Colorectal Cancer Flashcards
Colorectal Cancer - epidemiology
- Third most common cancer in the Western world
- Rare below 40 years of age
- distal colon (recto-sigmoid) more common
- commonly adenocarcinoma
- rarer types include lymphoma, adenosquamous and squamous cell carcinoma
Colorectal cancer - aetiology
- most cases are sporadic (genetic and/or environmental eg obesity)
- genetic = only 5-6% of cases, eg familial adenomatous polyposis (FAP) and Lynch syndrome
Familial adenomatous polyposis (FAP)
- autosomal dominant
- mutation in the adenomatous polyposis coli (APC) tumour suppressor gene
- inherited mutation of one APC allele is followed by a second hit mutation or deletion of the second allele
- multiple (can be thousands) adenomatous polyps in colon with malignant potential (refer for colectomy)
Hereditary non polyposis colorectal cancer (HNPCC) - Lynch syndrome
- mutations in DNA mismatch repair genes (MLH 1, MSH 2)
- more likely to occur in right colon
- a/w other tumours eg endometrial, ovarian, ureteric, small bowel
What is the adenoma –> carcinoma sequence?
- Normal mucosa –> (APC + MLH1/MSH2 + diet, inflammation, hormones) –> 2. Early adenoma –> (K-ras) –> 3. Late adenoma –> (p53) –> 4. adenocarcinoma
adenoma = benign tumour formed from glandular structures in epithelial tissue
Colorectal cancer - risk factors
increasing age APC mutation Lynch syndrome (HNPCC) MYH-associated polyposis hamartomatous polyposis syndromes inflammatory bowel disease (UC > Crohns) obesity smoking
Colorectal cancer - presentation
- older patients
- rectal bleeding
- change in bowel habit (Increased frequency or looser stools, particularly combined with rectal bleeding, is common in left-sided cancers)
- rectal mass
- anaemia (esp right sided colon cancer)
- wt loss
Colorectal cancer - investigations
FBC (anaemia)
liver biochemistry (normal)
renal function (normal unless ureter is compressed)
Faecal Immunochemical Test (FIT) screening. If positive:
1st line - colonoscopy –> ulcerating or exophytic mucosal lesion that may narrow the bowel lumen
(get biopsy if suspicious lesion)
CT scan of thorax, abdomen, and pelvis
- consider double-contrast barium enema or CT colonography as second line
- serum carcinoembryonic antigen (CEA): confirms Dx
(other marker is CA19-9)
- flexible sigmoidoscopy may be appropriate in a low-risk patient, such as isolated rectal bleed in younger pt
Suspected colorectal cancer - 2WW referral (NICE)
Refer people using a suspected cancer pathway referral (for an appointment within 2 weeks) if:
- They are aged 40 and over with unexplained weight loss and abdominal pain or
- They are aged 50 and over with unexplained rectal bleeding or
- They are aged 60 and over with:
Iron-deficiency anaemia or
Changes in their bowel habit
- Tests show occult blood in their faeces
Colorectal cancer - red flags
- rectal bleeding
- abdominal pain
- Change in bowel habit
- Weight loss
- Iron-deficiency anaemia
Classification - Primary tumour (T)
T0: No evidence of primary tumour
Tis: only the mucosa (carcinoma in situ)
T1: invades submucosa
T2: invades muscularis propria
T3: invades subserosa but not any neighbouring organs or tissues
T4a: through to the surface of the visceral peritoneum
T4b: directly invades other organs or tissues
Classification - Lymph nodes (N) and mets (M)
N0: No lymph node involvement is found
N1: Metastasis in 1 to 3 regional lymph nodes
N2: Metastasis in 4 or more regional lymph nodes
M0: No distant metastasis
M1: Distant metastasis (1a only 1 organ, 1b more than 1)
Stages based on classification
Stage 0 : Tis, N0, M0 Stage I: T1 or T2, N0, M0 Stage II: T3 or T4, N0, M0 Stage III: T1-T4a, N1 to N2, M0 Stage IV: Any T, any N, M1a or b
Stage determined by contrast‑enhanced CT of the chest, abdomen and pelvis
Dukes’ classification
A: Limited to the bowel wall (submucosa or musc propria)
B: Through the bowel wall (beyond musc propria)
C: Regional lymph nodes metastasis
D: distant metastasis
Management (Colonic)
Stages I-III
- surgical resection (open or laparoscopy)
- postoperative chemotherapy (fluorouracil and folinic acid and oxaliplatin)
Stage IV
- preoperative chemotherapy
- surgical resection
- consider monoclonal antibodies eg bevacizumab
- postoperative chemotherapy
