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The Korean Journal of Gastrointestinal Endoscopy Original Article 폐쇄된담도금속관치료에서피막형및비피막형금속관의유용성비교 정경식ㆍ정우진ㆍ김동욱ㆍ최철웅ㆍ강대환 부산대학교의학전문대학원내과학교실 Management of Occluded Biliary Uncovered Metal Stents: Covered Self Expandable Metallic Stent vs. Uncovered Self Expandable Metallic Stent Kyung Sik Jung, M.D., Woo Jin Jung, M.D., Dong Uk Kim, M.D., Cheul Woong Choi, M.D. and Dae Hwan Kang, M.D. Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea Background/Aims: Unresectable malignant biliary obstruction has usually been treated by placement of a self-expandable metallic stent (SEMS). One of the major complications of SEMS is occlusion of the stent by the ingrowth and overgrowth of tumor. The optimal management of an occluded SEMS is still an unresolved problem. We performed this study to evaluate the usefulness of placing a second stent with using an uncovered SEMS or a covered SEMS in patients with stent occlusion. Methods: From January 2006 to December 2007, a total of 163 patients were treated with the placement of an uncovered SEMS for treating malignant biliary obstruction, except for the cases with Klatskin s tumor. Thirty four patients were occluded and they underwent a second SEMS insertion. All the patients with an occluded uncovered SEMS were managed with placement of a covered SEMS or an uncovered SEMS by ERCP. Results: The median patent duration after intervention was 98 days (range: 8 300 days) after the second covered SEMS insertion, and the median patent duration after intervention was 90 days (range: 10 643 days) after the second uncovered SEMS insertion. No significant difference in the patent period was observed between the covered SEMS group and the uncovered SEMS group (P=0.832). Conclusions: The covered SEMS group and the uncovered SEMS group had similar patent periods for the management of occluded uncovered metal stents. (Korean J Gastrointest Endosc 2009;39:149-153) Key Words: Occluded SEMS, Uncovered SEMS, Covered SEMS 교신저자. 강대환부산대학병원소화기내과 (626-770), 경남양산시물급읍범어리전화 : 051-240-7869 팩스 : 051-244-8180 이메일 : hero0791@paran.com 이논문은부산대학교자유과제학술연구비 (2 년 ) 와 BK21 연구비에의하여연구되었음. 접수. 2008 년 11 월 29 일승인. 2009 년 8 월 18 일 서론악성췌담도종양으로인한폐쇄성황달환자는진단당시이미진행된상태로발견되어수술이불가능한경우가흔하다. 환자의소양감, 담도염, 지방흡수장애및간기능이상등을조절하기위해대증요법으로내시경역행성췌담관조영술 (endoscopic retrograde cholangiopancreatography, ERCP) 에의한자가팽창형금속배액관 (self-expandable metallic stent, SEMS) 을흔히유치하고있다. SEMS는 1989년부터도입되었고 1,2 플라스틱배액관에비해상대적으로장기간담도에유치할수있으나 1 종양의내증식과외증식으로인한담도폐쇄와높은비용및제거가어려운단점이있다. 3-8 종양의내증식에의한폐쇄비율은 20 40% 로알려져있다. 9-12 종양의내증식문제를극복하기위해 covered SEMS가도입되었지만췌장염, 담낭염, 일탈등의문제점을지니고있다. 폐쇄된 SEMS의가장효과적인치료방법이무엇인지는결론이나지않은문제이며 Tham 등 13 은폐쇄된 SEMS내로플라스 Vol. 39, No. 3 September, 2009 (149-153) 149

