1. Colorectal Carcinoma- An Overview
Dr C. L Chaw
ST4, Clinical Oncology
Tayside

2. Colorectal Cancer (CRC)
3rd most common form of cancer and the 3rd leading cause of death in the Western World.
Annual incidence in UK -54/ , and new cases per year,>16000 deaths per year, making it the 2nd most common cause of cancer death in UK
Peak incidence ages: yrs old
♂:♀ ratio for colonic and rectal cancer is 2:3 and 2:1
Colonic cancer ( 60%) is more common> than rectal cancer (40%)

3. Risk Factors & Aetioloy
Environmental Factors
Genetic
The aetiology is complex, involving interplay of environmental and genetic factors. These factors conspire to change the normal mucosa to a premalignant adenomatous polyp to a frank colorectal cancer over the course of many years

4. Environmental Factors
Diet
Total calories – obesity and ↑ BMI (25-30kg/m2 )↑risk of CRC
↑ consumption of Meat (red meat) /Fat (saturated) /Protein - ↑ risk of CRC
High Fiber - ↓ risk of CRC
Vegetables/ Fruits – Protective effects due to presence of antioxidants
Lifestyles
Physical inactivity -↑ risk of CRC
Cigarette smoking -↑ risk of CRC
↑ alcohol consumption -↑ risk of CRC

5. Genetics/Inherited predisposition
+ve family history of CRC, esp in 1st degree relative ≤ 40 yrs old --↑ risk of CRC
15% of CRC are familial in origins
FAP (Familial Adenomatous Polyposis)
HNPCC (Hereditary Nonpolyposis Colorectal Cancer) /Lynch Syndrome

6. FAP Autosomal Dominant, mutation of APC gene (5q21) 1% of all CRC
Development of hundred to thousands of polyps in patients in their teen-30s, almost 100% progress to CRC if not surgically resected
Extracolonic features: benign or malignant
Benign:mandibular osteoma, epidermal cyst
Gardner’s syndrome- desmoid tumour, osteoma and adematous polyps
Malignant: thyroid CA, brain tumours (Turcot’s Syndrome), duodenal and ampullary CA.

7. HNPCC
Autosomal Dominant, mutation of mismatch repair genes – hMLH1,hMLH2, hMSH6, hPMS1
3% of all CRC
Presence of up 100 colonic polyps ( hence nonpolyposis), preferentially in right or proximal colon
Type I and Type II (distinguished by extracolonic tumours originating in stomach, small bowel, bile duct. Pelvis, ureter, uterus, bladder, ovary, skin)
Mean age of developing Ca ≈40 yrs old
Lifetime risk of Ca in HNPCC is ≈80% for CRC, 40% for endometrial Ca.

8. HNPCC (Amsterdam Criteria)
≥ 3 family members with CRC, one of whom is 1st degree of the other 2
2 successive affected generations
1 or more cancer diagnosed < 50 years old
FAP excluded
Criteria 2:
≥ 3 family members with HNPCC related cancer, one of whom is the 1st degree of the other 2
2 successive affected generation
1 or more cancer diagnosed < 50yrs old
Lab testing of MSH 1&2 and PMS 1&2

9. Pathogenesis Vogelstein model Multistep to carcinoma formation
Mutation of APC gene –polyposis
K-RAS (40-50%), P53, SMAD mutation
DCC gene helps to initiate metastatic potential
Other pathway through MSI (DNA microsatellite instability) - HNPCC

10. Features of tumour

11. Spread Adjacent organs – small/ large bowel, bladder, uterus
Transcoelomic spread- peritoneal disease
Regional lymph node involvement ( 40-70%) at presentation – usually follows the supplying blood vessels– pararectal, hypogastric, pre-sacral)
Haematogenous – liver ≥ lung ≥ bone and brain
25-30% patients at presentations, the tumour will have spread either locally or distant sites, and will be unsuitable for radical treatment

12. Assessment & Management:
History
Presenting complaints
Family history
Systemic enquiries
Physical examination (PR examination)
Investigations
Treatments

13. Signs & Symptoms Symptoms Lower GI bleeding Altered bowel habits
Abdominal pain
Weight loss
Loss of appetite
Obstructive symptoms – vomiting, unable to pass wind, severe abdo pain

14. Signs
Inspection: Jaundice, pallor , (freckles around the lip, buccal mucosal –Peutze Jeghers)
Palpable abdominal / rectal mass–don’t forget about the liver –hepatomegaly – distant mets
PR bleeding – fresh red ( left-sided colon/ rectum), malena (right-sided colon)
Alarming signs –Abdominal distension, peritonism, rebound tenderness, tingling bowel sound – bowel obstruction, perforation.
Pulmonary signs and neurological signs can sometime present if the disease is advanced.

