AuthorsExpert Panel on Gastrointestinal Imaging
Kamel, Ihab R.
Goldstein, Alan J.
UMass Chan AffiliationsDepartment of Radiology
Document TypeJournal Article
Appropriate Use Criteria
Incidental pancreatic cyst
Intraductal papillary mucinous neoplasm
Neoplastic pancreatic cyst
Pancreatic cyst associated malignancy
Digestive System Diseases
Health Services Administration
MetadataShow full item record
AbstractIncidental pancreatic cysts are increasingly detected on imaging studies performed for unrelated indications and may be incompletely characterized on these studies. Adequate morphological characterization is critical due to the small risk of malignant degeneration associated with neoplastic pancreatic cysts, as well as the risk of associated pancreatic adenocarcinoma. For all pancreatic cysts, both size and morphology determine management. Specifically, imaging detection of features, such as pancreatic ductal communication and presence or absence of worrisome features or high-risk stigmata, have important management implications. The recommendations in this publication determine the appropriate initial imaging study to further evaluate a pancreatic cyst that was incidentally detected on a nondedicated imaging study. The recommendations are designed to maximize the yield of diagnostic information in order to better risk-stratify pancreatic cysts and assist in guiding future management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Expert Panel on Gastrointestinal Imaging, Fábrega-Foster K, Kamel IR, Horowitz JM, Arif-Tiwari H, Bashir MR, Chernyak V, Goldstein A, Grajo JR, Hindman NM, Kamaya A, McNamara MM, Porter KK, Scheiman JM, Solnes LB, Srivastava PK, Zaheer A, Carucci LR. ACR Appropriateness Criteria® Pancreatic Cyst. J Am Coll Radiol. 2020 May;17(5S):S198-S206. doi: 10.1016/j.jacr.2020.01.021. PMID: 32370963. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48437
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GLI-IKBKE Requirement In KRAS-Induced Pancreatic Tumorigenesis: A DissertationRajurkar, Mihir S. (2014-11-30)Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by KRAS activation. Here, we find that transcriptional activation mediated by the GLI family of transcription factors, although dispensable for pancreatic development, is required for KRAS induced pancreatic transformation. Inhibition of GLI using a dominant-negative repressor (Gli3T) inhibits formation of precursor Pancreatic Intraepithelial Neoplasia (PanIN) lesions in mice, and significantly extends survival in a mouse model of PDAC. Further, ectopic activation of the GLI1/2 transcription factors in mouse pancreas accelerates KRAS driven tumor formation and reduces survival, underscoring the importance of GLI transcription factors in pancreatic tumorigenesis. Interestingly, we find that although canonical GLI activity is regulated by the Hedgehog ligands, in the context of PDAC, GLI transcription factors initiate a unique ligand-independent transcriptional program downstream of KRAS, that involves regulation of the RAS, PI3K/AKT, and NF-кB pathways. We identify I-kappa-B kinase epsilon (IKBKE) as a PDAC specific target of GLI, that can also regulate GLI transcriptional activity via positive feedback mechanism involving regulation of GLI subcellular localization. Using human PDAC cells, and an in vivo model of pancreatic neoplasia, we establish IKBKE as a novel regulator pf pancreatic tumorigenesis that acts as an effector of KRAS/GLI, and mediates pancreatic transformation. We show that genetic knockout of Ikbke leads to a dramatic inhibition of initiation and progression of pancreatic intraepithelial viii neoplasia (PanIN) lesions in mice carrying pancreas specific activation of oncogenic Kras. Furthermore, we find that although IKBKE is a known NF-кB activator, it only modestly regulates NF-кB activity in PDAC. Instead, we find that IKBKE strongly promotes AKT phosphorylation in PDAC in vitro and in vivo, and that IKBKE mediates reactivation of AKT post-inhibition of mTOR. We also show that while mTOR inhibition alone does not significantly affect pancreatic tumorigenesis, combined inhibition of IKBKE and mTOR has a synergistic effect leading to significant decrease tumorigenicity of PDAC cells. Together, our findings identify GLI/IKBKE signaling as an important oncogenic effector pathway of KRAS in PDAC that regulates tumorigenicity, cell proliferation, and apoptosis via regulation of AKT and NF-кB signaling. We provide proof of concept for therapeutic targeting of GLI/IKBKE in PDAC, and support the evaluation of IKBKE as a therapeutic target in treatment of pancreatic cancer, and IKBKE inhibition as a strategy to improve efficacy of mTOR inhibitors in the clinic.
Evolution of pancreatic function during the first year in infants with cystic fibrosisO'Sullivan, Brian P.; Baker, Dawn; Leung, Katherine G.; Reed, George W.; Baker, Susan S.; Borowitz, Drucy (2013-04-01)OBJECTIVE: To describe pancreatic function during the first year of life in infants diagnosed with cystic fibrosis (CF) using serial fecal elastase measurements. STUDY DESIGN: This was a longitudinal study of 82 infants diagnosed with CF through newborn screening. Monthly stool samples were sent to a central laboratory for fecal elastase measurements. RESULTS: A total of 61 infants had an initial stool sample obtained at age 9 months. Twenty-six of 29 infants with a fecal elastase value /g at study entry had a fecal elastase value /g (the accepted cutoff value for pancreatic insufficiency) on all measurements during the year; all 29 had a value /g at the end of the study. Of the 48 infants with initial fecal elastase value /g, 13 had at least 1 fecal elastase value >200 mug/g but had a final stool fecal elastase value /g; however, 4 infants with an initial fecal elastase value /g ended the year with a value >200 mug/g. Eleven of 13 infants with an initial fecal elastase value of >200 mug/g still had a value >200 mug/g at the end of the first year. CONCLUSION: Infants with CF exhibit variability in fecal elastase values during the first year. Infants with a fecal elastase level of 50-200 mug/g at diagnosis should be treated with pancreatic enzyme replacement therapy, but fecal elastase should be remeasured at age 1 year to ensure that those with a falsely low value do not continue to receive pancreatic enzyme replacement therapy unnecessarily. Those with a fecal elastase value >200 mug/g initially can become pancreatic insufficient with time.
ACR Appropriateness Criteria(R) Acute PancreatitisExpert Panel on Gastrointestinal Imaging; Porter, Kristin K.; Goldstein, Alan J. (2019-11-01)Acute pancreatitis (AP) is divided into two types: interstitial edematous and necrotizing. AP severity is classified clinically into mild, moderately severe, and severe, depending on the presence and persistence of organ failure and local or systemic complications. The revised Atlanta classification divides the clinical course of AP into an early (first week) and late phase (after first week) and the clinical phase determines the role of imaging. Imaging has a limited role in the early phase. In the early phase with typical presentations of AP, ultrasound is usually the only appropriate modality and is used for the detection of gallstones. CT and MRI are appropriate in the early phase in equivocal presentations. In the late phase (or at least 48-72 hours after presentation), CT and MRI play a primary role in the imaging of patients with AP for evaluation of etiology, complications, extent of disease, intervention, and follow-up; CT is particularly useful in patients with suspected acute hemorrhage. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.