Analyses of registry data of patients with anti-GBM and antineutrophil cytoplasmatic antibody-associated (ANCA) vasculitis treated with or without therapeutic apheresis.

Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA. The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA. MATERIALS AND METHODS: Included were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL). RESULTS: Elderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43-0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12-0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL. CONCLUSION: PR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.

Analysis of extracorporeal photopheresis within the frame of the WAA register.

The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL). MATERIAL AND METHOD: 560 patients (33 % women) were treated with ECP for a total of 13,871 procedures during a 17-years period. Mean age was 48 years (±18, range 3-81 years). Self-estimation of QoL was graded: 0 (suicidal) up to 10 (best ever) and HC: 0 (Bed ridden, ICU condition) up to 10 (athletic). Adverse events were analyzed. ANOVA and paired comparisons were performed. RESULTS: Patients were treated due to graft versus host disease (GVHD, n = 317), skin lymphoma (n = 70), solid organ transplants (n = 47), skin diseases (n = 20) and other diseases (n = 106). Adverse events (AEs) were registered in 5.4 % of the first treatments and in 1.2 % of the subsequent procedures. Severe AEs were present in 0.04 % of all procedures. No patient died due to the procedure. Tingling and stitching were the most common AE. For those with GVHD an improvement was noticed within approximately 10 procedures of ECP in the severity stage, QoL (from a mean of 6.1 to 6.8, p < 0.002) and the HC (6.1 -> 6.4, p < 0.014) and improved further with added procedures. CONCLUSION: Photopheresis is an established therapy with few side effects. The present study of soft variables indicate that GVHD shows benefits upon ECP within approximately 10 procedures in regard to the severity of mainly skin GVHD, and lower baseline levels of HC and QoL.

Implanted vagus nerve stimulation in 126 patients: surgical technique and complications.

INTRODUCTION: Vagus nerve stimulation is a palliative treatment for patients with refractory epilepsy to reduce the frequency and intensity of seizures. A bipolar helical electrode is placed around the left vagus nerve at the cervical level and is connected to the pulse generator placed in a subcutaneous pocket, most commonly in the subclavian region. METHODS: Between March 1998 and October 2019, we performed 196 procedures related to the vagal nerve stimulation at the Neurosurgery Department in Motol University Hospital. Of these, 126 patients were vagal nerve stimulator implantation surgeries for intractable epilepsy. The cases included 69 female and 57 male patients with mean age at the time of the implantation surgery 22±12.4 years (range 2.158.4 years). RESULTS: Nine patients (7.1%) were afflicted by complications related to implantation. Surgical complications included postoperative infection in 1.6%, VNS-associated arrhythmias in 1.6%, jugular vein bleeding in 0.8% and vocal cord paresis in 2.4%. One patient with vocal cord palsy also suffered from severe dysphagia. One patient (0.8%) did not tolerate extra stimulation with magnet due to a prolonged spasm in his throat. The extra added benefit of vagus stimulation in one patient was a significant reduction of previously regular severe headaches. CONCLUSION: Vagus nerve stimulation is an appropriate treatment for patients with drug-resistant epilepsy who are not candidates for focal resective surgery. Implantation of the vagus nerve stimulator is a relatively safe operative procedure.

Circulating tumor DNA as a biomarker in metastatic colorectal carcinoma case report.

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignant disease worldwide. The stage of the disease at the time of diagnosis and the capture of an early recurrence have a direct impact on long-term survival. Existing control screening methods often do not reflect real-time metastatic disease. In patients with detectable circulating tumor DNA (ctDNA), liquid biopsy can be an effective monitoring tool. CASE REPORT: In 2012, we performed sigmoid resection in a 57 years old patient for advanced CRC. The follow-up assessments included: blood samples for CA 19-9 and CEA, endoscopy and imaging methods. We also sampled peripheral blood to determine the level of ctDNA. Its value corresponded to the development of the disease throughout the period. Twice it outperformed imaging methods. CEA showed some degree of unreliability, especially after prolonged illness. CA 19-9 was in the normal range at all times. CONCLUSION: Circulating tumor DNA is an effective tool in the diagnosis of recurrent metastatic CRC. In patients with detectable ctDNA, its level correlates with the tumoral mass in real time. It has a predictive value in monitoring the treatment response. Its implementation in the follow-up of patients with CRC may have an impact on the choice of treatment strategy and consequently on patient survival.

