Case report Ileal diverticulitis with covered perforation complicated by pulmonary embolism - case report.

Diverticulitis of the ileum is an inflammatory complication of diverticulosis. It is an uncommon cause of acute abdomen that can have a very serious course, leading, for example, to intestinal perforation or bleeding. Imaging findings are very often negative and the true cause of the condition is only revealed peroperatively. In this case report, we present a case of perforated ileal diverticulitis in a patient with bilateral pulmonary embolism. This was the main reason for conservative management in the first period of time. After resolution of the pulmonary embolism, resection of the affected bowel segment was performed at the time of the next attack.

[Glucose, Lactate, NGAL and Coefficient of Energy Balance in Synovial Fluid in Patients with Hip and Knee Prosthetic Joint Infection]. / Stanovení hladiny glukózy, laktátu, NGAL a KEB ve výpotku u infekcí TEP kolen a kyclí.

PURPOSE OF THE STUDY Laboratory methods are central to prosthetic joint infection (PJI) diagnosis. Most research teams focus on detection of specific inflammatory markers, causative pathogens, or on assessment of the tissue response. This study sought to determine the optimal cut-off values and diagnostic performance of selected synovial markers in relation to the diagnosis of hip or knee PJI. The studied markers were synovial level of glucose, lactate, coefficient of energy balance (CEB) and NGAL (neutrophil gelatinase-associated lipocalin). MATERIAL AND METHODS This prospective study includes 89 patients who underwent revision total knee or hip arthroplasty for septic or aseptic reasons in the period from 2014 to 2017. Among these 89 patients, there are 2 cases of prosthetic hip infection, 22 cases of prosthetic knee infection, 31 aseptic revision total hip arthroplasties and 34 aseptic revision total knee arthroplasties. The diagnostic characteristics of the studied methods were set in relation to the reference standard, the 2013 MSIS (Musculoskeletal Infection Society) criteria. The cut-off values were calculated using the ROC (receiver operating characteristic curve) analysis. RESULTS The synovial glucose test is considered positive if the glucose level drops below 2.65 mmol/L. The area under the curve is 0.813, sensitivity 75.0%, specificity 83.1%. The synovial lactate test is considered positive if lactate level rises above 8.87 mmol/L. The area under the curve is 0.882, sensitivity 70.8%, specificity 95.4%. Synovial NGAL is considered positive if its level exceeds 998 µg/L. The area under the curve is 1.000, sensitivity 100.0%, specificity 100.0%. CEB is considered positive if its value is lower than +4.665. The area under the curve is 0.883, sensitivity 91.7% and specificity 69.8%. Combining of these tests with other synovial markers does not improve the diagnostic performance of the studied tests. CONCLUSIONS The glucose and lactate levels and CEB undoubtedly reflect the presence of an inflammatory process in a prosthetic joint. However, the diagnostic characteristics of these tests are not better than those of other modern diagnostic techniques. As opposed to these tests, synovial NGAL shows excellent diagnostic performance. Nonetheless, the potential of this method shall be verified on larger cohorts of patients. Key words: prosthetic joint infection, periprosthetic infection, total knee arthroplasty, total hip arthroplasty, diagnosis, glucose, lactate, CEB, NGAL.

Quality of life after transanal total mesorectal excision - our experience.

