[ASSISTED REPRODUCTIVE TECHNOLOGIES AND OVARIAN CANCEROGENESIS].

Development of assisted reproductive technologies (ART) for treatment of infertility poses many questions about potential involvement of the drugs used in ART in the process of ovarian carcinogenesis. The presence of other etiological factors makes the assessment of risks implied by administering these drugs rather difficult. The results obtained in the study are controversial and inconclusive, yet theoretical and epidemiological data suggest that caution is needed in IVF patients, receiving such drug therapy.

[PROGNOSTIC MODELS IN MODERN MANAGEMENT OF VULVAR CANCER].

AIM: The aim of the research was to evaluate and analyse prognosis and prognostic factors in patients with squamous cell vulvar carcinoma after primary surgery with individual approach applied during the course of treatment. MATERIALS AND METHODS: In the period between January 2000 and July 2010, 113 patients with squamous cell carcinoma of the vulva were diagnosed and operated on at Gynecologic Oncology Clinic of Medical University, Pleven. All the patients were monitored at the same clinic. Individual approach was applied to each patient and whenever it was possible, more conservative operative techniques were applied. The probable clinicopathological characteristics influencing the overall survival and recurrence free survival were analyzed. Univariate statistical analysis and Cox regression analysis were made in order to evaluate the characteristics, which were statistically significant for overall survival and survival without recurrence. A multivariate logistic regression analysis (Forward Wald procedure) was applied to evaluate the combined influence of the significant factors. While performing the multivariate analysis, the synergic effect of the independent prognostic factors of both kinds of survivals was also evaluated. RESULTS: Approaching individually each patient, we applied the following operative techniques: 1. Deep total radical vulvectomy with separate incisions for lymph dissection (LD) or without dissection--68 (60.18 %) patients. 2. En-bloc vulvectomy with bilateral LD without vulva reconstruction--10 (8.85%) 3. Modified radical vulvactomy (hemivulvectomy, patial vulvactomy)--25 (22.02%). 4. wide-local excision--3 (2.65%). 5. Simple (total /partial) vulvectomy--5 (4.43%) patients. 6. En-bloc resection with reconstruction--2 (1.77%) After a thorough analysis of the overall survival and recurrence free survival, we made the conclusion that the relapse occurrence and clinical stage of FIGO were independent prognostic factors for overall survival and the independent prognostic factors for recurrence free survival were: metastatic inguinal nodes (unilateral or bilateral), tumor size (above or below 3 cm) and lymphovascular space invasion. On the basis of these results we created two prognostic models: 1. A prognostic model of overall survival 2. A prognostic model for survival without recurrence. CONCLUSIONS: Following the surgical staging of the disease, were able to gather and analyse important clinicopathological indexes, which gave us the opportunity to form prognostic groups for overall survival and recurrence-free survival.

[DIFFICULTIES IN DISSECTION OF URINARY BLADDER IN TOTAL LAPAROSCOPIC HYSTERECTOMY.]

The dissection of urinary bladder is a crucial phase of the laparoscopic operation of hysterectomy. The latter dissection may become even more difficult in the context of history of operative interventions as cesarean section or cervical conization, presence of cervical or isthmic myomatous nodes, as well as upon a bad operative technique. The obeying of some basic principles (knowledge of pelvic anatomy and topographic interrelations; considering of present risk factors; intraoperative screening for complications and their early treatment) results in the optimal performance of laparoscopic hysterectomy.

[Laparoscopic Operations in Ovarian Endometriosis.]

OBJECTIVE: The Sudy aimed to analyze performed laparoscopic operations in ovarian endometriosis. MATERIAL AND METHODS: A retrospective study was carried out including 336 patients with pelvic endometriosis who were operated laparoscopically in St.Marina Hospital - Pleven from January 2008 to July 2014. RESULTS AND DISCUSSION: The ovaries are the pelvic organs most affected (76%) by endometriosis. The most done intervention is laparoscopic cystectomy (64.9%), followed by cystadnexectomy- (6,8%). The rarest are radical interventions - laparoscopic hysterectomies with adnexa (4.8%). CONCLUSION: The size of the endometriotic cyst, the severity of disease, the age and the reproductive condition are crucial for makina decisions concernina the extent of suraical intervention.

[LAPAROSCOPIC SURGERY IN PELVIC ENDOMETRIOSIS AND STERILITY].

