Joo Ha Hwang, MD, PhD

All Publications

• Current Status of EUS in Gastrointestinal Subepithelial Tumors. Clinical endoscopy Kim, S. G., Song, J. H., Hwang, J. H. 2019

  Abstract

  Gastrointestinal subepithelial tumors (GSTs) are usually detected incidentally on endoscopic or radiologic examinations. In conventional endoscopy, a GST usually presents as a protuberant lesion with an intact mucosal surface. As the lesion is located beneath the mucosal layer of the gastrointestinal tract, conventional biopsy typically does not reveal the pathologic diagnosis. First, a GST should be differentiated from an extrinsic compression through the positional change of the patient during conventional endoscopic examination. In cases of GSTs originating from the gastrointestinal wall, endoscopic ultrasonography (EUS) can be beneficial for narrowing the differential diagnosis through delineation of echo findings and by determining the layer of origin. EUS findings can also help determine the management strategies for GSTs by making a differential diagnosis according to malignant potential.

  View details for DOI 10.5946/ce.2019.024

  View details for PubMedID 31286747

• Gastric per-oral endoscopic myotomy: Current status and future directions WORLD JOURNAL OF GASTROENTEROLOGY Podboy, A., Hwang, J., Nguyen, L. A., Garcia, P., Zikos, T. A., Kamal, A., Triadafilopoulos, G., Clarke, J. O. 2019; 25 (21): 2581–90

  View details for DOI 10.3748/wjg.v25.i21.2581

  View details for Web of Science ID 000470246400004

• ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GASTRIC NEOPLASIA: A LARGE MULTICENTER STUDY FROM NORTH AMERICA Ngamruengphong, S., Ferri, L. E., Aihara, H., Draganov, P. V., Yang, D., Perbtani, Y. B., Hanada, Y., Song, L., Kumta, N. A., Othman, M. O., Mercado, M. O., Javaid, H., Aadam, A., Siegel, A. B., James, T. W., Grimm, I. S., DeWitt, J. M., Novikov, A. A., Schlachterman, A., Kowalski, T. E., Samarasena, J. B., Hashimoto, R., Chehade, N. E., Lee, J., Chang, K. J., Su, B., Chen, A., Chen, M., Chen, Y., Ujiki, M., Mehta, A., Sharaiha, R. Z., Carr-Locke, D. L., Kumbhari, V., Khashab, M. A., Khoshknab, M., Wang, R., Kerdsirichairat, T., Tomizawa, Y., von Renteln, D., Bechara, R., Patel, N. J., Fukami, N., Lazkowska, M., Sethi, A., Wang, A. Y., Hwang, J., Friedland, S., Kalloo, A. N. MOSBY-ELSEVIER. 2019: AB102–AB103

  View details for Web of Science ID 000470094900099

• PER-ORAL ENDOSCOPIC MYOTOMY HAS SIMILAR EFFICACY COMPARED TO LAPAROSCOPIC HELLER MYOTOMY AFTER 4 YEARS: A SINGLE CENTER EXPERIENCE Podboy, A. J., Hwang, J., Rivas, H., Azagury, D., Hawn, M. T., Kamal, A., Triadafilopoulos, G., Zikos, T., Clarke, J. O. MOSBY-ELSEVIER. 2019: AB201–AB202

  View details for Web of Science ID 000470094901010

• OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION VERSUS SURGERY IN EARLY GASTRIC CANCER MEETING STANDARD AND EXPANDED INDICATIONS: A MULTICENTER NORTH AMERICAN COHORT Kerdsirichairat, T., Wang, R., Aihara, H., Draganov, P. V., Kumta, N. A., Tomizawa, Y., Truong, C. D., Lo, S. K., Jamil, L. H., Gaddam, S., Burch, M., Dhall, D., Perbtani, Y. B., Yang, D., Bartel, M. J., Goel, N., Reddy, S. S., Farma, J. M., Gong, Y., Ferri, L. E., Chen, A., Chen, M., Chen, Y., Sethi, A., Ansari, N., Trapp, G., Schrope, B., Del Portillo, A., DeLatour, R., Park, K. H., Khanna, L. G., Melis, M., Newman, E., Hatzaras, I., James, T. W., Grimm, I. S., DeWitt, J. M., Siegel, A. B., Aadam, A., Wang, A. Y., Bechara, R., Abe, S., Song, L., Gutierrez, O., Montgomery, E., Johnston, F. M., Duncan, M. D., Canto, M. I., Lennon, A., Hanada, Y., Hwang, J., Friedland, S., Ngamruengphong, S. MOSBY-ELSEVIER. 2019: AB350–AB351

  View details for Web of Science ID 000470094901340

• PROPHYLACTIC ENDOSCOPIC CLOSURE DOES NOT REDUCE ADVERSE EVENTS FOLLOWING ENDOSCOPIC SUBMUCOSAL DISSECTION: A CASE-MATCHED MULTICENTER STUDY Mehta, A., Ngamruengphong, S., Hajifathalian, K., Shah, S. L., Dawod, E., Ferri, L. E., Aihara, H., Song, L., Hanada, Y., Kumta, N. A., Aadam, A., Siegel, A. B., James, T. W., Grimm, I. S., Novikov, A. A., Kumbhari, V., Tomizawa, Y., von Renteln, D., Bechara, R., Hwang, J., Friedland, S., Kalloo, A. N., Nieto, J., Othman, M. O., Sampath, K., Mahadev, S., Mukewar, S., Carr-Locke, D. L., Khashab, M. A., Sharaiha, R. Z. MOSBY-ELSEVIER. 2019: AB97

  View details for Web of Science ID 000470094900090

• A Chance to Cut Is a Chance to Cure: Endoscopic Submucosal Dissection for Early Gastric Cancer DIGESTIVE DISEASES AND SCIENCES Huang, R. J., Charville, G. W., Hwang, J., Friedland, S. 2019; 64 (5): 1129–32

  View details for DOI 10.1007/s10620-018-5317-8

  View details for Web of Science ID 000466886100013

• How to decrease the risk of perforation in endoscopic submucosal dissection (ESD) TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY Kim, S., Hwang, J. 2019; 21 (2): 99–103

  View details for DOI 10.1016/j.tgie.2019.05.001

  View details for Web of Science ID 000471019800007

• Gastric per-oral endoscopic myotomy: Current status and future directions. World journal of gastroenterology Podboy, A., Hwang, J. H., Nguyen, L. A., Garcia, P., Zikos, T. A., Kamal, A., Triadafilopoulos, G., Clarke, J. O. 2019; 25 (21): 2581–90

  Abstract

  Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.

  View details for DOI 10.3748/wjg.v25.i21.2581

  View details for PubMedID 31210711

  View details for PubMedCentralID PMC6558440

• Boiling Histotripsy Ablation of Renal Cell Carcinoma in the Eker Rat Promotes a Systemic Inflammatory Response. Ultrasound in medicine & biology Schade, G. R., Wang, Y. N., D'Andrea, S., Hwang, J. H., Liles, W. C., Khokhlova, T. D. 2019; 45 (1): 137–47

  Abstract

  Boiling histotripsy (BH) is an experimental focused ultrasound technique that produces non-thermal mechanical ablation. We evaluated the feasibility, short-term histologic effects and the resulting acute inflammatory response to BH ablation of renal cell carcinoma (RCC) in the Eker rat. Genotyped Eker rats were monitored for de novo RCCs with serial ultrasound (US) imaging. When tumors were ≥8 mm, rats underwent ultrasound-guided extracorporeal ablation of the tumor with BH, a pulsed focused US technique that produces non-thermal mechanical ablation of targeted tissues, or a sham US procedure. Treatments targeted approximately 50% of the largest RCC with a margin of normal kidney. BH treated rats were euthanized at 1 (n = 4) or 48 (n = 4) h, and sham patients (n = 4) at 48 h. Circulating plasma cytokine levels were assessed with multiplex assays before and at 0.25, 1, 4, 24 and 48 h following treatment. Kidneys were collected and processed for histologic assessment, immunohistochemistry and intrarenal cytokine concentration measurements. For statistical analysis Student's t-test was used. US-guided BH treatment was successful in all animals, producing hypoechoic regions within the targeted volume consistent with BH treatment effect. Grossly, regions of homogenized tissue were apparent with evidence of focal intra-parenchymal hemorrhage. Histologically, BH produced a sharply demarcated region of homogenized tumor and non-tumor tissue containing acellular debris. BH treatment was associated with significantly increased relative concentration of plasma TNF versus sham treatment (p < 0.05) and transient elevations in high-mobility group box 1 (HMGB1), IL-10 and IL-6 consistent with acute inflammatory response to trauma. Intrarenal cytokine concentrations followed the same trend. At 48 h, enhanced infiltration of CD8+ T cells was observed by immunohistochemistry in both the treated and un-treated contralateral RCC/kidneys in BH-treated animals versus sham treatment. BH treatment was well tolerated with transient gross hematuria and a perinephric hematoma developing in one subject each. The study demonstrates the feasibility of BH ablation of de novo RCC and suggests activation of the acute inflammatory cascade following treatment that appears to stimulate CD8+ T cell infiltration of both treated and untreated tumors. Longer duration chronic studies are ongoing to characterize the longevity and robustness of this response.

  View details for DOI 10.1016/j.ultrasmedbio.2018.09.006

  View details for PubMedID 30340920

• GIE Editorial Board top 10 topics: advances in GI endoscopy in 2018. Gastrointestinal endoscopy Cohen, J., Desilets, D. J., Hwang, J. H., Kyanam Kabir Baig, K. R., Leung, F. W., Maranki, J. L., Okolo, P. I., Swanstrom, L. L., Chak, A. 2019

  Abstract

  The ASGE's GIE Editorial Board reviewed original endoscopy-related articles published during 2018 in GIE and 10 other leading medical and gastroenterology journals. Votes from each individual member were tallied to identify a consensus list of 10 topic areas of major advances in gastrointestinal endoscopy. Individual board members summarized important findings published in these 10 areas of adenoma detection, bariatric endoscopy, endoscopic mucosal resection (EMR)/submucosal dissection (ESD)/full thickness resection (EFTR), artificial intelligence, expandable metal stents for palliation of biliary obstruction, pancreatic therapy with lumen apposing metal stents, endoscope reprocessing, Barrett's esophagus, interventional EUS, and gastrointestinal bleeding. This document summarizes these "Top 10" endoscopic advances of 2018.

  View details for DOI 10.1016/j.gie.2019.03.020

  View details for PubMedID 30928425

• Routine gastric biopsies: Should we be doing more? Gastrointestinal endoscopy Huang, R. J., Hwang, J. H. 2019; 89 (6): 1150–51

  View details for DOI 10.1016/j.gie.2019.02.010

  View details for PubMedID 31104747

• Efficacy of a novel endoscopically deliverable muco-adhesive hemostatic powder in an acute gastric bleeding porcine model. PloS one Bang, B., Lee, E., Maeng, J., Kim, K., Hwang, J. H., Hyon, S. H., Hyon, W., Lee, D. H. 2019; 14 (6): e0216829

  Abstract

  This study investigated the effectiveness of new hemostatic adhesive powder (UI-EWD) in a swine mode of acute gastric bleeding. Gastric ulcer bleeding was induced endoscopically at two locations in each of eight heparinized mini-pigs. UI-EWD and saline were sprayed endoscopically in the experimental (n = 5) and control groups (n = 3), respectively. The hemostatic effect and hydrogel persistence on ulcers were periodically evaluated endoscopically. Initial hemostasis was achieved successfully in all lesions in the experimental group. Follow-up endoscopy showed minor delayed bleeding in 10% at 6 hours in the experimental group, whereas re-bleeding was observed in 50% at 6 hours in the control group. UI-EWD gel persisted at 90%, 80%, and 50% of ulcer bases at 6, 18, and 42 hours post-application, respectively. This study suggests that muco-adhesive UI-EWD may be effective in the endoscopic treatment of active ulcer bleeding.

  View details for DOI 10.1371/journal.pone.0216829

  View details for PubMedID 31185029

• Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Hanada, Y., Choi, A. Y., Hwang, J. H., Draganov, P. V., Khanna, L., Sethi, A., Bartel, M. J., Goel, N., Abe, S., De Latour, R. A., Park, K., Melis, M., Newman, E., Hatzaras, I., Reddy, S. S., Farma, J. M., Liu, X., Schlachterman, A., Kresak, J., Trapp, G., Ansari, N., Schrope, B., Lee, J. Y., Dhall, D., Lo, S., Jamil, L. H., Burch, M., Gaddam, S., Gong, Y., Del Portillo, A., Tomizawa, Y., Truong, C. D., Brewer Gutierrez, O. I., Montgomery, E., Johnston, F. M., Duncan, M., Canto, M., Ahuja, N., Lennon, A. M., Ngamruengphong, S. 2018

  Abstract

  BACKGROUND & AIMS: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US.METHODS: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% Caucasian) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999 through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined.RESULTS: The mean size of gastric adenocarcinomas was 23.0±16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively.CONCLUSION: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

  View details for PubMedID 30471457

• Double-Balloon Assisted Sigmoid Colon Complex EMR Sharma, S., Hwang, J. NATURE PUBLISHING GROUP. 2018: S1626

  View details for Web of Science ID 000464611006026

• ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) AS A SALVAGE THERAPY FOR PATIENTS WITH RECURRECE OR PROGRESSION OF BARRETT'S ESOPHAGUS (BE) RELATED EARLY NEOPLASIA AFTER STANDARD ENDOSCOPIC MANAGEMENT IS FEASIBLE AND SAFE : A US MULTI-CENTER STUDY Tomizawa, Y., Friedland, S., Hwang, J. MOSBY-ELSEVIER. 2018: AB281–AB282

  View details for Web of Science ID 000434248200494

• A Chance to Cut Is a Chance to Cure: Endoscopic Submucosal Dissection for Early Gastric Cancer. Digestive diseases and sciences Huang, R. J., Charville, G. W., Hwang, J. H., Friedland, S. 2018

  View details for PubMedID 30350240

• Hyperthermia-enhanced targeted drug delivery using magnetic resonance-guided focussed ultrasound: a pre-clinical study in a genetic model of pancreatic cancer. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group Farr, N., Wang, Y. N., D'Andrea, S., Starr, F., Partanen, A., Gravelle, K. M., McCune, J. S., Risler, L. J., Whang, S. G., Chang, A., Hingorani, S. R., Lee, D., Hwang, J. H. 2018; 34 (3): 284–91

  Abstract

  The lack of effective treatment options for pancreatic cancer has led to a 5-year survival rate of just 8%. Here, we evaluate the ability to enhance targeted drug delivery using mild hyperthermia in combination with the systemic administration of a low-temperature sensitive liposomal formulation of doxorubicin (LTSL-Dox) using a relevant model for pancreas cancer.Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre). LTSL-Dox or free doxorubicin (Dox) was administered via a tail vein catheter. A clinical magnetic resonance-guided high intensity focussed ultrasound (MR-HIFU) system was used to plan treatment, apply the HIFU-induce hyperthermia and monitor therapy. Post-therapy, total Dox concentration in tumour tissue was determined by HPLC and confirmed with fluorescence microscopy.Localized hyperthermia was successfully applied and monitored with a clinical MR-HIFU system. The mild hyperthermia heating algorithm administered by the MR-HIFU system resulted in homogenous heating within the region of interest. MR-HIFU, in combination with LTSL-Dox, resulted in a 23-fold increase in the localised drug concentration and nuclear uptake of doxorubicin within the tumour tissue of KPC mice compared to LTSL-Dox alone. Hyperthermia, in combination with free Dox, resulted in a 2-fold increase compared to Dox alone.This study demonstrates that HIFU-induced hyperthermia in combination with LTSL-Dox can be a non-invasive and effective method in enhancing the localised delivery and penetration of doxorubicin into pancreatic tumours.

