D-III. 만성췌장염에서내시경의역할에대한새로운개념확립 Room D 동국대학교의과대학동국대학교일산병원내과학교실 Guideline of Endoscopic Treatment for Stricture and Stone in Chronic Pancreatitis Jun Kyu Lee Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Dongguk University, Seoul, Korea Increased pancreatic ductal pressure caused by stricture and/or stones is considered to be one of the important mechanisms of pain in patients with chronic pancreatitis. Nowadays, endoscopic treatment for decompression is being used widely with excellent results. Because different lesions may be mixed even in a patient, endoscopic treatment includes various techniques such as ballooning, stenting, or basketing, in addition to endoscopic pancreatic sphincterotomy. Also, lithotriptic methods like extracorporeal shock wave lithotripsy are performed together when pancreatic stones are present. Recently, self expandable metallic stents and endosonography guided access and drainage were introduced with promising preliminary results. There were studies reporting surgery was superior to endoscopic treatment for the long term outcome. However, as endoscopic treatment is less invasive, it is chosen as the first line interventional therapy for a patient who cannot tolerate or refuses surgery. Also, endoscopic treatment is used as a bridge to surgery or a method to predict the potential response to surgery. In conclusion, complementary strategy would be the optimal management for a patient with intractable pain. 서론만성췌장염 (chronic pancreatitis) 은췌장실질의지속적 및연속적파괴로인하여췌장의외분비및내분비기능의장애가초래되는만성염증성질환이다. 지속적으로재발하는심한복통은만성췌장염환자의삶의질 (quality of life) 을저하시키는가장주된증상이므로적극적인조절이필요하다. 만성췌장염환자에서통증이발생하는기전은명확히알려져있지않지만, 췌장주위신경 (peripancreatic nerve) 및복강신경절 (celiac plexus) 의염증에의한췌장성신경병증 (pancreatic neuropathy), 췌액누출이나가성낭종같은합병증등과함께췌관협착및췌석에의한췌관및췌실질내압력상승및이로인한췌장혈류감소가중요한인자로작용하는것으로이해되고있다. 본고에서는주췌관협착및췌석치료에대하여 European Society of Gastrointestinal Endoscopy (ESGE) 등의각종가이드라인에소개된내용및최근의연구들을중심으로살펴보고자한다. 1 본론 1. 치료방법의선택 : 내시경적치료와수술적치료중어떤치료가효과적인가? 만성췌장염환자에서언제내시경또는수술적치료를시행할것인지에대해서는정확히연구된바가없지만, 일반적으로 3개월이상마약성진통제를복용해야하는환자에서사실상효과가없거나부작용이문제시될때시행한다. 2 췌관협착, 췌석또는양자가함께작용하여췌관폐쇄를유발할수있는데, 1,000명이상의환자를대상으로하였던대규모다기관연구에서주체관협착의원인으로협착이 제 51 회대한소화기내시경학회세미나 241
