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ObjectiveThe role and type of adjuvant therapy for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIA grade 1 endometrioid endometrial adenocarcinoma are controversial. This retrospective cohort study aimed to determine associations between adjuvant therapy use and survival among patients with stage IIIA grade 1 endometrial cancer.MethodsPatients who underwent primary surgery for stage IIIA (FIGO 2009 staging) grade 1 endometrial cancer between January 2004 and December 2016 were identified in the National Cancer Database. Demographics and receipt of adjuvant therapy were compared. Overall survival was analyzed using Kaplan–Meier curves, log-rank test, and multivariable Cox proportional hazard models.ResultsOf 1120 patients, 248 (22.1%) received no adjuvant treatment, 286 (25.5%) received chemotherapy alone, 201 (18.0%) radiation alone, and 385 (34.4%) chemotherapy and radiation. Five-year overall survival rate was 83.0% (95% CI 80.1% to 85.6%). Older age, increasing comorbidity count, and lymphovascular space invasion status were significant negative predictors of survival. Over time, there was an increasing rate of chemotherapy (45.4% in 2004–2009 vs 69.2% in 2010–2016; pConclusionsThe use of adjuvant chemotherapy for the treatment of stage IIIA grade 1 endometrial cancer increased over time and was associated with improved overall survival compared with radiation alone or chemoradiation. Patients with lymphovascular space invasion may benefit from combination therapy.

The 2018 publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial changed the surgical paradigm for women with early-stage cervical cancer. The study randomized 631 women with stage IA1 (with lymphovascular space invasion), IA2, and IB1 cervical cancer to minimally invasive or

Clinicopathologic risk factors previously were a guide to the indication for adjuvant treatment in early-stage endometrial cancer until the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines introduced

BackgroundAdjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial.ObjectiveTo determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes.MethodsA multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis.Results405 patients were included with the median age of 67 years (range 27–92, IQR 59–73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, pConclusionAdjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

ObjectiveSentinel lymph node (SLN) biopsy aims to assess lymph node status with reduced surgical morbidity. The aim of the study was to determine the accuracy and safety of SLN biopsy in the management of early cervical carcinoma using a double technique (technetium-99m (Tc-99m) nanocolloid and methylene blue dye injection).MethodsThis was a 10-year study from January 2009 to January 2019 that recruited 103 consecutive women undergoing surgery for early cervical carcinoma, FIGO 2009 stage IA1 (grade 3, and grade 2 with lymphovascular space invasion) to IB1 (ResultsAt least one SLN was detected in all 103 patients, using at least one of the combined methods (Tc-99m nanocolloid or blue dye). Bilaterally SLN were removed in 85/103 women with an 83% bilateral detection rate. The median SLN count was 2.3 (range 1–6) nodes. Of 103 patients, 7 (6.7%) patients had lymph node involvement. There were no pelvic or para-aortic lymph node recurrences with a median follow-up of 53 (range 8–120) months. The specificity and negative predictive value of a negative SLN was 100%. None of our 103 patients reported lower extremity lymphedema.ConclusionIn carefully selected patients with early cervical carcinoma, SLN biopsy alone appears to be a safe method for lymph node assessment of women undergoing surgical staging. Ultrastaging is an essential part of histologic examination of SLN.

IntroductionSentinel lymph node (SLN) dissection has been recognized as a valid tool for staging in patients with endometrial cancer. Several factors are predictors of recurrence and survival in endometrial cancer, including positive lymphovascular space invasion. The aim of this study is to formulate a pre-operative score that, in the event of no-SLN identification, may give an estimate of the true probability of lymphovascular space invasion and guide management.MethodologyThis was a multi-institutional retrospective study conducted from January 2007 to December 2017. We included all patients with any grade endometrial tumor with a complete pathological description of the surgical specimen and with a minimum follow-up of 12 months. All patients underwent a class A hysterectomy according to Querleu and Morrow and bilateral salpingo-oophorectomy. Lymphadenectomy was performed based on patient risk of node metastases. In order to verify the predictive capacity of the parameters associated with lymphovascular space invasion status, grading, abnormal CA125 (>35 units/ml), myometrial invasion, and tumor size, a synthetic score was calculated. The score was introduced in the receiver operating characteristic curve model in which the binary classifier was represented by the lymphovascular space invasion status. The ideal cut-off was calculated with the determination of the Youden index. Sensitivity and negative predictive value of lymphovascular space invasion score was calculated in patients with lymph node metastasis.ResultsSix hundred and fourteen patients were included in the study. The average age and BMI of patients were 64.8 (range 33–88) years and 30.1 (range 17–64) respectively. Of the 284 patients who underwent lymphadenectomy, 231 (81.3%) patients had no lymph node metastases, 33 (11.6%) patients had metastatic pelvic lymph nodes, 12 (4.2%) patients had metastatic aortic lymph nodes, and eight (2.8%) patients had both pelvic and aortic metastatic lymph nodes. Lymphovascular space invasion was associated with deep myometrial infiltration (PConclusionWe found that when lymphovascular space invasion score ≤4, there is a very low possibility of finding lymph nodal involvement. The preoperative lymphovascular space invasion score could complement the SLN algorithm to avoid unnecessary lymphadenectomies.