  View details for DOI 10.1080/02656736.2017.1336675

  View details for PubMedID 28715967

  View details for PubMedCentralID PMC6135238

• Guidelines for sedation and anesthesia in GI endoscopy. Gastrointestinal endoscopy Early, D. S., Lightdale, J. R., Vargo, J. J., Acosta, R. D., Chandrasekhara, V., Chathadi, K. V., Evans, J. A., Fisher, D. A., Fonkalsrud, L., Hwang, J. H., Khashab, M. A., Muthusamy, V. R., Pasha, S. F., Saltzman, J. R., Shergill, A. K., Cash, B. D., DeWitt, J. M. 2018; 87 (2): 327–37

  View details for DOI 10.1016/j.gie.2017.07.018

  View details for PubMedID 29306520

• Gastrointestinal Endoscopy Editorial Board top 10 topics: advances in GI endoscopy in 2017. Gastrointestinal endoscopy Desilets, D. J., Hwang, J. H., Kyanam Kabir Baig, K. R., Leung, F. W., Maranki, J. L., Mishra, G., Shah, R. J., Swanstrom, L. L., Chak, A. 2018; 88 (1): 1–8

  View details for DOI 10.1016/j.gie.2018.04.2333

  View details for PubMedID 29779609

• Evaluation of pancreatic tumor development in KPC mice using multi-parametric MRI. Cancer imaging : the official publication of the International Cancer Imaging Society Vohra, R., Park, J., Wang, Y. N., Gravelle, K., Whang, S., Hwang, J. H., Lee, D. 2018; 18 (1): 41

  Abstract

  Pancreatic ductal adenocarcinoma (PDA) is a fatal disease with very poor prognosis. Development of sensitive and noninvasive methods to monitor tumor progression in PDA is a critical and unmet need. Magnetic resonance imaging (MRI) can noninvasively provide information regarding underlying pathophysiological processes such as necrosis, inflammatory changes and fibrotic tissue deposition.A genetically engineered KPC mouse model that recapitulates human PDA was used to characterize disease progression. MR measures of T1 and T2 relaxation times, magnetization transfer ratio (MTR), diffusion and chemical exchange saturation transfer were compared in two separate phases i.e. slow and rapid growth phase of tumor. Fibrotic tissue accumulation was assessed histologically using Masson's trichrome staining. Pearson correlation coefficient (r) was computed to assess the relationship between the fibrotic tissue accumulation and different MR parameters.There was a negative correlation between amide proton transfer signal intensity and tumor volume (r = - 0.63, p = 0.003) in the slow growth phase of the tumor development. In the terminal stage of rapid growth phase of the tumor development MTR was strongly correlated with tumor volume (r = 0.62, p = 0.008). Finally, MTR was significantly correlated with % fibrosis (r = 0.87; p < 0.01), followed by moderate correlation between tumor volume (r = 0.42); T1 (r = - 0.61), T2 (r = - 0.61) and accumulation of fibrotic tissue.Here we demonstrated, using multi-parametric MRI (mp-MRI), that MRI parameters changed with tumor progression in a mouse model of PDA. Use of mp-MRI may have the potential to monitor the dynamic changes of tumor microenvironment with increase in tumor size in the transgenic KPC mouse model of pancreatic tumor.

  View details for DOI 10.1186/s40644-018-0172-6

  View details for PubMedID 30409175

  View details for PubMedCentralID PMC6225661

• Understanding Gastric Cancer Risk Factors: We Need to Close the Gap GUT AND LIVER Hwang, J. 2018; 12 (1): 1–2

  View details for DOI 10.5009/gnl17503

  View details for Web of Science ID 000423401300001

  View details for PubMedID 29284218

  View details for PubMedCentralID PMC5753676

• Objective Differences in Colonoscopy Technique Between Trainee and Expert Endoscopists Using the Colonoscopy Force Monitor. Digestive diseases and sciences Ende, A. R., De Groen, P., Balmadrid, B. L., Hwang, J. H., Inadomi, J., Wojtera, T., Egorov, V., Sarvazyan, N., Korman, L. 2018; 63 (1): 46–52

  Abstract

  Learning to perform colonoscopy safely and effectively is central to gastroenterology fellowship programs. The application of force to the colonoscope is an important part of colonoscopy technique.We compared force application during colonoscopy between novice and expert endoscopists using a novel device to determine differences in colonoscopy technique.This is an observational cohort study designed to compare force application during colonoscopy between novice and experienced trainees, made up of gastroenterology fellows from two training programs, and expert endoscopists from both academic and private practice settings.Force recordings were obtained for 257 colonoscopies by 37 endoscopists, 21 of whom were trainees. Experts used higher average forward forces during insertion compared to all trainees and significantly less clockwise torque compared to novice trainees.We present significant, objective differences in colonoscopy technique between novice trainees, experienced trainees, and expert endoscopists. These findings suggest that the colonoscopy force monitor is an objective tool for measuring proficiency in colonoscopy. Furthermore, the device may be used as a teaching tool in training and continued medical education programs.

  View details for DOI 10.1007/s10620-017-4847-9

  View details for PubMedID 29147876

• Noninvasive characterization of pancreatic tumor mouse models using magnetic resonance imaging CANCER MEDICINE Farr, N., Wang, Y., D'Andrea, S., Gravelle, K. M., Hwang, J. H., Lee, D. 2017; 6 (5): 1082-1090

  Abstract

  The preclinical models of pancreatic adenocarcinoma provide an alternative means for determining the mechanisms of malignancy and possibilities for treatments, thus representing a resource of immense potential for cancer treatment in medicine. To evaluate different tumor models, quantifiable magnetic resonance imaging (MRI) techniques can play a significant role in identifying valuable in vivo biomarkers of tumor characteristics. We characterized three models of pancreatic cancer with multiparametric MRI techniques. Tumor stromal density of each tumor was measured using diffusion-weighted imaging and magnetization transfer (MT-MRI). Histologic measurement showed a similar trend with tumor fibrosis levels. Results indicated that MRI measurements can serve as a valuable tool in identifying and evaluating tumor characteristics.

  View details for DOI 10.1002/cam4.1062

  View details for Web of Science ID 000401330300020

  View details for PubMedID 28390098

  View details for PubMedCentralID PMC5430104

• Release of Cell-free MicroRNA Tumor Biomarkers into the Blood Circulation with Pulsed Focused Ultrasound: A Noninvasive, Anatomically Localized, Molecular Liquid Biopsy. Radiology Chevillet, J. R., Khokhlova, T. D., Giraldez, M. D., Schade, G. R., Starr, F., Wang, Y., Gallichotte, E. N., Wang, K., Hwang, J. H., Tewari, M. 2017; 283 (1): 158-167

  Abstract

  Purpose To compare the abilities of three pulsed focused ultrasound regimes (that cause tissue liquefaction, permeabilization, or mild heating) to release tumor-derived microRNA into the circulation in vivo and to evaluate release dynamics. Materials and Methods All rat experiments were approved by the University of Washington Institutional Animal Care and Use Committee. Reverse-transcription quantitative polymerase chain reaction array profiling was used to identify candidate microRNA biomarkers in a rat solid tumor cell line. Rats subcutaneously grafted with these cells were randomly assigned among three pulsed focused ultrasound treatment groups: (a) local tissue liquefaction via boiling histotripsy, (b) tissue permeabilization via inertial cavitation, and (c) mild (<10°C) heating of tissue, as well as a sham-treated control group. Blood specimens were drawn immediately prior to treatment and serially over 24 hours afterward. Plasma microRNA was quantified with reverse-transcription quantitative polymerase chain reaction, and statistical significance was determined with one-way analysis of variance (Kruskal-Wallis and Friedman tests), followed by the Dunn multiple-comparisons test. Results After tissue liquefaction and cavitation treatments (but not mild heating), plasma quantities of candidate biomarkers increased significantly (P value range, <.0001 to .04) relative to sham-treated controls. A threefold to 32-fold increase occurred within 15 minutes after initiation of pulsed focused ultrasound tumor treatment, and these increases persisted for 3 hours. Histologic examination confirmed complete liquefaction of the targeted tumor area with boiling histotripsy, in addition to areas of petechial hemorrhage and tissue disruption by means of cavitation-based treatment. Conclusion Mechanical tumor tissue disruption with pulsed focused ultrasound-induced bubble activity significantly increases the plasma abundance of tumor-derived microRNA rapidly after treatment.©RSNA, 2016 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2016160024

  View details for PubMedID 27802108

  View details for PubMedCentralID PMC5375625

• A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound. Journal of therapeutic ultrasound Dababou, S., Marrocchio, C., Rosenberg, J., Bitton, R., Pauly, K. B., Napoli, A., Hwang, J. H., Ghanouni, P. 2017; 5: 9-?

  Abstract

  Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60-90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma.An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ(2), and Cochran's Q test for heterogeneity among studies. The I(2) was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias.The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ(2) (variance among studies) was 0.195, and I(2) (percentage of variation among studies) was 40% (95% CI: 1-64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76-86).HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

  View details for DOI 10.1186/s40349-017-0080-4

  View details for PubMedID 28373906

• EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-Summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop. Gastrointestinal endoscopy Lee, L. S., Andersen, D. K., Ashida, R., Brugge, W. R., Canto, M. I., Chang, K. J., Chari, S. T., DeWitt, J., Hwang, J. H., Khashab, M. A., Kim, K., Levy, M. J., McGrath, K., Park, W. G., Singhi, A., Stevens, T., Thompson, C. C., Topazian, M. D., Wallace, M. B., Wani, S., Waxman, I., Yadav, D., Singh, V. K. 2017; 86 (5): 768–78

  Abstract

  A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic EUS. The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

  View details for PubMedID 28941651

• Focused ultrasound for immuno-adjuvant treatment of pancreatic cancer: An emerging clinical paradigm in the era of personalized oncotherapy. International reviews of immunology Maloney, E., Khokhlova, T., Pillarisetty, V. G., Schade, G. R., Repasky, E. A., Wang, Y. N., Giuliani, L., Primavera, M., Hwang, J. H. 2017; 36 (6): 338–51

  Abstract

  Current clinical treatment regimens, including many emergent immune strategies (e.g., checkpoint inhibitors) have done little to affect the devastating course of pancreatic ductal adenocarcinoma (PDA). Clinical trials for PDA often employ multi-modal treatment, and have started to incorporate stromal-targeted therapies, which have shown promising results in early reports. Focused ultrasound (FUS) is one such therapy that is uniquely equipped to address local and systemic limitations of conventional cancer therapies as well as emergent immune therapies for PDA. FUS methods can non-invasively generate mechanical and/or thermal effects that capitalize on the unique oncogenomic/proteomic signature of a tumor. Potential benefits of FUS therapy for PDA include: (1) emulsification of targeted tumor into undenatured antigens in situ, increasing dendritic cell maturation, and increasing intra-tumoral CD8+/ T regulatory cell ratio and CD8+T cell activity; (2) reduction in intra-tumoral hypoxic stress; (3) modulation of tumor cell membrane protein localization to enhance immunogenicity; (4) modulation of the local cytokine milieu toward a Th1-type inflammatory profile; (5) up-regulation of local chemoattractants; (6) remodeling the tumor stroma; (7) localized delivery of exogenously packaged immune-stimulating antigens, genes and therapeutic drugs. While not all of these results have been studied in experimental PDA models to date, the principles garnered from other solid tumor and disease models have direct relevance to the design of optimal FUS protocols for PDA. In this review, we address the pertinent limitations in current and emergent immune therapies that can be improved with FUS therapy for PDA.

  View details for DOI 10.1080/08830185.2017.1363199

  View details for PubMedID 28961038

• Association of gastric intestinal metaplasia and East Asian ethnicity with the risk of gastric adenocarcinoma in a U.S. population. Gastrointestinal endoscopy Choi, A. Y., Strate, L. L., Fix, M. C., Schmidt, R. A., Ende, A. R., Yeh, M. M., Inadomi, J. M., Hwang, J. H. 2017

  Abstract

  Although the incidence of gastric cancer is higher than that of esophageal cancer in the United States, no screening or surveillance guidelines exist. The aim of this study is to evaluate the association between gastric intestinal metaplasia and the risk of gastric cancer in a U.S. tertiary care system with a large immigrant population.This is a retrospective case-control study with cases of biopsy-proven gastric cancer matched (by age and gender) to controls without gastric cancer who had undergone EGD. The presence of gastric intestinal metaplasia was ascertained from pathology reports. Other potential risk factors for gastric cancer were abstracted from medical records as follows: country of origin, Helicobacter pylori infection, family history of gastric cancer, alcohol consumption, smoking, and history of partial gastrectomy (Billroth I or II). Conditional logistic regression was used to identify independent risk factors for gastric cancer.One hundred fifty-two cases of gastric cancer were compared with 456 age- and gender-matched controls. The mean age was 66 years, and 57% were male. Multivariable analysis identified 2 significant predictors of gastric cancer: the presence of gastric intestinal metaplasia (odds ratio [OR], 9.3; 95% confidence interval [CI], 4.5-18.9; P < .001) and East Asian ethnicity (OR, 15.9; 95% CI, 5.8-43.6; P < .001).The presence of gastric intestinal metaplasia on endoscopy and East Asian ethnicity were significant risk factors for gastric cancer. Screening East Asian immigrants and surveying patients with gastric intestinal metaplasia may improve the rates of early detection of gastric cancer in the United States.