Evaluation of health and quality of life in apheresis patients - data from the WAA register.

OBJECTIVE: The World Apheresis Association (WAA) register contains data from more than 89 000 apheresis procedures in more than 12,000 patients. The aim of this study was to evaluate functional health and quality of life (QoL) in patients during apheresis treatment. MATERIAL AND METHODS: Estimates of health condition (HC) were made in 40,445 and of QoL in 22112 apheresis procedures. This study focused on a 10-step graded evaluation of HC (scale from: 'bedridden, unable to eat' to a level of 'athletic competition') and self-assessment of QoL (scale from: worst ever '0' to best ever '10'). Data were compared in relation to various apheresis procedures and if the patient underwent the first or subsequent apheresis procedure. RESULTS: Of the patients treated with plasma exchange (PEX) with centrifugation technique (n = 15787) 10% were 'bedridden, unable to come out of bed' while for patients treated with plasma filtration technique (n = 1018) the percentage was 27%. During the first procedure these figures were 16% and 30%, respectively. Self-estimates of QoL were graded 'zero' or '1' in 1.6% of patients during the first apheresis procedure; At the first contact patients undergoing PEX graded like this in 4.3%. CONCLUSION: Many of the patients undergoing apheresis treatment have poor HC and QoL at the start of therapy. Of all therapeutic apheresis procedures patients undergoing PEX had the lowest score of QoL.

Apheresis data registration in WWA registry-10-year experience of our center.

INTRODUCTION: The WAA Registry allows detailed registration of hemapheresis data. Our center registers results there as well. We summarize our results as compared to those of the WAA Registry. MATERIALS AND METHODS: Hemapheresis results are registered in the WAA Registry in Umea, Sweden. The patients' identity is protected by coding. General data (age, gender, weight, procedure, technique used etc.) or special data (occurrence and type of adverse reactions, health condition, quality of life etc.) are completed in a pre-defined form. RESULTS: In 2006-2016, we registered 7,927 hemaphereses in 956 patients in the WAA Registry; 40.4% in men and 59.6% in women aged 53±15years. There were mostly no significant differences in the individual interventions between our center and the WAA Registry; only the share of cascade filtrations/rheophereses is quite different (9 times higher in our center - 18.2% of interventions as compared to 2.1% in the WAA Registry). The share of photophereses (32.1%) is relatively high - due to cooperation with the bone marrow transplantations department. DISCUSSION AND CONCLUSION: In regular quality assessment, one center usually does not have enough data and experience with some diseases or interventions; therefore, comparison with the WAA Registry results is valuable not only for the quality of interventions but also for side effect prevention. On the other hand, the advantage is that every center has its unique code and may work quite independently (quick and independent non-competitive assessments). Five-minute duration of registration is advantageous in a time-demanding work; moreover, the registration is free.

Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry.

The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Adverse events in apheresis: An update of the WAA registry data.

Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

[Colorectal cancer in the elderly]. / Kolorektální karcinom ve stárí.

INTRODUCTION: High incidence of colorectal cancer in the Czech Republic is an actual and demographically significant health issue. Half of all of the patients is older than 70 years. Both surgical and non-surgical treatment options in this group of patients depend on factors that are difficult to measure only by current oncological and anesthesiological classifications (cTcNcM, ASA). The objective of this paper is to measure the impact of age on the use of various treatment modalities within the protocol and their results, and also to suggest alternative options for therapy tolerance assessment. METHODS: Analysis of data over a five-year period from the NOR database prepared by the Institute of Biostatistics and Analyses, Masaryk University. RESULTS: In all parameters a difference was demonstrated between patients below the age of 70 and those above the age of 70 years. Older patients were disadvantaged. Only 11.2% of patients younger than 70 years were not treated, whereas 25.2% over the age of 70 years were not treated. CONCLUSION: A complex geriatric examination could improve the indication process in various treatment modalities, including surgery. KEY WORDS: colorectal cancer - elderly - treatment - geriatric assesment.

[Technical background of data collection for parametric observation of total mesorectal excision (TME) in rectal cancer]. / Technické zajistení sberu dat pro parametrické sledování totální mezorektální excize (TME) pro karcinom rekta.

