ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis.

Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumor growth directly, but whether it also regulates the host anti-tumor immune response is not known. Here we show that constitutive activation of XBP1 in tumor-associated DCs (tDCs) drives ovarian cancer (OvCa) progression by blunting anti-tumor immunity. XBP1 activation, fueled by lipid peroxidation byproducts, induced a triglyceride biosynthetic program in tDCs leading to abnormal lipid accumulation and subsequent inhibition of tDC capacity to support anti-tumor T cells. Accordingly, DC-specific XBP1 deletion or selective nanoparticle-mediated XBP1 silencing in tDCs restored their immunostimulatory activity in situ and extended survival by evoking protective type 1 anti-tumor responses. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy.

Primary malignant ovarian carcinoid; management and outcomes.

OBJECTIVE: To investigate the clinicopathological characteristics and survival of patients with malignant ovarian carcinoid tumor (OC). MATERIALS AND METHODS: The National Cancer Database was accessed and patients diagnosed between 2004 and 2015 with a OC who did not have a personal history of a tumor at another site were selected. Overall survival (OS) was assessed for patients who had ≥1 month of follow-up. OS rates were estimated following generation of Kaplan-Meier curves and compared with the log-rank test. RESULTS: A total of 588 patients with a median age of 51.5 years were identified. The majority were White (71.6%), had unilateral tumors (94.2%) with a median size of 3.8 cm that were confined to the ovary (88%). Patients with early stage disease (n = 431) had excellent OS compared to those with advanced stage (II-IV) disease (n = 51), p < 0.001; 5-yr OS rates were 95.4% and 53.1% respectively. For patients with stage I disease, there was no difference in OS between those who did (n = 211) and did not (n = 175) have hysterectomy, p = 0.92. For patients with advanced stage disease, administration of adjuvant chemotherapy was not associated with better survival, p = 0.093. CONCLUSIONS: OCs are typically small, unilateral tumors confined to the ovary arising in perimenopausal patients. Survival outcomes are excellent for patients with early stage disease and unilateral salpingo-oophorectomy appears to be curative.

Low-grade serous ovarian cancer: State of the science.

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.

Outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix.

OBJECTIVE: Most studies evaluating the oncologic safety of minimally invasive surgery for endometrial cancer focus on patients with stage I disease. The aim of this study was to investigate the outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix. METHODS: Patients diagnosed between January 2010 and December 2015, with clinical stage II endometrial carcinoma, who underwent hysterectomy with lymphadenectomy, were drawn from the National Cancer Database. Inclusion criteria were clinical International Federation of Gynecology and Obstetrics (FIGO 2009) stage II, patients who underwent hysterectomy with lymphadenectomy, and known route of surgery (open or minimally invasive). Patients who received radiation therapy prior to surgery, those who had subtotal/supracervical hysterectomy, or unknown type of hysterectomy were excluded. The exposure of interest was performance of minimally invasive surgery either laparoscopic or robotic-assisted. Overall survival (primary endpoint) was assessed for patients diagnosed between January 2010 and December 2014 following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for confounders. RESULTS: A total of 2175 patients were identified and 1282 (58.9%) had minimally invasive surgery. Of these, 339 and 943 patients had laparoscopic or robotic-assisted laparoscopic hysterectomy, respectively. Minimally invasive surgery was converted to open surgery in 74 (5.8%) patients. Those undergoing minimally invasive surgery had shorter hospital stay (median 1 vs 3 days, p<0.001), lower unplanned readmission rate (2.7% vs 4.7%, p=0.014), and 90-day mortality (0.8% vs 1.8%, p=0.05). Patients who had open surgery (n=796) had worse overall survival compared with those who had minimally invasive surgery (n=1048, p=0.003); 3-year overall survival rates were 76.8% and 83.6%, respectively. After controlling for patient age, race, type of insurance, presence of co-morbidities, performance of extensive lymphadenectomy, presence of positive lymph nodes, tumor histology, presence of lymphovascular space invasion, tumor size, and administration of radiotherapy, performance of minimally invasive surgery was not associated with worse survival (HR 0.90, 95% CI 0.73 to 1.11). CONCLUSIONS: In this retrospective analysis, minimally invasive surgery in patients with stage II endometrial carcinoma was associated with superior short-term peri-operative outcomes and improved 3-year overall survival.

