대한내과학회지 : 제 83 권제 1 호 2012 http://dx.doi.org/10.3904/kjm.2012.83.1.40 특집 (Special Review) - 만성췌장염 만성췌장염의외과적치료 순천향대학교의과대학외과학교실 최동호 Surgical Treatment of Chronic Pancreatitis Dongho Choi Department of Surgery, Soonchunhyang University College of Medicine, Seoul, Korea Treatment of chronic pancreatitis (CP) is a challenging disease for surgeons. During the last several decades, increasing knowledge about pathophysiology of CP, improved results of major pancreatic resections, and development of sophisticated diagnostic methods in clinical practice have resulted in significant changes in surgery for CP. Main indications of CP for surgery are intractable pain, suspicion of malignancy, and involvement of adjacent organs. The goal of surgical treatment is to improve the quality of life of patients. The surgical approach to CP should be individualized according to pancreatic anatomy and pathophysiology, pain characteristics, baseline exocrine and endocrine function, and medical co-morbidity. The approach usually involves pancreatic duct drainage and resection including longitudinal pancreatojejunostomy, pancreatoduodenectomy (Whipple's procedure), pylorus-preserving pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy, duodenum preserving pancreatic head resection (Beger's procedure), and local resection of the pancreatic head with longitudinal pancreatojejunostomy (Frey's procedure). Surgical procedures provide long-term pain relief, a good postoperative quality of life with preservation of endocrine and exocrine pancreatic function, and are associated with low early and late mortality and morbidity. Even though available results from randomized controlled trials were published, new studies are needed to determine which procedure is the most effective for the management of patients with CP. (Korean J Med 2012;83:40-49) Keywords: Chronic pancreatitis; Surgical treatment 서론만성췌장염은만성적인음주, 담도계질환, 부갑상선기능항진증, 외상등여러원인에의하여내분비및외분비췌장의부전과함께췌장실질의파괴와췌장샘의소실, 췌장샘 의수축, 증식성섬유화, 석회화, 췌관의협착등이진행되는만성적이고비가역적인질환이다. 이에비해급성췌장염은담석, 음주, 대사장애, 약물, 복부손상등의다양한원인에의해췌장선세포의손상, 광범위한간질성부종, 출혈등이일어나는췌장의급격한염증성질환으로서환자의 70-80% Correspondence to Dongho Choi, M.D., Ph.D. Department of Surgery Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yonsan-gu, Seoul 140-743, Korea Tel: +82-2-709-9490, Fax: +82-2-795-1682, E-mail: dhchoi@hosp.sch.ac.kr - 40 -
