Ed Wang

Publications of Ed Wang

• Clinical and plasma proteomic markers correlating with chronic kidney disease after liver transplantation.

  Authors: J Levitsky, D R Salomon, M Abecassis, P Langfelder, S Horvath, J Friedewald, E Wang, S M Kurian, T Mondala, S Gil, R McDade, K Ballard, L Gallon

  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 07/2011; 11(9):1972-8.

  Chronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristicsChronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristics and biomarkers diagnostic of CKD to enable early diagnosis allowing preemptive interventions, as well as mechanistic insights into the progression from kidney injury to irreversible kidney failure. We analyzed 342 patients who had baseline glomerular filteration rate (GFR) >60 at the time of LT and are now >3 years post-LT. Risk factors for post-LT CKD were compared between three different groups defined by current GFR: >90 (n = 40), 60-90 (n = 146) and <60 (n = 156) mL/min. Age, cyclosporine use and pre-LT GFR were independently associated with new onset CKD. A subset (n = 64) without viral/immune disease or graft dysfunction underwent multianalyte plasma proteomic evaluations for correlation with CKD. Plasma proteomic analysis of two independent cohorts, test (n = 22) and validation (n = 42), identified 10 proteins highly associated with new onset CKD. In conclusion, we have identified clinical characteristics and a unique plasma proteomic signature correlating with new onset CKD after LT. These preliminary results are currently being validated in a prospective, multicenter study to determine if this signature precedes the onset of CKD and resolves with early interventions aimed at preserving kidney function.

• Role of the EASL, RECIST, and WHO response guidelines alone or in combination for hepatocellular carcinoma: radiologic-pathologic correlation.

  Authors: Ahsun Riaz, Khairuddin Memon, Frank H Miller, Paul Nikolaidis, Laura M Kulik, Robert J Lewandowski, Robert K Ryu, Kent T Sato, Vanessa L Gates, Mary F Mulcahy, Talia Baker, Ed Wang, Ramona Gupta, Ritu Nayar, Al B Benson, Michael Abecassis, Reed Omary, Riad Salem

  Journal of hepatology. 10/2010; 54(4):695-704.

  We sought to study receiver-operating characteristics (ROC) of the European Association for the Study of the Liver (EASL), Response Evaluation Criteria in Solid Tumors (RECIST), and World HealthWe sought to study receiver-operating characteristics (ROC) of the European Association for the Study of the Liver (EASL), Response Evaluation Criteria in Solid Tumors (RECIST), and World Health Organization (WHO) guidelines for assessing response following locoregional therapies individually and in various combinations. Eighty-one patients with hepatocellular carcinoma underwent liver explantation following locoregional therapies. Response was assessed using EASL, RECIST, and WHO. Kappa statistics were used to determine inter-method agreement. Uni/multivariate logistic regression analyses were performed to determine the variables predicting complete pathologic necrosis. Numerical values were assigned to the response classes: complete response=0, partial response=1, stable disease=2, and progressive disease=3. Various mathematical combinations of EASL and WHO were tested to calculate scores and their ROCs were studied using pathological examination of the explant as the gold standard. Median times (95% CI) to the WHO, RECIST, and EASL responses were 5.3 (4-11.5), 5.6 (4-11.5), and 1.3months (1.2-1.5), respectively. Kappa coefficients for WHO/RECIST, WHO/EASL, and RECIST/EASL were 0.78, 0.28, and 0.31, respectively. EASL response demonstrated significant odds ratios for predicting complete pathologic necrosis on uni/multivariate analyses. Calculated areas under the ROC curves were: RECIST: 0.63, WHO: 0.68, EASL: 0.82, EASL+WHO: 0.82, EASL×WHO: 0.85, EASL+(2×WHO): 0.79 and (2×EASL)+WHO: 0.85. An EASL×WHO Score of ⩽1 had 90.2% sensitivity for predicting complete pathologic necrosis. The product of WHO and EASL demonstrated better ROC than the individual guidelines for assessment of tumor response. EASL×WHO scoring system provides a simple and clinically applicable method of response assessment following locoregional therapies for hepatocellular carcinoma.

• Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma.

  Authors: Ahsun Riaz, Frank H Miller, Laura M Kulik, Paul Nikolaidis, Vahid Yaghmai, Robert J Lewandowski, Mary F Mulcahy, Robert K Ryu, Kent T Sato, Ramona Gupta, Ed Wang, Talia Baker, Michael Abecassis, Al B Benson, Albert A Nemcek, Reed Omary, Riad Salem

  JAMA : the journal of the American Medical Association. 03/2010; 303(11):1062-9.