Endometriosis associated sterility affects 30%-50% of patients with pelvic endometriosis and the pathogenesis is complicated and controversial. The laparoscopic approach in modern surgical conservative treatment includes laser/diathermy ablation to endometriotic implants, adhesiolysis, excision of endometriotic cyst, cyst wall ablation and drainage. In case of patient with bilateral tubal occlusion, recurrence, or if conception has not occurred by 12 months after surgery, assisted reproductive techniques should be considered.

[Uterine smooth muscle tumors--direction of differentiation and morphological features].

Uterine smooth muscle tumors /USMT/ are the most common tumors of the female reproductive system. The main aim of the clinical histological classification and the grading of MGMT is to predict their progression. The diagnosis of USMT has of the following stages: the determination of the direction of differentiation of the tumor and the defining the morphological features (the mitotic index, the tumor necrosis and the cellular atypia). In each of them there are specific problems. This indicates, that the USMT are therapeutic and clinical challenge.

[Case of encapsulated solid papillary carcinoma with triple-negative and basal-like phenotype occurred in pregnant woman with review of the literature].

The term breast cancer in pregnant women is used when the disease has been diagnosed during pregnancy or within first 12 months after delivery. The frequency of this type of breast cancer is about 7% of all cases in reproductive period. We present a case of breast cancer that occurred in pregnant 35 year old woman. We performed histological and immunohistochemical tests of excised tumor formation. We did not find sufficient evidence of both carcinoma in situ and invasive ductal carcinoma. The lesion was consisted with encapsulated/intracystic carcinoma, solid papillary variant with a low degree of differentiation-G3. Young age of patient, receptor status of the tumor the characteristic morphology of hereditary cancer, the presence of inflammatory infiltrates intratumorally, absence of reaction to IHC protein product of the tumor suppressor gene BRCA1 in combination with a positive p53 IHC makes this case suitable for genetic testing of BRCA1/BRCA2 susceptibility genes. The case is interesting because of the rarity of the histological variant, the young age of the patient, the combination with BC and pregnancy and the triple-negative phenotype.

[OPPORTUNITIES OF HIFU TECHNOLOGY FOR TREATMENT FIBROIDS DISEASES SUCH AS NON-INVASIVE AND ALTERNATIVE METHOD TO SURGERY].

Concepts of medical treatment are constantly evolving and improving. This opportunity provides treatment with High Intensity Focused Ultrasound (HIFU). In Europe and Asia more than 10,000 patients with uterine fibroids have been successfully treated with HIFU technology until now. This is completely innovative technology for non-invasive extracorporeal treatment of benign and malignant tumors. Neighboring healthy tissue is not damaged. The main indication in HIFU-Center in Pleven is uterine fibroid. It is the most common solid tumor in the female pelvis and is the leading cause of hysterectomy. The methods of treatment are hysterectomy, myomectomy or embolization of uterine arteries. HIFU-methodology allows non-invasive treatment of fibroids disease.

[LOCALIZATION AND SIZE OF THE LESIONS IN PELVIC ENDOMETRIOSIS].

OBJECTIVE: The study aimed to describe localization and size of the lesions in pelvic endometriosis MATERIAL AND METHODS: A retrospective study was carried out including 375 patients with pelvic endometriosis who were operated in St. Marina Hospital-Pleven from January 2008 to July 2014. RESULTS AND DISCUSSION: The ovaries are the pelvic organs most affected (76%) by endometriosis, the lesions being usually 4-5 cm in size. Peritoneal endometriosis ranks second, with 58.2%, and the rarest is DIE with 0.5%. CONCLUSION: Localization, number and size of the endometriosis lesions determine the severity of the condition. These parameters are crucial for making decisions concerning the type and extent of surgical intervention.

[THE ROLE OF THE CYTOKINE PROFILE IN TREATMENT IN WOMEN WITH ENDOMETRIAL CANCER FIRST STAGE].

Endometrial canceris the most common gynecological cancer. It is positive that more than 53% of diagnosed cases of endometrial cancer are in first stage when the therapeutic options are more successive. More and more gynecologists in addition to the normal clinical and histological tests expand the information for the neoplastic process with biochemical and immunological markers-tumor markers, hormones, lymphocyte population, cytokines, markers for lesion-inflammatory processes, etc. Several biological mechanisms track the connection between overweight and endometrial neoplastic risk. In the surgical practice is increasing the interest towards the cytokine group as independent prognostic factors, aggressiveness and options for treatment of the neoplastic process. The cytokine profile can be used as factor for evaluation of the primary neoplastic immune impairment as well as for a choice of surgical intervention. This is extremely important for obese patients because obesity is turning into worldwide medico-social problem.

[Morphologically qnd immunohistochemically based screening criteria for selection of patients with possible mutation of BRCA1 gene in primary ovarian cancer].

