Colonic Polyp.,U.S. Multi-Society Task Force recommendation,2021 ACG guidelines

Colonic Polyp.,classification,clinical features,managementU.S. Multi-Society Task Force recommendation,2021 ACG guidelines

1. Colonic Polyps Dr. Vijaya K.C. DM resident

2. Introduction CRC is 3 rd most common cancer in USA Adenomatous polyps and sessile serrated adenomas (SSAs), are precursors to CRCs Polyps , estimated to be present in 20% - 53% of > 50 years of age.

3. Definition ‘Polyp’ - derived from Greek - polypous - ‘morbid lump.’  A polyp is a discrete mass of tissue that protrudes into the lumen of the bowel. Classification: mucosal or submucosal neoplastic or non-neoplastic

4. E pidemiology: colonic polyp in nepal JNHRC Vol. 19 No. 3 Issue 52 Jul - Sep 2021

5. Epidemiology: colonic polyp Li et al. Journal of Translational Medicine (2024) 22:361

6. Prevalence of adenomatous colonic polyps

7. Conventional Adenomas Benign, premalignant neoplasm Most common neoplastic polyp V aries with patient age, sex, and family history M:F: 1.5:1 Prevalence in screening populations :20-60% E arly adenomas < 10 mm ;low risk of progression to CRC. Advanced adenomas : colon polyps ≥10 mm or with villous or HGD, up to a 5% annual progression rate to CRC.

8. Conventional Adenomas Always dysplastic 2/3 of all colonic polyps Precursor to most CRC At diagnosis: • Majority <10 mm • 30-50% synchronous adenomas • 3-5% invasive carcinoma. • 27 - 36 % flat • 1% are depressed • Often HGD or malignant

9. C onventional adenoma-Incidence F irst adenoma: 24-41 % Low risk for CRC prevalence: 12 % Intermediated and high risk for CRC:30-40 % Recurrence rate of new adenoma in 3-5 yrs: 20-50%. In prior h/o adenoma, 34.1% have a new adenoma on surveillance colonoscopy.

10. Conventional adenoma: location Distal adenomas -clinical attention because of bleeding or colon obstruction P roximal adenomas common in African americans & hispanics >>whites. J Taibah Univ Med Sci 2023 Jan 4;18(4):855–859

11. Multiple Adenomas and Carcinomas ≥2 adenomas. Synchronous lesions: adenoma & carcinoma ,diagnosed at same time Metachronous lesions: Carcinoma diagnosed 6 mths later 30-50% adenoma are synchronous, in elderly. CT colonography/colonoscopy strongly recommended before CRC surgery.

12. C onventional adenoma-pathology HGD -5% to 10% I nvasive carcinoma - 5% to 7%. HGD: L arger adenoma with greater villous content. D iminutive (1 - 5 mm), small (6 - 9 mm),& large (≥10mm). A denomas > 1 cm : higher prevalence -26-40 % L arger adenomas: distal colon.

13. C onventional adenoma-pathology Tubular adenoma: C omplex network of tubular glands,bunched or extensively branching, not extend below the muscularis layer. V illous adenomas: Adenomatous glands extend in a straight pattern upward from the polyp’s stroma to the surface, giving the appearance of long,finger -like projection. Tubulovillous adenomas : combination of these 2 histologic types.  Malignant Polyp: a/w invasive carcinoma Tubular adenoma:80-86 % Tubulovillious adenoma: 8-16% Villous adenoma: 3-16%

14. Histopathology-serrated lesions S aw-tooth like in-folding of the epithelial crypts. HPs: elongated crypts with serrated architecture @ upper ½ of crypts, proliferation @ basal ½ of crypt. SSAs: hyper serration and dilatation extending to lower 1/3 of crypt base , and T- or L-shaped branching. TSAs: classical cytological dysplasia and prominent serration, cytoplasmic eosinophilia, vesicular and stratified nuclei, ectopic crypt formation .

