Browsing by Author "Sandrasegaran, Kumar"
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Item Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-assigned Steatosis Grades of Liver Biopsies from Adults with Nonalcoholic Steatohepatitis(Elsevier, 2017) Middleton, Michael S.; Heba, Elhamy R.; Hooker, Catherine A.; Bashir, Mustafa R.; Fowler, Kathryn J.; Sandrasegaran, Kumar; Brunt, Elizabeth M.; Kleiner, David E.; Doo, Edward; Van Natta, Mark L.; Tonascia, James; Lavine, Joel E.; Neuschwander-Tetri, Brent A.; Sanyal, Arun; Loomba, Rohit; Sirlin, Claude B.; Department of Radiology and Imaging Sciences, IU School of MedicineBackground & Aims We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. Methods We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. Results At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0–1 vs 2–3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91–0.98), and grade 0–2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93–0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2–3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71–0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63–0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity. Conclusions Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.Item A dedicated paracentesis clinic decreases healthcare utilization for serial paracenteses in decompensated cirrhosis(Springer Nature, 2018-08) Cheng, Yao-Wen; Sandrasegaran, Kumar; Cheng, Katherine; Shah, Angela; Ghabril, Marwan; Berry, William; Lammert, Craig; Chalasani, Naga; Orman, Eric S.; Radiology and Imaging Sciences, School of MedicinePURPOSE: The purpose of the study is to describe the effect of a dedicated paracentesis clinic on healthcare utilization by patients with decompensated cirrhosis and refractory ascites. METHODS: This Institutional Review Board-approved retrospective study identified cirrhotic patients receiving paracenteses over a 6-month period before and after creating the paracentesis clinic. Patients were followed for 12 months to collect outcome data including characteristics of subsequent hospitalizations and paracenteses. Logistic regression was used to examine the association between the paracentesis clinic and outcomes. RESULTS: There were 183 patients and 1364 paracenteses performed during the study time period. Age, gender, cirrhosis etiology, MELD, Child-Pugh, and Charlson comorbidity index were comparable between the two groups. Rates of mortality, transplant, and hospitalization were also similar during 1 year follow-up. After establishment of the paracentesis clinic, median paracenteses per patient increased from 2 (IQR 1-7) to 4 (IQR 2-11) (P = 0.01); albumin replacement after paracenteses ≥ 5 L improved from 76.3% to 91.7% (P < 0.001); and the fraction of outpatient paracenteses performed in the emergency department decreased from 13.4% to 3.8% (P < 0.001). Major complications remained negligible at 0.81% across both time periods. While fewer patients were admitted for ascites after the paracentesis clinic (39.6% vs. 20.8%, P = 0.009), more patients had acute kidney injury (AKI) during follow-up (47.2% vs. 65.9%, P = 0.02), with a trend towards more AKI admissions (22.6% vs. 35.4%, P = 0.09). CONCLUSION: A dedicated paracentesis clinic can improve access and wait times, while also reducing admissions for ascites and paracenteses performed in the emergency department.Item Does providing routine liver volume assessment add value when performing CT surveillance in cirrhotic patients?(Springer, 2019-07-29) Patel, Milan; Puangsricharoen, Pimpitcha; Arshad, Hafiz Muhammad Sharjeel; Garrison, Sam; Techasatian, Witina; Ghabril, Marwan; Sandrasegaran, Kumar; Liangpunsakul, Suthat; Tann, Mark; Medicine, School of MedicineBackground: The measurement of liver volume (LV) is considered to be an effective prognosticator for postoperative liver failure in patients undergoing hepatectomy. It is unclear whether LV can be used to predict mortality in cirrhotic patients. Methods: We enrolled 584 consecutive cirrhotic patients who underwent computerized topography (CT) of the abdomen for hepatocellular carcinoma surveillance and 50 age, gender, race, and BMI-matched controls without liver disease. Total LV (TLV), functional LV (FLV), and segmental liver volume (in cm3) were measured from CT imaging. Cirrhotic subjects were followed until death, liver transplantation, or study closure date of July 31, 2016. The survival data were assessed with log-rank statistics and independent predictors of survival were