- Dongho Choi. Surgical treatment of chronic pancreatitis - 정도에서는경한임상양상을거쳐호전되지만 20-30% 에서는췌장조직의괴사및폐손상등의다발성장기부전과전신적인합병증을수반하여중증의임상양상을보인다 [1,2]. 중증의괴사성췌장염의경우 30% 정도의높은사망률이보고되고있다. 반면에만성췌장염은췌장의주된기능의장애로인한당뇨, 지방변, 체중감소등의증상과약물로조절되지않는심한복통이주증상이고주로복통의조절, 내분비췌장및외분비췌장의부전의치료가필요하게된다. 특히췌장관내에결석이박혀있는경우에는반복적으로만성췌장염을일으키고악화시키고이러한췌관내의돌은내시경적인제거가용이하지않아서수술을하게된다. 만성췌장염의주된치료는일련의보전적인치료법을먼저시행하게되는데금주와식이요법 ( 소식, 저지방, 고단백, 고당질식이 ), 그리고췌장효소의투여, octreotide (octapeptide analogue), 금식과수액요법이시행되지만, 약물로조절되지않은복통으로수술적치료가선택된다. 수술적치료의적응증은약물로조절되지않는복부통증, 만성췌장염으로인한합병증그리고악성종양과감별이어려운경우이며가능한한췌장의기능을유지시키면서시행한다. 수술적치료의일차적목표는통증의경감이다. 그리고이차적으로고려해야할것은최대한의내분비및외분비췌장의기능보존이다. 췌장의수술은그해부학적위치의특성상외과영역에서난이도가높은분야이고합병증의발생빈도또한타장기에비해많은편이다. 그리고췌장절제술후의당뇨의발생가능성등으로인해악성종양이아니면기피되어온것이사실이다. 하지만최근에는수술기법의발달로그안전성이많이확보되었으며많은수술방법이고안되어왔고현재는췌관의협착또는확장등의해부학적구조및종괴유무에따라췌장관배액술과췌장절제술등이주로시행되고있으며최근에는십이지장을보존하는췌장절제술등이시도되고있다. 이에저자들은만성췌장염시췌장절제술의여러임상적인요소와위험성및수술의효과에대해알아보고자하였다. 본문만성췌장염의병리는췌장섬세포와췌관세포의계속적이고비가역적인파괴를특징으로하며이세포들은섬유조 직과세포외기질로대체된다. 심한췌장염은그후유증으로조절되지않는통증, 당뇨, 그리고췌장부전을남긴다 [3]. 만성췌장염의병리기전은만성알코올중독에의한췌장염을제외하고는아직확실히밝혀지지않았다. 알코올에의해만성췌장염이생기는기전은과량의알코올의지속적인섭취로췌장액내의지질분해효소, 키모트립신, 그리고중탄산염의양이감소하고췌장액자체의양도감소한다 [4]. 혈액내의단백질농도가상승하게되고췌장액의점도가증가하여단백전색 (protein plug) 이발생하고이단백전색에의해췌관이폐쇄되고췌관의확장및협착등의이상이초래된다. 이단백전색에칼슘이침착되어췌실질의석회화와췌석등이발생하게되며췌석에의한췌관의폐쇄도췌실질의염증을일으켜동일한과정을밟는악순환으로들어선다 [5,6]. Sakakibara 등은실험동물에서췌관의부분폐쇄를시킨후 1년경과후에약 64% 에서췌석이나타난것을보고하였고단백질이풍부한췌장분비액의저류가결석을형성한다고하였다 [7]. 만성췌장염의주증상으로는상복부동통이반복적으로나타남을호소하는경우가가장흔하며, 병이진행되면췌장의외분비기능장애에따른지방성대변과체중감소등이나타나며내분비기능장애로인한당뇨가발생한다. 통증없이지방변, 체중감소, 당뇨등의증상을보이는경우도드물게있지만통증은거의모든환자에서나타나며발작적이고지속적인것이특징이며심한통증으로마약중독이되는경우도있다 [6]. 췌장염에의해통증이생기는기전은복합적인원인에의한것으로보이며두개의보완적인가설이외과적인치료의근간이된다. 첫번째는췌장구획설 (pancreatic compartment theory) 로만성췌장염시췌관내압 (20-80 mmhg) 과간질내압 (50-250 mmhg) 이정상 (7-15 mmhg, 20 mmhg) 에비하여증가되어국소적인내장구획증후군 (visceral compartment syndrome) 을일으키고이것이통증을유발한다는것이다. 두번째는췌장주위신경의염증에의한것으로췌장간질과췌장주위의신경에파급된염증으로인해분비된여러가지시토카인 (cytokine) 들이통각수용기를자극하여통증이생긴다는설로이두개의이론이복합적으로작용하여통증을일으키는것으로생각된다. 이러한이론은만성췌장염시수술적치료즉절제가통증을없애는데타당하다는사실을시사해준다 [8]. - 41 -
- 대한내과학회지 : 제 83 권제 1 호통권제 623 호 2012 - 만성췌장염의합병증으로인한증상은황달과위장관출혈등이있다. 황달은췌두부의섬유화로인하여충수담관의협착이유발되어발생한다. 위장관출혈은비교적드물지만비장정맥혈전에의하여좌측문맥압항진증이유발되고이에따른위정맥류로발생하게된다. 또한가성낭종이동반되기도한다. 수술적치료의적응증은반복적이고참기어려운통증에의한경우가가장많고, 췌장의내분비외분비기능의더이상의파괴를막기위하여, 가성낭종이나담관십이지장의폐쇄, 췌장농양누공의형성, 우측문맥고혈압등의합병증에의한경우, 그리고췌장암과의구별이불가능한경우등을들수있다. 수술은적어도식사후의동통, 위하부소화관의폐쇄, 담도의폐쇄, 또는내소장루등으로인하여영양적, 대사적장애가일어나기전에고려되어야하며, 특히환자가통증에의하여진통제에비가역적인중독이되기전에이에대한수술이고려되어야한다 (Table 1). 또한췌관의결석은반드시췌관의협착과연관이있다. 