State of Academic Radiology: Current Challenges, Future Adaptations.

There are approximately 200 academic radiology departments in the United States. While academic medical centers vary widely depending on their size, complexity, medical school affiliation, research portfolio, and geographic location, they are united by their 3 core missions: patient care, education and training, and scholarship. Despite inherent differences, the current challenges faced by all academic radiology departments have common threads; potential solutions and future adaptations will need to be tailored and individualized-one size will not fit all. In this article, we provide an overview based on our experiences at 4 academic centers across the United States, from relatively small to very large size, and discuss creative and innovative ways to adapt, including community expansion, hybrid models of faculty in-person vs teleradiology (traditional vs non-traditional schedule), work-life integration, recruitment and retention, mentorship, among others.

Biological evaluation of 9-thioansamitocin P3.

Highly cytotoxic maytansine derivatives are widely used in targeted tumor delivery. Structure-activity studies published earlier suggested the C9 carbinol to be a key element necessary to retain the potency. However, in 1984 a patent was published by Takeda in which the synthesis of 9-thioansamitocyn (AP3SH) was described and its activity in xenograft models was shown. In this article we summarize the results of an extended study of the anti-tumor properties of AP3SH. Like other maytansinoids, it induces apoptosis and arrests the cell cycle in the G2/M phase. It is metabolized in liver microsomes predominately by C3A4 isoform and doesn't inhibit any CYP isoforms except CYP3A4 (midazolam, IC50 7.84 µM). No hERG inhibition, CYP induction or mutagenicity in Ames tests were observed. AP3SH demonstrates high antiproliferative activity against 25 tumor cell lines and tumor growth inhibition in U937 xenograft model. Application of AP3SH as a cytotoxic payload in drug delivery system was demonstrated by us earlier.

Improved radiologic diagnosis of delayed gastric conduit emptying (DGCE) after esophagectomy using a functional upper gastrointestinal contrast study.

BACKGROUND: With increasing incidence of esophageal cancer, a growing number of patients are at risk of developing delayed gastric conduit emptying (DGCE) in the early postoperative phase after esophagectomy. This condition is of great postoperative concern due to its association with adverse outcomes. PURPOSE: To give a narrative review of the literature concerning radiological diagnosis of DGCE after esophagectomy and a proposal for an improved, functional protocol with objective measurements. MATERIAL AND METHODS: The protocol was designed at Virginia Mason Medical Center in Seattle and is based on the Timed Barium Esophagogram (TBE) concept, which has been adapted to assess the passage of contrast from the gastric conduit into the duodenum. RESULTS: The literature review showed a general lack of standardization and scientific evidence behind the use of radiology to assess DGCE. We found that our proposed standardized upper gastrointestinal (UGI) contrast study considers both the time aspect in DGCE and provides morphologic information of the gastric conduit. This radiological protocol was tested on 112 patients in a trial performed at two high-volume centers for esophageal surgery and included an UGI contrast study 2-3 days postoperatively. The study demonstrated that this UGI contrast study can be included in the standardized clinical pathway after esophagectomy. CONCLUSION: This new, proposed UGI contrast study has the potential to diagnose early postoperative DGCE in a standardized manner and to improve overall patient outcomes after esophagectomy.

Safety and clinical outcomes of early dual modality drainage (< 28 days) compared to later drainage of pancreatic necrotic fluid collections: a propensity score-matched study.

