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1 SMN SURGICAL METABOLISM AND NUTRITION Vol. 8, No. 2, December, 2017 pissn , eissn REVIEW ARTICLE 수술후췌장루및췌장염환자의영양공급 한인웅 성균관대학교의과대학삼성서울병원간담췌외과 Nutritional Support for Patients with Postoperative Pancreatic Fistula, or Pancreatitis In Woong Han, M.D., Ph.D. Division of Hepato-biliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea In terms of nutritional therapy after pancreatectomy, there is no need for routine use of artificial nutrition supplementation except in the case of malnutrition or complications. Postoperative pancreatic fistula (POPF) is one of the most representative complications of pancreatectomy, and adequate nutritional support is important for management of POPF. Oral diet or enteral nutrition (EN) treatment is preferred over parenteral nutrition (PN) since oral diet or EN results in higher POPF closure rates and lower complication rates than EN. Postoperative pancreatitis is usually managed according to the general principle of acute pancreatitis. There is no need to provide specialized nutrition therapy for mild pancreatitis, whereas moderate-to severe pancreatitis should be treated with early specialized nutritional therapy. EN is a more preferred nutritional supplement method over PN due to its lower complication rate, shorter hospital stay, less frequent multi-organ failure, and mortality. Long-term sequelae after POPF or pancreatitis include exocrine or endocrine insufficiency. In the case of exocrine insufficiency, exocrine replacement therapy should be administered. Moreover, endocrine insufficiency, commonly represented by diabetes mellitus (DM), should be managed based on guidelines for type 1 or 2 DM. (Surg Metab Nutr 2017;8:23-27) Key Words: Nutrition, Pancreatectomy, Pancreatic fistula, Pancreatitis 서론 췌십이지장절제술 (Pancreatoduodenectomy; PD) 또는유문보존췌십이지장절제술 (pylorus-preserving PD; PPPD) 는다양한유두부주위종양 (periampullary tumor) 의표준적인술기이다. 원위부췌절제술은췌장의몸통및꼬리에발생하는질환에대한대표적인술기이며, 이는비장또는비장혈관을보존하는술식, 복강동맥을합병절제하는술식 (distal pancreatectomy with celiac axis resection; DP-CAR), 근치적전향적췌미부-비장절제술 (Radical Antegrade Modular PancreatoSplenectomy; RAMPS) 등의다양한변형술식이임상에적용되어왔다.[1-4] 최근수술술기및수술전후관리의발달로인해, 수술경험이많은기관의경우수술후사망률은 1 5% 로상당히감소하였다.[5] 그러나수술전환자들의영양상태가불량한경우가많고, 수술적절제범위가타수술에비해서광범위해수술후합병증률은현재에도 40 60% 에이르고있다.[6] 췌절제술후가장대표적인합병증은위배출지연, 수술후췌장루, 수술후췌장염등이있다. 그중에서도수술후췌장루및췌장염은췌십이지장절제술과원위부췌절제술의공통적인 Received December 11, Accepted December 18, Correspondence to: In Woong Han, Division of Hepato-biliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Tel: , Fax: , cardioman76@gmail.com This article was presented at 23th conference of KSSMN. CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyrights c The Korean Society of Surgical Metabolism and Nutrition