  View details for DOI 10.1016/j.gie.2017.11.010

  View details for PubMedID 29155082

• The impact of medical tourism on colorectal screening among Korean Americans: A community-based cross-sectional study BMC CANCER Ko, L. K., Taylor, V. M., Yoon, J., Copeland, W. K., Hwang, J. H., Lee, E. J., Inadomi, J. 2016; 16

  Abstract

  Colorectal cancer (CRC) remains the most commonly diagnosed cancer among Korean Americans (KAs) in part due to low screening rates. Recent studies suggest that some KA patients engage in medical tourism and receive medical care in their home country. The impact of medical tourism on CRC screening is unknown. The purpose of this paper was to 1) investigate the frequency of medical tourism, 2) examine the association between medical tourism and CRC screening, and 3) characterize KA patients who engage in medical tourism.This is a community-based, cross-sectional study involving self-administered questionnaires conducted from August 2013 to October 2013. Data was collected on 193 KA patients, ages 50-75, residing in the Seattle metropolitan area. The outcome variable is up-to-date with CRC screening, defined as having had a stool test (Fecal Occult Blood Test or Fecal Immunochemical Test) within the past year or a colonoscopy within 10 years. Predictor variables are socio-demographics, health factors, acculturation, knowledge, financial concerns for medical care costs, and medical tourism.In multi-variate modeling, medical tourism was significantly related to being up-to-date with CRC screening. Participants who engaged in medical tourism had 8.91 (95% CI: 3.89-23.89) greater odds of being up-to-date with CRC screening compared to those who did not travel for healthcare. Factors associated with engaging in medical tourism were lack of insurance coverage (P = 0.008), higher levels of education (P = 0.003), not having a usual place of care (P = 0.002), older age at immigration (P = 0.009), shorter years-of-stay in the US (P = 0.003), and being less likely to speak English well (P = 0.03).This study identifies the impact of medical tourism on CRC screening and characteristics of KA patients who report engaging in medical tourism. Healthcare providers in the US should be aware of the customary nature of medical tourism among KAs and consider assessing medical tests done abroad when providing cancer care.Not applicable.

  View details for DOI 10.1186/s12885-016-2965-y

  View details for Web of Science ID 000389382000005

  View details for PubMedID 27905896

  View details for PubMedCentralID PMC5134124

• Screening and surveillance for gastric cancer in the United States: Is it needed? GASTROINTESTINAL ENDOSCOPY Kim, G. H., Liang, P. S., Bang, S. J., Hwang, J. H. 2016; 84 (1): 18-28

  Abstract

  Although the incidence of gastric cancer in the United States is relatively low, the incidence of gastric cancer is higher than for esophageal cancer, for which clear guidelines for screening and surveillance exist. With the increasing availability of endoscopic therapy, such as endoscopic submucosal dissection, for treating advanced dysplasia and early gastric cancer, establishing guidelines for screening and surveillance of patients who are at high risk of developing gastric cancer has the potential to diagnose and treat gastric cancer at an earlier stage and improve mortality from gastric cancer. The aims of this article were to review the data regarding the risk factors for developing gastric cancer, methods for gastric cancer screening, and results of national screening programs.A review of the existing literature related to the aims was performed.Risk factors for gastric cancer that were identified include race/ethnicity (East Asian, Russian, or South American), first-degree relative diagnosed with gastric cancer, positive Helicobacter pylori status, and presence of atrophic gastritis or intestinal metaplasia. Endoscopy has the highest rate of detecting gastric cancer compared with other gastric cancer screening methods. The national screening program in Japan has demonstrated a mortality reduction from gastric cancer based on cohort data.Gastric cancer screening with endoscopy should be considered in individuals who are immigrants from regions associated with a high risk of gastric cancer (East Asia, Russia, or South America) or who have a family history of gastric cancer. Those with findings of atrophic gastritis or intestinal metaplasia on screening endoscopy should undergo surveillance endoscopy every 1 to 2 years. Large prospective multicenter studies are needed to further identify additional risk factors for developing gastric cancer and to assess whether gastric cancer screening programs for high-risk populations in the United States would result in improved mortality.

  View details for DOI 10.1016/j.gie.2016.02.028

  View details for Web of Science ID 000378095000003

  View details for PubMedID 26940296

• Devices and techniques for ERCP in the surgically altered GI tract GASTROINTESTINAL ENDOSCOPY Enestvedt, B. K., Kothari, S., Pannala, R., Yang, J., Fujii-Lau, L. L., Hwang, J. H., Konda, V., Manfredi, M., Maple, J. T., Murad, F. M., Woods, K. L., Banerjee, S. 2016; 83 (6): 1061-1075

  View details for DOI 10.1016/j.gie.2016.03.018

  View details for Web of Science ID 000376181700002

  View details for PubMedID 27103361

• The use of carbon dioxide in gastrointestinal endoscopy GASTROINTESTINAL ENDOSCOPY Lo, S. K., Fujii-Lau, L. L., Enestvedt, B. K., Hwang, J. H., Konda, V., Manfredi, M. A., Maple, J. T., Murad, F. M., Pannala, R., Woods, K. L., Banerjee, S. 2016; 83 (5): 857-865

  View details for DOI 10.1016/j.gie.2016.01.046

  View details for Web of Science ID 000374441300001

  View details for PubMedID 26946413

• ENHANCEMENT OF SMALL MOLECULE DELIVERY BY PULSED HIGH-INTENSITY FOCUSED ULTRASOUND: A PARAMETER EXPLORATION ULTRASOUND IN MEDICINE AND BIOLOGY Zhou, Y., Wang, Y., Farr, N., Zia, J., Chen, H., Ko, B. M., Khokhlova, T., Li, T., Hwang, J. H. 2016; 42 (4): 956-963

  Abstract

  Chemotherapeutic drug delivery is often ineffective within solid tumors, but increasing the drug dose would result in systemic toxicity. The use of high-intensity focused ultrasound (HIFU) has the potential to enhance penetration of small molecules. However, operation parameters need to be optimized before the use of chemotherapeutic drugs in vivo and translation to clinical trials. In this study, the effects of pulsed HIFU (pHIFU) parameters (spatial-average pulse-average intensity, duty factor and pulse repetition frequency) on the penetration as well as content of small molecules were evaluated in ex vivo porcine kidneys. Specific HIFU parameters resulted in more than 40 times greater Evans blue content and 3.5 times the penetration depth compared with untreated samples. When selected parameters were applied to porcine kidneys in vivo, a 2.3-fold increase in concentration was obtained after a 2-min exposure to pHIFU. Pulsed HIFU has been found to be an effective modality to enhance both the concentration and penetration depth of small molecules in tissue using the optimized HIFU parameters. Although, performed in normal tissue, this study has the promise of translation into tumor tissue.

  View details for DOI 10.1016/j.ultrasmedbio.2015.12.009

  View details for Web of Science ID 000373384700014

  View details for PubMedID 26803389

  View details for PubMedCentralID PMC4775378

• The role of endoscopy in the evaluation and management of patients with solid pancreatic neoplasia GASTROINTESTINAL ENDOSCOPY Eloubeidi, M. A., Decker, G. A., Chandrasekhara, V., Chathadi, K. V., Early, D. S., Evans, J. A., Fanelli, R. D., Fisher, D. A., Foley, K., Hwang, J. H., Jue, T. L., Lightdale, J. R., Pasha, S. F., Saltzman, J. R., Sharaf, R., Shergill, A. K., Cash, B. D., Dewitt, J. M. 2016; 83 (1): 17-28

  View details for DOI 10.1016/j.gie.2015.09.009

  View details for Web of Science ID 000369230900004

  View details for PubMedID 26706297

• HIFU for Palliative Treatment of Pancreatic Cancer THERAPEUTIC ULTRASOUND Khokhlova, T. D., Hwang, J. H. 2016; 880: 83-95

  Abstract

  Pancreatic cancer is one of the deadliest malignancies, with only a 6 % 5-year survival rate and over 50 % of patients being diagnosed at the advanced stage. Current therapies are ineffective, and the treatment of patients with advanced disease is palliative. In the past decade, HIFU ablation has emerged as a modality for palliative treatment of pancreatic tumors. Multiple preclinical and non-randomized clinical trials have been performed to evaluate the safety and efficacy of this procedure. Substantial tumor-related pain reduction was achieved in most cases after HIFU treatment and few significant side effects were observed. In addition, some studies indicate that combination of HIFU ablation with chemotherapy may provide a survival benefit. This chapter summarizes the pre-clinical and clinical experience obtained to date in HIFU treatment of pancreatic tumors and discusses the challenges, limitations and new approaches in this modality.

  View details for DOI 10.1007/978-3-319-22536-4_5

  View details for Web of Science ID 000369481100006

  View details for PubMedID 26486333

• The management of antithrombotic agents for patients undergoing GI endoscopy GASTROINTESTINAL ENDOSCOPY Acosta, R. D., Abraham, N. S., Chandrasekhara, V., Chathadi, K. V., Early, D. S., Eloubeidi, M. A., Evans, J. A., Faulx, A. L., Fisher, D. A., Fonkalsrud, L., Hwang, J. H., Khashab, M. A., Lightdale, J. R., Muthusamy, V. R., Pasha, S. F., Saltzman, J. R., Shaukat, A., Shergill, A. K., Wang, A., Cash, B. D., Dewitt, J. M. 2016; 83 (1): 3-16

  View details for DOI 10.1016/j.gie.2015.09.035

  View details for Web of Science ID 000369230900003

  View details for PubMedID 26621548

• Endoscopic electronic medical record systems GASTROINTESTINAL ENDOSCOPY Manfredi, M. A., Manfredi, M. A., Chauhan, S. S., Enestvedt, B. K., Fujii-Lau, L. L., Konda, V., Hwang, J. H., Lo, S. K., Maple, J. T., Murad, F. M., Pannala, R., Woods, K. L., Banerjee, S. 2016; 83 (1): 29-36

  View details for DOI 10.1016/j.gie.2015.09.036

  View details for Web of Science ID 000369230900005

  View details for PubMedID 26616725

• Endoscopic resection of gastric and esophageal cancer. Gastroenterology report Balmadrid, B., Hwang, J. H. 2015; 3 (4): 330-338

  Abstract

  Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) techniques have reduced the need for surgery in early esophageal and gastric cancers and thus has lessened morbidity and mortality in these diseases. ESD is a relatively new technique in western countries and requires rigorous training to reproduce the proficiency of Asian countries, such as Korea and Japan, which have very high complete (en bloc) resection rates and low complication rates. EMR plays a valuable role in early esophageal cancers. ESD has shown better en bloc resection rates but it is easier to master and maintain proficiency in EMR; it also requires less procedural time. For early esophageal adenocarcinoma arising from Barrett's, ESD and EMR techniques are usually combined with other ablative modalities, the most common being radiofrequency ablation because it has the largest dataset to prove its success. The EMR techniques have been used with some success in early gastric cancers but ESD is currently preferred for most of these lesions. ESD has the added advantage of resecting into the submucosa and thus allowing for endoscopic resection of more aggressive (deeper) early gastric cancer.

  View details for DOI 10.1093/gastro/gov050

  View details for PubMedID 26510452

  View details for PubMedCentralID PMC4650978

• Therapeutic potential of ultrasound microbubbles in gastrointestinal oncology: recent advances and future prospects THERAPEUTIC ADVANCES IN GASTROENTEROLOGY Khokhlova, T. D., Haider, Y., Hwang, J. H. 2015; 8 (6): 384-394

  Abstract

  Microbubbles were initially invented as contrast agents for ultrasound imaging. However, lately more and more therapeutic applications of microbubbles are emerging, mostly related to drug and gene delivery. Ultrasound is a safe and noninvasive therapeutic modality which has the unique ability to interact with microbubbles and release their payload in situ in addition to permeabilizing the target tissues. The combination of drug-loaded microbubbles and ultrasound has been used in preclinical studies on blood-brain barrier opening, drug and gene delivery to solid tumors, and ablation of blood vessels. This review covers the basic principles of ultrasound-microbubble interaction, the types of microbubbles and the effect they have on tissue, and the preclinical and clinical experience with this approach to date in the field of gastrointestinal oncology.

  View details for DOI 10.1177/1756283X15592584

  View details for Web of Science ID 000363413400007

  View details for PubMedID 26557894

  View details for PubMedCentralID PMC4622285

• Is screening and surveillance for early detection of gastric cancer needed in Korean Americans? KOREAN JOURNAL OF INTERNAL MEDICINE Kim, G. H., Bang, S. J., Ende, A. R., Hwang, J. H. 2015; 30 (6): 747-758

  Abstract

  The incidence rate of gastric cancer in Korean Americans is over five times higher than that in non-Hispanic whites, and is similar to the incidence of colorectal cancer in the overall United States population. In Korea, the National Cancer Screening Program recommends endoscopy or upper gastrointestinal series for people aged 40 years and older every 2 years. However, the benefit of gastric cancer screening in Korean Americans has not been evaluated. Based on epidemiologic studies, Korean Americans appear to have more similar gastric cancer risk factors to Koreans as opposed to Americans of European descent, though the risk of gastric cancer appears to decrease for subsequent generations. Therefore, in accordance with recent recommendations regarding screening for gastric cancer in Korea, endoscopic screening for gastric cancer in Korean Americans should be considered, especially in those with known atrophic gastritis/intestinal metaplasia or a family history of gastric cancer. In the future, additional studies will needed to assess whether a screening program for gastric cancer in Korean Americans will result in a survival benefit.

