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The mechanisms underlying improvements in early-stage cancer at diagnosis following Medicaid expansion remain unknown. We hypothesized that Medicaid expansion allowed for low-income adults to enroll in Medicaid before cancer diagnosis, thus increasing the number of stably-enrolled relative to those who enroll in Medicaid only after diagnosis (emergently-enrolled).Using data from the 2011-2017 Ohio Cancer Incidence Surveillance System and Medicaid enrollment files, we identified individuals diagnosed with incident invasive breast (n=4850), cervical (n=1023), and colorectal (n=3363) cancer. We conducted causal mediation analysis to estimate the direct effect of pre- (vs. post-) expansion on being diagnosed with early-stage (-vs. regional-stage and distant-stage) disease, and indirect (mediation) effect through being in the stably- (vs. emergently-) enrolled group, controlling for individual-level and area-level characteristics.The percentage of stably-enrolled patients increased from 63.3% to 73.9% post-expansion, while that of the emergently-enrolled decreased from 36.7% to 26.1%. The percentage of patients with early-stage diagnosis remained 1.3-2.9 times higher among the stably-than the emergently-enrolled group, both pre-expansion and post-expansion. Results from the causal mediation analysis showed that there was an indirect effect of Medicaid expansion through being in the stably- (vs. emergently-) enrolled group [risk ratios with 95% confidence interval: 1.018 (1.010-1.027) for breast cancer, 1.115 (1.064-1.167) for cervical cancer, and 1.090 (1.062-1.118) for colorectal cancer.We provide the first evidence that post-expansion improvements in cancer stage were caused by an increased reliance on Medicaid as a source of stable insurance coverage.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Purpose To explain recent regulatory guidance for different types of stakeholders, including asset managers, fund complexes, and institutional investors. Design/methodology/approach Summary of recent regulatory guidance and explanation for different types of stakeholders, including asset managers, fund complexes, and institutional investors. Findings While the U.S. Department of Labor’s (DOL’s) letter does not open the door to direct access to Private Market Investments by 401(k) plan participants, it does provide a framework for the expanded use of private equity and, we believe, other types of Private Market Investments in managed asset allocation funds such as target date funds. Originality/value Practical guidance from experienced asset management and investment funds and ERISA lawyers.

The thermal scattering laws (TSL) take into account the crystalline structure and atomic motions of isotopes bound in materials. This paper presents the CINEL code, which was developed to generate temperature-dependent TSL for solid, liquid and free gas materials of interest for nuclear reactors. CINEL is able to calculate TSL from the phonon density of states (PDOS) of materials under the Gaussian-Incoherent approximations. The PDOS can be obtained by using theoretical approaches (e.g., ab initio density functional theory and molecular dynamics) or experimental results. In this work, the PDOS presented in the ENDF/BVIII.0 and NJOY-NCrystal libraries were used for numerical validation purposes. The CINEL results are in good agreement with those reported in these databases, even in the specific cases of TSL with the newly mixed elastic format. The coding flexibility offered by Python using the JupyterLab interface allowed to investigate limits of physical models reported in the literature, such as a four-site model for UO2, anharmonic behaviors of oxygen atoms bound in a Fm3m structure, texture in Zry4 samples and jump corrections in a roto-translational diffusion model for liquid water. The use of graphic processing units (GPU) is a necessity to perform calculations in a few minutes. The performances of the CINEL code is illustrated with the results obtained on actinide oxides having a Fm3m structure (UO2, ThO2, NpO2 and PuO2), low enriched fuel (UMo), cladding (Zry4) and moderators (H2O with a specific emphasis on ice).

During the SARS-CoV-2 (COVID-19) pandemic, an unusual outbreak of yellow-brown pigmentation on the skin of children was reported. Because of the restrictions on movement promulgated during the lockdown, most consultancies were performed using teledermatology. Data concerning personal care products and application of topical substances were collected, which revealed use of the same brand of wipes for all patients. A liquid chromatography-mass spectrometry analysis was performed to compare the components of the wipes before and after the observation of the pigmentation, in order to detect the responsible substance. This analysis revealed a level about 10-fold higher than normal of ascorbic acid and its oxidation products (dehydroascorbic acid and L-threonic acid) in the wipes associated with the pigmentation. These 'colouring wipes' represent a peculiar but harmless phenomenon that highlights the importance of careful questioning about personal care products used by patients.

