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Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.
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Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/terapia , Paraganglioma/diagnóstico , Paraganglioma/genética , Paraganglioma/terapia , Carcinogênese , Transformação Celular Neoplásica , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/terapiaRESUMO
BACKGROUND/AIM: To evaluate the prognostic value of Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST and volumetric analysis in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). PATIENTS AND METHODS: This single-center prospective cohort study included a total of 61 patients with HCC treated by transarterial chemoembolization (TACE). The response of TACE was evaluated on preprocedural and postprocedural CT by two radiologists using RECIST/mRECIST and volumetric response to treatment. Each response assessment method was used to classify the response as progressive disease, stable disease, partial response and complete response. Kaplan-Meier analysis with log-rank test was performed for each method to evaluate its ability to help predict overall survival and progression free survival. Interobserver variability and reproducibility was determined by the Pearson and Spearman correlation coefficients. RESULTS: The median overall survival was 17.1 months and the median progression-free survival was 11.1 months. Volumetric assessment was proved to be a prognostic factor for overall survival (p<0.01) and progression-free survival (p<0.001), contrasting with RECIST and mRECIST. All three methods featured very small interobserver variability (p<0.001 for Pearson and Spearman correlation coefficients). The patients classified as having stable disease had a 3.8-fold higher risk of death than the patients classified as having a complete/partial response (HR=3.82; 95% Confidence Interval (CI)=1.32-11.02; p=0.013) and a 4.5-fold higher risk of progression (HR=4.46; 95% CI=1.72-11.61; p=0.002). CONCLUSION: The prognostic value of volumetric analysis in patients with HCC treated by TACE appears to be superior to RECIST and mRECIST, with a real impact in everyday practice.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Humanos , Neoplasias Hepáticas/terapia , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid cystic carcinoma. Recent studies revealed its expression also in osteosarcoma cell lines and suggested its functional importance during bone development. However, the relevance of c-Myb in control of osteosarcoma progression remains unknown. A retrospective clinical study was carried out to assess a relationship between c-Myb expression in archival osteosarcoma tissues and prognosis in a cohort of high-grade osteosarcoma patients. In addition, MYB was depleted in metastatic osteosarcoma cell lines SAOS-2 LM5 and 143B and their growth, chemosensitivity, migration and metastatic activity were determined. Immunohistochemical analysis revealed that high c-Myb expression was significantly associated with poor overall survival in the cohort and metastatic progression in young patients. Increased level of c-Myb was detected in metastatic osteosarcoma cell lines and its depletion suppressed their growth, colony-forming capacity, migration and chemoresistance in vitro in a cell line-dependent manner. MYB knock-out resulted in reduced metastatic activity of both SAOS-2 LM5 and 143B cell lines in immunodeficient mice. Transcriptomic analysis revealed the c-Myb-driven functional programs enriched for genes involved in the regulation of cell growth, stress response, cell adhesion and cell differentiation/morphogenesis. Wnt signaling pathway was identified as c-Myb target in osteosarcoma cells. Taken together, we identified c-Myb as a negative prognostic factor in osteosarcoma and showed its involvement in the regulation of osteosarcoma cell growth, chemosensitivity, migration and metastatic activity.
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Neoplasias Ósseas , Osteossarcoma , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Osteossarcoma/patologia , Prognóstico , Estudos Retrospectivos , Via de Sinalização WntRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient's blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.
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BACKGROUND: The aim of the paper is to present the current recommendations and indications of venous access in oncology which reflect and recognize the opinions of national and international professional societies. It focuses exclusively on the indications of intravenous catheter placement for anticancer treatment, such as medium-term and long-term venous accesses. MATERIALS AND METHODS: The survey results obtained from a national questionnaire of 24 oncology centers identified the current situation in the Czech Republic. There were evaluated relevant data on the number of and the criteria for the introduction of venous accesses provided by physicians. Comparisons were made between current oncological practice and recommendations provided by evidence-based medicine. RESULTS: At each center surveyed in the Czech Republic, an average of 130 ports and 80 permanent implanted central catheters are introduced annually. The ports are increasingly indicated, with over a half of the centers surveyed introducing ports to more than 100 patients a year, with four centers introducing a total of 1,600 ports annually. In all centers, the decision for venous access is made by an oncologist. However, most procedures are performed by a doctor of another specialization, most often by a surgeon, a radiologist or an anesthesiologist. More than a half of the indications for venous access placement result from poor peripheral venous system or complications of parenteral therapy, not from comprehensive assessment prior to the initiation of the therapy. CONCLUSION: Based on our findings, we developed general indications and recommendations for venous access to cancer patients which represent the consensus of an interdisciplinary team of specialists, predominantly from the committee of professional societies - the Society for Ports and Permanent Catheters, the Working Group of Nutritional Care in Oncology of the Czech Oncological Society and the Society of Clinical Nutrition and Intensive Metabolic Care. The number of introduced venous access catheters remains insufficient to meet the needs in the Czech Republic, which necessitates increased awareness and possibilities for safe drug administration.