INTRODUCTION: Improvement in any human activity is preconditioned by inspection of results and providing feedback used for modification of the processes applied. Comparison of experts experience in the given field is another indispensable part leading to optimisation and improvement of processes, and optimally to implementation of standards. For the purpose of objective comparison and assessment of the processes, it is always necessary to describe the processes in a parametric way, to obtain representative data, to assess the achieved results, and to provide unquestionable and data-driven feedback based on such analysis. This may lead to a consensus on the definition of standards in the given area of health care. METHOD: Total mesorectal excision (TME) is a standard procedure of rectal cancer (C20) surgical treatment. However, the quality of performed procedures varies in different health care facilities, which is given, among others, by internal processes and surgeons experience. Assessment of surgical treatment results is therefore of key importance. A pathologist who assesses the resected tissue can provide valuable feedback in this respect. RESULTS: An information system for the parametric assessment of TME performance is described in our article, including technical background in the form of a multicentre clinical registry and the structure of observed parameters. CONCLUSION: We consider the proposed system of TME parametric assessment as significant for improvement of TME performance, aimed at reducing local recurrences and at improving the overall prognosis of patients. KEY WORDS: rectal cancer total mesorectal excision parametric data clinical registries TME registry.

[Parametric monitoring of the quality of total mesorectal excision and surgical treatment of rectal carcinoma results of a multicenter study]. / Parametrické sledování kvality totální mezorektální excize a chirurgické lécby karcinomu rekta výsledky multicentrické studie.

INTRODUCTION: Tumour size and the quality of its complete surgical removal are the main prognostic factors in rectal cancer treatment. The number of postoperative local recurrences depends on whether the mesorectum has been completely removed - total mesorectal excision (TME) - and whether tumour-free resection margins have been achieved. The surgery itself and its quality depend on the accuracy of preoperative diagnosis and detection of risk areas in the rectum and mesorectum, on the surgeons skills, and finally on pathological assessment evaluating whether complete tumour excision has been accomplished including circumferential margins of the tumour, and whether mesorectal excision is complete. The aim of our study was to implement and standardize a new method of evaluation of the quality of the surgical procedure - TME - in rectal cancer treatment using an assessment of its circumferential margins (CRO) and completeness of the excision. METHODS: The study consisted of two parts. The first, multi-centre retrospective phase with 288 patients analysed individual partial parameters of the diagnosis, operations and histological examinations of the rectal cancer. Critical points were identified and a unified follow-up protocol was prepared. In the second, prospective part of this study 600 patients were monitored parametrically focusing on the quality of the TME and its effect on the oncological treatment results. RESULTS: The proportion of patients with restaging following neoadjuvant therapy increased from 60.0% to 81.7% based on preoperative diagnosis. The number of specimens missing an assessment of the mesorectal excision quality decreased from 52.9% in the retrospective part of to the study to 22.8% in the prospective part. The proportion of actually complete TMEs rose from 22.6% to 26.0%, and that of nearly complete TMEs from 10.1% to 24.0%. CONCLUSION: The introduction of parametric monitoring into routine clinical practice improved the quality of pre-treatment and preoperative diagnosis, examination of the tissue specimen, and consequently improved quality of the surgical procedure was achieved. KEY WORDS: rectal cancer TME - parametric monitoring - quality control.

["Liver fist approach" in the management of synchronous liver metastases from colorectal cancer: Preliminary non-randomized study results]. / "Liver first approach" u synchronních metastáz kolorektálního karcinomu: Predbezné výsledky nerandomizované studie.

INTRODUCTION: Liver metastases are diagnosed in 60% of patients with colorectal cancer, both at the time of diagnosis or later in the course of their management. Surgical treatment is the sole potentially curable method with 5-year overall survival of approximately 50%. However, only less than 20% of patients underwent liver resection. A joint effort of medical oncologists and surgeons is to increase the numbers of resected patients. The "liver first approach" (LFA) is one of approaches aimed at increasing resecability. The authors present their preliminary results using this method. METHODS: 102 patients were included in the multicentre study supported by the grant IGA NT 13660 Evaluation of quality of multimodal treatment for patients with colorectal cancer liver metastases - conducted at the Central Military Hospital between September 2012 and January 2015. We used LFA in 12 patients (12%). Patients were indicated for liver resection based on good response to neoadjuvant systemic therapy. Multiple bilobar liver involvement (>4 metastases) was present in 11 cases and one large solitary metastasis in the right liver lobe in one case. The primary tumor was located in the rectum in 9 patients, in the rectosigmoid in 3 patients; 3 patients had a colostomy. Others showed no signs of bowel obstruction. RESULTS: We have performed R0 resections in 11 cases, and two-stage hepatectomy with portal vein embolisation was indicated 3 times (in one case we did not finish the second stage due to quick progression after PVE). We performed major resections 7 times, along with sever extraanatomic resections, incl. 11 RFA (6 times in combination with major resections). Perioperative mortality was 0%, morbidity 33% (Dindo-Clavien >2). Ten patients underwent adjuvant chemotherapy, in 7 cases including radiotherapy of the small pelvis due to a local advanced primary tumor. Resection of the primary tumor was done in 7 patients (58%). Two patients died recently because of disease progression (17%); progression was observed in 6 patients (50%). CONCLUSION: We deem the LFA suitable especially for patients with metastatic rectal tumors where adjuvant systemic therapy can be combined with radiotherapy. The timing of the resection of the primary tumor still remains a question: it is necessary to rule out potential recurrence of liver metastases, which affected more than 50% of the patients. The benefit of LFA must be confimed by randomised studies.

