2016 gastroenterology Winter School Session 3. 대장 목차 빈틈없고안아프게대장내시경하기 7 대장염증성병변의진단 35 대장종양성병변의진단과치료 73

2016 gastroenterology Winter School 빈틈없고안아프게대장내시경하기 김은란

2016 gastroenterology Winter School 7 빈틈없이안아프게하는대장내시경 Eun Ran Kim, M.D. Division of Gastroenterology, Department of Medicine Samsung Medical Center 대장내시경검사를시작하기에앞서.. 통증을유발하는원인 과신전에의한내장통 - 삽입된내시경이대장을밀어붙이는기계적인힘 - 과다한공기의주입 환자스스로느끼는지각과민 대장의해부학 고정되는부위 : 직장의복막반이하, 하행결장, 상행결장 고정되지않는부위 : 직장상부, S 자결장, 횡행결장 고정점 : 하부직장, S자-하행결장접합부, 비만곡부, 간만곡부, 맹장

8 2016 gastroenterology Winter School 대장의해부학적구조 Ideal Distance Cotton PB et al. Practical gastrointestinal endoscopy: the fundamentals. 6 th ed. UK. Blackwell Publishing, 2008

2016 gastroenterology Winter School 9 안아프게하는대장내시경 Eun Ran Kim, M.D. Division of Gastroenterology, Department of Medicine Samsung Medical Center 이런환자는내시경이어렵다!!! 대장이과도하게긴경우 - 여성 > 남성, 고령환자, 만성변비환자유동성이심한경우 - 성인의약 15% : 태아발생과정에서하행결장의장간막고정변이 - 횡경막결장인대의유동성이심한경우장유착이있는경우 - 자궁적출술과같은부인과수술, 복막염동반한복부수술게실질환이있는경우장의팽창에대해민감성이높은경우 (e.g. 과민성장증후군..) 대장정결이제대로안되었거나적절한전처치약물의투여가안된경우 자신의실력과포기할 timing 을잘알아야한다!!!

10 2016 gastroenterology Winter School 대장내시경삽입의기본수기 Always neutral or straight 선단부굴절 (Tip deflexion) 밀어넣기와뒤로빼기 (Push-in and pull-back) 축비틀기 (Torque) 송기와흡인 (Suction air frequently, less air) 가볍게흔들기 (Jiggling) 주름걸어당기기 (Hooking the fold) 시계방향으로축회전 (Right turn shortening) 미끄러져들어가기 (Push-through and sliding) 복부압박 (External compression) 체위변화 (Position change) Neutral or straight ( 중립 )

2016 gastroenterology Winter School 11 Torque ( 축비틀기 ) 한쪽으로비틀어통과한후에는반드시반대쪽으로비틀어중립상태로 Air suction ( 공기흡인 ) 굴곡이있는부위의앞쪽에서는흡인조작을충분히해서굴곡을최소한으로 상행결장삽입시유용 : 공기흡인만으로내강이끌어당겨지면서밀어넣는효과

12 2016 gastroenterology Winter School Push-in and pull-back ( 밀어넣기와뒤로빼기 ) 내시경을빼는목적 - 충분한시야확보 ( 무리한전진은합병증으로연결된다.) - loop를풀기위해 내시경을밀기만하면다양한형태의 loop 가만들어질수있다. Pull-back in transverse colon

2016 gastroenterology Winter School 13 Jiggling (rapid to and fro motion, 가볍게흔들기 ) 장을단축하거나직선화시키고싶은경우언제나 Hooking the fold ( 주름걸어당기기 )

14 2016 gastroenterology Winter School Hooking the fold ( 주름걸어당기기 ) Right turn shortening ( 시계방향축회전 ) 내시경의축을시계방향으로비틀면서뒤로빼는동작 그러나 atypical loop 가형성된경우에는시계반대방향으로비틀면서 뒤로빼는동작이유용하기도

2016 gastroenterology Winter School 15 Loop of the Sigmoid Colon N loop (79%/47%) α loop (12%/12%) reverse α loop (11%/6%) Cotton PB et al. Practical gastrointestinal endoscopy: the fundamentals. 6 th ed. UK. Blackwell Publishing, 2008 N loop of the Sigmoid Colon Clockwise twist and Withdrawal Cotton PB et al. Practical gastrointestinal endoscopy: the fundamentals. 6 th ed. UK. Blackwell Publishing, 2008

16 2016 gastroenterology Winter School Sliding ( 미끄러져들어가기 ) 굴곡이심한부위에서모든수단을동원해도관강이보이지않는경우, 관강이있을것으로생각되는방향을정확히예측할수있다면내시경선단부를그방향으로굴절시킨후관강을보지못한상태에서내시경을밀어서장관벽을따라미꾸러져들어가기도한다. External compression ( 복부압박 )

2016 gastroenterology Winter School 17 Position change ( 체위변화 ) 우측와위 : S- 자결장 - 하행결장이행부와비만곡부통과시 앙와위 : 횡행결장통과시 좌측와위 : 간만곡부통과시 Take-Home Message 충분한대장정결첫 1-2분이가장중요공기의주입은최소한으로삽입보다는단축 Torque와 Right turn shortening을적절히이용같은동작은 3회이상반복하지않기자세변화와복부압박을적절히이용

