( ) 의 의과 연 2014 외과전공의연수강좌 (Unit 2)

2014 0 ( ) 0 0 1 1 의 의과 연 2014 외과전공의연수강좌 (Unit 2)

일시 : 2014 년 6 월 7 일 ( 토 ) 08:30~17:15 장소 : 가톨릭대학교성의교정의과학연구원 1003 호 Time Table 08:30-09:00 유방의양성질환이지연 ( 경북의대 ) 005 09:00-09:30 유방의악성질환공경엽 ( 울산의대 ) 022 09:30-09:45 Coffee Break 09:45-10:15 유방암의수술적치료신혁재 ( 명지병원 ) 044 10:15-10:45 유방암의방사선치료신경환 ( 국립암센터 ) 060 10:45-11:00 Coffee Break 11:00-11:30 유방암의전신치료 ( 항암 / 호르몬 / 표적치료등 ) 노우철 ( 원자력병원 ) 074 11:30-12:00 유방보전술후 oncoplastic surgery 이정언 ( 성균관의대 ) 080 12:00-13:30 Lunch 13:30-14:00 1) 위의해부생리 (15 분 ) 2) 소화성궤양의수술적치료 (15 분 ) 정호영 ( 경북의대 ) 084 094 14:00-14:30 위암의진단과치료 / 위절제술후환자관리이혁준 ( 서울의대 ) 099 14:30-15:00 최소침습위암치료법위에서발생하는점막하종양 김형호 ( 서울의대 ) 118 130 15:00-15:30 위암의항암치료김용일 ( 이화의대 ) 139 15:30-15:45 Coffee Break 15:45-16:15 비만, 당뇨환자의외과적치료이상권 ( 가톨릭의대 ) 154 16:15-16:45 식도질환의외과적치료 : 해부및생리, 위식도역류질환, 식도주위탈장, 식도이완불능증, 손상, 종양 김진조 ( 가톨릭의대 ) 173 16:45-17:15 소장질환의외과적치료 : 해부및생리, 소장종양, 유착성장폐쇄조영걸 ( 양병원 ) 181

Unit 2 01 Benign Breast Disorders Jeeyeon Lee (KNUMC) 2014 외과전공의연수강좌 (Unit ) 5

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Unit 2 02 유방의악성질환 Gyungyub Gong (Department of Pathology, Asan Medical Center College of Medicine University of Ulsan) 22

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Unit 2 0 유방암의수술적치료 신혁재 ( 명지의료재단명지병원외과, 유방갑상선센터 ) 44

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Unit 2 04 유방암의방사선치료 신경환 ( 국립암센터유방암센터, 양성자치료센터 ) 60

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Unit 2 0 유방암의전신치료 : 항암치료, 호르몬치료, 표적치료 노우철 ( 한국원자력의학원외과유방암전공 ) 학습목표 1. 유방암의분자생물학적특성과병기에따른전신치료의치료원칙을이해한다. 2. 항암화학요법의개념과현재의표준요법을습득한다. 3. 호르몬요법의개념과현재의표준요법을습득한다. 4. 표적치료의개념과현재의표준요법을습득한다. I. 유방암의분자생물학적분류와치료원칙 1. 유방암의분자생물학적분류 2013 년 St. Gallen consensus meeting 에서정의된유방암의분자생물학적분류는다음과같다 (Table 1) Table 1. Surrogate definitions of intrinsic subtypes of breast cancer 74

2. 분자생물학적분류에따른전신치료권고안 2013년 St. Gallen consensus meeting 에서권고한유방암의분자생물학적분류에따른전신치료원칙은다음과같다 (Table 2) Table 2. Systemic treatment recommendations 75

2014 외과전공의연수강좌 (Unit 2) II. 보조화학요법 (Adjuvant chemotherapy) (2,3,4) 1. 정의 보조화학요법이란수술등의국소치료로근치적치료를한후항암화학요법제를이용하여미세전이에의 한암세포의재발을억제하기위해시행하는후속치료를의미한다. 2. 보조화학요법가이드라인보조화학요법에의해재발이줄어드는정도 (proportional reduction in recurrence rates) 가일정하다면항암화학요법에의해직접적인이득을보는환자의수 (absolute benefit) 는재발의위험도 (odds of recurrence) 가높은군에서많아지게된다. 이를바탕으로보조항암요법에관한여러가지 guideline이있고, 아직도다양한의견들이있으나비교적보편적인기준은다음과같다. 1) 병리학적, 생물학적예후인자종양의크기, 림프절전이상태, 호르몬수용체발현여부, HER2 유전자, 핵등급정도등. 2) 치료권고안 St.Gallen Consensus 권고안, NCCN 권고안, 한국유방암학회진료권고안등. 3) 유전자분석연구 Oncotype Dx (21 genes), Mammaprint (70 genes) 3. 현재임상에서보편적으로사용하는 regimen (1) 림프절음성인경우 1) CMF 6 cycle, 28일주기 2) AC 4 cycle, 21일주기 (CMF 6 cycle 과동등하나 HER2+ 종양에서더욱효과적으로보고됨 ) 3) FAC or FEC 6 cycle, 21일주기 (better than CMF) (2) 림프절양성인경우 1) FAC or FEC 6 cycle, 21일주기 2) AC 4 cycle -> Taxane (Paclitaxel or Docetaxel) 4 cycle, 21일주기 (better than AC or FAC) 76

3) TAC 6 cycle, 21 일주기 (better than FAC) III. 보조호르몬요법 (Adjuvant hormone therapy) 1. 정의 보조호르몬요법이란에스트로겐이유방암에미치는영향을차단하여유방암의재발이나진행을막는치료로호르몬수용체가양성인 (ER+ and /or PR+) 모든유방암에서적용된다. 2. 보조요법으로사용할수있는호르몬치료의종류는다음과같다. 1) 에스트로겐 (E2) 과에스트로겐수용체의결합을방해하는약제 4) Tamoxifen (SERM) 5) Fulvestrant (ER inhibiyor) 2) 에스트로겐의생성을차단하는약제 - 폐경전 : 난소절제술, LHRH agonist (Gosereline) - 폐경후 : Aromatase Inhibitors (Letrozole, Anastrozole, Exemestane) 3) 작용기전이분명치않은경우 - Progesteron 3. 현재까지보조호르몬요법에대한임상연구의결과를요약하면다음과같다. 1) 호르몬수용체가양성인유방암환자에서 5년간의타목시펜의치료는유방암의재발을의미있게줄여준다. 이효과는환자의나이나, 림프절전이여부나항암치료의여부에관계없이나타난다.; Tamoxifen 5 years used to be a gold standard for adjuvant hormonal therapy. 2) 폐경후여성에서 aromatase inhibitor의사용은 tamoxifen 요법에비하여유방암의재발을의미있게줄여준다.; AIs should be considered as an adjuvant therapy for postmenopausal women. 3) 폐경전여성에서타목시펜에난소기능억제제 (LHRH agonist) 를추가하는것이타목시펜단독에비하여더욱효과적인지는분명치않다. 특정군에서더욱효과적일가능성은있으며이에대한임상연구는현재진행중에있다.; LHRH agonists need to be considered as an adjuvant therapy for premenopausal women. IV. 표적치료 분자생믈학적연구를통한유방암의새로운지식은표적치료라물리는새로운치료법의개발로이어졌다. 이중 HER2 단백을표적으로하는 Trastuzumab는 HER2 양성인진행성유방암환자의생존율을향상시켰을뿐아니라조기유방암의재발을현저하게감소시키는좋은결과를보였다 (Figure 1). 77

