familial adenomatous polyposis

case discussion on fap

1. Familial adenomatous polyposis with Ca colon Dr. Ved Prakash Sah Moderator: Prof. Vikas Gupta

2. Name: Mrs. RK Age/sex: 39 yr /f Cr no: 201606368557 Admission no: 2017030707 Address: Firozpur , Punjab DOA: 02.05.2017 DOSx : 04.05.2017 DOD: 12.05.2017 Index Case

3. Pain abdomen x 3 years Insidious onset Dull aching, mild in intensity Diffuse whole abdomen Non-radiating Generalised weakness x 3 years a/w easy fatiguability and palpitation LOW and LOA + Clinical History

4. No h/o fever No h/o jaundice/vomiting No h/o abdominal distension/constipation No h/o lump abdomen No h/o hematemesis, hematochezia and dark colored stool Clinical History

5. No h/o any comorbidities Mixed diet No addictions No h/o blood transfusion Past and personal history

6. No h/o similar illness in any family members No h/o any malignancy in any family members Family tree Family history

7. General examination Pallor + No icterus / cyanosis / clubbing / generalized lymphadenopathy / pedal edema No supraclavicular LAP Vitals PR: 88/min BP: 110/70mmHg Afebrile Clinical examination

8. Scaphoid Soft No lump palpable No Free Fluid Bowel sounds + PR examination – normal Abdominal examination

9. INVESTIGATIONS Pre Op 03 /5/17 Post Op 05 /05/17 Post Op 09 /05/17 Hb (g/ dL ) 10.7 12.7 10.2 TLC 9200 13600 10500 Platelet 405k 241k 281k Bil (T/C)mg/ dL 0.4/0.02 0.7/0.25 0.3/0.1 TP/Alb(g/ dL ) 5.5/3.1 4.4/2.3 5.3/2.2 OT/PT(U/L) 16/18 23/18 15/20 ALP(U/L) 102 104 106

10. S. CEA- 39.6 U/ml (Normal range: <4 U/ml) IgA tTG - negative Investigations

11. USG Abdomen (01/11/2016)-outside Concentric bowel wall thickening in hepatic flexure region (>5 cm) Multiple (>6) hypoechoic masses , largest measuring upto 38x41 mm in post parametrium wall of uterus ?fibroid Imaging investigations

12. Mild thickening of the hepatic flexure and adjacent transverse colon upto 15 mm. Mild dilatation of the proximal colon also noted Multiple uterine fibroids, largest is subserosal and is 46 mm in size. CECT abdomen & pelvis (22/11/2016)- outside

13. A large proliferative growth obliterating lumen ?proximal ascending colon ?caecum Rest of the colonic mucosa studded with sessile polyps of varying size (0.5-1 cm), more in proximal colon than the distal colon. Bx (04/01/2017) S-284/17 Ascending colon- adenoma Transverse colon and rectosigmoid - polyadenomatous with high grade dysplasia Rectum (normal mucosa)- morphological description Colonoscopy (04/01/17) 4860/17

14. Gastric fundus- multiple small polyps + D2- 2 small polyps + Bx (04/01/17) S-317/17 Stomach, fundus- fundic gland polyp Duodenum- mild inflammation UGIE (04/01/17 )

15. FAP with Carcinoma Right Colon (Hepatic flexure) Diagnosis

16. Total Proctocolectomy + IPAA + covering loop ielostomy Surgery ( DOSx : 04.05.2017)

17. No ascites No liver/ omental /peritoneal deposits 6x7 cm hard mass in hepatic flexure Multiple enlarged paracolic lymphnodes + (max. 1x1.5 cm) Uterus enlarged, multiple fibroid uterus of variable number and size Intraop findings

18. Intraop image

19. Cut section images

20. Closer view

21. Colectomy specimen- Adenocarcinoma, moderately differentiated arising in adenomatous polyposis with high grade dysplasi Lymph node (1/18)- involved by the tumor Tumor infiltrating muscularis propria and reaching upto subserosal adipose tissue (T3) Lymphovascular invasion absent Proximal doughnut- free of tumor Distal doughnut- colonic mucosa with adenomatous polyp with low grade dysplasia HPR (S-11853/2017)

22. Immediate post op- hemodynamically stable RT removed on POD1 Oral sips started on POD1 Stoma functional on POD2 Stoma was healthy with average output 600 ml/day PUC out on POD2, self voided Drain removed on POD5 Discharged on POD8 Post op period

23. Patient doing well Wound healthy No fresh complaints Stoma healthy & functional Stoma output 600-800 ml/day PR- normal In view of lymph node positivity adjuvant chemotherapy started (FOLFOX regimen) Follow Up

24. DISCUSSION

25. Introduction Genetics of FAP Pathogenesis of ca colon in FAP Indications of surgery Postop surveillance Chemoprevention Genetic testing Family screening Conclusion DISCUSSION

26. Introduction Burt RW. Colon cancer screening. Gastroenterology . 2000 Sep 30;119(3):837-53.

27. Incidence: 1 in 10000 live births M:F=1:1 Classic FAP is c haracterised by Multiple colonic adenomatous polyps (>100) Early age of onset Inevitable development of colon cancer unless the colon is removed Familial Adenomatous Polyposis(FAP)

28. Inheritance: Autosomal dominant Penetrance: 100 % Family h/o FAP: upto 70% De novo mutation: upto 30% Genotype: APC gene, TSG, 5q21 Mutation: Truncated germline mutation Genetics

29. APC gene and FAP Jo WS, Chung DC. Genetics of hereditary colorectal cancer . InSeminars in oncology 2005 Feb 28 (Vol. 32, No. 1, pp. 11-23).