2 24 Surgical Metabolism and Nutrition Vol. 8, No. 2, 2017 합병증으로, 그치료법및영양공급법에대해서아직자세하게정립되어있지않다. 따라서이종설에서는췌절제술후발생할수있는수술후췌장루와췌장염에서의적절한영양공급에대해서논하고자한다. 되었으나, 아직획기적인예방법은알려져있지않다.[12-15] 또한췌장루치료에대한일치된견해도아직마련되어있지않다. 최근연구에따르면,[16] 일차적치료는경구영양섭취제한, 소마토스타틴등의췌장분비억제제사용, 적절한영양공 급, 필요시항생제투여등이다. 환자상태가급격히악화되는 본론 1. 췌절제술후일반적인영양공급 2012년출판된 ERAS guideline에따르면, 췌십이지장절제술전후의일반적인영양공급은 Table 1과같다. 심각한영양결핍이있는환자를제외하면, 대부분의경우수술전추가적인영양공급은불필요하다. 수술전후면역영양 (Immuno-nutrition) 은도움이된다고알려져있으며, 수술후경구영양이가능한환자는별도의추가영양공급은필요하지않다 (Table 1).[7] ASPEN [8] 및 ESPEN [9] 에서는일반적인복부수술에대한영양공급에대한지침은제시하고있으나, 췌절제술에대한특이적영양공급에대한지침은현재까지마련되어있지않다. 다만, 최근출판된 ASPEN guideline [10] 에서는수술후발생한췌장염에대한치료법에대해제시하고있으며, 이것은본종설의후반부에다루기로한다. 2. 수술후췌장루수술후췌장루는 International Study Group of Pancreatic Fistula (ISGPF) 의정의를가장많이사용하고있다. 2016년에개정된 ISGPF에따르면, 수술후췌장루는 췌장관상피와다른상피간의교통에따른췌장효소가풍부한췌장액의저류 로정의한다.[11,12] 수술후췌장루의예방에대해서는그간많은연구가이루어져왔다. 췌장-공장또는췌장-위문합법, 스텐트사용유무, 췌장절단방법등의수술술기에대한연구, 특정약물의효과, 수술전환자의인구학적특징등에대해다양한연구가시도 경우췌장저류액을배액하고, 재수술까지도고려할수있다. 3. 수술후췌장루환자의영양공급적절한영양공급은췌장루환자치료의핵심적인요소중의하나이다. 수술후부적절한영양공급으로인한영양불량은, 소위 high-output 췌장루의위험인자이다.[12] 전통적으로, 췌장루는그병태생리학적특징, 즉경구섭취를줄이면췌액의분비가줄어췌장루호전에도움이될거라는인식에기반하여경구영양섭취를제한해왔다.[12] 또한현재개발된인공영양 (Artificial nutrition) 의발전에힘입어, 경구영양금지에대한인식을공고히할수있었다.[12] 그러나잘알려진바와같이, 경구및경관영양 (Enteral nutrition) 은정맥영양 (Parenreral nutrition) 에비해위장관점막을보호하고, 장관내박테리아생태계를보존할수있는등의장점이있다.[17] 또한한전향적무작위배정연구는췌장루환자에서경장영양을공급했을때정맥영양에비해빠른췌장루회복률, 빠른회복시간을보임을보고하였다.[17] 또한 2015년발표된다기관전향적연구에서도경구영양을시행했을때췌장루악화률과배액관거치기간이금식군과비교하여차이가없음을보고한바있어췌장루에서금식이반드시필요한치료가아님을입증하였다.[18] 4. 수술후췌장염급성췌장염의전형적인병태생리는, 췌관선포세포 (acinar cell) 에서트립신 (trypsin) 의조절되지않는활성화가그중심이다.[19] 원인으로는췌관폐쇄, 약물, 수술, 유전적인자로다양하며, 검사실소견은특징적으로혈정아밀라아제및리파아제 Table 1. Nutritional supplement after pancreatectomy. ERAS guideline, 2012 [7] Item Summary and recommendations Evidence level Recommendation grade Preoperative nutrition Routine use of artificial nutrition: not warranted significantly malnourished patients: oral supplements or enteral nutrition preoperatively Very low Weak Perioperative Immuno-nutrition (IN) IN for 5 7 days perioperatively should be considered because it may reduce the rate of infectious complications Moderate Weak Postoperative artificial nutrition Normal diet after surgery without restrictions. Enteral tube feeding: only on specific indications Parenteral nutrition: should not be used routinely Early diet at will: moderate Strong

In Woong Han: Nutrition after Pancreatectomy Complications 25 아직그근거가충분하지않다.[20] 영양공급방법으로는정맥영양보다는경장영양이선호되며, 이는경장영양에서감염및재원기간, 수술적치료의필요성, 다기관부전, 사망률등의대부분의지표에서정맥영양에비해우월한것으로보고되기때문이다.

