Modern Breast Cancer Surgery 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

The role of selenium and vitamin E in a Transylvanian enzootic equine recurrent rhabdomyolysis syndrome.

A severe form of recurrent exertional rhabdomyolysis occurs enzootically in a well-defined region of Transylvania, Harghita county. At the highest lying two settlements (more than 800 m above sea level), the prevalence of equine rhabdomyolysis is between 17 and 23%, while in the neighbouring villages in the valley it is less than 2%. The objective of our study was to clarify the role of selenium and vitamin E in the high prevalence of rhabdomyolysis in that region. Soil and hay samples were collected from each area to evaluate mineral content. Ten horses from the non-affected and 20 horses from the affected area were tested for serum selenium, vitamin E, glutathione peroxidase (GSH-Px), muscle enzymes, lactate and electrolytes. Hay samples collected from the affected area had lower selenium content. Horses in the affected regions had significantly lower serum selenium (P = 0.006) and GSH-Px levels than animals living in the non-affected regions. A good correlation between erythrocyte GSH-Px and serum selenium concentration could be demonstrated (r = 0.777, P < 0.001). Serum vitamin E levels were low independently of the origin of the horse. Based on our results, selenium deficiency possibly has a role in the Transylvanian enzootic equine recurrent rhabdomyolysis syndrome.

[Modern surgical treatment of breast cancer. 4th Breast Cancer Consensus Conference]. / IV. Emlorák Konszenzus Konferencia ­ Az emlorák korszeru sebészi kezelése.

The surgical treatment is still the most effective method in curing of early breast cancer. Breast preservation and the application of oncoplastic principles became generally accepted, the sentinel lymph node biopsy in the surgical treatment of the axilla is primary, and the indication for axillary block dissection (ABD) is narrowing further. The neoadjuvant oncological treatment that is applied more and more widely presented surgery with new challenges. Hereunder we summarise our recommendations on the surgical treatment of breast cancer based on the content of the 3rd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.

Prevalence of Anal Human Papillomavirus Infection in Hungarian Men Who Have Sex with Men.

Anal cancer is one of the leading causes of death in non-AIDS defining cancers. Most of these cancers are associated with high risk HPV infection. So far, the prevalence and the significance of anal HPV infection have not been studied in the Hungarian MSM population. The main objective of our study was to determine the prevalence and associated risk factors of HPV-infection in the Hungarian MSM community, particularly in HIV-infected MSM. Out of 109 examinations 92 samples (80 HIV-infected and 12 HIV-negative MSM) were evaluated for both cytological abnormalities and HPV genotyping PCR. Using a questionnaire all enrolled individuals were interviewed about their sexual behavior, socioeconomic factors, drug use and other known or suspected risk factors. In the HIV-infected cohort 97.5% of the examined individuals were positive for any HPV type. In this group we detected high risk (HR) HPV in 88.8%, low risk (LR) HPV in 75.0% and probably high risk (PHR) HPV in 47.5% and multiple HPV infection was absolutely common (82.5%). In the HIV-negative MSM group the incidence of HPV-infection was 58.3%. The respective rate of HR-HPV, LR-HPV and PHR-HPV genotypes were 33.3%, 58.4%, and 16.7%. In the HIV-negative group both HPV infection frequency and the prevalence of the pertinent genotypes were much lower. The Hungarian MSM population is severely infected with HPV and HR-HPV. High-risk sexual behaviors are strong predictors for acquiring HR-HPV co-infections. Our results underline the necessity of anal cancer screening and the introduction of the vaccination program in the high-risk population.

[Modern surgical treatment of breast cancer. 3rd Breast Cancer Consensus Conference]. / Az emlorák korszeru sebészi kezelése. III. Emlorák-konszenzuskonferencia.

Therapy for breast cancer today is characterised by ever more precise diagnostic methods and ever more effective oncological treatments, a trend which will certainly continue into the future. Breast preservation and the application of oncoplastic principles are increasingly popular. A sentinel lymph node biopsy in the surgical treatment of the axilla is primary, with the indication for axillary block dissection (ABD) narrowing and radiation therapy becoming an alternative to ABD in certain cases. This publication summarises our recommendations on the surgical treatment of breast cancer based on the content of the 3rd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.

