Giorgio Bolis

Ovarian cancer risk and history of selected medical conditions linked with female hormones

To investigate the role of selected medical conditions on the risk of ovarian cancer, we analysed data from a case-control study. Cases were 971 women below the age of 75 years with histologically confirmed epithelial ovarian cancer, admitted to a network of hospitals including the major teaching and general hospitals in the greater Milan area. Controls were 2758 women admitted to the same network of hospitals for acute, non-gynaecological, non-hormone related, non-neoplastic conditions. Obesity/severe overweight were inversely associated with the risk of ovarian cancer (multivariate relative risk, RR, 0.66, 95% confidence interval, CI, 0.52-0.85). Hyperlipidaemia was also inversely related to ovarian cancer risk, (RR 0.64, 95% CI 0.45-0.89). No relationship emerged between ovarian cancer risk and diabetes (RR 0.80, 95% CI 0.54-1.19), hypertension (RR 0.85, 95% CI 0.68-1.06), thyroid diseases (RR 0.89, 95% CI 0.63-1.13) and cholelithiasis (RR 0.86, 95% CI 0.66-1.12). A decreased frequency of ovarian cancer was seen in women with a history of uterine leiomyomas (RR 0.66, 95% CI 0.47-0.92) and benign ovarian cysts (RR 0.69, 95% CI 0.41-1.13).

Single-dose Intraperitoneal Radioimmunotherapy with the Murine Monoclonal Antibody I-131 MOv18: Clinical Results in Patients with Minimal Residual Disease of Ovarian Cancer

Sixteen of 19 enrolled patients with minimal residual disease of ovarian cancer (macroscopic disease < 5 mm or positive blind biopsies and/or positive peritoneal washing), demonstrated by surgical second-look, underwent intraperitoneal radioimmunotherapy (RIT) with the radiolabelled monoclonal antibody I-131 MOv18 (mean dose 14 mg of MOv18 with 3700 GBq of I-131) 30-40 days after the second-look procedure. Clinical follow-up and/or third-look evaluation performed 90 days after RIT showed complete response (CR) in 5 patients, no change (NC) in 6 patients and progressive disease (PD) in 5 patients. Follow-up study showed long-term maintained CR in 1 patient (34 months) and relapses in the other 4 patients after a mean disease-free period of 10.5 months. 5 NC patients showed clinical or instrumental progression after a mean disease-free period of 13 months. The toxicity of RIT was negligible. Only 1 patient showed mild and transient bone marrow suppression (platelet count nadir 52,000 mm3 after 30 days). HAMA production was demonstrated in 94% (15/16) of patients. In conclusion, RIT appears to be a very promising therapeutic approach to treat minimal residual disease of ovarian cancer.

EMA/CO regimen in high-risk gestational trophoblastic tumor (GTT)

From June 1980 through December 1985, 36 high-risk GTT patients received Bagshawes EMA/CO regimen, 22 as first-line, and 14 as second-line treatment, after primary chemotherapy with CHAMOCA, or cyclic regimen, or MTX-CF. All treated patients were metastatic at the start of treatment with EMA/CO; three showed liver metastases and one brain metastasis. Seventeen patients had a high score, greater than 15. Nineteen patients had histologically confirmed diagnosis of choriocarcinoma. The overall response rate was 86% with 81% survival during a median observation time of 32 months. The median number of courses needed to achieve complete remission was 3 (range 3-7). Toxicity was acceptable, and was less than with CHAMOCA and MAC regimens. Only 1 out of 17 high-risk patients developed drug resistance, and 3 needed urgent surgery. The relapse rate of responders was 19% after a median of 5.5 months. The survival rate of high-risk patients was 88%, of which 76% are alive with no evidence of disease, while 12% have still detectable beta-chorionic gonadotrophin. The remission rate in the second-line treatment group was 64%, higher than using other regimens such as MAC or CHAMOCA. In conclusion, we consider EMA/CO to be the best choice for patients with high-risk GTT, because it is effective and well tolerated. In our opinion, the cure rate of high-risk GTT could perhaps be improved by starting trials to establish what salvage treatment to employ after EMA/CO failure and using more aggressive first-line chemotherapy in selected high-risk patients, on the basis of the scoring system.

Determinants of risk of invasive cervical cancer in young women.

We analysed determinants of risk of cervical cancer in women aged less than 45 years using data from a case-control study conducted in Italy. Cases were 261 women aged < 45 years with histologically confirmed invasive cervical cancer. Controls were 257 women aged < 45 years, with acute, non-neoplastic conditions, judged to be unrelated to any of the known or suspected risk factors for cervical cancer. In comparison with women reporting one or no sexual partner, the multivariate odds ratio (OR) of cervical cancer was 2.4 (95% confidence interval, CI, 1.3-4.6), for women reporting two or more sexual partners, and, in comparison with women reporting their first intercourse at 17 years of age or before, the multivariate OR was 0.5 (95% CI 0.3-0.9) in women aged > or =23 years at first intercourse. The risk of cervical cancer was higher in parous women and increased with number of births (OR = 8.1 for three or more births). Among parous women the risk tended to increase with later age at last birth; in comparison with parous women reporting their last birth before age 25, the OR was 1.9 in those reporting their last birth at > or =35 years. No clear association emerged between oral contraceptive use, smoking, education, social class and risk of cervical cancer.

