Role of sentinel lymph node evaluation during hysterectomy for preoperative pathology diagnosis of endometrial intraepithelial neoplasia in a community hospital setting.

OBJECTIVE: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC). METHODS: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling. RESULTS: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups. CONCLUSION: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.

Assessing the prognostic role of ATR mutation in endometrioid endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVE: We sought to validate the clinicopathologic implications and prognostic significance of ATR (ataxia telangiectasia mutated and Rad3-related) mutation in patients with endometrioid endometrial cancer and defective DNA mismatch repair enrolled in a cooperative group molecular staging study of endometrial cancer. METHODS: After pathology review, only endometrioid tumors with high neoplastic cellularity (≥70%) and high quality DNA for molecular analyses were included. MSI (microsatellite instability) typing was performed and the target sequence in exon 10 of ATR was evaluated by direct sequencing in all MSI-high tumors. Associations between ATR mutations and clinicopathologic variables were assessed using contingency table tests. Differences in overall survival (OS) and disease-free survival (DFS) were evaluated by univariate analyses and multivariable Cox proportional hazard models. RESULTS: A total of 475 eligible cases were identified. Of 368 MSI+ cases, the sequence of interest could be successfully genotyped in 357 cases. ATR mutations were exclusively identified in 46 tumors with high level microsatellite instability (MSI+) (12.9%, p<0.001) and were associated with higher tumor grade (p=0.001). ATR mutations were not associated with OS (HR 1.16; 95% CI, 0.58-2.32; p=0.68) or DFS (HR 0.61; 95% CI, 0.25-1.50; p=0.28). CONCLUSION: Truncating mutations in exon 10 of ATR occur exclusively in tumors with evidence of defective DNA mismatch repair. We were not able to confirm the prognostic value of these mutations in patients with endometrioid endometrial cancer.

High frequency strand slippage mutations in CTCF in MSI-positive endometrial cancers.

Tumors with defective mismatch repair acquire large numbers of strand slippage mutations including frameshifts in coding sequence repeats. We identified a mutational hotspot, p.T204fs, in the insulator-binding protein (CTCF) in MSI-positive endometrial cancers. Although CTCF was described as a significantly mutated gene by the endometrial cancer TCGA, the A7 track variants leading to T204 frameshifts were not reported. Reanalysis of TCGA data using Pindel revealed frequent T204fs mutations, confirming CTCF is an MSI target gene and revealed the same frameshifts in tumors with intact mismatch repair. We show that T204fs transcripts are subject to nonsense-mediated decay and as such, T204fs mutations are unlikely to act as dominant negatives. The spectrum and pattern of mutations observed is consistent with CTCF acting as a haploinsufficient tumor suppressor.

A phase II trial of a surgical protocol to decrease the incidence of wound complications in obese gynecologic oncology patients.

OBJECTIVES: Obese women have a high incidence of wound separation after gynecologic surgery. We explored the effect of a prospective care pathway on the incidence of wound complications. METHODS: Women with a body mass index (BMI) ≥30 kg/m(2) undergoing a gynecologic procedure by a gynecologic oncologist via a vertical abdominal incision were eligible. The surgical protocol required: skin and subcutaneous tissues to be incised using a scalpel or cutting electrocautery, fascial closure using #1 polydioxanone suture, placement of a 7 mm Jackson-Pratt drain below Camper's fascia, closure of Camper's fascia with 3-0 plain catgut suture and skin closure with staples. Wound complication was defined as the presence of either a wound infection or any separation. Demographic and perioperative data were analyzed using contingency tables. Univariable and multivariable regression models were used to identify predictors of wound complications. Patients were compared using a multivariable model to a historical group of obese patients to assess the efficacy of the care pathway. RESULTS: 105 women were enrolled with a median BMI of 38.1. Overall, 39 (37%) had a wound complication. Women with a BMI of 30-39.9 kg/m(2) had a significantly lower risk of wound complication as compared to those with a BMI >40 kg/m(2) (23% vs 59%, p<0.001). After controlling for factors associated with wound complications the prospective care pathway was associated with a significantly decreased wound complication rate in women with BMI <40 kg/m(2) (OR 0.40, 95% C.I.: 0.18-0.89). CONCLUSION: This surgical protocol leads to a decreased rate of wound complications among women with a BMI of 30-39.9 kg/m(2).