[3rd Hungarian Breast Cancer Consensus Conference - Surgery Guidelines]. / III. Emlõrák Konszenzus Konferencia - Az emlõrák korszerû sebészi kezelése.

Therapy for breast cancer today is characterised by ever more precise diagnostic methods and ever more effective oncological treatments, a trend which will certainly continue in the future. Breast preservation and the application of oncoplastic principles are increasingly popular. A sentinel lymph node biopsy in the surgical treatment of the axilla is primary, with the indication for axillary block dissection (ABD) narrowing and radiation therapy becoming an alternative to ABD in certain cases. This publication summarises our recommendations on the surgical treatment of breast cancer based on the content of the 2nd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.

Comparison of dual-color dual-hapten brightfield in situ hybridization (DDISH) and fluorescence in situ hybridization in breast cancer HER2 assessment.

The most optimal method for assessing HER2 status is still subject to controversy as far as the type of assay used, the optimal method to perform, and the costs of each assay are concerned. The current study was done as a validation study prior to setting up a clinical HER2 testing service using the new commercial dual-color dual-hapten brightfield in situ hybridization (DDISH), but it was felt that our experience may be of interest to other laboratories considering setting up HER2 diagnostic facilities. One hundred and five patients diagnosed with invasive breast cancer were selected. PathVysion FISH and DDISH assays were carried out. Concordance correlation coefficients showed near perfect agreement in average HER2 and centromere-specific signal counts per cell and in HER2/CEN17 ratios between the PathVysion and the DDISH assays, and also the Kappa measure showed near perfect agreement between the two assays (Kappa=0.8712, P<0.0001). Statistical analysis confirmed that the two assays are comparable in terms of detection of HER2 gene amplification and suggests its utilization in routine HER2 diagnostics.

[Predictive factors of invasion with initial diagnosis of ductal carcinoma in situ based on core biopsy]. / Az invazivitás prediktív faktorai hengerbiopsziával in situ ductalis carcinomának diagnosztizált emlodaganatokban.

INTRODUCTION: Previous studies suggest that sentinel lymph node biopsy (SLNB) should not be performed in case of pure ductal carcinoma in situ (DCIS) routinely. In order to avoid a second operation for invasive cancer detected postoperatively the chance of invasion need to be determined preoperatively. The purpose of our retrospective study was to evaluate the sensitivity of core biopsy and determine the predictive value of clinical and histological factors of invasion in cases when DCIS diagnosed preoperatively. MATERIAL AND METHODS: Between January 2006 and December 2011, 1311 patients were treated for breast cancer in our institute, of whom preoperative core biopsy showed DCIS in 50 cases. Wide excision or quadrantectomy was performed in 41 cases, re-excision was necessary in 6 cases for positive surgical margins and mastectomy was carried out in four patients for multicentricity. In further 9 cases extensive tumour size indicated mastectomy straight away. SLNB was carried out in 31 patients, axillary block dissection (ABD) in 8 patients, while ABD for positive sentinel nodes in another two cases. Pathology showed invasion in 17 (34,7 %) cases. RESULTS: Multivariate analysis showed that tumour grade, symptomatic disease, patients' age were significant predictors of invasion. Although preoperative tumour size also showed correlation with invasiveness, this was statistically not significant. CONCLUSION: Evaluation of a larger patient population might be helpful to identify women who should undergo tumour excision and SLNB as a single step operation due to increased risk of invasive disease despite the preoperative diagnosis of DCIS.

Preparation and spectral characterization of fluorescence probes based on 4-N,N-dimethylamino benzoic acid and sterically hindered amines.

