JMBS J Metab Bariatr Surg 2017;6(1):12-18 https://doi.org/10.17476/jmbs.2017.6.1.12 REVIEW ARTICLE 고려대학교의과대학내과학교실소화기내과, 위장관의료기기개발연구소 김승한, 최혁순, 전훈재 Endoluminal Gastroplasty for Obesity Treatment: Emerging Technology and Obstacles Seung Han Kim, Hyuk Soon Choi, Hoon Jai Chun Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Gastrointestinal Medical Instrument Research, Korea University College of Medicine, Seoul, Korea Obesity is a complex metabolic disease. Currently, obesity treatment includes lifestyle modification, obesity drug treatment, and bariatric surgery. Lifestyle modification is an essential part of obesity treatment, but it is limited by itself. And anti-obesity treatment drugs also showed limited weight loss effect, about 3-9% per year, and can cause serious side effects such as cardiovascular side events. Surgical treatment requires high cost, permanent resection of the gastrointestinal tract and can cause complication related to surgery. Recently, several promising endoscopic bariatric therapies are emerging. Endoluminal bariatric treatment using flexible gastrointestinal endoscopy could offer a minimally invasive treatment aimed at achieving an effect comparable to obesity surgery, while offering advantages of low cost and safety. In this paper, we described a new technological method, recent clinical data, and the latest findings on obstacles to be overcome for endoscopic gastroplasty using endoscopic suture instruments. Endoscopic gastroplasty presented reduced gastric volume, effective weight loss and maintenance effect without severe adverse events. It could suggest an attractive treatment option for obesity. Key Words: Endoscopy, Bariatrics, Endoscopic bariatric treatment, Gastroplasty, Obesity 서론 비만은체지방이과다하게축적되어건강에나쁜영향을미치는상태를말하는복합적인대사질환이다 [1]. 비만은다양한질환의유병률을높이는데특히당뇨, 고혈압, 심혈관질환, 수면무호흡증, 뇌혈관질환, 담낭질환, 비알코올성지방간, 악성종양등과연관이있다. 현재많이시행하는비만치료로는생활습관 개선, 비만약물치료, 외과비만대사수술등이있다. 하지만생활습관개선은제한적인체중감소효과만을보였고, 여러치료약제들이비만대사질환치료에사용되나 1년에 3-9% 정도의체중감량효과만을보였다 [2,3]. 또한이런약제들은중추신경계에작용하여남용의우려가있으며장기간사용시심혈관부작용등심각한부작용을초래할수있다 [4]. 외과비만대사수술은고도비만및고도비만에동반된대사질환치료에시행되며 투고일 : 2017 년 5 월 10 일, 심사일 : 2017 년 5 월 24 일, 게재확정일 : 2017 년 5 월 30 일책임저자 : 최혁순, 서울시성북구인촌로 73 고려대학교안암병원소화기내과우 : 02841 Tel: 02-920-6555, Fax: 02-953-1943, E-mail: mdkorea@gmail.com CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2017, The Korean Society for Metabolic and Bariatric Surgery
