The Korean Journal of Gastrointestinal Endoscopy Room D Prevention for Post-ERCP Pancreatitis: Interventional Aspect 울산대학교의과대학서울아산병원소화기내과학교실 서론 ERCP후발생하는췌장염 (post-ercp pancreatitis, PEP) 은드물지않은시술후합병증이면서위중한결과를초래할수있다. PEP은고위험군의분포에따라드물게 1% 에서많게는 30% 정도의빈도를보이나일반적으로 6% 정도로알려져있으며 1 고위험군인오디괄약근기능장애환자군에서는많게는 22% 정도의빈도로 PEP이발생한다고알려져있다. 1,2 PEP의위험인자는크게환자인자와시술과관련된인자로나눌수있다. PEP의위험인자를가진환자군은 1) 이전에 PEP을경험한경우, 2) 젊은여자, 3) 정상범위의총담관내경및빌리루빈수치, 3) 오디괄약근기능장애가의심되는환자등이며시술과관련된위험인자는 1) 담도삽관이어려운경우, 2) 예비절개술을시행한경우, 3) 췌관에조영제주입등이다. 시술관연관된 PEP의발생요인으로는복합적인인자 (mechanical, chemical, hydrostatic, enzymatic, microbiologic, allergic, thermal injury) 가관여하는것으로알려져있다. 3 구체적으로는반복적인삽관시도에의한유두부의주췌관입구에물리적인손상과, 조영제의췌장주입에동반되는압력에의한췌장의손상, 조영제주입에따른화학적반응, 예비절개술 (pre-cutting) 에의한췌관의열성손상등이알려져있다. 4 따라서이러한병인을이해하고이를줄이려는연구가많이시도되고있다. 이에 PEP을줄이기위한시술과연관된 intervention에대해알아보고자한다. 시술전 Intervention 1. ERCP이전에 PEP의위험인자분석및대상환자의평가시술자는 ERCP이전에상기의위험인자를가진환자가 ERCP 가반드시필요한지평가하는게필요하다. MRCP나 EUS를통하여진단적인목적의 ERCP를대체하고치료적기대가낮은 Table 1. Model for Determining Baseline Probability of Bile Duct Stones in Patients Screened for Eligibility Criteria (from Ref. 7) Risk facors for bile duct stones Age >55 years Bilirubin level: CBD dilatation Bile duct stones on >30 μmol/l on ultrasound* abdominal ultrasound Probability of bile duct stones + + + + 94% + + + ( ) 72% + + ( ) + 85% + + ( ) ( ) 50% + ( ) + + 90% + ( ) + ( ) 61% + ( ) ( ) + >67% + ( ) ( ) ( ) 38% ( ) + + + 85% ( ) + + ( ) 49% ( ) + ( ) + 69% ( ) + ( ) ( ) 28% ( ) ( ) + + >67% ( ) ( ) + ( ) 38% ( ) ( ) ( ) + 58% ( ) ( ) ( ) ( ) 19% CBD, common bile duct. *>6 mm in patients with gallbladder in situ or >10 mm in patients after cholecystectomy, Patients with probability of bile duct stones of no more than 67% were admitted into the study. Vol. 38 (Suppl 1), 2009 (253-257) 253
환자군을미리확인하여불필요한 ERCP를피한다면 PEP의가능성을줄일수있다. 최근보고에의하면 intermediate risk 의담도결석이의심되는환자를대상으로 EUS후 ERCP를한경우와 ERCP를시행한경우를비교하였을때 EUS를먼저시행한군이다변량분석에서유의하게 ERCP를시행한군보다 PEP의빈도나시술과연관된합병증이유의하게낮았으며불필요한 ERCP 시행을줄일수있었다. 5-7 따라서 intermediate risk (Table 1) 를가진담도결석환자에서 EUS를 ERCP이전에시행한다면발생가능한 PEP의빈도를줄일수있을것으로생각된다. 시술중 Intervention 1. Prophylactic pancreatic ductal stenting 실제임상에서접하는 PEP의경우시술자가시술하는동안예측할수있는경우가많다. 예를들어오디괄약근기능장애가의심되는젊은여자에서반복적인췌관삽관과췌장에조영제가들어가는경우, 유두부선종을내시경절제술하는과정에서주췌관조영후조영제의배출이원할하지않는경우가있을수있다. 이러한경우 ERCP하는과정에서예방적인 pancreatic duct stenting은여러연구에서 PEP의빈도및중증도를줄일수있다고알려져있다. 