Risk factors for lymph node metastasis in apparent early-stage epithelial ovarian cancer: implications for surgical staging.

OBJECTIVES: The extent of lymphadenectomy to be performed in apparent early-stage epithelial ovarian cancer (EOC) is not well defined. We evaluated the patterns of lymphatic spread in apparent early-stage EOC and risk factors for lymph node metastasis, as these have potential implications for clinical decision making. METHODS: All cases of apparent early-stage EOC diagnosed at our institution between January 1994 and December 2003 were retrospectively identified. Apparent early-stage EOC was defined as gross disease that appeared confined to the pelvis without abdominal spread at the time of initial exploration. Demographics, pathologic findings, staging procedures performed, and clinical impression at surgery were analyzed. Patterns of lymph node positivity and risk factors associated with upstaging were assessed. RESULTS: One hundred and ninety patients with apparent early-stage EOC undergoing primary surgical staging met criteria for inclusion. All patients had at least some pathologic assessment of lymph nodes, with 115 having both bilateral pelvic and paraaortic lymphadenectomy performed. After review of pathology and operative reports, the final FIGO staging within the cohort was 54 IA (28.4%), 10 IB (5.3%), 51 IC (26.8%), 1 IIA (0.5%), 4 IIB (2.1%), 37 IIC (19.5%), 8 IIIA (4.2%), 25 IIIC (13.2%). Overall 25/190 (13%) had lymph nodes metastasis as follows: 8 (32%) had positive pelvic nodes, 12 (48%) had positive paraaortic nodes, and 5 (20%) had both positive pelvic and paraaortic lymph nodes. Significant risk factors for lymph node metastasis included bilateral vs. unilateral primary lesion (26.8% vs. 7.5%, p<0.001), positive cytologic washings vs. negative (22.4% vs. 9.1%, p=0.012), ascites vs. no ascites (28.2% vs. 9.3%, p=0.002), serous vs. other histology (28% vs. 9%, p=0.001), grade 1 vs. grade 2 vs. grade 3 disease (2.7% vs. 1.9% vs. 23.2%, p<0.001), and preoperative CA 125 levels of >35 vs. ≤ 35 U/ml (22.4% vs.0% p=0.006). No patients with mucinous cancers (n=29) had lymph node metastases. Patterns of LN metastases were largely independent of laterality of primary lesions: among those with unilateral lesions and positive nodes (n=10), 5 (50%) had ipsilateral lymph node involvement, 4 (40%) had bilateral involvement, and 1 (10%) had isolated contralateral lymph nodes positive. CONCLUSIONS: Complete surgical staging in EOC patients with gross disease confined to the ovaries and pelvis should include bilateral pelvic and paraaortic lymphadenectomy. Even in patients with unilateral lesions, lymph node metastases are commonly bilateral. Bilateral ovarian lesions, positive cytology, presence of ascites, high grade histology, and serous histology are risk factors for lymph node involvement. This information may be helpful in counseling patients presenting for consideration of re-staging after unexpected findings of malignancy.

Postural tachycardia syndrome complicating pregnancy.

OBJECTIVE: To review clinical experience at our institution on postural tachycardia syndrome (POTS) complicating pregnancy. METHODS: In a retrospective review, we identified nine pregnancies in seven patients with POTS syndrome at our institution. RESULTS: Patients who did not require treatment for POTS before conception were less likely to have an exacerbation of symptoms or need reintroduction of treatment. Exacerbations of POTS during pregnancy are variable. Of our patients with exacerbations of symptoms, increases in the existing pharmacologic treatments, such as increasing beta-blocker dosage, was effective in palliation of symptoms. There were seven vaginal deliveries. Two patients delivered without neuraxial anesthesia; the other five deliveries were done using epidural anesthesia without associated complications. POTS does not seem to contribute to pregnancy-related complications. Importantly, there were no adverse intrapartum events attributable to POTS. CONCLUSIONS: Pregnant women with POTS may undergo safe regional anesthesia and vaginal delivery. This contradicts earlier reports in the literature recommending cesarean delivery.

Is there a high-risk subgroup of stage I epithelial ovarian cancer that is most likely to benefit from 6 versus 3 cycles of adjuvant chemotherapy?

