Shared Immunogenic Poly-Epitope Frameshift Mutations in Microsatellite Unstable Tumors.

Microsatellite instability-high (MSI-H) tumors are characterized by high tumor mutation burden and responsiveness to checkpoint blockade. We identified tumor-specific frameshifts encoding multiple epitopes that originated from indel mutations shared among patients with MSI-H endometrial, colorectal, and stomach cancers. Epitopes derived from these shared frameshifts have high population occurrence rates, wide presence in many tumor subclones, and are predicted to bind to the most frequent MHC alleles in MSI-H patient cohorts. Neoantigens arising from these mutations are distinctly unlike self and viral antigens, signifying novel groups of potentially highly immunogenic tumor antigens. We further confirmed the immunogenicity of frameshift peptides in T cell stimulation experiments using blood mononuclear cells isolated from both healthy donors and MSI-H cancer patients. Our study uncovers the widespread occurrence and strong immunogenicity of tumor-specific antigens derived from shared frameshift mutations in MSI-H cancer and Lynch syndrome patients, suitable for the design of common "off-the-shelf" cancer vaccines.

Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy.

OBJECTIVE: The objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/- para-aortic lymphadenectomy (LND). METHODS: Patients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Out of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3-84.0%) in the SLN group and 71.3% (95% CI 62.0-78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56-2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47-2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1-93.7%) in the SLN group and 95.1% (95% CI 89.4-97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39-10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94-8.95, p = 0.06). CONCLUSIONS: There was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.

COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic.

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.

Racial disparities in patients with coronavirus disease 2019 infection and gynecologic malignancy.

BACKGROUND: Mounting evidence suggests disproportionate coronavirus disease 2019 (COVID-19) hospitalizations and deaths because of racial disparities. The association of race in a cohort of gynecologic oncology patients with severe acute respiratory syndrome-coronavirus 2 infection is unknown. METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City area hospital systems. A multivariable mixed-effects logistic regression model accounting for county clustering was used to analyze COVID-19-related hospitalization and mortality. RESULTS: Of 193 patients who had gynecologic cancer and COVID-19, 67 (34.7%) were Black, and 126 (65.3%) were non-Black. Black patients were more likely to require hospitalization compared with non-Black patients (71.6% [48 of 67] vs 46.0% [58 of 126]; P = .001). Of 34 (17.6%) patients who died from COVID-19, 14 (41.2%) were Black. Among those who were hospitalized, compared with non-Black patients, Black patients were more likely to: have ≥3 comorbidities (81.1% [30 of 37] vs 59.2% [29 of 49]; P = .05), to reside in Brooklyn (81.0% [17 of 21] vs 44.4% [12 of 27]; P = .02), to live with family (69.4% [25 of 36] vs 41.6% [37 of 89]; P = .009), and to have public insurance (79.6% [39 of 49] vs 53.4% [39 of 73]; P = .006). In multivariable analysis, among patients aged <65 years, Black patients were more likely to require hospitalization compared with non-Black patients (odds ratio, 4.87; 95% CI, 1.82-12.99; P = .002). CONCLUSIONS: Although Black patients represented only one-third of patients with gynecologic cancer, they accounted for disproportionate rates of hospitalization (>45%) and death (>40%) because of COVID-19 infection; younger Black patients had a nearly 5-fold greater risk of hospitalization. Efforts to understand and improve these disparities in COVID-19 outcomes among Black patients are critical.

Development and validation of a comprehensive clinical risk-scoring model for prediction of overall survival in patients with endometrioid endometrial carcinoma.

