David S. Chung

Acute liver injury induced by weight-loss herbal supplements

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.

Fluorescence in situ hybridization and K-ras analyses improve diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses.

Objectives: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is the main diagnostic modality for pancreatic mass lesions. However, cytology is often indeterminate, leading to repeat FNAs and delay in care. Here, we evaluate whether combining routine cytology with fluorescence in situ hybridization (FISH) and K-ras/p53 analyses improves diagnostic yield of pancreatic EUS-FNA. Methods: Fifty EUS-FNAs of pancreatic masses in 46 patients were retrospectively analyzed. Mean follow-up was 68 months. Thirteen initial cytologic samples (26%) were benign, 23 malignant (46%), and 14 atypical (28%). We performed FISH for p16, p53, LPL, c-Myc, MALT1, topoisomerase 2/human epidermal growth factor receptor 2, and EGFR, as well as K-ras/p53 mutational analyses. Results: On final diagnosis, 11 (79%) of atypical FNAs were malignant, and 3 benign (21%). Fluorescence in situ hybridization was negative in all benign and all atypical samples with final benign diagnosis. Fluorescence in situ hybridization plus K-ras analysis correctly identified 60% of atypical FNAs with final malignant diagnosis. Combination of routine cytology with positive FISH and K-ras analyses yielded 87.9% sensitivity, 93.8% specificity, 96.7% positive predictive value, 78.9% negative predictive value, and 89.8% accuracy. Conclusions: Combining routine cytology with FISH and K-ras analyses improves diagnostic yield of EUS-FNA of solid pancreatic masses. We propose to include these ancillary tests in the workup of atypical cytology from pancreatic EUS-FNA.Abbreviations: EUS - endoscopic ultrasound, FNA - fine-needle aspiration, FISH - fluorescence in situ hybridization, EGFR - epidermal growth factor receptor, HER2 - human epidermal growth factor receptor 2, TOP2 - topoisomerase 2

Hypervitaminosis A Inducing Intra-hepatic Cholestasis—A Rare Case Report

The use of over-the-counter supplements is commonplace in todays health conscious society. We present an unusual case of intrahepatic cholestasis caused by vitamin A intoxication. The patient consumed one Herbalife shake with two multivitamin tablets of the same brand for 12 years. When calculated this equated to more than the recommended daily allowance for vitamin A consumption. Deranged liver function tests were consistent with a cholestatic process. Liver biopsy was obtained and revealed features pathognomonic of vitamin A toxicity, without the usual fibrosis. When the supplements were ceased, his jaundice and alkaline phosphatase completely normalized. This case highlights the importance of health care providers documenting non-prescribed dietary supplements and considering them in the etiology of cholestatic liver disease.

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

AIM To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose pancreatic malignancy. METHODS Patients who underwent EUS-FNA were retrospectively identified. Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA) and CA19-9. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated in order to evaluate the performance of each test to detect malignancy. RESULTS Sixty-one specimens had complete sets of stains, yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis, respectively. Cytology alone had sensitivity and specificity of 41% and 100% to detect malignancy, respectively. In 46% of the specimens, routine cytology alone was deemed indeterminate. The addition of either p53 or Ki-67 increased the sensitivity to 51% and 53%, respectively, with perfect specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination increased the sensitivity to 57%. While additional staining with CEA and CA19-9 further increased the sensitivity to 86%, the specificity, PPV and PLR were significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27 and 0.70). CONCLUSION Immunohistochemical staining for p53 and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.

