Reprogrammed transsulfuration promotes basal-like breast tumor progression via realigning cellular cysteine persulfidation.

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast tumors with poor prognosis and limited molecular-targeted therapy options. We show that BLBC cells have a high Cys demand and reprogrammed Cys metabolism. Patient-derived BLBC tumors from four different cohorts exhibited elevated expression of the transsulfuration enzyme cystathione ß-synthetase (CBS). CBS silencing (shCBS) made BLBC cells less invasive, proliferate slower, more vulnerable to oxidative stress and cystine (CySSCy) deprivation, prone to ferroptosis, and less responsive to HIF1-α activation under hypoxia. shCBS xenograft tumors grew slower than controls and exhibited impaired angiogenesis and larger necrotic areas. Sulfur metabolite profiling suggested that realigned sulfide/persulfide-inducing functions of CBS are important in BLBC tumor progression. Supporting this, the exclusion of serine, a substrate of CBS for producing Cys but not for producing sulfide/persulfide, did not exacerbate CySSCy deprivation-induced ferroptosis in shCBS BLBC cells. Impaired Tyr phosphorylation was detected in shCBS cells and xenografts, likely due to persulfidation-inhibited phosphatase functions. Overexpression of cystathione γ-lyase (CSE), which can also contribute to cellular sulfide/persulfide production, compensated for the loss of CBS activities, and treatment of shCBS xenografts with a CSE inhibitor further blocked tumor growth. Glutathione and protein-Cys levels were not diminished in shCBS cells or xenografts, but levels of Cys persulfidation and the persulfide-catabolizing enzyme ETHE1 were suppressed. Finally, expression of enzymes of the oxidizing Cys catabolism pathway was diminished, but expression of the persulfide-producing CARS2 was elevated in human BLBC tumors. Hence, the persulfide-producing pathways are major targetable determinants of BLBC pathology that could be therapeutically exploited.

Characterization of Danube Swabian population samples on a high-resolution genome-wide basis.

BACKGROUND: German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcso-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3-6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples. RESULTS: Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany. CONCLUSION: This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns.

[Role of MRI and CT in the evaluation of postirradiation status and complications in head and neck cancer]. / Az MRI és a CT szerepe a sugárterápia utáni státusz értékelésében, szövõdményeinek vizsgálatában, fej-nyaki daganatoknál.

Most head and neck cancer patients are treated with combined modalities such as surgery, radiotherapy (RT), chemotherapy (ChT). Concurrent chemo-radiation has improved treatment outcomes with increased toxic effects. Reactions after RT are divided into early and late changes. Early reactions are seen during the course of therapy or within 3 months; these are reversible in most cases. Late complications are observed 3 months to years after RT and they are generally irreversible. As typical late reaction radiation induced necrosis may occur in soft tissues, cartilage, bones and brain. Tumor recurrence and post-radiation necrosis typically appear at the same time, within 2-3 years after RT; the differentiation may be difficult. Computed tomography (CT) and magnetic resonance imaging (MRI) have become the gold standards not only for staging and assessing tumor response, but also to evaluate posttreatment status, to distinguish residual or recurrent tumor and RT complications. Using baseline CT or MRI between 2-3 months after treatment and performing standard follow-up imaging with strict clinical follow-up are required to establish early salvage treatment.

Challenging tumour immunological techniques that help to track cancer stem cells in malignant melanomas and other solid tumours.

AIM OF THE STUDY: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells. MATERIALS AND METHODS: As a novel approach, we investigated B cells infiltrating breast carcinomas and melanomas (TIL-B) in terms of their tumour antigen binding potential. By developing the TIL-B phage display technology we provide here a new technology for the specific detection of highly tumour-associated antigens. Single chain Fv (scFv) antibody fragment phage ELISA, immunofluorescence (IF) FACS analysis, chamber slide technique with IF confocal laser microscopy and immunohistochemistry (IHC) in paraffin-embedded tissue sections were set up and standardized. RESULTS: We showed strong tumour-associated disialylated glycosphingolipid expression levels on various cancer cells using scFv antibody fragments, generated previously by uniquely invasive breast carcinoma TIL-B phage display library technology. CONCLUSIONS: We report herein a novel strategy to obtain antibody fragments of human origin that recognise tumour-associated ganglioside antigens. Our investigations have the power to detect privileged molecules in cancer progression, invasiveness, and metastases. The technical achievements of this study are being harnessed for early diagnostics and effective cancer therapeutics.