3 In Woong Han: Nutrition after Pancreatectomy Complications 25 아직그근거가충분하지않다.[20] 영양공급방법으로는정맥영양보다는경장영양이선호되며, 이는경장영양에서감염및재원기간, 수술적치료의필요성, 다기관부전, 사망률등의대부분의지표에서정맥영양에비해우월한것으로보고되기때문이다. 경장영양의공급방법으로는비위관과비장관을이용하는방법이있으며, 둘간의우위는분명하지않다.[20] 활생균 (probiotics) 의투여는고려해볼수있으나그임상적근거는아직적고, 췌장염발병후 1주이상경장영양이불가능한경우정맥영양을투여해야한다.[21,22] 6. 수술후췌장루및췌장염의만성경과 Fig. 1. Abdominal computed tomography in patients with postoperative pancreatitis. 의증가및칼슘의감소등이있다.[19] 전형적인영상소견은 Fig. 1과같다 (Fig. 1). 이중수술로인해발생하는췌장염의원인은잘알려져있지않다. 그러나임상적으로문제가될만큼악화하는소견은흔하지않으며, 대부분단백효소저해제 (protease inhibitor) 나소마토스타틴같은췌액분비억제제에반응이좋은것으로알려져있다.[19] 따라서급성기치료에대한가이드라인은통상적인급성췌장염의그것과다르지않다. 수술후췌장염의임상경과를고려할때급성기의치료보다는만성후유증 (sequalae) 이더중요하다. 5. 수술후췌장염의영양공급 전술한바와같이수술후췌장염의급성기치료에대한지침은현재까지발표되지않아, 급성췌장염의영양공급으로갈음해도충분하다. 가장대표적으로사용되는급성췌장염의영양공급은 ASPEN guideline이다.[20] 이에따르면, 급성췌장염의영양공급을위해서는병의중증도를자주측정하고, 경구및경장영양의가능성을지속적으로파악할것을권고한다. 경증 (mild) 의급성췌장염에서는정맥영양을포함한별도의특별한영양공급은필요하지않으나, 합병증이동반되었거나 7일이상의금식을요할경우정맥영양을고려해야한다. 중등도 (moderate) 이상의췌장염에서는영양공급이중요한치료항목으로격상된다. 환자의임상상악화로인해경구영양이불가능한경우가많으므로, 입원후 24 48시간이내에비위관 (naso-gastric tube) 또는비장관 (naso-enteric tube) 을통한경장영액을시작해야한다. 이에도움이되는특별한경장영양제제는알려진바가없고, 면역영양은시도해볼수는있으나 2013년국내연구진들에의해, 췌장절제술후환자들의회복기간은 6개월에달한다는보고가발표되었다.[23] 이에따르면, 환자들중특히 60세이상의고령, 췌십이지장절제술, 만성췌장염합병여부, 악성질환을가진경우주의깊은추적관찰및보존적치료가요구된다.[23] 통상적인췌절제술에서양성질환의경우술후 2 3개월이면정상체중을회복하고, 6개월정도면술전체중을회복한다고알려져있다.[23] 그러나악성질환의경우항암방사선치료등의시행여부에따라회복기간이상대적으로더필요하다.[23] 급성기경과후의만성경과에서보일수있는기능적문제들은악액질 (Cachexia), 내분비및외분비기능장애가있다. 악액질은대부분원발질환의재발과관련이있어본종설에서는다루지않기로한다. 내분비및외분비기능의장애는앞서살펴본췌장루및췌장염이대표적인원인이다. 췌장루및췌장염으로인한췌실질의위축 (atrophy) 및췌관의확대가췌장기능의상실을불러오기때문이다.[24,25] 최근발표된메타분석은 19개의기존연구총 1,295명의환자를대상으로연구한결과, 췌절제술자체가새로이발생한당뇨의유의미한증가및외분비기능을상실을일으킴을보고하였다.[26] 췌절제술을요하는양성및악성종양환자들은대부분진단당시또는수술이후외분비기능장애를겪을수있다.[27] 외분비기능장애를진단받은환자들은췌장효소보충치료 (Pancreatic exocrine replacement treatment; PERT) 를시행받을필요가있으며, 이의구체적인방법은최근발표된호주그룹의기준에따르면 Table 2와같다.[28] 흥미로운사실은, 이러한췌장효소보충치료는외분비기능의회복뿐만아니라, 팽대부주위종양으로췌십이지장절제술을시행받은환자에게서생존률을개선시키는효과가있다는보고도있다.[29] 상기연구진들은 2007년부터 2015년까지 469명의환자를대상으로후향적연구를시행한결과 PERT

4 26 Surgical Metabolism and Nutrition Vol. 8, No. 2, 2017 Table 2. PERT recommendation from Australia study group [28] No Recommendation 1 Any patient requiring pancreatic resection should be assessed for the presence of PEI postoperatively. 2 Patients having total or subtotal pancreatectomy, including pancreatic head resection, require PERT postoperatively. 3 After pancreatectomy an individual s nutritional status (including serum levels of vitamins and minerals) should be monitored so that appropriate treatment can be provided. 4 Patients who are pancreatic-sufficient in the early period after any pancreatic resection should have long-term assessment for the development of PEI. 5 PERT is required in patients after pancreaticogastrostomy because of the effect of acid on endogenous enzymes. 6 PERT following pancreatectomy should be individualized and titrated to indicators of PEI, bearing in mind asynchrony and bacterial overgrowth. 시행군에서대조군에비해생존에미치는위험률 (hazard ratio) 이다변량분석후 0.75 (95% confidence interval , P=0.046) 으로보고하였다.[29] 실제 PERT를시행하는방법은, 권고안마다약간의차이는있으나, 다음과같다.[30] 반응이있을때까지투여량을점진적으로증가시키고, 환자의복약순응도를확인한다. 