In vitro chemoresponse to cisplatin and outcomes in cervical cancer.

OBJECTIVE: The aim of this study was to report clinical outcomes of cervical cancer patients treated with weekly cisplatin chemo-radiation therapy (chemoRT) stratified by pre-treatment cisplatin in vitro chemosensitivity. METHODS: This was a retrospective analysis of patients with cervical cancer seen at our institution between May 2009 and August 2011. Patients underwent pre-treatment in vitro chemoresponse testing (Precision Therapeutics, Inc.) and were treated with concurrent weekly cisplatin chemoRT. The study consisted of 33 patients with FIGO tumor stages Ib2 to IIIb. Pre-treatment cisplatin chemoresponse of individual patient tumors was determined from chemoresponse dose response curves and scored as responsive (R), intermediate response (IR), or nonresponsive (NR). RESULTS: There were 28 patients with squamous cell carcinoma and 5 with adenocarcinoma. Cisplatin chemosensitivity was R and IR in 18 patient specimens and NR in 15. The 2-year recurrence-free survivals (RFS) were 87% for patients whose specimens tested R+IR to cisplatin compared to 58% for those whose specimens were NR (p=0.036). The 2-year RFS were 86% for the R+IR group compared to 46% for the NR group for patients with tumors of squamous cell histology (p=0.009). Stepwise proportional hazards modeling for RFS demonstrated that chemoresponsiveness to cisplatin (p=0.029) and FDG-PET lymph node status (p=0.011) were the only independent predictors of RFS for patients with tumors of squamous cell histology. CONCLUSION: Pre-treatment in vitro cisplatin chemoresponse testing of cervix cancer biopsies was technically feasible and prognostic of RFS in patients treated with weekly cisplatin chemoRT.

Frequent mutations in the RPL22 gene and its clinical and functional implications.

OBJECTIVE: To determine the frequency and spectrum of mutations in RPL22 a gene identified by The Cancer Genome Atlas (TCGA) as mutated in endometrioid endometrial cancer, and determine the relationship between RPL22 defects and clinicopathologic features. METHODS: Direct sequencing of the entire coding region of the RPL22 cDNA and exons 2/4 was performed in tumors with/without microsatellite instability (MSI). RPL22 expression was assessed by immunofluorescence microscopy in the KLE, RL952 and AN3CA cell lines, wildtype, heterozygous and homozygous mutants, respectively. Relationships between RPL22 mutation and clinicopathological features were assessed using Chi-squared analysis and Student's t test. Progression-free survival (PFS) was calculated from the date of diagnosis to the date of recurrence. RESULTS: A single nucleotide deletion in an A8 coding repeat was identified in exon 2 of the RPL22 gene in 116/226 (52%) of MSI-high tumors. No mutations were identified in MSI-stable tumors. Only 2% of the tumors expressed a homozygous A deletion. RPL22 mutation was not associated with stage, grade, race and lymphovascular space invasion. Women whose tumors harbored RPL22 mutations were significantly older (67 vs. 63years, p=0.005). There was no difference in PFS between patients with the wildtype and mutant genotypes. CONCLUSIONS: RPL22 is frequently mutated in MSI-high endometrioid endometrial cancers. The A8 mutation identified was not reported in the whole exome sequences analyzed by the TCGA. The demonstration of frequent mutation in RPL22 may point to a limitation of the exome capture and next generation sequencing analysis methods for some mononucleotide string mutations. Functional assessment of the RPL22 knockdown may be warranted.

Phase II study of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer.

