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1 The Korean Journal of Gastrointestinal Endoscopy Room B 식도스텐트 심찬섭 건국대학교의학전문대학원건국대학교병원소화기병센터 Esophageal Stent Chan Sup Shim, M.D., Ph.D. Digestive Diseases Center, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea 서론 리고개발의미래에대해서간단히알아보고자한다. 소화관스텐트삽입은식도에있어서는 100여년전부터사용되어져왔으며첫금속스텐트의삽입은 1885년에시도되었었다. 1 식도스텐트는지난 20년동안극적인진화를이루었다. 1990년도이전에는사실상모든식도스텐트가단단한폴리비닐플라스틱또는고무로만들어졌다. 국내에서처음으로식도스텐트사용은플라스틱스텐트로, 1986년에시도되었다. 2 이러한스텐트들은종양에의해막힌식도를넓힐수는있었지만식도에거치하기가어려웠을뿐만아니라자주통증을야기하였으며시술중또는시술후출혈과천공을일으키기도하였다. 스텐트를거치한후에도상대적으로두꺼운스텐트로인해환자들은액상음식이외에는삼킬수가없는경우도있었다. 1990년대초기에막미부착형 (uncoverd) 자가팽창형금속스텐트 (self-expanding metal stents, SEMS) 가도입되면서고전적플라스틱스텐트는사실상사라졌다. 하지만막미부착형 SEMS는종양이스텐트내강으로자라들어와스텐트의폐색을유발시키는단점이있었다. 이를극복하기위하여스텐트의중반부또는전체를얇은실리콘이나플라스틱으로덮은부분막부착형자가팽창형금속스텐트 (partially covered self-sxpanding metal stents, PCSEMS) 와완전막부착형자가팽창형금속스텐트 (fully covered self-expanding metal stents, FCSEMS) 가개발되었다. 최근 10년간 PCSEMS 와 FCSEMS 의적응증은악성협착, 폐쇄또는상부위장관의외부압박, 악성위장관천공과누공그리고반복적인풍선확장술또는수술적부지법으로효과가없는양성식도및위십이지장협착등으로점진적으로확장되어가고있다. 1,3-6 특히식도스텐트와관련해서는최근내시경기기및부속기구등의눈부신개발로다양한재질, 형태와특성을가진스텐트가개발되었고단순히악성종양에의한식도폐색뿐만아니라외부압박, 악성식도천공과기관식도누공등의양성식도질환에서도스텐트의유용성과적응이확장되고있다 (Table 1). 본세미나에서는이러한최근개발된다양한스텐트와시술적응과문제점, 그 스텐트디자인 기본적으로자가팽창형금속스텐트 (self-expandable metal stent, SEMS) 는소화관내부를폐쇄시킬수있는어떠한질환이라도확장시키는충분한힘을가지고, 소화관내강을지지해준다. SEMS 는개방성을유지하고다시폐색되는것을방지해주며스텐트의위치변화를최소화하도록고안되었다. 식도암의경우병기가진행되어수술이불가능한경우에대부분연하곤란이발생하며고식적치료가주치료가되는데식도는구강에서가깝고, 원통구조이 Table 1. Indications and Contraindications of Esophageal Self- Expanding Metal Stents 1,7-10 Indications Inoperable malignant esophageal obstruction Extrinsic esophageal compression by primary or secondary mediastinal tumors Actual or impending tracheoesophageal fistulae Iatrogenic esophageal perforation Malignant gastroesophageal anastomotic leaks Tumor recurrence after surgery or chemoradiotherapy Contra-indication to chemoradiotherapy Benign strictures refractory to balloon dilatation and not amenable to surgery Contraindications Curable disease by multimodality treatment Uncorrectable coagulopathy Stricture within 2 cm of upper esophageal sphincter Risk of airway compression Recent high-dose chemoradiotherapy (within previous 3-6 weeks) Terminally ill patients limited life expectancy Gastroduodenal and/or small bowel obstruction Sepsis Vol. 43 (Suppl 1), 2011 (87-92) 87