  View details for DOI 10.3904/kjim.2015.30.6.747

  View details for Web of Science ID 000366667300001

  View details for PubMedID 26552450

  View details for PubMedCentralID PMC4642004

• Pulsed High-Intensity Focused Ultrasound Enhances Delivery of Doxorubicin in a Preclinical Model of Pancreatic Cancer CANCER RESEARCH Li, T., Wang, Y., Khokhlova, T. D., D'Andrea, S., Starr, F., Chen, H., McCune, J. S., Risler, L. J., Mashadi-Hossein, A., Hwang, J. H. 2015; 75 (18): 3738-3746

  Abstract

  Pancreatic cancer is characterized by extensive stromal desmoplasia, which decreases blood perfusion and impedes chemotherapy delivery. Breaking the stromal barrier could both increase perfusion and permeabilize the tumor, enhancing chemotherapy penetration. Mechanical disruption of the stroma can be achieved using ultrasound-induced bubble activity-cavitation. Cavitation is also known to result in microstreaming and could have the added benefit of actively enhancing diffusion into the tumors. Here, we report the ability to enhance chemotherapeutic drug doxorubicin penetration using ultrasound-induced cavitation in a genetically engineered mouse model (KPC mouse) of pancreatic ductal adenocarcinoma. To induce localized inertial cavitation in pancreatic tumors, pulsed high-intensity focused ultrasound (pHIFU) was used either during or before doxorubicin administration to elucidate the mechanisms of enhanced drug delivery (active vs. passive drug diffusion). For both types, the pHIFU exposures that were associated with high cavitation activity resulted in disruption of the highly fibrotic stromal matrix and enhanced the normalized doxorubicin concentration by up to 4.5-fold compared with controls. Furthermore, normalized doxorubicin concentration was associated with the cavitation metrics (P < 0.01), indicating that high and sustained cavitation results in increased chemotherapy penetration. No significant difference between the outcomes of the two types, that is, doxorubicin infusion during or after pHIFU treatment, was observed, suggesting that passive diffusion into previously permeabilized tissue is the major mechanism for the increase in drug concentration. Together, the data indicate that pHIFU treatment of pancreatic tumors when resulting in high and sustained cavitation can efficiently enhance chemotherapy delivery to pancreatic tumors. .

  View details for DOI 10.1158/0008-5472.CAN-15-0296

  View details for Web of Science ID 000363335800010

  View details for PubMedID 26216548

  View details for PubMedCentralID PMC4629806

• Endoscopic mucosal resection GASTROINTESTINAL ENDOSCOPY Hwang, J. H., Konda, V., Abu Dayyeh, B. K., Chauhan, S. S., Enestvedt, B. K., Fujii-Lau, L. L., Komanduri, S., Maple, J. T., Murad, F. M., Pannala, R., Thosani, N. C., Banerjee, S. 2015; 82 (2): 215-226

  Abstract

  EMR has become an established therapeutic option for premalignant and early-stage GI malignancies, particularly in the esophagus and colon. EMR can also aid in the diagnosis and therapy of subepithelial lesions localized to the muscularis mucosa or submucosa. Several dedicated EMR devices are available to facilitate these procedures. Adverse event rates, particularly bleeding and perforation, are higher after EMR relative to other basic endoscopic interventions but lower than adverse event rates for ESD. Endoscopists performing EMR should be knowledgeable and skilled in managing potential adverse events resulting from EMR.

  View details for DOI 10.1016/j.gie.2015.05.001

  View details for Web of Science ID 000357898100003

  View details for PubMedID 26077453

• The role of endoscopy in benign pancreatic disease GASTROINTESTINAL ENDOSCOPY Chandrasekhara, V., Chathadi, K. V., Acosta, R. D., Decker, G. A., Early, D. S., Eloubeidi, M. A., Evans, J. A., Faulx, A. L., Fanelli, R. D., Fisher, D. A., Foley, K., Fonkalsrud, L., Hwang, J. H., Jue, T. L., Khashab, M. A., Lightdale, J. R., Muthusamy, V. R., Pasha, S. F., Saltzman, J. R., Sharaf, R., Shaukat, A., Shergill, A. K., Wang, A., Cash, B. D., Dewitt, J. M. 2015; 82 (2): 203-214

  View details for DOI 10.1016/j.gie.2015.04.022

  View details for Web of Science ID 000357898100002

  View details for PubMedID 26077456

• The role of endoscopy in the management of premalignant and malignant conditions of the stomach GASTROINTESTINAL ENDOSCOPY Evans, J. A., Chandrasekhara, V., Chathadi, K. V., Decker, G. A., Early, D. S., Fisher, D. A., Foley, K., Hwang, J. H., Jue, T. L., Lightdale, J. R., Pasha, S. F., Sharaf, R., Shergill, A. K., Cash, B. D., Dewitt, J. M. 2015; 82 (1): 1-8

  View details for DOI 10.1016/j.gie.2015.03.1967

  View details for Web of Science ID 000356182600001

  View details for PubMedID 25935705

• Endoscopic submucosal dissection GASTROINTESTINAL ENDOSCOPY Maple, J. T., Abu Dayyeh, B. K., Chauhan, S. S., Hwang, J. H., Komanduri, S., Manfredi, M., Konda, V., Murad, F. M., Siddiqui, U. D., Banerjee, S. 2015; 81 (6): 1311-1325

  Abstract

  ESD is an established effective treatment modality for premalignant and early-stage malignant lesions of the stomach, esophagus, and colorectum. Compared with EMR, ESD is generally associated with higher rates of en bloc, R0, and curative resections and a lower rate of local recurrence. Oncologic outcomes with ESD compare favorably with competing surgical interventions, and ESD also serves as an excellent T-staging tool to identify noncurative resections that will require further treatment. ESD is technically demanding and has a higher rate of adverse events than most endoscopic procedures including EMR. As such,sufficient training is critical to ensure safe conduct and high-quality resections. A standardized training model for Western endoscopists has not been clearly established,but will be self-directed and include courses, animal model training, and optimally an observership at an expert center.Numerous dedicated ESD devices are now available in the United States from different manufacturers. Although the use of ESD in the United States is increasing, issues related to technical difficulty, limited training opportunities and mentors, risk of adverse events, long procedure duration,and suboptimal reimbursement may limit ESD adoption in the United States to a modest number of academic referral centers for the foreseeable future.

  View details for DOI 10.1016/j.gie.2014.12.010

  View details for Web of Science ID 000354558800002

  View details for PubMedID 25796422

• Learning models for endoscopic ultrasonography in gastrointestinal endoscopy WORLD JOURNAL OF GASTROENTEROLOGY Kim, G. H., Bang, S. J., Hwang, J. H. 2015; 21 (17): 5176-5182

  Abstract

  Endoscopic ultrasonography (EUS) has become a useful diagnostic and therapeutic modality in gastrointestinal endoscopy. However, EUS requires additional training since it requires simultaneous endoscopic manipulation and ultrasonographic interpretation. Obtaining adequate EUS training can be challenging since EUS is highly operator-dependent and training on actual patients can be associated with an increased risk of complications including inaccurate diagnosis. Therefore, several models have been developed to help facilitate training of EUS. The models currently available for EUS training include computer-based simulators, phantoms, ex vivo models, and live animal models. Although each model has its own merits and limitations, the value of these different models is rather complementary than competitive. However, there is a lack of objective data regarding the efficacy of each model with recommendations on the use of various training models based on expert opinion only. Therefore, objective studies evaluating the efficacy of various EUS training models on technical and clinical outcomes are still needed.

  View details for DOI 10.3748/wjg.v21.i17.5176

  View details for Web of Science ID 000353774100008

  View details for PubMedID 25954091

  View details for PubMedCentralID PMC4419058

• Endoscopic high-intensity focused US: technical aspects and studies in an in vivo porcine model (with video) GASTROINTESTINAL ENDOSCOPY Li, T., Khokhlova, T., Maloney, E., Wang, Y., D'Andrea, S., Starr, F., Farr, N., Morrison, K., Keilman, G., Hwang, J. H. 2015; 81 (5): 1243-1250

  Abstract

  High-intensity focused US (HIFU) is becoming more widely used for noninvasive and minimally invasive ablation of benign and malignant tumors. Recent studies suggest that HIFU can also enhance targeted drug delivery and stimulate an antitumor immune response in many tumors. However, targeting pancreatic and liver tumors by using an extracorporeal source is challenging due to the lack of an adequate acoustic window. The development of an EUS-guided HIFU transducer has many potential benefits including improved targeting, decreased energy requirements, and decreased potential for injury to intervening structures.To design, develop, and test an EUS-guided HIFU transducer for endoscopic applications.A preclinical, pilot characterization and feasibility study.Academic research center.Studies were performed in an in vivo porcine model.Thermal ablation of in vivo porcine pancreas and liver was performed with EUS-guided focused US through the gastric tract.The transducer successfully created lesions in gel phantoms and ex vivo bovine livers. In vivo studies demonstrated that targeting and creating lesions in the porcine pancreas and liver are feasible.This was a preclinical, single-center feasibility study with a limited number of subjects.An EUS-guided HIFU transducer was successfully designed and developed with dimensions that are appropriate for endoscopic use. The feasibility of performing EUS-guided HIFU ablation in vivo was demonstrated in an in vivo porcine model. Further development of this technology will allow endoscopists to perform precise therapeutic ablation of periluminal lesions without breaching the wall of the gastric tract.

  View details for DOI 10.1016/j.gie.2014.12.019

  View details for Web of Science ID 000352706600023

  View details for PubMedID 25759124

  View details for PubMedCentralID PMC4452137

• The role of endoscopy in inflammatory bowel disease GASTROINTESTINAL ENDOSCOPY Shergill, A. K., Lightdale, J. R., Bruining, D. H., Acosta, R. D., Chandrasekhara, V., Chathadi, K. V., Decker, G. A., Early, D. S., Evans, J. A., Fanelli, R. D., Fisher, D. A., Fonkalsrud, L., Foley, K., Hwang, J. H., Jue, T. L., Khashab, M. A., Muthusamy, V. R., Pasha, S. F., Saltzman, J. R., Sharaf, R., Cash, B. D., Dewitt, J. M. 2015; 81 (5): 1101-U389

  View details for DOI 10.1016/j.gie.2014.10.030

  View details for Web of Science ID 000352706600004

  View details for PubMedID 25800660

• Endoscopes and devices to improve colon polyp detection GASTROINTESTINAL ENDOSCOPY Konda, V., Chauhan, S. S., Abu Dayyeh, B. K., Hwang, J. H., Komanduri, S., Manfredi, M. A., Maple, J. T., Murad, F. M., Siddiqui, U. D., Banerjee, S. 2015; 81 (5): 1122-1129

  View details for DOI 10.1016/j.gie.2014.10.006

  View details for Web of Science ID 000352706600005

  View details for PubMedID 25746978

• Emerging HIFU applications in cancer therapy INTERNATIONAL JOURNAL OF HYPERTHERMIA Maloney, E., Hwang, J. H. 2015; 31 (3): 302-309

  Abstract

  High intensity focused ultrasound (HIFU), is a promising, non-invasive modality for treatment of tumours in conjunction with magnetic resonance imaging or diagnostic ultrasound guidance. HIFU is being used increasingly for treatment of prostate cancer and uterine fibroids. Over the last 10 years a growing number of clinical trials have examined HIFU treatment of both benign and malignant tumours of the liver, breast, pancreas, bone, connective tissue, thyroid, parathyroid, kidney and brain. For some of these emerging indications, HIFU is poised to become a serious alternative or adjunct to current standard treatments--including surgery, radiation, gene therapy, immunotherapy, and chemotherapy. Current commercially available HIFU devices are marketed for their thermal ablation applications. In the future, lower energy treatments may play a significant role in mediating targeted drug and gene delivery for cancer treatment. In this article we introduce currently available HIFU systems, provide an overview of clinical trials in emerging oncological targets, and briefly discuss selected pre-clinical research that is relevant to future oncological HIFU applications.