OBJECTIVE: To develop and validate a comprehensive overall survival (OS) risk-scoring model in women with endometrioid endometrial cancer (EC). METHODS: Patients with EC diagnosed from 2004 to 2013 were identified through the National Cancer Database (NCDB). Patients with known lymphovascular space invasion (LVSI) status who were treated surgically (with or without adjuvant therapy) were included. Cox proportional hazards analysis was used to identify prognostic factors for OS. This model was used to assign points based on hazard ratios for risk factors and a risk score was obtained. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups. Results were internally validated in a cohort of patients from our institution (CCF cohort). Risk scores were calculated and assessed in a Cox regression model, and Harrell's c-index was calculated to assess model fit. RESULTS: Among 349,404 women with EEC during the study period, 42,107 fulfilled inclusion criteria. Factors associated with worse OS were age ≥ 60, African American race, Charlson-Deyo score 1 or 2+, higher grade, LVSI, tumor size ≥2 cm, and no lymphadenectomy performed. Six risk groups were identified (scores 0-30) and OS estimated for each risk group. Risk score per 1-point increase in HR were comparable between NCDB and CCF cohorts (HR 1.21 (1.20-1.22 p < 0.001 vs 1.18 (1.12-1.25), p < 0.001), and c-index 0.80 (0.79-0.81) vs. 0.77 (0.68-0.86). Similar analysis was done in stage IA and IB. Adjuvant therapy had a beneficial effect on survival in the majority of stage IB patients, but only one of the six risk groups in stage IA EC. CONCLUSIONS: We report a comprehensive validated OS risk-scoring model for patients with.

Short- and long-term outcomes for single-port risk-reducing salpingo-oophorectomy with and without hysterectomy for women at risk for gynecologic cancer.

INTRODUCTION: Risk-reducing salpingo-oophorectomy has been established as one of the most effective strategies in risk reduction for ovarian and breast cancers among women at increased genetic risk. However, there are limited data regarding the single-port laparoscopic platform in the field of risk-reducing surgery. Our objective was to describe outcomes after single-port risk-reducing salpingo-oophorectomy with or without hysterectomy for reduction of ovarian, breast, or endometrial cancer risk. METHODS: A retrospective, single institution (Canadian Task Force Classification II.2) analysis was performed in women at high genetic or familial risk for ovarian/tubal/primary peritoneal cancer or with personal history of breast cancer who underwent single-port laparoscopic risk-reducing salpingo-oophorectomy with or without hysterectomy between October 2009 and December 2015. Data were collected on patient demographics, surgical procedure and characteristics, intra-operative findings, and post-operative outcomes. RESULTS: In total, 187 single-port laparoscopic surgeries were performed with a median follow-up of 204 (IQR 25-749) days. BRCA1/2, Lynch syndrome, or Cowden syndrome was diagnosed in 64.0% of patients. Additionally, 32.1% had a personal history of breast cancer, and 3.2% reported strong family history of ovarian and/or breast cancer. Single-port risk-reducing salpingo-oophorectomy with hysterectomy was performed in 53.5% of patients. The rate of adverse outcomes, including conversion to multiport laparoscopy or laparotomy (1.6%), intra-operative injury (1.6%), deep vein thrombosis (0.5%), urinary tract infection (2.7%), and/or incisional cellulitis (4.3%) were low. Three patients (1.6%) were diagnosed with malignancy on final pathology. All three patients were BRCA1-positive and their CA125 values were significantly lower than those without malignancy (p=<0.0001). CONCLUSIONS: Single-port laparoscopy is a safe option for patients undergoing risk-reducing salpingo-oophorectomy with or without hysterectomy. Standardized pre-operative evaluation criteria are needed to determine absolute risk of incidental malignancy, and the risk of identifying a malignancy should be reiterated to patients during pre-operative counseling.

Clinicopathologic characteristics and outcomes of endometrial Cancer patients with mismatch repair deficiency in the era of universal Lynch syndrome screening.