약물의효과를위해제산제를병합투여하고, 식후뿐만아니라식간투여도진행한다. 위내에서불활성화를고려하여미세구체 (microspheres) 를사용하며, 위장관내의내재적문제가병합되어있는지확인한다.[30] 수술후췌장루및췌장염으로인해발생하는당뇨는, type 3c로분류되는수술후당뇨에해당된다.[31-33] 실제로췌절제술후발생하는당뇨의빈도는대략 5 40% 이며, 이의위험인자로는인종, 기저질환, 수술후합병증유무, 췌장염동반유무, 절제된췌장의양, 추적관찰기간등이다.[31-33] 원위부췌절제술이췌십이지장절제술보다당뇨의위험성이더크다는사실은잘알려져있으며, 국내의한연구진은술전당뇨가있었던 40% 의환자가췌십이지장절제술후오히려당뇨가개선되었다는사실을보고하였다. 이는췌절제술이당내증 (insulin resistance) 을개선시켜당촉진인슐린분비 (glucose stimulated insulin secretion) 를강화하는것으로해석하였다. [34] 수술후당뇨는기존의제 1형및제 2형당뇨와혈관합병증발생위험성이비슷한것으로알려져있다.[35] 따라서그치료법은제 1형및제 2형당뇨의치료에준해서진행된다. 특징적으로 type 3c 당뇨의경우인슐린과글루카곤의분비능이모두저해되어있다. 목표당화혈색소 (HbA1c) 수치는 7% 미만이며, 평소혈당치는삶의질향상을위해정상치보다약간높게유지하여도무방하다. 통상적으로경구혈당강하제보다는인슐린이반응이더좋으며, 기저췌장의염증완화를위해금주및금연이반드시필요하다. 외분비동반기능장애가흔하기때문 에, PERT 를적극적으로고려해야한다.[35] 결론 일반적으로, 합병증이나심각한영양결핍이없는췌절제술환자에게인공영양공급은필요하지않다. 임상적으로유의미한수술후췌장루가발생한경우에는적절한영양공급이필수불가결하며, 공급방법으로는췌장루소실및동반합병증발생여부를고려할때경구또는경장영양이정맥영양에비해선호된다. 수술후췌장염의치료는일반적인급성췌장염의치료에준하며, 경중인경우특별한영양공급이중요하지않지만중등도이상인경우적극적인영양공급을시행해야하며, 이경우에도경구및경장영양을정맥영양보다먼저고려해야한다. 췌장루및췌장염의만성경과를고려할때내분비및외분비기능의저하가동반되는경우가흔하므로, 적극적인혈당관리및췌장효소보충제투여를고려해야한다. REFERENCES 1. Rutz DR, Squires MH, Maithel SK, Sarmiento JM, Etra JW, Perez SD, et al. Cost comparison analysis of open versus laparoscopic distal pancreatectomy. HPB (Oxford) 2014;16: Ome Y, Hashida K, Yokota M, Nagahisa Y, Michio O, Kawamoto K. Laparoscopic radical antegrade modular pancreatosplenectomy for left-sided pancreatic cancer using the ligament of Treitz approach. Surg Endosc 2017;31: Drymousis P, Raptis DA, Spalding D, Fernandez-Cruz L, Menon D, Breitenstein S, et al. Laparoscopic versus open pancreas resection for pancreatic neuroendocrine tumours: a systematic review and meta-analysis. HPB (Oxford) 2014;16: Yamamoto T, Satoi S, Kawai M, Motoi F, Sho M, Uemura KI, et al. Is distal pancreatectomy with en-bloc celiac axis resection effective for patients with locally advanced pancreatic ductal adenocarcinoma? -Multicenter surgical group study. Pancreatology doi: /j.pan [In press]. 5. La Torre M, Ziparo V, Nigri G, Cavallini M, Balducci G, Ramacciato G. Malnutrition and pancreatic surgery: prevalence and outcomes. J Surg Oncol 2013;107: Bozzetti F, Mariani L. Perioperative nutritional support of patients undergoing pancreatic surgery in the age of ERAS.

5 In Woong Han: Nutrition after Pancreatectomy Complications 27 Nutrition 2014;30: Lassen K, Coolsen MM, Slim K, Carli F, de Aguilar-Nascimento JE, Schäfer M, et al. Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS ) Society recommendations. Clin Nutr 2012;31: Boullata JI, Carrera AL, Harvey L, Escuro AA, Hudson L, Mays A, et al. ASPEN safe practices for enteral nutrition therapy [Formula: see text]. JPEN J Parenter Enteral Nutr 2017;41: Weimann A, Braga M, Carli F, Higashiguchi T, Hübner M, Klek S, et al. ESPEN guideline: clinical nutrition in surgery. Clin Nutr 2017;36: McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). 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황지웅

황지웅 Comparison of Laparoscopy and Exploration in the Distal Pancreatectomy BACKGROUND: To determine the benefits of laparoscopic surgery compared with exploration, the clinical outcomes of open and laparoscopic