Citations

Accurate risk stratification of smooth muscle tumors (SMTs) is essential for appropriate patient management. Yet, the rarity of SMTs of the vagina and vulva makes development of a prognostically meaningful classification system challenging. While 2 classification methods for vulvar SMTs and 1 for vaginal SMTs have been proposed, it is our experience that many pathologists tend to apply criteria for uterine SMTs when evaluating vulvovaginal tumors. We retrospectively reviewed a large cohort of vulvovaginal SMTs with clinical follow-up and evaluated which method most accurately classified tumors according to patient outcome. A total of 71 tumors, 53 vaginal (75%) and 18 vulvar (25%), from 71 patients were identified. All tumors were centrally examined for degree of cytologic atypia, morphology (spindled, epithelioid, myxoid), mitotic index per 10 high power fields, atypical mitotic figures, tumor cell necrosis, ischemic necrosis, tumor interface (circumscribed or infiltrative) and margin status. Clinical features were recorded for each patient. Follow-up was available for 63 patients (89%), and ranged from 1 to 234 months (median: 64 mo). While site-specific and uterine criteria showed equally excellent sensitivity in classifying smooth muscle neoplasms as leiomyosarcoma according to patient outcome, uterine criteria showed improved specificity relatively to site-specific methods in classifying tumors as nonsarcoma according to patient outcome. We recommend that uterine SMT criteria and nomenclature be adopted for evaluation and classification of vulvovaginal SMTs.

Abstract Background: Endometrial cancer is highly curable when detected early, but clinical symptoms are often missed. Most cancers arise in women with abnormal postmenopausal bleeding (PMB). However, PMB is not specific for endometrial cancers. In previous reports, the prevalence of endometrial cancer in women with PMB was reported to range from 3-25%. Because of the importance for guiding clinical management and endometrial cancer risk prediction, we conducted a systematic review and meta-analysis to obtain precise prevalence estimates of endometrial cancer in women with PMB. Methods: A systematic review and meta-analysis summarized all peer-reviewed studies reporting endometrial cancer prevalence in women with PMB, published before Sept. 1, 2016. We calculated a pooled prevalence estimate and 95% confidence interval (CI) using a random-effects model, and quantified heterogeneity across studies using the I2 statistic. Subgroup meta-analyses were performed to investigate sources of variability according to selection criteria for endometrial thickness (ET) and hormone replacement therapy (HRT). We also stratified by study location to determine whether prevalence estimates varied by country or region if ≤5 studies included per country. Results: 105 studies were included, contributing data for 37,000 women with PMB and 3,028 with cancer from 34 countries. Overall, the pooled prevalence of endometrial cancer in women with PMB was 11% (95% CI 10-12%), with I2 =94.3%. Among studies that selected women with a minimum ET (≥ 4mm; n=14), the pooled prevalence of endometrial cancer was 17% (95% CI 14-20%) compared with studies that did not select for ET (10%, 95% CI 9-11%). In studies that excluded women using HRT (n=34), the pooled prevalence of endometrial cancer was 15% (95% CI 12-17%) compared with studies that did not exclude women using HRT (9%, 95% CI 8-10%). Stratification by study location revealed variation in prevalence estimates. For example, in the United States (n=9) and the United Kingdom (n=16), prevalence of endometrial cancer was 4% (95% CI 2-7%) and 5% (95% CI 4-6%), respectively, whereas in Italy (n=14), the prevalence was 11% (95% 8-14%). Regional differences were also observed, ranging from 8% (95% CI 3-14%) in South Central Asia (n=5) to 18% (95% CI 12-23%) in Southern Europe (n=11). Conclusions: The overall prevalence of endometrial cancer among unselected women with PMB is approximately 10% with substantial heterogeneity across studies. Marked geographic differences in the prevalence endometrial cancer were observed. Factors related to selection for ET and/or HRT use may partially contribute to this variability. Risk prediction models depend on precise prevalence estimates for accurate prediction and utility in clinical management. More research is needed to test the applicability of endometrial cancer risk prediction models in high-risk subgroups and in study populations from diverse geographic regions. Citation Format: Megan A. Clarke, Beverly J. Long, Arena Del Mar Morillo, Jamie N. Bakkum-Gamez, Nicolas Wentzensen. The prevalence of endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 275. doi:10.1158/1538-7445.AM2017-275