BACKGROUND: Necrotizing pancreatitis can be complicated by Necrotic Fluid Collections (NFC). Guidelines recommend waiting for 4 weeks from the onset of acute pancreatitis (AP) before considering endoscopic drainage. We aimed to compare outcomes and safety in patients undergoing early versus late drainage of NFC. METHODS: We performed a retrospective review of all patients who underwent Dual Modality Drainage (DMD) [combined endoscopic and percutaneous drainage] for NFC from January 2007 to December 2020. Patients were stratified into the "early" group (DMD < 28 days from AP onset) and were matched to "late" (DMD ≥ 28 days) drainage group using propensity- core-matching. Primary outcomes of interest were technical success and adverse events. Secondary outcomes included clinical success, late complication rates, and mortality. RESULTS: We identified 278 patients who underwent DMD for NFC. Thirty-nine belonged to the early group and were matched to 174 patients from the late group. Technical success was similar in both early and late groups (97.4% vs 99.4%: P = 0.244) as were the procedural and early post-procedural (< 14 days) adverse events rates (23.1% vs 27.6%: P = 0.565). Clinical success (92.3% vs 93.1%; P = 0.861) and late complication rates (23.1% vs 31.6%; P = 0.294) were similar. There were 2 deaths (5.7%) in the early vs. 9 (5.2%) in the late group, P = 0.991. CONCLUSIONS: When performed in a tertiary care center with expertise in therapeutic endoscopic ultrasound, early drainage of NFC appears to be feasible and safe. Further studies are needed to validate our results.

Tagging incidental finding of fatty liver on ultrasound: A novel intervention to improve early detection of liver fibrosis.

BACKGROUND: It is not uncommon to see that a large proportion of patients with cirrhosis due to nonalcoholic steatohepatitis never had any prior evaluation or diagnosis of liver disease, and most of the times their first clinical presentation is decompensated cirrhosis. Acknowledging incidental finding of fatty liver on abdominal imaging and identifying patients at risk of having advanced liver fibrosis may help in preventing its progression to cirrhosis. AIM: We aimed to increase acknowledgement and improve evaluation of steatosis through radiology recommendation to consider hepatology referral, and to identify the predictors of hepatology referral and significant fibrosis. METHODS: We performed a retrospective study of 812 patients with hepatic steatosis tagged on ultrasound (US), over 18 months, at a single center. Patients with secondary causes of fatty liver were excluded from the study. We evaluated the yield of this intervention and factors correlated with hepatology referral and presence of significant fibrosis. RESULTS: Diagnosis of fatty liver was acknowledged for 69% of patients with tagged US, although only 29% were ultimately seen by hepatology. Patients who had US ordered by a primary care provider (PCP) were more likely to have hepatology evaluation (64.8% vs. 56.9%, P = 0.0183). Sixty-six percent of patients seen by hepatology had elevated alanine transaminase (ALT) compared to 52% not seen by hepatology (P < 0.0005). Among patients further evaluated, 53% underwent staging, and 18% had ≥stage 2 (F2) fibrosis. Type II diabetes correlated with significant to advanced fibrosis (43.5% vs. 21.4%, P = 0.0357), while ALT and Body Mass Index did not. CONCLUSIONS: Tagging US reports led to clinical acknowledgement of fatty liver in 7 of 10 patients, although fewer than 1 in 3 had further hepatology evaluation. Of those who underwent staging for incidentally noted steatosis, 18% had significant fibrosis, suggesting that we are failing to evaluate patients with potentially advanced liver disease. RELEVANCE FOR PATIENTS: Identifying incidental finding of fatty liver on US provides a unique opportunity in diagnosing liver fibrosis at an early stage and can help prevent its progression to cirrhosis. PCP should consider using noninvasive scoring systems on a regular basis to assess the risk of fibrosis in patients with fatty liver, and timely referral to hepatology should be provided in patients at high risk of having advanced fibrosis.

Opportunistic Screening of Patients for Hepatic Steatosis: Clinical Follow-Up and Diagnostic Yield.

