Prediction of cervical infiltration in Stage II endometrial cancer by different preoperative evaluation techniques (D&C, US, CT, MRI).

OBJECTIVE: Our clinical practice for FIGO Stage II endometrial cancer consists of Wertheim's radical hysterectomy as first choice of treatment. The evaluation of patients is based on D&C. The accuracy of this preoperative staging method is examined here. METHODS: Twenty-nine patients with endometrial cancer with suspected cervical involvement (FIGO Stage II) based on endocervical curettage underwent Wertheim's radical hysterectomy between January 1, 1989 and December 31, 2001 at the Gynaecological Department of the National Institute of Cancer, Budapest, Hungary. In all cases surgico-pathological staging was performed to examine the accuracy of preoperative D&C and to find out whether radical surgery was necessary in all patients and how the preoperative evaluation of patients should be improved. RESULTS: Out of 29 patients who underwent Wertheim's hysterectomy the pathological examination found primary cervical cancer in two patients. These two patients were eliminated from further evaluation. Out of the remaining 27 patients only eight (29.6%) had cervical involvement of endometrial cancer documented by a pathologic review on the hysterectomy specimen. Extrauterine disease was documented in one of the patients with cervical infiltration (1/8) and in one in the cervix-negative group (1/19). Ovarian spread was found in the first case and ovarian infiltration with penetration of the tumour into the parametric tissue in the second case. According to the FIGO classification 18 (66.6%) patients had less extensive disease and two (7.4%) had more extensive disease. Only 26% of the patients (7/27) had surgical findings consistent with the Stage II disease. CONCLUSION: We can conclude that "overtreatment" seems to have occurred in 19 patients, whose cervical infiltration by endometrial cancer could not be proved by pathological staging. It can also be assessed that understaging took place in two cases, which can be explained by two reasons; we did not make use of preoperative imaging techniques since US was applied in six patients, CT in 16 and the most accurate, MRI, on three patients only. The other possible reason, which can point out the bad efficacy of the imaging techniques as well, could be that a major part of the patients received preoperative AL treatment, which could also have influenced the cervical progression. This is possible, but has not been proved. The difference in the number of cervical infiltrations in the group of patients who received preoperative radiotherapy and in the group where they did not, is not significant (p = 0.9742), and infiltration of the endometrium was present in all cases. In the future, proper selection of imaging modalities can improve the staging of gynaecological disorders and preclude unnecessary procedures. In endometrial cancer cases US, especially with the use of TVUS, is often considered to be the primary imaging approach. However, in patients where ultrasound is suboptimal, where there is a large tumour present or the result of imaging studies will directly influence the choice of therapy and guide therapy planning then the higher accuracy of MRI warrants its use. CT is of use in the later stages of disease; differentiation between Stage I and II is difficult and CT is limited in the assessment of myometrial invasion.

Detection of high-risk HPV (16, 18, 33) in situ cancer of the cervix by PCR technique.

OBJECTIVE: The purpose of this study was to collect data about the incidence of high-risk HPV (16, 18, 33) types in in situ cervical cancers, and to evaluate the reliability of the morphological signs of HPV infection by comparing the presence of these signs to the PCR-proven HPV virus infection. METHODS: Fifty patients who underwent conisation at the Department of Obstetrics and Gynecology of Semmelweis University, Budapest, Hungary because of in situ cervical cancer were examined retrospectively for the presence of HPV infection by the PCR technique. The direct and indirect morphological signs of HPV infection identified in the histological and cytological samples were compared to the actual results of virus DNA amplification by PCR in the identical histological sections. The evaluation of the cytological smears and the histological sections was accomplished independently by two different pathologists. RESULTS: E6 open reading frame of HPV 16, 18 or 33 was detected by PCR in 56% (28 cases) of the histological sections of the 50 examined patients with in situ cancer. In 92% (26 patients) of the 28 HPV positive patients one HPV type was detected, while in one of the remaining two cases two HPV types (16/33), or all three types could be detected. The direct morphological signs for HPV infection proved to be 75% sensitive and 50% specific when compared to the results of PCR. Their predictive value for HPV infection was 65%. For the indirect HPV signs the sensitivity was 64% and specificity 31%. The predictive value, prognosticating the presence of HPV 16, 18, 33 infection was 54% in the same sections. Using significance analysis no significant relationship (p = 0.7728) could be detected between the positivity of indirect signs and the presence of HPV 16, 18, 33 infection, while in case of direct signs the relationship was almost significant (p = 0.0675). The joint testing of the direct and indirect signs did not improve the results (p = 0.1338). During the review of the cytological smears the specificity of the cytology in predicting true HPV infections was found to be 68% and sensitivity was 20%. The predictive value was only 50%. A significance analysis was not accomplished by this diagnostic method because of the missing data (see text). CONCLUSION: The method of Nawa et al. seems to be a reliable approach for the detection of HPV DNA in paraffin-embedded material. The three main types of HPV (16, 18, 33) are probably represented in lower percentages in CIN III in Hungary, but a larger survey is needed to obtain reliable data. The direct and indirect morphological signs of HPV infection failed to show a significant relationship with the PCR proven presence of HPV 16, 18, 33.

[Prognostic value of cell heterogeneity in cervical cancer determined by digital image analyzer of DNA content]. / A cervixdaganatok citometriai heterogenitásának vizsgálata sejtenkénti DNS-analízissel, a daganatheterogenitás prognosztikai értékének meghatározása céljából.

