Kathleen M. Schmeler

BACKGROUND: Women with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have a 40 to 60 percent lifetime risk of endometrial cancer and a 10 to 12 percent lifetime risk of ovarian cancer. The benefit of prophylactic gynecologic surgery for women with this syndrome has been uncertain. We designed this study to determine the reduction in the risk of gynecologic cancers associated with prophylactic hysterectomy and bilateral salpingo-oophorectomy in women with the Lynch syndrome. METHODS: Three hundred fifteen women with documented germ-line mutations associated with the Lynch syndrome were identified. Women who had undergone prophylactic hysterectomy (61 women) and women who had undergone prophylactic bilateral salpingo-oophorectomy (47 women) were matched with mutation-positive women who had not undergone the procedure in question (210 women for the analysis of endometrial cancer and 223 for the analysis of ovarian cancer). Women who had undergone prophylactic surgery and their matched controls were followed from the date of the surgery until the occurrence of cancer or until the data were censored at the time of the last follow-up visit. RESULTS: There were no occurrences of endometrial, ovarian, or primary peritoneal cancer among the women who had undergone prophylactic surgery. Endometrial cancer was diagnosed in 69 women in the control group (33 percent), for an incidence density of 0.045 per woman-year, yielding a prevented fraction (the proportion of potential new cancers prevented) of 100 percent (95 percent confidence interval, 90 to 100 percent). Ovarian cancer was diagnosed in 12 women in the control group (5 percent), for an incidence density of 0.005 per woman-year, yielding a prevented fraction of 100 percent (95 percent confidence interval, -62 to 100 percent). CONCLUSIONS: These findings suggest that prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for preventing endometrial and ovarian cancer in women with the Lynch syndrome.

OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy in the United States. The mean age at diagnosis is 61 years; however, 5-30% of women are aged younger than 50 years at the time of diagnosis. The objective of this study was to conduct a clinical and pathologic review of endometrial cancers diagnosed in premenopausal women aged younger than 50 years, to better identify the risk factors for this subgroup of women. METHODS: We conducted a retrospective cohort study of patients with histologically confirmed endometrial cancer treated at the University of Texas, M. D. Anderson Cancer Center from 1989 to 2003. Clinical characteristics including age, body mass index (BMI), parity, diabetes, and personal or family history of cancer were obtained from the medical record. Pathologic information was obtained from pathology reports. RESULTS: Twelve percent (188/1531) of all patients with endometrial adenocarcinoma were aged younger than 50 years. The mean age at diagnosis was 41 years (range 21-49 years). Mean BMI was 34 kg/m(2) (range 18-68); 58% of patients had a BMI of 30 or greater. Fifty-five percent were nulliparous and 39% reported irregular menstrual cycles. The incidence of both diabetes and hypertension was 23%. Thirty-six patients (19%) had synchronous ovarian cancers. CONCLUSION: We found that the majority of patients diagnosed with endometrial cancer at a young age were obese and nulliparous. In addition, we found a high incidence of synchronous primary ovarian cancers in this cohort of young, premenopausal women.

OBJECTIVE: To estimate whether the delay of surgery impacts the risk of adverse maternal and fetal outcomes in patients diagnosed with an adnexal mass during pregnancy. METHODS: A review was performed of pregnant patients diagnosed with an adnexal mass 5 cm or greater in diameter. Data collected included age, gravity/parity, gestational age at diagnosis, and presenting symptoms. Ultrasound examinations were evaluated for mass size and complexity. Pregnancy outcome, complications, and surgical pathology were reviewed. RESULTS: Between 1990 and 2003, 127,177 deliveries were performed at our institution. An adnexal mass 5 cm in diameter or greater was diagnosed in 63 (0.05%) patients. Pathologic diagnosis was available for 59 (94%) patients. The remaining 4 patients were lost to follow-up and excluded from the analysis. Antepartum surgery was performed in 17 patients (29%): 13 because of ultrasound findings that suggested malignancy and 4 secondary to ovarian torsion. The remaining patients were observed, with surgery performed in the postpartum period or at time of cesarean delivery. The majority of masses were dermoid cysts (42%). Four patients were diagnosed with ovarian cancer (6.8% of masses, 0.0032% of deliveries), and one patient (1.7%) had a tumor of low malignant potential. Antepartum surgery due to ultrasound findings that caused concern was performed on all 5 women diagnosed with a malignancy or borderline tumor, compared with 12 (22%) of the patients with benign tumors (P < .01). CONCLUSION: In select cases, close observation is a reasonable alternative to antepartum surgery in patients with an adnexal mass during pregnancy.

BACKGROUND: Obesity is a well known risk factor for the development of endometrial cancer; however, weight alone does not account for all cases. The authors hypothesized that insulin resistance also contributes to an increased risk for endometrial cancer. Adiponectin is a protein secreted by adipose cells and has been shown to be a surrogate marker for insulin resistance, with low levels of adiponectin correlated with hyperinsulinemia and degree of insulin resistance. The purpose of the current study was to determine whether there was an independent association between adiponectin level and endometrial cancer. METHODS: A case-control study was performed on 117 endometrial cancer patients (cases) and 238 women with no history of cancer (controls). Serum adiponectin levels were measured using enzyme-linked immunoadsorbent assay and examined for their association with endometrial cancer. Univariate and multivariate logistic regression analyses were performed with adjustment for confounding factors. RESULTS: The mean serum adiponectin levels were significantly lower among cases (88.8+/-63.3 ng/mL) than among controls (148.2+/-68.3; P<.001). This inverse correlation continued to be observed after controlling for age, body mass index, diabetes, and hypertension. Cases were significantly more likely to have serum adiponectin levels in the lowest (odds ratio [OR] of 10.5; 95% confidence interval [95% CI], 4.49-24.57 [P<.001]) and intermediate tertiles (OR of 2.5; 95% CI, 1.01-6.21 [P=.05]) when compared with controls. CONCLUSIONS: Adiponectin level was found to be independently and inversely associated with endometrial cancer. Women with endometrial cancer were more likely to have low adiponectin levels than controls, even after adjusting for body mass index. This suggested that insulin resistance is independently associated with endometrial cancer.