대한춰 l 담도연구회지 2003; 8: 춰1 담도종양의수술에있어수술전담도배액은 반드시필요한가? 원광대학교의과대학소화기내과 김 현를향상에도움이되는가?, 환자의건강상태를 서론과거에는쉐십이지장절제술은 20% 이상의수술후사망률과 60% 에달하는높은합병증으로수술이극히

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1 대한춰 l 담도연구회지 2003; 8: 춰1 담도종양의수술에있어수술전담도배액은 반드시필요한가? 원광대학교의과대학소화기내과 김 현를향상에도움이되는가?, 환자의건강상태를 서론과거에는쉐십이지장절제술은 20% 이상의수술후사망률과 60% 에달하는높은합병증으로수술이극히제한적으로이루어져왔다 l 하 향상시키는가?, 근치적절제술을가능하게하는가? 는의문시되고있다. 본고에서는담춰l 관악성질환으로인한황달의치료에있어이러한목적들에중점을두고수술전경피담도배액술이나내시경적담도배액술에의한감황술의득실 지만최근들어수술술기발달및수술전후의 을분석하고, 배액술의선택, 이에따른합병증 환자처치술발달로쉐십이지장절제술은합병 등에대한국내외의문헌을고찰하고자한다. 증및사망률이계속적으로감소하고있어수술 사망률이 5% 이하로보고되고있고, 합병증도 30-40% 정도로보고된다 2-5 아직도이같은사망률과합병률은타수술에비해높다고여겨지고있으며, 수술전이를예측할수있는변수로환자의연령, 암종의종류, 수술전담도배액술, 황달의중등도, 환자의영양상태, 감염, 신장의기능등과병원규모등이제시되고있다 6,7 그중술전담도배액술은아직도논쟁이많은데수술전배액술을시행함으로써환자의증상의경감과장문합에도움이된다는주장8, 9 과감염, 출혈, 담도누공형성, 입원기간등이오히려증가하여해서는안된다는주장이있어아직도논란이되고있다 10, 11 경피적담도배액술과내시경적담도배액술의기술적발전에많은진보가있어왔고전세계적으로많이보급되어왔다. 따라서현재많은병원에서는폐쇄성황달로인한소양감, 복통등의증상경감, 담도염치유, 수술지연, 담도촬영등의이유로이러한배액술들이시행되고있 다 12 그러나이러한담도매액술이수술의결과 PTBD (Percutaneous transhepatic Biliary Drainage; 겸피적경간담도배액술 ) 의발전 1960년대말경피적담도조영술이도입될무렵에는복부 Computed Tomography (CT), Magnetic resonance imaging (MRI), Magnetic resonance cholangiopancreatography (MRCP), Endosonographic ultrasound (EUS) CT, Endoscopic Retrograde cholangiopancreatography (ERCP) 등의춰l 담도의영상방법이발전되지않았던시기였S므로많은황달환자들이단지간염으로오랜기간치료받기도하였고수술은단지신체검사에서복부의종양이만져지거나 Courboisier 증후가있을때시행되었다이때당시에경피적담도조영술과담도배액술은폐쇄성황달환자에서담도의양질의영상을얻고자하는진단목적, 담도조영술로인한합병증을감소시키려는목적으로시행되었다그후그수기의안정성이점차확립됨에따라지속적으로널리보급되어있다. 또한담도배액의누공을통하여경피적담도내시경이 33

2 34 대한쉐담도연구회지 : 제 8 권제 l 호 2003 시도되어직접적으로담도의병변을확인할수있고조직검사도가능하게되었다하지만경피담관배액술은시술후에출혈, 복강내담즙누출, 복막염, 흉막하농양, 고열, 담도염및속, 기흉, 혈흉, 담냥총수담관및십이지장천공, 도관기능부전, 춰l장염등의합병증이보고되고있다 1 3, 1 4 폐쇄성황달은당대사와사럽체 (mitochodria) 그리고세망내피작용 (reticuloendotherial function) 과면역계에영향을미치고, 내독소 (endotoxin) 상승과응고인자생성의저하를일 켜감염률을높이는것으로알려지고있다 15, 16 심한폐쇄성황달의수술후합병률과사망률에영향을주는인자중 10 mg/dl 이상의고빌리루빈혈증, 악성종양으로인한폐쇄, 빈혈, 백혈구증가증, 크레아티닌증가, 저알부민혈증등을들수있고, 특히고빌리루빈혈증은응고장애, 신기능장애및면역기능저하를초래하므로혈중빌리루빈치를낮추게되면수술위험요소를줄일수있다는근거를제시하였다 수술후이환율과사망률을높이는인자인황딸을교정하고자 1935 년 Al1en O. Whipple l9 은초기에는 2단계에걸쳐시행하였는데, 첫단계수슐에서시행하는위담낭문합술은담도폐쇄로인한장애로부터환자를보호하기위한것이었다, 그후 2단계술식의단점즉반흔형성및유착등이수술시간을연장시키게되고수술을어렵게함으로써종양을완전하게제거하는데장애가된다는점과누공형성빛이물질에의한수술시야의오염가능성을이유로 1 단계술식을취하였다 20 그런데경피적경간담도배액술과내시경적담도배액술같은비수술적인첫단계의도입으로쉐십이지장절제술에단계적접근에대한관심을다시불러일으켰다수술전담도배액술은반드시필요한가? 