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To investigate the feasibility and predictive factors for same day discharge (SDD) following robotic hysterectomy (RH) for benign indications to optimize patient selection by incorporating pre-, intra-, and postoperative variables.A single-center retrospective cohort study SETTINGS: : Tertiary Academic Hospital.Patients undergoing RH for benign indications.Patients were designated for SDD by implementing enhanced recovery after surgery (ERAS) protocol.The study included 890 patients who underwent RH for benign indications between the years 2016-2021. Of these, 618 (69.4%) were discharged the same day and 272 (30.5%) were admitted for overnight stay. Both groups had similar age (46.4 vs 46.2 years), BMI (28.3 vs. 28.9) and similar indications for surgery. In multivariable logistic regression, factors that were significant for overnight stay were: American society of Anesthesiology (ASA) score 3, Charlson Comorbidity Index, previous laparotomy, and operative time. Other factors such as surgery start time and preoperative hemoglobin levels were not statistically significant. Post operative outcomes were comparable for both groups with similar readmission and reoperation rates.The likelihood of SDD following robotic hysterectomy in this cohort after implementing ERAS protocol was almost 70% and most of the predictive factors for overnight stay were non-modifiable. Importantly, both groups had similar outcomes following surgery.

PURPOSE The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor–positive ovarian cancer. METHODS This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light. RESULTS From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor–positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported. CONCLUSION This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

To determine whether advancing a manipulator increased the distance of the ureter to the cervix and/or vagina.Prospective.Academic institution.A total of 22 intact fresh-frozen female pelvises.A total of 6 ureteral distances were measured per pelvis. Included were the following measurements on each side: (1) from the lateral cervical wall to the ureter at the intersection with the uterine artery; (2) from the lateral cervical wall to the parametrial ureter; and (3) from the vagina to the ureter at the intersection with the uterine artery. All measurements were obtained with and without advancement of a uterine manipulator.The average distance from the ureter to the cervix and vagina without advancing the manipulator was 2.8 and 3.1 cm, respectively, and the distance from the parametrial ureter to the cervix was 3.3 cm. When the manipulator was advanced, all ureteral distances increased by 0.8, 0.6, and 0.6 cm, respectively, in 12 of the 22 pelvises (55%). Advancing the manipulator did not increase at least 1 of the distances in 10 of the 22 pelvises (45%). The advancement of the manipulator lengthened the 2 shortest ureteral distances of 1 cm noted in 1 pelvis (4.5%) by 0.9 and 0.4 cm.The uterine manipulator increased the distance of the ureter to the cervix and vagina for all measurements in 55.5% of the pelvises. The greatest increase was 0.9 cm. The manipulator did not increase at least 1 of the distances in 10 of the 22 pelvises (45.4%).

PDF file - 298K, 1) Ki67 IHC staining of patient & Avatars; 2) pan-CK, CD45, vimentin staining of Avatars; 3) graph of gains/losses by aCGH in Avatars; 4) Ca125 levels in serum of patients/Avatars.

Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics.Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described. Fresh ovarian, primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking surgery and injected intraperitoneally into severe combined immunodeficient mice.Results: Tumorgrafts demonstrated a 74% engraftment rate with microscopic fidelity of primary tumor characteristics. Low-passage tumorgrafts also showed comparable genomic aberrations with the corresponding primary tumor and exhibit gene set enrichment of multiple ovarian cancer molecular subtypes, similar to patient tumors. Importantly, each of these tumorgraft models is annotated with clinical data and for those that have been tested, response to platinum chemotherapy correlates with the source patient.Conclusions: Presented herein is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment. Clin Cancer Res; 20(5); 1288–97. ©2014 AACR.

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Terminal lakes are important archives of continental hydroclimate and in some cases contain important economic resources. Here, we present an ∼2.9 m.y. lacustrine carbonate carbon and oxygen stable isotope record from a Great Basin continental drill core. We paired these measurements with bulk lithium concentrations to reveal a relationship between past climate and lithium enrichment in authigenic lacustrine clays. Further, we explored the possible effects of changing seasonality on the isotope record through the use of paired air mass trajectories and modern isotope data. Our findings show the evolution of the basin’s moisture balance over million-year time scales, which we attribute to variations in precipitation seasonality as well as fluctuations in the amount of evaporation associated with changes in atmospheric moisture convergence and divergence. We found a positive correlation between the oxygen isotope values of the lake carbonate and the bulk sediment lithium concentrations, which we argue is indicative of evapoconcentration of the lake environment and subsequent enrichment of the authigenic clays. Our results suggest a link between past hydroclimate changes and the formation of lithium-rich authigenic clays feeding high lithium concentrations in this modern brine aquifer system.