47%, 췌석이 18%, 협착및췌석이함께있는경우가 32% 이었다. 3 이환자들을내시경적치료후평균 4.9년동안추적하였을때전체적으로는 86% 에서, 치료의도 (intention totreatment) 군에서는 65% 에서성공적으로통증이경감되었는데치료성공률은협착만있는경우, 췌석만있는경우, 협착과췌석이있는경우모두비슷하였다. 같은환자에서도여러병변이혼재되어나타나는만성췌장염의특성상내시경적치료는췌관괄약근절개술 (endoscopic pancreatic sphincterotomy, EPST) 을기본으로하여바스켓, 풍선카테터, 겸자등을이용한췌석제거술, 풍선확장술, 스텐트삽입술등이복합되어효과를나타내며개별환자의상태에맞추어시술방법이선택된다. 4 또한, 췌석이동반된경우에는체외충격파쇄석술 (extracorporeal shock wave lithotripsy, ESWL) 등의쇄석술이함께시행되기도한다. 참고로담관괄약근절개술 (biliary sphincterotomy) 은담관협착이동반된경우나선택적췌관삽관이어려운경우에한하여시행된다. 수술은오랫동안통증을동반한만성췌장염환자에있어서표준치료로서여겨져왔다. 하지만내시경적역행성담췌관조영술 (endoscopic retrograde cholangiopancreatography, ERCP) 을근간으로하는치료내시경분야의발전에따라그역할이변화되고있다. 현재까지연구결과내시경적치료는위험성으로인하여당장은수술이어려운환자에있어서향후췌장수술의효과를증대할수있는가교적치료 (bridge treatment) 로써효과적이며, 5,6 향후수술적치료의반응도예측할수있는것으로알려져있다. 7 또한, 재발시에도추가적위험성없이쉽게재시술할수있으며, 실패하더라도수술적치료를시행할수있다는점등이내시경적치료의장점이다. 하지만일반적인경우에내시경적치료가수술을대신할수있는최적의우선치료인지에대해서는논란의여지가있다. 8 내시경적치료와수술을비교한두편의전향적무작위대조연구에서 Dite 등은 5년, Cahen 등은 2년 ( 이후 5 년추적의결과를별도로발표함 ) 추적하였을때내시경적치료는수술에비하여통증경감의효과가낮고유지기간이짧은것으로나타났다. 9 11 하지만통증의평가가주관적이었고눈가림되지않았으며특히수술군에있어서는췌관협착이나췌석의위치나양상에대한자세한기술이되어있지않으므로해석상의주의를요한다. 그리고수술을시행하더라도많은환자에서통증이경감되지않거나재발하였으며이러한환자에서는해부학적구조의비가역적변화에의하여재수술시기술적난이도가높고합병증이빈발한다는사실역시간과해서는안된다. 또한, 자연경과상통증소진 (burn out) 이드물지않다는점도만성췌장염환자에서수술을신중히결정하여야하는이유이다. 2. 주췌관협착에대한내시경적치료의방법과효과는어떠한가? 일반적으로복통이없는만성췌장염에서는내시경적치료가추천되지않는다. 통증이있더라도다음중한가지이상에해당할때주췌관협착이자명 (dominant) 하다고정의되며, 대부분의연구가이러한환자를치료의대상으로한다 12 1) 협착부위상부의주체관이 6 mm 이상확장된경우, 2) 카테터를통하여협착부위상부로주입된조영제가자연배출되지않는경우, 3) 협착상부에삽입된비췌관카테터 (nasopancreatic catheter) 를통해 1 L의생리식염수를 12 24시간에걸쳐주입하였을때복통이유발되는경우이다. 주췌관협착에대하여내시경적치료를시행할때에는적어도한개이상의스텐트가협착부위상부로적절하게삽입되어야한다. 시술성공률은연구에따라 85 98% 로보고되고있는데, 13 16 췌관의협착이두부에있으면서췌관확장이동반된경우치료성적이가장좋으며, 협착이미부에있거나다발성으로서염주모양을보이는경우에좋지않다. 17,18 많은경우에스텐트삽입을용이하게하거나동반된췌석을제거하기위하여풍선확장술이시행되지만협착치료를목적으로하는단독풍선확장술은더이상사용되지않는다. 풍선확장술이여의치않을경우에는부지 (bougie) 또는 Soehendra stent retriever를이용한시술을시도하여볼수있다. 내시경적치료의통증경감효과의단기적성공률은 70 94%, 스텐트제거후 1년이상통증이재발되지않는경우로정의되는장기적성공률은 52 82% 로보고되고있다. 16,19 23 3. 어떠한스텐트를삽입하여얼마나오랫동안유지하여야하는가? 주췌관의형태와협착의길이를고려하여스텐트가선택되는데, ESGE 가이드라인에서는 8.5 Fr의가는스텐트의경우 10 Fr 스텐트와비교하여복통으로인한입원빈도가높은것으로보고한연구에근거하여 10 Fr 폴리에틸렌스텐트의사용을추천하고있다. 24 스텐트를 6개월이하단기간유지할때에는효과적이지않은경우가많으므로, 스텐트의제거시기에대하여 6 12개월동안유지하고주췌관의협착소실유무와관계없이제거하는방법과협착이소실될때까지계속스텐트를교체하는두가지방법이사용되고있다. 25 일반적으로협착상부를조영제로충만시켰을때 1 2분후에정상적으로배출되거나 6 Fr 242 Korean Society of Gastrointestinal Endoscopy
