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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 (1.25mg/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/m(2) (range, 18-60 kg/m(2)). 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Lymph node involvement affects prognosis/treatment in endometrial carcinoma patients. We assessed various histological features associated with nodal metastasis in patients with grade I, stage I endometrial endometrioid carcinoma (EEC)., Methods and Results: Eighteen stage I EECs with occult positive lymph nodes and 36 controls were assessed for depth of myoinvasion; microcystic, elongated and fragmented (MELF) pattern of myometrial invasion; lymphovascular invasion (LVI); and epithelial metaplasia. Nodal metastases were subclassified as isolated tumour cells (ITCs; ≤0.2 mm), micrometastasis (>0.2 mm and <2 mm), or macrometastasis (≥2 mm). Node-positive cases had significantly higher rates of LVI (P < 0.001) and MELF invasion (P = 0.003) on univariate analysis. Only LVI was associated significantly with nodal metastasis on multivariate analysis (P = 0.002). Tumours with MELF invasion demonstrated reduced E-cadherin expression. Macrometastases were identified in seven cases (39%) with or without micrometastasis/ITCs. Eight (44%) contained only ITCs. Eleven (61%) had histiocyte-like nodal metastases. Biopsy material from four of six (67%) and five of 17 (29%) cases with and without nodal metastasis showed detached eosinophilic tumour cell buds. Of the former, three were associated with histiocyte-like nodal metastases - a feature absent in biopsies without tumour budding., Conclusions: Lymph nodes from grade I EEC exhibiting cellular budding or LVI should be examined for occult metastases, especially in the form of histiocyte-like cells., (© 2013 John Wiley & Sons Ltd.)

Objective: To describe the learning curve associated with training fellows in completing robotic assisted total laparoscopic hysterectomies., Methods: All patients scheduled to undergo a robotic procedure at our institution from 5/15/07 to 5/22/12 were identified. Fellow participation per procedure was documented. The learning curve of fellows for the time to complete a hysterectomy (from initiation of developing the retroperitoneal space to the completion of the colpotomy) was analyzed., Results: Of the 1754 planned robotic cases, 1626 were completed robotically and 128 were converted to laparotomy. Fifty-seven fellows participated in 99.7% of the cases. Eleven gynecologic oncology fellows completed at least 1 robotic assisted total laparoscopic hysterectomy. From 7/7/08 to 5/21/12, 981 hysterectomies were completed robotically, 254 of these (25.9%) by the 11 fellows. Prior to completing a hysterectomy, the median number of hysterectomies in which a fellow participated was 16 (range, 11-40). Median amount of time for a fellow to complete a hysterectomy decreased from 60 min in 2009 (N=27 cases) to 31 min in 2011 (N=148 cases). Based on the recorded completion times in which the 11 fellows completed a hysterectomy, it required ~33 cases per fellow to be able to perform the hysterectomy and overcome the learning curve., Conclusions: The learning curve associated with hysterectomy requires completion of ~33 cases by the fellow after an initial median experience of 16 cases. Our data suggest that a minimum of 50 total cases is required during fellowship to complete a robotic hysterectomy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Melanomas arising in the vulva and vagina are rare and therefore there is minimal data specific to these malignancies. Data are often extrapolated from other cutaneous melanomas, which may or may not be appropriate. Surgery remains the primary treatment modality at initial diagnosis and in select recurrent cases. Wide local excision of the primary lesion not requiring an exenteration, along with sentinel lymph node (SLN) mapping, should be routinely considered in vulvar melanomas. Local excision and SLN mapping is difficult and often not considered for vaginal melanomas. Primary exenterative procedures should not be routinely offered. In locally advanced cases potentially requiring an exenterative procedure, radiation therapy with or without concurrent immunotherapy is a consideration. The role of adjuvant therapy remains unclear. Surgery or radiation therapy can be considered in recurrent cases. Systemic chemotherapy agents have a modest response rate with associated poor survival outcomes. Novel immunotherapeutic and targeted agents have been reported to improve survival in melanoma and should be considered in cases of vulvovaginal melanoma. All cases should be tested for at least c-KIT and BRAF V600E mutations. Patients with vulvovaginal melanomas should be strongly encouraged to participate in clinical trials.

Objective: 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., Methods: 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 with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells., Results: Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology-13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion., Conclusions: 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., (© 2013.)

Objective: 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., Methods: 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 of <1cm were included. Intraoperative hypothermia was defined as temperature of <36.0 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., Results: Two hundred ninety-seven patients met the inclusion criteria. An intraoperative temperature <36°C was noted in 72.1% of patients, and a temperature <36°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 (P<0.05), 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)., Conclusions: 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., (© 2013.)

Objective: We 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., Methods: We 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 invasionIB. High-grade carcinoma with no myometrial invasionIC. Low-grade carcinoma with half or greater myometrial invasionID. High-grade carcinoma with any myometrial invasion, Results: Data 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., Conclusions: By 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).

Purpose: 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., Methods: 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., Results: 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 (P < 0.001). 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)., Conclusions: 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.