INTRODUCTION: Functional outcomes and quality of life (QoL) after transanal total mesorectal excision (TaTME) are very important factors in the evaluation of TaTME in comparison with other approaches to TME. The most common functional problems after resection of the rectum include bowel, urologic and sexual dysfunctions. In this study, we present our experience with QoL after TaTME; the results are compared with worldwide literature in the discussion. METHODS: QoL was assessed by a questionnaire. The total of 54 patients were analysed. A general questionnaire for oncological diseases was used - European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30, together with EORTC-QLQ-CR29 - a specific questionnaire for colorectal cancer. The Low Anterior Resection Syndrome (LARS) score was also obtained in all patients. Mean follow-up was 42.65 months (range 9-91 months). RESULTS: The mean LARS score in patients undergoing TaTME was 30.7 while a major LARS was observed in 64.2% of those with LARS. Of all of the symptoms in the EORTC-QLQ-C30 survey, the most serious problems which affected patients undergoing TaTME were diarrhoea (30.25), fatigue (23.87) and insomnia (20.37). In the QLQ-CR29 survey the problems included flatulence (50.94), faecal incontinence (45.06) and stool frequency (35.19). The results of EORTC-QLQ-C30 and QLQ-CR29 are quite heterogeneous. CONCLUSION: In this study the QoL of patients with advanced rectal tumours (of whom 81.5% received neoadjuvant therapy) undergoing TaTME is comparable to results in the current literature. The most severe symptoms affecting QoL after TaTME are flatulence, faecal incontinence, and stool frequency. Other serious symptoms include fatigue and insomnia. LARS was recorded in 73.6% of patients undergoing TaTME, mostly a major LARS.

Appendiceal mucocele - a radiologists view.

Appendiceal mucocele is an obstructive dilatation of the appendix, which results from the filling of its lumen with mucus. This is a rare condition that is asymptomatic in half of the patients. Its severity depends on the cause of appendiceal dilatation. In a small percentage of cases, the dilated appendix ruptures, leading to the development of serious complication; this is termed as pseudomyxoma peritonei. Due to the possibility of malignant etiology of the mucocele, surgical resection remains an essential part of the treatment.

Different chromosome damage in lymphocytes of newly diagnosed gastrointestinal and breast cancer patients.

Structural chromosome aberrations are a predictive biomarker of cancer risk. Conventional chromosome analysis widely used for these purposes detects unstable chromosome aberrations that are eliminated during cell division. Stable aberrations that may persist in the body and tend to accumulate during a lifetime can be detected by fluorescence in situ hybridization (FISH). The aim of the study was to investigate the level of chromosome damage in newly diagnosed cancer patients and control subjects by FISH. Both groups of untreated cancer patients had increased frequency of aberrant cells. However, chromosome damage affected different cytogenetic endpoints. Stable translocations and cells with complex rearrangements were elevated in breast cancer patients whereas unstable chromosome aberrations (dicentric chromosomes and acentric fragments) were elevated in gastrointestinal cancer patients. These associations observed in nonsmokers were typically not pronounced in smokers (with the exception of dicentric chromosomes in gastrointestinal patients). Exposure to tobacco smoke increased aberrations in healthy controls but not in the cancer patients. Our study suggests an association between cancer and stable chromosomal rearrangements in breast cancer patients. Unstable aberrations elevated in gastrointestinal cancer patients may be at least partly ascribed to the exposure to diagnostic X-rays.

Our experience with transanal total mesorectal excision (TaTME) procedures in middle and distal rectal tumors.

INTRODUCTION: Transanal total mesorectal excision (TaTME) is a relatively new approach in surgical treatment of rectal cancer. There are no clear indications when to choose this strategy. It is a technically demanding procedure for the surgeon with a long learning curve, which should also be taken into account in evaluation of this method. The results of both oncological and postoperative complications must be properly evaluated to explore the benefit of TaTME. The aim of this study is to assess the potential benefit of TaTME compared to other alternatives in middle and distal rectal tumors. METHODS: Retrospective evaluation of patients undergoing TaTME procedure performed by one team of surgeons between October 2014 and June 2019. The authors analyzed demographic indicators of the group of patients, tumor characteristics, specimen quality, early postoperative complications and the possibility of stoma reversal. RESULTS: A total of 93 patients underwent TaTME procedure for middle and distal rectal cancer. Mean BMI was 27.6 (4.8). T3 or T4 tumor was found in 73 (78.5%) patients, 68 (73.1%) patients had positive lymph nodes and 12 (12.9%) patients were treated for synchronous metastatic rectal cancer. Neoadjuvant therapy was used in 80 (86%) patients. Conversion to open laparotomy was necessary in one case (1%). Stapled anastomosis was performed in 37 (39.7%) cases, handsewn in 56 (60.2%). A positive circumferential resection margin (CRM) was found in 10 (10.7%) cases. Distal resection margin (DRM) was positive in 3 (3.2%) patients. Pathological analysis showed a complete mesorectum in 18 patients (19.4%), nearly complete in 39 (41.9%) and an incomplete mesorectum in 36 (38.7%). Complications in the first 30 days after primary surgery were observed in 38 (40.8%) patients, mainly for anastomotic leak (19 patients, 20.4%). Reoperation was required in 7 (7.5%) patients. Permanent colostomy had to be performed in 4 (4.3%) cases. No patient died after surgery. CONCLUSION: In a selected group of patients it is possible to perform resection using this approach with acceptable postoperative morbidity and quality of the specimen. We used TaTME procedure in patients expected to have difficult TME due to obesity, size and distal localization of tumor. The incidence of conversion to open surgery was very low. Further studies for long term oncological outcomes are needed.

