Novel spectroscopic biomarkers are applicable in non-invasive early detection and staging classification of colorectal cancer.

Colorectal cancer (CRC) remains a significant threat to human health because of the lack of awareness of physical examination or the limitations of an early diagnostic level. Despite the improving standard of modern medicine, mortality from CRC is still remarkably high and the prognosis remains poor in many cases because of disease detection at advanced clinical stages. Raman spectroscopy yields precise information, not only regarding the secondary structure of proteins but also regarding the discrimination between normal and malignant tissues. We investigated whether this method can be used for the diagnosis of CRC including initial stages. To acquire more detailed structural information, we tested a novel diagnostic approach based on a suitable combination of conventional methods of molecular spectroscopy (Raman and Fourier transform infrared) with advanced, highly structure-sensitive chiroptical techniques as electronic circular dichroism (ECD) and Raman optical activity (ROA) to monitor the CRC pathogenesis relating compositional, structural and conformational changes in blood biomolecules, some of which may be caused by pathological processes occurring during cancer growth, also at the beginning of the disease. Sixty-three blood plasma samples were analyzed using the combination of ECD and ROA supplemented by Raman and Fourier transform infrared (FT-IR) spectroscopies. The obtained spectra were evaluated together by linear discriminant analysis. The accuracy of sample discrimination reached 100% and the subsequent leave-one-out cross-validation resulted in 90% sensitivity and 75% specificity. There were also found the differences between the patients according to the clinical stage. The achieved results suggest a panel of promising biomarkers and indicate that chiroptical methods combined with conventional spectroscopies might be a new minimally invasive powerful tool for producing high-quality data, obtaining an accurate diagnosis of colorectal cancer through a peripheral blood sample, which is also able to determine the extent of this pathology. Further work needs to be carried out for these techniques to be implemented in the clinical setting.

Multidisciplinary team in colorectal cancer treatment - analysis of our patients in 2017.

INTRODUCTION: Multidisciplinary teams (MDTs) have become a standard part of treating oncological patients. Based on the available data, they have lead to significantly higher survival rates in the treatment of colorectal cancer (CRC). Reported negatives include potentially longer times between diagnoses and the start of appropriate treatment, and the lack of quality controls over the MTDs actions. This report aims to assess the benefits of MDTs using our own data set for 2017. METHODS: Year 2010 saw the institution of an MDT at the Central Military University Hospital in Prague, with the obligation to refer CRC patients to the MDT before the start of treatment. Having standardized the registration, we have implemented a simple procedure to track the quality of our MDTs involvement and its patient benefits: number of patients, number of referrals with proposed diagnostic and therapeutic procedure, frequency and reason of changes to original strategies, and the frequency of variations from the MDTs conclusions. RESULTS: 405 CRC patients were referred to the MDT in 2017; we have found 499 referrals in this group. The data set was formed predominantly by men (61%), with the mean age of 63 (21-91), and the median age of 64.5 years. Surgical treatment was the most commonly proposed procedure (59%), followed by systemic treatment or, as the case may be, radiotherapy. In 24% of the cases, the conclusion did not match the originally proposed procedure. The decision not to go through with the proposed surgical treatment was the most common change (66 %). We have found a difference in the quality of referral in patients examined specifically by the referring doctor, as opposed to patients whose medical records have just been sent in. We have found therapeutic variation in the MTDs conclusions in less than 5% of patients. CONCLUSION: Having analyzed our data for CRC patients referred to the MDT in 2017, we have found out that in 24% of the patients, the MDT referral leads to a change in the originally proposed diagnostic and therapeutic procedure. Consensus among the MDTs members on the CRC patients treatment guarantees an optimum procedure. What is fundamental is that the referring doctor knows the patient. Constant tracking of the MDTs outputs forms a condition for sustaining the quality of its work and a base for assessing its benefits to the patients.

[The Inclusion of a Gemcitabine + Nab-paclitaxel Regimen as a 2nd Line Treatment for Advanced Pancreatic Cancer - First Experience]. / Zarazení rezimu gemcitabin + nab-paklitaxel do 2. linie lécby pokrocilého karcinomu slinivky brisní - první zkusenosti.