췌관결석은내시경적인치료와수술적치료로접근할수있다. 내시경적치료는협착의확장과결석의제거그리고스텐트의삽입으로이루어진다. 유럽에서는체외충격파쇄석술도사용되고있다. 수술적치료로는주췌관내결석이있을경우는결석을제거하고감압술을시행하지만췌두부와갈고리돌기에있을경우절제술이적응증이된다 [3]. 췌결석이두부의주체관에있을경우췌십이지장절제술은안전하고필요충분조건을만족하는치료라고할수있다. 특히만성췌장염중췌석이동반된경우는내시경적제거가어렵고재발가능성이많으며담도의협착이잇는경우가많아수술적치료가더욱필요하리라사료된다. 더구나결석을동반할때는단순만성췌장염에비하여췌장암이발생될가능성이 4배에달하므로수술적인절제술이더욱타당하다고할수있다. 만성췌장염의수술시기는문헌마다차이는있지만우선내과적인치료를시행하다가치료에반응이없을때시행하는것이전반적인치료방침인데환자들의자연경과를보면 3-4년후에내과적치료를한후에 50-80% 정도의통증의소실을경험하는것으로보고가되고있다. 하지만내과적치료가주로통증완화에국한이되어있기때문에통증이없더라고췌장내분비및외분비기능은지속적으로감소할수있기때문에적극적으로수술을권장하는보고도있다 [9]. 일반적으로내과적치료를 3년정도시행후치료가어려운경우수술을시행하는것이좋다는보고도있다 [10]. 만성췌장염의수술적술기는직접적인방법과간접적인방법으로두가지로크게나눌수있고간접적인방법은위장또는담도의배액술, 췌관괄약근절제술이나괄약근성형술, 췌장주위의신경절제술등이있다. 직접적인술기로는췌장관의내배액술, 절제술, 절제술과췌장도세포의자기이식, 그리고췌장관의결찰등이있다. 또다른분류방법으로나누면췌관배액술, 췌절제술, 혹은신경절제술의세가지로나눌수도있다 [10]. 담도배액술은급성담도염, 담도결석형성, 이차적인폐쇄성간경화, 그리고한달이상지속되는황달등이적응증이된다. 또한영상검사상담도의폐쇄가있거나담도염의과거력이있는환자에서도고려할수있다 [11,12]. 담도배액술의하나인괄약근성형술은췌장관전체가일정하게늘어나있으면서주췌장관의개구부에폐쇄가있는경우에적응증이되지만 [11,12] 만성췌장염에서이러한환자 Table 1. Surgical indication of chronic pancreatitis Intractable pain Suspicion of malignancy Obstruction of common bile duct Symptomatic duodenal obstruction Symptomatic pseudoaneurysm Obstruction of major abdominal vessels Obstruction of pancreatic duct Figure 1. Duval procedure. - 42 -
- 최동호. 만성췌장염의외과적치료 - Figure 2. Peustow and Gillesby procedure. Figure 4. Partington and Rochelle procedure. Operative finding of chronic pancreatitis patients. Dilated pancreatic duct was open and pancreatic stones were removed prior to side to side pancreaticojejunostomy. Figure 3. Partington and Rochelle procedure. 는흔하지않고현재는내시경을사용하여괄약근성형술을시행하는경우가많다 [13-18]. 1911년 Link [19] 에의하여체외배액술이시행된이후에 1954년 DuVal [20] 은췌장미부를절제하고공장을이용하여공장과췌장을단단문합하여췌관을배액한수술을시행하였으나수술결과가양호하지않아서현재는많이사용되고있지는않다 (Fig. 1). 1958년 Peustow 와 Gillesby [21] 는측측췌공장문합술을시행하여수술후통증소실의효과도좋았고특히여러곳에췌관의협착이있는경우에증상호전이확실히있었으나췌미부를절제하면서비장절제를같이시행하여야하는단점이있었다 (Fig. 2). 1960년 Partington과 Rochelle [22] 에췌장미부나비장을절제하지않아서췌장절제로인한당뇨의악화를 Figure 5. Partington & Rochelle procedure. Operative finding of chronic pancreatitis patients. Dilated pancreatic duct was bypassed with side to side pancreaticojejunostomy. 줄일수있고췌장주위의혈관에생길수있는합병증을줄일수있게췌관을췌미부부터췌두부까지종으로절개하여췌관과공장을측측문합을하는술기로변형되었으며현재가장흔하게사용되는술기가되었다 (Figs. 3-5). 이러한췌관배액술을췌관의확장이동반된경우즉췌관이최소한 7-8 mm 이상은되어야시행되며, 80% 이상의환자에서통증의소실을보고하고있다. 저자들의경우에있어서도췌관의확장이동반된 13예에서측측췌공장문합술 11예, 그외췌미부절제및단단췌공장문합술을 2예에서시행하였으며그중 - 43 -