[Current status in the treatment of rectal cancer in the Czech Republic regarding the rate of complete pathological response after neoadjuvant therapy--PATOD C20 study 2011-2012]. / Soucasný stav strategie lécby karcinomu rekta v Ceské republice s ohledem na výskyt kompletní patologické odpovedi pri neoadjuvantní lécbe--studie PATOD C20 2011-2012.

INTRODUCTION: Deciding on the strategy in rectal cancer´s treatment requires a complex and multidisciplinary approach. The primary rectal resection is indicated in early stages, while locally advanced tumors should be pretreated by one of the modes of neoadjuvant (chemo) radiotherapy. The main goal of this study was to explore the therapeutic strategy in patients with rectal cancer in the Czech Republic. The second aim was to determine the incidence of the pathological complete response after neoadjuvant therapy. METHODS: This is a retrospective multicenter clinical study, which includes data from all patients with rectal cancer who were treated at participating centers in the period from 01/01/2011 to 31/12/2012. The required data has been passed into the online registry PATOD C20.Three issues have been set up: 1. Characteristics of the center and cooperation with the oncological department; 2. Characteristics of the treatment of patients with rectal cancer; and 3. Detailed analysis of the group of patients with complete pathological response. The analysis was performed with regard to the nature of individual departments, i.e. departments of surgery in university hospitals with complex oncological centres, departments of surgery within complex oncologic centers, and departments of surgery outside complex oncologic centers. RESULTS: In total, 21 departments of surgery in the Czech Republic provided data about 1860 patients with rectal cancer for the study. The treatment strategy for rectal cancer was determined at multidisciplinary seminars at 19 centers (90.5%). Statistically significant differences between the centers were found in the indication for neoadjuvant treatment (p<0.001), rectal resection with anastomosis (p=0.048), and resection without anastomosis (p=0.022). Complete pathological response was found in 61 (8.7%) patients. Positivity of mesorectal lymph nodes (ypN+) was found in the case of ypT0 stage in 7 (9.7%) patients. CONCLUSION: PATOD study showed that therapy of rectal cancer is highly heterogeneous in the Czech Republic. Despite the best conditions provided, university hospitals and large departments within complex oncologic centers do not fully utilize this benefit.

Planktonic or non-planktonic food in young-of-the-year European perch Perca fluviatilis in ponds.

Higher biomass especially of some aquatic macrophyte species offered a higher density of phytophilous zoobenthos, but did not increase the proportion of non-planktonic to planktonic prey in young-of-the-year perch Perca fluviatilis. Both abundance and biomass of non-planktonic prey dominated over planktonic prey in the pond with lower biomass of aquatic macrophytes and lower food. Survival of P. fluviatilis was lower (20%) in the pond with lower food than in the other pond (34%), however, specific growth rate (1.3% day(-1) ) and final Fulton's condition factor of P. fluviatilis were similar in both ponds.

[State and development of background information for the evaluation of Czech cancer screening programmes]. / Stav a vývoj informacní základny pro hodnocení onkologických screeningových programu v Ceské republice.

