Korean Journal of Clinical Oncology 2015;11: pissn eissn Review 위암의최소침습수술 박도중, 안상훈, 김형호

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1 Korean Journal of Clinical Oncology 2015;11: pissn eissn Review 위암의최소침습수술 박도중, 안상훈, 김형호 서울대학교의과대학외과학교실, 분당서울대학교병원외과 Minimally invasive surgery in gastric cancer Do Joong Park, Sang Hoon Ahn, Hyung-Ho Kim Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea Gastric cancer surgery with curative intent comprises subtotal or total gastrectomy with radical lymph node dissection. Recently, as the incidence of early gastric cancer (EGC) is increasing, minimally invasive surgery can be applied to gastric cancer treatment. Minimally invasive gastric surgery has four aspects such as minimally invasive access, modified function-preserving gastrectomy, limited lymphadenectomy, and no reconstruction. Laparoscopic gastrectomy became popular for EGC and its indication is being expanded to advanced gastric cancer. Reduced or single port gastrectomy can be performed for selective EGC. For middle or upper EGC, laparoscopic pylorus-preserving gastrectomy or proximal gastrectomy is applicable as function-preserving gastrectomy. D1+ node dissection is enough for EGC without lymph node metastasis and sentinel node biopsy will be helpful for avoiding unnecessary lymph node dissection in EGC patients. Keywords: Gastric cancer, Minimally invasive surgery, Laparoscopy, Sentinel lymph node 서론 위암은우리나라에서두번째로흔한암이며사망률도폐암, 간암에이어세번째로높다 [1]. 위암의치료에있어서수술은근치적치료의가장중요한방법이며근치적위암수술은광범위한위및림프절절제를필요로한다. 위암수술은 1881 년 Billroth 가처음으로성공적으로시행한이후위암발생이많은한국, 일본을중심으로많은발전이있어왔다. 20 세기후반에복강경수술기법이도입되면서위암에서도 1991 년에복강경위암수술을성공적으로시행하게되었다. 최근국가암검진사업으로위내시경이활발하게시행됨에따라조기위암의발견이증가하였다. 따라서복강경위암수술이활발하 Received: Dec 15, 2015 Accepted: Dec 21, 2015 Correspondence to: Do Joong Park Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: , Fax: Copyright Korean Society of Surgical Oncology 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. 게시행되고일부조기위암환자에게는축소공또는단일공수술도가능하게되었다. 또한절제범위도축소되어위를보존하는기능보존위절제술이가능하게되었는데, 중부조기위암에서는유문보존위절제술이, 그리고상부조기위암에서는근위부위절제술이시행되었다. 림프절절제범위도기존의 D2 림프절절제에서조기위암의경우에 D1+ 절제로축소되고감시림프절개념을위암수술에서도적용하고자하는노력이계속되고있다. 이에저자들은현재위암치료에시행되고있는최소침습수술의최신지견을최소침습접근 (minimally invasive access), 기능보존위절제 (function-preserving gastrectomy), 축소림프절절제 (limited lymph node dissection), 수술후조기회복 (enhanced recovery after surgery, ERAS) 프로그램부분으로나누어문헌고찰과저자들의경험을바탕으로정리하고자한다. 본론 최소침습접근 (Minimally invasive access) 복강경위암수술 (Laparoscopic gastrectomy) 1991 년 Kitano 등 [2] 이조기위암에서복강경위암수술을처음시행한이후로조기위암에서복강경위암수술은해마다증가해왔으며많은발전이있었다. 복강경수술의장점으로는수술후통증, 염증반응및합병증이적고회복이빠르다고할수있다 [3]. 현재조기위 37