8 따라서 ERCP를하는과정에서시술자는다양한위험인자를분석하여 PEP의고위험군환자에서예방적인 p-duct stenting을고려할수있다. 하지만예방적인 pancreatic duct stenting의경우 flap이없어스텐트유치후자연배출이가능한 3F stent가연구가많이되어있으나 3F stent의경우 0.018 inch의유도철사가필요하여조작이어려울뿐아니라췌관의해부학적인형태에 (acute angulation) 따라스텐트의유치가어려울수있다. 이러한경우반복적인조작이오히려췌관에손상을유발할수있다. 9 따라서이러한경우에는과감히시술을중단하거나 5F stent의 proximal flap 을제거한후유치하는게도움이될수있다. 2. 예비절개술 : PEP의원인인가아니면 PEP을줄일수있는가? 예비절개술 (precut sphincterotomy, pre-cutting) 은반복적인췌관삽관에의한담도삽관이어려운경우에시도될수있다. 이는반복적인췌관삽관이췌관의부종을유발하여 PEP 을일으킬수있기때문이다. 5회이하의삽관시도는비교적안전하지만 10회이상또는 10분이상의삽관시간은 PEP과연관된다고알려져있다. 10 예비절개술에는크게유두부입구에서 papillary mound 방향으로절개하는방법과반대로 papillary mound에서유두부입구전까지절개하는방법이있다. 전자의방법의장점은담도의축 (axis) 인 11 12시방향으로절개하여담도의방향을예측하기가수월할수있다. 후자 의경우유두부입구까지절개를하지않아전자보다 PEP의발생가능성을이론적으로줄일수있다. 후자의경우는 free hand이면서일종의 blind technique으로초심자가시도하는경우십이지장천공등의위험성이있을수있다. 예비절개술을반대하는연구자들의주장으로는이러한시술자의충분한경험이필요한예비절개술에대한초심자의사용이오히려 PEP이나다른시술합병증의위험도를높일수있어초심자의경우사용을하지말것을권고하고있다. 기존의연구에서도예비절개술이 PEP에대한독립적인위험인자로알려져있어이러한이론적배경이 PEP에있어예비절개술을가능한피하자는주장이있다. 하지만이에반대하는이론으로는대부분의연구에서반복적인담도삽관시도가안되는경우예비절개술을시도하므로반복적인삽관에의한 PEP인지아니면예비절개술단독에의한 PEP인지명확치않고대상환자수가적어적절한예비절개술에대한 PEP의연관성에대해서는더많은연구가필요하다. 3,11,12 최근보고에의하면조기예비절개술 (5 회또는 10분이내의일상적인삽관후시행하는 ) 이담도삽관율의성공율을높이면서췌장염의빈도는높이지않을수있다는보고가있었다. 13 하지만예비절개술의시기와 PEP의빈도는상관이없다는연구도있어이에대한더많은연구가필요할것으로보여진다. 14 따라서예비절개술의경우 PEP의예방적인역할을확인하기위해서는다양한경험을가진연구자가참여하는다기관연구가필요할것으로보여진다. 3. Wire-guided cannulation (WGC) 의도되지않은췌관의조영제주입이 PEP의원인이될수있어조영제주입없이유도철사를이용한삽관방법이소개되고있다. 3,10-12,15 WGC의이론적인근거로는조영제의췌관내주입을피하여조영제에의한췌장손상을예방하고췌관내조영제주입보다 WGC가췌관내압력을줄여 PEP을줄일수있다는데있다. 환자의체위를 prone position으로하고 papillotome을이용하여담도방향으로삽관을 3 4 mm정도하고유도철사를삽입하여담도로들어간경우조영제를주입하고췌관으로유도철사가들어간경우유도철사를빼거나 3 유도철사를췌관에유치한후다시담도로유도철사를이용한삽관을시도 (double guidewire technique) 16,17 가있다. 이때유도철사를올리는과정에서과도한힘을주는경우천공이발생할수있으므로숙련된간호사의도움이필요하며 0.025 inch 유도철사가천공이흔한것으로알려져있어가능한일반적인 0.035 inch의유도철사를이용하는게바람직하다. 기존의연구에서는이러한 WGC가삽관성공율을높이는데는이견이없다. 11,18 하지만 PEP의경우결과는상반되어보고되고있다. 우선 Lella, Artifon, Lee 등 3,11,15 의 single-operator WGC의경우 PEP을예방할수있다고보고하고있으나 (Table 2) Bailey 등의연구에서는 WGC가 PEP을예방할수없다고보고하고있다. 우 254 The Korean Journal of Gastrointestinal Endoscopy