Use of preperitoneal wound catheter for continuous local anaesthesia after laparoscopic colorectal surgery.

INTRODUCTION: The main cause of postoperative pain after abdominal surgery is the wound where laparotomy is made. Recently, laparoscopic procedures have become common in colorectal surgery. Although improving the tolerance of the surgery, postoperative pain management still remains a discussed problem. The use of an epidural catheter used to be generally recommended in the open surgery era; however, an ideal strategy for postoperative analgesic therapy after laparoscopy remains unclear. Reduced administration of opioid analgesic drugs after colorectal resection is a generally accepted goal. Preperitoneal catheter insertion for continuous local anaesthetic (LA) infusion in the wound after surgery is a simple alternative to other pain management methods. METHODS: Retrospective analysis of analgotherapy outcomes in patients undergoing laparoscopic colorectal resection procedures, divided in three patient groups according to the type of analgesia: Group 1: use of a catheter for local wound infusion (KAT) n=73; group 2: epidural analgesia (EPI) n=23; and control group 3 with combined parenteral and subcutaneous analgesia (CON) n=66. The main objective of this study was to analyse postoperative pain and the consumption of opioid analgesics in the first three days from the surgery and the incidence of any complications related to the analgesic therapy. RESULTS: Opioid consumption in KAT and EPI groups was significantly lower compared to CON in the first 72 hours from the surgery. The lowest postoperative pain was measured in the EPI group. Subjective perception of pain, measured using VAS, was not significantly different between the KAT and CON groups. In KAT patients, vomiting was statistically less frequent than in CON patients. There was no significantly different incidence of paralytic ileus in the KAT and CON groups and no paralytic ileus was observed in the EPI group. There was no increased incidence of SSI (surgical site infections) in the KAT group compared to the other groups. CONCLUSION: The use of the catheter was assessed as safe. Insertion and management of the catheter is unsophisticated, and we did not observe any complications in terms of application of the catheter or toxic side effects of the LA. The use of the catheter clearly reduced opioid administration in the postoperative period compared to the control group (CON) with combined parenteral and subcutaneous analgesics. The best pain control measured using the visual analog scale (VAS) was observed in the EPI group.

Flow Cytometric Analysis of Nucleoside Transporters Activity in Chemoresistant Prostate Cancer Model.