18 2016 gastroenterology Winter School Take-Home Message 절대무리하지않는다!!! 빈틈없이하는대장내시경 Eun Ran Kim, M.D. Division of Gastroenterology, Department of Medicine Samsung Medical Center 24

Scrutinize : 면밀히검사하다 2016 gastroenterology Winter School 19

20 2016 gastroenterology Winter School Polyp Miss Rates by Tandem Colonoscopy : A systemic review Rijn J. Am J Gastro 2006;101:343-350 Miss rate for colorectal neoplastic polyps : a prospective multicenter study of back to back colonoscopy Endoscopy 2008; 40: 284-290

2016 gastroenterology Winter School 21 Miss rate for colorectal neoplastic polys : a prospective multicenter study of back to back colonoscopy Endoscopy 2008; 40: 284-290 What is optimal withdrawal technique? Two experienced endoscopists (miss rate 17% vs 48%) Video-taped 10 consecutive colonoscopic withdrawals- assessed by 4 experts Criterion 17% 48% p Looking on the proximal sides of folds 31.5 19.6 <0.001 Adequacy of cleaning 33.1 21.9 <0.001 Adequacy of distention 33.5 24.0 <0.001 Adequacy of time spent viewing 32.4 21.0 <0.001 Rex DK. Gastrointest Endosc 2000;51:33-36

22 2016 gastroenterology Winter School 대장내시경의맹점부위 Viewing behind the Fold

2016 gastroenterology Winter School 23 Impact of withdrawal speed on polyp yield Simmons DT, et al. Aliment Pharmacol Ther 2006: 24, 965 971 Withdrawal Times and Adenoma Detection during Screening Colonoscopy N Engl J Med 2006;355:2533-41

24 2016 gastroenterology Winter School Long mean withdrawal time is associated with increased adenoma detection Lee TJ Wet al. Endoscopy 2013; 45: 20 26 Modifiable endoscopic factors that influence the adenoma detection rate Gastrointest Endosc 2013;77:381-9

2016 gastroenterology Winter School 25 Withdrawal Times Continuous Quality Improvement Targets - Mean withdrawal times should average at least 6-10 min. Rex DK (ASGE) Gastrintest Endosc 2006;63(suppl):S16-S28 Mean inspection time 6 minutes on withdrawal from caecal pole to anus in negative procedures. NHS BCSP Publication No 6 February 2011 Recommend that the average withdrawal time is audited during screening colonoscopies and propose a minimum of 6 minutes in at least 90% of purely diagnostic examinations. Rembacken B et al. (ESGE) Endoscopy 2012; 44: 957 968 Detection of Adenomas in Asymptomatic Individuals Continuous Quality Improvement Targets - Adenoma prevalence rates detected during colonoscopy in persons undergoing first-time examinations 25% in men older than 50 15% in women older than 50 Rex DK Gastrintest Endosc 2006;63(suppl):S16-S28 NHS BCSP Publication No 6 February 2011

26 2016 gastroenterology Winter School Proposed minimum colonoscopic withdrawal time Polyp detection rate is improved with position change East J. GIE 2007;65:263-269

2016 gastroenterology Winter School 27 Polyp detection rate is improved with position change East J. GIE 2007;65:263-269 Polyp detection rate is improved with position change East J. GIE 2007;65:263-269

28 2016 gastroenterology Winter School Potential methods to improve detection See behind folds better Wide angle colonoscopy Colonoscopy in retroflexion Cap-fitted colonoscopy Third eye retroscope See flat lesions better Chromoendoscopy High definition Narrow band image Autofluorescence Wide angle colonoscopy A. Standard (140 angle of view) B. wide angle (170 angle of view) Third eye retroscope

2016 gastroenterology Winter School 29 Cap-fitted colonoscopy Various imaging colonoscopy A.White light B. Autofluorescence C. NBI D. Chromoendoscopy The efficacy of cap-assisted colonoscopy in polyp detection and cecal intubation : a meta-analysis of randomized controlled trials Forest plot on the proportion of patients with polyps detected. Am J Gastroenterol 2012; 107:1165 1173

30 2016 gastroenterology Winter School The efficacy of cap-assisted colonoscopy in poly detection and cecal intubation : a meta-analysis of randomized controlled trials Forest plot on the proportion of patients with adenomas detected. Am J Gastroenterol 2012; 107:1165 1173 Transparent Cap-Assisted Colonoscopy Versus Standard Adult Colonoscopy : A Systematic Review and Meta-analysis Dis Colon Rectum 2012; 55: 218 225

2016 gastroenterology Winter School 31 Take-Home Message Looking on the proximal sides of folds Adequate of cleaning Adequate of distention : air, position changes Adequate of time spent viewing : a minimum of 6 minitues

2016 gastroenterology Winter School 대장염증성병변의진단 김영호

2016 gastroenterology Winter School 35 염증성장질환 Winter School 20166 성균관대학교의과대학삼성서울병원소화기내과 김영호 Stomach Bx : No malignant cell H. pylori-associated chronic gastritis Tx : PPI

36 2016 gastroenterology Winter School Colon Bx : No malignant cell, Chromic active inflammation PMH : Oral ulcer Tx : Steroid/Mesalazine Today s Topic Colonoscopy with biopsy is not enough.