2 므로내시경또는투시를이용한방사선학적인방법을이용하여스텐트를삽입하기가용이하다. 특히 SEMS는도관의직경이작아협착을미리확장할필요가없으며삽입이용이하여수술의대상이되지않는식도암, 천공을동반한식도암, 재발성식도암등에대한고식적치료에매우효과적이라할수있다. 11 SEMS의기술적인성공률은 95% 정도이며, 성공적인삽입후에는 90% 이상에서연하곤란증상이호전되는것으로보고되고있다. 12 식도의악성협착에사용되는 SEMS는제품마다다양한특성들이있어서협 착의성질과누공의유무, 협착의위치등에따라선택하여야한다. Table 2는국내외에서현재사용되고있는식도스텐트의종류와특징을보여주고있다. 식도자가팽창형금속스텐트 (SEMS) 는다음과같이나누어볼수있다. (1) 막부착형 : 부분막부착형 (PCSEMS), 완전막부착형 (FCSEMS), (2) 재질 : 니티놀 (Nitinol), 스테인레스강철 (stainless steel), 플라스틱 (plastic), (3) 기능 : 완전개통형 (open type), 역류방지형 (anti-reflux valve type). Table 2. Self-Expanding Esophageal Stents currently Available in Korea and Internationally 13,14 Stent Manufacturer Material Length (cm) Diameter shaft/flare (mm) Hanarostent M.I. Tech 9/12/16 18/24 22/28 Covering PC/Covered Anti reflux valve Choostent M.I. Tech 8/11/14/17 18/24 PC/Covered Hanarostent (Upper stricture) M.I. Tech 6/9/11/13 18/24 PC/Covered Bonastent Esophageal Standard Sci Tech. Inc Nitinol/ silicone 6/8/10/12/14/16 9/11/13/15 18/24 22/28 Full Covered Full Covered S-type Double stent Taewoong 6/8/10/12/15 16/22 18/24 NC/Covered Proximal release S type Double Taewoong 6/8/10/12/15 16/22 18/24 PC/Covered Anti-reflux S type Double Taewoong 6/8/10/12/15 18/24 16/22 PC/Covered EGIS Esophageal S&G Biotech 8/10/12/14/16 16/24 18/26 20/28 NC/Covered Wallflex Scientific Boston Nitinol 10/12/15 18/23 23/28 PC/covered Ultraflex Scientific Boston Nitinol 7/10/12/15 18/23 23/28 NC/PC Esophageal Z Cook Stainless steel 8/10/12/14 18/25 (Dua variant) PC Evolution Cook Nitinol 8/10/12.5/15 20/25 PC Alimaxx-E Alveolus Nitinol 7/10/12 18/22 Covered Polyflex Boston Scientific Polyester 9/12/15 16/20 18/23 21/25 Covered FerX-Ella Ella-CS Stainless steel NC, not covered; PC, partially covered. 9/10.5/12/ 13.5/15/16.5/ 18/ /36 Covered /no 88 The Korean Journal of Gastrointestinal Endoscopy