The role of pelvic sentinel lymph node dissection (SLND) is increasing in oncological pelvic surgery, especially in the management of cervical and endometrial cancer.SLND using indocyanine green (ICG) is safe and effective, and its sensitivity is higher than with other detection methods. The advantages of ICG are its low toxicity, its confinement within the vascular compartment, its rapid excretion, and the rarity of allergic reaction. These advantages confer to this fluorescent dye a superiority over blue, which can cause anaphylactic reactions. Using ICG does not require advance planning involving nuclear protection and delayed surgery, as are mandatory when using 99Tc detection. ICG allows the surgeon to visualize the lymph nodes through the peritoneum and thus avoid wide dissection.According to European guidelines,1 the indications for SLND in cervical cancer are for patients with FIGO (International Federation of Gynecology and Obstetrics) IA1–IA2 disease, lymphovascular space involvement - positive status, without systematic pelvic lymphadenectomy – and patients with FIGO IB1–IIA1 disease, prior to systematic pelvic lymphadenectomy. Guidelines1 2 for endometrial cancer management state that SLND is indicated in cases of low-risk endometrial cancer (FIGO IA, grade 1–2), without systematic lymphadenectomy in cases of non-detection, with the technique being preferable to systematic lymphadenectomy in cases of intermediate-risk endometrial cancer (FIGO IB, grade 1–2, or FIGO IA, grade 3).2 Our objective is to review the technique of ICG injection and the real-time detection of pelvic SLNs using near-infrared imaging by means of a step-by-step explanation of the procedure using an instructional Video 1.

ObjectiveThe purpose of this study was to assess the prognostic significance of lymphovascular space invasion in women with low-risk endometrial cancer.MethodsA dual-institutional, retrospective department database review was performed to identify patients with ‘low-risk endometrial cancer’ (patients having ResultsWe identified 912 women with low-risk endometrial cancer; 53 patients (5.8%) had lymphovascular space invasion. When compared with lymphovascular space invasion-negative patients, lymphovascular space invasion-positive patients were more likely to have post-operative grade 2 disease (pConclusionsAge ≥60 years and positive lymphovascular space invasion status appear to be important prognostic parameters in patients with low-risk endometrial cancer who have undergone complete surgical staging procedures including pelvic and para-aortic lymphadenectomy. Lymphovascular space invasion seems to be associated with an adverse prognosis in women with low-risk endometrial cancer; this merits further assessment on a larger scale with standardization of the lymphovascular space invasion in terms of presence/absence and quantity.

ObjectiveThe role of lymphadenectomy in intermediate risk endometrial cancer remains uncertain. We evaluated the impact of lymphadenectomy on overall survival and relapse-free survival for patients with intermediate risk endometrial cancer.MethodsWe retrospectively reviewed patients from the FRANCOGYN database with intermediate risk endometrial cancer, based on pre-operative and post-operative criteria (type 1, grade 1–2 tumors with deep (> 50%) myometrial invasion and no lymphovascular space invasion), who received primary surgical treatment between November 2002 and August 2013. We compared overall survival and relapse-free survival between staged and unstaged patients.ResultsFrom 1235 screened patients, we selected 108 patients with intermediate risk endometrial cancer. Eighty-two (75.9%) patients underwent nodal staging (consisting of pelvic +/- para-aortic lymphadenectomy). Among them, 35 (32.4%) had lymph node disease. The median follow-up was 25 months (range 0.4 to 155.0). The overall survival rates were 82.5% for patients staged (CI 64.2 to 91.9) vs 77.9 % for unstaged patients (CI 35.4 to 94.2) (P = 0.73). The relapse-free survival rates were 68.9% for staged patients (CI 51.2 to 81.3) vs 68.8% for unstaged patients (CI 29.1 to 89.3) (P=0.67).ConclusionSystematic nodal staging does not appear to improve overall survival and relapse-free survival for patients with IR EC but could provide information to tailor adjuvant therapy. Sentinel lymph node dissection may be an effective and less invasive alternative staging technique and should provide a future alternative for this population.