OBJECTIVE: Despite results from Gynecologic Oncology Group (GOG) 157 showing no statistically significant survival differences in patients treated with 3 versus 6 cycles of carboplatin and paclitaxel, further analysis of GOG 157 data suggested that certain early-stage epithelial ovarian cancers (EOCs) might benefit from extended chemotherapy. We sought to determine those stage I EOC cases at highest risk of failing 3 cycles of therapy. METHODS: All patients with surgical International Federation of Gynecology and Obstetrics stage I EOC operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified through retrospective chart review. A cohort of patients who received 6 cycles of adjuvant carboplatin and paclitaxel chemotherapy was compared with a cohort of patients who received 3 cycles. Disease-free survival and disease-specific survival were primary outcomes analyzed. RESULTS: There were 107 patients who received either 3 or 6 cycles of adjuvant carboplatin and paclitaxel. Among all stage I EOCs, the number of cycles did not influence disease-free survival or disease-specific survival. The highest recurrence rate (7 [46.7%] of 15 cases) was among stage IC cases with fixed tumors and positive cytology and/or surface involvement. Among this cohort, 6 (66.7%) of the 9 patients who received 3 cycles recurred, whereas only 1 (16.7%) of the 6 patients who received 6 cycles recurred (hazard ratio, 5.97; 95% confidence interval [CI], 0.98-114.46; P = 0.05, Cox proportional hazards regression model) for an odds ratio of 3.94. The absolute risk reduction for 6 cycles in this highest risk cohort was 50%. CONCLUSIONS: Patients with stage IC cancer and with fixed tumors and positive cytology and/or tumor surface involvement appear to have a higher risk of recurrence after 3 cycles (compared with 6) of platinum-based chemotherapy. The clinical behavior of this highest risk cohort implies a more aggressive tumor biology, and further understanding of such stage I EOCs is warranted.

Random peritoneal biopsies have limited value in staging of apparent early stage epithelial ovarian cancer after thorough exploration.

OBJECTIVE: The relative value of abdominal exploration, lymphadenectomy, omentectomy and random peritoneal biopsies in the staging of apparent early stage epithelial ovarian cancer (EOC) has not been rigorously evaluated. We sought to define the clinical significance of random peritoneal biopsies of otherwise benign appearing tissues in staging of grossly early EOC. METHODS: All patients with apparent early stage EOC undergoing staging from 1/1994 to 12/2003 were evaluated to identify surgical-pathologic findings responsible for upstaging at time of exploratory surgery. Demographics, surgical findings and operative outcomes were abstracted. RESULTS: A total of 211 patients with apparent early EOC were included. Only 9 patients were upstaged based on pathology indicating a high negative predictive value of thorough exploration and lymphadenectomy. One patient (1/118; 0.8%) was upstaged from stage I disease to stage II disease based on random biopsy of pelvic peritoneum: all other stage II patients had visible disease. No patients were upstaged from stage I disease to stage III disease due to random biopsies or microscopic omental disease. Eight patients (3.8%) were upstaged from stage II to stage III disease based on random biopsies of upper abdominal peritoneum or the omentum. CONCLUSIONS: In our study of apparent early stage EOC, random peritoneal biopsies and omentectomy added little diagnostic value beyond careful inspection of all peritoneal surfaces when EOC is grossly limited to the ovaries. Within our study, less than 4% of patients with pelvic metastasis were upstaged due to these particular staging procedures. No patients in our cohort had a change in treatment recommendations based on these biopsies.

Influence of intraoperative capsule rupture on outcomes in stage I epithelial ovarian cancer.

OBJECTIVE: To evaluate the effect of tumor capsule rupture on disease prognosis in stage I epithelial ovarian cancer. METHODS: All patients with International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified. Relevant tumor characteristics, procedures performed, adjuvant therapies, and follow-up were recorded and analyzed. Inclusion criteria included comprehensive staging. Cox proportional hazards, Kaplan-Meier estimation, log rank test, and chi test were used for statistical analyses. RESULTS: There were 161 cases that met inclusion criteria. Seventy-four (46%) patients had intact capsules without positive cytology or surface involvement; 61 (38%) had capsule rupture; 33 (20%) had positive cytology; and 22 (14%) had surface involvement. Overall, 22 of 161 (14%) patients recurred and 12 of 161 (7%) patients died of their disease. In univariable analysis, both intraoperative capsule rupture and positive cytologic washings portended worse disease-free survival (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-8.9; P=.004 and HR 5.2, 95% CI 2.1-12.3; P<.001, respectively) and disease-specific survival (HR 4.1, 95% CI 1.3-15.4; P=.018 and HR 5.9, 95% CI 1.8-19.3; P=.005, respectively). In multivariable analysis, capsule rupture (HR 4.2, 95% CI 1.8-10.9; P=.001) and positive cytologic washings (HR 6.4, 95% CI 2.5-16.0; P<.001) remained independent predictors of worse disease-free survival. Disease-free survival and disease-specific survival were shortest for stage IC cases with positive cytology, surface involvement, or both, that also had intraoperative rupture. CONCLUSION: In stage I epithelial ovarian cancer, intraoperative capsule rupture portends a higher risk of disease recurrence and death from disease. Careful intraoperative removal of ovarian masses is important, and recognizing the higher-risk nature of such cases is imperative. LEVEL OF EVIDENCE: III.