김승한외 : 위조절밴드술 (Adjustable gastric banding), 위소매절제술 (Sleeve gastrectomy), 루엔와이위우회술 (Roux-En-Y Gastric Bypass Surgery) 등이있다. 외과적비만대사수술은그효과는가장좋다고밝혀져있지만, 고가의비용, 위장관의영구적절제, 수술로인한높은합병증및사망률등으로환자들의선호도가낮아수술적응증환자의약 1% 정도만실제수술을받고있다 [5,6]. 위장관내시경을이용한최소침습치료분야는최근조기위암및전암성병변을치료하는분야로많은각광을받고있다 [7]. 치료내시경분야에서내시경비만대사치료는외과적비만대사수술에상응하는효과를노리면서비용및안전성측면에서는비만수술보다환자와의사들이부담없이접근하고자하는치료를목표로한다. 최근내시경비만대사치료는여러내시경적용기기와방법이개발되어임상적으로적용되고있으며, 여러임상실험등도진행되고있다. 미국소화기내시경학회 (American Society for Gastrointestinal Endoscopy, ASGE) 에서도최근내시경비만대사치료에대한적응증, 기술적요소, 합병증, 효과등에대해여러연구결과를바탕으로한의견들을개진하고있다 [8]. 대표적인내시경비만대사치료로는위에풍선을삽입하여용적을인위적으로작게만드는위풍선삽입술 (Intragastric balloon) 이있고, 위및십이지장에흡수억제스텐트를삽입하여흡수를억제하여비만및당뇨등의대사질환치료를위한위장관내흡수억제스텐트삽입술 (Endoscopic malabsorptive stent and duodenal-jejunal bapass sleeve insertion) 이있다. 또한섭취한음식물을바로외부로내보내는흡인치료 (Aspiration therapy), 위장관에전기자극을주어위장관연동운동을억제하는치료 (Gastro electrical stimulator therapy) 및위를외과적수술치료와비슷한방법으로위내봉합기구 (endoluninal suture device) 를통해위용적을줄이는내시경위성형술 (Endoscopic gastroplasty) 등이있다 [7,9]. 본논문에서는내시경및봉합기구를이용하여위용적을감소하는내시경위성형술에대해서새로운기술적방법, 최근임상적자료및극복해야할장애물과한계에대한최신지견을설명하고자한다. 야한다는거부감또한극복해야하는중요한장애물이다. 내시경소매위성형술 (Endoscopic sleeve gastroplasty) 은위장관봉합기기를이용하여, 위소매절제외과수술의기법과비슷하게내시경시술에적용하여위장관의구조를변형시켜위용적을줄인다 [10,11]. 내시경으로시술하기때문에전신마취가필요없고시술관련위험도가낮으며, 적은비용으로높은체중감소효과를기대할수있다 [12]. 하지만아직임상적으로많은연구가진행되고있고, 장기연구결과가나오지않아내시경위성형술이어떤환자에서얼마만큼의효과를보일것인지에대해서는추후많은연구자료가뒷받침되어야할것으로보인다. 이에대한임상적인연구들을바탕으로내시경위성형술의방법, 효과안정성에대해서확인해보았다 (Table 1). 1) 내시경위성형술의방법기존에여러내시경봉합기구들이개발되었고, 이를내시경위성형술에적용하려고하였다. 하지만실제로임상에서사용되고있는것은많지않다. 대부분의연구자들은내시경위성형술을위해미국식품의약안전청 (Food and Drug Administration, FDA) 승인을획득한오버스티치내시경봉합기구 (OverStitch; Apollo Endosurgery, Inc., Austin, Texas, USA) 를사용하였다. Abu Dayyeh 등 [12] 은 4명의환자를대상으로위유문부에서위식도접합부위까지 2열의위벽전층을봉합 (full thickness suture) 하는방법으로시술을시행하였으며각각 23-28개의봉합을시행하였다. 이후연구에서 Abu Dayyeh 등 [13] 은 25명의환자를대상으로다른형태의 2열봉합을시행하였고첫열의봉합은위의전벽, 대만부, 후벽의 3부분의삼각형봉합패턴을이용하였고, 평균적으로 16±5개의봉합을이용하였으며이는좀더좁은위소매를만들기위한방법이었다. 본론 1. 내시경위성형술 내시경위성형술은내시경을이용한비만대사치료중에위장관의해부학적구조를변형시켜위장관용적을줄이는방법이다 (Fig. 1). 위소매절제술이나루엔와이위우회술등은체중감소에가장효과적이고효과가오래유지되는방법이지만위험도및비용이높고위장관을다시원래의구조로변환시키기힘들다는단점이있다. 또한환자들이전신마취하에외과적수술을해 Fig. 1. Diagram of endoscopic gastroplasty. 13