Intraoperative radiotherapy; Overall survival; Progression-free survival Radioterapia intraoperatoria; Supervivencia global; Supervivencia libre de progresión Radioteràpia intraoperatòria; Supervivència global; Supervivència lliure de progressió Objective To report survival outcomes in patients with locally recurrent gynecologic cancers managed with curative-intent radical extirpation, perioperative external beam radiotherapy, and intraoperative radiotherapy (IORT). Patients and Methods We conducted a retrospective cohort analysis of 44 patients with locally recurrent gynecologic cancer treated at a single tertiary-care center (Mayo Clinic in Arizona) over a 15-year period (January 1, 2004, to July 31, 2019). This cohort included patients with uterine (n=21, 47.7%), ovarian (n=3, 6.8%), cervical (n=11, 25.0%), vaginal (n=2, 4.5%), vulvar (n=1, 2.3%), and unknown primary (n=6, 13.6%) cancer. Curative-intent radical extirpation included pelvic exenteration (n=13, 29.5%), laterally extended endopelvic resection (n=22, 50.0%), excision of para-aortic lymph node metastasis (n=8, 18.2%), and radical vaginectomy (n=1, 2.3%). Of the 44 patients in our cohort, 37 (84.1%) received IORT and 7 (15.9%) had intended to receive IORT but did not receive it. Results The median follow-up for the 44 patients was 12 months (range, 1 to 161 months). For patients who received IORT, the median progression-free survival (PFS) and overall survival (OS) were 13 and 21 months, respectively, and the 3-year cumulative incidence of central, locoregional, and distant recurrence was 27.0% (10 of 37), 40.5% (15 of 37), and 37.8% (14 of 37), respectively. Surgical margins were classified as negative (28 of 44, 63.6%), microscopic (11 of 44, 25.0%), or macroscopic (5 of 44, 11.4%). Negative, microscopic, and macroscopic surgical margins resulted in 3-year PFS of 51.8%, 20.5%, and 0%, respectively (P=.01) and 3-year OS of 62.9%, 20.0%, and 0%, respectively (P=.035). Progression-free survival (P=.69) and OS (P=.88) were not different between patients with negative surgical margins who received (n=21) and did not receive (n=7) IORT. Ten of 37 patients (27.0%) had development of grade 3 or higher toxicities, with 1 death due to sepsis. Conclusion Complete tumor resection at the time of curative-intent radical extirpation achieved higher rates of PFS and OS regardless of IORT administration.

BackgroundIncreased infiltration of T cells into ovarian tumors has been repeatedly shown to be predictive of enhanced patient survival. However, despite the evidence of an active immune response in ovarian cancer (OC), the frequency of responses to immune checkpoint blockade (ICB) therapy in OC is much lower than other cancer types. Recent studies have highlighted that deficiencies in the DNA damage response (DDR) can drive increased genomic instability and tumor immunogenicity, which leads to enhanced responses to ICB. Protein phosphatase 4 (PP4) is a critical regulator of the DDR; however, its potential role in antitumor immunity is currently unknown.ResultsOur results show that the PP4 inhibitor, fostriecin, combined with carboplatin leads to increased carboplatin sensitivity, DNA damage, and micronuclei formation. Using multiple OC cell lines, we show that PP4 inhibition orPPP4Cknockdown combined with carboplatin triggers inflammatory signaling via Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 1 (STAT1) activation. This resulted in increased expression of the pro-inflammatory cytokines and chemokines:CCL5,CXCL10, andIL-6. In addition,IFNB1expression was increased suggesting activation of the type I interferon response. Conditioned media from OC cells treated with the combination of PP4 inhibitor and carboplatin significantly increased migration of both CD8 T cell and natural killer (NK) cells over carboplatin treatment alone. Knockdown of stimulator of interferon genes (STING) in OC cells significantly abrogated the increase in CD8 T-cell migration induced by PP4 inhibition. Co-culture of NK-92 cells and OC cells withPPP4CorPPP4R3Bknockdown resulted in strong induction of NK cell interferon-γ, increased degranulation, and increased NK cell-mediated cytotoxicity against OC cells. Stable knockdown of PP4C in a syngeneic, immunocompetent mouse model of OC resulted in significantly reduced tumor growthin vivo. Tumors with PP4C knockdown had increased infiltration of NK cells, NK T cells, and CD4+T cells. Addition of low dose carboplatin treatment led to increased CD8+T-cell infiltration in PP4C knockdown tumors as compared with the untreated PP4C knockdown tumors.ConclusionsOur work has identified a role for PP4 inhibition in promoting inflammatory signaling and enhanced immune cell effector function. These findings support the further investigation of PP4 inhibitors to enhance chemo-immunotherapy for OC treatment.

Epithelial ovarian cancer (EOC) represents the most frequently occurring gynecological malignancy, accounting for more than 70% of ovarian cancer deaths. Preoperative imaging plays an important role in assessing the extent of disease and guides the next step in surgical decision-making and operative planning. In this article, we will review the multimodality imaging features of various subtypes of EOC. We will also discuss the role of imaging in the staging, management, and surveillance of EOC.

ObjectiveTo evaluate trends in outpatient versus inpatient hysterectomy for endometrial cancer and assess enabling factors, cost and safety.MethodsIn this retrospective cohort study, patients aged 18 years or older who underwent hysterectomy for endometrial cancer between January 2008 and September 2015 were identified in the Premier Healthcare Database. The surgical approach for hysterectomy was classified as open/abdominal, vaginal, laparoscopic or robotic assisted. We described trends in surgical setting, perioperative costs and safety. The impact of patient, provider and hospital characteristics on outpatient migration was assessed using multivariate logistic regression.ResultsWe identified 41 246 patients who met inclusion criteria. During the time period studied, we observed a 41.3% shift from inpatient to outpatient hysterectomy (pConclusionsA significant shift from inpatient to outpatient setting was observed for hysterectomies performed for endometrial cancer over time. Minimally invasive surgery, particularly the robotic approach, facilitated this migration, preserving clinical outcomes and leading to reduction in costs.