Is hysterectomy necessary for the treatment of preinvasive stratified mucin producing intraepithelial lesions of the cervix?

OBJECTIVES: Stratified mucin producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical intraepithelial lesion, characterized by histopathologic features resembling those observed in high grade squamous intraepithelial lesions and adenocarcinoma in situ of the cervix. Its hybrid morphology poses a pathologic challenge with no specific management guidelines. The goal of this study was to review the natural history of SMILE and treatment based outcomes. METHODS: A retrospective pathology review of all cases of cervical intraepithelial lesions, with confirmation of all SMILE lesions, at one institution between 2007 and 2019, was performed. Clinical and pathologic characteristics, management options, and patient outcomes were reviewed and analyzed. Inclusion criteria included all patients diagnosed initially with SMILE on biopsy, excisional procedure, or simple hysterectomy. Patients diagnosed with SMILE had to fulfill the following pathologic features: stratified columnar epithelium with nuclear atypia and mucin production throughout the epithelial thickness with increased mitotic activity, and/or apoptotic bodies. Pathologic slides were re-evaluated by a pathologist to confirm the diagnosis and review margin status. RESULTS: 24 patients with SMILE were identified. Mean age at diagnosis was 36.2 years (range 25-53) with 67% (16/24) diagnosed before the age of 40. The majority (54%, 13/24) were nulliparous and 63% (15/24) had a past history of abnormal Pap smears. 92% (22/24) of patients were positive for high risk human papillomavirus, with 13% (n=3) presenting with a normal Pap smear. Diagnosis was made primarily on colposcopy (n=16), cold knife cone/loop electrosurgical excision procedure (n=7), or hysterectomy (n=1). Most patients (71%, 17/24) had a co-existing precancerous lesion at the time of diagnosis and the most common was high grade squamous intraepithelial lesion (53%). Five invasive lesions were also identified at the time of diagnosis of SMILE (2 adenocarcinoma, 3 adenosquamous), 1 of which underwent chemoradiation. Among all patients, 25% (6/24) underwent hysterectomy (4 simple, 2 radical), while 63% (17/24) of patients underwent a fertility sparing excisional procedure; 4% (1/24) were incidentally diagnosed on hysterectomy. 18 patients had negative margins and 2 patients had positive margins. Over a median follow-up of 29 months (range 3-105), all of the fertility sparing patients with negative margins had no recurrence. Among the two patients with positive margins, one had no recurrence on repeat excision and the other underwent repeat excision with persistent SMILE identified, subsequent negative margin, and no recurrence since. DISCUSSION: Our data showed that most patients with SMILE were young, positive for high risk human papillomavirus, nulliparous, and presented with coexisting lesions. Excisional procedures with negative margins may be sufficient fertility sparing treatment in patients with preinvasive SMILE with a low risk of recurrence. There should be consideration of hysterectomy at the completion of childbearing.

Primary total hip replacement in Ficat-Arlet stage 3 and 4 osteonecrosis: a retrospective study at a minimum 12-year follow-up.

INTRODUCTION: Results of total hip replacement (THR) for aseptic osteonecrosis are controversial and conflicting according to implant type and generation. The present study consisted in a retrospective assessment of implant survival in primary THR for aseptic osteonecrosis, using a cemented stem, standard polyethylene press-fit acetabular component, and metal-metal bearing. The study hypothesis was that THR results are equivalent between aseptic osteonecrosis and osteoarthritis of the hip. MATERIAL AND METHOD: A single-center retrospective study included 54 patients with metal-on-metal THR for femoral head osteonecrosis. The main endpoint was revision surgery for all causes, whether implant related or procedure related; secondary endpoints were complications and progression in clinical scores. RESULTS: Mean follow-up was 13.9 ± 1.6 years (range 12.0-17.1 years). Eighteen of the 54 patients (33.3%) died. Implant survival at last follow-up was 93.8% (95% CI, 87.1-100). There were 12 complications (22.2%): 1 intraoperative, 5 (9.3%) immediate postoperative, and 6 (11.1%) long term. Clinical assessment found a significant 43.1 point improvement in mean Harris score (p = 8.4E-33) and a 5.6 point improvement in mean PMA score (p = 2.9E-22). CONCLUSION: Survival in primary THR for aseptic osteonecrosis was good. Follow-up needs to be rigorous to screen for onset of complications. Primary THR is thus justified in Ficat-Arlet stage 3 and 4 aseptic osteonecrosis of the hip. LEVEL OF EVIDENCE: IV.

Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center.

BACKGROUND: Genetic assessment in Ashkenazi Jewish (AJ) patients often is limited to BRCA1/2 founder mutation testing. With access to time-efficient and cost-efficient multigene panel testing, some advocate expanding genetic testing in this population. However, to the best of the authors' knowledge, rates of nonfounder BRCA1/2 mutations and mutations in cancer-associated genes other than BRCA1/2 among AJ are not known. In the current study, the authors sought to assess the prevalence of mutations other than BRCA1/2 founder mutations among AJ patients undergoing genetic assessment. METHODS: The authors reviewed the medical records for all AJ patients who underwent genetic assessment at a single institution between June 2013 and December 2016. Mutations were categorized as 1) BRCA1/2 AJ founder mutations (BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT); 2) nonfounder BRCA1/2 mutations; or 3) mutations in non-BRCA1/2 cancer-associated genes. RESULTS: A total of 732 AJ patients underwent genetic assessment. Of these, 371 patients (51%) had a personal history of breast or ovarian cancer, 540 patients (73.8%) had a family history of breast cancer, and 132 patients (18%) had a family history of ovarian cancer. In the study population, 101 patients (13.8%) were found to have a pathogenic mutation, 78 patients (10.7%) had a BRCA1/2 founder mutation, 3 patients (0.4%) had a nonfounder BRCA1/2 mutation, and 20 patients (2.7%) had a mutation in a non-BRCA1/2 cancer-associated gene. Non-BRCA1/2 cancer-associated genes harboring mutations included RAD51D, TP53, mutS homolog 6 (MSH6), checkpoint kinase 2 (CHEK2), adenomatous polyposis coli (APC), and Fanconi anemia group C protein (FANCC). CONCLUSIONS: Among AJ patients found to have a pathogenic mutation on genetic assessment, approximately 22.8% had a mutation that would be missed with BRCA1/2 AJ founder mutation testing. Comprehensive multigene panel sequencing can provide clinically relevant genetic information for AJ patients and should be considered for genetic assessment in this population.

Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?

BACKGROUND: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome. However, the effectiveness of these screening methods in identifying individuals with Lynch syndrome across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), mutL homolog 1 (MLH1) methylation, and microsatellite instability (MSI) analysis among patients with endometrial cancer. METHODS: A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for 1990-2018 was performed. A DerSimonian-Laird random effects model meta-analysis was used to estimate the weighted prevalence of Lynch syndrome diagnoses. RESULTS: The comprehensive search produced 4400 publications. Twenty-nine peer-reviewed studies met the inclusion criteria. Patients with endometrial cancer (n = 6649) were identified, and 206 (3%) were confirmed to have Lynch syndrome through germline genetic testing after positive universal tumor molecular screening. Among 5917 patients who underwent tumor IHC, 28% had abnormal staining. Among 3140 patients who underwent MSI analysis, 31% had MSI. Among patients with endometrial cancer, the weighted prevalence of Lynch syndrome germline mutations was 15% (95% confidence interval [CI], 11%-18%) with deficient IHC staining and 19% (95% CI, 13%-26%) with a positive MSI analysis. Among 1159 patients who exhibited a loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation-negative among those who underwent methylation testing, and 32 demonstrated a germline MLH1 mutation (2.8% of all absent MLH1 staining cases and 22.4% of all MLH1 methylation-negative cases). Forty-three percent of patients with endometrial cancer who were diagnosed with Lynch syndrome via tumor typing would have been missed by family history-based screening alone. CONCLUSIONS: Despite the widespread implementation of universal tumor testing in endometrial cancer, data regarding testing results remain limited. This study provides predictive values that will help practitioners to evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling.

Impact of hospital surgical volume on complete gross resection (CGR) rates following primary debulking surgery for advanced stage epithelial ovarian carcinoma.

