[ADHERING TO MEDICAL STANDARTS, EVIDENCE-BASED STAGING IN GYNECOLOGICAL CANCER].

Among the key factors that influence the survival of patients is adherence to medical treatment standards. Indicators are assessing the degree of adherence to medical standards and represent the relative shares (%) of patients who fulfilled the relevant aspect of any subject. Data from the BNCR of 9842 cases of patients with malignant diseases of the female reproductive diagnosed in 2011-2013 in Bulgaria has been analyzed. Patients with tumors of the vulva were incorrectly staged in 15% to 30% of the cases, and those with vaginal tumors were incorrectly staged in 20% to 23% of cases. In patients with malignant tumors of the cervix incorrect staging was established in 19% to 47% of the cases. Patients with tumors of the uterus were incorrectly staged in 6% to 26% of the cases. Among the patients with ovarian tumors were incorrectly staged in 18% to 43%. Our results show that one in three patients with gynecological cancer in Bulgaria was incorrectly staged. We recommend using the current TNM and FIGO systems.

[OBESITY AND GYNECOLOGICAL CANCER].

An analysis of 329 patients with gynecological cancer, 120 of them were without obesity and 209 of them were with obesity. Only 36.47% of the cases were with normal weight. There is a trend of increasing obesity with age, with a peak in the age group 60-69 years. The distribution of patients according to BMI and stage of the disease there is a downward trend in the obesity with increasing stage. In both groups of patients (with and without obesity), the volume and type of surgery were carried out depending on the type of tumor process (localization) and stage of the disease. Radical histerectomy with pelvic lymph node dissection (with or without omentectomy) is carried out in 141 patients, of which only 6 were of normal weight, and 135 patients (95.7%) were of different stage of obesity. Total hysterectomy with pelvic lymph node dissection (with or without omentectomy) is carried out in 123 patients, of which only 2 were of normal weight, and 121 patients (98.4%) were of different stage of obesity. Our results show that the volume of surgery in patients with gynecological cancer does not depend the obesity and depend the stage of disease.

[COMORBIDITIES IN PATIENTS WITH ONCOGYNECOLOGICAL CANCER].

Comorbidities may directly affect the prognosis of the disease of interest or may indirectly affect the prognosis by affecting the choice of treatment. The aim of this study is to determine comorbidities in pacients with gynecological cancer. The study included 100 consecutive pacients for the period 01.01.2014-08.-5.2014 in Gynecological department of Specialized Hospital for ActivTratament in Oncology. The most common disease are arterial hipertony diabetes and obesity. In most patients, establish one or more accompanying illnesses that increase with age.

[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.

Cancer burden of breast and gynecological cancers in Bulgaria: epidemiology and clinical aspects.

PURPOSE: In Bulgaria, there are over 3700 cases diagnosed with breast cancer annually and over 3300 with gynecological cancers. The purpose of this study was to estimate the burden of breast and gynecological cancers in Bulgaria, analyzing trends of incidence, mortality and survival for the past two decades. METHODS: Data from the Bulgarian National Cancer Registry for women diagnosed with cancer of breast (C50, ICD10), cervix uteri (C53), corpus uteri (C54) and ovary (C56) during 1993 - 2009 were analyzed. Age-standardized incidence and mortality rates (ASR) per 100,000 persons were calculated using the world standard population. Average annual percent changes (AAPC) for 1993-2009 were estimated by Joinpoint regression. The observed survival was analyzed with the Life Table method for two periods: 1993-1997 and 2005-2009. RESULTS: Incidence rates of the most frequent cancers among Bulgarian women are increasing - from 1.7% to 2.6% annually. Mortality rates are decreasing significantly for breast (-0.8% annually) and increasing for corpus uteri cancers (4.9% annually). Survival for all sites increased from 3 to 8% over the study period. We observed greater proportion of cases diagnosed in stage I in 2009 than in 1993, for the 4 sites. CONCLUSION: These results indicate some differences in trends in incidence and mortality of the reviewed sites compared with other European countries, highlighting the need for more strict adherence to integrated treatment standards and the necessity of introduction of population screening programs.

[Therapeutic results in patients with endometrial cancer].