BACKGROUND: Nucleoside analogues represent a relevant class of antimetabolites used for therapy of various types of cancer. However, their effectivity is limited by drug resistance. The nucleoside transport capability of tumour cells is considered to be a determinant of the clinical outcome of treatment regimens using antimetabolites. Due to hydrophilic properties of antimetabolites, their transport across the plasma membrane is mediated by two families of transmembrane proteins, the SLC28 family of cation-linked concentrative nucleoside transporters (hCNTs) and SLC29 family of energy-independent equilibrative nucleoside transporters (hENTs). Loss of functional nucleoside transporters has been associated with reduced efficacy of antimetabolites and their derivatives and treatment failure in diverse malignancies including solid tumours, such as pancreatic adenocarcinoma. MATERIAL AND METHODS: The effectivity and kinetics of antimetabolite uptake were analysed using control and docetaxel-resistant PC3 cells. For this purpose, fluorescent nucleoside analogue probe uridine-furane and inhibitor of nucleoside transporters, S-(4-nitrobenzyl) -6-thioinosine were exploited. Combination of flow cytometry, confocal microscopy and real-time quantitative polymerase chain reaction methodology were used for the analysis. RESULTS: Here we utilized flow cytometric assay for analysis of nucleoside transporters activity employing fluorescent nucleoside analogue, uridine-furane. We have determined the long-time kinetics of uridine-furane incorporation and quantified its levels in the parental prostate cancer cell line PC3 and its chemoresistant derivative. Finally, we have shown an association between the activity and mRNA expression of nucleoside transporters and sensitivity to various nucleoside analogues. CONCLUSION: Fluorescent techniques can serve as an effective tool for the detection of nucleoside transporter activity which has the potential for application in clinical oncology.Key words: nucleoside transporter proteins - drug resistance - prostatic neoplasm - chemotherapy.

[Pilot Study on MicroRNAs as Biomarkers of Response to Sunitinib Treatment in Patients with Metastatic Renall Cell Carcinoma]. / MikroRNA jako biomarkery odpovedi na lécbu sunitinibem u pacientu s metastatickým karcinomem ledvin - pilotní studie.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2-3% of all malignant tumours. Metastatic RCC (mRCC) is commonly treated with tyrosine kinase inhibitors (TKI). Effective TKIs administration can be achieved only by accurate prediction of therapeutical response. Therefore, the aim of this study was to analyse papers concerning predictive potential of microRNA (miRNA). MATERIAL AND METHODS: We chose seven candidate miRNAs and analysed their expression on 44 patients divided into cohort with poor and good response to sunitinib treatment. Patients were divided into two groups according to progression-free survival. RNA from tissue samples was isolated and expression of selected miRNAs was measured using quantitative PCR with miRNA-specific TaqMan probes. RESULTS: We successfully validated two miRNAs to be differentially expressed in responding and non-responding patients to sunitinib treatment. Other analysed miRNAs have not shown predictive potential. CONCLUSION: From miRNAs studied so far, two miRNAs had predictive value according to present study.Key words: microRNA - renal cell carcinoma - sunitib 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. Supported by Ministry of Health of the Czech Republic, grant No. 15-34678A. All rights reserved.Submitted: 19. 3. 2018Accepted: 20. 3. 2018.

[Biomonitoring of Work with Genotoxic Substances and Factors in a Cancer Treatment Facility]. / Biomonitoring práce s genotoxickými látkami a faktory v onkologickém zdravotnickém zarízení.

BACKGROUND: A long-term occupational exposure of healthcare staff to cytostatics and ionizing radiation is associated with a possible manifestation of their genotoxic, carcinogenic and teratogenic effects. MATERIAL AND METHODS: A total number of 101 employees working with cytostatics or ionizing radiation were examined (some of them repeatedly) in a cancer treatment facility. The control group consisted of 119 persons excluded from the risk exposure. Fluorescence in situ hybridization with three pairs of whole-chromosomal probes and a pancrossomeric probe was used and the translocation frequency was determined. RESULTS: The total number of chromosomal rearrangements of healthcare professionals and control group correlates with age. Taking into account the age dependence, an increased level of chromosomal reconstruction was found in the case of 11 individuals, 10 of which were female, working on the positions of pharmacist, general nurse, physician. A total of 9 of those case involved the work with cytostatics. Five of these cases were re-examined two years later and the observed levels dropped to the control level. CONCLUSION: The results of biomonitoring should be evaluated on a group basis and individually, taking into account the personal history and possible non-professional effects on individuals - in particular those related to specific environmental measurement results.Key words: preventive medicine - occupational exposure - cytostatic agents - chromosome aberrations - in situ hybridization - fluorescence The authors declare they have no potential conflicts of interest concern ing drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. This work was supported by project of Ministry of Health Czech Republic. reg. No. 15-33968A.Submitted: 12. 4. 2018Accepted: 16. 4. 2018.

