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ObjectiveTo explore whether patient-reported lymphedema-related symptoms, as measured by the Gynecologic Cancer Lymphedema Questionnaire (GCLQ), are associated with a patient-reported diagnosis of lymphedema of the lower extremity (LLE) and limb volume change (LVC) in patients who have undergone radical surgery, including lymphadenectomy, for endometrial, cervical, or vulvar cancer on Gynecologic Oncology Group (GOG) study 244.MethodsPatients completed the baseline and at least one post-surgery GCLQ and LVC assessment. The 20-item GCLQ measures seven symptom clusters-aching, heaviness, infection-related, numbness, physical functioning, general swelling, and limb swelling. LLE was defined as a patient self-reported LLE diagnosis on the GCLQ. LVC was measured by volume calculations based on circumferential measurements. A linear mixed model was fitted for change in symptom cluster scores and GCLQ total score and adjusted for disease sites and assessment time.ResultsOf 987 eligible patients, 894 were evaluable (endometrial, 719; cervical, 136; vulvar, 39). Of these, 14% reported an LLE diagnosis (endometrial, 11%; cervical, 18%; vulvar, 38%). Significantly more patients diagnosed versus not diagnosed with LLE reported ≥4-point increase from baseline on the GCLQ total score (p10% was significantly associated with reported general swelling (p&nbsp

ObjectiveTo assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244.MethodsThe prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy [FACT]), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14days before surgery), and at 6, 12, 18, and 24months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%.ResultsIn 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p&nbsp

BACKGROUND. The elderly population is expanding world-wide but is underrepresented in clinical trials. We sought to assess the safety of robotic gynecologic surgery in an elderly cohort and to identify factors associated with unfavorable outcomes. METHODS. All patients ≥ 65 years who underwent a robotically assisted procedure at a single institution between May 2007 to December 2016 were divided into three age groups: 65–74 (Group 1); 75–84 (Group 2); ≥ 85 (Group 3). Perioperative outcomes were recorded in patients who did not require conversion to laparotomy. We compared clinical variables among groups and performed multivariate logistic regression to detect variables associated with major complications (≥ Grade 3) or 90-day mortality. RESULTS. We retrospectively identified 982 cases: 685 in Group 1; 249 in Group 2; 48 in Group 3. Median age = 71 years. Median BMI = 28.9. Malignancy was documented in 72.8% of cases; the majority were endometrial cancer (61.8%). Thirty-four patients (3.5%) were read-mitted within 30 days. Seventy-seven (7.8%) had a postoperative complication, and 23 (2.3%) had a major complication. Ninety-day mortality was 0.5%. There was significant difference between groups with respect to body mass index (P = 0.026), ECOG PS (P ≤ 0.001), > 5 comorbidities (P = 0.005), hospital stay (P < 0.001), major complications (P = 0.001), and 90-day mortality (P < 0.001). On multivariable logistic regression, age ≥ 85 years was associated with major complications. Body mass index, age ≥ 85 years, and major complications were significantly associated with 90-day mortality. CONCLUSIONS. Robotic-assisted surgery appears to be safe in an elderly cohort. The incidence of overall and major complications is consistent with those reported in the literature. Patients ≥ 85 years old appear to be at higher risk of unfavorable outcomes.

To compare the incidence of trocar site hernia in women who underwent robotically assisted laparoscopic surgery (RBT) for endometrial cancer staging with the incidence of ventral hernia formation in patients who underwent laparotomy (LAP) for the same indication. To analyze risk factors for hernia formation in women undergoing RBT for endometrial cancer.We retrospectively identified all patients who underwent surgical staging for endometrial cancer via RBT or LAP from 2009-2012. Clinicopathologic data were analyzed. Appropriate statistical tests were used.738 patients were staged via RBT (n=567) or LAP (n=171). Overall median age was 61 years (RBT range, 33-90; LAP range,28-86; p=0.4). Median BMI was 29.5 kg/m(2) (range, 17.9-66) and 30.3 kg/m(2) (range, 16.8-67.2), respectively (p=1.0). Eleven (1.9%) of 567 patients in the RBT cohort developed a trocar site hernia compared with 11 (6.4%) of 171 LAP patients who developed a ventral hernia (p=0.002). Median time to diagnosis was 18 months (range, 3-49) and 17 months (range, 7-30), respectively (p=0.7). Of the 11 RBT patients who developed a trocar site hernia, 10 (91%) were midline defects and 1 (9%) was a lateral defect of a prior inferior epigastric port site. No hernias required emergent operative intervention. Four (0.7%) of 567 RBT patients compared with 2 (1.2%) of 171 LAP patients required surgical hernia repair (p=0.4).Trocar site herniation after RBT staging for endometrial cancer is uncommon and less likely to occur than ventral hernia formation with LAP staging. Furthermore, surgical revision rates are low.

Minimally invasive surgery (MIS) is associated with decreased complication rates, length of hospital stay, and cost compared with laparotomy. Robotic-assisted surgery—a method of laparoscopy—addresses many of the limitations of standard laparoscopic instrumentation, thus leading to increased rates of MIS. We sought to assess the impact of robotics on the rates and costs of surgical approaches in morbidly obese patients with uterine cancer. Patients who underwent primary surgery at our institution for uterine cancer from 1993 to 2012 with a BMI ≥40 mg/m2 were identified. Surgical approaches were categorized as laparotomy (planned or converted), laparoscopic, robotic, or vaginal. We identified two time periods based on the evolving use of MIS at our institution: laparoscopic (1993–2007) and robotic (2008–2012). Direct costs were analyzed for cases performed from 2009 to 2012. We identified 426 eligible cases; 299 performed via laparotomy, 125 via MIS, and 2 via a vaginal approach. The rates of MIS for the laparoscopic and robotic time periods were 6 % and 57 %, respectively. The rate of MIS was 78 % in this morbidly obese cohort in 2012; 69 % were completed robotically. The median length of hospital stay was 5 days (range 2–37) for laparotomy cases and 1 day (range 0–7) for MIS cases (P

ObjectivePhase 3 trials have demonstrated a survival advantage for patients with optimally debulked epithelial ovarian cancer who received intravenous (IV) and intraperitoneal (IP) chemotherapy compared with IV therapy alone. This was despite a significant proportion of patients in the IV/IP arms not completing all 6 planned cycles. Our objective was to evaluate the prognostic significance of the number of IV/IP cycles administered.Methods/MaterialsData were analyzed for all patients with stage III to IV epithelial ovarian cancer who underwent optimal primary cytoreduction followed by 1 or more cycles of IV/IP chemotherapy from January 2005 to July 2011 at our institution. A landmark analysis was performed to associate progression-free survival (PFS) and overall survival (OS) with the number of IV/IP cycles given.ResultsWe identified 201 patients; 26 (13%) received 1 to 2 cycles of IV/IP chemotherapy, 41 (20%) received 3 to 4 cycles, and 134 (67%) received 5 to 6 cycles. The 5-year PFS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 18%, 29%, and 17%, respectively. The 5-year OS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 44%, 54%, and 57%, respectively. There was no significant difference in PFS (P= 0.31) or OS (P= 0.14) between the 3 groups. The most common reason for discontinuing IV/IP therapy was treatment-related toxicity (77%). Postoperative complications were the most common reason for not initiating IV/IP therapy (42%) in patients who subsequently transitioned to it.ConclusionsWe did not detect a significant survival difference between patients who received 1 to 2, 3 to 4, or 5 to 6 IV/IP chemotherapy cycles. Women may still derive a survival benefit if they receive fewer than 6 IV/IP cycles.

Objectives To compare the incidence and potential risk factors of trocar site hernia formation in women undergoing robotically assisted versus standard laparoscopic staging (RBT vs. LSC, respectively) for endometrial cancer. Methods We retrospectively identified all patients who underwent MIS staging for endometrial cancer at our institution from 01/09–12/12. Data collection involved the review of all operative notes, postoperative follow-up visit notes, and postoperative imaging reports. Appropriate statistical tests were used. Results We identified 760 eligible patients (LSC, 193; RBT, 567). The overall median age was 61years (range, 33–90). The median BMI was 28.5kg/m 2 for LSC (range, 16.6–67.6) and 29.5kg/m 2 for RBT (range, 17.9–66) patients (p=0.8). A trocar site hernia developed in 16 patients (2.1%)—5 (2.6%) of 193 LSC and 11 (1.9%) of 567 RBT patients (p=0.6). Median time to hernia diagnosis was 13months (range, 5–20.5) and 18months (range, 3–49), respectively (p=0.5). All hernias in the LSC cohort developed at the camera trocar site. In the RBT cohort, 10 developed at the camera trocar site and 1 at a lateral trocar site. Only BMI was associated with the development of hernias. A hernia was diagnosed in 7 (6.9%) of 101 patients with a BMI ≥40kg/m 2 compared with 9 (1.4%) of 659 with a BMI 2 (p=0.001). Conclusion MIS for endometrial cancer is associated with a low rate of trocar site hernia formation, with similar rates associated with RBT and standard LSC. Higher BMI is associated with the development of postoperative trocar site hernias.