악성종양에의해발생한황달을가진환자에서담도배액은환자의소양증경감, 담도염해 소, 수술의연기가필요하거나간기능이정상화된후수술이필요한경우에필요하다. 이러한이론적배경하에경피적경간담관애액술이보급된 70년대초에는이병률및사망률을줄일수있다는보고가주를이루었다폐쇄성황달에대한수술을시행한환자를대상으로한연구에서 Nakayam 등 8 Gun따y 등 9 Dening 등 13은수술전경피적담관배액숨을시행한경우수술후이병율및사망률의감소를보고하였으며배액술에의한사망은없고이병률은 10% 미만에서발생한다고하였다. 그러나이러한보고들은후향적연구였으며, 전향적인연구에서수술전경피담관애액술이수술후이병율및사망률을감소시키지못하며오히려도관삽입에의한이병률이높다고보고하여논란이되었다 10, 년대초, Hatfield 등 10 Pitt 등6의전향적인연구에서는수술전담도매액술을시행한군과시행하지않은군사이에이병률과사망률에차이가없다고보고하였다 년 Peter 등22 0] 1 의하면웨십이지장절제술을시행한 300명의환자에서수술전담도배액술은수술후창상감염을높였으나출혈이나누출등의중요한합병증및사망률은도관삽관에의해영향을받지않는다고하였다 1999년 Povoski 등2 3은후향적연구지만다변량분석을통하여수술전내시경적또는경피적담도배액숭이수술후전체합병증, 감염, 복강내농양, 수술후사망과연관이있음을확인하였고, 이러한합병증들은담도배액방법이나담도배액의수와관련이없다고보고하였다. 이러한것들은담도배액시술그자체와는연관이없고담도와장또는외부와의통로가형성되기때문에발생하였을것으로생각하였다폐쇄의위치와원인이치료계획을수립하거나예후를결정하는데중요한인자이므로담춰l 관을조영하는 ERCP가경피적담도조영술보다최근까지많이이용되고있다. ERCP는공간해상도가우수하며담관협착의길이, 담관의비대칭성이나불규척성유무등의자세한분석이가능하

3 깅태현쉐담도종양의수솔에있어수술전담도매액은반드시필요한가 35 고또한시술중조영제를주입하여협착부를확장시킴흐로서악성과양성및내인성과외인성협착부위의구분등형태학적인특성의파악이용이하다. 특히유두부종양의경우는 ERCP 검사중에육안적으로종양을확인할수있고조직검사가가능하다는장점이있다. 그러나폐쇄성황달을가진환자에서는진단적목적의 ERCP 검사중에조영제가주업되므로시술후담도염을예방하기위하여내시경적배액술이일반적으로시행되어왔다. 담도폐쇄환자에서내시경적역행성담도배액술 (endoscopic retrograde biliary drainage, ERBD) 은 1979년 Soehendra와 R yyenders-frederix 2 4에의 담관배액법은 1976년 Nagai 등26에의해처음보고된이래 1977년 Wurbs 등 27이담도에잘유치하도록고안한특수한형태를지닌불투과성튜브를이용하고있다 1980년대중반, 이러한내시경적담도배액술이경피적담도배액슐에비하여황달의배액속도가월등하여이병률과사망률이작고 28 내시경적스텐트를시행한후신장기능의향상이있음29을보고한이후널리이용되고있다 Lygidakis 등30은전향적무작위연구에서내시경적담도스텐트를시행후쉐십이지장절제술을받은 19명의환자에서이병율은 16%, 사밍률 0% 였고, 수술전에스텐트로배액을받지않은 19명의환자에서는 74 % 의 해 최초로시도된이래현재까지악성담관및 이병률, 사망률 10 % 였다고보고하였다. 이보고는 헤장질환흐로인한폐쇄성황달치료에기본적인치료법으로널리이용되고있다. 그후 E뼈D 법은 Huibregtse 등 이고안한더큰구경의플라스틱스텐트가많이사용되어지게되었고이러한스텐트는 3 ~ 4개월후에폐쇄가발생하므로 담도스텐트를한후수술을시행하여월등하게이병률이감소됨을보여주었다- 다른전향적연구중의하나인 Lai 등 3 1 의보고에서는스텐트를시행한군과시행하지않은군사이에수술후, 이병률과사망률에서차이가없었다고하였다. 