Fabio Parazzini

A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: The @RISTOS Project

Summary Background Data:The epidemiology of venous thromboembolism (VTE) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis (DVT). However, the clinical relevance of asymptomatic venography-detected DVT is unclear, and the population of these clinical trials is not necessarily representative of the overall cancer surgery population. Objective:The aim of this study was to evaluate the incidence of clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE. Methods:@RISTOS was a prospective observational study in patients undergoing general, urologic, or gynecologic surgery. Patients were assessed for clinically overt VTE occurring up to 30 ± 5 days after surgery or more if the hospital stay was longer than 35 days. All outcome events were evaluated by an independent Adjudication Committee. Results:A total of 2373 patients were included in the study: 1238 (52%) undergoing general, 685 (29%) urologic, and 450 (19%) gynecologic surgery. In-hospital prophylaxis was given in 81.6% and postdischarge prophylaxis in 30.7% of the patients. Fifty patients (2.1%) were adjudicated as affected by clinically overt VTE (DVT, 0.42%; nonfatal pulmonary embolism, 0.88%; death 0.80%). The incidence of VTE was 2.83% in general surgery, 2.0% in gynecologic surgery, and 0.87% in urologic surgery. Forty percent of the events occurred later than 21 days from surgery. The overall death rate was 1.72%; in 46.3% of the cases, death was caused by VTE. In a multivariable analysis, 5 risk factors were identified: age above 60 years (2.63, 95% confidence interval, 1.21–5.71), previous VTE (5.98, 2.13–16.80), advanced cancer (2.68, 1.37–5.24), anesthesia lasting more than 2 hours (4.50, 1.06–19.04), and bed rest longer than 3 days (4.37, 2.45–7.78). Conclusions:VTE remains a common complication of cancer surgery, with a remarkable proportion of events occurring late after surgery. In patients undergoing cancer surgery, VTE is the most common cause of death at 30 days after surgery.

The epidemiology of endometrial cancer

The descriptive and analytical epidemiology of endometrial cancer is reviewed. Over the last few decades, age-standardized incidence rates have been rising in several countries. The rise has been even greater in terms of absolute numbers of cases, and hence public health implications, due to the aging of the population. Although endometrial cancer rates were found to be higher in richer countries and urban populations, there is now evidence of some changes in the socioeconomic determinants of the disease in developed countries. In etiological terms, any factor that increases exposure to unopposed estrogens (such as menopausal replacement treatment, obesity, and irregular menstrual cycles) tends to increase the risk of the disease, while factors that decrease exposure to estrogens or increase progesterone levels (such as oral contraceptives or smoking) tend to be protective. Less well defined, or more difficult to explain in biological terms, is the role of other factors, such as births, miscarriages, or diabetes and hypertension, and only suggestive evidence is available on diet from analytical epidemiology. The data reviewed herein are discussed in terms of models of carcinogenesis, as well as attributable risks and public health implications.

Endometriosis and pelvic pain: relation to disease stage and localization *

OBJECTIVES To determine whether prevalence and severity of pain symptoms are related to endometriosis stage and site, with particular reference to deep infiltrating vaginal lesions. DESIGN Systematic assessment of chronic pelvic pain symptoms. SETTING University hospital endometriosis center. PATIENTS A total of 244 consecutive symptomatic patients with endometriosis diagnosed at laparoscopy or laparotomy. INTERVENTIONS Assessment of dysmenorrhea and nonmenstrual pain by means of a 10-point linear analog scale, a 7-point multidimensional rating scale, and a 3-point verbal scale; evaluation of deep dyspareunia with the first and third systems only. MAIN OUTCOME MEASURES Prevalence and severity of pain symptoms in relation to endometriosis stage and site of lesions. Correlation between revised American Fertility Society score and symptoms severity, as well as between two pain scales to assess dysmenorrhea and nonmenstrual pain. RESULTS Eighty-eight women had stage I and II disease and 156 had stage III and IV disease. Only ovarian endometriosis was present in 108 patients, only peritoneal implants were present in 37, combined ovarian and peritoneal lesions were present in 57, and histologically confirmed vaginal endometriosis was present in 42. The frequency and severity of deep dyspareunia and the frequency of dysmenorrhea were less in patients with only ovarian endometriosis than in those with lesions at other sites. Patients with vaginal endometriosis had a significantly increased risk of deep dyspareunia compared with those whose lesions were at other sites (odds ratio, 2.55; 95% confidence interval, 1.21 to 5.39). Stage per se, independent of lesion site, was not correlated with frequency and severity of dysmenorrhea and nonmenstrual pain. The severity of deep dyspareunia was related inversely to the endometriosis score (Spearman correlation coefficients for linear analog and verbal rating scales, respectively, -0.22 and -0.20). Kendall test by ranks revealed a correlation between linear analog and multidimensional pain scales in the rating of both dysmenorrhea and nonmenstrual pain (respectively, tau-b, 0.59 and tau-b, 0.68). CONCLUSIONS Endometriosis stage in the current classification was not related consistently to pain symptoms. The presence of vaginal lesions was associated frequently with severe deep dyspareunia. Dysmenorrhea and nonmenstrual pelvic pain were assessed with equal accuracy by a linear analog and a multidimensional scale.

