The use of neoadjuvant chemotherapy in advanced endometrial cancer.

The objective of this retrospective cohort study was to review the use of neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients presenting with advanced, unresectable endometrial cancer at two large cancer centers. Patients with advanced endometrial cancer treated with neoadjuvant chemotherapy between 2008 and 2015 were identified from an institutional database. Clinical and surgical variables were analyzed and time to recurrence and death was calculated and compared between surgical groups. Thirty-three patients were identified (mean age 64.8 (range 42-86 years)). Overall, 28% of patients had endometrioid histology, 48% serous, 4% clear cell, 4% carcinosarcoma, 12% mixed and 4% other. Ineligibility for primary surgery was due to unresectable disease (85%), comorbidities (6%) and unknown reasons (9%). All patients received neoadjuvant chemotherapy with 91% of patients receiving carboplatin and paclitaxel. On reimaging, 12% of patients had progressed, 76% had a partial response and 3% had a complete response to chemotherapy. 76% of patients underwent interval surgery, with cytoreduction to no visible residual disease achieved in 52%. Overall, 91% of patients recurred and 85% died during follow-up. Patients undergoing surgery after chemotherapy had significantly longer progression-free survival (11.53 vs. 4.99 months, p = 0.0096) and overall survival (24.13 vs. 7.04 months, p = 0.0042) when compared to patients who did not have surgery. Neoadjuvant chemotherapy is a feasible treatment option to allow for interval cytoreductive surgery in patients with advanced endometrial cancer not amenable to primary debulking. Patients who undergo surgery after chemotherapy have significantly improved progression free and overall survival.

Effect of surgical approach on risk of recurrence after vaginal brachytherapy in early-stage high-intermediate risk endometrial cancer.

OBJECTIVE: The objective was to determine if surgical approach affects time to recurrence in early-stage high-intermediate risk endometrial cancer (HIR-EC) treated with adjuvant vaginal brachytherapy (VBT). METHODS: In this retrospective cohort study, HIR-EC patients treated with VBT between 2005 and 2017 were identified and those who received open or minimally invasive hysterectomies (MIS) were included. Clinical and surgical variables were analyzed and time to recurrence was compared between surgical groups. RESULTS: We identified 494 patients, of which 363 had MIS hysterectomies, 92.5% had endometrioid histology, 45.7% were stage IA and 48.0% stage IB. Open hysterectomy patients had higher BMIs (p = 0.007), lower rates of lymph node sampling (p < 0.001) and lymphovascular space invasion (LVSI) (p = 0.036), however in patients who recurred, no differences were noted between groups. Overall, 65 patients (13.2%) recurred, 14 in the open group (10.7%) and 51 in the MIS group (14.0%) (p = 0.58), while vaginal recurrences were noted in 4.6% and 6.1% respectively. When compared to the open group, the MIS group had a significantly shorter time to any recurrence (p = 0.022), to pelvic (p = 0.05) and locoregional recurrence (p = 0.021) and to death from any cause (p = 0.039). After adjusting for age, BMI, grade, LVSI and surgery date, the MIS group had a higher risk of any recurrence (HR 2.29 (1.07-4.92), p = 0.034) and locoregional recurrence (HR 4.18 (1.44-12.1), p = 0.008). CONCLUSIONS: Patients with HIR-EC treated with VBT after MIS hysterectomy have a shorter time to recurrence and higher risk of recurrence when compared to open hysterectomy patients. Further studies into the safety of MIS in high-intermediate risk patients are required.

Comparison of robot-assisted total laparoscopic hysterectomy and total abdominal hysterectomy for treatment of endometrial cancer in obese and morbidly obese patients.

The objective of our study was to compare clinical and pathologic outcomes of robot-assisted and open abdominal techniques for treatment of uterine cancer in obese patients. Institutional review board approval was obtained. Patient demographic data, pathological data, and surgical data were collected by retrospective chart review. Data were analyzed using SAS statistical software. One-hundred and eighty-nine consecutive cases of suspected uterine cancer were identified from October 2003 until January 2009. Of these, 116 patients (61%) had a body mass index (BMI) over 30. There were 66 completed robot-assisted hysterectomies (RAHs), 43 total abdominal hysterectomies (TAHs), and seven patients that were converted from RAH to open abdominal hysterectomy. There were no significant differences in preoperative patient demographics, including body mass index (BMI), medical co-morbidities, or preoperative cytology, except for parity. There were no differences in postoperative grade, stage, lymph vascular space invasion, positive pelvic washings, mean number of pelvic lymph nodes, or proportion of patients undergoing pelvic lymphadenectomy. Length of stay and estimated blood loss were lower for the robotic technique; RAHs had a significantly longer operative time, however. Postoperative blood transfusions and wound infections were more frequent in the TAH group. Of the RAH group there were seven conversions to TAH (10%). Differences in surgical times with and without lymphadenectomy were least in patients in the largest BMI category of >50. Length of time required for RAH was significantly longer then TAH in obese and morbidly obese patients, however benefits to patients of a minimally invasive approach included reduced incidence of wound infections, reduced transfusion rates, reduced blood loss, and shortened length of stay. These data also suggest the greatest advantage of robotic technology over laparotomy in patients with BMI over 50.