To assess sexual/vaginal health issues and educational intervention preferences in women with a history of breast or gynecologic cancer. Patients/survivors completed a cross-sectional survey at their outpatient visits. Main outcome measures were sexual dysfunction prevalence, type of sexual/vaginal issues, awareness of treatments, and preferred intervention modalities. Descriptive frequencies were performed, and results were dichotomized by age, treatment status, and disease site. Of 218 eligible participants, 109 (50%) had a history of gynecologic and 109 (50%) a history of breast cancer. Median age was 49 years (range 21–75); 61% were married/cohabitating. Seventy percent (n = 153) were somewhat-to-very concerned about sexual function/vaginal health, 55% (n = 120) reported vaginal dryness, 39% (n = 84) vaginal pain, and 51% (n = 112) libido loss. Many had heard of vaginal lubricants, moisturizers, and pelvic floor exercises (97, 72, and 57%, respectively). Seventy-four percent (n = 161) had used lubricants, 28% moisturizers (n = 61), and 28% pelvic floor exercises (n = 60). Seventy percent (n = 152) preferred the topic to be raised by the medical team; 48% (n = 105) raised the topic themselves. Most preferred written educational material followed by expert discussion (66%, n = 144/218). Compared to women ≥50 years old (41%, n = 43/105), younger women (54%, n = 61/113) preferred to discuss their concerns face-to-face (p = 0.054). Older women were less interested in online interventions (52%, p

Objectives To assess the perioperative outcomes of minimal access surgery (MAS) in secondary surgical cytoreduction (SSCR) for recurrent epithelial ovarian cancer (ROC); to compare oncologic outcomes with laparotomy (LAP). Methods Using an institutional database, we identified all patients with ROC undergoing SSCR from 1/5/09–6/14/14. Selection for MAS or LAP was based on surgeon preference. To minimize selection bias, preoperative imaging was reviewed for all LAP cases. In this manner, we identified potential MAS candidates, who were used in the comparison. Intent-to-treat analyses were undertaken using statistical testing. Results 170 cases were identified (131 LAP, 8 LSC, 31 RBT). 68/131 (52%) LAP cases were deemed potential candidates for MAS. Feasibility analyses included 68 LAP and 39 MAS cases. Six (15%) MAS cases were converted to LAP. Median age, BMI, operative time did not differ significantly between the groups. Complete gross resection was achieved in 37/39 (95%) MAS, 63/68 (93%) LAP ( P =1.0). Median estimated blood loss was 50cm 3 (range, 5–500) MAS, 150cm 3 (range, 0–1500) LAP ( P =0.001). Median length of stay was 1day (range, 0–23) MAS, 5days (range, 1–21) LAP ( P P =0.06). The 2-year progression-free survival was 56.1% (SE 9%) MAS, 63.5% (SE 6%) LAP ( P =1.0). The 2-year overall survival was 92.2% (SE 5.4%) MAS, 81.4% (SE 5.5%) LAP ( P =0.7). Conclusions MAS for SSCR is feasible in properly selected cases. MAS is associated with favorable perioperative outcomes and similar oncologic outcomes, compared to LAP.

Objectives Minimally invasive surgery for recurrent ovarian cancer is generally not performed. The aim of this study was to assess the feasibility and surgical outcomes of robotic-assisted surgery in the management of recurrent ovarian cancer. Methods Eligible patients included those with confirmed recurrent ovarian cancer amenable to surgical resection and in which a complete resection was thought to be feasible with the use of the robotic platform. Patients with evidence of carcinomatosis were not considered for a robotic approach. Clinical and pathologic data were abstracted from the medical records. Appropriate statistical tests were performed using SPSS statistical software program (SPSS 20.0 Inc., Chicago, IL). Results A total of 48 patients were identified. Thirty-six (75%) patients had a recurrent mass or masses isolated to one anatomic region (pelvis or abdomen). Conversion to laparotomy was necessary in 4 (8.3%) cases. In cases not requiring conversion to laparotomy, the median operative time, EBL, and length of stay were 179.5min, 50cc, and 1day, respectively. An optimal debulking was achieved in 36 (82%) cases. Complications occurred in 6 (13.6%) cases. The median operative time, EBL, length of stay, and complications were all statistically significantly lower in the cases not converted to laparotomy compared to those that were (p Conclusions This study suggests that select patients with recurrent ovarian cancer in the absence of carcinomatosis may be candidates for secondary surgical cytoreduction via a robotic approach. Surgical and postoperative outcomes appear to be favorable compared to reports of laparotomy in recurrent ovarian cancer.

Objectives Our primary objective was to assess the detection rate of sentinel lymph nodes (SLNs) using indocyanine green (ICG) and near-infrared (NIR) fluorescence imaging for uterine and cervical malignancies. Methods NIR fluorescence imaging for the robotic platform was obtained at our institution in 12/2011. We identified all cases planned for SLN mapping using fluorescence imaging from 12/2011–4/2013. Intracervical ICG was the fluorophobe in all cases. Four cc (1.25 mg/mL) of ICG was injected into the cervix alone divided into the 3- and 9-o'clock positions, with 1 cc deep into the stroma and 1 cc submucosally before initiating laparoscopic entry. Blue dye was concurrently injected in some cases. Results Two hundred twenty-seven cases were performed. Median age was 60 years (range, 28–90 years). Median BMI was 30.2 kg/m2 (range, 18–60 kg/m2). The median SLN count was 3 (range, 1–23 ). An SLN was identified in 216 cases (95%), with bilateral pelvic mapping in 179 (79%). An aortic SLN was identified in 21 (10%) of the 216 mapped cases. When ICG alone was used to map cases, 188/197 patients mapped, for a 95% detection rate compared to 93% (28/30) in cases in which both dyes were used (P = NS). Bilateral mapping was seen in 156/197 (79%) ICG-only cases and 23/30 (77%) ICG and blue dye cases (P = NS). Conclusions NIR fluorescence imaging with intracervical ICG injection using the robotic platform has a high bilateral SLN detection rate and appears favorable to using blue dye alone and/or other modalities. Combined use of ICG and blue dye appears unnecessary.

Objective Primary cytoreductive surgery in patients with stage IIIC–IV epithelial ovarian cancer frequently includes diaphragm peritonectomy or resection, which can lead to symptomatic pleural effusions when the resection specimen is ≥10cm. Our objective was to evaluate whether the placement of an intraoperative thoracostomy tube decreased the incidence of symptomatic pleural effusions in these cases. Methods We identified 156 patients who underwent primary debulking surgery involving diaphragm peritonectomy or resection for stage III–IV ovarian cancer from 1/01–12/09. Using standard statistical tests, the incidence of symptomatic pleural effusions and other variables were compared between patients who did and did not have intraoperative chest tubes placed. Results Forty-nine patients had a resected diaphragm specimen ≥10cm in largest dimension; 28 (57%) did not undergo chest tube placement (NCT group) while 21 (43%) did (CT group). Mediastinal lymph node dissection (0% vs 19%, P=0.028) and liver resections (11% vs 38%, P=0.037) were higher in the CT group. Postoperatively, 57% of the NCT group developed a moderate or large pleural effusion compared to 19% of the CT group (P=0.007). Thirteen patients (46%) in the NCT group developed respiratory symptoms requiring either placement of a postoperative chest tube or thoracentesis compared to 3 patients (14%) in the CT group (P=0.018). Conclusions Diaphragm peritonectomy or resection can often lead to moderate or large pleural effusions that may become symptomatic. In these patients, intraoperative chest tube placement may be considered to decrease the incidence of symptomatic effusions and the need for postoperative chest tube placement or thoracentesis.

To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging.All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (HE). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells.Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology-13 cases on routine HE, 12 cases after ultrastaging. Patients whose tumors had a DMI50% were more likely to have positive SLNs on routine HE (p0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion.Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases.