2016 gastroenterology Winter School 37 Ulcerative Colitis Bloody diarrhea Abdominal pain Urgency Tenesmus Endoscopic Features of UC Continuous, superficial inflammation from rectum confined to rectum and colon Mild loss of vascular tranasluscency, fine granularity, redness, minute yellow spots Moderate coarse mucosal erosions, small ulcers, friability, attachment of mucopurulent exudates Severe extensive ulcers, profuse spontaneous bleeding

38 2016 gastroenterology Winter School Endoscopic Findings of Ulcerative Colitis Endoscopic Findings of Ulcerative Colitis

2016 gastroenterology Winter School 39 Mayo Endoscopic Subscore Nat Rev Gastroenterol Hepatol 2010;7:15 Histologic Findings of Ulcerative Colitis

40 2016 gastroenterology Winter School Differential Diagnosis of Lower Gastrointestinal Bleeding Inflammatory bowel disease Benign anorectal disease : hemorrhoids, anal fissure, fistulain-ano, varices Neoplasia Diverticular disease Arteriovenous malformation Radiation enterocolitis Hemorrhoids

2016 gastroenterology Winter School 41 Hemorrhoids Hemorrhoids bright red blood not mixed with stool on the toilet tissue dripping into the toilet when straining or at the end of defecation Ulcerative colitis - diarrhea - mucoid stool - urgency - tenesmus Nonspecific Colitis

42 2016 gastroenterology Winter School Nonspecific Colitis Case 69 yr old man 8 days ago, lower abdominal pain 6 days ago, diarrhea with fever 3 days ago, hematochezia WBC 15240/ L, CRP 24.08 g/dl

2016 gastroenterology Winter School 43 Stool Culture : Shigella sonnei Infectious Colitis Symptoms acute onset fever, vomiting, abd pain, frequent bowel movement Endoscopy severe hyperemia, profuse exudate rectal sparing, patchy distribution

44 2016 gastroenterology Winter School Infectious Colitis Pathologic findings suggesting UC crypt architecture distortion mixed lamina propria cellularity basal lymphoid aggregates villous surface crypt atrophy surface erosion Infectious Colitis Regardless of the etiology, clinical symptoms are quite similar. It is hard to prove the existence of pathogens. Patients whose symptoms have not improved within 1 week should undergo a sigmoidoscopy or colonoscopy.

2016 gastroenterology Winter School 45 M/52 5 days ago, mild fever, mucoid stool, diarrhea, low abdominal pain PMH : Tx with pneumonia 3 weeks ago C. difficele toxin assay (+) UC (ulcertive colitis)-like Colonoscopic Findings of Infectious Colitis Shigella, Salmonella, Campylobacter, Amoeba CD (Crohn s disease)-like Salmonella, Campylobacter, Yersinia, Amoeba

46 2016 gastroenterology Winter School Infectious Colitis Shigella UC-like Yersinia CD-like Salmonellosis UC-like CD-like

2016 gastroenterology Winter School 47 Amoebic Colitis UC-like CD-like Case 51 yr old man Previously healthy 1 day ago, sudden onset of abdominal pain, followed by hematochezia

48 2016 gastroenterology Winter School Ischemic Colitis Old age Sudden onset of abdominal pain & hemtochezia Endoscopy hyperemia, edema, ulceration rectal sparing resolved within 1-2 weeks Bx : coagulation necrosis

2016 gastroenterology Winter School 49 Case 29 yr old female 2001.1. cervix ca -> radiation + chemotherapy 2001.8. hematochezia

50 2016 gastroenterology Winter School Radiation Colitis Radiation history due to cervix ca or prostatic ca Endoscopy proximal rectum & distal sigmoid colon mucosal friability granularity with spontaneous bleeding multiple telangiectasia Radiation Colitis Vienna Rectoscopy Score Telangiectasia: Grade 0: none; Grade 1: single telangiectasia; Grade 2: multiple non-confluent telangiectasia; Grade 3: multiple confluent telangiectasia Congested mucosa: Grade 0: none; Grade 1: focal reddening of the mucosa combined with edematous mucosa; Grade 2: diffuse non-confluent reddening of the mucosa combined with edematous mucosa; Grade 3: diffuse con-fluent reddening of the mucosa combined with edematous mucosa Ulceration: Grade 0: none; Grade 1: micro-ulceration with or without superficial < 1 cm 2 ; Grade 2: superficial > 1 cm 2 ; Grade 3: deep ulceration; Grade 4: fistula, perforation Stricture: Grade 0: none; Grade 1: more than two-thirds of the regular diameter; Grade 2: One-third to two-third of the regular diameter; Grade 3: less than one-third of the regular diameter; Grade 4: complete obstruction Necrosis: Grade 0: none; Grade 1: necrosis Types of mucosal reactions were then subsumed according to the Vienna Rectoscopy Score (Score 0 5; Table 1). Wachter S et al. Radiother Oncol 2000;54:11