이를보완하기위하여많은연구가진행되었다, 하지만이 연구는치료적수술을모두받지않 플라스틱스텐트의최대단점인구경의한계를 극복하기위한방법으로금속제팽창성스텐트가 개발되어 1990 년대중반부터현재까지다양한 았고, 보존적치료인담도 - 장문합술을시행받 은환자가포함되어있다 (Table 1) 여러후향적연구에서, 쉐십이지장절제술전 형태로개발되어이용되고있다 내시경적경비 에내시경적담도스텐트를시행하고서수솔한 Table 1. Effect of preoperative EBS VS. no preoperative EBS on postoperative morbidity and mortality after radical surgery for periampullary tumor Postoperative complications Postoperative death Author Design n EBS EBS No EBS EBS No EBS Lygidakis et al. 30 RCT (50) 3 (1 6) 14 (74) 0 2 (l l) Lai et al. 31 RCT (52) NA NA 0 1 (9) Marcus et al. 32 RS (42) 8 (36) 19 (63) 0 2 (7) Heslin et al 35 RS (53) 23 (59) 12 (34) 1 (3) 0 Sohn et al. 33 RS (48) 51 (35) 48 (30) 7 (3) 4 (3) Martignoni et al. 34 RS (39) 49 (49) 71 (45) 3 (3) 3 (2) Total 4 RS, 2 RCT (45) 134 (40) 164 (40) 8 (2) 12 (3) Numbers in parentheses are per cents of the lotal number in the relevant subgroup. RCT; Randomized controlled study, RS; retrospective studies, NA ; not available

4 36 대한쉐담도연구회지저 1 8 권제 l 호 2003 Stent betler OR=1 No stent better 녁 Estimated overall odds rati Prospective randomized c ntro lled study Lygidakis et al Marcus et al -.-, Heslin et al 뉴 을 - Sohn et al 뉴 용 ---i Martignoni et al Odds ratio for 10 complications (Iog scale) Fig. 1. Odds ratios for prstoperative complications after radical surgery for peripapi llary cancer according to preoper-ative stent placement versus no stent placement 군과그렇지않는군간에이환률과사망률은유의한차이가없었고 뿐만아니라스텐트를삽입한군에서이병률과수술후창상감염이유의하게많았고입원기간도더길었다 고보고하였다 Saleh 등 3 6은 1985년부터 2001 년까지의메드라 Level 2에서는전체적인사망률이배액군이배액을하지않은군보다약간낮았고 (3.2 % vs 4.9%), 전체적인합병증발생률은배액군에서의의있게높았다 (Tab l e 3). Level 1 과 level 2에서모두통계학적으로는유의성이없었지만배액군에서입원기간의연장이보였다, 그러나 meta-analysis는수술 인 검색을통하여수술전내시경적담도배액 기법이다양하고, 수술자들마다의수술숙련도, ( 주로스텐트 ) 의유용성에대한논문을분석하였 수술전담도염의여부등이 혼재되어있어정 다 (Fig. 1) 이논문에서는 749명의환자를 ( 수술전담도배액 337 명, 대조군 412명 ) 포함하고있고수술후합병률의비차비 (odd ratio) 가 0.81, 사망률의비차비는 0.93으로팽대부주위종양의수술전에내시경적담도배액술은수술결과에좋은영향도나쁜영향도미치지않는다고보고하였다. Sewnath 등 37은수술전배액의효과를평가한논문들을무작위코호트연구 (l evel 1 ) 과비교코호트연구 (l evel 2) 로나누어메타분석을 확하게담도배액의필요성에대한평가가절하될수있을것으로생각한다여러연구보고에서수술전담도배액술이수술후합병율과사망률에영향을미치지못하는이유로배액기간과의관계가제시되고있다. 몇몇동물실험에의하면간기능검사수치와당대사기능은 2-5 일이내회복되지만사립체작용이나관증식 (ductal proliferation) 과섬유화 (fibrosis) 는회복되는데 4-6주가소요된다고하였다 하였다. Level 1 에서는수술전사망률과수술 사람에 있어서는간대사가정상으로회복되는데 후사망률이 통계학적으로의의는없었지만수 수주가소요되며, 면역계나간세망내피작용, 내독 술전배액군에서약간높았고, 담도배액술로 인한합병증이 27% 로보고되었는데, 합병증들은 십이지장천공, 출혈, 쉐장염등이다 (Table 2). 소등도 2-3 주이상필요한것으로알려지고있 다 결국수술전담도배액후간기능의뚜렷한