The objective of this study was to evaluate the risk factors and potential morbidity associated with intraoperative hypothermia (IH) during cytoreductive surgery (CRS) for advanced ovarian cancer.Demographic and perioperative data were collected for all patients with stage IIIC-IV ovarian, fallopian tube, and primary peritoneal carcinoma who underwent primary CRS at our institution from 2001 to 2010. Only patients with carcinomatosis and/or bulky upper abdominal disease and residual disease of1cm were included. Intraoperative hypothermia was defined as temperature of36.0 degrees Celsius (°C). Associations with 21 perioperative factors, 12 systems-based complications, and specific complications including but not limited to venous thromboembolism and surgical site infection were evaluated.Two hundred ninety-seven patients met the inclusion criteria. An intraoperative temperature36°C was noted in 72.1% of patients, and a temperature36°C at the time of abdominal closure was noted in 45.5%. Intraoperative vasopressors (P=0.02), epidural anesthesia (P=0.01), transfusion of fresh frozen plasma (P0.05), and blood loss (P=0.01) were associated with IH. There was no association between IH and postoperative complications in general (P=0.48) or specifically grade 3-5 complications (P=0.34). Univariate analysis did show an association between hematologic complications and IH; however, this did not persist on multivariate analysis (P=0.14).In patients who underwent optimal primary CRS for advanced ovarian cancer, IH alone was not associated with the development of postoperative complications. Postoperative morbidity in these patients is multifactorial and further investigation into modifiable risk factors is warranted.

ObjectiveRisk-reducing salpingo-oophorectomy (RRSO) is recommended for women with BRCA mutation due to increased risk of pelvic serous carcinoma. Serous tubal intraepithelial carcinoma (STIC) is a pathologic finding of unknown clinical significance. This study evaluates the clinical outcome of patients with isolated STIC.Materials/MethodsWe retrospectively reviewed the medical records of consecutive patients with a germline BRCA1/2 mutation or a high-risk personal or family history of ovarian cancer who underwent RRSO between January 2006 and June 2011. All patients had peritoneal washings collected. All surgical specimens were assessed using the sectioning and extensively examining the fimbria protocol, with immunohistochemistry when indicated. p53 signature lesions and secretory cell outgrowths were excluded.ResultsOf 593 patients who underwent RRSO, isolated STIC was diagnosed in 12 patients (2%). Five patients (42%) were BRCA1 positive, 5 patients (42%) were BRCA2 positive, and 2 patients (17%) had high-risk family history. Preoperatively, all patients with STIC had normal CA-125 levels and/or pelvic imaging results. Seven patients underwent hysterectomy and omentectomy, 6 patients (46%) had pelvic node dissections, and 5 patients (39%) had para-aortic node dissections. With the exception of positive peritoneal washings in 1 patient, no invasive or metastatic disease was identified. No patient received adjuvant chemotherapy. At median follow-up of 28 months (range, 16–44 months), no recurrences have been identified.ConclusionsAmong the cases of isolated STIC after RRSO reported in the literature, the yield of surgical staging is low, and short-term clinical outcomes are favorable. Peritoneal washings are the most common site of disease spread. Individualized management is warranted until additional data become available.

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

Objective The optimal adjuvant therapy in advanced endometrial cancer is controversial. One regimen is concurrent external beam pelvic irradiation (RT) and cisplatin, then carboplatin/paclitaxel. This study reports an institutional experience using this approach in stage III (FIGO 2009) endometrial cancer. Methods Patients with stage III (FIGO 2009) endometrial cancer who underwent total hysterectomy and bilateral salpingo-oophorectomy at a single institution from 01/2004 to 12/2009 were identified retrospectively. Those treated with adjuvant RT/cisplatin, followed by carboplatin/paclitaxel comprised the study population. Results Of the 40 eligible patients, 7 (18%) were stage IIIA and 33 (82%) IIIC. Nineteen patients (48%) were ≥60years of age. Twenty-three (58%) had ≥50% myometrial invasion, 30 (75%) lymphovascular invasion, 11 (28%) cervical stromal invasion, and 5 (12%) positive peritoneal cytology. Histology was endometrioid in 32 (80%), serous in 6 (15%), and clear cell in 2 (5%). At a median follow-up of 49months, the 5-year freedom from relapse was 79% and overall survival 85%. The 5-year rate of vaginal recurrence was 3%, non-vaginal pelvic recurrence 3%, para-aortic recurrence 11%, peritoneal recurrence 5%, and other distant recurrence 11%. Thirty-one patients (78%) were able to complete the planned RT/cisplatin and 4cycles of carboplatin/paclitaxel. Acute grade 3 toxicity occurred in 10 patients (4 neutropenia, 2 anemia, 1 fatigue, 2 diarrhea). No late toxicity was grade ≥3. Conclusion These favorable outcomes corroborate those of RTOG 9708. Until prospective data that compare adjuvant therapy regimens mature, concurrent chemoradiation should be strongly considered in stage III endometrial cancer.

Objective The objectives of the study are to evaluate which clinicopathologic factors influenced overall survival (OS) in endometrial carcinoma and to determine if the surgical effort to assess para-aortic (PA) lymph nodes (LNs) at initial staging surgery impacts OS. Methods All patients diagnosed with endometrial cancer from 1/1993–12/2011 who had LNs excised were included. PALN assessment was defined by the identification of one or more PALNs on final pathology. A multivariate analysis was performed to assess the effect of PALNs on OS. A form of recursive partitioning called classification and regression tree (CART) analysis was implemented. Variables included: age, stage, tumor subtype, grade, myometrial invasion, total LNs removed, evaluation of PALNs, and adjuvant chemotherapy. Results The cohort included 1920 patients, with a median age of 62years. The median number of LNs removed was 16 (range, 1–99). The removal of PALNs was not associated with OS ( P =0.450). Using the CART hierarchically, stage I vs. stages II–IV and grades 1–2 vs. grade 3 emerged as predictors of OS. If the tree was allowed to grow, further branching was based on age and myometrial invasion. Total number of LNs removed and assessment of PALNs as defined in this study were not predictive of OS. Conclusion This innovative CART analysis emphasized the importance of proper stage assignment and a binary grading system in impacting OS. Notably, the total number of LNs removed and specific evaluation of PALNs as defined in this study were not important predictors of OS.

Objectives Radical trachelectomy has enabled select women with stage I cervical cancer to maintain fertility after treatment. Tumor size greater than 2 cm has been considered a contraindication, and those patients denied trachelectomy. We report our trachelectomy experience with tumors measuring 2 to 4 cm. Methods We retrospectively reviewed the medical records of all patients planned for fertility-sparing radical trachelectomy. Largest tumor dimension was determined by physical examination, preoperative magnetic resonance imaging, or pathologic evaluation. No patient received neoadjuvant chemotherapy. Results Twenty-nine (26%) of 110 patients had stage IB1 disease with tumors 2 to 4 cm. Median age was 31 years (range, 22–40 years), and 83% were nulliparous. Thirteen patients (45%) had squamous cell carcinoma, 12 patients (41%) had adenocarcinoma, and 4 patients (14%) had adenosquamous carcinoma. Thirteen (45%) of 29 patients had positive pelvic nodes. All para-aortic nodes were negative. Owing to intraoperative frozen section, 13 patients (45%) underwent immediate hysterectomy and 1 patient (3%) definitive chemoradiation. Owing to high-risk features on final pathology, 6 patients (21%) who had retained their uterus received chemoradiation. Nine patients (31%) underwent a fertility-sparing procedure. At a median follow-up of 44 months (range, 1–90 months), there was one recurrence. Conclusions Expanding radical trachelectomy inclusion criteria to women with 2- to 4-cm tumors allows for a fertility-sparing procedure in 30% of patients who would otherwise have been denied the option, with no compromise in oncologic outcome.

