Pentti Lehtovirta

Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome

The estimated lifetime risk for endometrial carcinoma (EC) in hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is 32–60%, thus supporting surveillance. The survival rate of EC patients is, however, favourable questioning the need for surveillance. Yet, the effectiveness of gynecological surveillance remains to be shown. The 2 previously published studies were based on transvaginal ultrasound (TVUS) alone. Intrauterine biopsy has not been tested in surveillance for EC in HNPCC families. The effect of gynecological surveillance was evaluated among 175 Finnish mutation carriers. During 759 person years at risk, there were 503 surveillance visits including TVUS and intrauterine biopsy of endometrium at 94% and 74% of the visits, respectively. EC occurred in 14 cases, 11 of which were diagnosed by surveillance, 8 by intrauterine biopsies. TVUS indicated only 4 EC patients but missed 6 other cases. Intrauterine sampling detected 14 additional cases of potentially premalignant hyperplasia. The stage distribution and survival tended to be more favorable in the 14 EC cases of the surveilled group (no deaths) than in the group of 83 symptomatic mutation carriers of whom 6 died of EC, but with no statistical significance. Four cases of ovarian cancer occurred but none was detected by surveillance in TVUS examinations. In conclusion, EC surveillance in HNPCC seems more effective with endometrial biopsies than with TVUS alone. A definite improvement in survival remains to be shown. The detection of early cancer stages and premalignant lesions offers the opportunity to avoid extensive adjuvant treatment.

Transvaginal sonography and hysteroscopy in postmenopausal bleeding

We compared transvaginal sonography and hysteroscopy with dilatation and curettage findings in 45 women with atypical postmenopausal bleedings. The histological diagnosis was atrophy in eight (17.8%) women. hormonal effects in 14 (31.1%), endometrial polyp in 19 (42.2%) xnd adenocarcinoma in four (8.8%). Hysteroscopy detected 16 (78.9%) of the 19 cases wirh polyps and two of the four with carcinoma. Sensitivity and specificity for endometrial pathology were 86.9% and 91.7% respectively. A polyp was directly diagnosed by transvaginal sonography in 13 (57.9%) women and an infiltrative endometrial cancer in two. Sensitivily and specificity for endometrial pathology were 73.9%) and 95.7% respectively. All but one case of endometrial pathology were found when the endometrium (both layers) was thicker than 5 mm. Thus, an endometrial thickness of ≥ 5 mm had a sensitivity of 95.7%, a specificity of 45.5% and a positive predictive value of 64.7% for endometrial pathology. This study shows that transvaginal scanning allows detection of an endometrial pathology in the vast majority of cases and it may be used as the first diagnostic step in the investigation of women with atypical postmenopausal bleeding.

Preoperative sonographic evaluation of endometrial cancer

Preoperative sonography was performed in 93 patients with a histologic diagnosis of endometrial cancer. Uterine volume was enlarged (mean, 164 +/- 143.7 cm3; range, 25 to 800) but did not significantly correlate with the degree of myometrial invasion. Endometrial echoes were identified in 93.5% of the cases. A significant correlation (p less than 0.01, Newman-Keuls test) was found between endometrial echoes volume and myometrial invasion. Myometrial invasion was correctly predicted by sonography in 80% of the cases. Polypoid intraluminal growth was the most common factor affecting sonographic accuracy. Sonographic staging was accurate in 91% of the cases. Sonography appears to be an efficient, economic, and practical tool for clinical staging of endometrial cancer.

Endometrial carcinoma in the cancer family syndrome

The study group consisted of 26 women with endometrial adenocarcinoma belonging to 19 cancer families. Age at the onset of cancer, the stage and histologic differentiation of the tumor, initial symptoms, other malignancies, 5‐year survival, and transmission of cancer to descendants were studied. The focus was on the importance of endometrial carcinoma in the tumor spectrum. The diagnosis of cancer family was delayed in 14 of the 19 families because endometrial carcinoma was not included in the primary diagnostic criteria. This delay may have been harmful to 16 family members who had carcinomas later in life. In ten of the 14 women with multiple malignancies, endometrial adenocarcinoma was the primary malignancy diagnosed, thus enabling the suspicion of a gene carrier and screening for subsequent malignancies. The authors concluded that endometrial carcinoma is a significant component of cancer family syndrome and should be included in the main criteria of Lynch syndrome II.