Objective To analyze clinical characteristics and survival of patients with primary vaginal cancer. Methods Retrospective analysis of patients with primary squamous, adenocarcinoma and adenosquamous cell carcinoma of the vagina identified from the Mayo Clinic Cancer Registry between 1998 and 2018. Results A total of 124 patients were identified: stage I, 39 patients; stage II, 44, stage III, 20 and stage IV, 21. Patients with stage III and IV were older as compared to stage I and II. (mean ages 61 vs 67) (p = 0.024). Squamous cell carcinoma made up 71% of tumors. History of other malignancy was present in 24% patients. Median follow-up time was 60 months (range 1–240). Five-year PFS in stage I, II, III and IV was 58.7%, 59.4%, 67.3% and 31.8%, respectively (p = 0.039). Five-year DSS was 84.3%, 73.7%, 78.7% and 26.5% respectively (p 4 cm, entire vaginal involvement, and lymph node (LN) metastasis were poor prognosticators in univariate analysis. Primary surgery in stage I/II patients had similar survival outcomes as compared to primary radiation, but post-operative RT rate was 55%. Brachytherapy alone was associated with a high local recurrence (80%) in stage I/II patients. The addition of brachytherapy had improved 5-year PFS and DSS than EBRT alone in patients with stage III/IVA. (p Conclusion Surgery or radiation is effective treatment for vaginal cancer stage I and II. The addition of brachytherapy to external pelvic radiation increases survival in stages III-IV.

Objective To compare the survival outcomes and surgical radicality between women who underwent open versus robotic radical hysterectomy (RH) for early cervical cancer. Methods In this institutional retrospective study, patients with clinical stage IA2- IIA (FIGO 2009) squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who underwent either open or robotic RH between 2000 and 2017 were identified. Parametrial width and vaginal length were re-measured from pathology slides. An inverse propensity score weighting model was used to adjust selection bias. Results A total of 333 patients were included (181 open, 152 robotic). The median follow-up time was 130 months for the open group and 53 months for the robotic group. There were 31 (17.1%) recurrences in the open and 21 (13.8%) in the robotic group. The 5-year progression-free survival (PFS) for the robotic and open group were 79.0% and 90.5%, respectively (HR 2.37, 95% CI 1.40–4.02). Five-year overall survival (OS) were 85.8% and 95.3%, respectively (HR 3.17, 95% CI 1.76–5.70). The mean parametrial width was similar between the open and robotic groups (2.5 vs 2.4 cm, p = 0.99). Unique recurrences (38.1%, 8/21) were noted in the robotic group: 2 port-site, 4 peritoneal, and 2 carcinomatosis. The time to vaginal recurrence was shorter in the robotic group than the open group (p = 0.001). Conclusion Patients who underwent robotic RH had inferior PFS and OS compared to open surgery. Surgical radicality according to pathology measurements was similar between the two approaches.

To investigate the relation of pathologic tumor-free margins and local recurrence in patients who underwent primary surgery for vulvar squamous cell carcinoma.In this retrospective analysis, patients with stage I-III vulvar squamous cell carcinoma who underwent primary surgery between 2000 and 2018 were identified from the Mayo Clinic Cancer Registry.A total of 335 patients were included and divided into three groups according to tumor-free margins: group 1 (3 mm, n = 32); group 2 (≥3 to8 mm, n = 151); group 3 (≥8 mm, n = 152). The median follow-up time was 73 months (range 2-240). A total of 78 (23.3%) patients developed local recurrence. With the inverse propensity score weighing method adjusting baseline characters, margins8 mm had inferior local control (HR 1.98, 95% CI 1.13-3.41). The 5-year local disease-free survival (DFS) was 48.2%, 81.5% and 84.6% for group 1, 2 and 3 respectively (p 0.001). There were no differences in groin lymph nodes relapse (p = 0.850), distant metastases (p = 0.253), or disease-specific survival (DSS) (p = 0.289) among the three groups. Margins8 mm, midline involvement, multifocal disease, precancerous lesions on margins and depth of invasion1 mm were found to be poor prognosticators for local DFS in univariate analysis. Multifocal disease was the strongest predictor for local recurrence in multivariate analysis (HR 4.32, 95% CI 2.67-6.99).Patients undergoing primary surgery for vulvar squamous cell carcinoma with tumor free-margins8 mm have a higher local recurrence rate.

Ovarian borderline tumors are neoplasms of epithelial origin that are typically present in young patients and tend to have a less aggressive clinical course than malignant tumors. Accurate diagnosis and staging of borderline tumors has important prognostic and management implications (like fertility-sparing procedures) for women of child-bearing age. This article will review the sonographic, CT, and MRI features of borderline epithelial ovarian tumors with histopathologic correlation. Borderline tumors have less soft tissue and thinner walls/septations than malignant tumors. Serous borderline tumors more commonly have papillary projections, which can simulate the appearance of a sea anemone. Mucinous borderline tumors often are larger, multi-cystic, and more commonly unilateral. The borderline mucinous tumors may also present with pseudomyxoma peritonei, which can make it difficult to distinguish from malignant mucinous carcinoma. Ultrasound is usually the first-line modality for imaging these tumors with MRI reserved for further characterizing indeterminate cases. CT is best used to stage tumors for both locoregional and distant metastatic disease. Overall, however, the imaging features overlap with both benign and malignant ovarian tumors. Despite this, it is important for the radiologist to be familiar with the imaging appearances of borderline tumors because they can present in younger patients and may benefit from different clinical/surgical management.