2016 gastroenterology Winter School 51 Radiation Colitis Vienna Rectoscopy Score Wachter S et al. Radiother Oncol 2000;54:11 Case 48 yr old female 10 years ago, constipation with straining Anal bleeding, mucoid stool, tenesmus, lower abdominal pain

52 2016 gastroenterology Winter School Colonoscopy Colonoscopic Biopsy : Tubular Adenoma with Erosion Defecography

2016 gastroenterology Winter School 53 Solitary Rectal Ulcer Syndrome A chronic course characterized by rectal bleeding, disordered defecation, tenesmus and mucorrhea Endoscopy anterior wall, 4 to 15 cm from the anal verge shallow ulcers with white, sloughy base surrounded by a thin rim of erythematous mucosa Solitary Rectal Ulcer Syndrome Histology characteristic obliteration of lamina propria by fibromuscular proliferation of the muscularis mucosa streaming of fibroblasts and muscle fibers up between crypts thickening of muscularis mucosa branching, distorted glandular crypts diffuse collagen infiltration of lamina propria

54 2016 gastroenterology Winter School Skip? Patchy? Rectal Sparing? Endoscopic Findings Ulcerative colitis Crohn s disease Ractal sparing rarely frequently Continuous disease yes occasionally Cobblestone no yes Granulaoma on biopsy no occasionally Case 37 yr old female 2001.9. hematochezia -> sigmoidoscopy Diagnosed as ulcerative proctitis Maintenance with 5-ASA suppository 2003.1. RLQ pain -> colonoscopy

2016 gastroenterology Winter School 55 Crohn s Disease Discontinuous, transmural inflammation from esophagus to rectum Aphthous ulcer Longitudinal ulcer Cobblestone appearance

56 2016 gastroenterology Winter School 크론병진단기준개정안 ( 일본후생청, 1995) Crohn s Disease Endoscopic Index of Severity

2016 gastroenterology Winter School 57

58 2016 gastroenterology Winter School Crohn s Disease

2016 gastroenterology Winter School 59 Crohn s Disease Crohn s Disease

60 2016 gastroenterology Winter School Tuberculous Colitis Tuberculous Colitis

2016 gastroenterology Winter School 61 결핵성장염 _ 조직검사 어디서? 균배양 : 궤양저부 건락성육아종 : 궤양저부와변연부 크론병과다른점 AFB +, Caseating granuloma + 육아종이많고크다. 육안적으로정상인부위에서조직검사를하면정상소견이다. Prospective Evaluation of the Clinical Utility of Interferon-ɣ Assay in the Differential Diagnosis of ITB & CD Kim BJ et al, Inflamm Bowel Dis 2011;17:1308

62 2016 gastroenterology Winter School Diagnosis of Tuberculous Colitis_Korean Guideline Case Male, 34 years old Abdominal pain, diarrhea & weight less (5 Kg) for 2 months Past history of anal fistula CRP 9.67 mg/dl

2016 gastroenterology Winter School 63 Case Focal active inflammation with non-caseating granulomas and erosions AFB (1+) 1-9/100HPF Case Colonoscopic biopsy focal active inflammation with non-caseating granuloma AFB smear (-) M. tuberculosis PCR (-) Tuberculin skin test (-)

64 2016 gastroenterology Winter School Case Therapeutic trial with anti-tb medication Colonoscopy F/U 2 mo later Tuberculous Colitis

2016 gastroenterology Winter School 65 Intestinal Tuberculosis vs Crohn s Disease Characteristic of Tb Involvement of fewer than 4 segments A patulous IC valve Transverse ulcers Scars or pseudopolyps Characteristic of CD Anorectal lesions Longitudinal ulcers Aphthous ulcers Cobblestone appearance PPV for CD : 94.9% PPV for TB : 88.9% Lee YJ, et al. Endoscopy 2006;38:592 Behçet s Disease

66 2016 gastroenterology Winter School Behçet s Disease Behçet s Disease Lee CR, et al. Inflammatory Bowel Disease 2001;7:243

2016 gastroenterology Winter School 67 Behçet s Disease Typical colonoscopic finding ; Single or a few deep round/oval ulcers with discrete margin in ileocecal area Behçet s Disease

68 2016 gastroenterology Winter School Differential Diagnosis of Crohn s Disease & BD by Colonscopic Findings Sensitivity 94.3% Specificity 90.0% Lee SK et al, Endoscopy 2009;41:9 M/52 Low abdominal discomfort Bx : focal active inflammation, terminal ileum

2016 gastroenterology Winter School 69 M/52 Diarrhea (-) Hematochezia (-) Wt loss (-) Oral ulcer (-) ESR/CRP : normal 복통이나설사가심해지거나혈변이생기면들리세요 Colonoscopy, 1 year later F/24 2 개월전외부병원에서건강검진으로대장내시경시행

70 2016 gastroenterology Winter School 현재특이증상없음 F/24 건강검진 1 주일전발열, 복통, 설사 Colonoscopy 6 mo later Conclusion Colonoscopy with biopsy is not enough.

