[Firs Case Report of Intraoperative Radiotherapy (IORT) for Early Breast Cancer in Bulgaria].

The intraoperative radiotherapy (IORT) is an innovative method for treatment of breast cancer, which can be used as a substitute of postoperative external beam radiotherapy )EBRT), or boost treatment to EBRT (1). Radiobiological advantages of IORT compared to EBRT are higher relative biologic effectiveness of low-dose radiation therapy and the presence of high dose in the tumor bed (where the possibility of remaining vital tumor cells is the highest), as this dose reduces rapidly with the distance from the applicator (2). Important feature of IORT alone is that it can be applied as a single fraction during the surgical intervention and spares 3 to 5 weeks of following radiation therapy. This means less time spent in hospital for the patients and for the radiotherapeutical units - reduced waiting lists and more machine time for other patients. Prolonged operative time as well as the need of additional staff are assumed as relative flaws of IORT (3). The INTRABEAM® system (Carl Zeiss Surgical Gmbh, Oberkochen, Germany) uses a single high dose of low-energy X-rays (mas 50kV), applied to the tumor bed immediately after the surgical excision of the tumor. These rays have high degree of absorption and low penetrating ability. This determines their advantage in comparison to EBRT to protect the surrounding healthy tissues (2). The data from the Targeted Intraoperative radioTherapy (TARGIT-A) and the Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomized controlled equivalence trial show that when following the recommendations of The Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) Breast Cancer Working Group (2009) for an accelerated partial breast irradiation (APBI), IORT can be used as an equivalent of the postoperative radiotherapy (1,4,5,6). The purpose of this article is to show the results of the performed on 15 December 2015 for the first time in Bulgaria breast conserving surgery with intraoperative radiotherapy on a patient with early breast cancer.

EPIDEMIOLOGICAL REGISTRY OF NEUROENDOCRINE TUMORS IN BULGARIA--A PILOT SURVEY.

The National registry of patients with neuroendocrine tumors (NET) in Bulgaria was established in 2013 as a joint initiative of the Bulgarian Surgical Society and the Institute for Rare Diseases. The register aims to explore the epidemiology of NET in Bulgaria, as well as the different diagnostic and treatment approaches for the disease throughout the country. This the first of its kind retrospective study of NET in the country is covering the period January 2012 - January 2013. A total of 127 patients with NET were identified. At the time of the survey the average age of patients with NET was 58.61 ± 15.59 years. The data show almost equal distribution between the genders with a slight predominance of women. The largest relative part of NET is those of NET located in the gastrointestinal tract (54.10 ± 4.51%), followed by those located in the pancreas (12.30 ± 2.97%) and in the lungs (10.66 ± 2.79%). In 72.44 ± 3.96% of the patients a immunohistochemical diagnosis was performed. The study confirmed the leading role of the surgery method of the NET management. In 65.83 ± 4.33% of the patients a radical removal of the tumor was conducted, while the relative part of the undertaken partial resection was 7.50 ± 2.40%. A statistically significant association between the type of surgical treatment and during the follow-up of patients was found. An update of the information in the register will allow a more precise determining of the distribution and management of NET in Bulgaria.

Selective or radical surgical strategy in functional autonomy of the thyroid in endemic areas.

BACKGROUND: The purpose of the research is to compare two surgical methods in the treatment of functional autonomy of the thyroid regarding postsurgical complications and functional results. METHODS: 212 patients were examined--divided into two groups. Group 1 (n = 148)--in which selective thyroid resection have been done and Group 2 (n = 64)--in which radical resection have been undertaken. RESULTS: For both groups the following postoperative complications have been determined: In 4 (1.8%) patients transitory recurrent palsy is determined and in 1 (0.5%) patient-permanent recurrent palsy. The frequency of the transitory hypoparathyroidism is 7.5% (n = 16) and that of the permanent hypoparathyroidism is 0%. 148 patients from the two groups were followed up with respect to the functional results obtained at the eight postsurgical week and from 1 to 7 years after the operation. In the selective group (eight postsurgical week) 3 from the patients were with hyperthyroidism and 4 with hypothyroidism. From 1 to 7 years after the operation the following functional results have been determinated: in 7 patients relapse of the hyperthyroidism, in 8 patients new hypothyroidism and in 3 patients- morphological recurrence In radically operated patients the frequency of the postsurgical hypothyroidism during the 8 postsurgical week was 50% (n = 26). For the period from 1 to 7 years after the operation the following functional results were observed: 1 patient with relapse of hypothyroidism, 11 patients with new hypothyroidism. Not one morphological recurrence was observed. CONCLUSIONS: The residual and recurrent hyperthyroidism are related to the insufficient extent of resection. A functionally confirmed surgical strategy has been imposed in the endemic areas striving to remove all nodular structures at the same preserving the normal thyroid tissue.