[The current situation of cancer morbidity and mortality in the light of the National Cancer Registry]. / A rákmorbiditás és -mortalitás jelenlegi helyzete a Nemzeti Rákregiszter tükrében.

In a previous issue of this journal the authors presented and summarized the basic objectives and tasks of the Hungarian National Cancer Registry positioned in an international environment. The recent publication is a continuation of the previous one. Based on the presentation and analysis of current statistical data, the public health background with the possible risk factors is examined. Considering changes in recent years, the mortality data are relatively stable, although slightly wavering. The trends are promising in some cancers (for example lip and oral cavity, breast, prostate cancers) however. Contrary to the barely changing nature of the total cancer deaths the number of annually reported new cases has increased significantly, which indicates a more effective role in both diagnostics and therapy. In light of the above, it is confirmed that the restructure of the national oncology care system and the European conformation is inevitable. Orv. Hetil., 2017, 158(3), 84-89.

[Human papillomavirus associated cervix uteri morbidity in Hungary: epidemiology and correlation with the HPV types and the simultaneous cytological diagnosis]. / Humán papillomavírus asszociált méhnyak-megbetegedések Magyarországon: epidemiológia és a HPV-típusok összefüggése a párhuzamosan végzett citológiai diagnózissal.

INTRODUCTION: Persistent infection of human papillomavirus is known to cause cervical intraepithelial neoplasia or cancer in the cervix uteri and other HPV-associated cancers in different localization. Based on epidemiological and biological data, principally the high risk HPV is responsible for development of cervical these cancers. However, we have no information about the frequently distribution of different HPV types and what is the correlation between the HPV types and cytological diagnosis in cervical intraepithelial neoplasia (CIN). AIM: In this paper, we are going to present new data involving incidence and mortality of HPV-associated cancers during the period of 2009-2015 in Hungary. We are also going to investigate the correlation of cervical cytological diagnosis and HPV typing, and the preventive effect of HPV vaccination. METHOD: The epidemiological data spring from the National Cancer Registry. HPV typing was performed by Linear Array HPV Genotyping Test. Simultaneous cytological diagnosis and HPV typing was carried out on 2048 cytological samples collected in period of 2009-2016. RESULTS: According to the epidemiologic data, the most frequently occurring HPV-associated cancer is the laryngeal carcinoma in man, and the cervical cancer in woman in Hungary. During the 2009-2015 time intervals, the frequency distribution of head and neck cancers was not changed in man, but the incidence of tongue root squamous cell carcinomas was gradually increasing in woman. We have defined the clinical significance of single and simultaneously multiple HPV infection and have investigated the correlation of the HPV frequency distribution and cytological diagnosis in CIN. It was found that in the cytological negativity of probably/possibly carcinogen pHR-HPV group classified by IACR was much more frequent as in HR-HPV group (56% versus 47%). The presence of simultaneous multiplex HPV infection betokens an increased cancer risk. According to the international publications, the ratio of HPV16 just twice as big as in cervical cancer, what we found in CIN (60% versus 30%). The frequency order of the HPV18 is 2nd in cancer, and 9th in CIN. Comparing the frequency distribution of HR/pHR-HPVs in cervical cancer and CIN, the HR-HPV35 is very rarely occurring in CIN, the pHR-HPV56, 66, and 73 is more frequently seen in CIN as in carcinoma. Appreciated the preventive value of anti-HPV vaccines, we have found a significant differences in group with 1 HPV/sample and in group with more than 1 HPV/sample. CONCLUSION: The frequency distribution of tongue root squamous cell carcinoma and cervical cancer was gradually increasing in woman. The overall preventive effect of 9-valent vaccine is 80.3%. This preventive value should be higher because of the transformation ability of the different HPV types is not same. Out of consideration for HPV incidence in cancer, the preventive effect of 9-valent or 4-valent vaccines might reach to 93% or 73%. However, the pHR-HPVs are biologically active, it is not sufficient for the inclusion of these HPV types into population-wide HPV-DNA based cervical screening programs. Orv Hetil. 2017; 158(31): 1213-1221.