PURPOSE: Hepatic steatosis is a common incidental finding on abdominal imaging that is not always reported or recognized as having clinical significance. Because of its association with liver disease, cirrhosis, and diabetes, the aim of this study was to bring attention to this finding and provide clinical guidance to referring clinicians by inserting standardized text into radiology reports of patients with incidentally detected hepatic steatosis. METHODS: Patients with incidentally discovered hepatic steatosis on abdominal ultrasound or CT had standard text inserted into the impression sections of their diagnostic imaging reports. A total of 1,256 patients whose reports were tagged between April 2016 and September 2017 were retrospectively identified and their electronic medical records reviewed to determine subsequent acknowledgment in the medical record or clinical action in response to the tagged report. Information regarding patient demographics, the type of provider who ordered the examination, and the acuity of the examination results was also recorded. RESULTS: Acknowledgment and subsequent clinical action were more likely in patients whose examinations was ordered by primary care providers, whose examination results were not urgent, and who were in the ultrasound group. The overall diagnostic yield in patients who underwent clinical evaluation was nonalcoholic fatty liver disease in 70%, nonalcoholic steatohepatitis in 6%, and alcoholic hepatitis in 17%. CONCLUSIONS: Opportunistic screening for incidental hepatic steatosis on abdominal CT and ultrasound is feasible, with substantial yield for patients with clinically important entities including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Contrast-enhanced paravertebrogram to confirm paravertebral catheter position in elective thoracic surgery: a proof of concept study.

BACKGROUND: Paravertebral pain catheters have been shown to be equally effective as epidural pain catheters for postoperative analgesia after thoracic surgery with the possible additional benefit of less hemodynamic effect. However, a methodology for verifying correct paravertebral catheter placement has not been tested or objectively confirmed in previous studies. The aim of the current study was to describe a technique to confirm the correct position of a paravertebral pain catheter using a contrast-enhanced paravertebrogram. METHODS: A retrospective cohort proof of concept study was performed including 10 consecutive patients undergoing elective thoracic surgery with radiographic contrast-enhanced confirmation of intraoperative paravertebral catheter placement (paravertebrogram). RESULTS: The results of the paravertebrograms, which were done in the operating room at the end of the procedure, verified correct paravertebral catheter placement in 10 of 10 patients. The radiographs documented dissemination of local anesthetic within the paravertebral space. CONCLUSION: This proof of concept study demonstrated that a contrast-enhanced paravertebrogram could be used in conjunction with standard postoperative chest radiography to add valuable information for the assessment of paravertebral catheter placement. This technique has the potential to increase the accuracy and efficiency of postoperative analgesia, and to set a quality standard for future studies of paravertebral pain catheters.

Erosion of Mesh Mid-urethral Sling Into a Complex Urethral Diverticulum: Diagnosis, Evaluation, and Surgical Management.

We present a case of an eroded mesh mid-urethral sling into a urethral diverticulum. Preoperative MRI and 3-dimensional translabial ultrasound aided in the identification and surgical approach. Vaginal excision of sling with urethral diverticulectomy and complex urethral reconstruction was performed. To the author's knowledge, this is the first case documented in the literature describing an eroded mesh mid-urethral sling into a urethral diverticulum.

Osteochondroma of the Pubic Symphysis Involved With Aberrantly Placed Minisling: A Case Report.

Osteochondromas are benign bone tumors that rarely involve the pubic symphysis. This case report describes a 41-year-old woman with a pubic symphyseal osteochondroma associated with an aberrantly placed single incision sling. After an outside surgeon placed a single incision midurethral sling for stress urinary incontinence, she developed pelvic pain, dyspareunia and vaginal mesh sling exposure. Imaging demonstrated a 2.6 centimeter calcified mass posterior to the pubic symphysis. The patient underwent excision of the mass and the eroded mesh sling via vaginal and abdominal approaches. Pathology demonstrated osteochondroma aggregated around mesh. This is a rare case of a single incision sling placed aberrantly into a pubic symphyseal osteochondroma that required excision.

Current Imaging Standards for Nonmetastatic Benign and Malignant Liver Tumors.

The accurate diagnosis of a liver mass can usually be established with a thorough history, examination, laboratory inquiry, and imaging. The necessity of a liver biopsy to determine the nature of a liver mass is rarely necessary. Contrast-enhanced computed tomography and magnetic resonance are the standard of care for diagnosing liver lesions and high-quality imaging should be performed before performing a biopsy. This article discusses current consensus guidelines for imaging of liver masses, as well as masses found on surveillance imaging. The ability to accurately characterize lesions requires proper use and understanding of the technology and expert interpretation.

The antimicrobial peptides and their potential clinical applications.