The adducts of simple chromophore 4-N,N-dimethylamino benzoic acid with 2,2,6,6-tetrametyl-4-hydroxy- or 4-amino-piperidine were examined as fluorescence probes (spin double sensors) to monitor radical processes. The links in the adducts were either an ester or amide group, and the sterically hindered amines were in the form of -NH, -NO• and -NOR. The spectral properties of the three related derivatives (esters or amides) were quite similar. The maxima of the absorption spectra were in the range of 295-315 nm, and the maximum of fluorescence was located in the range of 330-360 nm, depending on the polarity of the solvent. In polar solvents, a red-shifted fluorescence band at 460-475 nm was observed. The fluorescence of these derivatives was rather weak as compared to anthracene under the same conditions. The Stokes shift was large, as high as 6,000 cm(-1), indicating the formation of a twisted intra-molecular charge transfer (TICT) state. No large differences in Stokes shifts were observed in polymer matrices of poly(methyl methacrylate), polystyrene and poly(vinyl chloride). The extent of intramolecular quenching was expressed as Φ(NX)/Φ(NO) (X = H, NOR) and was in the range of 1-3 in solution and as high as 8 in polymer matrices. The low efficiency of intramolecular quenching limits the application of these new adducts as fluorescence probes for the monitoring of radical processes in solution but favors their application in polymer matrices.

Impact of chromosome 17 centromere region assessment on HER2 status reported in breast cancer.

Recent studies have indicated that polysomy 17 is a rare event in breast cancer, and polysomy is usually mimicked in FISH analysis by gain or amplification of the centromere covered by the chromosome 17 centromere probe. To estimate the impact of chromosome 17 centromere assessment on routine practice, we conducted a retrospective re-classification study. Four hundred and five consecutive cases were selected. The original molecular pathology reports were available. Centromere 17 copy counts were ignored in the reassessment. Altogether, nineteen (4.69%) discrepant cases were found, from which five (1.23%) were considered originally non-amplified but had an HER2 copy number >6. Therefore, we reclassified them as HER2-amplified, while fourteen (3.46%) cases were originally considered amplified with 6 or fewer HER2 signals/cell. The discrepant cases found in our reassessment study would require further high-resolution genetic analysis to resolve the disagreement. On the other hand, our result also highlights that for the vast majority of breast cancer cases traditional FISH examination is still adequate to reach the correct diagnosis. This diagnostic gap must be filled by more sophisticated genetic examinations. Moreover, upcoming HER2 guidelines should consider the aid that high-resolution karyotyping can give to the diagnostic algorithm.

Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies.

BACKGROUND: In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non-AIDS-defining malignancies. METHODS: A total of 14,453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virus-related, non-virus-related epithelial, and other. The incidence of non-AIDS-defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non-AIDS-defining malignancies. RESULTS: A total of 356 non-AIDS-defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow-up (95% confidence interval [CI], 3.8-4.7); 172 (48.3%) were virus-related, 135 (37.9%) were non-virus-related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non-AIDS-defining malignancies within each group. After adjustment, current CD4 was associated with virus-related non-AIDS-defining malignancies (incidence rate ratio [IRR], 0.81 per doubling; 95% CI, 0.75-0.88; P < .0001) and non-virus-related epithelial non-AIDS-defining malignancies (IRR, 0.84; 95% CI, 0.75-0.95; P = .004), but not with other non-AIDS-defining malignancies (IRR, 1.04; 95% CI, 0.83-1.31; P = .73). Current CD4 count was also associated with anal cancer (IRR, 0.86; 95% CI, 0.75-0.99; P = .03), Hodgkin lymphoma (n = 52; IRR, 0.83; 95% CI, 0.73-0.95; P = .005), and lung cancer (IRR, 0.76; 95% CI, 0.64-0.90; P = .0002). CONCLUSIONS: A low current CD4 count was associated with an increased incidence of certain non-AIDS-defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS-related malignancies. A randomized trial to explore this strategy is urgently needed.

Photo-crosslinking of polyethylene by mono- and diacetophenone derivatives and their precursors.