INTRODUCTION: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The outcomes at all stages of the disease are the worst among patients with solid tumors. PATIENTS AND METHODS: Analyses were conducted on 19 patients treated with gamcitabine + nab-paclitaxel for locally advanced or metastatic pancreatic cancer as a second line treatment between October, 2014, and December, 2016, at Department of Oncology of First Faculty of Medicine and General University Hospital in Prague. Patients were treated with gemcitabine (1,000 mg/sqm) + nab-paclitaxel (125 mg/sqm) at days 1, 8 and 15 of each 28-day cycle. Antitumor efficacy (disease control rate (DCR), time to progression (TTP), and overall survival (OS)) and adverse events were monitored. RESULTS: Disease control according to RECIST criteria was achieved in nine cases (56.3%, two partial regressions were observed). The median TTP was 5.5 months and median OS was 10.1 months. CONCLUSION: In patients with advanced or metastatic pancreatic cancer with good performance statuses (0-1) gemcitabine + nab-paclitaxel as a second line treatment led to a prolongation in time to progression and higher overall survival with good quality of life.Key words: pancreatic cancer - gemcitabine - nab-paclitaxel - efficiency - toxicity This project was supported by grant PROGRES-Q-25/LF1, The League Against Cancer a AZV CR 15-28188A. 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.Submitted: 11. 7. 2017Accepted: 20. 9. 2017.

[Isolated Perfusion of the Upper Extremity with TNF-α - Double Venous Cannulation]. / Izolovaná perfuze horní koncetiny s TNF-α - dvojitá kanylace zilního systému.

BACKGROUND: The authors present a technical variation of the standard cannulation for cardiopulmonary bypass perfusion during hyperthermic isolated limb perfusion (ILP) procedures in selected patients with unresectable soft tissue sarcoma or malignant melanoma. PATIENTS: Of 55 ILP procedures performed at our institution since the procedure was established in 2009, nine were performed at the upper extremity. Standard single venous cannulation was used in five cases, and extended, double venous cannulation in the last four. The standard technique for brachial vein cannulation in a small compartment of the upper extremity entails a problematic and longer perfusion of the upper extremity. This is due to the lower flow rate in the venous system and relatively large surface area with respect to weight. We present a simple technique based on a "Y" cannulation of the venous system via the deep brachial vein and superficial venous system via the basilic vein, delivering a 20% increase in flow rate in the extracorporeal circulation. Faster heating of the upper extremity and a stable thermal environment throughout upper-extremity ILP are essential for successful treatment. CONCLUSION: Extended technique of venous cannulation for extracorporeal circulation setting, due to their advantages, became standard in the upper limb ILP procedure at our institution.Key words: isolated limb perfusion - malignant melanoma - soft tissue sarcoma - upper limb - extracorporeal circulation 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.Submitted: 8. 1. 2017Accepted: 15. 1. 2017.

Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative irreversible electroporation: general hospital cancer center experience.

The aim of this study was to evaluate the safety of irreversible electroporation (IRE) and the outcome of patients undergoing IRE of locally advanced pancreatic cancer (PC). Twenty-one patients with unresectable PC underwent open (n=19) or percutaneous (n=2) IRE of the tumor using the Nanoknife system with two electrodes that were repositioned several times to affect the whole mass. The size of the tumor was 39±10mm with a range from 21 to 65mm. Five patients underwent neoadjuvant chemotherapy and seven patients were treated with chemotherapy after IRE. Complications occurred in five patients, which resulted in prolongation of the average hospital stay from 10 to 34 days. There was no mortality in the first postoperative month. Median survival after IRE was 10.2 months compared to 9.3 months in a matched cohort (hazard ratio = .54, p = .053). The quality of life was declining slowly. 81% of time after IRE the Karnofsky performance status was ≥70 and sharp decline occurred approximately 8 weeks before death.In conclusion, IRE is a safe palliative treatment option for a percentage of patients with locally advanced pancreatic carcinoma. The patients treated with open IRE lived a decent life until 8 weeks before their death. We believe that IRE of pancreatic carcinoma can be regarded as an option, if imaging or explorative laparotomy show that R0 resection in not possible.

