Oncosurgery in the Czech Republic.

The article describes the development of oncosurgery in the Czech Republic since the beginning of the century, as well as other perspectives regarding this specialty. The development of surgical treatment of solid malignant tumours in the Czech Republic was evaluated according to the National Cancer Register database and compared to the neighbouring countries, and the educational system of surgeons in oncosurgery was assessed. Although surgery plays a key role in cancer therapy, starting from the beginning of this millennium it has been pushed aside as a service specialty for other disciplines in oncology. In 2002, these changes were supported by the activities of the newly founded Division of Oncosurgery under the Czech Society for Oncology, which became part of the Czech Surgical Society in 2016. An official educational programme of surgeons in oncology was successfully implemented and since 2011, a specialization examination in oncosurgery has been introduced, organized by the subdepartment of oncosurgery of the Institute of Postgraduate Medical Education (IPVZ), Prague. To date, this examination has been completed by 112 physicians and approximately the same number is currently registered in the educational programme. Currently, 34 centres are accredited for education in oncosurgery. The establishment of Complex Oncology Centres based on an initiative of the Czech Society for Oncology of 2006 only addressed pharmaceutical and radiation oncology. Despite progress in oncosurgery, more clearly defined conditions for this specialty are needed. Conclusion: The education of surgeons in oncosurgery should be continued. It is necessary to expand the number of centres with accreditation for oncosurgery and develop a concept for oncosurgery in the Czech Republic which would be associated with rational concentration of this treatment in connection with organization and provision of continuous urgent and acute surgical care in the Czech Republic, including control mechanisms to ensure its quality. This proposal should be discussed by the Czech Surgical Society in order to further enhance the quality of oncosurgery in the Czech Republic.

[SentiMag--the magnetic detection system of sentinel lymph nodes in breast cancer]. / Magnetická detekce sentinelových uzlin u karcinomu prsu metodou SentiMag.

INTRODUCTION: The aim of this study was to assess the feasibility of the new detection system of sentinel lymph nodes in breast cancer (SentiMag) and to compare its use to the standard method of detection with a radioisotope and a gamma-probe. METHODS: Twenty breast cancer patients scheduled for sentinel lymph node biopsy underwent standard lymphatic mapping with a radioisotope and also with the Sienna+ tracer. During the surgery, sentinel lymph nodes were identified preferably with the SentiMag system. The gamma-probe was used only at the end of the surgery to verify whether all sentinel lymph nodes had been harvested. RESULTS: The sentinel lymph node was detected in all cases. Both methods agreed in 18 cases, i.e. the lymph node with the highest magnetic value ex vivo was the same node as the one with the highest radioactivity. A metastasis in the sentinel lymph node was found in three patients. It is very likely that with the sole use of the SentiMag system, the results would have been identical to those of using the standard method with a radioisotope and the gamma-probe. CONCLUSION: The new magnetic detection method of sentinel lymph nodes (SentiMag) is feasible and clinically comparable to the gold standard method of detection with a radioisotope and the gamma-probe in patients with breast cancer. The new method could find its use not only in hospitals where the department of nuclear medicine is not available but in all hospitals performing sentinel lymph node biopsies in breast cancer and possibly other types of cancer.

[Specialization in oncosurgery is not against the surgeons best interest]. / Specializace v onkochirurgii není proti zájmum chirurgu

An analysis of the current situation in the surgical treatment of solid malignant tumors in the Czech Republic demonstrates the need to impose a concept of oncosurgical care, which would lead to a steady improvement in the quality of care provided by surgeons in oncosurgery. The primary aim is that surgery plays an appropriate role in the complex care of oncology patients and that surgeons become equal partners to radiation and internal oncologists in the determination of diagnostic - therapeutic plans and in other decision-making processes. This aim is not possible without increasing the qualification of surgeons in oncosurgery. Our more than ten year effort culminated in 2011 with the introduction of the specialized field of oncosurgery into the postgradual education of surgeons; and as such, similarly to most other developed countries, provided the official opportunity to educate surgeons in the field of oncology. Other important tasks which would contribute to increasing the quality of oncosurgery include rational concentration of oncosurgical operations to a smaller number of surgical departments, where it is necessary to ensure both the improvement of surgeon qualification by way of oncosurgical specialization, as well as adequate material and financial support for complex oncosurgical procedures.

[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.

[NoT restinG surGEONs--brief parametric standard for oncosurgery]. / NoT restlnG surGEONs aneb strucný parametrický standard pro onkochirurgii.

Standardization of therapeutic schedules becomes now more requested not only in oncology and oncosurgery. In fact, simple parametrisation and regular evaluation of oncological algorithms is more needed than files of instructions on diagnosis and therapy, which should be already contained in medical education. An original simple system of basic parameters is presented under acronyme NoT ReStInG SurGEONs,which includes five indicators of quality of diagnosis and three characteristics documenting quality of care and experience of therapeutic teams. Key indicators for parametrisation in solid tumors are: nodal status (No), T category and typing (T), resection margins (Re),postoperative clinical stage (St), investigation on grade and biological features (InG), survival rate achieved in hospital or team (Sur), guaranty of team decision and multidisciplinary expert opinion (GEO) and numbers of treated cases reflecting experience of hospital or team with particular oncological diagnoses (Ns). Considered and discussed are also some problems with interpretation and implementation of this parametric approach.