OBJECTIVE: We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC). METHODS: Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500 mg/m(2) IV and bevacizumab 15 mg/kg IV were administered every 3 weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS). RESULTS: Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Median follow-up was 25.7 months (range, 3.0-47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38-71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25-59), 18 stable disease (53%; 35-70) and 2 progressive disease (6%; 1-20). Median PFS was 7.9 months (95% CI, 4.6-10.9), with a median OS of 25.7 months (95% CI, 15.4-29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6 months prior to enrollment. Grade 3-4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment. CONCLUSIONS: Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted.

Multicenter phase II trial of topotecan, cisplatin and bevacizumab for recurrent or persistent cervical cancer.

OBJECTIVE: We evaluated the activity and safety of the combination of topotecan, cisplatin and bevacizumab in patients with recurrent or persistent carcinoma of the cervix. METHODS: Eligible patients had persistent or recurrent cervical cancer not amenable to curative intent treatment. No prior chemotherapy for recurrence was allowed. Treatment consisted of cisplatin 50 mg/m(2) day 1, topotecan 0.75 mg/m(2) days 1, 2 and 3 and bevacizumab 15 mg/kgday 1 every 21 days until disease progression or limiting toxicity. The primary endpoint was progression free survival at 6 months. We explored PET/CT as a potential early indicator of response to therapy. RESULTS: Twenty-seven eligible patients received a median of 3 treatment cycles (range, 1-19). Median follow-up was 10 months (range, 1.7-33.4). The 6-month PFS was 59% (80% CI: 46-70%). In 26 evaluable patients, we observed 1 CR (4%; 80% CI: 0.4-14%) and 8 PR (31%; 80% CI: 19-45%) lasting a median of 4.4 months. Ten patients had SD (39%; 80% CI: 25-53%) with median duration of 2.2 months. Median PFS was 7.1 months (80% CI: 4.7-10.1) and median OS was 13.2 months (80% CI: 8.0-15.4). All patients were evaluated for toxicity. Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities. CONCLUSION: The addition of bevacizumab to topotecan and cisplatin results in an active but highly toxic regimen. Future efforts should focus on identification of predictive biomarkers of prolonged response and regimen modifications to minimize toxicity.

The risk of lymph node metastasis with positive peritoneal cytology in endometrial cancer.

OBJECTIVE: To determine the correlation between positive peritoneal cytology (PPC) and lymph node metastasis in patients with endometrial cancer grossly confined to the uterus. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Only patients with endometrial cancer grossly confined to the uterus who had undergone a complete staging procedure (lymph node removal) were included. Statistical analysis used the χ2 test and logistic regression models. RESULTS: A total of 22,947 patients were identified. Positive peritoneal cytology was present in 3.5% of the patients. The incidence of lymph node metastasis was significantly higher among patients with PPC compared to those with negative peritoneal cytology for all histologic types examined (P < 0.0001): endometrioid adenocarcinoma, 28.7% versus 6.9%; adenocarcinoma not otherwise specified, 35.4% versus 5.8%; clear cell/serous carcinoma, 41.4% versus 19.0%, and carcinosarcoma,; 38.4% versus 14.4%. After adjusting for other contributing factors in the multivariable model, PPC remained an independent predictor of lymph node metastasis (P < 0.0001). CONCLUSION: Our data indicate that patients with positive washings are at significant risk of nodal metastasis and adverse prognosis. Although no longer a part of the current International Federation of Gynecology and Obstetrics staging criteria, peritoneal cytology status should continue to inform clinical decision making in endometrial cancer.

Lithium chloride and inhibition of glycogen synthase kinase 3ß as a potential therapy for serous ovarian cancer.

