Phyllodes tumor and its malignization into invasive ductal carcinoma a case report.

INTRODUCTION: Phyllodes tumors of the breast are rare and very distinct types of mammary neoplasms. They are characterized by their biphasicity, i.e. the presence of stromal and epithelial components at the same time. Malignancy is determined by the degree of stromal differentiation. The coexistence of the malignant epithelial component is a very rare phenomenon. Dozens of cases of simultaneous phyllodes tumor and epithelial malignancy have been reported so far. Nevertheless, the biological nature of this process is still an unexplained and a controversial topic. CASE REPORT: In this paper, we present a case of a patient with a suddenly enlarging lesion in the breast. According to the first surgical resection, a diagnosis of high-grade malignant phyllodes tumor was made with fibrosarcoma differentiation, stromal overgrowth and suppression of the epithelial component. Examination of scar resistence in early postoperative period revealed a triple-negative invasive low-differentiated breast carcinoma with very high proliferative activity, thus malignization of the epithelial component of the tumor occurred. Shortly, a diagnosis of second recurrence was made, treatment included axillary lymph node dissection (ALND) with a negative histological findings. The patient underwent complex adjuvant chemotherapy and radiotherapy and remained disease free 3 years after the surgery. CONCLUSION: Coexistence of phyllodes tumor and the breast carcinoma is very rare. The article describes the first published case, which documents the subsequent development of invasive low-differentiated ductal carcinoma immediately after resection of high-grade phyllodes tumor. Treatment and prognosis are generally determined by the characteristics of the carcinomatous component.

Is There a Benefit of HER2-Positive Breast Cancer Subtype Determination in Clinical Practice?

BACKGROUND: Breast cancer (BC) with increased expression of human epidermal growth factor receptor 2 with tyrosine kinase activity (HER2+) is a clinically and bio-logically heterogeneous dis-ease. In terms of gene expression, there are four major molecular subtypes - Luminal A, Luminal B, HER2-enriched (HER2-E), and Basal-like. The most common subtype is HER2-E (50- 60%). In hormone-dependent (HR+) HER2-positive tumors, the subgroup HER2-E represents 40- 50% of cases; others are luminal A and B subtypes. PURPOSE: The aim of this review is to provide information on the significance of the distribution of HER2-positive tumors accord-ing to subtype, which is considered a predictive parameter for guid-ing treatment decisions. For example, HER2-E subtype is characterized by a higher probability of achiev-ing complete pathological remission when treated with chemother-apy and antiHER2 ther-apy, and it is thought that it could be treated us-ing a dual HER2 blockade without chemother-apy. Currently, triple-positive tumors, a specific subtype of breast cancer characterized by HER2+ and HR+, are more often subjects of interest. Their unique bio-logical properties are due to complex interactions between HER2 and estrogen receptor (ER) signalling, which result in lower effectiveness of endocrine ther-apy in these patients than in HR+ and HER2-negative patients and, at the same time, the ER positivity in HER2+ tumors can result in resistance to antiHER2 ther-apy. This type of BC is a non-homogeneous group where the impacts of HER2 positivity on tumor malignant behavior and activity of the estrogen-driven signal-ing pathway are inconsistent. Current studies focus on test-ing new treatments such as dual HER2 block-ing or immunother-apy, in combination with antiHER2 targeted ther-apy with fulvestrant, aromatase inhibitors, cyclin dependent kinase 4/ 6 inhibitors, or inhibitors of the PI3K (phosphatidylinositol-3-kinase) pathway. CONCLUSION: The distribution of HER2+ BC accord-ing to individual subtype provides information that can contribute to achiev-ing more accurate decisions about the most appropriate ther-apy. Key words breast cancer - subtype - HER2 - trastuzumab - HER2 positive - triple positive - HER2 enriched The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 27. 9. 2018 Accepted: 26. 11. 2018.

[New Drugs in the Treatment of Acute Myeloid Leukemia in the Elderly]. / Nové léky v terapii akutní myeloidní leukemie u starsích pacientu.