The aim of the present study is to analyze the patients with endometrial cancer, treated at Gynecology Clinic of the National Oncology Hospital, Sofia according to the stage of the disease, histological type, differentiation, the peculiarities of the spreading and metastases, the therapeutic methods applied and the obtained results. For the period 2002-2004, 152 women with endometrial cancer were treated at the clinic. Predominate the patients with first stage cancer 117 (77%) and with endometroid adenocarcinoma/adenoacantoma 116 (76.3%), as well as these who were treated with surgery 134 (88.2%), followed by radio, hormonotherapy. Among the surgical procedures the simple total hysterectomy with bilateral salpingoophorectomy was the most frequent applied method - 119 (79.2%) patients, followed by radical hysterectomy with bilateral salpingoophorectomy and lymph node dissection 25 (16.7%). At the end of the 3 years study period 118 (77.6%) women are alive and 34 (22.4%) are dead. For 28 (18.5%) patients the reason for the death was the oncological disease and for 6 (3.9%)--other type of disease. Our results demonstrate once again, that therapeutic success of patients with endometrial cancer depends directly of the exact determination of the prognostic factors and administration of complex approach in the treatment of every patient.

[A case of 11 operation because of genitourilal abnormalites and cervical carcinoma].

A case of young woman with 11 operation because of genitourinal abnormalities and cancer of the uterine cervix. The patient was with bladder exstrophy and 2nd stage cervical cancer, treated operatively and with chemotherapy. Because local recurrence she was operated 3 times. The patient died 3 years after initial treatment of the cervical cancer.

The surgical management of recurrent carcinoma of the vulva.

One hundred and two patients with recurrent vulvar cancer were treated with surgical re-excision. At follow-up 57 patients (56%) were free of disease and 45 were dead of disease. The cumulative 2-year and 5-year survivals were 74% and 61%, respectively. Fifty-seven patients had a recurrence within 2 years and 27 were free of disease, 30 patients relapsed between 2-10 years of whom 21 were free of disease, 15 patients relapsed after 10 years and 9 were free of disease. At the time of recurrence progression of metastatic disease to the groin lymph nodes was found in 30 cases, and all of these patients died of disease. Fifty-seven of 72 patients remained free of disease when the lymph nodes were not involved (P < .00001). Radical excision of localized recurrent vulvar cancer provides acceptable survival results when the regional lymph nodes are not involved.

Invasive cervical carcinoma in women up to age 30.

One hundred and seventy patients with invasive cervical cancer up to age 30 were treated and observed from 1970 to 1989. Twenty seven were in stage Ia, 81 in stage Ib, 38 in stage II, 20 in stage III and 4 in stage IV. The cases with poorly differentiated histological types predominated. Sixteen women were gravid at the moment of discovering the cervical carcinoma. Six patients were treated by conisation, total hysterectomy was used in 11 cases. Wertheim-Meigs' operation in 27 cases, Wertheim-Meigs' operation and postoperative radiation in 105 cases and intracavitary radium with external radiotherapy in 14 cases. Seven women were treated conservatively. Five, ten and fifteen year survival rates are 62%, 45% and 45%. Patients with stage I and without lymphogenic metastases have the highest survival rates. The young women with stage Ia and Ib have optimistic prognoses.

Local immunosuppression determined by class II HLA antigen expression in patients with preclinical cervical carcinoma.

Class II HLA antigen expression was investigated in biopsy material from patients with preclinical cervical carcinoma. Class II molecules were determined immunohistochemically by MoAb against HLA-DR antigens. A significant reduction of class II positive cells was established in the tumor tissue compared to the normal cervical epithelium. A correlation between the tumor progression and the inhibition of the class II antigen expression was found.

Local administration of interferon-alpha in cases of cervical intraepithelial neoplasia associated with human papillomavirus infection.