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 62 years. 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To determine if extensive upper abdominal surgery (UAS) affected overall survival (OS) in patients left with ≤ 1 cm but visible residual disease after undergoing primary cytoreductive surgery for ovarian cancer. Our secondary objective was to determine if leaving ≤ 1cm but visible residual throughout the small bowel (SB) conferred a worse prognosis., Methods: All stage IIIB-IV ovarian cancer patients who had visible but ≤ 1 cm residual disease at time of primary cytoreductive surgery from 2001 to 2010 were identified. Extensive UAS procedures and residual SB involvement were recorded., Results: The 219 patients identified with ≤1 cm but visible residual disease had a median OS of 51 months. In this cohort, 127 had extensive UAS performed, and 87 had residual disease involving the SB. Univariate OS analysis was performed. There was no significant difference in OS between patients who did or did not have extensive UAS (45 vs. 52 months, P=0.56), or between patients with or without residual SB disease (45 vs. 51 months, P=0.84). Factors that were significantly associated with OS were age, ASA score, family history, and stage., Conclusions: Patients cytoreduced to ≤ 1 cm but visible residual disease who required UAS did not have a worse OS than those who did not require UAS. OS was similar if residual disease involved the SB or not. For ovarian cancer patients with disease not amenable to complete gross resection, extensive surgery should still be considered to achieve ≤ 1 cm but visible residual disease status, including cases where the residual disease involves the SB., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

Objective: To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment., Methods: Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used., Results: We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0)., Conclusions: The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: Uterine adenosarcomas (AS) are rare tumors composed of malignant stromal and benign epithelial components. We sought to evaluate the role of primary surgery, adjuvant treatments, and salvage therapies for patients with uterine adenosarcomas., Methods: We identified all patients diagnosed with AS from 1990 to 2009 at our institution. Patient demographics, surgical procedures, sites of metastatic disease, and histologic features (e.g., presence of sarcomatous overgrowth, and heterologous elements) were collected. Treatment regimens and survival outcomes were evaluated., Results: Thirty-one patients were evaluable for this study: 19 (61%) received up-front treatment at our institution and 12 (39%) received treatment for recurrent disease. Most of the up-front treated patients (15, 79%) were diagnosed with stage I disease and underwent hysterectomy (100%) with bilateral salpingo-oophorectomy (84%). Of the 19 patients treated at our institution from time of initial diagnosis, 5 (26%) patients recurred (median follow-up, 72.9 months; range, 3-154). In 5 patients with sarcomatous overgrowth (AS+SO), the 2-year progression-free and overall survival rates were both 20% versus 100% for 14 patients without sarcomatous overgrowth. Responses to systemic treatment of measurable disease were observed in patients with and without sarcomatous overgrowth, but no optimal treatment strategy could be identified for either groups., Conclusions: Unlike AS without sarcomatous overgrowth, AS+SO is an aggressive disease with a high recurrence rate. In our series, no optimal adjuvant or systemic treatment strategy was identifiable but standard sarcoma chemotherapy regimens appear to have efficacy in both AS and AS+SO., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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<0.001). The majority of the patients with RH and tumor present in the tubes had Stage I disease (9/16, 56.2%) and Grade 1 tumors (9/16, 56.2%). Four (4/16, 25%) patients had Stage IIIa disease detected by a pelvic wash. Patients with contaminants had a higher body mass index, but the difference was not statistically significant and was possibly due to small numbers. In conclusion, our data demonstrate an association between RH and tubal contamination. The clinical significance of this phenomenon remains to be determined.