OBJECTIVE: Lithium chloride (LiCl) has been shown to demonstrate anticancer properties at supratherapeutic doses. This study was designed to determine whether LiCl, as a single agent or in combination with cytotoxic agents, reduces ovarian cancer cell growth and metabolic activity at clinically achievable levels. METHODS: We studied the effects of LiCl on 2 high-grade serous ovarian cancer cell lines, SKOV3 and OVCA 433, and primary cultures developed from ascitic fluid collected from patients with metastatic high-grade serous ovarian cancer. We assessed proliferation and metabolism using cell cycle analysis, MTT assays, and cellular proliferation and clonogenic potential assays. RESULTS: Treatment with 1 mM LiCl had no effect on the cell cycle distribution or metabolic activity of the SKOV3 and OVCA 433 cell lines. Combination treatment with cisplatin or paclitaxel led to statistically significant decreases in metabolic activity in the OVCA 433 cell line and 50% of cultures investigated. The decreased metabolic activity was not, however, associated with decreased cell growth or clonogenic potential. CONCLUSIONS: Combination treatment with LiCl and cytotoxic agents at physiologically achievable drug concentrations reduces ovarian cancer cell metabolism but does not appear to affect cellular proliferation. The potential for combined lithium/cytoxic therapies appears to be limited based on our analysis of both established cell lines and short-term ovarian cancer cultures.

Timing of referral for genetic counseling and genetic testing in patients with ovarian, fallopian tube, or primary peritoneal carcinoma.

OBJECTIVE: The objective of this study was to assess patients' preferences of the timing of referral for genetic counseling and testing in relation to the diagnosis, treatment, and recurrence of ovarian, tubal, or primary peritoneal cancers. METHODS: Ninety-two patients who underwent counseling and testing by 1 certified genetic counselor were identified. An introductory letter, consent form, and questionnaire were mailed to gather information regarding factors influencing the decision to undergo genetic counseling and testing and opinions regarding optimal timing. Medical records were reviewed for demographic and clinical data. RESULTS: Of 47 consenting women, 45 underwent testing. Eight (18%) were found to have a genetic mutation. Women lacked consensus about the optimal time for referral for and to undergo genetic testing, although women with stage I disease preferred testing after completion of chemotherapy. Most women were comfortable receiving the results by phone, but one third preferred an office visit. CONCLUSIONS: Patients' views regarding the best time to be referred for and undergo counseling and testing varied greatly. Because of the high mortality of this disease, clinicians should discuss referral early and personalize the timing to each patient. The subset of patients who prefer results disclosure during an office visit should be identified at the time of their initial counseling.

Common obstetrics and gynecologic topics in critical care: A narrative review.

The fields of Obstetrics and Gynecology and Critical Care often share medically and surgically complex patients. Peripartum anatomic and physiologic changes can predispose or exacerbate certain conditions and rapid action is often needed. This review discusses some of the most common conditions responsible for the admission of obstetrical and gynecological patients to the critical care unit. We will consider both obstetrical and gynecologic concepts including postpartum hemorrhage, antepartum hemorrhage, abnormal uterine bleeding, preeclampsia and eclampsia, venous thromboembolism, amniotic fluid embolism, sepsis and septic shock, obstetrical trauma, acute abdomen, malignancies, peripartum cardiomyopathy, and substance abuse. This article aims to be a primer for the Critical Care provider.

Implementation of an enhanced recovery after surgery (ERAS) protocol for total abdominal hysterectomies in the division of gynecologic oncology: a network-wide quality improvement initiative.

