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Open access

Savelina Popovska and Ivan Ivanov

Abstract

Objective: The aim of this study was to examine the relationship between the immunohistochemical subtypes of invasive breast cancer and lymphatic vascularization.

Material and Method: One hundred and seventy nine cases of randomly selected invasive breast cancer patients, surgically treated between 2004 and 2007, were retrospectively studied. These were classified into steroid receptor positive (steroid receptor positive/ HER2 negative), triple positive (steroid receptor and HER2 positive), triple negative (steroid receptor and HER2 negative) and HER2 overexpressing (steroid receptor negative /HER2 positive) carcinomas. Appropriate immunostaining and in-situ hybridization techniques were applied and results were statistically analyzed.

Results: The median intra-tumor lymphatic vascular density and the median intra-tumor relative lymphatic vascular area were found to differ significantly among the studied groups of breast cancer (KW =49.8611; p<0.0001 and KW =21.5122; p=0.0001 respectively). There was no significant difference in the incidence rate of axillary node involvement among the studied groups of breast cancer (χ2=1.66; Df=3; p=0.6460).

Conclusion: The present study indicates that HER2 overexpressing breast carcinomas have a consistent increase of intra-tumor lymphatic vessel counts as compared to all other subtypes. It is suggested that the newly formed vessels are probably not the only essential factor for lymphogenic spread of HER2 overexpressing breast carcinomas as they are not related to an increased incidence of lymph node metastases compared to the other studied subgroups.

Open access

Savelina L. Popovska, Tatyana M. Betova and Кrasimir T. Petrov

Abstract

Fibromatoses are a group of benign proliferations of fibrous tissue with clinical behaviour ranging from that of truly malignant tumours to that of benign reactive fibrous proliferations. Some of the superficial fibromatoses are fairly common but deep ones, also known as desmoid tumours or musculoaponeurotic fibromatoses, are rare. We describe a case of extra-abdominal musculo- aponeurotic fibromatosis in a 22-years old male. He underwent 14 operations for a period of 9 years for fibromatosis of the posterior surface of the right lower limb. The histological findings of the lesions were similar consistent across surgeries and consistent with a diagnosis of aggressive extra-abdominal fibromatosis.

Open access

Savelina L. Popovska, Ivan N. Ivanov and Akishi Ooi

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer which is clinically negative for expression of steroid hormones and HER2 protein. According to DNA microarray profiling, breast cancer was divided into several molecular subgroups, including Luminal A and Luminal B; HER2 overexpressing; normal breast- like and basal-like subtype. TNBC comprises tumours that express heterogeneous molecular and immunohistochemical phenotype, thus determining different prognosis. The majority of TNBC carry the “basal-like” molecular profile on gene expression arrays. Basal-like carcinomas of the breast associated with poor prognosis often correlate with expression of Caveolin-1. The study aimed to investigate the expression of caveolin-1 in the tumour cells and in the stromal component of the tumour among the group of TNBC and compare it to the expression of caveolin-1 in a control group with non-TN breast cancer. Whole tissue sections were used. Formalin fixed, paraffin embedded tissue materials from 101 patients diagnosed with invasive breast cancer during the period 2004-2007 were investigated in a retrospective study. A multistep approach was used to separate the different subtypes of breast cancer. During the first step the breast tumours were separated according to their ER, PgR, HER 2 and proliferative activity, using the Ki-67 index. The triple- negative tumours were additionally tested for EGFR and CK5/6. The basal breast cancer group was finally subdivided into basal and baso-luminal according to the type of expression of basal cytokeratins. caveolin-1 expression was examined in the tumour parenchyma and stroma. According to our results, caveolin-1 expression in breast cancer was significantly associated with basal biomarkers expression (basal and baso-luminal type of BC) χ2= 33.4; p<0.0001. Caveolin-1 can be used as a potential marker to examine the presence of basal phenotype in breast cancer.