틱배액관을삽입하는것이가장비용효과적이며 Jason 등 14 은 SEMS를다시유치하는것이플라스틱배액관과비교해서비용효과적이라고보고하였다. 그리고 Toqawa 등 15 은폐쇄된 SEMS내로 covered SEMS를유치하는것을효과적이며안전한치료방법으로제시하였으나소규모이며후향적으로진행된연구라는제한점이있다. 본연구는폐쇄된 SEMS를가진환자에서 covered SEMS와 uncovered SEMS의유용성을알아보기위해시행하였다. 대상및방법 1. 대상 2006년 1월부터 2007년 12월까지부산대학병원에서간문부담도암을제외한악성담도폐쇄로 uncovered SEMS 시술을하였고이후폐쇄되어 SEMS를다시유치한환자 34명을대상으로하였다. ERCP를통하여 15명에서 uncovered SEMS를, 19 명에서 covered SEMS를유치하는시술이시행되었다 (Table 1). 2. 방법 환자에게 10% lidocaine spray로목마취를하였고 midazolam과 pethidine hydrochloride 정맥주사로수면내시경을유도하여 ERCP를시행하였다. 십이지장의이완을위해 cimetropium-bromide를정맥주사하였다. ERCP는진단및치료십이지장내시경 (Olympus, Tokyo, Japan JF-240, TJF-240) 을이용하였다. 급성담도염이동반된경우에는플라스틱배액관이나 endoscopic nasobiliary drainage (ENBD) 를유치한뒤상태가호전 Table 1. Patient Characteristics Second stent type Uncovered SEMS Covered SEMS No. of patients 15 19 Age (range) 71.2 (39 85) 72 (54 89) Sex, M/F 10/5 12/7 Causative disease Pancreatic cancer 5 8 Bile duct cancer 8 9 Gallbladder cancer 1 1 LN metastasis 1 1 Cause of first stent occlusion Ingrowth 12 15 Overgrowth 3 4 Sludge/debris 0 1 Patency of first stent, 200 (48 535) 113 (46 512) day, median (range) LN, lymph node; SEMS, self-expandable metal stent. 된후에스탠트시술을시행하였다. 2차 SEMS는 uncovered SEMS (Niti-S, Tae Woong, Seoul, Korea) 또는 covered SEMS (Niti-S) 를사용하였다. 자료는후향적으로내시경결과지및차트를조사하여정리하였다. 스텐트의개통기간은 2차스텐트가유치된시점에서다시폐쇄되거나환자의사망시점까지의기간으로정의하였다. 스텐트개존기간은 Kaplan-Meier 방법으로통계처리하였고두군사이의비교는 log-rank test를사용하였다. 통계분석은 SPSS version 12.0을이용하였고유의성을보이는경우는 p-value <0.05로하였다. 결과 2차스텐트로 uncovered SEMS를유치한환자는 15명이었고평균나이는 71.2세 (39 85) 이며남자는 10명여자는 5명이었다. Covered SEMS의경우, 환자는 19명이었고평균나이는 72 세 (54 89) 이며남자는 12명여자는 7명이었다. 악성담도폐쇄의원인으로는 uncovered SEMS의경우담도암 8명, 췌장암 5 명, 담낭암 1명, 임파선전이 1명으로진단되었고, covered SEMS는담도암 9명, 췌장암 8명, 담낭암 1명, 임파선전이가 1 명이었다. 2차 uncovered SEMS군과 covered SEMS군에서최초 SEMS의폐쇄원인은종양의내증식이각각 12명과 16명, 외증식이각각 3명과 4명으로나타났다. 최초 SEMS의중앙개통기간은 uncovered SEMS군에서 200일 ( 범위 : 48 535) 였고 covered SEMS군에서는 113일 ( 범위 : 46 512) 이었다 (Table 1). SEMS의폐쇄증상과증후는간기능이상, 황달, 담도염, 복통등이있었다 (Table 2). 2차 uncovered SEMS군과 covered SEMS군에서각각의중앙개통기간은 90일 ( 범위 : 10 643) 과 98일 ( 범위 : 8 300) 로나타났으며통계학적차이는없었다 (Fig. 1) (p=0.832). 또한생존기간의중앙값도 183일 ( 범위 : 11 643) 과 313일 (38 1,054) 로측정되었고 (Table 3) 두군사이에통계적으로의미를보이진않았다 (Fig. 2) (p=0.326). Table 2. Clinical Presentation at Insertion of Second SEMS Sign or symptom Uncovered SEMS Covered SEMS Abnormal liver function 12 (80%) 16 (84%) test, no (%) Total bilirubin, mg/dl, mean 5.9 6.7 Alanine aminotransferase, 57 82.8 IU/L, mean Jaundice, no (%) 6 (40%) 13 (68%) Suspected cholangitis, no (%) 7 (46%) 14 (73%) Pneumobilia, no (%) 4 (26%) 7 (36%) Abdominal pain, no (%) 9 (60%) 9 (47%) SEMS, self-expandable metal stent. 150 The Korean Journal of Gastrointestinal Endoscopy