3 Nitinol은 nickel과 titanium의합금으로형상유지및굴곡성이뛰어난특성이있어최근 SEMS의금속재료로주로사용되고있다. Nitinol 스텐트로는 Ultraflex Esophageal Stent (Boston Scientific, Natick, MA, USA) 와 NiTi-S Stent (Taewoong Medical, Seoul, Korea), Choo stent (M. I. Tech, Seoul, Korea), Bona stent (Standard Sci-Tech, Seoul, Korea), Evolution (Cook Endoscopy Winston-Salem, NC, USA), Alimaxx- E (Aveolus, Charolotte, NC, USA) 등이있다. Stainless steel 스텐트에는 Esophageal Z Stent (Cook), FerX-Ella (Ella-CS, Hradec, Kralove, Czech Republic) 등이있으며, 플라스틱재질인 polyester/silicone 으로제작된 Polyflex (Boston Scientific) 이미국에서많이사용되고있다. 역류방지형벨브 (anti-reflux valve) 가있는스텐트로는 Esophageal Z Stent(Cook), Hanarostent (M.I. tech), Bona stent (Standard Sci-Tech), FerX-Ella (Ella-CS), Antireflux S-type (Taewoong Medical) 등이있다. 다양한스텐트종류중에서어떤것을사용할것인가하는것은협착의양상, 위치, 누공의유무, 쉽게구할수있는스텐트종류에따라결정된다. 11 SEMS는피막여부에따라합병증발생양상이다르다. 막미부착형 (uncoverd) 스텐트의경우에약 17-30% 에서종양이스텐트내부로자라들어오는내발육 (ingrowth) 으로재협착이발생한다. 스텐트삽관후 2개월정도에서내발육은 50% 정도에서관찰된다. 15 그러나막부착형 (coverd) 스텐트인경우에는종양이자라들어오지는못하지만스텐트가충분히지지되지못하는경우스텐트의일탈 (migration) 이발생한다. 실을이용하여스텐트의이동을방지하는 SHIM's technique 을이용하면일탈예방에도움이될수있다. 16 막부착형스텐트에서도피막이손상되면종양의내발육이발생할수있는데, polytetrafluoroethylene (PTFE) 막보다 polyurethane 막에서더잘발생한다. 최근에는 PTFE막보다안정성이더뛰어난 silicone을많이사용한다. 부분막부착형 (partially covered) SEMS는악성누공 (fistula) 치료에있어좋은치료방법으로부각되고있으며특히악성기관식도누공치료의기본이되고있다. 그러나부분막부착형 SEMS의주요제한점은피막이되어있지않은스텐트주위로조직이과증식하는경우스텐트장착후제거가어렵기때문에이런문제를해결하기위한방법의하나로금속스텐트보다는플라스틱으로만들어진완전막부착형자가팽창형플라스틱스텐트 (self-expandable plastic stent, SEPS) 가최근에많이시도되고있다. 경부또는상부식도 (cervical or upper esophagus) 에협착이있어스텐트를삽입하는경우시술의기술적또는임상적성공률과천공, 흡인성폐렴등의합병증발생률이중간또는하부식도의스텐트삽입시와크게다르지않다고보고되었다. 17 그러나통상상부식도괄약근 (upper esophageal sphincter) 에서 1.5 cm 이내에스텐트의상단이위치하게되면이물감을심하게느낄수있다. 상부 flare의길이를줄인상부식도전용의스텐트 (Choo stent) 를이용하면증상호전에도움이될수있다. 18 하부식도및 위분문부 (GE junction) 암에의한폐색이있는경우에통상의식도스텐트를삽입하는경우위산역류가발생하고, 이에따라흉통, 기침이발생하며흡인성폐렴의위험이증가한다. 