[Surgical management of solid tumors in the Czech Republic]. / Chirurgická lécba solidních nadoru v Ceské republice.

AIM: The aim of this work was to point out the role and the significance of surgery in the management of oncology patients in the Czech Republic (CR). MATERIAL AND METHODOLOGY: Involvement of surgery in the management of patients with solid tumors is documented based on statistical data collected from the National Oncologic Registry. RESULTS: In the Czech Republic, the number of patients operated for newly diagnosed malignant tumors is constantly increasing, e.g. over 44,000 patients in 2005. Considering tumor locations, various surgical specialists are involved in the surgical management of solid tumors. Overall, during the studied period, surgeons were involved in 32,760 surgical procedures, i.e. 73.6 % of all newly diagnosed malignant solid tumors. Oncosurgical procedures are, to a certain extent, performed in all surgical clinics in the Czech Republic (currently, there are 157 surgical clinics in the Czech Republic). The rates of procedures for individual diagnoses do not correspond with the "high volume hospital" principle. CONCLUSION: Based on the analysis of the current situation in the management of solid tumors in the Czech Republic, the authors recommend rational concentration of oncosurgical procedures to fewer surgical clinics, adequate financing of sophisticated oncosurgical procedures in these clinics and classification of oncosurgery as a recognized official medical specialty.

[Surgical oncology specialty in the Czech Republic]. / Specializace v chirurgické onkologii v Ceské republice.

AIM: The aim of this work was to create a proposal design of the educational programme in surgical oncology (oncosurgery) in the Czech Republic, which would provide a recognized official specialty training for surgeons. MATERIAL AND METHODOLOGY: The programme was designed based on experience with this specialty in Europe and USA, as well as on the authors' own long-term practical experience in oncosurgery. The material was discussed by the Committee of the Czech Surgical Association and ammended based on the comments. OUTCOMES: The proposed surgical oncology (oncosurgery) educational programme is designed as a subspecialty of general surgery and its aim is to gain high qualification for the treatment of solid tumors. The course duration is 3 years and is aimed at theoretical and clinical knowledge on tumor disorders. The practical training includes the following modules: Melanomas and sarcomas, Gastrointestinal surgery, Endocrine surgery, Breast surgery and Thoracic surgery. The trained doctor must gain practical experience in at least one module. CONCLUSION: The surgical oncology (oncosurgery) educational programme proposal was submitted to the Czech Republic Ministry of Health at the end of 2008. The authors applied for the programme to be included in the postgradual training system.

Basin characteristics and nutrient losses: the EUROHARP catchment network perspective.

The EC-funded EUROHARP project studies the harmonisation of modelling tools to quantify nutrient losses from diffuse sources. This paper describes a set of study areas used in the project from geographical conditions, to land use and land management, geological and hydro-geological perspectives. The status of data availability throughout Europe in relation to the modelling requirements is presented. The relationships between the catchment characteristics and the nutrient export are investigated, using simple data available for all the catchments. In addition, this study also analyses the hydrological representativity of the time series utilised in the EUROHARP project.

Nitrogen and phosphorus retention in surface waters: an inter-comparison of predictions by catchment models of different complexity.

Nitrogen and phosphorus retention estimates in streams and standing water bodies were compared for four European catchments by a series of catchment-scale modelling tools of different complexity, ranging from a simple, equilibrium input-output type to dynamic, physical-based models: source apportionment, MONERIS, EveNFlow, TRK, SWAT, and NL-CAT. The four catchments represent diverse climate, hydrology, and nutrient loads from diffuse and point sources in Norway, the UK, Italy, and the Czech Republic. The models' retention values varied largely, with tendencies towards higher scatters for phosphorus than for nitrogen, and for catchments with lakes (Vansjø-Hobøl, Zelivka) compared to mostly or entirely lakeless catchments (Ouse or Enza, respectively). A comparison of retention values with the size of nutrient sources showed that the modelled nutrient export from diffuse sources was directly proportional to retention estimates, hence implying that the uncertainty in quantification of diffuse catchment sources of nutrients was also related to the uncertainty in nutrient retention determination. This study demonstrates that realistic modelling of nutrient export from large catchments is very difficult without a certain level of measured data. In particular, even complex process oriented models require information on the retention capabilities of water bodies within the receiving surface water system and on the nutrient export from micro-catchments representing the major types of diffuse sources to surface waters.

[Chemosensitivity prediction in tumor cells ex vivo--difficulties and limitations of the method]. / Predikce citlivosti nádorových bunek k chemoterapeutikum ex vivo--úskali a limitace vlastní metody.