Nowadays, the bacterial drug resistance leads to serious healthy problem worldwide due to the long-term use and the abuse of traditional antibiotics result in drug resistance of bacteria. Finding a new antibiotic is becoming more and more difficult. Antimicrobial peptides (AMPs) are the host defense peptides with most of them being the cationic (positively charged) and amphiphilic (hydrophilic and hydrophobic) α-helical peptide molecules. The membrane permeability is mostly recognized as the well-accepted mechanism to describe the action of cationic AMPs. These cationic AMPs can bind and interact with the negatively charged bacterial cell membranes, leading to the change of the electrochemical potential on bacterial cell membranes, inducing cell membrane damage and the permeation of larger molecules such as proteins, destroying cell morphology and membranes and eventually resulting in cell death. These AMPs have been demonstrated to have their own advantages over the traditional antibiotics with a broad-spectrum of antimicrobial activities including anti-bacteria, anti-fungi, anti-viruses, and anti-cancers, and even overcome bacterial drug-resistance. The natural AMPs exist in a variety of organisms and are not stable with a short half-life, more or less toxic side effects, and particularly may have severe hemolytic activity. To open the clinical applications, it is necessary and important to develop the synthetic and long-lasting AMP analogs that overcome the disadvantages of their natural peptides and the potential problems for the drug candidates.

Significance of radiographic splenic vessel involvement in the pancreatic ductal adenocarcinoma of the body and tail of the gland.

BACKGROUND AND OBJECTIVES: Unlike pancreatic head tumors, little is known about the biological significance of radiographic vessel involvement with pancreatic body/tail adenocarcinoma. We hypothesized radiographic splenic vessel involvement may be an adverse prognostic factor. METHODS: All distal pancreatectomies performed for resectable pancreatic adenocarcinoma between 2000 and 2016 were reviewed and clinicopatholgic data were collected, retrospectively. Preoperative computed tomography imaging was re-reviewed and splenic vessel involvement was graded as none, abutment, encasement, or occlusion. RESULTS: Among a total of 71 patients, splenic artery or vein encasement/occlusion was present in 41% (29 of 71) of patients, each. There were no significant differences in tumor size or grade, margin positivity, and perineural or lymphovascular invasion. However, splenic artery encasement/occlusion (P = 0.001) and splenic vein encasement/occlusion (P = 0.038) both correlated with lymph node positivity. Splenic artery encasement was associated with a reduced median overall survival (20 vs 30 months, P = 0.033). Multivariate analysis also showed that splenic artery encasement was an independent risk factor of worse survival (hazard ratio, 2.246; 95% confidence interval, 1.118-4.513; P = 0.023). CONCLUSION: Patients with cancer of the body or tail of the pancreas presenting with radiographic encasement of the splenic artery, but not the splenic vein, have a poorer prognosis and perhaps should be considered for neoadjuvant therapy before an attempt at curative resection.

Does mesenteric venous imaging assessment accurately predict pathologic invasion in localized pancreatic ductal adenocarcinoma?

BACKGROUND: Accurate prediction of mesenteric venous involvement in pancreatic ductal adenocarcinoma (PDAC) is necessary for adequate staging and treatment. METHODS: A retrospective cohort study was conducted in PDAC patients at a single institution. All patients with resected PDAC and staging CT and EUS between 2003 and 2014 were included and sub-divided into "upfront resected" and "neoadjuvant chemotherapy (NAC)" groups. Independent imaging re-review was correlated to venous resection and venous invasion. Sensitivity, specificity, positive and negative predictive values were then calculated. RESULTS: A total of 109 patients underwent analysis, 60 received upfront resection, and 49 NAC. Venous resection (30%) and vein invasion (13%) was less common in patients resected upfront than those who received NAC (53% and 16%, respectively). Both CT and EUS had poor sensitivity (14-44%) but high specificity (75-95%) for detecting venous resection and vein invasion in patients resected upfront, whereas sensitivity was high (84-100%) and specificity was low (27-44%) after NAC. CONCLUSIONS: Preoperative CT and EUS in PDAC have similar efficacy but different predictive capacity in assessing mesenteric venous involvement depending on whether patients are resected upfront or received NAC. Both modalities appear to significantly overestimate true vascular involvement and should be interpreted in the appropriate clinical context.