15. Malignant Potential of Adenomatous Polyps S ize, histologic type, and degree of dysplasia  Malignant risk: larger adenoma size, more villous,& HGD Advanced adenoma: >1 cm in diameter, or if <1 cm,and >25% villous architecture HGD or carcinoma

16. Diminutive Polyps 1-5 mm ≅ 90% of polyps are diminutive on routine colonoscopy. In screening colonoscopy, reported up to 64 %.

17. Flat Adenomas Macroscopically: completely flat or slightly raised ± central depression. Polyp’s diameter twice its thickness small(< 1cm) likely missed in endoscopy C hromoendoscopy or NBI: higher detection rates 8.5%-12% of all adenomas. 10 times more likely to harbor a carcinoma, Low incidence of K- ras,APC gene mutation.

18. Risk factors for adenomas Inherited Susceptibility Familial:2-3 times risk Diet and Lifestyle cigarette smoking, excess alcohol intake, excess dietary fat, and obesity Predisposing Conditions Ureterosigmoidostomy Sites Acromegaly Bacterial and Viral Infections The Colonic Microbiome Cholecystectomy P rotective measures: physical activity intake of calcium, and folate cereal fiber intake vitamin D intake use of NSAIDs(inc. aspirin)

19. Predisposing Conditions for adenoma 3 conditions: Ureterosigmoidostomy Acromegaly Streptococcus gallolyticus bacteremia. C olorectal examination and, periodic surveillance : Ureterosigmoidostomy , Acromegaly Cholecystectomy: modest risk to women and in the proximal colon.

20. Risk factors-SSA,HP,TSA S moking Tobacco use advancing age W omen O besity Diabetes Mellitus

21. Pathogenesis-Cellular Growth C olonocytes: cycles of division, proliferation, differentiation, and shedding. C omplete renewal of colonic epithelium approx every 5 days. C olonocytes renewal process interrupted by: genomic alterations alone or mutagenic environmental factors

22. Pathogenesis- Molecular Pathogenesis A denoma to carcinoma sequence Sessile serrated pathway. C onventional adenoma and SSA develop via chromosomal instability (CIN) microsatellite instability (MSI) Major drivers : somatic mutations of 30 genes. Tumor suppressors genes: APC,TP53 Oncogens: KRAS,PI3KCA, BRAF, and NRAS 85% sporadic CRC arise from con. adenoma A ctivation of oncogenes I nactivation of tumor suppressor genes

23. Molecular Pathogenesis-Adenoma-carcinoma pathway

24. Molecular pathogenesis: Sessile serrated pathway BRAF oncogene K- ras mutations of APC, TP53, and MSI are infrequent

25. Clinical Features A symptomatic to nonspecific O ccult or overt PR bleeding Intermittent bleeding doesn’t cause anemia Large polyps in distal colon : constipation, cramping pain. McKittrick-Wheelock syndrome: secretory diarrhea

26. Methods for Detection Fecal Occult Blood Testing Fecal Immunochemical Testing Barium Enema Sigmoidoscopy Colonoscopy CT Colonography Stool DNA Testing

27. Fecal Occult Blood Testing-Guaiac test S ensitivity for adenomas < 9 mm ≅ 7.0% A symptomatic persons >40 years,1%-3% occult blood + ve . C hemical peroxidase reaction F alse positives can occur  False positive: Ingestion of nonhuman heme ( eg , meat products) Ingestion of peroxidases ( eg , broccoli) Ingestion of non- Gl blood ( eg , epistaxis) Use of aspirin, NSAIDs, or anticoagulant medication False Negative: Ingestion of antioxidants ( eg , Vitamin C)

28. Fecal Immunochemical Testing Ab -based detection of human Hb in stool D oes not require dietary restrictions Q uantitative test D etects more cancers >> adenomas CRC detection Sn/ Sp =79%/94% A dvanced adenomas Sn:10-70% S uperior to guaiac-based FOBT I nadequate for adenoma screening False positive: Use of aspirin, NSAIDs, or anticoagulant medication False negative: Bleeding from the upper Gl or proximal lower Gl tracts

29. Stool M ulti-target DNA test F irst multi-target DNA test (Cologuard) was approved by the FDA in 2014. Sn/Sp.: 92%/ 87%,respectively, for CRC D etected only 42% of advanced adenomatous polyps.