Objective To investigate progression-free survival (PFS) and overall survival (OS) between women who underwent surgical versus radiographic assessment of pelvic lymph nodes (PLN) and para-aortic lymph nodes (PALN) prior to chemoradiation therapy for cervical cancer. Methods In this retrospective cohort analysis, patients with stage IB2 - IIIB squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who completed concurrent chemoradiation therapy (CCRT) between 2000 and 2017 from the Mayo Clinic Cancer Registry were identified. A 1:2 propensity score matching between surgical and imaging groups was performed and PFS and OS were compared between groups. Results 148 patients were identified and after propensity score matching, 35 from the surgical group and 70 from the imaging group were included in the analysis. There were no statistical differences in baseline characteristics between the 2 groups. The median follow-up time was 41 months (range 7–218) for the surgical group and 51.5 months (range 7–198) for the imaging group. Five-year PFS was 62.6% for the surgical group and 72.4% in imaging group (HR 1.11, 95% CI 0.54–2.30, p = 0.77). Five-year OS was 70.2% for the surgical group and 70.5% for the imaging group (HR 1.02, 95% CI 0.46–2.29, p = 0.96). FIGO stage, PALN metastasis, and parametrial involvement were found to be poor prognosticators for PFS and OS in univariate analysis. Only PALN metastasis significantly predicted unfavorable PFS (HR 2.76, 95% CI 1.23–6.18, p = 0.01) and OS (HR 3.46, 95% CI 1.40–8.55, p = 0.01) in multivariate analysis. There were no differences in locoregional recurrence and distant metastasis between the two groups (p = 0.33 and 0.59 respectively). Conclusion Patients with cervical cancer who underwent radiographic assessment of PLN and PALN had comparable survival outcomes to surgical assessment.

Simple Summary Metabolism is the process by which living organisms and cells generate energy to sustain life. At the organismal level, metabolic homeostasis is a tightly controlled balance between energy consumption and energy expenditure. Many studies have shown that disruption of this homeostasis leads to an inflammatory phenotype within adipose tissue. The aim of this review is to provide an overview of the dynamic metabolic interplay within adipose tissue and its implications for cancer progression and metastasis. Abstract Disruption of metabolic homeostasis at the organismal level can cause metabolic syndrome associated with obesity. The role of adipose tissue in cancer has been investigated over the last several decades with many studies implicating obesity as a risk factor for the development of cancer. Adipose tissue contains a diverse array of immune cell populations that promote metabolic homeostasis through a tightly controlled balance of pro- and anti-inflammatory signals. During obesity, pro-inflammatory cell types infiltrate and expand within the adipose tissue, exacerbating metabolic dysfunction. Some studies have now shown that the intracellular metabolism of immune cells is also deregulated by the lipid-rich environment in obesity. What is not fully understood, is how this may influence cancer progression, metastasis, and anti-tumor immunity. This review seeks to highlight our current understanding of the effect of adipose tissue on immune cell function and discuss how recent results offer new insight into the role that adipose tissue plays in cancer progression and anti-tumor immunity.

Epithelial ovarian cancer (EOC) represents the most frequently occurring gynecological malignancy, accounting for more than 70% of ovarian cancer deaths. Preoperative imaging plays an important role in assessing the extent of disease and guides the next step in surgical decision-making and operative planning. In this article, we will review the multimodality imaging features of various subtypes of EOC. We will also discuss the role of imaging in the staging, management, and surveillance of EOC.

Background Increased immune infiltration in ovarian tumors has been linked to improved patient outcome. Nonetheless, responses to checkpoint blockade therapies have been disappointing in ovarian cancer patients. This has been attributed to the low mutational burden present in ovarian tumors. However, many tumor antigens have been identified in ovarian cancer, which underscores the critical need to identify new treatment strategies that will trigger anti-tumor immunity in ovarian cancer. Recent studies have revealed that defects in DNA damage repair (DDR) pathways can contribute to improved responses to immune-directed therapies.1 2 We previously discovered that CT45 expression sensitizes ovarian cancer cells to chemotherapy via its interaction with the protein phosphatase 4 (PP4) complex.3 PP4 is known to play a key role in DDR pathways; however, its potential effects on anti-tumor immunity remain unknown. Methods Using fostriecin, a commercially available inhibitor of PP4, we studied the effect of fostriecin on chemosensitivity using cell cycle analysis and cell viability assays. To study the effect of fostriecin on DNA damage, we performed comet assays and measured micronuclei along with FANCD2 foci formation. Furthermore, using western blot, qPCR, and T cell activation assays, we assessed the role of fostriecin in promoting an inflammatory response. We tested the efficacy of combining fostriecin with carboplatin and PD-1 inhibition in a syngeneic mouse model of ovarian cancer. Results Our results show that fostriecin treatment combined with carboplatin leads to increased carboplatin sensitivity, DNA damage, and micronuclei formation. Using a panel of ovarian cancer cells, we show that fostriecin treatment triggers an anti-tumor immune response via STAT1 activation resulting in increased expression of pro-inflammatory cytokines. Furthermore, in a syngeneic mouse ID8 ovarian cancer cell line, we demonstrate that combination treatment of fostriecin and carboplatin significantly increased CD8 T cell activation over carboplatin treatment alone. Conclusions Our work has identified a role for PP4 inhibition in promoting anti-tumor immunity. These findings form the groundwork for the rationale design of a clinical trial combining PP4 inhibitors with chemo-immunotherapy as a new approach in ovarian cancer treatment. References Rodier F, Coppe J-P, Patil CK, Hoeijmakers WAM, Munoz DP, Raza SR, et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nature Cell Biology 2009; 11: 973–979. Zhang H, Christensen CL, Dries R, Oser MG, Deng J, Diskin B, et al. CDK7 Inhibition potentiates genome instability triggering anti-tumor immunity in small cell lung cancer. Cancer cell 2020;37:37–54.e39. Coscia F, Lengyel E, Duraiswamy J, Ashcroft B, Bassani-Sternberg M, Wierer M, et al. Multi-level proteomics identifies CT45 as a chemosensitivity mediator and immunotherapy target in ovarian cancer. Cell 2018;175:159–170.e116.