BACKGROUND: At the time of diagnosis, most patients with acute myeloid leukemia are older than 65 years of age. Treatment of this group of patients is challenging because they become less tolerant to aggressive chemotherapy with increasing age. Less than one-third of elderly patients are considered eligible for intensive treatment; nevertheless, the survival analysis for this population remains poor. Due to numerous comorbidities and an overall deteriorating condition, most elderly patients with acute myeloid leukemia receive only palliative or best supportive care, which are associated with a high mortality rate. New therapeutic approaches are expected to improve the overall survival and quality of life of this group of patients. These promising treatments include cell kinase inhibitors, cytotoxic agents, monoclonal antibodies, and epigenetic therapy including hypomethylating agents and inhibitors of isocitrate dehydrogenase and histone deacetylase. In monotherapy, these new drugs show lower levels of toxicity than those commonly used in chemotherapy; however, they do not lead to a better long-lasting treatment response. To enhance therapeutic efficacy, combinations of the above-mentioned treatments are often used, and, during clinical trials, combinations with standard cytostatics are also common. The promising results of these studies show that even low-toxicity therapies can lead to a better overall treatment response and to longer overall survival. AIM: This article provides a brief overview of new drugs that are evaluated for their mechanism of effect, efficacy and toxicity in therapy of patients suffering from acute myeloid leukemia.Key words: acute myeloid leukemia - elderly - FLT3 inhibitors - epigenetic therapy - monoclonal antibodies The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 11. 2016Accepted: 13. 12. 2016.

[Molecular Genetic Testing for Acute Myeloid Leukemia]. / Molekulárne genetické vysetrení u akutní myeloidní leukemie.

BACKGROUND: Acute myeloid leukemia (AML) is a clinically complex and very heterogeneous disease at the molecular level. Conventional cytogenetic analysis and FISH (fluorescence in situ hybridization) tests provide important information about the biological and clinical background of the disease and enable the classification of AML patients into three risk groups. However, up to half of patients have normal cytogenetics. Determining prognosis and treatment strategies in this group of patients is challenging. The development of molecular genetic methods, including next generation sequencing in the last decade, has led to the discovery of a number of recurrent mutations that have contributed to increasing the accuracy of prognosis of those patients with cytogenetically normal AML. Besides the prognostic value of these mutations, they may also be used to monitor minimal residual disease during and after treatment of AML and additionally constitute potential targets for the development of new therapeutic agents. The importance of molecular genetic testing of all patients with AML is highlighted by the WHO classification of 2008 in which subgroups of AML are purely defined by molecular genetics markers. AIM: In this article, we provide an overview of the most significant mutations in patients with cytogenetically normal AML. We describe their significance for prognosis, their importance in monitoring minimal residual disease, and their potential for the development of new targeted therapies. Further, we briefly draw attention to the significance of gene mutation accumulation in clonal disease development and how it affects the time of AML relapse.

[Treatment of Keratoconus with Corneal Cross-linking--Results and Complications in 2 Years Follow-up]. / Corneal cross-linking v liecbe keratokónusu--výsledky a komplikácie v dvojrocnom sledovaní.

OBJECTIVE: The objective of the study was to assessment of changes of monitored parameters after CXL. Incidence of complications were assessed in the whole group and in groups of patients divided according to the selected criteria. Evaluated parameters were also relations between them and in time. METHODS: The 86 eyes of patients with progressive keratoconus who underwent CXL according to the Dresden protocol in the years 2007-2009 at the Ophthalmic clinic FN Brno Bohunice were included in this study. RESULTS: There was observed significant increase of BCVA (letters--before CXL 42,30±10,35, 1st year after CXL (1Y) 44,68±10,04, p<0,01, 2nd year after CXL (2Y) 44,44±10,57, p<0,01) and SE (-5,95±3,98D, -5,27±3,84D, p<0,01, -4,94±3,68D, p<0,01), and decrease of maximum curvature of the cornea (MAX--before CXL 50,39±4,17D, 1Y 49,46±4,13D, p<0,01, 2Y 49,42±4,14D, p<0,01). Change of ultrasound CCT, polymegatisms, pleomorfisms and corneal endothelial cell density was not significant. The value of MAX is the most important parameter in estimating the effect of CXL. The highest incidence of corneal opacity after CXL was observed in the eyes of patients with III. stage of keratoconus over 40 years old, carrying hard contact lenses and with biomikroskopic symptom of keratoconus on the cornea. We found that corneal thickness measurement with Orbscan II and the mesurement of IOP with noncontact method is incorrect by patients after CXL. CONCLUSION: Corneal cross-linking of the cornea is safe and effective procedure of stopping the progression of keratoconus in 97% of eyes in the period up to 2 years after CXL.

