Current recommendations and recent progress in endometrial cancer.

Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite-instable, metastatic disease, anti- programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.

Targeting RAS-ERK pathway alterations with MEK inhibitors to improve chemosensitivity in high grade serous ovarian cancers.

OBJECTIVE: Assess if MEK inhibitor blockade of RAS-ERK pathway adaptive response in high grade serous ovarian cancers (HGSOC) improves platinum sensitivity. METHODS: Three HGSOC cell lines and three patient derived organoid (PDOs) samples from ascites of platinum resistant HGSOC patients were collected. Cell lines and PDOs were exposed to carboplatin and MEK inhibitors cobimetinib or trametinib. Cytotoxic effects of MEK inhibitors alone or combined with carboplatin were established. Western blots demonstrated RAS-ERK pathway blockage after MEK inhibitor treatment. RNA sequencing assessed gene expression after MEK inhibitor treatment. Cell line NF1 gene knockdown was performed with corresponding chemosensitivity levels. RESULTS: High carboplatin IC50 levels indicated platinum resistance in cell lines and PDOs. Cobimetinib induced cytotoxicity in cell lines and PDOs, while trametinib was less effective. Western blot confirmed MEK-ERK pathway blockage at minimal concentrations of MEK inhibitors in cell lines and PDOs. Phosphorylated-ERK levels of untreated cells indicated higher levels of RAS-ERK pathway activation in OVSAHO and OVCAR7 compared to OVCAR3. OVSAHO harbors a NF1 mutation and had highest levels of RAS-ERK activation. Cotreatment with carboplatin and MEK inhibitors showed varying synergistic cytotoxic effects at different combinations. Synergistic effect was most prominent in the OVSAHO carboplatin and cobimetinib combination. RNA sequencing identified downregulation of c-MYC and FOXM1 gene expression after MEK inhibitor treatment. NF1 gene knockdown showed an acquired increased IC50 compared to parental cells. CONCLUSION: MEK inhibitors block RAS-ERK pathways in platinum resistant HGSOC cells and PDOs. MEK inhibitors with carboplatin have select synergistic effects which may indicate a strategy to improve platinum sensitivity.

Gestational choriocarcinoma.

Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.

Time to completion of radiation treatment in locally advanced squamous cell carcinoma of the vulva and the impact on survival.

OBJECTIVE: To assess whether radiation completion within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS). METHODS: The National Cancer Database from 2004 to 2017 was used to identify women ≥18 years old with stage II-IVA squamous cell vulvar cancer. We included women who received radiation alone (RT) or concurrent chemoradiation (CRT) for initial vulvar cancer treatment. Primary outcome was overall survival associated with time of delay in radiation completion. RESULTS: There were 2378 women identified (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78), majority (88.35%) were white with advanced stage III or IVA (72.29%) disease. Median radiation dose was 5720 c-Gray (IQR 5040-6300). Radiation completion with delay ≥7 days resulted in reduction in survival compared to delay of <7 days (unadjusted HR 1.183 [95%CI: 1.066-1.313], p = 0.0016). When delays extended to ≥14 days compared to <14 days there was increased hazard of death (unadjusted HR: 1.263 [95%CI:1.126-1.416], p < 0.0001). Survival improved for patients with <7 versus ≥7 days delay whether treatment was with RT (median OS: 34.9 months versus 21.6 months, p < 0.01) or CRT (Median OS:58 months versus 41.3 months, p < 0.01). Stage IVA disease was associated with the greatest increase in hazard of death (HR 1.759 [95%CI 1.517-2.039], p < 0.0001) compared to stage II. CONCLUSION: Radiation completion with <7 days delay is associated with improved overall survival, independent of concurrent chemotherapy. This suggest that strategies to minimize delays in radiation are crucial in locally advanced vulvar cancer.

GOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study.

OBJECTIVES: The ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients. METHODS: Surgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated. RESULTS: 361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables. CONCLUSION: SNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.