Laparoscopy (LSC) offers superior patient outcomes compared to laparotomy. Small retrospective/prospective series have suggested robotics offers further reduction in postoperative pain and pain medication use compared to standard LSC. Our objective was to compare postoperative pain in patients undergoing robotically assisted (RBT) versus standard LSC for newly diagnosed endometrial cancer.All preoperative endometrial cancer cases scheduled for RBT and LSC from May 1, 2007 to June 9, 2010 were identified. For this analysis, we only included cases not requiring conversion to laparotomy. All patients were offered intravenous (IV) patient-controlled analgesia (PCA) postoperatively. Intraoperative equivalent fentanyl doses (IEFDs) and pain scores in the postanesthesia care unit (PACU) were assessed.IV PCA was used in 206 RBTs (86 %) and 208 LSCs (88 %). Median IEFD was 425 μg for LSCs and 500 μg for RBTs (P = 0.03). Median pain scores on PACU arrival were similar in both groups. Median highest pain score was 5 for LSCs and 4 for RBTs (P = 0.007). Linear regression demonstrated that the IEFD was not correlated with the highest pain score (R = 0.09; P = 0.07). Fentanyl was used postoperatively in 196 of 206 RBTs (95 %) and 187 of 208 LSCs (90 %). The total fentanyl doses were 242.5 (range 0-2705) μg and 380 (range 0-2625) μg, respectively (P0.001). The median hourly fentanyl doses were 16.7 (range 0-122.5) μg and 23.5 (range 0-132.4) μg, respectively (P = 0.005). Simultaneous multiple regression analysis further demonstrated RBT was independently associated with a lower total fentanyl dose compared to LSC (P = 0.02).RBT is independently associated with significantly lower postoperative pain and pain medication requirements compared to LSC. The amount of intraoperative fentanyl analgesia does not appear to correlate with postoperative pain.Endometrial cancer is the most common gynecologic malignancy in the United States, with an estimated 47,130 new cases in 2012.1 An estimated 287,100 women were diagnosed with endometrial cancer worldwide in 2008.2 Surgery is the primary treatment of choice for the majority of these women.3 The standard surgical approach has been total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging via laparotomy. Multiple retrospective series have shown that a less invasive surgical approach via laparoscopy (LSC) is feasible and safe, and also associated with improved perioperative outcomes compared to laparotomy in these patients.4 The Gynecologic Oncology Group (GOG) published results of the largest randomized trial (LAP2) comparing LSC to laparotomy in patients with newly diagnosed endometrial carcinoma in 2009.5,6 This landmark study essentially changed the accepted standard surgical approach in this group. Postoperative complications, median blood loss, and median length of stay (LOS), despite increased operative time, were significantly lower in LSC patients despite 25 % requiring conversion to laparotomy.5 The first 802 eligible patients randomized in LAP2 also participated in a quality-of-life (QOL) study. Within 6 weeks of surgery, patients assigned to LSC reported significantly better QOL on all scales other than fear of recurrence.6 Overall, during this 6-week postoperative period, patients assigned to LSC had superior QOL, fewer physical symptoms, less pain and pain-related interference with functioning, better physical functioning and emotional state, earlier resumption of normal activities, earlier return to work, and better body image compared to those assigned to laparotomy.6 Recurrence-free and overall survivals were the same in both groups.7 Multiple published retrospective series have shown possible benefits, such as reduced postoperative pain, using the robotic (RBT) platform compared to LSC or laparotomy in patients with endometrial cancer.8-11 In a randomized trial, LSC was found to be associated with less postoperative pain compared to vaginal approaches in patients undergoing hysterectomy for benign gynecologic disease.12 A small retrospective series reported further reductions in postoperative pain in patients who had undergone an RBT hysterectomy compared to a standard total LSC hysterectomy for benign indications.13 A recent cost analysis suggested that patients experienced less pain and required less pain medication use after RBT procedures compared to LSC for endometrial cancer.14 Based on these reports, we sought to analyze postoperative pain and the use of pain medication in patients undergoing RBT compared to standard transperitoneal LSC procedures for newly diagnosed endometrial cancer during a concurrent time period. Of note, current RBT surgery is not truly robotic in that it is not autonomous. A more appropriate term is “computer-assisted surgery,” but to satisfy current convention, we refer to it as “robotic surgery” in this manuscript.

ObjectiveIt is well documented that recurrence after pelvic exenteration remains high (up to 50%), and patients may require a prolonged period of recuperation following this aggressive surgery. We conducted a retrospective review to evaluate the feasibility of administering adjuvant chemotherapy after pelvic exenteration for gynecologic malignancies.MethodsWe reviewed the medical records of patients with any gynecologic cancer who underwent exenterative surgery between January 2005 and February 2011 at our institution. Patients were referred for postexenteration adjuvant chemotherapy based on surgeon’s discretion and/or presence of high-risk features: positive margins, positive lymph nodes, and/or lymphovascular space invasion. Suitability for chemotherapy was assessed by a gynecologic medical oncologist. Regimens consisted of 4 to 6 cycles of platinum-based doublet chemotherapy. Chemotherapy-related toxicities were assessed using the Common Terminology Criteria for Adverse Events version 4.ResultsWe identified 42 patients who underwent pelvic exenteration during the study period. Eleven (26%) were referred for adjuvant chemotherapy. Three (27%) of the 11 patients did not receive chemotherapy because of delayed postoperative recovery or physician choice. Seven (88%) of the remaining 8 patients completed all scheduled chemotherapy. Grade 2 toxicities or greater were documented in 6 patients (75%), the most common being neutropenia, neuropathy, and fatigue. Median follow-up time was 25 months (range, 6–56 months). The 3-year progression-free and overall survival rates of the 8 patients who received chemotherapy were 58% (95% confidence interval, 18%–84%) and 54% (95% confidence interval, 13%– 83%), respectively.ConclusionsThe administration of adjuvant chemotherapy is feasible for a select group of patients after pelvic exenteration for gynecologic malignancies. Our results need to be interpreted with caution because of the small and heterogeneous cohort of patients included.

Objectives High-grade serous ovarian cancer (HGSOC) mostly presents at an advanced stage and has a low overall survival rate. However, a subgroup of patients are seemingly cured after standard initial therapy. We hypothesize that the molecular profiles of these patients vary from long-term survivors who recur. Methods Patients with advanced HGSOC who underwent primary cytoreductive surgery and platinum-based chemotherapy were identified from The Cancer Genome Atlas (TCGA) and institutional (MSKCC) samples. A curative-intent group was defined by recurrence-free survival of >5years. A long-term recurrent group was composed of patients who recurred but survived >5years. RNA was hybridized to Affymetrix U133A transcription microarrays. The NanoString nCounter gene expression system was used for validation in an independent patient population. Results In 30 curative and 84 recurrent patients, class comparison identified twice as many differentially expressed probes between the groups than expected by chance alone. TCGA and MSKCC data sets had 19 overlapping genes. Pathway analyses identified over-represented networks that included nuclear factor kappa B (NFkB) transcription and extracellular signal-regulated kinase (ERK) signaling. External validation was performed in an independent population of 28 curative and 38 recurrent patients. Three genes ( CYP4B1 , CEPT1 , CHMP4A ) in common between our original data sets remained differentially expressed in the external validation data. Conclusions There are distinct transcriptional elements in HGSOC from patients likely to be cured by standard primary therapy. Three genes have withstood rigorous validation and are plausible targets for further study, which may provide insight into molecular features associated with long-term survival and chemotherapy resistance mechanisms.

Objective According to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with or without chemotherapy in high-risk endometrial cancer. Methods From 11/2004 to 12/2009, 46 patients underwent hysterectomy/bilateral salpingo-oophorectomy for stage I-III (22% stage I/II and 78% stage III) endometrial cancer. Median IMRT dose was 50.4Gy. Adjuvant chemotherapy was given to 30 (65%) patients. Results With a median follow-up of 52months, 4 patients recurred: 1 vaginal plus lung metastasis, 2 isolated para-aortic recurrences, and 1 lungs and liver metastasis. Five-year relapse rate was 9% (95% CI, 0–13.6%). Five-year disease-free survival (DFS) was 88% (95% CI, 77–98%) and overall survival (OS) was 97% (95% CI, 90–100%). There were 2 patients with non-hematological grade 3 toxicity: 1 (2%) acute and 1 (2%) chronic gastrointestinal toxicity. In patients treated with IMRT and chemotherapy ( n =30), 5 had grade 3 leukopenia, 8 grade 2 anemia, and 2 grade 2 thrombocytopenia. Conclusions Oncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of >88% at median follow-up of 52months, despite a preponderance (78%) of stage III disease. Toxicity was minimal even in the setting of an aggressive trimodality (65% of patients) approach. Data from this study and emerging data from RTOG trial 0418 demonstrate the advantages of IMRT in high-risk endometrial cancer.