2016 gastroenterology Winter School 대장종양성병변의진단과치료 장동경

2016 gastroenterology Winter School 73 2016 Winter School 대장종양성병변의진단과치료 Dong Kyung Chang Sungkyunkwan University, School of Medicine Samsung Medical Center Colon Polyps (Epithelial origin) Neoplastic Premalignant polyp Tubular adenoma Tubulovillous adenoma Villous adenoma Non-neoplastic Mucosal tag Hyperplastic Inflammatory Juvenile Carcinoma in situ: D01.0~01.2 (by 2010 AJCC staging) High-grade dysplasia Intraepithelial cancer (CIS) Intramucosal cancer (infiltrating into lamina propria) Invasive carcinoma: C18 ~20 Submucosal cancer (Malignant polyp) beyond the m.m.

74 2016 gastroenterology Winter School Paris endoscopy classification for superficial (type 0) lesions (tumors with superficial invasion:m,sm) Ip *Protruding lesions are elevated more than 2.5 mm. Adenomatous Polyp Ip Isp Is 0.2 cm IIa

2016 gastroenterology Winter School 75 LST: Lateral spreading tumor (> 1cm) G-H (Granular type Homogeneous) NG-F (flat elevated) Classification of LSTs LST-G (granular) 46% Kudo: LST-G-H (homogeneous) Paris: IIa 30% LST-G-M (nodular mixed) IIa + Is 16% LST-NG (non-granular) 54% Kudo: LST-NG-F(flat elevated) Paris: IIa 41% LST-NG-PD (pseudodepressed) IIc + IIa, IIa + IIc 13% Kudo S. 1993 Kudo S et al. Stomach and Intestine. 2005. 40;1367 Kudo S et al. Gastrointest Endosc 2008;68(S4):S3

76 2016 gastroenterology Winter School Proportion of M/SM cancers according to the type and the size of the LST LST-G M/SM total (%) < 2 cm(%) > 2 cm(%) LST-G-H M 22.9 13.5 39.5 SM 1.8 1.0 3.4 LST-G-M M 33.5 25.4 38.0 SM 18.0 5.1 25.0 LST-NG LST-NG-F M 12.7 11.3 17.9 SM 4.1 1.9 11.9 LST-NG-PD M 23.5 19.6 31.8 SM 25.0 15.2 45.5 Yamano H et al. Stomach and Intestine. 2007. Multifocal submucosa-invading cancer LST-G: 1/7 (14.3%) LST-NG: 5/20 (25.0%) Shinji Tanaka 2006. Basic Technique of EMR and ESD for colorectal tumors

2016 gastroenterology Winter School 77 LST-G-MN type An invasive cancer focus in the large nodule Rectal LST-G-M, 5 cm Adenocarcinoma, (well differentiated) in the pre-existing adenoma Adenoma size: 5.0 x 4.5 cm Cancer Size: 0.4 x 0.2 cm Depth of invasion: intraepithelial carcinoma(ptis)

78 2016 gastroenterology Winter School Three steps to observe polyps for treatment plan Neoplastic vs. Non-neoplastic Neoplastic : benign vs. malignant Malignant : mucosal vs. submucosal or deeper Methods: Gross endoscopic appearance Vascular pattern analysis Pit pattern analysis etc. Hyperplastic Polyp

2016 gastroenterology Winter School 79 Inflammatory polyp Ascending colon Sigmoid colon Ulcerative colitis Inflammatory polyp Cecum Ascending colon Tuberculosis scar

80 2016 gastroenterology Winter School Adenomatous Polyp Hyperplastic Polyp Cecal fold thickening? tubular adenoma

2016 gastroenterology Winter School 81 염증? Tubular adenoma with High grade dysplasia! Serrated Adenoma, ascending colon

82 2016 gastroenterology Winter School Early colon cancer: IIc+IIa de-novo cancer? Endoscopic Appearance of Depressed type Early Colon Cancers Color change: hyperemic, rarely whitish (ddx. with hyperplastic polyp) Spontaneous bleeding, or bleeding induced by air-inflation Wall deformity Irregular-edged depression

2016 gastroenterology Winter School 83 Gross Endoscopic Appearances suggestive of Massive Malignant Submucosal Invasion Size & Gross type: depressed >1 cm, flat or superficial elevated > 2 cm, protruded or LST > 3 cm Hardness, stiffness, or rigidity Severe depression, erosion, or ulcer Polyp on polyp (Buddha) appearance Fold convergence Loss of air-induced deformity Pit pattern : type Vn (nonstructural) Non-lifting sign Air-induced deformity in M/SM1 cancer Increased air volume Decreased air volume

84 2016 gastroenterology Winter School Hardness, non-lifting Adenocarcinoma, W/D - extension to the Muscularis Propria Fold convergence, Polyp on polyp appearance Adenocarcinoma, W/D - extension to submucosa

2016 gastroenterology Winter School 85 Fold convergence, hardness, erosions, Loss of air-induced deformity, non-lifting Adenocarcinoma, W/D - extension to submucosa 바늘이고유근층을뚫으면융기되지않는다. cf) Non-lifting sign (+) 인경우 : 주위점막은잘융기.

