Chemotherapy for advanced colorectal patients: daily practice results may not reflect the outcomes of prospective clinical trials

Introduction. Colorectal cancer is the second cause of cancer deaths worldwide. The development of new drugs in recent years has improved the outcomes, but it is not clear whether this progress also includes patients managed in daily clinical practice. Treatment outcomes in patients with advanced colorectal cancer treated in Poland outside of clinical trials are scare. Methods. We analyzed the results of first-line chemotherapy in 165 patients with advanced colorectal cancer treated between May 2010 and December 2013 in two institutions. Results. The mean patient age was 61 ± 8.7 years; 105 patients received irinotecan-based regimens (CLF1 or XELIRI), 41 oxaliplatin-based regimens (FOLFOX4 or XELOX) and 19 patients received single-agent 5-fluorouracil. A partial response was achieved in 48 patients (29%), stable disease in 71 (43%) and 46 patients (28%) progressed during treatment. Median survival in the entre group was 14 months. Respective average response rate and median overall survival in recent clinical trials were 39% and 17 months, respectively. Compared to single agent treatment, multidrug chemotherapy was associated with increased general toxicity (p = 0.039), in particular with higher occurrence of diarrhea (p = 0.003) and peripheral neuropathy (p < 0.001). There was no apparent impact of chemotherapy on overall quality of life. Conclusions. Treatment results of advanced colorectal cancer in daily practice may be worse than those obtained in prospective clinical trials. The use of palliative chemotherapy has no noticeable impact on quality of life

Automatic Diachronic Normalization of Polish Texts

The paper presents a method for the automatic diachronic normalization of Polish texts – the procedure, which, for a given historical text, returns its contemporary spelling. The method applies finite-state transducers, defined in a sublanguage of the Thrax formalism. The paper discusses linguistic issues, such as evolution in spelling of the Polish language, as well as implementation aspects, such as efficiency or testing the proposed method.The paper presents a method for the automatic diachronic normalization of Polish texts – the procedure, which, for a given historical text, returns its contemporary spelling. The method applies finite-state transducers, defined in a sublanguage of the Thrax formalism. The paper discusses linguistic issues, such as evolution in spelling of the Polish language, as well as implementation aspects, such as efficiency or testing the proposed method

Lack of association between serotonin transporter gene polymorphism 5-HTTLPR and smoking among Polish population: a case-control study

<p>Abstract</p> <p>Background</p> <p>A better understanding of the genetic determinants of tobacco smoking might help in developing more effective cessation therapies, tailored to smokers' genotype. Insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (<it>5-HTTLPR</it>) has been linked to vulnerability to smoking and ability to quit. We aimed to determine whether <it>5-HTTLPR </it>genotype is associated with smoking behavior in Caucasians from Northern Poland and to investigate other risk factors for tobacco smoking.</p> <p>Methods</p> <p><it>5-HTTLPR </it>genotypes were determined in 149 ever smokers (66 females; mean age 53.0 years) and 158 gender and ethnicity matched never smoking controls (79 females; mean age 45.0 years) to evaluate the association of this polymorphism with ever smoking status. Analysis of smokers was performed to evaluate the role of <it>5-HTTLPR </it>in the age of starting regular smoking, the number of cigarettes smoked daily, pack-years, FTND score, duration of smoking, and the mean length of the longest abstinence on quitting. Genotype was classified according to the presence or absence of the short (<it>S</it>) allele vs. the long (<it>L</it>) allele of <it>5-HTTLPR </it>(i.e., <it>S/S </it>+ <it>S/L </it>vs. <it>L/L</it>). Logistic regression analysis was also used to evaluate correlation between ever smoking and several selected variables.</p> <p>Results</p> <p>We found no significant differences in the rates of <it>S </it>allele carriers in ever smokers and never smokers, and no relationship was observed between any quantitative measures of smoking and the polymorphism. Multivariate analysis demonstrated significant association between the older age (OR = 4.03; 95% CI: 2.33–6.99) and alcohol dependence (OR = 10.23; 95% CI: 2.09–50.18) and smoking.</p> <p>Conclusion</p> <p><it>5-HTTLPR </it>seems to be not a major factor determining cigarette smoking in Poles. Probably, the risk of smoking results from a large number of genes, each contributing a small part of the overall risk, while numerous non-genetic factors might strongly influence these genetic undergrounds of susceptibility to smoking.</p