  View details for DOI 10.3109/02656736.2014.969789

  View details for Web of Science ID 000355926300011

  View details for PubMedID 25367011

• American Gastroenterological Association Technical Review on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts GASTROENTEROLOGY Scheiman, J. M., Hwang, J. H., Moayyedi, P. 2015; 148 (4): 824-U283

  View details for DOI 10.1053/j.gastro.2015.01.014

  View details for Web of Science ID 000351639000029

  View details for PubMedID 25805376

• The role of ERCP in benign diseases of the biliary tract GASTROINTESTINAL ENDOSCOPY Chathadi, K. V., Chandrasekhara, V., Acosta, R. D., Decker, G. A., Early, D. S., Eloubeidi, M. A., Evans, J. A., Faulx, A. L., Fanelli, R. D., Fisher, D. A., Foley, K., Fonkalsrud, L., Hwang, J. H., Jue, T. L., Khashab, M. A., Lightdale, J. R., Muthusamy, V. R., Pasha, S. F., Saltzman, J. R., Sharaf, R., Shaukat, A., Shergill, A. K., Wang, A., Cash, B. D., Dewitt, J. M. 2015; 81 (4): 795-803

  View details for DOI 10.1016/j.gie.2014.11.019

  View details for Web of Science ID 000351668700002

  View details for PubMedID 25665931

• Bowel preparation before colonoscopy GASTROINTESTINAL ENDOSCOPY Saltzman, J. R., Cash, B. D., Pasha, S. F., Early, D. S., Muthusamy, V. R., Khashab, M. A., Chathadi, K. V., Fanelli, R. D., Chandrasekhara, V., Lightdale, J. R., Fonkalsrud, L., Shergill, A. K., Hwang, J. H., Decker, G. A., Jue, T. L., Sharaf, R., Fisher, D. A., Evans, J. A., Foley, K., Shaukat, A., Eloubeidi, M. A., Faulx, A. L., Wang, A., Acosta, R. D. 2015; 81 (4): 781-794

  View details for DOI 10.1016/j.gie.2014.09.048

  View details for Web of Science ID 000351668700001

  View details for PubMedID 25595062

• ASGE Technology Committee systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointestinal endoscopy Abu Dayyeh, B. K., Thosani, N., Konda, V., Wallace, M. B., Rex, D. K., Chauhan, S. S., Hwang, J. H., Komanduri, S., Manfredi, M., Maple, J. T., Murad, F. M., Siddiqui, U. D., Banerjee, S. 2015; 81 (3): 502 e1-502 e16

  Abstract

  In vivo real-time assessment of the histology of diminutive (≤5 mm) colorectal polyps detected at colonoscopy can be achieved by means of an "optical biopsy" by using currently available endoscopic technologies. This systematic review and meta-analysis was performed by the American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable performance thresholds outlined by an ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) document for clinical adoption of these technologies have been met. We conducted direct meta-analyses calculating the pooled negative predictive value (NPV) for narrow-band imaging (NBI), i-SCAN, and Fujinon Intelligent Color Enhancement (FICE)-assisted optical biopsy for predicting adenomatous polyp histology of small/diminutive colorectal polyps. We also calculated the pooled percentage agreement with histopathology when assigning postpolypectomy surveillance intervals based on combining real-time optical biopsy of colorectal polyps 5 mm or smaller with histopathologic assessment of polyps larger than 5 mm. Random-effects meta-analysis models were used. Statistical heterogeneity was evaluated by means of I(2) statistics. Our meta-analyses indicate that optical biopsy with NBI, exceeds the NPV threshold for adenomatous polyp histology, supporting a "diagnose-and-leave" strategy for diminutive predicted nonneoplastic polyps in the rectosigmoid colon. The pooled NPV of NBI for adenomatous polyp histology by using the random-effects model was 91% (95% confidence interval [CI], 88-94). This finding was associated with a high degree of heterogeneity (I(2) = 89%). Subgroup analysis indicated that the pooled NPV was greater than 90% for academic medical centers (91.8%; 95% CI, 89-94), for experts (93%; 95% CI, 91-96), and when the optical biopsy assessment was made with high confidence (93%; 95% CI, 90-96). Our meta-analyses also indicate that the agreement in assignment of postpolypectomy surveillance intervals based on optical biopsy with NBI of diminutive colorectal polyps is 90% or greater in academic settings (91%; 95% CI, 86-95), with experienced endoscopists (92%; 95% CI, 88-96) and when optical biopsy assessments are made with high confidence (91%; 95% CI, 88-95). Our systematic review and meta-analysis confirms that the thresholds established by the ASGE PIVI for real-time endoscopic assessment of the histology of diminutive polyps have been met, at least with NBI optical biopsy, with endoscopists who are expert in using this advanced imaging technology and when assessments are made with high confidence.

  View details for DOI 10.1016/j.gie.2014.12.022

  View details for PubMedID 25597420

• Electronic chromoendoscopy GASTROINTESTINAL ENDOSCOPY Manfredi, M. A., Abu Dayyeh, B. K., Bhat, Y. M., Chauhan, S. S., Gottlieb, K. T., Hwang, J. H., Komanduri, S., Konda, V., Lo, S. K., Maple, J. T., Murad, F. M., Siddiqui, U. D., Wallace, M. B., Banerjee, S. 2015; 81 (2): 249-261

  Abstract

  Electronic chromoendoscopy technologies provide image enhancement and may improve the diagnosis of mucosal lesions. Although strides have been made in standardization of image characterization, especially with NBI, further image-to-pathology correlation and validation are required. There is promise for the development of a resect and discard policy for diminutive adenomas by using electronic chromoendoscopy; however, before this can be adopted, further community-based studies are needed. Further validated training tools for NBI, FICE, and i-SCAN will also be required for the use of these techniques to become widespread.

  View details for DOI 10.1016/j.gie.2014.06.020

  View details for Web of Science ID 000348201600001

  View details for PubMedID 25484330

• Confocal laser endomicroscopy GASTROINTESTINAL ENDOSCOPY Chauhan, S. S., Abu Dayyeh, B. K., Bhat, Y. M., Gottlieb, K. T., Hwang, J. H., Komanduri, S., Konda, V., Lo, S. K., Manfredi, M. A., Maple, J. T., Murad, F. M., Siddiqui, U. D., Banerjee, S., Wallace, M. B. 2014; 80 (6): 928-938

  View details for DOI 10.1016/j.gie.2014.06.021

  View details for Web of Science ID 000346441600002

  View details for PubMedID 25442092

• High-definition and high-magnification endoscopes GASTROINTESTINAL ENDOSCOPY Bhat, Y. M., Abu Dayyeh, B. K., Chauhan, S. S., Gottlieb, K. T., Hwang, J. H., Komanduri, S., Konda, V., Lo, S. K., Manfredi, M. A., Maple, J. T., Murad, F. M., Siddiqui, U. D., Banerjee, S., Wallace, M. B. 2014; 80 (6): 919-927

  View details for DOI 10.1016/j.gie.2014.06.019

  View details for Web of Science ID 000346441600001

  View details for PubMedID 25442091

• A New Active Cavitation Mapping Technique for Pulsed HIFU Applications-Bubble Doppler IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Li, T., Khokhlova, T. D., Sapozhnikov, O. A., O'Donnell, M., Hwang, J. H. 2014; 61 (10): 1698-1708

  Abstract

  In this work, a new active cavitation mapping technique for pulsed high-intensity focused ultrasound (pHIFU) applications termed bubble Doppler is proposed and its feasibility is tested in tissue-mimicking gel phantoms. pHIFU therapy uses short pulses, delivered at low pulse repetition frequency, to cause transient bubble activity that has been shown to enhance drug and gene delivery to tissues. The current gold standard for detecting and monitoring cavitation activity during pHIFU treatments is passive cavitation detection (PCD), which provides minimal information on the spatial distribution of the bubbles. B-mode imaging can detect hyperecho formation, but has very limited sensitivity, especially to small, transient microbubbles. The bubble Doppler method proposed here is based on a fusion of the adaptations of three Doppler techniques that had been previously developed for imaging of ultrasound contrast agents-color Doppler, pulse-inversion Doppler, and decorrelation Doppler. Doppler ensemble pulses were interleaved with therapeutic pHIFU pulses using three different pulse sequences and standard Doppler processing was applied to the received echoes. The information yielded by each of the techniques on the distribution and characteristics of pHIFU-induced cavitation bubbles was evaluated separately, and found to be complementary. The unified approach-bubble Doppler-was then proposed to both spatially map the presence of transient bubbles and to estimate their sizes and the degree of nonlinearity.

  View details for DOI 10.1109/TUFFC.2014.006502

  View details for Web of Science ID 000345085200011

  View details for PubMedID 25265178

  View details for PubMedCentralID PMC4454370

• Technologies for monitoring the quality of endoscope reprocessing GASTROINTESTINAL ENDOSCOPY Komanduri, S., Abu Dayyeh, B. K., Bhat, Y. M., Chauhan, S. S., Gottlieb, K. T., Hwang, J. H., Konda, V., Lo, S. K., Manfredi, M., Maple, J. T., Murad, F. M., Siddiqui, U. D., Wallace, M. B., Banerjee, S. 2014; 80 (3): 369-373

  View details for DOI 10.1016/j.gie.2014.01.044

  View details for Web of Science ID 000341153400001

  View details for PubMedID 25012558

• The role of endoscopy in the management of variceal hemorrhage GASTROINTESTINAL ENDOSCOPY Hwang, J. H., Shergill, A. K., Acosta, R. D., Chandrasekhara, V., Chathadi, K. V., Decker, G. A., Early, D. S., Evans, J. A., Fanelli, R. D., Fisher, D. A., Foley, K. Q., Fonkalsrud, L., Jue, T., Khashab, M. A., Lightdale, J. R., Muthusamy, V. R., Pasha, S. F., Saltzman, J. R., Sharaf, R., Cash, B. D. 2014; 80 (2): 221-227

  View details for DOI 10.1016/j.gie.2013.07.023

  View details for Web of Science ID 000341151700002

  View details for PubMedID 25034836

• PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS ULTRASOUND IN MEDICINE AND BIOLOGY Li, T., Chen, H., Khokhlova, T., Wang, Y., Kreider, W., He, X., Hwang, J. H. 2014; 40 (7): 1523-1534

  Abstract

  Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped over the first few pulses ex vivo. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors.

  View details for DOI 10.1016/j.ultrasmedbio.2014.01.007

  View details for Web of Science ID 000341459000019

  View details for PubMedID 24613635

  View details for PubMedCentralID PMC4048799

• Scanning fiber endoscopy: a novel platform for cholangioscopy GASTROINTESTINAL ENDOSCOPY Templeton, A. W., Webb, K., Hwang, J. H., Seibel, E. J., Saunders, M. 2014; 79 (6): 1000-1001

  View details for DOI 10.1016/j.gie.2013.12.005

  View details for Web of Science ID 000336497700018

  View details for PubMedID 24462166

• The role of endoscopy in the patient with lower GI bleeding GASTROINTESTINAL ENDOSCOPY Pasha, S. F., Shergill, A., Acosta, R. D., Chandrasekhara, V., Chathadi, K. V., Early, D., Evans, J. A., Fisher, D., Fonkalsrud, L., Hwang, J. H., Khashab, M. A., Lightdale, J. R., Muthusamy, V. R., Saltzman, J. R., Cash, B. D. 2014; 79 (6): 875-885

  View details for DOI 10.1016/j.gie.2013.10.039

  View details for Web of Science ID 000336497700001

  View details for PubMedID 24703084

• Modifications in endoscopic practice for pediatric patients GASTROINTESTINAL ENDOSCOPY Lightdale, J. R., Lightdale, J. R., Acosta, R., Shergill, A. K., Chandrasekhara, V., Chathadi, K., Early, D., Evans, J. A., Fanelli, R. D., Fisher, D. A., Fonkalsrud, L., Hwang, J. H., Kashab, M., Muthusamy, V. R., Pasha, S., Saltzman, J. R., Cash, B. D. 2014; 79 (5): 699-710

  Abstract

  We recommend that endoscopy in children be performed by pediatric-trained endoscopists whenever possible. We recommend that adult-trained endoscopists coordinate their services with pediatricians and pediatric specialists when they are needed to perform endoscopic procedures in children. We recommend that endoscopy be performed within 24 hours in symptomatic pediatric patients with known or suspected ingestion of caustic substances. We recommend emergent foreign-body removal of esophageal button batteries, as well as 2 or more rare-earth neodymium magnets. We recommend that procedural and resuscitative equipment appropriate for pediatric use should be readily available during endoscopic procedures. We recommend that personnel trained specifically in pediatric life support and airway management be readily available during sedated procedures in children. We recommend the use of endoscopes smaller than 6 mm in diameter in infants and children weighing less than 10 kg. We recommend the use of standard adult duodenoscopes for performing ERCP in children who weigh at least 10 kg. We recommend the placement of 12F or 16F percutaneous endoscopic gastrostomy tubes in children who weigh less than 50 kg.

  View details for DOI 10.1016/j.gie.2013.08.014

  View details for Web of Science ID 000334299300001

  View details for PubMedID 24593951

• The role of endoscopy in the evaluation and management of dysphagia GASTROINTESTINAL ENDOSCOPY Pasha, S. F., Acosta, R. D., Chandrasekhara, V., Chathadi, K. V., Decker, G. A., Early, D. S., Evans, J. A., Fanelli, R. D., Fisher, D. A., Foley, K. Q., Fonkalsrud, L., Hwang, J. H., Jue, T. L., Khashab, M. A., Lightdale, J. R., Muthusamy, V. R., Sharaf, R., Saltzman, J. R., Shergill, A. K., Cash, B. 2014; 79 (2): 191-201

  View details for DOI 10.1016/j.gie.2013.07.042

  View details for Web of Science ID 000329759200001

  View details for PubMedID 24332405

• Gastric Cancer in Asian American Populations: a Neglected Health Disparity ASIAN PACIFIC JOURNAL OF CANCER PREVENTION Taylor, V. M., Ko, L. K., Hwang, J. H., Sin, M., Inadomi, J. M. 2014; 15 (24): 10565-10571

  Abstract

  Gastric cancer incidence rates vary dramatically by world region with East Asia having the highest rate. The Asian population of the United States (US) is growing rapidly and over 17 million Americans are of Asian descent. A majority of Chinese, Korean and Vietnamese Americans are immigrants. Americans of East and Southeast Asian descent experience marked gastric cancer disparities and the incidence rate among Korean men in the US is over five times higher than the incidence rate among non-Hispanic white men. Randomized controlled trials have provided evidence for the effectiveness of helicobacter pylori identification and eradication in preventing gastric cancer. Additionally, Japan and South Korea have both experienced improvements in gastric cancer mortality following the implementation of programs to detect early stage gastric cancers. There are currently no clear US guidelines regarding the primary and secondary prevention of gastric cancer in high-risk immigrant populations. However, it is likely that a proportion of US physicians are already recommending gastric cancer screening for Asian patients and some Asian immigrants to the US may be completing screening for gastric cancer in their native countries. Surveys of US primary care physicians and Asian American communities should be conducted to assess current provider practices and patient uptake with respect to gastric cancer prevention and control. In the absence of clinical guidelines, US health care providers who serve high-risk Asian groups could consider a shared decision-making approach to helicobacter pylori identification and eradication, as well as gastric endoscopy.

