Contemporary Incidence of Medical Inoperability in Clinical Stage I Endometrial Cancer.

BACKGROUND: Minimally invasive surgical (MIS) staging is the standard treatment approach for clinical stage I endometrial cancer. Historical rates of inoperability in endometrial cancer are approximately 10%. Given surgical and medical advancements against increasing population obesity, we aimed to describe a contemporary incidence of medical inoperability in clinical stage I endometrial cancer. PATIENTS AND METHODS: Patients diagnosed with clinical stage I endometrial cancer of any histology from April 2014 to December 2018 were included in this retrospective cohort study. The primary outcome, medical inoperability, was defined as (1) patients deemed inoperable by a gynecologic oncologist at initial consultation, (2) patients deemed inoperable during preoperative clearance, or (3) an aborted hysterectomy. Fisher's exact or χ2, and Student's t-test or Wilcoxon rank sum test were used, as appropriate, for data analysis. Multivariable logistic regression was also employed. RESULTS: Overall, 767 patients were included, of which 4.6% (35/767) were determined to be inoperable. The inoperable group had a higher body mass index (52.7 vs. 33.9, p < 0.001), and increased rates of diabetes (62.8%, 22/35 vs. 27.1%, 199/732, p < 0.001), coronary artery disease (31.4%, 11/35 vs. 7.1%, 52/732, p < 0.001), and hypertension (94.3%, 33/35 vs. 70.2%, 514/732, p < 0.001). Of those with attempted surgical staging, hysterectomy was aborted intraoperatively in 0.68% (5/737). The overall complication rate was 11.6% (86/737). CONCLUSIONS: With maximal surgical effort and MIS, hysterectomy is possible in > 95% of patients with newly diagnosed endometrial cancer treated at a high-volume center. Complication rates were comparable to other trials evaluating the safety of MIS staging for endometrial cancer.

Accuracy of preoperative cross-sectional imaging in cervical cancer patients undergoing primary radical surgery.

OBJECTIVE: We aim to describe the false negative (FN) and false positive (FP) rates of preoperative cross-sectional imaging (PCI) prior to radical surgery for cervical cancer. METHODS: A retrospective cohort study of patients who underwent radical hysterectomy for early-stage cervical cancer from January 2010 until December 2017 at a single tertiary care center was performed. Patients were included if they underwent preoperative PCI and radical surgery. Patient demographics and clinicopathologic information were recorded from medical record review. Descriptive statistics were used. RESULTS: Overall, 106 patients met inclusion criteria. Eighty-four percent (89/106) of patients had no suspicion for metastatic disease on PCI, while 16% (17/106) had suspicion for metastatic disease. Of the 89 without suspicion for metastatic disease on PCI, 16% (14/89) had a false negative study with metastatic disease identified on final surgical pathology. False negative rates by modality were 16% (11/70) for PET/CT and 6% (2/33) for diagnostic CT. Of the 17 cases with suspicion for metastatic disease on imaging, 53% (9/17) were false positive studies with no metastatic disease identified histologically. False positive rates by modality were 7% (5/70) for PET/CT and 12% (4/33) for diagnostic CT. CONCLUSION: PCI is a tool to help identify patients who are optimal candidates for radical surgery. In this sample, the false negative rate was 16%, and false positive rate was 53% for PCI among women who underwent primary radical surgery. Further study is needed to explore preoperative testing that may more accurately identify optimal surgical candidates.

The Role of Obesity in the Development and Management of Gynecologic Cancer.

IMPORTANCE: Endometrial cancer is the most common gynecologic malignancy, with an estimated 54,000 new cases and 10,000 deaths in the United States in 2015. The obesity epidemic directly contributes to the escalating prevalence of chronic diseases, including obesity-related cancers. Patient body weight and nutritional status markedly impact perioperative oncologic care, chemotherapy administration, recurrence risk, and survivorship goals. OBJECTIVES: The objective of this review is to explore the association between obesity and the development, treatment, and survival outcomes of gynecologic cancers. EVIDENCE ACQUISITION: A systematic literature review was performed utilizing PubMed and ClinicalTrials.gov. CONCLUSIONS AND RELEVANCE: Caring for obese women with gynecologic cancers presents unique challenges. A coordinated multidisciplinary and system effort is required to address the prevention and treatment of obesity, as the sequela of this disease is a clear risk factor for the development of gynecologic malignancy and other comorbidities. Health care providers must be ready to address this worldwide health problem.

Sarcopenia as a predictor of survival and chemotoxicity in patients with epithelial ovarian cancer receiving platinum and taxane-based chemotherapy.