- The Korean Journal of Medicine: Vol. 83, No. 1, 2012-91% 에서통증의소실이나감소율을경험하였다. 췌장절제는배액술이불가능하거나적당치않은경우, 췌실질의대부분이소실된말기의경우, 술전이미내분비외분비기능의심한저하가있는경우, 기존의배액술로통증이나다른증상의호전이없는경우등에서시행하게된다. 췌장의절제술식은 1944년 Priestley 등 [23] 에의하여췌전절제술이시행되었고 1946년 Whipple [24] 에의하여췌십이지장절제술이시행되었다. 1958년 Eliason과 Welty [25] 에의하여미부췌장절제술이처음시도되었고, 1978년 Traverso와 Longmire [26] 에의하여유문부보존췌십이지장절제술이시행되었다 (Fig. 6). 췌장절제술은주병변의위치에따라다양하게시술된다. Moosa [27] 는만성췌장염시췌십이지장절제술이추천되는이유를다음과같이정리하였다. 첫째, 만성췌장염시세포의변화는주로췌두부와갈고리돌기 (uncinate process) 에서일어난다. 둘째, 췌장섬세포의대부분은췌체부와체미부에존재한다. 셋째, 담도와십이지장의폐쇄가해결된다. 넷째, 현미경적인수준의놓칠수있는췌장암이수술로완치된다 [27-33]. 췌전절제술은병변이전췌장을모두포함하거나췌장의부분절제술로통증이완화되지않거나재발한경우, 그리고이미췌장의내분비, 외분비기능이거의소실된경우에적응 증이된다. 췌전절제술을시행한후에는췌장효소와인슐린의공급이필요하며혈당의조절이쉽지않아세심한관찰이필요하다 [34-36]. 미부췌장절제술은만성췌장염으로수술한환자의 5-15% 정도를차지하며질환이췌장의미부와체부에국한된질환과췌장관의지름이 5 mm 이하인경우시행하게되며 Sawyer와 Frey [37] 는 90% 에서평균 4년이상의통증완화의결과를보고하였다. 저자들의경우에있어서도췌관의확장이동반된 31예에서췌십이장절제술 14예, 그외췌미부절제 17예에서시행하였으며그중 87% 에서통증의소실이나감소를경험하였다. 병변이주로두부에존재하며배액술을시행할정도의췌관확장이없는경우그리고십이지장이나담도의폐쇄가동반된경우췌두부절제술을시행한다 [38-41]. 십이지장이나담도의폐쇄가없는경우는십이지장을보존하는췌두부절제술을시행하기도한다. 이러한수술을시행하게되면십이지장을보존하게되므로각종위장관호르몬의분비가정상적으로유지가되며조절이가능하며추가로췌두부를절제함으로써만성췌장염의진행을정지시킬수있고술식에따라서는가능하면총수담관의폐쇄도한번에해소할수있는술식이다 [38-41]. 수술사망률이다른수술들에비해서적고당뇨발생률이 5-10% 내외이고통증소실률이 80% 이상되 Figure 6. Pylorus preserving panceaticoduodenectomy. Figure 8. Frey procedure. Figure 7. Beger procedure. Figure 9. Bern procedure. - 44 -
- Dongho Choi. Surgical treatment of chronic pancreatitis - 기때문에결과가비교적양호한수술법이다. 이러한십이지장보존췌장두부절제술은미부췌장과공장을단단문합하는 Beger 술식 [42-44], 측측문합하는 Frey 술식 [45,46], Beger 술식에서췌장미부공장문합을생략하게한 Bern 술식 [47] 등으로나눈다. Beger 술식 [42-44] 은췌장미부나췌부의췌관이확장되있지않았을때시행하게되는데췌장을문맥위에서분리하여췌두부를절제해내고공장으로췌미부의췌관은단단문합하고췌두부의췌관은측측문합하는방법으로췌관의배액술을시행한다 (Fig. 7). Frey 술식 [45,46] 은췌두부의복측벽을절제해내서췌두부의췌관을완전히감압하고췌석도제거를한후에공장을이용하여췌두부에서부터췌미부까지측측문합을하는것으로서 Beger 술식과다른점은췌장을분할하지않는것이다 (Fig. 8). 이에반해 Bern 술식 [47] 은 Beger 술식과췌두부의수술은동일하나췌장을절단하지않는것이달라서문합은췌장두부와공장을한번만측측문합하면된다 (Fig. 9). 만성췌장염에대한수술로여러가지수술법들이개발이되었고비교가되었지만지금까지의결과는다른모든수술보다월등히좋은수술보다는그환자에맞는환자에증상과상태에따른적절한치료법을선택하는것이좋을것으로사료된다 (Table 2). 또한이러한모든수술을동시에비교하는것이현실적으로어렵기때문에앞으로의무작위적인잘짜인연구가필요할것이절실하다 [48-65]. 또한만성췌장염에의한통증과합병증의치료는수술로기대할만한결과를얻을수있지만계속적으로진행하는내분비, 외분비기능의저하에대한해결방법을제시해주지는못한다. 