CONTEXT: Enhanced Recovery After Surgery (ERAS) protocols have been shown to decrease length of stay and postoperative opioid usage in colorectal and bariatric surgeries performed at large academic centers. Hysterectomies are the second most common surgical procedure among women in the United States. Hysterectomies performed in an open fashion, or total abdominal hysterectomies (TAHs), account for a large portion of procedures performed by gynecologic oncologists secondary to current oncology guidelines and surgical complexity. Implementation of an ERAS protocol for gynecologic oncology TAHs is one way in which patient outcomes may be improved. OBJECTIVES: An ERAS protocol for gynecologic oncology surgeries performed in a community hospital was instituted with the goal to optimize patient outcomes preoperatively. The primary outcome of interest was to reduce patient opioid usage. Secondary outcomes included compliance with the ERAS protocol, length of stay, and cost. Thirdly, this study aimed to demonstrate the unique challenges of implementing a large-scale protocol across a community network. METHODS: An ERAS protocol was implemented in 2018, with multidisciplinary input from the Departments of Gynecologic Oncology, Anesthesia, Pharmacy, Nursing, Information Technology, and Quality Improvement to develop a comprehensive ERAS order set. This was implemented across a 12-site hospital system network that consisted of both urban and rural hospital settings. A retrospective review of patient charts was performed to assess measured outcomes. Parametric and nonparametric tests were utilized for statistical analysis with p<0.05 denoting statistical significance. If the p value was >0.05 and <0.09, this was considered a trend toward significant. RESULTS: A total of 124 patients underwent a TAH utilizing the ERAS protocol during 2018 and 2019. The control arm consisted of 59 patients who underwent a TAH prior to the ERAS protocol intervention, which was the standard of care in 2017. After 2 years of implementation of the ERAS protocol intervention, we found that 48 % of the ERAS patients had minimal opioid requirements after surgery (oral morphine equivalent [OME] range 0-40) with decreased postoperative opioid requirements in the ERAS group (p=0.03). Although not statistically significant, utilization of the ERAS protocol for gynecologic oncology TAHs trended toward shorter hospital length of stay from 5.18 to 4.17 days (p=0.07). The median total hospital costs per patient also showed a nonsignificant decrease in cost from $13,342.00 in the non-ERAS cohort and $13,703.00 in the ERAS cohort (p=0.8). CONCLUSIONS: A large-scale quality improvement (QI) initiative is feasible utilizing a multidisciplinary team to implement an ERAS protocol for TAHs in the division of Gynecologic Oncology with promising results. This large-scale QI result was comparable to studies that conducted quality-improvement ERAS initiatives at single academic institutions and should be considered within community networks.

Phosphatase and tensin homolog (PTEN) pseudogene expression in endometrial cancer: a conserved regulatory mechanism important in tumorigenesis?

OBJECTIVES: The PTEN pseudogene, PTENP1, was recently shown to play a role in cell proliferation in a prostate cancer model. In the present study, we sought to determine whether PTENP1 is expressed in endometrial cancer (EMCA) cell lines and primary tumors along with the microRNAs (miRNAs) that are predicted to regulate PTEN and PTENP1 transcript levels. METHODS: RNA was prepared from six EMCA cell lines, three normal endometrial samples, and 61 primary tumors. TaqMan® RT-PCR was used to quantitate PTEN expression in all specimens and PTENP1 expression in cell lines, and normal endometrial (NE) samples. PTENP1 expression was evaluated using conventional RT-PCR in primary tumors. MicroRNA profiling was undertaken using NanoString(TM) technology in AN3CA and KLE cell lines. The relationship between PTEN transcript levels, PTENP1 expression, and PTEN mutation status was investigated. RESULTS: All NE samples, cell lines, and primary tumors expressed PTEN. PTENP1 transcript was expressed in NE, cell lines, and 34/61 (56%) primary tumors. The median relative PTEN level was 2.9 arbitrary expression units in PTENP1-positive tumors and 2.3 in PTENP1-negative tumors (p=0.09). PTEN levels in wild-type and haploinsufficient tumors were variable compared to PTEN-null tumors (p=0.015). Four microRNAs predicted to bind PTEN/PTENP1 ranked in the top 20 most abundant microRNA subtypes in the AN3CA and KLE cell lines. CONCLUSIONS: PTENP1 is expressed in NE and EMCA cell lines, as are PTEN/PTENP1 targeting inhibitory miRNAs (cell lines). Further studies are needed to evaluate the impact of PTEN/PTENP1/miRNA interactions on tumorigenesis regulation in EMCA.

Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer.