[Genomic Tests as Predictors of Breast Cancer Patients Prognosis]. / Genomové testy jako prediktory prognózy pacientek s karcinomem prsu.

Hormonal dependent breast cancer is a heterogeneous disease from a molecular and clinical perspective. The relapse risk of early breast cancer patients treated with adjuvant hormonal therapy varies. Validated predictive markers concerning adjuvant cytotoxic treatment are still lacking in ER+/ HER2-  breast cancer, which has a good prognosis in general. This can lead to the inefficient chemotherapy indication. Molecular classification of breast cancer reports evidence about the heterogeneity of hormonal dependent breast cancer and its stratification to different groups with different characteristics. Multigene assays work on the molecular level, and their aim is to provide patients risk stratification and therapy efficacy prediction. The position of multigene assays in clinical practice is not stabile yet. Non uniform level of evidence connected to patients prognosis interpretations and difficult comparison of tests are the key problems, which prevent their wide clinical use. The article is a summary of some of the most important multigene assays in breast cancer and their current position in oncology practice.

Predictive factors for the presence of tumor cells in bone marrow and peripheral blood in breast cancer patients.

UNLABELLED: Simultaneous detection of disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) was shown to be associated with an especially poor prognosis and increased incidence of disease-related deaths in non-metastatic breast cancer patients. We analyzed the occurance of DTCs and CTCs in patients with primary breast cancer and evaluated the correlation of their presence with other prognostic markers and investigated the changes in DTCs/CTCs number at different time points during treatment.Blood of 50 patients with primary breast cancer were used for immunomagnetic separation and detection of circulating tumor cells using the commercial available system the AdnaTest Breast Cancer™ (AdnaGen GmbH, Langenhagen, Germany). Bone marrow aspirates from 50 patients were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibody conjugated with FITC (Monoclonal Anti-Cytokeratin antibody F3418, Sigma Aldrich).DTCs were identified in 30% (15/50) and CTCs in 22% (11/50) of patients. We found that DTC positivity could point to a significantly high risk of larger primary tumor size (p-value 0.011) and significantly higher risk of lymph node involvement (p-value 0.002). For CTC positivity, no such relationship was proven. DTCs have shown significantly higher prevalence in ER/PR-negative females and in HER2-positive cases. CTCs were equally prevalent in patients with the presence and absence of standard prognostic and predictive markers such as ER, PR and HER2. We found no correlation between CTCs and DTCs findings (r = -0.097, p = 0.504). We used DTCs/CTCs analysis for therapy monitoring in a small group of 29 patients, who underwent neoadjuvant chemotherapy (NACT). We find out no significant correlation between DTCs/CTCs detection and the primary tumor response to NACT. A pathologic complete response (pCR) was achieved by 31% (9/29) of the patients in our study, however, no association was observed between pCR and the detection of DTCs after NACT.These results support the use of DTCs/CTCs analysis in early breast cancer to generate clinically useful prognostic information. The study of these cells apart from the impact on refining prognosis, has the exciting potential of individualising treatment for women with breast cancer. KEYWORDS: breast cancer, disseminated tumor cells, circulating tumor cells, bone marrow aspiration, prognostic/predictive markers, therapy monitoring.

Trefoil factor family (TFF) proteins as potential serum biomarkers in patients with metastatic colorectal cancer.

Trefoil factor family (TFF) is composed of three secretory proteins (TFF1, TFF2 and TFF3) that play an important role in mucosal protection of gastrointestinal tract. Their overexpression in colorectal tumors seems to be associated with more aggressive disease. We collected serum samples from 79 healthy controls and 97 patients with metastatic colorectal cancer at the time of diagnosis or at progression. Serum levels of TTF1-3, CEA and CA19-9 were measured by ELISA. Serum TFF1 and TFF3 levels were significantly higher in patients with colorectal cancer compared to healthy controls (p < 0.0001). Moreover, serum levels of TFF3 correlated with extent of liver involvement in patient without pulmonary metastases and patients with higher TFF3 levels had significantly worse outcome (p < 0.0001). Compared to CEA and CA19-9, TFF3 had higher sensitivity and the same specificity. Our results indicate that TFF3 is an effective biomarker in patients with metastatic colorectal cancer with higher sensitivity than CEA a CA19-9. TFF3 levels strongly correlate with extension of liver disease and seem to have prognostic value.