Microsatellite instability and promoter hypermethylation of MLH1 and MSH2 in patients with sporadic colorectal cancer.

PURPOSE: Inactivation of the genes involved in DNA mismatch repair (MMR) is associated with microsatellite instability (MSI) and loss of heterozygosity (LOH). The aim of the current study was to assess the presence of MSI and promoter hypermethylation of MLH1 and MSH2 in Bulgarian PATIENTS WITH SPORADIC COLORECTAL CANCER (CRC) AND TO ANALYZE THEIR POSSIBLE EFFECT ON THE DEVELOPMENT, PROGRESSION AND PROGNOSIS OF THE DISEASE. METHODS: We examined MSI in 126 patients with sporadic CRC and the methylation status of the MLH1 and MSH2 promoter regions in the cases with MSI/LOH by using a panel of 5 microsatellite markers (BAT26, D5S346, D18S35, D2S123 and FGA) and methyl-specific PCR (MSP) of bisulfite converted DNA. RESULTS: MSI/LOH was found in 36 (28.6%) patients. Among them, 30 were analyzed for promoter hypermethylation of MLH1 and we detected hypermethylation in 15 (50%) of them, whereas promoter hypermethylation of MSH2 was observed only in one case. The presence of MSI/LOH was associated with younger age (p=0.002), more advanced stage (III/IV stage) (p=0.029), lower degree of differentiation (p=0.001), and right-sided tumor localization (p=0.0002), but not with overall survival (log rank, p=0.566). CONCLUSION: Our data suggest that sporadic CRCs with MSI/LOH are more aggressive, develop earlier and progress faster to more advanced stage. The most frequent cause of failure of DNA MMR system appeared to be the hypermethylation of CpG islands of the promoter region of MLH1, whereas the methylation of MSH2 was a rare event.

CHEK2 I157T and colorectal cancer in Bulgaria.

PURPOSE: Germline variants of the CHEK2 gene have been shown to act as low-penetrance cancer susceptibility alleles for a wide range of human malignancies. CHEK2 I157T has particularly been linked to colorectal cancer (CRC) risk. We aimed at establishing the population frequency and contribution of this variant to colorectal carcinogenesis in Bulgaria. METHODS: We have genotyped 802 population controls and 343 CRC patients from Bulgaria for the CHEK2 I157T variant. RESULTS: Heterozygous were 9 of 343 patients (2.62%, odds ratio/OR=1.0, 95% confidence interval/CI = 0.42 - 2.33, p=0.99% and 21 of 802 controls (2.62%). Higher frequencies were found among patients with multiple polyposis (2/40, 5%, p=0.28) and the rarer mucinous histology (1/11, 9.09%, p= 0.26). CONCLUSION: We conclude that CHEK2 I157T is not relevant for CRC risk in Bulgaria, but studies on a larger scale might help evaluate its possible significance in respect to disease characteristics.

A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer.

