Presentation on theme: "Colorectal Carcinoma- An Overview Dr C. L Chaw ST4, Clinical Oncology Tayside."— Presentation transcript:
Colorectal Carcinoma- An Overview Dr C. L Chaw ST4, Clinical Oncology Tayside
Colorectal Cancer (CRC) 3 rd most common form of cancer and the 3 rd 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 2 nd 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%)
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/m 2 )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 1 st 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 1 st 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 mass–dont 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.
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
Screening years old FOB; higher false positive rate Colonoscopy; more specific and better at picking proximal lesion.
Staging (TMN & Dukes ) DukesStageDescriptionStage (AJCC) TNM A In situ Cancer confined to submucosa or muscularis propria but not through it 0I0I Tis N 0 M 0 T1N 0 M 0 T2N 0 M 0 B(1)Into but not beyond muscularis propria;no LN spread IIT3N 0 M 0 T4N 0 M 0 B(2)Through the muscularis propria with no nodes involved C(1)Nodes positive but not apical nodeIIIAny T, N1-2, M0 C(2)Apical node positive DMetastaticIVAny T, Any N, M1
Prognosis ( 5-yr survival) Stage I (Dukes A): 95% Stage II (Dukes B 1/2 ): 70-80% Stage III (Dukes C 1/2 ): 40% Stage IV (Dukes D): 5%
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
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