Direct Endoscopic Necrosectomy With Lumen Apposing Metal Stents for Pancreatic Walled Off Necrosis The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Zhai, Yaqi. 2020. Direct Endoscopic Necrosectomy With Lumen Apposing Metal Stents for Pancreatic Walled Off Necrosis. Master's thesis, Harvard Medical School. Citable link https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37365245 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA DIRECT ENDOSCOPIC NECROSECTOMY WITH LUMEN-APPOSING METAL STENTS FOR PANCREATIC WALLED-OFF NECROSIS By Yaqi Zhai A Dissertation Submitted to the Faculty of Harvard Medical School In Partial Fulfillment of the Requirements for the Degree of Master of Medical Sciences in Clinical Investigation (MMSCI) Harvard University Boston, Massachusetts March 26th, 2020 Area of Concentration: Internal Medicine/Gastroenterology Project Advisors (Thesis Committee): Dr. Christopher C. Thompson, Dr. Linda Lee, Dr. Amil M. Shah, Dr. Finnian R. McCausland, Dr. Ajay K. Singh I have reviewed this thesis. It represents work done by the author under my guidance/supervision. Primary Mentor: Dr. Christopher C. Thompson TABLE OF CONTENTS TABLE OF CONTENTS ........................................................................................ ii ACKNOWLEDGEMENTS ................................................................................... iii OVERVIEW ............................................................................................................5 PAPER 1 ..................................................................................................................7 ABSTRACT .................................................................................................8 INTRODUCTION .....................................................................................10 METHODS ................................................................................................11 RESULT ....................................................................................................15 DISCUSSION ............................................................................................18 CONCLUSION ..........................................................................................23 BIBLIOGRAPHY ......................................................................................24 FIGURES AND TABLES .........................................................................29 PAPER 2 ................................................................................................................37 ABSTRACT ...............................................................................................38 INTRODUCTION .....................................................................................40 METHODS ................................................................................................41 RESULTS ..................................................................................................45 DISCUSSION ............................................................................................47 CONCLUSION ..........................................................................................50 BIBLIOGRAPHY ......................................................................................51 FIGURES AND TABLES .........................................................................55 SUMMARY OF CONCLUSIONS ........................................................................60 DISCUSSION AND PERSPECTIVE ...................................................................61 ii ACKNOWLEDGEMENTS Here I sincerely acknowledge those who incessantly supported and motivated me in the past two years and have made this journey an exhilarating experience. First and foremost, I would like to express my sincere gratitude to my mentor and supervisor Dr. Christopher C. Thompson. He is a well-known master endoscopist with great innovativeness and creativity. Since the day he generously accepted to provide me with mentorship, he has never stopped being tolerant, patient, supportive and encouraging. He tries to provide every chance to improve my endoscopic skills and research ability. I’m deeply inspired by his high enthusiasm for work and am greatly appreciative of his stringent requirements for my research. The quote by Einstein- “If we knew what it was we were doing, it would not be called research, would it?”, is markedly posted in his office. It is his innovativeness and creativity that impressed me most. Also, he is one of the most amicable persons I have ever met, who is always ready to help others. I am greatly honored to be his first student from mainland China, and his words and deeds have set an excellent model for me to follow. Second, I would like to express my deepest appreciation to my thesis committee- Dr. Linda Lee and Dr. Amil M. Shah, as well as Dr. Marvin Ryou. Without their dedicated involvement and constructive criticism in my research, I would have never accomplished it. The Thompson’s Endoscopy Lab is phenomenal and has been a great source of inspiration and support. I'd like to give special thanks to Dr. Ahmad Najdat Bazarbashi, Dr. Pichamol Jirapinyo, Dr. Ryan Michele and Dr. Aoife Devery, who teach and help me immensely. iii Third, I am grateful to our program directors-Dr. Ajay K. Singh and Dr. Finnian R. McCausland. Without their inexorable efforts to this program, we would never have this extraordinary experience in the clinical research journey, and I should also thank them for being so supportive and encouraging since the very beginning. Heartfelt thanks go to Dr. Miguel Hernan, Dr. Brian Healey, Dr. Julie Buring and all faculties, thanks for your cutting-edge knowledge and excellent training. The pure passion and humor of Dr. Brian Healey in teaching impressed me deeply, and I expect to be a nice teacher like him in the future. Also, I would like to extend my sincere thanks to Ms. Katie Cacioppo and Ms. Claire O’ Connor, who have offered excellent coordination and timely help over the last two years. Meantime, my sincere thanks should also go to my supervisors in China- Dr. Guo-quan Ren, Dr. En-qiang Linghu and Dr. Ning-li Chai. Without their long-lasting support behind me, I can’t fully focus my mind on the course and research. Lastly, my deep and sincere gratitude goes to my family for their continuous and unparalleled love and support. I am forever indebted to my parents who are not highly-educated but teach me the most valuable courses, namely the truth in life and conducting myself with loyalty, justice, goodness, and perseverance. No words of gratitude can address plenty of thanks I owe to my wife- Dr. Zhen-zhen Xu, who is always encouraging me in all my pursuits and inspiring me to seek my destiny. Over the past two years, she endures suffering from departure and sacrifices a lot for our common family. This journey would not be possible if without them. To all the above I declare my sincerest gratitude. iv OVERVIEW Acute pancreatitis (AP) is the most common gastrointestinal disorder requiring acute hospital admission, leading to tremendous emotional, physical, and financial human burden. Despite the majority of patients (80%) are mild and self-limited with favorable outcomes, acute necrotizing pancreatitis (ANP) will develop in up to 20% of cases. Acute post-necrotic fluid collection will occur due to liquefaction of necrosis tissue and will be encapsulated by a thick fibrous shell without an epithelium lining over 4 weeks, known as pancreatic walled-off necrosis (WON). WON is associated with substantial mortality of 10-30%, especially when infected. Therefore, timely and effective debridement of necrotic tissues is usually required. Over the past decade, the management of WON has evolved from open surgical necrosectomy to the minimally invasive endoscopic approach. Endoscopic step-up approach is increasingly accepted as the first-line therapy for the management of WON. Recently, a novel lumen-apposing metal stents (LAMS) further promotes its popularity. The bilateral dumbbell-shaped design of LAMS with wide flanges enhances the drainage and reduces risks of stent migration and occlusion, as well as peritoneal leakage. Meantime, LAMS also simplifies endoscopic procedures and provides easy access for direct endoscopic necrosectomy (DEN). Currently, LAMS has been recommended as the standard care for patients with WON. DEN with LAMS has widely used by endoscopists in the management of patients with WON. Early identification of high-risk patients irresponsive to DEN with LAMS 5 will facilitate closer postoperative surveillance and optimal clinical decision-making. However, the prediction study on successful DEN with LAMS for pancreatic WON is lacking. Meantime, there has been a global trend to perform endoscopic interventions on an outpatient basis, which has advantages of convenience, efficiency, economy, and satisfaction. Now most patients undergoing DEN with LAMS for WON are hospitalized due to perceived increased risk of adverse events. Whether outpatient DEN with LAMs is safe and feasible, and which patients could be performed in an outpatient setting remain unknown. In this project, we retrospectively reviewed and analyzed a prospectively maintained database,