Frequency and Determinants of Erectile Dysfunction in Italy

Objective: To analyze the prevalence and risk factors for erectile dysfunction (ED) in Italy in a cross–sectional study.Methods: Eligible for the study were men aged 18 years or more, randomly identified by 143 general practitioners among their registered patients during the period January 1996 to February 1997. ED was defined as the impossibility to achieve and maintain an erection sufficient for satisfactory sexual performance.Results: Of the 2,010 men interviewed, 257 (12.8%) reported ED. The prevalence increased with age, from 2% in men aged 18–39 to 48% in those >70 years (tested for trend, p = 0.0001). A history of cardiopathy, diabetes, hypertension, neuropathy, thrombotic/hemorrhagic stroke, peripheral vascular disorders, pelvic/medullary injury and pelvic surgery/radiation all increased the risk of ED. The association of hypertension and diabetes tends to increase the risk of ED. In comparison with nondiabetic and nonhypertensive men, the odds ratio (OR) was 1.4 (95% confidence interval (CI), 0.7–3.2) for hypertensive men without diabetes, 4.6 (95% CI, 1.6–13.7) for diabetic men without hypertension and 8.1 (95% CI, 1.2–55.0) for men with diabetes and hypertension. In comparison with never smokers, the OR of ED was 1.7 (95% CI, 1.2–2.4) for current smokers and 1.6 (95% CI, 1.1–2.3) for ex–smokers and increased with duration of the habit.Conclusions: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men.

Reproductive factors and risk of endometrial cancer

The role of reproductive factors in endometrial cancer risk has been analyzed in a case-control study conducted since 1983 in the greater Milan area on 568 women (cases) with histologically confirmed endometrial cancer and 1925 women (controls) who were admitted for acute, nonmalignant, hormonal, gynecologic conditions to hospitals that cover a comparable catchment area. Compared with nulliparous women, parous women had a 30% lower risk of endometrial cancer, but there was no evidence of a decline in risk with increasing number of births. The risk of the disease decreased with number of spontaneous or induced abortions; the multivariate relative risk estimates were, compared respectively with no spontaneous or induced abortions, 0.5 for women with two or more spontaneous abortions and 0.3 for women with two or more induced abortions; both trends in risk were statistically significant. When parous women only were considered, no association emerged between endometrial cancer and age at first birth, but the risk decreased with increasing age at last birth: compared with women whose last birth occurred before age 25, the relative risk was 0.5 for women who were greater than or equal to 35 years old at last birth, and the multivariate trend in risk was statistically significant. For most of the reproductive factors that were considered, the risk estimates tended to be greater at younger age or among premenopausal women and to flatten off in subsequent strata of age. An association between endometrial cancer and age at first birth was observed in women who were less than or equal to 49 years old, but not in older groups. The observation that later age at last birth as well as later first birth in younger women decreases the risk of endometrial cancer suggests a short-term protective effect of pregnancy. This finding is consistent with a late-stage (promotional) effect of reproductive factors on endometrial carcinogenesis.

Reproductive factors, family history, occupation and risk of urogenital prolapse.