Objective: There is an increased awareness of pelvic insufficiency fractures (PIF) as a potential morbidity of pelvic radiotherapy (RT). The purpose of this study was to determine the incidence of PIF and assess prognostic factors, including intensity-modulated RT (IMRT), in gynecologic oncology patients treated with postoperative pelvic RT., Methods: We performed a retrospective review of all patients with endometrial or cervical carcinoma who received postoperative pelvic RT at our institution during 2000-2008. Patients who received definitive or palliative RT were excluded., Results: A total of 222 patients were identified, of whom 11 (5%) developed PIF at a median time of 11.5months (range, 5.5-87.3months) from RT completion. The 5-year actuarial rate was 5.1% (95% CI 3.3-6.9). In patients with osteoporosis, the 5-year rate was 15.6% compared with 2.9% for those without (P=0.01). Similarly, patients who were on prior hormone-replacement therapy (HRT) had a higher rate (14.8% vs 4.1%, P=0.009). The median body-mass index (BMI) for patients who developed PIF was significantly lower than those who didn't (25.9 vs 27.2, P=0.016). The rate of PIF was 4.9% whether patients received IMRT or conventional RT., Conclusions: The 5-year risk of PIF for postoperative pelvic RT in cervical and endometrial cancer is 5.1%. Women with history of osteoporosis, prior HRT, or low BMI need to be counseled about the risk of PIF. The use of IMRT did not decrease PIF, but further studies are needed to determine if a dose/volume relationship exists between RT and PIF., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Current histologic criteria endorsed by World Health Organization for surface epithelial ovarian tumors suffer from less than optimal reproducibility and correlation with clinical outcomes. A modified approach for histologic subclassification of ovarian carcinomas (OCs), proposed by the group of Gilks and colleagues, has been shown to be reproducible and clinically meaningful. We hypothesized that this approach could be validated using a well-annotated, external cohort of OCs with detailed immunophenotypic, genotypic, and clinical data. The cohort comprised 91 patients with low-stage (FIGO stage I/II) OC who underwent primary surgical management at our institution from 1980 to 2000. The clinical and histologic features of this cohort were reported in 2004. In this study we rereviewed the hematoxylin and eosin slides and reassigned histologic type using the criteria proposed by Gilks and colleagues. p53 and Wilms tumor 1 (WT1) expressions were evaluated using standard immunohistochemical techniques on a tissue microarray. Absence of (null) or strong and diffuse p53 staining in >75% of tumor cells (overexpression) was interpreted as aberrant p53 expression, in contrast to the 2004 study in which the "null" result had been interpreted as negative. Direct TP53 gene sequencing of the entire coding region had been performed on all cases with available tissue. Relationships between survival and the following parameters were studied: tumor cell type, histologic grade, stage, p53 and WT1 expression, TP53 mutation, and presence of associated endometriosis. Results were compared with those of the 2004 study, at which time only TP53 mutation was shown to correlate with adverse survival; notably, TP53 mutation did not correlate with p53 expression by immunohistochemical analysis. After review, presence of TP53 mutations, WT1 positivity, and aberrant p53 expression were strongly associated with high-grade serous histology (P=0.0001). Modification of p53 staining assessment revealed strong correlations with TP53 mutation status, which was superior to the positive versus negative approach used previously (P=0.0005). Redefined histologic criteria revealed a stronger association between the high-grade serous type and WT1 positivity (P=0.02). Prolonged 10-year disease-specific and progression-free survival were associated with endometrioid histology (P<0.02; 94%±4% vs. 53%±7% and 96%±4% vs. 50%±7%, respectively). Inferior 10-year disease-specific survival and progression-free survival were associated with high histologic grade (vs. low and intermediate; P<0.01; 54%±7% vs. 89%±6% and 56%±7% vs. 89%±6%, respectively), presence of TP53 mutation (P<0.04; 54%±12% vs. 64%±10% and 34%±12% vs. 70%±6%, respectively), aberrant p53 expression (P<0.02; 35%±12% vs. 75%±7% and 36%±12% vs. 73%±7%, respectively), and absence of associated endometriosis (P=0.01; 48%±9% vs. 80%±6% and 51%±9% vs. 80%±6%, respectively). In addition, inferior 10-year PFS was associated with WT1 positivity (P=0.01; 42%±7% vs. 72%±7%) and high substage (IA-IB vs. IC-IIC; P=0.04; 53%±7% vs. 81%±8%). These results validate updated approaches to scoring p53 expression as well as the revised criteria proposed by the group of Gilks and colleagues.

Objective: To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results., Methods: Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal-femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2cm from midline), midline, or lateral ambiguous (LA) if located within 2cm, but not involving the midline., Results: Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors., Conclusion: The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate the significance of parenchymal splenic metastasis (PSM) in ovarian (OC), fallopian tube (FTC), and primary peritoneal cancer (PPC)., Methods: All patients with stage IIIB-IV OC, FTC, and PPC undergoing primary cytoreduction from 2001 to 2010 at our institution were identified. In patients undergoing splenectomy, pathology was reviewed for the presence of PSM. Multivariate Cox regression and Kaplan-Meier survival analysis were used to evaluate factors associated with overall survival (OS)., Results: Of 576 patients identified, stage was: IIIB - 23 (4%), IIIC - 468 (81.2%), and IV - 85 (14.8%). Optimal cytoreduction was achieved in 430 patients (74.7%), including 85 of 97 patients (87.6%) undergoing splenectomy. PSM was identified in 20 patients (20.6%) undergoing splenectomy, including 3 of 5 patients (60%) with radiographically identified parenchymal liver metastases and 17 of 92 patients (18.5%) without such radiographic findings (P=0.059). Age, preoperative albumin, residual disease, stage, bulky upper abdominal disease, IP chemotherapy, and PSM were associated with OS on univariate analysis. Splenectomy was not associated with survival. Age, preoperative albumin, residual disease, stage, and PSM (HR=0.46; 95% CI, 0.27-0.77) were associated with OS on multivariate analysis. In the subset of patients undergoing splenectomy, OS was lower for patients with PSM versus those without PSM (28.5 v 51.2months, P=0.004)., Conclusions: PSM is independently associated with decreased OS in patients with advanced OC, FTC, and PPC. PSM occurs in the setting of other evidence of hematogenously disseminated disease, but also occurs outside this setting. PSM should be considered a criterion for stage IV disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer., Patients and Methods: Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed., Results: In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%)., Conclusion: Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.

Purpose: 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., Methods: 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., Results: 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%)., Conclusion: 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To estimate the incidence of postoperative venous thromboembolism among patients undergoing minimally invasive surgery for endometrial cancer, and to characterize risk factors associated with the development of venous thromboembolism., Methods: Patients with newly diagnosed endometrial cancer who were scheduled to undergo a planned minimally invasive surgery procedure from May 1, 2007 to December 31, 2010 were identified. The incidence of symptomatic postoperative venous thromboembolism was estimated in the patients who did not require conversion to laparotomy. Various clinicopathologic variables were tested for an association with the development of a postoperative venous thromboembolism using standard statistical tests., Results: A total of 573 cases were identified. Postoperative low molecular weight heparin was administered to 125 (22%) patients during their immediate postoperative hospital stay. All patients had sequential compression devices placed intraoperatively. Seven (1.2%) patients had development of a symptomatic venous thromboembolism. The factors associated with development of a postoperative venous thromboembolism were: body mass index (BMI) (P=.005); estimated blood loss (P=.03); and operative time (P=.01). A high-risk group was determined to be patients with BMIs of 40 or higher and an operative time of 180 minutes or more. In this group, the incidence of venous thromboembolism was 9.5% (4 of 42) compared with 0.6% (3 of 531) in all others (P=.001)., Conclusion: The incidence of venous thromboembolism in patients with newly diagnosed endometrial cancer undergoing minimally invasive surgery is very low. There appears to be no clear justification for the routine use of a heparin for perioperative thromboprophylaxis in the majority of these patients. Thromboprophylaxis with heparin, however, may be a consideration in morbidly obese patients (BMI of 40 or higher) after a procedure that lasts 3 hours or more., Level of Evidence: II.

