[PRIMARY CYTOREDUCTIVE SURGERY VERSUS NEOADJUVANT CHEMOTHERARY IN TREATMENT OF ADVANCED OVARIAN CANCER (STAGE III C-IV). OUR AND FOREIGN EXPERIENCE].

INTRODUCTION: The advanced ovarian cancer usually have bad prognosis. The main methods for treatment of these types of tumors are: primary cytoreductive surgery and platin-based chemotherapy. AIM: Our aim was to evaluate our and foreign experience in treatment of advanced ovarian cancer stage III C--IV treated by neodjuvant chemotherapy followed by cytoreductive surgery and patients treated by primary cytoreductive surgery followed by adjuvant chemotherapy. We wanted to research the survival rate, postoperative adverse effects, mortality rate, the size of residual tumor and the metastases in these patients. MATERIAL AND METHODS: We researched for 10 years period--50 patients treated by primary cytoreductive surgery and 50 patients treated by neoadjuvant chemotherapy. RESULTS: The postoperative adverse effects and mortality rate are lower by neoadjuvant chemotherapy followed by cytoreductive surgery. The most important independent prognostic factor for overall survival rate was the lack of residual tumor in both types of treatment. CONCLUSION: The neoadjuvant chemotherapy followed by cytoreductive surgery in ovarian cancer stage III C--IV is considered as a standard treatment.

[RECONSTRUCTIVE AND COSMETIC SURGERY IN TREATMENT OF VULVAR CANCER].

UNLABELLED: The aim of our research work was to show our results in the field of reconstructive and cosmetic surgery for vulvar cancer. MATERIAL AND METHODS: We evaluated 18 patients for 10 years period. RESULTS: We applied all surgical techniques that are possible at the moment in the world: laps from mons pubis, rhomboid flaps, myocutaneous flaps from gluteal region. We used surgical techniques with the following muscle groups: musculus gracilis, musculus gluteus maximus, musculus tensor fasciae latae, musculus rectus abdominis. CONCLUSIONS: With our research work we tried to better the quality of life of our patients, to achieve better esthetic and cosmetic effect after very radical surgical interventions connected with vulvar cancer.

[FEMALE STEROID HORMONES - MODULATORS OF IMMUNE RESPONSE TO GENITAL CHLAMYDIA TRACHOMATIS INFECTION.]

In the recent years according to WHO, genital chlamydia is the mos't common sexually transmitted infection. Chlamydia Trachomatis is an intracellular parasite which target are the tubular epithelial cells of the urethra, endocervix, endometrium, endosalpinx, conjunctiva, synovial lining of the joints, Glisson's capsule of the liver Our study, as well as some international researches, shows that in the cases of genital chlamydia there are changes in the ovarian hormones (estradiol and progesterone), their impact on the immune system and their importance for the development and the complications of the infection with Chlamydia trachomatis. The physiological level of the steroid hormones in its turn contributes for the normalization of the local immunity and reduces the possibility of recurrences.

[GLYCYRRHIZINIC ACID--AN ALTERNATIVE METHOD FOR TREATMENT OF CONDYLOMATA ACUMINATA].

Condylomata acuminata are benign proliferations of skin and mucosa caused by the human papilloma virus infection (hereinafter referredto as HPV). It is one of the most common sexually transmitted diseases in the world, whose incidence rate has increased in the last three decades. Current treatment involves the physical destruction of the infected cells. The fact that there are many different types of treatment goes to show that none of them are uniformly effective or directly antiviral.

[SOME DIAGNOSTIC ASPECTS OF CHLAMYDIA TRACHOMATIS UROGENITAL INFECTIONS].