BACKGROUND: To investigate the impact of hospital surgical volume on the rate of complete gross resection for patients with advanced stage epithelial ovarian carcinoma undergoing primary debulking surgery. METHODS: The National Cancer Data Base was used to identify patients undergoing between 2010 and 2014 for an advanced stage (III-IV) epithelial ovarian cancer. For analyses purposes facility surgical volume was divided into tertiles (high, intermediate and low). Patients with bulky stage III disease who underwent primary debulking surgery with known residual disease status were selected for further analysis. RESULTS: A total of 8894 patients with macroscopic peritoneal disease were included. Rates of complete gross resection for patients managed in low, intermediate and high-volume centers were 41.0%, 41.6% and 43.3% respectively (p = 0.20). After controlling for year of diagnosis, age, insurance status, presence of co-morbidities, histology, size of peritoneal implants, stage, and complexity of surgery, patients undergoing primary debulking surgery at low (OR: 0.85, 95% CI: 0.74, 0.97, p = 0.013) and intermediate (OR: 0.90, 95% CI: 0.82, 0.99, p = 0.043) volume centers had a lower likelihood of achieving complete gross resection compared to those managed in high volume centers. CONCLUSIONS: After controlling for multiple potential confounders, patients receiving surgery in high volume centers had a higher likelihood of complete gross resection following primary debulking surgery for advanced-stage epithelial ovarian cancer.

Prognostic significance of residual disease in advanced stage malignant ovarian germ cell tumors.

OBJECTIVE: To investigate the prognostic significance of complete gross resection following cytoreductive surgery for patients with advanced stage malignant ovarian germ cell tumors. METHODS: The National Cancer Data Base was accessed and patients diagnosed with an advanced stage (II-IV) malignant ovarian germ cell tumor who underwent primary cytoreductive surgery between 2011 and 2014 were selected for further analysis. For analysis purposes two groups were formed: patients with complete gross resection and those with macroscopic residual disease. Demographic and clinico-pathological characteristics were compared with the chi-square and Mann-Whitney U test. Univariate survival analysis was performed with the log-rank test after generation of Kaplan-Meier curves, while a Cox proportional hazard model was constructed to evaluate mortality after controlling for confounders. RESULTS: A total of 343 patients who met the inclusion criteria were identified. Residual disease status was available for 276 patients: the rate of complete gross resection was 69.2 %. By univariate analysis there was no difference in overall survival between patients in the complete gross resection and macroscopic residual disease groups, P= 0.26; 3-year overall survival rates: 86.4 % and 82.8 %, respectively. No difference in overall survival was noted following stratification by histology; P = 0.64 and P = 0.24 for dysgerminoma and non-dysgerminoma tumor groups. After controlling for stage IV disease, histology and the administration of chemotherapy, macroscopic residual disease was not associated with a worse mortality (HR: 1.22, 95% CI: 0.61 to 2.46). CONCLUSIONS: Macroscopic residual disease following primary cancer-directed surgery was not associated with a worse prognosis in a cohort of patients with advanced stage malignant ovarian germ cell tumors.

Minimally Invasive Staging of Apparent Stage I Malignant Ovarian Germ Cell Tumors: Prevalence and Outcomes.

STUDY OBJECTIVE: Evaluate the prevalence, trends, and outcomes of minimally invasive surgical (MIS) staging of malignant ovarian germ cell tumors (MOGCTs) apparently confined to the ovary. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Participating hospitals in the National Cancer Data Base. PATIENTS: Women diagnosed between 2010 and 2014 with a MOGCT apparently confined to the ovary with information on the planned surgical approach. INTERVENTIONS: Staging with MIS or laparotomy. MEASUREMENT AND MAIN RESULTS: A total of 918 patients were identified. MIS was planned for 294 patients (32%): a laparoscopic approach for 237 patients and a robotic-assisted approach for 57 patients. Rate of conversion to laparotomy was 11% (46 cases), 1.7% and 15.6% in the robotic and laparoscopy groups, respectively (p = .003). No difference in the use of MIS was noted based on year of diagnosis (p = .38). By multivariate analysis white race, higher level of education, and smaller tumor size were associated with the receipt of MIS. Patients in the MIS group were less likely to undergo lymph node dissection (39.6% vs 51.3%, p = .001) and omentectomy (18.7% vs 28.5%, p = .002). Hospital stay after surgery was shorter for patients who had MIS (median, 2 vs 3 days; p <.001). Unplanned 30-day readmission rate was also lower in the MIS group (1.4% vs 3.9%, p = .043). No difference in overall survival was noted between the 2 groups (p = .81). CONCLUSION: MIS for apparent early-stage MOGCTs was less comprehensive but associated with a decreased hospital stay and unplanned readmission rate.