OBJECTIVE: To evaluate clinicopathologic characteristics and survival impact associated with mismatch repair (MMR) deficient subgroups of endometrial cancer (EC) in patients undergoing universal screening for Lynch Syndrome. METHODS: A retrospective cohort study using a prospectively maintained gynecologic oncology registry of patients who underwent surgery for EC was conducted. All pathology specimens underwent tumor testing using immunohistochemistry for MMR deficiency with reflex MLH1 promotor methylation testing. Tumors were classified as MMR-I (intact MMR expression), MMR-DM (MMR deficient due to MLH1 methylation), and MMR-DU (MMR deficient without MLH1 methylation). Univariate and multivariate analysis performed to determine factors associated with MMR-DM. Progression-free survival (PFS) and overall survival (OS) analyzed by stage and endometrioid subgroup. RESULTS: From 2012 to 2016, 1018 EC patients were identified and screened. Overall, 71.6% were classified as MMR-I, 23.8% MMR-DM, and 4.6% MMR-DU. In comparison to MMR-DU, MMR-DM tumors were associated with older age, postmenopausal status, lymphovascular space invasion, and pure endometrioid histology. Compared to MMR-I, MMR-DM tumors were associated with older age, endometrioid histology, lymphovascular space invasion, and higher grade on multivariable analysis. There was no difference in PFS and OS between the three groups overall. In patients with endometrioid EC, MMR-DM tumors were associated with lower PFS vs. MMR-I (HR:2.51, CI:1.54, 4.10, P < 0.001). This effect persisted for stage I/II endometrioid EC (HR 2.66, CI:1.34, 5.26 p = 0.005). No difference in PFS or OS was noted among stage III/IV endometrioid tumors. CONCLUSION: MMR deficiency is associated with adverse prognostic factors and worse PFS among endometrioid tumors, particularly in early stage EC. MMR testing outside of LS screening has prognostic value, warranting consideration for inclusion as a biomarker in prospective clinical trials.

Inflammatory markers in gynecologic oncology patients hospitalized with COVID-19 infection.

OBJECTIVE: Elevated inflammatory markers are predictive of COVID-19 infection severity and mortality. It is unclear if these markers are associated with severe infection in patients with cancer due to underlying tumor related inflammation. We sought to further understand the inflammatory response related to COVID-19 infection in patients with gynecologic cancer. METHODS: Patients with a history of gynecologic cancer hospitalized for COVID-19 infection with available laboratory data were identified. Admission laboratory values and clinical outcomes were abstracted from electronic medical records. Severe infection was defined as infection requiring ICU admission, mechanical ventilation, or resulting in death. RESULTS: 86 patients with gynecologic cancer were hospitalized with COVID-19 infection with a median age of 68.5 years (interquartile range (IQR), 59.0-74.8). Of the 86 patients, 29 (33.7%) patients required ICU admission and 25 (29.1%) patients died of COVID-19 complications. Fifty (58.1%) patients had active cancer and 36 (41.9%) were in remission. Patients with severe infection had significantly higher ferritin (median 1163.0 vs 624.0 ng/mL, p < 0.01), procalcitonin (median 0.8 vs 0.2 ng/mL, p < 0.01), and C-reactive protein (median 142.0 vs 62.3 mg/L, p = 0.02) levels compared to those with moderate infection. White blood cell count, lactate, and creatinine were also associated with severe infection. D-dimer levels were not significantly associated with severe infection (p = 0.20). CONCLUSIONS: The inflammatory markers ferritin, procalcitonin, and CRP were associated with COVID-19 severity in gynecologic cancer patients and may be used as prognostic markers at the time of admission.

Adjuvant therapy for early stage, endometrial cancer with lymphovascular space invasion: Is there a role for chemotherapy?

OBJECTIVES: Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/-RAD. METHODS: This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/-lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/-RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/-RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/-RAD (HR = 0.18, 95% CI: 0.09-0.39) and RAD (HR = 0.31, 95% CI: 0.18-0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/-RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12-0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03-0.32). Overall survival did not differ by treatment. CONCLUSIONS: In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone.

Endometrial cancer in young women: prognostic factors and treatment outcomes in women aged ≤40 years.