OBJECTIVES: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. Our goal was to evaluate if sarcopenia was associated with worse survival outcomes and chemotoxicity in EOC patients undergoing primary platinum and taxane-based chemotherapy. METHODS: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic - version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and unpaired t-tests were used to compare the means by groups. RESULTS: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). No difference in frequency of dose reduction, dose delay, hospital admissions, changes in regimen, blood transfusion, or toxicity was noted. There was no difference in distribution of toxicity grade. CONCLUSION: Sarcopenia was not associated with worse survival outcomes or chemotoxcity in EOC patients receiving first-line platinum and taxane-based chemotherapy in this cohort. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival, performance status, and quality of life.

Malignant Brenner tumor of the ovary: Case series and review of treatment strategies.

Malignant Brenner tumor (MBTs) is a rare histological subtype of epithelial ovarian cancer, accounting for <0.05% of all ovarian neoplasms. As such, current evidence on the treatment of MBTs is predominantly limited to case studies and small case series. To add to existing literature, we performed a retrospective review of 10 cases of MBT diagnosed and treated at a single institution between 1999 and 2018. For the 10 cases included in our cohort, the median age was 64 and the median tumor stage was IIa/IIb. All patients underwent either a primary or interval debulking surgery and achieved an R0 resection per classifications set by the Union for International Cancer Control (UICC). Lymph node dissections were performed on 6 patients and found no evidence of positive nodal disease. 7 patients received platinum-based adjuvant chemotherapy and experienced a median progression-free survival (PFS) of 37 months. Recurrent disease was varied in terms of locoregional versus distant spread, and these patients had largely suboptimal responses to salvage chemotherapy with doxorubicin, gemcitabine, and eribulin. Sites of metastatic disease included the liver, lungs, bone, and brain. While there is no consensus for the optimal treatment of this rare disease, MBTs seem to respond well to adjuvant platinum-taxane treatment after complete surgical resection, consistent with the current management approach of other epithelial ovarian cancers. Recurrent disease is considerably more difficult to manage, and clinicians may consider a wider avenue of treatment options to include hormonal, biologic, and radiation therapies.

Prenatal Contraceptive Counseling by Video.

OBJECTIVE: Effective postpartum contraception can improve interpregnancy intervals. Opportunities exist for counseling and education during prenatal care. Few studies have assessed the use of multimedia as a tool to improve long-acting reversible contraception (LARC) use postpartum. The objective of this study was to evaluate whether LARC-focused video counseling during prenatal care increases uptake of postpartum LARC and overall contraception use. METHODS: In this randomized controlled trial, women receiving their prenatal care at a university-based resident clinic were randomized to receive LARC FIRST video contraceptive counseling along with routine prenatal care or routine prenatal care alone. All of the participants received information regarding access to free LARC methods in the postpartum period. The primary outcome was LARC uptake by 12 weeks postpartum. Secondary outcomes included overall contraception use at 12 weeks postpartum, postpartum visit attendance, and acceptability of video counseling. RESULTS: LARC use at 12 weeks postpartum rose from an estimated 6% preintervention to 39.4% (13/33) in the video group compared with 29.4% (10/34) of the control group. The difference between groups was not statistically significant. Although overall contraceptive use (72.7% vs 54.8%) and postpartum visit attendance (91% vs. 76.5%) were higher in the video group relative to the control group, these differences were not statistically significant. Participants overwhelmingly liked the video (95.2%, 41/42) and believed viewing it was a good use of their appointment time (92%, 38/42). CONCLUSIONS: LARC use increased 32% across the entire study cohort; however, video-based contraceptive counseling did not increase LARC uptake at 12 weeks postpartum compared with routine prenatal care alone. Patients viewing the video reported high levels of acceptability and improved contraceptive knowledge. Video counseling may be a useful adjunct in many clinical settings.

Epstein-Barr Virus-Induced Mononucleosis as an Imitator of Severe Preeclampsia.

Background In pregnancy, conditions presenting with hematologic abnormalities, transaminitis, and proteinuria pose diagnostic challenges in pregnancy. Case We present the case of an 18-year-old woman, G1P0, at 33 weeks' gestation with fever of unknown cause, who developed progressively elevated liver enzymes, proteinuria, and thrombocytopenia, due to Epstein-Barr virus (EBV) infection. Conclusion Acute infection with EBV should be included in the differential diagnosis of preeclampsia with severe features, particularly in the setting of fever. Supportive treatment and observation may prevent iatrogenic preterm birth.