카테터가자유롭게통과될때스텐트를제거한다. 스텐트의폐쇄는보통 2 3개월사이에나타나지만스텐트주위를통하여췌액이흘러나올수있으므로폐쇄에의한증상재발은 6 12개월사이에발생한다는점을고려하여스텐트의교환시점을결정한다. 이러한사실에근거하여 ERCP 횟수를감소시키기위하여정기적인스텐트교체를대신하여필요시에 (on demand) 스텐트를교체하는방법이시도되었다. 13,19,21 하지만이러한방법은드물게농양이나패혈증을유발할가능성이있으며실제로 ERCP 횟수가줄어들지않는것으로나타났다. 한편 Costamagna 등은여러개의스텐트를동시에삽입할경우 ERCP 시술횟수는줄일수있는반면치료효과가장기적으로유지됨을보고하였으며, 26 ESGE 가이드라인에서는이에근거하여 12개월이상단일스텐트삽입상태를유지하였음에도불구하고주췌관협착이지속되는환자에있어서는다수 (multiple) 스텐트삽입술을고려하여볼수있다고언급하였다. 단, 이때치료방침은다학제적으로결정됨을명시하고있다 ( 권고수준 D). 4. 스텐트삽입술은어떠한합병증을유발할수있는가? 스텐트삽입술과관련된합병증은 6 39% 에서발생하는데, 췌장염의급성악화가가장흔하지만대개경증으로서보존적치료로호전된다. 13 16,19,21,22,27 드물게췌장농양이나스텐트의이탈 (migration) 이발생할수있다. 드물지만원위부 (distal) 이탈에의하여반대편십이지장벽의천공이발생할수있으며, 근위부 (proxima) 이탈의경우에는내시경적제거가쉽지않으므로주의하여야한다. 5. 금속스텐트는안전하게사용할수있는가? 여러연구에서완전피막형 (fully covered) 금속스텐트는안전하며주췌관협착의해소와함께통증완화효과가있는것으로보고되었다. 하지만양성담관협착의경우와마찬가지로개통기간이 1년을넘지는못하므로반드시제거하여야한다. 비피막형금속스텐트의경우에는내시경을통한제거가불가능할수있으므로주췌관협착환자에게삽입되어서는안된다. 28 총 51명의환자를대상으로 2 3개월간금속스텐트를유지하였던 2개의국내연구를포함한 3개의전향적연구를분석하였을때스텐트제거가시도되었던 46명모두에서성공적으로스텐트가제거되었다. 29 31 스텐트제거이후평균 5개월동안추적하였을때 50명중 43명에서통증이재발하지않았다. 한연구에서는스텐트이탈이 13명의환자중 13% 에서발생하였고, 29 새로운주췌관협착이 32명중 16% 에서발생하였다. 31 ESGE 가이드라인에서는 1년이상의추적기간에대해서는연구결과가부족함을고려하여현상황에서금속스텐트는 1년이내에교환이예정된임상시험에서만사용되어야한다고언급하고있다. 6. 초음파내시경유도하배액술은어떠한역할을하는가? 주췌관의초음파내시경유도하배액술 (endosonographyguided access and drainage, ESGAD) 은증상이있지만기존의경유두배액술 (transpapillary drainage) 이실패한환자에있어서통증경감에효과적인것으로보고되고있다. 하지만적은수의환자를대상으로단기간추적한연구만수행되었으므로현상황에서는적절한장비와경험을보유하고있는병원에서만시행되어야한다. 현재까지발표된약 75명의환자를대상으로한 6개의연구를살펴보면 32 37 추적기간은수주에서 55개월 ( 평균 1년 ) 사이로범위가넓었는데, 대다수의환자에서시술직후에통증경감효과가있는것으로나타났다 ( 범위 : 50 100%). 이중 36명의환자를대상으로한가장큰규모의연구에서통증소실은 69% 의환자에서나타났으나시간이경과할수록빠르게재발이증가하여 450일시점에서는약 20% 에불과하였다. 35 주췌관의완전협착환자에있어서는악성의가능성을항상염두에두어야하는데위의연구에서 36명중 5명이시술 1년이내에췌장암을진단받았다. 시술관련합병증은 0 44% 에서발생하는것으로보고되었는데주로가벼운통증이었지만때로는중증의췌장염, 천공, 출혈, 혈종형성등이보고되었다. 아직까지사망례는보고되지않았다. 또한, 재시술을요하는스텐트의이탈이나폐쇄가 20 55% 에서발생할정도로흔하였다. 7. 어떠한방법으로췌석을제거할것인가? 췌석은방사선투과성 ( 투과성혹은비투과성 ) 이나위치 ( 두부, 체부, 미부또는주체관, 이차분지, 실질내 ) 등에의해서분류된다. ESWL 후성공적인췌석분쇄는 2 3 mm 이하로조각난경우, 방사선촬영에서췌석밀도가감소한경우등으로정의된다. 췌석을제거하는비수술적방법에는내시경적제거술, ESWL, ESWL과내시경적제거술의병용등이가장많이사용되고있다. 췌석이 3개이하인경우, 췌장두부혹은체부에국한된경우, 췌석하류에협착이없는경우, 췌석직경이 5 mm 이하인경우, 감돈되지않은경우등에있어서는내시경적방법만으로제거를시도하여볼수있는데약 50 75% 에서내시경을이용하여성공적으로제거될수있다. 38,39 하지만췌석의크기가크거나협착의정도가심하여내시경을이 제 51 회대한소화기내시경학회세미나 243
