1. Colorectal Cancer Alex Ashby aca2g11@soton.ac.uk A full version of this PowerPoint will go up after the session – do not worry about filling in all the blanks if you don’t have time!

2. The Plan Colorectal anatomy and physiology Background to cancer Colorectal cancer DAPSICAMP Some Past Questions if we have time

3. Background Anatomy & Physiology

4. Colorectal Anatomy I ______ up until 2/3 along transverse colon ________Mesenteric artery branches _______up until 2/3 along anal canal (________line) ________Mesenteric artery branches Lower 1/3 anal canal ______________ artery from internal _________ artery from internal iliac artery

5. Colorectal Anatomy II Midgut up until 2/3 along transverse colon Superior Mesenteric artery branches Hindgut up until 2/3 along anal canal (pectinate line) Inferior Mesenteric artery branches Lower 1/3 anal canal Inferior rectal artery from internal pudendal artery from internal iliac artery

6. Colorectal Physiology ______ H 2 O absorbed per day Absorbs electrolytes Stores stool Peristalsis to anorectal area in response to distension

7. Background to Cancer

8. Hallmarks of Cancer Genetic instability underlies all “IM SARCOMA” Inflammatory Microenvironment Self-sufficiency in growth signalling Apoptosis evasion Resistance to growth inhibition Continuous replication Metastasis/tissue invasion Angiogenesis

9. Tumour nomenclature Cancer = ____________________ Does not incliude benign tumours Benign Well differentiated, slow growing, well circumscribed, no metastasis -oma vs –sarcoma vs –carcinoma vs –blastoma vs germ cell tumours Leukaemia/lymphoma -adeno-

10. Colorectal Cancer DAPSICAMP

11. Definition Cancer of the colon Includes caecum, appendix, ascending, transverse, descending, sigmoid, rectum 98% __________________ 2 nd most common cancer in Western world 55k/100k/yr men 40k/100k/yr women

12. Aetiology Risk factors Non modifiable Gender (male) Age FHx Genetics Previous cancer Modifiable Exercise Smoking Obesity Diet (low fibre/red meat) Long-standing Ulcerative Colitis Protective factors High fibre Vegetables Exercise Aspirin HRT in females

13. Pathophysiology I

14. Pathophysiology II Cancer genetics Types of genes related to cancer ___________ Help turn normal cells into tumour cells Before they become mutated they are proto-oncogenes __________________ Follow 2 hit hypothesis _________________ (e.g. DNA mismatch repair genes – mutated in HNPCC)

15. Pathophysiology III Cancer genetics II Specific cancer genes ______ (oncogene) Activation of ras signalling →cell growth, differentiation, survival ______(oncogene) Codes for DNA synthesis Mutated by red meat _______ (TSG) Guardian of the genome Triggers apoptosis/growth arrest after DNA damage

16. Pathophysiology IV Adenoma-carcinoma sequence Precursor lesion to invasive cancer is a type of polyp called an _________ Polyps showing dysplasia of colonic epithelium Stepwise accumulation of genetic mutations in TSGs and oncogenes Risk of cancer directly related to number of adenomas Adenomas form due to RFs Loss of both APC genes →accumulation of beta catenin = earliest event in formation of adenomas KRAS mutation typically follows

17. Specific genetic diseases which cause CRC I Familial adenomatous polyposis FAP Autosomal ___________ Mutations in the APC tumour suppressor gene The first step of the 2-hit hypothesis has already happened Many polyps Start out benign Malignant transformation when untreated Almost guaranteed to progress to cancer without Tx Prophylactic _________ <20yrs of age

18. Specific genetic diseases which cause CRC II Hereditary non-polyposis colorectal cancer HNPCC Autosomal dominant Colon cancer in mid 40s 100% get cancer Due to mutations that impair ____________________

19. Signs and Symptoms I Depends on site Left sided Change in bowel habits (diarrhoea) Rectal bleeding/rectal mucus Tenesmus Pain on defecation Palpable mass Can cause large bowel obstruction

20. Signs and Symptoms II Depends on site Right sided Often asymptomatic Anaemia (____________) Abdo pain Weight loss Palpable lump (often RIF) Melena Can cause small bowel obstruction in proximal disease

21. Signs and Symptoms III Depends on site Mets Liver Often asymptomatic Brain Confusion Delirium Lungs SOB

22. Investigations I Screening Bowel Cancer Screening Program Faecal occult blood sample in ______YOs Every __ years If test +ve then Colonoscopy Surveillance colonoscopy is beneficial at risk ratios of ≥1:12 Identifies early disease ↓death by 16% NNT 1 Dx191 NNT 1 death prevention 489 One off flexi sigmoidoscopy being introduced for 55YOs

23. Investigations II Routine investigations Bloods FBC Microcytic hypochromic anaemia due to Fe deficiency U&E LFT Search for mets CRP CEA carcinoembryonic antigen Tumour marker Not useful in Dx Useful to monitor response to Tx and identify relapse

24. Investigations III Routine Investigations Imaging USS CT Always – spread to liver and lungs MRI Of pelvis in planning surgery for rectal Ca Barium enema rarely Increasingly replaced by CT colonography

25. Investigations IV Routine Investigations Other Scopics Rigid sigmoidoscopy Flexible sigmoidoscopy Colonoscopy Has highest sensitivity and specificity for colorectal cancer Dx

26. Staging (p)TNM Tumour size – 1-4 Dukes A – Confined to ______ →90% survival 5Y B – Through to _______ but no lymphatic involvement →65-75% 5Y survival C 1 - Local _______ 2 - Widespread lymph 50-40% 5Y survival D – __________– <1% 5Y survival

27. Complications Bowel obstruction Perforation Metastasis

28. Alternative Diagnoses Crohn Disease or Ulcerative colitis Ileus Small Intestinal Diverticulosis Also Arteriovenous malformation (AVM) Ischemic bowel Small-intestine cancer

29. Management I Conservative ↓smoking Diet Weight loss Medical Chemotherapy 5FU

30. Management II Radiological Preoperative chemo-irradiation to down-stage rectal tumours Surgical Main Removal of the tumour ________________– 2cm Can be laparoscopic Hartman’s = 1/3 descending colon & rectum Stomas Colostomy ileostomy

31. Management III FU/2 o prevention Patients w/ prior Hx of colorectal cancer have surveillance colonoscopy Palliation Surgery is often appropriate Tx of patients w/ impending bowel obstruction but stenting of tumours is alternative palliative relief

32. Prognosis Prognosis depends on Duke’s stage 2 nd most common cause of cancer death Metastases are mostly the cause of death ¼ patients present with metastasis

33. Previous Exam Questions

34. Previous exam Qs -1

35. Previous exam Qs -2

36. Previous exam Qs -3

37. Previous exam Qs - 4