PAX8-positive, Cytokeratin-positive Intra-abdominal Ewing Sarcoma Masquerading as a Mullerian Carcinoma in a Postmenopausal Female.

Extraskeletal Ewing sarcoma presenting as intra-abdominal or pelvic disease in adult female patients is very rare and may lead to diagnostic difficulty due to clinical and histologic overlap with Mullerian adenocarcinomas, which are far more common. We report a case of an intra-abdominal Ewing sarcoma in a postmenopausal female patient whose clinical and radiological presentation closely resembled that of peritoneal carcinomatosis. Biopsy of an omental nodule revealed numerous histologic features suggestive of a Mullerian carcinoma, including gland-like rosettes, strong, diffuse PAX8 immunoreactivity and cytokeratin expression. After excluding other differential diagnostic considerations, the possibility that this might represent an intra-abdominal Ewing sarcoma was entertained. Reverse transcriptase polymerase chain reaction testing demonstrated the presence of an EWSR1-ERG fusion transcript, confirming the diagnosis. The differential diagnostic considerations when dealing with this unusual clinical scenario and the uncommon yet important pitfall of PAX8 immunoreactivity in Ewing sarcoma are discussed.

Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) as a Neoadjuvant Chemotherapy for Non-metastatic Esophageal Cancer (nMEC).

Objective: Perioperative chemotherapy can potentially downstage esophageal cancer, reducing the risk of early systemic dissemination. One recommended neoadjuvant regimen for managing gastroesophageal junction and esophageal cancer is docetaxel, cisplatin, and 5-fluorouracil (DCF). To address the high toxicity profile of DCF, modifications in dosages and treatment intervals have been studied. We integrated a modified DCF regimen (mDCF) into a multimodal treatment approach for non-metastatic esophageal cancer (nMEC). Retrospectively, we sought to describe our community experience of administrating neoadjuvant mDCF to patients with nMEC.Design: Patients diagnosed with nMEC between August 2008 and November 2017 and prescribed mDCF were identified for retrospective review. Outcomes of interest included disease-free survival (DFS), overall survival (OS), and hematologic toxicities. Analyses were performed using SAS 9.4.Results: Thirty patients met inclusion criteria with a median age of 64.9 years; 90% were male. The 2-year and 5-year DFS was 60.8% and 41.7%, respectively, for adenocarcinoma and 71.4% and 71.4% for squamous cell carcinoma (SCC). The 2-year and 5-year OS was 64.9% and 44.5%, respectively, for adenocarcinoma and 71.4% and 71.4% for SCC. Both DFS and OS decreased with increasing disease stage, histology (adenocarcinoma versus squamous), esophageal compared to esophagogastric-junction involvement, and without surgical intervention. Frequent toxicity grades for leukopenia and thrombocytopenia were Grades I and II.Conclusion: Using an mDCF regimen in combination with chemoradiation +/- surgical resection in a community setting appears to have an acceptable toxicity profile as well as DFS and OS outcomes compared to chemotherapeutic regimens reported in other similar studies.

Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ.

BACKGROUND: The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. METHODS: Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. RESULTS: DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. CONCLUSIONS: Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society.

Use of information technology for medication management in residential care facilities: correlates of facility characteristics.

The effectiveness of information technology in resolving medication problems has been well documented. Long-term care settings such as residential care facilities (RCFs) may see the benefits of using such technologies in addressing the problem of medication errors among their resident population, who are usually older and have numerous chronic conditions. The aim of this study was two-fold: to examine the extent of use of Electronic Medication Management (EMM) in RCFs and to analyze the organizational factors associated with the use of EMM functionalities in RCFs. Data on RCFs were obtained from the 2010 National Survey of Residential Care Facilities. The association between facility, director and staff, and resident characteristics of RCFs and adoption of four EMM functionalities was assessed through multivariate logistic regression. The four EMM functionalities included were maintaining lists of medications, ordering for prescriptions, maintaining active medication allergy lists, and warning of drug interactions or contraindications. About 12% of the RCFs adopted all four EMM functionalities. Additionally, maintaining lists of medications had the highest adoption rate (34.5%), followed by maintaining active medication allergy lists (31.6%), ordering for prescriptions (19.7%), and warning of drug interactions or contraindications (17.9%). Facility size and ownership status were significantly associated with adoption of all four EMM functionalities. Medicaid certification status, facility director's age, education and license status, and the use of personal care aides in the RCF were significantly associated with the adoption of some of the EMM functionalities. EMM is expected to improve the quality of care and patient safety in long-term care facilities including RCFs. The extent of adoption of the four EMM functionalities is relatively low in RCFs. Some RCFs may strategize to use these functionalities to cater to the increasing demands from the market and also to provide better quality of care.

Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma.

Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m 2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients.

Extraskeletal Ewing Sarcoma of the Gastrointestinal and Hepatobiliary Tract: Deceptive Immunophenotype Commonly Leads to Misdiagnosis.

Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2 cm and 18 cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.

Long Noncoding RNA Expression in Adrenal Cortical Neoplasms.