2014 외과전공의연수강좌 (Unit 2) OS benefit Median follow-up, years HERA CTx H 1 year 4 B-31 / N9831 AC PH 3 BCIRG 006 AC TH 3 TCarboH 3 FinHer VH / TH CEF n=231 5 0 Favours 1 Favours no 2 Herceptin HR Herceptin Gianni et al 2009; Joensuu et al 2009; Slamon et al 2006; Perez et al 2007; Smith et al 2007 Figure 1. 1 year Trastuzumab treatment consistently reduces the risk of death by one-third 그외혈관내피성정인자 (VEGF) 를표적으로하는 bevacizumab 가개발되었으며, 그이후에는 PI3K/Akt/ mtor신호전달경로, tyrosine kinase, PARP, heat shock protein (HSP90) 등을표적으로하는다양한표적치료제들이개발되어임상시험중에있다. V. 선행보조항암화학요법 (Neoadjuvant chemotherapy) 1. 정의 선행보조화학요법이란수술을하기전에종양의크기를줄이거나없앨목적으로화학요법을시행하는것을의미한다. 2. 임상연구의결과현재까지선행화학요법의관한임상연구의결과는다음과같다. 1) 수술이불가능한국소진행성, 혹은염증성유방암을수술이가능하게줄여준다. 2) 수술이가능한유방암에서유방보존술의가능성을높여준다. 3) 수술이가능한유방암에서선행화학요법은일반적보조항암요법과예후면에서동등한효과를보인다. 4) 선행화학요법에의해완전관해 (pcr) 가온군은그렇지않은군에비하여좋은예후를보인다. 78

VI. 전이성유방암의화학요법 1. 목표 전이성유방암의치료목표는첫째, 증상의완화및삶의질개선이며둘째는약제의부작용을최소화한 상태에서환자의생존을증가시키는데있다. 2. 치료원칙 - ER+ 이며즉각적생명위협이없는경우 ( 골전이, 림프절전이등 ) 인경우는호르몬치료를우선적으로한다. - ER- 이거나즉각적생명위협이있는경우 ( 간전이, 광범위한폐전이등 ) 은화학요법을우선적으로한다. (Anthracycline 과 Taxane의병용요법을가장많이사용 ) - HER2+ 인경우는 Trastuzumab을포함한치료를원칙으로한다. 참고문헌 1. Chaptor 10. Oncology In: Brunicard FC, Schwartz s Priniciples of Srgery 9th ed 2010 2. Chaptor 34 Disease of the breast In: Sabiston DC editors. Testbook of Surgery: The Biologic Basis of Modern Surgical Practice 18th ed. Philadelphia: WB Saunders; 2007 3. 각론제4장유방대한외과학회 In: 외과학군자출판사 2010 4. EBCTCG Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials Lancet Oncol 2005;365:1687-1717 5. Chaptor 74 Breast Disease In: Mutholland MW editors. Green field s Surgery: Scientific Principles and Practice 5th edi 2010 79

Unit 2 0 유방보존술과 Oncoplastic Breast Surgery 이정언 ( 성균관대학교외과학교실 ) 1894년 Dr. Halsted가근치적유방절제술 (RM: radical mastectomy) 을시행한이후, 대흉근과소흉근을보존하는방법으로수정된변형근치적유방절제술 (MRM: modified radical mastectomy) 이나오기까지 50년가까운세월이걸렸다. 그리고, 20세기중반이후에들어서는과거보다유방암의크기가상대적으로작을때유방암을찾아서수술하기시작하면서유방을수술하되보존할수있지않을까하는노력을기울이게되었다. 유럽과미국에서 1970년경에시작된밀라노임상시험과 NSABP B-06 임상시험결과, 유방보존술은유방절제술과생존율에서차이가나지않는다는사실이확인되었다. 유방보존술의경우에는아무래도남은유선조직에서암이국소적으로재발할가능성이있기때문에, 육안으로보이거나만져지는종양은수술로제거하고그주위에남아있을수도있는미세한병소는방사선으로치료하여국소적으로재발할가능성을줄이는것이원칙이다. 유방암의진단과치료과정에서유방이가진여성성과관련된문제때문에유방수술후에불가피하게발생하는신체적인변화는삶의질에까지영향을미치는경우가많다. 유방보존술에대한경험이쌓이는것과함께, 유방보존술을받은뒤에도상당수의사람들이미용적으로만족하지못한다는연구보고들이나오면서최근들어서는수술후미용적인결과에대한관심도훨씬높아졌다. 이런움직임에발맞추어유방보존술을시행받는환자들에게그저 유방을남겨놓는것 이아닌 유방을예쁘게남기는것 을목적으로성형적유방암수술 (oncoplastic breast surgery) 을시행하는경우가점점더많아지고있다. 성형적유방암수술 (oncoplastic breast surgery) 은유방의환부를부분적으로절제하는기존의유방보존술에성형외과적술기를결합하여수술후에생기는유방모양의변형을최소화하고자하는수술방법이다. 성형적유방암수술은크게두가지방법이있다. 첫번째는유방종양의절제술후에남아있는유방조직을이동하여수술로제거된결손부위를채워주도록하여수술로인한모양의변형을최소화하는방법이고, 두번째는유방외의다른신체부위에서결손부위를대신할만큼의조직을떼어옮김으로써유방을재건하는방법이다. 후자의경우는대부분유방암의침윤범위가넓거나유두의침범등으로유방의부분절제범위가넓거나유방을모두절제하는것이불가피할때다양한방법으로유방의모양을재건하는방법이며수술시간이길고수술후회복기간도긴경향이있다. 한편, 이보다적은양의유방조직을절제하는전자의경우에는종양을절제한뒤남아있는주위의유방조직을이용한리모델링 (remodeling) 을통하여절제부위의결손을채 80

워주므로수술후유방모양변형을최소화하고자연스러운유방의모양을유지할수있도록함으로써수술시간이그리길지않고수술절개상처도눈에쉽게띄지않게회복할가능성을높여준다. 이렇게하기위하여환자에특성에맞게여러가지절개법을이용할수있으며, ㄱ 모양혹은부메랑모양의절개선, 기존의박쥐날개모양절개선을응용한 Hemi-batwing 절개선, 라운드블록술식등의절개방법이있다. 점차적으로 oncoplastic surgery는유방보존술이후미용적인만족도를높이기위해시행하는것으로, 어떤특정한방법이아니라종양의크기와위치, 유방과의비율, 유두에서부터의거리등여러경우에알맞게여러가지로응용되어시행하는방법으로발전할것이다. 우리나라의유방외과의사들은 oncoplastic surgery technique을시행함에있어서백인들과다른동양인의 keloid와관련된특징을이해하고, 유방의흉터와모양을함께고려하며적절하게이용할수있어야하겠다. 그림 1. 성형적유방암수술은종양을남김없이안전하게완전절제한후남아있는주위조직을움직여수술후결손부위를최소화하고, 유두의위치가수술전과같이유지되도록하는등미용적효과를높이고자한다. ( 그림출처 : Anderson et al., Lancet Oncol 2005;6:145-57) 그림 2. 왼쪽사진은유방보존수술후유방조직의결손부위방향으로유두-유륜복합체가치우쳐짐으로인해양측유방의대칭성이훼손된경우로, 오른쪽사진과같이성형적유방암수술을통해유두위치를유지함으로써발생을줄일수있다. 81