Objectives/HypothesisSarcomatoid carcinoma is a rare variant of squamous cell carcinoma of the head and neck. No consensus exists on its management. Our aim was to present our outcomes.Study DesignRetrospective study. Median follow‐up 45 months.MethodsThere were 38 patients with pathologically confirmed sarcomatoid carcinoma of the larynx treated at the Mayo Clinic from 1990 to 2014. Statistical analysis of overall survival (OS), progression‐free survival (PFS), and local control (LC) were conducted using the Kaplan‐Meier method.ResultsThe majority of patients were elderly males (92%) with a smoking history (74%) presenting with early‐stage disease (71%). Surgery alone was the primary treatment in 27 patients (71%). Nine patients (25%) were treated with adjuvant radiation due to initial stage or high‐risk pathologic features. Median radiation dose to the primary/surgical bed was 65 Gy (range, 60.3–75.0 Gy). A total of 15 patients (39%) had tumor recurrence, majority being local (n = 12). Sixty percent (n = 9) had multiple local recurrences. Five‐year OS, PFS, and LC were 63%, 46%, and 72%, respectively. Subgroup analysis by stage I versus higher stages (II–IV) showed an OS of 80% versus 43% (P = .030), PFS of 65% versus 18% (P = .003), and LC of 84% versus 57% (P = .039).ConclusionsSarcomatoid carcinoma of the larynx is rare, and frequently presents at an early stage in older men with history of smoking. Based on our outcomes and patterns of failure, it appears early‐stage tumors are treated appropriately with single‐modality therapy, whereas more advanced tumors require multimodality therapy. Validation in a larger cohort is warranted.Level of Evidence4. Laryngoscope, 128:373–377, 2018

AbstractBackgroundUnilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low‐volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced‐stage oropharyngeal cancer undergoing unilateral RT.MethodsThirty‐seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected.ResultsAt median follow‐up of 32 months, 3‐year locoregional control, contralateral regional failure, distant metastasis‐free survival, and disease‐free survival were 96%, 0%, 7%, and 93%, respectively.ConclusionLow rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

BACKGROUND: Increasing numbers of robotic hysterectomies (RH) are being performed. To provide ventilation (with pneumoperitoneum and steep Trendelenburg position) for these procedures, utilization of lung protective strategies with limiting airway pressures and tidal volumes is difficult. Little is known about the effects of intraoperative mechanical ventilation and high peak airway pressures on perioperative complications. We performed a retrospective review to determine whether patients undergoing RH had increased pulmonary complications compared to total abdominal hysterectomy (TAH). METHODS: We performed a single center retrospective review comparing the intraoperative, anesthetic, and immediate and 30-day postoperative course of patients undergoing RH to TAH, including intraoperative ventilatory parameters and respiratory complications. Patients undergoing TAH (201) from 2004 to 2006 were compared to RH (251) from 2009 to 2012. It was our hypothesis that patients undergoing RH would have increased incidence of postoperative pulmonary complications. A secondary hypothesis was that morbid obesity predicts pulmonary complications in patients undergoing RH. Complications were compared between groups using Fisher’s exact test. To account for potential confounders, the primary analysis was performed for a subgroup of patients matched on the propensity for RH. RESULTS: A total of 351 RH and 201 TAH procedures are included. Higher inspiratory pressures were required in ventilation of the RH group (median [25th, 75th] 31 [26, 36] cm H 2 O) than the TAH group (23 [19, 27] cm H 2 O) ( P < .001) at 30 minutes after incision. Peak inspiratory pressures at 30 minutes after incision for RH increased according to increasing body mass index group ( P < .001). There were 163 RH and 163 TAH procedures included in the propensity matched analysis. From this analysis, there were no significant differences in cardiopulmonary complications between RH and TAH (0.6% vs 1.2%; odds ratio = 2.0, 95% confidence interval = 0.2–2.4; P = 1.00). Surgical site infection was significantly lower in the RH compared to TAH group (0.6% vs 8.6%; P < .001). Hospital length of stay was longer for those who underwent TAH versus RH (median [25th, 75th] 2 [2, 3] vs 1 [0, 2] days; P < .001). CONCLUSIONS: There was no significant difference in perioperative complications in obese and morbidly obese women compared to nonobese undergoing RH. Patients undergoing RH had shorter hospital stays, fewer infectious complications, and no increase in overall complications compared to TAH. Higher ventilatory airway pressures (RH versus TAH and obese versus nonobese) did not result in an increase in cardiopulmonary or overall complications. We believe that peritoneal insufflation attenuates the effect of high airway pressures by raising intrapleural pressure and reducing the gradient across terminal bronchioles and alveoli. Thus, we propose that lung protective strategies for patients undergoing RH account for the markedly elevated intraperitoneal and intrapleural pressures, whereas transpulmonary airway pressures remain static. This reduced transpulmonary gradient attenuates the strain on lung tissue that would otherwise be imposed by ventilation at high pressures.