30. Barium Enema Single(barium) vs Double contrast ( barium+air ) barium enema (DCBE) technique Colonoscopy preparation Barium+air insufflation inside colon via rectal tube (e.g. Miller) and take xray of colon. Detection depends upon size National Polyp Study, the detection rates <6 mm:32% 6-10 mm:53% >10 mm :48% Contraindications: Suspected colonic perforation Toxic megacolon Pseudomembranous colitis Rectal biopsy within 7-10 days. A naphylaxis to barium

31. Sigmoidoscopy/Colonoscopy S creening sigmoidoscopy a/w 21%-38% ↓in mortality from distal CRCs. Colonoscopy preferred to sigmoidoscopy G old standard for detecting adenomas Current guidelines recommend ADR 20% in women 30% in men ADR vs colonoscopy withdrawl time 28.3% ≥6 mins 11.8 % <6 mins Chromoendoscopy-small increment in ADR.

32. A ssessment of colonic polyp 1.Surface pattern NICE classification Kudo Pit Pattern classification 2. Morphology Paris classification Laterally spreading tumor Non-lifting sign 3. Histology Haggitt classification Kikuchi classification

33. NBI International Colorectal Endoscopic classification system: NICE-2009 C lassifies polyp based on morphology : Color Distribution of vessels Surface pattern. Importance of potential malignant polyp recognition Type 3 polyps : needs tattoo localization & surgery.

34. Kudo pit pattern classification-1990 R equiring magnification colonoscopy with dye spray T o evaluate polyps for malignancy by characterization of pits A ccuracy: NICE vs Kudo:82% vs. 81%

35. P aris classification-2002 Consortium of endoscopists, pathologists & surgeons at Paris Types II and III -nonpolypoid forms T ype I-Pedunculated/sessile polyp

36. Non lifting sign Fluid injected under the polyp fails to lift the lesion Suggests deep submucosal invasion Also seen in fibrosis from prior biopsy, cautery, tattoo

37. L ateral spreading tumor Superficial non-polypoid lesions >10 mm diameter extending laterally than vertically . I ncidence: 9 % T ypes: Granular (LST-G) Non-granular (LST-NG) types LST-G + homogenous nodular pattern : low risk of local invasion (< 2%) LST-G + mixed-size nodules,>30 mm: up to 30% risk LST-NG + pseudo-depression : highest risk of SMI LST-G mixed type or LST-NG in rectosigmoid: highest risk for CRC. World J Gastrointest Endosc 2021 September 16; 13(9): 356-370

38. H aggit classification Histopathological assessment Determining adequacy of endoscopic resection. Level of invasion in pedunculated and sessile polyps

39. Kudo and K ikuchi classification Classifying sessile polyps into 3 levels based on the degree of SMI: SM1–invasion into the upper third of the submucosa SM2–invasion into the middle third SM3–invasion into the lower third

40. AI in screening colonoscopy Emerging technologies that improve polyp detection A pproved by the FDA in 2021 computer-assisted polyp detection ADR was also increased by AI approx. 4% U se in endoscopic polyp classification. DING et al: THE COMBINATION OF AI AND COLONOSCOPY 2023

41. CT Colonography Virtual colonoscopy Helical or spiral CT scanner P roduce both 2D/3D images Standard bowel preparation Colon is distended with air or carbon dioxide Images are taken in the supine and prone positions without sedation Sensitivity : 29% -59% for small polyps 47% -82% for medium polyps 63%- 92% for large polyps.