Clinical outcomes in ovarian cancer patients receiving three versus more cycles of chemotherapy after neoadjuvant treatment and interval cytoreductive surgery.

OBJECTIVES: To compare clinical outcomes for stage IIIC and IV ovarian cancer patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery followed by up to three versus more cycles of post-operative chemotherapy. METHODS: We conducted a multi-institution retrospective cohort study of patients treated from January 2005 to February 2016 with neoadjuvant platinum-based therapy followed by interval surgery and post-operative chemotherapy. The following were exclusion criteria: more than four cycles of neoadjuvant chemotherapy, bevacizumab with neoadjuvant chemotherapy, non-platinum therapy, prior chemotherapy, and elevated CA125 values after three post-operative chemotherapy cycles. Progression-free and overall survival and toxicity profiles were compared between groups receiving up to three cycles versus more that three cycles post-operatively. RESULTS: A total of 100 patients met inclusion criteria: 41 received up to three cycles and 59 received more than three cycles. The groups were similar in terms of age, body mass index, performance status, tumor histology, optimal cytoreduction rates, and median number of neoadjuvant chemotherapy cycles. Median progression-free survival was 14 vs 16.6 months in those receiving up to three cycles versus more than three cycles, respectively (HR 0.99, 95% CI 0.58 to 1.68, p=0.97). Similarly, median overall survival was not different at 47.1 vs 69.4 months, respectively (HR 1.96, 95% CI 0.87 to 4.42, p=0.10). There were no differences in grade 2 or higher chemotherapy-related toxicities. CONCLUSIONS: Extending post-operative chemotherapy beyond three cycles in patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery with normalization of CA125 levels was not associated with improved survival or greater toxicity. Future study in a larger cohort is warranted to define optimal length of cytotoxic treatment.

Adult Comorbidity Evaluation 27 score as a predictor of survival in endometrial cancer patients.

BACKGROUND: The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. Although a few cohort studies of <500 patients showed an association between comorbidity and survival in patients with endometrial cancer, the degree of association must be better described. The Adult Comorbidity Evaluation 27 is a validated comorbidity instrument that provides a score of 0-3 based on the number of and severity of medical comorbidities. OBJECTIVE: This study was performed to explore the association between medical comorbidities and survival of patients with endometrial cancer. STUDY DESIGN: Patients who were diagnosed with endometrial cancer from 2000-2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients who underwent primary surgical treatment for endometrioid, serous, and clear cell endometrial carcinoma were included. Patients who primarily were treated with radiation, chemotherapy, or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing Adult Comorbidity Evaluation 27 scores were also excluded from analysis. Information that included patient demographics, Adult Comorbidity Evaluation 27 score, tumor characteristics, adjuvant treatment, and survival data were extracted from the database. The association of Adult Comorbidity Evaluation 27 and overall and recurrence-free survival was explored in a multivariable Cox regression analysis after being controlled for variables that have been found to be associated significantly with survival in univariable analysis. RESULTS: A total of 2073 patients with a median age of 61 years (range, 20-94 years) at diagnosis were identified. The Adult Comorbidity Evaluation 27 score was 0, 1, 2, and 3 in 22%, 38%, 28%, and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%), and IV (7%), and grade distribution was 1 (52%), 2 (23%), and 3 (25%). Most patients had endometrioid histologic condition (87%) followed by serous (11%) and clear cell (3%) endometrial carcinoma. The median overall survival time for the entire cohort was 54 months (95% confidence interval, 3-154 months), and the median recurrence-free survival was 50 months (95% confidence interval, 2-154 months). On univariable analysis, age, race, marital status, stage, grade, histologic condition, and treatment type were associated significantly with overall survival and recurrence-free survival. After adjustment for these covariates, patients with an Adult Comorbidity Evaluation 27 score of 2 had a 52% higher risk of death (95% confidence interval, 1.16-2.00); patients with an Adult Comorbidity Evaluation 27 score of 3 had a 2.35-fold increased risk of death (95% confidence interval, 1.73-3.21) compared with patients with an Adult Comorbidity Evaluation 27 score of 0. Similarly, patients with an Adult Comorbidity Evaluation 27 score of 2 had a 38% higher risk of recurrence (95% confidence interval, 1.07-1.78); patients with Adult Comorbidity Evaluation 27 score of 3 had a 2.05-fold increased risk of recurrence (95% confidence interval, 1.53-2.75) compared with patients with an Adult Comorbidity Evaluation 27 score of 0. We found no interaction between Adult Comorbidity Evaluation 27 score and age, stage, or treatment type. CONCLUSION: Our findings demonstrate the importance of comorbidities in the estimation of the prognosis of patients with endometrial cancer, even after adjustment for age and known tumor-specific prognostic factors such as stage, grade, histologic condition, and adjuvant treatment.

