Colorectal Carcinoma- An Overview Dr C. L Chaw ST4, Clinical Oncology Tayside Colorectal Cancer (CRC) 3rd most common form of cancer and the 3rd leading cause of death in the Western World.
Annual incidence in UK -54/100 000, and 35000 new cases per year,>16000 deaths per year, making it the 2 nd most common cause of cancer death in UK Peak incidence ages: 60-70 yrs old : ratio for colonic and rectal cancer is 2:3 and 2:1 Colonic cancer ( 60%) is more common> than rectal cancer (40%) 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 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 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
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 Gardners syndrome- desmoid tumour, osteoma and adematous polyps Malignant: thyroid CA, brain tumours (Turcots Syndrome), duodenal and ampullary CA. 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. HNPCC (Amsterdam Criteria)
Criteria 1: 3 family members with CRC, one of whom is 1 st 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 FAP excluded Lab testing of MSH 1&2 and PMS 1&2
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 Features of tumour 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 Assessment & Management: History Presenting complaints
Family history Systemic enquiries Physical examination (PR examination) Investigations Treatments 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 Signs
Inspection: Jaundice, pallor , (freckles around the lip, buccal mucosal Peutze Jeghers) Palpable abdominal / rectal massdont 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.
Signs 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
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 Investigations Investigations Investigations Screening 50-75 years old
FOB; higher false positive rate Colonoscopy; more specific and better at picking proximal lesion. Staging (TMN & Dukes ) DukesStage Description Stage (AJCC) TNM In situ Cancer confined to submucosa or
muscularis propria but not through it 0 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 A 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% Management Radical/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 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 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 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 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. References: SIGN Guidelines no 67 Practical Clinical Oncology Louise Hanna Cancer, Principle & Practice of Oncology DeVita, Hellman et al
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