Open access

Savelina L. Popovska, Ivan N. Ivanov and Dorian Y. Dikov

Summary

Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer (LABS). The aim of this study was to determine the effects of neoadjuvant chemotherapy on metastatic and nonmetastatic breast cancer axillary lymph nodes (ALNs). Seventy-seven patients with LABS and cytologically documented ALN metastases were treated in two prospective trials. Patients had breast surgery with level I and level II axillary dissection followed by additional chemotherapy or radiation treatment. Clinical nodal status was determined by physical examination and compared with histological and immunohistochemical findings. The regressive changes in primary tumor and ALNs were achieved using scoring systems. Objective clinical response in primary tumor was seen in 48.05% of patients. Histologic evidence of regression was noted in 46 cases (59.75%), with complete histologic regression achieved in 5 cases (6.49%). The number of cases according to the ALNs regression scoring system was as follows: 0 grade - viable metastases without effect - 21 patients (30%); 1 grade - cytotoxic effect in metastases - 20 patients (28.58%), 2 grade - micrometastasis - only3 patients (4.28%); 3 grade - no residual metastatic disease - 1 patient (1.43%); 4 grade - negative ALNs before and after treatment - 25 patients (35.71%). Nodular fibrotic area and iron-loaded macrophages suggested previous presence of tumor metastasis. There was significant relationship between histologic regression in the primary tumor and the presence of effect of cytotoxic agents on ALNs metastases (r=0.9123; p<0.00001). As chemotherapy is widely used in the treatment of breast carcinoma, pathologists should be aware of chemotherapy-induced changes in metastatic and in non­metastatic ALNs.

Open access

Paulina Tr. Vladova, Sergey D. Iliev and Savelina L. Popovska

Summary

According to the consensus and the recommendations of the European Neuroendocrine Tumor Society (ENETS), the frequency of appendicular neuroendocrine tumors (NETs) is 0.15-0.6/100 000 a year. They are found a little more often in women aged between 40 and 50. Neuroendocrine neoplasms of the appendix are about 30 to 80% of all appendicular tumors. Their evolution is usually asymptomatic. They are diagnosed accidentally during a conventional or laparoscopic appendectomy. In the past, the surgical approach used to depend on the localization of the tumor. Currently, its localization is not a significant factor in the choice of a surgical approach. Our purpose wass to present the consensus guideline and the recommendations of ENETS 2017 for surgical procedures in neuroendocrine neoplasms of the appendix and analyze the difference in the survival rate in different surgical interventions. The literature overview includes studies on surgical treatment of neuroendocrine neoplasms of the appendix and takes into consideration the last consensus guideline of ENETS 2017 on the topic. ENETS recommends a simple appendectomy in well- differentiated appendix tumors smaller than 2 cm, regardless of their localization. Right hemicolectomy is performed for in tumors sized between 1 cm and 2 cm with positive resection lines, with deep mesoappendiceal invasion, high proliferation activity (G2) and vascular invasion. For tumors over larger than 2 cm – right hemicolectomy is recommended. Although current studies have pointed out no significant differences in survival rates between appendectomy for neuroendocrine neoplasms of the appendix and right hemicolectomy, ENETS 2017 suggests that the latest consensus guidelines should be followed.

Open access

Savelina L. Popovska, Tereza B. Dineva and Polina D. Damyanova

Summary

Lung cancer is still the leading cancer-related cause of death with a high incidence rate in the whole world. Treatment options – surgery, radiotherapy, and chemotherapy, depending on the stage of the disease. During the last decade, many molecular alterations were discovered that led to impressive changes in treatment. Personalized approaches, including target therapies with specific inhibitor drugs, became a part of the standard therapies. This article reviews current molecular biomarkers used in clinical practice to treat lung cancer patients.

Open access

Ivan N. Ivanov, Savelina L. Popovska, Emilian A. Ivanov, Sergey D. Iliev and Pencho T. Tonchev

Summary

The phenomenon “vessels within vessels” was initially described by Merchant S et al. as arteries found free-floating inside the lumen of veins. We have described another version of the “vessels within vessels”complex, composed of arteries found inside the lumen of lymphatic vessels. The purpose of the present study was to describe the structure of the lympho-arterial vascular complex in a breast tissue specimen from a male subject using three- dimensional tissue reconstruction. A histological specimen from a 64 year-old male subject diagnosed with gynecomastia was used. The tissue sample was sectioned in a multi-step manner. An overall of approximately 150pm thick tissue material was sampled. Immunostaining with anti-CD34 antibody and anti-podoplanin antibody was performed. Three-dimensional reconstruction of the vessel within the vessel structure was performed with “Reconstruct” software When the reconstruction of the breast parenchyma was revealed as a 3D image, it became apparent that the arterial vessel was situated inside the lymphatic vessel and could be followed along the entire length of the vascular segment studied. We have proved that these vascular complexes are not artificial phenomenon and do exist. The function of the vascular complexes is still uncertain, and is probably related to lymph propulsions in the initial collector vessels.