Table 2. Prospective Trial of WGC to Reduce the Incidence of Post-ERCP Pacreatitis (from Ref.3) No. Disign Suspected SOD Pancreatitis/ SOD (WGC) (No.) Pancreatitis/ unintentional PD (WGC vs CC) (No.)* Pancreatitis (WGC) Pancreatitis (CC) p=.04 Vandervoort 1,223 Prospective 83/1,233 (6.8%) 16/83 NA 33/322 (10.2%) 55/896 (6.1%) et al 7 p<.01 Lella et al 14 400 Prospective 5/400 (1.3%) 0/4 0/82 a, 0/197 (0%) 8/195 (4.1%) randomized 5/113 b p=.02 Artifon et al 13 300 Prospective 20/300 (6.7%) 0/16 0.27 c, 13/150 (8.6%) 25/150 (16.6%) randomized 4/21 d p=.001 Current study 300 Prospective 7/300 (2.3%) 2/6 2/39 e, 3/150 (2%) 17/150 (11.3%) randomized 8/44 f p-values: a vs b,.08; c vs d,.05; e vs f,.09 by fisher exact test. p-values for pancreatitis (WGC) versus pancreatitis (CC) shown in table. CC, conventional cannulation; NA, not available. *The number of cases of post-ercp pancreatitis after unintentional PD injection or cannulation in CC and WGC groups, The number was not associated with whether the procedure was conventional or wire guided. 선상반되는결과의이유로는 Bailey 등 10 의연구에서는경험이풍부하지않은내시경의사가먼저삽관을시도하고삽관이안되는경우 expert 가삽관을시도하였다. 따라서반복적인삽관을이미시도한상태에서 WGC의효과는봤다는점과 contrast group과 WGC group을 cross overt trial하여두군간의 PEP의빈도를해석하기어려운문제가있을수있다. 19 또한 Wang 등 20 의연구에따르면 1번이상의유도철사의주췌관통과가 PEP 의독립적인위험인자로알려져있다. 하지만이연구는대조군이없는전향적다기관연구로 WGC와조영제를통한주췌관조영을시행한군이모두포함되어결과해석에어려움이있다. 한편저자의연구에따르면 WGC가 SOD가의심되는환자에서반복적인췌관에유도철사삽관이 PEP을예방하지못한다는점을고려해볼때조영제에의한삽관에비해저위험고군에서 PEP을줄일수있으나고위험도에서는 WGC에의한반복적인췌관삽관도주의를요한다. 3 4. Second attempt, percutaneous approach or transfer ERCP의성공률은 90 95% 정도로 1 expert의경우에도예비절개술을시행하고도담도삽관에실패할수있다. 이러한경우 48시간후다시시도하는경우성공적인담도삽관을기대할수있다. 따라서시술이길어지는경우당황하지말고 1 2일후다시재시도하는방법이 PEP을줄이는하나의방법이다. 21 이러한두번째시도에도성공적인담도삽관이안되는경우 interventional radiologist와협의하여경피적접근을시 도하는것이 PEP을줄일수있는방법으로생각된다. PEP이생긴경우중증도에따라심한경우는사망에이를수있다. 따라서시술자의경험정도에따라무리하지말고상급병원으로전원하는것도 PEP을줄일수있는하나의대안이될수있다. 22 5. Interventional EUS 최근 linear EUS가도입되면서치료적인시술이많이소개되고있다. 23-29 이중하나가 EUS-guided biliary drainage (EUSBD) 이다. 반복적인 cannulation 시도나 pre-cutting이 PEP와연관되어있어 EUSBD를이용한 choledochoduodenostomy나 hepaticogastrostomy가 PEP을줄일수있는대안이될수있다. 특히저자의경험으로는궤양형의 ampullary cancer에서반복적인담도삽관시도에따른 PEP 또는출혈을유발할수있어이러한경우 EUSBD가도움이될수있다. 이러한 EUSBD는악성담도폐색환자에서유두부를통한스텐트삽입보다스텐트개통율이높다는장점이있다. 23 이는 tumor growth상방에배액이이루어지기때문이다. 따라서향후에악성담도폐색에있어중요한역할을할것으로보여진다. 더욱이 ERCP로담도의삽관이실패한경우 PTBD 등의경피적접근보다환자의선호가높다는장점이있다. 하지만 EUSBD는계속발전하는분야로 1) standard한술기가정립되지않았고 2) 이시술과관련된합병증인 bile peritonitis, pnuemoperitoneum이드물지않으므로경험이풍부한의사가시행해야하는제한점이있다. 23,25,26,30 Vol. 38 (Suppl 1), 2009 (253-257) 255