[The effectiveness of corneal cross-linking in stopping the progression of keratoconus]. / Efektivita corneal cross-linkingu v zastavení progresie keratokónusu.

OBJECTIVE: Objective of the study was to prove the efficiency of corneal cross-linking (CXL) in stopping the progression of keratoconus. METHODS: In this study were included 58 eyes of patients with progressive keratoconus who underwent CXL according to the Dresden protocol in the years 2007-2009 at the Ophthalmic clinic FN Brno Bohunice. The eyes of patients were divided into four groups according to the change of maximum curvature of the cornea two years after CXL. RESULTS: Stabilization of maximum curvature of the cornea have been reported in 40 % of eyes, regression in 57 % of eyes by an average of 1,92D and disease progression in 3 % of eyes 2 years after CXL. The eyes with regression over 2D had significantly higher best-corrected visual acuity before and after the procedure compared to the group with stabilization. Spherical equivalent increased significantly in all groups, on average, in the group with stabilization of 0,54D, in the group with mild regression of 0,71D and in the group with a large regression of 2,09D. In the group with a large regression 100 % of eyes had stabilization or increase in SE. Our observations showed that, when a decrease in the patient keratometric values of cornea is present after CXL, it is comprehensive and applies to all parameters. CONCLUSION: We have confirmed that corneal cross-linking stops the progression of the disease in 97 % of eyes two years after the procedure.

[Molecular biological diagnostics of KRAS and BRAF mutations in patients with colorectal cancer - laboratory experience]. / Molekulárne biologická diagnostika mutací genu KRAS a BRAF u pacientu s kolorektálním karcinomem - zkusenosti laboratorního pracoviste

BACKGROUND: Targeted biological therapy based on blocking growth factor receptors and inhibition of cancer-inducing signaling pathways is a new treatment facility for patients with colorectal cancer (CRC). Therapeutic agents are monoclonal antibodies targeting epidermal growth factor receptor (EGFR). Gene aberrations in the EGFR-induced pathways are negative predictors of therapeutic response. Determination of -non-mutated KRAS is a requirement for the indication of targeted anti-EGFR therapy in the present time, BRAF mutation analysis is recommended. Comparison of our results with published data and verification of routine laboratory methods in relation to diagnostic kits were the purposes of this study. PATIENTS AND METHODS: In addition to routine methods based on PCR, direct sequencing as well as two diagnostic kits for KRAS (codon 12 and 13) and BRAF (codon 600) mutation analysis were used for 132 patients. RESULTS: KRAS mutations were detected in 45 patients (34%), V600E mutation of the BRAF gene in 9 patients (7%). Both mutations simultaneously were not detected. Tissues from primary tumor and metastases were available from 33 patients. KRAS mutation was detected in 13 cases of this group. KRAS mutations in tumor and metastasis were of the same type in 9 patients; types of mutation in both tissues were different in one case. KRAS mutation only in one tissue was detected in 3 cases. BRAF mutation in both tissues was detected in the 4 patients. A low percentage of tumor cells in 17 patients specimen did not allow performance of routine analysis and diagnostic kit was used. CONCLUSION: The frequency of KRAS and BRAF mutations in our cohort of patients corresponds to published data. The suitability of metastatic tissue analysis due to tumor heterogeneity was confirmed. KRAS analysis requires a comprehensive methodological approach with regard to reduced DNA quality and different percentage of tumor cells in tissue. For this reason, commercial diagnostic kits constitute a suitable supplement to standard methods.

Perioperative interstitial CT-based brachytherapy boost in breast cancer patients with breast conservation after neoadjuvant chemotherapy.