10561 Background: Disruptions to cancer care during the COVID-19 pandemic due to disease mitigation efforts, supply-chain issues, and fear of COVID-19 have all been reported, but study of their extent has been limited. The purpose of this study is to evaluate the extent and associations with patient reported disruptions to cancer treatment and other care during the COVID-19 pandemic using nationally representative data. Methods: This cross-sectional study uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults who reported requiring current cancer treatment or other care related to their cancer in the second half of 2020 were included. Rates of patients with self-reported changes, delays, or cancellations to cancer treatment or other cancer-related care due to the COVID-19 pandemic were calculated and their associations with demographic and other variables were analyzed. All data were adjusted using sample weights and specific variables to account for stratification and other survey characteristics using the Stata svy command. Chi-square testing was used to compare proportions across variable groups. Univariable logistic regression analysis was utilized to assess variable associations with change, delay, or cancellations to cancer care during the COVID-19 pandemic. Multivariable logistic regression analysis was used to create a model adjusted for select demographic variables. Results: A sample-weighted 2,867,326 adults (n=574) reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. Of these, 189 (32.1%) reported any change, delay, or cancellation due to the pandemic. On univariable analysis, patients who were younger, female, had comorbidities, and uninsured were significantly more likely to report care disruptions. On adjusted analysis, younger age and female sex remained significant predictors. In a sample-weighted subset of 1,600,587 patients (n=331), 291 (87.9%) reported virtual appointment use. There was no association with disruptions across breast, prostate, lung, and colorectal cancer groups. Conclusions: Approximately 1/3 of patients experienced disruptions to cancer care during the COVID-19 pandemic. Patients with younger age or female sex were more likely to have disruptions in care, which may reflect risk stratification strategies in the early stages of the pandemic. The longitudinal impact of these disruptions on outcomes merits further study. [Table: see text]

Between 150 and 230.6 K, bulk supercooled water freezes upon cooling, and amorphous ice crystallizes upon heating: bulk water thus exists only in its stable ice form. To circumvent this problem, experiments are generally performed on water adsorbed in SiO2 based porous systems. In this work, we take advantage of Monte Carlo simulations to explore this metastable supercooled region inaccessible to experiments. Using three rigid, non-polarizable water models, namely SPC, TIP4P and TIP4P/2005, we investigate the isobaric specific heat capacity (Cp), between 100 and 300 K, of bulk water and water films of few monolayers adsorbed on different SiO2 surfaces: a smooth surface, a non-hydroxylated (0001) surface of quartz, and a fully hydroxylated (001) surface of cristobalite. As Cp is directly related to the entropy fluctuations and we focus on low temperatures, the convergence of the Monte Carlo simulations is a critical point of this work. Also, due to the small mass of the hydrogen atoms, quantum corrections are taken into account, and lead to an excellent agreement of the simulated and experimental Cp values at low temperature (100 K region). Altogether, we conclude that, in bulk, Cp is shown to exhibit a broad peak around 225 K for the SPC and TIP4P models, and around 250 K for the TIP4P/2005 model, in qualitative agreement with the experimentally observed features in Cp measurements. For interfacial water, in all cases, the broad Cp peak disappears. This result, at odds with experimental observations, suggests that disorder and hydrogen bonding at the interface (not yet taken into account) have a fundamental role in confined water transitions.

Objective No standardization of quality of operative reporting currently exists, and this represents a missed opportunity for communication among health care providers. This study proposed a method to improve operative notes by structuring the findings by six anatomical zones of the pelvis. Objective I was to validate the method of documenting six zones of the pelvis by using intraoperative photography. Objective II was to compare this method with dictations from operative reports created before introducing this method. Methods This retrospective cohort study evaluated pre- and post-intervention results of using six zones to guide operative reporting. Reports were collected from participating surgeons and were scored using a validated scoring tool. Each participant was taught to photograph six zones and use the zones in the operative report. Pre- and post-intervention cases were compared using generalized linear mixed models. Results Scores of study participants using the zones were significantly higher than those without ( P 0.0001). Surgeons showed an ability to improve their reporting. The detail illustrated in the cases was qualitatively richer, and the anatomy within the six zones was referenced more frequently. Conclusion Compared with reports without the technique, incorporating the six zones greatly enhances operative reporting and likely would improve communication among care providers. More reliable communication of intraoperative findings has the potential to enhance the value of laparoscopy greatly as a diagnostic tool across gynaecological subspecialties.

Background: Minimally invasive surgery is the preferred approach for performing many gynecologic procedures. Occasionally, supraumbilical port placement may be preferable to optimize visibility and maneuverability although the risks of complications are less well characterized compared to umbilical entry. Methods: We conducted a retrospective review of computed tomograms from 92 patients to evaluate the anatomic considerations for umbilical and supraumbilical port entry based on patient age, body mass index (BMI), parity, abdominal wall thickness, and distance to the great vessels. Results: Supraumbilical entry was not associated with differences in distance to the great vessels compared to the umbilicus. However, supraumbilical location and BMI were associated with greater abdominal wall thickness. Age and BMI were associated with greater distance to the great vessels, while age was associated with thinner abdominal wall. Multiple linear regression confirmed independent effects of age and BMI. No association between parity and distance to retroperitoneal vessels was observed. Conclusion: Younger patients may be at increased risk for great vessel injury and pre-peritoneal insufflation. Obese patients may be at risk for pre-peritoneal insufflation, while patients with BMI < 30, particularly with a skin-to-aorta distance < 7 cm, may be at an increased risk for great vessel injury. Surgeons should consider these factors when considering supraumbilical port entry.