Objective The requirement for and extent of lymphadenectomy in endometrial cancer is still controversial. Clinicopathological prognostic factors could be helpful to predict lymph node involvement and avoid therefore unnecessary lymphadenectomy. The aim of this study was to investigate which factors can predict lymph node involvement and how lymph node metastases are distributed in the pelvic and para-aortic regions. Methods This retrospective analysis was performed by analyzing data from patients with endometrial cancer treated with standard surgery and lymphadenectomy at the Department of Gynecology and Obstetrics of the University Hospital Ulm in 2000 to 2013. Results One hundred twenty-five patients received pelvic lymphadenectomy with a median of 25 removed nodes, and 111 patients additionally received para-aortic lymphadenectomy with a median of 12 removed nodes. Metastatic lymph nodes were found in 24.8% of the patients, and a multivariate logistic regression showed that lymphovascular space invasion, histological type, and tumor stage significantly and independently predicted lymph node involvement. Of the 111 patients with both pelvic and para-aortic lymphadenectomy, 18 (16.2%) patients had metastatic para-aortic nodes, and 3 (2.7%) patients had isolated positive para-aortic lymph nodes without involvement of pelvic lymph nodes. Discussion Lymphovascular space invasion, histological type, and tumor stage are significant predictors of lymph node involvement in endometrial cancer. In patients at high risk of nodal involvement, lymphadenectomy should be performed systematically up to the renal vein. Large and carefully designed prospective studies are needed to evaluate patient cohorts for which a complete lymphadenectomy provides a survival benefit. In the future, the increasing use of sentinel node biopsy may facilitate a more personalized treatment of patients with endometrial cancer.

ObjectiveThe aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer.Methods/MaterialsPreoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters.ResultsReceiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P < 0.001). Addition of TVR to standard radiologic assessment of deep MI increased the sensitivity from 90.5% to 95.2%.ConclusionsTumor volume ratio, based on preoperative MR volumetry, seems to predict deep MI independently in stage I endometrial cancer with insufficient sensitivity and specificity. Its value in clinical practice for risk stratification models in endometrial cancer has to be studied in larger cohort of patients.

ObjectiveThe aim of this study was to compare Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination in patients with endometrial cancer (EC).MethodsA total of 904 patients with EC underwent surgical treatment between 2004 and 2016 at Hacettepe University Hospital, and clinicopathological data of patients were retrieved from the computerized database of the Hacettepe University. Patients who did not undergo lymphadenectomy and who had nonendometrioid histology, stage-IV disease, and synchronous epithelial ovarian and EC were excluded. All slides of the cases were reviewed by the same gynecologic pathology subspecialist.ResultsThe study group consisted of 307 consecutive patients with a mean age of 59.4 years (range, 26–86 years). Lymph node metastasis was detected in 28 subjects (9.1%). Primary tumor diameter, depth of myometrial invasion, lymphovascular space invasion, and cervical stromal and glandular involvement were associated with lymph node metastasis. Patients with low-risk histological features based on Mayo risk stratification system in our study group had a 0% rate of lymph node positivity. However, of the 28 patients with lymph node metastasis, 3 (10.7%) had low-risk features based on Milwaukee model. The sensitivity, specificity, false negative rate (FNR) and false positive rate of Mayo and Milwaukee risk stratification models for predicting lymphatic dissemination among women with endometrioid EC were 100%, 27.3%, 0%, and 72.7%; and 89.3%, 61.3%, 10.7%, and 38.7%, respectively.ConclusionsAlthough Milwaukee risk stratification model had a lower false positive rate and can decrease the number of lymphadenectomies, FNR of this new model was found as 10.7% in the present study. Furthermore, we found that Mayo model had a lower FNR and higher sensitivity. Therefore, Mayo model still looks more beneficial to predict lymph node metastasis in patients with endometrioid EC and Milwaukee risk stratification model still requires external validation.