5 김태현 - 쉐담도종양의수술에있어수술전담도배액은반드시필요한가? 37 Table 2. Deaths, complications, and postoperative hospital stay, level 1 studies Total number of patients Preoperative Preoperative deaths Drainage procedure-related Complications Stent dysfunction Mean prehospitalizati on, drain-related (days) :t SE Treatment modality O verall deaths Overall complications Mean total length of hospital stay (days) :t SE Postoperative Postoperative deaths Postoperative complications Mean postoperative hospital stay (days):t SE PBD 157 (60.3%) 8 (5.1%)* 43 (27.4%) 53 (33.8%) 14.6:t (15.9%) 90 (573%) f 42 :t 5 ~ 17 (1 0.8%) 47 (29.9%) " 27 :t40 Surgery without PBD 155 (49.7%) 2 (1.3 %) 21 (13.5 %) 65 (4 1.9%) 24 :t 4 21 (13.5 %) 65 (4 1.9 %) 24:t 3.4 PBD, preoperative biliary drainage; standard error. *; Resulting from: the drainage procedure, t ; In the trial of Hatfield 10 et al patients had died after randomization but before resection lo f, ; Peto odds ration (95 % CI): 1.99 ( ) ~; P <.OOI, PBD vs. surgery without PBD, " Peto odds ratic (95% CI): 0.59 ( ). Table 3. Deaths, complications, and postoperative hospital stay, level 2 studies Total number or patients Preoperative Preoperative deaths Drainage procedure-related complications Stent dysfunction Mean prehospitalization, drain-related (days) :t SE Treatment modality Overall deaths Overall complications Mean total length of hospital stay (day) :t SE Postoperati ve Postoperative omplications Mean postoperative hospital stay (days) :t SE PBD 1,688 (59.2 %) 2/595 (0.3%) 59/595 (9.9%) (26.1 %) 18.7:t4.2 54/1,688 (3.2 %) 350/595 (58.8 %) 33 :t5* 807/1,636 (49.3%) 18 :t 1.4 Surgery wityout PBD 1,165 (40.8%) 57/1,165 (4.9%) 127/302 (42.1 %) 18 :t5 538/1,086 (49.5%) 18 :t4.2 PBD, preoperative biliary drainage;se, standard error. *; P <.001, PBD vs. surgeray without PBD, 기 Peto odds ration (95%CI): 1.64 ( ) 호전에필요한최소한의시간은적어도 4-6 주폭될수있고그질환의병기가낮아질수는 를기다려야한다, 경과시간동안에종양은커없다내시경적스텐트삽입후외과의사의어려 질수도있고환자의수술에대한거부감이증운점은담도의확장이감소됨으로인하여적절