2014 외과전공의연수강좌 (Unit 2) 그림 3. 부메랑모양절개선의수술후임상결과. 종양이크거나다발성종양등으로인해절제범위가넓을 때적용하는부메랑모양의절개선으로종양의완전한절제와미용적인리모델링을용이하게해주는유용한절개선이다. 그림 4-1. 라운드블록술식의수술방법도식과수술사진으로이술식은유륜주위로두개의원모양의절 개하여유방암이남아있지않도록충분히절제하고, 남아있는유방조직을모아서결손부위를채운뒤에이두원을봉합하기때문에수술상처가유륜주위에만남는다. 82

그림 4-2. 라운드블록수술후경과. 유방의모양변형을최소화하면서수술상처가유륜가장자리에국한 되어쉽게눈에띄지않는다. 83

Unit 2 0 1 위의해부와생리 정호영 ( 경북대학교의학전문대학원외과학교실위장관외과 ) 학습목표 1. 위의해부학적구분에대하여이해한다. 2. 음식물섭취에대한위의생리학적반응과그기능을이해한다. I. 위의해부 A. Gross Anatomy 1. Divisions - cardia : most proximal region, attach to the esophagus - fudus : superior-most part of the stomach, floppy, distensible : bounded by the diaphragm and the spleen - body(corpus) : the largest portion, contains most of the parietal cells - angularis incisura : the lesser curvature abruptly angles to the right : a point that the body ends and the antrum begins 2. Blood supply - most of the blood supply to the stomach is from the celiac artery - 4 main arteries : left & right gastric arteries along the lesser curvature left & right gastroepiploic arteris along the greater curvature - minor arteries : inferior phrenic arteries & short gastric arteries - left gastric artery : the largest artery : 15%-20% aberrant left hepatic artery originate -> proximal ligation result in acute left-sided hepatic ischemia 84

- right gastric artery : arises from the hepatic artery - left gastroepiploic art. : originate from the splenic artery - right gastroepiploic art. : originate from the gastroduodenal artery - In general, the veins of the stomach parallel the arteries 3. Lympatic drainage - generally, the lymphatic drainage parallels the vasculature - essentially drains into 4 zones of the lymph nodes : superior gastric group : suprapyloric group : pancreaticolienal group : inferior gastric subpyloric group - all four zones of lymphatic nodes -> celiac group -> thoracic duct 4. Innervation (Fig. 1) - extrinsic innervation of the stomach : parasympathetic through the vagus : sympathetic through the celiac plexus B. Gastric Morphology (Fig. 2) - serosa - muscularis propria : 3 layers of smooth muscles - submucosa : collagen-rich layer of connective tissue strongest layer of the gastric wall contains the rich blood vessels, lymphatics and Meissner's plexus - mucosa : surface epithelium, lamina propria, muscularis mucosae C. Gastric Glandular Organization (Fig. 3) Table 1 Gastric cell types, Location, and Function 85

2014 외과전공의연수강좌 (Unit 2) II. 위의생리 A. General Consideration - principal function : to prepare ingested food for digestion and absorption - receptive relaxation : process whereby the proximal portion of the stomach relax in anticipation of food intake : liquid to pass easily from the stomach along the lesser curvature : solid food settles along the greater curvature of the fundus : antrum - pump solid food components into and through the pylorus B. Regulation of Gastric Funtion - gastric funtion is under both neural and hormonal control - hormonal mediators of gastric function : usually peptides or amines C. Gastric Peptides 1 Gastrin - produced by antral G cells - release stimulation : food components contained within a meal, esp. protein digestion products - release inhibiton : luminal acid, Somatostatin - gastrin is a major hormonal regulator of the gastric phase of acid secretion : histamine is a principle mediator of this action - prevent gastric injury from luminal irritants - trophic effects on the parietal cells and ECL cells - Causes of Hypergastrinemia (Table 2) 2 Somatostatin - produced by D cells 86

- release stimulated by antral acidification - release inhibited by acetylcholine from vagal fibers - action : acid secretion inhibition : directly - inhibit parietal cell acid secretion : indirectly - down-regulation of histamine release from ECL cells - inhibition of gastrin release 3 Effects of Helicobacter pylori on somatostatin : infection with H.pylori decrease antral D cells & somatostain levels increase gastrin release increase gastric acid secretion 4 Histamine - a prominent role in parietal cell stimulation (Fig. 4) 5 Ghrelin - appetite-stimulating hormone - stimulate appetite centers in hypothalamus - produced by endocrine cells of the oxyntic mucosa of the stomach D. Gastric acid secretion - stimulated by acetylcholine, gastrin, histamine - inhibited by somatostatin 1 Basal acid secretion - roughly 10% of maximal acid output - 1 to 5 mmol/hour - a combination of cholinergic and histaminergic input : vagotomy : 75% to 90% reduction : H2-Receptor blockade : 90% reduction 2 Stimulated acid secretion - cephalic phase 87

2014 외과전공의연수강좌 (Unit 2) : originates with the sight, smell, thought, or taste of food stimulate neural centers in the cortex and hypothalamus : CNS center vagus nerve acetylcholine release : 20% to 30% of total volume of gastric acid - gastric phase : begin with food enters the gstric lumen : food - stimulate gastrin release and gastric distention : 60% to 70% of meal-stimulated acid output - intestinal phase : initiated by entry of chyme into the small bowel : 10% of the acid secretory response 3 Cellular basis of Acid secretion (Fig. 5) - Gastrin receptors - Muscarinic receptors - Histamine receptors - Somatostatin receptors - Secondary messengers 4 Medical control of acid secretion (Fig. 6) 5 Surgical control of acid secretion (Fig. 7) 6 Postprandial gstric motility - Fundus : receptive relaxation - relaxated as foods enter the esophagus : adaptive relaxation - further relaxated as foods actually enter the fundus : liquid - pool in the fundic pouch : solid - remain in the mainstream of flow toward the pylorus - Corpus & Antrum : upper corpus, greater curvature - primary electrical pacemaker : propulsion of the luminal contents toward the pylorus - Pylorus : acts as a sieve and barricade 7 MMC (Myoelectric Migrating Complex) 88

- net effect of MMC : frequent clearance of gastric contents - each cycle of the MMC lasts 90 to 120 minutes - phase 3 : forceful gastric contraction : clearance of large indigestible food within the stomach 8 Gastric Barrier Function 참고문헌 1. Townsend CM, Beauchamp RD, Evers BM, Mattox KL, editors. Sabiston textbook of surgery: The biological basis of modern surgical practice. 18th ed. Philadelphia: Saunders; 2008. p.1223-1236 2. FC Brunicardi, DK Anderson, TR Billiar, DL Dunn, JG Hunter, JB Matthews, et al. Schwartz's Principles of Surgery 9th ed. McGraw-Hill; 2010. p. 890-904 3. Soybel DI. Anatomy and physiology of the stomach. Surg Clin North Am 2005 Oct;85 (5):875-94 89