[Immunoscore and Its Predictive Value for Colorectal Cancer]. / Immunoscore a jeho prediktivní hodnota u kolorektálního karcinomu.

Recent studies suggest that immune  classification (immune-score) in cancer patients has a prognostic value in some cases that seems to be superior to the AJCC/ UICC TNM  classification. The clinical outcome can vary significantly among patients with a particular diagnosis within the same TNM stage. Immunoscore methodology quantifies and detects different types of immune cells in tumor tissue, and also determines the density of their infiltration and localization at the tumor site. Currently within an international collaboration of 23 centers in 17 countries (including our department), immunoscore is being evaluated in more than 7,000 colorectal cancer patients in terms of the tumor microenvironment, focusing on the presence of immune cells both in the tumor tissue and the tumor invasive margin. Immunoscore results are assessed in correlation with: 1. patients response to the treatment, 2. rate of progression, disease prognosis and other immune parameters. It appears that the TNM classification and tumor invasiveness is statistically dependent on the immune response of the patient (there is an inverse correlation between the density of the infiltration of CD8⁺, CD3⁺ lymphocytes and the tumor stage). High densities of T-lymphocytes (CD8⁺, CD3⁺) both in the core and the invasive margin of the primary tumor are associated with longer term asymptomatic survival, overall survival, lower risk of relapse and reduced likelihood of metastases. The project of the international collaboration aims to introduce immunoscore in routine diagnostics.

Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses.

BACKGROUND: The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen. METHODS: Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg(-1) days 1 and 15 plus paclitaxel 90 mg m(-2) days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg(-1) day 1 plus capecitabine 1000 mg m(-2) bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs. RESULTS: The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP. CONCLUSIONS: A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).

Cellular and humoral immunodeficiency in breast cancer patients resistant to hormone therapy.

In view of the fact that insufficiency in immune response often correlates with poor prognosis, research in recent years has focused on the task of describing the precise status and function of the immune system and its possible effect on cancer patients. Although more than two thirds of treated patients respond to endocrine therapy, most patients with metastatic breast cancer develop a resistance to it. Estrogen modulates angiogenesis, partially through its effects on vascular endothelial growth factor (VEGF). It also appears that transforming growth factor-beta (TGF beta) could be another factor contributing to this resistance. TGF beta is a highly immunosuppressive factor that inhibits natural and specific immunity against tumors and stimulates the production of VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer who were resistant to hormone therapy. The examination of cellular components (CD4, CD8, HLA-DR, NK cells) and humoral immunity (IgG, IgG subclasses, IgA, IgM,). TGF beta and VEGF production were monitored with special attention, along with an analysis of the changes that occurred during the hormonal treatment. 68 patients included in the research project were implemented with routine cancer treatment with endocrine therapy. Basic parameters (the histological type and grade, the degree of expression of estrogen receptors (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta and VEGF were measured by ELISA and antitumor cellular immunity (CD4, CD8) was measured by flow cytometry. Patients who failed in the first line of hormone therapy treatment were considered as resistant to hormone therapy.Depression in cellular immunity was found especially in patients with resistance to endocrine therapy. In addition, immunoglobulin plasma levels were decreased (mainly IgG4 subtype). Most patients showed clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections). Significant increases in TGF beta and VEGF plasma were also detected.The correlation of these factors with resistance to hormonal therapy and the state of anticancer immunity could be helpful in the task of predicting resistance to hormonal therapy and could contribute to the selection of targeted immune therapy in cancer patients in the future.

Predicting axillary sentinel node status in patients with primary breast cancer.