AimThe aim of this study was to evaluate whether adenomyosis had an effect on myometrial tumor invasion, stage of the disease, and survival in endometrial cancer.MethodsEndometrial cancer patients encountered between 2007 and 2016 were identified from pathology records. Patients who underwent suboptimal surgical or medical treatment or with insufficient clinical or surgical data were excluded. Patients diagnosed as having concurrent adenomyosis constituted the study group. Control group patients were randomly selected in a paired design according to the tumor grades in the study group, and for each tumor grade, 4 times as many as patients were included. Tumor stage, histologic type and grade, myometrial invasion, lymphovascular space invasion, presence and location of the adenomyosis in myometrial wall, distance from endometrial line, tumor in adenomyosis, adjuvant treatment, and relapse were primary outcomes.Age, body mass index, medical comorbidities, and type of operation were also recorded. Univariate and multivariate Cox proportional hazards regression models were performed for overall survival.ResultsOf those 1242 endometrial cancer patients, 80 with concurrent adenomyosis were identified and compared with 320 patients without adenomyosis following a paired selection based on tumor grade. Higher rates of myometrial invasion, lymphovascular space invasion, tumor diameter, and adjuvant treatments were found in the nonadenomyosis group compared with adenomyosis group (P ≤ 0.001). In patients with adenomyosis, rates of early-stage disease and overall survival were significantly higher compared with the control group (P = 0.001 and 0.01, respectively).ConclusionsOur results showed that adenomyosis is significantly associated with lower stage in endometrial cancer that may suggest a possible limiting effect on endometrial cancer spread. In addition, despite similar rates in disease-free survival and endometrial cancer–related death, overall survival rate was significantly higher in the presence of adenomyosis and might be considered as a good prognostic factor for endometrial cancer.

Objectives The objectives of our study were to demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary cancers of the endometrium and ovary. Methods A retrospective analysis of 43 pathologically proven cases of synchronous primary endometrial and ovarian cancers diagnosed between January 2005 and December 2015 was carried out. Patients with uterine sarcomas, carcinosarcomas, borderline tumors, and nonepithelial tumors of the ovary and patients who received neoadjuvant chemotherapy were excluded from the study. Disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis to determine independent prognostic factors was performed using the Cox regression model. Results Mean age at diagnosis was 48.49 years. The most common presenting symptom was abnormal uterine bleeding in 58.2% of the patients. Nineteen patients (44.2%) were obese, and 13 patients (30.2%) were overweight. Twelve patients (30%) were nulliparous, and 25 (58.2%) were premenopausal; 76.7% of the patients received adjuvant treatment after surgery. Mean follow-up period was 48.9 months. Twelve patients developed recurrence, and 7 patients died of recurrent disease. The 5-year DFS for all patients was 65.13%, and the 5-year OS was 79.75%. The 118-month DFS and 118-month OS were 65.13% and 72.50%, respectively. On multivariate analysis, grade 3 disease for both endometrial and ovarian cancers and presence of lymphovascular space invasion were associated with significantly worse 118-month DFS and OS, respectively. Conclusions Women with synchronous primary endometrial and ovarian cancers are young, nulliparous, obese, and premenopausal and have a favorable overall prognosis. Grade 3 disease at both sites and presence of lymphovascular space invasion are independent prognostic factors for recurrence and survival, respectively.

The study aims to investigate effect of tumor size on lymphatic spread in patients with low-risk endometrial cancer (EC).This study included patients with EC who underwent staging surgery with systematic lymphadenectomy between 2002 and 2015 at the Hacettepe University Hospital. Patients with grade 1 or 2 endometrioid type tumor who had 50% or lower myometrial invasion were included. Patients who had no myometrial invasion or had uterine high-risk features (nonendometrioid histology, grade 3, and deep myometrial invasion) were excluded.The study group consisted of 191 patients, and the mean age of the patients was 57.8 years. Of these patients, 124 (64.9%) had tumor size of more than 2 cm and 67 (35.1%) had tumor size of 2 cm or less. Lymph node metastasis was detected in 12 (9.7%) of the 124 patients with tumor size of more than 2 cm. On the other hand, none of the 67 patients (0%) with tumor size of 2 cm or less was found to have lymphatic involvement. Of the factors analyzed for correlation with lymph node metastasis in patients with low-risk EC, the presence of lymphovascular space invasion (LVSI) and primary tumor size were found to be significant predictors of lymphatic spread in univariate analysis (P0.001 and P = 0.009, respectively). In multivariate analysis, tumor size (odds ratio, 6.86; 95% confidence interval, 1.007-infinite; P0.05) and LVSI (odds ratio, 14.261; 95% confidence interval, 3.4-59.6; P0.001) were 2 independent predictors associated with lymphatic involvement.Our trial supports that tumor size of more than 2 cm and LVSI are 2 independent factors for lymph node metastasis in patients with low-risk EC. Both factors can be used together to select patients with traditional low-risk histologic features who would absolutely benefit from lymph node dissection.