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Antineoplásicos/administração & dosagem , Cateterismo Venoso Central/normas , Cateteres de Demora/normas , Neoplasias/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Humanos , Sociedades Médicas , Inquéritos e QuestionáriosRESUMO
RATIONALE: The Ewing sarcoma family of malignant tumors is a group of tumors characterized by morphologically similar round-cell neoplasms and by the presence of a common chromosomal translocation; Ewing sarcoma family of tumors typically occur in children and young adults between 4 to 15âyears of age. The primary tumor usually originates in the bone, extraskeletal localization is rare. PATIENT CONCERN: We present a case report concerning a 32-year-old male patient with a primary involvement of the penis. DIAGNOSIS: The histopathology from the first penile biopsy showed a small-cell neuroendocrine carcinoma; however, that result was based on a sample obtained at a different facility than the Sarcoma Center, where the investigating pathologist did not have the adequate expertise. The patient then underwent a radical penectomy and a second reading of the histology was demanded after a radical penile amputation when Ewing sarcoma with R1 resection was confirmed. INTERVENTIONS: The patient was referred to the national Sarcoma Center, where - using a multidisciplinary approach - the treatment was started with curative intent. However, it was preceded by a non-standard initiation of the therapy due to the poor primary diagnosis. OUTCOMES: The non-standard therapy at the onset of the disease caused a poor prognosis of an otherwise curable diagnosis. Despite all that, the patient survived for a relatively long time. LESSONS: The treatment of sarcomas with atypical localizations should be conducted by an experienced multidisciplinary team in a center with experience in sarcoma treatment.
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Neoplasias Penianas/patologia , Sarcoma de Ewing/patologia , Adulto , Humanos , Masculino , Pênis/patologiaRESUMO
BACKGROUND: Rechallenge with oxaliplatin is common in the treatment of colorectal cancer and increases the risk of a detrimental oxaliplatin-induced immune reaction. Allergic reactions to oxaliplatin may be partially avoided by desensitization protocols involving immune suppressive drugs, slow administration and gradually increasing chemotherapeutic doses. However, non-IgE-mediated immunopathologic reactions to oxaliplatin remain challenging and may be potentially life-threatening. CASE PRESENTATION: Here we report two potentially fatal cases of type II hypersensitivity to oxaliplatin in metastatic colorectal cancer patients. Both patients manifested with severe thrombocytopenia, intravascular haemolysis, and acute kidney injury 4-6â¯h after oxaliplatin administration in a rechallenge setting. Serology revealed that the reactive entity for immune haemolysis was an IgG oxaliplatin-induced antibody. The course of anti-cancer treatment and severe adverse event after oxaliplatin rechallenge including diagnostic dilemma and the results of detailed routine clinical chemistry and hematology testing are described. Extended immunohaematology/serology testing revealed that the oxaliplatin-induced IgG antibody was present in the circulation prior to the onset of hypersensitivity, persisted for months and elicited cross-reactivity with other platinum agents. CONCLUSION: Development of type II hypersensitivity reaction manifesting as a sudden onset of severe thrombocytopenia and immune haemolysis must be considered in patients treated with oxaliplatin, especially those on long-term therapy or when rechallenged. Step-wise diagnosis involves clinical presentation, detection of haemolysis in patient's blood and/or urine, evaluation of platelet count, and direct anti-globulin Coombs test.