Objectives: High grade undifferentiated uterine sarcomas (HGUS) are rare, aggressive malignancies. Data regarding management are limited. We aimed to describe disease stage, response to treatment, and survival outcomes among patients with HGUS at our institution., Methods: We identified all patients with HGUS who received treatment at our institution from 1/2000 to 3/2011. Demographics, surgical procedures, disease stage, treatment response, and survival outcomes were abstracted from the medical records., Results: Twenty-one patients were identified. FIGO 2008 stage distribution was: I-7 (33%), II-1 (5%), III-2 (10%), IV-11 (52%). Eighteen of 21 patients (86%) undergoing primary surgical resection achieved a complete gross resection; however, progression within the abdominal cavity was identified in 11 patients (61%) by the time they underwent postoperative imaging. Of 13 patients who received first-line chemotherapy for measurable disease, the overall response rate was 62%. Responses were observed in patients treated with gemcitabine/docetaxel (6 of 8) and doxorubicin-based regimens (2 of 5). Progression-free and overall survivals for the entire cohort were 7.3 months and 11.8 months, respectively. In 14 patients with measurable disease at the time of treatment, 1-year survival was 35.7% versus 80% in 5 patients without measurable disease at time of treatment (P=0.112). Nine patients received second- or additional chemotherapy for progressive disease, with response rate of 19%. Time to progression was short among responders., Conclusions: HGUS represents a distinct histologic subtype of uterine sarcoma with poor outcomes regardless of stage at diagnosis. A majority rapidly develops distant metastases despite surgical resection. Gemcitabine-docetaxel and doxorubicin-based treatment achieved objective, but short-lived, responses in patients with measurable disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The robotic surgical platform is increasingly used in gynecology and, similar to laparoscopy, it has risks of electrocautery-associated injury., Case: We present three cases of injury caused by failures of the monopolar scissors' insulating sheath while coagulation and cutting currents were set at 35 W. In case 1, an external iliac vein injury required blood transfusion and emergent laparotomy. In case 2, a full-thickness external iliac artery injury was repaired robotically. In case 3, a partial-thickness external iliac artery injury also was repaired robotically., Conclusion: Unintended electrosurgical arcs can occur from monopolar instruments. Insulation failure is a common finding in this type of injury. Surgeons should avoid excessive instrument collisions and should change the monopolar scissors' insulating sheath if there are any concerns of a defect in its integrity.

