Selected articles

06/2018 Prof. MUDr. Jiří Hoch, CSc., FCMA
Surgery is a basic, irreplaceable and yet the only curative way of oncotherapy of colon and rectum cancer. In the review, the important moments of the tumors of both two localities are mentioned - the extent of resection on the gut or the rectum, the extent of lymphadenectomy, the removal of the mesocolon or mesorectum, conventional and mini-invasive surgical approach, anastomosis, anastomotic complications and their prevention, some perioperative aspects such as intestinal preparation and antibiotic prophylaxis, solution of acute conditions and the position of surgery among other modalities of oncological treatment.

06/2018 Doc. MUDr. Igor Kiss, Ph.D.
Diagnosis and treatment of colorectal cancer is a typical example of interdisciplinary collaboration. Individualized treatment is based on well-established diagnostics, taking into account the extent of the disease, molecular predictors, general condition, and patient preferences. Patients with advanced disease should be presented at an interdisciplinary indication board.

06/2018 MUDr. Michal Voška, MUDr. Tomáš Grega, MUDr. Gabriela Vojtěchová, Mgr. Ondřej Ngo, RNDr. Ondřej Májek, Ph.D., Mgr. Barbora Bůčková, MUDr. Ilja Tachecí, Ph.D., MUDr. Marek Beneš, prof. MUDr. Jan Bureš, CSc., prof. MUDr. Julius Špičák, CSc., prof. MUDr. Miroslav Zavoral, Ph.D., doc. MUDr. Štěpán Suchánek, Ph.D.
Background: Fecal immunochemical tests havebeen used as an initial test in colorectal cancer screening programs. However, majority of patients don't have advanced neoplasia on colonoscopy. Colon capsule endoscopy has the potential to reduce the need for optical colonoscopy. The main aim of the study was a negative predictive value of the second generation of colon capsule endoscopy for large polyps (? 10 mm). The secondary aims were: accuracy of detection of all polyps (polyps ? 6 mm and ? 10 mm) and cancers, the number of complications and target population acceptance of both methods (colon capsule endoscopy and optical colonoscopy).
Material and methods: In this multicentre (three gastroenterology units) feasibility study, the second generation of colon capsule endoscopy (CCE2) has been prospectively compared with OC in persons with positive semi-quantitative FIT with cut-off level 75 ng/ml. Colonoscopy was performed within 10 hours after capsule ingestion. CCE2 videos were viewed independently by a nurse and a physician, both blinded to the results of OC. Complications were assessed as severe (bleeding, perforation) or mild to moderate. The methods of acceptance were evaluated based on the questionnaire completed after both procedures (CCE2 and OC) were finished. The interim analysis of results is presented.
Results: From April 2016, 167 individuals have been enrolled; data from 95 persons have been analyzed. During the optical colonoscopy, polyps were diagnosed in 70 persons (74%), polyps ? 6 mm and ? 10 mm in 42 (44 %) and 26 (27 %) persons, respectively. The sensitivity of CCE2 for polyps ? 6 mm and ? 10 mm was 88 % (95% confidence interval [CI] 74-96 %) and 85 % (95% CI 65-96 %), respectively. The specificity for polyps ? 6 mm and ? 10 mm reached 85 % (95% CI 72-93 %) and 93 % (95% CI 84-98 %), respectively. The negative predictive value of CCE2 for polyps ? 10 mm was 94 % (95% CI 86-98 %). Nurses identified 36 polyps ? 6 mm of 42 (86 %) and 23 polyps ? 10 mm of 26 (88 %) found on OC. A total of 64 patients (68 %) preferred CCE2 as the primary screening method.
Conclusion: The second generation of colon capsule has appeared to have a high negative predictive value for the detection of clinically relevant colorectal neoplasia in a screening population. This method might be considered as an adequate tool for colorectal cancer screening.