Czech cancer screening programmes feature a comprehensive multimodal information system which covers all the levels of assessment needed - population-based monitoring (Czech National Cancer Registry), monitoring of results in the diagnostic databases of centres, as well as the quantification of coverage and outputs of primary care according to the administrative data of health care payers. A system of personalised invitations to cancer screening programmes was launched in 2014, based on a stand-alone component of the information system which makes it possible to identify eligible clients in health care payers databases. The system was fully standardised and uniformly implemented in all health insurance companies; its functionalities also involve both continuous and retrospective assessment of the results of personalised invitation. The legislative framework in force will have to be applied and implemented for a more comprehensive and integrated employment of all involved data sources, i.e. cancer registries, screening registries, and administrative data. The system must be able to analyse de-identified individual records on clients participation in screening programmes, and thus to ensure an adequate analysis of performance indicators in compliance with international recommendations.

[Approach to population-based screening in the Czech Republic, methodology and first results of the personalised invitation of citizens to cancer screening programmes]. / Koncepce populacního screeningu v Ceské republice, metodika a první výsledky adresného zvaní obcanu do preventivních onkologických programu

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

[Cost analysis of radiotherapy provided in inpatient setting -  testing potential predictors for a new prospective payment system]. / Analýza nákladu na radioterapii v luzkové péci - hledání vhodných prediktoru pro potreby nového prospektivního úhradového modelu.

BACKGROUND: As a part of the development of a new prospective payment model for radiotherapy we analyzed data on costs of care provided by three comprehensive cancer centers in the Czech Republic. Our aim was to find a combination of variables (predictors) which could be used to sort hospitalization cases into groups according to their costs, with each group having the same reimbursement rate. We tested four variables as possible predictors -  number of fractions, stage of disease, radiotherapy technique and diagnostic group. METHODS: We analyzed 7,440 hospitalization cases treated in three comprehensive cancer centers from 2007 to 2011. We acquired data from the I COP database developed by Institute of Biostatistics and Analyses of Masaryk University in cooperation with oncology centers that contains records from the National Oncological Registry along with data supplied by healthcare providers to insurance companies for the purpose of retrospective reimbursement. RESULTS: When comparing the four variables mentioned above we found that number of fractions and radiotherapy technique were much stronger predictors than the other two variables. Stage of disease did not prove to be a relevant indicator of cost distinction. There were significant differences in costs among diagnostic groups but these were mostly driven by the technique of radiotherapy and the number of fractions. Within the diagnostic groups, the distribution of costs was too heterogeneous for the purpose of the new payment model. CONCLUSION: The combination of number of fractions and radiotherapy technique appears to be the most appropriate cost predictors to be involved in the prospective payment model proposal. Further analysis is planned to test the predictive value of intention of radiotherapy in order to determine differences in costs between palliative and curative treatment.

Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig.

To define signaling pathways that drive FSH- and epidermal growth factor (EGF)-like peptide-induced cumulus expansion and oocyte meiotic resumption, in vitro cultured pig cumulus-oocyte complexes were treated with specific protein kinase inhibitors. We found that FSH-induced maturation of oocytes was blocked in germinal vesicle (GV) stage by protein kinase A (PKA), MAPK14, MAPK3/1, and EGF receptor (EGFR) tyrosine kinase inhibitors (H89, SB203580, U0126, and AG1478 respectively) whereas phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene homolog (PI3K/AKT) inhibitor (LY294002) blocked maturation of oocytes in metaphase I (MI). Amphiregulin (AREG)-induced maturation of oocytes was efficiently blocked in GV by U0126, AG1478, and low concentrations of LY294002; H89, SB203580, and high concentrations of LY294002 allowed the oocytes to undergo breakdown of GV and blocked maturation in MI. Both FSH- and AREG-induced cumulus expansion was incompletely inhibited by H89 and completely inhibited by SB203580, U0126, AG1478, and LY294002. The inhibitors partially or completely inhibited expression of expansion-related genes (HAS2, PTGS2, and TNFAIP6) with two exceptions: H89 inhibited only TNFAIP6 expression and LY294002 increased expression of PTGS2. The results of this study are consistent with the idea that PKA and MAPK14 pathways are essential for FSH-induced transactivation of the EGFR, and synthesis of EGF-like peptides in cumulus cells and MAPK3/1 is involved in regulation of transcriptional and posttranscriptional events in cumulus cells required for meiotic resumption and cumulus expansion. PI3K/AKT signaling is important for regulation of cumulus expansion, AREG-induced meiotic resumption, and oocyte MI/MII transition. The present data also indicate the existence of an FSH-activated and PKA-independent pathway involved in regulation of HAS2 and PTGS2 expression in cumulus cells.