Intraoperative placement of catheters in the tumor bed during breast-conserving surgery (BCS) enables postponed targeted boost irradiation in high risk breast cancer patients. Twenty-three patients with high risk breast cancer underwent neoadjuvant chemotherapy and multifractionated perioperative brachytherapy as a boost to the tumor bed using three-dimensional (3D) CT-based planning. Plastic catheters for brachytherapy were implanted during surgery and targeted irradiation was delivered in the course of 2-3 weeks. Acute and late toxicities were scored according to the RTOG Common Toxicity Criteria. Cosmetic outcomes were assessed using the Harvard criteria. No major perioperative complications were recorded. Circumscribed wound infection occurred in one patient (4.3%). Only 3 patients (13%) experienced acute skin toxicity Grade 1. We observed no teleangiectasias or pigmentations. The cosmetic outcome at last follow-up visit was rated as excellent/good, in 82.6%, fair, in 13% and poor in 4.4% of patients, respectively. There was no evidence of disease recurrence after median follow-up of 43. 4 months. Systematic integration of the perioperative fractionated 3D CT-based HDR brachytherapy as a boost for patients with breast cancer after BCS is feasible and seems safe. It might be beneficial especially for women with high risk of local recurrence.

Long-term results of allogeneic hematopoietic stem cell transplantation after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin.

UNLABELLED: Reduced-intensity conditioning (RIC) is widely used for allogeneic stem cell transplantation (SCT). Here we present our long-term experience with RIC regimen consisting of fludarabine (30 mg/m2/day on days -10 to -5), busulfan (4mg/kg/day on days -6 and -5) and antithymocyte globulin (ATG Fresenius, 10 mg/kg/day on days -4 to -1) (Flu-Bu-ATG) in a cohort of 71 patients with various hematological malignancies including chronic myeloid leukemia (24 patients), acute myeloid leukemia (19 patients), lymphoma (20 patients), multiple myeloma (3 patients), myelodysplastic syndrome (3 patients), and myelofibrosis (2 patients). The median age was 50 years. The overall response rate was 87%, including 83% CR and 4% PR. The incidence of acute and chronic GVHD was 35% and 52% and the cumulative incidence of non-relapse mortality at 1 year and 4 years was 8% and 14%. With the median follow-up of 55.0 months, the 2- and 4-year event-free survival (EFS) was 49.0% and 40.3%, and the overall survival (OS) was 73.2% and 62.6%, respectively. Gender, age at SCT, type of donor, disease status at SCT, previous autologous transplantation, and complete chimerism by day +100 did not significantly influence EFS and OS. In a multivariate analysis, no presence of chronic GVHD (p=0.029, HR: 2.5),and diagnosis other than CML (p=0.018, HR: 4.6), and CD34+ dose < 5x106/kg (p=0.010, HR: 2.8) were significant predictors of poor OS. Flu-Bu-ATG protocol is a RIC regimen that combines effective disease control with low non-relapse mortality and acceptable toxicity profile. KEYWORDS: reduced-intensity conditioning, fludarabine, busulfan, antithymocyte globulin.

Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse.

INTRODUCTION: The reoccurrence or increase in autologous hematopoiesis after allogeneic transplantation has been linked to incipient leukemia relapse. However, the importance of such an emergency regarding microchimerism (i.e. mixed chimerism below 1% of autologous cells) still remains controversial, as fluctuating microchimerism can be observed for a very long time after transplantation. METHODS: Using real-time PCR (RQ-PCR), we compare peripheral blood samples obtained from patients with acute myeloid leukemia (AML) before hematological relapse and those taken during complete remission (i.e. either complete cytogenetic remission or complete molecular remission where applicable). By comparison of these two groups, we describe microchimerism dynamics clearly connected with imminent AML relapse. Additionally, we compare applicability of RQ-PCR and conventional PCR with fragment analysis. RESULTS: Mere reappearance of autologous hematopoiesis within patients with complete donor chimerism is alarming, and another sample with further increase confirms ongoing relapse. In case of patients with continuous microchimerism, another two consecutive samples with increasing trend are required. RQ-PCR predicted a significantly higher number of hematological relapses (87%vs. 39%) with a median anticipation period of 33 days, 26 days earlier than conventional PCR (P= 0.0002). Moreover, the outcome of microchimerism dynamics was in complete agreement with monitoring of minimal residual disease when analyzed from the same cell compartment. CONCLUSION: Within this paper, we emphasize the importance of microchimerism monitoring as a reliable indicator of incipient AML relapse, especially in patients where no other specific molecular marker is available.