2014 외과전공의연수강좌 (Unit 2) Fig.1 Fig.2 90

Fig.3 Fig.4 91

2014 외과전공의연수강좌 (Unit 2) Fig.5 Fig.6 92

Fig.7 93

Unit 2 0 2 소화성궤양의수술적치료 정호영 ( 경북대학교의학전문대학원외과학교실위장관외과 ) 학습목표 1. 위궤양의외과적치료의적응증에대해이해한다. 2. 위궤양의외과적치료의목적과방법을이해한다. I. Indications for Surgery on Peptic Ulcer Disease (PUD) - Surgery remains important in managing patients with PUD, despite advances in medical therapy to inhibit acid secretion and to eradicate H. pylori. - Intractability: Elective surgery for intractability is becoming more rare as medical therapy becomes more effective. (The recognition of H. pylori and its eradication / H2 blocker, proton-pump inhibitor (PPI) / The recognition of the need for NSAID control) - Hemorrhage, perforation, and obstruction: The incidence of ulcers with complications requiring surgery does not appear to have diminished. - The goal of ulcer surgery is to eliminate ulcer and/or its complication and to prevent gastric acid secretion. A. Four Classic Indications of Surgery 1. Intractability 2. Hemorrhage 3. Perforation 4. Obstruction II. Surgical Prevention of Gastric Acid Secretion - Vagotomy decreases peak acid output by about 50%, whereas vagotomy plus antrectomy, which removes the gastrin-secreting portion of the stomach, decreases peak acid output by about 85% (Fig. 1) 94

Fig. 1 The physiology of gastric acid secretion (Targets of surgery) A. Truncal Vagotomy (+ Drainage Procedure) (Fig. 2) - Division of the left and right vagus nerves above the hepatic and celiac branches just above the GE junction - Drainage procedure to encourage gastric emptying and to prevent stasis : Pyloroplasty (Heineke-Mikulicz, Finney, Jaboulay...), gastrojejunostomy Fig. 2. Truncal vagotomy and Heineke-Mikulicz pyloroplasty B. Highly Selective Vagotomy (Parietal Cell Vagotomy) (Fig. 3) - Selective division of the vagus nerves supplying the acid-producing portion of the stomach within the corpus and fundus. - Preservation of the vagal innervation of the gastric antrum : No need for routine drainage procedures - The nerves of Latarjet are identified anteriorly and posteriorly, and the crow's feet innervating the fundus and body of the stomach are divided. (About 7 cm proximal to the pylorus ~ at least 5 cm proximal to the gastroesophageal junction) - The criminal nerve of Grassi : A very proximal branch of the posterior trunk of the vagus : May result in ulcer recurrence if left intact. - Reportedly, higher rate of recurrence, compared to that after truncal vagotomy. 95

2014 외과전공의연수강좌 (Unit 2) Fig. 3. Highly selective vagotomy C. Truncal Vagotomy & Antrectomy (Fig. 4) - Antrectomy: Removal of the gastrin-secreting portion of the stomach - The loweest recurrence rate (about 0% to 2%) - Postgastrectomy syndrome should be considered. - Requires reconstruction of GI continuity (Billroth I gastroduodenostomy, Billroth II gastrojejunostomy) - Although vagotomy and antrectomy are clearly effective at managing ulcerations, operations of lesser magnitude are performed more frequently in the H. pylori era. Fig. 4. Truncal Vagotomy & Antrectomy D. Others (subtotal gastrectomy, laparoscopic surgery) 96

III. Surgical Treatment Recommendation for PUD - Goal: : Salvage of patients from life-threatening complications (bleeding (e.g. oversewing, resection), perforation (e.g. patch closure, resection), obstruction (e.g. bypass, resection)) : Prevention of gastric acid secretion - Efforts must be made to rule out the potential for malignancy in the case of gastric ulcerations. - Recommended operations for patients suffering from complications related to PUD (Table 1) Table 1. Surgical recommendation for complications related to peptic ulcer disease Duodenal ulcer Intractable Bleeding Perforation Obstruction Gastric ulcer (Fig. 5) Intractable Type I Type II/III Type IV Parietal cell vagotomy ± antrectomy Oversewing of bleeding vessel + treatment of H. pylori Patch closure + treatment of H. pylori (Rule out malignancy) Gastrojejunostomy + treatment of H. pylori Distal gastrectomy Distal gastrectomy with truncal vagotomy (depends on ulcer size, distance from GE junction, and degree of inflammation) Resection without gastrectomy Gastrectomy (total or variants of distal gastrectomy (Fig.6)) 97

2014 외과전공의연수강좌 (Unit 2) Fig. 5. Types of gastric ulcer. Like duodenal ulcer, type II and type III ulcers are highly associated with excess acid secretion. Fig. 6. Operations for type IV gastric ulcer 참고문헌 1. Townsend CM, Beauchamp RD, Evers BM, Mattox KL, editors. Sabiston textbook of surgery: The biological basis of modern surgical practice. 18th ed. Philadelphia: Saunders; 2012. p.1191-1201 2. Townsend CM, Beauchamp RD, Evers BM, Mattox KL, editors. Sabiston textbook of surgery: The biological basis of modern surgical practice. 18th ed. Philadelphia: Saunders; 2008. p.1230-1251 3. 대한위암학회. 위암과위장관질환. 1st ed.: 일조각 : 2011. p.206-216 98

Unit 2 0 위암의진단과치료 이혁준 ( 서울의대외과학교실및암연구소 ) 암의 의 (Tumor) 가 가, (Benign) - 가. (Malignant) - 가. 암 암 한국의암발생률 (crude incidence, 2011) 2011 년국가암등록통계 99

2014 외과전공의연수강좌 (Unit 2) 암의 ( 암 국 ) 70 60 50 40 30 20 10 0 Proportion of EGC 57.6% 47.4% 32.8% 28.6% 1995 1999 2004 2009 EGC KGCA nationwide survey (for surgical gastric cancer patients) Gastric adenocarcinoma classification system (WHO) Papillary adenocarcinoma Tubular adenocarcinoma Mucinous adenocarcinoma Poorly cohesive carcinoma including Signet-ring cell carcinoma Mixed carcinoma Adenosquamous carcinoma Squamous cell carcinoma Hepatoid adenocarcinoma Carcinoma with lymphoid stroma Choriocarcinoma Carcinosarcoma Parietal cell carcinoma Malignant rhabdoid tumor Mucoepidermoid carcinoma Paneth cell carcinoma Undifferentiated carcinoma Mixed adeno-neuroendocrine carcinoma Endodermal sinus tumor Embryonal carcinoma Pure gastric yolk sac tumor Oncocytic adenocarcinoma / 암 : 양성위궤양조기위암진행위암 100

암 100 80 60 40 20 0 1 2 3 4,, 통 1999 암? 암 Anemic conjunctiva : 암 암 Icteric sclera : 암국 Virchow s node : Abdominal mass : 암 가, Ascites : Palpated Liver : Sister Marry-Joseph sign: 가 nodule Rectal shelf : 암 암의 CBC, Stool blood, LFT Tumor maker (CEA, CA19-9, AFP) ( ) (CT) 101

2014 외과전공의연수강좌 (Unit 2) 암의 ( ), ( ),, CT,, MRI 가 PET 가 EUS (T) (N) Biopsy) Adenocarcinoma, poorly differentiated 한 : CT, 102