The economic impact of surgical care for morbidly obese endometrial cancer patients: a nationwide study.

BACKGROUND: Obesity significantly impacts the cost of cancer treatment, yet the impact of morbid obesity on inpatient hospital charges related to endometrial cancer treatment is not well-defined. OBJECTIVES: The purpose of this study was to determine the charges that are associated with inpatient surgery, hospitalization, and postoperative care of morbidly obese patients with endometrial cancer. STUDY DESIGN: Data were obtained from the National Inpatient Sample from 2010. Chi-square test, t-test, and linear regression were used for statistical analyses. RESULTS: Six thousand five hundred sixty patients who underwent hysterectomy for endometrial cancer were identified. Mean age was 62 years (range, 22-99 years). The majority were white (78%), and the remainder were black (10%), Hispanic, (8%), Asian (3%), and Native American (1%). Insurance types were private (45%), Medicare (45%), Medicaid (5%), and uninsured (7%). One thousand eighty-eight of these patients (17%) were coded as morbidly obese. The mean postoperative stay for the morbidly obese was 4.0 days (range, 0-46 days) compared with 3.5 days (range, 0-81 days) for the non-morbidly obese patients (P < .01). Morbidly obese patients required more intensive care with mechanical ventilation (5.5% vs 1.6%; P < .01). The median hospital charges were higher for morbidly obese patients compared with their counterparts ($46,654 vs $41,164; P < .01). After adjustment for charges that were associated with insurance type, hospital type, and the surgery that was performed, the incremental increase in hospital charges that were associated with treating the morbidly obese patient was $5096 per patient (95% confidence interval, $2593-$7598; P < .01). CONCLUSION: In this economic analysis, the health care charges that were associated with inpatient endometrial cancer treatment in the morbidly obese patient was significantly higher compared the non-morbidly obese patient. Resources are needed to support the needs of this population, and programs to encourage weight loss and optimize general health should be encouraged.

Transvaginal Ultrasound-Guided Biopsy of Deep Pelvic Masses: How We Do It.

The purpose of this review is to discuss the rationale and indications for transvaginal ultrasound-guided biopsy. Transvaginal ultrasound-guided biopsy can be a helpful tool for diagnosis and treatment planning in the evaluation of pelvic masses, particularly when the anatomy precludes a transabdominal or posterior transgluteal percutaneous biopsy approach. A step-by-step summary of the technique with preprocedure and postprocedure considerations is included.

Survival differences of Asian and Caucasian epithelial ovarian cancer patients in the United States.

