Colorectal Neoplasia. Dr. Smita Devani MBChB, MRCP. Consultant Physician and Gastroenterologist Aga Khan University Hospital, Nairobi

Transcription

1 Colorectal Neoplasia Dr. Smita Devani MBChB, MRCP Consultant Physician and Gastroenterologist Aga Khan University Hospital, Nairobi

2 Case History BT, 69yr male Caucasian History of rectal bleeding No change in bowel habit Non smoker FHx - father died of stomach cancer at 85yrs Examination normal

3 Case History Colonoscopy Caecum reached 3.5cm sessile polyp found in the ascending colon - biopsy showed tubulovillous adenoma Smaller polyps in the sigmoid colon which were hot biopsied

4 Case History Patient informed of need to do mucosal injection and piecemeal biopsy Warned of risk of perforation and possible need for surgery

5 Case History Repeat colonoscopy 6mls of diluted methylene blue and normal saline injected to raise the polyp and piecemeal polypectomy done Histopathology showed tubulovillous adenoma

6 Colonoscopy

7 Colonoscopy

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9 Colorectal Carcinoma (CRC) In 2006, > 500,000 deaths worldwide due to CRC * Population screening effective in reducing mortality ** * Jemal A, Tiwari RC, Murray T, et al. Cancer statistics CA Cancer J Clin 2004;54: ** Winawer SJ, Zauber AG, Ho MN, et al. The National Polyp Study Workgroup. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993;329:

10 Colorectal Carcinoma Usually a premalignant precursor precedes cancer Natural history of cancer progression 5-10 yrs

11 Colorectal Neoplasia

12 Colorectal Neoplasia

13 Colorectal Neoplasia Types of polyps Frank Cancer Malignant polyps Villous Tubulovillous Adenomatous Serrated Hyperplastic

14 Colorectal Polyps Tubular adenoma Adenomatous polyp Serrated polyp

15 Colorectal neoplasia

16 Colorectal Neoplasia Malignant polyps Whole polyps should be surrendered Check for invasion of stalk histologically and ultrasound Tumour differentiation Vascular or lymphatic invasion Lymphatic channels not visible under light microscopy Immunohistochemistry helpful but not widely used

17 Normal Adenoma (early) 2-5 yrs Adenoma (advanced) Early Cancer 2-4 yrs Late Cancer

18 Aetiology familial risk HNPCC FAP Hamartomatous polyposis syndromes sporadic cases

19 Aetiology Inherited types FAP (familial adenomatous polyposis) - constitute about 1% HNPCC (Hereditary non polyposis colorectal carcinoma) - constitute about 5-10%

20 FAP Autosomal dominant Thousands of polyps Extracolonic findings eg osteomas, desmoid tumours, pigmented retinal lesions, periampullary tumours, upper GI tract polyps, brain tumours

21 FAP

22 MAP Attenuated FAP R sided predominance UGI lesions present usually in the teens mean age of CRC yrs

23 FAP Deletion of chromosome 5q21 (known as the APC gene) in neoplastic cells (somatic mutation) Genetic testing standard of care DNA testing for APC gene mutations has a sensitivity of 70% to 90% and a specificity of 100%

24 FAP Flexible sigmoidoscopy from 10 to 12 years of age Colonoscopy from 18 to 20 years of age If adenomas are detected, surgery considered Routine OGD surveillance as there is high risk for potentially precancerous gastric and duodenal adenomas

25 HNPCC Autosomal dominant Median age of developing cancer is <50yrs Unusually have proximal bowel cancers Can have multiple cancers In women increased association with endometrial and ovarian cancers

26 HNPCC Lifetime risk % Endometrial ovarian gastric urinary tract renal cell biliary CNS small bowel

27 HNPCC

28 HNPCC

29 Sensitivity of Clinical Criteria Criteria Specificity Sensitivity Amsterdam 1 54% 62% Amsterdam 2 78% 48% Bethesda 89% 53% Kievit W, Clinical Genetics 2004: 65;

30 HNPCC In addition to testing for MSI, genetic testing is available for three mismatch repair genes, hmsh2, hmlh1, and hmlh6, which account for about 90% of all HNPCC cases