(UGIS) ; 가 가 한 MRI ; 의 한 PET ; 의 103

2014 외과전공의연수강좌 (Unit 2) Mucosa (high) Muscularis mucosae (low) Submucosa (high) Muscularis propria (low) Serosa (high) Macroscopic Types 암의 Japanese classification of gastric carcinoma: 3 rd English edition 암 (EGC) 의 JGCA 3 rd English edition 104

암 (AGC) 의 -Borrmann type- JGCA 3 rd English edition T staging T1: Tumor invades mucosa (T1a) or submucosa (T1b) T2: Tumor invades proper muscle T3: Tumor penetrates subserosal connective tissue T4: Tumor invades serosa (T4a) or adjacent structure (T4b) T1 T2 T3 T4a T4b mucosa mm submucosa pm subserosa serosa 105

2014 외과전공의연수강좌 (Unit 2) N staging N0: No regional lymph node metastasis N1: Metastasis in 1 2 regional lymph nodes N2: Metastasis in 3 6 regional lymph nodes N3: Metastasis in 7 or more regional lymph nodes N3a: Metastasis in 7 15 regional lymph nodes N3b: Metastasis in 16 or more regional lymph nodes TNM system (AJCC/UICC) for gastric cancer 6 th AJCC staging system No. of involved LN Depth Mucosa, T1 submucosa T2a Muscularis propria M0 T2b Subserosa M0 N0 N1 N2 N3 0 1~6 7~15 16 ~ IA IB II IV IB II IIIA IV T3 Serosa II IIIA IIIB IV 7 th AJCC staging system T1 T2 No. of involved LN Depth Mucosa, submucosa Muscularis propria M0 N0 N1 N2 N3a N3b 0 1~2 3~6 7~15 16~ IA IB IIA IIB IIB IB IIA IIB IIIA IIIA M0 T3 Subserosa IIA IIB IIIA IIIB IIIB T4a Serosa IIB IIIA IIIB IIIC IIIC T4 Adjacent structure IIIA IV IV IV T4b Adjacent structure IIIB IIIB IIIC IIIC IIIC 암의 - JGCA Guideline 3 rd Edition 106

Extended Indication for EMR/ESD According to the American Society of Clinical Oncology Histology Depth Mucosal cancer Submucosal cancer Ulcer(-) Ulcer(+) SM1 SM2 <20mm >20mm <30mm >30mm <30mm Any size Differentiated Undifferentiated Conventional criteria for ESD Surgery Expanded criteria for ESD Consider surgery Soetikno R et al. J Clin Oncol 2005;23:4490 4498. Indication of ESD Absolute Criteria for Endoscopic Resection - Mucosal cancer - Size 2cm - Differentiated histology - No ulcerative finding Risk of incomplete resection and LN metastasis UL, ulcerative findings SM, submucosal invasion Gotoda T. Gastric cancer 2007;10:1-11 암 의 (1) (radicality) 암 (2) (safety) (3) (function preservation) (1), (2) 가 가 (QOL) 107

2014 외과전공의연수강좌 (Unit 2) 암 의 (1) R-category R0 resection: no residual tumor, complete resection R1 resection: microscopic residual tumor (resection margin +) R2 resection: macroscopic residual tumor (2) Extent of resection (local control of T) Distal (subtotal) gastrectomy Total gastrectomy Proximal gastrectomy Pylorus preserving (subtotal) gastrectomy Gastric cancer surgery Extent of resection Distal gastrectomy (DG) Total gastrectomy (TG) Pylorus-preserving gastrectomy (PPG) Proximal gastrectomy (PG) 암 의 (1) R-category (2) Extent of resection (local control of T) (3) Combined resection for cancer control : with splenectomy, T-colon resection for combined disease : with cholecystectomy (for GB stone) (4) Extent of regional lymph node dissection (local control of N) D0 : no regional LN dissection D1 : perigastric LN dissection D1+ : beyond perigastric LN dissection (between D1 and D2) D2 : whole regional LN dissection 108

암 의 (1) R-category (2) Extent of resection (local control of T) (3) Combined resection for cancer control : with splenectomy, T-colon resection for combined disease : with cholecystectomy (for GB stone) (4) Extent of regional lymph node dissection (local control of N) D0 : no regional LN dissection D1 : perigastric LN dissection D1+ : beyond perigastric LN dissection (between D1 and D2) D2 : whole regional LN dissection STATION of Regional lymph nodes JGCA 3 rd Ed. Gastric Cancer 2011;14:101 암 의 : 암 의 (1) R-category (2) Extent of resection (local control of T) (3) Combined resection (4) Extent of regional lymph node dissection (local control of N) (5) Approach method open, minimally invasive approach (laparoscopy, robot) (6) Anastomosis according to extent of resection (7) Details of anastomosis 109

2014 외과전공의연수강좌 (Unit 2) 암 의 : 암 의 (1) R-category (2) Extent of resection (local control of T) (3) Combined resection (4) Extent of regional lymph node dissection (local control of N) (5) Approach method open, minimally invasive approach (MIS; laparoscopy, robot) (6) Anastomosis according to extent of resection (7) Details of anastomosis Gastric cancer surgery Approach open Laparoscopy/robot 의 : 통 (0.5-1.5cm) 통 (cf., ) : 암, 암, 암, 암, 암, 암, 암, 암, 암등 ( 암 ) : - 의 - 통 - ( ) : - 암 암 가 ( ) - - 110

가 (master-slave surgery) 가 가 암의 Distal Gastrectomy 0 : Lymphadenectomy less than D1 D1 1, 3, 4sb, 5, 6, 7 D1+ D1, 8a, 9 D2 D1+, 11p, 12a 암의 Distal Gastrectomy Billroth I : Gastro-duodenostomy Billroth II : Gastro-jejunostomy 111

2014 외과전공의연수강좌 (Unit 2) 암의 Distal Gastrectomy Roux-en Y Gastro-jejunostomy 암의 Total Gastrectomy 0 : Lymphadenectomy less than D1 D1 1 ~ 7 D1+ D1, 8a, 9, 11p D2 D1+, 10, 11d,12a 암의 Total Gastrectomy Roux-en Y Esophago-jejunostomy 112

암의 Proximal Gastrectomy 0 : Lymphadenectomy less than D1 D1 1,2,3,4sa,sb,7 D1+ D1, 8a, 9, 11p 암의 Proximal Gastrectomy Esophago-gastrostomy Double tract reconstruction World J Surg Oncol. 2014; 12: 20. 암의 Pylorus Preserving Gastrectomy 0 : Lymphadenectomy less than D1 D1 1,3,4sb,4d,6,7 D1+ D1, 8a, 9 113

2014 외과전공의연수강좌 (Unit 2) 암의 PPG - - - 가 Function preserving surgery Gastro-gastrostomy Radicality of Gastrectomy R0 = a microscopically margin negative Curative resection R1 = a microscopically margin positive R2 = gross residual disease Non -Curative resection Lymph node station 1 Rt paracardial LN including 1 st branch of LGA 2 Lt paracardial LN including esophagocardial branch of subphrenic artery 3a LC LN along LGA 3b LC LN along 2 branch and distal part of RGA 4sa Lt GC along short gastric artery 4sb Lt GC along lt gastroepiploic artery 4d Rt GC 2 nd branch and distal part of Rt gastroepiploic artery 5 Suprapyloric LN 1 st branch of RGA 6 Infrapyloric LN 1 st branch of Rt gastroepiploic artery 7 LN along the trunk of LGA between its root and the origin of its ascending branch 8a Anterosuperior LN along the CHA 8p Posterior Lns along the CHA 9 Celiac artery LN 114

