Polyps – Where do they come from and what do you do with them?! Ron G. Landmann, MD Grand Rounds Department of Surgery St. Luke’s-Roosevelt Hospital Center March 21, 2007

Polyps Cancer epidemiology Definition of the malignant polyp Natural history of adenomatous polyps Biology of polyps The anatomy of the polyp Correlations with Malignancy Endoscopic polypectomy alone??? Special considerations * No discussion of technique

Colorectal Cancer – Epidemiology Incidence: Approx. 150,000 cases/year Deaths: Approx. 50,000 deaths/year At diagnosis 10% in situ disease 30% local disease 30% regional disease 30% distant disease 5 year survival, all patients: 50% local - 90% regional - 60% distant - 5% U.S. Cancer Statistics Working Group. United States Cancer Statistics: 2003 Incidence and Mortality (preliminary data). Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2006.

Incidence/Prevalence of Polyps Adenomatous polyps 30% of Western population Most cancers arise from polyps *excludes syndromes

Carcinoma in situ vs. cancer  Think Carcinoma in situ = high grade dysplasia Carcinoma in situ ≠ cancer Histology Colorectal cancer is defined by invasion of/through muscularis mucosa

Colorectal cancer is defined by invasion of muscularis mucosa Histology Colorectal cancer is defined by invasion of muscularis mucosa Lymphatics are located in submucosa Genetic model of colorectal tumorigenesis

Colon Cancer Staging T-stage Tis Intraepithelial or invasion of lamina propria T1 Invades submucosa T2 Invades muscularis propria T3 Invades subserosa or pericolic/rectal tissues T4 Into other organs/perforates visceral peritoneum N-stage 0 LN 1 1-3 positive LNs 2 > 3 positive LNs

Colon Cancer Staging AJCC 5 Stage T N M 5 year DSS (%) Colon Rectum Tis I 1-2 75 70 II 3-4 65 55 III Any 45 40 IV 1 5

Relationship Between TNM Stage and Survival in Colorectal Carcinoma CA Cancer J Clin 2004;54;295-308

Treatment of CRC  Pathology is key! Polypectomy Colonic Resection Treatment depends on the risk of lymph node metastasis.  Pathology is key! Colorectal cancer is defined by invasion of muscularis mucosa Lymphatics are located in submucosa

Incidence of malignant polyps Definition Malignant polyps or T1 lesions (limited to the submucosa) Represent 5% of all adenomas Colonoscopy polypectomy series: 2 – 12% Colorectal resection series: 4 – 9%

Haggitt Level (1985) Classification of polyps with invasive cancer Definition Resected (N) + LN (N) Carcinoma in situ 1 Invasion of head 6 0 (< 1%) 2 Invasion of neck 3 Invasion of stalk 4 Invasion of submucosa of bowel wall below polyp 13 4 (31%, 12-25%) Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD. Prognostic factors in colorectal carcinoma arising in adenomas: Implications for lesions removed by endoscopic polypectomy. Gastroenterology 89:328-36, 1985, p 330. Villuous/sessile (flat) polyps with invasive cancer are by definition Haggitt 4.

Sessile Polyps Kudo, 1993 Risk of lymph node metastasis in each sessile lesion is not the same Haggitt’s: no detail for sessile lesions Classification of submucosal invasion: Sm1—Invasion into the upper third of the submucosa Sm2—Invasion into the middle third of the submucosa Sm3—Invasion into the lower third of the submucosa High rate of LN metastasis: 12-25%

Sm system Able to determine Sm1, Sm2, Sm3 in 97% of cases Haggitt Level 1, 2, 3 = Sm1 Haggitt Level 4 = Sm1, Sm2, or Sm3 Endoscopist must properly resect and prepare specimen Pathologist must properly section and examine all layers

Correlations with Malignancy Morphology Incidence % Malignant Tubular 75 5 Tubulovillous 15 20 Villous 10 40

Correlations with Malignancy Grade Dysplasia % malignant Mild 5 Moderate 20 Severe 30

Correlations with Malignancy Size Size (cm) % malignant < 1 1 1 – 2 10 ≥ 2 50 Muto, 1975