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Adenocarcinoma/diagnóstico , Antineoplásicos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Oxaliplatina/efeitos adversos , Neoplasias Retais/diagnóstico , Injúria Renal Aguda , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Corticosteroides/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Dessensibilização Imunológica , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/uso terapêutico , Neoplasias Retais/complicações , Neoplasias Retais/tratamento farmacológico , TrombocitopeniaRESUMO
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) represent a group of medicaments inhibiting cyclooxygenase (COX) enzyme, and, in parallel, these drugs show also analgesic, antipyretic and anti-inflammatory effects. Due to their efficiency, good tolerance and easy availability, they belong to the worlds most used drugs. For decades, evidence of their anti-tumor activity has been growing, with the largest amount of published work being related to colorectal cancer (CRC). Based on both in vitro and in vivo experiments and data obtained from epidemiological and clinical studies, potential application of NSAID as chemo-preventive treatment for CRC patients is recently discussed in order to prevent development or recurrence of precanceroses and tumors. Promising treatment for such indication would be acetylsalicylic acid (ASA), which is the oldest, more than 100 years used member of the NSAID family. Nonselective irreversible COX inhibition is an important but probably not solely mechanism of its anticancer activity. Notably, wider use of ASA in chemoprevention is also prevented due to particular concerns about gastrointestinal and renal toxicity caused especially by its long-term use. AIMS: This review introduces the role of COX in tumor biology of CRC and highlights the results of the most interesting experiments illustrating the anti-tumor effect of ASA. Moreover, our work evaluates the most important published clinical analyzes of the ASA chemopreventive effect on CRC and discusses the current state. Key words: non-steroidal anti-inflammatory agents - acetylsalicylic acid - colorectal carcinoma - cyclooxygenase - chemoprevention This work was supported by the projects MEYS - NPS I - LO1413, MH CZ - DRO (MMCI, 00209805) and by Czech Science Foundation project no. 16-14829S. 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. Accepted: 10. 9. 2017.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Anticarcinógenos/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Quimioprevenção , Neoplasias Colorretais/metabolismo , Humanos , Prostaglandina-Endoperóxido Sintases/metabolismoRESUMO
Ewing sarcoma (ES) is an exceptionally rare tumor in adults. Data regarding outcomes of adult patients with ES and experiences with age-adapted therapeutic strategies are very limited. The aim of this study was to evaluate prognostic factors and clinical outcome in a cohort of adult patients treated according to pediatric protocols in the Czech Republic. The records of 58 adult ES patients diagnosed between 2002 and 2013 were reviewed and factors relevant to prognosis and survival were analyzed. The median age of study cohort was 29 years (range, 18-59). The most frequent location was axial (36.2%), followed by involvement of extraskeletal tissues (34.5%) and bones of the extremities (29.3%). Twenty-eight (48.3%) patients had metastatic disease. In cases with localized ES, the 5-year overall survival (OS) was 76.5%. Using the log-rank test, the presence of metastasis at diagnosis, local treatment without surgery and a failure to achieve complete remission were associated with significantly shorter survival. In a multivariate Cox proportional hazard analysis, the achievement of complete remission was an independent predictor of patients's survival time. Outcomes of adults with localized ES treated according to multimodal pediatric protocols are similar to children. The achievement of complete remission is an independent predictor of survival time in ES patients. Severe hematological toxicity is foreseeable and manageable. Prognosis of patients with metastases or progression remains dismal.
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Neoplasias Ósseas/terapia , Neoplasias Pulmonares/terapia , Sarcoma de Ewing/terapia , Adolescente , Adulto , Neoplasias Ósseas/patologia , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoma de Ewing/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on malnutrition or systemic inflammatory response in 91 metastatic or recurrent gastric cancer patients considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute. We investigated their overall survival according to the following measures: Onodera's Prognostic Nutritional Index (OPNI), Glasgow Prognostic Score (GPS), nutritional risk indicator (NRI), Cancer Cachexia Study Group (CCSG), as previously defined, and a simple preadmission weight loss. The OPNI, GPS, and CCSG provided very significant prognostic values for survival (log-rank test P value < 0.001). For example, the median survival for patients with GPS 0 was 12.3 mo [95% confidence interval (CI): 7.7-16.7], whereas the median survival for patients with GPS 2 was only 2.9 mo (95% CI: 1.9-4.8). A significantly worse survival of malnourished patients was also suggested by a multivariate model. The values of GPS, OPNI, and CCSG represent useful tools for the evaluation of patients' prognosis and should be part of a routine evaluation of patients to provide a timely nutrition support.