[Experimental processing of corrosion casts of large animal organs]. / Experimentální príprava korozivních preparátu orgánu velkého zvírete.

INTRODUCTION: Corrosion casts (CCs) are used for the visualization and assessment of hollow structures. CCs with filled capillaries enable (with the help of imaging methods) to obtain data for mathematical organ perfusion modelling. As the processing is more difficult in case of organs with greater volume of the vasculature, mainly organs from small animals have been cast up to now. The aim of this study was to optimize the protocol of corrosion casting of different organs of pig. Porcine organs are relatively easily accessible and frequently used in experimental medicine. METHOD: Organs from 10 healthy Prestice Black-Pied pigs (6 females, body weight 35-45 kg), were used in this study (liver, spleen, kidneys and small intestine). The organs were dissected, heparin was administered into the systemic circulation and then the vascular bed of the organs was flushed with heparinized saline either in situ (liver) or after their removal (spleen, kidney, small intestine). All handling was done under the water surface to prevent air embolization. The next step was an intraarterial (in case of the liver also intraportal) administration of Biodur E20® (Heidelberg, Germany) resin. After hardening of the resin the organ tissue was dissolved by 15% KOH and the specimen was rinsed with tap water. Voluminous casts were stored in 70% denatured alcohol, the smaller ones were lyophilized. The casts were assessed with a stereomicroscope, computed and microcomputed tomography (CT and microCT), a scanning electron microscope (SEM) and high-resolution digital microscope (HRDM). RESULTS: High-quality CCs of the porcine liver, kidneys, spleen and small intestine were created owing to the sophisticated organ harvesting, the suitable resin and casting procedure. Macroscopic clarity was improved thanks to the possibility of resin dying. Scanning by CT was performed and showed to be a suitable method for the liver cast examination. MicroCT, SEM and HRDM produced images of the most detailed structures of vascular bed. Despite the fact that SEM seems to be an irreplaceable method for CCs quality control, it seems that this modality could be partly replaced by HRDM. MicroCT enabled to obtain data about three-dimensional layout of the vascular bed and data for mathematical modelling of organ perfusion. With regard to the quality of the CCs, they could also be used to teach human anatomy. CONCLUSIONS: The protocol of the corrosion casting of the porcine liver, kidneys, spleen and small intestine CCs was optimized. Thanks to different imaging methods, the CCs can be used as a source of data on three-dimensional architecture of the vascular bed. These data can be used for mathematical modeling of organ perfusion which can be helpful for example for optimization of organ resections.Key words: corrosion casts microvasculature Biodur E20® domestic pig animal model.

[Current Possibilities for Predicting Responses to EGFR Blockade in Metastatic Colorectal Cancer]. / Soucasné moznosti predikce odpovedi na cílenou anti-EGFR lécbu metastatického kolorektálního karcinomu.

BACKGROUND: The combination of modern systemic chemotherapy and anti-EGFR monoclonal antibodies improves overall survival and quality of life for patients with metastatic colorecal cancer. By contrast, the addition of anti-EGFR therapy to the treatment regime of resistant patients may lead to worse progression-free survival and overall survival. Therefore, identifying sensitive and resistant patients prior to targeted therapy of metastatic colorecal cancer is a key point during the initial decision making process. Previous research shows that primary resistance to EGFR blockade is in most cases caused by constitutive activation of signaling pathways downstream of EGFR. Of all relevant factors (mutation of KRAS, NRAS, BRAF, and PIK3CA oncogenes, inactivation of tumor suppressors PTEN and TP53, amplification of EGFR and HER2, and expression of epiregulin and amphiregulin, mikroRNA miR-31-3p, and miR-31-5p), only evaluation of KRAS and NRAS mutations has entered routine clinical practice. The role of the other markers still needs to be validated. The ongoing benefit of anti-EGFR therapy could be indicated by specific clinical parameters measured after the initiation of targeted therapy, including early tumor shrinkage, the deepness of the response, or hypomagnesemia. The accuracy of predictive dia-gnostic tools could be also increased by examining a combination of predictive markers using next generation sequencing methods. However, unjustified investigation of many molecular markers should be resisted as this may complicate interpretation of the results, particularly in terms of their specific clinical relevance. AIM: The aim of this review is to describe current possibilities with respect to predicting responses to EGFR blockade in the context of the EGFR pathway, and the utilization of such results in routine clinical practice.