  View details for DOI 10.7314/APJCP.2014.15.24.10565

  View details for Web of Science ID 000351058900003

  View details for PubMedID 25605140

• Endoscopic ultrasound-guided tumor ablation Gastrointest Interv Ende, A. R., Hwang, J. 2014; 3: 27-29
• A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance ENDOSCOPY Konda, V. J., Meining, A., Jamil, L. H., Giovannini, M., Hwang, J. H., Wallace, M. B., Chang, K. J., Siddiqui, U. D., Hart, J., Lo, S. K., Saunders, M. D., Aslanian, H. R., Wroblewski, K., Waxman, I. 2013; 45 (12): 1006-1013

  Abstract

  Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) of pancreatic cystic lesions (PCL) is flawed by inadequate diagnostic yield. Needle-based confocal laser endomicroscopy (nCLE) utilizes a sub-millimeter probe that is compatible with an EUS needle and enables real-time imaging with microscopic detail of PCL. The aims of the In vivo nCLE Study in the Pancreas with Endosonography of Cystic Tumors (INSPECT) pilot study were to assess both the diagnostic potential of nCLE in differentiating cyst types and the safety of the technique.Eight referral centers performed nCLE in patients with PCL. Stage 1 defined descriptive terms for structures visualized by an off-line, unblinded consensus review. Cases were reviewed with a gastrointestinal pathologist to identify correlations between histology and nCLE. Stage 2 assessed whether the specific criteria defined in Stage 1 could identify pancreatic cystic neoplasms (PCN) including intraductal papillary mucinous neoplasms, mucinous cystic adenoma, or adenocarcinoma in an off-line blinded consensus review.A total of 66 patients underwent nCLE imaging and images were available for 65, 8 of which were subsequently excluded due to insufficient information for consensus reference diagnosis. The presence of epithelial villous structures based on nCLE was associated with PCN (P=0.004) and provided a sensitivity of 59%, specificity of 100%, positive predictive value of 100 %, and negative predictive value of 50%. The overall complication rate was 9% and included pancreatitis (1 mild case, 1 moderate case), transient abdominal pain (n=1), and intracystic bleeding not requiring any further measures (n=3).These preliminary data suggested that nCLE has a high specificity in the detection of PCN, but may be limited by a low sensitivity. The safety of nCLE requires further evaluation.

  View details for DOI 10.1055/s-0033-1344714

  View details for Web of Science ID 000327471700005

  View details for PubMedID 24163192

• Endoscopic Ultrasound-Fine Needle Aspiration versus Core Biopsy for the Diagnosis of Subepithelial Tumors. Clinical endoscopy Webb, K., Hwang, J. H. 2013; 46 (5): 441-444

  Abstract

  Subepithelial lesions are frequently encountered and remain a diagnostic challenge. Imaging of subepithelial lesions using endoscopic ultrasound (EUS) can be helpful in narrowing the differential diagnosis of the lesion; however, definitive diagnosis typically requires tissue. Many methods for acquiring tissue exist including EUS-guided fine needle aspiration, Trucut biopsy, and fine needle biopsy. Obtaining adequate tissue is important for cytologic and histologic exams including immunohistochemical stains, thus a great deal of effort has been made to increase tissue acquisition in order to improve diagnostic yield in subepithelial lesions.

  View details for DOI 10.5946/ce.2013.46.5.441

  View details for PubMedID 24143299

  View details for PubMedCentralID PMC3797922

• The use of twinkling artifact of Doppler imaging to monitor cavitation in tissue during high intensity focused ultrasound therapy. Proceedings of meetings on acoustics . Acoustical Society of America Khokhlova, T., Li, T., Sapozhnikov, O., Hwang, J. H. 2013; 19 (1)

  Abstract

  In high intensity focused ultrasound (HIFU) therapy, it is important to monitor the presence and activity of microbubbles in tissue during treatment. The current methods, - passive cavitation detection (PCD) and B-mode imaging - have limited sensitivity, especially to small-size, non-violently-collapsing microbubbles. Here, a new method for microbubble detection is proposed, based on "twinkling" artifact (TA) of Doppler imaging. TA occurs when Color Doppler ultrasound is used to image hard objects in tissue (e.g., kidney stones), and is displayed as brightly colored spots. As demonstrated recently, TA can be explained by irregular scattering of the Doppler ensemble pulses from the fluctuating microbubbles trapped in crevices of the kidney stone. In this work, TA was used to detect cavitation in tissue and in polyacrylamide gel phantoms during pulsed 1 MHz HIFU exposures with different peak negative pressures (1.5-11 MPa). At each pressure level, the probability of cavitation occurrence was characterized using TA and the broadband signals recorded by PCD, aligned confocally with the HIFU transducer. The results indicate that TA is more sensitive to the onset of cavitation than conventional PCD detection, and allows for accurate spatial localization of the bubbles. Work supported by RFBR and NIH (EB007643, 1K01EB015745, R01CA154451).

  View details for PubMedID 26185591

  View details for PubMedCentralID PMC4501386

• HISTOLOGICAL AND BIOCHEMICAL ANALYSIS OF MECHANICAL AND THERMAL BIOEFFECTS IN BOILING HISTOTRIPSY LESIONS INDUCED BY HIGH INTENSITY FOCUSED ULTRASOUND ULTRASOUND IN MEDICINE AND BIOLOGY Wang, Y., Khokhlova, T., Bailey, M., Hwang, J. H., Khokhlova, V. 2013; 39 (3): 424-438

  Abstract

  Recent studies have shown that shockwave heating and millisecond boiling in high-intensity focused ultrasound fields can result in mechanical fractionation or emulsification of tissue, termed boiling histotripsy. Visual observations of the change in color and contents indicated that the degree of thermal damage in the emulsified lesions can be controlled by varying the parameters of the exposure. The goal of this work was to examine thermal and mechanical effects in boiling histotripsy lesions using histologic and biochemical analysis. The lesions were induced in ex vivo bovine heart and liver using a 2-MHz single-element transducer operating at duty factors of 0.005-0.01, pulse durations of 5-500 ms and in situ shock amplitude of 73 MPa. Mechanical and thermal damage to tissue was evaluated histologically using conventional staining techniques (hematoxylin and eosin, and nicotinamide adenine dinucleotide-diaphorase). Thermal effects were quantified by measuring denaturation of salt soluble proteins in the treated region. According to histologic analysis, the lesions that visually appeared as a liquid contained no cellular structures larger than a cell nucleus and had a sharp border of one to two cells. Both histologic and protein analysis showed that lesions obtained with short pulses (<10 ms) did not contain any thermal damage. Increasing the pulse duration resulted in an increase in thermal damage. However, both protein analysis and nicotinamide adenine dinucleotide-diaphorase staining showed less denaturation than visually observed as whitening of tissue. The number of high-intensity focused ultrasound pulses delivered per exposure did not change the lesion shape or the degree of thermal denaturation, whereas the size of the lesion showed a saturating behavior suggesting optimal exposure duration. This study confirmed that boiling histotripsy offers an effective, predictable way to non-invasively fractionate tissue into sub-cellular fragments with or without inducing thermal damage.

  View details for DOI 10.1016/j.ultrasmedbio.2012.10.012

  View details for Web of Science ID 000314872200007

  View details for PubMedID 23312958

  View details for PubMedCentralID PMC3570648

• Ultrasound-targeted microbubble destruction for chemotherapeutic drug delivery to solid tumors. Journal of therapeutic ultrasound Chen, H., Hwang, J. H. 2013; 1: 10-?

  Abstract

  Ultrasound-targeted microbubble destruction (UTMD) is a promising technique for non-invasive, targeted drug delivery, and its applications in chemotherapeutic drug delivery to solid tumors have attracted growing interest. Ultrasound, which has been conventionally used for diagnostic imaging, has evolved as a promising tool for therapeutic applications mainly because of its ability to be focused deep inside the human body, providing a modality for targeted delivery. Although originally being introduced into clinics as ultrasound contrast agents, microbubbles (MBs) have been developed as a diagnostic and therapeutic agent that can both be tracked through non-invasive imaging and deliver therapeutic agents selectively at ultrasound-targeted locations. Whereas free drugs often possess harmful side effects, their encapsulation in MBs and subsequent local release at the targeted tissue by ultrasound triggering may help improve the margin of safety. In the past 10 years, the feasibility and safety of UTMD have been extensively tested using normal animal models. Most recently, a growing number of preclinical studies have been reported on the therapeutic benefits of UTMD in the delivery of chemotherapeutic drugs to various malignant tumors, such as brain, liver, eyelid, pancreas, and breast tumors. Increased drug concentration in tumors and reduced tumor sizes were achieved in those tumors treated with UTMD in combination with chemotherapeutic drugs, when compared to tumors treated with chemotherapy drugs alone. This review presents an overview of current preclinical applications of UTMD in chemotherapeutic drug delivery for the treatment of cancers along with a discussion of its future developments.

  View details for DOI 10.1186/2050-5736-1-10

  View details for PubMedID 25512858

  View details for PubMedCentralID PMC4265893

• The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus. Journal of therapeutic ultrasound Aubry, J., Pauly, K. B., Moonen, C., Haar, G. t., Ries, M., Salomir, R., Sokka, S., Sekins, K. M., Shapira, Y., Ye, F., Huff-Simonin, H., Eames, M., Hananel, A., Kassell, N., Napoli, A., Hwang, J. H., Wu, F., Zhang, L., Melzer, A., Kim, Y., Gedroyc, W. M. 2013; 1: 13-?

  Abstract

  Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.

  View details for DOI 10.1186/2050-5736-1-13

  View details for PubMedID 25512859

• Controllable in vivo hyperthermia effect induced by pulsed high intensity focused ultrasound with low duty cycles APPLIED PHYSICS LETTERS Tu, J., Hwang, J. H., Chen, T., Fan, T., Guo, X., Crum, L. A., Zhang, D. 2012; 101 (12)

  Abstract

  High intensity focused ultrasound (HIFU)-induced hyperthermia is a promising tool for cancer therapy. Three-dimensional nonlinear acoustic-bioheat transfer-blood flow-coupling model simulations and in vivo thermocouple measurements were performed to study hyperthermia effects in rabbit auricular vein exposed to pulsed HIFU (pHIFU) at varied duty cycles (DCs). pHIFU-induced temperature elevations are shown to increase with increasing DC. A critical DC of 6.9% is estimated for temperature at distal vessel wall exceeding 44 °C, although different tissue depths and inclusions could affect the DC threshold. The results demonstrate clinic potentials of achieving controllable hyperthermia by adjusting pHIFU DCs, while minimizing perivascular thermal injury.

  View details for DOI 10.1063/1.4754113

  View details for Web of Science ID 000309425700105

  View details for PubMedID 23112347

• Multicenter, randomized, controlled trial of confocal laser endomicroscopy assessment of residual metaplasia after mucosal ablation or resection of GI neoplasia in Barrett's esophagus GASTROINTESTINAL ENDOSCOPY Wallace, M. B., Crook, J. E., Saunders, M., Lovat, L., Coron, E., Waxman, I., Sharma, P., Hwang, J. H., Banks, M., Depreville, M., Galmiche, J. P., Konda, V., Diehl, N. N., Wolfsen, H. C. 2012; 76 (3): 539-?

  Abstract

  Endoscopic ablation is an accepted standard for neoplasia in Barrett's esophagus (BE). Eradication of all glandular mucosa in the distal esophagus cannot be reliably determined at endoscopy.To assess if use of probe-based confocal laser endomicroscopy (pCLE) in addition to high-definition white light (HDWL) could aid in determination of residual BE.Prospective, multicenter, randomized, clinical trial.Academic medical centers.Patients with Barrett's esophagus undergoing ablation.After an initial attempt at ablation, patients were followed-up either with HDWL endoscopy or HDWL plus pCLE, with treatment of residual metaplasia or neoplasia based on endoscopic findings and pCLE used to avoid overtreatment.The proportion of optimally treated patients, defined as those with residual BE who were treated and had complete ablation plus those without BE who were not treated and had no evidence of disease at follow-up.The study was halted at the planned interim analysis based on a priori criteria. After enrollment was halted, all patients who had been randomized were followed to study completion. Among the 119 patients with follow-up, there was no difference in the proportion of patients achieving optimal outcomes in the two groups (15/57, 26% for HDWL; 17/62, 27% with HDWL + pCLE). Other outcomes were similar in the two groups.The study was closed after the interim analysis due to low conditional power resulting from lack of difference between groups as well as higher-than-expected residual Barrett's esophagus in both arms.This study yields no evidence that the addition of pCLE to HDWL imaging for detection of residual Barrett's esophagus or neoplasia can provide improved treatment.

  View details for DOI 10.1016/j.gie.2012.05.004

  View details for Web of Science ID 000307948600013

  View details for PubMedID 22749368

• In vivo hyperthermia effect induced by high-intensity pulsed ultrasound CHINESE PHYSICS B Cui, W., Tu, J., Hwang, J., Li, Q., Fan, T., Zhang, D., Chen, J., Chen, W. 2012; 21 (7)

  View details for DOI 10.1088/1674-1056/21/7/074301

  View details for Web of Science ID 000306558300054

• The role of endoscopy in the management of acute non-variceal upper GI bleeding GASTROINTESTINAL ENDOSCOPY Hwang, J. H., Fisher, D. A., Ben-Menachem, T., Chandrasekhara, V., Chathadi, K., Decker, G. A., Early, D. S., Evans, J. A., Fanelli, R. D., Foley, K., Fukami, N., Jain, R., Jue, T. L., Khan, K. M., Lightdale, J., Malpas, P. M., Maple, J. T., Pasha, S., Saltzman, J., Sharaf, R., Shergill, A. K., Dominitz, J. A., Cash, B. D. 2012; 75 (6): 1132-1138

  View details for DOI 10.1016/j.gie.2012.02.033

  View details for Web of Science ID 000305453700002

  View details for PubMedID 22624808

• TARGETED LONG-TERM VENOUS OCCLUSION USING PULSED HIGH-INTENSITY FOCUSED ULTRASOUND COMBINED WITH A PRO-INFLAMMATORY AGENT ULTRASOUND IN MEDICINE AND BIOLOGY Zhou, Y., Zia, J., Warren, C., Starr, F. L., Brayman, A. A., Crum, L. A., Hwang, J. H. 2011; 37 (10): 1653-1658

  Abstract

  Esophageal and gastric varices are associated with significant morbidity and mortality for cirrhotic patients. The current modalities available for treating bleeding esophageal and gastric varices, namely endoscopic band ligation and sclerotherapy, require frequent sessions to obtain effective thrombosis and are associated with significant adverse effects. A more effective therapy that results in long-term vascular occlusion has the potential to improve patient outcomes. In this study, we investigated a new potential method for inducing long-term vascular occlusion by targeting segments of a rabbit's auricular vein in vivo with low-duty-cycle, high-peak-rarefaction pressure (9 MPa), pulsed high-intensity focused ultrasound in the presence of intravenously administered ultrasound microbubbles followed by local injection of fibrinogen and a pro-inflammatory agent (ethanol, cyanoacrylate or morrhuate sodium). The novel method introduced in this study resulted in acute and long-term complete vascular occlusions when injecting a pro-inflammatory agent with fibrinogen. Future investigation and translational studies are needed to assess its clinical applicability.