Lymph node station 10 Splenic hilar LN and proximal to 1 st lt gastroepiploic artery 11p Proximal splenic artery 11d Distal splenic artery 12a Hepatoduodenal ligament LNs along the proper hepatic artery, in the caudal half between hepatic ducts and the upper border of the pancreas 12b Hepatoduodenal ligament LNs along the bile duct, in the caudal half between hepatic ducts and the upper border of the pancreas 12p Hepatoduodenal ligament LNs along the portal vein in the caudal half between hepatic ducts and the upper border of the pancreas 13 LNs on the posterior surface of the pancreatic head 14v LNs along the superior mesenteric vein 15 LNs along the middle colic vessels 16a1 Paraaortic LNs in the diaphragmatic aortic hiatus 16a2 Paraaortic LNs between the upper margin of the origin of the celiac artery and the lower border of the left renal vein 16b1 Paraaortic LNs between the lower border of the left renal vein and the upper border of the origin of the inferior mesenteric artery Survival according TNM stage 6 th ed. AGCC Staging system 7 th ed. AGCC Staging system 5 year P < 0.001 Ia (3398, 34.0%) : 95.1% Ib (1669, 16.7%) : 85.5% II (1914, 19.1%) : 70.2% IIIa (1474, 14.7%) : 49.0% IIIb ( 730, 7.3%) : 32.4% IV ( 813, 8.1%) : 20.8% 5 year P < 0.001 Ia (3401, 34.0%) : 95.1% Ib ( 885, 8.9%) : 88.4% IIa (1044, 10.4%) : 84.0% IIb (1112, 11.1%) : 71.7% IIIa (1001, 10.0%) : 58.4% IIIb (1256, 12.6%) : 41.3% IIIc (1299, 13.0%) : 26.1% 생 의 의 : 암 가 : 암 가 가 115

2014 외과전공의연수강좌 (Unit 2) Adjuvant Chemotherapy (CLASSIC trial) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 3 years disease free survival 85% 71% 66% 61% 51% 33% II IIIa IIIb Stage II / III (6 th ) gastric cancer CTx + Surgery Surgery alone Bang YJ et al. CALSSIC trial investigators. Lancet 2012;379:315-21 Adjuvent chemotherapy- XELOX XELOX 8 cycles ( Capecitabine + Oxaliplatin ) 1 Cycle (3weeks) 1week 2week 3week Oral Capecitabine (1000 mg/m² twice daily on days 1 14 Rest IV Oxaliplatin (130 mg/m² on day 1 of each cycle) Bang YJ et al. CLASSIC trial investigators. Lancet 2012;379:315-21 Adjuvent chemotherpy (ACTS-GC trial) Stage II / III (6 th ) gastric cancer S-1 Therapy Surgery only Sasako M, et al, and ACTS-GC Group. J Clin Oncol 2011;29:4387-4393 116

Adjuvent chemotherapy S-1 S-1 chemotherapy for 8 cycles 1 Cycle (4weeks S-1 + 2 weeks rest) 1week 2week 3week 4week 5week 6week Rest S-1 twice daily on day 1-28 (dosage according to BSA) BSA <1.25 1.25-<1.5 > 1.5 Per dose 40mg 50mg 60mg Sasako M, et al, and ACTS-GC Group. J Clin Oncol 2011;29:4387-4393 TNM system (AJCC/UICC) for gastric cancer 6 th AJCC staging system No. of involved LN Depth Mucosa, T1 submucosa T2a Muscularis propria M0 T2b Subserosa M0 N0 N1 N2 N3 0 1~6 7~15 16 ~ IA IB II IV IB II IIIA IV T3 Serosa II IIIA IIIB IV 7 th AJCC staging system T1 T2 No. of involved LN Depth Mucosa, submucosa Muscularis propria M0 N0 N1 N2 N3a N3b 0 1~2 3~6 7~15 16~ IA IB IIA IIB IIB IB IIA IIB IIIA IIIA M0 T3 Subserosa IIA IIB IIIA IIIB IIIB T4a Serosa IIB IIIA IIIB IIIC IIIC T4 Adjacent structure IIIA IV IV IV T4b Adjacent structure IIIB IIIB IIIC IIIC IIIC T3(ss)N0M0 : Ib (6 th ) IIa (7 th ) T1N2(3-6)M0 : Ib (6 th ) IIa (7 th ) SUMMARY 암 : 가 암 ( 1, 4 ) but 가 : vs. / 암 : / CT / / UGIS, MRI, PET 암 : EGC vs. AGC 0~5 암 : UICC/AJCC 6 vs. 7 암 1) ESD ( ) : LN 가 암 2) : / / / 3) 암 : stage II (TS-1, XELOX ) but 6 stage 암 : I 90%, II 70~80%, III 30~60% 5년 : Randomized controlled trial (RCT) 가가 117

Unit 2 0 1 Minimally Invasive Surgery for Gastric Cancer Hyung-Ho Kim (Department of Surgery Seoul National University Bundang Hospital Seoul National University of Medicine) Gastric Cancer in worldwide 5th most common malignancy & 3rd cause of cancer death (Worldwide) Current concept of MIS 118

Laparoscopic Gastrectomy Increased Publications mean Oncologic Safety? Contents Surgery in Gastric Cancer MIS for Standard Gastrectomy MIS for Function-Preserving Surgery Conclusion Surgery in Gastric Cancer Radical Gastrectomy LND: D1 vs. D2 119

2014 외과전공의연수강좌 (Unit 2) Principle of gastric cancer surgery Curative gastrectomy Wide excision of primary tumor En bloc removal of the draining lymphatic network Resection margine EGC : over 2cm or Frozen (-) AGC : over 3-5cm or Frozen(-) Gastric resection Distal gastrectomy : lower two third Total gastrectomy : upper third 위암진료표준권고안, 대한의학회위암과위장관질환, 대한위암학회 Lymph Node Dissection D1~D2 LND: D1 vs. D2 meta-analysis Memon et al.: Meta-analysis based on 6 RCTs D1 is favorable. Parameters (D1 vs. D2) No. of Studies OR 95% CI P value Total complications 6/ 1876 0.42 0.27 0.66 0.0002 Anastomotic leakage 6/ 1876 0.40 0.25 0.63 0.0001 Mortality 6/ 1876 0.59 0.40 0.85 0.0054 5-year survival 5/ 1714 1.10 0.78 1.20 0.7662 Jiang et al.: Meta-analysis based on 6 RCTs D2 with spleen preserving is favorable. Parameters (D1 vs. D2) Study/Case (N) OR 95% CI P value Overall Survival 3/ 1332 0.92 0.77 1.10 0.36 Recurrence Free Survival 3/ 1332 0.79 0.69 0.91 0.0009 Overall Survival (D2 spleen preserving) 3/ 862 0.65 0.52 0.80 <0.0001 Memon et al. Ann Surg, 2011 Jiang et al. J Surg Oncol, 2013 MIS for Standard Gastrectomy: Distal & Total Gastrectomy MIS for EGC: LDG & LTG MIS for AGC Latest Evidence: JCO 2014 120

Laparoscopic Surgery Laparoscopic Surgery (distal gastrectomy): Guidelines Korean Japanese NCCN EORTC Recommendation Weak recommendation Investigational treatment Not mentioned Not mentioned Evidence Low quality evidence Awaiting for JCOG 0912 KLASS trials Requires further larger RCTs Not mentioned Treatment Indication of Gastric Cancer RCTs about LADG for EGC 121