Time trends in axilla management among early breast cancer patients: Persisting major variation in clinical practice across European centers.

Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79-96% and 49-92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary.

Human papilloma virus status evaluation and survival description in selected oropharyngeal and laryngeal squamous cell carcinoma patients from Hungary.

PURPOSE: Many patients with oropharyngeal squamous cell carcinomas do not have any of the traditional risk factors associated with head and neck squamous cell cancers (HNSCC). Epidemiologic and molecular studies have identified human papillomavirus (HPV) as a causative agent, viral tumors presenting a better survival and being important risk factors together with the long established ones, tobacco and alcohol consumption, in head and neck cancers. The purpose of this study was to establish the incidence of HPV-associated HNSCCs, to identify the most frequent HPV type and to evaluate the overall survival and recurrence rates of HPV-positive cases in comparison with HPV-negative HNSCCs. METHODS: A retrospective analysis from the database of the National Institute of Oncology from Budapest was performed and the following parameters were analyzed: age, age at diagnosis, gender, primary tumor location, tumor histopathology, TNM stage, HPV status, date of recurrence, last visit and date of death. RESULTS: Out of 81 patients with HNSCCs 55 (67.9%) were male and 26 (32.1%) female. HNSCCs were more frequent in men (2.11:1) and the majority of the patients (81.7%) were diagnosed in advanced stages (TNM III and IV). HPV status was evaluated in nearly half (48.14%) of the patients and HNSCCs were positive for HPV in 43.6% of the cases. These were more frequent in patients over 50 years (76.66%), in men (76.47%) and in oropharyngeal location (94.1%). HPV-16 type was associated with malignancy in 82.35% of the cases. Disease recurrence was more frequent in HPV-negative (31.81%) vs HPV-positive cases (29.41%) and mortality rate was inferior in HPV-positive 33.33% vs negative (38.09%) tumors (p=0.52). CONCLUSIONS: In Hungary HNSCCs are more frequent in men than in women. HPV positivity is higher in men vs women and in oropharyngeal vs laryngeal location. Overall survival rate was superior in HPV-positive vs HPV-negative cases. Disease recurrence was more frequent in HPV-negative vs HPV-positive cases.

[Evaluation of clinicopathological findings and cosmetic outcome of 100 immediate postmastectomy breast reconstruction cases]. / Azonnali, postmastectomiás emlorekonstrukciókkal szerzett tapasztalatok. Száz eset klinikopatológiai utánkövetése és a kozmetikai eredmények felmérése.

INTRODUCTION: Immediate breast reconstruction provides oncological safety, requires longer operation time. It does not influence the initiation of adjuvant therapy and radiological control, and results in favourable cosmetic outcome. AIM: Assessing the Hungarian data of immediate postmastectomy breast reconstructions, and comparing them to international findings. METHOD: Between May, 2011 and September, 2014 121 therapeutic and prophylactic, postmastectomy immediate breast reconstructions were performed in 100 patients. The clinico-pathological findings were assessed retrospectively, and surgical, oncological and cosmetic outcomes were evaluated statistically. RESULTS: The mean age of patients was 42.6 years, the follow up time was 29.4 months, and the duration of operation was 132 minutes. Skin-sparing mastectomy was performed most commonly (64%) with submuscular tissue expander placement (70%). Early postoperative complication was identified in 18 patients, and loco-regional recurrence in 1 patient. Most patients (89%) were satisfied with the cosmetic outcome. The average initiation time of adjuvant therapy was 4.8 weeks. CONCLUSIONS: Immediate breast reconstruction is a safe and effective option in line with international findings. Orv. Hetil., 2016, 157(46), 1830-1838.

