COLORECTAL CANCER Flashcards
Whats the incidence of colorectal cancer?
Common
13% of all cancer cases and 10% of cancer deaths in the UK
4th most common cancer
Second most common cause of cancer death
95% of pt are aged over 50 at time of diagnosis
Equally common in men and women
Incidence increasing due to ageing population but mortality is decreasing
What is the adenoma-carcinoma sequence?
Most colorectal cancers develop via a progression of normal mucosa to colonic adenoma (‘polyps’) to invasive adenocarcinoma
Adenomas may be present for >10 years before becoming malignant and 10% of adenomas progress to adenocarcinoma
Hyperproliferation of mucosa -> APC gene mutation -> early adenoma -> K-RAS mutation -> intermediate adenoma -> DCC mutation -> late adenoma -> p53 mutation -> adenocarcinoma
What genetic mutations are associated with colorectal cancer?
Adenomatous polyposis coli (APC) - note: more than half colon cancer show allelic loss of this gene
MSH-2, MSH6, MLH1, PMS2 (DNA mismatch repair genes) - HNPCC/lynch syndrome
Activation of the K-ras oncogene
Delection of DCC tumour suppressor gene
Deletion of P53 tumour suppressor gene
MYH - MYH-associated polyposis
Is colorectal cancer inherited?
Only 5% of cases are truly inherited
The vast majority occur spontaneously
What are adenomas?
a benign, dysplastic tumour of columnar cells or glandular tissue.
What are the hereditary syndromes that increase the risk of colorectal cancer?
Hereditary non polyposis colorectal cancer (lynch syndrome)
Familial adenomatous polyposis
MYH-associated polyposis
Serrated polyposis syndrome
Peutz-jeghers syndrome
Juvenile polyposis syndrome
What is HNPCC? What proportion of cases of colorectal cancer is it responsible for?
Autosomal dominant condition where there are mutations to DNA mismatch repair genes (usually MSH2 60% of cases or MLH1 in 30% of cases) 0 cases microsatellite instability
It increases the incidence of many malignancies (stomach, small intestine, bladder, skin, brain, hepatobilliary system, endometrial and ovarian cancer). Lifetime risk of colorectal cancer in mutation carriers is 70-80%
3%
What is FAP? What proportion will develop colorectal cancer?
an autosomal dominant condition arising from germiline mutations of The (APC) gene - a tumour suppressor gene.
Penetrance is virtually 100%
Accounts for <1% of all colorectal cancers
characterized by the presence of hundreds to thousands of colorectal and duodenal adenomas, some of which undergo malignant change.
90% will develop CRC before the age of 45 if not treated.
What screening is done for FAP?
Annual colonoscopies from age 12-14
Prophylactic surgical resection can be offered if anything is found
What is Gardner’s syndrome?
A form of FAP
It can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin
What is MYH-associated polyposis?
An autosomal recessive condition characterised by colorectal adenomas and cancers caused by a mutation to MYH (MUT Y homologue) gene.
MUTYH is a base excision repair gene and failure of its normal action increases the risk of colorectal cancer.
What are serrated polyps?
a heterogeneous group of colorectal lesions that includes the benign hyperplastic polyps, and the pre-malignant sessile serrated adenoma and traditional serrated adenoma. They are characterized by the saw-tooth appearance of the crypt epithelium.
Supposedly BRAF gene mutations and gene promoter hypermethylation
What is peutz-jeghers syndrome? Whats the risk of colorectal cancer?
An autosomal dominant condition characterised by hamartomatous polyps in the gastrointestinal tract, pigmented mucocutaneous lesions and an increased risk of gastrointestinal and extragastrointestinal malignancies.
The polyps, which are hamartomas, can occur anywhere in the gastrointestinal tract but are most frequent in the small bowel.
There is an estimated 40% lifetime risk of colorectal cancer.
What is juvenile polyposis syndrome?
