[Prognostic and Predictive Factors for Pancreatic Adenocarcinoma]. / Prognostické a prediktivní faktory u adenokarcinomu pankreatu.

BACKGROUND: Pancreatic ductal adenocarcinoma is a highly aggressive disease with 5-year overall survival not exceeding 5%. In the Czech Republic, the incidence of this tumor has been increasing; according to recent statistics, the Czech Republic is already number one worldwide in the occurrence of this malignancy. Delayed diagnosis due to asymptomatic course of the disease in the early stages is characteristic for this disease. AIM: The objective of this article is to give an overview of the most important factors, which according to current knowledge of pancreatic adenocarcinoma have a prognostic and predictive potential. This work describes both traditional prognostic factors, such as tumor resectability, its extent and localization, application of adjuvant chemotherapy, microscopically positive resection margin, presence of metastases in lymph nodes, histological grade, vascular and perineural invasion. Further, the paper lists a number of different biological markers that could contribute to early detection of cancer, better prognosis and optimization of treatment, for example hENT1 (human equilibrative nucleoside transporter-1), SPARC (secreted protein acidic and rich in cysteine), AGR2, Bcl-2, VEGF, Ki-67, COX-2 and more. Also, genetic mutations and significance of microRNA are discussed. CONCLUSION: Despite great efforts that have been devoted to the research of biological markers, so far the only clinically accepted and used marker is CA 19-9. Its use is primarily in patients already diagnosed with adenocarcinoma of the pancreas. A lot of attention has recently been focused on other potential biomarkers, their application in clinical practice would however still require further research.Key words: carcinoma pancreatic ductal biological tumor markers prognosis prognostic factorsThe authors declare they have no potential confl icts 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: 16. 2. 2016Accepted: 17. 2. 2016.

[A case report: patient with metastatic goblet cell carcinoid]. / Pacientka s metastatickým karcinoidem z pohárkových bunek.

BACKGROUND: Goblet cell carcinoid represents a unique entity of appendiceal neoplasia. Its pathological features and clinical behavior are distinct from the classic carcinoid tumor as well as primary adenocarcinoma of the appendix. Correct histopathological classification and diagnosis provide guidelines for treatment and prognosis. Morphological transformation of the Goblet cell carcinoid from typical Goblet cell carcinoid to adenocarcinoma morphology is likely associated with accumulation of additional genetic changes that is why subclassification of this group of tumors is needed. Investigation of molecular genetic changes could increase our understanding of this exotic but clinically important group of tumors. CASE: We present the case of a patient with metastatic goblet cell carcinoid involving terminal ileum, ascendent colon, ovary, omentum and peritoneal spreading, treated with debulking surgery and chemotherapy (FOLFOX4 regimen) with good response, reduction of disease on CT and PET complete remission. Improvement of clinical symptoms as well as quality of life was reached by combined palliative treatment. CONCLUSION: Correct diagnostics and therapeutic efforts bring patient benefit even in metastatic setting. Better knowledge of rare tumors and understanding of their biology help improve therapeutic approaches.

Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer.

PURPOSE: To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m(2) intravenously weekly x 7 for 8 weeks, then weekly x 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. RESULTS: Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P =.75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade > or = 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. CONCLUSION: The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

[Concomitant chemoradiotherapy in tumors of the pancreas]. / Konkomitantní chemoradioterapie u nádoru pankreatu.

Pancreatic tumors are malignancies with poor prognosis. The total five-year survival is achieved only in 1-2% of patients of all stages. Only the surgical approach represent a curative treatment. Unfortunately, in the time of diagnosis, only 10-20% of tumours are in the resectable stages. The main reason is probably the low specificity of initial symptoms. Local control of this disease can be improved by adjuvant chemoradiotherapy, however, without effects on the overall survival. In potential resectable tumours the concomitant chemoradiotherapy can increase the probability of curative resection. Treatment of locally advanced inoperable tumours is considered as palliative treatment and therefore it is focused namely on the improvement of the quality of the patient's life. Supporting care must become an inseparable part of the concomitant chemoradiotherapy.

[Diagnosis and therapy of pancreatic tumors]. / Komplexní diagnostika a terapie nádoru slinivky brisní.

Pancreatic tumours belong among oncological diseases with a very poor prognosis. The total five-year survival is 1-2%. Surgical resection with a curative intention increases the probability of five-year survival to 10-20%. However only some 10% tumours are diagnosed in the resectable stage. The reason is the low specificity of initial symptoms. Earlier diagnosis and improvement of survival could be promoted by improvement of imaging methods and endoscopic techniques. Improvement of therapeutic results in selected indications can be achieved by adjuvant treatment (chemotherapy, radiotherapy, possibly their combination). Treatment of inoperable stages of the disease is focused in particular on improvement of the quality of the patient's life. Its aim is specially to mitigate pain and reduce the consumption of analgesics, to ensure bile derivation or release the passage through the digestive tract. This can lead also to improvement of the patient's general condition. Despite advances in molecular biology of pancreatic cancer the results of systemic treatment remain unsatisfactory in advanced tumours. Nevertheless therapeutic nihilism must not prevail nowadays. It is necessary to use new findings in diagnosis and therapy. Patients with this disease should be included in clinical trials investigating optimal therapeutic procedures.