42. C olon capsule endoscopy 81% sensitivity and 93% specificity for polyps ≥6 mm Minimally invasive Does not require sedation Requires bowel preparation Positive examinations require colonoscopy Am J Gastroenterol 2021;116:458–479

43. Adenoma: Natural History without Treatment A denoma to carcinoma: slow progression, 5-10 yrs S ize of the index polyp affects the interval to carcinoma. 1 cm polyp: risk of CRC: 2.5 %@5 yrs,8% @10 yrs,24% @20 yrs of diagnosis A more recent CTC study followed 306 patients with polyps <9 mm for a mean of 2.3 yrs. Results: 22% of polyps grew in size 50% remained stable 28% regressed(10% -complete regression)

44. Natural History: SSA, HP, TSA  SSA-85%-non-dysplastic, 12%-LGD, 2%-HGD and 1%-adenocarcinoma.  32.4% of SSAs ≥ 20 mm with dysplasia and 3.9% -SMI. 10-year risk for CRC for SSA≅ 3.2% SSAs a/w : synchronous and metachronous cancers + MSI cancers.

45. Treatment If a polyp is detected by BE or CTC, colonoscopy is recommended All polyps should be removed if decetcted Removal of a polyp : histologic diagnosis L arger polyps: piecemeal resection S essile polyp: lifting the polyp then EMR/ESD.

46. Resection for pedunculated polyps pedunculated polyps <20 mm,stalk <5 mm : Hot snare polypectomy pedunculated polyps >20 mm,stalk >5 mm : Hot snare polypectomy+ bleeding prophylaxis like : Clipping Inj. epinephrine L igation with detachable loop devices

47. Resection for nonpedunculated polyps S essile lesions :stratified based on size D iminutive lesions: C old snare polypectomy Large cold forceps polypectomy S essile lesions ≥10 mm: risk of malignancy Polyp, NICE Type 3 or Kudo V-VI, confirmatory biopsy : refer to surgeon N oninvasive lesions 10–19 mm : C old snare polypectomy or Cold EMR N oninvasive, nonpedunculated lesions ≥20 mm: EMR

48. Gastroenterology Report, 11, 2023, goad027 World J Gastrointest Endosc 2021 September 16; 13(9): 356-370

49. Management of the Malignant Polyp CA, invaded beyond the muscularis mucosae into the submucosa EMR/ESD with clear margin: HGD or intra-mural adeno CA ;curative Surgery : main stay of treatment

50. Polyp Recurrence Rates C olonoscopic polypectomy a/w reduction in CRC mortality 20% at 5 yrs, 50% at 15 yrs after polypectomy 1/3 pts will develop recurrent adenomas . R isk factors for adenoma Recurrence: P olyp>1 cm HGD Villous histology Older age Adenoma at proximal location

51. Surveillance Colonoscopy H istory of adenomas or cancer. A complete colonoscopy at the time of polypectomy >1 colonoscopy sessions : Large or multiple polyps family h/o CRC : every 10 years Journal of Gastroenterology and Hepatology 38 (2023) 854-864

52. Recommendations for follow-up after colonoscopy and polypectomy Gupta et. al Gastroenterology 2020;158:1131–1153

53. CRC screening AVERAGE RISK CATEGORY: No history of colorectal cancer or adenomatous polyps. No family history of colorectal cancer. No history of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. No known or suspected h/o colon cancer (Lynch disease or HNPCC), FAP, or Peutz-Jeghers syndrome and MUTYH-associated polyposis. No history of undergoing radiation therapy as a previous cancer treatment for the abdominal or pelvic area. HIGH RISK CATEGORY: all positive history RECOMMENDATIONS Colorectal cancer screening should begin before the age of 45 and should be tested more frequently with specific RECOMMENDATIONS - Colorectal cancer screening should start at the age of 45 by either using a stool-based test or a visual exam of the colon or rectum. Stool-based screening tests for colorectal cancer: Fecal Immunochemical Test (FIT)- every year Guaiac-based Fecal Occult Blood Test ( gFOBT )- every year Multi-targeted stool DNA Test (mt- sDNA )- every 3 years Visual exam for colon and rectum: Colonoscopy- every 10 years CT colonography- every 5 years Flexible sigmoidoscopy (FSIG)- every 5 years OTHER RECOMMENDATIONS • People who have a life expectancy of more than 10 years and who are in good health should continue to get routine colorectal cancer screening until they are 75 years of age. • From age 76 to 85, the colorectal cancer screening should be done according to the person’s preferences, also considering the previous screening history, general health of the person, and his/her life expectancy. • ACS doesn't recommend colorectal cancer screening after the age of 85 years. 2023 Jayasinghe et al. Cureus 15(4): e37509. DOI 10.7759/cureus.37509 