  View details for DOI 10.1016/j.ultrasmedbio.2011.06.007

  View details for Web of Science ID 000295541600013

  View details for PubMedID 21821352

• Assessment of a simple, novel endoluminal method for gastrotomy closure in NOTES SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Lee, S. S., Oelschlager, B. K., Wright, A. S., Soares, R. V., Sinan, H., Montenovo, M. I., Hwang, J. H. 2011; 25 (10): 3448-3452

  Abstract

  A reliable method for gastrotomy closure in NOTES will be essential for NOTES to become viable clinically. However, methods using existing and widely available endoscopic accessories have been ineffective. The objective of this study was to evaluate the feasibility and safety of a new simple method for gastric closure (retracted clip-assisted loop closure) that uses existing endoscopic accessories with minor modifications.The retracted clip-assisted loop closure technique involves deploying 3-4 Resolution(®) clips (modified by attaching a 90-cm length of suture to the end of each clip) along the margin of the gastrotomy with one jaw on the serosal surface and the other jaw on the mucosal surface. The suture strings are threaded through an endoloop. Traction is then applied to the strings causing the gastric wall to tent. The endoloop is secured below the tip of the clips, completing a full-thickness gastrotomy closure. The main outcome measures were feasibility, efficacy, and safety of the new retracted clip-assisted loop closure technique for NOTES gastrotomy closure.An air-tight seal was achieved in 100% (n = 9) of stomachs. The mean leak pressure was 116.3 (±19.4) mmHg.The retracted clip-assisted loop closure technique can be used to perform NOTES gastrotomy closure by using existing endoscopic accessories with minor modifications.

  View details for DOI 10.1007/s00464-011-1730-1

  View details for Web of Science ID 000294964600052

  View details for PubMedID 21556990

• THE EFFECT OF THE SCANNING PATHWAY IN HIGH-INTENSITY FOCUSED ULTRASOUND THERAPY ON LESION PRODUCTION ULTRASOUND IN MEDICINE AND BIOLOGY Zhou, Y., Kargl, S. G., Hwang, J. H. 2011; 37 (9): 1457-1468

  Abstract

  Because tumors are much larger in size compared with the beam width of high-intensity focused ultrasound (HIFU), raster scanning throughout the entire target is conventionally performed for HIFU thermal ablation. Thermal diffusion affects the temperature elevation and the consequent lesion formation. As a result, the lesion will grow continuously over the course of HIFU therapy. The purpose of this study was to investigate the influence of scanning pathways on the overall thermal lesion. Two new scanning pathways, spiral scanning from the center to the outside and spiral scanning from the outside to the center, were proposed with the same HIFU parameters (power and exposure time) for each treatment spot. The lesions produced in the gel phantom and bovine liver were compared with those using raster scanning. Although more uniform lesions can be achieved using the new scanning pathways, the produced lesion areas (27.5 ± 12.3 mm(2) and 65.2 ± 9.6 mm(2), respectively) in the gel phantom are significantly smaller (p < 0.05) than those using raster scanning (92.9 ± 11.8 mm(2)). Furthermore, the lesion patterns in the gel phantom and bovine liver were similar to the simulations using temperature and thermal dose-threshold models, respectively. Thermal diffusion, the scanning pathway and the biophysical aspects of the target all play important roles in HIFU lesion production. By selecting the appropriate scanning pathway and varying the parameters as ablation progresses, HIFU therapy can achieve uniform lesions while minimizing the total delivered energy and treatment time.

  View details for DOI 10.1016/j.ultrasmedbio.2011.05.848

  View details for Web of Science ID 000293449400012

  View details for PubMedID 21775048

• Barrett's esophagus: surveillance and reversal 10th World Congress of the World Organization for Specialized Studies on Diseases of the Esophagus (OESO) Caygill, C. P., Dvorak, K., Triadafilopoulos, G., Felix, V. N., Horwhat, J. D., Hwang, J. H., Upton, M. P., Li, X., Nandurkar, S., Gerson, L. B., Falk, G. W. BLACKWELL SCIENCE PUBL. 2011: 196–209

  Abstract

  The following on surveillance and reversal of Barrett's esophagus (BE) includes commentaries on criteria for surveillance even when squamous epithelium stains normally with a variety of biomarkers; the long-term follow-up of surgery versus endoscopic ablation of BE; the recommended surveillance intervals in patients without dysplasia; the sampling problems related to anatomic changes following fundoplication; the value of tissue spectroscopy and optical coherence tomography; the cost-effectiveness of biopsy protocols for surveillance; the quality of life of Barrett's patients; and risk stratification and surveillance strategies.

  View details for DOI 10.1111/j.1749-6632.2011.06052.x

  View details for Web of Science ID 000301188400012

  View details for PubMedID 21950814

• Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer GUT AND LIVER Jang, H. j., Lee, J., Lee, D., Kim, W., Hwang, J. H. 2010; 4: S57-S61

  Abstract

  High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

  View details for DOI 10.5009/gnl.2010.4.S1.S57

  View details for Web of Science ID 000281932700009

  View details for PubMedID 21103296

• Robust High-Resolution Fine OCT Needle for Side-Viewing Interstitial Tissue Imaging IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS Wu, Y., Xi, J., Huo, L., Padvorac, J., Shin, E. J., Giday, S. A., Lennon, A. M., Canto, M. I., Hwang, J. H., Li, X. 2010; 16 (4): 863-869

  View details for DOI 10.1109/JSTQE.2009.2035362

  View details for Web of Science ID 000283541100017

• Imaging of subsquamous Barrett's epithelium with ultrahigh-resolution optical coherence tomography: a histologic correlation study GASTROINTESTINAL ENDOSCOPY Cobb, M. J., Hwang, J. H., Upton, M. P., Chen, Y., Oelschlager, B. K., Wood, D. E., Kimmey, M. B., Li, X. 2010; 71 (2): 223-230

  Abstract

  Optical coherence tomography (OCT) is being developed as a potentially valuable method for high-resolution cross-sectional imaging of the esophageal mucosal and submucosal layers. One potential application of OCT imaging is to identify subsquamous Barrett's epithelium in patients who have undergone ablative therapy, which is not visible on standard endoscopic examination. However, histologic correlation confirming the ability of OCT to image subsquamous Barrett's epithelium has yet to be performed.Histologic correlation study.To perform histologic correlation of ultrahigh-resolution optical coherence tomography (UHR-OCT) imaging for identification of subsquamous Barrett's epithelium.Academic Medical Center (University of Washington, Seattle, WA).Fourteen patients with pathologic biopsy specimens, proven to be high-grade dysplasia or adenocarcinoma underwent esophagectomy.UHR-OCT imaging was performed on ex vivo esophagectomy specimens immediately after resection.Correlation of UHR-OCT images with histologic images.Subsquamous Barrett's epithelium was clearly identified by using UHR-OCT images and was confirmed by corresponding histology.Difficulty distinguishing some subsquamous Barrett's glands from blood vessels in ex vivo tissue (because of the lack of blood flow) in some cases. Imaging was performed with a bench-top system.Results from this study demonstrate that UHR-OCT imaging is capable of identifying subsquamous Barrett's epithelium.

  View details for DOI 10.1016/j.gie.2009.07.005

  View details for Web of Science ID 000274777200001

  View details for PubMedID 19846077

• Targeted Venous Occlusion Using Pulsed High-Intensity Focused Ultrasound IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Hwang, J. H., Zhou, Y., Warren, C., Brayman, A. A., Crum, L. A. 2010; 57 (1): 37-40

  Abstract

  Targeted vascular occlusion is desirable for clinical therapies such as in the treatment of esophageal and gastric varices and varicose veins. The feasibility of ultrasound-mediated endothelial damage for vascular occlusion was studied. A segment of a rabbit auricular vein was treated in vivo with low duty cycle, high peak rarefaction pressure (9 MPa) high-intensity focused ultrasound pulses in the presence of intravenously administered circulating microbubbles, followed by fibrinogen injection, which resulted in the formation of an acute occlusive intravascular thrombus. Further investigation and refinements of treatment protocols are necessary for producing durable vascular occlusion.

  View details for DOI 10.1109/TBME.2009.2029865

  View details for Web of Science ID 000273565600009

  View details for PubMedID 19709959

• High-resolution OCT balloon imaging catheter with astigmatism correction OPTICS LETTERS Xi, J., Huo, L., Wu, Y., Cobb, M. J., Hwang, J. H., Li, X. 2009; 34 (13): 1943-1945

  Abstract

  We report new optics designs for an optical coherence tomography (OCT) balloon imaging catheter to achieve diffraction-limited high resolution at a large working distance and enable the correction of severe astigmatism in the catheter. The designs employed a 1 mm diameter gradient-index lens of a properly chosen pitch number and a glass rod spacer to fully utilize the available NA of the miniature optics. Astigmatism caused by the balloon tubing was analyzed, and a method based on a cylindrical reflector was proposed and demonstrated to compensate the astigmatism. A catheter based on the new designs was successfully developed with a measured diffraction-limited lateral resolution of approximately 21 microm, a working distance of approximately 11-12 mm, and a round-shape beam profile. The performance of the OCT balloon catheter was demonstrated by 3D full-circumferential imaging of a swine esophagus in vivo along with a high-speed, Fourier-domain, mode-locked swept-source OCT system.

  View details for Web of Science ID 000268376200011

  View details for PubMedID 19571960

  View details for PubMedCentralID PMC4259896

• PRECLINICAL IN VIVO EVALUATION OF AN EXTRACORPOREAL HIFU DEVICE FOR ABLATION OF PANCREATIC TUMORS ULTRASOUND IN MEDICINE AND BIOLOGY Hwang, J. H., Wang, Y., Warren, C., Upton, M. P., Starr, F., Zhou, Y., Mitchell, S. B. 2009; 35 (6): 967-975

  Abstract

  Extracorporeal high-intensity focused ultrasound (HIFU) can be used to ablate tissue noninvasively by delivering focused ultrasound energy from an external source. HIFU for clinical treatment of pancreatic cancer has been reported; however, systematic evaluation of the safety and efficacy of pancreatic ablation with HIFU has not been performed. The objectives of this in vivo study are as follows: (1) assess the safety and feasibility of targeting and ablating pancreatic tissue using the FEP-BY02 HIFU system (Yuande Bio-Medical Engineering, Beijing, China); (2) evaluate a method for estimating in situ acoustic treatment energy in an in vivo setting; and (3) identify the optimal treatment parameters that result in safe and effective ablation of the pancreas. The pancreata of 12 common swine were treated in vivo. Prior to therapy, blood was drawn for laboratory analysis. Animals were then treated with extracorporeal HIFU at three different acoustic treatment energies (750, 1000 and 1250 J). Endoscopy was performed prior to and immediately following HIFU therapy to assess for gastric injury. Blood was drawn after completion of the treatment and on days 2 and 7 following treatment to assess for biochemical evidence of pancreatitis. Animals were then euthanized 7 d following treatment and a necropsy was performed to assess for unintended injury and to obtain pancreatic tissue for histology to assess efficacy of HIFU ablation. Histologic scoring of pancreatic tissue changes was performed by a pathologist blinded to the treatment energy delivered. The degree of ablation identified on histology correlated with the treatment energy. No collateral tissue damage was seen at treatment energies of 750 and 1000 J. At 1250 J, thermal injury to the abdominal muscles and gastric ulcers were observed. There were no premature deaths, serious illnesses, skin burns or evidence of pancreatitis on biochemical analysis. HIFU treatment of the pancreas is feasible, safe and can be used to ablate tissue noninvasively. A clinical trial in humans examining the use of extracorporeal HIFU for palliation of pain related to pancreatic cancer is planned.

  View details for DOI 10.1016/j.ultrasmedbio.2008.12.006

  View details for Web of Science ID 000267110700011

  View details for PubMedID 19201519

• Current Status of Clinical High-Intensity Focused Ultrasound 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 Hwang, J. H., Crum, L. A. 2009: 130-133

  Abstract

  High-intensity focused ultrasound (HIFU) is being promoted as a noninvasive method to treat certain primary solid tumors, metastatic disease, and enhance drug delivery. The field of medicine is evolving towards increasing use of noninvasive and minimally invasive therapies such as HIFU. This article provides an overview of current clinical applications of HIFU and future requirements to expand the clinical applications of this technique.

  View details for Web of Science ID 000280543600034

  View details for PubMedID 19965122

• Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy JOURNAL OF GASTROENTEROLOGY Schlansky, B., Hwang, J. H. 2009; 44: 44-52

  Abstract

  Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, antipyretic, and antiinflammatory properties, and aspirin is increasingly employed in the primary and secondary prevention of cardiovascular disease and ischemic stroke. Despite undisputed therapeutic efficacy for these indications, all NSAIDs impart a considerable risk of peptic ulcer disease and upper gastrointestinal hemorrhage. A growing body of evidence supports an association between non-aspirin NSAIDs and acute coronary syndromes, and an expanding understanding of the gastroduodenal effects of aspirin, COX-2 selective agents, clopidogrel, and Helicobacter pylori synergism fuel controversies in NSAID use. In this review, we discuss risk stratification of patients taking NSAIDs and the appropriate application of proven gastro-protective strategies to decrease the incidence of gastrointestinal hemorrhage based upon an individualized assessment of risk for potential toxicities. Prevention of NSAID-related gastropathy is an important clinical issue, and therapeutic strategies for both the primary and secondary prevention of adverse events are continually evolving.

  View details for DOI 10.1007/s00535-008-2275-5

  View details for Web of Science ID 000262689000008

  View details for PubMedID 19148793

• Endomicroscopy and Biocompatible Fluorescent Nanocomplexes for Clinical Translation of High-resolution Optical Molecular Imaging 2009 IEEE/NIH LIFE SCIENCE SYSTEMS AND APPLICATIONS WORKSHOP Xi, J., Wu, Y., Kim, T. H., Chen, Y., Zheng, D., Huo, L., Cobb, M. J., Pun, S., Hwang, J. H., Li, X. 2009: 48-?