The efficiency of photochemical crosslinking of low-density polyethylene (PE) films by molecules containing one or two acetophenone groups and their precursors have been correlated with the relative rates of carbonyl group depletion under equivalent irradiation conditions. The acetophenone derivatives are found to be equally or more efficient than benzophenone as crosslinkers of PE. Because some additives are not thermodynamically equilibrated in the PE matrices and crystallize on standing at 30 degrees C, doped films were irradiated usually as soon as possible after their preparation. However, others were aged to determine the influence of equilibration on the efficiency of crosslinking. Thus, the effect of crystallization of some of the crosslinker additives in the PE matrices and the competition between photochemical addition of the carbonyl groups to C-H or C=C bonds of the polymer were investigated. GC-MS and FTIR analyses of photoproducts from irradiation of alkanophenones bearing a gamma-hydrogen atom in PE films showed that (intramolecular) Norrish Type II splitting and Yang cyclization processes proceed efficiently, and are more rapid than subsequent intermolecular hydrogen abstraction reactions by the acetophenone photoproducts.

[Incidence of local recurrence after breast preserving surgery]. / A lokális recidíva elofordulása emlo-megtartásos mutéteink után.

Breast preserving surgery combined with adjuvant radiotherapy became more frequent in the last 20 years in the surgical treatment of early stage (Std. I-II) breast cancer in Hungary. Those who refuse this method usually allude to the frequent multifocality and the high recurrence rate of breast cancer. In the 1st Department of Surgery, Medical and Health Science Center, University of Debrecen, 825 patients underwent breast preserving surgery with a recurrence rate of 9.1% between January 1996 and December 2003. The time of appearance of recurrence varied between 5 and 102 months after surgery. There was no difference between the premenopausal and postmenopausal group. The 6.7% rate in pT1N0 tumors elevated to 16.7% in patients with pT2N1. According to histological grade the Grade 1 tumors had a recurrence rate of 2.3%, in Grade 2 we found 6.2% and in Grade 3 as high as 15.8%. Other unfavorable histo-morphological signs are the absence of estrogen receptors, the presence of extensive intraductal component and vessel invasion. Their opinion is that in case of local recurrence with favorable prognostic factors excision should be performed if acceptable cosmetic result can be achieved.

[The effect of mammographic screening on tumor size, axillary node status and the degree of histologic anaplasia]. / A mammográfiás emlorákszurés hatása a tumorméretre, a hónalji nyirokcsomó státuszra és a szövettani anaplázia fokára.

UNLABELLED: Breast cancer is the most frequent malignant tumor in women in Hungary. Significant reduction of mortality has been brought about not only by the increasing efficiency of complex therapy but also by regular mammographic screening. Of the histopathological data of 633 patients operated with primary breast tumor at the 1st Surgical Clinic of the Debrecen Medical University between January 1st 2000 and December 31st 2004, the authors analyzed tumor diameter, axillary node status and the degree of histologic anaplasia and compared them with the data of mammographic screening. RESULTS: Of the "screened"patients, 70.7% were diagnosed with T1 size tumors, 28.5% with T2 size, and 0.8% with tumors bigger than that. In the "unscreened" patients, our findings were 44.3%, 45.9% and 9.8% respectively. Within T1 tumors, Tla tumors were found in 11%, TIb in 37.6% and T1c in 51.4% in the "screened" group of patients, while the "unscreened" group's results were 2.3%, 12.6% and 85% respectively. 72.7% of the "screened" patients and 56.2% of the "unscreened" patients were found to be axillary node-negative. A study of the degree of histologic anaplasia showed G-I tumors in 15.6%, G-IIs in 62.1% and G-IIIs in 22.3% of the "screened" patients. The corresponding values for the "unscreened" patients were 6.1%, 53.8% and 40.1%, respectively. The differences were highly significant (p < 0.001) in all the parameters investigated. The authors have found a significant increase in the proportion of node-negative patients and patients with smaller tumors even after the first round of mammographic screening and at less than 50% participation. It is to be hoped that a 20% reduction in mortality can be achieved by further increasing the rate of participation.