Dasatinib in imatinib-resistant or -intolerant CML patients: data from the clinical practice of 6 hematological centers in the Czech Republic.

Dasatinib is effective second line treatment for patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. We report here the first experiences with dasatinib therapy in 71 CML patients resistant or intolerant to imatinib from the real clinical practice of 6 hematological centers in the Czech Republic. Dose 100 mg daily and 70 mg twice daily was administered to patients with chronic phase (CP) and advanced phases (AP) CML. In chronic phase (n=46), complete hematological reponse (CHR) was achieved in 97%, major cytogenetic reponse (MCgR) in 77% and complete cytogenetic response (CCgR) in 67%. Major molecular reponse (MMR) was achieved in 19/31 patients in median of 10 months. In advanced phase (n=25), CHR was attained in 77%, MCgR in 39%, CCgR in 33% and MMR in 2/18 patients. Eleven different baseline mutations were followed up in 15 patients. Dasatinib eliminated mutations in most of the patients, but 3 patients acquired a new one. Novel mutations were detected under dasatinib therapy in 2 patients. Dasatinib was well tolerated, cytopenias were common and was managed by dose modification. The estimated progression free survival (PFS) at 12 months was 97+/-3% in CP and 62+/-21% in AP. The median time to treatment failure was 605 days in AP while it was not reached in CP patients. Our clinical experiences, described here, confirmed that dasatinib is associated with high response rates especially in imatinib resistant or intolerant CML patients in chronic phase.

[Patients older than 80 years with de novo acute myeloid leukemias without erythroblastic and/or megakaryocytic dysplasia achieve complete remission and longer survival after classical chemotherapy 3 + 7]. / Nemocní starsí 80 let s de novo akutními myeloidními leukemiemi bez dysplazie v erytroblastické 8/nebo megakaryocytární rade dosahují kompletní remise a delsího prezlití po klasické chemoterapii 3+7.

Chemotherapy in most patients with AML over 80 years of age is not recommended because their median survival is about 1 month. The aim of our study was to identify patients in this age group who might achieve complete remission with standard dose chemotherapy. We report 9 consecutive patients with de novo AML diagnosed and treated in 1992-2008. All bone marrow samples were hypercellular, classified as FAB types M2 in 2 cases, M4 in 6, and M5 in one case. Three patients opted for supportive or palliative therapy and survived 1-4 months. Six patients received standard dose chemotherapy. Two patients with a normal karyotype had resistant AML and survived 1.0 and 2.7 months; one patient with a complex karyotype died of septic shock on the 10th day of therapy. All these three patients exhibited erythroblastic and/or megakaryocytic dysplasia (EMD) at presentation (two in more than 26% erythroblasts, all three in a half or more of megakaryocytes). Three remaining patients with AML M4, a normal karyotype but without EMD, achieved complete remission in spite of co-morbidities and a poor performance status. Two of them survived 18.6 and 28 months on maintenance therapy, the third 16.5 months without it. Very elderly AML patients without EMD appear to represent a favorable prognostic biological category (single-lineage AML) that show a good response to standard dose chemotherapy.

[Corneal cross-linking--modern method of keratoconus treatment]. / Corneal cross-linking--moderná metóda liecby keratokónusu.