Objectives: To evaluate the impact of operative start time (OST) on surgical outcomes in patients with advanced ovarian cancer., Methods: All stage IIIB-IV serous ovarian cancer patients who underwent primary surgery at our institution from 1/01 to 1/10 were identified. Fourteen factors were evaluated for an association with surgical outcomes including OST and OR tumor index (1 point each for carcinomatosis and/or bulky [≥ 1 cm] upper abdominal disease). Univariate logistic regression considering within-surgeon clustering was performed for cytoreduction to ≤ 1 cm versus >1cm residual disease. In patients with ≤ 1 cm residual disease, univariate logistic regression considering within-surgeon clustering was performed for 1-10mm residual disease versus complete gross resection (CGR, 0mm residual). A multivariate logistic model was developed based on univariate analysis results in the ≤ 1 cm residual disease cohort., Results: Of 422 patients, residual disease was: 0mm, 144 (34.1%); 1-10mm, 175 (41.5%); >10mm, 103 (23.3%). OST was not associated with cytoreduction to ≤ 1 cm residual disease on univariate analysis. In the ≤ 1 cm residual disease cohort, albumin, CA-125, ascites, ASA score, stage, OR tumor index, and OST were associated with CGR on univariate analysis. Earlier OSTs were associated with increased rates of CGR. On multivariate analysis, CA-125 was independently associated with CGR. OST was associated with CGR in patients with an OR tumor index of 2 but not an OR tumor index<2., Conclusions: OST was not associated with cytoreduction to ≤ 1 cm residual disease in patients with advanced serous ovarian cancer. In the cohort of patients with ≤ 1 cm residual disease, later OSTs were associated with reduced rates of CGR in patients with greater tumor burden., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 134 months, 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To report the reproductive outcomes of patients undergoing fertility-preserving radical trachelectomy (RT) for the treatment of early-stage cervical cancer., Methods: We analyzed data from our institution's first 105 patients who underwent attempted fertility-sparing surgery with radical trachelectomy, pelvic lymphadenectomy, and cerclage from November 2001 to October 2010., Results: Of the 105 patients who underwent attempted RT, 77 (73%) did not require a conversion to radical hysterectomy or postoperative treatment. The median age was 32 (range, 25-38 years). Most patients (75%) had stage IB1 disease. Sixty-six patients (63%) were nulliparous. Thirty-five women were actively attempting conception 6 months after surgery, and 23 (66%) women were successful in conceiving: there were 20 live births, 3 elective terminations, and 4 spontaneous miscarriages. Four patients had 2 pregnancies each; all delivered their second pregnancy between 32 and 36 weeks. Cerclage erosion through the vaginal wall occurred in 6 cases and was treated by transvaginal removal of protruding suture material. One of these patients experienced a second trimester miscarriage., Conclusions: The majority of women who attempted to conceive after radical trachelectomy were successful, and most of their pregnancies resulted in full-term births. Assisted reproduction played an important role in select women. Cerclage likely contributed to a post-trachelectomy uterine ability to carry a pregnancy to the third trimester. The second post-trachelectomy pregnancy appears to be at higher risk for preterm delivery than the first pregnancy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess the introduction of computer-based surgery (ie, robotic surgery [RBT]) in the treatment of patients with newly diagnosed uterine cancer., Methods: 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., Results: 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 (P<0.001). 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 (P<0.001). The median total room and operative times were longer for RBT cases (P<0.001), mainly due to cases in which the surgeon had less than ~40 RBT cases of experience., Conclusions: 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 54 years (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 9.7 months (range, 6.7-10.9) and 20.2 months (range, 15.5-24.8), respectively. All 8 non-surgical cases died within 30 months of diagnosis. Median PFS was 14.2 months (range, 11.4-16.9) for those with a complete gross resection versus 6.8 months (range, 4.1-9.5) for those with any residual disease (P=0.002). Median OS was 31.9 months (range, 3.3-60.4) versus 20.2 months (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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 16.9 months for ER(-) cases (95% CI: 8.1-25.7; P=0.03) and 13.5 months 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The clinical course of patients with uterine leiomyosarcoma (LMS) is difficult to predict with the currently available categorical staging systems of the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). The objective of the current study was to develop and validate a novel, clinically relevant, individualized prognostic model for patients with uterine LMS., Methods: Patients with uterine LMS who presented at the authors' institution from 1982 to 2008 were analyzed. The nomogram model was chosen based on the clinical evidence and statistical significance of the predictors, including age at diagnosis, tumor size, histologic grade, uterine cervix involvement, extrauterine spread, distant metastases, and mitotic index. Five-year overall survival (OS) was the predicted endpoint. The concordance probability (CP) was used as a predictive accuracy measure and compared with the CP of current staging systems. The model was internally validated using 200 bootstrap samples to correct for over fitting., Results: One hundred eighty-five of 270 patients were eligible for the nomogram analysis. The median follow-up was 5.4 years, and the median OS was 3.75 years (95% confidence interval, 3-6 years). The CP of the newly developed nomogram was 0.67 (95% confidence interval, 0.63-0.72). This was superior to predictions based on AJCC and FIGO staging. The bootstrap-validated CP was 0.65 with good calibration accuracy., Conclusions: The authors developed and internally validated a uterine LMS-specific nomogram to predict 5-year OS. This novel, individualized prognostic model outperforms traditionally used categorical staging systems and may be useful for patient counseling and for better selection of patients for adjuvant therapy trials., (Copyright © 2011 American Cancer Society.)

Objectives: 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., Methods: 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., Results: 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 (P<0.0001). 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 (P<0.001). On multivariate analysis, only complete gross resection and the ability to receive adjuvant therapy were independently associated with OS., Conclusions: Cytoreductive surgery, with a goal of achieving a complete gross resection, is associated with an improvement in OS among patients with advanced uterine CS., (Copyright © 2011. Published by Elsevier Inc.)