[Breast cancer care quality analysis of the National Institute of Oncology in Hungary according to the requirements of European Society of Breast Cancer Specialists (EUSOMA)]. / A European Society of Breast Cancer Specialists (EUSOMA) eloírásainak megfelelo emlorákellátás minoségbiztosítási elemzése az Országos Onkológiai Intézetben.

INTRODUCTION: The European Society of Breast Cancer Specialists has created quality indicators for breast units to establish minimum standards and to ensure specialist multimodality care with the conscious aim of improving outcomes and decreasing breast cancer mortality. AIM: The aim of this study was to analyse the breast cancer care in the National Institute of Oncology according to the European Society of Breast Cancer Specialists requirements and in a large number of cases in order to present representative clinico-pathological data on the incidence of breast cancer in Hungary. METHOD: According to the European Society of Breast Cancer Specialists uniformed criteria clinico-pathological data of multimodality treated breast cancer cases were retrospectively analysed between June 1, 2011 and May 31, 2012. RESULTS: During the period of interest 906 patients underwent breast surgery for malignant or benign lesions. According to the European Society of Breast Cancer Specialists quality indicators the breast cancer care of the National Institute of Oncology is eligible. CONCLUSIONS: The diagnostic modalities and multimodality care of breast cancer of the National Institute of Oncology breast unit meets the critical mass and minimum standards of the European Society of Breast Cancer Specialists criteria. Orv. Hetil., 2016, 157(42), 1674-1682.

[Genetic information from tumor-infiltrating B lymphocytes as a driver tool ("GPS") for anti-tumor T cell CARs]. / A tumorban felhalmozódó B-limfociták genetikai információja, mint az immun T-sejt vezette tumorellenes "autó" (CAR, kiméra antigénreceptor) célba irányító "GPS"-e.

The rapidly growing field of gene therapy techniques to modify T cells with chimeric antigen receptors (CARs) for cancer care solutions, reached considerable achievements. However, there is an urgent need of reliable, well tolerable tumor-associated antigen specific antibodies. Tumor-infiltrating B (TIL-B) cell originated single chain Fv (scFv) gene regions could be selected with tumor specificity. DNA sequences of these antibody variable regions were subjects to get engineered into new CAR constructs. Our novel strategy harnesses tumor-infiltrating B cells' unique capacity to reveal highly tumor-associated disialylated glycosphingolipids (GD3 gangliosides). We used these human antibody fragments for generating GD3 ganglioside specific CAR gene constructs for potential usage in solid tumors.

Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III-IV unresectable head and neck cancer: Results of a randomized phase II study.

PURPOSE: Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer. PATIENTS AND METHODS: Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed. RESULTS: Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53-82 months). The rate of radiologic complete response was 63% following ICT + CRT, whereas 70% after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57%), LRTC (42 vs. 50%), OS (43 vs. 55%), and PFS (41 vs. 50%) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3-4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12%; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42% in the ICT + CRT and CRT groups, respectively. CONCLUSION: The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of adequate patient selection if ICT is considered.

[On-site fine-needle aspiration cytology of thyroid nodules. Quality assurance of the Bethesda System for Reporting Thyroid Cytopathology (2008)]. / Pajzsmirigygöbök vékonytu-aspirációs citológiai vizsgálata. A Bethesda-rendszer (2008) minoségbiztosítása.

