Clinical audit of patients with cervical cancer in Slovenia. Data analysis from 2003-2006.

PURPOSE OF INVESTIGATION: From 2003 to 2006 the data on Slovenian cervical cancer patients who regularly attended a gynecologist were gathered. Data were analyzed in order to improve the efficiency of the cervical cancer screening program. METHODS: Data on all patients newly diagnosed with cervical cancer were collected at three central clinics in Slovenia. The results are a presentation and comparison of detailed information on some characteristics of cervical cancer patients of the group that regularly visited a gynecologist and of the other group who did not. Data were processed by descriptive epidemiological methods. Mantel-Haenzel chi2 and Fisher's p tests were used to evaluate statistical significance. RESULTS: On average, 55% of patients with cervical cancer underwent a gynecological examination five years before the diagnosis. The patients who regularly attended their gynecologist were, in all age groups, statistically significantly younger, the stage of cervical cancer at diagnosis was statistically significantly lower (p = 0.01) and were, in statistically significantly higher percentage, treated surgically (p < 0.01). From 2003 to 2006, each patient had on average five examinations at her gynecologist within the period of five years to six months before the diagnosis of cervical cancer. The average number of collected smear samples was 3.2. CONCLUSION: From the results of our analysis, it may be concluded that improvements are needed in Slovenia in the field of screening for and early detection of cervical cancer.

Clinical audit of patients with cervical cancer in Slovenia--data analysis for the year 2003.

PURPOSE OF INVESTIGATION: The data gathered in 2003 on the patients with cervical cancer who regularly attended their gynecologist were analyzed with the purpose of clinical audit. METHODS: The data on newly detected patients with cervical cancer in 2003 who regularly attended their gynecologist were gathered simultaneously at three Advisory Boards for Gynecology in Slovenia. RESULTS: Of 149 patients in whom, according to our data, invasive cervical cancer had been diagnosed, 92 (61.7%) patients were examined by a gynecologist in the previous five years. In the majority of these patients, cervical cancer was diagnosed in early, localized disease stage. In the periods of 13-24 and of seven to 12 months before the diagnosis of cervical cancer, almost half the patients had Pap II, and three to six months before diagnosis, 67.6% of patients had Pap II. CONCLUSION: These results encourage us to proceed with clinical audits to analyze individual cervical cancer cases, including another independent reevaluation of cervical smears in the five-year period before diagnosis. A suitable calendar of refresher training courses on colposcopy, which should be obligatory for all performing this examination method, also needs to be set up.

Risk factors and prognostic factors in patients with double primary cancer: epithelial ovarian cancer and breast cancer.

BACKGROUND AND OBJECTIVE: The most important known risk factor for ovarian cancer is the BRCA1-2 mutation, which is clinically often manifested through a positive family history of cancer of the breast and/or ovary. Whether other risk factors and prognostic factors in women with a positive family history of cancer of the breast and/or ovary and/or with BRCA1-2 mutation are important remains to be elucidated. Recent studies have shown that in the double primary breast and ovarian cancer (DPBOC), BRCA1-2 mutation is present in at least 86% of cases. Therefore, the group of patients with DPBOC, especially with epithelial ovarian cancer and breast cancer, is the most suitable for such an analysis. The aim of this study was to verify the hypothesis that, in this group, some other risk factors, in addition to a specific family history of cancer, as well as unfavourable pathomorphological prognostic factors, are more expressed than in a control group of patients with sporadic epithelial ovarian cancer only. METHODS: We compared the study group of 31 patients with DPBOC (epithelial ovarian cancer) to a control group of 62 patients with a single, sporadic epithelial ovarian cancer and negative specific family history. The data were obtained from the Cancer Registry of Slovenia and from clinical records. For every patient, we filled-in a protocol and analysed the data, comparing other risk factors in addition to specific family history and prognostic, clinical, and pathomorphological factors. Statistical analysis was performed using descriptive statistics, chi-square test and t-test. Multivariate analysis was also planned, but the necessary conditions were not met. RESULTS: In the study group, we found a higher percentage of positive non-specific family histories than in the control group, but the difference was not statistically significant. No difference in procreative risk factors was observed between the groups. There was a higher percentage of borderline significance of women from the study group that developed ovarian cancer between 45 and 59 years of age. In the study group, ovarian cancer was significantly more often found at Stage I, although the groups did not differ in detection procedures. Also, we did not find any differences in the distribution of tumour grades or histologic tumour types. CONCLUSION: The results did not confirm our hypothesis, yet they indicated some differences between the groups regarding the risk factors for ovarian cancer. Regarding the prognostic factors, we even found a significantly higher percentage of Stage I epithelial ovarian cancer in the study group, with no difference in the mode of detection. Considering the results that are not typical of BRCA-related cancer (what double primary cancer of the ovary and breast is supposed to be) and previous reports, we find it more likely that the patients with BRCA1-2 mutations represent only a subgroup within the group of patients with double primary breast and ovarian cancer.