86 2016 gastroenterology Winter School Do not try submucosal injection if you are not prepared to do complete resection! D0 Fibrosis 생겨서 en bloc resection 안됨. -> Piecemeal EMR 과 coagulation 으로제거 D7 LST 는 ESD 를고려하는경우라면 biopsy 도 1 2 개만가볍게!! Pit Pattern Classification & Treatment Non-neoplastic : No treatment I: normal II: stellate Adenoma : Endoscopic resection III L : large tubular III S :small round IV: branched, gyriform V I : irregular Cancer : Endoscopic resection (en bloc) V N : non-structural SM Cancer : Surgery Kudo S et al, Endosccopy 2001;33:367

2016 gastroenterology Winter School 87 NBI Vascular pattern: Sano classification Tanaka S, Sano Y. Dig Endosc. 2011 May;23 Suppl 1:131-9 NBI international colorectal endoscopic (NICE) classification No treatment or Endoscopic Resection Endoscopic Resection Surgery Tanaka S, Sano Y. Dig Endosc. 2011 May;23 Suppl 1:131-9

88 2016 gastroenterology Winter School Serrated Polyps Dong Kyung Chang Sungkyunkwan University, School of Medicine Samsung Medical Center Hyperplastic polyp, ascending colon

2016 gastroenterology Winter School 89 Sessile Serrated Adenoma, ascending colon Sessile Serrated Adenoma, ascending colon

90 2016 gastroenterology Winter School PROBLEM POSING Colonoscopies have resulted in an overall reduction of -CRC-related deaths by 29% -Deaths from distal CRC by 47% -No observed reduction in deaths caused by proximal CRC * More right-sided CRC cases in the setting of previous negative colonoscopic examinations (interval carcinomas) Singh H, Nugent Z, Demers AA, et al. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology 2010;139:1128-37 Frequency and Location of Interval CRCs Study Data source Total detected cancers, n Overall, n (%) Interval cancers Proximal, n (%) Distal, n (%) Baxter et al 2011 Ontario Ca Registry (2000 2005) 34,312 1260 (9.0) 676 (12.4) 584 (6.8) Singh et al 2010 Manitoba Ca Registry (1992 2008) 4883 388 (7.9) 225 (11.3) 147 (5.3) Cooper et al 2012 SEER-Medicare DB (1994 2005) 57,839 4192 (7.2) 2851 (9.9) 1253 (4.5) Patel SG, Ahnen DJ. Clinical Gastroenterology and Hepatology 2014; 12:7-15

2016 gastroenterology Winter School 91 Etiology of Interval Colorectal Cancers Pabby et al 21 and Robertson et al 37 50% - 75% of interval CRCs : missed or incompletely resected lesions less than 30% : rapidly progressing lesions. Missed Lesions Adenoma detection rates (ADRs) : 17 47% (serrated polyps : 1 18%) Tandem colonoscopy (van Rijn et al 2006)/colonoscopy in tandem with CT colonography ( Pickhardt et al 2003) overall adenoma miss rate : 22%, miss rate for adenomas of 10 mm or greater : 2% - 12% Incomplete Polypectomy Overall incomplete resection rate: 10.1% (6.5% 22.7%) (Pohl et al 2013) - Larger polyps :5.8% (for 5-7mm) vs 23.3% (for 15-20 mm) - Sessile serrated polyps (vs adenomas): 31% vs 7.2% Rapid Progression Lynch syndrome MSI, CIMP, and lower rates of KRAS mutations serrated polyp pathway Sessile serrated polyps : common in the right colon, missed frequently during endoscopy, and a higher rate of incomplete resection. 42 Patel SG, Ahnen DJ. Clinical Gastroenterology and Hepatology 2014; 12:7-15 SERRATED POLYPS Serrated = saw-tooth like 36% of colonic polyps Past: Hyperplastic polyp - the only recognized serrated polyp A heterogeneous family of polyps - Hyperplastic polyp - Sessile Serrated adenoma/polyp - Traditional Serrated adenoma

92 2016 gastroenterology Winter School Normal colon GASTROINTESTINAL ENDOSCOPY 2013:77(3);360-375 Hyperplastic polyp (Microvesicular type) GASTROINTESTINAL ENDOSCOPY 2013:77(3);360-375

2016 gastroenterology Winter School 93 Sessile serrated adenoma/polyp (SSA/P) GASTROINTESTINAL ENDOSCOPY 2013:77(3);360-375 Sessile Serrated Adenoma/Polyp (SSA/P) - 5% (1 ~ 9%) of all colonic polyps - median 62years, 50 65% in women

94 2016 gastroenterology Winter School SSA/P Endoscopic features - predilection for the right colon - flat or sessile - usually > 5 mm - tends to be redder than the other serrated polyps, (less red than the conventional adenomas) - a yellow-tinged mucus cap, a rim of debris or bubbles, alteration of mucosal fold contour, indistinct borders, and obscuring of submucosal vasculature SSA/P is typically flat with indistinct borders, making recognition and complete excision challenging. Pit pattern : type II open shape pit pattern (type II-O) - represent dilated crypt bases (wider and rounder) SSA/P Histological features - serrations in the whole length of crypts - boot-, inverted T- shaped, horizontally oriented crypt bases - tends to lack both a thickened subepithelial collagen table and a prominence of neuroendocrine cells Recent expert consensus opinions have simplified the diagnostic difficulties: First, a single crypt with unequivocal dilation, distortion, and/or horizontally branched crypt is sufficient to establish a dx of SSA/P Second, clinicians are advised to manage any hyperplastic polyp >10 mm proximal to the sigmoid as an SSA/P.