6 38 대한쉐담도연구회지제 8 권제 l 호 2003 Table 4. Preoperative biliary drainage for hilar bile duct carcinoma Author Year Method Beneficial Lmeris et al Vauthey and Blumgart Nimura et al Miyagawa et al Takada and Yasuda Cheng-Hsi et al Cherqui et al Review Case comparison study No No 한크기의담도루 (stoma) 를만드는데문제가발 생하고담도의염증과섬유화로절개를어렵게 로유의한차이가없다는보고도있다 42,4 3 담도염은간절제술전에해결해야할매우중 할수있다. 황등 44 의보고에의하면내시경적 요한문제중의하나로서반드시 담도배액을 담도배액술을시행한군이경피적담도배액술 을시행한군에비해수술부위에염증반응이심 필요로한다. 그리고간문부담도종양의경우에 수술여부의결정과적절한치료적수술방법을 하다는것을확인하였으나수술후합병증과임 구상또는디자인하는하는데있어서좌, 우측 상적인결과는통계적으로유의하지않았지만수술부위의염증으로수술의어려움을초래하였다고보고하였다이보고는표본대상환자수가적고수술후임상적결과가추적되지않은취약한문제점이있다. 담도분지의침범을정확하게판단하는것이중요하다이를위해서는여러가지방사선적검사들, 즉 MRCP, 경피적담도조영술, 내시경적역행성담도조영슐등이이용되고있지만한계가있어경피적담도배액을시행한경로를통하여 담도내시경을시행함으로써양성과악성종양 간문부담도종양의수술전담도배액 의감별그리고종양의침범범위를판단하는데 더정확도를높일수있다 간문부 Hilar 담도종양은침습적이며광범위 한간절제술을필요로하고, 일본에서는수술전 황달이있으면광범위한간절제술후간부전을 간문부담도종양의경우에담도의완전폐쇄 가있는경우가많아종양의상부에있는담도 를조영할수있는경피적담도매액술이 ERCP 막기위하여담도배액숨을주로시행하고있 보다더많이이용되고있다. 이는폐쇄된담도 다 40 Table 4 는간문부담도종양에서수술전 의분지를배액할수있을뿐만아니라수술중 담도배액의유익성을논한영어로기술된대표 에좌우측간내담도를확인하고분리하는데보 적인논문들이다. 간문부종양환자에서우엽은 조적인역할을할수있고수술중에 Silastic 스 배액을하지않고좌엽만을배액하면좌엽의대 상성비대의소견을보여확장된우엽절제술을 텐트를유치하는데경피적담도배액관이많은 도움을주고있다 48 가능하게할수있는장점이있고, 수술전적극적인담도배액을통해서정확한병기결정과근치적간절제율을높일수있다 41 반대로수 결 론 술전에감황후간절제술을실시한군과실시 수술전담도매액술은수술전담도배액술 하지않은군간의이병률과사망률에통계적으이필요한가? 그렇지않은가? 그것이문제로다

7 김태현쉐당도종양의수슐에있어수술전담도배액은반드시필요한가 39 라는셰익스피어의명언과비슷한상황이다. 대 부분의논문들이상당한다양성이있기때문에그질문에답을하기위해서는대단위무작위전향적연구가더필요하리라생각된다. 그러나황달을초래한쉐담도종양의경우, 수술전내시경적또는경피적배액술이시행되면수술결과가양호하다는증거가부족하고, 입원기간의연장, 입원비상승, 그리고담도염증가등의문제점들이제시되고있다쉐십이지장절제술이예정된환자에서는치명적인담도염이나간기능저하에따른출혈경향등의경우가없는한황달이있거나간효소수치가높다는이유로담도배액술을시행할필요는없다고여겨진다. 춰l 십이지장절제술후에수술합병증에큰영향을미치는쉐장루, 감염등을줄일수있는여러가지방법들이발표되고있지만, 각각의술자에따라수술수기의특성이반영되어다른결과를보여주고있으므로이러한수술적숙련도가수술결과에큰영향을줄수있다고생각된다최근에는다른비침습적인복부 spiral CT, MRI, MRCP, EUS가쉐담도질환에서많이이용되고있고정확도가높다고보고되고있다따라서최선의치료방법을선택하는진단단계에있어서복부 CT 또는 MRI 검사에서황달을초래한춰l 담도종양이절제가가능하다고판단이되는환자에서담도영상이필요한경우에는비침습적인조영방법을시행한후즉각적인수숨을시행하고, 더욱정확한진단을위해서담도의세밀한조영이나팽대부의검사가필요하면수술전 ERCP를이용한검사와담도배액이필요로할것으로생각된다. 