Objective We describe a phase II clinical trial of the combination of ribociclib and letrozole for treatment of relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) and endometrial cancer (EC). The primary endpoint was the proportion of patients alive, progression-free survival (PFS), and still on treatment at 12 weeks (PFS12), with 45% or greater considered positive. Methods Patients with measurable, relapsed ER-positive OC or EC (platinum-sensitive or resistant) were eligible and treated with 400 mg of oral ribociclib and 2.5 mg of oral letrozole daily. Patient-derived xenografts (PDXs) were created from imaging-guided tumour biopsies. Results Forty patients (20 OC and 20 EC) were enrolled. A PFS12 of 55% was observed in the EC cohort and 50% in the OC cohort. A PFS greater or equal to 24 weeks (PFS24) was seen in 20% (4/20) of the OC cohort and 35% (7/20) of the EC cohort. The greatest benefit was seen in low-grade serous OC (LGSOC) (3/3, 100% PFS24) and grades 1 and 2 EC (5/11, 45% PFS24). All three LGSOC patients obtained at least a partial response lasting for over 2 years, with two of the three patients still on treatment. PDX tumour engraftment was feasible in 45% of patients. Positive survival effects of the combination of ribociclib and letrozole were observed in two of three EC PDX models. Conclusion Ribociclib and letrozole have promising clinical activity in relapsed ER-positive OC and EC, particularly in LGSOC and relapsed ER-positive grade 1 and 2 EC. Generation of PDX models is feasible with positive survival effects observed in EC models. Trial registration number ClinicalTrials.gov registry ( NCT02657928 ).

OBJECTIVE To evaluate the survival impact of imaging vs surgical nodal assessment in patients with cervical cancer stage IB2-IVA prior to definitive chemoradiotherapy (CRT). METHODS PubMed, MEDLINE, Cochrane Library, and ClinicalTrials.gov were used to search for publications in English and Chinese over a 50-year period. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols was used to conduct this review. Inclusion criteria were studies that compared survival outcomes in International Federation of Gynecology and Obstetrics 2009 stage IB2-IVA cervical cancer patients with pre-therapy pelvic and/or aortic lymphadenectomy (LND) or imaging. One or more of the following modalities were used for nodal assessment: computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT. The National Institutes of Health Quality Assessment Tool was utilized to assess study quality. RESULTS The initial search identified 65 studies, and five met the inclusion criteria. There were a total of 1,112 patients. Seven hundred and fifty-four underwent pelvic and/or aortic LND and 358 had imaging. When compared to LND, imaging had a sensitivity and specificity of 88.9% and 22.2% for pelvic lymph node (LN), and 33%-62.5% and 92%-95.5% for para-aortic LN. There were no differences in progression-free survival (PFS) (hazard ratio [HR]=1.13; 95% confidence interval [CI]=0.73-1.74; I²=75%; p

ispartof: JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY vol:27 issue:2 pages:462-463 ispartof: location:United States status: published

Decoding the earliest orogenic stages in the Andes, the largest subduction orogen on Earth is fundamental to understanding changes in climate, drainage organization, and biodiversity in South America. Furthermore, it is crucial to unraveling the driving mechanism behind the initiation of orogeny. To track the earliest stages of Andean growth, we studied the Aysén/Río Mayo basin (ARB) in the North Patagonian Andes. The small degree of Cenozoic tectonic overprinting in this part of the Andes has allowed outstanding preservation of the deformational and sedimentary record of the earliest Andean deformation. In this study, we employ a multidisciplinary approach involving structural geology, sedimentology, geochronology, and provenance studies from the Early Cretaceous Apeleg Formation (~130?122 Ma) in the ARB and geochemical analysis of intrusive Cretaceous igneous rocks. Particularly, the recognition of syncontractional growth strata at several localities indicate a syntectonic origin for this unit and provide additional structural evidence of Early Cretaceous contraction in the North Patagonian Andes. Thus, the Apeleg Formation is interpreted as deposited during a contractional basin stage. Geochemical data from Aptian-Albian intrusive igneous rocks indicate that initial contraction emplaced over thinned crust likely inherited from the Jurassic extension in the ARB. This stage is then compared with a new synthesis of the earliest Cretaceous contraction along the Andes. This analysis reveals that the ARB likely holds the oldest post-Gondwanic synorogenic unit along the orogen and more significantly, that Andean birth was a diachronous process which propagated northward since the late Early Cretaceous. The latter findings have major implications for the evolution of the Andes and shed light into the driving mechanism behind initial orogeny. Fil: Gianni, Guido Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Navarrete Granzotto, César Rodrigo. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Echaurren Gonzalez, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Díaz, Marianela Ximena Yasmin. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Butler, Kristina L.. University of Texas at Austin; Estados Unidos Fil: Horton, Brian K.. University of Texas at Austin; Estados Unidos Fil: Encinas, Alfonso. Universidad de Concepción; Chile Fil: Folguera Telichevsky, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina

The retroarc region of central Patagonia recorded three contractional stages (Late Triassic, Late Cretaceous, and Miocene) coincident with eastward broadening of arc magmatism. Inboard arc migration may be linked to shallowing of the subducted slab, subduction erosion of forearc regions, or a combination of both. Contractional episodes were followed by slab rollback, producing a series of extensional depocenters and magmatic belts across Patagonia at ~170-130 Ma, ~55-22 Ma and ~5 Ma. These rollback events weakened Patagonian crust through fracturing, mantle upwelling, and magmatic injection, favoring inception and propagation of subsequent contractional episodes. Phases of slab rollback and retroarc extension are reflected in εHf and εNd isotopic trends, with more juvenile trajectories corresponding to mantle upwelling into a broad asthenospheric wedge during slab retreat. Periods of crustal shortening are recorded by evolved εHf and εNd isotopic trajectories, demonstrating modified mantle sources. Mesozoic-Cenozoic extensional basins of Patagonia, such as the Chubut Basin, Cañadón Asfalto Basin, Río Mayo-Aysén Basin, Pilcaniyeu and Auca Pan-El Maitén magmatic belts/volcanogenic basins, and the Traiguén Basin were generated during episodes of slab rollback. In contrast, the extension-related San Jorge Gulf Basin constitutes an east-west-trending anomaly developed in an interval of the Cretaceous when the rest of western Patagonia experienced shortening. During this time, crustal evolution trends shifted from juvenile to more evolved and the arc expanded toward the continental interior most likely under a flat-slab regime. The San Jorge Gulf Basin is linked to Neocomian extensional structures in an intracratonic basin later influenced by compressional stresses linked to subduction zone in the west and incipient opening of the south Atlantic to east. Fil: Folguera Telichevsky, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Fernández Paz, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Iannelli, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Navarrete Granzotto, César Rodrigo. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina Fil: Echaurren Gonzalez, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Gianni, Guido Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Butler, Kristina L.. University of Texas at Austin; Estados Unidos Fil: Horton, Brian K.. University of Texas at Austin; Estados Unidos Fil: Litvak, Vanesa Dafne. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Encinas, Alfonso. Universidad de Concepcion del Uruguay. Facultad de Ciencias Economicas.; Argentina Fil: Orts, Darío Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina

To examine the effect of robotic-assisted surgery implementation for treatment of endometrial cancer in the United States on 30-day clinical outcomes and costs.We retrospectively reviewed data of adult patients who underwent total hysterectomy for endometrial cancer in the US hospitals in Premier Healthcare Database between January 1, 2008 and September 30, 2015. We conducted trend analyses comparing the proportions of surgical approaches with the associated clinical outcomes and costs over the study period using Mann-Kendall tests. Clinical outcomes and costs of robotic-assisted surgery, laparoscopic and open surgery have been compared after propensity score 1:1 matching in the most recent 3 years (January 1, 2013-September 30, 2015).Of a total of 35,224 patients, use of robotic-assisted surgery increased from 9.48% to 56.82% while open surgery decreased from 70.4% to 28.1% over the study period. A 2.5% decrease in major complications (P .001), a 2.9% decrease in minor complications (P = .001), and a 2.0% decrease 30-day readmissions (P = .001) was observed across all surgical approaches. Perioperative 30-day total cost slightly decreased from US $11,048 to US $10,322 (P = .08). Among propensity-score matched patients, robotic-assisted surgery was associated with shorter hospitalization than open surgery (median [interquartile range], 2.0 [2.0-3.0] vs 4.0 [3.0-6.0] days) and laparoscopic surgery (2.0 [2.0-3.0] vs 3.0 [2.0-4.0] days), fewer 30-day complications (20.1% vs 33.7%) (all P .001), and comparable perioperative 30-day total costs (median [interquartile range], US $12,200 [US $9,509-US $16,341] vs US $12,018 [US $8,996-US $17,162]; P = .34) with open surgery.Robotic-assisted surgery facilitated the widespread diffusion of a minimally invasive approach nationally for endometrial cancer, with reduction of perioperative morbidity and no increase in overall treatment-related 30-day costs at national level.

5503 Background: Pafolacianine sodium is under investigation as an adjunct to visual inspection and palpation by providing intra-operative imaging of folate receptor positive (FR+) ovarian cancer. Since complete resection (R0) is the strongest predictor of overall survival, methods to enhance detection of lesions are expected to benefit patient outcomes. Methods: For this phase 3, randomized, multicenter, single dose, open-label pivotal trial (NCT03180307), patients with ovarian cancer who were scheduled to undergo cytoreductive surgery were recruited from 11 sites in the US and Netherlands from March 2018 through April 2020. The study objectives were to confirm efficacy and safety of pafolacianine sodium (0.025 mg/kg i.v., ≥1 h prior to imaging) in combination with intraoperative near-infrared fluorescence (NIRF) imaging to detect additional lesions not detected by palpation and normal white light alone. Results: Pafolacianine sodium was administered to 150 total patients (safety analysis set); 109 patients comprised the full analysis set for efficacy analyses. Patients had primarily serous adenocarcinoma (n = 72; 68.6%) and advanced stage disease (n = 83; 76.1%). In 33% of patients (36 of 109), NIRF imaging with pafolacianine sodium identified additional lesions that were not planned for resection and were not detected by normal white light and palpation ( P < 0.001, 95% CI [0.243, 0.427]). Among patients who underwent interval debulking surgery, the rate was higher, at 39.7% of patients (23 of 58; 95% CI [0.270, 0.534]). At the individual lesion level, the accuracy of pafolacianine sodium with NIRF to detect ovarian cancer is reflected by sensitivity of 83% (95% CI [73.9, 89.4]) and a false positive rate of 32.7% (95% CI [25.6, 40.7]). Investigators reported achieving complete resection (R0) in 62.4% (68 of 109) of patients. Drug-related adverse events (AEs) were reported by 30% of patients (45 out of 150). The most frequently reported drug-related AEs were nausea (18.0%), vomiting (5.3%), and abdominal pain (4.7%). Infusion reactions at the time of the procedure were mostly (96%) mild or moderate in severity; 89% resolved within 24 hours of onset. No drug-related serious AEs or deaths were reported. Conclusions: This phase 3 trial of pafolacianine sodium with NIRF imaging met its primary endpoint, intraoperatively identifying additional cancer not planned for resection in a statistically significant number of patients. Therefore, pafolacianine sodium may offer a novel real-time adjunct to current surgical imaging practice in ovarian cancer surgery. Clinical trial information: NCT03180307.

Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX) or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID) mice from Epstein-Barr virus (EBV)-infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab) to 5.6% (n = 160 with rituximab), and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

Background: Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of endometrial reassessment for women with endometrial intraepithelial neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. Methods: We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Results: Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m2 vs. 31 kg/m2; p

Two compositionally different volcanic cycles are documented by geological mapping, lithofacies and petrographic analyses of Jurassic volcanic rocks in the northeastern sector of the Deseado Massif, constituting the western counterpart of the Karoo-Ferrar LIPs in Patagonia. The first cycle is of intermediate composition and is represented by andesitic lava flows, phenoandesitic moderate-grade ignimbrites and volcaniclastic deposits. These rocks constitute a previously unknown large outcrop (~100 km2) of the Bajo Pobre Formation. The second cycle (Chon Aike Formation) is acidic in composition and constituted by several pyroclastic deposits (ignimbrites and co-ignimbrite lag breccias), lavic bodies (rhyolitic lava domes, dykes, and coulees) and rhyolitic pyroclastic dykes. Structural measurements collected in the studied area suggest an extensional tectonic control on the emplacement of, at least, the Chon Aike Formation rocks. We document two major NE-striking (SE-dipping) normal faults, which constitute direct field evidence of the extensional tectonic control on the Jurassic Chon Aike Silicic LIP in the Deseado Massif at the time when southern Gondwana broke up.

The arrival and subsequent stagnation of the Farallon/Nazca slab at the mantle transition zone below southern South America triggered seemingly unrelated large-scale geological processes in the second half of the Cenozoic. During this period, three poorly understood regional events have characterized the more recent geological history of Patagonia: i) the development of intense intraplate magmatism, ii) two large-scale marine transgressions, and iii) abnormally accelerated topographic uplift. We propose a geodynamic model that connects the subducting slab mechanisms to these events based on seismic tomography, 2-D kinematic reconstructions, dynamic subsidence models and a detailed literature review. According to our kinematic reconstruction, after the Paleocene-Eocene opening of the Aluk (Phoenix)/Farallon slab window, the Farallon oceanic slab arrived to the mantle transition zone below Patagonia at ~36–32 Ma. This event caused the physical perturbation of this mantle layer, and dehydration melting of the uplifted portions by wadsleyite breakdown, triggering an intense Oligocene-middle Miocene intraplate magmatism significantly influenced by subduction-derived fluids. Simultaneously, due to increasing disturbance of the lower mantle during the Farallon slab penetration and stagnation in the mantle transition zone, a large subduction-induced mantle flow cell began to tilt the South American plate. Tilting drove the two large marine transgressions which inundated much of the southern Argentina and Chile. Finally, in the latest Miocene-Pleistocene, Farallon-Nazca slab break-off induced the decompression melting of the sub-slab asthenosphere, generating the most recent magmatic episode in the north-central Patagonia. This magmatism was partially contemporaneous with the Chile ridge (Nazca/Antarctic) slab window-related southern Patagonian igneous activity; and although both episodes show evidence of mantle metasomatic inheritance, the north-central magmatism shows higher Th/La and 87Sr/86Sr ratios, and lower εNd values, suggesting possible contributions from the stagnant Farallon slab (wet plumes). These modern magmatic episodes can be directly linked to the Quaternary uplift of Patagonia by mantle upwelling. Fil: Navarrete Granzotto, César Rodrigo. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gianni, Guido Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina Fil: Massaferro, Gabriela Isabel. Universidad Nacional de la Patagonia. Facultad de Ciencias Naturales. Sede Puerto Madryn; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Geología y Paleontología; Argentina Fil: Butler, Kristina. University of Texas at Austin; Estados Unidos

Women considering risk reduction surgery after a diagnosis of breast/ovarian cancer and/or inherited cancer gene mutation face difficult decisions. The safety of combined breast and gynecologic surgery has not been well studied; therefore, we evaluated the outcomes for patients who have undergone coordinated multispecialty surgery.We conducted a retrospective review of patients undergoing simultaneous breast and gynecologic surgery for newly or previously diagnosed breast cancer and/or an inherited cancer gene mutation during the same anesthetic at a single institution from 1999 to 2013.Seventy-three patients with a mean age of 50 years (range 27-88) were identified. Most patients had newly diagnosed breast cancer or ductal carcinoma in situ (62 %) and 28 patients (38 %) had an identified BRCA mutation. Almost all gynecologic procedures were for risk reduction or benign gynecologic conditions (97 %). Mastectomy was performed in 39 patients (53 %), the majority of whom (79 %) underwent immediate reconstruction. The most common gynecologic procedure involved bilateral salpingo-oophorectomy, which was performed alone in 18 patients (25 %) and combined with hysterectomy in 40 patients (55 %). A total of 32 patients (44 %) developed postoperative complications, most of which were minor and did not require surgical intervention or hospitalization. Two of the 19 patients who underwent implant reconstruction (11 %; 3 % of the entire cohort) had major infectious complications requiring explantation.Combined breast and gynecologic procedures for a breast cancer diagnosis and/or risk reduction in patients can be accomplished with acceptable morbidity. Concurrent operations, including reconstruction, can be offered to patients without negatively impacting their outcome.

BACKGROUND Patients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODS A total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTS Overall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P 65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. Conclusions The results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016. © 2016 American Cancer Society.