BACKGROUND: Identification of appropriate markers for predicting clinical benefit with erlotinib in non-small-cell lung cancer (NSCLC) may be able to guide patient selection for treatment. This open-label, multicentre, phase II trial aimed to identify genes with potential use as biomarkers for clinical benefit from erlotinib therapy. METHODS: Adults with stage IIIb/IV NSCLC in whom one or more chemotherapy regimen had failed were treated with erlotinib (150 mg/day). Tumour biopsies were analysed using gene expression profiling with Affymetrix GeneChip microarrays. Differentially expressed genes were verified using quantitative RT-PCR (qRT-PCR). RESULTS: A total of 264 patients were enrolled in the study. Gene expression profiles found no statistically significant differentially expressed genes between patients with and without clinical benefit. In an exploratory analysis in responding versus nonresponding patients, three genes on chromosome 7 were expressed at higher levels in the responding group [epidermal growth factor receptor (EGFR), phosphoserine phosphatase (PSPH) and Rap guanine nucleotide exchange factor 5 (RAPGEF5)]. Independent quantification using qRT-PCR validated the association between EGFR and PSPH overexpression, but not RAPGEF5 overexpression, and clinical outcome. CONCLUSIONS: This study supports the use of erlotinib as an alternative to chemotherapy for patients with relapsed advanced NSCLC. Genetic amplification of the EGFR region of chromosome 7 may be associated with response to erlotinib therapy.

Two components of potassium outward current in smooth muscle cells from the circular layer of human jejunum.

Two components of the outward K+ currents (Ik) of cells isolated from the circular layer of human jejunum were investigated using the conventional whole-cell voltage clamp method. A fast transient Ik component could only be elicited by depolarization in cells dialysed with pipette solution of pCa < 7.4. This Ik component was strongly voltage dependent, and could be selectively abolished by 30 mumol/l quinidine. Its amplitudes decreased in the absence of Ca entry, the decrease depending on the duration of cell exposure to media containing calcium-blockers, and disappeared after depletion of intracellular Ca2+ stores. The steady-state component of Ik was sensitive to tetraethylammonium. This component had comparable amplitudes at pCa = 8.4 or pCa = 7.4 of the pipette solution, and was present during a long-lasting exposure of cells to solutions containing Ca(2+)-blocking drugs.

Clinical study of the effect of the preparation DEODAN on leukopenia, induced by cytostatics.

The aim of the study is to establish the effect of the preparation DEODAN on leukopenia induced by chemotherapeutics in oncological patients. DEODAN is an oral preparation, obtained from lyzozyme lysates of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B-51" ATCC 21815, called shortly LB51. In the study there are included two groups of patients--from National Oncological Centre, Sofia, the other from Clinic of Medicine, Bertha Academic Hospital, Clinics of Duisburg, Duisburg. All the patients, (78) have undergone combined chemotherapy. In all patients, leukopenia has been established in moderate and medium levels. The scheme of the application of DEODAN has been 3 g, three times a day before meals, from the first day of establishing the disturbances of the haemopoesis. The treatment lasted until the restoration of the haematological values. Only DEODAN was applied. The results obtained show that the recovery of the WBC count (values above 3000) took place in all of the patients between days 3 and 5. None of the patients displayed any infectious or febrile complications, as a result of the applied chemotherapy and the treatment with the preparation. DEODAN also improves the general condition of the patients.

Polyamine oxidase activity and concentration of polyamines in tissues and serum of hamsters with transplantational pigmented melanoma IC-Sofia.

The activity of polyamine oxidase (PAO) participating in the intracellular catabolitic interconversion of the polyamines and the total concentration of polyamines in some tissues of hamsters with transplantational pigmented melamoma IC-Sofia were studied. The experiments were carried out on day 0, as well as on the 11th, 15th, 21st and 27th day after the tumor transplantation. The PAO activity and the polyamine concentration were determined in tumor tissue (with the exception of day 0), in the liver, kidneys, lung and serum (without PAO). A gradual decrease of the PAO activity and a marked rise in the total concentration of polyamines were observed in the growing tumor. In the remaining tissues the PAO activity initially rose slightly until the 15th day, then dropped, whereas the polyamine concentration increased all the time. The dynamics of the enzyme activity and the polyamine concentration were most pronounced in the lung. Tumor growth was not accompanied by changes in the polyamine concentration in the serum.