OBJECTIVE: To compare the racial differences in treatment and survival of Asian-Americans and White patients with epithelial ovarian cancer. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results Program between 1988 and 2009 and analyzed using Chi-squared tests, Kaplan-Meier methods, and Cox regression analysis. RESULTS: Of the 52,260 women, 3932 (7.5%) were coded as Asian, and 48,328 (92.5%) were White. The median age of Asians at diagnosis was 56 vs. 64 years for the Whites (p<0.001). Asians were more likely to undergo primary surgery, have an earlier stage of disease, have a diagnosis of a non-serous histology, and have lower grade tumors. The 5-year disease-specific survival (DSS) of Asians was higher compared to Whites (59.1% vs. 47.3%, p<0.001). On a subset analysis, Vietnamese, Filipino, Chinese, Korean, Japanese, and Asian Indian/Pakistani ethnicities had 5-year DSS of 62.1%, 61.5%, 61.0%, 59.0%, 54.6%, and 48.2%, respectively (p=0.015). On multivariate analysis, age at diagnosis, year of diagnosis, race, surgery, stage, and tumor grade were all independent prognostic factors for survival. Asians were further stratified to U.S. born versus those who were born in Asia and immigrated. Asian immigrants presented at a younger age compared to U.S. born Asians. Immigrants were found to have an improved 5-year DSS when compared to U.S. born Asians and Whites of 55%, 52%, and 48%, respectively (p<0.001). CONCLUSION: Asians were more likely to be younger, undergo primary surgery, have an earlier stage of disease, non-serous histology, lower grade tumors, and higher survival.

Perspectives of gynecologic oncology fellowship training and preparedness for practice.

We aimed to examine the preparedness of recent gynecologic oncology fellowship graduates for independent practice.We conducted a web-based survey study using REDCap targeting Society of Gynecologic Oncology (SGO) members who graduated gynecologic oncology fellowship within the last six years. The survey included 52 items assessing fellowship training experiences, level of comfort in performing core gynecologic oncology surgical procedures and administering cancer-directed therapies. Questions also addressed factors driving participants' selection of fellowship programs, educational experience, research and preparedness for independent practice. A total of 296 participants were invited to complete the survey. Response rate was 42% with n = 124 completed surveys included for analysis. The highest ranked factor for fellowship selection was fit with program 36% (n = 45). Upon completing fellowship, most were uncomfortable performing ureteral conduit formation 84% (n = 103), ureteroneocystostomy 77% (n = 94), exenteration 68% (n = 83), splenectomy 67% (n = 83) and lower anterior resection 41% (n = 51). Most were comfortable managing intraoperative complications 85% (n = 104) and standard cancer staging procedures (range: 61%-99%). Majority were comfortable providing cancer directed therapies with chemotherapy 99% (n = 123), immunotherapy 84% (n = 104), and poly ADP-ribose polymerase (PARP) inhibitors 97% (n = 120). Upon completing fellowship, 77% (n = 95) report having mentorship that met their expectations during fellowship and 94% (n = 116) felt they were ready for independent practice. Majority of fellowship graduates were prepared for independent practice and felt comfortable performing routine surgical procedures and cancer directed treatment. However, most are not comfortable with ultra-radical gynecologic oncology procedures. Maximizing surgical opportunities during fellowship training and acquiring early career mentorship may help.

Factors associated with publication of plenary presentations at the Society of Gynecologic Oncologists annual meeting.

OBJECTIVE: To determine the rate and factors associated with publication of plenary abstract presentations from the Society of Gynecologic Oncologists annual meeting. METHODS: Plenary presentations were reviewed from 2000 to 2005. A PubMed search was performed to identify subsequent peer-reviewed publication of these presentations. Chi-squared test and logistic regression were used for statistical analyses. RESULTS: Of 378 main, focused or express plenary presentations, 173 (45.8%) involved multiple and 205 (54.2%) single institutions. The types of study include: chart review (29.4%), cohort study (28.0%), translational (23.5%), and randomized clinical trial (6.9%). 309 (81.7%) of presentations were subsequently published. The median time from presentation to publication was 14months (range: 1-85). Studies from multiple vs. single institutions were more likely to be published (87.9% vs. 76.6%; p=0.005). In addition, randomized controlled trials were more likely to be published compared with chart review, cohort, and translation research (92.3% vs. 83.8%, 77.4%, and 74.2%; p<0.01). On multivariate analysis, multi-institutional studies (OR=2.28, 95% CI=1.28-4.04; p=0.005) and type of study (OR=1.64, 95% CI=1.19-2.26; p=0.002) were independent factors associated with publication. In addition, multi-institutional studies had longer times from presentation to publication compared with their counterparts. CONCLUSIONS: A high percentage of plenary presentations at the Society of Gynecologic Oncologists annual meeting resulted in subsequent publication. Multi-institutional studies and randomized clinical trials were more likely to be published.