Lymphangiography in patients with ovarian epithelial cancer: an evaluation of 289 consecutive cases.

From January, 1973, to June, 1976, 226 patients with palpable ovarian masses were evaluated preoperatively by lymphography. Histology showed 166 cases of malignant epithelial tumors, 26 benign tumors, and 34 malignant special tumors (not included in this report). Furthermore, the group of patients included 99 recurrences of ovarian epithelial cancer and 24 patients who underwent restaging diagnostic procedures without clinical evidence of disease. Lymphography was negative in all patients with benign tumors. In the 289 cases of epithelial cancer, lymphangiography gave evidence of nodal metastases in 88 (30%). When the histological subtype was considered, the highest incidence of metastases was in undifferentiated carcinoma (50%) and the lowest, in mesonephroid carcinoma (14%). According to the stage before lymphography, nodal metastases were found in 8% of Stage I, 0% of Stage II, 29% of Stage II, and 53% of Stage IV cases. The incidence of metastases was 46% in patients studied for recurrent disease and 17% in patients studied for restaging. Fifty‐four percent of patients had metastases only in the pelvic nodes and 18% only in the para‐aortic chains; in 28% both chains were involved simultaneously. Bilateral involvement was found in 63% of the positive cases. Retroperitoneal node biopsies were performed in 68 patients (36%). The radiologic/histologic correlation was 100% in the lymphangiographically positive cases; 81% in the negative cases, with nine false‐negative reports; and 87% in all cases.

Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.

Indications, advantages, and limits of laparoscopy in ovarian cancer

Abstract Ninety-two patients with ovarian cancer (72 epithelial and 20 special) underwent 123 laparoscopies for restaging (23 patients), follow-up (46 patients), and second look (28 patients), All cases are analyzed according to the indications, characteristics of procedure, and morbidity. The results are discussed. Isolated diaphragmatic metastases were absent in the restaging of referred localized cancer (017); the number of positive peritoneal washings in the same patients, on the contrary, was significant (517). Laparoscopy seems to be a very useful procedure in the follow-up of patients without clinically followable disease or showing questionable response to chemotherapy. Combined laparoscopy/laparotomy procedures show the limits of sole laparoscopy: All this notwithstanding, the present 2-year study emphasizes the great value of this minor surgery in the surveillance of ovarian cancer.

Salvage chemotherapy for ovarian cancer recurrence: Weekly cisplatin in combination with epirubicin or etoposide

From December 1986 to April 1990, 40 consecutive ovarian cancer patients who relapsed after response to cisplatin-based chemotherapy regimens were treated with seven courses of weekly cisplatin, in combination with epirubicin or etoposide. The overall response rate obtained with the intensive schedule was 60% and the complete response rate was 25%; median duration of response was 7 months and median survival time, 13.5 months. Responsive cases seem to have longer survival; a prognostic factor for response to salvage treatment and longer survival is the disease-free interval after the first-line chemotherapy. Weekly cisplatin as intensive treatment was very well tolerated and showed acceptable toxicity in both the combination protocols with epirubicin or etoposide.

Cell Kinetics: A prognostic marker in epithelial ovarian cancer

Abstract The proliferative activities (3H-thymidine labeling index, LI) of 72 primary ovarian cancers and 76 metastatic lesions from untreated patients were evaluated. Overall, median LI values for primary and metastatic lesions were similar (7.8 vs 7.0%), but cell kinetics significantly differed in metastases from different sites. The LI of the primary tumor was unrelated to pathologic stage and histology, but was significantly correlated with histologic grading ( P = .014). The prognostic relevance of LI was assessed for 43 untreated patients at stage III–IV (90% with bulky residual disease), treated after staging laparatomy with five cycles of cisplatin or of carboplatin. For 19 patients the LI was determined for both primary tumor and metastases, for 15 for the primary, and for 12 for the metastatic lesions. Complete remission (CR) was unrelated to pretreatment LI, although a trend toward a higher rate of CR was observed with rapidly proliferating tumors. Patients with slowly proliferating primary tumors had a higher probability of 1.5-year survival than patients with rapidly proliferating tumors (83 vs 50%). The difference was even greater between patients with both primary and metastatic lesions proliferating slowly (100%) and patients with at least one (61%) or both lesions proliferating rapidly (60%). Pretreatment LI was not predictive for survival in subgroups of patients who attained CR, but it was quite predictive for survival in patients responding only partially or not at all (90 vs 32%, P = .025).

Frequency of hydatidiform mole in Lombardy, Northern Italy

The frequency of hydatidiform mole in Lombardy (a region in Northern Italy with 8.9 million inhabitants) over the period 1979-1982 was estimated using the Regional Hospital Discharge Registration System, where information is collected on all discharges from public and private hospitals. After revision of registrations and clinical records, 347 cases of hydatidiform mole were confirmed. The estimated frequency was 66.22 per 100,000 pregnancies (SE = 3.56), or 1 in 1510 pregnancies. The risk of hydatidiform mole was not elevated in teenage women, but rose markedly above age 40, and was almost 300 times higher for women age 50 or older. The frequency of hydatidiform mole observed in the nine provinces of Lombardy was significantly heterogeneous, and this variation could not be explained in terms of differences in maternal age distribution.