ObjectiveThe aim was to explore the factors associated with parametrial involvement (PI) in patients with stage IB to IIA cervical cancer.Materials and MethodsMedical records of 507 patients were reviewed. Nine factors were analyzed by univariate analysis using χ2 test and multivariate analysis using logistic regression analysis to screen for factors associated with PI.ResultsThere were 46 patients with PI. Result of univariate analysis suggested depth of stromal invasion, lymphovascular space invasion (LVSI), and lymph node metastasis, and uterine involvement was associated with PI (P < 0.05 for all). The multivariate analysis model included factors that could be diagnosed by a cone biopsy, and the result suggested nonsquamous histological type and LVSI was the independent factor of PI. The incidence of PI in the patients with no LVSI and squamous cancer was 6.97%. When the patients with inner 1/3 stromal invasion were stratified into those with squamous cancer and no LVSI, the incidence of PI was 1.17%. The incidence of PI in the patients with LVSI and nonsquamous cancer was 33.33%.ConclusionsThe patients with inner 1/3 stromal invasion, no LVSI, and squamous histological type may be considered for less radical surgery. The patients with nonsquamous histological type and LVSI may be considered for radical hysterectomy including a complete resection of parametrium.

ObjectiveThe prognostic significance of lymphovascular space invasion (LVSI) in patients with early-stage endometrial cancer is not established. We sought to determine if LVSI status in patients with early-stage low-risk endometrial cancer correlates with recurrence and survival.MethodsThe records of all women who underwent hysterectomy for primary treatment of endometrial cancer from January 2006 through January 2011 at 1 academic institution were reviewed. Patients with grade 1 or 2 endometrioid histology, myometrial invasion less than 50%, and disease confined to the uterus (clinical International Federation of Obstetrics and Gynecology stage IA) were analyzed. Fisher exact test and the Wilcoxon rank-sum test were applied to compare patients with and without LVSI. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method.ResultsTwo hundred forty patients met the inclusion criteria. Forty (16.7%) had LVSI. Ninety-one patients (37.9%) underwent lymphadenectomy. Median tumor size was 30 mm in patients with and 26 mm in patients without LVSI (P = 0.150). Thirty patients (12.5%) received adjuvant therapy. Site of recurrence did not differ between patients with and without LVSI. Patients with LVSI were more likely to have myometrial invasion (P < 0.001), postoperative pathologic grade 2 disease (P < 0.001), to undergo lymphadenectomy (P = 0.049) and receive adjuvant therapy (P < 0.001). The 5-year cumulative incidence of recurrence was 3.8% in the no-LVSI group and 14.2% in the LVSI group (P = 0.053). The presence of LVSI was significantly associated with worse RFS (P = 0.002) and OS (P = 0.013).ConclusionsPatients with low-risk endometrial cancer and LVSI have worse RFS and OS despite being more likely to undergo lymphadenectomy and adjuvant therapy.

ObjectiveThe objectives of this study were to analyze the clinicopathologic features of villoglandular adenocarcinoma (VGA) of the uterine cervix, a variant of cervical adenocarcinoma with good prognosis, and to discuss the association of human papillomavirus (HPV) infection with VGA.MethodsA retrospective review of medical records was performed to identify the patients with VGA between 1999 and 2007 at the Samsung Medical Center.ResultsFifteen patients were identified among 171 women diagnosed with adenocarcinoma of the cervix. The median age was 40 years (range, 32–72 years). Four patients were treated by cone biopsy and 10 patients by hysterectomy with or without pelvic lymphadenectomy. Five patients had invasion of more than half of the depth of tumor in the cervix. Lymphovascular space invasion was present in 2 patients, one of whom also had lymph node metastases. Three recurrences were identified during the median follow-up of 64 months (range, 9–149 months). An HPV test was positive in 6 of 7 patients. Of the 6 patients with HPV infection, 2 were positive for HPV type 18, one for HPV type 6, and the remaining 3 were positive for 1 or more types of high-risk HPV.ConclusionsAlthough VGA has been reported to have a favorable prognosis, we observed recurrences in those patients with close margins by the tumor, lymph node metastasis, or advanced stage. Human papillomavirus DNA, mostly HPV types 16 and 18, was associated with VGA. Further studies are warranted on prognostic factors and the pathogenetic role of HPV infections.