  View details for Web of Science ID 000268062300013

• Flexible miniature compound lens design for high-resolution optical coherence tomography balloon imaging catheter JOURNAL OF BIOMEDICAL OPTICS Fu, H. L., Leng, Y., Cobb, M. J., Hsu, K., Hwang, J. H., Li, X. 2008; 13 (6)

  Abstract

  We report on a new optics design for an optical coherence tomography (OCT) balloon imaging catheter. The design involves a miniature compound gradient-index (GRIN) rod lens, which consists of a fiber optic mode-field reducer and relay rod lenses to achieve predictable high lateral resolution at a desired large working distance. The compound lens design significantly simplifies the engineering process for an OCT catheter and enables 3-D full circumferential cross sectional imaging of large luminal organs such as human esophagus. An as-designed OCT catheter is developed and demonstrated for real-time in vivo swine esophagus imaging in a 3-D spiral fashion.

  View details for DOI 10.1117/1.3037340

  View details for Web of Science ID 000263100900002

  View details for PubMedID 19123643

  View details for PubMedCentralID PMC2697562

• High-intensity focused ultrasound: Current potential and oncologic applications AMERICAN JOURNAL OF ROENTGENOLOGY Dubinsky, T. J., Cuevas, C., Dighe, M. K., Kolokythas, O., Hwang, J. H. 2008; 190 (1): 191-199

  Abstract

  The objective of this article is to introduce the reader to the principles and applications of high-intensity focused ultrasound (HIFU).Although a great deal about HIFU physics is understood, its clinical applications are currently limited, and multiple trials are underway worldwide to determine its efficacy.

  View details for Web of Science ID 000252030700050

  View details for PubMedID 18094311

• High-resolution OCT Balloon Catheter for Systematic Imaging of the Esophagus 2007 CONFERENCE ON LASERS & ELECTRO-OPTICS/QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2007), VOLS 1-5 Fu, H. L., Cobb, M. J., Leng, Y., Macdonald, D. J., Hwang, J. H., Li, X. 2007: 1660-?

  View details for Web of Science ID 000268751001272

• Intravascular inertial cavitation activity detection and quantification in vivo with optison ULTRASOUND IN MEDICINE AND BIOLOGY Tu, J., Hwang, J. H., Matula, T. J., Brayman, A. A., Crum, L. A. 2006; 32 (10): 1601-1609

  Abstract

  Inertial cavitation (IC) is an important mechanism by which ultrasound (US)-induced bioeffects can be produced. It has been reported that US-induced in vitro mechanical bioeffects with the presence of ultrasound contrast agents (UCAs) are highly correlated with quantified IC "dose" (ICD: cumulated root-mean-squared broadband noise amplitude in the frequency domain). The ICD has also been used to quantify IC activity in ex vivo perfused rabbit ear vessels. The in vivo experiments reported here using a rabbit ear vessel model were designed to: (1) detect and quantify IC activity in vivo within the constrained environment of rabbit auricular veins with the presence of Optison and (2) measure the temporal evolution of microbubble IC activity and the ICD generated during insonation treatment, as a function of acoustic parameters. Preselected regions-of-interest (ROI) in the rabbit ear vein were exposed to pulsed focused US (1.17 MHz, 1 Hz PRF). Experimental acoustic variables included peak rarefaction pressure amplitude ([PRPA]: 1.1, 3.0, 6.5 or 9.0 MPa) and pulse length (20, 100, 500 or 1000 cycles). ICD was quantified based on passive cavitation detection (PCD) measurements. The results show that: (1) after Optison injection, the time to onset of measurable microbubble IC activity was relatively consistent, approximately 20 s; (2) after reaching its peak value, the IC activity decayed exponentially and the half-life decay coefficient (t(1/2)) increased with increasing PRPA and pulse length; and (3) the normalized ICD generated by pulsed US exposure increased significantly with increasing PRPA and pulse length.

  View details for DOI 10.1016/j.ultrasmedbio.2006.07.015

  View details for Web of Science ID 000241592500019

  View details for PubMedID 17045881

• Correlation between inertial cavitation dose and endothelial cell damage in vivo ULTRASOUND IN MEDICINE AND BIOLOGY Hwang, J. H., Tu, J., Brayman, A. A., Matula, T. J., Crum, L. A. 2006; 32 (10): 1611-1619

  Abstract

  Previous in vivo studies have demonstrated that vascular endothelial damage can result when vessels containing gas-based microbubble ultrasound contrast agent (UCA) are exposed to MHz-frequency pulsed ultrasound (US) of sufficient pressure amplitudes, presumably as a result of inertial cavitation (IC). The hypothesis guiding this research was that IC is the primary mechanism by which the vascular endothelium (VE) is damaged when a vessel is exposed to pulsed 1-MHz frequency US in the presence of circulating UCA. The expectation was that a correlation should exist between the magnitude and duration of IC activity and the degree of VE damage. Rabbit auricular vessels were exposed in vivo to 1.17-MHz focused US of variable peak rarefaction pressure amplitude (1, 3, 6.5 or 9 MPa), using low duty factors (0.04% or 0.4%), pulse lengths of 500 or 5000 cycles, with varying treatment durations and with or without infusion of a shelled microbubble contrast agent. A broadband passive cavitation detection system was used to measure IC activity in vivo within the targeted segment of the blood vessel. The magnitude of the detected IC activity was quantified using a previously reported measure of IC dose. Endothelial damage was assessed via scanning electron microscopy image analysis. The results supported the hypothesis and demonstrate that the magnitude of the measured IC dose correlates with the degree of VE damage when UCA is present. These results have implications for therapeutic US-induced vascular occlusion.

  View details for DOI 10.1016/j.ultrasmedbio.2006.07.016

  View details for Web of Science ID 000241592500020

  View details for PubMedID 17045882

• American gastroenterological association institute technical review on the management of gastric subepithelial masses GASTROENTEROLOGY Hwang, J. H., Rulyak, S. D., Kimmey, M. B. 2006; 130 (7): 2217-2228

  Abstract

  This literature review and the recommendations therein were prepared for the American Gastroenterological Association Institute Clinical Practice and Economics Committee. The paper was approved by the Committee on January 19, 2006, and by the AGA Institute Governing Board on April 20, 2006.

  View details for DOI 10.1053/j.gastro.2006.04.033

  View details for Web of Science ID 000238207500028

  View details for PubMedID 16762644

• A prospective study comparing endoscopy and EUS in the evaluation of GI subepithelial masses GASTROINTESTINAL ENDOSCOPY Hwang, J. H., Saunders, M. D., Rulyak, S. J., Shaw, S., Nictsch, H., Kimmey, M. B. 2005; 62 (2): 202-208

  Abstract

  The purpose of this study is to prospectively evaluate the performance characteristics of endoscopy and EUS in the diagnosis of GI subepithelial masses.A total of 100 consecutive patients referred for the evaluation of a suspected GI subepithelial lesion were prospectively studied with endoscopy followed by EUS. Size, color, mobility, location (intramural or extramural), consistency (solid, cystic, or vascular), and presumptive diagnosis were recorded at the time of endoscopy. EUS then was performed, and size, echogenicity, location, and presumptive diagnosis were determined.A total of 100 subepithelial lesions were evaluated. Endoscopy had 98% sensitivity and 64% specificity in identifying intramural lesions. Size measurement by endoscopy correlated with size measurement by EUS (r = 0.88). Histology was obtained in 23 cases, with the presumptive EUS diagnosis correct in only 48% of cases. Most incorrect EUS diagnoses occurred with hypoechoic 3rd and 4th layer masses.Endoscopy has high sensitivity but low specificity in identifying the location (intramural or extramural) of subepithelial lesions. In addition, EUS imaging alone is insufficient to accurately diagnose 3rd and 4th layer hypoechoic masses, and histologic confirmation should be obtained whenever possible.

  View details for Web of Science ID 000231031000002

  View details for PubMedID 16046979

• Optical coherence tomography imaging of the pancreas: a needle-based approach. Clinical gastroenterology and hepatology Hwang, J. H., Cobb, M. J., Kimmey, M. B., Li, X. 2005; 3 (7): S49-52

  Abstract

  A novel, high-resolution, needle-based optical coherence tomography (OCT) device for improving the ability to detect early epithelial dysplasia in solid tissues/organs in vivo is currently in development. An instrument capable of real-time imaging of tissue microstructures in vivo could improve the ability to detect pathologic conditions such as dysplasia, and consequently improve patient outcomes. OCT is an emerging technology that can perform real-time cross-sectional imaging of tissue structures at micron-scale resolution in vivo. OCT has been shown to be effective in the imaging of luminal epithelium, capable of detecting epithelial dysplasia in Barrett's esophagus, and colonic polyps. However, OCT imaging depth with conventional probes is limited to the luminal surface (approximately 1-2 mm). The development of a technology and device that enables high-resolution, real-time imaging of solid tissues beyond 1- to 2-mm deep at or near the cellular level in vivo could improve the diagnosis of diseases of the pancreas and other solid organs.

  View details for PubMedID 16012997

• Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo ULTRASOUND IN MEDICINE AND BIOLOGY Hwang, J. H., Brayman, A. A., Reidy, M. A., Matula, T. J., Kimmey, M. B., Crum, L. A. 2005; 31 (4): 553-564

  Abstract

  Previous in vivo studies have demonstrated that microvessel hemorrhages and alterations of endothelial permeability can be produced in tissues containing microbubble-based ultrasound contrast agents when those tissues are exposed to MHz-frequency pulsed ultrasound of sufficient pressure amplitudes. The general hypothesis guiding this research was that acoustic (viz., inertial) cavitation, rather than thermal insult, is the dominant mechanism by which such effects arise. We report the results of testing five specific hypotheses in an in vivo rabbit auricular blood vessel model: (1) acoustic cavitation nucleated by microbubble contrast agent can damage the endothelia of veins at relatively low spatial-peak temporal-average intensities, (2) such damage will be proportional to the peak negative pressure amplitude of the insonifying pulses, (3) damage will be confined largely to the intimal surface, with sparing of perivascular tissues, (4) greater damage will occur to the endothelial cells on the side of the vessel distal to the source transducer than on the proximal side and (5) ultrasound/contrast agent-induced endothelial damage can be inherently thrombogenic, or can aid sclerotherapeutic thrombogenesis through the application of otherwise subtherapeutic doses of thrombogenic drugs. Auricular vessels were exposed to 1-MHz focused ultrasound of variable peak pressure amplitude using low duty factor, fixed pulse parameters, with or without infusion of a shelled microbubble contrast agent. Extravasation of Evans blue dye and erythrocytes was assessed at the macroscopic level. Endothelial damage was assessed via scanning electron microscopy (SEM) image analysis. The hypotheses were supported by the data. We discuss potential therapeutic applications of vessel occlusion, e.g., occlusion of at-risk gastric varices.

  View details for DOI 10.1016/j.ultrasmedbio.2004.12.014

  View details for Web of Science ID 000228440800011

  View details for PubMedID 15831334

• The incidental upper gastrointestinal subepithelial mass GASTROENTEROLOGY Hwang, J. H., Kimmey, M. B. 2004; 126 (1): 301-307

  View details for DOI 10.1053/j.gastro.2003.11.040

  View details for Web of Science ID 000187803300033

  View details for PubMedID 14699508

• High-intensity focused US: a potential new treatment for GI bleeding GASTROINTESTINAL ENDOSCOPY Hwang, J. H., Vaezy, S., Martin, R. W., Cho, M. Y., Noble, M. L., Crum, L. A., Kimmey, M. B. 2003; 58 (1): 111-115

  Abstract

  High-intensity focused US has been shown to achieve hemostasis in lacerated large veins and arteries. High-intensity focused US was studied as a potential endoscopic treatment for GI bleeding.A segment of the auricular vein of the rabbit was lacerated longitudinally and then treated with a high-intensity focused US transducer driven at 3.9 MHz (focal intensity of 750 W/cm(2)) in 15 animals until hemostasis was achieved. Sham treatment was delivered to 3 vessels. Rabbits were euthanized on days 0, 2, 7, 14, and 28 to allow for histologic evaluation of the response to treatment.Hemostasis was achieved in all treated vessels and in none of the sham treatments. Mean treatment time was 13 seconds. Histology initially demonstrated acute thermal injury with subsequent thrombus formation and chronic inflammation leading to replacement of the vessel by fibrous scar tissue.High-intensity focused US causes hemostasis in acutely bleeding veins and results in occlusion of treated vessel with subsequent granulation tissue formation.

  View details for DOI 10.1067/mge.2003.322

  View details for Web of Science ID 000183971500024

  View details for PubMedID 12838236

• Race and clinical outcome in patients with carcinoma of the uterine cervix treated with radiation therapy GYNECOLOGIC ONCOLOGY Mundt, A. J., Connell, P. P., Campbell, T., Hwang, J. H., Rotmensch, J., Waggoner, S. 1998; 71 (2): 151-158

  Abstract

  The aim of this study was to examine factors underlying differences in outcome between African-American (AA) and Caucasian (C) patients undergoing radiation therapy (RT).Patient, tumor, treatment characteristics, and the outcome of 316 AA and 94 C cervical cancer patients who underwent RT were compared. Median follow-up was 72.4 months.AA patients had a trend to a poorer 8-year cause-specific survival (47.9 vs 60.6%) (P = 0.10) compared to C patients with a significant difference seen in stage IIB-IVA disease (34.3 vs 59.5%) (P = 0.04). Several factors correlated with poor outcome were present in the AA group including lower mean hemoglobin levels during RT (P = 0.001), lower median income (P = 0.001), and less frequent intracavitary RT (P = 0.09). In addition, while uncommon in C patients, health problems were major reasons for treatment protraction and inability to undergo intracavitary RT in the AA patients. Multivariate analysis demonstrated that race was not an independent prognostic factor after controlling for difference in patient, tumor, and treatment factors.AA cervical cancer patients possess multiple factors that adversely impact upon the efficacy of RT. These findings may add further insight into the observed differences in outcome of cervical cancer patients based on race.

  View details for Web of Science ID 000077351700002

  View details for PubMedID 9826453