Retrospektywna analiza wyników paliatywnej chemioterapii chorych na zaawansowanego raka jelita grubego na tle danych z badań klinicznych

Wstęp. Nowotwory jelita grubego są w skali świata drugą przyczyną zgonów spowodowanych nowotworami. Rozwój nowych leków w ostatnich latach rozszerzył możliwości leczenia tych nowotworów, jednak nie jest jasne, czy postęp ten dotyczy także chorych leczonych w ramach codziennej praktyki klinicznej. Dane dotyczące wyników paliatywnej chemioterapii u chorych na zaawansowanego raka jelita grubego w Polsce poza badaniami klinicznymi są skąpe. Metody. Przeprowadzono analizę wyników paliatywnej chemioterapii, uwzględniającą odpowiedź na leczenie, czas przeżycia, toksyczność i jakość życia, u chorych na raka jelita grubego leczonych w dwóch ośrodkach w latach 2010–2013. Wyniki. Przedmiotem badania było 165 chorych w wieku od 41 do 84 lat (średnia 61 ± 8,7 roku), spośród których 105 otrzymywało chemioterapię z udziałem irynotekanu (CLF1/XELIRI), 41 — schematy zawierające oksaliplatynę (FOLFOX4/ XELOX) i 19 — 5-fluorouracyl w monoterapii. Częściową odpowiedź uzyskano u 48 chorych (29%), stabilizację u 71 (43%), a u 46 chorych (28%) doszło do progresji. Mediana czasu przeżycia w całej grupie chorych wynosiła 14 miesięcy. Wyniki te są gorsze niż uzyskiwane we współczesnych badaniach klinicznych (odsetek odpowiedzi około 40%, mediana czasu przeżycia średnio około 17 miesięcy). Chemioterapia wielolekowa w porównaniu z jednolekową związana była z większą toksycznością ogółem (p = 0,039) oraz większym nasileniem biegunek (p = 0,003) i neuropatii obwodowej (p &lt; 0,001). Nie stwierdzono widocznego wpływu chemioterapii na ogólną jakość życia. Wnioski. Wyniki chemioterapii raka jelita grubego w codziennej praktyce mogą być gorsze od uzyskiwanych w prospektywnych badaniach klinicznych ze względu na inną populację leczonych chorych. Zastosowanie chemioterapii nie miało istotnego wpływu na jakość życia

Combining radiotherapy with hormonotherapy and targeted therapies in breast cancer

Breast cancer is one of the most important global health problems. Over the last years introduction of screening mammography and increased efficacy of adjuvant therapies resulted in the reduction of mortality in this malignancy. Many patients with breast cancer have indications for adjuvant radiotherapy and hormonotherapy, however optimal schedules of combining these two modalities remain controversial. In clinical practice typically radiotherapy and hormonotherapy are used both sequentially and concomitantly. Similarly, the most effective and safe strategies for combining radiotherapy and targeted therapies remain to be developed. It is expected that further preclinical and clinical studies, as well as rapid development of molecular oncology will contribute to better selection of patients for particular therapeutic strategies and their optimization.Rak piersi jest jednym z najważniejszych problemów zdrowotnych na świecie. W ostatnich latach w grupie chorych na ten nowotwór uzyskano znaczące zmniejszenie umieralności, co przypisuje się wprowadzeniu masowych badań przesiewowych i większej skuteczności pooperacyjnego leczenia. U wielu chorych na raka piersi istnieją wskazania do pooperacyjnej radioterapii i hormonoterapii, jednak optymalna strategia kojarzenia tych dwóch metod pozostaje nadal przedmiotem kontrowersji. W praktyce klinicznej pooperacyjną radioterapię i hormonoterapię stosuje się zarówno sekwencyjnie, jak i równocześnie, bowiem nie przeprowadzono badań z losowym doborem porównujących te dwie strategie. Dotychczas nie określono także najbardziej skutecznych i bezpiecznych metod kojarzenia radioterapii i terapii ukierunkowanych molekularnie. Oczekuje się, że dalsze badania przedkliniczne i odpowiednio zaprojektowane badania kliniczne, a także szybki rozwój onkologii molekularnej przyczynią się do lepszego doboru chorych do poszczególnych strategii leczenia oraz ich optymalizacji

Typing safe antibiotics in amoxicillin hypersensitive patients — development of a stepwise protocol