Endometrial adenocarcinoma with clinical evidence of cervical involvement: Accuracy of diagnostic procedures, clinical course, and prognostic factors

Background. The accuracy of clinical staging is known to be insufficient in stage II endometrial carcinoma. Also the optimal management of this disease is controversial. In this study we evaluate diagnostic accuracy and prognostic factors with special reference to treatment modalities of stage II endometrial carcinoma.

Progesterone and estradiol receptors in the cytosol of the human uterine artery.

The binding of progesterone and estradiol to their specific cytoplasmic receptors was studied in cytosols of uterine arteries from 33 women undergoing hysterectomy. Twenty-five patients were premenopausal and one of them was pregnant. The regularly menstruating women were operated on at different phases of the menstrual cycle. Eight patients were postmenopausal with their last menstruation 4 to 30 years ago. Both progesterone and estradiol receptor concentrations were highest during the follicular phase. Decline in both receptors was observed during the early luteal phase, and this decline coincided with the luteal rise of serum progesterone. Significant correlations between steroid receptors and serum estradiol and progesterone levels were not found. The highest amounts of both receptors were found in the youngest patients. The concentrations decreased with age to undetectable levels. The decrease in progesterone receptor concentration after the menopause was statistically significant. Myometrial biopsies were taken as control material from eight women. No association could be observed between myometrial and arterial receptor concentrations.

Preoperative serum concentration of hCGβ as a prognostic factor in ovarian cancer

In spite of a gradual improvement, survival in epithelial ovarian cancer is disappointingly low. New therapeutic regimens are emerging, and it would be important to be able to predict the prognosis and to stratify patients for clinical trials before therapy. We have evaluated the prognostic value of the pretreatment serum concentrations of 3 tumor markers. The free β subunit of human chorionic gonadotropin (hCGβ), CA125 and tumor‐associated trypsin inhibitor (TATI) were measured in pretreatment serum samples from 146 patients treated for ovarian cancer between 1990–1995. The patients were followed up until 1998. Elevated concentrations of hCGβ, CA125 and TATI were observed in 29%, 79% and 33%, respectively. When tested as single variables in Coxs proportional hazards model, stage, grade, size of residual tumor and hCGβ (all p < 0.001) and CA125 (p = 0.004) correlated with prognosis. However, when fitted as multiple variables together with stage, grade and age in the same model, hCGβ (RR = 3.42) stage (RR = 2.77) and grade (RR = 3.80) were the only significant variables. When serum hCGβ was normal, 5‐year survival was 80%, but it was only 22% when hCGβ was elevated. In patients with stage III or IV and minimal residual disease, 5‐year survival was 75% if hCGβ was normal compared with 0% if hCGβ was elevated. hCGβ in serum is a strong independent prognostic factor in epithelial ovarian cancer, and its prognostic value is similar to that of grade and stage. The availability of this marker before surgery could facilitate selection of treatment modalities.

Pre‐operative serum level of tumour‐associated trypsin inhibitor and residual turnour size as prognostic indicators in Stage III epithelial ovarian cancer

Objective To evaluate the use of the pre‐operative tumour‐associated trypsin inhibitor (TATI) level and residual tumour size at primary surgery as a prognostic indicators for patients with Stage III epithelial ovarian cancer.

Serum CA 125 levels during the menstrual cycle

Summary. Serum concentrations of CA 125 were measured in different phases of the menstrual cycle in 16 women with ovulatory and 12 women with anovulatory cycles. CA 125 levels were significantly elevated during menstruation in both groups. In women with anovulatory cycles, but not in those with ovulatory cycles, CA 125 levels were already increased in the premenstrual phase. A negative correlation was found between serum CA 125 and progesterone concentrations in the premenstrual phase of the cycle. We suggest that premenstrual elevation of serum CA 125 in women with anovulatory cycles is related to premature endometrial vascular changes which are the result of the low serum progesterone concentration leading to insufficient endometrial control. Thus the effect of progesterone seems to be indirect rather than a direct effect on CA 125 synthesis. When the CA 125 assay is used for diagnosis of cancer, sampling should not be done immediately before or during menstruation because the physiological elevation of the CA 125 levels may give false positive results.

Estradiol and progesterone receptors in two cases of endometrial stromal sarcoma

The presence of estradiol and progesterone receptors in endometrial stromal sarcoma (ESS) has not been studied previously. Two cases of ESS are reported in which high concentrations of these receptors were found in the tumor tissue. One of these patients had retained the reactivity to hormone treatment for several years. It is suggested that the steroid receptors should be analyzed in all cases of ESS to find tumors with a high receptor content. Hormone treatment of these patients should be part of the primary adjuvant therapy. In cases of a good response the therapy should be prolonged and continued for the rest of the patients life.