The following tests were used to make the diagnosis of Chlamydia Trachomatis: Ensime Immunoassay (EIA), Enzyme-Linked FluorescentAssay (ELFA), Polymerase Chain Reaction DNA amplification for Chlamydia Trachomatis, Neisseria Gonorrhoeae, Mycoplasma Genitalium and Ureaplasma Urealyticum. The subject of this study were 486 outpatients between the ages of 17 and 62, diagnosed with urethritis, epidydimitis, prostatitis, cervicitis, endocervicitis, pelvic inflammatory disease and sterility. Comparison PCR and EIA showed statistically significant difference between the positive results obtained by the two methods (p<0.001). Comparing PCR and ELFA on the other hand, did not show any statistically significant difference (p>0.1). EIA is the method that gives a higher percentage of nonspecific positive reactions, while the results obtained with ELFA are much closer to the ones obtained by PCR. According to contemporary evidence based medicine, the development of unified standart methods for diagnosis and evaluation is of vital importance, not only for the patient and the treating physician but also concerns for the healthcare system, the general public and the pharmaceutical companies as well.

[COMBINED APPLICATION OF FETAL FIBRONECTIN AND INSULIN-LIKE GROWTH FACTOR IN PRETERM DELIVERY DIAGNOSIS--OUR RESULTS].

The insulin-like growth factor IGFBP-1 is a binding protein (IBP-1), also known as placental protein (PP12), is encoded in people as IGFBP-1 gene. The IGFBP-1 is an especially vital hormone in the female reproductive physiology. The presence of it in large quantities in the amniotic fluid can be used as a biochemical marker for preterm birth and premature rupture of membranes. Fetal fibronectin is a high-molecular glycoprotein, that is produced during pregnancy and has a role as biological glue, binding the foetus membranes to the endometrium. fFN can be found in the cervicovaginal secretions until 22nd gestational week and later on during the last trimester (1 to 3 weeks before birth). fFN is usually absent between 24th and 34th gestational week. Thirty sixth (30%) of all the 120 females tested had positive fFN test results and were, therefore, at high risk for preterm delivery. Despite the implemented tocolytic therapy, 15 (12.5%) of them delivered before the 37th gestational week. The results from the investigation for the presence of pLGFBP-1 in 120 pregnant women show that 35.8% (43 women) were positive and 15(12,5%) of them delivered before the 37th gestational week despite the implemented tocolytic therapy In both tests, the average gestational age of the premature fetus was 32.5 ÷ 2.8 gestational weeks.

[The insulin-like growth factor IGFBP-1--specific marker for preterm delivery in pregnant women with clinical symptoms].

The insulin-like growth factor IGFBP-1 is a binding protein (IBP-1), also known as placental protein (PP12), is encoded in people as IGFBP-1 gene. This gene encodes a protein in the domain of IGFBP-1 and domain thyroglobulin. During the last years highly phos-phorylated versions of IGFBP-1 (IGFBP-1 pM) have been found in decidual cells--a marker of threat for preterm birth. The quantity analysis of the insulin-like growth factor in the serum or heparinized plasma is used to locate diseases related to growth. Its levels in the plasma can scarcely be determined after birth and steadily rise with age while they reach their maximum during puberty. These levels rise constantly during pregnancy.

[Lymph node dissection in early ovarian cancer].

AIM: Our aim was to evaluate and summarize our experience in surgical treatment for early ovarian cancer, the way and extend of metastases, as well as the need and effectiveness of applying radical pelvic and paraaortic lymph node dissection. We compared our results with the results of prominent clinics all over the world in this special field. MATERIAL AND METHODS: We researched retrospectively patients, operated for early ovarian cancer for 15 years period. We evaluated the use of lymph node dissection and the level of its radicality. Examining the volume and borders of the lymph node dissection we tried to sintesize the main practical conclusions and refferences, which can be applied practically by the colleagues working in gynaecological and oncogynaecological clinics in our country RESULTS: According to us and the most foreign authors the ovarian cancer, must be removed intact, and frozen section biopsy must be used. The surgical staging includes: total abdominal histerectomy, bilateral salpingooophorectomy and total pelvic and/or paraaortic lymph node dissection. The surgical staging in all patients is obligatory and includes: a) cytological examination of ascites. b) when ascites is absent--cytological smear. c) Examination of intraabdominal organs and surfaces. d) Biopsies are taken from all suspicious regions. e) The diaphragm is examined by biopsy and scraping. f) Infracolic omentectomy is performed. g) Retroperitoneal spaces are dissected and examined. h) The paraaortal area is examined. When enlarged lymph nodes are found--they are resected and examined. If enlarged paraaortal lymph nodes are found--total paraaortic lymph node dissection is performed. DISCUSSION: The extend of the lymph node dissection in early ovarian cancer is connected with better survical rate in these patients. CONCLUSIONS: The lymph node dissection helps for precise surgical staging in early ovarian cancer. The volume of the lymph node dissection is significant prognostic factor for better survical rate, as well as age, stage, histological type and the grade of the disease.