Introduction: A history of an adverse reaction to amoxicillin, irrespective of the mechanism involved, significantly elevates patients’ anxiety and affects therapeutic decisions in the future, leading to unnecessary avoidance of antibiotics. As a consequence, it would be useful to find a safe and reliable protocol for typing safe alternative antibiotics. The aim of the study was to determine negative predictive value of typing safe antibiotic in patients with a history of hypersensitivity reaction to amoxicillin. Material and methods: 71 patients, aged 20−83, with a history of an adverse reaction to amoxicillin were retrospectively analysed. On the basis of the reaction type they were divided into three groups: A — symptoms not typical for hypersensitivity reactions, B — allergy manifested by urticaria and/or angioedema, C — anaphylaxis. In group A amoxicillin was tested, in group B — cefuroxime, and in group C — macrolide: azithromycin or clarithromycin. Telephone follow-up visits were performed twice: 6−12 months and 3−5 years after the clinical assessment to evaluate tolerance of antibiotics. On the basis of the follow-up results, the negative predictive value (NPV) of the protocol was calculated. Results: The full diagnostic protocol was applied in 62 participants. Amoxicillin was found safe in 22, cefuroxime — in 21 and macrolide — in 19 patients. No anaphylactic reactions were observed during the tests. On the basis of the telephone follow-up, the NPV of the protocol was 96% in the first follow-up and 97% in the second one. Conclusion: A stepwise approach including SPTs, ICTs and provocations with amoxicillin / cefuroxime/macrolide — depending on a patient’s history — is safe and allows typing an antibiotic in the vast majority of patients.Introduction: A history of an adverse reaction to amoxicillin, irrespective of the mechanism involved, significantly elevates patients’ anxiety and affects therapeutic decisions in the future, leading to unnecessary avoidance of antibiotics. As a consequence, it would be useful to find a safe and reliable protocol for typing safe alternative antibiotics. The aim of the study was to determine negative predictive value of typing safe antibiotic in patients with a history of hypersensitivity reaction to amoxicillin. Material and methods: 71 patients, aged 20−83, with a history of an adverse reaction to amoxicillin were retrospectively analysed. On the basis of the reaction type they were divided into three groups: A — symptoms not typical for hypersensitivity reactions, B — allergy manifested by urticaria and/or angioedema, C — anaphylaxis. In group A amoxicillin was tested, in group B — cefuroxime, and in group C — macrolide: azithromycin or clarithromycin. Telephone follow-up visits were performed twice: 6−12 months and 3−5 years after the clinical assessment to evaluate tolerance of antibiotics. On the basis of the follow-up results, the negative predictive value (NPV) of the protocol was calculated. Results: The full diagnostic protocol was applied in 62 participants. Amoxicillin was found safe in 22, cefuroxime — in 21 and macrolide — in 19 patients. No anaphylactic reactions were observed during the tests. On the basis of the telephone follow-up, the NPV of the protocol was 96% in the first follow-up and 97% in the second one. Conclusion: A stepwise approach including SPTs, ICTs and provocations with amoxicillin / cefuroxime/macrolide — depending on a patient’s history — is safe and allows typing an antibiotic in the vast majority of patients

Hepatic hydrothorax - complication of end-stage hepatic cirrhosis

62-year-old woman admitted to the hospital with dyspnoea, elevated body temperature, cough for two days. Patient has been treated for alcoholic hepatic sclerosis for 12 years and hepatitis C infection for 5 years. The chest X-ray revealed hydrothorax of right pleura. Continuous drainage of the right pleura was applied. In spite of intensive treatment effusion excuded 1000 ml/day making pleurodesis impossible, and eventually pleuro-peritoneal shunt was performed. Shunt drainage however turned out to be insufficient to evacuate the pleural fluid. The shunt was removed and continuous pleural drainage was reopen. Due to subsequent disseminated intravascular coagulation, patient was treated with fresh frozen plasma, heparin, blood and platelets. The clinical status alleviated, but patient still required chest tube because of the refractory hydrothorax.62-year-old woman admitted to the hospital with dyspnoea, elevated body temperature, cough for two days. Patient has been treated for alcoholic hepatic sclerosis for 12 years and hepatitis C infection for 5 years. The chest X-ray revealed hydrothorax of right pleura. Continuous drainage of the right pleura was applied. In spite of intensive treatment effusion excuded 1000 ml/day making pleurodesis impossible, and eventually pleuro-peritoneal shunt was performed. Shunt drainage however turned out to be insufficient to evacuate the pleural fluid. The shunt was removed and continuous pleural drainage was reopen. Due to subsequent disseminated intravascular coagulation, patient was treated with fresh frozen plasma, heparin, blood and platelets. The clinical status alleviated, but patient still required chest tube because of the refractory hydrothorax