2016 gastroenterology Winter School 95 Nomenclature Why SSA/P? (SSA = SSP) The term adenoma historically implied low-grade dysplasia SSA/P without cytologic dysplasia lacks the cytologic features typically seen in low-grade dysplasia in the tubular adenoma - sessile serrated polyp : no or serrated dysplasia (not conventional dysplasia) - sessile serrated adenoma : malignant potential Clinical significance of SSA/P - Precancerous lesion as itself - A greater polyp burden, and synchronous and metachronous neoplastic lesions Identification of SSA/Ps requires increased vigilance for lesions elsewhere in the colon - Common cause of interval cancer * Interval cancer - Missed precursor lesions - Incomplete subtotal polyp resection - Rapidly growing precursor lesions Small, flat, indistinct-bordered, and right-sided polyps (such as SSA/Ps) are a high risk of interval cancer

96 2016 gastroenterology Winter School Traditional serrated adenoma (TSA) - TSA was introduced in 1990 - < 1% of all colonic polyps Endoscopically, - usually left-side predominant, - pedunculated or sub-pedunculated - usually > 5 mm - granulonodular and lobular appearance (like conventional adenoma) Pit pattern: often combined pit patterns: type II and/or IIIS/IIIL (not common in the conventional adenoma) Traditional serrated adenoma, Descending colon

2016 gastroenterology Winter School 97 MOLECULAR ASPECTS OF THE SERRATED NEOPLASTIC PATHWAY Molecular genetics of CRC - 3 most established pathways (1) Chromosome instability pathway: APC, K-RAS-P53 (2) DNA mismatch repair pathway: MMR(MSH2, MLH1, MSH6, PMS2) MSI (3) CpG island hypermethylation (CIMP) pathway the central defect of the serrated pathway of neoplasia. Sessile serrated neoplastic pathway GASTROINTESTINAL ENDOSCOPY 2013:77(3);360-375

98 2016 gastroenterology Winter School Serrated polyposis (formerly, hyperplastic polyposis) WHO criteria for serrated polyposis - At least 5 serrated polyps proximal to the sigmoid colon, at least 2 polyps 10 mm, or - Any number of serrated polyps proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis, or - 20 serrated polyps of any size distributed throughout the colon Serrated polyposis - 1.8 4 % of colonoscopy patients - Median ages: 50 62 years - Up to nearly 40% risk of CRC A study of 4,462 polyps from 100 pts with serrated polyposis - 83% were serrated polyps (156 MVHPs, 25 GCHPs, 138 SSAs, 18 TSAs) - 17% were conventional adenomas (55 tubular adenomas, 14 tubulovillous adenomas).

2016 gastroenterology Winter School 99 CLINICAL MANAGEMENT RECOMMENDATIONS Given the malignant potential of the SSA/P, TSA, and filiform SA, complete endoscopic resection is critical. - All proximal serrated polyps (proximal to the sigmoid colon) should be removed - All proximal serrated polyps > 10 mm diagnosed as hyperplastic polyps should be clinically managed as SSA/Ps When SSA/P margins cannot be fully resected, residual tissue can be removed by cold forceps or burned by APC, and close endoscopic follow-up is advised - 1 year per the U.S. Multi-Society Task Force guidelines - 3 ~ 6 months per expert consensus opinions Management of Serrated Polyposis All proximal colon polyps or all serrated polyps > 5 mm should be completely removed, if numerous diminutive polyps are observed. Colon resection can be advised for colorectal cancer or when endoscopic control of polyps is no longer feasible.

100 2016 gastroenterology Winter School 대장용종조직검사 vs. 용종제거술 Natural History of Untreated Polyp A study using serial sigmoidoscopy for tattooed colorectal polyps < 1 cm (not all of which would have been adenomas) over the course of 3 to 5 years 4% increased in size 70% remained unchanged 8% were smaller 18% disappeared A diminutive adenoma(<0.5 cm) requires 2 to 3 years to reach 1 cm size Kozuka S. Dis Colon Rectum 1975

2016 gastroenterology Winter School 101 Cumulative risk for cancer in 1cm adenoma - 2.5% at 5 yrs, - 8% at 10 yrs, - 25% at 20 yrs Carroll RLA Prev Med 1980 Percentage of containing cancer in adenoma Surgical polypectomies Colonoscopic polypectomies Adenoma Size <1cm 1.3% 0.5% 1-2cm 9.5% 4.6% >2cm 46.0% 10.8% Histologic Type tubular 4.8% 2.8% villotubular 22.5% 8.4% villous 40.7% 9.5% Degree of dysplasia mild 5.7% 2.8% moderate 18.0% 8.4% severe 34.5% 9.5% Muto T. Cancer 1975