1572 Background: Studies to date have shown post-Medicaid expansion (M-exp) decreases in the percentage of cancer patients who are uninsured and improvements in cancer stage at diagnosis in states that expanded Medicaid as part of the Affordable Care Act. However, most studies have examined impact of M-exp on stage outcomes at the population level, or among Medicaid and uninsured, rather than solely in the Medicaid population. Using cancer registry data from a non M-exp state (Georgia (GA)) and two M-exp states (Ohio (OH) and New Jersey (NJ)), we compared changes in cancer stage in patients on Medicaid, accounting for individual- and contextual-level characteristics at the Zip Code Tabulation Area (ZCTA) level. Methods: We used GA, OH, and NJ cancer registry data for individuals 20-64 years of age and diagnosed with incident invasive female breast (BC), cervical (CC), and colorectal cancer (CRC). Data spanned from 2010-2017 for GA and OH, and from 2011-2016 for NJ (for BC and CRC only), with 2014 marking the year in which Medicaid was expanded in OH and NJ. We retrieved demographic data (age, race/ethnicity, sex for CRC, insurance status, and cancer stage from the cancer registries), and obtained ZCTA-level data from the American Community Survey (e.g., income, education, and female-headed households). We defined late-stage diagnosis as regional- or distant- stage. We conducted multivariable logistic regression models by state and cancer site to examine changes in late-stage cancer diagnosis pre- and post-M-exp, accounting for individual- and ZCTA-level covariates. Results: The number of patients with incident cancer who were on Medicaid increased by 41.7% (n = 1757 to 2490), 59.6% (327 to 522), and 76.4% (953 to 1681) for BC, CC, and CRC cancers, respectively, in Ohio; by 92.4% (433 to 833) for BC and by over 100% for CRC (232 to 496) in NJ; but by 12.7% (662 to 746) among CRC patients in GA, where the number of BC and CC patients on Medicaid remained relatively stable. Adjusting for individual and contextual-level factors, the adjusted risk ratio (ARR and (95% Confidence Interval)) for late-stage disease was lowest for BC patients in OH (0.93 (0.87, 0.99)) and for CRC patients in GA (0.94 (0.89, 0.99)). The ARR for BC and CRC in NJ were not statistically significant, though they trended towards improvement. Similarly, changes in late-stage for CC were not statistically significant in OH or in GA. Conclusions: The increased number of cancer patients in Medicaid and the reductions in late-stage diagnosis observed may potentially translate into reduced, or at least stabilized, cancer-related morbidity and mortality burden among Medicaid beneficiaries over time. However, reductions in late-stage diagnosis were not consistent across cancer sites or states, possibly due to differences in population demographics, health behaviors, healthcare seeking patterns, and state-level cancer prevention efforts.

Study Objectives To identify morphometric characteristics of obese patients that best predict pulmonary intolerance to robotic pelvic surgery using a novel method for quantifying adipose distribution. Design Retrospective study (Canadian Task Force classification II-2). Setting University hospital. Patients Fifty-nine patients with endometrial cancer who underwent robotic hysterectomy and lymphadenectomy between April 2008 and May 2014 and also underwent perioperative computed tomography (CT) imaging within 1 year. Intervention Visceral fat volume (VFV) and subcutaneous fat volume (SFV) were quantified through waist circumference measurements along with average volume estimation of slices taken at 3 levels: mid-waist, L2-L3, and L4-L5. Mean and maximum values were obtained for intraoperative physiological data. Measurements and Main Results The patients' mean body mass index (BMI) was 34 (range, 20–59). Along with waist circumference, VFV and SFV quantified by CT at the mid-waist, L2-L3, and L4-L5 levels were all significant independent predictors for peak airway pressure (PAP; average and maximum) and plateau airway pressure (Pplat; average and maximum) on multivariate regression analysis after adjustment for age, ethnicity, diabetes, hypertension, pulmonary disease, smoking, obstructive sleep apnea, American Society of Anesthesiologists classification, and duration of anesthesia. Compared with the other CT parameters, L2-L3 VFV was the best predictor of average PAP (β = 0.398; p = .002), maximum PAP (β = 0.493; p Conclusion These novel CT morphometric measurements represent valid predictors of pulmonary intolerance to robotic surgery in obese patients. Of the measures analyzed, VFV at L2-L3 best predicts pulmonary tolerance in obese patients.