OBJECTIVE: Adjuvant radiotherapy improves local control but not survival in women with endometrial cancer. This benefit was shown in staged patients with "high intermediate risk" (HIR) disease. Other studies have challenged the need for systematic staging including lymphadenectomy. We sought to determine whether LVSI alone or in combination with other histologic factors predicts lymph node (LN) metastasis in patients with endometrioid endometrial cancer. METHODS: A retrospective review was conducted of patients with endometrioid endometrial carcinoma who had confirmed presence/absence of LVSI and clinicopathologic data necessary to identify HIR criteria. Kaplan-Meier curves were generated and univariate and multivariate analyses performed as appropriate. RESULTS: We identified 757 eligible patients and 628 underwent systematic lymphadenectomy for staging purposes. In the surgically staged group, 242 (38%) patients met uterine HIR criteria and 196 (31%) had LVSI. Both HIR and LVSI were significantly associated with LN metastasis. Among the HIR positive group, 59 had LN metastasis (OR 4.46, 95% CI 2.72-7.32, P<0.0001). Sixty-six LVSI positive patients had nodal metastasis (OR 11.04, 95% CI 6.39-19.07, P<0.0001). The NPV of LVSI and HIR negative specimens was 95.6% and 93.4% respectively. In multivariate analysis, PFS and OS were significantly reduced in both LVSI positive (P<0.0001) and HIR patients (P<0.0001) when compared to patients who were LVSI and HIR negative. CONCLUSIONS: HIR status and LVSI are highly associated with LN metastasis. These features are useful in assessing risk of metastatic disease and may serve as a surrogate for prediction of extrauterine disease.

A Search for Novel Risk Factors for Obstetric Anal Sphincter Injury.

OBJECTIVE: The objective of this study is to evaluate factors associated with obstetric anal sphincter injury and identify modifiable risks. METHODS: A retrospective case-control study was performed in women who gave birth at our institution between May 2008 and December 2012. Patients who had a third- or fourth-degree lacerations were compared with those who did not. Parity, stretch marks, age, body mass index, tobacco use, fetal weight, operative delivery, labor, and second stage duration were compared between groups. Multivariate direct logistic regression was conducted on all patients who had complete data to calculate the adjusted odds ratio. RESULTS: We identified 299 patients with third- or fourth-degree lacerations and 8,459 patients without third- or fourth-degree lacerations during the time frame. Duration of second stage between 1 hour and 2 hours (P < 0.0001), duration of second stage greater than 2 hours (P < 0.0001), midline or unknown type episiotomy (P < 0.0001), mediolateral episiotomy (P < 0.0001), vacuum delivery (P < 0.0001), forceps delivery (P < 0.0001), fetal weight greater than 4,000 g (P < 0.0001), and antepartum stress urinary incontinence (P < 0.006) were associated with a significant increase in high-risk lacerations. This study did not find a statistically significant association between parity and these lacerations. CONCLUSIONS: We, as others, found that episiotomy and operative delivery were modifiable risks of obstetrical care. Furthermore, even a short second stage of labor (1-2 hours) was associated with significant risk of injury.

Lower uterine segment involvement is associated with poor outcomes in early-stage endometrioid endometrial carcinoma.

BACKGROUND: The clinicopathologic significance of lower uterine segment involvement (LUSI) in endometrial cancer patients remains unclear. Although LUSI has been reported to be a prognostic indicator, literature is limited. METHODS: We studied 481 surgically staged endometrioid endometrial cancers with disease confined to the uterus (FIGO 1988 stage I or II). Primary outcomes were overall survival (OS) and disease-free survival (DFS). The relationships between LUSI and OS and DFS were assessed using the Kaplan-Meier method and Cox proportional hazard models. The t test or Fisher exact test was used for evaluating relationships between variables of interest. RESULTS: LUSI was present in 223 cases (46.4%), and was associated with both decreased disease free survival (P = 0.02) and overall survival (P = 0.01) in univariate analysis. Multivariate analysis confirmed the association between LUSI and increased risk for recurrence [hazard ratio (HR) 2.27; 95% confidence interval (95% CI) 1.09-4.7; P = 0.03] and increased mortality (HR 1.76; 95% CI 1.12-2.78; P = 0.01). CONCLUSIONS: LUSI in patients with early-stage endometrioid endometrial cancer is associated with decreased survival.

