Marcela Tomíšková, Lenka Jakubíková, Bohdan Kadlec, Jana Špeldová, Jana Skřičková
Jana Skřičková, Blanka Robešová, Ondřej Venclíček, Bohdan Kadlec, Marcela Tomíšková, Lenka Jakubíková, Jana Špeldová, Zdeněk Merta
Ondřej Urban, Přemysl Falt
Vít Martin Matějka
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.
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.
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.
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.
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.
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.
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.
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.
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.
Morphology, staging, prognostic and predictive factors of colorectal carcinoma – the pathologist’s point of view
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.
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.
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.
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.
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.
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.