Vol. 6, No. 1, 2017 Table 1. Details of each study related to endoscopic gastroplasty Author Study subjects Techniques Abu Dayyeh BK et al. [12] Lopez-Nava G et al. [15] Sharaiha RZ et al. [14] Lopez-Nava G et al. [17] Lopez-Nava G et al. [18] 4 (Male:Female 1:3) 20 (Male:Female 4:16) 10 (Male:Female 3:7) 50 (Male:Female 13:37) 25 (Male:Female 5:20) 1. Suture: full thickness opposing anterior and posterior gastric wall 3. Sutures number (range): 23-28 1. Suture: full thickness with triangular stitch 3. Sutures number: n/a 1. Suture: full thickness with anterior to mid line to posterior site (M ) and interrupted 2. Suture rows: 2 3. Sutures number: 4-8 stitches per each suture 1. Suture: full thickness with triangular stitch 3. Sutures number: 3-6 stitches per each suture 1. Suture: full thickness with interrupted 2. Suture layers: 1 3. Sutures number: n/a López-Nava Breviere G et al. [19] Sharaiha RZ et al. [20] Abu Dayyeh BK et al. [13] 55 (Male:Female 13:42) 91 (Male:Female 29:62) 25 (Male:Female 4:21) 1. Suture: full thickness with triangular suturing 3. Sutures number: 3-6 stitches per each suture 1. Suture: full thickness with interrupted Z and interrupted stitch 3. Sutures number (median): 6 (first layer) and 3 (second layer) 1. Suture: full thickness with interrupted triangular and interrupted 3. Sutures number (mena) 16±5 EWL = excess weight loss; MWL = mean weight loss, n/a = not available. Procedure time (minutes) Outcome Follow up Complications 172-245 n/a 3 mons Acid reflux symptoms (1/4) Abdominal pain and nausea (3/4) 75 (range 40-120) EWL 24.6±14.3% (1 mons) 36.9±19.9% (3 mons) 53.9±26.3% (6 mons) 157 (range 118-360) EWL 30% (6 mons) MWL 33.0 kg (6 mons) 6 mons None 6 mons Abdomina pain and nausea (8/10) Chest pain (2/10) 66 80 (first 25 cases) 52 (last 25 cases) EWL 22.6±10.5% (1 mons) 40.2±17.3% (3 mons) 53.5±26.2% (6 mons) 57.0±33.9% (12 mons) 80 (range 50-120) EWL 24.0±11.8% (1 mons) 40.5±16.5% (3 mons) 53.9±24.8% (6 mons) 54.6±31.9% (12 mons) n/a EWL 23.1±10.2% (1 mons) 430.±16.2% (3 mons) 55.3±23.8% (6 mons) 12 mons Epigastric pain (50%) Nausea (20%) 12 mons Abdominal pain (50%) Nausea (20%) 6 mons Abominal pain (50%) Nausea (20%) 98.3±39.3 TBWL 14.4% (6 mons) 17.6% (12 mons) 20.9% (24 mons) 24 mons Nausea (38.4%) Abdominal pain (27.4%) Perigastric leak (1.1%) 217±17 (first 5 cases) 98±4 (last 5 cases) EWL 53±17% (6 mons) 56±23% (9 mons) 54±40% (12 mons) 45±41% (20 mons) 20 mons Abdominal pain (68%) Perigastric inflammatory serous fluid collection (4%) Pulmonary embolism (4%) Pneumoperitoneum and pneumothorax (4%) 14