PURPOSE: To investigate the efficacy and the optimal dose of topical interferon-alpha in cases of cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) infection. PATIENTS AND METHODS: From January 1995 to December 1997, 75 patients with CIN (45 with CIN I-III, and 30 with CIS) associated with HPV infection were treated with local administration of interferon-alpha (group 1). From January 2002 to June 2003, after polymerase chain reaction (PCR) determination of HPV types 6, 11, 16, 18, 31 and 33, treatment with interferon-alpha was administered to 21 patients with CIN I-II (group 2). HPV 16 was found in 11 cases and HPV 31 in 10 cases. In cases of CIS, the interferon treatment followed conization. In all cases interferon was injected intralesionally or at periphery of the conization, 3 times per week at dose of 3 million (m) IU. Ten interferon administrations were given in all of the cases. RESULTS: In group 1 after 5 administrations the cytological findings returned to normal in 48 (64%) cases, and in 27 (36%) cases only dyskaryotic cells were found. In all cases the cytological findings reverted to normal after 10 administrations of interferon. In 45 cases with CIN I-III treated with interferon only (without conization), biopsy was carried out, and all of the patients were found free of dysplastic lesions. In group 2 the cytological findings of all 21 cases returned to normal after 10 administrations of interferon. As of December 2003, both the cytological and histological findings were negative for CIN and HPV. CONCLUSION: These results suggest that treatment with interferon-alpha is an effective therapeutic method for CIN associated with HPV infection, and 10 administrations of 3 mIU constitute the optimal dose.

[Organ-preserving operations on patients with microinvasive carcinoma of the cervix uteri]. / Organosukhraniavashti operatsii pri bolni s mikroinvaziven kartsinom na matochnata shiika.

Organ-preserving operative treatment was performed on 29 women with microinvasive operative microinvasive carcinoma of the uterine cervix at lal clinical stages. After conization of the uterine cervix the patients were observed actively by cytology, colposcopy and, when it was necessary, a colposcopic-directed biopsy was made during a period of 3-98 as there was no relapse of the disease in neither case. The authors think that it is possible to perform conization in young women with minimal stromal invasion up to 1000 microns as their reproductive function is preserved without any risk for occurrence of a relapse.

[The volume of the surgical treatment and follow-up of patients with malignant ovarian tumors in the first stages]. / Obem na khirurgichnoto lechenie i proslediavane na bolni sus zlokachestveni tumori na iaichnitsite v purvi stadii.

From 1987 till 1997 110 patients with stage-I ovarian malignant tumors were treated and follow-up at the Department of Gynaecological Oncology, National Oncological Center. Papillifery-adenocarcinoma were in 40 cases, serous carcinoma were in 26 cases, mucinous carcinoma were in 15 cases, malignant granulosa cell tumor were in 14 cases, endometrioid carcinoma were in 6 cases, dysgerminoma were in 6 cases, Teilum's tumour were in 2 cases, and 1 case of ovary sarcoma were detected. Radical operated on the first operation were 69 patients (62.8%), and in 37 cases (33.6%) second operation for radicality were performed. In 4 cases only adnexectomy were done. In all cases post operative adjuvant chemotherapy were used. The patients were follow-up by tumour markers, sonography and CT. Follow-up period is from 5 months till 11 years. Alive were 80 patients (73%), and 30 patients (27%) were died. The patients with stage Ic and those nonradical operated in the first operation have worst prognosis then patients with stage Ia and stage Ib. The patients with ovarian tumours must be operated only in the hospitals with possibility of urgent hystological diagnosis for better prognosis in the cases of stage-I malignant ovarian tumours.

[Metastasis in patients with uterine tube carcinoma]. / Metastazirane pri bolni s kartsinom na matochnata truba.

Lymphogenic, hematogenic and implanted metastases in 10 women with carcinoma of the uterine tube, treated at the gynecological clinic of the National Oncological Center for the period of 1977-1988, were described. The patients were of the age of 44 to 65 years. Lymphogenic metastases were discovered in: iliac lymph nodes (l. n.) in 4 women, inguinal l. n.--in 2 patients, supraclavicular l. n. in 1 woman and paraaortic l. n.--in one woman. Metastases were found on the anterior abdominal wall in 3 patients, but in two cases in ovaries, omentum, liver, lung. They were discovered in other abdominal organs in single cases. Metastases occurred from 5 months to 8 years since the onset of the disease. Eight patients died from 1 to 3 years after establishment of metastases, but 2 women continued treatment for 2 and 3 years respectively.