Utilization of and charges for robotic versus laparoscopic versus open surgery for endometrial cancer.

BACKGROUND AND OBJECTIVES: To analyze the utilization and hospital charges associated with robotic (RS) versus laparoscopic (LS) versus open surgery (OS) in endometrial cancer patients. METHODS: Hospital discharge data were extracted from Florida Agency for Health Care Administration between October 2008 and December 2009. RESULTS: Of 2,247 patients (median age: 64 years), 29% had RS, 10% had LS, and 61% had OS. The mean length of hospital stay was 1.6, 1.8, and 3.9 days for RS, LS, and OS, respectively (P < 0.001). The median hospital charge was $51,569, $37,202, and $36,492, for RS, LS, and OS (P < 0.001), with operating room charges ($22,600, $13,684, and $11,272) accounting for the major difference. Robotic surgery utilization increased by 11% (23-34%) over time. CONCLUSIONS: In this statewide analysis of endometrial cancer patients, the utilization of robotic surgery increased and is associated with higher hospital charges compared to laparoscopic and open procedures.

The influence of sexual activity on athletic performance: a systematic review and meta-analyses.

Several anecdotal reports suggest that sex before competition can affect performance. Our objective was to perform a systematic review and meta-analysis to determine whether athletic performance or some physical fitness measure is affected by prior sexual activity. Web of Science (all databases) and Google Scholar were used to identify studies from which adult healthy subjects were included. As all studies were crossover trials, an inverse variance statistical method with random effects was used to minimize the uncertainty of the pooled effect estimate. Bias was assessed via the revised Cochrane Risk of Bias tool (RoB 2) with a "per protocol" analysis. Nine crossover studies (133 subjects, 99% male) were used in this meta-analysis. All those studies did not examine athletic performance per se, but all studies assessed one or more physical fitness parameters. The RoB 2 suggested that overall, there were some concerns with bias. As there was moderate heterogeneity amongst the different outcomes (Tau2 = 0.02, Chi-square = 17.2, df = 8, p = 0.03, I2 = 54%), a random-effects model was used. The results neither favored abstinence nor sexual activity before a physical fitness test [standardized mean difference = 0.03 (- 0.10 to 0.16), Z = 0.47, p = 0.64, where a negative standardized mean difference favors abstinence, and a positive standardized mean difference favors sexual activity]. The results demonstrate that sexual activity within 30 min to 24 h before exercise does not appear to affect aerobic fitness, musculoskeletal endurance, or strength/power.

Stability of Whole Blood Electrolyte Specimens at Room Temperature vs. Slushed Ice Conditions.

BACKGROUND: Data on the stability of whole blood electrolytes is limited to small sample sizes. We sought to determine the stability of whole blood electrolytes under room temperature and slushed iced conditions in human patients at a major hospital center. METHODS: Whole blood samples were obtained from 203 patients hospitalized for various pathophysiological conditions. Electrolyte concentrations of sodium, potassium [K+], ionized calcium, and chloride were measured at 5 different timepoints spanning 3 h. Samples were stored at room temperature (22-24 °C) or under slushed ice conditions (0.1-0.2 °C) before analysis. RESULTS: Under both conditions, sodium, ionized calcium, and chloride did not show a measurable change up to 109 min compared to baseline; however, the mean increase in [K+] over 138 min of storage in slushed ice was 0.0032 (0.0021 [5th percentile] to 0.0047 [95th percentile]) mmol/L/min (adjusted R2 = 0.62, P < 0.001). Five percent of the specimens demonstrated a ≥0.3 mmol/L change in [K+] from baseline after 67 min of storage in slushed ice. In contrast, 1% of the specimens stored at room temperature showed the same change at the same timepoint. CONCLUSIONS: Whole blood sodium, [K+], ionized calcium, and chloride concentrations remain stable for at least 109 min at room temperature. However, whole blood specimens stored in slushed ice for not more than 67 min exhibit a 5% probability that the [K+] concentration will increase by at least 0.3 mmol/L compared to baseline. The other analytes do not destabilize for up to 178 min of slushed ice storage.