Novel Fumarate Hydratase Mutation in Siblings With Early Onset Uterine Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.

Hereditary leiomyomatosis renal cell cancer syndrome is an autosomal dominant disorder characterized by uterine and cutaneous leiomyomas and increased predisposition to renal cell carcinoma, papillary type II. The syndrome is caused by heterozygous mutations to the fumarate hydratase (FH) gene located on chromosome 1. Affected females generally present with early onset, atypical uterine leiomyomas and cutaneous findings, however, delays in diagnosis are very common in patients with isolated uterine findings. We present a case series of 2 sisters in their 20s who presented with isolated uterine leiomyomas and were found to carry a novel mutation for the fumarate hydratase gene. One patient was referred for treatment of infertility and recurrent miscarriages and the other was referred for acute symptomatic anemia due to myomas. Prompt diagnosis of hereditary leiomyomatosis renal cell cancer was made due to a high index of clinical suspicion based on early onset disease and familial clustering as well as characteristic pathologic findings on uterine leiomyoma surgical specimen. Timely diagnosis not only allowed for genetic counseling and renal cancer surveillance, but also for fertility counseling given the increased morbidity associated with uterine leiomyoma due to hereditary leiomyomatosis and renal cell cancer syndrome.

Small Cell Carcinoma of the Ovary: A Rare Tumor With a Poor Prognosis.

OBJECTIVE: The aim of this study was to investigate the demographic and clinicopathological characteristics and prognosis of women diagnosed with small cell carcinoma of the ovary. METHODS: The National Cancer Data Base was accessed, and women diagnosed with small cell carcinoma of the ovary, between 2004 and 2014 were identified. Median and 3- and 5-year overall survival (OS) rates were calculated following generation of Kaplan-Meir curves and compared with the log-rank test. A Cox multivariate model was constructed to identify variables associated with mortality. RESULTS: A total 469 women were identified with a median age of 39 years; 81.7% of tumors were unilateral, whereas median size was 13 cm. Only 20.1% of patients had stage I disease. Women who underwent cancer-directed surgery had a 5-year OS rate of 24.1%. Five-year OS rates were 48.6%, 30.7%, 18%, and 12.3% for those with stages I, II, III, and IV disease, respectively, P < 0.001. Younger age (P = 0.013) and the combination of surgery with chemotherapy (CT) (P < 0.001) were associated with superior OS. By multivariate analysis, earlier disease stage and use of CT, but not patient age or performance of lymphadenectomy, were associated with lower mortality. CONCLUSIONS: Small cell carcinomas of the ovary are unilateral tumors primarily arising in premenopausal women. Multimodal treatment with cancer-directed surgery and CT results in a modest increase of a generally poor survival.

Management and prognosis of ovarian yolk sac tumors; an analysis of the National Cancer Data Base.

OBJECTIVE: To evaluate the clinico-pathological characteristics, management and prognosis of women diagnosed with ovarian yolk sac tumors (OYSTs). METHODS: The U.S National Cancer Data Base was queried for women diagnosed with OYST between 2004 and 2014. Overall survival (OS) was calculated following generation of Kaplan-Meir curves. Univariate analysis was performed with the log-rank test. A Cox model was constructed to determine independent predictors of mortality. RESULTS: A total of 561 women were identified with a median age of 23years. The majority (58.5%) had early stage (I-II), while 29.6% and 11.9% had stage III and IV disease respectively. Five-year OS for women with stage I, II, III and IV disease were 94.8%, 97.1%, 70.9% and 51.6% respectively, p<0.001. Better 5-yr OS was observed for adolescents (94.4%) and young adults (89.3%) compared to older premenopausal (67.6%) and postmenopausal women (30.6%), p<0.001. Omentectomy, hysterectomy and lymph node sampling/dissection (LND) were not associated with better OS. Women who received adjuvant chemotherapy had superior OS compared to those who did not, p=0.016. Early disease stage, younger age and receipt of adjuvant chemotherapy, but not LND were independently associated with better mortality. CONCLUSIONS: Women with OYST commonly present with early stage disease. Administration of adjuvant chemotherapy, early stage and younger age are associated with superior outcomes.

