Presentation on theme: "Colorectal Carcinoma- An Overview"— Presentation transcript:
1Colorectal Carcinoma- An Overview Dr C. L ChawST4, Clinical OncologyTayside
2Colorectal 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 UKPeak incidence ages: yrs old♂:♀ ratio for colonic and rectal cancer is 2:3 and 2:1Colonic cancer ( 60%) is more common> than rectal cancer (40%)
3Risk Factors & Aetioloy Environmental FactorsGeneticThe 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
4Environmental Factors DietTotal calories – obesity and ↑ BMI (25-30kg/m2 )↑risk of CRC↑ consumption of Meat (red meat) /Fat (saturated) /Protein - ↑ risk of CRCHigh Fiber - ↓ risk of CRCVegetables/ Fruits – Protective effects due to presence of antioxidantsLifestylesPhysical inactivity -↑ risk of CRCCigarette smoking -↑ risk of CRC↑ alcohol consumption -↑ risk of CRC
5Genetics/Inherited predisposition +ve family history of CRC, esp in 1st degree relative ≤ 40 yrs old --↑ risk of CRC15% of CRC are familial in originsFAP (Familial Adenomatous Polyposis)HNPCC (Hereditary Nonpolyposis Colorectal Cancer) /Lynch Syndrome
6FAP 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 resectedExtracolonic features: benign or malignantBenign:mandibular osteoma, epidermal cystGardner’s syndrome- desmoid tumour, osteoma and adematous polypsMalignant: thyroid CA, brain tumours (Turcot’s Syndrome), duodenal and ampullary CA.
7HNPCCAutosomal Dominant, mutation of mismatch repair genes – hMLH1,hMLH2, hMSH6, hPMS13% of all CRCPresence of up 100 colonic polyps ( hence nonpolyposis), preferentially in right or proximal colonType 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 oldLifetime risk of Ca in HNPCC is ≈80% for CRC, 40% for endometrial Ca.
8HNPCC (Amsterdam Criteria) ≥ 3 family members with CRC, one of whom is 1st degree of the other 22 successive affected generations1 or more cancer diagnosed < 50 years oldFAP excludedCriteria 2:≥ 3 family members with HNPCC related cancer, one of whom is the 1st degree of the other 22 successive affected generation1 or more cancer diagnosed < 50yrs oldLab testing of MSH 1&2 and PMS 1&2
9Pathogenesis Vogelstein model Multistep to carcinoma formation Mutation of APC gene –polyposisK-RAS (40-50%), P53, SMAD mutationDCC gene helps to initiate metastatic potentialOther pathway through MSI (DNA microsatellite instability) - HNPCC
11Spread Adjacent organs – small/ large bowel, bladder, uterus Transcoelomic spread- peritoneal diseaseRegional lymph node involvement ( 40-70%) at presentation – usually follows the supplying blood vessels– pararectal, hypogastric, pre-sacral)Haematogenous – liver ≥ lung ≥ bone and brain25-30% patients at presentations, the tumour will have spread either locally or distant sites, and will be unsuitable for radical treatment
16Investigations 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
17Investigations AXR ( if suspicious of SBO/ BO) Double contrast barium enemaColonoscopy with biopsy, Flexi/ rigid sigmodoscopyCT scan –Thorax, abdoUSS liver - liver metastasisPelvic MRI –particularly for rectal Ca – To asses CRM (Circumferential resection margin)Endo-anal USS to asses nodal involvement in rectal Ca
21Screening 50-75 years old FOB; higher false positive rate Colonoscopy; more specific and better at picking proximal lesion.
22Staging (TMN & Dukes ) Dukes’Stage Description Stage (AJCC) TNM A In situCancer confined to submucosa or muscularis propria but not through itITis N0M0T1N0M0T2N0M0B(1)Into but not beyond muscularis propria;no LN spreadIIT3N0M0T4N0M0B(2)Through the muscularis propria with no nodes involvedC(1)Nodes positive but not apical nodeIIIAny T, N1-2, M0C(2)Apical node positiveDMetastaticIVAny T, Any N, M1
23Prognosis ( 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%
25Management (Surgery- Curative) Depending on site of lesions:Caecum, ascending colon, hepatic flexure – right hemicolectomyTransverse colon – extended hemicolectomySplenic flexure, descending colon –left hemicolectomySigmoid colon – high anterior resectionUpper rectum- anterior resectionDefunctioning loop ileostomy is anastomosis <12cm from anal marginLower rectum- Abdominal –perineal resectionTotal mesorectal resection- high rectum
26Management (Chemothrapy) Adjuvant ChemotherapyT3 disease or node positive tumours (Dukes C disease, selective in Dukes B) – 4-13% survival benefitsSerosal involvement, perforated tumours, extramural vascular invasion or involvement of circumferential margin5- Flourouracil based chemo, platinum based chemoSide effects: nausea, myelosuppression, diarrhoea, neuropathy
27Management ( Radiotherapy ) Rectal cancer – reduce rate of local recurrence, downstaging of inoperable diseasePre-operatively or post-operatively25Gy in 5#, 45Gy in 25#Side effects: erythema (local skin reaction), cystitis, diarrhoea, sterility, urge incotinence, bowel dysfunction
28Management ( Palliative ) Inoperable disease, medically unfit patientsDefunctiong Colostomy, Surgical/ endoscopic stenting – for obstructing lesions, aiming to improve quality of lifeResection for isolated liver and pulmonary metastasis if patients are fit.Radiotherapy – palliation of local symtoms, bony pain, rectal bleeding
29Management ( palliative ) ChemotherapyPatients selection- performance status 1-2Aiming to improve quality of life and control of diseaseImproves survival by 3-6 months5-FU based chemo, platinum based.
30References: SIGN Guidelines no 67 Practical Clinical Oncology – Louise HannaCancer, Principle & Practice of Oncology – DeVita, Hellman et al