Purpose: The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of the anti-EGFR antibody cetuximab, in persistent or recurrent carcinoma of the cervix., Patients and Methods: Eligible patients had cervical cancer, measurable disease, and GOG performance status ≤2. Treatment consisted of cetuximab 400 mg/m(2) initial dose followed by 250 mg/m(2) weekly until disease progression or prohibitive toxicity. The primary endpoints were progression-free survival (PFS) at 6 months and response. The study used a 2-stage group sequential design., Results: Thirty-eight patients were entered with 3 exclusions, leaving 35 evaluable for analysis. Thirty-one patients (88.6%) received prior radiation as well as either 1 (n=25, 71.4%) or 2 (n=10) prior cytotoxic regimens. Twenty-four patients (68.6%) had a squamous cell carcinoma. Grade 3 adverse events possibly related to cetuximab included dermatologic (n=5), GI (n=4), anemia (n=2), constitutional (n=3), infection (n=2), vascular (n=2), pain (n=2), and pulmonary, neurological, vomiting and metabolic (n=1 each). No clinical responses were detected. Five patients (14.3%; two-sided 90% CI, 5.8% to 30%) survived without progression for at least 6 months. The median PFS and overall survival (OS) times were 1.97 and 6.7 months, respectively. In this study, all patients with PFS at 6 months harbored tumors with squamous cell histology., Conclusion: Cetuximab is well tolerated but has limited activity in this population. Cetuximab activity may be limited to patients with squamous cell histology., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the role of surgical cytoreduction and the amount of residual disease in patients with newly diagnosed stage IV endometrioid endometrial carcinoma (EC)., Methods: Patients with stage IV EC of endometrioid histology who underwent surgery at our institution from 1977 to 2003 were identified. Patients with microscopic stage IV disease were excluded. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier method and compared with log-rank test., Results: A total of 58 patients were identified, of which 9 (15.5%) had no gross residual (NGR) after surgery, 11 (19.0%) had residual disease ≤1 cm, 32 (55.1%) had residual disease >1 cm, and 6 (10.3%) had no cytoreduction attempted. The median PFS was 11.1 months (95% CI, 9.8-12.3) and the median OS was 19.2 months (95% CI, 8.5-29.9) for the cohort. The median PFS was 40.3 months (95% CI, 0-93.9) for patients with NGR disease, 11 months (95% CI, 9.9-12.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients who did not have attempted cytoreduction (P<0.001). The median OS was 42.2 months (95% CI, not estimable) for patients with NGR disease, 19 months (95% CI, 13.9-24.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients that did not have attempted cytoreduction (P<0.001)., Conclusion: Though stage IV endometrioid EC has a poor prognosis, surgical cytoreduction to no gross residual disease in a highly select group of patients is associated with improved survival., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To determine the incidence of adnexal and lymph node (LN) metastasis in newly diagnosed endometrial stromal sarcoma (ESS)., Methods: We identified all cases with a diagnosis of ESS evaluated at our institution from January 1, 1980 to October 31, 2009. All uterine pathology was reviewed at our center. High-grade or undifferentiated tumors and ESS arising in extrauterine sites were excluded. Pertinent clinical data were abstracted from electronic medical records. Appropriate statistical tests were performed using SPSS16.0., Results: We identified 94 cases of ESS. LN metastasis was identified in 7 (19%) of 36 patients who underwent LN evaluation. Six of the 7 cases with LN metastasis had lymphovascular invasion (LVI). LVI status was not reported in the other case. Five of the 7 patients with LN metastasis had grossly positive LNs with or without other gross extrauterine disease. Of 20 patients with disease grossly limited to the uterus and grossly normal LNs, 2 (10%) had LN metastasis. Both of these cases had LVI and extensive myoinvasion. Eighty-seven cases (93%) underwent salpingo-oophorectomy. Adnexal metastasis was identified in 11 (13%) of 87 cases, all manifested by gross adnexal tumor and occurring in patients with other gross pelvic extrauterine disease., Conclusion: The incidence of LN metastasis in ESS is commonly associated with gross extrauterine disease, extensive myoinvasion, and LVI. Since myoinvasion and LVI status often are not assessable at the time of hysterectomy, LN dissection remains a reasonable option at primary surgery. The rate of adnexal metastasis appears to be negligible in the absence of gross adnexal and extrauterine tumor., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: The revised 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer included many changes over the 1988 system, particularly for stage I subgroups. We sought to describe the overall survival (OS) of women with stage I endometrial cancer and examine how the estimated stage-specific OS is altered in the 2009 system., Methods: A prospectively maintained institutional endometrial database was analyzed. All patients underwent primary surgery between January 1993 and June 2009., Results: Data from 1658 women were analyzed, including 1307 patients with FIGO 1988 stage I disease. The 5-year OS for the 1988 stages IA (92.4%), IB (87.3%), and IC (75.7%) significantly differed (P < 0.001). When patients were restaged using the 2009 system, we identified 1411 stage I patients with 5-year OS for 2009 stage IA of 89.2%, versus OS of 75.1% for IB (P = 0.001). The adjusted concordance probabilities for the 1988 stage I group and 2009 stage I group were 0.612 (SD, 0.0014) and 0.536 (SD, 0.0111), respectively., Conclusions: The 1988 FIGO classification of stage I endometrial cancer correctly identified 3 subgroups of patients who had significantly different OS. Specifically, 1988 FIGO stages IA and IB had distinct oncologic outcomes. The revised 2009 system eliminates the most favorable group from the new classification system, and estimates of stage-specific OS for stage IB are substantially altered by the changes made in 2009. The revised system for stage I did not improve its predictive ability over the 1988 system. These data highlight the importance of developing individualized risk-prediction models and nomograms in endometrial cancer.

This article focuses on the most important neoplastic epithelial lesions of the uterus, endometrial hyperplasia and carcinoma. The primary management of hyperplastic lesions and carcinoma is often surgical but nonsurgical options are possible for both, depending on specific patients and tumor characteristics. Many controversies still exist regarding the optimal medical and surgical treatments of hyperplasias and carcinomas of the endometrium. There is a need to more accurately select patients for lymph node sampling or dissection. The role of adjuvant therapies for endometrial carcinomas is still under investigation. This review covers current understanding in the diagnosis and clinical management of endometrial hyperplasias and carcinomas., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the incidence and risk factors for ventral hernia development following primary laparotomy for ovarian, fallopian tube, and peritoneal cancers., Methods: All patients who underwent primary laparotomy for ovarian, tubal, or peritoneal cancer from 3/05 to 12/07 were identified. Hernias were identified radiographically or during physical exam. One-year and 2-year hernia rates were calculated. Clinicopathologic factors were evaluated for an association with the development of hernia using univariate and multivariate analysis., Results: We identified 239 cases with 12 months of follow-up. Median age was 60 years (17-89 years), and median body mass index (BMI) was 25.0 kg/m(2) (16.9-58.5 kg/m(2)). Advanced stage disease (FIGO stage III/IV) was diagnosed in 182/239 (76%). The 1-year hernia rate was 8.8% (21/239): 13/21 (61.9%) were symptomatic, and 8/21 (38.1%) underwent hernia repair operations. On multivariate analysis, only BMI (p=0.004) and intraperitoneal (IP) chemotherapy (p=0.016) retained their independent association with hernia development by 12 months. Of the 239 patients, 167 had 24 months of follow-up. The 2-year hernia rate was 23.4% (39/167): 25/39 (64.1%) were symptomatic, and 17/39 (43.6%) underwent hernia repair operations. Multivariate analysis in this group demonstrated that advanced stage (p=0.033), wound complications (p=0.029), and BMI (p=0.012) were independently associated with hernia development by 24 months., Conclusions: The development of ventral hernia is a significant postoperative morbidity in patients undergoing primary surgery for ovarian, tubal, or peritoneal cancer. Independent associations with hernia development include: BMI and IP chemotherapy by Year 1, and BMI, wound complications and advanced stage by Year 2., (Copyright © 2010. Published by Elsevier Inc.)

