Transcript Colorectal Carcinoma- An Overview

Colorectal Carcinoma- An Overview
Dr C. L Chaw
ST4, Clinical Oncology
Tayside
Colorectal Cancer (CRC)
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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 2nd
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
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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
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Diet
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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
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Physical inactivity -↑ risk of CRC
Cigarette smoking -↑ risk of CRC
↑ alcohol consumption -↑ risk of CRC
Genetics/Inherited
predisposition
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+ve family history of CRC, esp in 1st degree
relative ≤ 40 yrs old --↑ risk of CRC
15% of CRC are familial in origins
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FAP (Familial Adenomatous Polyposis)
HNPCC (Hereditary Nonpolyposis Colorectal
Cancer) /Lynch Syndrome
FAP
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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.
HNPCC
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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)
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Criteria 1:
 ≥ 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
 FAP excluded
Lab testing of MSH 1&2 and PMS 1&2
Pathogenesis
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Vogelstein model
Multistep to carcinoma formation
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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
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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:
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History
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Presenting complaints
Family history
Systemic enquiries
Physical examination (PR examination)
Investigations
Treatments
Signs & Symptoms
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Symptoms
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Lower GI bleeding
Altered bowel habits
Abdominal pain
Weight loss
Loss of appetite
Obstructive symptoms – vomiting, unable to pass
wind, severe abdo pain
Signs
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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.
Signs
Investigations
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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
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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
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50-75 years old
FOB; higher false positive rate
Colonoscopy; more specific and better at picking
proximal lesion.
Staging (TMN & Dukes )
Dukes’Stage
Description
Stage
(AJCC)
TNM
In situ
Cancer confined to submucosa or
muscularis propria but not through
it
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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)
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Stage I (Dukes A): 95%
Stage II (Dukes B1/2): 70-80%
Stage III (Dukes C1/2): 40%
Stage IV (Dukes D): 5%
Management
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Radical/Curative
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Non-metastatic disease
Multimodality approaches
Surgery, chemotherapy, radiotherapy
Palliative
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Metastatic disease, inoperable disease
Surgery, chemotherapy, radiotherapy
Symptoms control
Management (SurgeryCurative)
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Depending on site of lesions:
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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
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Lower rectum- Abdominal –perineal resection
Total mesorectal resection- high rectum
Management (Chemothrapy)
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Adjuvant Chemotherapy
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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 )
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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 )
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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 )
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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:
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SIGN Guidelines no 67
Practical Clinical Oncology – Louise Hanna
Cancer, Principle & Practice of Oncology –
DeVita, Hellman et al