[Recommended Extension of Indication Criteria for Genetic Testing of BRCA1 and BRCA2 Mutations in Hereditary Breast and Ovarian Cancer Syndrome]. / Doporucení rozsírení indikacních kriterií ke genetickému testování mutací v genech BRCA1 a BRCA2 u hereditárního syndromu nádoru prsu a ovarií.

Genetic testing for hereditary breast and ovarian cancer syndrome is indicated by a genetic counselor on the basis of personal and family history evaluation, with regards to consensual criteria, reflecting the current knowledge. The latest recommendation accepted by Czech Oncology Society and Society of Medical Genetics was published in the supplement 22 to the Journal of Clinical Oncology in 2009. Since the availability of PARP inhibitors for treatment of ovarian cancer in BRCA1/ 2 mutation carriers, an update of these guidelines is urgently needed. Another reason is a higher incidence of other malignancies in high-risk families, such as prostate or pancreatic cancer. The goal is to refine the detection of mutations in selected families, to improve preventive care and collect data necessary for targeted cancer treatment.

[Retrospective NGS Study in High-risk Hereditary Cancer Patients at Masaryk Memorial Cancer Institute]. / Retrospektivní NGS studie u vysoce rizikových pa-cientu s hereditární predispozicí k nádorovému onemocnení v Masarykove onkologickém ústavu.

BACKGROUND: Currently, more than 200 hereditary cancer syndromes have been described, yet, in most countries genetic testing is restricted to a narrow spectrum of genes within a limited group of people tested. METHODS: For this retrospective study we used the TruSight cancer panel (Illumina)--NGS panel targeting 94 cancer predisposition genes in order to analyze 50 high-risk cancer patients with significant personal and family history of cancer who did not carry mutations in BRCA1, BRCA2, MLH1, MSH2, MSH6, TP53 or APC genes. All pathogenic and potentially pathogenic mutations detected by NGS technology have been confirmed by Sanger sequencing. RESULTS: There were several deleterious (frame-shift/nonsense) mutations detected in ATM, BAP1, FANCC, FANCI, PMS2, SBDS, ERCC2, RECQL4 genes. Various pathogenic or potentially pathogenic (missense, predicted splice site, in-frame insertion/deletion) mutations were detected in ATM, BRIP1, CDH1, CHEK2, ERCC2, ERCC3, ERCC4, FANCA, MC1R, MEN1, MRE11A, MUTYH, PALB2, RAD51C, RET, SDHB, STK11. These mutations affect highly conserved protein domains and affect their function as proved by the available functional assays. They were confirmed to be pathogenic as an "Parent No2 " in serious recessive diseases such as Ataxia telangiectasia or Fanconi anemia. The clinical significance of the majority of detected missense variants still remains to be identified. CONCLUSION: Moderate or low penetrance variants are of limited clinical importance. Panel genetic testing in high-risk individuals with cancer provides important information concerning the cause of the investigated cancer, and may assist in the risk assesment and optimal management of the cancer, as well as in further preventive care.

Occurrence and Fate of Trace Contaminants during Aerobic and Anaerobic Sludge Digestion and Dewatering.

