The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast

BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004–2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Approach to radiation therapy in the Jehovah’s Witness patient: An overview

Jehovah’s Witnesses are well-known in the medical community for their inability to accept blood products. Novel methods of treatment are often needed to avoid anemia and hematologic toxicity as inability to receive blood products may increase the risk of treatment related complications. We provide an overview of radiation treatment for Jehovah’s Witness patients with an emphasis on bone marrow sparing strategies with intensity modulated radiation therapy (IMRT) to minimize hematologic toxicity

A rare presentation of choroidal metastasis from primary esophageal adenocarcinoma successfully treated with intensity-modulated radiation therapy

Purpose: In this case report, we present a case of choroidal metastasis from a primary esophageal adenocarcinoma that was treated successfully with intensity-modulated radiation therapy. Observations: A 65-year-old male with known stage IV esophageal adenocarcinoma presented with a central scotoma in his left eye and was ultimately found to have a large choroidal metastatic lesion with overlying subretinal fluid. IMRT was administered over the course of four weeks, resulting in restoration of the patient's vision, regression of the metastatic lesion, and resolution of the subretinal fluid. As of 16 months following completion of radiation, there remains no evidence of choroidal recurrence or radiation-associated ocular complications. Conclusions: and Importance: To our knowledge, this is the first published case report of a choroidal metastasis from esophageal cancer responding durably to IMRT. IMRT should therefore be considered a viable treatment option for this rare disease. Keywords: Choroidal metastasis, Esophageal adenocarcinoma, Intensity-modulated radiation therapy, External beam radiation therapy, Retin

Acute Appendicitis: Use of Clinical and CT Findings for Modeling Hospital Resource Utilization

OBJECTIVE. The purpose of this study was to retrospectively investigate associations between baseline CT findings in suspected acute appendicitis and subsequent hospital resource utilization. MATERIALS AND METHODS. One hundred thirty-eight patients (76 male and 62 female patients; mean [+/- SD] age, 40 +/- 21 years) who were admitted for suspected acute appendicitis and underwent baseline CT were included. A single radiologist reviewed CT examinations for appendiceal-related findings. Linear and logistic regressions were performed to identify independent predictors of payer and hospital resource utilization. Combined performance of identified independent factors for predicting outcomes was determined. RESULTS. Greater age, lower Charlson comorbidity index (CCI), lesser appendiceal wall thickness, absence of loculated fluid collection, and absence of periappendiceal fluid were significant independent predictors of inpatient surgery (joint sensitivity, 92.7%; specificity, 65.8%). Smaller appendiceal diameter, absence of periappendiceal fluid, and laparoscopic surgery were significant independent predictors of same-day discharge (joint sensitivity, 79.1%; specificity, 64.2%). Greater CCI, greater wall thickness, and presence of periappendiceal fluid were significant independent predictors of repeat abdominopelvic CT (joint sensitivity, 82.5%; specificity, 68.1%). Presence of an appendicolith was the only significant predictor of repeat emergency department visit within 30 days (sensitivity, 61.2%; specificity, 68.8%) and the only significant predictor of repeat inpatient admission within 30 days (sensitivity, 63.6%; specificity, 68.5%). Greater appendiceal diameter and presence of free air were significant predictors of inpatient costs, and predicted costs were as follows: $8047 + ($745 x appendiceal diameter) if free air was absent; and $-39,261 + ($ 4426 x appendiceal diameter) if free air was present. However, costs were poorly predicted when greater than $ 45,000. Sex, WBC count, and payer category were not independent predictors, relative to CT findings, of any outcome. CONCLUSION. Admission CT findings serve as independent predictors of hospital resource utilization in suspected acute appendicitis