2 암에서의복강경위암수술의효용성을평가하기위한대규모의다기관전향적무작위비교연구가진행중이다 (Table 1). 한국에서진행되고있는 Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) 01 연구는 2006 년부터 2010 년까지등록된 1,416 명의 ct1-2n0 위암환자를대상으로복강경과개복원위부위절제술을비교하는연구로서최종결과인 5 년생존율이 2015 년에나올예정이다 [4]. 일본의 Japan Clinical Oncology Group (JCOG) 0912 는 I 기위암환자 920 명을대상으로 2010 년부터시작된연구이다 [5]. 이전에보고된작은규모의전향적비교연구도있었지만 [6], 최근의두연구가조기위암에서의복강경수술의효용성을입증해줄것으로기대한다. 복강경수술의술기와기구가발전함에따라복강경수술의적응증을진행위암까지확대하고자하는노력이진행되고있다. Park 등 [7] 의 239 명의진행성위암환자를대상으로시행한다기관후향적연구에의하면복강경위암수술후장기생존결과는개복위암수 술의결과와비슷하였다. 현재진행위암에서진행되고있는 3 상연구는한국의 KLASS 02, 일본의 Japanese Laparoscopic Surgery Study Group (JLSSG) 0901, 중국의 Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) 01 이있다 (Table 1). KLASS 02 는 1,050 명의 ct2-4a 위암환자를대상으로복강경과개복위암수술후 3 년무재발생존율을평가하는연구이며이결과는향후진행위암에서복강경수술의적용을확대하는중요한근거가될것이다 [8]. 다른한편으로는, 절제불가능한 4 기위암환자에서항암치료후절제가능하게전환되어근치적수술을하는전환수술 (conversion surgery) 에서복강경위수술을시행하여수술후적시에항암치료가이어지도록도움을주는역할에대한연구도이루어지고있다. 축소공및단일공위암수술 (Reduced or single port gastrectomy) 개복위암수술에서복강경위암수술로의발전이있었고, 최근에는자연개구부를통하여복강내로접근하는방법 (natural orifice Table 1. Current clinical trials on minimally invasive surgery in gastric cancer Study Year Nation Phase Design Patients Enroll Primary endpoint KLASS Korea III LDG vs. ODG cstage I 1,400 5-year overall survival KLASS Korea III LDG vs. ODG ct2-4a 1,050 3-year relapse-free survival KLASS Korea II LTG for EGC Stage I 168 Morbidity, motality KLASS Korea III LPPG vs. LDG Stage I 256 Dumping syndrome KLASS Korea III LPG vs. LTG Stage I 180 Hemoglobin change JCOG Japan III LDG vs. ODG Stage I year overall survival JLSSG Japan II/III LDG vs. ODG ct2-4a 180/500 Mobidity/relapse-free survival CLASS China III LDG vs. ODG ct2-4a 1,056 3-year relapse-free survival KLASS, Korean Laparoscopic Gastrointestinal Surgery Study; LDG, laparoscopic distal gastrectomy; ODG, open distal gastrectomy; LTG, laparoscopic total gastrectomy; EGC, early gastric cancer; LPPG, laparoscopic pylorus-preserving gastrectomy; LPG, laparoscopic proximal gastrectomy; JCOG, Japan Clinical Oncology Group; CLASS, Chinese Laparoscopic Gastrointestinal Surgery Study. Table 2. Studies on single port gastrectomy Author Year Nation N Journal Method Results Characteristics Omori et al. [9] 2011 