Robotic surgery is increasingly being performed for endometrial cancer. Robotic hysterectomies (RH), like traditional laparoscopic hysterectomies (LH), involve a significant amount of uterine manipulation. The use of a manipulator is thought to possibly increase the incidence of artifactual tumor displacement beyond the endometrium, including the fallopian tube. The objective of this study was to determine whether there is an association between RH and tumor present in the fallopian tube lumina. All RH and LH cases performed for endometrial cancer from May 2007 to August 2009 were reviewed. Of the cases not converted to laparotomy, 137 RH and 184 LH were identified. Age, body mass index, operative and hysterectomy time, type and grade of tumor, stage, pelvic wash results, and the presence of detached tumor fragments (contaminants) in the lumina of the fallopian tubes were recorded. Appropriate statistical tests were applied. Of the 184 LH, 4 (2.2%) were reported to have detached fragments of tumor in the lumina of the fallopian tubes compared with 16 of the 137 (11.7%) RH cases (P

ObjectiveThe purpose of this study was to assess the rate of lymph node (LN) metastasis in comprehensively staged ovarian clear cell carcinoma (OCCC) clinically confined to the ovary and determine factors associated with LN metastasis.MethodsWe identified all cases of OCCC treated at 4 institutions from January 1994 through December 2011. We included cases with disease grossly confined to the ovary that had surgical staging performed, including at least 10 LNs sampled. Clinical and pathologic data were abstracted from electronic medical records, and a deidentified data set was compiled and processed at a single institution. Factors potentially associated with LN metastasis were tested. Appropriate statistical tests were performed.ResultsWe identified 145 eligible cases that met the criteria for this analysis. Median age was 52.9 years (range, 30–81 years), and median total LN count was 19 (range, 10–74). Seven (4.8%) of 145 comprehensively staged cases had LN metastasis; 6 of these cases (4.1%) were isolated metastasis. Cytologic washings, peritoneal, omental, and fallopian tube involvement were not associated with nodal metastasis. Cases with ovarian surface involvement and positive cytology had a 37.5% incidence of LN positivity, which was statistically meaningful when compared with all other cases (P = 0.003).ConclusionsWomen who underwent comprehensive staging for clinical stage I OCCC had an LN metastasis rate of 4.8%. The subgroup of cases with both ovarian surface involvement and positive cytology had the highest incidence of LN metastasis. This may influence clinical decision making on whether to perform lymphadenectomy in patients with incidental OCCC found after salpingo-oophorectomy.

To investigate the frequency of patient characteristics, causative factors and imaging features associated with pathology-proven peritoneal inclusion cysts (PICs). From a retrospective search of all available hospital records—dating back 19 years—we identified 228 patients with pathology-proven PICs. Descriptive statistics were calculated for patients’ demographic and clinical characteristics. Imaging features of pathology-proven PICs were recorded on a total of 77 computed tomography (CT), magnetic resonance imaging (MRI) and/or ultrasound (US) studies from patients who underwent imaging before surgery. PICs occurred over a wide age range (18–89 years); 82.5 % of patients were women and 17.5 % were men. A history of prior insult to the peritoneum was identified in 70.6 % of patients. Imaging appearances of PICs ranged from loculated, simple fluid collections to complex, multi-septated lesions. In the absence of haemorrhage or debris, PICs were never found to have thick walls. The presence of nodularity, papillary excrescences or other solid components also excluded a diagnosis of PIC, as did the presence of more than a physiological amount of ascites, provided the ascites had no alternate explanation. PICs are more common than suggested by previously published reports. Knowledge of patient characteristics and typical PIC imaging appearances may prevent unnecessary or unnecessarily aggressive therapy. • Peritoneal inclusion cysts (PIC) occur in women and men at all ages • PICs may be incidental findings, both at imaging and during surgery • Especially in symptomatic patients, PICs may be mistaken for cystic neoplasms • Knowledge of demographics and typical imaging features may prevent unnecessarily aggressive therapy • Thick walls, solid component and ascites are inconsistent features of a PIC

The purposes of this study are to evaluate the feasibility of capturing patient-reported outcomes (PROs) electronically and to identify the most common distressing symptoms in women recovering from major gynecologic cancer surgery.This was a prospective, single-arm pilot study. Eligible participants included those scheduled for a laparotomy for presumed or known gynecologic malignancy. Patients completed a Web-based "STAR" (Symptom Tracking and Reporting for Patients) questionnaire once preoperatively and weekly during the 6-week postoperative period. The questionnaire consisted of the patient adaptation of the NCI CTCAE 3.0 and EORTC QLQ-C30 3.0. When a patient submitted a response that was concerning, an automated email alert was sent to the clinician. The patient's assessment of STAR's usefulness was measured via an exit survey.Forty-nine patients completed the study. The procedures included the following: hysterectomy±staging (67%), resection of tumor (22%), salpingo-oophorectomy (6%), and other (4%). Most patients (82%) completed at least 4 sessions in STAR. The CTC generated 43 alerts. These alerts resulted in 25 telephone contacts with patients, 2 ER referrals, one new appointment, and one pharmaceutical prescription. The 3 most common patient-reported symptoms generating an alert were as follows: poor performance status (19%), nausea (18%), and fatigue (17%). Most patients found STAR useful (80%) and would recommend it to others (85%).Application of a Web-based, electronic STAR system is feasible in the postoperative period, highly accepted by patients, and warrants further study. Poor performance status, nausea, and fatigue were the most common distressing patient-reported symptoms.

Objective To describe the surgical technique, complications, and outcomes after anterior pelvic exenteration with total vaginectomy (AETV) for recurrent or persistent genitourinary malignancies. Methods We reviewed the medical records of all patients who underwent AETV between 12/2002 and 07/2011. Relevant demographic, clinical, and pathological information was collected. Postoperative complications and rates of readmission and reoperation (up to 180days after surgery) were examined, and preliminary survival data were obtained. Results We identified 11 patients who underwent AETV. The median age at the time of the surgery was 55years (range, 36–71). The median tumor size was 0.9cm (range, microscopic — 4). Primary tumor sites included: cervix, 6; uterus, 3; vagina, 1; and urethra, 1. Complete surgical resection with negative pathologic margins was achieved in all 11 patients. Major postoperative complications occurred in 4 patients (36%). Six patients (55%) required readmission to the hospital. No operative mortalities were observed, and none of the patients required a re-operation. With a median follow-up after the procedure of 25months (range, 6–95), none of the patients developed a pelvic recurrence. Ten patients (91%) were alive without evidence of disease and one patient (9%) developed a pancreatic recurrence. Conclusion AETV sparing the rectosigmoid and anus is feasible in highly selected patients with central pelvic recurrences. Compared to previously reported studies on total pelvic exenteration, data from this case series suggest that AETV may be associated with a lower rate of complications without compromising the oncologic outcome, while also preserving rectal function.

The purpose of this article is to determine whether early postoperative CT provides prognostic information in patients with advanced ovarian, tubal, or primary peritoneal carcinoma with optimal debulking reported at primary cytoreduction.Our study included 63 patients who underwent primary cytoreductive surgery for presumed advanced ovarian cancer, who had optimal debulking (residual disease ≤ 1 cm) reported at surgery, and who underwent CT before and 7-49 days after surgery. Two radiologists independently retrospectively interpreted all postoperative CT scans and scored lesions on a 5-point scale, where 1 indicates normal and 5 indicates definitely malignant. Lesions larger than 1 cm with a CT score of 4 or 5 were considered suboptimally debulked residual disease.Suboptimally debulked residual disease on CT (range, 1.1-5.8 cm) was reported by reader 1 for 29 of 63 patients (46%) and by reader 2 for 31 of 63 patients (49%), with substantial interobserver agreement (κ = 0.75). Patients with suboptimally debulked residual disease on CT had significantly worse median progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.010, both readers). By univariate and multivariate analyses, suboptimally debulked residual disease on CT remained a significant independent predictor of progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.006, both readers).Our study showed that residual disease larger than 1 cm was present on early postoperative CT in almost half of the patients deemed to have optimally debulked disease at primary cytoreduction. Residual disease larger than 1 cm detected on early postoperative CT was associated with significant decreases in both progression-free and overall survival.

Objectives Nomograms are predictive models that provide the overall probability of a specific outcome. Nomograms have shown better individual discrimination than currently used staging systems in numerous tumor entities. Recently, a nomogram for predicting overall survival (OS) in women with endometrial cancer was introduced by Memorial Sloan–Kettering Cancer Center (MSKCC). The aim of this study was to test the validity of the MSKCC endometrial cancer nomogram using an independent, external patient cohort. Methods The MSKCC nomogram is based on five readily available clinical characteristics. A multi-institutional endometrial cancer database was used to test the nomogram's validity. All consecutive patients treated for endometrial cancer between December 1995 and May 2011 and who had all nomogram variables documented were identified for analysis. Results Seven hundred sixty-five eligible patients were identified and used for external validation analysis. In the Austrian patient cohort, median OS was 134months, and 3-year and 5-year OS rates were 83.8% (95% CI, 80.6–86.5%) and 77.2% (95% CI, 43.5–80.5%), respectively. The nomogram concordance index was 0.71 (SE=0.017; 95% CI, 0.68–0.74). The correspondence between the actual OS and the nomogram predictions suggests a good calibration of the nomogram in the validation cohort. Conclusion The MSKCC endometrial cancer nomogram was externally validated and was shown to be generalizable to a new and independent patient population. The nomogram provides a more individualized and accurate estimation of OS for patients diagnosed with endometrial cancer following primary therapy. The nomogram can be used for counseling patients more accurately and for better stratifying patients for clinical trials.