Pituitary adenylate cyclase-activating polypeptide is a potent broad-spectrum antimicrobial peptide: Structure-activity relationships.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally occurring cationic peptide with potent immunosuppressant and cytoprotective activities. We now show that full length PACAP38 and to a lesser extent, the truncated form PACAP27, and the closely related vasoactive intestinal peptide (VIP) and secretin had antimicrobial activity against the Gram-negative bacteria Escherichia coli in the radial diffusion assay. PACAP38 was more potent than either the bovine neutrophil antimicrobial peptide indolicidin or the synthetic antimicrobial peptide ARVA against E. coli. PACAP38 also had activity against the Gram-positive bacteria Staphylococcus aureus in the same assay with comparable potency to indolicidin and ARVA. In the more stringent broth dilution assay, PACAP38 had moderate sterilizing activity against E. coli, and potent sterilizing activity against the Gram-negative bacteria Pseudomonas aeruginosa. PACAP27, VIP and secretin were much less active than PACAP38 in this assay. PACAP38 also had some activity against the Gram-positive bacteria Bacillus cereus in the broth dilution assay. Many exopeptidase-resistant analogs of PACAP38, including both receptor agonists and antagonists, had antimicrobial activities equal to, or better than PACAP38, in both assays. PACAP38 made the membranes of E. coli permeable to SYTOX Green, suggesting a classical membrane lytic mechanism. These data suggest that analogs of PACPAP38 with a wide range of useful biological activities can be made by judicious substitutions in the sequence.

HDAC inhibitors suppressed small cell lung cancer cell growth and enhanced the suppressive effects of receptor-targeting cytotoxins via upregulating somatostatin receptor II.

Small cell lung cancer (SCLC) is a malignant human cancer and patients have very limited benefit from traditional anticancer treatments, with a poor five-year survival rate being 10% less. In present study, we observed that Notch signalling activation induced SCLC cell growth suppression via overexpressing Notch active fragments (ICN1, ICN2, ICN3 and ICN4), implying its tumor suppressive role. The histone deacetylase (HDAC) inhibitors also displayed their suppressive effects. Valproic acid (VPA) as a HDAC inhibitor was found to suppress SCLC cell growth and cell cycle arrest at phase G1, and observed to decrease HDAC4 and increase acetylation of histone H4 (AcH4) while activating Notch signalling with an increase of Notch1, Notch target gene HES1 and p21. Meanwhile, we also observed that VPA greatly stimulated the expression of somatostatin receptor type II (SSTR2) that is usually overexpressed in many cancer cells and is used as a target for anticancer drug development, providing a combination therapy with VPA and the SSTR2-targeting cytotoxins. Thus, VPA was investigated in combination with SSTR2-targeted cytotoxins captothecine-somatostatin conjugate (CPT-SST) and colchicine-somatostatin conjugate (COL-SST). Our assays showed that these combination treatments strongly led to a greater suppression as compared to each alone. In conclusion, we found that VPA suppressed SCLC cell growth and increased the expression of SSTR2. These may provide a novel clinical opportunity for enhanced anticancer therapy using the combination strategy of Notch signalling regulator and SSTR2-targeting cytotoxins in SCLC treatments.

New guidelines for use of endoscopic ultrasound for evaluation and risk stratification of pancreatic cystic lesions may be too conservative.