ABSTRACT Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill‐defined. In this study, we evaluated the contribution of major histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)–infected transgenic FVB mice that express the D b class I molecule. FVB/D b and wild‐type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2‐weighted MRI and subsequent 3‐dimensional volumetric analysis. Significant brain atrophy and hippocampal neuronal loss were observed in TMEV‐infected FVB/D b mice, but not in wild‐type FVB mice. Brain atrophy was observed at 1 mo postinfection and persisted through the 4‐mo observation period. Of importance, virus‐infected FVB/D b mice elicited a strong CD8 T‐cell response toward the immunodominant D b ‐restricted TMEV‐derived peptide, VP2 121–130 , and cleared TMEV from the CNS. In addition, immunofluorescence revealed CD8 T cells near virus‐infected neurons; therefore, we hypothesize that class I restricted CD8 T‐cell responses promote development of brain atrophy. This model provides an opportunity to analyze the contribution of immune cells to brain atrophy in a system where persistent virus infection and demyelination are not factors in long‐term neuropathology.—Huseby Kelcher, A. M., Atanga, P. A., Gamez, J. D., Cumba Garcia, L. M., Teclaw, S. J., Pavelko, K. D., Macura, S. I., Johnson, A. J. Brain atrophy in picornavirus‐infected FVB mice is dependent on the H‐2Db class I molecule. FASEB J. 31, 2267–2275 (2017). www.fasebj.org

Purpose: To report the outcomes of patients with favorable risk oropharyngeal cancer that underwent adjuvant radiation therapy with omission of the primary site from the clinical target volume (CTV). Material/Methods: A retrospective study of 40 patients treated with transoral surgery (TOS) followed by neck only radiation using intensity modulated radiation therapy (IMRT) with exclusion of the primary site. For all patients, a CTV of the primary surgical bed was contoured to obtain the estimated incidental dose to the primary site. Results: Median follow-up was 51 months (range, 13-155 months). The median radiation therapy (RT) dose to the neck was 6000 cGy (range, 5400-6400 cGy). The mean incidental dose to the primary tonsillar site was 4320 cGy (SD ± 480 cGy) and to the primary base of tongue site was 4060 cGy (SD ± 420 cGy). There were no local failures and only 1 regional failure, resulting in 97.5% locoregional control rate at 4 years. Two patients developed distant metastases, without evidence of locoregional recurrence, for a 4-year overall survival rate of 97%. Conclusions: Our analysis suggests that mucosal sparing RT after TOS in favorable risk oropharyngeal cancer patients may provide comparable oncologic and improved functional outcomes compared to conventional treatment in selected patients.

Purpose of reviewDetection of endometrial cancer at an early stage leads to better oncologic outcomes. To date, a screening test for endometrial cancer does not exist.Recent findingsEvolving knowledge of molecular changes involved in endometrial cancer carcinogenesis paired with sensitive and high-throughput technological advancements are a promising combination that can be leveraged to detect tumor DNA and proteins. These molecular biomarkers can be identified in biospecimens collected via minimally invasive and noninvasive approaches. Exploiting lower genital tract secretions as a biospecimen also allows for patient self-sampling.SummarySuccessful development of a screening test for endometrial cancer using self-collected lower genital tract biospecimens has the potential to increase accessibility to care and improve patient compliance.

ABSTRACT Inflammatory response of blood–brain barrier (BBB) endothelial cells plays an important role in pathogenesis of many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB endothelial cell inflammatory response remains unclear. In this study, we first observed that knockdown of neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, suppressed interferon-γ (IFNγ)-induced C-X-C motif chemokine 10 expression and activation of STAT1 in brain microvascular endothelial cells in a Rac1-dependent manner. Moreover, endothelial-specific NRP1-knockout mice, VECadherin-Cre-ERT2/NRP1flox/flox mice, showed attenuated disease progression during experimental autoimmune encephalomyelitis, a mouse neuroinflammatory disease model. Detailed analysis utilizing histological staining, quantitative PCR, flow cytometry and magnetic resonance imaging demonstrated that deletion of endothelial NRP1 suppressed neuron demyelination, altered lymphocyte infiltration, preserved BBB function and decreased activation of the STAT1–CXCL10 pathway. Furthermore, increased expression of NRP1 was observed in endothelial cells of acute multiple sclerosis lesions. Our data identify a new molecular mechanism of brain microvascular endothelial inflammatory response through NRP1–IFNγ crosstalk that could be a potential target for intervention of endothelial cell dysfunction in neuroinflammatory diseases.