Objectives: A prior analysis of patients undergoing laparotomy for ovarian malignancies at our institution revealed an increased rate of intra-abdominal collections using HA-CMC film during debulking surgery. The primary objective of the current study was to determine whether the use of HA-CMC is associated with the development of postoperative intra-abdominal collections in patients undergoing laparotomy for uterine or cervical malignancies., Methods: We retrospectively identified all laparotomies performed for these malignancies from 3/1/05 to 12/31/07. We identified cases involving the use of HA-CMC via billing records and operative reports. Intra-abdominal collections were defined as localized intraperitoneal fluid accumulations in the absence of re-accumulating ascites. We noted incidences of intra-abdominal collections, as well as other complications. Appropriate statistical tests were applied using SPSS 15.0., Results: We identified 169 laparotomies in which HA-CMC was used and 347 in which HA-CMC was not used. The following were statistically similar in both cohorts: age, body mass index (BMI), primary site, surgery for recurrent disease, prior intraperitoneal surgery, and extent of current surgery. Intra-abdominal collections were seen in 6 (3.6%) of 169 HA-CMC cases compared to 10 (2.9%) of 347 non-HA-CMC cases (p=0.7). The rate of infected collections was similar in both groups (1.2% vs. 1.4%). In the subgroup that underwent tumor debulking, intra-abdominal collections were seen in 3 (11.5%) of 26 HA-CMC cases compared to 2 (5.4%) of 37 non-HA-CMC cases (p=0.6)., Conclusions: HA-CMC use does not appear to be associated with postoperative intra-abdominal collections in patients undergoing laparotomy for uterine or cervical cancer., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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 30 days of surgery., Results: There were 141 eligible patients, with a median age of 60 years (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 57 months., 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 57 months in a cohort of patients with a large tumor burden, this rate of morbidity and mortality appears acceptable., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: The objective of the study was to identify additional factors that may improve the ability to predict underlying carcinoma risk in patients with complex atypical hyperplasia (CAH) of the uterus., Study Design: All subjects diagnosed with CAH of the uterus on endometrial sampling from March 1994 to May 2008 were identified. CAH was classified as CAH suspicious, CAH polypoid, CAH focal, or CAH not otherwise specified (NOS). Subjects were then exclusively assigned to 1 of 3 categories: CAH suspicious, CAH NOS, or CAH focal and/or polypoid., Results: We identified 197 cases of CAH diagnosed on preoperative endometrial sampling. Carcinoma was subsequently diagnosed in the hysterectomy specimen in 67 subjects (34%). The risk of underlying carcinoma if assigning subjects as CAH suspicious, CAH NOS, or CAH polypoid and/or focal was 56%, 36%, and 20%, respectively (P < .001)., Conclusion: The risk of underlying carcinoma in patients with CAH on preoperative endometrial sampling is associated with the method of sampling and age and can be significantly modified by the nature of pathologic assessment., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objective: Surgical cytoreduction is an integral therapeutic modality for patients with epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) cancer in the primary setting. The role of surgical cytoreduction in the recurrent setting is not clearly defined and remains controversial. The objective of this study was to assess this potential survival benefit in a large cohort of patients with a long follow-up period., Methods: We performed a retrospective chart review of all patients with recurrent EOC, FTC, or PPC who underwent tertiary cytoreduction at our institution from 2/98 to 2/08. Disease-specific survival (DSS) was calculated from the time of tertiary cytoreduction to death or last follow-up. Univariate and multivariate analyses were used to analyze outcomes and to identify potential prognostic factors., Results: A total of 77 patients were identified, of which 38 (49%) have died of disease. The median time from secondary to tertiary cytoreduction was 25.7 months (range, 4.1-99.4 months). The median follow-up after tertiary cytoreduction was 28.9 months (range, 0.7-123.7 months), with a median DSS for the entire cohort of 47.7 months (95% CI, 25.5-69.9 months). On univariate analysis, residual disease after tertiary cytoreduction and TFI were found to be significant prognostic factors. On multivariate analysis, only residual disease after tertiary cytoreduction retained prognostic significance (P<0.001)., Conclusion: Tertiary surgical cytoreduction may offer a survival benefit in a highly select group of patients with recurrent EOC, FTC, or PPC. This benefit appears to be greatest in patients in whom a complete gross resection can be achieved., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to determine posthysterectomy pathologic findings in patients with a preoperative endometrial sampling diagnosis of International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrial adenocarcinoma with a background of complex atypical hyperplasia (CAH)., Study Design: We reviewed 1423 consecutive cases of endometrial cancer to identify cases with a preoperative endometrial biopsy that demonstrated FIGO grade 1 endometrial adenocarcinoma. Final uterine pathologic findings were grouped into low- and high-risk based on FIGO and Gynecologic Oncology Group criteria., Results: We identified 123 cases with a background of CAH and 367 cases without a background of CAH. FIGO grade in the hysterectomy specimen was more than FIGO grade 1 in 11 of 123 cases (8.9%) with a background of CAH, compared with 60 of 359 cases (16.7%) without a background of CAH (P = .04)., Conclusion: An endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma with a background of CAH is more likely to correlate with final posthysterectomy grade than a diagnosis not arising with a background of CAH., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objectives: To assess the utility of thoracoscopy in defining the extent of intrathoracic disease and survival outcomes in patients with moderate to large pleural effusions at the time of diagnosis of advanced ovarian carcinoma., Methods: We reviewed the records of all patients with untreated advanced ovarian carcinoma and moderate to large pleural effusions who underwent video-assisted thoracoscopic surgery (VATS) our institution between 6/01 and 10/08. Demographic, clinicopathologic and outcome data were collected for all patients with a final diagnosis of ovarian carcinoma., Results: Forty-two patients met eligibility criteria, with a median age of 58 years; median CA-125 level of 1747 U/mL; and medium serum albumin of 3.9 g/dl. VATS was performed for right-sided effusions in 30 patients (71%). Macroscopic pleural disease was found in 29 patients (69%). Of the 11 patients with negative cytology, macroscopic pleural disease was found in 4 (36%). Intrathoracic cytoreductive surgery was performed in 6 (33%) of the 18 patients with intrathoracic disease >1 cm. After VATS, 29/42 (69%) patients underwent attempted primary abdominal surgical debulking. Thirteen patients (31%) received neoadjuvant chemotherapy. Twelve (92%) of these patients underwent interval cytoreductive surgery. Patients who were directed after VATS to neoadjuvant chemotherapy instead of primary surgical cytoreduction had a 2-year PFS rate of 22% compared to 42% for the primary cytoreductive group (P=0.36)., Conclusions: Overall, management was altered based on VATS findings in 43% of cases. Further investigation is needed to define the prognostic significance of VATS evaluation of the burden of pleural disease.