Difficulties in management of tuberculous pneumonia in a patient with liver failure in the course of chronic hepatitis B and concomitant failure of the transplanted kidney

A 62-year-old woman with liver failure in the course of chronic hepatitis B and concomitant failure of the transplanted kidney was treated for tuberculous pneumonia. The treatment was initiated with rifampin, isoniazid and pyrazinamide. Both renal and hepatic side effects required modification of this scheme. After 1 month of treatment sputum smears tested for acid-fast bacilli converted to a negative result and the chest X-ray demonstrated complete resolution of pulmonary infiltrates. Further therapy resulted in serious deterioration of the liver failure and fatal outcome.A 62-year-old woman with liver failure in the course of chronic hepatitis B and concomitant failure of the transplanted kidney was treated for tuberculous pneumonia. The treatment was initiated with rifampin, isoniazid and pyrazinamide. Both renal and hepatic side effects required modification of this scheme. After 1 month of treatment sputum smears tested for acid-fast bacilli converted to a negative result and the chest X-ray demonstrated complete resolution of pulmonary infiltrates. Further therapy resulted in serious deterioration of the liver failure and fatal outcome

Combining chemotherapy with radiation in breast cancer

Rak piersi jest jednym z najważniejszych problemów zdrowotnych na świecie. W ostatnich latach osiągnięto zmniejszenie stopnia umieralności wskutek tego nowotworu, co przypisuje się upowszechnieniu badań przesiewowych i większej skuteczności leczenia pooperacyjnego. U wielu chorych na raka piersi istnieją wskazania do pooperacyjnej radioterapii i chemioterapii, jednak optymalna strategia kojarzenia tych metod pozostaje nadal kontrowersjną kwestią. W praktyce klinicznej pooperacyjną chemioterapię i radioterapię stosuje się na ogół sekwencyjnie, jednak strategii tej nie potwierdzają wyniki dużych badań klinicznych. Istnieją teoretyczne przesłanki ku temu, by równocześnie stosować radioterapię i chemioterapię, ale z powodu nasilenia kardiotoksyczności i odczynów skórnych nie jest to możliwe w przypadku schematów zawierających antracykliny. Oceny wymaga także bezpieczeństwo stosowania schematów zawierających taksoidy w połączeniu z równoczesną radioterapią, zwłaszcza w odniesieniu do toksyczności płucnej. Jednoczasowa chemio-radioterapia przy użyciu wybranych schematów może być natomiast rozważana u chorych z miejscowo zaawansowanym nowotworem, ale strategię tę powinno się zweryfikować w dużych badaniach klinicznych z losowym doborem chorych.Breast cancer is one of the most important global health problems. Over the last years introduction of mammography screening and increased efficacy of adjuvant therapies resulted in the reduction of mortality in this malignancy. A proportion of patients with breast cancer has indications for adjuvant radiotherapy and chemotherapy, however optimal schedules of combining these two modalities remain controversial. In clinical practice typically chemotherapy and radiotherapy are used sequentially, but this strategy is not supported by the results of large clinical trials. There is theoretical rationale for the concomitant use of both modalities, but increased cardiotoxicity and skin reactions of anthracycline-based regimens do not allow for this strategy. Further investigations are essential to determine the safety of taxane-based schedules combined with radiotherapy, particularly with regard to pneumotoxicity. Concurrent chemo-radiotherapy with the use of selected schemes may be considered in patients with locally advanced cancer, but this strategy still should be verified in large randomized studies

Case report of Churg-Strauss syndrome - signs and symptoms suggesting disseminated neoplasmatic disease

Churg-Strauss syndrome (CSS) is characterized by asthma, sinusitis, hypereosinophilia and eosinophilic infiltrates, with particular pulmonary, gastrointestinal, neural and cardiovascular involvement. We presented a case of CSS complicated by weight loss, pulmonary embolism and non-traumatic rib fractures. The case confirms that the clinical course of the disease is highly heterogeneous.Churg-Strauss syndrome (CSS) is characterized by asthma, sinusitis, hypereosinophilia and eosinophilic infiltrates, with particular pulmonary, gastrointestinal, neural and cardiovascular involvement. We presented a case of CSS complicated by weight loss, pulmonary embolism and non-traumatic rib fractures. The case confirms that the clinical course of the disease is highly heterogeneous