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma–specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo. Furthermore, small molecule–mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo. These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations. Significance: This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development. See related commentary by Haines and Huang, p. 4009

A novel method for the production of important medical radioisotopes has been developed. The approach is based on performing the nuclear reaction in inverse kinematics, namely sending a heavy-ion beam of appropriate energy on a light target (e.g. H, d, He) and collecting the isotope of interest. In this work, as a proof-of-concept, we studied the production of the theranostic radionuclide 67 Cu (T 1/2 = 62 h) via the reaction of a 70 Zn beam at 15 MeV/nucleon with a hydrogen gas target. The 67 Cu radionuclide alongside other coproduced isotopes, was collected after the gas target on an aluminum catcher foil and their radioactivity was measured by off-line γ-ray analysis. After 36 h post irradiation, apart from the product of interest 67 Cu, the main radioimpurity coming from the 70 Zn + p reaction was 69m Zn (T 1/2 = 13.8 h), which can be reduced by further radio-cooling. Moreover, along with the radionuclide of interest produced in inverse kinematics, the production of additional radioisotopes is possible by making use of the forward-focused neutrons from the reaction and allowing them to interact with a secondary target. A preliminary successful test of this concept was realized in the present study. The main requirement to obtain activities appropriate for preclinical studies is the development of high-intensity heavy-ion primary beams. © 2019 Elsevier Ltd

Background Chemo-radiation (chemoRT) has improved the overall survival for locally advanced cervical cancer (LACC) though women whose disease involves the para-aortic nodes (PAN) experience recurrence rates and worse survival outcomes compared to those without PAN involvement. This Phase I study determined if additional cycles of systemic chemotherapy could be safely added to extended field chemoRT in this population of patients. Methods Women with LACC and documented positive PAN were eligible for treatment. All women were treated with extended field radiation and brachytherapy and concurrent cisplatin 40 mg/m2 weekly for six weeks. Four to six weeks after completion of chemoRT, patients were treated with four cycles of paclitaxel 135 mg/m2 and escalating doses of carboplatin (Dose Level (DL) 1 = AUC 4, DL2 = AUC 5). Results Eleven women were entered on study and 9 were evaluable for dose limiting toxicities (DLT). Two women (1 in each of 2 DLs) did not complete chemoRT and so were not evaluable for DLT. Three women completed all 10 cycles at DL 1 with no DLTs. Six women were then treated at DL 2. For the 10 patients evaluable for response, the ORR was 60% (CR + PR). PFS and OS at 12 months were 60% and 90%, respectively. The predominant grade 3 or 4 acute toxicities were hematologic. There were no grade 5 events. Conclusion Extended field chemoRT followed by paclitaxel 135 mg/m2 and carboplatin AUC 5 is feasible in women with LACC and positive PAN.

// Anil Belur Nagaraj 1 , Peronne Joseph 1 , Olga Kovalenko 1 , Sareena Singh 2 , Amy Armstrong 2 , Raymond Redline 3 , Kimberly Resnick 2 , Kristine Zanotti 2 , Steven Waggoner 2 and Analisa DiFeo 1 1 Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA 2 Department of Gynecology, Division of Gynecological Oncology, University Hospital Case Medical Center, Cleveland, OH, USA 3 Department of Pathology, University Hospital Case Medical Center, Cleveland, OH, USA Correspondence to: Analisa DiFeo, email: // Keywords : patient derived xenograft, platinum resistance, tumor spheres, cancer initiating cells, β-catenin Received : April 23, 2015 Accepted : June 01, 2015 Published : June 29, 2015 Abstract Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/β-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/β-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/β-catenin signaling is activated in ovarian CICs, and targeted inhibition of β-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/β-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/β-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option.

A 33-year-old nulliparous patient who desires fertility presents with a 6-month history of deep dyspareunia. She reports a history of renal cell carcinoma and heavy periods but is otherwise healthy. Her exam is significant for multiple cutaneous nodules and a mildly enlarged uterus. Pelvic ultrasound shows a 7 cm lower uterine segment subserosal fibroid.