31 HNPCC Colonoscopy from 20 to 25 yrs of age Recommended screening for women includes annual transvaginal ultrasound or endometrial aspiration, beginning at age 25 to 35 years

32 When To Use Genetic Testing When inherited syndrome suspected Syndrome FAP HNPCC relatives PJ JP Setting >10 adenomas CRC<50, 2 CRC PJ polyps, pigment >5 JPs

33 Colorectal Carcinoma Other conditions Inflammatory bowel disease Obesity, cigarette smoking increase the risk?increased fat intake, red meat, fruits and fibre Possibly calcium supplements help Folate, ASA compounds, HRT,NSAIDs, physical activity

34 Pathogenesis About 30% of pts over >50yrs have colonic polyps 5% of these polyps will progress to carcinoma Flat polyps more likely to become malignant

35 Pathogenesis Certain amount of genetic instability already present in small adenomas Existence of multiple chromosomal instability causes progression Cell biologic processes, such as proliferation, differentiation, apoptosis, and invasion

36 Microsatellite Instability APC gene Ras gene TGFβ p53 Other mutations Normal Small adenoma Large adenoma Cancer metastasis Chromosome or microsatellite instability

37 Microsatellite Instability Microsatellites are genomic regions in which short DNA sequences or a single nucleotide is repeated During DNA replication, mutations occur in some owing to misalignment of their repetitive subunits and result in contraction or elongations These are usually repaired by mismatch repair proteins

38 Microsatellite Instability However repair is inefficient in tumors with these protein deficiency This occurs in >50% of microsatellites in the tissue and is easy to detect HNPCC - MSH2 and MLH1 not tested if MSI absent. Not so for MSH6 Most microsatellites occur in non coding DNA no effect on protein synthesis Some genes have MIS in coding regions and results in altered proteins

39 Pathogenesis NSAIDS / ASA Reduce mortality from colorectal carcinoma by 40-50% 1 Reduce the number and size of the polyps 2 Induce regression of polyps in FAP 3 1 Smalley W,Dubois RN.Colorectal cancer and non-steroidal anti- inflammatory drugs.adv Pharmacol 1997;39: Shiff SJ,et al.nonsteroidal anti-inflammatory drugs and colorectal cancer:evolving concepts of their chemopreventive actions.gastroenterology 1997;113:

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41 Polyp Cancer Sequence

42 Diagnosis Faecal Occult Blood Testing (FOBT) Risks missed cancers 50% of cancers will be +ve FOBT while in advanced neoplasia 21%* Reduce mortality by 15-33% false reassurance *Lieberman et al Veterans Affairs Cooperative Study Group 380. One-time screening for colorectal cancer with combined fecal occult-blood test and examination of the distal colon. N Engl J Med 2001; 345:

43 Diagnosis Faecal immunochemical test (FIT) Done annually No dietary restrictions Positive test indication for colonoscopy

44 Diagnosis Stool DNA tests DNA FOBT 10 0 cancer cancer + HGD advanced

45 Diagnosis CT Colonography Effectiveness sensitivity good interobserver variability evaluation of extracolonic features referral to colonoscopy

46 Diagnosis Double contrast barium enema Every 5 years Decision based on Patient preference Cost Radiologist training

47 Diagnosis Colonoscopy best tool for polyp detection and cancer prevention 2-12% of polyps >1 cm not found requires highly qualified endoscopist

48 Diagnosis Complications of Colonoscopy Serious complications 2-3/1000 incomplete exams missed lesions incompletely removed lesions

49 Current Guidelines for Screening Colonoscopy every 10 years If adenomatous polyps, family history of CRC or polyps Inflammatory bowel disease

50 Treatment Polypectomy Endomucous resection NSAIDs for polyps Chemoradiotherapy for downgrading tumours

51 Treatment Surgery Laparoscopy Open surgery Surgery for metastases - liver or lung resection CEA - guide for recurrence

52 Treatment Palliative Chemotherapy Stenting for stenosing tumours Surgery To stop bleeding Stenosing tumours Urethral blockage

53 Low Public Compliance!