The aim of this study is to determine the combination of characteristics in early breast cancer that could estimate the risk of occurrence of metastatic cells in axillary sentinel lymph node(s). If we were able to reliably predict the presence or absence of axillary sentinel involvement, we could spare a considerable proportion of patients from axillary surgery without compromising therapeutic outcomes of their disease. The study is based on retrospective analysis of medical records of 170 patients diagnosed with primary breast cancer. These women underwent primary surgery of the breast and axilla in which at least one sentinel lymph node was obtained. Logistic regression has been employed to construct a model predicting axillary sentinel lymph node involvement using preoperative and postoperative tumor characteristics. Postoperative model uses tumor features obtained from definitive histology samples. Its predictive capability expressed by receiver operating characteristic curve is good, area under curve (AUC) equals to 0.78. The comparison between preoperative and postoperative results showed the only significant differences in values of histopathological grading; we have considered grading not reliably stated before surgery. In preoperative model only the characteristics available and reliably stated at the time of diagnoses were used. The predictive capability of this model is only fair when using the data available at the time of diagnosis (AUC = 0.66). We conclude, that predictive models based on postoperative values enable to reliably estimate the likelihood of occurrence of axillary sentinel node(s) metastases. This can be used in clinical practice in case surgical procedure is divided into two steps, breast surgery first and axillary surgery thereafter. Even if preoperative values were not significantly different from postoperative ones (except for grading), the preoperative model predictive capability is lower compared to postoperative values. The reason for this worse prediction was identified in imperfect preoperative diagnostic.

[Is preoperative bone scintigraphy in early stage of breast cancer T1N0 indicated and meaningful?]. / Je predoperacní scintigrafie skeletu v casném stadiu karcinomu prsu T1N0 indikovaná a smysluplná?

In the Czech Republic bone scintigraphy has still been performed routinely as a part of preoperative staging examinations of early breast carcinomas, which had been in 42% diagnosed in the national breast cancer screening program. The incidence of synchronnous distant metastases was analysed for a subgroup of T1N0 breast carcinomas using the database of the Czech National Cancer Registry. Out of 21,675 women with T1N0 breast carcinomas diagnosed in the decade of 2001-2010 the potential occurence of various distant metastases (M1) was estimated in 147 cases (0,68%). Since only approximately 40% of all distant metastases were skeletal (M1 OSS), the pro-bability of bone metastases in T1N0 breast cancer does not exceed 0,3-0,4%. Distant metastases were present in 0,5% in a subgroup of well and moderately differentiated carcinomas and up to 1,2% in poorly differentiated and anaplastic tumors, however, only a minor part (0,2% and 0,5%, respectively) involved bones. We conclude that preoperative bone scintigraphy is overused and undue in more than 99% of Czech women with early breast cancer T1N0. Skeletal scintigraphy as a staging procedure for small breast carcinoma T1N0 may perhaps be recommended only postoperatively and very selectively with regards to individual risk factors and symptomatology.

Postoperative radiochemotherapy with weekly cisplatin in patients with head and neck cancer single-institution outcome analysis.

The objective of this study was to evaluate the feasibility, toxicity and efficacy of postoperative radiochemotherapy with weekly cisplatin in locoregionally advanced or high risk head and neck cancer in a single institutional setting. Patients with head and neck cancer of stage III/IV or patients with insufficient margins of resection were included in the study. Radiotherapy consisted of 70 Gy/ 7 weeks/ 35 fraction after R1/2 resection and 60-64 Gy/ 6-6,5 weeks/ 30-32 fraction after R0 resection, respectively. All patients received concurrent cisplatin 40 mg/m2 weekly. Between 7/2002 and 12/2008, 100 consecutive patients [WHO ≤ 2, male to female ratio 84/16, median age 54 years] were treated. Tumors of the oropharynx were the most frequent (49%) and stage IV was predominant (86%). 96% patients received the full radiation treatment as planned, median total tumor dose was 66 Gy. Omission of weekly cisplatin had been occurring frequently, the most frequent reason for its early cessation were hematological toxicities (34%). Grade 3/4 mucosal toxicity developed in 32%. No death was observed during the treatment. The late toxicities were acceptable, predominantly subcutaneous fibrosis and xerostomia in most of the cases. We recorded six cases of osteonecrosis. Two and half year overall survival, locoregional control, time to progression and disease free survival were 64%, 88%, 79% and 59%, respectively. Postoperative radiochemotherapy with weekly cisplatin is toxic, but tolerable and highly effective in terms of locoregional control and survival. Multivariete analysis revealed that the only prognostic factor for survival was primary surgery at the University centre.

PET/CT significance for planning radiotherapy of head and neck cancer.