Purpose To evaluate the role of 3T-MRI–guided adaptive high-dose-rate (HDR) combined intracavitary and interstitial brachytherapy for cervical cancer using a novel intracavitary split-ring (ICSR) applicator adapter. Methods and Materials We retrospectively reviewed all HDR brachytherapy cases from 2013 to 2015 using an ICSR applicator. Initial optimization was performed using 3T multiparametric MRI (mpMRI) series with an applicator in place. The mpMRI series were discretionarily acquired before subsequent fractions for possible target adaptation. When necessary, interstitial needles (ISNs) were inserted through a novel ICSR adapter or freehand. Dosimetric parameters, clinical outcomes, and toxicities were compared between groups. Results Seventeen patients were included, with a mean followup of 32 months. An mpMRI series preceded each initial fraction and 52.9% of patients underwent ≥1 additional pretreatment mpMRI. Among these subsequent fractions, the high-risk clinical target volume was reduced in 80% vs. 41% without pretreatment mpMRI. Five patients had ISN placement (seven insertions) to improve extracervical target coverage. Mean D90 (Gy) per fraction to the high-risk clinical target volume and intermediate-risk clinical target volume with and without an ISN were 7.51 ± 1.07 vs. 6.14 ± 0.52 (p = 0.028) and 6.35 ± 0.75 vs. 5.21 ± 0.49 (p = 0.007), respectively. Mean fractional D2cc (Gy) for organs at risk was comparable. No Grades 3–4 toxicity was reported. Disease-free survival and local control for the ICSR-ISN and ICSR-alone groups were 29.8 months/80.0% and 31.2 months/83.3%, respectively. Conclusions The mpMRI acquisition with ICSR applicator in place immediately before HDR brachytherapy for cervical cancer guided successful adaptive treatment optimization and delivery. Our initial experience with a novel interstitial adapter for the split-ring applicator demonstrated excellent target coverage without compromising organs at risk, resulting in good local control and disease-free survival.

Background Obesity is a leading risk factor for endometrial cancer (EC), particularly Type I forms, which are increasing in the U.S. Although death rates from most cancers have been decreasing, overall mortality in EC is increasing in the U.S. EC survivors' poor fitness combined with their surgical treatments may make weight loss particularly challenging. High intensity exercise increases neurotrophins and neurological reward via altered striatal dopamine in animals, and, in humans, chronic high intensity exercise enhances meal-induced satiety and may reduce hedonic eating. “Assisted” exercise, a mode of exercise whereby a patient's voluntary exercise rate is augmented mechanically, may modulate brain dopamine levels in Parkinson's Disease patients but has not been previously evaluated as a treatment for obesity. Methods We describe the rationale and design of the REWARD trial, which has the overarching goal of randomizing 120 obese EC survivors to “assisted” or voluntary rate cycling to evaluate the efficacy of “assisted” exercise in enhancing and sustaining weight loss. Patients in both arms will receive 3 days/week of supervised exercise and 1 day/week of a group dietary behavioral intervention for 16 weeks and, then, will be followed for 6 months. Outcomes The primary outcome is weight loss. Secondary outcomes include measures for body composition, fitness, eating behavior, exercise motivation and, quality of life as well as cognition and food reward and motivation as assessed by functional magnetic resonance imaging (fMRI) tasks. Conclusions If successful, the REWARD program could be extended to help sustain weight loss in obese cancer and non-cancer patients.

Objectives Whereas previous studies have shown that lymphovascular space invasion (LVSI) is associated with an increased risk for recurrent endometrioid endometrial cancer and worse survival, the magnitude of this risk in relationship to the other high-risk features is poorly understood. Our aim was to study the impact of LVSI in comparison with the other high-risk features in recurrence and survival. Materials and Methods Women with stage I or II endometrial cancer were included in this study if they had LVSI, International Federation of Gynecology and Obstetrics grade 2 or 3 histology, or outer-half myometrial invasion. We performed multivariate regression analyses to identify prognostic factors for recurrence. We performed Kaplan-Meier survival curve predictions of progression-free survival (PFS), overall survival (OS), and disease-specific survival; and Cox proportional hazard models to adjust for other variables. Results Three hundred eighty-eight patients met the inclusion criteria; their median follow-up was 59 months. The rates of recurrence were the following: overall, 17%; pelvic, 11%; vaginal cuff, 8%, and distant, 11%. Twenty-six percent of the patients died during follow-up. After adjusting for age, body mass index, grade, depth of invasion, cervical invasion, lymphadenectomy, and adjuvant treatment(s), LVSI was the only significant independent risk factor for total (odds ratio, 2.6) and distant (odds ratio, 3.3) recurrences and was also a risk factor for local and vaginal recurrences. Lymphovascular space invasion was also a significant poor prognostic factor for PFS (hazard ratio [HR], 2.8), OS (HR, 2.8), and disease-specific survival (HR, 7.0). Among the other risk factors, age was significantly associated with worse PFS and OS, whereas grade 3 histology was significantly associated with worse OS. Conclusion In our study, LVSI is the only significant and consistent poor prognostic factor for all the outcomes studied: recurrences and survival. Lymphovascular space invasion seems to be a better predictor than the other risk factors. This suggests a potential role for adjuvant systemic therapies in patients with LVSI, even in the absence of other high-risk features.