Figure 1. Cumulative patent period of second stenting with uncovered SEMS and covered SEMS (p=0.832). Figure 2. Cumulative survival time of patients with second uncovered SEMS and covered SEMS (p=0.326). Table 3. Outcomes of Second Stenting Second stent type Uncovered SEMS Covered SEMS Patency of second stent, 90 (10 643) 98 (8 300) day, median (range) Survival time, day, 183 (11 643) 313 (38 1,054) median (range) 2차스텐트를유치하였을때합병증으로 uncovered SEMS군에서는스텐트유치후담낭염과담도염이병발한경우가 1예, 담도염이악화되어사망한경우도 1예있었다. Covered SEMS 군에서는담낭염, 담도염이각각 1예가있었다. 고찰 기능부전을보이는 SEMS의치료에쓰이는여러가지방법들로 mechanical cleaning과악성조직의내증식를제거하는투열요법, 1차배액관에 2차배액관을유치하는방법, 경피경간담즙배액술 (percutaneous tanshepatic biliary drainage, PTBD), 십이지장내로튀어나온스텐트를아르곤플라스마로절단하는방법, 그리고 SEMS를내시경으로제거하는방법들이제시되고있다. 13,16,17 그중 1차 stent내로 2차 stent를유치하는방법이흔히이용되며경피경간담즙배액술에비해서생리적인상태로담즙을배액하며체외에관이노출되지않아환자의불편함을감소시키는장점이있다. 수술로제거할수없는악성담도폐쇄의경우에는일반적으로 SEMS를담도내에유치함으로써담도폐쇄에따른합병증을조절하였다. SEMS는종종종양의내증식및외증식으로인해다시폐쇄되는문제점을가지고있다. 또한 SEMS는한번유치 하면제거가곤란하기때문에 2차담도폐쇄에대한치료방법들중스텐트내에스텐트를유치하는방법이사용되는데플라스틱배액관은영구적이지못하고 2 4개월후에폐색되어교환해야하는단점이있어서 18 보다넓은배액관의직경을확보하고장기간의기능유지가용이한금속스텐트를많이이용하고있다. 9,11,19 그러나경제적측면에서환자의여명을고려했을때그기간이짧을것이라예상되는경우는플라스틱배액관이효과적이며생존기간이장기간으로예상되는경우는금속성스텐트가좀더유용하리라생각되나여명을예측하기가어렵기때문에시술자의경험에의존하는경향을보인다. Tham 등 13 은 uncovered Wallstent 폐쇄환자 38명에서치료방법으로 mechanical cleaning과 uncovered Wallstent 삽입하는방법및플라스틱배액관삽입하는방법을후향적으로비교하여세가지방법이비슷한유용성를보였지만플라스틱배액관을삽입하는것이가장비용효과적임을보고하였다. Bueno 등 17 은 Wallstent 폐쇄환자 34명에서세가지방법중에 uncovered Wallstent삽입이유용하다고보고하였으나 uncovered Wallstent 삽입환자가단지 4명이었다. 앞의연구 13,17 에서는 covered SEMS가도입되지않았고대상환자의수가적은문제점이있다. SEMS 폐쇄의가장흔한원인으로종양의내증식이며이런합병증을극복하기위해 1990년대들어 covered SEMS가개발되었다. 20 Covered SEMS는스텐트를관통해서자라는종양조직의침투를방지하기위해그물망에 polyurethane, silicone, polytetrafluoroethylene (PTFE), Gore-Tex 등의막이부착되어있다. Covered SEMS의합병증은조기에는스텐트의이동, 후기에는종양의외증식과찌꺼기에의한폐쇄가발생할수있다. 2차 covered SEMS가 uncovered SEMS보다우수한성적을보인다는연구에서 7명의 uncovered SEMS군과 26명의 covered SEMS군사이의개통기간의의미있는차이를보고하였고 Vol. 39, No. 3 September, 2009 (149-153) 151

(p=0.0404), 15 생존기간에서는의미있는차이가없었다. 그러나본연구에서 2차 stent로서 15명의 covered SEMS와 19명의 uncovered SEMS사이의개통기간과생존기간에서비슷한유용성을보여, 피막의유무에따른영향은없었다. Covered SEMS의합병증중담낭염이가장우려되며 21,22 이전에는 SEMS의피막이담낭관의입구를막아서발생하는것으로생각하였다. 본연구에서는담낭염이두군에서똑같이 1예씩발생하였고다른원인을고려하면조영제의담낭내주입, 종양성장으로인한담낭관폐쇄등을고려하여야한다. 최근에연구에서담낭염의발생은담낭관의입구까지침범하는종양과밀접하게연관되며 covered SEMS와 uncovered SEMS에서공히발생하는것으로보고하였다. 22 미리종양의담낭관입구침범을파악한다면 2차스텐트시술에따른담낭염의발생을예측할수있을것이다. Kaplan-Meier 생존분석에서 30일, 60일, 90일개통비율은 uncoverd SEMS군 86%, 80%, 53%, covered SEMS군 94%, 68%, 63% 였으며장기적으로 covered SEMS군이우수하게보였지만의미있는차이는없었다. 정확한원인을알수없지만대부분의악성종양환자가 2차스텐트의폐쇄가일어날만큼충분한기간동안생존하지못한것이하나의원인으로추정된다. 이번연구의제한점으로는 uncovered SEMS가폐쇄되어치료받는경우가많지않기때문에연구대상자수가적었다는점과후향적으로분석하였기때문에 selection bias가개입했을가능성이있었다는점이다. 결론적으로폐쇄된 biliary uncovered metal stent의치료에있어서 covered SEMS사용은 uncovered SEMS와비슷한결과를보였다. 앞으로폐쇄된 uncovered SEMS의가장효과적인치료방법에대해서, 여러종류의스텐트에대한, 대규모전향적인연구가필요할것으로생각한다. 요약목적 : 수술이불가능한악성췌담도종양으로인한폐쇄성황달은자가팽창형금속배액관 (self-expandable metallic stent, SEMS) 을이용하여치료하고있다. SEMS의흔한합병증으로종양의내증식과외증식이있으며아직까지폐쇄된 SEMS에대한가장효과적인치료법에대해서는연구가미흡한실정이다. 