OBJECTIVE: Endometrial cancer in pre-menopausal patients aged ≤40 years is rare and poses both diagnostic and management challenges. The goal of this study was to investigate the clinical and pathologic factors associated with endometrial cancer in this group and their impact on survival. METHODS: Patients with endometrial cancer treated between January 2004 and August 2016 were retrospectively reviewed. Patients who underwent either primary surgical treatment or fertility-sparing therapy were included. Exclusion criteria were age >60 years and patients who received neoadjuvant chemotherapy or primary radiation. Age at diagnosis was used to classify patients into two groups: ≤40 and 41-60 years. Clinical and pathologic variables were compared between the groups. Progression-free survival and overall survival were estimated using Cox proportional hazards. RESULTS: A total of 551 patients were evaluated, of which 103 (18.7%) patients were ≤40 years and 448 (81.3%) were 41-60 years. Age ≤40 years was associated with higher body mass index (38.8 vs 35.8 kg/m2, p=0.008), non-invasive cancers (54.2% vs 32.6%, p<0.001), lower uterine segment involvement (27.2% vs 22.5%, p<0.001), and less lymphovascular space invasion (16.8% vs 29.1%, p=0.015). The rate of synchronous ovarian cancer was 9.2% vs 0.7% in age 41-60 years (p<0.001), and 19% of women with endometrial cancer aged ≤40 years underwent fertility-sparing therapy. Grade, stage, myometrial invasion, lymphovascular space invasion, and lymph node status were associated with survival, and fertility-sparing therapy adversely affected the recurrence rate of the age ≤40 years cohort. Among all patients aged ≤60 years, mismatch repair deficiency due to MLH1 methylation was associated with worse progression-free survival, 48.6% vs 83.3% (HR 1.98, 95% CI 1.06 to 3.17, p=0.032), and overall survival, 56.5% vs 90.0% (HR 2.58, 95% CI 1.13 to 5.90, p=0.025). CONCLUSIONS: Patients aged ≤40 years with endometrial cancer have more favorable prognostic factors and higher rates of synchronous tumors. Fertility-sparing therapy was associated with higher recurrence rates. The prognostic value of MLH1 methylation in this population warrants further investigation.

Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion.

BACKGROUND: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial. OBJECTIVE: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes. METHODS: A 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. RESULTS: 405 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, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively). CONCLUSION: Adjuvant 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.

Does surgical platform impact recurrence and survival? A study of utilization of multiport, single-port, and robotic-assisted laparoscopy in endometrial cancer surgery.

BACKGROUND: Minimally invasive hysterectomy is the standard of care in the majority of women diagnosed with endometrial cancer via robotic-assisted, multiport, and single-port laparoscopy technology. Although safe and efficacious, it is unclear how oncologic outcomes are impacted by surgical platform. OBJECTIVE: To identify differences in progression-free survival and overall survival in women undergoing minimally invasive surgery for endometrial cancer staging via either multiport, single-port, or robotic-assisted laparoscopy. STUDY DESIGN: A multicenter, single-institution retrospective cohort study was performed in women with a diagnosis of endometrial cancer who underwent minimally invasive surgery from 2009 to 2015. Data were collected for demographics, pathologic information, adjuvant treatment, and disease status. Pearson χ2 and Fisher exact tests were used to evaluate risk factors for outcomes, Kaplan-Meier estimates and Cox proportional hazards were used to evaluate differences in time to progression or death, and multivariate regression analysis was performed. RESULTS: In total, 1150 women with endometrial cancer underwent robotic-assisted laparoscopy (n=652), multiport laparoscopy (n=214), or single-port laparoscopy (n=284). The median age and body mass index of women was 62.0 years and 33.5 kg/m2, respectively. The majority of patients had endometrioid histology (88.1%), stage IA (74.7%) or IB disease (13.1%) and International Federation of Gynecology and Obstetrics grade 1 (57.4%) or 2 (26.0%) histology. Lymphovascular space invasion was present in 24.7% (n=283). Adjuvant radiation was given in 34.2% of cases, with 21.9% receiving vaginal brachytherapy, 6.6% pelvic radiation, and 5.4% both. For the entire cohort, there were no differences in progression-free survival at 2, 3, and 5 years for multiport laparoscopy (94.2%, 91.4%, 87.4%), robotic-assisted laparoscopy (94.5%, 92.9%, 88.8%), and single-port laparoscopy (93.6%, 91.2%, 90.0%) (P=.93), respectively. Similarly, there were no differences in overall survival at 2, 3, and 5 years for multiport laparoscopy (94.4%, 91.8%, 91.8%), robotic-assisted laparoscopy (95.6%, 93.4%, 90.7%), and single-port laparoscopy (95.0, 93.1, 91.8) (P=.99), respectively. Among women with stage IA and IB disease, no difference existed for progression-free survival at 2, 3, and 5 years for multiport laparoscopy (94.2%, 91.4%, 87.4%), robotic-assisted laparoscopy (94.5%, 92.9%, 88.8%), and single-port laparoscopy (93.6, 91.2, 90.0) (P=.93), respectively. Similarly, among women with stage I disease, there was no difference in overall survival at 2, 3, and 5 years for multiport laparoscopy (96.2%, 95.0%, 95.0%), robotic-assisted laparoscopy (96.6%, 95.4%, 93.3%), and single-port laparoscopy (96.6%, 95.0%, 93.4%) (P=.89). Rather, progression-free survival and overall survival were predicted by age >65 years, stage, grade, and histology (P<.05). On multivariate analysis, modality of surgery did not impact overall survival or progression-free survival (robotic-assisted laparoscopy, hazard ratio, 1.28, P=.50; single-port laparoscopy, hazard ratio, 0.84, P=.68 vs multiport laparoscopy). Age >65 years (hazard ratio, 5.42, P<.001) and advanced stage disease (P=.003) were associated with decreased overall survival. CONCLUSION: In this retrospective cohort, there was no difference in progression-free survival or overall survival in women undergoing surgery for endometrial cancer via robotic-assisted laparoscopy, single-port laparoscopy, or multiport laparoscopy.