요약 PEP의예방에서가장중요한 intervention 은 less frequent, traumatic한삽관이필요하다는데있다. 따라서가능한 5회이하또는 10분이내의삽관을통해성공적인담도삽관을하는것이바람직하다. 이를위해서는 WGC이도움이될수있으며경험자의경우조심스럽게 pre-cutting을시도해볼수있다. 5회이상의반복적인삽관이나췌관에조영제가들어간경우등 PEP이예측되는경우예방적인췌관 stenting 등의 intervention을고려할수있다. 결론 PEP을완전히예방할수는없으나 PEP의빈도와중증도를줄이기위해서는적절한치료 ERCP 적응증의확립과의도되지않는췌관삽관및조영의빈도를줄이려는다양한노력이필요하다. 참고문헌 1. Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for post-ercp pancreatitis: a prospective, multicenter study. Gastrointest Endosc 2001;54:425-434. 2. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996;335: 909-918. 3. Lee TH, Park do H, Park JY, et al. Can wire-guided cannulation prevent post-ercp pancreatitis? A prospective randomized trial. Gastrointest Endosc 2009;69:444-449. 4. Cheon YK, Cho KB, Watkins JL, et al. Frequency and severity of post-ercp pancreatitis correlated with extent of pancreatic ductal opacification. Gastrointest Endosc 2007;65:385-393. 5. Lee YT, Chan FK, Leung WK, et al. Comparison of EUS and ERCP in the investigation with suspected biliary obstruction caused by choledocholithiasis: a randomized study. Gastrointest Endosc 2008;67:660-668. 6. Ang TL, Teo EK, Fock KM. Endosonography- vs. endoscopic retrograde cholangiopancreatography-based strategies in the evaluation of suspected common bile duct stones in patients with normal transabdominal imaging. Aliment Pharmacol Ther 2007;26:1163-1170. 7. Polkowski M, Regula J, Tilszer A, Butruk E. Endoscopic ultrasound versus endoscopic retrograde cholangiography for patients with intermediate probability of bile duct stones: a randomized trial comparing two management strategies. Endoscopy 2007;39:296-303. 8. Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PD, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998;115:1518-1524. 9.Freeman ML, Overby C, Qi D. Pancreatic stent insertion: consequences of failure and results of a modified technique to maximize success. Gastrointest Endosc 2004;59:8-14. 10. Bailey AA, Bourke MJ, Williams SJ, et al. A prospective randomized trial of cannulation technique in ERCP: effects on technical success and post-ercp pancreatitis. Endoscopy 2008; 40:296-301. 11. Artifon EL, Sakai P, Cunha JE, Halwan B, Ishioka S, Kumar A. Guidewire cannulation reduces risk of post-ercp pancreatitis and facilitates bile duct cannulation. Am J Gastroenterol 2007;102:2147-2153. 12. Vandervoort J, Soetikno RM, Tham TC, et al. Risk factors for complications after performance of ERCP. Gastrointest Endosc 2002;56:652-656. 