INTRODUCTION: The methods available for the diagnosis of thyroid nodules include physical examination, imaging, laboratory and fine-needle aspiration cytology tests. AIM: The aim of this study was to determine the quality assurance of fine-needle aspiration cytology of thyroid nodules. METHOD: Cytology results were rated to 6 categories according to the Bethesda System for Reporting Thyroid Cytopathology (2008) (I. nondiagnostic; II. benign; III. atypia of undetermined significance; IV. follicular neoplasia; V. suspicious for malignancy; VI. malignant). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 1384 patient with thyroid nodule underwent fine-needle aspiration biopsy cytology. Smears were classified I. inadequate in 214 (15.9%); II. benign 986; III. atypical 56; IV. follicular neoplasm 41; V. suspicious for malignancy 18; VI. malignant 33 cases. Two hundred and twenty seven (16.8%) of the cases were operated and histologically verified. The positive predictive value in the benign category was 98.25% and in the malignant 88.46%. The sensitivity of the follicular neoplasm was 66.67%. CONCLUSION: The results suggest that fine-needle aspiration cytology of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology has a high diagnostic accuracy. The auditing values of the results meet the proposed threshold values.

[Status report of Hungarian radiotherapy based on treatment data, available infrastucture, and human resources]. / A magyar sugárterápia helyzete a betegellátási adatok, a rendelkezésre álló infrastruktúra és emberi eroforrás tükrében.

The purpose of the study is to report the status of Hungarian radiotherapy (RT) based on the assessment of treatment data in years 2012 to 2014, available infrastructure, and RT staffing. Between December 2014 and January 2015, a RT questionnaire including 3 parts (1. treatment data; 2. infrastructure; 3. staffing) was sent out to all Hungarian RT centers (n=12). All RT centers responded to all questions of the survey. 1. Treatment data: In 2014, 33,162 patients were treated with RT: 31,678 (95.5%) with teletherapy, and 1484 (4.5%) with brachytherapy (BT). Between 2012 and 2014, the number of patients treated with radiotherapy increased with 6.6%, but the number of BT patients decreased by 11%. Forty-two percent of all patients were treated in the two centers of the capital: 9235 patients (28%) at the National Institute of Oncology (NIO), and 4812 (14%) at the Municipial Oncoradiology Center (MOC). Out of the patients treated on megavoltage RT units (n=22,239), only 901 (4%) were treated with intensity-modulated RT (IMRT), and 2018 (9%) with image-guided RT (IGRT). In 2014, 52% of all BT treatments were performed in Budapest: NIO - 539 patients (36%); MOC - 239 patients (16%); and BT was not available in 3 RT centers. Prostate I-125 seed implants and interstitial breast BT was utilized in one, prostate HDR BT in two, and head&neck implants in three centers. 2. Infrastructure: Including ongoing development projects funded by the European Union, by the end of year 2015, 39 megavoltage teletherapy units, and 12 HDR BT units will be in use in 13 available Hungarian RT centers. 3. Staffing: Actually, 92 radiation oncologists (RO), 29 RT residents, 61 medical physicists, and 229 radiation therapy technologists are working in 12 RT centers. There are 23 vacant positions (including 11 RO positions) available at the Hungarian RT centers. According to the professional minimal requirements and WHO guidelines, the implementation of 11 new linear accelerators, and 1 BT units are needed in Hungary. Further resources for the development and upgrade of RT infrastructure and capacity should be allocated to RT centers in Budapest. Brachytherapy and modern teletherapy (e.g. IMRT and IGRT) are underutilized in Hungary compared to other European countries. Implementation of continuous education and practical training programs in leading Hungarian and international RT centers are suggested in an effort to a wider implementation of modern RT techniques in Hungarian RT centers.

Evaluation of patient knowledge, desire, and psychosocial background regarding postmastectomy breast reconstruction in Hungary: a questionnaire study of 500 cases.