Correlations with Malignancy Size Size (cm) % malignant < 1 1 1 – 2 10 ≥ 2 50 Size (cm) % malignant ≤ 0.5 Negligible 0.6 – 1.5 2 1.6 – 2.5 19 2.6-3.5 43 ≥ 3.5 76 Muto, 1975 Nusco, 1997

Relationship between Size and Morphology Tubular Tubulovillous Villous < 1 cm 76% 25% 14% 1-2cm 20% 47% 26% > 2 cm 4% 28% 60% St. Mark’s Hospital Data

Increased risk of LN Metastasis Unfavorable pathologic features of malignant CR polyps Poor differentiation (only on univariate) Lymphovascular invasion (P < 0.009) Invasion below submucosa (Haggitt Level 4) Depth of invasion in Sm3 (P < 0.001) Site in lower 1/3 of the rectum (P < 0.001) Positive resection margin (< 1 mm or 1 HPF) Not really – this is inadequate treatment, not an adverse risk factor! P-values from Nascimbeni et al. N = 353 T1 colorectal sessile lesions

Management of Pedunculated Malignant Polyps Haggitt Level 1, 2, 3 Complete excision or snaring Risk of LN metastasis < 1% Haggitt Level 4 Treat as sessile lesions

Management of Sessile Malignant Polyps < 2cm in diameter Adequate snare in one piece via colonoscopy Requires microscopic free margin of at least 2mm Piecemeal removal Requires further excision/follow-up or resection High risk factors (LVI, Sm3, distal 1/3 rectum) Oncologic resection Full thickness transanal excision

Lesions amenable to colonoscopic polypectomy Pedunculated or sessile < 2cm Well/moderately differentiated No lymphovascular invasion Haggitt Level 1-3 or Sm1 Close follow-up available Endoscopically complete excision Negative resection margins (2mm)

Criteria for Treatment of Malignant CR Polyps by Polypectomy Alone Determined by risk of metastasis Low risk of Lymph Node Metastasis Pedunculated Haggitt Level 1, 2, 3 Level 4 Sm1, Sm2 Sessile Sm1, Sm2 High risk of Lymph Node Metastasis Lower 1/3 of the submucosa (Sm3) LVI Distal 1/3 of rectum

Malignant Colorectal Polyps that Should have an Oncologic Bowel Resection Lesions in colon Pedunculated Haggitt Level 4 with invasion into distal third of submucosa (Sm3) or LVI Sessile lesions removed with margin < 2mm Sessile lesions removed piecemeal Sessile lesions with depth of invasion into distal third of submucosa (Sm3) Sessile lesions with LVI Lesions in middle third and upper third rectum Same as lesions in colon Lesions in distal third rectum Pedunculated Haggitt Level 4 with invasion into distal third of submucosa (Sm3) or pedunculated lesions with LVI All sessile lesions

Why not just resect anyway?!

What if ??? What if it’s clipped in ½? Pedunculated Repeat endoscopy. Require good resection with margin (2mm) Sessile Requires operative oncologic resection (even if Sm1, Sm2) Unable to determine exact pathologic depth What if it’s shredded by forceps? Requires operative oncologic resection What if it’s a very small lesion? Requires marking/tattoo CIRCUMFERENTIALLY What if it’s carcinoma in situ? It’s not cancer. This is high grade dysplasia. Requires close follow-up. Unless, poor margins: repeat endoscopy with good margins Piecemeal resection: discussion with pathologist and patient What if it’s a large, non-endoscopically resectable polyp? Repeat endoscopy (2nd MD?) Oncologic resection

Other considerations… When in doubt Repeat colonoscopy (endoscopy) Personally review pathology Get a second opinion Have a frank discussion with patient

Polyps Natural history of adenomatous polyps Biology of polyps Cancer epidemiology The anatomy of the polyp Correlations with Malignancy Endoscopic polypectomy alone??? Special considerations Indications for Polypectomy What if it’s clipped in ½ What if it’s shredded by forceps? Pathology… Marking/tattoo Chances of Malignancy by histopath and size/morphology * NO technique **