[Diabetes and pregnancy].

UNLABELLED: We tried to summarize our and foreign experience in the field of diabetes and pregnancy AIM: Our aim was to detect pregnant women with diabetes mellitus, as well as to introduce screening method for early detection and apply a suitable diet and treatment for these patients. MATERIAL AND METHODS: Patients with diabetes and pregnancy were researched for the period of 2007-2014 (70 patients). RESULTS: Introducing a screening method in the second trimester between 24-28 gestational week, applying a suitable diet and treatment lead to better outcome of this disease and to more safe delivery outcome. CONCLUSION: Future research work will give additional light in this field.

[Contemporary methods for preterm labor diagnostics].

Authors track current trends in preterm labor diagnostics. The emphasis is laid on biochemical tests for examination of fibronectin (fFN) and insulin-like growth factor-binding protein (IGFBP-1) in cervical and vaginal secretions, as well as ultrasound assessment of cervical length.

[A case of bilateral tubal pregnancy after IVF - ET].

The authors describe a rare case of bilateral tubal pregnancy after IVF. The patient is with secondary infertility. The preceding diagnostic laparoscopy excluded the presence of tubal factor. The results of the spermogram show average to severe form of Oligoasthenozoospermia. Short protocol with GnRH-antagonist was performed and two embryos were transferred on the third day. On the 36th day after the embryo transfer the patient was hospitalized with abdominal pain in the right hypogastric region, clinical and ultrasound indications for hemoperitoneum. Urgent laparotomy was performed followed by salpingectomy dextra due to hemoperitoneum caused by tubal abortion. The examination of the left adnexa reveals uruptured tubal pregnancy in the isthmic part of the tube and the decision for salpingectomy sinistra was taken. Histological examinations confirmed the diagnosis of ectopic pregnancy in both tubes. The frequency of some rare forms and localizations of ectopic as well as heterotopic pregnancies increase after ART.

Assessment of students' satisfaction with virtual robotic surgery training.

Objective: Nowadays, in Bulgaria there is a trend of increasing entry into the surgical field of robot-assisted surgery operations, which suggests a need for the establishment of a large number of specialists in this field in a short period. Based on these arguments, the Medical University of Varna was the first university in the country to introduce a robotic surgery training program for medical students. The study aims to investigate the medical students' satisfaction on robotic surgery training provided at Medical University of Varna with da Vinci Skills Simulator. Design: During the summer semester of the academic 2020/2021 and 2021/2022 years, a pilot training of robotic surgery was conducted with 5th year students in Medicine. Within one month, the students had the opportunity to get acquainted with the simulator of da Vinci Xi robotic system. The training was divided into two modules: a two-week theoretical module and a two-week practical module. After completing the training, students filled out a questionnaire dedicated to assess their satisfaction with the proposed training. Correlation between their responses and the objective parameters assessed on the simulator was calculated. Results: Thirty participants (16 men and 14 women) shared their opinion on easiness of use and usefulness of the robotic simulator in training of surgery activities. Students' responses highly evaluated both aspects with average five-point Likert scale scores of 4.3 and 4.5, respectively. 93% of the participants would continue their further education and training in robotic surgery field. In addition, there was no correlation between objective evaluation by the simulator and students responses. Conclusions: Training in robotic surgery proves to be a useful approach for training students to develop skills and profession in the field of surgery. The results suggest that training in this field may be accomplished even at the student level, by exploiting the robotic surgery in realistic scenario and thus, in a timely manner to find out the surgical direction they want to be further evolved.