Single-port laparoscopy in gynecologic oncology: seven years of experience at a single institution.

BACKGROUND: Single-port laparoscopy has gained popularity within minimally invasive gynecologic surgery for its feasibility, cosmetic outcomes, and safety. However, within gynecologic oncology, there are limited data regarding short-term adverse outcomes and long-term hernia risk in patients undergoing single-port laparoscopic surgery. OBJECTIVE: The objective of the study was to describe short-term outcomes and hernia rates in patients after single-port laparoscopy in a gynecologic oncology practice. STUDY DESIGN: A retrospective, single-institution study was performed for patients who underwent single-port laparoscopy from 2009 to 2015. A univariate analysis was performed with χ2 tests and Student t tests; Kaplan-Meier and Cox proportional hazards determined time to hernia development. RESULTS: A total of 898 patients underwent 908 surgeries with a median follow-up of 37.2 months. The mean age and body mass index were 55.7 years and 29.6 kg/m2, respectively. The majority were white (87.9%) and American Society of Anesthesiologists class II/III (95.5%). The majority of patients underwent surgery for adnexal masses (36.9%) and endometrial hyperplasia/cancer (37.3%). Most women underwent hysterectomy (62.7%) and removal of 1 or both fallopian tubes and/or ovaries (86%). Rate of adverse outcomes within 30 days, including reoperation (0.1%), intraoperative injury (1.4%), intensive care unit admission (0.4%), venous thromboembolism (0.3%), and blood transfusion, were low (0.8%). The rate of urinary tract infection was 2.8%; higher body mass index (P = .02), longer operative time (P = .02), smoking (P = .01), hysterectomy (P = .01), and cystoscopy (P = .02) increased the risk. The rate of incisional cellulitis was 3.5%. Increased estimated blood loss (P = .03) and endometrial cancer (P = .02) were independent predictors of incisional cellulitis. The rate for surgical readmissions was 3.4%; higher estimated blood loss (P = .03), longer operative time (P = .02), chemotherapy alone (P = .03), and combined chemotherapy and radiation (P < .05) increased risk. The rate of incisional hernia rate was 5.5% (n = 50) with a mean occurrence at 570.2 ± 553.3 days. Higher American Society of Anesthesiologists class (P = .04), diabetes (P < .001), hypertension (P = .043), increasing age (P = .017; hazard ratio [HR], 1.03), and body mass index (P < .001; HR, 1.08) were independent predictors for incisional hernia development. Previous abdominal surgeries (P = .24) and hand assist (P = .64) were not associated with increased risk for incisional hernia. Patients with American Society of Anesthesiologists class III/IV had a 3 year hernia rate of 12.8% (HR, 1.81). Patients with diabetes mellitus had a 3 year hernia rate of 23.0% (HR, 3.60). CONCLUSION: In this large cohort of patients undergoing single-port laparoscopy, the incidence of short-term adverse outcomes is low. While the rate of incisional hernia was 5.5%, incidence reached 23.0% at 3 years in high-risk groups. Previous studies with short follow-up duration may underestimate the risk of hernia, especially in patients with significant comorbidities.

The use of Instagram by gynecologic oncology providers as a patient education tool for patients at high-risk of gynecologic cancer.