performed using Cox hazards model. Results: Cirrhotic subjects had significantly lower TLV, FLV, and segmental (all except for segments 1, 6, 7) volume when compared to controls. Subjects presenting with hepatic encephalopathy had significantly lower TLV and FLV than those without HE (p=0.002). During the median follow up of 1,145 days, 112 (19%) subjects were transplanted and 131 (23%) died. TLV and FLV for those who survived were significantly higher than those who were transplanted or dead (TLV:1740 vs 1529 vs 1486, FLV 1691 vs 1487 vs 1444,p <0.0001). In the Cox regression model, age, MELD score, TLV or FLV were independent predictors of mortality. Conclusion: Baseline liver volume is an independent predictor of mortality in subjects with cirrhosis. Therefore it may be useful to provide these data while performing routine surveillance CT scan as an important added value. Further studies are needed to validate these findings and to better understand their clinical utility.Item A Multidisciplinary Approach to Pancreas Cancer in 2016: A Review(Nature, 2017) Fogel, Evan L.; Shahda, Safi; Sandrasegaran, Kumar; DeWitt, John; Easler, Jeffrey J.; Agarwal, David M.; Eagleson, Mackenzie; Zyromski, Nicholas J.; House, Michael G.; Ellsworth, Susannah; El Hajj, Ihab I.; O'Neil, Bert H.; Nakeeb, Attila; Sherman, Stuart; Medicine, School of MedicineIn this article, we review our multidisciplinary approach for patients with pancreatic cancer. Specifically, we review the epidemiology, diagnosis and staging, biliary drainage techniques, selection of patients for surgery, chemotherapy, radiation therapy, and discuss other palliative interventions. The areas of active research investigation and where our knowledge is limited are emphasized.Item Phase I, Pharmacogenomic, Drug Interaction Study of Sorafenib and Bevacizumab in Combination with Paclitaxel in Patients with Advanced Refractory Solid Tumors(AACR, 2020-10) Chiorean, E. Gabriela; Perkins, Susan M.; Strother, R. Matthew; Younger, Anne; Funke, Jennifer M.; Shahda, Safi G.; Hahn, Noah M.; Sandrasegaran, Kumar; Jones, David R.; Skaar, Todd C.; Schneider, Bryan P.; Sweeney, Christopher J.; Matei, Daniela E.; Medicine, School of MedicineVEGF blockade does not uniformly result in clinical benefit. We evaluated safety, dose-limiting toxicities (DLT), recommended phase II dose (RP2D), antitumor efficacy, and exploratory biomarkers including pharmacogenomics and pharmacokinetics with sorafenib, bevacizumab, and paclitaxel in patients with refractory cancers. The study had a “3 + 3” design, using paclitaxel 80 mg/m2 every week for 3 weeks, in every 4 week cycles, bevacizumab 5 mg/kg every 2 weeks, and sorafenib 200 or 400 mg twice a day, 5 or 7 days/week (5/7, 7/7). The MTD cohort was expanded. Twenty-seven patients enrolled in 3 cohorts: sorafenib 200 mg twice a day 5/7, 200 mg twice a day 7/7, and 400 mg twice a day 5/7. DLTs were grade 3 neutropenia >7 days (cohort 1, 1), grade 3 hypertension (cohort 2, 1), grade 3 hand–foot skin reaction (HFSR; cohort 3, 2). MTD was sorafenib 200 mg twice a day 7/7. Six DLTs occurred in cohort 2 expansion: grade 3 HFSR (2), grade 2 HFSR with sorafenib delay >7 days (2), grade 4 cerebrovascular accident (1), grade 3 neutropenia >7 days (1). RP2D was sorafenib 200 mg twice a day 5/7. Most patients (62%) dose reduced sorafenib to 200 mg daily 5/7 after a median 3 (range, 2–17) cycles. Response rates were 48% overall (27) and 64% for ovarian cancers (14). VEGF-A-1154AA and -7TT recessive homozygous genotypes conferred worse overall survival versus alternative genotypes (7 vs. 22 months). Intermittent, low-dose sorafenib (200 mg twice a day 5/7) combined with bevacizumab and paclitaxel was tolerable and had high antitumor efficacy in patients with refractory cancer (NCT00572078).Item Secretin-Enhanced MRCP: How and Why—AJR Expert Panel Narrative Review(American Roentgen Ray Society, 2021-05) Swensson, Jordan; Zaheer, Atif; Conwell, Darwin; Sandrasegaran, Kumar; Manfredi, Riccardo; Tirkes, Temel; Radiology and Imaging Sciences, School of MedicineSecretin-enhanced MRCP (S-MRCP) has advantages over standard MRCP for imaging of the pancreaticobiliary tree. Through the use of secretin to induce fluid production from the pancreas and leveraging of fluid-sensitive MRCP sequences, S-MRCP facilitates visualization of ductal anatomy, and the findings provide insight into pancreatic function, allowing radiologists to provide additional insight into a range of pancreatic conditions. This narrative review provides detailed