또한간문부종양에서광범위간절제술이계획된경우나정확한종양의침범범위를결정이필요한경우, 심각한영양실조, 심한소양증, 담도폐혈증, 신부전, 간부전등과같은문제가있을때담도배액을수술전에필요로할것으로생각된다 참고문헌 1. Gudsjonsson B: Carcinoma of the pancreas: critical analysis of costs, results of resections and the need for standarized reporting. J Am Coll Surg 1995; Trede M, Schwall G, Saeger HD: Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg 1990; 216: Miedema BW, Saπ MG, Heerden van JA, et al: complications following pancreaticoduodenectomy: current management. Arch Surg 1992; 127: Femandez del Castillo C, Rattner DW, Warshaw AL: Standards for pancreatic resection in the 1990s. Arch Surg 1995; 130: Yeo CJ, Cameron JL, Sohn TA, et al: Six hundred and fifty consecutive pancreaticoduodenectomies in the 1990s. Ann Surg 1997; 226: Pitt HA, Cameron JL, Postier RG, Gadacz TR: Factors affecting mortality in biliary tract surgery. Am J Surg 1981; 141: Blamey SL, Fearon KCH, Gilmour WH, et al Prediction of risk in biliary surgery. Br J Surg 1983; 70: Nakayama T, Ikeda A, Okuda K: Percutaneous transhepatic drainage of the biliary tract: technique and results in the 104 cases. Gastroenterology 1978; 74: Gundry SR, Strodel WE, Knol JA, et al: Efficacy of preoperative biliary tract decompression in patients with obstructive jaundice. Arch Surg 1984; 119: Hatfield AR, Tobias R, Terblanche J, et al : Preoperative external biliary drainage in obstructive jaundice. A prospective controlled clinical trial Lancet 1982; 2: McPherson GA, Benjamin IS, Hodgson HJ, et al Pre-operative percutaneous transhepatic biliaη drainage: the results of a controlled trial. Br J Surg 1984; 71: Keith D: Preoperative biliary drainage and surgical outcome. 1999; 230: Denning DA, Ellison EC, Carey LC: Preoperative percutaneous transhepatic biliary decompression 10- wers operative morbidity in patients with obstructive jaundice. Am J Surg 1981 ;141:

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<C1A63439C8B820BCBCB9CCB3AA2DC6EDC1FD2E687770> D-IV. 췌담도질환에서내시경치료의근거중심전략적접근 Room D 악성담도협착에서최선의수술전담도배액술 이우진 우상명 국립암센터췌담도암클리닉 Best Preoperative Biliary Drainage: Endoscopic or Percutaneous Approach Woo Jin Lee, Sang Myung Woo Pancreatobiliary Cancer