102 2016 gastroenterology Winter School Cumulative Incidence of Colorectal Cancer in the National Polyp Study Cohort - 76 ~ 90 % reduction in cancer incidence - Winawer, S. J. et al. N Engl J Med 1993;329:1977-1981 Incidence/mortality of CRC and screening uptake rates over time (US) Source: Clinical Gastroenterology and Hepatology 2014; 12:7-15 (DOI:10.1016/j.cgh.2013.04.027 ) Copyright 2014 AGA Institute

2016 gastroenterology Winter School 103 용종의최종진단은조직학적검사필요. 겸자생검후, 종양성용종만제거할것인가? : Two-stage polypectomy 발견즉시제거할것인가? : One-stage polypectomy One-stage polypectomy 의장점 Two-stage polypectomy 에서조직결과불일치율 : 15 30 % 대장용종의 60 70 % 가선종 : 결국다수에서용종제거필요 미소대장암에서겸자생검이조직구조를파괴하여다음의 EMR 을곤란하게할수있다. Second-stage 에서용종을찾지못하는경우가적지않다. : 생검결과가암인데, 찾을수없다면심각한낭패 One-stage polypectomy: 환자의불편, 시간 - 경제적손실감소

104 2016 gastroenterology Winter School Rex RK. et al. Quality indicators for colonoscopy. Gastrointestinal endoscopy 63:4;S16 -S28: 2006 Consistent referral of small routine colorectal polyps identified during diagnostic colonoscopy for repeat colonoscopy and polypectomy by others is unacceptable. Referral of technically difficult polyps to more experienced endoscopists for endoscopic resection is encouraged. 그렇다면, 용종을모두 one-stage 로제거할것인가?

2016 gastroenterology Winter School 105 불필요한용종제거는하지말자 명백한 Inflammatory Polyps 불필요한용종제거는하지말자 Rectosigmoid area 의명백한 multiple hyperplastic Polyps

106 2016 gastroenterology Winter School 자신이없으면제거하지말자 Biopsy only! 기술적한계 : Endoscopist-dependent 절제가어려운위치에있는용종 : 간만곡부원위부내측, 비만곡부원위부하방, 경사진위치등. -> 시야확보곤란, 올가미접근곤란 너무큰용종 편평형또는함몰형으로완전절제가어려운용종 : Two-stage polypectomy or Surgery 내시경으로제거해서는안되는용종도있다. : 내시경으로완치불가능한악성용종 림프절전이 원격전이 Biopsy only! 점막하층암세포대량침윤-> 림프절전이율 10 % 점막하대량침윤이강력히의심되면, 내시경절제하지말자

2016 gastroenterology Winter School 107 Diminutive polyp (<5 mm) 의절제는필요한가, 불필요한가? Risk vs. Benefit Clinical Significance of Small Colorectal Polyps Size (mm) <6 4,381 6-10 666 >10 675 n Neoplastic TA TVA VA Severe Cancer (% (%) dysplasia Neoplastic) 2,066 (49) 2,002 51 2 418 (67) 359 50 4 496 (77) 235 211 26 39 15 89 2 (0.1) 1 (0.2) 21(4.2) High Risk 4.4% 15.6% 100% Total 5,722 2,980 (54) 2,596 312 32 143 24 (0.8) High risk adenomas (Atkin et al. 1992. NEJM 326: 658) those containing >25 percent villous architecture, those with severe dysplasia, and those over 10 mm in size. 적어도선종은크기와상관없이제거하는것을권장. Church JM 2004. Dis Colon Rectum 47:481

108 2016 gastroenterology Winter School Summary: Tips for polyp treatment Endoscopic differential diagnosis for polyps has limitations Tissue diagnosis is mandatory for confirmation Symptomatic polyps should be removed. Neoplastic polyps should be removed. Asymptomatic, definite non-neoplastic polyps can be followed-up. Removal of diminutive polyps: controversial ->cold biopsy or snaring If prepared, one-stage polypectomy is desirable. Malignant polyps that are highly suggestive of massive submucosal invasion should be surgically removed. (Non-lifting sign) Safe endoscopy skill provides wide range of management options. (One-stage polypectomy, two-stage polypectomy, or surgery) Independent risk factors for failed endotherapy Feature Previous intervention Ileocaecal valve involvement Difficult position Lesion size >40 mm Previous APC use Statistical association (n=479) OR: 3.75; 95% CI 1.77 to 7.94; p=0.001 OR=3.38; 95% CI 1.20 to 9.52; p=0.021 OR=2.17; 95% CI 1.14 to 4.12; p=0.019 OR=4.37; 95% CI 2.43 to 7.88; p<0.001 OR=3.51; 95% CI 1.69 to 7.27; p=0.001 APC, argon plasma coagulation. Rutter MD et al. British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps. Gut. 2015; 64(12): 1847 1873. Moss A, Bourke MJ, Williams SJ, et al. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology 2011;140:1909 18.

2016 gastroenterology Winter School 109 Major histopathological considerations in the management of large non-pedunculated colorectal polyps (LNPCPs). Rutter MD et al. British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps. Gut. 2015; 64(12): 1847 1873. Non-pedunculated colorectal polyps Rutter MD et al. British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps. Gut. 2015; 64(12): 1847 1873.

110 2016 gastroenterology Winter School Endoscopic management Rutter MD et al. British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps. Gut. 2015; 64(12): 1847 1873.