The epidemiology of ovarian granulosa cell tumors: a case-control study.

OBJECTIVE: This study identified risk factors for ovarian granulosa cell tumors (GCT) through a case-control study comparing women with GCT to women with epithelial ovarian cancers (OC) and general population (GP) controls. METHODS: Women with GCT and OC were identified from our hospital tumor board and the Massachusetts and New Hampshire Statewide Cancer Registries between January, 1988 and November, 2008. Age, gender and county matched GP controls were identified through town books in Massachusetts and drivers' license lists in New Hampshire. Epidemiologic factors including age, race, obesity, pregnancy history, smoking, and family history were evaluated. Odds ratio (OR) was calculated and adjusted for race and age. RESULTS: Seventy-two women with GCT, 1578 GP controls, and 1511 OC controls were identified. Patients with GCT were significantly more likely to be non-white (OR 8.49; 4.07, 17.7), obese with a BMI >30 (OR 5.80; 3.01, 11.2), and have a family history of breast (OR 2.13; 1.19, 3.80) or ovarian cancer (OR 2.89; 1.08, 7.72) than GP controls. The risk of developing GCT was significantly decreased in women who smoked (OR 0.46; 0.27, 0.78), used oral contraceptive pills (OR 0.32; 0.17, 0.63) or were parous with 1-2 (OR 0.30; 0.16-0.56) or greater than 2 births (OR 0.50; 0.27, 0.94) when compared to GP controls. CONCLUSION: These findings suggest an independent association between non-white race and obesity as a hyperestrogenic state in the development of GCT while parity and OCP use may be protective. An unknown familial predisposition for GCT may exist.

Placental site trophoblastic tumor: a 17-year experience at the New England Trophoblastic Disease Center.

OBJECTIVE: We reviewed cases of placental site trophoblastic tumors from the New England Trophoblastic Disease Center (NETDC) database from 1982-1999 in an effort to identify prognostic factors for recurrent disease. METHODS: A chart review was performed utilizing patients identified from the NETDC database. Data obtained included patient age at diagnosis, antecedent pregnancy, duration and extent of disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and therapeutic procedures, treatment and outcome of patients. Statistical analysis was performed using Student's t test and chi(2) test when appropriate. RESULTS: Thirteen patients were identified. All ultimately underwent hysterectomy although initial treatment of 1 patient was uterine resection. There were 5 recurrences (43%)--3 among the 9 patients who had no metastases on presentation (33%) and 2 of 3 patients who presented with metastases (66%). The 5 patients who recurred were among 8 who had received peri- or postoperative chemotherapy (62.5%). Treatment of recurrences included continued or alternate chemotherapy, radiotherapy, and/or excision of locally recurrent disease. Follow up time averaged 56.2 months (range 12-182 months). One of the 4 patients receiving chemotherapy < or =1 week after hysterectomy recurred, whereas all 4 patients who received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine tumor volume was significantly greater, 154.1 cm(3), in patients with initial metastases versus 42.3 cm(3) in patients without initial metastases (P = 0.04). Mitotic index (P = 0.04) was significantly increased in patients who developed recurrent disease. CONCLUSION: High mitotic index appears to be an adverse prognostic indicator for recurrence. Hysterectomy remains the mainstay of treatment. Chemotherapy is indicated for patients with metastases and may be indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may play a role in recurrent disease but must be evaluated on a case-by-case basis.

Predictors of recurrence in surgical stage II endometrial adenocarcinoma.