06/2018 MUDr. Tomáš Grega, doc. MUDr. Štěpán Suchánek, Ph.D., prof. MUDr. Miroslav Zavoral, Ph.D.
Colorectal cancer screening is an effective tool for reducing the incidence and mortality of this disease. This is demonstrated by epidemiological data and microsimulation models too. Effective colorectal cancer screening can be achieved based on a population screening program where each individual is addressed and invited to the screening. Screening in the Czech Republic does not reach the minimum recommended coverage according to the international recommendation, where the target coverage by screening is at least 45 % of population. These results show that there is still space for improvement, especially there is needed to continue with address invitation to screening and continue in efforts to increase coverage by screening, for example by lowering the age limit for screening colonoscopy and introducing a central office for address invitations with a central evaluation of occult blood tests.

05/2018 Doc. MUDr. Samuel Vokurka, Ph.D.
The role of supportive and nursing care is crucial in oncology. It prevents and solves the difficulties and complications caused by cancer and oncological treatment. It has a proven effect on improving the quality of life and oncological treatment outcomes. It addresses both physical and psychosocial and educational issues. Multidisciplinary collaboration among specialists, nurses and patients is essential.

05/2018 MUDr. Mária Zvariková
Treatment of epithelial ovarian cancer is historically based on surgery and platinum doublet chemotherapy and is associated with high risk of relapse and poor prognosis in recurrent disease. Innovative treatment with PARP inhibitors has demonstrated an outstanding activity in epithelial ovarian cancer and is currently changing clinical practice in patients with BRCA mutation in genes.

05/2018 MUDr. Vít Martin Matějka
These two case studies describe panitumumab in the management of patients with metastatic colorectal carcinoma. There was rapid response in both cases. In the first case report, we describe complete remission of disease after six courses of biochemotherapy. In the second case the patient has recurrence of the disease after surgery. However the treatment continued with panitumumab and time to progression was about two years. Both patients benefited from targeted therapy of panitumumab with a very good quality of life.

05/2018 Doc. MUDr. Ondřej Urban, Ph.D., MUDr. Přemysl Falt, Ph.D.
Endoscopic resection of precancerous colorectal lesions is one of the most effective methods of oncological prevention. It reduces the incidence and mortality of colorectal cancer. Endoscopic resection is also the first-choice method for carcinomas with a zero or very low risk of metastasis. The methods of endoscopic polypectomy and endoscopic mucosal resection are now practiced in the Czech Republic in virtually all endoscopic workplaces. Conversely, endoscopic submucosal dissection and endoscopic transmural resection are still available only in several endoscopic centers.

05/2018 MUDr. Stanislav John
Colorectal carcinoma is heterogenous disease. Methods of molecular testing reveals new alterations, often without better understanding. However, some of these molecular tests, such as KRAS/NRAS or BRAF mutations, are already projected into daily practice. Microsatellite instability represents one of these detectable changes. Nor it helps us to decide on adjuvant chemotherapy, but it is increasingly important with the advent of drugs that affect the immune system.

05/2018 MUDr. Kateřina Kamarádová
Colorectal carcinoma is morphologically, phenotypically and genetically hererogeneous disease. Accurate evaluation of the extent of the bowel, lymph nodes and other organs (pathological and clinical staging) is necessary for a selection of adequate treatment options according to the valid guidelines. Currently, there is a focus on finding and evaluation parameters and markers defining biological behavior of colorectal carcinoma or influencing treatment response of the tumor (prognostic and predictive factors). These factors include morphological, imunophenotypical and molecular factors concerning the tumor itself as well as its non-neoplastic microenvironment. The aim of the article is to review the standardly used as well as potentially new factors underlining the heterogeneity of colorectal carcinoma but also playing role in patient treatment and prognosis stratification.