Social media outlets have increased in popularity within the last decade and are influencing the ways in which patients interact with the healthcare system. The objective of this study is to examine the presence of gynecologic oncology divisions on Instagram and to analyze the content of their posts. Secondary objectives included examining and analyzing the use of Instagram as a tool for patient education among people at increased genetic risk of gynecologic cancers. Seventy-one NCI-Designated Cancer Centers, their gynecologic oncology divisions and hereditary gynecologic cancer related posts were searched on Instagram. Content was reviewed and authorship was analyzed. Of the 71 NCI-designated Cancer Centers, 29 (40.8 %) had Instagram accounts, whereas, four (6 %) gynecologic oncology divisions had Instagram accounts. The search of the seven most common gynecologic oncology genetic terms yielded 126,750 posts with the majority under BRCA1(n = 56,900) and BRCA2 (n = 45,000) followed by Lynch syndrome (n = 14,700) and hereditary breast and ovarian cancer (n = 8,900). In terms of authorship, 93 (66 %) of all top 140 posts were written by patients, 20 (14.2 %) were written by health care providers and 27 (19.3 %) were written by "other." This study highlights the lack of presence of divisions of gynecologic oncology at NCI-designated Cancer Centers on Instagram but does demonstrate the existence of active discussion on hereditary gynecologic cancers on Instagram by patients.

Metastatic ovarian carcinosarcoma in a patient undergoing in-vitro fertilization: A case report.

INTRODUCTION AND IMPORTANCE: Ovarian carcinosarcomas (OCS) are highly aggressive tumors containing both carcinomatous and sarcomatous elements. Patients are typically older postmenopausal women who present with advanced disease, however rarely young women can be affected. CASE PRESENTATION: A 41-year-old woman undergoing fertility treatment was found to have a new 9-10 cm pelvic mass on routine transvaginal ultrasound (TVUS) 16 days after embryo transfer. Diagnostic laparoscopy revealed a mass in the posterior cul-de-sac that was surgically excised and sent to pathology for evaluation. Pathology was consistent with carcinosarcoma of gynecologic origin. Further work-up revealed advanced disease with apparent rapid progression. Patient underwent interval debulking surgery after four cycles of neoadjuvant chemotherapy with carboplatin and paclitaxel with final pathology consistent with primary ovarian carcinosarcoma and complete gross resection of disease. CLINICAL DISCUSSION: In the setting of advanced disease neoadjuvant chemotherapy with a platinum-based chemotherapy regimen followed by cytoreductive surgery is a standard approach to treatment of OCS. Given the rarity of disease, most data regarding treatment has been extrapolated from other forms of epithelial ovarian cancer. Specific risk factors for disease development of OCS including the long-term effects of assisted reproductive technology remain understudied. CONCLUSION: While OCS are rare highly aggressive biphasic tumors that primarily affect older postmenopausal woman, we present a unique case of OCS incidentally found in a young woman undergoing fertility treatment via in-vitro fertilization.

Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock.

BACKGROUND: Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI. METHODS: Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine. RESULTS: AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine. CONCLUSION: 5-LO and FLAP colocalize in the interstitium of the renal medulla following T/HS. MLD attenuates this phenomenon, which coincides with pathologic changes seen in tubules during kidney injury and biochemical evidence of AKI. These data suggest that gut-derived leukotriene substrate predisposes the kidney and the lung to subsequent injury.

Visuomotor training improves stroke-related ipsilesional upper extremity impairments.

BACKGROUND: Unilateral middle cerebral artery infarction has been reported to impair bilateral hand grasp. METHODS: Individuals (5 males and 5 females; age 33-86 years) with chronic unilateral middle cerebral artery stroke (4 right lesions and 6 left lesions) repeatedly lifted a 260-g object. Participants were then trained to lift the object using visuomotor feedback via an oscilloscope that displayed their actual grip force (GF) and a target GF, which roughly matched the physical properties of the object. RESULTS: The subjects failed to accurately modulate the predictive GF when relying on somatosensory information from the previous lifts. Instead, for all the lifts, they programmed excessive GF equivalent to the force used for the first lift. The predictive GF was lowered for lifts following the removal of the visual feedback. The mean difference in predictive GF between the lifts before and after visual training was significant (4.35 +/- 0.027 N; P

Role of ultrasound surveillance of transjugular intrahepatic portosystemic shunts in the covered stent era.