만성췌장염에의한당뇨의해결을위하여는자 Table 2. Comparison of surgical outcome of chronic pancreatitis Author (year) Technique N Results RCTS comparing PD vs. DPPHR Klempa (1995) [48] Beger 21 22 Beger is better in terms of hospital stay, exocrine insufficiency, need of analgesics Buchler (1995) [55] Beger 20 Beger is better in terms of impaired glucose metabolism, gain of weight, frequent 20 pain relief Follow-up: Muller (1997) [65] Follow-up: Muller (2008) [66] Izbicki (1998) [59] Follow-up: Strate (2008) [64] Follow-up: Izbicki (1997) [62] Follow-up: Strate (2005) [56] Koninger (2008) [57] Beger Beger Frey Frey 10 10 20 20 31 30 23 23 RCTs comparing different techniques of DPPHR Izbicki (1995) [60] Beger 20 Frey 22 Beger Frey Beger Frey Beger Bern 38 36 34 33 32 33 is worse in terms of frequent delayed gastric empting, frequent pathologic secretion of enteral hormones Similar in pain relief, exocrine and endocrine function equal in QoL Frey is better in morbidity, QoL, and professional rehabilitation Equal in pain relief, QoL, and exocrine & endocrine function Similar in pain relief, QoL, exocrine & endocrine function, management of local complications Equal in pain relief, QoL, professional rehabilitation, exocrine & endocrine function Comparable in pain relief, QoL, exocrine & endocrine function Bern is better in operative time & hospital stay RCT, randomized control trial; PD, pancreaticoduodenectomy;, pylorus preserving pancreaticoduodenectomy; QoL, quality of life; DPPHR, Duodenum preserving pancreatic head resection. - 45 -
- 대한내과학회지 : 제 83 권제 1 호통권제 623 호 2012 - 가췌장또는기증췌장의도세포이식과췌장이식등이있다. 1977년 Najarian 등 [66] 에의하여사람에있어서첫번째췌장자가도세포이식이시행되었다. 도세포이식은술기가비교적간단한반면에도세포분리에따른수적확보의어려움, 간내주입후착상의어려움그리고이식후야기되는거부반응의진단과치료의어려움등이아직해결되지못하고있다. 한편췌장이식은수술후면역반응과그에대체로면역억제제를사용해야하나현재도세포이식에비해더효과적인당뇨의조절을기대할수있는것으로보고되고있다 [67-72]. 신경절제술은이론적으로는췌실질에손상을주지않아이상적인방법이다. 내장신경절제술과복강신경절제술이처음에는좋은결과를보여서많이시행이되었으나추적조사에서인정을받지못해서현재는많이사용되고있지않은술식이다. 최근에흉강경을이용한방법들이개발이되고시행되고있지만지속적인추적관찰이필요하다고하겠다 [73-81]. 결 췌장질환에서는수술기법의어려움과많은합병증으로수술적치료는악성종양의경우에만주로선택되었다. 그러나최근수술전환자평가와수술술기의발달, 그리고술후환자관리발달로최근양성질환에서의선택이점차늘어가는추세이다. 그이유는췌장질환에서는많은경우술전조직진단이어렵고진단의정확도가떨어져악성질환의근치적치료기회를놓칠가능성이있기때문이며만약악성질환일경우그악성도가타장기에비해상대적으로높기때문이다. 따라서경험많은외과의의경우수술적치료를선택하게된다. 만성췌장염의수술적치료는적응증만잘선택된다면통증을완화시키고삶의질을개선하는데안전하고좋은결과를가져올수있다. 론 중심단어 : 만성췌장염 ; 외과적치료 REFERENCES 1. Kim CD. Current status of acute pancreatitis in Korea. Korean J Gastroenterol 2003;42:1-11. 2. Kang MS, Lee YS, Park JH, Lee BC. Surgical treatment of acute necrotizing pancreatitis. J Korean Surg Soc 1998;54: 283-290. 3. Cooperman AM. Surgery and chronic pancreatitis. Surg Clin North Am 2001;81:431-455. 4. Haggard WD, Kirtley JA. Pancreatic calculi: a review of sixty-five operative and one hundred thirty-nine non-operative cases. Ann Surg 1939;109:809-826. 