  Response Evaluation Criteria in Solid Tumors (RECIST) (unidimensional), World Health Organization (WHO) (bidimensional), and European Association for Study of the Liver (EASL) (necrosis) guidelinesResponse Evaluation Criteria in Solid Tumors (RECIST) (unidimensional), World Health Organization (WHO) (bidimensional), and European Association for Study of the Liver (EASL) (necrosis) guidelines are commonly used to assess response following therapy for hepatocellular carcinoma (HCC). No universally accepted standard exists. To evaluate intermethod agreement between these 3 imaging guidelines and to introduce the concept of the "primary index lesion" as a biomarker for response. Single-center comprehensive imaging analysis including 245 consecutive patients with HCC who were treated with chemoembolization or radioembolization between January 2000 and December 2008. Computed tomography and magnetic resonance imaging scans (N = 1065) were reviewed to assess response in the "primary index lesion," defined as the largest tumor targeted during first treatment. Intermethod agreement (kappa statistics) between RECIST, WHO, and EASL guidelines response; correlation of WHO and EASL response in the primary index lesion with time to progression and survival. Kappa coefficients were 0.86 (95% confidence interval [CI], 0.80-0.92) between the WHO and RECIST guidelines, 0.24 (95% CI, 0.16-0.33) between RECIST and EASL, and 0.28 (95% CI, 0.19-0.36) between WHO and EASL. Disease progressed in 96 patients; 113 died. The hazard ratio for time to progression in responders compared with nonresponders was 0.36 (95% CI, 0.23-0.57) for WHO, 0.38 (95% CI, 0.24-0.58) for RECIST, and 0.38 (95% CI, 0.22-0.64) for EASL. Hazard ratios for survival in responders compared with nonresponders in univariate and multivariate analyses were 0.46 (95% CI, 0.32-0.67) and 0.55 (95% CI, 0.35-0.84) for WHO and 0.36 (95% CI, 0.22-0.57) and 0.54 (95% CI, 0.34-0.85) for EASL. Hazard ratios for survival in responders vs nonresponders in patients with solitary and multifocal HCC were 0.39 (95% CI, 0.19-0.77) and 0.51 (95% CI, 0.32-0.82) for WHO and 0.26 (95% CI, 0.10-0.67) and 0.47 (95% CI, 0.28-0.79) for EASL. Among a group of patients with HCC, agreement for classification of therapeutic response was high between the RECIST and WHO guidelines but low between each of these and EASL. Application of these methods to measure response in a primary index lesion resulted in statistically significant correlations with disease progression and survival.

• Radiologic-Pathologic Correlation of Hepatocellular Carcinoma Treated with Chemoembolization.

  Authors: Ahsun Riaz, Robert Lewandowski, Laura Kulik, Robert Ryu, Mary Mulcahy, Talia Baker, Vanessa Gates, Ritu Nayar, Ed Wang, Frank Miller, Kent Sato, Reed Omary, Michael Abecassis, Riad Salem

  Cardiovascular and interventional radiology. 12/2009;

  To correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients withTo correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients with postchemoembolization follow-up imaging underwent liver transplantation/resection. Pre- and posttreatment contrast-enhanced magnetic resonance imaging were used to evaluate radiologic findings. Imaging characteristics using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria after treatment were evaluated. Treated lesions were examined by pathology (gold standard) for the assessment of necrosis. Radiologic findings on magnetic resonance imaging were correlated to pathologic findings to assess the predictability by imaging of actual necrosis. Kappa (kappa) statistics were used to determine intermethod agreement between WHO and EASL criteria. Fourteen (40%) of 35 lesions had biopsy-proven hepatocellular carcinoma. Thirteen (37%) of 35 target lesions showed complete pathologic necrosis. Complete pathologic necrosis was seen in 35% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 1 (100%) of 1, 6 (67%) of 9, 6 (33%) of 18, and 0 (0%) of 7 of the lesions that exhibited complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by WHO criteria, respectively. Complete pathologic necrosis was seen in 9 (82%) of 11, 4 (36%) of 11, 0 (0%) of 8, and 0 (0%) of 5 of the lesions that showed CR, PR, SD, or PD by EASL criteria, respectively. EASL CR and WHO response were shown to have >/=85% specificity for predicting complete pathologic necrosis. The kappa coefficient for agreement between WHO and EASL was 0.29. EASL and WHO criteria had minimal intermethod agreement. EASL CR and WHO response were able to predict pathologic necrosis.

• Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes.