Inferior vena cava filter placement in the gynecologic oncology patient: A 15-year institutional experience.

OBJECTIVE: Venous thrombosis is a frequent complication of gynecologic cancer. Data regarding the use of inferior vena cava (IVC) filters in this population is limited. The aim of this study was to review our experience with gynecologic oncology patients who received an IVC filter, specifically to evaluate indications for filter placement and survival outcomes. METHODS: This was a retrospective, single-institution study of patients who had an IVC filter placed after a histologically confirmed gynecologic malignancy. Patients were identified from a prospectively collected interventional radiology (IR) database. Clinicopathologic characteristics, procedure details, and outcome data were obtained from outpatient and inpatient medical records. Survival after IVC filter placement was analyzed using the Kaplan-Meier product limit method and compared by log-rank test. RESULTS: A total of 128 patients were identified and 103 were found to be eligible for analysis. Most patients had ovarian cancer (52%), followed by cervical cancer (25%) and endometrial cancer (21%). Two-thirds had advanced stage disease (III/IV). The procedure complication rate was 2%. Median survival after IVC filter placement was 7.8months (95% CI, 4.1-13.6). The most common indication for IVC filter placement was contraindication to anticoagulation secondary to hemorrhage (44%), followed by perioperative indications (30%) and failed anticoagulation (14%). There was no difference in survival by IVC filter placement indication (p=0.18). The majority of the IVC filters placed were permanent (90.5%) and in an infrarenal position (95.8%). There was no difference in survival according to specific thromboembolic event (DVT vs. PE vs. both). Patients able to receive anticoagulation after IVC filter placement had improved survival (HR 0.45, 95%CI 0.45-0.27, p=0.003). CONCLUSIONS: We present the largest series of gynecologic oncology patients treated with IVC filters. Long-term survival after IVC filter placement is uncommon. Patients who receive anticoagulation after IVC filter placement have an improved survival over those who do not receive anticoagulation; this difference in survival may be secondary to worsening disease causing contraindications to anticoagulation.

Wound complications after gynecologic cancer surgery.

OBJECTIVE: To explore clinical correlates of wound complications in high-risk women undergoing abdominal gynecologic surgery in a tertiary referral center. METHODS: Retrospective analysis of patient demographics, pre-operative and intra-operative information, and outcomes was performed in a cohort of patients who underwent abdominal surgery for suspected gynecologic malignancy between 1/2005 and 6/2008. The primary outcome was wound complication within 6 weeks of surgery. Univariate and multivariate logistic regression analyses were employed. A nomogram predicting post-operative wound complications was created and validated by receiver operating characteristic (ROC) curve analysis and 10-fold cross-validation. RESULTS: Median age of 373 women analyzed was 57years (range 25-88), median body mass index (BMI) 32.3kg/m(2) (range 14.0-70.7). A total of 150 patients (40%) had prior abdominal surgery; 40 (11%) had a pre-operative serum albumin <3.5g/dl; and 78 (21%) had pulmonary disease. Wound complications occurred in 125 patients (34%). In multivariate analysis wound complications were correlated with BMI of 30-39.9kg/m(2) (OR=5.62, 95% CI 2.08-15.19, p<0.0001) and BMI≥40kg/m(2) (OR=10.27, 95% CI 3.66-28.88, p<0.0001), prior abdominal surgery (OR 3.28, 95%CI1.89-5.70, p<0.0001), serum albumin≤3.5g/dl (OR 4.24, 95%CI 1.87-9.61, p=0.0005), pulmonary disease (OR 2.22, 95%CI 1.09-4.51, p=0.03), lysis of adhesions (OR 3.57, 95%CI 1.04-12.26, p=0.04), and length of surgery (OR 2.42, 95%CI 1.35-4.35, p=0.003). Risk for wound complication was lower with pelvic drain placement (OR 0.26, 95%CI 0.11-0.64, p=0.003). CONCLUSIONS: Wound complications are common in gynecologic oncology. Further studies should explore whether risk factor modification decreases complications.

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.