The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia.

BACKGROUND: Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. OBJECTIVE: We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. STUDY DESIGN: We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecology and Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes. Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the χ(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normally or not normally distributed. RESULTS: Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P = .03), but there was no difference in recurrence (13% vs 11%, P = .89). Patients with high-risk gestational trophoblastic neoplasia lived 63 miles farther (92 vs 28 miles, P < .001) than patients with low-risk gestational trophoblastic neoplasia. Long-distance travelers had a longer period between antecedent pregnancy and gestational trophoblastic neoplasia diagnosis (10 weeks vs 4.5 weeks, P = .009) and were more likely to receive multiagent chemotherapy (86% vs 61%, P = .03). CONCLUSION: In this cohort, long distance traveled to obtain care for gestational trophoblastic neoplasia was associated with an increased risk of presenting with high-risk disease and requiring multiagent chemotherapy for treatment. Patients with high-risk gestational trophoblastic neoplasia traveled nearly 100 miles to obtain care. There may be a delay in diagnosis in women traveling more than 50 miles to obtain care; however, we found no difference in recurrence risk for long-distance travelers.

Structure of an unsymmetrical isomer from the attempted synthesis of 1,8-dicyclooctatetraenylnaphthalene.

Attempted synthesis of 1,8-dicyclooctatetraenylnaphthalene (1) by the palladium(0)-catalyzed coupling of 1,8-dibromonaphthalene with cyclooctatetraenyltrimethylstannane afforded a single unsymmetrical isomer of 1 in 88% yield. Two-dimensional NMR methods and spectral synthesis were employed to assign the structure of the isomer (2). AM1 geometry-optimized structures of 2 and its isomers showed that the unexpected unsymmetrical structure of 2 results from the minimization of repulsive inter-ring H-H interactions. Compound 2 is postulated to arise via tandem [2 + 2] cycloaddition and 6 pi --> 4 pi + 2 sigma electrocyclization reactions of 1.

Mechanism of a novel exchange process in alkali metal salts of 1,5-dicyclooctatetraenylnaphthalene dianion.

A novel low-temperature intramolecular exchange was detected by (13)C NMR spectrometry in the Na(+) and K(+) salts of the title compound. The process causes the pairwise exchange in the dianion ring of C(2"), C(3"), and C(4") with C(8"), C(7"), and C(6"), respectively. The free energy of activation (DeltaG()(exch)) for the dipotassium salt (2(2-)/2K(+)) in THF-d(8) at 230 K is 12.6 kcal mol(-1). Two key questions are addressed: (1) Why are these carbons anisochronous and (2) what is the mechanism of exchange? NMR data for 1-cyclooctatetraenylnaphthalenedipotassium (3(2-)/2K(+)) as well as ab initio HF/3-21G(++) calculations for 3, 3(2-), and 3(2-)/2K(+) indicate that the nonequivalence is due to both slow rotation across a barrier at which the naphthalene and COT(2)(-) rings are approximately coplanar and slow inversion of the neutral COT ring. This results in the noteworthy circumstance of diastereotopic carbons being observed in a molecule that does not possess either a stereogenic or a prostereogenic center. Comparison of DeltaG()(exch) and DeltaG(++)(BS) for 2(2-)/2K(+) with the corresponding values for 2(2-)/2Na(+) and 2(2-)/2Li(+) and of DeltaG(++)(exch) with DeltaG(++) for ring inversion in 1,4-dicyclooctatetraenylnaphthalene leads to the conclusion that COT(2-) ring rotation and COT ring inversion both contribute to exchange in 2(2-)/2K(+) in a 3:1 ratio, but that exchange occurs exclusively by ring rotation in 2(2-)/2Li(+). The latter result is attributed to looser ion pairing in the dilithium (and disodium) salts.

Effect of para substituents on the rate of bond shift in arylcyclooctatetraenes.