Objective To determine the false-negative rate of a surgical sentinel lymph node (SLN) mapping algorithm that incorporates more than just removing SLNs in detecting metastatic endometrial cancer. Methods A prospective database of all patients who underwent lymphatic mapping for endometrial cancer was reviewed. Cervical injection of blue dye was used in all cases. The surgical algorithm is as follows: 1) peritoneal and serosal evaluation and washings; 2) retroperitoneal evaluation including excision of all mapped SLNs and suspicious nodes regardless of mapping; and 3) if there is no mapping on a hemi-pelvis, a side-specific pelvic, common iliac, and interiliac lymph node dissection (LND) is performed. Paraaortic LND is performed at the attendings' discretion. The algorithm was retrospectively applied. Results From 9/2005 to 4/2011, 498 patients received a blue dye cervical injection for SLN mapping. At least one LN was removed in 95% of cases (474/498); at least one SLN was identified in 81% (401/498). SLN correctly diagnosed 40/47 patients with nodal metastases who had at least one SLN mapped, resulting in a 15% false-negative rate. After applying the algorithm, the false-negative rate dropped to 2%. Only one patient, whose LN spread would not have been caught by the algorithm, had an isolated positive right paraaortic LN with a negative ipsilateral SLN and pelvic LND. Conclusions Satisfactory SLN mapping in endometrial cancer requires adherence to a surgical SLN algorithm and goes beyond just the removal of blue SLNs. Removal of any suspicious node along with side-specific lymphadenectomy for failed mapping are an integral part of this algorithm. Further validation of the false-negative rate of this algorithm is necessary.

Objective To determine whether cytoreduction is associated with improved outcome in patients newly diagnosed with metastatic uterine leiomyosarcoma (LMS). Methods We retrospectively identified all patients treated at our institution for high-grade uterine LMS with extrauterine disease at the time of initial diagnosis from 7/1/82 to 7/31/07. Pattern of disease spread was classified as intraperitoneal (IP) or extraperitoneal (EP). Progression-free survival (PFS) and overall survival (OS) were determined from date of initial surgery using Kaplan–Meier estimates. Results We identified 96 cases. Median age was 54years (range, 23–81). IP disease was seen in 48 (50%) and EP in 48 (50%). A complete gross resection of all tumor was achieved in 41/84 (49%). Recurrence or progression was noted in 93 (97%); 81 (84%) have died. Median PFS and OS for the entire cohort was 9.7months (range, 6.7–10.9) and 20.2months (range, 15.5–24.8), respectively. All 8 non-surgical cases died within 30months of diagnosis. Median PFS was 14.2months (range, 11.4–16.9) for those with a complete gross resection versus 6.8months (range, 4.1–9.5) for those with any residual disease (P=0.002). Median OS was 31.9months (range, 3.3–60.4) versus 20.2months (range, 11.8–28.6), respectively (P=0.04). On multivariate analysis, no residual disease was independently associated with PFS when adjusting for disease distribution (IP vs EP) and the use of chemotherapy but not OS. Conclusions Surgical cytoreduction of metastatic uterine LMS was independently associated with PFS but not OS in cases selected for surgery. The improvement in PFS must be weighed against the morbidity of surgery.

To assess the introduction of computer-based surgery (ie, robotic surgery [RBT]) in the treatment of patients with newly diagnosed uterine cancer.We identified all patients who presented to our institution for initial surgical care of newly diagnosed uterine cancer from 5/1/07-12/31/10. Perioperative outcomes of laparotomy cases were compared to those of laparoscopic (LSC) or RBT cases. Complications within 30 days of surgery were graded.Of 752 patients, the planned approach was laparotomy in 103 (14%), LSC in 302 (40%), and RBT in 347 (46%). The rate of laparotomy for any reason (planned or converted) was 39% in 2007 compared to 18% in 2010 (P0.001). Preoperative characteristics for LSC and RBT cases were similar, except 10% versus 15%, respectively, were morbidly obese (P=0.049). The extent of procedure, total nodal counts, and overall complications were similar between the LSC and RBT cases. The median length of stay was shorter for RBT cases (P0.001). The median total room and operative times were longer for RBT cases (P0.001), mainly due to cases in which the surgeon had less than ~40 RBT cases of experience.Robotics can be efficiently introduced into the surgical care of patients with newly diagnosed uterine cancers. RBT cases require the same operative times as LSC cases after accounting for the 40-case learning curve. Both approaches result in similar excellent patient outcomes and remain reasonable approaches for this disease. The introduction of robotics may lead to further reduction in the rate of laparotomy.

Objective To update our report on the outcome of patients who underwent extended pelvic resection (EPR) for recurrent or persistent uterine and cervical malignancies. Methods We reviewed the records of all patients who underwent EPR between 6/2000 and 07/2011. EPR was defined as an en-bloc resection of a pelvic tumor with sidewall muscle, bone, major nerve, and/or major vascular structure. Complications up to 180 days post surgery were analyzed. Survivals were estimated using the Kaplan–Meier method. Results We identified 22 patients. Median age at the time of EPR was 58 years (range, 36–74). Median tumor diameter was 5.4 cm (range, 1.5–11.2). Primary tumor sites included: uterus, 13; cervix, 7; synchronous uterus/cervix, 1; and synchronous uterus/ovary, 1. The EPR structures were: muscle, 13; nerve, 10; bone, 8; vessel, 5. Complete gross resection with microscopically negative margins (R0 resection) was achieved in 17 patients (77%). There were no perioperative mortalities. Major postoperative complications occurred in 14 patients (64%). The two most common morbidities were pelvic abscesses and peripheral neuropathies. Median follow-up time was 28 months (range, 6–99). The 5-year overall survival (OS) for the entire cohort was 34% (95% CI, 13–57). For the 17 patients who had an R0 resection, the 5-year OS was 48% (95% CI, 19–73). In patients with positive pathologic margins (n = 5), the 5-year OS was 0%. Conclusion EPR was associated with prolonged survival when an R0 resection was achieved. The high rate of postoperative complications remains a hallmark of these procedures and properly selected patients should be extensively counseled preoperatively.

To evaluate patterns of recurrence in 1988 FIGO stage IC endometrioid endometrial adenocarcinoma.A prospectively maintained endometrial cancer database was utilized to identify all patients with stage IC endometrioid endometrial adenocarcinoma treated between 2/93 and 6/09. Patterns of recurrence and risk factors were analyzed.One hundred thirty-four patients with stage IC endometrial cancer were identified. Median age was 66 years (range, 31-91 years). All patients were initially treated surgically, and 79% underwent comprehensive surgical staging with lymphadenectomy. Median number of lymph nodes removed was 18 (range, 1-45). Fifty-one patients (38%) had FIGO grade 1 tumors, 55 (41%) had grade 2 tumors, and 28 (21%) had grade 3 tumors. The majority of patients (91%) received adjuvant radiation therapy. With a median follow-up of 36 months (range, 0.6-141.4 months), 10 patients recurred. Of these, 2 (20%) were grade 1, 2 (20%) were grade 2, and 6 (60%) were grade 3. Nine (90%) of these recurrences had a distant component and 7 (70%) were fatal. Overall, the 3 year cumulative incidence failure rate for grade 1/2 tumors was 5.4%; for grade 3 tumors it was 28.9% (P0.001). Age, BMI, and lymphovascular invasion were not associated with an increased risk of recurrence.Patients with stage IC, grade 3 endometrial cancer had a significantly increased risk of recurrence (28.9%). All of these recurrences had a distant component and the majority were fatal. Further investigation into the addition of adjuvant systemic therapy in these high-risk patients is warranted.