The utility of peritoneal biopsy and omentectomy in the upstaging of apparent early ovarian cancer.

HYPOTHESIS: The hypothesis of this study is that routine blind peritoneal biopsies performed during the surgical staging of apparent early ovarian cancers rarely influence final cancer stage and thus are of little benefit to staging. Few studies have been done examining this question of whether the biopsies of grossly normal-appearing peritoneal tissue are of benefit to the surgical staging procedure. METHODS: Operative and pathology reports from 122 patients with early-stage epithelial ovarian cancer staged by gynecologic oncologists at Barnes-Jewish Hospital from 1995 to 2009 were reviewed. All had full surgical staging resulting in a final stage of IA to IIIA. The operative findings were assessed to determine how frequently the peritoneal biopsies upstaged the cancer. Other findings including age, grade, histological type, and preoperative CA-125 were assessed. RESULTS: The median age of the patients was 53 years (range, 23-81 years). The distribution of cancer types was endometrioid (42), serous (23), clear cell (19), mucinous (16), and mixed or other (22). The most frequent stage was IC (n = 50; 41%), followed by IA (n = 40; 33%). A total of 19 patients had positive peritoneal biopsies (16%). Of these, only 6 (5%) were microscopically positive, or from normal-appearing tissue. Five (4%) of these 6 subjects were upstaged by the random peritoneal biopsies alone. Five (4%) of the patients had microscopic metastases to the omentum, 4 (3%) of whom were upstaged by this finding alone. One patient had both microscopic peritoneal and omental disease. CONCLUSIONS: Although the rate of microscopic metastases to peritoneal tissue is low, random peritoneal biopsies are still indicated in early-stage disease owing to the low morbidity of the procedure and a small but present possibility of upstaging and altered management. Furthermore, systematic peritoneal biopsies ensure careful palpation and examination of all surfaces.

Clinical and pathologic features of vulvar intraepithelial neoplasia in premenopausal and postmenopausal women.

OBJECTIVE: To explore the clinical and pathologic differences between vulvar intraepithelial neoplasia (VIN) in premenopausal and postmenopausal women cared for in a tertiary referral center. METHODS: Between January 1997 and June 2008, 145 women received care at our institution for VIN and VIN-associated squamous cell carcinoma (SCC). All patients' demographic characteristics and recurrence histories were recorded throughout the study period and were retrieved retrospectively. Menopausal status was self-reported at the time of initial diagnosis. χ, odds ratio, and logistic regression analyses were used. RESULTS: The median age was 50 years (range = 19-91 y) with 77% (111/145) of patients white, 20% (29/145) African American, and 3% (5/145) other ethnicity. Sixty percent of patients diagnosed with VIN were current smokers, 18% (26/145) were immunocompromised (positive for human immunodeficiency virus/transplant/steroids), and 30% (44/145) had concomitant or previous lower genital tract dysplasia. Vulvar intraepithelial neoplasia or VIN-related cancer recurred in 57 (39%) of 145 patients; of these, 40 (71%) had recurrence of VIN and 18 (29%) had recurrence of cancer. Fifty-one percent (74/145) of patients were menopausal at initial VIN diagnosis. Among women with VIN, the odds of initially presenting with a VIN-related SCC was 3.2 times greater in postmenopausal than in premenopausal women (confidence interval = 1.5-7.1, p < .01), and postmenopausal women were more likely to present with stage II to IV SCC (p = .021). Recurrence risk of SCC, but not VIN, was associated with menopause status (p < .05). CONCLUSIONS: Among women with VIN, the risk of SCC is higher in postmenopausal than in premenopausal women both initially and at recurrence. Excisional therapies to identify occult invasion are especially important for postmenopausal women with VIN.