김승한외 : Sharaiha 등 [14] 은내시경봉합기구를이용하여 2열의위벽전층봉합을시행하였으며첫열은전벽, 대만부, 후벽으로이어지는 M 형태의봉합이이루어졌고이는 2차적인내강이생기는것을방지하기위함이었다. 두번째열은단절봉합형식 (Interrupted suture ) 으로시술이이루어졌다. Lopez-Nava 등 [15] 의연구에서는위의전벽, 대만부, 후벽으로이어지는삼각형형태의봉합을시행하였다. 각각의삼각형봉합은 3-6개의위벽전층봉합으로이루어졌으며 6-8번정도의봉합이위저부의방향으로시행되었다. 최근에는여러연구들에서는절개없는수술플랫폼 (Incisionless Operating Platform, IOP; USGI Medical, San Clemente, CA, USA) 을새로운기구를이용하여진행되었다. IOP 시스템은여러채널접근이가능한기구 (multi-lumen access device, Transport R ) 와내시경조직집게 (endoluminal tissue approximator, G Prox R ), 그리고봉합앵커 (suture anchors, Snowshoe R ) 로이루어져있다. 최근 IOP 시스템을이용한시술을 Primary Obesity Surgery Endolumenal (POSE) 시술이라고명명하여관련연구를진행해왔다 [16]. 이시스템은위의체부의여러부분을전층봉합을이용하여위의총면적을줄이는방법으로진행되었다. 2) 내시경위성형술의효과연구자들은내시경위소매성형술시행이후체중변화를비교하였다. Abu Dayyeh 등 [13] 은오버스티치기구를이용한 25 명대상의한연구에서시술시행 6, 9, 12, 20개월후각각 53±17%, 56±23%, 54±40%, 45±41% 의초과체중감량률 (excess weight loss, EWL) 을보고하였다. Sharaiha 등 [14] 은위소매성형술시행후평균체중감량 (mean weight loss, MWL) 과초과체중감량률을보고하였으며첫 1개월에 11.5 kg 의평균체중감량과 18% 의초과체중감량률을보여주었다. 또한 3개월후에 19.4 kg, 26%, 6개월후에 33.0 kg, 30% 의평균체중감량과초과체중감량률을보고하였다. 6개월후신체질량지수 (Body mass index, BMI) 는평균 4.9 kg/m 2 (P=0.0004) 감소하였고평균복부둘레는 21.7 cm (P=0.003) 감소하였다. 이후연구에서도내시경위소매성형술시행 12개월후신체질량지수와평균복부둘레는통계학적으로유의하게감소하였으며, 시술후 6, 12, 24개월후총체중감량률 (total body weight loss, TBWL) 은각각 14.4%, 17.6% 및 20.9% 였다. Lopez-Nava 등 [15] 은내시경위소매성형술시행 1, 3, 6개월후몸무게가 108.5±14.9 kg에서각각 100.2±13.8 kg, 94.9±13.2 kg, 87±11.3 kg (P<0.05) 으로감소하였다. 신체질량지수변화에서도비슷한경향을보였으며내시경위소매성형술시행후 1, 3, 6개월에초과체중감량률은 24.6±14.3%, 39.3±19.9%, 53.9± 26.3% 였고체중감량률 (percent weight loss) 는 7.6±2.2%, 12.4±3.9%, 17.8±7.5% 였다. Lopez-Nava 등 [17] 은 50명의환자를대상으로내시경위소매성형술시행후평균몸무게가 107.0±18.4 kg에서 1, 3, 6, 12개월추적관찰시각각 98.5±16.5 kg, 93.5±16.5 kg, 89.2±17.8 kg, 88.1±12.0 kg (P<0.05) 였다. 1년추적관찰시총체중감량률및초과체중감량률은평균 19.0±10.8%, 57.0±33.9% 였다. 이후연구 [18] 에서 25명환자를대상으로 1년추적관찰하였을때평균신체질량지수, 평균체중감량, 총체중감량률, 초과체중감량률은각각 7.3±4.2 kg/m 2, 21.1±12.6 kg, 18.7±10.7% 과 54.6±31.9% 였다. 이연구에서는모든환자에서고형식이가제한되는첫째달에가장큰몸무게감소가발생하였다고보고했다. López-Nava Breviere 등 [19] 은 55명의환자에서내시경위소매성형술을시행하였고 6개월간관찰했을때, 평균몸무게는 1개월때 106.6±18.3 kg에서 98.9±16.4 kg, 3개월후 92.2±15.6 kg, 6개월후 87.6±14.7 kg으로감소하였으며신체질량지수는 37.7±4.5 kg/m 2 에서 1개월후 35.0± 4.2 kg/m 2, 3개월후 32.7±4.3 kg/m 2, 6개월후 31.1±4.5 kg/m 2 (P<0.05) 로감소하였다. 