A novel one-sided NMR magnet has been validated for accurate measurements of diffusion in thin samples. Results are presented from the measurement of self-diffusion in several solvents, including the room temperature ionic liquid 1-butyl-3-methyl imidazolium bis(trifluoromethane)sulfonimide (BMIM-TFSI). We also present results from diffusion measurements of BMIM-TFSI confined in nanoporous anodized aluminum oxide (AAO) membranes (thickness 100 μm), a promising electrolyte/membrane combination for portable energy devices. A reduction in the diffusion coefficient, compared to the bulk, has been observed in BMIM-TFSI confined in narrow pores (55 nm). The possible application of this instrument to in situ measurements of portable energy devices is discussed.

Computation-based drug-repurposing/repositioning approaches can greatly speed up the traditional drug discovery process. To date, systematic and comprehensive computation-based approaches to identify and validate drug-repositioning candidates for epithelial ovarian cancer (EOC) have not been undertaken. Here, we present a novel drug discovery strategy that combines a computational drug-repositioning system (DrugPredict) with biological testing in cell lines in order to rapidly identify novel drug candidates for EOC. DrugPredict exploited unique repositioning opportunities rendered by a vast amount of disease genomics, phenomics, drug treatment, and genetic pathway and uniquely revealed that non-steroidal anti-inflammatories (NSAIDs) rank just as high as currently used ovarian cancer drugs. As epidemiological studies have reported decreased incidence of ovarian cancer associated with regular intake of NSAIDs, we assessed whether NSAIDs could have chemoadjuvant applications in EOC and found that (i) NSAID Indomethacin induces robust cell death in primary patient-derived platinum-sensitive and platinum- resistant ovarian cancer cells and ovarian cancer stem cells and (ii) downregulation of β-catenin is partially driving effects of Indomethacin in cisplatin-resistant cells. In summary, we demonstrate that DrugPredict represents an innovative computational drug- discovery strategy to uncover drugs that are routinely used for other indications that could be effective in treating various cancers, thus introducing a potentially rapid and cost-effective translational opportunity. As NSAIDs are already in routine use in gynecological treatment regimens and have acceptable safety profile, our results will provide with a rationale for testing NSAIDs as potential chemoadjuvants in EOC patient trials.

Background.The objective of this study was to determine whether female surgical residents underestimate their surgical abilities relative to males on a standardized test of laparoscopic skill.Methods.Twenty-six male and female general surgery residents and 25 female obstetrics and gynecology residents at two academic centers were asked to predict their score prior to undergoing the Fundamentals of Laparoscopic Surgery standardized skills exam. Actual and predicted score as well as delta values (predicted score minus actual score) were compared between residents. Multivariate linear regression was used to determine variables associated with predicted score, actual score, and delta scores.Results.There was no difference in actual score based on residency or gender. Predicted scores, however, were significantly lower in female versus male general surgery residents (25.8 ± 13.3 versus 56.0 ± 16.0;p<0.01) and in female obstetrics and gynecology residents versus male general surgery residents (mean difference 20.9, 95% CI 11.6–34.8;p<0.01). Male residents more accurately predicted their scores while female residents significantly underestimated their scores.Conclusion.Gender differences in estimating surgical ability exist that do not reflect actual differences in performance. This finding needs to be considered when structuring mentorship in surgical training programs.

Robotic-assisted laparoscopic surgery appears to be safe and feasible for definitive management of patients with severe endometriosis., Objectives: The primary objective was to examine the safety and feasibility of robotic-assisted laparoscopy in a cohort of women treated surgically for stage III and IV endometriosis. The secondary objective was to explore whether the stage of endometriosis affected surgical outcome. Methods: In this cohort study, 43 women with severe endometriosis were treated with robot-assisted laparoscopic hysterectomy with unilateral or bilateral salpingo-oophorectomy for stage III (n = 19) or stage IV (n = 24) disease. Results: Histopathologic evaluation confirmed endometriosis in all patients, and fibroids were also shown in 12 patients. The median actual operative time was 145 min (range, 67–325 min), and the median blood loss was 100 mL (range, 20–400 mL). All but one of the procedures were completed successfully robotically. The length of hospital stay was 1 d for 95% of patients (41 of 43), and 2 patients had prolonged stays of 4 d and 5 d, respectively. One patient was readmitted for a vaginal cuff abscess; this represented the only complication identified in this series. Conclusions: Robot-assisted laparoscopic surgery appears to be a reasonably safe and feasible method for the definitive surgical management of women with severe endometriosis.