30. S.No Benign Lesions Malignant lesions 1. Congenital hypertrophy of the retinal pigment epithelium (70-80%) Duodenal tumors (3-5%) 2. Epidermoid cyst (50%) Brain tumors (2%) ( Turcot syndrome ) 3. Osteoma (50-90%) (Gardener syndrome) Thyroid cancer (2%) 4. Desmoid tumour (10-15%) Pancreatic cancer (1.7%) 5. Supernumery teeth (11-27%) Ampullary carcinoma(1.7%) 6. Adrenal gland adenomas (7-13%) Hepatoblastoma (1.6%) 7. Gastric cancer (0.6%) Extra-intestinal features in FAP Galiatsatos P, Foulkes WD. Familial adenomatous polyposis . The American journal of gastroenterology. 2006 Feb 1;101(2):385.

31. Attenuated familial adenomatous polyposis (AFAP) Mutations close to the 5’ end of the APC gene Autosomal dominant MUTYH-Associated Polyposis (MAP) Caused by mutation in the MutY homolog (MYH) gene, a base excision repair gene, 1p34 Autosomal recessive Variants of FAP

32. Adenoma-carcinoma sequence Ivanovich JL, Read TE. A practical approach to familial and hereditary colorectal cancer . The American journal of medicine. 1999 Jul 31;107(1):68-77.

33. Once FAP has been diagnosed, the aim is to perform prophylactic surgery Timing of surgery: late teens to early twenties Indications of early surgery Documented or suspected cancer Significant symptoms Polyps >10 mm diameter Polyps with high grade dysplasia Marked increase in polyp number on consecutive examinations Management of large bowel Syngal S et al. ACG clinical guideline. The American journal of gastroenterology. 2015 Feb;110(2):223.

34. Surgical options available Total proctocolectomy with permanent end ileostomy Total proctocolectomy with continent ileostomy ( Kock ) Total colectomy with IRA Pros-Superior functional results Cons-Leaves the rectum intact Total proctocolectomy with IPAA ± covering loop ileostomy Choice of operation

35. Includes: Annual endoscopy of rectum or ileal pouch Examination of an ileostomy every 2 years Postsurgical surveillance

36. The goal is to reduce the appearance of new polyps and possibly induce regression of existing ones. However they don’t prevent cancer. These are: NSAID: Sulindac Selective COX-2 inhibitor: Celecoxib O mega-3 PUFA: Eicosapentaenoic acid (EPA) West N et al: Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut 59:918, 2010 Chemoprevention

37. Genetic counselling Integral part of genetic testing Genetic testing APC gene mutation can be found in 80-90% of FAP families with present technology Laboratory method available Protein truncation testing Gene sequencing Linkage testing Genetic Testing

38. S.No Family Setting Approximate lifetime risk of colon cancer 1. General population risk in the US 6% 2. One first-degree relative with colon cancer 2-3 fold increased 3. Two first-degree relatives with colon cancer 3-4 fold increased 4. First-degree relative with colon cancer diagnosed at ≤50 years 3-4 fold increased 5. One second- or third-degree relative with colon cancer About 1.5 fold increased 6. Two second-degree relatives with colon cancer About 2-3 fold increased 7. One first-degree relative with an adenomatous polyp About 2-fold increased Family risk Winawer S et al. Colorectal cancer screening and surveillance : clinical guidelines and rationale—update based on new evidence. Gastroenterology . 2003 Feb 1;124(2):544-60.

39. Colonoscopy annually starting at the age of 10-12 yrs , continuing until age of 35 if negative Flexible proctosigmoidoscopy at age 12-14 yrs ; repeat every 1-2 yr until age 35 and thereafter every 3 yr Upper GIE every 1-3 yr starting when polyps first identified Family screening Syngal S et al. ACG clinical guideline. The American journal of gastroenterology. 2015 Feb;110(2):223. S.No Site Age to begin surveillance (years) Surveillance interval (years) Surveillance procedures and comments 1. Colon 10-15 1-2 Flexible sigmoidoscopy or colonoscopy 2. Upper gastrointestinal 25-30 1-5 EGD 3. Thyroid Late teenage years 1 Annual thyroid examination; annual thyroid USG 4. Intrabdominal desmoids 1 Annual abdominal palpation.

40. Conclusion Hereditary component to be evaluated and ruled out in young patients with CRC Family members- counselling Correct and effective screening- reduces mortality and morbidity due to syndromic malignancy

41. THANK YOU!!!