13. Kaffes AJ, Sriram PV, Rao GV, Santosh D, Reddy DN. Early institution of pre-cutting for difficult biliary cannulation: a prospective study comparing conventional vs. a modified technique. Gastrointest Endosc 2005;62:669-674. 14.Cennamo V, Fuccio L, Repici A, et al. Timing of precut procedure does not influence success rate and complications of ERCP procedure: a prospective randomized comparative study. Gastrointest Endosc 2009;69:473-479. 15. Lella F, Bagnolo F, Colombo E, Bonassi U. A simple way of avoiding post-ercp pancreatitis. Gastrointest Endosc 2004;59: 830-834. 16. Gyokeres T, Duhl J, Varsanyi M, Schwab R, Burai M, Pap A. Double guide wire placement for endoscopic pancreaticobiliary procedures. Endoscopy 2003;35:95-96. 17. Maydeo A, Borkar D. Techniques of selective cannulation and sphincterotomy. Endoscopy 2003;35:S19-23. 18. Katsinelos P, Paroutoglou G, Kountouras J, et al. A comparative study of standard ERCP catheter and hydrophilic guide wire in the selective cannulation of the common bile duct. Endoscopy 2008;40:302-307. 19. Park DH, Lee SS, Seo DW, Lee SK, Kim MH. Is the rate of post-ercp pancreatitis not reduced by guide-wire cannulation? Endoscopy 2008;40:784-785. 20. Wang P, Li ZS, Liu F, et al. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol 2009;104: 31-40. 21. Kumar S, Sherman S, Hawes RH, Lehman GA. Success and yield of second attempt ERCP. Gastrointest Endosc 1995;41: 445-447. 22. Choudari CP, Sherman S, Fogel EL, et al. Success of ERCP at a referral center after a previously unsuccessful attempt. Gastrointest Endosc 2000;52:478-483. 23. Yamao K, Bhatia V, Mizuno N, et al. EUS-guided choledochoduodenostomy for palliative biliary drainage in patients with malignant biliary obstruction: results of long- term follow-up. Endoscopy 2008;40:340-342. 24. Tarantino I, Barresi L, Repici A, Traina M. EUS-guided biliary drainage: a case series. Endoscopy 2008;40:336-339. 25. Bories E, Pesenti C, Caillol F, Lopes C, Giovannini M. Transgastric endoscopic ultrasonography-guided biliary drainage: results of a pilot study. Endoscopy 2007;39:287-291. 26. Will U, Thieme A, Fueldner F, Gerlach R, Wanzar I, Meyer F. Treatment of biliary obstruction in selected patients by 256 The Korean Journal of Gastrointestinal Endoscopy
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