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After menopause when ovulation has ceased, EH is more common in women with conditions that increase levels of circulating estrogen such as obesity or estrogen replacement therapy. Women with EH are at increased risk for both concurrent and subsequent endometrial cancer. The risk of coexisting cancer in women with a diagnosis of EH at endometrial sampling is due to limitations in both endometrial sampling and the diagnostic reproducibility among pathologists. These diagnostic uncertainties add to the complexity of managing EH. This review offers a rational approach to prevention, diagnosis, and treatment of EH, including hormone therapy and conservative surgical methods.

The study aim was to compare outcomes in women with high-grade endometrial cancer (EC) who underwent surgical staging via minimally invasive surgery (MIS) versus laparotomy.This is a retrospective, multi-institutional cohort study of patients with high-grade EC who were comprehensively surgically staged by either MIS or laparotomy. Demographic, surgical variables, complications, and survival were analyzed.Three hundred and eighty-three patients met criteria: 191 underwent laparotomy and 192 MIS (65% robotic, 35% laparoscopy). Subgroups were well matched by age (mean 66 years), stage, body mass index, histology and adjuvant therapies. Median operative time was longer in the MIS group (191 vs. 135 min; p.001). However, the MIS cohort had a higher mean lymph node count (39.0 vs. 34.0; p=.03), shorter hospital stay (1 vs. 4 days) and significantly fewer complications (8.4% vs. 31.3%; p.001). There was no significant difference in lymph node count with laparoscopic versus robotic staging. With a median follow-up time of 44 months, progression-free (PFS) and overall survival were not significantly different between the surgical cohorts. On multivariable analysis, stage, treatment were associated with PFS.Women with high grade endometrial cancers staged by minimally invasive techniques experienced fewer complications and similar survival outcomes compared to those staged by laparotomy. As this population is elderly and most will receive adjuvant therapies, minimization of surgical morbidity is of interest. When managed by expert laparoscopists or robotic surgeons, a high-risk histologic subtype is not a contraindication to minimally invasive surgery in women with apparent early-stage disease.

Objectives Stage I–II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC. Methods A retrospective, multi-institution analysis of surgically staged I–II UPSC patients was performed. Patients were treated by various adjuvant modalities. Age, race, sub-stage, percentage UPSC histology, lymphvascular space invasion (LVSI), tumor size and adjuvant treatment modality were evaluated for their effect on recurrence and survival outcomes. Results We identified 206 patients. Forty patients (19.4%) had 5–49% UPSC, 55 (26.7%) had 50–99% and 111 patients (53.9%) had 100% UPSC in their respective uterine specimens. Twenty one percent of patients experienced a primary recurrence. On univariate analysis, age, increasing %UPSC, LVSI, and tumor size were not significantly associated with recurrence or progression-free survival (PFS). However, substage (p = 0.005) and treatment with platinum/taxane-based chemotherapy (p = 0.001) were associated with recurrence/PFS. On multivariate analysis, only chemotherapy (p = 0.01) was a significant factor affecting PFS, whereas age (p = 0.05), substage (p = 0.05), and chemotherapy (p = 0.02) were associated with overall survival. Conclusions Traditional risk factors for recurrence and survival in patients with early-stage endometrial cancer may not be relevant in patients with UPSC. Patients with any percentage UPSC in their uterine specimens are at a significant risk for recurrence and poor survival outcomes. Given that current clinicopathologic data does not accurately identify women most likely to benefit from adjuvant therapy, alternative prognostic markers based on novel techniques should be explored.

Summary. Blood samples from 54 animals were exchanged between 15 laboratories in nine countries to improve and expand BoLA class I and class II typing. A total of 27 out of 33 (82%) of previously accepted BoLA-w specificities were represented within the cell panel. Seventeen new serum-defined BoLA specificities were accepted by the workshop participants, thus expanding the number of internationally recognized BoLA specificities to 50. The large number of new specificities detected resulted from the number of serological reagents used (n= 1139) and the genetic diversity of the cell panel. Confidence derived from the high percentage of agreement between the laboratories on antigen detection (97.3%; r= 0.84) permitted the removal of the workshop (w) notation from 23 BoLA-w specificities and their acceptance as full status BoLA-A antigens. Two new non-BoLA antigens were also detected, one completely included within the red blood cell factor S' (BoLy-S'), whereas a second (BoLy-w1) did not show any association with tested red blood cell factors. A comparison between serological, isoelectric focusing (IEF) and DNA typing for BoLA class II polymorphism was conducted with a subset of workshop cells. Correlation between the three methods was significant for three combinations of alleles. Three other serologically defined class II specificities were correlated with DR and/or DQ restriction fragment length polymorphism (RFLP) types, whereas six additional IEF types were correlated with DR and/or DQ RFLP types (r≥ 0.50). Several new IEF, DRB, DQA and DQB RFLP patterns were identifed. In 46 animals that were typed for BoLA-DR and DQ genes by RFLP analysis, 46 different BoLA haplotypes were tentatively defined. These 46 haplotypes were distinguished by 31 serologically-defined BoLA-A alleles (and 2'blanks'), 15 DRB RFLP types (plus up to 10 new DRB RFLP patterns) and 23 DQA-DQB haplotypes.