The rate constants for bond shift (k(BS)) in phenylcyclooctatetraene (1b) and its p-nitro and p-methoxy analogues (1a and 1c, respectively) in THF-d(8) were determined by dynamic NMR spectrometry to be identical, but k(BS) is eight times greater at 280 K relative to 1b when the para substituent is cyclooctatetraenyldipotassium (2(2-)/2K(+)). These results are discussed in the context of (a) possible intrinsically small substituent effects (as determined by (13)C chemical shifts in the ground state (GS)) for 1a-c and (b) differences in steric interactions and resonance stabilization between the ground and BS transition state (TS). The latter factor was modeled by employing HF/3-21G(*) ab initio molecular orbital calculations of the GS and ring inversion TS. It is concluded that k(BS) is unchanged in 1a-c because the potentially greater pi interaction in the BS TS is counterbalanced by a greater degree of twist between the aryl and COT rings resulting from increased steric hindrance relative to the GS. However, pi interaction assumes a greater importance in the TS of 2(2-)/2K(+) owing to a decreased HOMO-LUMO energy gap compared to 1a-c, particularly when the counterions are solvated. This causes a decrease in the inter-ring twist angle and, together, these changes are responsible for the observed increase in k(BS) in 2(2-)/2K(+). The effect of substituents on a possible contribution of heavy atom tunneling to the reaction mechanism is also discussed.

Conformational analysis and kinetics of ring inversion for methylene- and dimethylsilyl-bridged dicyclooctatetraene.

Dicyclooctatetraenylmethane (1) and dicyclooctatetraenyldimethylsilane (2) in THF-d(8) at 272 K exist as mixtures of diastereomers in ratios of 1:0.8 and 1:1, respectively. Nine energy minima (four meso and five racemic conformers) were located for each compound by geometry optimization at the HF/6-31G level of theory. The effects of torsional strain, steric interactions and dynamic electron correlation were analyzed. The diastereomeric ratios for 1 and 2 were reproduced reasonably well from the total energy calculated for each conformer corrected for its conformational enthalpy and entropy contributions. The ratio of rate constants for bond shift (BS) (k(BS)(1)/k(BS)(2)) is three times greater than the corresponding ratio for ring inversion. This suggests that additional substituent effects, such as pi interactions, are operative in the transition state for BS.

Naphthalene carboxamides as inhibitors of human cytomegalovirus DNA polymerase.

ortho-Hydroxynaphthalene carboxamides have been identified as inhibitors of HCMV DNA polymerase. SAR investigations have demonstrated that both the amide and hydroxy functionalities are required for activity. Substitution on the naphthalene ring has led to inhibitors with submicromolar IC50s against HCMV polymerase. These compounds have been found to be >100-fold selective for inhibition of HCMV polymerase versus human alpha polymerase and display antiviral activity in a cell-based plaque reduction assay.

Planning factors for developing an enterprise-wide picture archiving and communication system maintenance program.

Picture archiving and communication system (PACS) maintenance on an individual site basis has historically been a complex and costly challenge. With the advent of enterprise-wide PACS projects such as the Virtual Radiology Environment (VRE) project, the challenge of a maintenance program with even more complexities has presented itself. The approach of the project management team for the VRE project is not one of reactive maintenance, but one of highly proactive planning and negotiations, in hopes of capitalizing on the economies of scale of an enterprise-wide PACS maintenance program. A proactive maintenance program is one aspect of life-cycle management. As with any capital acquisition, life-cycle management may be used to manage the specific project aspects related to PACS. The purpose of an enterprise-wide warranty and maintenance life-cycle management approach is to maintain PACS at its maximum operational efficiency and utilization levels through a flexible, shared, yet symbiotic relationship between local, regional, and vendor resources. These goals include providing maximum operational performance levels on a local, regional, and enterprise basis, while maintaining acceptable costs and resource utilization levels. This goal must be achieved without negatively impacting point of care activities, regardless of changes to the clinical business environment.

Firesetting during the preschool period: assessment and intervention issues.

OBJECTIVE: To describe a methodology of assessing preschoolers involved in firesetting incidents, and outline the psychiatric implications of firesetting incidents in young children. METHOD: To outline The Arson Prevention Program for Children and present case vignettes. RESULTS: The heightened risk of burn injury or fatality in fires caused by young children is highlighted and practical suggestions for facilitating the immediate safety of the child and family are presented. CONCLUSION: Despite the popular notion that fire interest and play is relatively benign in young children, the cases show that, as with older children, firesetting in preschoolers can be associated with serious child and/or family psychopathology.

Delinquent firesetters: a comparative study of delinquency and firesetting histories.

Twenty-five male delinquents (aged nine to 16) who had legal charges for setting fires filed against them were compared to a group of age and sex matched delinquents who had legal charges filed against them that were not related to firesetting. Groups were compared on demographic variables and on their delinquency and fire related histories. The only significant difference to emerge was a higher proportion of past firesetting in the group with fire-related charges. The present results indicate that a subgroup of antisocial recidivist firesetters exists among young offenders and underscore the importance of obtaining a thorough fire related history from youth who are before the court on fire related charges.