Objective This study aimed to evaluate the influence of intrauterine manipulation on the surgical outcome in patients with early-stage endometrial cancer treated with 2 different laparoscopic approaches. Methods In a randomized parallel trial, 110 patients with clinical stage I endometrial cancer were randomly assigned for laparoscopic staging surgery with (group A, 55) or without (group B, 55) the use of a uterine manipulator (RUMI), between June 2009 and June 2011. Two sets of peritoneal washings were obtained, 1 before and 1 after the insertion of the uterine manipulator. Primary end points were the rates of positive cytology and lymphovascular space invasion. Results No difference was detected in patient characteristics between the groups. Mean operative time, estimated blood loss, and postoperative complications were similar between the groups. Group A had a similar incidence of lymphovascular space invasion compared with group B (12.7% vs 9.1%, respectively; P = 0.761). Four patients (7.3%) in group A had positive peritoneal cytology in the initial washing. One of these patients was classified as stage IIIA. One patient in group B was positive in the second washing. The agreement rate between the 2 sets of washings for both groups was 98.2%. During the median follow-up of 19 months, 6 patients had tumor recurrence without significant difference between the groups. Conclusions Despite concerns that the use of uterine manipulators may predispose the spread of early-stage disease, insertion of such uterine-manipulating systems did not increase rate of positive peritoneal cytology or lymphovascular space invasion in this study.

Objective The aim of this study was to assess whether lymphovascular space invasion (LVSI) and nodal status provide adequate prognostic information in comparison with the entire set of traditional prognostic factors in intermediate- and high-risk endometrial cancer patients treated and staged with primary surgery and adjuvant radiotherapy. Methods Three hundred twenty-four previously untreated high-intermediate- and high-risk endometrial cancer patients with FIGO (International Federation of Gynecology and Obstetrics) stage I to IIIC; endometrioid, serous, or clear cell histology; diagnosed between November 1995 and December 2006; who presented to Peter MacCallum Cancer Centre for adjuvant radiotherapy were included in these analyses. All traditionally recognized prognostic factors and newly created 4 pairs of combination of LVSI and nodal status were studied with respect to survival and patterns of failure. Results The median follow-up time was 4.8 years. Five-year failure-free survival for all patients according to FIGO stage I, II, and III were 87.4%, 89.0%, and 62.4 %, respectively. In multivariable analysis for relapse, positive LVSI had a hazard ratio of 4.9 (P = 0.000), which increased to 8.8 (P = 0.004) in the presence of positive nodes. For overall survival, only LVSI was significant, with a hazard ratio of 3.02 (P = 0.003). In particular, in the presence of LVSI and nodes, histological type, grade, and myometrial invasion were not significant prognosticators for relapse or overall survival. Conclusions This model enables the separation of good prognosis patients even among poorly differentiated endometrioid, serous, and clear cell carcinoma patients and can be used in simplifying the staging of endometrial cancer and for selecting patients for high-risk endometrial cancer studies.

Objective: In this study, we aimed to investigate the diagnostic accuracy of preoperative assessment and frozen-section analysis (FSA) in endometrial cancer by comparing postoperative histopathology. Methods: A total of 72 consecutive patients with endometrial cancer were included in this study. Comprehensive surgical staging was performed in all patients. After abdominal hysterectomy, the uterus was investigated for FSA. For preoperative analysis, histological grade and histological subtypes were investigated. In FSA, all the specimens were reviewed for histological subtype, histological grade, depth of myometrial invasion, lymphovascular space invasion (LVI), and cervical involvement. These results were compared with final histopathology. Data were statistically analyzed. Results: The accuracy of preoperative examination was 95.8% (69/72) for histological type and 90% (65/72) for histological grade. In the frozen section, the accuracies of histological grade and subtype were found to be 92% and 98%, respectively. However, histological grade had 43% sensitivity in preoperative and intraoperative assessments. Myometrial invasion and LVI were correctly diagnosed in 93% and 94% of the cases, respectively. The risk assessment was correctly determined in 63 (87%) of 72 patients. Five patients were underclassified, and there was no lymph node invasion in these patients after final histopathology. Lymph node invasion was higher in patients with grade 3 classification, deep myometrial invasion, positive cervical involvement, and LVI. Conclusions: Frozen-section analysis is a feasible method for the management of the patients with endometrial cancer. However, preoperative and intraoperative assessment of histological grade has lower sensitivity in endometrial cancer.