The Iglesia basin hosts a key sedimentary archive of the evolution of the southern Central Andes. This basin is classically interpreted as recording the transition from an outer- to an inner-wedge-top (piggyback basin) depozone in the early Bermejo foreland basin system. In this study, we reevaluate the tectonic evolution of the Iglesia basin based on the interpretation of 2D seismic reflection data, structural geology, zircon U Pb geochronology, and provenance analysis. We report an extensional event that initiated the basin opening. Our results indicate normal faulting development and synextensional deposition from the latest Oligocene (?)-earliest Miocene to middle Miocene. Since the middle Miocene, extensional activity experienced a progressive decrease in changing to shortening and basin inversion between the middle-late Miocene. The latter stage coincided with the full development of Pampean flat-slab subduction indicating maximum plate coupling at that time. Our findings challenge the idea of uninterrupted Paleogene to Neogene flexural subsidence related to the Andean orogenic-load in the backarc area. Therefore, the results of this study have important consequences for the early evolution of the Bermejo foreland basin and ultimately, for the growth of the southern Central Andes.

Detailed geological mapping of 900 km2, newly defined volcanic and volcaniclastic lithofacies, multiple stratigraphic profiles, and a new zircon U/Pb eruption age (178.7 ± 1.9 Ma) describe an early Jurassic extensional-related piece-meal collapsed graben caldera in the eastern sector of Deseado Massif, at southern Patagonia. This volcano-tectonic structure, here referred to as The Deseado Caldera, collapsed at least twice controlled by two major NW-striking normal faults, during which a large acidic ignimbrite (predominantly moderate to extremely high-grade) and co-ignimbrite lag breccias were extruded through multiple NW-fissure vents. During the two post-collapse periods, alluvial fans, lagoons and laharic sedimentary environments re-worked the intra-caldera volcaniclastic deposits. Finally, numerous elongated and aligned rhyolitic lava domes and dykes were emplaced during the final magmatic resurgence stage. This caldera represents the first clear evidence of the extensional tectonic regime influence, associated with the inception of Gondwana breakup, on the eruptive mechanisms of the Jurassic Chon Aike Silicic LIP in the Deseado Massif.

Video Objective To describe surgical techniques used to resect abdominal wall endometriosis. Setting The patient is a 49 year old female who presents to a tertiary care academic institution with complaints of cyclic pelvic pain. Interventions Minimally invasive excision of extrapelvic endometriosis. Conclusion The goals of resection of abdominal wall endometriosis are restoration of normal anatomy and adequate excision of pathology in order to decrease risk of recurrence. Robotic excision of abdominal wall endometriosis is feasible with understanding of anatomy and mastery of basic surgical techniques.

Background Catamenial epilepsy refers to cyclic seizure exacerbation in relation to the menstrual cycle. Three distinct patterns have been described: C1-perimenstrual, C2-periovulatory, and C3-inadequate luteal. There is experimental and clinical evidence that gonadal steroid hormones affect neuronal excitability with estrogens being mainly proconvulsant and progesterone anticonvulsant. If reproductive steroids have a role in seizure occurrence, they may also have a role in treatment. Objective The objective of this study was to critically assess current evidence regarding the efficacy of progesterone as adjunctive therapy in women with intractable catamenial epilepsy. Methods The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the fields of epilepsy and gynecology. Results A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the efficacy of adjunctive cyclic natural progesterone therapy versus placebo for seizures in women with intractable partial epilepsy, stratified by catamenial and noncatamenial status. There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation is a significant predictor of the responder rate for progesterone therapy. Conclusions Cyclic natural progesterone is not superior to placebo in reducing seizure frequency in women with intractable partial epilepsy. Posthoc findings suggest that progesterone may benefit a subset of women with perimenstrually exacerbated seizures.

To assess how the widespread adoption of minimally invasive surgery in the United States is associated with changes in 30-day morbidity and mortality in endometrial cancer treatment.In this retrospective cohort study, the American College of Surgeons' National Surgical Quality Improvement Project database for 2008-2014 was reviewed for patients who had undergone surgery for endometrial cancer according to their primary Current Procedural Terminology (CPT) codes. Women with CPT codes for advanced cancer or with disseminated disease were excluded. A trend analysis across the time period by surgical approach (open surgery through laparotomy, vaginal surgery, and minimally invasive surgery) was performed using a Cochran-Armitage test for trend. Thirty-day surgical outcomes were compared between patients who had minimally invasive surgery and open surgery. Inverse probability of treatment weighting models were used to investigate the independent effect of minimally invasive surgery on 30-day outcomes.Overall, 12,283 patients met the inclusion criteria. A significant implementation of minimally invasive surgery (24.2-71.4%) and a concomitant decrease in open surgery through laparotomy (71.1-26.4%) were observed from 2008 to 2014 (both P.001). Rate of vaginal surgery did not change over time (1.5-2.2%, P=.06). After adjusting for possible confounders, open surgery (compared with minimally invasive surgery) was independently associated with increased odds of major complications (n=347 versus n=274, adjusted odds ratio [OR] 2.4, 95% CI 2.0-2.8), readmission (n=269 versus n=238, adjusted OR 2.2, 95% CI 1.8-2.6), reoperation (n=80 versus n=93, adjusted OR 1.5, 95% CI 1.2-2.1), superficial surgical site infection (n=190 versus n=55, adjusted OR 6.8, 95% CI 5.0-9.2), perioperative transfusion (n=430 versus n=149, adjusted OR 5.9, 95% CI 4.8-7.1), and death (n=41 vs, n=20, adjusted OR 3.8, 95% CI 2.2-6.6). A comprehensive decrease in 30-day morbidity for the treatment of endometrial cancer overall was observed from 2008 to 2014 (P.001), whereas 30-day mortality remained stable (P=.24).The widespread adoption of minimally invasive surgery is associated with substantial decreases in 30-day morbidity, readmission, and reoperation for women treated for endometrial cancer in the United States.