05/2018 MUDr. Bohdan Kadlec, Ph.D.
Atezolizumab (Tecentriq®) is a new drug from a number of immunotherapeutics and the first programmed death-ligand (PD-L1) antibody approved for metastatic non-small cell lung cancer patients who have progressed during frontline chemotherapy. Atezolizumab is an antibody to PD-L1 engineered to avoid antibody-dependent cell-mediated cytotoxicity of activated T cells that may express PD-L1 and activates the tumor-specific immune response while preserve immune homeostasis in normal tissue by sparing the interaction of PD-L2 with PD-1. The approval was based on two open-label phase II/IM multicenter trials, that demonstrates good safety profile and benefit for atezolizumab in overall survival, progression-free survival, and response rate when compared to docetaxel regardless of PD-L1 expression. A prospective role in the first line in combination with chemotherapy and bevacizumab appears to be a promising one.

05/2018 MUDr. Libor Havel
Immunotherapy as a new treatment modality is currently widely accepted and perceived as a modality in NSCLC treatment, which is changing the prognosis of patients in the long term. But it is not entirely clear how immunotherapy is suitable for patients of advanced age.

05/2018 MUDr. Lenka Jakubíková, Ph.D.
Vinorelbine is a second generation semisynthetic vinca alkaloid that has a low affinity for neurotubules, resulting in lower neurotoxicity. Vinca alkaloids are mitotic poisons that prevent the proper formation of microtubules by binding to tubulin. They cause depolymerization of microtubules and dissolution of the mitotic spindle, thereby blocking cell division and causing damage to other processes depending on the proper functioning of the microtubules. In oncology vinorelbine has a wider use, especially in metastatic breast cancer and non-small cell lung cancer, where it is applicable at all stages of non-adjuvant and palliative treatment.

05/2018 Prof. MUDr. Jana Skřičková, CSc., Mgr. Blanka Robešová, Ph.D., MUDr. Ondřej Venclíček, MUDr. Bohdan Kadlec, Ph.D., MUDr. Marcela Tomíšková, MUDr. Lenka Jakubíková, Ph.D., MUDr. Jana Špeldová, MUDr. Zdeněk Merta, CSc.
In the case of non-small cell lung cancer (NSCLC), the existence of somatic mutations in the epidermal growth factor receptor (EGFR) gene and their effect on the sensitivity to the treatment of tyrosine kinase inhibitors (TKI) is known. Mutations occur in the tyrosine kinase domain between EGFR exon 18 and 21, predominantly point deletions and deletions, eventually insertions. In exons 19 and 21, 80-90% of known activating mutations of EGFR are concentrated. The so-called activation mutations include the G719X point mutation in exon 18, the L858R and L861Q point mutations in exon 21 and the deletion in exon 19. Among so-called resistant mutations are the insertions in exon 20, the T790M and S768I point mutations in exon 20, and the D761Y mutation in exon 19. The mutation rate of the EGFR gene in the Caucasian population is 10%. In NSCLC patients experiencing activation mutations for EGFR, the most effective treatment is with tyrosine kinase inhibitors. In our paper, we investigate the activation and resistance mutations of the EGFR gene and provide an overview of the results of first, second and third generation of TKI treatment.

05/2018 Prof. MUDr. Miloš Pešek, CSc.
In a review author present the state - of the art of diagnostics and therapy of advanced non-small cell lung cancer with ALK and ROS1 genes rearrangements. Diagnostic processes are realized in specialized pathologic departments with the help of histology, imunohistochemistry and fluorescent in situ hybridization. Patients suffering by either with ALK positive NSCLC, or ROS1 positive non-small cell lung cancer reach significant benefits from targeted therapy with ALK and ROS1 tyrosinkinase inhibitors. In ALK positive advanced non-small cell lung cancer international guidelines recommend to treat with crizotinib, ceritinib or alectinib, while in cases of failure of this therapy, brigatinib should be the second line biologic treatment. In ROS1 positive advanced NSCLC, crizotinib or ceritinib are recommended accordingly to international guidelines. However, in the Czech Republic, there is no approval of those drugs in first line setting.