15. Signs

16. Investigations FBC ( Iron –deficiency anaemia ) U+E
LFT ( metastatic disease )
CEA (carcinoembryonic antigen), is raised in 85% of patients with CRC, higher value associated with worse prognosis

17. Investigations AXR ( if suspicious of SBO/ BO)
Double contrast barium enema
Colonoscopy with biopsy, Flexi/ rigid sigmodoscopy
CT scan –Thorax, abdo
USS liver - liver metastasis
Pelvic MRI –particularly for rectal Ca – To asses CRM (Circumferential resection margin)
Endo-anal USS to asses nodal involvement in rectal Ca

18. Investigations

19. Investigations

20. Investigations

21. Screening 50-75 years old FOB; higher false positive rate
Colonoscopy; more specific and better at picking proximal lesion.

22. Staging (TMN & Dukes ) Dukes’Stage Description Stage (AJCC) TNM A
In situ
Cancer confined to submucosa or muscularis propria but not through it I
Tis N0M0
T1N0M0
T2N0M0
B(1)
Into but not beyond muscularis propria;no LN spread II
T3N0M0
T4N0M0
B(2)
Through the muscularis propria with no nodes involved
C(1)
Nodes positive but not apical node
III
Any T, N1-2, M0
C(2)
Apical node positive D
Metastatic IV
Any T, Any N, M1

23. Prognosis ( 5-yr survival)
Stage I (Dukes A): 95%
Stage II (Dukes B1/2): 70-80%
Stage III (Dukes C1/2): 40%
Stage IV (Dukes D): 5%

24. Management Radical/Curative Palliative Non-metastatic disease
Multimodality approaches
Surgery, chemotherapy, radiotherapy
Palliative
Metastatic disease, inoperable disease
Symptoms control

25. Management (Surgery- Curative)
Depending on site of lesions:
Caecum, ascending colon, hepatic flexure – right hemicolectomy
Transverse colon – extended hemicolectomy
Splenic flexure, descending colon –left hemicolectomy
Sigmoid colon – high anterior resection
Upper rectum- anterior resection
Defunctioning loop ileostomy is anastomosis <12cm from anal margin
Lower rectum- Abdominal –perineal resection
Total mesorectal resection- high rectum

26. Management (Chemothrapy)
Adjuvant Chemotherapy
T3 disease or node positive tumours (Dukes C disease, selective in Dukes B) – 4-13% survival benefits
Serosal involvement, perforated tumours, extramural vascular invasion or involvement of circumferential margin
5- Flourouracil based chemo, platinum based chemo
Side effects: nausea, myelosuppression, diarrhoea, neuropathy

27. Management ( Radiotherapy )
Rectal cancer – reduce rate of local recurrence, downstaging of inoperable disease
Pre-operatively or post-operatively
25Gy in 5#, 45Gy in 25#
Side effects: erythema (local skin reaction), cystitis, diarrhoea, sterility, urge incotinence, bowel dysfunction

28. Management ( Palliative )
Inoperable disease, medically unfit patients
Defunctiong Colostomy, Surgical/ endoscopic stenting – for obstructing lesions, aiming to improve quality of life
Resection for isolated liver and pulmonary metastasis if patients are fit.
Radiotherapy – palliation of local symtoms, bony pain, rectal bleeding

29. Management ( palliative )
Chemotherapy
Patients selection- performance status 1-2
Aiming to improve quality of life and control of disease
Improves survival by 3-6 months
5-FU based chemo, platinum based.

30. References: SIGN Guidelines no 67
Practical Clinical Oncology – Louise Hanna
Cancer, Principle & Practice of Oncology – DeVita, Hellman et al