BACKGROUND: A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients. METHODS: A retrospective, multi-institutional study of stage I UPSC patients diagnosed from 1993 to 2006 was performed. Patients underwent comprehensive surgical staging; postoperative treatment included observation (OBS); radiotherapy alone (RT); or platinum/taxane–based chemotherapy (CT) ± RT. RESULTS: The authors identified 142 patients with a median follow-up of 37 months (range, 7-144 months). Thirty-three patients were observed, 20 received RT alone, and 89 received CT ± RT. Twenty-five recurrences (17.6%) were diagnosed, and 60% were extrapelvic. Chemotherapy-treated patients experienced significantly fewer recurrences than those treated without chemotherapy (P = .013). Specifically, CT ± RT patients had a lower risk of recurrence (11.2%) compared with patients who received RT alone (25%, P = .146) or OBS (30.3%, P = .016). This effect was most pronounced in stage IB/IC (P = .007). CT- and CT + RT–treated patients experienced similar recurrence. After multivariate analysis, treatment with chemotherapy was associated with a decreased risk of recurrence (P = .047). The majority of recurrences (88%) were not salvageable. Progression-free survival (PFS) and cause-specific survival (CSS) for chemotherapy-treated patients were more favorable than for those who did not receive chemotherapy (P = .013 and .081). Five-year PFS and CSS rates were 81.5% and 87.6% in CT ± RT, 64.1% and 59.5% in RT alone, and 64.7% and 70.2% for OBS. CONCLUSIONS: Stage I UPSC patients have significant risk for extrapelvic recurrence and poor survival. Recurrence and survival outcomes are improved in well-staged patients treated with platinum/taxane–based chemotherapy. This multi-institutional study is the largest to support systemic therapy for early stage UPSC patients. Cancer 2009. © 2009 American Cancer Society.

Since recent literature has indicated that white lupin (Lupinus albus) may be a useful source of hypocholesterolemic proteins to be used in functional food formulation, our final goal is the development of a fast and automated high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) method for the detection and the label-free semi-quantitation of the main lupin globulins in lupin foods and food ingredients. We present here some preliminary results in this direction. As a first step a total protein extract (TPE-WF) from lupin flakes was pre-fractionated by anion-exchange chromatography and each fraction was digested with trypsin and analyzed by HPLC/ESI-MS/MS. Subsequently, the tryptic digest of TPE-WF was directly analyzed by HPLC/ESI-MS/MS without any pre-fractionation. Eventually, in order to test the applicability of the method to real samples, a lupin beverage and two lupin protein isolates were analyzed. Both Mascot and Spectrum Mill MS Proteomics Workbench software were used to identify the protein composition in these samples and Spectrum Mill was used also to test the possibility of developing a label-free semi-quantitation method based on peptide hits. Encouraging results were obtained especially in the detection of the hypocholesterolemic component β-conglutin. Copyright © 2006 John Wiley & Sons, Ltd.

Our strategy for cervical cancer screeing is being revolutionized by our new understanding of how human papillomavirus (HPV) contributes to carcinogenesis and the natural history of cervical cancer. The American Cancer Society and the American College of Obstetricians and Gynecologists now recommend combined HPV and Papanicolaou (Pap) testing for cervical cancer screening in women age 30 or older. However, although incorporation of HPV DNA testing into primary screening provides clear benefits, it also raises new questions.

The genetic variability of the mitochondrial D-loop DNA sequence in seven horse breeds bred in Italy (Giara, Haflinger, Italian trotter, Lipizzan, Maremmano, Thoroughbred and Sarcidano) was analysed. Five unrelated horses were chosen in each breed and twenty-two haplotypes were identified. The sequences obtained were aligned and compared with a reference sequence and with 27 mtDNA D-loop sequences selected in the GenBank database, representing Spanish, Portuguese, North African, wild horses and an Equus asinus sequence as the outgroup. Kimura two-parameter distances were calculated and a cluster analysis using the Neighbour-joining method was performed to obtain phylogenetic trees among breeds bred in Italy and among Italian and foreign breeds. The cluster analysis indicates that all the breeds but Giara are divided in the two trees, and no clear relationships were revealed between Italian populations and the other breeds. These results could be interpreted as showing the mixed origin of breeds bred in Italy and probably indicate the presence of many ancient maternal lineages with high diversity in mtDNA sequences.