60 years and older, a significant increase was found predominantly in men. The mortality rates were only comparable between men and women in the 20 to 29 year age group. In all other categories there was a higher mortality for men. CONCLUSIONS: The number of melanoma cases in the Czech Republic is increasing faster than any other cancer. Despite improved survival rates, the death rate from CM continues to climb as a result of exponential increases in incidence. Thus primary and secondary prevention campaigns are essential for future reductions in CM incidence and mortality in the Czech Republic.

Expression of selected proteins in breast cancer brain metastases.

The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.