54. Non-neoplastic polyps Juvenile polyps and Peutz-jeghers polyps Inflammatory polyps

55. Juvenile Polyps M ucosal tumors with excess of lamina propria and dilated cystic glands. C ommon age :1 - 7 years O ften single than multiple P edunculated, and size: 3 - 20 mm C ommon site: R ectum Highly vascular N o malignant potential when solitary No recurrence after removal or spontaneous loss.

56. Peutz-Jeghers Polyps Unique hamartomatous lesion S mooth muscle core arising from the muscularis mucosae and extending into the polyp E xtraintestinal Features: perioral freckles or pigmentation. Colonoscopy screening begin at age 8. If polyps are present : every 3 years If no polyps : repeat at age 18, then every 3 years, or earlier if any symptoms occur.

57. Inflammatory Polyps- Pseudopolyps Found in the regenerative and healing phases of inflammation Full-thickness ulceration of the epithelium f/b regenerative process leading to polyps formation. Large and solitary mimics a neoplastic mass Severe colitis: IBD, amebic colitis, ischemic colitis , bacterial dysentery. Giant or grouped pseudopolyps : colonic obstruction

58. Mucosal Prolapse Polyps Consisting of stromal and epithelial components and inflammatory cells Submucosa has elevated the normal tissue overlying it Mechanical trauma No clinical significance.

59. Colitis Cystica Profunda and Superficialis R are submucosal lesions consisting of dilated, mucus-filled glands S olitary or multiple polyps a /w Peutz-Jeghers disease in children A ssociation: S urgical trauma C olitis Adenocarcinoma N iacin deficiency (pellagra ) T ropical sprue L eukemia.

60. Pneumatosis Cystoides Coli Multiple gas-filled cysts within the mucosa, submucosa and subserosa. Site :C olon & small Intestine C/F: Abdominal distention: volvulus or pneumoperitoneum B leeding A scites-rare R x: Oxygen therapy

61. Other polyps Benign lymphoid polyps Malignant lymphoma and CLL . Colonic lipomas Carcinoids Metastatic neoplasms Fibromas, neurofibromas, leiomyomas, granular cell tumors, Hemangiomas, and endometriosis.

62. T ake home message C olonic polyps are common Most c olonic polyps are asymptomatic C orrect identification and Mx of polyps to prevent CRC. Endoscopic classification of a polyp specify management plan Hot snare ,gold standard for pedunculated polyp resection Diminutive polyps removed by large forceps Nonpedunculated noninvasive lesions (3-20 mm) removed by cold snare Large polyp >20 mm removed by EMR/ESD Advances in AI may revolutionize endoscopic polyp classification and overall outcomes of colonoscopy.

63. References Sleisenger and fordtran’s gastrointestinal and liver disease, 11th Edition Curr Opin Gastroenterol 2024, 40:14–20 N Engl J Med 2016;374:1065-75 Journal of Gastroenterology and Hepatology 38 (2023) 854-864 U.S. Multi-Society Task Force recommendation,2021 ACG guidelines Gupta et al Gastroenterology Vol. 158, No. 4 Ann Laparosc Endosc Surg 2023;8:30 | https://dx.doi.org/10.21037/ales-23-10 Ther Adv Gastrointest Endosc 2021, Vol. 14: 1–14 World J Gastroenterol 2012 May 28; 18(20): 2452-2461

64. T hank you!