  Authors: Riad Salem, Robert J Lewandowski, Mary F Mulcahy, Ahsun Riaz, Robert K Ryu, Saad Ibrahim, Bassel Atassi, Talia Baker, Vanessa Gates, Frank H Miller, Kent T Sato, Ed Wang, Ramona Gupta, Al B Benson, Steven B Newman, Reed A Omary, Michael Abecassis, Laura Kulik

  Gastroenterology. 09/2009;

  PURPOSE:: Hepatocellular carcinoma (HCC) has limited treatment options; long-term outcomes following intra-arterial radiation are unknown. We assessed clinical outcomes of patients treated withPURPOSE:: Hepatocellular carcinoma (HCC) has limited treatment options; long-term outcomes following intra-arterial radiation are unknown. We assessed clinical outcomes of patients treated with intra-arterial Yttrium-90 microspheres (Y90). METHODS:: Patients with HCC (n=291) were treated with Y90 as part of a single-center prospective longitudinal cohort study. Toxicities were recorded using the Common Terminology Criteria version 3.0. Response rate and time-to-progression (TTP) were determined using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines. Survival by stage was assessed. Uni/multivariate analyses were performed. RESULTS:: Five hundred twenty-six treatments were administered (mean: 1.8, range: 1-5). Toxicities included fatigue (57%), pain (23%), and nausea/vomiting (20%); 19% exhibited grade 3/4 bilirubin toxicity. The 30-day mortality rate was 3%. Response rates were 42% and 57% based on WHO and EASL criteria, respectively. The overall TTP was 7.9 mo (95% confidence interval [CI]:6-10.3). Survival times differed between Child-Pugh A and B patients (A:17.2 mo, B:7.7 mo, P=0.002). Child-Pugh B patients with portal vein thrombosis (PVT) survived 5.6 mo (95% CI:4.5-6.7). Baseline age; sex; performance status; presence of portal hypertension; tumor distribution; levels of bilirubin, albumin, and alpha-fetoprotein; and WHO/EASL response rate predicted survival. CONCLUSION:: Child-Pugh A patients, with or without PVT, benefited most from treatment. Child-Pugh B patients with PVT had poor outcomes. TTP and overall survival varied by patient stage at baseline. These data can be used to design future Y90 trials and to describe Y90 as a potential treatment option to patients with HCC.

• Radioembolization for Hepatocellular Carcinoma Using Yttrium-90 Microspheres: A Comprehensive Report of Long-term Outcomes

  Authors: Riad Salem, Robert J. Lewandowski, Mary F. Mulcahy, Ahsun Riaz, Robert K. Ryu, Saad Ibrahim, Bassel Atassi, Talia Baker, Vanessa Gates, Frank H. Miller, Kent T. Sato, Ed Wang, Ramona Gupta, Al B. Benson, Steven B. Newman, Reed A. Omary, Michael Abecassis, Laura Kulik

  Gastroenterology.

  Background & AimsHepatocellular carcinoma (HCC) has limited treatment options; long-term outcomes following intra-arterial radiation are unknown. We assessed clinical outcomes of patients treatedBackground & AimsHepatocellular carcinoma (HCC) has limited treatment options; long-term outcomes following intra-arterial radiation are unknown. We assessed clinical outcomes of patients treated with intra-arterial yttrium-90 microspheres (Y90).MethodsPatients with HCC (n = 291) were treated with Y90 as part of a single-center, prospective, longitudinal cohort study. Toxicities were recorded using the Common Terminology Criteria version 3.0. Response rate and time to progression (TTP) were determined using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines. Survival by stage was assessed. Univariate/multivariate analyses were performed.ResultsA total of 526 treatments were administered (mean, 1.8; range, 1–5). Toxicities included fatigue (57%), pain (23%), and nausea/vomiting (20%); 19% exhibited grade 3/4 bilirubin toxicity. The 30-day mortality rate was 3%. Response rates were 42% and 57% based on WHO and EASL criteria, respectively. The overall TTP was 7.9 months (95% confidence interval, 6–10.3). Survival times differed between patients with Child–Pugh A and B disease (A, 17.2 months; B, 7.7 months; P = .002). Patients with Child–Pugh B disease who had portal vein thrombosis (PVT) survived 5.6 months (95% confidence interval, 4.5–6.7). Baseline age; sex; performance status; presence of portal hypertension; tumor distribution; levels of bilirubin, albumin, and α-fetoprotein; and WHO/EASL response rate predicted survival.ConclusionsPatients with Child–Pugh A disease, with or without PVT, benefited most from treatment. Patients with Child–Pugh B disease who had PVT had poor outcomes. TTP and overall survival varied by patient stage at baseline. These data can be used to design future Y90 trials and to describe Y90 as a potential treatment option for patients with HCC.