[Malignant melanoma of the vulva and vagina (a report of 4 cases and review of the literature)]. / Malignen melanom na vulvata i vlagalishteto (s prinos na 4 sluchaia i literaturen obzor).

Three women with malignant melanocarcinoma of the vulva and one woman with malignant melanocarcinoma of the vagina were treated at the gynecological clinic of the National Oncological Center for the period of 1983-1988. The mean age of the patients was 52 years. In all patients melanocarcinoma was IV-V degree according to Crark as in 2 women it was pigmented, but in 2 women--achromatic. Radical vulvectomy was performed on patients with melanocarcinoma of the vulva as in 2 patients inguino-femoral lymph dissection according to Ducuing was made, but pelvic lymph dissection according to Taussing was performed in 1 woman as well. The operation of Werthaim-Meigs and extirpation of the vagina was performed in the woman with melanocarcinoma of the vagina. Two of the patients died after 13 and 28 months after the primary treatment due to generalization of the process, but 2 of the patients developed a relapse of the disease 10 and 14 months after treatment. Anterior and posterior exenteration of the pelvis was performed in the woman with a relapse of the vaginal melanocarcinoma. Two patients are still alive for a period of 6 and 8 months and chemotherapy continues. A literary review is presented and possibilities for more effective treatment are discussed.

[The reproductive function in women with preinvasive and microinvasive carcinomas of the cervix uteri treated by conization]. / Reproduktivna funktsiia pri zheni s preinvaziven i mikroinvaziven kartsinom na matochnata shiika, lekuvani s konizatsiia.

An inquiry was carried out on 46 women with preclinical carcinoma of the uterine cervix, treated with conization at the gynecological clinic of the National Oncological Center. Women were at the age of 22 to 38 years. Conization was made on 8 women on account of microinvasive carcinoma with invasion up to 1000 mkm, but on 38 women--on account of carcinoma of 0 degree. 26 women became pregnant after conization but 9 of them performed induced abortion and 2-therapeutic abortion. Pregnancy of 5 women ended with spontaneous abortion during the first trimester, one woman waited for delivery and 9 women delivered on term and without interventions. One woman delivered twice. The first trimester was risky for women with preclinical carcinoma of the uterine cervix, treated with conization.

[Suppression of cellular immunity in patients with carcinoma in situ and microinvasive cancer of the cervix uteri]. / Supressiia kletochnogo immuniteta u bol'nogo s kartsinomoi in situ i mikroinvazivnym rakom sheiki matki.

Monoclonal antibodies (Ortho type) were used for immunocytochemical evaluation of cell-mediated immunity in peripheral blood from 29 patients with in situ (TisNoMo) and microinvasive (T1aNoMo) cervical carcinoma. The total number of T cells (OKT3+) was decreased in both patient groups compared to healthy volunteers. Marked difference between OKT4+ (helper/inducer) and OKT8+ (suppressor/cytotoxic) cells was observed OKT8+ level rose with advancement of disease, resulting in inverted OKT4+/OKT8+ ratio in T1aNoMo cancer patients. Antitumor immune resistance proved inhibited in both study groups manifesting itself in suppression of cell-mediated immunity.

[The conservative treatment of carcinoma in situ of the cervix uteri by the local application of 5-fluorouracil]. / Konservativno lechenie na kartsinom in situ na matochnata shiika s lokalno aplitsirane na 5-fluorouracil.

Local treatment with 5% of 5-Fluorouracil (5-Fu) in the form of globules was carried out on 37 patients with carcinoma in situ of the uterine cervix, established histologically, as the application was performed once daily for a period of 14-20 days. There was a complete correlation between the cytological investigation after the conservative treatment and the histological examination of the operative material from the conization, which was made within 1-2 weeks after local application of 5-Fu. It could be possible to use cytology for objective determination of the therapeutic effect as well as a possible usage of colposcopic-directed biopsy. The conservative treatment with 5-Fu should be the first stage of treatment of these patients, but in the absence of therapeutic effect conization of the uterine cervix should be made, which reduces the risk of spontaneous abortion. The conservative treatment with local application of 5% of 5-Fu is recommended in young women, with not large lesions of carcinoma in situ of the uterine cervix and still at their reproductive age.