Endometrial and other primary cancers after tamoxifen treatment of breast cancer -- results of retrospective cohort study.

OBJECTIVES: The aim of the retrospective cohort study was to evaluate the relationship between the influence of tamoxifen on the development of endometrial and other second primary cancers in the patients with invasive breast cancer. STUDY DESIGN: A cohort of 630 women diagnosed with breast cancer from 1987 to 1994 was selected from a population-based registry; 440 patients were treated with tamoxifen and 190 patients without it. The observation period was 8.5 years (range 5-12 years). The data were analysed by the relative risk (RR) calculation at a confidence interval (CI) of 95%, using a Mantel-Haenszel chi(2)-test and Fisher's p-test to evaluate statistical significance. RESULTS: There were no statistically significant differences between the group of breast cancer patients treated with tamoxifen and without it as regards the age at the breast cancer diagnosis, family medical histories, body mass, age at menopause, fertility, diabetes, hormone replacement therapy and oestrogen-hormone replacement therapy. In 41/440 (9.3%) tamoxifen-treated patients and in 8/190 (4.2%) non-users of tamoxifen, diagnostic curettage was performed due to benign endometrial changes and endometrial cancer (EC). The difference in the proportions of patients with diagnostic curettage in both group was statistically significant (chi(2)=4.45, p=0.03). In the group of patients treated with tamoxifen, with the median treatment duration of 40 months (range 1-97 months) and in the group of patients without tamoxifen, EC was diagnosed in 11 and in two patients, respectively. The evaluated RR was 2.38 (0.53-10.61, 95% CI). The second primary cancer, excluding contralateral breast cancer and EC, was diagnosed in the group of breast cancer patients treated with tamoxifen and without it in almost the same percentage, i.e. in 12 patients (3%) in the group of patients who were treated with tamoxifen and in 10 patients (5%) in the group of patients without tamoxifen treatment. CONCLUSION: Despite the fact that the calculated RR of EC in our study (2.4) was not statistically significant, due to a small number of patients, our results support the IARC evaluation that tamoxifen is carcinogenic to humans. Our data also suggest that tamoxifen does not increase the risk of other second primary cancers. However, the risk of individual second primary cancers cannot be reliably assessed due to a limited number of patients.

Hormone replacement therapy after invasive ovarian serous cystadenocarcinoma treatment: the effect on survival.

AIM: Our report deals with the presumed influence of hormone replacement therapy (HRT) on the survival of patients with invasive ovarian serous cystadenocarcinoma. MATERIALS AND METHODS: We selected a group of 24 patients with the diagnosis of invasive ovarian serous cystadenocarcinoma who were treated with HRT after primary surgical treatment. Each patient from the selected group was compared with two patients from the control group with the same diagnosis who did not receive HRT. The matching criteria were the age at the time of the diagnosis, year of the diagnosis, stage of the disease, differentiation, residual tumor after first operation, and disease-free interval until receiving HRT. We used Cox regression to calculate odds ratios as estimates of the effect of HRT on overall survival in the patients with invasive ovarian serous cystadenocarcinoma who did or did not receive HRT after diagnosis. RESULTS: HRT was started an average of 21 months (range, 1-25 months) after diagnosis, and lasted for an average of 24 months (range, 1-70 months). After taking into account the effects of other known prognostic factors (the age at the time of the diagnosis, stage of the disease, differentiation, type of operation, residual tumour before the first operation), the estimated risk of death in patients with invasive ovarian serous cystadenocarcinoma who received HRT was 0.90 (odds ratio = 0.90; 95% confidence interval, 0.24-5.08). CONCLUSION: The results of our small study are only preliminary and suggest that HRT does not have a pronounced effect on survival. A single center can scarcely obtain a sufficient number of such a specific group of cancer patients; therefore, the collaboration of different institutions, preferably in a randomized, controlled trial, is needed for more reliable results.