Digestion of municipal wastewater biosolids is a necessary prerequisite to their beneficial use in land application, in order to protect public health and the receiving environment. In this study, 13 pharmaceuticals and personal care products (PPCPs), 11 musks, and 17 polybrominated diphenyl ethers were analyzed in 84 samples including primary sludge, waste activated sludge, digested biosolids, dewatered biosolids, and dewatering centrate or filtrate collected from five wastewater treatment plants with aerobic or anaerobic digestion. Aerobic digestion processes were sampled during both warm and cold temperatures to analyze seasonal differences. Among the studied compounds, triclosan, triclocarban, galaxolide, and BDE-209 were the substances most frequently detected under different treatment processes at levels up to 30,000 ng/g dry weight. Comparing aerobic and anaerobic digestion, it was observed that the levels of certain PPCPs and musks were significantly higher in anaerobically digested biosolids, relative to the residues from aerobic digestion. Therefore, aerobic digestion has the potential advantage of reducing levels of PPCPs and musks. On the other hand, anaerobic digestion has the advantage of recovering energy from the biosolids in the form of combustible gases while retaining the nutrient and soil conditioning value of this resource.

[Immunotherapy for the Prevention and Treatment of Breast Cancer]. / Imunoterapie v prevenci a lécbe karcinomu prsu.

The immune system is believed to play a dual role in carcinogenesis. On one hand, it could prompt tumorigenesis and cancer progression, on the other hand, it has the capacity to eradicate tumor cells. There has been an evidence of natural immunogenicity in breast cancer and we have also witnessed several attempts to stimulate non-specific antitumor immune response (Coleys toxin, BCG vaccine etc.). New technologies and further knowledge of molecular basis of immune system and its function encouraged the development of effective immunotherapy capable of inducing a solid antitumor activity. These agents appear promissing in the prevention and therapy of breast carcinoma as well. The assumption is based on the results of several antitumor vaccine trials targeted against HER2, MUC1, CEA and mammaglobin-A, as well as immune checkpoint inhibitors (e.g. CTLA-4, PD-1/ PD-L1, LAG3). With regards to different mech-anisms of action of these agents, their combination might bring about synergistic antitumor effects. Nonetheless, monoclonal antibodies and cytostatic agents already approved for breast cancer treatment might be exploited for their immunomodulation effect as well. This article addresses prospects for immunotherapy of breast carcinoma in detail.

[Triple Negative Breast Cancer]. / Triple negativní karcinom prsu.

BACKGROUND: In the Czech Republic, around 6,500 women get breast cancer each year; out of this number, nearly 1,000 women are triple negative subtype. Triple negative breast cancer is characterized by lack of expression of α-estrogen, progesterone, and HER2 receptors. Vast majority of these cases are low-differentiated carcinomas, majority belonging to the basal-like subgroup defined originally by DNA chips. Clinically, they are characterized by greater aggressiveness, frequent rate of local recurrence and organ metastases. They are more common in younger women and are associated with the occurrence of hereditary forms of breast cancer caused by pathogenic mutations in the BRCA1 gene and in rare cases also BRCA2. AIM: The objective of this review is to provide comprehensive information about current knowledge of triple negative breast cancer. This paper summarizes information about epidemiology and etiopathogenesis of this disease, describes risk factors for both sporadic and hereditary forms of triple negative breast cancer, addresses histopathologic and molecular classification of triple negative breast cancer, and these characteristics associates with treatment and prediction of disease development. The article also addresses new anticancer drugs tested for triple negative breast cancer. CONCLUSION: Triple negative breast cancer is a heterogeneous group of diseases with limited therapeutic options. The key to further shift in therapy is detailed knowledge of its clinical and molecular diversity and identification of predictive biomarkers. Further improvement of therapy results of triple negative breast cancer cannot be expected before targeted therapy of this disease is found.

[Function of CDK12 in Tumor initiation and progression and its clinical consequences]. / Úloha CDK12 v iniciaci a rozvoji nádoru a její klinické konsekvence.