Objective To develop a nomogram based on established prognostic factors to predict the probability of 5-year disease-specific mortality after primary surgery for patients with all stages of epithelial ovarian cancer (EOC) and compare the predictive accuracy with the currently used International Federation of Gynecology and Obstetrics (FIGO) staging system. Methods Using a prospectively kept database, we identified all patients with EOC who had their primary surgery at our institution between January 1996 and December 2004. Disease-specific mortality was estimated using the Kaplan–Meier method. Twenty-eight clinical and pathologic factors were analyzed. Significant factors on univariate analysis were included in the Cox proportional hazards regression model, which identified factors utilized in the nomogram. The concordance index (CI) was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. Results A total of 478 patients with EOC were included. The most predictive nomogram was constructed using seven variables: age, FIGO stage, residual disease status, preoperative albumin level, histology, family history suggestive of hereditary breast/ovarian cancer (HBOC) syndrome, and American Society of Anesthesiologists (ASA) status. This nomogram was internally validated using bootstrapping and shown to have excellent calibration with a bootstrap-corrected CI of 0.714. The CI for FIGO staging alone was significantly less at 0.62 ( P =0.002). Conclusion We have developed an all-stage nomogram to predict 5-year disease-specific mortality after primary surgery for epithelial ovarian cancer. This tool is more accurate than FIGO staging and should be useful for patient counseling, clinical trial eligibility, postoperative management, and follow-up.

Objective We assessed the IHC expression of ER and PR and their prognostic significance in uterine leiomyosarcoma (LMS). Methods We identified 43 "high-grade" uterine LMS cases from 7/82–7/07 for whom ER/PR IHC analysis was performed at initial diagnosis at our institution. Results Disease was confined to the uterine body in 20/43 (47%). Eighteen (42%) of 43 were ER(+); 17/42 (41%) were PR(+). At last follow-up, 33 (77%) had recurred or progressed, and 23 (54%) had died. PR expression was associated with improved progression-free survival (PFS; P=0.002) and overall survival (OS; P=0.03) overall; ER expression was not. After adjusting for stage, ER expression was associated with PFS (P=0.01), not OS (P=0.3), and PR expression maintained a significant association with PFS (P=0.002) and approached a significant association with OS (P=0.05). Neither ER nor PR expression was associated with outcome in cases with disease outside the uterine body. In cases with confined disease, median PFS for ER(+) or PR(+) cases was not reached compared to 16.9months for ER(−) cases (95% CI: 8.1–25.7; P=0.03) and 13.5months for PR(−) cases (95% CI: 5.9–21.1; P=0.001). Only 1/10 PR(+) cases recurred and died; 9/10 PR(−) cases recurred, and 5 died. Two of 9 ER(+) cases recurred and died; 8/11 ER(−) cases recurred, and 4 died. Conclusion ER/PR expression is associated with survival outcomes in patients with high-grade uterine LMS confined to the uterine body. PR expression seems capable of identifying cases confined to the uterine body, which have better outcomes.

Objective Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy. Methods Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests. Results Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra-abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P =0.018). Conclusions Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution.

Uterine carcinosarcoma (CS) is a rare but aggressive malignancy frequently associated with extrauterine metastasis at the time of diagnosis. The objective of this study was to assess the role of cytoreductive surgery in patients with stage IIIC-IVB uterine CS.We conducted a retrospective review of all patients with uterine CS treated at our institution from 1990 to 2009. Clinicopathologic factors, surgical procedures, adjuvant therapy, and survival outcomes were collected for all patients. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Factors predictive of survival outcomes were compared using the log-rank test and Cox regression analysis.An analysis of 44 patients was performed (stage IIIC, n=14; stage IVB, n=30). Complete gross resection was achieved in 57% of patients. PFS and OS for the entire cohort were 8.6 months and 18.5 months, respectively. Complete gross resection was associated with a median OS of 52.3 months versus 8.6 months in patients with gross residual disease (P0.0001). Stage IIIC disease was associated with a median OS of 52.3 months versus 17.5 months for patients with stage IVB disease. In patients who received adjuvant therapy, OS was 30.1 months versus 4.7 months in patients who did not receive adjuvant therapy (P0.001). On multivariate analysis, only complete gross resection and the ability to receive adjuvant therapy were independently associated with OS.Cytoreductive surgery, with a goal of achieving a complete gross resection, is associated with an improvement in OS among patients with advanced uterine CS.

To establish an algorithm that incorporates sentinel lymph node (SLN) mapping to the surgical treatment of early cervical cancer, ensuring that lymph node (LN) metastases are accurately detected but minimizing the need for complete lymphadenectomy (LND).A prospectively maintained database of all patients who underwent SLN procedure followed by a complete bilateral pelvic LND for cervical cancer (FIGO stages IA1 with LVI to IIA) from 03/2003 to 09/2010 was analyzed. The surgical algorithm we evaluated included the following: 1. SLNs are removed and submitted to ultrastaging; 2. any suspicious LN is removed regardless of mapping; 3. if only unilateral mapping is noted, a contralateral side-specific pelvic LND is performed (including inter-iliac nodes); and 4. parametrectomy en bloc with primary tumor resection is done in all cases. We retrospectively applied the algorithm to determine how it would have performed.One hundred twenty-two patients were included. Median SLN count was 3 and median total LN count was 20. At least one SLN was identified in 93% of cases (114/122), while optimal (bilateral) mapping was achieved in 75% of cases (91/122). SLN correctly diagnosed 21 of 25 patients with nodal spread. When the algorithm was applied, all patients with LN metastasis were detected; with optimal mapping, bilateral pelvic LND could have been avoided in 75% of cases.In the surgical treatment of early cervical cancer, the algorithm we propose allows for comprehensive detection of all patients with nodal disease and spares complete LND in the majority of cases.

Objective To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate. Methods All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC). Results Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p=0.0003). Conclusion Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread.

Objectives MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression primarily through post-transcriptional modification. We tested the hypothesis that miRNA expression is associated with overall survival in advanced ovarian cancer. Methods Cases included newly diagnosed patients with stage III or IV serous ovarian cancer. RNA from a training set of 62 cases was hybridized to an miRNA microarray containing 470 mature human transcripts. Cox Regression was performed to identify miRNAs associated with overall survival. External validation was performed using quantitative RT-PCR miRNA assays in an independent test set of 123 samples. MiRNA targets and associated biologic pathways were predicted in silico . Results Of all patients, 80% had high-grade, stage IIIC tumors and 64% underwent optimal cytoreduction. The median survival for the entire cohort was 49±4months. The training set identified 3 miRNAs associated with survival — miR-337 , miR-410 , and miR-645 . An miRNA signature containing miR-410 and miR-645 was most strongly associated with overall survival in the training set (HR=2.96, 95% CI: 1.51–5.78). This miRNA survival signature (MiSS) was validated in the test set (HR=1.71, 95% CI: 1.05–2.78). The MiSS was independent of FIGO stage and surgical debulking. Conclusions The data suggest that an MiSS that contains miR-410 and miR-645 is negatively associated with overall survival in advanced serous ovarian cancer. This signature, when further validated, may be useful in individualizing care for the ovarian cancer patient. Pathway analyses identify biologically plausible mechanisms.

Background Patients with BRCA-associated ovarian cancer (OC) have a survival advantage over those with sporadic OC. To further explore this, we examined the impact of prognostic factors on disease-free survival (DFS) and overall survival (OS) in patients with known BRCA mutation status. Patients and methods We reviewed stage III–IV OC patients treated at our institution between 1 December 1996 and 30 September 2006 and also tested on protocol for BRCA mutations. Impact on DFS and OS was determined by Kaplan–Meier analysis and a Cox proportional hazards model. Results Of the 110 patients, 36 had deleterious BRCA mutations [BRCA (+)] and 74 were BRCA wild type [BRCA(-)]. Thirty-one of 36 (86%) BRCA (+) and 60 of 74 (81%) BRCA (-) patients were platinum sensitive (P = 0.60). Median OS was longer for BRCA (+) patients (not reached versus 67.8 months; P = 0.02), but DFS was similar (26.9 versus 24.0, P = 0.3). On multivariate analysis, OS correlated with primary platinum sensitivity [HR = 0.15; 95% CI (confidence interval) 0.06–0.34] and BRCA (+) mutation status (HR = 0.33; 95% CI 0.12–0.86). Conclusions BRCA mutation status predicted OS independent of primary platinum sensitivity, suggesting that underlying tumor biology contributes to disease outcome and may be worthy of consideration in future clinical trial design.