Frequency and prognostic value of cell heterogeneity in FIGO 1a-2a cervical cancer was examined, in 66 of patients underwent Wertheim type hysterectomy between 1989 and 1995 in National Institute of Cancer, Budapest, Hungary. A newly developed DNA image analyses (DNACE) was used in paraffin embedded tissues after enzymatic hydrolyses for evaluation of the DNA content in cervical cancer. In 30.3% of examined tissues (20/66) two subgroups was found. There was significant differences in the DNA indexes (DI) between the subgroups (p = 0.0001). In the remaining 69.7% of the cases only one subgroup was present. The frequency of two subgroups was higher between aneuploid (78.4%), or hyperploid (81.5%) type cervical cancer, however there was no significant difference between the two groups. On the other hand there was significant difference in the presence of two subgroups between the well and less differentiated cervical cancer. The frequency was higher between the less differentiated groups (p = 0.02). Looking at the prognostic value of subgroups, there was no significant correlation between the heterogeneity of cervical cancer and FIGO stage, or lymph node metastasis (p = 0.6855), or vascular/lymphatic space infiltration (p = 0.2558), or invasiveness of cancer (0.0823). There was neither significant value found between the outcome of disease and the number of subgroups present (p = 0.8738). It is though that the present of cellular heterogeneity in cervical cancer is connected with the differentiation of the cancer cells, and can be a good prognostic value in the anticipation of the aggressiveness of cervical cancer. Looking at the present result, there was no significant connection between the heterogeneity of cervical cancer and the outcome of the disease, so further examination should be done.

The value of colposcopy in screening cervical carcinoma.

The value of colposcopy and cytology in screening CIN was analyzed in a retrospective study of 1,504 patients treated at the Department of Gynecologic Oncology, National Institute of Oncology, Budapest from 1980 to 1991. The majority (1,451) of the patients were admitted for histological confirmation of atypical colposcopic and/or cytologic findings, and 53 women were treated for cervical repair. All women underwent either cervical excision or conization. Cytologic and colposcopic findings were compared with the histological results. Sensitivity and specificity rates of cytology were 47% and 77%, respectively. The corresponding figures for colposcopy were 87% and 15% and for cytology and colposcopy together, 96% and 14%. The low sensitivity of cytology suggests that as many as 50% of CIN lesions may be overlooked if cytology alone is used for screening, i.e. in 50% of CIN associated with abnormal colposcopy the cytology was negative. We found 194 asymptomatic patients with carcinoma in situ, 40 with microinvasive and 8 with frank invasive carcinoma. This finding emphasizes the importance of cervical cancer screening. Our data suggest that, with colposcopy as a screening tool, the rate of false-negative cytology can be significantly reduced. Clinical implications of the "cytology-negative abnormal colposcopy and cytology-negative CIN" have yet to be determined. The major drawback of primary colposcopy is its low specificity with the consequence of high false-positive rate and over-treatment in a substantial number of cases. To overcome the problem of low specificity, further studies are required to identify those atypical colposcopic changes that most likely represent CIN--and high-grade CIN in particular.

The fate of the retained ovaries following radical hysterectomy.

UNLABELLED: The authors studied the function of the preserved ovaries following radical hysterectomy in 65 patients with early stage cervical carcinoma. The ovaries were not displaced and fixed out of the pelvis. Squamous cell carcinoma was diagnosed in 91 cases and adenocarcinoma in 19 cases. Histologic studies of the 110 ovaries removed from 45 patients revealed no metastatic disease. None of the 65 women suffered from recurrent disease. Ovarian function was evaluated by: 1) the presence or absence of postmenopausal symptoms; 2) basal body temperature charts; 3) blood tests for FSH, LH, progesterone, and prolactin; and 4) evaluation of the cervical and vaginal epithelium (vaginal smears). The diagnosis of ovarian failure was based on high levels of FSH (> 30 U/L) on at least three occasions. Basal body temperature studied in 90 cycles of 25 patients revealed various curves indicating occasional anovulatory cycles and luteal-phase deficiency which were confirmed by low serum levels of progesterone. Serum prolactin levels were within the normal range in all cases. Ovarian failure was diagnosed in two instances. Both occurred within three years of radical hysterectomy. Three of the six patients experienced unilateral ovarian cyst formation following surgery, the other three had subsequent unilateral salpingo-oophorectomy at 6, 11, and 24 months after radical hysterectomy. CONCLUSIONS: Preservation of the ovaries at the time of radical hysterectomy and lymphadenectomy does not seem to compromise patient care. Impaired function or failure of the retained ovaries, however, is not uncommon; close post-treatment surveillance is therefore important in terms not only of recurrent disease but of function of the ovaries as well.

[Prospective study of K-cell activity in patients with malignant gynecologic tumors. Effect of radiation therapy]. / Rosszindulatú nögyógyászati daganatos megbetegedésben szenvedö betegek K-sejt aktivitásának prospectiv vizsgálata. A sugárkezelés és mütét hatása.

K cell activity was measured in the enzyme-like kinetic model of cytotoxicity against O, Rh (D) positive erythrocytes in 127 patients with carcinoma of the uterine cervix, 55 with carcinoma of the corpus uteri and 30 with malignant tumors of the ovary. The control groups included 62 healthy age matched women and 39 patients with benign tumor of the ovary. The cytotoxic activity was measured in a number of cases before any treatment and after irradiation and surgery in patients with cervical and endometrial cancer. The target cells were obtained from the same donor. ADCC activity of cervical and ovarian tumor patients enhanced depends on the stage of the disease. K cell activity of endometrial carcinoma patients was similar to the controls. ADCC activity of patients with carcinoma of the uterine cervix was increased, with carcinoma of the uterine corpus was indicated an increasing tendency following irradiation. There was connection with the dose of the irradiation and K cell activity. On the contrary, operation did not influence ADCC activity.