The Utility of Immunohistochemical Staining with CEA, CA19-9, P53, and MIB to Improve the Diagnostic Yield of Endoscopic Ultrasonography Guided Fine Needle Pancreatic Aspirates

The Utility of Immunohistochemical Staining with CEA, CA19-9, P53, and MIB to Improve the Diagnostic Yield of Endoscopic Ultrasonography Guided Fine Needle Pancreatic Aspirates Alia Dadabhai, Stephen L. Chen, Steve Tsai, Rose Venegas, Samuel French, Sartaj Arora, Mehrdad Vasdoghi, Ben Garrett, David Chung, Shahid H. Sial, Viktor Eysselein In a study of 100 specimens obtained by EUS-FNA, P53, MIB, CA19-9 and CEA were used in an analysis of 71 samples to determine if tumor markers increased the diagnostic yield of cytologically atypical or benign samples. A prospective analysis was performed of all patients undergoing EUS-FNA of pancreatic lesions. Methods: Four antibodies were used for immunohistochemical labeling: p53 (DO-7)Zymed and MIB (Ki-67)Zymed, CEA (monoclonal ab) – Zymed and CA19-9. Cytology smears and cell blocks were reviewed by two cytopathologists who were blinded to the tumor markers and the final diagnoses. The specimens were categorized as tumor marker positive if there was O 5% nuclear staining by MIB ab, and if there was positive labeling for p53, CEA and CA19-9 in one or more cells. Follow-up data for each patient was determined by surgical pathology or clinical follow-up. Results: In 100 consecutive pancreatic EUS-FNAs, an adequate amount of aspirate was obtained for cytology smear in 89% (89/100) of patients, and for immunohistochemical labeling in 71% (71/100) of specimens. The cytology smears showed 24 benign lesions, 23 malignant lesions, 24 with atypical cells, with 11 hypocellular aspirates. Of the adequate cytology smears were 34% (24/71) were atypical. 58% of the atypical aspirates (14/24), 29% (7/24) of the benign aspirates, and 100% of the malignant smears, were malignant on clinical or surgical follow-up. Combined tumor markers and cytology increased the sensitivity of aspirates to 89% and increased the number of patients detected with malignant disease from 23 to 39 out of the total 44 patients with cancer. Sensitivity of cytologic diagnosis alone was 52%. This sensitivity increased to 89% when combined tumor markers were used. The specificities of the individual tumor markers ranged from 80-100%. Conclusions: The addition of immunohistochemical labeling with p53, MIB, CEA and CA19-9 to cytology enhances the diagnostic yield and sensitivity for finding pancreatic malignancy by EUS-FNA by 31%. Immunohistochemical labeling may be useful to detect well-differentiated tumors when diagnosis by cytology is nonconclusive or benign and may reduce the need for repeat EUS-FNA.

Time-of-day effect and the yield of endoscopic ultrasound fine needle aspiration.

Background and Objectives: The timing of the endoscopic procedures has been recently proposed to be a factor in the quality of colonoscopic polyp detection. We aimed to investigate whether the time-of-day has an effect on the diagnostic yield and specimen adequacy of endoscopic ultrasound fine needle aspiration (EUS-FNA). Materials and Methods: The retrospective study was set in a safety net community hospital. The 212 EUS-FNAs performed at our institution between July 2011 and January 2014 were retrospectively analyzed. Pancreatic masses, pancreatic cysts, and lymphadenopathy were most common indications for EUS-FNAs. Data were collected with regard to the timing of the procedure, presence of on-site cytopathologic evaluation, the number of needle passes, diagnosis, and specimen adequacy for cytopathologic evaluation. Statistical analysis was performed using unpaired two-tailed Students t-test. Results: There was no difference in the diagnostic yield for malignancy across all indications between the AM and PM groups. In the morning group 31/87 (36%) procedures and in the afternoon group 50/125 (40%) procedures were diagnostic for malignancy (P = 0.522). There was no difference in the specimen adequacy for cytopathologic evaluation across all indications between the AM and PM groups. In the morning group, 58/87 (67%) procedures and in the afternoon group 90/125 (72%) procedures were adequate for cytopathologic evaluation (P = 0.408). On-site cytopathologist was more available for AM than PM procedures; however, the lack of AM vs. PM difference in the yield and specimen adequacy persisted regardless of on-site cytopathologist presence. Conclusions: Time-of-day of the procedure (morning vs. afternoon) does not affect EUS-FNA diagnostic yield for malignancy or specimen adequacy for cytopathologic evaluation.