BACKGROUND: According to European guidelines, breast cancer patients requiring mastectomy should be informed about available options regarding breast reconstruction. There are clear differences in the quality standards of oncoplastic care throughout Europe, with slight improvements in Central European countries like Hungary. The aim of the present investigation was to evaluate patients' knowledge and demand for postmastectomy breast reconstruction, as well as their psychosocial background regarding decision-making. MATERIAL AND METHODS: A questionnaire containing 15 structured questions was given to 500 breast cancer patients on the day before undergoing mastectomy. The questions focused on the emotional impact of the malignant disease and the loss of a breast; the importance of environmental conditions; the desire for breast reconstruction; and patients' knowledge and sources of information about the procedure. All answers were statistically analyzed in the context of patient age, marital status, educational level, and place of residence. RESULTS: Descriptive statistical results of the answers to all questions, as well as associations of the different aspects of the decision-making process, are presented. CONCLUSIONS: Hungarian breast cancer patients have very limited knowledge regarding breast reconstruction. We confirmed that patients scheduled for mastectomy have a great degree of anxiety due to their disease and breast loss. Almost 50% of the responders declared their desire for postmastectomy breast reconstruction. Patient's age, residence, educational level, marital status, and profession were confirmed as predictive factors in the decision-making process for breast reconstruction.

[National Cancer Registry. Significance of a reliable database in the implementation of the required structural changes of cancer care in Hungary]. / Nemzeti Rákregiszter. A hiteles adatok gyujtésének jelentosége a hazai onkológiai ellátás szükségszeru szerkezetváltásában.

The authors summarize the basic objectives and scope of the Hungarian Cancer Registry. They review more than 100-year history of the national cancer database and its effects on current cancer data collection activities, which is outstanding in Europe. The compilation deals with the development of information technology, covers points of principle and practical issues such as parallel display and evaluation of mortality and morbidity statistics and their national and international importance concerning public health. The authors underline that reliable data collection and services of the National Cancer Registry are important for the society because they are public health issues with a critical importance for a better understanding of risk factors, prevention and patient care. Restructuring and European harmonization of the Hungarian cancer system are inevitable using a reliable information exchange and service, taking into account national specificities and international requirements.

[Modern breast reconstruction with endoscopically assisted latissimus dorsi flap harvesting]. / Endoszkóposan asszisztált latissimus dorsi izomlebeny alkalmazása a korszeru rekonstrukciós emlosebészetben.

Skin- and nipple-sparing mastectomies made immediate breast reconstruction possible on a systemic level within breast cancer surgery. Mass reconstruction needs brought by the most common malignancy in women can only be met by the use of implant-based techniques, providing excellent cosmetic results and high patient satisfaction. For these postmastectomy reconstructions the replacement of the skin is no longer a challenge, but the well vascularized, good quality soft tissue coverage of the implant. Oncoplastic breast surgery today is able to conduct oncologically radical complete removal of the glandular tissue through an incision of 6-10 cm made in the armpit, with the nearly scarless retention of the natural skin envelope of the breast, and in the same time adequate axillary staging (sentinel node biopsy/axillary lymphadenectomy) is performed, then using the same incision, the implementation of one-step or multi-step breast reconstruction is possible. During these complex interventions, the latissimus dorsi flap formed by endoscopic technique (leaving no scar on the back), rotated to the anterior chest wall can be used for total autologous reconstruction of low-volume breasts as complete coverage of implants placed under the spared skin-envelope or for revitalization of thin or radiation damaged breast skin. This paper presents 4 cases of breast reconstruction with endoscopically assisted latissimus dorsi muscle flap, and the authors demonstrate the surgical technique in detail and conduct a literature review, for the first time in Hungarian.

[Minimally invasive breast surgery]. / Minimálisan invazív emlosebészet.