Fertility-preserving surgery for advanced stage ovarian germ cell tumors.

OBJECTIVE: To evaluate the prevalence and safety of uterine preservation among premenopausal women diagnosed with a malignant ovarian germ-cell tumor (MOGCT) of advanced stage (stage II-IV). MATERIALS AND METHODS: The National Cancer Database was accessed and a cohort of women aged <40years, diagnosed with a MOGCT were identified. Those with stage II-IV disease who underwent cancer-directed surgery and received chemotherapy were selected for further analysis. Performance of hysterectomy was assessed from site-specific surgery codes. Overall survival (OS) was determined following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox multivariate model was constructed to control for possible confounders. RESULTS: A total of 526 eligible patients were identified; rate of hysterectomy was 20.2%. Women who had a hysterectomy were older (median age 30.5 vs 20years, p<0.001) and more likely to present with bilateral tumors (12.6% vs 3.8%, p<0.001). No differences were noted based on tumor histology (p=0.67). Rate of uterine preservation was 82.8%, 79.5% and 75% for those with stage II, III and IV disease respectively (p=0.46). There was no difference in OS between women who had hysterectomy and those who did not (p=0.051); five-year OS rates were 87.1% and 94.4% respectively. After controlling for disease stage, tumor histology and patient race, uterine preservation was not associated with a decreased survival (HR: 0.59, 95% CI: 0.28, 1.24, p=0.19). CONCLUSIONS: Uterine preservation was not associated with decreased survival and should be considered in women with advanced stage GCTs interested in future fertility.

Should epithelial ovarian carcinoma metastatic to the inguinal lymph nodes be assigned stage IVB?

OBJECTIVE: According to the revised FIGO staging system women with ovarian carcinoma and inguinal lymph node (LN) metastases, formerly stage III, are now considered stage IVB. In this study we compare their survival to that of women with stage III and stage IV disease. METHODS: Women diagnosed with epithelial ovarian carcinoma were drawn from the Surveillance, Epidemiology, and End Results database (2004-2013). Four groups were formed: group 1 (stage IV due to positive inguinal nodes), group 2 (stage III with positive para-aortic/pelvic nodes), group 3 (stage IV with positive distant nodes) and group 4 (stage IV with distant metastases). Overall (OS) and cancer-specific survival (CSS) rates were evaluated with the Kaplan-Meier method. The log-rank test and Cox-hazard models were employed for univariate and multivariate survival analysis. RESULTS: A total of 11,152 women were identified. Five-year OS for women in group 1 (n=151) was 46.3% compared to 44.9% for those in group 2 (n=4,403) (p=0.4), 32.9% in group 3 (n=642) (p<0.001) and 25.3% in group 4 (n=5,956) (p<0.001). After controlling for age, race and histology, group 1 had improved overall and cancer-specific mortality compared to groups 3 and 4 but not group 2. CONCLUSIONS: Ovarian cancer patients with stage IV ovarian cancer due solely to inguinal nodal metastases have similar survival as those with pelvic/para-aortic nodal involvement and improved survival compared to those harboring distant metastases. Our findings do not support the reclassification of these patients as stage IVB.

Feasibility and Learning Curve of Robotic Laparoendoscopic Single-Site Surgery in Gynecology.