Autosomal dominant condition with incomplete penetrant
It is characterised by hamartomatous polyps throughout the GI tract but mainly found in the colon. It causes an increased risk of CRC and gastric cancer.
Occurs mainly in children and teenagers
Characterised by >3-5 juvenile colonic polyps, juvenile polyps throughout the GIT or any number of polyps with a family history
Polyps are a cause of bleeding and intussesception in the first decade of life
Whats the onset of cancer in lynch syndrome?
40-50 or younger (earlier than in sporadic cases!)
Whats the mean age of adenoma development in FAP? Whats the average age at which colorectal cancer develops?
16 years
39 years
How should FAP be managed?
Affected individuals should be offered a prophylactic colectomy
What is attenuated FAP?
A type of FAP which presents slater in life at about 44 years and has fewer polyps (<100) which tend to occur on the right side of the colon
What proportion of colorectal cancers originate from serrated polyps?
30%
What are the risk factors of colorectal cancer?
FHx of colorectal cancer/polyps - most common risk factor
Longstanding/chronic IBD
PMHx of colorectal cancer/polyps
Genetic syndrome e.g. FAP or lynch syndrome
Obesity
Red and processed meat
Eating too little fibre
Alcohol and smoking
Increasing age
Medical conditions - gallstones, diabetes, acromegaly
Radiation exposure
H.pylori infections
What are the protective factors for colorectal cancer?
Regular physical exercise
Dietary fibre
Non-starchy vegetables
Pulses
High calcium intake
Garlic
What proportion of cases of colorectal cancer have a positive family history?
10-20%
What are the most common sites for colorectal cancer to develop?
Rectum 40%
Sigmoid colon 30%
Caecum 15%
Transverse colon 10%
Descending colon 5%
(2/3rds occur distal to splenic flexure)
What proportion of colorectal cancers have metastatic spread at diagnosis?
25%
What are the 4 modes of spread of colorectal cancer?
Direct invasion of adjacent organs e.g. bladder
Lymphatic to adjacent lymph nodes
Haematogenous to distant organs (most commonly liver but also likely lungs)
Trans-coelomic e.g. peritoneum or ovaries
Whats the process for referral of colorectal cancer
Referred as a fast track - have to be seen in secondary care within 14 days and begin treatment within 62 days 1
How does colorectal cancer typically first present
20% acutely - due to obstruction, bleeding or perforation
Often diagnosed through screening or incidentally due to investigations for other reasons, also commonly found due to unexplained FDA
How does colorectal cancer present?
Change in bowel habit
Rectal bleeding
Unexplained weight loss (when associated with metastasis)
Abdominal pain
Symptoms of anaemia
What are the features of right-sided colon cancers?
Abdominal pain - relative late symptom!
IDA (due to chronic occult bleeding)
Palpable mass in RIF
Often presents later than left sided colon cancers
What are the clinical features of left-sided colon cancers
Rectal bleeding
Change in bowel habit
Tenesmus
Abdominal pain
Palpable mass in LIF or on PR exam
What does it suggest if someone with colorectal cancer has had unexplained weight loss?
Metastatic disease
What does NICE recommend for who should be referred for urgent investigation of suspected bowel cancer?
Urgent referral within 2 weeks:
≥40yrs with unexplained weight loss and abdominal pain
≥50yrs with unexplained rectal bleeding
≥60yrs with iron‑deficiency anaemia or change in bowel habit
Positive occult blood screening test
Consider it for pt with a rectal or abdominal mass
Consider for unexplained anal mass or ulceration
Consider for adults under 50 with rectal bleeding and any of the following: abdo pain, change in bowel habit, weight loss or IDA
What investigations should be done for colorectal cancer?