PURPOSE: The aim of research study was to evaluate the effect of corneal cross-linking (CXL) in the frame of patients with progressive keratoconus 1 year after treatment. METHODS: There were 40 eyes of 35 patients with mean age 28, 45 +/- 9.3 (SD) (15 to 48 years) included in the study. Patients were treated with standard protocol of CXL with abrasion of corneal epithelium. Complete ophthalmological examination included best corrected spectacles visual acuity (BCSVA), slit-lamp microscopic finding, corneal topography and corneal thickness measured with ultrasound method was performed before, on the 5-th day, 1. 6., 12. month after CXL. We divided patients according to the stage of keratoconus into 2 groups (stage I. and stage II.) and according to the age into 3 groups (until 20, from 21 to 39, over 40 years). RESULTS: In all treated eyes, the CXL was without relevant complications. The only complication was stromal haze of cornea. In the evaluation based on stage of keratoconus, in the first group any patient became a haze of cornea in 1 year after CXL. In the second group 35.7% of patients had a haze of cornea. The average BCSVA 1 year after treatment was improved in the 1. group about 5.38 letter and in the 2. group about 1.25 letter. Topographic analysis showed decrease of simulated keratometry and refraction (1. group--0.1 D, 2. group--0.17 D), maximal keratometry and refraction (1. group--0.67 D, 2. group--0.76 D). Minimal keratometry and refraction in the 1. group decreased (1.17 D) and increased in the 2. group (1.09 D). In the evaluation based on the age was haze monitored in the first group one year after CXL in 12.5% of researched eyes. In the second group was haze of cornea in 20% of eyes and in the third group consisting of patients over 40 years old, in 50% of eyes. The average BCSVA was improved in the 1. group (2.85 letter), and in the 2. group (3.68 letter).The average BCSVA was decreased in the oldest patients in about 1.43 letter. In the 1. and 2. group the topographic analysis showed decrease of simulated keratometry and refraction (1. group--0.12D, 2. group--0.21D), maximal keratometry and refraction (1. group--1.13 D, 2. group--0,68D), minimal keratometry and refraction (1. group--1.17D, 2. group--0,69 D). In the 3. group the topography analysis showed increase of simulated keratometry and refraction (0,8D), maximal keratometry and refraction (0,98D), minimal keratometry and refraction (0,28D). Corneal pachymetry remained stable in all researched groups of patients. CONCLUSIONS: CXL is considered as safe procedure to stop progression of keratoconus also for patients until 19 years old. The best effect and minimal complications were by patients until 40 years old and by patients with the I. grade.

Intramuscular olanzapine vs. intramuscular short-acting antipsychotics: safety, tolerability and the switch to oral antipsychotic medication in patients with schizophrenia or acute mania.

BACKGROUND: This study compared the safety, tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular (IM) olanzapine or other IM antipsychotics for the treatment of acute agitation. METHODS: Patients (N = 2011) from 15 countries participated in this prospective, observational, non-interventional study. Inpatients requiring treatment with at least one IM injection of a short-acting antipsychotic were assessed at baseline and within 7 days after the first IM injection. Treatment groups comprised: (i) patients prescribed IM olanzapine at baseline; and (ii) patients prescribed any other IM antipsychotic medication at baseline. Outcome measures included: treatment-emergent adverse events, concomitant psychotropic medication and the time taken to switch to oral medication. RESULTS: Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group (34.4% vs. 46.2%, p < 0.001). The most frequently reported adverse events in both groups were: sedation, Parkinsonism, disturbance in attention, akathisia, dystonia and orthostatic hypotension. Fewer patients in the IM olanzapine group used anticholinergics (13.9% vs. 42.5%, p < 0.001) or anxiolytics/hypnotics (47.6% vs. 51.6%, p = 0.023). Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group (median time = 46.5 vs. 48.0 h, p = 0.009). CONCLUSIONS: These findings suggest that IM olanzapine may have a favourable impact on individual patients. However, the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone.

[Contrast sensitivity and higher order aberration after conventional LASIK treatment]. / Kontrastní citlivost a aberace vyssích rádu po konvencním LASIKu.