Cyclin-dependent kinases (CDKs) participate in many cellular processes and play a crucial role in the regulation of cell cycle and transcription processes. Recently, CDK12 was identified as a key factor orchestrating transcription of genes, such as BRCA1, ATM, ATR, FANCI and FANCD2, which are involved in the DNA-damage response pathway. Importantly, inhibition of function of these genes commonly leads to induction of genomic instability followed by cancer development, but the precise contribution of CDK12 to these processes is to be unveiled. Nevertheless, several mutations affecting function of CDK12 were already identified in a variety of tumors of different origin (ovary, breast, prostate, intestine) making tumors sensitive to cytostatics promot-ing DNA damage (platin derivatives, alkylating regimens) and inhibitors of DNA repair (PARP inhibitors). Such an effect has been already observed in the model of high grade serous ovarian carcinomas. Thus, CDK12 is becoming a potential therapeutic target of drugs causing synthetic lethality in these cells. Our review summarizes most recent information about CDK12 function in cancer and discusses potential use of CDK12 in clinics.

[Lobular breast cancer in man - case report and review of the literature]. / Lobulární karcinom prsu u muze - kazuistikaa prehled literatury.

CASE: Herein we report a case of a man with a B- cell non-Hodgkin lymfoma, primarily diagnosed by topographic and morfology tokens as lobular breast carcinoma and, as such, it was treated by chemotherapy and endocrine therapy. The treatment resulted in complete remission for 3,5 years. However, the subsequent relapses that arised in retrocrural and left axilary area did not respond adequately to breast cancer targeted chemotherapy. Therefore the patient underwent re-exstirpation of axillary lymph node yielding a surprising histology finding of folicular lymphoma. The primary biopsy specimen was histologicaly reevaluated and the initial dia-gnosis was reclassified as folicular lymphoma. The patient was given an adequate chemotherapy and targeted treatment that established a complete remission. Six months afterwards there was a relapse detected in the retrocrural area. The patient underwent palliative radiotherapy that brought about complete remission and, so far, he is in good condition. It has been eight years since the cancer dia-gnosis was established. This case report is appended by review of literature dealing with diagnostic confusion of these two malignancies. CONCLUSION: Re -biopsy plays a significant role in case of treatment strategy controversies, predominantly on condition of atypical course of malignant disease. It should always be considered in case of cancer relapse, especially if the phenotype specfication could affect the treatment decision.

Cancer incidence and mortality in the Czech Republic.

BACKGROUND: The Czech Republic ranks among the countries with the highest cancer burden in Europe as well as worldwide. The purpose of this study is to summarize longterm trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates after 2011. DATA AND METHODS: The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information collected over a 34-year period of standardized registration covering 100% of cancer diagnoses within the entire Czech population. The CNCR analysis is supported by demographic data and by the Death Records Database. An overview of the epidemiology of malignant tumors in the Czech population is available online at www.svod.cz. RESULTS: All neoplasms, including nonmelanoma skin cancer, reached a crude incidence rate of almost 802 cases per 100,000 men and 681 cases per 100,000 women in 2011. The annual mortality rate exceeded 258 deaths per 100,000 individuals; in other words, more than 27,000 individuals die of cancer each year. The overall incidence of malignancies has increased with a growth index of +27.6% during the last decade (2001- 2011), while the mortality rate has been stabilized over the time span (growth index in 2001- 2011: - 5.0%). Consequently, the prevalence has significantly increased in the observed period and exceeded 475,000 cases in 2011. In addition to demographic aging of the Czech population, the cancer burden has also increased due to the growing incidence of multiple primary tumors (recently more than 15% of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer, and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e. g. the proportion of stage I or II was 75.3% for female breast cancer and 84.2% for skin melanoma), the numbers of early diagnosed cases are generally insufficient, even in the case of highly prevalent cancers such as colorectal carcinoma (only 46.1% of incident cases are diagnosed at stage I or II, according to recent data). CONCLUSION: Population-based data on malignant tumors are available in the Czech Republic. The data survey can help us define national cancer management priorities. The current priority is to achieve a sustained reduction of cases diagnosed at an advanced stage and reduction of the significant regional differences in diagnostic efficiency.