Due to the development in medical science and industrial technology, minimally invasive procedures have appeared in the surgery of benign and malignant breast diseases. In general , such interventions result in significantly reduced breast and chest wall scars, shorter hospitalization and less pain, but they require specific, expensive devices, longer surgical time compared to open surgery. Furthermore, indications or oncological safety have not been established yet. It is quite likely, that minimally invasive surgical procedures with high-tech devices - similar to other surgical subspecialties -, will gradually become popular and it may form part of routine breast surgery even. Vacuum-assisted core biopsy with a therapeutic indication is suitable for the removal of benign fibroadenomas leaving behind an almost invisible scar, while endoscopically assisted skin-sparing and nipple-sparing mastectomy, axillary staging and reconstruction with latissimus dorsi muscle flap are all feasible through the same short axillary incision. Endoscopic techniques are also suitable for the diagnostics and treatment of intracapsular complications of implant-based breast reconstructions (intracapsular fluid, implant rupture, capsular contracture) and for the biopsy of intracapsular lesions with uncertain pathology. Perception of the role of radiofrequency ablation of breast tumors requires further hands-on experience, but it is likely that it can serve as a replacement of surgical removal in a portion of primary tumors in the future due to the development in functional imaging and anticancer drugs. With the reduction of the price of ductoscopes routine examination of the ductal branch system, guided microdochectomy and targeted surgical removal of terminal ducto-lobular units or a "sick lobe" as an anatomical unit may become feasible. The paper presents the experience of the authors and provides a literature review, for the first time in Hungarian language on the subject. Orv. Hetil., 2014, 155(5), 162-169.

[Clinical application of 18F-FDG PET/CT in the treatment of sarcomas]. / A 18F-FDG PET/CT klinikai alkalmazása és lehetõségei a sarcomák kezelésében.

[18F]-Fluoro-deoxyglucose positron emission tomography / computer tomography (18F-FDG PET/CT) is able to detect and assess the abnormal metabolism, enabling visualization and quantification in vivo with integration into CT anatomic information. The clinical usefulness of FDG PET/CT in the management of patients with sarcomas has been assessed by numerous investigators. Sarcomas are solid malignant tumors with distinct clinical and pathological features. Effective management of patients with sarcoma requires accurate diagnosis and staging. The authors discuss the major indications of PET/CT on the basis of literature data for diagnosis, staging, guidance of biopsy and monitoring response to therapy in both primary bone and soft tissue tumors. The consistent use of PET molecular imaging methods is of high importance in characterizing and understanding sarcoma behavior in clinical practice.

[Selective 12-lipoxygenase inhibition potentiates the effect of radiation on human prostate cancer cells in vitro and in vivo]. / Humán prosztatarák sugárérzékenységének fokozása szelektív 12-lipoxigenáz-gátlással preklinikai modellben.

Prostate cancer is one of the leading cancer types in males in the developed world. Radiotherapy is a major method in the curative treatment of prostate cancer however, up to 30% of the patients experience local relapse. Arachidonic acid metabolites have been shown to have important role in cancer. 12-lipoxygenase (12-LOX) has been proven to significantly influence prostate cancer progression, by apoptosis regulation and by promoting cancer cell survival. In this study we examined whether 12-LOX inhibition may increase radiation sensitivity of prostate cancer cells in vitro and in vivo. Prostate cancer cell lines were treated with 12-LOX inhibitors, different doses of radiation and the combination of 12-LOX inhibitors and radiation. We measured the effect of these treatments through clonogenic survival and apoptosis in vitro and tumor growth in vivo in a tumor xenograft model. 12-LOX inhibition and radiation both increased apoptosis and decreased clonogenic survival of prostate cancer cell lines in vitro. Combined treatment resulted in a supra-additive effect in vitro. In vivo both 12-LOX inhibition and radiotherapy caused delay in growth of the xenograft tumors but the combined treatment resulted in the strongest growth inhibition. The presented data prove that 12-LOX and its metabolite 12(S)-HETE have a major role in prostate cancer cell progression and radiosensitivity. We have shown by different methods in vitro and in vivo that inhibition of 12-LOX activity significantly sensitizes prostate cancer cells to radiation. Therefore we can state that 12-LOX inhibitors are promising compounds to be developed to become a new class of clinical radiation sensitizers in prostate cancer.