UNLABELLED: SUMMARY AND AIM: Breast cancer (BC) and Ovarian cancer (OC) are some of the most common cancers affecting women. Environmental factors and genetic alterations are involved in the etiology of both cancers. The main susceptibility genes that predisposed to BC and OC are BRCA1 (BReast CAncer 1) and BRCA 2 (BReast CAncer 2). Those of BC and OC which are due to germline mutation in BRCA 1/2 are defined as hereditary. Because of the expensiveness of genetic testing for mutations in BRCA1 we aimed to select patients with ovarian cancer suitable for genetic testing, on the base of certain morphological and immunohistochemical criteria. MATERIAL AND METHODS: We have conducted a retrospective analysis of 29 cases with serous papillary OC, taken from the archives of the Department of Clinical Pathology, University Hospital "Dr. G. Stranski" Pleven. We performed morphological assessment and subsequent immunohistochemical study with antibodies against p53, anti BRCA1 and anti proliferative marker Ki-67. RESULTS: Nineteen (65.52%) of all 29 cases were found with loss of immunohistochemical expression of BRCA1 and we defined them as suitable for genetic testing of BRCA1 mutations. CONCLUSION: A set of morphological and immunohistochemical criteria allows screening of women that should be referred for genetic testing, as it is expensive, and the incidence of BRCA1 mutations in the general population is very low.

[Uterine smooth muscle tumors--determination of clinical behavior and classification].

The establishment of the clinical behavior of uterine smooth muscle tumors /USMT/ is an essential stage of modern diagnostics. There are significant differences in the criteria determining the malignant potential of smooth muscle gynecological tumors. Generally USMT generating diagnostic problems are classified into: clinically benign tumors; clinically malignant tumors with benign morphological features; smooth muscle tumors of uncertain malignant potential (SMTUMP) and lesions whose smooth muscle differentiation is not obvious. The knowledge in this area is essential for an adequate therapeutic approach.

[Deep infiltrating endometriosis-diagnosis and principles of surgical treatment].

"Deep endometriosis" includes rectovaginal lesions as well as infiltrative forms that involve vital structures such as bowel, ureters, and bladder. Deep endometriosis, defined as adenomyosis externa, mostly presents as a single nodule, larger than 1 cm in diameter, in the vesicouterine fold or close to the lower 20 cm of the bowel. Its prevalence is estimated to be 1% -2%. This disease is suspected clinically and can be confirmed by ultrasonography or magnetic resonance imaging. The surgical treatment of deep infiltrating endometriosis is challenging and complex. Currently, the gold standard for patient care is the referral to centers with a multidisciplinary team including gynecologists, colorectal surgeon and urologist with adequate training in advanced laparoscopic surgery.

[Laparoscopic complications of gynecologic surgery].

Despite the growth of laparoscopic surgery, its complications must not be underestimated and patients must be informed of the risks of so-called 'minimally' invasive surgery.

[Sentinel lymph node biopsy in endometrial cancer--our experience].

PURPOSE: The objective of the study was to determine the feasibility of a method described for the first time by Altgassen et al. of labeling sentinel lymph nodes in patients with endometrial cancer using blue dye. PATIENTS AND METHODS: 4 ml of blue dye was administreted in 12 patients with endometrial cancer subserosaly at eigth sites. After 10 min sentinel lymph nodes were harvested. RESULTS: Detection rate was 91.6%., In only one patient there was no detection of sentinel lymph node and in one patient the sentinel lymph node was marked only in one hemipelvis. CONCLUSIONS: This method for detection of sentinel lymph nodes in patients with endometrial cancer is promising, fast and easy to implement, but need to conduct additional studies to become part of the standard for the surgical treatment of endometrial cancer

[Primary malignant melanoma of the vagina and treatment options: a case report].

OBJECTIVE: To present and analyze the clinical characteristics, treatment, and treatment options for a patient with primary malignant melanoma of the vagina and review of literature. CLINICAL CASE: A 71-year-old patient with a history of vaginal bleeding caused by four tumor growths located in the vagina is presented. The size of each formation was about 2 cm. Three of them were located in the proximal two-thirds of the anterior wall of the vagina and one in the distal third. Excisional biopsy was performed of the lesion located near the entrance of the vagina. Histopathological examination revealed that it was a malignant melanoma of the vagina, which was confirmed immunohistochemically. After ruling out a tumor of an unknown primary site, the patient underwent radical hysterectomy type IV total vaginectomy and pelvic lymph node dissection. Hystological examination proved a clinically asymptomatic melanoma lesion of the uterine cervix. After surgery, the patient was given chemotherapy with Dacarbasine and monthly immunotherapy with BCG vaccine. The patient survived 21 months after surgery without developing a local relapse and died of distant metastases in the spine. CONCLUSION: Radical surgery for primary melanoma of the vagina is a secure way of achieving locoregional control of multifocal disease. The wide local excision can be used in unifocal lesions with security in achieving clean surgical margins.