Hormone replacement therapy after epithelial ovarian cancer treatment.

PURPOSE: Our report deals with the presumed influence of hormone replacement therapy (HRT) on the recurrence of epithelial ovarian cancer. MATERIALS AND METHODS: Our study group consisted of 31 patients who had been treated for invasive epithelial carcinoma of the ovaries. In all the patients the primary treatment was surgery. The mean duration of follow-up was 55 months. All the patients received HRT with non-conjugated estrogens. The data were analyzed using analytical descriptive epidemiological methods. RESULTS: The mean duration of HRT was 25 months, starting on average 18 months after completed therapy for ovarian cancer. Progression of the disease was established in 3 patients with advanced disease, 2 patients with moderately- and poorly-differentiated serous adenocarcinoma respectively, and in one patient with well-differentiated endometrioid adenocarcinoma. The progression of ovarian cancer occurred 1, 2 and 10 months after the beginning of HRT. Two patients died due to progressive disease, while one patient is still alive with evidence of the disease. Eleven months after the beginning of HRT, one patient without evidence of ovarian cancer progression presented with a new primary cancer--carcinoma of the breast. CONCLUSIONS: According to the results of our review study, HRT does not seem to have a noteworthy effect on the progression of epithelial carcinoma of the ovary. However, only further--carefully designed--prospective studies could provide more conclusive results.

Hormone replacement therapy after uterine leiomyosarcoma treatment. Case reports.

Uterine sarcomas are extremely rare uterine malignancies; with a review of the literature we could not find any data dealing with exogenous oestrogens or combined hormone replacement therapy (HRT) after leiomyosarcoma treatment. We report two cases of patients with leiomyosarcoma of the uterine corpus. Both patients were without pelvic irradiation or exogenous oestrogen treatment before the diagnosis. Leiomyoma of the uterus was found during surgery in both cases. Both patients were receiving HRT with non-conjugated oestrogens, after an intensive non-hormonal treatment had failed. No recurrence was established after surgical treatment in the patient with 12 mitoses per 10 high power fields (HPF). The patient is still on HRT (61 months). The other patient with a leiomyosarcoma with very high mitotic activity (40 mitoses per 10 HPF) received cytostatic and irradiation therapy after surgery because of locally widespread disease. Ten months after the diagnosis and 3 months after beginning HRT, recurrence was observed. The patient thereupon stopped HRT. After two additional operations, the patient is alive and without evidence of disease. We presume that the present case reports observations might suggest that HRT did not appear to have a pronounced adverse effect on the leiomyosarcoma outcome in our patients. Nevertheless, until more collected data determine that HRT is safe, caution is needed.

A case-control study of hormone replacement therapy after primary surgical breast cancer treatment.

AIMS: To investigate the presumed influence of hormone replacement therapy (HRT) on the progression of and death due to breast cancer. METHODS: In order to make a detailed analysis, we selected a group of 21 patients with the diagnosis of invasive breast cancer who had HRT after primary surgical treatment. Each patient from the selected group was compared with two patients from the control group with the diagnosis of invasive breast cancer who did not have HRT after primary surgical treatment. The control cases were matched to selected HRT patients with regard to age at time of the diagnosis, year of diagnosis, diameter of the tumour, metastatic spread in the axillary lymph nodes, and disease-free interval until applying HRT. The same criteria were applied in all analyses. The data were analysed by odds ratio (OR) calculation with a confidence interval of 95%, taking into account residual malignancy and death due to breast cancer in both groups (including carcinoma in the contralateral breast). RESULTS: HRT was applied in 21 patients treated for breast cancer. In 33% of them, radical mastectomy revealed metastases in the axillary lymph nodes. Hormone receptors could not be found in 57% of patients. In the majority of patients the tumour measured 17.6mm in diameter. HRT was started on average 62 months (range 1-180 months) after diagnosis, and lasted an average of 28 months (range 3 72 months). All 21 patients used oestradiol as HRT, i.e. a non-conjugated oestrogen. Combined hormonal therapy (oestrogens + progestagens) was given to 95% of patients with median age of 47 years (range 41-59 years) at the beginning of HRT. Relapse was observed in four patients (19%) of the HRT group; of these, one had a carcinoma of the contralateral breast. In the control group, relapse was observed in five patients (11%); one of these five patients had a carcinoma of the contralateral breast. In the HRT group, there were no deaths among the patients with confirmed relapse, while one patient died in the control group. The estimated risk (OR= 1.74, 95%S CI 0.34-8.88) of relapse of breast cancer was calculated by comparing data from HRT users, who had received HRT for 28 months (range 3-72 months) on average, with data from the control group. The estimated risk of breast cancer relapse in HRT users who had been receiving HRT for less than 24 months was 0.65 (OR = 0.65, 95% CI 0.02-7.85). CONCLUSION: Despite the inherent limitations of retrospective data and the need for prospective randomized trials to assess the possible influence of HRT on progression after breast cancer treatment, the present observations suggest that HRT treatment for less than 24 months does not appear to have a pronounced adverse effect on cancer outcome. Nevertheless, until appropriate clinical trials determine that HRT is safe, caution is needed.