The combination of positron emission tomography and computed tomography (PET/CT) offers metabolic mapping in addition to anatomic information of the primary lesion, nodal and distant metastases in patients with head and neck tumors, and may be therefore beneficial for radiotherapy planning. The aim of our study was to evaluate benefits of combined PET and CT imaging for staging and target volume delineation in this group of patients.Fifty three patients (40 men and 13 women) with confirmed advanced, inoperable or non-radically operated head and neck cancer were assessed based on the results of PET/CT as well as standard diagnostic examinations. All patients were subsequently treated with intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) of 6 MV X-rays. There was an agreement between the standard examinations results and results of PET/CT in 30 cases. In 23 cases there was disagreement either in tumor size, nodal involvement or presence of distant metastases. Results of the tumor size assessment differed significantly in 5 cases. There was no agreement found in nodal involvement in 10 cases. The cancer confirmed by standard examination was not found by PET/CT in 2 cases; 3 PET/CT positive findings were not confirmed by standard examinations. In 3 patients PET-CT revealed new distant metastatic disease. Based on PET/CT assessment we changed treatment strategy and applied potentially curative dose of radiotherapy to previously undiscovered regions in 9 patients. We decided to change the treatment intent in 3 cases and only palliative treatment was applied. Based on our experience and the literature review, PET/CT may be considerable contribution to the standard diagnostic procedures in approximately one third of cases.

Local treatment of hand-foot syndrome with uridine/thymidine: in vitro appraisal on a human keratinocyte cell line HaCaT.

5-fluorouracil (5-FU) is one of the most commonly used antineoplastic drugs in the anticancer therapy. The hand-foot (HF) syndrome (palmar-plantar erythrodysesthesia) is an adverse effect frequently related to long-term i.v. administration of 5-FU or its orally applicable prodrug capecitabine. Its severity can even lead to interruption of the otherwise effective anticancer therapy. Tentative practice in some clinics has shown that topical application of 10% uridine ointment is beneficial for calming down the HF syndrome. This study is focused on verifying the alleged protective activity of uridine in the in vitro model of cultured human keratinocyte cell line HaCaT. We also tested the protective effects of thymidine alone or uridine-thymidine combination. The cellular viability time progression was measured in order to evaluate the effect of protective agents by three different types of cytopathogenicity tests-NTCA test (non-destructive test of cellular activity), modified MTT test and RTCA (real-time cell analyser, Roche). All three methods proved the ability of uridine and uridine-thymidine combination to protect keratinocytes against 5-FU damage in vitro. While thymidine alone did not show any remarkable effect, the thymidine-uridine combination demonstrated enhanced protective activity compared to uridine alone. Our findings provided the supporting rationale for using uridine or uridine-thymidine ointments in the HF syndrome local therapy.

Outcomes of patients with oesophageal cancer treated with preoperative chemoradiotherapy, followed by tumor resection: influence of nutritional factors.

PURPOSE: To assess the impact of clinical and nutritional factors on overall survival (OS) and time to disease progression of oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: We retrospectively studied and analysed several clinical and nutritional factors, such as performance status, weight changes before and during CRT, dysphagia, nutritional support, and serum albumin to see whether they exerted any impact on OS and time to disease progression. RESULTS: In 107 patients the average weight loss was 9.7% from the onset of signs of disease to the beginning of therapy and 3% during CRT. In univariate analysis, significant unfavorable impact on survival was proved for low performance status, severe dysphagia, need for nasogastric tube insertion, above-average weight loss before treatment, weight loss >5% during CRT, and serum albumin ≤ 35 g/l before or after CRT. Patients supported by oral nutritional supplements (ONS) had higher probability to attain full dosage of CRT and radical resection than did those obtaining dietary advice alone. In multivariate analysis, serum albumin level, nasogastric (NG) tube insertion and pretreatment body weight loss were independent prognostic factors for OS, while serum albumin level after CRT and NG tube insertion were prognosticators for time to progression. CONCLUSION: Serum albumin level can serve as a useful prognostic factor for the outcome of patients with oesophageal cancer treated with neoadjuvant CRT and surgery. Appropriate nutritional support of these patients increased the probability of attaining full dosage of CRT and radical disease resection.

Fecal microbiota transplantation - new possibility to influence the results of therapy of cancer patients.