Objective: To evaluate whether tumor vascularity as assessed by 3-dimensional power Doppler angiography (3D-PDA) correlates with some tumor features in cervical cancer. Methods: Clinical, sonographic, and histologic data on 56 women (mean age, 47.8 years; range, 27-81 years) with a diagnosis of carcinoma in the uterine cervix were analyzed. Tumor volume and 3D-PDA indexes (vascularization index, flow index, and vascularization flow index) were calculated in all cases. These data were correlated with some tumoral features such as histologic type, histologic grade, lymphovascular space involvement, lymph node metastases, and tumor stage. Results: Intratumoral blood flow was found in all cases. No correlation was found between tumor volume and 3D-PDA indexes with histologic type, lymphovascular space involvement, and lymph node metastases. Moderately and poorly differentiated tumors and advanced-stage tumors had larger volume and 3D-PDA indexes (P Conclusions: Our data indicate that tumor vascularization as assessed by 3D-PDA correlates with some tumor features in cervical cancer.

The purpose of this study was to analyze prognostic factors for ovarian metastases from primary gastric cancer, helping establish optimal strategy in ameliorating survival for this entity. Clinical data of 68 consecutive patients histologically diagnosed with ovarian metastases from primary gastric cancer were accrued from 1096 cases with female gastric cancer. Metachronous surgery was performed on 36 patients and 32 received synchronous surgery. There were 14 patients treated with surgery alone and 54 with combined modality therapy. After the median follow-up time of 9.1 months, the median survival time (MST) of 12.4 months was observed for all patients. Patients treated with synchronous surgery tended to have an inferior survival compared with those treated with metachronous surgery (MST: 10.9 vs 14.3 months; P = 0.100). Combined modality showed a significantly better MST compared with surgery alone (13.6 vs 7.9 months; P = 0.004). Chemotherapy cycles (more than four or less than or equal to four) were found to have an impact on survival (MST: 14.3 vs 9.4 months; P = 0.031). Peritoneal metastases, lymphovascular involvement, and unilateral ovarian metastasectomy were independent unfavorable prognostic factors. Combined modality therapy as primary therapy resulted in good outcome, and more aggressive chemotherapy (more than four cycles) was accompanied by an improvement in survival. Innovative systemic treatments need to be explored in treatment of peritoneal metastases and lymphovascular involvement. Bilateral oophorectomy was considered when ovarian metastases were histologically diagnosed.

The objective of the study was to compare cyclooxygenase-2 (COX-2) expression in cervical intraepithelial neoplasia III (CIN III) and squamous cell carcinoma (SCC) of the cervix, and its correlation with clinicopathologic factors of SCC with a review of the available literature. This study included 25 patients with CIN III and 67 patients with stage I–IIa SCC. All patients in the SCC group were treated with radical hysterectomy plus pelvic and para-aortic lymphadenectomy and postoperative chemoradiotherapy based on their histopathologic risk factors. Immunohistochemical analysis was performed on paraffin-embedded sections with COX-2 antibody. COX-2 expression in the SCC group was significantly higher than in the CIN III group (55.2% [37/67] vs 24% [6/25]; P= 0.008). Significantly higher expression of COX-2 was observed in patients with lymphovascular space invasion (LVSI) compared to patients without LVSI (61.9% [34/55] vs 33.3% [3/9]; P= 0.02). Additionally, patients with tumor sizes >4 cm had significantly higher COX-2 expression than patients with tumor sizes P= 0.028). There was no significant relationship with respect to COX-2 expression and parametrial involvement, lymph node metastasis, recurrences, and survival. In multivariate analysis, LVSI was the only statistically significant determinant for COX-2 expression (P= 0.024; OR = 2.35; 95% CI = 1.1–4.9). Our results and a review of the literature both suggest that COX-2 expression may have a role in the development and progression of CIN III and it is related to some clinicopathologic variables of cervical carcinoma. Further studies are needed to clarify the role of COX-2 inhibitors in the management of CIN and SCC.

Isolated recurrences of squamous cell vulvar carcinoma treated by surgical re-excision have excellent outcomes. There is a subset of these patients who develop multiple local recurrences that are difficult to manage and have a high risk of dying from their cancers. We reviewed women presenting with vulvar cancer (200 patients) to Massachusetts General Hospital from 1990 to present and identified 12 women with aggressive, locally recurrent squamous cell carcinomas of the vulva. The identified women all had successful primary radical vulvectomy and groin node dissections with negative surgical margins (except patient 2) and lymph nodes with no lympho-vascular space invasion. Seven women had underlying lichen sclerosis. Eight had a history of vulvar intraepithelial neoplasia or persistent carcinoma in situ. Ten patients had greater than three recurrences after primary surgical therapy. One died of recurrent vulvar cancer 10 months after her initial diagnosis. Two patients died after three recurrences. The only unifying clinicopathologic factor among these women was persistent lichen sclerosis and persistent carcinoma in situ. Understanding the underlying mechanisms that predisposed these premalignant lesions to transform into carcinomas will help predict in which women these are likely to re-occur and may help determine which women require more aggressive initial treatment.