Association of risk factors for cervical cancer and human papilloma viruses in invasive cervical cancer.

Our study was carried out on 70 patients with invasive squamous carcinoma of the uterine cervix (CC) or invasive adenocarcinoma of the uterine cervix at all stages, admitted to the University Department of Gynecology and/or to the Institute of Oncology in Ljubljana. The patients were not selected by age. A questionnaire on known risk factors in CC was filled in for each of the 70 patients, and two tumor smears were taken for the determination of human papilloma viruses (HPV) 16 and 18 by means of in situ hybridization and polymerase chain reaction (PCR). Each patient also had the serum level of vitamin A determined. The results of our study revealed a correlation between HPV 16 or 18 infection (60:40) and CC. When analysing some already known risk factors, no statistically significant difference could be established for any of the factors studied, except for the age at first birth.

Detection of human papillomaviruses (HPV-16,18) in cervical smears by in situ hybridization.

The rate of human papillomaviruses (HPV) 16 and 18 infections were measured in 109 women with histologically or cytologically determined lesions of the uterine cervix and in 42 healthy women. Cervical swabs were taken as the source of the target viral DNA. In situ hybridization with biotinylated probes was used. HPV-16 was the predominant type in patients and in healthy women. The percentage of positive cases was the highest in cervical cancer patients: 43.3% in squamous cell carcinoma and 33.3% in adenocarcinoma followed by cervical intraepithelial neoplasia (CIN), III, II (21.4%), CIN I (14.3%) and low grade squamous intraepithelial lesions (13.6%). HPV-18 type was detected in a lower percentage in the three groups of patients. In healthy women HPV-16 was determined in 12% and HPV-18 in 4.8%. We believe that the described noninvasive method of obtaining clinical material should be the method of choice for estimating papillomavirus infections in patients and in the general population. Our results are in agreement with suggestions that HPV genotype could be an important prognostic indicator in cervical carcinoma.

Adenocarcinoma in a sigmoid neovagina 22 years after Wertheim-Meigs operation. Case report.

The development of carcinoma in the neovagina has rarely been reported. Depending on the type of tissue that has been used for the transplant, the tumor appears either as a squamous cell carcinoma or adenocarcinoma. It is important to draw a distinction not only between the patients with squamous cell carcinoma and adenocarcinoma, but also between those with neovagina performed due to congenital absence of the vagina and others in whom the procedure was performed because of an advanced cancer in the true pelvis. In the latter group of patients, it is generally difficult to distinguish a residual disease from a second primary of the same histology. There is no dilemma, however, when the histology differs as in the case presented. The patient reported here underwent surgery for squamous cell carcinoma of the cervix, stage Ib, in 1967. The intervention comprised a Wertheim-Meigs resection and sigmoid vaginoplasty. Considering the favourable histological findings, postoperative irradiation was not indicated. Following the procedure, the patient had been well and free of any major complaint for 22 years after surgery when she presented with a moderately differentiated adenocarcinoma of the neovagina. She was successfully operated upon and had no evidence of disease at the last follow-up examination, two and a half year after surgery.