Colonoscopy - gold standard (advantage is it can take biopsies)
CT colonography - visualises colon and other organs (CXR AXR and PXR to look for metastases also)
FBC - microcytic anaemia, LFTs, clotting
MRI to evaluate mesorectal in pt with tumours lying below the peritoneal reflection
Double contrast barium enema - used less often
Conventional CT - less sensitive for small lesions but doesnt require full bowel prep
Flexible sigmoidoscopy (will identify any lesions distal to the splenic flexure so should be sufficient for pt with fresh bleeding PR)
Who is not suitable for a colonoscopy?
Frailty >75 years old
Intolerance
Recent MI
Haemodynamic instability
Peritonitis
Recent surgery with colonic anastomosis or bowel injury and repair
Known/suspected colon perforation
Fulminant colitis and severe toxic megacolon
Whats the aim of screening in colorectal cancer?
To diagnose the disease at an earlier stage so more pt undergo curative treatment, thus reducing overall mortality
When did the national bowel cancer screening programme start?
2006
Outline the screening for colorectal cancer?
Pt aged 60-74 are sent a FIT testing kit every 2 years (in Scotland its 50-74)
If test is positive, pt is offered a colonoscopy
After the age of 75, pt can request further tests every 2 years
What proportion of those with a positive FIT test done in the colorectal cancer screening will polyps or cancer be found?
5/10 normal exam
4/10 polyps
1/10 cancer
What will happen to the pt in who an adenoma is found during colorectal cancer screening?
They will undergo subsequent colonoscopic surveillance
Whats a serum marker indicative of colorectal cancer?
Carcinoembryonic antigen - not useful for screening but can be useful for follow up as rising levels suggest recurrence and it can suggest metastatic disease
Whats the old staging tool for colorectal cancer?
Dukes staging
What staging is done for colorectal cancer?
TNM staging
What additional investigation should be done for rectal cancers?
MRI of rectum to assess the extent of spread through the rectal wall and mesorectal nodes
Outline the TNM staging for colorectal cancer?
Tx - primary tumour cannot be assessed
T0 - no evidence of primary tumour
Tis - carcinoma in situ, intramuscular carcinoma (involvement of laminate propria)
T1 - tumour invades submucosa
T2 - tumour invades muscularis propria
T3 - tumour invades into pericolorectal tissues
T4a - tumour invades through visceral peritoneum
T4b - tumour directly invades or adheres to other adjacent organs or structures
Nx - regional lymph nodes can’t be assessed
N0 - no regional lymph node metastasis
N1a - metastasis in 1 regional lymph node
N1b - metastasis in 2-3 regional lymph nodes
N1c - no regional lymph nodes positive but tumour deposits in subserosa, mesentery or nonperitonealized pericolic or perirectal/mesorectal tissues
N2a - metastasis in 4-6 regional lymph nodes
N2b - metastasis in 7 or more regional lymph nodes
M0 - No distant metastasis by imaging; no evidence of tumor in other sites or organs
M1a - metastasis confined to 1 organ/site without peritoneal metastasis
M1 - metastasis to 2 or more sites/organs without peritoneal metastasis
M1 - metastasis to peritoneal surface
Whats the curative treatment for colorectal cancer?
Surgery often in combination with chemotherapy
Radiotherapy for rectal cancers only
What surgery is performed for colorectal cancer?
Radical resection of segment of colon containing the tumour plus its blood supply and draining lymph nodes
This is often done laparoscopically but is dependant on site + size of tumour, patients build, previous abdo surgery and experience of surgeon
What does rectal excision include?
Removal of the surrounding mesorectal - total mesorectal excision (TME)
It may involve a temporary de functioning ileostomy due to high risk of anastomotic failure. If the tumour is too low, abdominoperineum excision of rectum is formed with a permemantn colostomy
What medications should be given when a pt is undergoing colorectal cancer?
Prophylactic antibiotics - single dose at induction
VTE prophylaxis (TEDs, daily injections of LMWH continued 28 days post op, flowtrons)
What is ‘enhanced recovery’?