BACKGROUND: The role of EUS in managing asymptomatic pancreatic cystic lesions (PCLs) remains unresolved. We retrospectively evaluated EUS in risk stratification of PCLs when adhering to the most recent AGA guidelines. METHODS: Asymptomatic PCLs that were evaluated by EUS from January 2014 to December 2014 were retrospectively reviewed including associated cytology, fluid analysis, and relevant surgical pathology. Cross-sectional imaging reports were reviewed blindly by an expert radiologist using AGA risk stratification terminology. Accepted imaging high-risk features (HRF) included cyst diameter > 3 cm, dilated upstream pancreatic ducts, and a solid component in the cyst. RESULTS: We reviewed 125 patients who underwent EUS. Expert review of cross-sectional imaging resulted in a different interpretation 25% of the time including 1 malignant cyst. Ninety-three patients (75%) had no HRFs on cross-sectional imaging; 28 patients (22%) were diagnosed with 1 HRF and 4 patients (3%) had 2 HRFs. Adhering to AGA guidelines using 2 HRF as threshold for use of EUS, the diagnosis of malignant and high-risk premalignant lesions (including pancreatic adenocarcinoma, mucinous cystadenoma, neuroendocrine tumors, and IPMN with dysplasia) had a 40% sensitivity and 100% specificity. Had EUS been utilized based on a threshold of 1 HRF on imaging, malignant and high-risk premalignant lesions would have been identified with 80% sensitivity and 95% specificity. By adding EUS to radiographic imaging, the specificity for detecting carcinomas (p = 0.0009) and detection of all premalignant lesions (p = 0.003) statistically improved. Furthermore, EUS allowed 14 patients (11%) to avoid further surveillance by lowering their risk stratification. CONCLUSION: EUS remains an essential risk stratification modality for incidental PCLs. Current guideline suggestions of its utility may be too stringent. Our study justifies expert radiology review when managing PCLs. Further studies are required to identify the optimal approach to PCL management.

Pituitary adenylate cyclase-activating polypeptide (PACAP) protects against mitoxantrone-induced cardiac injury in mice.

Mitoxantrone (MXT) is an androstenedione that is used to treat cancers and progressive forms of multiple sclerosis; however, its use is limited by its cardiotoxicity. Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the secretin/growth hormone-releasing hormone/vasoactive intestinal peptide family and has many functions, including cytoprotection and immunosuppression. We tested the hypothesis that PACAP can protect against MXT-induced cardiotoxicity in mice. Female BALB/c mice were treated once weekly for 4 weeks with saline (n=14) or MXT (3mg/kg, i.p.; n=14). Half of the mice in each group received PACAP (10µg, i.p.) 1h before and 24 and 48h after MXT, while the remaining mice received injections of saline on the same schedule. Echocardiography was used to assess cardiac structure and function. In mice treated with MXT and saline, body weight was significantly reduced after the third dose of MXT. PACAP significantly attenuated the reduction in body weight; however, the weights did not return to control level. Compared to controls, MXT-treated mice had significantly increased left ventricular (LV) diameter and LV volume and decreased LV posterior wall thickness. Fractional shortening (FS) and ejection fraction (EF) were also significantly decreased. Treatment with PACAP prevented MXT-induced LV dilation and significantly attenuated the reductions in FS and EF, although FS and EF did not return to control level. PACAP38 did not prevent MXT-induced decreases in LV posterior wall thickness. MXT dose-dependently decreased the viability of cultured U937 (human leukemia) cells; PACAP did not protect cultured U937 cells from MXT-mediated cell death. In conclusion, PACAP can attenuate MXT-mediated LV dilation and dysfunction in mice.

Activated Notch signaling augments cell growth in hepatocellular carcinoma via up-regulating the nuclear receptor NR4A2.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional therapies are limited due to the human liver being such a unique organ and easily showing side-effects. The unclear molecular mechanisms are tough challenges for scientists searching for new and effective anti-HCC targeting drugs. We identified that the nuclear receptor NR4A2 is a novel oncogene in HCC progression. In this study, we show that NR4A2 and the notch recceptor Notch1 were expressed highly in primary HCC tissues and immortal HCC cells by using qPCR, western blot and immuno-histochemistry assays. Both genes were observed to stimulate HCC cell proliferation, anti-apoptosis and cell cycle arrest by using cell proliferation assays and FACS assays. We also observed that the four notch receptor subtypes (Notch1-4) displayed different effects on HCC cell growth. The over-expression of Notch1 by transiently transfecting the intracellular domain of Notch1 (ICN1, Notch1 active form) increased the expression of NR4A2, with the knockdown of Notch1 decreasing NR4A2. This indicates that NR4A2 is one of the Notch-mediated downstream genes. Moreover, both NR4A2 and Notch1 suppressed the expression of tumor suppressors p21 and p63. These findings support that Notch1/NR4A2 co-regulate HCC cell functions by playing oncogenic roles and regulating the associated downstream signaling pathways. Novel Notch1/NR4A2-mediated oncogenic signaling may provide us a great opportunity for anti-HCC drug development.

