This is the February 2012 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
This is the January 2012 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
This is the November 2011 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
This is the October 2011 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
This is the September 2011 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
Since the publication of the National Lung Screening Trial results, there has been increasing interest among radiologists to establish computed tomography (CT) screening centers. During the past 10 years, we have operated a CT screening center in suburban Boston, MA. The purpose of this paper is to describe our process for performing self-referred CT lung screening exams, including our organizational structure, marketing, patient selection process, and standardized workflow. Direct communication between the patient and radiologist, both before and after the CT scan, in our opinion, is critical to a successful screening program. In many ways, CT screening offers radiologists a wonderful opportunity to interact directly with patients. Showing abnormal lung findings to patients on their CT scans may help create a unique "teachable" moment for current smokers and may help motivate patients to quit smoking.
Quality initiatives: lean approach to improving performance and efficiency in a radiology department
Many hospital radiology departments are adopting "lean" methods developed in automobile manufacturing to improve operational efficiency, eliminate waste, and optimize the value of their services. The lean approach, which emphasizes process analysis, has particular relevance to radiology departments, which depend on a smooth flow of patients and uninterrupted equipment function for efficient operation. However, the application of lean methods to isolated problems is not likely to improve overall efficiency or to produce a sustained improvement. Instead, the authors recommend a gradual but continuous and comprehensive "lean transformation" of work philosophy and workplace culture. Fundamental principles that must consistently be put into action to achieve such a transformation include equal involvement of and equal respect for all staff members, elimination of waste, standardization of work processes, improvement of flow in all processes, use of visual cues to communicate and inform, and use of specific tools to perform targeted data collection and analysis and to implement and guide change. Many categories of lean tools are available to facilitate these tasks: value stream mapping for visualizing the current state of a process and identifying activities that add no value; root cause analysis for determining the fundamental cause of a problem; team charters for planning, guiding, and communicating about change in a specific process; management dashboards for monitoring real-time developments; and a balanced scorecard for strategic oversight and planning in the areas of finance, customer service, internal operations, and staff development.
In the past decade, new therapeutic agents have been developed that permit gastroenterologists to treat virtually all forms of Crohn's disease. The success of these treatments depends on an accurate diagnosis of the nature and extent of disease. Fortunately, radiologists now possess a powerful arsenal of imaging techniques to guide the choice of therapy. This article discusses the usefulness of both traditional and newer imaging techniques in the management of Crohn's disease and its various clinical presentations.
Graphic representation of clinical symptoms: a tool for improving detection of subtle fractures on foot radiographs
OBJECTIVE. The purpose of this study was to assess changes in accuracy, degree of confidence, and evaluation time in radiography of subtle foot fractures when the text history is supplemented by a graphic indicating the site of pain.
MATERIALS AND METHODS. Radiographs from 226 foot examinations (three views), including 126 examinations showing one subtle fracture ( < 1-mm displacement) and 100 examinations with normal findings were selected. In the first interpretation session, only a text history was given for 112 examinations, and both text and a graphic indicating the site of pain for 114 examinations. Six months later, a graphic and text history were provided for the 112 cases interpreted without a graphic in the first session, and only text was provided for the other 114 cases. Seven radiologists evaluated the study sets. Sensitivity, specificity, degree of confidence (1-10 scale), and mean interpretation time in seconds were calculated.
RESULTS. Use of a graphic increased overall sensitivity for any subtle fracture from 67% to 73% (p < 0.001), increased degree of confidence from 8.1 without a graphic to 8.4 with a graphic (p < 0.0001), and decreased the time for interpretation by 6%, from 53 seconds without a graphic to 50 seconds with a graphic (p = 0.006). Specificity changed from 93% without a graphic to 94% with a graphic (p = 0.33). Fractures of the third metatarsal were missed most frequently (74%); this percentage improved to 61% with use of a graphic.
CONCLUSION. A graphic complements the text history by improving sensitivity, degree of confidence, and time for interpretation.
Mismatch in breast and detector size during screening and diagnostic mammography results in increased patient radiation dose
RATIONALE AND OBJECTIVES: When using mammographic detectors of different sizes, it can be difficult to match patient breast size to optimal detector size. We studied whether a mismatch between breast size and optimal detector size resulted in increased radiation exposure.
MATERIALS AND METHODS: All screening and diagnostic (Dx) mammography patients during a 6-week period in November-December 2009 (864 patients) were evaluated (institutional review board exemption for quality assurance studies). Data gathered included breast size (large or small), detector size used, number of views obtained, mean glandular dose (MGD) per breast, and patient waiting time. Average MGD and average waiting time was calculated for imaging performed on appropriately matched or mismatched breast size-detector size pairs.