PURPOSE: To assess the value of magnetic resonance (MR) imaging in determining the site of origin of newly diagnosed uterine cancer (corpus vs cervix) when clinical and/or histologic evaluation is indeterminate. MATERIALS AND METHODS: The Institutional Review Board approved and waived informed consent for this HIPAA-compliant study of 59 women (median age, 59 years; range, 28–84 years) who underwent pelvic MR imaging to determine the anatomic origin of uterine cancer. Two radiologists independently retrospectively assessed all MR imaging studies. In 48 patients who underwent hysterectomy, surgical pathologic findings were the reference standard, and overall test yields and diagnostic likelihood ratios were measured. Accuracy in detecting invasion of adjacent structures was also calculated. For the remaining patients, imaging and biopsy findings are presented descriptively. RESULTS: At hysterectomy, 32 patients had uterine corpus cancer and 16 had cervical cancer. Overall test yields for reader 1 and reader 2 were 0.85 and 0.88, respectively. When a reader attributed a tumor’s origin to either the uterine corpus or cervix, the odds of the tumor originating from that site were 4.80–6.35 times greater than they would have been if no other information were available. Accuracy levels in detecting invasion of the myometrium, cervical stroma, parametria and/or adnexae, and vagina, respectively, were 72%, 69%, 74%, and 85% for reader 1 and 78%, 77%, 76%, and 85% for reader 2. CONCLUSION: MR imaging is useful for determining the anatomic origin of uterine cancer and provides helpful information regarding invasion of adjacent structures. © RSNA, 2011

Objective To determine if micrometastasis (MM) and isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) of endometrial cancer patients are artifactual and related to uterine manipulation at the time of diagnosis and surgery. Methods We reviewed a prospectively maintained database of all patients with endometrial cancer undergoing SLN mapping between 2005 and 2009. MM was defined as a focus of metastatic cancer ranging from 0.2 to 2mm. ITCs were defined as metastasis measuring ≤0.2mm, including the presence of single, non-cohesive cytokeratin-positive tumor cells. We reviewed the effect of diagnostic procedure such as dilatation and curettage (D&C) versus biopsy and type of hysterectomy performed on the presence of MM and ITCs in SLNs. Results In all, 175 patients had successful SLN mapping. Of these, 145 (83%) had negative nodes, 11 (6%) had positive nodes, and 19 (11%) met the criteria for MM and ITC. The uterine procedure used to diagnose endometrial cancer, type of hysterectomy, tumor grade, histology, positive pelvic washings, and type of uterine manipulator utilized, did not appear to be associated with MM/ITC. However, the presence of lymphovascular invasion ( P P =0.01) were significantly higher in the MM/ITC group. Conclusions These data demonstrate that the presence of MM and ITCs in SLNs of endometrial cancer patients is not an artifact of uterine manipulation or instrumentation. Rather, it is a real pathologic finding likely associated with lymphovascular invasion and depth of myoinvasion.

Objective. To assess the morbidity and mortality associated with extensive upper abdominal surgery (EUAS) performed during primary cytoreduction for advanced ovarian carcinoma. Methods. We identified all patients who underwent EUAS during primary cytoreduction for advanced ovarian, tubal, or peritoneal cancer at our institution from 1/01 to 12/06. Major grade 3–5 complications were those that led to invasive radiologic intervention, re-operation, unplanned ICU admission, chronic disability, or death within 30days of surgery. Results. There were 141 eligible patients, with a median age of 60years (range, 38–82). The majority of patients had stage IIIC disease, 103 (73%); serous histology, 131 (93%); and ascites, 118 (84%). There were 229 EUAS procedures performed—diaphragm peritonectomy, 101 (72%); splenectomy, 45 (32%); full-thickness diaphragm resection, 19 (14%); partial hepatectomy, 18 (13%); distal pancreatectomy, 17 (12%); cholecystectomy, 15 (11%); and resection of porta hepatis tumor, 14 (10%). Cytoreductive outcomes were: no gross residual, 42 (30%); residual≤1cm, 85 (60%); and residual >1cm, 14 (10%). Grade 3–5 complications occurred in 31 (22%) patients, including 2 mortalities (1.4%). In 21/31 (68%), the complication was successfully managed with percutaneous drainage of infected or non-infected collections. Overall median survival for all patients was 57months. Conclusions. Rates of major morbidity and mortality following EUAS for primary cytoreduction were 22% and 1.4%, respectively. Approximately two-thirds of complications were readily managed by percutaneous drainage of collections. With an overall median survival of 57months in a cohort of patients with a large tumor burden, this rate of morbidity and mortality appears acceptable.

This study aimed to determine the feasibility and efficacy of using the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) as a symptom scale for lymphedema of the lower extremity (LLE).Twenty-eight gynecologic cancer survivors with documented LLE and 30 without a history or presence of lymphedema completed the GCLQ and provided feedback about their satisfaction with and feasibility of using the GCLQ at their oncology follow-ups. The study survey took approximately 5-10 min to complete, and it was easily understood by the majority of the sample.Participants had a mean age of 59.6 years (range, 28-80 years). Twenty-eight women (48%) had LLE, and 30 (52%) had no history or presence of LLE (confirmed by limb volume [LV] measurements at assessment). Type of cancer history included endometrial, 38 (66%); cervical, 13 (22%); and vulvar, 7 (12%). GCLQ scores differed significantly by lymphedema diagnosis; LLE patients had higher scores (P0.01). The large area under the curve (AUC) of 0.95 (95% CI: 0.90-1.000) suggests that the GCLQ can distinguish between patients with and without LLE. Although all 28 (100%) of the LLE patients were aware of their LLE diagnosis, only 23 (82%) underwent treatment. The GCLQ was easily understood by most (55/58, 95%), and overall, patients showed a high willingness (56/58, 96%) to complete the questionnaire at future appointments. Twenty-five (88%) of the LLE patients found the GCLQ to be helpful in identifying symptoms of lymphedema.The GCLQ effectively distinguished between gynecologic cancer survivors with and those without LLE, with good sensitivity and specificity. The patients, particularly those with LLE, showed high confidence in the GCLQ's ability to detect LLE symptoms.

Objective The objective of this study was to examine the incidence and management of bevacizumab-associated gastrointestinal (GI) perforations in patients with recurrent ovarian carcinoma. Methods We identified all patients who received bevacizumab off protocol from August 2004–August 2008. We examined their medical records for reports of confirmed GI perforation, associated clinicopathological factors, treatment, and outcomes. Results Six (4%) of 160 patients with ovarian carcinoma who had been treated with bevacizumab developed GI perforations, with a median of 4 (range, 2–8) previous cytotoxic regimens. The median serum CA-125 at the start of treatment was 228 U/mL (range, 50–3106 U/mL). The median number of bevacizumab cycles prior to perforation was 10.5 (range, 2–20). The median time from the last bevacizumab dose to diagnosis of GI perforation was 13 days (range, 1–28 days). Four (67%) patients underwent an exploratory surgery. At laparotomy, one had a gastric perforation and one had an appendiceal perforation; the site of perforation could not be identified in the other 2 Two patients (33%) were managed conservatively—one with a PEG tube and the other with supportive care. The median time of death from the date of diagnosis of GI perforation was 27 days (range, 4–326 days). Only two patients—one with a gastric and the other with an appendiceal perforation—survived > 65 days. The 30-day mortality rate following a bevacizumab-associated GI perforation was 50%. Conclusion Bevacizumab-associated GI perforations in patients with recurrent ovarian carcinoma occurred in 4% of our patients. The prognosis of patients diagnosed with bevacizumab-associated GI perforations in this study was poor, and treatment should be individualized.

Traditionally we have relied mainly on final FIGO stage to estimate overall oncologic outcome in endometrial cancer patients. However, it is well known that other patient factors may play equally important roles in outcome. Our objective was to develop a clinically useful nomogram in the hope of providing a more individualized and accurate estimation of overall survival (OS) following primary therapy.Using a prospectively maintained endometrial cancer database, 1735 patients treated between 1993 and 2008 were analyzed. Characteristics known to predict OS were collected. For each patient, points were assigned to each of these 5 variables. A total score was calculated. The association between each predictor and the outcome was assessed by multivariable modeling. The corresponding 3-year OS probabilities were then determined from the nomogram.The median age was 62 years (range, 25-96). Final grade included: G1 (471), G2 (622), G3 (634), and missing (8). Stage included: IA (501), IB (590), IC (141), IIA (36), IIB (75), IIIA (116), IIIB (6), IIIC (135), IVA (7), and IVB (128). Histology included: adenocarcinoma (1376), carcinosarcoma (100), clear cell (62), and serous (197). Median follow-up for survivors was 29.2 months (0-162.2 months). Concordance probability estimator for the nomogram is 0.746+/-0.011.We developed a nomogram based on 5 easily available clinical characteristics to predict OS with a high concordance probability. This nomogram incorporates other individualized patient variables beyond FIGO stage to more accurately predict outcome. This new tool may be useful to clinicians in assessing patient risk when deciding on follow-up strategies.