Predictors of residual carcinoma or carcinoma-in-situ at hysterectomy following cervical conization with positive margins.

OBJECTIVES: Identify predictors of residual carcinoma or carcinoma-in-situ (CIS) at hysterectomy following cervical conizations with CIS and positive margins or endocervical curettage (ECC) or microinvasive cervical cancer. METHODS: Patients with cervical conization with CIS and positive margins, ECC or microinvasive carcinoma who underwent hysterectomy within 6 months of conization were identified. Conization and hysterectomy specimens were re-reviewed to assess volume of disease, ECC and margin status and residual carcinoma. Standard statistical tests were used. RESULTS: 83 patients were included. 34 (41%) had residual carcinoma in the hysterectomy specimen: 23 CIS, 9 microinvasive and 2 invasive disease. In patients with squamous histology predictors of residual disease included a positive ECC (p=0.04), combined endocervical margin and ECC (69% if both positive, 38% either positive, 11% if both negative, p=0.01) and volume of disease ≥ 50% (p=0.01). In patients with glandular histology no factor predicted residual disease. Type of conization, >2 involved quadrants, and the presence of microinvasion in the conization specimen did not predict residual disease. No patient with squamous histology had >Stage IA1 disease at hysterectomy, whereas 2 (2.4%) with adenocarcinoma had >Stage IA1 disease at hysterectomy. CONCLUSIONS: Residual carcinoma or CIS is present in nearly half of hysterectomies after conization with CIS and positive ECC, margins or microinvasion. Patients with squamous histology may not require repeat conization prior to definitive therapy. No factors predict residual disease with adenocarcinoma. In women with AIS with negative margins and ECC and no microinvasion, it appears reasonable to proceed with simple hysterectomy.

Obesity-associated adipokines correlate with survival in epithelial ovarian cancer.

OBJECTIVES: Obesity impacts outcome in women with epithelial ovarian cancer (EOC), although its exact role and the molecular mechanisms remain poorly defined. Adipocytes secrete leptin and adiponectin, and the leptin to adiponectin (L:A) ratio is correlated with poor survival in other malignancies. We hypothesized that the L:A ratio is associated with survival in women with EOC. METHODS: We queried the institutional tumor registry for patients with advanced stage EOC and identified a cohort of 161 women with banked fasting prediagnostic serum samples. Patients underwent cytoredutive surgery followed by platinum-based chemotherapy. Sera were assayed for leptin and adiponectin, and clinico-pathologic data were abstracted. Standard statistical tests were performed. RESULTS: 161 patients met inclusion criteria. We identified a significant correlation between BMI and leptin and the L:A ratio, but not adiponectin, in this cohort (r=0.46, 0.46, and -0.13, respectively; p=0.001, 0.001, and 0.106). Women with low L:A ratios demonstrated statistically longer disease-specific survival (57 months) compared to those with median or high levels (49 and 37 months, respectively; p=0.02). On multivariate analysis, we determined that BMI and age, but not L:A ratio, retained significance as independent prognostic factors for survival (p=0.04, 0.004, and 0.895, respectively). CONCLUSIONS: In this cohort, the L:A ratio correlated statistically with clinical outcome, but did not independently predict survival. Obesity remains a modifiable risk factor in women with EOC. Further studies are needed to determine if leptin and/or adiponectin may be potential therapeutic targets in obese women with EOC.

Venous thromboembolism during primary treatment of ovarian clear cell carcinoma is associated with decreased survival.

OBJECTIVES: To determine the impact of venous thromboembolism (VTE) during primary treatment of ovarian clear cell carcinoma (OCCC) on survival. METHODS: After Institutional Review Board approval, 74 cases of OCCC were retrieved from our pathology files. Clinical and pathological data were obtained by medical record and pathology review. Standard statistical analyses were performed. RESULTS: Among 74 patients with OCCC, VTE was diagnosed in 11 (15%) during primary treatment and 7 (9%) at time of cancer recurrence. 56 (76%) patients never developed VTE. Patients with VTE during OCCC primary treatment had shorter progression-free survival (PFS) and overall survival (OS) than OCCC patients without VTE (median PFS 11 vs. 76 months, p=0.01, median OS 19 vs. 90 months, p=0.001). Patients with VTE during OCCC primary treatment had a 3.9-fold increase in risk of recurrence (p=0.007) and a 6.3-fold increase in risk of death (p<0.001). After controlling for cancer stage, VTE during OCCC primary treatment remained an independent prognostic factor for death (HR=3.6, p=0.005). No patient died of VTE. CONCLUSIONS: VTE during OCCC primary treatment is associated with a significantly higher risk of cancer recurrence and death. This increased risk is not attributable to VTE-related mortality and raises the possibility that a paracrine circuit involving thrombosis might contribute to a more aggressive tumor biology.

Impact of beta blockers on epithelial ovarian cancer survival.

OBJECTIVE: Stress may promote ovarian cancer progression through mechanisms including autonomic nervous system mediators such as norepinephrine and epinephrine. Beta blockers, used to treat hypertension, block production of these adrenergic hormones, and have been associated with prolonged survival in several malignancies. We sought to determine the association between beta blocker use and epithelial ovarian cancer (EOC) disease progression and survival. METHODS: We performed an institutional retrospective review of patients with EOC treated between 1996 and 2006. Patients underwent cytoreductive surgery followed by platinum-based chemotherapy. Women were considered beta blocker users if these medications were documented on at least two records more than 6 months apart. Statistical tests included Fisher's exact, Kaplan-Meier, and Cox regression analyses. RESULTS: 248 met inclusion criteria. 68 patients used antihypertensives, and 23 used beta blockers. Median progression-free survival for beta blocker users was 27 months, compared with 17 months for non-users (p=0.05). Similarly, overall disease-specific survival was longer for beta blocker users (56 months) compared with non-users (48 months, p=0.02, hazard ratio=0.56). Multivariate analysis identified beta blocker use as an independent positive prognostic factor, after controlling for age, stage, grade, and cytoreduction status (p=0.03). Overall survival remained longer for beta blocker users (56 months) when compared with hypertensive patients on other medications (34 months) and patients without hypertension (51 months) (p=0.007). CONCLUSIONS: In this cohort of patients with EOC, beta blocker use was associated with a 54% reduced chance of death compared with that of non-users.