[Investigation of the role of tubal factor sterility in pelvic endometriosis].

OBJECTIVE: To investigate frequency and characteristics of tubal factor in patients, diagnosed with endometriosis and sterility. MATERIAL AND METHODS: The invastigation includes 124 patients, diagnosed with endometriosis and history of sterility, who underwent diagnostic or operative laparoscopy for the period from 2008 to 2013. For each of the patients were registrated the results of chromopertubation, stage, according to rASRM, concomitant gynaecological diseases, sort and complexity grade of the operation. RESULTS AND DISCUSSION: According to the results, patients were divided in 3 groups, as each of them includes cases with similar prognosis and treatment models: 1. With maintained reproductive potentiality (75 patients); 2. With restricted reproductive potentiality, according to the uterine tubes (32 patients); 3. With absent reproductive potentiality, according to the uterine tubes (16 patients). CONCLUSION: The mini-invasive approach to women, suspicious for endometriosis and sterility, gives us the opportunity to make an accurate diagnosis and to determinate the severity of disease, to estimate the morphology and the presence of tubal occlusion, such as to accomplish the necessary range operative intervention of endometriosis lesions and other concomitant gynaecological diseases.

[Sentinel lymph node dissection: preliminary results in vulvar cancer].

AIM: The aim of the study was to investigate and assess sentinel lymph node dissection methods in squamous cell vulvar cancer in cases of individualized therapeutic approach. MATERIALS AND METHODS: In the period January 2000-2010, 113 patients with squamous cell vulvar carcinoma were diagnosed, treated and followed up at the Clinic of Gynecologic Oncology of University Hospital - Pleven. All patients underwent primary surgical treatment and were surgically staged. Groin dissection was performed on 77 (72.64%) patients with invasive carcinoma (deep stromal invasion > 1 mm). Sentinel lymph node dissection was performed on seven patients after preoperative application of subcutaneous peritumor infiltration of Blue V in four places. The sentinel lymph nodes were identified following skin incision parallel to the inguinal ligaments. The nodes were dissected and sent for prompt frozen section histological evaluation. All patients underwent inguinal lymph node dissection as indicated by findings. RESULTS AND DISCUSSION: In the seven patients, one to three lymph nodes were found and frozen sections were histologically analyzed. The analysis did not reveal metastases. Primary tumor diameters varied from 0.5 to 4 cm. During follow-up, no cancer recurrences were found in any of the seven patients. CONCLUSION: Sentinel lymph node dissection is a reliable method in early vulvar cancer when certain criteria are applied in patient selection. The method allows avoiding inguinofemoral lymphadenectomy in a group of carefully selected patients with vulvar cancer.

[Sentinel lymph node biopsy in endometrial cancer--a part of modern operative treatment].

After brest cancer the endometrial cancer is the most common gynaecological malignancy. The lymphno destatus is with great prognostic value. There is no agreement for the therapeutic valuae and the contents of the lymph node desectionin early stages. That is why the sentinel lymph node biopsy is a part of modern operative treatment of endometrial cancer.

[Mini-invasive treatment by cases of moderate and severe pelvic endometriosis].

OBJECTIVE: The purpose is to investigate the characteristics of the performed mini-invasive surgical treatment by patients with III-IV stage of pelvic endometriosis and to establish the advantages of this surgical approach, such as the concomitant complications. MATERIAL AND METHODS: 90 patients, who underwent operation, with histologically proved endometriosis were studied for a period of 2 years: 60 of them with moderate and 14--with severe endometriosos, determinated by the revised ASRM classification. RESULTS AND DISCUSSION: The most commonly done laparoscopic operation is the cystectomy--totally 57 (77%) for the whole group, followed by the cystadnexectomy--11 cases (14.9%). By 4 of the cases (5.5%) there was a conversion into laparotomy and by 2 of the cases (2.7%) mini-invasive surgical procedures were accomplished. CONCLUSION: Mini-invasive approach by patients with pelvic endometriosis offers several options: to stage the condition, to diagnose the tubal sterility and to perform surgical treatment. In this study we establish the structure of the accomplished operations, noting the low count of complications and conversions, such as the short operative time and recovery days.