2014 외과전공의연수강좌 (Unit 2) Laparoscopic Total Gastrectomy for EGC Laparoscopic Total Gastrectomy vs. Open Total Gastrectomy Wang et al.: meta-analysis based on 17 studies Parameters Study/Case (N) WMD 95% CI P value Operative time 17/ 2313 47.00 31.67 62.33 <0.001 Blood loss 14/ 1459-179.60-251.80-107.39 <0.001 Harvested lymph nodes 16/ 2253 2.33-0.04 4.71 0.054 Proximal resection margin 5/ 1315 0.06-0.26 0.39 0.706 First flatus day 14/ 1767-0.80-1.11-0.50 <0.001 Postoperative hospital stay 15/ 2077-3.37-4.58 - -2.16 <0.001 Parameters Study/Case (N) RR 95% CI P value Complications 16/ 2274 0.78 0.66 0.94 0.007 5 Year Overall Survival 4/ 770 0.81 0.51 1.28 0.360 5 Year Disease Free Survival 3/ 536 0.62 0.30 1.27 0.191 LTG is favorable. Wang et al. PloS One, 2014 Laparoscopic Surgery Laparoscopic Total Gastrectomy: Ongoing Trials Study Nation Phase Design Patients Enroll KLASS01 (2006~) III LADG vs ODG Stage I Cancer 1400 Primary endpoint Overall survival JCOG0912 (2010~) III LADG vs ODG Stage I Cancer 920 Overall survival KLASS 03 (2012~) II LATG vs. OTG Stage I Cancer 168 Morbidity & Mortality KLASS 04 (2014~) III LATG vs. LAPG Stage I Cancer 194 Iron Deficiency Anemia NCT02085031 (2014~) II Intracorporeal vs. Extracorporeal Roux-en-Y after LTG Stomach Cancer 136 Anastomotic complication Systematic Review & Meta-Analysis Laparoscopic gastrectomy for AGC Author Country Type of Study Surgery type No. of patients (1819) No. of retrieved LN OG (960) LG (859) OG LG Scaitzzi Italy Matched Cohort DG 30 30 37 31 Shuang China Matched Cohort DG 35 35 38 35 Moisan Chile Matched Cohort DG, TG 16 16 39 35 Kim Korea Matched Cohort DG, TG 88 88 41.8 38.3 Sica Italy Cohort DG, TG 25 22 30 29 Zhao China Cohort DG, TG 313 346 32.8 33.2 Hamabe Japan Cohort DG, TG 101 66 44 63.7 MacLellan Canada Cohort DG, TG 182 21 16 19 Shinohara Japan Cohort DG, TG 123 186 43.8 45.3 Cai China RCT DG, TG 47 49 22.87 22.98 YY Choi et al. J Surg Oncol. 2013 122

Systematic Review & Meta-Analysis Laparoscopic gastrectomy for AGC Disease Free Survival HR: 1.03 (95% CI: 0.76-1.40, P = 0.86) Overall Survival HR: 0.90 (95% CI: 0.76-1.06, P = 0.22) YY Choi et al. J Surg Oncol. 2013 Treatment Indication of Gastric Cancer Latest Evidence, 2014 Journal of Clinical Oncology (IF 18.038) 123

2014 외과전공의연수강좌 (Unit 2) Stage Large-Scale Korean Multicenter Study Laparoscopic gastrectomy (N 2976) Open (n = 1499) Lapa. (n = 1477) P value IA 382 (25.5%) 1134 (76.8%) <0.001 IB 168 (11.2%) 158 (10.7%) IIA 156 (10.4%) 77 (5.2%) IIB 188 (12.5%) 52 (3.5%) IIIA 170 (11.3%) 23 (1.6%) IIIB 173 (11.5%) 24 (1.6%) IIIC 262 (17.5%) 9 (0.6%) Matching by BMI, Operative Methods, Extent of Lymphadenectomy, Operator, and Stage Stage Open (n = 635) Lapa. (n = 635) IA 334 320 IB 130 150 IIA 69 62 IIB 51 50 IIIA 20 21 IIIB 16 23 IIIC 15 9 HH Kim & KLASS. JCO. 2014 Overall Long-term Survival Rate According to Stage Stage IB Stage IIA Stage IIB Stage IIIA Stage IIIB Stage IIIC HH Kim & KLASS. JCO. 2014 MIS for Function-Preserving Gastrectomy EMR MIS for Proximal Gastrectomy MIS for Pylorus Preserving Gastrectomy MIS for Sentinel Node Navigation Surgery 124

Endoscopic Resection Extended Indication of ESD Endoscopic Resection Safety of Extended Indication Extent of Gastrectomy: Guidelines Proximal Gastrectomy Korean Japanese NCCN EORTC Total Gastrectomy Principle Principle Principle Not mentioned Proximal Gastrectomy Limited indication Modified gastrectomy for ct1n0 Reconstruction after Proximal Gastrectomy: Guidelines Discussion Not mentioned Korean Japanese NCCN EORTC Proximal Gastrectomy EG stomy Jejunal interposition EG stomy Jejunal interposition Double tract method Not mentioned Not mentioned 125

2014 외과전공의연수강좌 (Unit 2) Reconstruction Proximal Gastrectomy: Double Tract Reconstruction (DTR) SH Ahn, HH Kim et al.: DTR after laparoscopic proximal gastrectomy(lpg) Reduced Reflux Nomura et al.: DTR (n=10) vs. Jejunal interposition (JIP, n=10) after LPG JIP: Function Preserving DTR: impaired glucose tolerance SH Ahn, HH Kim et al. Gastric Cancer, 2013 Nomura et al. World J Surg Oncol, 2014 Laparoscopic Proximal Gastrectomy Laparoscopic Proximal Gastrecotmy: Ongoing Trials Study Nation Phase Design Patients Enroll Primary endpoint KLASS 04 (2014~) III LATG vs. LAPG Stage I Cancer 194 Iron Deficiency Anemia Pylorus Preserving Gastrectomy Indication Located : the middle one-third Tumor size 5cm Depth : Intramucosal or Submucosal carcinoma w/o LN metastasis Naoki Hiki et al. Ann Surg Oncol (2013) Indication Location : middle portion of the stomach Distal tumor border at least 4cm proximal to the pylorus 126

LADG vs. LAPPG Recurrence-free survival after LADG and LAPPG Cumulative incidence of gallstone after gastrectomy. Suh et al. Annals of Surgery, 2014 LADG vs. LAPPG B -A /A (%) LADG (n=110) LAPPG (n=84) Postoperative 1-6mo Univariate P Multivariate* Protein -0.2 ± 7.7 3.9 ± 10.5 0.003 0.008 Albumin -0.68 ± 8.3 4.0 ± 11.9 0.003 0.012 Postoperative 7-12 mo Protein 0.6 ± 8.7 3.8 ± 9.3 0.015 0.145 walbumin 0.3 ± 9.4 3.9 ± 10.9 0.014 0.180 *Calculated by analysis of covariance adjusted by preoperative parameters. A : Preoperative Laboratory B : Postoperative Laboratory Suh et al. Annals of Surgery, Volume 259, Number 3, March 2014 SNNS for EGC Concept of SNNS Current issues on SNNS in Gastric Cancer Firstly suggested by Kitagawa et al. Background of SNNS in Gastric Cancer. LN metastasis in EGC : 2-20% No precise preoperative diagnostic to predict LN metastasis Few reports on laparoscopic SNNS : feasibility? Oncologic safety? No optimal tracer/method : dual vs. single? Optimal isotope & concentration? No standard pathologic examination : intraop. IHC, RT-qPCR Kitagawa Y et al. Surg Clin N Am 2000 Kitagawa Y et al. Dig Surg 2013 127