Japan 7 Surg Endosc 2.5 cm incision Two 2 mm assistant ports Park et al. [10] 2012 Korea 2 Surg Laparosc Endosc Percutan Tech 2.5 cm incision One 2 mm assistant port Ahn et al. [11] 2013 Korea 22 J Am Coll Surg 2.5 cm incision No assistant port Ahn et al. [12] 2014 Korea (control) J Am Coll Surg 2.5 cm incision No assistant port Operation time: 344 minutes Estimated blood loss: 25 ml Examined lymph nodes: 67 Operation time: 275 minutes Estimated blood loss: 85 ml Examined lymph nodes: 32 Operation time: 178 minutes Operation time: 144 minutes Estimated blood loss: 50 ml Examined lymph nodes: 52 Ahn et al. [13] 2014 Korea 2 Gastric Cancer 2.5 cm incision Operation time: 190 minutes Estimated blood loss: 55 ml Examined lymph nodes: 77 Billroth I Billroth I Uncut Roux-en-Y Billroth I, Uncut Roux-en-Y Comparative study Total gastrectomy 38 Korean Journal of Surgical Oncology

3 Do Joong Park et al. MIS in gastric cancer transluminal endoscopic surgery, NOTES) 에대하여많은전임상및임상연구가진행되고있다 [14]. 하지만아직은임상에적용할정도의근거를가지지는못하고있다. 그중간단계로축소공 (reduced port) 또는단일공 (single port) 수술이활발하게연구가되고있고담낭절제술, 충수돌기절제술등양성질환에대하여점차적으로많이시행되고있다 [15]. 하지만아직위암에서의축소공또는단일공수술은아직보고가많지않은데, 복강경경험이많은몇개의기관에서조기위암에서의단일공수술을보고하고있다 (Table 2) [9-12,16-19]. Ahn 등 [12] 에의하면단일공수술을받은환자들이기존의복강경수술을받은환자들에비하여미용적인만족도가높았고출혈량과수술당일및익일의수술후통증이적었다고보고를하였다. 향후단일공위암수술에대한연구가연구회를통하여계속활발하게이어질것으로기대한다. 기능보존위절제 (Function-preserving gastrectomy) 위암의근치적인수술로는위아전절제와위전절제만이있었지만최근조기위암의증가로인하여위의절제범위도줄어들게되었다. 조기위암에서는약 2 cm 정도의절제연을확보하면되기때문에위아전절제에서원위부위절제술로명칭도바뀌었으며조기위암의위치에따라서기능보존위절제술도가능해졌다. 유문보존위절제술 (Pylorus-preserving gastrectomy) 유문보존위절제술은대표적인기능보존위절제술중의하나로서 Maki 등 [20] 에의하여 1967 년위궤양의수술적치료방법으로소개되었다. 유문을보존하기위하여 1 번, 5 번, 12 번림프절절제가불가능하므로위암에서는그림프절에전이가없다고예상되는중부조기위암에서선택적으로적용이가능하다. 유문보존위절제술은기존의원위부위절제술에비하여유문을보존함으로써덤핑증후군과담즙역류와같은위절제후에생길수있는여러가지소화기증상을줄여주고, 미주신경간분지를보존함으로써담석의발생을줄여준다는장점이있다 [21,22]. 반면에유문보존위절제술은수술후위배출지연을유발시킨다는보고도있다 [23]. 하지만이와같은보고들은모두후향적연구이며, 따라서유문보존위절제술에대한장점을입증하기위하여현재다기관전향적무작위비교연구인 KLASS 04 가진행중이다. KLASS 04 는유문보존위절제술과기존의원위부위절제술간에일차유효성평가변수인수술후덤핑증 후군발생의차이를비교하고이차적인변수로서영양, 삶의질, 담석발생률등을비교할것이다. 근위부위절제술 (Proximal gastrectomy) 상부에생기는위암의경우위전절제술이표준수술이었다. 최근건강검진위내시경의시행으로조기위암이증가하고또한서구와같이상부위암이증가하고있다 [24]. 상부에생긴조기위암의경우원위부위주위의림프절전이는드물기때문에근위부위절제술만으로도위전절제술과같은장기생존율을가진다고보고하고있다 [11,25,26]. 또한근위부위절제술은위전절제술에비하여영양이좋고빈혈이적으며위장관호르몬분비면에서장점을가진다고알려져있다 [27,28]. 그런데국내전국조사에의하면근위부위절제술은 2004 년 1.1%, 2009 년에 1.0% 밖에시행되지않았다 [24]. 근위부위절제술이여러가지이론적인장점을가지고있음에도불구하고많이시행되지않는이유는후기합병증인위식도역류와그로인한궤양및협착때문이다 [11,29]. 