5. Planche NE, Palasciano G, Meullenet J, Laugier R, Sarles H. Effects of intravenous alcohol on pancreatic and biliary secretion in man. Dig Dis Sci 1982;27:449-453. 6. Ahn CS, Jang HJ, Kim SC, Han DJ. Surgical treatment of chronic pancreatitis. J Korean Surg Soc 1999;56:410-419. 7. Sakakibara A, Okumura N, Hayakawa T, Kanzaki M. Ultrastructural changes in the exocrine pancreas of experimental pancreatolithiasis in dogs. Am J Gastroenterol 1982;77:498-503. 8. Sakorafas GH, Farnell MB, Nagorney DM, Sarr MG. Surgical management of chronic pancreatitis at the Mayo Clinic. Surg Clin North Am 2001;81:457-465. 9. Ihse I, Borch K, Larsson J. Chronic pancreatitis: results of operations for relief of pain. World J Surg 1990;14:53-58. 10. Ammann RW, Akovbiantz A, Largiader F, Schueler G. Course and outcome of chronic pancreatitis: longitudinal study of a mixed medical-surgical series of 245 patients. Gastroenterology 1984;86(5 Pt 1):820-828. 11. Doubilet H, Mulholland JH. The surgical treatment of recurrent acute pancreatitis by endocholedochal sphincterotomy. Surg Gynecol Obstet 1948;86:295-306. 12. Doubilet H, Mulholland JH. Eight-year study of pancreatitis and sphincterotomy. J Am Med Assoc 1956;160:521-528. 13. Rösch T, Daniel S, Scholz M, et al. Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up. Endoscopy 2002;34:765-771. 14. Morgan DE, Smith JK, Hawkins K, Wilcox CM. Endoscopic stent therapy in advanced chronic pancreatitis: relationships between ductal changes, clinical response, and stent patency. Am J Gastroenterol 2003;98:821-826. 15. Gabbrielli A, Pandolfi M, Mutignani M, et al. Efficacy of main pancreatic-duct endoscopic drainage in patients with chronic pancreatitis, continuous pain, and dilated duct. Gastrointest Endosc 2005;61:576-581. 16. Eleftherladis N, Dinu F, Delhaye M, et al. Long-term outcome after pancreatic stenting in severe chronic pancreatitis. Endoscopy 2005;37:223-230. 17. Vitale GC, Cothron K, Vitale EA, et al. Role of pancreatic duct stenting in the treatment of chronic pancreatitis. Surg Endosc 2004;18:1431-1434. 18. Ponchon T, Bory RM, Hedelius F, et al. Endoscopic stenting for pain relief in chronic pancreatitis: results of a standardized protocol. Gastrointest Endosc 1995;42:452-456. - 46 -
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