초과체중감량률또한 1, 3, 6개월후각각 23.1± 10.2%, 43.0±16.2%, 55.3±23.8% 였고총체중감량률은각각 7.1±2.2%, 13.3±4.0%, 17.3±7.0% (P<0.05) 였다. Sharaiha 등 [20] 의연구에서내시경위소매성형술시행후당화혈색소 (HbA1c) 는평균 6.1±1.1% 에서 5.5±0.5% 로감소하였고 (P=0.05), 수축기혈압 (systolic blood pressure) 은 129.0± 13.4 mmhg에서 122.2±11.7 mmhg로감소 (P=0.023), 중성지방 (triglycerides) 은 131.8±83.2 mmol/dl에서 92.4±39.4 mmol/dl로감소 (P=0.017) 하였다. ALT 는평균 32.3±16.4 mg/dl 에서 20.7±11.4 mg/dl로감소 (P<0.001) 하였다. POSE 시술을통한연구에서도유의한체중감소효과와안정성에대해서발표하였다. POSE 시술을이용한조기전향적관찰연구가 45명의환자를대상으로진행되었다. 평균 8.2번의봉합을통해진행되었고, 6개월후에신체질량지수는 5.8 kg/m 2 감소하였고 (P<0.001), 초과체중감량률은 49.4% 이었고, 총체중감량률은 15.5% 였다 [21]. POSE 시술 1년후추적연구에서는 116명의환자를대상으로시행하였는데, 평균총체중감량은 16.6±9.7 kg, 총체중감량률은 15.1±7.8%, 그리고초과체중감량률은 44.9±24.4% 로유의한체중감량효과를보였다 [16]. 3) 안정성내시경위소매성형술시행중중대한합병증은보고되지않았다 [12-14,18-20]. Lopez-Nava 등 [15] 은시술중 10% 의환자에서소량출혈을발견하였고모두내시경치료를통해해결하였다. 내시경위소매성형술시술후에오심, 복통, 흉부불편감, 무증상기복증, 위식도역류가발생하였다. 경한합병증이발생하 15
Vol. 6, No. 1, 2017 였을경우에는진통제, 제산제등의투약및경과관찰을하면서보존적으로치료하였고모두호전되었다. Abu Dayyeh 등 [13] 은내시경위소매성형술시행후약 30% 정도의환자에서통증및오심으로입원이필요하였고평균재원기간은 1.5일이었다고보고하였다. 대부분의연구에서중대한시술후합병증은발생하지않았지만 Sharaiha 등 [20] 은내시경위소매성형술시술후 8일째위주변부누출을보고하였다. 이환자는항생제투여및경피적배액 (percutaneous drain) 을시행하여좋은경과를보였다. Abu Dayyeh 등 [12,13] 은내시경위소매성형술시술후 3건의중대한합병증발생을보고하였으며폐색전증, 기복증및기흉, 위주변염증성장액고임등이었다. 위주변염증성장액고임은경피적배출및항생제투여하며호전을보였고기흉환자에서는흉관을삽입하였다. 모든환자는외과적처치없이회복되었으며, 이런중대한합병증의발생이후연구자들은내시경위소매성형술시술의프로토콜을변경하였으며이후비슷한합병증의빈도는감소하였다. POSE 시술을통한내시경위성형술에서도안정성에대해서는큰문제를보이지않았다. 시술후 1년후연구결과에서논문발표당시진행되고있는 1,500명의임상자료를발표하였다. 그중에가장심각한합병증은수혈이필요한출혈, 위천공, 기흉, 복강내농양이었다. 총부작용은 1% (5/1,500) 환자에서보였으며, 그중에수술이필요한입원환자는 0.33% (5/1,500) 였다 [16]. 2. 내시경위성형술의장애물내시경위소매성형술은여러전향적연구가활발하게이루어지고있지만연구의전체적인수나연구당대상자수가많지않다. 임상연구는활발하게진행되지만아직실제임상에서활발하게사용되고있지는않다. 내시경위소매성형술의안정성에대해서지금까지보고된문헌에서중대한합병증의빈도는높지않았지만위주변염증성장액의고임 [12,22] 등이보고되었고, 폐색전증및기복증에 [13] 대한보고도있었으므로시술시이에대한충분한설명및시술중및시술후적절한경과관찰및영상검사시행이필요하겠다. 내시경위소매성형술후얼마간의기간동안시행된위장관봉합을유지할것인지, 또얼마후에다시위장관을원래상태로회복시키는것이효과적인것인지에대한연구결과혹은기준이없다. 이또한추후연구를통한자료가수집되어야할것이다. 최근한연구의저자는최소 6개월정도의기간동안위장관봉합을유지하는것을제시하고있다 [19]. 위장관봉합의방법에대해서도많은논란이있다. 전층봉합은내구성에는좋은효과를보이겠지만, 안정성의문제가있다. 반대로부분층봉합은 (partial thickness suture) 안정성은확보 되지만내구성및효과의문제가있을수있다. 또한봉합방법도어느부위를어떻게얼마만큼봉합해야하는것에대한구체적인연구는부족한실정이다 [20]. 