Long noncoding RNAs (lncRNAs) consist of nucleic acid molecules that are greater than 200 nucleotides in length and they do not code for specific proteins. A growing body of evidence indicates that these lncRNAs have important roles in tumorigenesis. Separating adrenal cortical adenomas from carcinomas is often a difficult problem for the surgical pathologist. This is especially true when only small needle biopsies are available for examination. We used in situ hybridization (ISH) analysis to study normal adrenal cortical tissues and adrenal cortical tumors to determine the role of specific lncRNAs in tumor development and classification. The lncRNAS studied included metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), psoriasis susceptibility-related RNA gene induced by stress (PRINS), and HOX antisense intergenic RNA myeloid 1 (HAM1). We constructed a tissue microarray (TMA) for the studies and also analyzed a subset of cases by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Two 1-mm duplicate cores of normal adrenal cortex (NAC) (n = 23), adrenal cortical adenomas (ACAs) (n = 95), and adrenal cortical carcinomas (ACCs), (n = 20) were used on the TMA. The results of ISH were analyzed by image analysis. ISH showed predominantly nuclear expression of lncRNAs in adrenal cortical tissues. MALAT1 showed more expression in ACCs than in NAC and ACA (p < 0.05). PRINS had higher expression in NACs and ACAs than in ACCs. The lncRNAs MALAT1, PRINS, and HAM1 are all expressed in normal and neoplastic adrenal cortical tissues. MALAT1 had the highest expression in ACC compared to ACAs and may have a role in ACC development.

A principal factor analysis to characterize agricultural exposures among Nebraska veterans.

Agricultural workers are at an increased risk of developing chronic respiratory disorders. Accurate estimation of long-term agricultural exposures based on questionnaires has been used to improve the validity of epidemiologic investigations and subsequent evaluation of the association between agricultural exposures and chronic diseases. Our aim was to use principal factor analysis (PFA) to distill exposure data into essential variables characterizing long-term agricultural exposures. This is a cross-sectional study of veterans between the ages of 40 and 80 years and who worked on a farm for ≥2 years. Participant characteristics were: 98.1% were white males with a mean age 65±8 (SD) years and 39.8% had chronic obstructive pulmonary disease. The final model included four factors and explained 16.6% of the variance in the exposure data. Factor 1 was a heterogeneous factor; however, Factor 2 was exclusively composed of exposure to livestock such as hogs, dairy and poultry. Factor 3 included exposures from jobs on or off the farm such as wood dust, mineral dust, asbestos and spray paint. Crop exposure loaded exclusively in Factor 4 and included lifetime hours of exposure and maximum number of acres farmed in the participants' lifetime. The factors in the final model were interpretable and consistent with farming practices.

Emerging Trends in Family History of Breast Cancer and Associated Risk.

Background: Increase in breast cancer incidence associated with mammography screening diffusion may have attenuated risk associations between family history and breast cancer.Methods: The proportions of women ages 40 to 74 years reporting a first-degree family history of breast cancer were estimated in the Breast Cancer Surveillance Consortium cohort (BCSC: N = 1,170,900; 1996-2012) and the Collaborative Breast Cancer Study (CBCS: cases N = 23,400; controls N = 26,460; 1987-2007). Breast cancer (ductal carcinoma in situ and invasive) relative risk estimates and 95% confidence intervals (CI) associated with family history were calculated using multivariable Cox proportional hazard and logistic regression models.Results: The proportion of women reporting a first-degree family history increased from 11% in the 1980s to 16% in 2010 to 2013. Family history was associated with a >60% increased risk of breast cancer in the BCSC (HR, 1.61; 95% CI, 1.55-1.66) and CBCS (OR, 1.64; 95% CI, 1.57-1.72). Relative risks decreased slightly with age. Consistent trends in relative risks were not observed over time or across stage of disease at diagnosis in both studies, except among older women (ages 60-74) where estimates were attenuated from about 1.7 to 1.3 over the last 20 years (P trend = 0.08 for both studies).Conclusions: Although the proportion of women with a first-degree family history of breast cancer increased over time and by age, breast cancer risk associations with family history were nonetheless fairly constant over time for women under age 60.Impact: First-degree family history of breast cancer remains an important breast cancer risk factor, especially for younger women, despite its increasing prevalence in the mammography screening era. Cancer Epidemiol Biomarkers Prev; 26(12); 1753-60. ©2017 AACR.

Financial sustainability of academic health centers: identifying challenges and strategic responses.

Academic health centers (AHCs) play a vital role in the health care system. The training of health care personnel and delivery of health care services, especially to the most complex and financially challenged patients, has been a responsibility increasingly shouldered by AHCs over the years. Additionally, AHCs play a significant role in researching and developing new treatment protocols, including discovering and validating new health technologies. However, AHCs face unique financial challenges in fulfilling their social mission in the health care system. Reforms being implemented under the Affordable Care Act and shifting economic patterns are threatening the financial sustainability of AHCs.The authors review challenges facing AHCs, including training new health care professionals with fewer funding resources, disproportionate clinical care of complex and costly patients, charity care to uninsured and underinsured, and reduced research funding opportunities. Then, they provide a review of some potential solutions to these challenges, including new reimbursement methods, improvements in operational efficiency, price regulation, subsidization of education, improved decision making and communication, utilization of industrial management tools, and increasing internal and external cooperation. Devising solutions to the evolving problems of AHCs is crucial to improving health care delivery in the United States. Most likely, a combination of market, government, and system reforms will be needed to improve the viability of AHCs and assist them in fulfilling their social and organizational missions.