이러한문제를해결하기위하여역류를방지하는 valve를장착한스텐트가개발되었다. Gianturco-Rosch-Z valve stent with the Dua antireflux valve (Cook), Hanaro antireflux stent (M.I. Tech), NiTi-S with an antireflux skirt (Taewoong Medical), FerX-Ella stent (ELLA-CS) 와같은폴리에틸렌혹은폴리우레탄밸브를가지는스텐트들은 SEMS가위-식도접합부를가로질러거치된이후위산의역류에따른식도염증상을막기위해서고안되었다. Hanaro antireflux stent는 silicone 재질의피막을갖는스텐트로내부에 S-자형의두겹으로된긴 valve를갖고있어음식물과위산의역류를방지한다. 24시간식도-pH 검사에서식도 ph가 4 이하로내려가는시간이기존의스텐트가 15~29% 였으나 Hanaro antireflux stent로장착한경우에는 3% 에불과하였다. 19 그러나 FerX-Ella stent (Ella-CS) 를사용하여진행된연구에서는 anti-reflux 스텐트가역류현상및증상을호전시키지못하였고, 23% 에서스텐트의일탈이관찰되었다. 20 Anti-reflux Z -stent (Gianturco-Z stent, WilsonCook Europe, Bjaeverskov, Denmark) 를사용한연구에서도 50% 에서역류증상이심하였고, 10명에서일탈이관찰되어 21 antireflux 스텐트의유용성에는아직논란이있다. 그러나 Hanaro antireflux stent 는 Shim's technique 을이용한경우라서일탈이없었으나후자두연구에서는 Shim's technique 을이용하지않아서스텐트의일탈률이높았다. 또이들연구등에서는통상스텐트삽입후역류증상에대한일관된평가기준의부족과역류로인한흡입성폐렴유무에대한평가가반영되지않은점을고려해볼필요가있다. SEMS의삽입은기관식도혹은기관지식도천공같은인접장기로의악성천공이나, 의인성천공같은경우에도도움이될수있다. 1,3,22 막부착형식도스텐트는특히악성의기관식도천공에서호흡곤란을빠르게호전시키는최소한의침습적인치료방법으로적용될수있으나반면에상부식도에거치한스텐트가기관압박이나침습을가할수있다. 악성질환으로기관식도의누공이있는경우, 기관지와식도에동시에막부착형스텐트를삽입하면연하곤란과, 기도의오염을동시에완화할수있어식도의스텐트를시행하면서기도확보를위한예방적차원의기관지스텐트거치도고려해볼만한치료법이다. 23,24 양성식도질환에서의스텐트의역할 소화관의양성질환에서 SEMS의사용은담도의양성협착을제외하고논란이많다. 7 현재로서는반복적인풍선확장술이필요한심한양성협착인경우나수술적인치료가어려운경우에한하여스텐트삽입이제한되어있다. 25 반복적인풍선확장술에도불구하고재발되는난치성식도협착에있어서막미부착형 SEMS의임상적성공률은매우좋으나스텐트삽입후스텐트내부와주위로 Vol. 43 (Suppl 1), 2011 (87-92) 89

4 ingrowth 나 overgrowth 가일어나반복적인연하곤란이생기기때문에마지막수단으로이용하기도한다. 1 Choo, Song, NiTi-S, Ella-CS stent 같은제거가용이한막부착형스텐트는양성식도협착에서일시적인삽관후제거할목적으로사용되고있다. 이경우스텐트의제거는내시경이나 X선투시하에서쉽게제거가가능하다. 최근자가팽창형플라스틱스텐트 (self expanding plastic stent, SEPS) 양성식도협착치료에비교적좋은결과를보이고있다. 26 Dua 등 27 은 Polyflex stent (Boston scientific) 로양성협착을치료한 40례의보고를하였는데스텐트삽입과제거의기술적인성공률은각각 95% 와 94% 였으며 40% 환자가추가적인시술없이연하곤란증상의개선을보였다. 나머지 60% 에서는재발을보였고한명은심한출혈로사망하였다. 양성식도협착에서 SEPS 의성공률은여러연구에서 % 를보이고있어좀더신중한판단이필요하다 Boerhaave 증후군환자에서 SEMS (Song /NiTi-S stent) 를이용하여천공을해결한증례보고가있으며 SEPS를이용한치료를보고한증례도있다. 36 또한내시경을이용한식도확장술, 종양제거술시발생한천공 11례중 9례에서 SEMS 거치로천공을치료한보고가있다. 38 또다른전향적연구에서도 13례의식도천공중 12례에서 PCSEMS 로치료가능하였다. 39 수술문합부누출이나양성식도기관누공환자에서 SEMS 삽입술이시도되었는데식도문합부 3증례 40 양성식도기관누공 12 증례 41 에서 SEMS 삽입이모두효과적이었다. 또한식도절제술후발생한문합부누출 19례중 9례에서대구경 SEPS를삽입후 8례에서증상이호전되었다. 42 결론적으로 SEMS와 SEPS 삽입술은선택적인식도천공환자에있어서치료의한방법으로생각해볼수있다. 