Also need to restore continuity of bowel: anastomosis or end stoma
(Mx is different for rectal cancer)
Open resection vs laparoscopy
- Laparoscopic surgery is being increasingly used for colon cancer and is fast becoming the gold standard
- Benefits = reduced postoperative pain, shorter hospital stay, and a shorter recovery period
Management (not suitable for surgery)
- chemotherapy
- monoclonal antibodies
- endoscopic stenting (for some patients with obstructing tumours of the sigmoid colon)
post-treatment monitoring
- minimum of two CTs of the chest, abdomen, and pelvis in the first 3 years (look for mets)
- regular serum CEA tests
- colonoscopy at 1 year after initial treatment
- If normal, consider further colonoscopy after 5 yrs
Colorectal cancer - complications
- bone marrow suppression during chemotherapy
- oxaliplatin-associated hepatotoxicity or neuropathy
- chemotherapy-associated GI (diarrhoea, nausea, vomiting, abdominal pain), allopecia
- radiotherapy-associated faecal incontinence
- bladder or erectile dysfunction post rectal excision
- metastasis (liver, lungs, bones, brain or spinal cord)
- post surgical: DVT, infection, haemorrhage
Bowel cancer national screening programme
Bowel cancer screening is offered every 2 years to men and women aged 60 to 74. *
An additional one-off test called bowel scope (flexible sigmoidoscopy) screening is being introduced in England for men and women at the age of 55.
*There are 2 different kits in use in England:
the faecal immunochemical test (FIT) kit
the faecal occult blood (FOB) test kit
aim is to detect haemoglobin in faeces (occult blood)
patients with abnormal results are offered a colonoscopy
Peutz-Jeghers syndrome
Genetics
- autosomal dominant
- responsible gene - LKB1 or STK11
Features
- hamartomatous polyps in GI tract (mainly small bowel)
- pigmented freckles/lesions on lips, oral mucosa, face, palms and soles
- intestinal obstruction e.g. intussusception
- gastrointestinal bleeding
- Around 50% of patients will have died from another gastrointestinal tract cancer by the age of 60 years.
Management
- conservative unless complications develop
Site of cancer and type of resection
Caecal, ascending or proximal transverse colon = Right hemicolectomy
Distal transverse, descending colon = Left hemicolectomy
Sigmoid colon = High anterior resection (aka sigmoid colectomy, or sigmoidectomy)
Upper rectum = Anterior resection (total mesorectal excision - TME)
Low rectum = Anterior resection (Low TME)
Anal verge = Abdomino-perineal excision of rectum
Hartmann’s Procedure
The Hartmann’s procedure (proctosigmoidectomy) with a proximal end colostomy or ileostomy is the most common operation carried out by general surgeons for management of malignant obstruction of the distal colon. During this procedure, the lesion is removed, the distal bowel closed intraperitoneally, and the proximal bowel diverted with a stoma - end colostomy.
The indications for this procedure include:
a. Localized or generalized peritonitis caused by perforation of the bowel secondary to the cancer
b. Viable but injured proximal bowel that, in the opinion of the operating surgeon, precludes safe anastomosis
c. Complicated diverticulitis
Rectal Cancer - Management
- High anterior resection –> sigmoid colectomy
- Lower anterior resection –> cancer in the proximal 2/3 of the rectum leaving the sphincter intact
- Involvement of the sphincter or very low tumours require abdomino-perineal excision of rectum (APER)
- In addition to excision of the rectal tube an integral part of the procedure is a meticulous dissection of the mesorectal fat and lymph nodes (total mesorectal excision/ TME).
- Patients with T1 and 2 /N0 disease on imaging do not require irradiation and should proceed straight to surgery.
- Those with T3 , N0 tumours may be offered short course radiotherapy prior to surgery.
- Patients with T4 disease will typically have long course chemo radiotherapy.
- Patients presenting with large bowel obstruction from rectal cancer should not undergo resectional surgery without staging as primary treatment (very different from colonic cancer). They are managed with a defunctioning loop colostomy (as rectal resection and anastomosis is more complicated than colonic)