근위부절제를시행한후식도와잔위를바로이어주는식도 - 위문합후에위식도역류문제가심각하기때문에많은술자들이식도 - 위문합에여러가지방법을추가해보았지만일관되게위식도역류를해결하지는못하였다 [29]. 따라서식도와잔위를바로이어주지않고소장을삽입하여식도 - 소장 - 잔위를이어주는문합을비롯하여식도 - 소장을이어준후잔위를 cm 하방에이어주는이중통로문합 (double tract reconstruction) 도시행하게되었다 [30]. Ahn 등 [30] 은근위부위절제술후이중통로문합을하였을때위식도역류증상이위전절제술하였을때와비슷하게적었음을보고하였다. 따라서상부조기위암의치료로서근위부위절제술이표준치료로인정받기위해서 3 상비교연구가필요하게되었고현재상부조기위암에서복강경하근위부위절제술후이중통로문합과복강경위전절제술을비교하는전향적무작위비교연구인 KLASS 05 연구가진행중에있다. 축소림프절절제 (Limited lymphadenectomy) 위암의근치적수술에서가장중요한요소는광범위한림프절절제이다. 현재진행위암에서는 16a2/b1 에전이가의심되지않는다면예방적인 D2+ 대동맥주위림프절절제는불필요하며 D2 림프절절제가표준수술로인정받고있다 [31]. 조기위암에서는 D1+ 림프절절제만으로도근치적인수술로받아들여지고있다 [32]. 조기위암 Table 3. Clinical trials on sentinel node mapping Study Year Nation Phase Design Patients N Primary endpoint Status JCOG Japan II Single arm, open T1< 4 cm 440/1,550 False negative rate Terminated JSSNNS Japan II Single arm, open ct1,2 < 4 cm 300 Sensitivity Published Laparoscopic Korea II Single arm, laparoscopy ct1 < 4 cm year disease-free survival Follow-up SNNS SENORITA 2013 Korea III Open label, double arm, laparoscopy, SNNS vs. LDG ct1 < 3 cm year disease-free survival Recruiting JCOG, Japan Clinical Oncology Group; JSSNNS, Japanese society of Sentinel Node Navigation Surgery; SNNS, sentinel node navi gation surgery; SENORITA, sentinel node oriented tailored approach; LDG, laparoscopic distal gastrectomy. 39

4 중에점막암인경우에림프절전이율은 5% 이내이고점막하암인경우에는 15% 20% 가림프절전이가있다고알려져있다. 따라서조기위암일경우약 80% 이상에서불필요한광범위위절제및림프절절제를시행하고있다. 조기위암의경우절제연을 2 cm 이하로하고림프절절제도 D1+ 정도로축소되었지만내시경점막하절제술에비하면여전히광범위위절제및림프절절제라고볼수있다. 만일조기위암환자에서림프절전이여부를정확하게알수있다면불필요한광범위절제를피할수있겠지만, 현재수술전시행하고있는위내시경또는위내시경초음파, CT 검사로는림프절전이여부를 100% 정확하게알지못하기때문에광범위절제가불가피한현실이다. 감시림프절이란원발암으로부터림프절전이가일어나는첫번째림프절을의미한다. 따라서감시림프절의전이여부를조사하여전이가없다면다른두번째세번째, 그이후의림프절에도전이가없기때문에불필요한림프절곽청을피할수가있다. 현재유방암과악성흑색종에서는활발하게감시림프절생검이이루어지고있고많은환자들이불필요한림프절곽청을생략함으로써림프부종, 감각이상, 운동장애등의합병증을피할수있게되었다. 위암은유방암과악성흑색종과달리림프절경로가복잡하여감시림프절생검의적용이어렵다고생각하였으나많은연구에서긍정적인결과들이나오게되었다 [33-37]. 현재진행되고있는 2 상또는 3 상연구는 Table 3 과같으며이들의결과에따라조기위암에서감시림프절생검의적용이표준술식으로자리잡을수있는계기를마련하게될것이다. 수술후조기회복 (Enhanced or early recovery after surgery) 수술후조기회복프로그램은여러외과수술분야, 특히대장항문수술에서수술후회복을향상시키기위하여연구가많이되었지만아직위암수술분야에는보고가적다. 몇저자들의보고에의하면위암수술후에도 enhanced or early recovery after surgery (ERAS) 프로그램적용이가능하며국소적인합병증이적었다고하였다 [38,39]. 최근 97 명의복강경위암수술을받은환자들을대상으로 ERAS 군 (n = 46) 과그렇지않은군 (n = 51) 으로무작위배정을하여비교하였을때 ERAS 군에서수술후회복률과시간이더빨랐고통증이적었다는좋은결과가미국복강경학회에서발표되었다 [40]. 