Validation of pre- and postoperative nomograms used to predict the pathological stage and prostate cancer recurrence after radical prostatectomy: a multi-institutional study.

PURPOSE: To validate the preoperative and postoperative predictive tables of Johns Hopkins hospital, Baltimore, Maryland (JHH) and the prostate nomograms of Memorial Sloan Kettering Cancer Center, New York (MSKCC), most commonly used to predict the pathological tumor stage and postoperative freedom from recurrence, in a mixed cohort of Bulgarian prostate cancer patients. METHODS: Clinical and laboratory data of 282 prostate cancer patients, who underwent radical prostatectomy, were supplied from three different institutions in Bulgaria. Preoperative prostate specific antigen (PSA) values, clinical stage, biopsy Gleason score and the pathological features of the radical prostatectomy specimens were collected from each center and evaluated. Nomogram-predicted probabilities for the presence of unfavorable pathological parameters (extracapsular extension, seminal vesicle invasion/SVI, and lymph node involvement/LNI), and the 5-year freedom from recurrence were compared with actual patient outcomes. Areas under the receiver operating characteristic (ROC) curves (AUC) were determined for each variable to assess the predictive accuracy of the nomograms applied. RESULTS: The MSKCC prostate cancer nomograms showed superior accuracy for all parameters studied, as compared with the JHH predictive tables. AUC values for organ-confined disease (OCD), SVI and LNI were calculated as 0.763, 0.750, 0.756 and 0.868, 0.787, 0.874 for JHH and MSKCC nomograms, respectively. The AUC values for 5-year freedom from recurrent disease were 0.751, 0.812, 0.813 and 0.894 for pre- and postoperative JHH and MSKCC nomograms, respectively. CONCLUSION: Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. All studied nomograms showed reasonable predictive values for the fi nal pathological features, like OCD, SVI and LNI, and for the 5-year freedom from recurrent disease. This multi-institutional study showed that each of the predictive tools studied could be used in Bulgarian patients with comparable accuracy. Compared with the JHH tables, the MSKCC prostate cancer nomograms showed higher predictive accuracy and should therefore be preferred.

A rare case of isolated lung metastasis in the kidney.

Renal metastases are very rare condition in the clinical practice. The treatment is individualized and it depends on general status of the patient, involving of other organs and also the control of primary tumor. We are presenting a 64 years old woman, who had episodes of intermittent hematuria for two weeks. CT scan showed a large heterogeneous left kidney mass. The patient underwent open transabdominal radical left nephrectomy and the final diagnosis was isolated lung adenocarcinoma metastasis of the kidney.

A rare case of extramedullary hematopoiesis in adrenal mass.

Extramedullary hematopoiesis (EMH) is a compensatory mechanism for deficient formation or function of red blood cells. Very rarely, extramedullary hematopoiesis is finding out in the kidneys as well as adrenals. We present a 50 year old man, who was admitted in the Urology Department with symptoms of renal colic. A contrast enhanced computed tomography (CT) of the abdomen and pelvis revealed right adrenal lesion of 80/79 mm in coronary size. The final diagnosis was myelolipoma of the right adrenal gland. We presented a rare case of adrenal tumor mass in patient without any haemotological disease that requires surgical excision.

Management of Leydig cell tumors of the testis-a case report.

We report 1 case of Benign Leydig cell tumor. A 45-year-old male was admitted to the Urology department with a large painless mass in the right testis of 1 year duration. The patient underwent radical high right orchiectomy, with a preliminary diagnosis of right testicular tumor. On the basis of the pathologic and immunohistochemical findings, the testicular mass was diagnosed as a benign Leydig cell tumor. Long-term follow-up is necessary to exclude recurrence or metastasis and also the endocrine profile and imaging investigations need to be repeated periodically.

A rare case of liposarcoma of the spermatic cord.