그러나아직까지는식도천공이나, 누출, 누공환자의치료방법으로식도스텐트삽입술은신중히판단해야한다. 28 제거가능스텐트의기타용도 제거가능한금속또는플라스틱재질의완전막부착형스텐트는다양한경우에성공적으로사용되어왔다. 두개의소규모연구에서국소적진행성식도암환자에서제거가능한스텐트의일시적인유치로수술전공장영양주입관 (jejunal feeding tube) 을유치할필요없이적절한영양공급이가능하였다. 43 심한연하곤란이있는환자에서스텐트를진단당시삽입하고항암화학요법또는항암화학-방사선치료종료전에 stent를제거하였다. 44 한연구에서는식도정맥류조절을위하여풍선과 FCSEMS 를혼합한 SX Ella±Danis 스텐트를이용하였다. 45 식도이완불능증 (achalasia) 의치료에일시적인 SEMS 삽관법이시도되었는데 46 75명의식도이완불능증 (achalasia) 환자는주문생산한 PCSEMS ( 길이 30 mm) 로치료하였고 4-5일후제거하였으며 10년동안 83.3% 의관해소견을보였다. 그러나또다른연구에서는식도이완불능증의치료를위한스텐트사용의시도는대부분성공적이지못하였다. 47 스텐트디자인의새로운개발 Polydioxanone monofilament로직조된생분해성의식도자가팽창스텐트는최근유럽에서시판되고있다 (Ella-BD, Ella-CS). 이스텐트는몸속에유치된후 11-12주이내에분해되고, 산성위장내용물의역류에의해서흡수과정이가속된다. 스텐트의위치가이동된경우에는위장에서분해되도록남겨둘수있다. 이스텐트의임상경험은아직제한적이기는하나주로양성식도협착에서스텐트를제거하기위해또다시내시경검사를시행하는것을피할수있을것으로기대된다. 48,49 Absorbable polylactic polymer로만들어진생분해성스텐트 (biodegradable stent) 는부식성약물복용후생긴양성협착이나의료과실로생긴내시경점막하박리의경우에사용되기도한다. 50,51 약물방출형부분막부착형스텐트역시스텐트삽입후식도스텐트일탈예방과막미부착형부위로의조직과증식을억제하는목적으로시도되고있다 fluorouracil 이나 paclitaxel 가포함된약물방출형스텐트 (drug-eluting stent) 는암조직성장이나세포과증식을저해하는것으로알려졌다. 53 식도질환에서는약물방출형스텐트가임상적으로유용하게쓰이기위해서는연구가더진행되어야할것같다. 최근식도근접방사선치료 (brachytheraphy) 방법으로베타방출방사성핵종 (beta-emitting radionuclide) 을이용한막부착형 SEMS도동물실험중에있다. 54 결론 자가팽창성스텐트는단점이있음에도불구하고악성연하곤란의완화를위해매우유용하게이용될수있다. 스텐트소재와디자인의발전으로스텐트유치로인한합병증과단점들을개선해왔으며, 악성질환만이아니고양성질환을포함해스텐트의사용범위를넓혀왔다. 쉽게제거가가능한 SEPS의개발로인해양성식도협착과누출의치료는최근 10년간괄목할만한성장을이루었다. 더욱지속적인연구개발이필요하겠지만, FCSEMS 는양성식도누출및협착의치료에있어서훨씬많은용도를갖게되었다. 또한악성질환의치료에있어서도수술및기타치료의중간단계에서더많은용도를갖게되었다. 추가적인발전으로스텐트삽입은광범위한점막절제또는박리후에예방적용도로도사용이가능해졌다. 기술이발전하면서새로운적용이더늘어날것은의문의여지가없다. 하지만, 악성그리고양성질환에의적용에있어서합병증의비율을낮추는것이중요하며, 신중한환자선택과집중관찰이필수적이다. 참고문헌 1. Sabharwal T, Morales JP, Irani FG, Adam A. Quality improvement guidelines for placement of esophageal stents. Cardiovasc 90 The Korean Journal of Gastrointestinal Endoscopy

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untitled The Korean Journal of Gastrointestinal Endoscopy Review 상부위장관스텐트삽입술의현황과미래 박종재ㆍ양창헌 * 고려대학교의과대학소화기내과학교실, 동국대학교의과대학내과학교실 * The Current Status and the Future of Upper GI Stenting Jong-Jae Park, M.D. and Chang-Hun