OBJECTIVE We conducted a case-control study to analyze risk factors for urogenital prolapse requiring surgery. METHODS Cases were 108 women with a diagnosis of II or III degree uterovaginal prolapse and/or third degree cystocele. Controls were 100 women admitted to the same hospitals as the cases, for acute, non-gynecological, non-neoplastic conditions. RESULTS Occupation showed an association with urogenital prolapse: in comparison with professional/managerial women, housewives had an odds ratios (OR) of urogenital prolapse of 3.1 (95% confidence interval (CI), 1.6-8.8). Compared with nulliparae, parous women tended to have a higher risk of genital prolapse (OR 2.6, 95% CI 0.9-7.8). In comparison with women reporting no vaginal delivery, the ORs were 3.0 for women reporting one vaginal delivery (95% CI 1.0-9.5), and 4.5 (95% CI 1.6-13.1) for women with two or more vaginal deliveries. Forceps delivery and birthweight were not associated with risk of prolapse after taking into account the effect of number of vaginal deliveries. The risk of urogenital prolapse was higher in women with mother or sisters reporting the condition: the ORs were, respectively, 3.2 (95% CI 1.1-7.6) and 2.4 (95% CI 1.0-5.6) in comparison with women whose mother or sisters reported no prolapse. CONCLUSIONS Our data support the clinical suggestion that parous women are at a higher risk of prolapse and the risk increases with number of vaginal deliveries. First-degree family history of prolapse seems to increase the risk of prolapse.

Stage and localization of pelvic endometriosis and pain

We analyzed the prevalence of dysmenorrhea, pelvic pain, and dyspareunia in relation to the disease stage in 160 women with endometriosis but no other associated pelvic disease who underwent their first gynecologic surgery (laparoscopy or laparotomy) at the First Obstetric and Gynecology Clinic of the University of Milan between 1985 and 1987. Dysmenorrhea was reported by 78% of the patients, pelvic pain by 39%; and deep dyspareunia by 32%. No relation was found between severity of the pain symptoms and stage of the disease or site of the endometriotic lesions.

Risk of recurrence after myomectomy

Summary. The risk of recurrence of uterine myomas was analyzed in 622 patients who underwent myomectomy between 1970 and 1984 at the First Department of Obstetrics and Gynecology of the University of Milan. The cumulative 10‐year recurrence rate was 27%, and this increased steadily up to the end of the observation period. Differences were not observed in frequency of recurrence by age at diagnoses or by the site of the myomas at surgery. Patients with a single myoma tended to experience a lower rate, but this finding was not statistically significant. Women who gave birth to a child after myomectomy had a 10‐year recurrence rate of 15%, against 30% for those who did not; this difference was statistically significant.

Endometriosis and ovarian cancer

In 556 patients undergoing surgery for ovarian cancers the frequency of endometriosis ranged from 3.6% to 5.6% in serous, mucinous, and miscellaneous neoplasms versus 26.3%, 21.1%, and 22.2%, respectively, in endometrioid, clear cell, and mixed subtypes; the differences were statistically significant (chi 2 heterogeneity 50.0, p < 0.001) and consistent in strata of age, parity, menopausal status, and disease stage.

Dietary factors and the risk of breast cancer

We evaluated the risk of breast cancer in relation to the frequency of consumption of a few selected dietary items. Data were used from a case-control study of 1,108 histologically confirmed breast cancer patients and 1,281 control subjects who were in the hospital for acute conditions unrelated to any of the established or suspected risk factors for breast cancer. Moderately elevated risk estimates were associated with higher levels of fat consumption in seasonings [butter, margarine, and oil, relative risk (RR) = 1.34, 95% confidence interval (CI) = 1.06-1.71] and meat (RR = 1.36, 95% CI = 1.12-1.65), whereas a reduced risk (RR = 0.42, 95% CI = 0.34-0.51) was associated with a more frequent green vegetable consumption. It was not possible to show that these associations were incidental, because allowance for several identified potential confounding factors, including the major identified or potential risk factors for breast cancer, did not materially modify the risk estimates. Further, no appreciable interaction emerged with age or menopausal status, because the diet-related risk estimates were similar in pre- or postmenopausal women. However, the implications of these findings in terms of specific micronutrients (e.g., retinol or beta-carotene) and biological correlates are still unclear. Alcohol consumption was significantly greater among breast cancer cases, with a multivariate risk estimate of 2.92 for the highest level. Thus, the present findings confirm that various aspects of diet may influence the risk of breast cancer, although the small amount of available knowledge does introduce serious uncertainties in any discussion of the potential implications in terms of prevention on a public health scale.