05/2018 MUDr. Petr Jakubec, Ph.D.
Pulmonary epithelioid hemangioendothelioma (PEH) is a rare sarcomatous tumor. The disease affects more women and has the highest incidence in lower middle age. There is currently no diagnostic clinical or laboratory PEH marker. The clinical picture of the disease is nonspecific and very variable. The PEH diagnosis is based on histological, immunohistochemical examination of a biopsy tumor sample. Because of the low degree of malignancy, a relatively good prognosis for solitary disorder and sometimes spontaneous remission occurs. The opposite is the case for multiple lesions, including metastases or multicenter affections of different organs, where they behave very aggressively, and any treatment is usually ineffective. The only standard treatment is resection for operable lesions. There is currently no demonstrably effective PEH therapy. The course of the disease is very variable, and the prognosis of the disease is unpredictable.

05/2018 MUDr. Eva Sedláčková
Thymomas and thymic carcinomas are relatively rare tumours, some of them are often accompanied by autoimmune diseases. Article deals with epidemiology, diagnosis, classification, therapy and dispensarisation of epithelial thymic tumours based on contemporary ESMO guidelines¹ and own 38 years experience.

05/2018 Prof. MUDr. Vítězslav Kolek, DrSc.
In clinical practice, the majority of tumors affecting pleura are tumors of other primary location, as they generalize. The most common primary tumor in this area is malignant mesothelioma.
Its cause is mostly contact with asbestos and the incidence is increasing even though working with asbestos in European countries is already prohibited. Diagnosis is based primarily on immunohistochemical examination of the tumor. The main treatment has been chemotherapy with the combination of cisplatin and pemetrexed in the last 10 years. Tumor aggression is high, and it cannot be fully cured. The surgical approach is limited by appropriate selection of patients and sufficient experience of the workplace. Extrapleural pneumonectomy is performed and lately preferred enlarged pleurectomy in combination with adjuvant or neoadjuvant chemotherapy or radiotherapy. However, randomized trials did not show any significant prolongation of survival compared to standard chemotherapy. Unfortunately, the same can still be said of a large number of studies with biologically targeted treatment, immunotherapy and other drugs. However, research into the genetic and biological characteristics of the tumor is still ongoing and endeavor to improve patient prognosis is enormous.

05/2018 MUDr. Marcela Tomíšková, MUDr. Lenka Jakubíková, Ph.D., MUDr. Bohdan Kadlec, Ph.D., MUDr. Jana Špeldová, prof. MUDr. Jana Skřičková, CSc.
Neuroendocrine pulmonary neoplasms are a group of rare tumors. Their incidence is 1.35 cases per 100,000 inhabitants. They form a heterogeneous group from well and moderately differentiated carcinoids to very aggressive low differentiated carcinomas. Diagnosis is based on pathomorphology, immunohistochemical examination and neuroendocrine differentiation. Individual types of neuroendocrine pulmonary neoplasms (differ from one another by localization, biological behavior, clinical picture, diagnosis, and treatment approaches. Low differentiated carcinomas (LCNEC, SCLC) are aggressive, sensitive to chemotherapy and radiation but have a poor prognosis. For well and moderately differentiated neuroendocrine pulmonary neoplasms (typical and atypical carcinoid) captured in operable stage, surgical removal of the tumor leads to its complete cure. Analogs of somatostatin receptors, peptide receptor radionuclide therapy or m-TOR inhibitor (mammalian target of rapamycin) represent a new therapeutic potential in treatment of recurrent or inoperable neuroendocrine pulmonary neoplasms grade I and II.

04/2018 PharmDr. Lenka Vostalová, Ph.D.
The review explains historical development of pricing and reimbursement regulation of pharmaceuticals in the Czech Republic. It mentions time milestones with references to the key parts of the legislation related to the process of appraisal and assessment in pricing and reimbursement of therapies. In the CR, the determined reimbursement prices and conditions are a result of a complex evaluation of the added value represented by the assessed pharmaceutical, which reflects its level of comparative efficacy, safety, and quality-of-life benefits, compared to the other medicinal approaches and technologies reimbursed from the public health insurance resources in the relevant indication.