Assuntos
Inflamação/complicações , Desnutrição/complicações , Neoplasias Gástricas/diagnóstico , Idoso , Caquexia , Feminino , Humanos , Masculino , Análise Multivariada , Metástase Neoplásica/terapia , Recidiva Local de Neoplasia , Avaliação Nutricional , Estado Nutricional , Prognóstico , Qualidade de Vida , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico , Redução de PesoRESUMO
BACKGROUND/AIMS: Urokinase (uPA) is a serine protease, which together with uPAR, tPA, PAI 1 and PAI 2 forms the plasminogen activator system, a component of metastatic cascade contributing to the invasive growth and angiogenesis of malignant tumours. METHODOLOGY: Both preceding therapy and after 6-8 weeks of the treatment, plasma PAI 1 levels (photometric microplate method on the ELISA) and uPA, uPAR, PAI 1 and PAI 2 tissue expression (immunohistochemical reaction) were analysed from 80 colorectal carcinoma patients. RESULTS: Analysis showed higher pre-treatment plasma levels of PAI 1 in patients with advanced tumours, which decreased after surgery or the start of therapy (p=0.004); Patients with higher plasma level PAI 1 before (0.013) and after therapy (0.004) had significantly shorter survival. There was a higher expression of uPA (p<0.001), uPAR (p<0.001), PAI 1 (p=0.042) and PAI 2 (p<0.001) in advanced colorectal carcinoma. A relationship between PAI 2 (p=0.010) and uPAR (p=0.019) expression and survival was demonstrated. There is a correlation between pre-treatment plasma PAI 1 levels and PAI 2 (p=0.028) and uPAR (p=0.043) expression. CONCLUSIONS: Immunohistochemical analysis of PAS in tumour tissue and plasma PAI 1 levels was found to be a useful prognostic factor in colorectal carcinoma patients. Plasma PAI 1 could be advantageous in evaluating the effectiveness of a mode of treatment.
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Neoplasias Colorretais/metabolismo , Inibidor 1 de Ativador de Plasminogênio/sangue , Inibidor 2 de Ativador de Plasminogênio/análise , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Ativador de Plasminogênio Tipo Uroquinase/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/análiseRESUMO
BACKGROUND/AIMS: To prospectively evaluate our palliative management of unresectable cholangiocarcinoma (CC) treated with tailored multimodal oncological therapy. METHODS: Between January 2005 and January 2010, 50 consecutive patients with unresectable CC and jaundice were palliated with percutaneous drainage. Forty-three patients underwent metallic-stent implantation followed by brachytherapy. Patients were divided into two arms: the intra-arterial chemotherapy arm (IA arm, n=17) consisted of patients treated with locoregional treatment (IA admission of Cisplatin and 5-fluorouracil, or chemoembolization with Lipiodol) and/or systemic chemotherapy, while the systemic chemotherapy arm (IV arm, n=23) included all the other patients, who were treated only with systemic chemotherapy. RESULTS: In total, 78 metal self-expandable stents were placed. Hilar involvement with mass-forming and periductal infiltrating types of CC (84%) was predominant. The average number of percutaneous interventional procedures was 11.61 per patient (range, 4-35). The median overall survival from diagnosis of disease for all patients was 13.5 months (range, 11.0-18.8 months). The median overall survival times were 25.2 months (range, 15.2-31.3 months) and 11.5 months (range, 8.5-12.6 months) in the IA and IV arms, respectively (p<0.05). The 1-, 2-, and 3-year survival rates in the IA and IV arms were 88.2%, 52.9%, and 10.1% and 43.5%, 25.4, and 0%, respectively. There were no major complications (WHO III/IV) due to interventional procedures. CONCLUSIONS: We could reach acceptable prognosis in patients with unresectable CC using complex tailored oncological therapy. However, the main limitations of prolonging survival are performance status, patient compliance and the maintaining of biliary tract patency.