We present a 42 year old man, who was admitted in the Urology Department with symptoms of unilateral, painless, hard and firm slow-growing mass of the left scrotum for 4 months. Pelvic computed tomography (CT) scan showed a 8 cm3 mass lesion in the left hemiscrotum. Left radical orchiectomy and wide excision were performed and a yellowish soft tissue mass measuring closely attached to the spermatic cord was resected during surgery. Histopathologic evaluation revealed a tumor mass composed of well-differentiated liposarcoma.

Management and diagnosis of Nutcracker syndrome-a case report.

Nutcracker syndrome (NCS), also known as left renal vein (LRV) entrapment syndrome is a condition that leads to stenosis of the aorto-mesenteric region of the LRV, with dilatation of the distal portion of the vessel. A 43-year-old woman was admitted to the Urology department with symptoms of intermittent painless hematuria and mild to moderate left lumbar pain for the last three months. The patient underwent cystoscopy under general anesthesia. Bloody urine was noticed to appear from the left ureter ostium and an intra-venous contrast CT of the abdomen was performed. The final diagnosis was anterior Nutcracker syndrome.

Intraoperative sentinel lymph node mapping in patients with colorectal cancer.

BACKGROUND/AIMS: In about 1/3 of the patients with colorectal cancer without metastases which have been radically operated recurrences are observed and these patients die from cancer. This requires improvement of the surgical methods radicality as well as a more accurate determination of the indications for adjuvant chemotherapy administration. The introduction of a method for evaluating the degree of the metastases in colorectal cancer would highlight these issues. To this purpose we apply the method of sentinel mapping. METHODOLOGY: For a period of one year we performed intraoperative sentinel mapping on 103 patients who had been operated for colon or rectal cancer. We used the dying method with Patent Blue V. An algorithm was worked out for sentinel mapping in colorectal cancer. RESULTS: We achieved 100% performance success and 97% sensitivity. We increased the volume of the surgical intervention in 100% of the patients and elevated the clinical stage of 20% of the patients in Ist and IInd stage by means of ultrastaging with immunohistochemistry. CONCLUSIONS: We conclude that sentinel lymph nodes mapping in colorectal cancer is a diagnostic method which is convenient for the surgeons allowing them for an individualized approach toward each patient.

Comparative analysis of prognostic significance of molecular markers of apoptosis with clinical stage and tumor differentiation in patients with colorectal cancer: a single institute experience.

BACKGROUND/AIMS: The most important parameter determining the outcome of colorectal cancer (CRC) is the presence of metastases, which occur in 45-50% of all cases. The balance between proliferation and apoptosis is a key factor for tumor growth, and thus--for metastasis. Evaluation of markers for proliferation and apoptosis could therefore be helpful in predicting tumor behavior in early stage of carcinogenesis. METHODOLOGY: Seventy-two biopsies from cases of colorectal cancer (CRC) were immunostained for the proliferation/apoptosis-related proteins Bcl-2, Bax and p53. The resected specimens were also subjected for routine pathologic assessment as part of Tumor, Node and Metastases (TNM) staging. RESULTS: Comparing the marker protein expression with standard prognostic factors such as clinical stage and grade of differentiation revealed a lack of correlation between markers and standard prognostic factors in cases where clinical stage favors good prognosis (I and II stage). We found lack of correlation in 52% of diagnosed patients by tumor grade and 46% in patients by clinical stage. CONCLUSIONS: Co-expression of Bax with p53 protein is associated with poor clinical outcome, especially in cases without concomitant expression of bcl-2. The blocked apoptosis and inability of the organism to "liquidate" the neoplastic transformation of the cell (loss/mutation of p53), which we establish in our study in the half the patients with high and moderately differentiated carcinoma and separately in 46% of the patients with favorable prognosis by clinical stage is a reason for fast progression, too. The presence of a low correlation between the staging and the results of the molecular profiling suggest that the staging system needs to improve to address more precisely the issues of therapeutic options and patient survival. Using a panel of markers rather than a single marker is a step in this direction.