RESULTS: Screening mammography patients with large breasts imaged on a small detector received a significantly higher radiation dose (4.9 vs. 3.3 mGy, P < .05) and a greater number of views (5.9 vs. 4.6, P < .05) compared to optimally matched breast-detector pairs. Dx mammography patients with large breasts imaged on a small detector received a higher radiation dose (8.2 vs. 6.7 mGy, P < .05) compared to optimally matched breast-detector pairs, although without an increased number of views. Waiting times were longer for a large detector.
CONCLUSIONS: A mismatch in breast-detector sizes results in a significantly greater radiation dose to patients with large breasts imaged on a small detector. Pressure to minimize patient waiting time may inadvertently result in increased radiation dose. Detector size should be matched to breast size whenever possible, but particularly for patients with larger breast sizes.
Acute right upper quadrant pain is a common presenting symptom in patients with acute cholecystitis. When acute cholecystitis is suspected in patients with right upper quadrant pain, in most clinical scenarios, the initial imaging modality of choice is ultrasound. Although cholescintigraphy has been shown to have slightly higher sensitivity and specificity for diagnosis, ultrasound is preferred as the initial study for a variety of reasons, including greater availability, shorter examination time, lack of ionizing radiation, morphologic evaluation, confirmation of the presence or absence of gallstones, evaluation of bile ducts, and identification or exclusion of alternative diagnoses. CT or MRI may be helpful in equivocal cases and may identify complications of acute cholecystitis. When ultrasound findings are inconclusive, MRI is the preferred imaging test in pregnant patients who present with right upper quadrant pain. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. rights reserved.
Reviewing imaging examination results with a radiologist immediately after study completion: patient preferences and assessment of feasibility in an academic department
OBJECTIVE: The purpose of this study was to assess patient preferences about receiving radiology results and reviewing the images and findings directly with a radiologist after completion of an examination.
SUBJECTS AND METHODS: A prospective survey of English-speaking outpatients undergoing either nononcologic CT of the chest, abdomen, and pelvis or nonobstetric ultrasound examinations was completed between December 2010 and June 2011. Responses to survey items such as preferences regarding communication of results, knowledge of a radiologist, and anxiety level before and after radiologist-patient consultation were recorded. The average wait time between the end of the imaging examination and the consultation and the duration of consultation were documented.
RESULTS: Eighty-six patients (43 men, 43 women; mean age, 52 years) underwent 37 CT and 49 ultrasound examinations). Forty-eight patients (56%) identified a radiologist as a physician who interprets images. Before imaging, 70 patients (81%) preferred hearing results from both the ordering provider and the radiologist. This percentage increased to 78 (91%) after consultation (p=0.03). Before consultation, 84 of the 86 patients (98%) indicated they would be comfortable hearing normal results or abnormal results from the person interpreting the examination; the number increased to 85 (99%) after consultation. Eighty-five patients (99%) agreed or strongly agreed that reviewing their examination findings with a radiologist was helpful. Eighty-four patients (98%) indicated they wanted the option of reviewing or always wanted to review future examination findings with a radiologist. After consultation, anxiety decreased in 41 patients (48%), increased in 13 (15%), and was unchanged in 32 (37%) (p=0.0001). The average wait for consultation and the duration of consultation were 9.9 and 10.4 minutes for CT and 1.2 and 7.1 minutes for ultrasound.
CONCLUSION: Patients prefer hearing examination results from both their ordering provider and the interpreting radiologist. Most patients find radiologist consultation beneficial. Patients are comfortable hearing results from the radiologist, with most displaying decreased anxiety after consultation.
The diagnostic imaging of patients presenting with right lower quadrant pain and suspected appendicitis may be organized according to age and gender and to the presence or absence of "classic" signs and symptoms of acute appendicitis. Among adult patients presenting with clinical signs of acute appendicitis, the sensitivity and specificity of CT are greater than those of ultrasound, with improved performance when CT is performed with intravenous contrast. The use of rectal contrast has been associated with decreased time in the emergency department. Computed tomography has also been shown to reduce cost and negative appendectomy rates. Both CT and ultrasound are also effective in the identification of causes of right lower quadrant pain unrelated to appendicitis. Among pediatric patients, the sensitivity and specificity of graded-compression ultrasound can approach those of CT, without the use of ionizing radiation. Performing MRI after inconclusive ultrasound in pregnant patients has been associated with sensitivity and specificity of 80% to 86% and 97% to 99%, respectively. The ACR Appropriateness Criteria((R)) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. rights reserved.