Background: Primary, secondary, and possibly tertiary surgical cytoreduction in patients with recurrent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) cancer appears to be associated with a survival benefit. The objective of this study was to assess if cytoreduction of recurrences after tertiary cytoreduction offers any potential benefit in these patients., Methods: We performed a retrospective chart review of all patients with recurrent EOC, FTC, or PPC who underwent additional cytoreductive procedures after a prior tertiary cytoreduction (quaternary cytoreduction) at our institution between 1991 and 2008. Disease-specific survival (DSS) was calculated from the time of quaternary cytoreduction to last follow-up. Univariate analyses were used to analyze outcomes and to identify potential prognostic factors., Results: A total of 15 patients were identified, of which 7 (47%) have died of disease. All patients had undergone prior optimal secondary and tertiary surgical cytoreductive procedures. The size of residual disease varied from 0 (in 10 cases/67%) to >1 cm (in 2 cases, 13%). Residual disease (1 cm) and number of recurrence sites (single vs multiple) were found to be significant prognostic factors on univariate analysis., Conclusions: Cytoreductive surgery beyond tertiary cytoreduction may be a reasonable option in highly select patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, especially in the setting of a single site of recurrent disease.

Objective: Our objective was to analyze the effect of surgical outcome on progression-free survival (PFS) and overall survival (OS) of patients with advanced ovarian carcinoma stratified by the initial presence and volume of upper abdominal disease cephalad to the greater omentum (UAD) found at the time of exploration., Methods: We evaluated all patients with FIGO stage IIIC ovarian carcinoma who underwent primary cytoreduction followed by platinum-based chemotherapy at our institution between January 1989 and December 2006. The effect of surgical outcome was investigated using a time-to-event analysis. A Cox proportional hazards model was fit using clinical, surgical, and postoperative variables., Results: We identified 526 evaluable patients. Optimal versus suboptimal cytoreduction was significantly associated with improved median PFS and OS in patients with no, minimal (1 cm) UAD. On multivariate analysis, patients with bulky UAD who underwent optimal cytoreduction had a 28% decreased risk of relapse (hazard ratio, 0.72; 95% confidence interval: 0.53-0.99; P=0.04) and a 33% decreased risk of death (hazard ratio, 0.67; 95% confidence interval: 0.47-0.96; P=0.03) compared to patients who underwent suboptimal cytoreduction., Conclusion: The presence of large-volume disease found during surgical exploration does not preclude the benefit of optimal cytoreduction. The findings support the management strategy of maximizing surgical efforts with increasing tumor burden in patients with stage IIIC ovarian cancer. Prospective studies are needed to more precisely quantify tumor burden and accurately determine the specific impact of cytoreduction on outcome.