폐쇄된 SEMS 환자치료에서 covered SEMS와 uncovered SEMS 의유용성을비교분석하였다. 대상및방법 : 2006년 1월부터 2007년 12월까지간문부담도암을제외한악성담도폐쇄로 uncovered SEMS를시술한 163 명의환자중추적기간동안폐쇄되어 SEMS를유치한 34명의환자를대상으로하였다. 폐쇄된 SEMS는 ERCP를통해서 uncovered SEMS나 covered SEMS를유치하였다. 자료는후향적 으로분석하여정리하였다. 결과 : 폐쇄된 SEMS에서 2차스텐트유치한후개통기간의중앙값은 covered SEMS군 98일 ( 범위 : 8 300), uncovered SEMS군 90일 ( 범위 : 10 643) 였다. Covered SEMS와 uncovered SEMS 사이의통계적으로유의한개존기간차이는없었다 (p=0.832). 결론 : 폐쇄된 SEMS의치료에있어서 covered SEMS와 uncovered SEMS는비슷한개통기간을보였다. 색인단어 : 폐쇄된 SEMS, Uncovered SEMS, Covered SEMS 참고문헌 1. Huibregtse K, Cheng J, Coene PP, Fickems P, Tygat GN. Endoscopic placement of expandable metal stents for biliary strictures - a preliminary report on experience with 33 patients. Endoscopy 1989;21:280-282. 2. Irving JD, Adam A, Dick R, Dondeliger RE, Lunderquist A, Roche A. Gianturco expandable metallic biliary stents: results of a European clinical trial. Radiology 1989;172:321-326. 3. Lee MJ, Dawson SL, Mueller PR, et al. Percutaneous management of hilar biliary malignancies with metallic endoprostheses: results, technical problems, and causes of failure. Radiographics 1993;13:1249-1263. 4. Mueller PR. Metallic endoprotheses: boon or bust? Radiology 1991;179:603-605. 5. Lee MJ, Dawson SL, Mueller PR, Krebs TL, Saini S, Hahn PF. Palliation of malignant bile duct obstruction with metallic biliary endoprotheses: technique, results, and complications. J Vasc Interv Radiol 1992;3:665-671. 6. Gillams A, Dick R, Dooley JS, Wallsten H, El-Din A. Self expandable stainless steel braided endoprothesis for biliary strictures. Radiology 1990;174:137-140. 7. Maccioni F, Rossi M, Salvatori FM, Ricci P, Bezzi M, Rossi P. Metallic stents in benign biliary strictures: three-year followup. Caridovasc Intervent Radiol 1992;15:360-366. 8. Bezzi M, Orsi F, Salvatori FM, Maccioni F, Rossi P. Self expandable nitinol stent for the management of biliary obstruction: long-term clinical results. J Vasc Interv Radiol 1994; 5:287-293. 9. Davids PH, Groen AK, Rauws EA, Tytgat CN, Huibregtse K. Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 1992;340:1488-1492. 10. Wagner HJ, Knyrim K, Vakil N, Vakil N. Plastic endoprostheses versus metal stents in the palliative treatment of malignant hilar biliary obstruction. A prospective and randomized trial. Endoscopy 1993;25:213-218. 11. Knyrim K, Wagner HJ, Pausch J, et al. A prospective, randomized, controlled trial of metal stents for malignant obstruction of the common bile duct. Endoscopy 1993;25:207-212. 12. O Brien S, Hatfield AR, Craig PI, Williams SP. A three-year follow-up of self-expanding metal stents in the endoscopic palliation of longterm survivors with malignant biliary obs- 152 The Korean Journal of Gastrointestinal Endoscopy

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