2014 외과전공의연수강좌 (Unit 2) SNNS for EGC Protocol of SNNS Hyung-Ho Kim et al. J Korean Surg Soc. Sep 2011 SNNS for EGC Diagnostic Value Early T stage, Dual tracers, SM injection method, open surgery, usage of IHC were associated with higher SN identification rate and sensitivity Zhen Wang et al. Ann Surg Oncol (2012) 19:1541 1550 MIS: Robot Gastrectomy 128

Robot vs. Laparoscopy 8 studies include, 1875 patients analysis. RAG was associated with a longer operative time Lower estimated blood loss Longer distal margin Shen et al. Surg Endosc, 2014 Conclusion Minimally Invasive Surgery for Gastric Cancer The application of laparoscopic surgery to gastric cancer still remains on the investigational treatment, however all open procedure are reproducing in a laparoscopic way. The short-term and long-term outcomes of laparoscopic gastrectomies for gastric cancer seem comparable those of open procedures. This result will be confirmed by long-term results of KLASS-01, 01 trials in the near future. The tailor-made strategy will improve the surgical outcomes and quality of life in patients with gastric cancer. 129

Unit 2 0 2 Submucosal Tumor in Stomach Hyung-Ho Kim (Department of Surgery Seoul National University Bundang Hospital Seoul National University of Medicine) Submucosal Tumor (SMT) 130

Introduction Submucosal Tumor (SMT) : commonly used but misnomer : Subepithelial Tumor Prevalence 0.4% 5% of Stomach tumor Mostly asymptomatic Incidentally detected by screening endoscopy Classification Endoscopy Diagnosis EUS ( Endoscopic UltraSonography ) EUS-FNA ( Endoscopic Ultrasound guided fine needle aspiration ) CT 131

2014 외과전공의연수강좌 (Unit 2) Endoscopy Mostly covered by normal mucosa Smooth & well-circlewise lesion Sometimes ulceration When compressed by a forcep not Lipoma Endoscopic biopsy all the time! (for exclusion mucosal lesions) Endoscopy Endoscopic Ultrasonography (EUS) Stomach layers in EUS Hypoechogenecity : Muscle 132

EUS findings Histologic Diagnosis Endoscopic biopsy mucosa area, difficulty in SMT diagnosis EUS guided FNA (fine needle aspiration) cytology, useful in benign vs. malignancy ddx. difficulty in specific diagnosis EUS guided core needle biopsy Recently introduced, but needs more study for clinical use Treatment Symptomatic patients : Operation Obstruction, Bleeding, Abdominal pain, Palpable mass, Weight loss. Asymptomatic patients 133

2014 외과전공의연수강좌 (Unit 2) Gastrointestinal Stromal Tumor (GIST) Pathogenesis & Diagnosis GIST cells derived from the Interstitial Cells of Cajal (ICC) (a/w Aurebach s plexus) ICC - pacemaker roles in normal gut motility, express KIT (CD117) GIST highly expression of KIT protein (± KIT mutation) the tyrosine kinase KIT, inhibited by STI-571 (imatinib mesylate, Gleevec or Glivec ) Pathogenesis & Diagnosis 134

Diagnosis of GIST Endoscopy Endoscopy Ultrasound (EUS) Gastrography Computed Tomography (CT) MRI, PET Biopsy CT Well defined enhanced mass Malignant GIST Large size, Direct invasion, Metastasis (Liver, Lung, Bone) Cystic degeneration, Ulceration, Mesenteric fat infiltration Necrosis, Hemorrhage LN metastasis, Calcification - rare Prognostic factors Tumor Size & Mitotic count : most important Tumor stage at presentation peritoneal Px. Cellularity & Nuclear atypia Muscle invasion Mucosal invasion, Ulceration Ki67 analogues (MIBI, Ki-S5) 135

2014 외과전공의연수강좌 (Unit 2) Prognostic factors Treatment Invasion into adjacent tissue layers Generally Not! Lymphatic involvement Extremely Rare Tumor rupture Poor Px. Treatment Main treatment of resectable localized GIST is SURGERY Local Resection with grossly negative margins 136

Indication for Surgery Size > 2cm or Growing or Symptomatic Resection recommended Size < 2cm Maybe observed & followed up. However!!! Potential for malignant transformation!!! Patients should be informed about the possibility of malignancy Any lesion >1cm can behave in a malignant fashion and may recur. Symptomatic tumors or Size>1cm should be removed Schwartz. Principle of Surgery. 9 th ed. Surgical Approach Enucleation Wedge resection Segmental resection Distal gastrectomy Proximal gastrectomy Total gastrectomy Extended total gastrectomy Laparoscopic Surgery Successful and safe laparoscopic resection of GISTs more than 2cm Iwahashi et al. World J Surg. 2006 Novitsky et al. Ann Surg. 2006 Treatment of choice for Tumor< 5cm is Laparoscopic Wedge Resection Otani Y et al. Surgery. 2006 J Natl Compr Canc Netw, 2010 137

2014 외과전공의연수강좌 (Unit 2) Treatment Zubin et al. Surg Oncol Clin N Am. 2012 Conclusion Surgery remains the mainstay of therapy for patients with primary GIST. The goal is complete gross resection with an intact pseudocapsule and negative microscopic margins. Laparoscopic resection is a reasonably safe and feasible procedure for patients with low-risk smaller gastric GISTs. Gastric GISTs 5 cm or smaller may be removed through laparoscopic wedge resection. GISTs larger than 5 cm may be resected using a laparoscopic or laparoscopicassisted technique No lymphadenectomy is needed. Treatment Main treatment of resectable localized GIST is SURGERY Local Resection with grossly negative margins 138

Unit 2 10 위암의항암치료 김용일 ( 이화여자대학교의과대학외과학교실 ) 139

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Unit 2 11 비만, 당뇨환자의외과적치료 이상권 ( 가톨릭대학교외과학교실 ) 154

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Unit 2 12 식도질환의외과적치료 김진조 ( 가톨릭대학교의과대학외과학교실인천성모병원외과 ) 173

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Unit 2 1 Surgical Treatment for Small Intestinal Disease Yong Geul Joh (Seoul Yang Hospital Constipation-Incontinence Center) 이강의를통하여다음의내용을배운다. - 소장의해부학적구조와생리학적기능 - 소장의유착에대한원인과기전, 경과과정, 보존적치료, 수술, 예방법 - 소장에서발생하는신생물의종류, 특성, 위험요소, 검사방법, 병기, 수술방법 - 양성신생물 leiomyomas benign GIST,, adenomas, lipomas - 악성신생물 carcinoid, adenocarcinoma, lymphoma, malignant GIST - 소장게실십이지장게실, 멕켈씨게실 - 장피누공의원임, 경과, 치료 - 짧은창자증후군 (short bowel syndrome) 의원인과치료 181

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