Colorectal cancer is the third leading cause of cancer deaths in the United States. Most colorectal cancers can be prevented by detecting and removing the precursor adenomatous polyp. Individual risk factors for the development of colorectal cancer will influence the particular choice of screening tool. CT colonography (CTC) is the primary imaging test for colorectal cancer screening in average-risk individuals, whereas the double-contrast barium enema (DCBE) is now considered to be a test that may be appropriate, particularly in settings where CTC is unavailable. Single-contrast barium enema has a lower performance profile and is indicated for screening only when CTC and DCBE are not available. CTC is also the preferred test for colon evaluation following an incomplete colonoscopy. Imaging tests including CTC and DCBE are not indicated for colorectal cancer screening in high-risk patients with polyposis syndromes or inflammatory bowel disease. This paper presents the updated colorectal cancer imaging test ratings and is the result of evidence-based consensus by the ACR Appropriateness Criteria Expert Panel on Gastrointestinal Imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. rights reserved.
The effect of imaging capacity on the imaging workup of patients with stroke: a preliminary case for a cross-country comparison
PURPOSE: Medical imaging is a large and growing component of health care expenditures. To better understand some of the determinants of imaging ordering behavior, the authors analyzed the effect of differential capacity on the imaging workup of patients with acute nonhemorrhagic stroke.
METHODS: All patients at a US teaching hospital and a two-campus Canadian teaching hospital between 2001 and 2005 discharged with diagnoses of acute nonhemorrhagic stroke were identified. Billing data were linked with clinical information systems to identify all imaging studies performed, comorbidities, and patient disposition.
RESULTS: Nine hundred eighteen patients at the US hospital and 1,759 patients at the Canadian hospital were included. Patients were similar in age and distribution of comorbid illnesses. The rate of MRI scans at the US hospital was more than twice that at either of the Canadian hospitals (95.75 scans per 100 patients vs 41.39 scans per 100 patients). The length of stay was significantly shorter and the inpatient mortality rate significantly lower at the US hospital compared with the Canadian hospital. A multivariate regression analysis demonstrated that only patient age and site (US vs Canada) were significant predictors of MRI use, controlling for patient gender, comorbidities, and use of anticoagulants.
CONCLUSIONS: Scanning utilization varied at hospitals with differential access to scanning technologies. There was less frequent use of MRI scanning at hospitals with limited access to this modality. Patient and health system factors are important considerations when interpreting the mechanisms for this variation, its importance, and the potential relationship of imaging use with patient outcomes. rights reserved.
A survey of 100 women living inside Gaza (WIG) and 55 Gaza women residing outside Gaza (WOG) was conducted to investigate barriers and opportunities for breast cancer screening, and to better understand possible differences based on residency. The survey found that over 90% of both groups were willing to undergo a diagnostic mammogram for a breast complaint and 86% of WIG and 85% of WOG believed survival was increased with early detection. However, only 27% of WIG and 50% WOG were willing to undergo screening mammography. Religion and culture were not barriers to mammography for over 94% of WIG and 98% of WOG. Limited resources and lack of access to medical facilities were identified as barriers in up to 55% of WIG compared to 15% of WOG. Misconceptions about breast cancer were reported more frequently by WIG, including beliefs that breast cancer is not very common and that breast cancer can be contagious.
The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains the repressive function of Snai1. Disruption of the complex by depleting Id2 resulted in Snai1-mediated beta4 repression with a concomitant increase in H3K27Me3 modification on the beta4 promoter. These findings establish a novel function for Id2 in regulating Snai1 that has significant implications for the regulation of epithelial gene expression.
The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches.
Regulated splicing of the alpha6 integrin cytoplasmic domain determines the fate of breast cancer stem cells
Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of an autocrine vascular endothelial growth factor (VEGF) signaling that culminates in the transcriptional repression of a key RNA-splicing factor. These data alter our understanding of how alpha6beta1 contributes to breast cancer, and they resolve ambiguities regarding the use of total alpha6 (CD49f) expression as a biomarker for CSCs.
IMP3 expression is associated with poor outcome and epigenetic deregulation in intrahepatic cholangiocarcinoma
IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in cancer cells but not in the surrounding normal tissue, and 59 (82%) of 72 ICCs were IMP3 positive by immunohistochemistry. Among 35 cases with lymphovascular invasion, 26 (74%) showed IMP3 positivity in lymph node metastases. IMP3 expression was significantly correlated with tumor size, pathological grade, metastasis, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between IMP3 expression and overall survival rate. Multivariate analysis revealed that IMP3 was the only risk factor associated with survival. To further explore the mechanism of IMP3 expression in cancers, we identified 2 CpG islands at IMP3 proximal promoter. Interestingly, the IMP3 promoter was almost completely demethylated in ICCs in contrast to densely methylated promoter in normal liver tissues. IMP3 expression is a useful biomarker for ICCs and can provide an independent prognostic value for patients with ICC. To our knoweldge, this is the first direct evidence of epigenetic deregulation of IMP3 in human cancer.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.