Open access

Katia S. Kovacheva, Zornica B. Kamburova, Savelina L. Popovska, Ivan N. Ivanov, Maria N. Simeonova and Petia N. Angelova

Summary

Genetic testing for BRCA 1/2 mutation is a well recognized medical management tool. Identification of healthy carriers of such mutations allows effective risk reduction procedures to be performed. There is no data reported on the founder mutations in the Bulgarian population. To evaluate the contribution of genetic factors to breast cancer (BC), we investigated the carrier state of Bulgarian women with BC for five common (according to BIC database) deleterious BRCA1/2 mutations. The list of patients diagnosed with BC between January 2011 and April 2012 was obtained from the Cancer Registry of University Hospital, Pleven. Eighty-two women with BC were interviewed and a pedigree was constructed of each of them. The patients were classified into seven categories, according to personal, disease and family history. Based on the preliminary prepared selection criteria and the personal family history, we defined a target group of 33 Bulgarian women with BC. They were screened for five deleterious mutations: 5382insC in BRCA1 and 6174delT, 6079del4, 8138del5, 5946delCT in BRCA2, by DNA sequencing. The genetic analysis detected none of the tested mutations. Two polymorphic variants were found in BRCA2 gene: c.5744C>T (rs4987117, SNP database) in exonl 1E in one patient and c.7806-14T>C (rs9534262, SNP database) in exonl7 in 22 patients. In conclusion, without basic information on the founder mutations in the population, the genetic screening for the specific mutations in a small group of tested patients is ineffective.

Open access

Slavcho T. Tomov, Grigor A. Gortchev, Latchesar S. Tantchev, Todor I. Dimitrov, Chavdar A. Tzvetkov and Savelina L. Popovska

Summary

Selection of an appropriate surgical method for hysterectomy in an individual patient is currently an issue that remains open and debatable. This study aimed to analyze perioperative outcomes in gynecologic patients who underwent laparoscopic hysterectomy at a single institution during a 6-year period and to compare the data for simple hysterectomy patients treated with different surgical approaches. The study included a retrospective analysis of demographics, pre- and post-operative characteristics of 1,023 patients, operated on using four types of simple hysterectomy approaches: 635 laparoscopic hysterectomies (62.1%), 289 total abdominal hysterectomies (28.3%), 45 total vaginal hysterectomies (4.4%) and 54 robotic-assisted hysterectomies (5.3%). For the laparoscopic hysterectomy group, the mean operative time was shorter as compared to the abdominal and vaginal hysterectomy groups (p<0.05), as well as a significantly shorter hospital length-of-stay when compared to the abdominal, robotic or vaginal hysterectomy groups (p<0.05). Regression analysis revealed significant linear correlation between operative time and body-mass index of laparoscopic hysterectomy patients (R2 =0.008; p=0.026). Complications emergence and hemotransfusion often prolonged the mean operative time significantly by 17.8 min (p=0.002) and 15.5 min, respectively (p<0.001). The rate of major complications was significantly higher in the laparoscopic vs. abdominal groups (p<0.05). Clinical outcomes in patients operated on with laparoscopic hysterectomy were better than in those operated with total abdominal and vaginal hysterectomy in terms of operative time and hospital length-of-stay. Prospective randomized multi-center studies would be desirable to further define the place of the modern minimally invasive hysterectomy approaches.

Open access

Valeri Y. Andreev, Nikolay A. Yanev, Stefan K. Stanimirov, Temenuzhka V. Mircheva, Ivan N. Ivanov, Savelina Popovska, Petkana A. Hristova and Yavor Y. Ivanov

Abstract

As part of a retrospective study on bronchoscopies performed at the Clinic of Pneumonology and Phthisiatry of the University Hospital – Pleven by autofluorescence bronchoscopy we found 3 cases diagnosed with carcinoma in situ. They were treated in different ways – endobronchial electrocoagulation, extraction by forceps biopsy and open surgery, but the result was the same – clinical healing. The paper presents the three clinical cases and the analysis of the treatment.