Changes in Physician Decision Making after CT: A Prospective Multicenter Study in Primary Care Settings.

Purpose To determine the effect of computed tomography (CT) results on physician decision making in three common clinical scenarios in primary care. Materials and Methods This research was approved by the institutional review board (IRB) and was HIPAA compliant. All physicians consented to participate with an opt-in or opt-out mechanism; patient consent was waived with IRB approval. In this prospective multicenter observational study, outpatients referred by primary care providers (PCPs) for CT evaluation of abdominal pain, hematuria, or weight loss were identified. Prior to CT, PCPs were surveyed to elicit their leading diagnosis, confidence in that diagnosis (confidence range, 0%-100%), a rule-out diagnosis, and a management plan if CT were not available. Surveys were repeated after CT. Study measures were the proportion of patients in whom leading diagnoses and management changed (PCP management vs specialist referral vs emergency department transfer), median changes in diagnostic confidence, and the proportion of patients in whom CT addressed rule-out diagnoses. Regression analyses were used to identify associations between study measures and site and participant characteristics. Specifically, logistic regression analysis was used for binary study measures (change in leading diagnosis, change in management), and linear regression analysis was used for the continuous study measure (change in diagnostic confidence). Accrual began on September 5, 2012, and ended on June 28, 2014. Results In total, 91 PCPs completed pre- and post-CT surveys in 373 patients. In patients with abdominal pain, hematuria, or weight loss, leading diagnoses changed after CT in 53% (131 of 246), 49% (36 of 73), and 57% (27 of 47) of patients, respectively. Management changed in 35% (86 of 248), 27% (20 of 74), and 54% (26 of 48) of patients, respectively. Median absolute changes in diagnostic confidence were substantial and significant (+20%, +20%, and +19%, respectively; P ≤ .001 for all); median confidence after CT was high (90%, 88%, and 80%, respectively). PCPs reported CT was helpful in confirming or excluding rule-out diagnoses in 98% (184 of 187), 97% (59 of 61), and 97% (33 of 34) of patients, respectively. Significant associations between primary measures and site and participant characteristics were not identified. Conclusion Changes in PCP leading diagnoses and management after CT were common, and diagnostic confidence increased substantially. © RSNA, 2016 Online supplemental material is available for this article.

Notch Signaling Activation in Cervical Cancer Cells Induces Cell Growth Arrest with the Involvement of the Nuclear Receptor NR4A2.

Cervical cancer is a second leading cancer death in women world-wide, with most cases in less developed countries. Notch signaling is highly conserved with its involvement in many cancers. In the present study, we established stable cervical cell lines with Notch activation and inactivation and found that Notch activation played a suppressive role in cervical cancer cells. Meanwhile, the transient overexpression of the active intracellular domain of all four Notch receptors (ICN1, 2, 3, and 4) also induced the suppression of cervical cancer Hela cell growth. ICN1 also induced cell cycle arrest at phase G1. Notch1 signaling activation affected the expression of serial genes, especially the genes associated with cAMP signaling, with an increase of genes like THBS1, VCL, p63, c-Myc and SCG2, a decrease of genes like NR4A2, PCK2 and BCL-2. Particularly, The nuclear receptor NR4A2 was observed to induce cell proliferation via MTT assay and reduce cell apoptosis via FACS assay. Furthermore, NR4A2's activation could reverse ICN1-induced suppression of cell growth while erasing ICN1-induced increase of tumor suppressor p63. These findings support that Notch signaling mediates cervical cancer cell growth suppression with the involvement of nuclear receptor NR4A2. Notably, Notch/NR4A2/p63 signaling cascade possibly is a new signling pathway undisclosed.