PURPOSE: To assess ultrasound (US) surveillance of expanded polytetrafluoroethylene (ePTFE)-covered stents in transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: Procedural data, including stent size and portosystemic gradients (PSG) before and after creation of TIPS, were obtained retrospectively in 55 patients (33 men, 22 women). Chart review provided clinical information, including etiology of liver disease, indication for TIPS creation, and Child-Pugh class. Radiology reports provided US venography data and pathology reports confirmed shunt status in transplant recipients. Patients had baseline US examinations 3-7 days after TIPS creation with scheduled follow-up at 1, 3, 6, and 12 months after the procedure. Clinical and radiology reports were compared to evaluate US surveillance of Viatorr stents. RESULTS: One hundred fifty-nine US examinations were performed on 52 patients, for an average 3.1 studies per patient (range, 1-7) over a mean follow-up duration of 173 days (range, 0-1,013 d). Sixty-four US studies (40%) were baseline studies, 88 studies (55%) were routine follow-up studies, and seven (4%) were interval studies. US predicted TIPS abnormalities in 30 of 159 studies (19%); venography followed 15 of 30 abnormal US findings (50%) and clinical examinations complemented 10 of 15 venograms (67%). Venography and US were concordant in eight of 15 paired studies (53%); clinical examinations, when conducted, accurately predicted shunt status in all but one case. US findings changed management in six of 159 studies (4%): five of six (83%) were baseline evaluations and the other one (17%) was a routine follow-up examination. A total of five baseline US examinations (8%) and one surveillance examination (1%) altered patient management. CONCLUSIONS: A single US examination after a TIPS procedure to confirm immediate function may be valuable, but routine US is not effective for long-term surveillance of ePTFE-covered stents.

Comparison of sequential versus simultaneous methods of adrenal venous sampling.

PURPOSE: To compare two methods of adrenal venous sampling (AVS) in preoperative localization of adrenal lesions in primary hyperaldosteronism. MATERIALS AND METHODS: Twenty-one patients (13 men, eight women) underwent selective adrenal venous sampling between July 2001 and May 2003. One of the 21 patients underwent repeat AVS, for a total of 22 procedures. In half the procedures (n = 11), simultaneous bilateral adrenal venous catheterization and sampling was performed before and after intraprocedural adrenocorticotropic hormone (ACTH) administration; in the remaining half (n = 11), sequential catheterization of the left and right adrenal veins was performed during continuous ACTH infusion 1 hour before and throughout AVS. Chart review provided procedural data, including sampling intervals and aldosterone/cortisol ratios. Patient records provided clinical data, including blood pressure, serum aldosterone levels, and computed tomography and magnetic resonance imaging findings. Surgical pathology reports confirmed unilateral disease but were not applicable to bilateral disease. RESULTS: Selective AVS was completed successfully in 21 of 22 procedures (95%); the unsuccessful sampling was repeated successfully. Disease lateralized in 13 of 22 cases. Simultaneous bilateral AVS localized unilateral disease in seven of eight cases (88%) and was nondiagnostic in one case (13%), with cases confirmed by surgical pathology reports. Sequential bilateral AVS localized unilateral disease in four of four cases (100%) confirmed by surgical pathology reports, with one lost to follow-up. Bilateral disease was diagnosed in six of 22 cases: two of 11 by simultaneous AVS and four of 11 by sequential AVS. Three of 22 cases demonstrated borderline hormone levels that failed to meet the diagnostic threshold for recommended adrenalectomy. Mean elapsed time between acquisition of right and left samples did not differ between simultaneous and sequential AVS (P = .09). Baseline (prestimulation) sampling did not contribute unique diagnostic information in any case and provided contradictory or confounding information in three of 11 simultaneous AVS procedures (27%). CONCLUSIONS: Sequential bilateral catheterization does not compromise the reliability of time-sensitive AVS. Both simultaneous and sequential AVS are adequate studies; however, obtaining baseline prestimulation samples during simultaneous AVS is unnecessary and increases the cost of the procedure.