장기간의추적관찰시행하여봉합제거시위장관협착및유착등위의구조적문제및내시경위소매성형술시술후위장관운동장애등환자의삶의질을저하시킬가능성이있는합병증의발생여부를파악하여적절한시술유지기간을정해야할것이다. 대부분의내시경시술이그렇듯이내시경위소매성형술는내시경시술자의술기수준에따라서그효과가영향을받아서각센터마다시술의효용성이일정하지못할가능성을배제하지못한다. 극동아시아등위암발생률이높은지역에서내시경위소매성형술시술후위구조변형으로인한위암의조기발견이어려울수있다는점도고려되어야한다. 하지만봉합후봉합부위의실을절제함으로써다시위를원상복구함도예상할수있으나, 오랫동안의봉합으로인해위안에서의유착의가능성도있다. 무엇보다기구의편의성과안정성이문제가될것이고, 대규모의연구및오랜기간추적관찰을통해시술의안전성및유효성을높여야할것이다. 아직까지는오버스티치, POSE 시스템외에다른기기는임상적으로활발한연구가진행되고있지는않다. 현재이기구들은구입비용이고가이며, 그로인해내시경위장관봉합기기의비용이높아서임상에적용이되어도저비용, 고효율의내시경비만치료시술이불가능할수도있다. 따라서결국다양한내시경봉합기기의개발을통해시술의비용을감소시키려는노력이필요하겠다. Fig. 2. Intragastric balloon placement. 16
김승한외 : 결론 REFERENCES 비만대사치료는다양한방향으로지속적인발전이이루어지고있으며, 단지한번의시술및수술만으로해결할수는없다. 수술과함께식이조절, 운동요법등생활습관개선을위한꾸준한관리가필요하다. 결국이를위해서는다학제적인접근이필요하다. 최근미국소화기학회 (American Gastroenterology Association, AGA) 에서도비만치료에있어서내시경치료, 비만대사수술적치료의필요성과함께다학제치료의중요성을강조하였다 [23]. 내시경비만치료는생활습관조정및비만약물치료와외과적비만수술간의간극을메우기위한치료방법으로제시되었다. 안전하고효율적인비만치료를위해비만내시경치료의역할이점차중요해지고있다. 내시경비만치료는비만환자의치료의저변을확대시키고, 비용효과측면에서보다나은치료법을제시함으로환자들의비만연관질환감소와결과적으로연관사망률을감소시킬것이다. 특히위풍선삽입술은안전성측면이나효과측면에서많은연구를통해그효용성을입증하였다 (Fig. 2). 또한내시경위성형술은내시경위장관봉합을통해위의구조변형및위용적을감소시키고동시에생리학적변화를통해효과적인체중감량및유지효과를보여주었다. 추후내시경봉합기기및기술의발전, 내시경의사의봉합술기향상을통해서내시경위성형술의시술효과및안전성은점차향상될것이고, 이를통해위내시경성형술은효과적인최소침습적비만치료로사용될수있을것이다. 현재상태에서위내시경성형술은아직한계가있으며극복해야할장애물들이있다. 그를위해여러내시경기기개발이이루어지고있고, 그를이용한연구가활발히진행되고있다. 현재국내에서비만에대한치료가단지미용부분으로치우쳐있고, 비만대사질환에대한의학적인치료에대한관심도가떨어져있는것도사실이다. 실제비만대사질환수술의중요성이강조되기위해서도내시경비만치료가그중간적다리의역할뿐아니라, 어느부분에서나름대로의역할을할수있을것이라기대된다. 감사의글 This research was supported by the Ministry of Trade, Industry & Energy (MOTIE, Korea) under Industrial Technology Innovation Program. No.10060251, Development of diagnostic device for functional dyspepsia based on Korean-Western medicine fusion abdominal diagnosis and the Basic Research Program through the National Research Foundation of Korea (NRF-2017R1C1B2006425). 1. Kim SH, Chun HJ, Choi HS, Kim ES, Keum B, Jeen YT. Current status of intragastric balloon for obesity treatment. World J Gastroenterol 2016;22:5495-504. 2. Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the diabetes prevention program outcomes study. Lancet 2009;374:1677-86. 3. Gregg EW, Chen H, Wagenknecht LE, et al. Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA 2012;308:2489-96. 4. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 2014;311:74-86. 