OBJECTIVE: A retrospective review of surgical stage II endometrial carcinoma was performed to evaluate clinical course, treatment, recurrence rate, and survival. METHODS: A list of patients with clinical and surgical stage II endometrial carcinoma was obtained through the tumor registry and from the pathology department from 1988 to 1996. Data were collected on all cases of patients with endometrial carcinoma meeting stage II criteria by FIGO surgical staging. Variables including stage, histology, grade, lymph vascular space invasion (LVI), type and extent of surgery, radiation type and amount, smoking, menstrual status, parity, and age were evaluated for their predictive ability of disease recurrence. Cox proportional hazard regression models were used to examine the potential predictors of time to relapse univariately and multivariately. RESULTS: Of patients identified, 65 underwent primary surgical staging. Only adenocarcinomas were included. Mean follow-up time was 4.7 years (range 0.2-9.6 years). Postoperative radiation was given to 85.7% of patients. There were 10 patients (15.4%) with recurrence of disease with a mean time to recurrence of 25 months. Five-year disease-specific survival was 93%. The only significant predictor of time to relapse was LVI (P = 0.002) in the multivariate analysis. CONCLUSION: This retrospective review suggests that primary surgery followed by postoperative radiation therapy gives excellent results in surgical stage II disease. LVI appears to be a strong predictor of disease recurrence regardless of postoperative radiation therapy. It is difficult to draw conclusions about the type and amount of radiation given because recurrence rate is so low; however, it is reasonable to continue adjuvant radiation especially in cases where LVI is identified.

Helical computed tomography in differentiating appendicitis and acute gynecologic conditions.

OBJECTIVE: To determine the accuracy and effect of helical computed tomography (CT) in women clinically suspected of having either appendicitis or an acute gynecologic condition. METHODS: One hundred consecutive nonpregnant women suspected of having appendicitis or an acute gynecologic condition prospectively had helical CT. Interpretations were correlated with surgical and pathologic findings (41 cases) and clinical follow-up for at least 2 months (59 cases). The accuracy for confirming or excluding both appendicitis and acute gynecologic conditions was determined. The effect on patient care was determined by comparing pre-CT plans with actual treatment. RESULTS: Thirty-two women had appendicitis, 15 had acute gynecologic conditions, 27 had other specific diagnoses, and 26 had nonspecific abdominal pain. For diagnosing appendicitis or acute gynecologic conditions, CT had 100% and 87% sensitivity, 97% and 100% specificity, 94% and 100% positive predictive value, 100% and 98% negative predictive value, and 98% and 98% accuracy, respectively. After CT was done, 36 planned hospital admissions, 25 planned hospital observations, and six planned appendectomies were deferred; six women had alternative surgical procedures on the basis of CT results. One patient had an unnecessary appendectomy on the basis of CT findings. CONCLUSION: Helical CT is an excellent imaging option for differentiating appendicitis from most acute gynecologic conditions.

Effect of acute ethanol ingestion on prolactin in menopausal women using estradiol replacement.

Epidemiologic studies suggest that women who consume ethanol are at an increased risk for developing breast cancer. Two randomized, crossover studies were performed to examine the effects of ethanol on prolactin in menopausal women using transdermal estradiol. In study 1, transdermal estradiol patches (0.15 mg) were administered to menopausal women (n = 7) the day before ethanol administration. At 8.00 h, the women ingested ethanol (1 ml/kg, 95% ethanol) or an isocaloric carbohydrate drink. Prolactin levels were measured frequently for 6.3 h. Serum ethanol levels reached a broad peak from 40 to 100 min after initiation of ethanol ingestion. Serum prolactin levels were significantly higher after ethanol ingestion than after the isocaloric carbohydrate drink ingestion (p < 0.03). Study 2 was identical to study 1 except that the transdermal estradiol patches were removed after completion of ethanol or carbohydrate ingestion. In study 2, serum prolactin was greater after ethanol ingestion than after carbohydrate ingestion (p < 0.001). In menopausal women using transdermal estradiol, acute ethanol ingestion is associated with an increase in serum prolactin.

The effect of acute ethanol ingestion on estrogen levels in postmenopausal women using transdermal estradiol.

OBJECTIVE: To determine whether acute alcohol ingestion raises estradiol (E2) and estrone (E1) levels in a randomized, controlled, crossover study on postmenopausal women using transdermal E2. METHODS: Healthy, non-smoking postmenopausal women (n = 7) using no medications were enrolled. Transdermal E2, 0.15 mg, was applied 13 hours before the subjects ingested alcohol (1 mL/kg 95% ethanol) or isocaloric carbohydrate punch. Serum samples were obtained for 40 minutes before drink ingestion and 6 hours after drink ingestion and were assayed for E2 and E1. RESULTS: Ethanol levels peaked 60 minutes after the start of ethanol-drink ingestion, at 25.4 mmol/L (117 mg/dL). Estradiol levels rose significantly above the mean baseline of 657 pmol/L (179 pg/mL) after ethanol-drink ingestion (P < or = .01), with a mean peak of 804 pmol/L (219 pg/mL) 35 minutes after the start of drink ingestion, and were significantly greater than the E2 levels that followed the carbohydrate drink (P < or = .0001). There were no significant changes in E2 or E1 levels after carbohydrate-drink ingestion. CONCLUSIONS: We conclude that ethanol ingestion may acutely raise circulating E2 concentrations in women using transdermal E2.