Pressurised liquid extraction of ketones of polycyclic aromatic hydrocarbons from soil.

Pressurised liquid extraction (PLE) was used in the extraction of three ketones of polycyclic aromatic hydrocarbons from the sample of a soil highly contaminated with polycyclic polyaromatic compounds. The choice of solvent was the only factor that considerably influenced the extraction efficiency of PLE under the conditions recommended in Method 3545A promulgated by the United States Environmental Protection Agency. The dichloromethane-ethanol solvent mixture was found to be the most efficient solvent. PLE using this mixture provided better recoveries of all analysed ketones relative to Soxhlet extraction.

Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.

BACKGROUND: Irinotecan is active against colorectal cancer in patients whose disease is refractory to fluorouracil. We investigated the efficacy of these two agents combined for first-line treatment of metastatic colorectal cancer. METHODS: 387 patients previously untreated with chemotherapy (other than adjuvant) for advanced colorectal cancer were randomly assigned open-label irinotecan plus fluorouracil and calcium folinate (irinotecan group, n=199) or fluorouracil and calcium folinate alone (no-irinotecan group, n=188). Infusion schedules were once weekly or every 2 weeks, and were chosen by each centre. We assessed response rates and time to progression, and also response duration, survival, and quality of life. Analyses were done on the intention-to-treat population and on evaluable patients. FINDINGS: The response rate was significantly higher in patients in the irinotecan group than in those in the no-irinotecan group (49 vs 31%, p<0.001 for evaluable patients, 35 vs 22%, p<0.005 by intention to treat). Time to progression was significantly longer in the irinotecan group than in the no-irinotecan group (median 6.7 vs 4.4 months, p<0.001), and overall survival was higher (median 17.4 vs 14.1 months, p=0.031). Some grade 3 and 4 toxic effects were significantly more frequent in the irinotecan group than in the no-irinotecan group, but effects were predictible, reversible, non-cumulative, and manageable. INTERPRETATION: Irinotecan combined with fluorouracil and calcium folinate was well-tolerated and increased response rate, time to progression, and survival, with a later deterioration in quality of life. This combination should be considered as a reference first-line treatment for metastatic colorectal cancer.

[Regional chemotherapy of liver tumors]. / Regionální chemoterapie nádoru jater.

Based on experience with regional intrahepatic chemotherapy in 67 patients with inoperable primary, and in particular secondary liver tumours, which comprises several hundred administered cycles of mostly continuous regional regimens, the authors summarize briefly the main principles and possibilities of this treatment. In a review of randomized studies they provide evidence for the advantage of regional chemotherapy, as compared with systemic treatment, in particular with regard to the higher percentage of therapeutic responses. In correctly indicated, and if possible early cases of hepatic tumourous affections, it is possible to potentiate the effect of regional chemotherapy by local destruction of tumourous foci by alcoholization, cryodestruction or resection. An integral part of this treatment is also monitoring of the effect by following up the dynamics of serum levels of tumour markers and by imaging methods. Because the most frequent cause of failure of this method are extrahepatic secondaries and secondary chemoresistance of the tumourous foci, improvement of results can be expected in particular from a combination of regional and systemic chemotherapy and the inclusion of cytokines into the therapeutic schemes.

[Cytokines in regional immunochemotherapy of liver tumors]. / Cytokiny v regionální imunochemoterapii nádoru jater.

Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve, as compared with the little effective systemic chemotherapy, a higher percentage of therapeutic responses. The objective of regional chemoimmunotherapy, i.e. the use of cytokines, in particular interferon alpha (IFN-a) and interleukin-2 (IL-2) in the therapeutic regimens is to improve the survival of patients with malignant liver tumours. One of the main prerequisites of the effect of locally administered cytokines is activation of hepatic lymphocytes (LAL)-liver associated lymphocytes, effectors with specific phenotype and potential anti-tumourous effect directly in the target area. Although in regional monotherapy the effectiveness of cytokines is low, regimens combining the administration of cytostatics with IL-2 achieve a 50-70% therapeutic response. The authors summarize basic data on the regional administration of cytokines and present an review of combined regimens of regional chemoimmunotherapy, including their own protocol of the Masaryk Oncological Institute in Brno.