5. Ochner CN, Gibson C, Carnell S, Dambkowski C, Geliebter A. The neurohormonal regulation of energy intake in relation to bariatric surgery for obesity. Physiol Behav 2010;100:549-59. 6. Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg 2013;23:427-36. 7. Choi HS, Chun HJ, Seo MH, et al. Endoscopic submucosal tunnel dissection salvage technique for ulcerative early gastric cancer. World J Gastroenterol 2014;20:9210-4. 8. ASGE Bariatric Endoscopy Task Force; ASGE Technology Committee, Abu Dayyeh BK, et al. Endoscopic bariatric therapies. Gastrointest Endosc 2015;81:1073-86. 9. Choi HS, Chun HJ. Recent trends in endoscopic bariatric therapies. Clin Endosc 2017;50:11-6. 10. Song Y, Choi HS, Kim K, et al. A simple novel endoscopic successive suture device: a validation study for closure strength and reproducibility. Endoscopy 2013;45:655-60. 11. Choudhary NS, Puri R, Saraf N, et al. Intragastric balloon as a novel modality for weight loss in patients with cirrhosis and morbid obesity awaiting liver transplantation. Indian J Gastroenterol 2016;35:113-6. 12. Abu Dayyeh BK, Rajan E, Gostout CJ. Endoscopic sleeve gastroplasty: a potential endoscopic alternative to surgical sleeve gastrectomy for treatment of obesity. Gastrointest Endosc 2013; 78:530-5. 13. Abu Dayyeh BK, Acosta A, Camilleri M, et al. Endoscopic sleeve gastroplasty alters gastric physiology and induces loss of body weight in obese individuals. Clin Gastroenterol Hepatol 2017; 15:37-43.e1. 14. Sharaiha RZ, Kedia P, Kumta N, et al. Initial experience with endoscopic sleeve gastroplasty: technical success and reproducibility in the bariatric population. Endoscopy 2015;47:164-6. 15. Lopez-Nava G, Galvão MP, da Bautista-Castaño I, et al. Endoscopic sleeve gastroplasty for the treatment of obesity. Endoscopy 2015;47:449-52. 16. López-Nava G, Bautista-Castaño I, Jimenez A, de Grado T, Fernandez-Corbelle JP. The Primary Obesity Surgery Endolumenal (POSE) procedure: one-year patient weight loss and safety outcomes. Surg Obes Relat Dis 2015;11:861-5. 17. Lopez-Nava G, Galvão MP, Bautista-Castaño I, Jimenez-Baños A, Fernandez-Corbelle JP. Endoscopic sleeve gastroplasty: how I do it? Obes Surg 2015;25:1534-8. 18. Lopez-Nava G, Galvao M, Bautista-Castaño I, Fernandez-Corbelle 17
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