Certain hope is entertained in the prediction of chemosensitivity in vitro/ ex vivo for the purpose of selecting the most effective treatment of malignant diseases with minimal patient loading. The possible choice of an effective substance based on the results of a simple ex vivo test would increase the success of the treatment in case of standard chemotherapy failure or in the treatment of primary chemoresistant tumor. MTT test seems to be an easy process for the prediction of chemosensitivity of isolated malignant cells ex vivo, however each method represents a simple tool, which can provide false results if incorrectly preformed. Numerous limitations significantly reduce the successful evaluation and constituent aspects of the methodic press to further reflections about the proper application of the test.

[Actual state of ex vivo chemoresistance testing of malignant tumors in Masaryk Memorial Cancer Institute Brno]. / Soucasný stav testování chemorezistence nádoru ex vivo v Masarykove Onkologickém Ustavu v Brne.

Chemoresistance assay results may play a role in cancer management decision process. Since August 2006 testing chemoresistance has been tested according to a protocol that was designed for this reason in our institute (Masaryk Memorial Cancer Institute). Five groups of different types of cancer in particular clinical stages were defined for chemosensitivity testing with: (1) metastatic malignant melanoma, (2) soft tissue sarcoma (STS), either primary or recurrent/metastic, (3) primary or metastatic renal cancer, (4) recurrent ovarian cancer and (5) other diagnosis "on clinician's request". In the period from September 2006 to November 2007, 25 samples of malignant melanoma (reproducible results in 9 cases), 29 samples of STS (relevant data in 11 cases), 36 samples of renal cancer (relevant results in 20 samples) and 16 samples of ovarian cancer (reproducible results in 11 cases) were acquired. Sensitivity to certain chemotherapy agent observed ex vivo does not necessarily mean that the cancer would also be sensitive to the same agent in vivo, however, ex vivo resistance with following in vivo sensitivity of the tumour has not been observed to date. The cultivation of malignant cells is very uncertain in solid tumours, which consist of several malignant cell multiclones (benign/stromal cells may outgrow malignant cells). This cultivation uncertainty as well as the unique complexity of human metabolism makes clinical application of chemoresistance testing at least very questionable. The small number of successfully evaluated samples has not yet provided us to carry out proper statistical evaluation and clinical application.

Identification of alphaB-crystallin, a biomarker of renal cell carcinoma by SELDI-TOF MS.

Spectrometric-based surface-enhanced laser desorption/ionization ProteinChip (SELDI-TOF) facilitates rapid and easy analysis of protein mixtures and is often exploited to define potential diagnostic markers from sera. However, SELDI- TOF is a relatively insensitive technique and unable to detect circulating proteins at low levels even if they are differentially expressed in cancer patients. Therefore, we applied this technology to study tissues from renal cell carcinomas (RCC) in comparison to healthy controls. We found that different biomarkers are identified from tissues than those previously identified in serum, and that serum markers are often not produced by the tumors themselves at detectable levels, reflecting the nonspecific nature of many circulating biomarkers. We detected and characterized áB-crystallin as an overexpressed protein in RCC tissues and showed differential expression by immunohistochemistry. We conclude that SELDI-TOF is more useful for the identification of biomarkers that are synthesized by diseased tissues than for the identification of serum biomarkers and identifies a separate set of markers. We suggest that SELDI-TOF should be used to screen human cancer tissues to identify potential tissue-specific proteins and simpler and more sensitive techniques can then be applied to determine their validity as biomarkers in biological fluids.

Preoperative radiotherapy and concomitant capecitabine treatment induce thymidylate synthase and thymidine phosphorylase mRNAs in rectal carcinoma.

This work is intended to study the effect of preoperative capecitabine and radiotherapy treatment on the levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) mRNAs in rectal carcinoma. 55 patients with locally advanced rectal carcinoma (cT3-4, N0, M0 or cT2-4,N+, M0) were treated with capecitabine 825 mg/m2 twice a day and pelvic radiotherapy 1,8 Gy daily up to cumulative dose of 45 Gy, boosting up to 50,4 Gy. Patients underwent surgery 6th week after the completion of chemoradiotherapy. Biopsies of rectal carcinoma were taken before starting therapy and 14 days after its cesation. Biopsies were examined for TS, DPD and TP mRNA levels. CEA in serum was examined to monitor relapses. Both TP and TS mRNA increase two weeks after starting therapy (p<0,001). TP mRNA median levels were elevated 2,3x after starting therapy. Moreover responders exhibit 1,5x higher induction than non-responders both before and after starting therapy, but difference is significant before therapy only (p=0,017). Non-responders have most frequent TS induction. Complete remission was observed in 17% and substantial responses with microscopic residuum only in additional 19% of cases were achieved. The pathologic downstaging rate was 76%. Our data show that TS and TP mRNA are induced by preoperative chemoradiotherapy in both responders and nonresponders. TP induction is in accordance with the expected role of TP in the activation of capecitabine and the known promoting role of TP in tissue fibrosis frequently associated with tumor regression.