[Cost analysis of XELOX and FOLFOX-4 chemotherapy regimens for colorectal carcinoma]. / Porovnání nákladu u rezimu XELOX a FOLFOX-4 v lécbe kolorektálního karcinomu.

BACKGROUND: The aim of our study was to compare healthcare-related costs of treatment with XELOX and FOLFOX4 chemotherapeutic regimens in patients with colorectal cancer. We have evaluated costs claimed to the health insurance by the hospital administering these cancer therapies. This study is a pilot project utilising the new I-COP database developed by the Institute of Biostatistics and Analyses of the Masaryk University in Brno, Czech Republic. PATIENTS AND METHODS: First, we estimated the costs based on current prices of procedures, medication, and materials from public sources. Using the I-COP database, we then carried out a matched-pair comparison of 26 patients treated with FOLFOX4 or XELOX for colorectal cancer. We evaluated a period of three months of therapy (i.e. 6 cycles of FOLFOX4 or 4 cycles of XELOX). Statistical analysis was done using the Wilcoxon matched pairs test. RESULTS: The estimated cost for three months of therapy was 148,288 Czech crowns (CZK) for FOLFOX4 (including CZK 101,064 for chemotherapy drugs) and CZK 123,756 for XELOX. The overall costs claimed to the insurance companies were CZK 160,158 and CZK 151,176 for FOLFOX4 and XELOX, respectively (p = 0.221). The XELOX regimen had significantly higher costs for chemotherapy drugs (CZK 131,705 versus 114,531, p = 0.023) whereas other costs were lower than those for FOLFOX4. CONCLUSIONS: FOLFOX4 and XELOX regimens can be considered as equivalent in terms of costs claimed by the hospital administering cancer treatment.

RHEOPHERESIS IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Evaluation of the long-term effect of rheopheresis treatment of dry form of age-related macular degeneration (AMD). MATERIALS AND METHODS: The treatment group consisted of 65 patients and 55 patients in the control group, with a minimum follow-up period of 60 months. The basic treatment consisted of 8 rheopheresis procedures, and the additional treatment (booster therapy) of 2 rheopheresis procedures 1.5-2 years after the basic treatment. We evaluated changes in best corrected visual acuity, anatomical effect, electrical activity of the retina, haematological, biochemical and immunological parameters. RESULTS: Rheopheresis treatment contributed significantly: 1) to stabilisation of best corrected visual acuity of the treated patients, which initially showed an insignificant increased during the 2-years follow-up period, and then slightly decreased. By contrast, visual acuity decreased in the control group, to an insignificant degree up to 4 years, then statistically significantly. 2) to an improvement of the morphological findings in 62.4% of treated patients compared to 7.5% in the control group, while disease progression to stage 3 (neovascular form of the disease or geographic atrophy) with a significant decrease of visual acuity occurred in only 7.1% of treated patients, versus 37.0% in the control group. 3) to regression, even to the attachment of drusenoid pigment epithelial detachment (DPED). To a reduction of the area of DPED in 80.4% of treated patients, in contrast with an steaincrease in the area of DPED in 47.1% of patients in the control group, and the development of new DPED in only 2 eyes of treated patients compared with 16 eyes of patients in the control group. 4) to a preservation of the integrity of the ellipsoid layer in the fovea in 68.2% of the treated patients, while by contrast we found a damaged ellipsoid layer in the fovea in 66.6% of the control patients. 5) to a stabilisation of the activity of ganglion cells, the pineal system and the activity of the central area of the retina, with eccentricity between 1.8° and 30° in the treated patients, compared to alteration in the control group manifested mainly after 3.5 years of the follow-up period. 6) to a statistically significant improvement in rheological parameters, thereby increasing flow in microcirculation and positively influencing the metabolism in the retina. Also to a positive effect on the classical, alternative and lectin pathway of complement activation, a reduction in the level of proprotein convertase subtilisin kexin 9 (PCSK9), and thus also the level of LDLcholesterol, and 7) Additional treatment with 2 RHF procedures (so-called "booster therapy") seems to be a safe and suitable method of prolonging the stabilisation phase, or even improving visual acuity, anatomical and functional findings. CONCLUSION: We demonstrated positive changes in anatomical, functional and humoral parameters upon rheopheresis treatment of AMD. Their correlation provides a real possibility to identify patients at risk and to manage an individualised regime of rheopheresis therapy. This method of treatment is effective and safe, with a low percentage of non-serious adverse effects.