The purpose of this study is to evaluate the efficacy of postoperative adjuvant therapy in preventing treatment failure after primary treatment with surgery in early invasive cervical cancer patients associated with the following histopathologic high-risk factors: lymph node metastasis (either macroscopic or microscopic), parametrial extension, lymphovascular permeation and depth of invasionor =10 mm. Postoperative adjuvant concurrent chemoradiotherapy (PCCRT), postoperative adjuvant chemotherapy (PCT), or postoperative adjuvant radiotherapy (PRT) alone was administered to the 80 early invasive cervical cancers with at least one of the high-risk factors. Each of 61 patients received three to six cycles of chemotherapy at intervals of approximately 3 weeks. Twenty three patients were treated with PCCRT, 38 patients were treated with PCT alone, and 19 patients received PRT. The 5-year survival rates of patients with macroscopic lymph node metastasis were 66.7% and 35.7% in PCCRT and PRT, respectively. With microscopic lymph node metastasis, the 5-year survival rates were 83.3%, 60.0%, and 70.1% in PCCRT, PCT, and PRT, respectively. With parametrial extension, the 5-year survival rate was 58.1% in PCCRT. The 5-year survival rates of patients with lymphovascular permeation were 100%, 90.9%, and 66.7% in PCCRT, PCT, and PRT, respectively. With depth of invasionor =10 mm, the 5-year survival rates were 100% and 91.3%, in PCCRT and PCT, respectively. PCCRT appears to be superior to PRT or PCT alone in early invasive cervical cancer patients with histopathologic high-risk factors.

Adhesion molecules such as CD44 play an important role in the metastatic cascade by mediating tumor cell interaction with the endothelium and the subendothelial matrix. As a so-called "lymphocyte homing receptor," CD44 is physiologically involved in migration of circulating lymphocytes to lymphatic tissue. In the present study, we investigated the expression of CD44v3 and v6 in 237 patients with stage IB, N0 cervical carcinoma by means of immunohistochemistry. These results were correlated with the GOG score and other prognostic variables. Median follow-up was 82.6 months (39-110 months). Thirty-nine patients recurred and 35 died from disease within the observation period. In univariate analysis, the GOG score, histologic subtype, and CD44v6 expression were statistically significant predictors for poor overall survival (OS). In multivariate (Cox regression) analysis, the GOG score (40 vs. 40-120, RR: 1.37 (95% CI: 1.10-1.71); 40-120 vs.120, RR: 2.23 (95% CI: 1.28-3.88); P = 0.004), histologic subtype (adenosquamous carcinomas) (RR: 4.56 (95% CI: 1.49-13.92), P = 0.007) and CD44v6 expression (RR: 2.42 (95% CI: 1.14-5.10), P = 0.021) were independent predictors for poor OS. The expression of CD44v3 did not correlate with prognosis. Furthermore we found a strong correlation between CD44v6 expression and lymphovascular space invasion (LVSI) (chi2 = 17.01, P = 0.0001). Tumor expansion into the loco-regional lymphatic system is the preferred way of tumor spread in cervical carcinoma. The strong correlation of CD44v6 with LVSI produces a significant degree of suspicion that cervical carcinoma cells expressing CD44v6 could, by mimicking lymphocytes, exploit their pathways.

This study includes 183 patients with clinical stage I endometrial cancer subjected to peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy and omental biopsy during a 12-year period in a single institution. The factors analyzed were age, menopausal state, cell type, grade, mitotic activity, myometrial invasion, lymphovascular space invasion, cervical involvement, microscopic vaginal metastases, adnexal metastases, peritoneal cytology, presence of concomitant endometrial hyperplasia and lymph node status. The overall incidences of pelvic and para-aortic lymph node metastases were found to be 15.3% (28/183) and 9.3% (17/183), respectively. In five of 17 patients (29.4%) with para-aortic nodal metastases, pelvic nodes were free of tumor. The most significant prognostic factors for positive pelvic and/or para-aortic nodes were found to be the depth of myometrial invasion, grade of tumor and age.