Single-site laparoscopy has proven to be a desirable option for patients undergoing gynecologic surgery, with some studies indicating improved cosmesis and less perioperative pain compared with standard approaches. This study describes the safety and feasibility of a novel robotic laparoendoscopic single-site surgery (R-LESS) platform as it is incorporated into a surgeon's practice with extensive multiport robotic surgical experience but limited LESS experience. We reviewed 83 women undergoing R-LESS by a single surgeon from September 2013 through August 2015. Operative times (total operative time, console time, docking time) were collected prospectively for the first 53 cases, and total operative time was collected retrospectively for the next 30 cases. Clinical parameters, including age, estimated blood loss, body mass index (BMI), prior abdominal surgeries, conversion to laparotomy, procedure type, uterine weight, length of hospital stay, and complications, were retrospectively collected from medical charts. Eighty-two of 83 surgeries were completed successfully with a single incision. One surgery was converted to multiport robotics for para-aortic lymph node dissection. Twelve surgeries were performed for cancer (ovary 1, uterus 8, and cervix 3). Eight patients underwent pelvic lymph node biopsy. The median total operative time for hysterectomies was 128 minutes (range, 60-275). After the first 13 hysterectomies the total operative time and the console time decreased significantly from 165.3 to 131.1 minutes (p = .032) and from 84.9 to 57.1 minutes (p = .028), respectively. Mean docking time halved from 7.8 minutes to 3.4 minutes comparing the first 10 cases to the last 10 cases. Surgical times were longer with larger BMIs, but the console time decreased with experience regardless of BMI. The mean uterine weight was 164 g (range, 30-460). Complications included 2 umbilical hernias (2.4%) and 1 conversion to multiport. In conclusion, R-LESS is a feasible and safe surgical platform for gynecologic procedures. A small number of cases are needed to significantly improve operative times when it is introduced on a surgeon's practice with limited experience in LESS but familiar with robotic surgery. Further study is needed to investigate the cost, benefits, and long-term outcomes of R-LESS.

Does the Presence of Endometriosis Affect Prognosis of Ovarian Cancer?

Ovarian cancers diagnosed between 2000 and 2013 were examined and cases with and without endometriosis compared. Among 139 epithelial ovarian, there were 49 (35%) with endometriosis and 90 (65%) without endometriosis. Endometriosis associated ovarian cancers were more likely to be confined to the pelvis (54% vs. 9%, p < 0.0001) and lower grade (51% vs. 29%, p = 0.014). Younger age and earlier stage independently predicted the presence of endometriosis (p = 0.0011 and p < 0.0001, respectively). Ovarian cancer patients with endometriosis had improved PFS and OS [(HR = 0.20; 95% CI, 0.09-0.43), (HR = 0.18; 95% CI, 0.04-0.81)], compared to patients without endometriosis; however, endometriosis had no independent prognostic significance.

Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes.

OBJECTIVE: To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. METHODS: Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival. RESULTS: 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; p<0.01). African Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; p<0.06). We observed better overall and cause-specific survival in the aRT group: 42 vs. 22 (p<0.0001) and 57 vs. 28months (p<0.0001), respectively. Black race, diagnosis in 1999-2004, advanced stage and age≥65years carried a higher risk of UCS death. CONCLUSIONS: We observed greater survival rate in the aRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer.

Inhibition of autophagy in peripheral blood mononuclear cells by vaginal fluid from women with a malignant adnexal mass.

Inhibition of autophagy is a characteristic of ovarian cancer. We determined whether inhibition of autophagy by vaginal fluid could provide a non-invasive test for cancer risk stratification in women presenting with an adnexal mass. Vaginal fluid supernatants from 90 women undergoing evaluation for a suspicious adnexal mass were incubated with peripheral blood mononuclear cells (PBMCs) obtained from healthy women under conditions that induce autophagy. Rapamycin, an autophagy inducer, was added to some cultures. After 48 hr the cells were collected, lysed and assayed by ELISA for intracellular p62 concentration. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration is inversely proportional to the extent of autophagy induction. Clinical information including pathological diagnoses was obtained after completion of laboratory studies. Mean p62 levels were 9.4 ng/ml in the 21 women with a subsequent malignant diagnosis, 4.5 ng/ml in the eight women with a borderline tumor diagnosis and 3.6 ng/ml in the 61 women with benign disease (p < 0.0001, malignant vs. others). When rapamycin was added to the vaginal fluid-PBMC co-incubation, p62 levels in samples from women with a malignant diagnosis decreased to 3.3 ng/ml, a level comparable to what was observed with the nonmalignant samples. Vaginal fluid inhibition of autophagy can differentiate between women with malignant and benign adnexal masses.