BACKGROUND: The intestinal microbio-me is essential for the function of the human body, it affects not only metabolism and digestion, but also the immune and neurobehavioral systems. The composition of the human intestinal microbio-me has been of interest to many scientific teams around the world in recent years, aided by the rapid development of molecular genetics methods. Intestinal microbio-me imbalance (so-called dysbio-sis) can help develop several pathological conditions such as autoimmune diseases or can be involved in the process of carcinogenesis. Microbio-me research in oncology has so far focused most on the effect of intestinal microbio-me composition on the effectiveness of checkpoint inhibitors. Differences in the relative proportions of individual bacterial strains and the overall microbio-me diversity in patients treated with checkpoint inhibitors appear to be related to the efficacy of this therapy. Many projects are currently studying the possibility of manipulating the composition of the intestinal microbio-me, especially by means of fecal microbial transplantation (FMT). Two published clinical studies have confirmed that it is possible to overcome resistance to checkpoint inhibitor therapy in malignant melanoma with this method and to re-establish a clinical response after FMT. One of the problems of this effort is the significant diversity in the composition of the microbio-me in different populations. Therefore, knowledge of the microbial composition in a particular population is of key importance. The Department of Oncology of the 1st Faculty of Medicine at Charles University and the General University Hospital in Prague is part of this effort, where a program to investigate intestinal microbio-me composition in patients with non-small cell lung cancer, renal cell carcinoma and malignant melanoma during checkpoint inhibitor therapy has been running for several years. PURPOSE: The aim of the publication is to demonstrate the current information and the importance of fecal transplantation in oncology and also to present our currently ongoing research project.

Study of the effect of neoadjuvant chemotherapy on the status of Her2/neu.

Her2/neu proto-oncogene amplification and protein over-expression is observed in 20-40 % of patients with breast cancer and plays a crucial role in invasive breast cancer and its treatment. A number of studies postulated the stability of Her2/neu gene expression, showing that in most patients the status of expression had not significantly changed after the neoadjuvant treatment. In the present study, we investigated samples from 20 patients with invasive breast carcinoma who had undergone neoadjuvant chemotherapy and subsequent surgery. In all cases, the expression level of Her2/neu was evaluated in both pre-therapeutically obtained tumour tissue by core needle biopsy and from specimens obtained during final surgery using immunohistochemistry. Fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction methods were used for verifying the results obtained by immunohistochemistry. Her2/neu status determined by immunohistochemistry remained unchanged in 12 of 20 (60%) patients after neoadjuvant treatment. In six cases (30%) minor changes were observed after the treatment. However, in two cases (10%) we found altered Her2/neu expression from strongly positive in the pre-treatment biopsy to negative in the post-treatment surgery specimen. Moreover, this is the first report describing the changes in Her2/neu status at all protein, RNA and DNA levels by using immunohistochemistry, quantitative reverse transcription polymerase chain reaction and fluorescence in situ hybridization, respectively. By using variable methods we demonstrated possible new ways for Her2/neu detection and their dependability. Improvement in specific molecule detection can prevent the use of tailored targeted therapy in an untargeted manner.

[Targeted biological treatment of solid tumours]. / Cílená biologická lécba solidních nádoru.

Clinical use of targeted biological treatment was initiated in 1970s following a discovery of hormonal receptors and targeted clinical use of tamoxifen. Deeper understanding of molecular principles of the process of metastasizing and cell communication and signalling have contributed to the development of targeted molecular biological treatments based on direct impact on the key target structures ofa tumour cell. Clinical effectiveness of targeted biological treatment has been shown in phase III clinical studies in advanced and metastasising solid tumours and importantly expanded our armamentarium of pharmacotherapeutic treatment options in breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer, hepatocellular carcinoma and gastrointestinal stromal tumour. Full implementation of targeted therapy is precluded by a lack of reliable predictors of efficacy of a number of targeted drugs. Therefore, full identification of such predictors is a subject to intensive clinical research. At present, selection of biological treatment is based on morphological, immunohistochemical and partly also molecular profile ofa tumour. The future of biological treatment lies in a selection that is based on full molecular characterization of the primary tumour as well as metastasis.