결론 위암의치료에서최소침습수술은접근방법, 위절제, 림프절절제범위면에서다양하게적용이되고있다. 접근방법면에서는복강경위암수술의많은발전이있었으며조기위암뿐만이아니라진행위암으로도복강경위암수술의적응증이확대되고있다. 특히조기위암의경우에는축소공또는단일공수술을선택적으로적용할수있다. 위절제범위에서는중부조기위암에서유문보존위절제술을, 상부조기위암에서는근위부위절제술을시행할수있겠다. 림프절절제범위에서는조기위암의경우 D1+ 림프절절제가가능하며, 가까운미래에감시림프절생검의 3 상시험이긍정적인결과가나오면감시림프절전이가없는조기위암은국소위절제만으로도근치 적인치료가될것이다. 또한수술후조기회복프로그램으로위암수술후환자의회복률을향상시킬수있을것으로기대한다. CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported. REFERENCES 1. Jung KW, Won YJ, Kong HJ, Oh CM, Cho H, Lee DH, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in Cancer Res Treat 2015;47: Kitano S, Maeo S, Shiraishi N, Shimoda K, Miyahara M, Bandoh T, et al. Laparoscopically assisted distal partial gastrectomy for early-stage gastric carcinomas. Surg Technol Int 1995;Iv: Lee SI, Choi YS, Park DJ, Kim HH, Yang HK, Kim MC. Comparative study of laparoscopy-assisted distal gastrectomy and open distal gastrectomy. J Am Coll Surg 2006;202: Kim HH, Han SU, Kim MC, Hyung WJ, Kim W, Lee HJ, et al. Prospective randomized controlled trial (phase III) to comparing laparoscopic distal gastrectomy with open distal gastrectomy for gastric adenocarcinoma (KLASS 01). J Korean Surg Soc 2013;84: Nakamura K, Katai H, Mizusawa J, Yoshikawa T, Ando M, Terashima M, et al. A phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric Cancer (JCOG0912). Jpn J Clin Oncol 2013;43: Huscher CG, Mingoli A, Sgarzini G, Sansonetti A, Di Paola M, Recher A, et al. Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: five-year results of a randomized prospective trial. Ann Surg 2005;241: Park DJ, Han SU, Hyung WJ, Kim MC, Kim W, Ryu SY, et al. Longterm outcomes after laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective study. Surg Endosc 2012;26: Hur H, Lee HY, Lee HJ, Kim MC, Hyung WJ, Park YK, et al. Efficacy of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer: the protocol of the KLASS-02 multicenter randomized controlled clinical trial. BMC Cancer 2015; 15: Omori T, Oyama T, Akamatsu H, Tori M, Ueshima S, Nishida T. Transumbilical single-incision laparoscopic distal gastrectomy for early gastric cancer. Surg Endosc 2011;25: Park DJ, Lee JH, Ahn SH, Eng AK, Kim HH. Single-port laparoscopic distal gastrectomy with D1+beta lymph node dissection for gastric cancers: report of 2 cases. Surg Laparosc Endosc Percutan Tech 2012;22:e Korean Journal of Surgical Oncology

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