information on the practical implementation of S-MRCP, including patient preparation, logistics of secretin administration, and dynamic secretin-enhanced MRCP acquisition. Also discussed are radiologists' interpretation and reporting of S-MRCP examinations, including assessments of dynamic compliance of the main pancreatic duct and of duodenal fluid volume. Established indications for S-MRCP include pancreas divisum, anomalous pancreaticobiliary junction, Santorinicele, Wirsungocele, chronic pancreatitis, main pancreatic duct stenosis, and assessment of complex postoperative anatomy. Equivocal or controversial indications are also described along with an approach to such indications. These indications include acute and recurrent acute pancreatitis, pancreatic exocrine function, sphincter of Oddi dysfunction, and pancreatic neoplasms.Item Technical advancements and protocol optimization of diffusion-weighted imaging (DWI) in liver(Springer, 2016-01) Ni, Ping; Lin, Yuning; Zhong, Qun; Chen, Ziqian; Sandrasegaran, Kumar; Lin, Chen; Department of Radiology and Imaging Sciences, IU School of MedicineAn area of rapid advancement in abdominal MRI is diffusion-weighted imaging (DWI). By measuring diffusion properties of water molecules, DWI is capable of non-invasively probing tissue properties and physiology at cellular and macromolecular level. The integration of DWI as part of abdominal MRI exam allows better lesion characterization and therefore more accurate initial diagnosis and treatment monitoring. One of the most technical challenging, but also most useful abdominal DWI applications is in liver and therefore requires special attention and careful optimization. In this article, the latest technical developments of DWI and its liver applications are reviewed with the explanations of the technical principles, recommendations of the imaging parameters, and examples of clinical applications. More advanced DWI techniques, including Intra-Voxel Incoherent Motion (IVIM) diffusion imaging, anomalous diffusion imaging, and Diffusion Kurtosis Imaging (DKI) are discussed.Item The Value of Secretin-Enhanced MRCP in Patients With Recurrent Acute Pancreatitis(American Roentgen Ray Society(ARRS), 2017-02) Sandrasegaran, Kumar; Tahir, Bilal; Barad, Udaykamal; Fogel, Evan; Akisik, Fatih; Tirkes, Temel; Sherman, Stuart; Radiology and Imaging Sciences, School of MedicineOBJECTIVE The purpose of this study is to assess the additional value of secretin-enhanced MRCP over conventional (non–secretin-enhanced) MRCP in diagnosing disease in patients with recurrent acute pancreatitis. MATERIALS AND METHODS A retrospective review of a radiology database found 72 patients with recurrent acute pancreatitis who had secretin-enhanced MRCP and ERCP correlation within 3 months of each other between January 2007 and December 2011. Of these patients, 54 had no history of pancreatic tumor or surgery and underwent MRI more than 3 months after an episode of acute pancreatitis. In addition, 57 age- and sex-matched control subjects with secretin-enhanced MRCP and ERCP correlation and without a diagnosis of recurrent acute pancreatitis or chronic pancreatitis were enrolled as the control group. All studies were anonymized, and secretin-enhanced MRCP images (image set A) were separated from conventional 2D and 3D MRCP and T2-weighted images (image set B). Image sets A and B for each patient were assigned different and randomized case numbers. Two blinded reviewers independently assessed both image sets for ductal abnormalities and group A image sets for exocrine response to secretin. RESULTS There were statistically significantly more patients with recurrent acute pancreatitis with reduced exocrine function compared with patients in the control group (32% vs 9%; p < 0.01) on secretin-enhanced images. Patients with recurrent acute pancreatitis were more likely to have side branch dilation (p = 0.02; odds ratio, 3.6), but not divisum, compared with the control group. Secretin-enhanced images were superior to non–secretin-enhanced images for detecting ductal abnormalities in patients with recurrent acute pancreatitis, with higher sensitivity (76% vs 56%; p = 0.01) and AUC values (0.983 vs 0.760; p < 0.01). CONCLUSION Up to one-third of patients with recurrent acute pancreatitis showed exocrine functional abnormalities. Secretin-enhanced MRCP had a significantly higher yield for ductal abnormalities than did conventional MRI and should be part of the MRCP protocol for investigation of patients with recurrent acute pancreatitis.