AIM: The aim of the prospective study was to evaluate photopic high-contrast visual acuity, mesopic contrast sensitivity, and high order aberrations, to compare changes and post-operative development of those parameters and to analyze the dependence among aberrations and contrast sensitivity after conventional LASIK treatment. MATERIALS AND METHODS: The authors followed-up patients treated by means of refractive LASIK treatment during the period from November 2006 to November 2007. The authors analyzed 51 eyes (31 patients). The average age of the group was 28.5 +/- 5.4 years (range, 18 - 41 years), preoperative average spherical equivalent was -4.95 +/- 1.24 D (from -3 to -8,25 D). Before the treatment and 1, 3, 6, and 12 months after LASIK treatment we evaluated the visual acuity (Snellen optotypes), contrast sensitivity under mesopic circumstances (CSV-1000E, VectorVision) and monochromatic aberrations (aberometer Zywave, Bausch & Lomb). RESULTS: One year after the treatment the average uncorrected visual acuity was 1.07 +/- 0.15, index of effectiveness 0.99, and index of safety 1.02. The contrast sensitivity was in month 12 significantly decreased comparing to the preoperative level at the frequency 12 c/deg, in other already tested frequencies after 3-6 moths did not differed from preoperative values. During the follow-up period the curvature of contrast sensitivity average values was in the upper half of the normal interval range. Conventional LASIK treatment significantly induced the higher order aberration (twice), as well as the spherical aberration (four times).The same level of higher order aberrations root mean square (HOA-RMS), or increased maximally by 0.1 microm was detected by 10 % of cases; the spherical aberration was, compared to the preoperative value, lower, or increased maximally by 0.05 microm in almost one half of the cases. The increase of the higher order aberrations depended directly proportionally to the preoperative value of the spherical equivalent. Before the treatment, the values of total aberrations correlated to the contrast sensitivity of low space frequencies; however, there was not found any correlation between the higher order aberrations and contrast sensitivity. Six months after the LASIK treatment the values of higher order aberrations correlated to the contrast sensitivity except of the lowest frequency tested. The higher order aberrations increased together with decreasing contrast sensitivity. The data from the one-year follow up control did not show statistically significant correlation between the contrast sensitivity and the higher order aberrations. There was not found any correlation between the contrast sensitivity and the spherical aberration at any follow-up control after the surgery. CONCLUSION: Although after the conventional LASIK treatment the curve of mesopic contrast sensitivity was located in the upper half of the normal range, in the medial space frequency it remained decreased comparing to the preoperative stage. The induction of higher order aberrations was twice as much and was directly correlated to the degree of the laser correction. The spherical aberration was four-times higher comparing to the preoperative values and was independent to the level of the initial refractive error. Significant correlation between the contrast sensitivity and the higher order aberrations was not proven.

[Changes of higher order aberrations and contrast sensitivity after standard photorefractive keratectomy]. / Zmeny aberací vyssích rádu a kontrastní citlivosti po standardní fotorefrakcní keratektomii.

UNLABELLED: The aim of the prospective study was to evaluate higher order aberrations and contrast sensitivity after photorefractive keratectomy (PRK) using the standard photoablation profile. MATERIALS AND METHODS: The group consisted of 37 patients (69 eyes), the mean age 27.2 +/- 4.5 years, who underwent PRK with target emetropia during the period January 2007 -December 2007. In 19 cases, it was correction of myopia, in 50 cases myopia with astigmatism.The preoperative spherical equivalent was -3.14 +/- 0.95 D. The PRK was performed by means of excimer laser system Technolas 217 (Bausch & Lomb) with the standard phoptoablation profile (PlanoScan 2000), using the 6.5 mm optical zone. The visual acuity, contrast sensitivity (CS; CSV-1000E, VectorVision) under mesopic circumstances and monochromatic aberrations (Zywave, Bausch & Lomb) were evaluated before the surgery, and 1,3, 6, and 12 months thereafter. The pair t-test, Wilcoxon test, and the Mann - Whitney U test (alpha = 0.05) were used for the statistical analysis. RESULTS: The PRK showed high index of effectiveness and safety (0.98, respectively 1.03 in the first year after the procedure). The contrast sensitivity under mesopic circumstances was not significantly involved after the PRK. The main value of the CS remained during the whole follow-up period within the physiological range in all spatial frequencies. Postoperatively, the part of spherical aberration on the higher order aberrations increased from 13.1% preoperatively to 16.6% one year after the PRK. In one half of the cases, the change of the higher order aberrations was within the range +/- 0.1 microm. In 66% of cases, the change of the spherical aberration was +/- 0.05 microm. The higher order aberrations comparing to the preoperative values decreased or remained unchanged approximately in one third of the cases, and the spherical aberration in one quarter of the cases. There was not established dependence between monochromatic aberrations values and the contrast sensitivity. CONCLUSION: Although the conventional RPK for low myopia treatment induces higher order aberrations including the spherical aberration, the impact on the contrast sensitivity under mesopic circumstances in our group were not significant. The contrast sensitivity of the most of patients was near the upper limit of the normal range.