용한췌석제거및췌관감압술이어려운경우에는쇄석술이필요하다. 기계적쇄석술 (mechanical lithotripsy) 이외에 ESWL, 전기수압쇄석술 (electrohydraulic lithotripsy, EHL), 레이저쇄석술 (laser lithotripsy) 등의방법이있는데세가지방법을직접비교한연구는없지만시행이쉽고 90% 이상에서효욜적으로췌석을분쇄할수있는 ESWL이가장많이사용된다. 40 기계적쇄석술은감돈되어있는췌석에대해서는사용이불가능하고, 담관담석의경우보다합병증이 3배정도빈발한다. 38 EHL 또는레이저쇄석술의경우에는 mother baby 내시경이나 SpyGlass 등의특수장비가필요하며, 아직많은경험이축적되지않은상태이다. 41,42 따라서 ESGE 가이드라인에서는이러한방법들은 ESWL이실패할경우에이차적으로고려되어야한다고언급하고있다. 8. 내시경적치료와함께 ESWL 을시행하여야하는가? ESWL은방사선비투과성췌석의분쇄에있어매우효과적이며, 내시경적제거를용이하게한다. 총 1,149명의환자를대상으로한 11개의연구에대한체계적문헌고찰 (systematic review) 에서분쇄성공률은 89% 였다. 43 최근에시행되었던대규모전향적단일기관연구에서 1,006명의환자중 935명 (93%) 에서췌석이성공적으로분쇄되었다. 44 반면사전에 ESWL을시행하지않고바스켓을사용하여췌석을제거하는경우에는성공률이높지않아서, 125명의환자를대상으로한후향적연구에서성공률은 9% 로보고되었다. 45 따라서 ESGE 가이드라인에서는다른합병증이동반되지않은복통을호소하는만성췌장염환자에있어서주췌관을폐쇄하는 5 mm 이상의방사선비투과성췌석을치료할때에는 ESWL을우선적으로시행하고이어서분쇄된췌석을내시경적방법으로제거할것을권고하고있다. 한편 Dumonceau 등이시행하였던전향적무작위연구에서 ESWL과내시경동시치료는 ESWL 단독치료와비교하였을때통증경감효과는비슷한반면입원기간이길고비용높은것으로나타났다. 46 또한, ESWL을시행할경우약 80% 의환자에서분쇄된췌석의자연적배출을기대할수있으므로 ESGE 가이드라인에서는 ESWL에대한경험이풍부한병원에서는내시경적치료의병용시행보다 ESWL 단독치료를우선적으로고려할것을권고하고있다. 9. 췌석제거술과관련된합병증이나금기증에는어떠한것이있는가? 내시경적췌석제거술과 ESWL에있어서가장흔한합병증은췌장염이다. 100명이상의환자를대상으로하였던 4개의 대규모연구에서 ESWL 후내시경적치료시심각한합병증은 1,801명중 104명 (5.8%) 에서발생하였으며한예 (0.05%) 의사망례도보고되었다. 44,47 49 ESWL 단독치료의경우 165 명의환자를대상으로한세개의연구에서합병증발생률은 6.0% 였다. 46,50,51 또한, ESWL의합병증으로서일시적통증이나충격파전달부위피부에멍이발생할수있다. 52,53 한편협착이심한경우에는내시경적치료에의하여주변의췌장실질의손상이발생할수있는데, 특히기계적쇄석술을시행할때에는췌관의파열이나바스켓의감돈이나골절등의심각한합병증이발생할수있으며담석제거목적으로시행할때보다합병증이세배높게보고되었다. 38 ESWL의금기증에는응고장애, 임산부, 충격파의경로안에뼈, 석화화된동맥류, 폐조직이포함되는경우, 심박동기나제세동기의이식등이있는데이중심박동기이식의경우에는논란의여지가있다. 54 결론 만성췌장염환자에서통증이발생하는기전은명확히알려져있지않지만췌관협착및췌석에의한췌관및췌실질내압력상승이중요한인자로작용하는것으로이해되고있다. 따라서췌관의압력을낮추기위한내시경적치료가널리시행되고있으며좋은성적을나타내고있다. 같은환자에서도여러병변이혼재되어나타나는만성췌장염의특성상내시경적치료는 EPST를기본으로하여바스켓, 풍선카테터, 겸자등을이용한췌석제거술, 풍선확장술, 스텐트삽입술등이복합되어효과를나타내며개별환자에상태에맞추어시술방법이선택된다. 또한, 췌석이동반된경우에는 ESWL 등을이용한쇄석술이함께시행되기도한다. 최근에는금속스텐트나초음파내시경유도하배액술이도입되어기대를모으고있다. 수술이장기적인치료효과에있어서내시경적치료에비하여우월하다는보고가있었다. 하지만내시경적치료는덜침습적이므로수술적치료에적합하지않거나거부하는환자에서일차적중재술로선택될수있다. 또한, 수술시까지의가교치료또는수술적치료의반응을예측하기위한수단으로서유용한역할을할수있다. 결국내시경적치료와수술이개별환자의상황에맞추어상호보완적으로시행될때최적의치료가이루어질수있다. 참고문헌 1. Dumonceau JM, Delhaye M, Tringali A, et al. Endoscopic 244 Korean Society of Gastrointestinal Endoscopy
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