Stability of Whole Blood Lactate Specimens at Room Temperature Versus Slushed Ice Conditions.

BACKGROUND: There are limited data on lactate stability in whole blood. The purpose of this study was to determine whole blood lactate stability at room temperature and in slushed ice conditions. METHODS: An equal number of arterial and venous samples were obtained from 202 subjects hospitalized for various pathophysiological conditions. Whole blood lactate concentration was measured over 5 different times spanning 80-90 min in a blood gas lab at a major hospital center. Samples were stored at room temperature (22-24°C) or in slushed ice conditions (0.1-0.2°C) before analysis. RESULTS: The mean increase in lactate concentration was 0.001 mmol/L/min in samples on slushed ice over 90 min. However, at room temperature conditions, the mean increase in lactate concentration was 0.008 mmol/L/min regardless of whether the sample was arterial or venous. An increase in whole blood lactate concentration of ≥ 0.4 mmol/L occured after 45 min at room temperature, with 5% of all whole blood specimens demonstrating a meaningful change at ≤ 20 min. The ≥ 0.4 mmol/L change in whole blood lactate is considered significant based on the College of American Pathologists instrument peer-group standards. CONCLUSIONS: Considering that a change in whole blood lactate concentration of ≥ 0.4 mmol/L is unacceptable instrument peer-group variation as defined by the College of American Pathologists, ice is no longer needed to stabilize whole blood lactate specimens when the draw time to analyze time is < 45 min. Samples remain stable even at 90 min when left on ice.

The role of neoadjuvant chemotherapy in the management of patients with advanced stage ovarian cancer: survey results from members of the Society of Gynecologic Oncologists.

OBJECTIVE: Recent randomized controlled data suggest that neoadjuvant chemotherapy (NACT) with interval debulking (ID) may produce similar overall survival and progression free survival compared to standard primary cytoreduction followed by chemotherapy. The object of our study was to assess current patterns of care among members of the Society of Gynecologic Oncologists (SGO), specifically collating their opinions on and use of NACT for advanced stage ovarian cancer. METHODS: A 20-item questionnaire was sent to all working e-mail addresses of SGO members (n=1137). The data was collected and analyzed using descriptive statistics with commercially available online survey software. The Chi-square test for independence was used to determine differences in responses between groups. RESULTS: Of 339 (30%) responding members, most rarely employ NACT, with 60% of respondents using NACT in less than 10% of advanced stage ovarian cancer cases. Respondents did not consider available evidence sufficient to justify NACT followed by ID (82%), nor did most think it should be preferred (74%). Sixty-two percent of respondents thought it was impossible to accurately predict preoperatively whether an optimal cytoreduction is possible. Thirty-nine percent believed that women with bulky upper abdominal disease on preoperative imaging would benefit from NACT versus primary debulking. If gross disease were found at ID, 43% would continue to treat with IV chemotherapy, and 42% would place an IP port if optimally cytoreduced. When ID reveals microscopic disease, 51% would continue IV treatment and the remaining IP therapy. Eighty-six percent of the respondents believed that both biological and surgical factors determine patient outcomes. CONCLUSIONS: The majority of responding SGO members do not treat patients with NACT followed by ID. Currently available studies of NACT/ID have been insufficient to convince most gynecologic oncologists to incorporate it into practice. Our results provide a benchmark against which further research can assess the penetration of NACT/ID into clinical practice.