[Therapy of acute promyelocytic leukemia in Czechia: results and analysis of prognostic factors]. / Lécba akutní promyelorytárni leukemie v Cesku: výsledky a analýza prognostických faktoru.

We have retrospectively evaluated a cohort of 144 patients (including 17 pediatric ones) with de novo acute promyelocytic leukemia registered in databases of institutions cooperating within the CELL group (The Czech Leukemia Study Group for Life). The patients were diagnosed according to WHO criteria from 1989 until 2006. The aim was to check how well fared the patients, the majority of whom was not included into clinical trials, in real life. Of 140 evaluable patients, 97 (69.3%) attained complete remission (CR). The projected overall survival (OS) 4 years after diagnosis was 58.9%, and 55.3% at 6 years. In 8 patients (6.0%), no antileukemic therapy at all was given (either they died shortly after admission to the ward or therapy was not feasible due to their clinical status). Of 125 patients with documented commencement of some kind of therapy, 96 (76.8%) achieved CR. Of 102 patients with induction treatment with a combination of anthracycline and tretinoin (ATRA), 84 individuals (82.4%) attained CR (typically, this cohort might have been subjected to clinical trials). This result was better than that of patients treated by chemotherapy only (n = 15; CR 46.7%; P = 0.003) or by ATRA monotherapy (n = 13; CR 62.5%; P = 0.17). Another parameter with a significant impact on attaining CR was the leukocyte (WBC) count at diagnosis: its median values in patients achieving and not achieving CR were 2.1 and 24.0 x 10(9)/l, respectively (P < 0.0001). The WBC counts affected OS as well (P = 0.0001). However, when only patients after attaining CR were evaluated, the initial WBC counts no longer affected OS (P = 0.18). Achieving CR was also influenced by the performance status (PS) 0-1 (P = 0.005), which was in turn closely correlated to WBC counts (P = 0.0006). Additional factors (most likely connected with leukocytosis) influenced attaining CR with borderline statistical significance: e.g. FAB M3v morphology, LDH serum level, fibrinogen level, presence of internal tandem duplication (ITD) of the FLT3 gene (which was strongly associated with leukocytosis and also with the short PML/RARalpha transcript resulting from the bcr3 break in the PML gene). It may be speculated that FLT3-ITD is just one of the possible factors that lead to leukocytosis. The platelet counts at diagnosis had no impact on entering CR. Thus, we have not validated the current PETHEMA risk stratification in distinguishing intertermediate and low risk patients. Our study points to a significant difference of the results obtained in real life and of the results that could be achieved in patients who were fit to enter clinical trials. Among the prognostic factors, the most important one was the WBC count, the PS (which is highly affected by the WBC count), and feasibility of administration of the most potent induction therapy with anthracyclines and ATRA.

Identification of somatic hypermutations in the TP53 gene in B-cell chronic lymphocytic leukemia.

Abnormalities of the TP53 gene are associated with a particularly severe prognosis in patients with B-cell chronic lymphocytic leukemia (B-CLL). This tumor-suppressor is mostly inactivated by the deletion of one and point mutation of the other allele and has not been previously shown to be hypermutated in B-CLL. We identified two patients whose lymphocytes showed repeatedly an extensive proportion of TP53 mutated cells by FASAY analysis (the yeast functional assay) and harbored various TP53 mutations, mostly single-base substitutions, in individual cells. The mutation targeting exhibited characteristic traits of the somatic hypermutation process. In the first patient (harboring the unmutated IgVH locus) a significant bias to point mutations at CG pairs (21/25; P=0.009), their remarkable preference for the RGYW/WRCY motives (28%) and the highest expression of the activation-induced cytidine deaminase (AID) mRNA among the 34 tested B-CLL samples. In the second patient no CG bias was observed but the targeting of point mutations into the RGYW/WRCY motives was even more prominent here (7/16; 44%). Moreover, six out of eight point mutations affecting AT pairs were localized in the WA/TW motives, which are also characteristic for the somatic hypermutations. This patient, who was IgVH-mutated, already did not express any significant amount of the AID transcript. Our findings add a new aspect to the mosaic of the p53 mutability in B-CLL.