An evidence-based approach that helps people recover more quickly after having major surgery
It includes…
pre-operative - carbohydrate loading with drinks (avoid starvation and avoid post-op insulin resistance) and avoidance of bowel prep if possible (to reduce risk of dehydration
perioperative - thermoregulation, goal-directed fluid therapy by monitoring cardiac output, epidural or spinal anaesthesia, avoidance of drains/nasogastric tube unless necessary, laparoscopic surgery if feasible
Postoperative - early oral intake and mobilisation, avoidance of opiate analgesia (as have inhibitory effect on gut)
What is dukes criteria?
Dukes A - tumour con fined beneath muscularis propria (90% 5 year survival)
Dukes B - tumour through muscularis propria (65% 5YS)
Dukes C - involvement of regional lymph nodes (30% 5YS)
Dukes D - distant metastasis (<10% 5YS)
What is Hartmann’s procedure?
Use din emergency bowel surgery
Complete resection of the rectosigmoid colon with the formation of an end colostomy and closure of the rectal stump
What proportion of pt with colorectal carcinoma undergo surgery?
About 80%
What is a total mesorectal excision?
Removal of the entire package of mesorectal tissue surrounding the cancer and then a low rectal anastomosis is performed
It is required for rectal cancers
What is an abdominal-perineal excision? What are the indications?
a surgery in which the anus, rectum and sigmoid colon are removed. It requires a permenant colostomY
It’s reserved for very low tumours within 5cm of the anal margin
What surgery is used for removing colorectal cancer that is a Nyerere but the rectum?
Segmental resection
When is chemotherapy indicated for colorectal cancer?
For patients who have undergone potentially curative surgery but are at high risk of developing recurrent disease
What are the risk factors for relapse of colorectal cancer?
Local regional lymph node involvement
Extramural vascular invasion
Poorly differentiated tumour
T4 disease
Young age at presentation
Emergency surgery
When should chemo be started for colorectal carcinomas?
6-8 weeks after surgery
For 3 months (SCOT trial)
It can sometimes be given pre-operative LH or downstage the tumour to allow subsequent surgical resection
What chemotherapy agents are used for colorectal cancer?
5-fluorouracil which can be combined with oxaliplatin in fit high-risk pt
Alternative is oral capecitabine
When is radiotherapy used in colorectal cancer?
For rectal cancer only due to risk of radiation damage to small bowel!
Almost always given pre-operatively as tissues are more radio sensitive, intact anatomy aids targeting of radiotherapy
Being used less now.
What radiotherapy should be used to reduce the risk of recurrence in high risk but resectable tumours?
Short course radiotherapy followed by surgery within 7-10 days
What radiotherapy should be used in unresectable tumours in colorectal cancer?
Long course chemoradiotherapy followed by surgery 6-8 weeks later - hope is to shrink tumour and make it resectable
How can some early rectal cancers be treated?
Trans anal surgery
How can early polyp cancers be treated?
Endoscopic polypectomy
Is metastatic colorectal cancer treatable?
Yes!
How is metastatic colorectal cancer treated?
Liver and lung metastases can be respected
Up to 40% 5 year survival for pt undergoing liver resection
how can colorectal cancer present as an emergency?
Obstruction
Perforation
Bleeding
What is FOLFOX?
FOLinic acid, Fluorouracil and OXaliplatin - adjuvant therapy for colorectal cancer
What is CAPOX?
CAPecitabine and OXaliplatin - adjuvant therapy for colorectal cancer
What are the complications of colorectal cancer?
Bowel obstruction
Metastasis
IDA
Jaundice
Perforation
What is the SORT score?
a surgical preoperative risk prediction tool.
It provides a percentage estimate of death within 30 days of inpatient surgery for adults
Why may a pt need palliative treatment for colorectal cancer?
Inoperable metastases
Pt isnt fit enough
What are the palliative treatment options for colorectal cancer?
Palliative resection of the primary tumour
De functioning stoma
Bypass procedure
Colonic stent for obstructive left sided tumours
Radio frequency ablation for liver/lung metastases
Palliative chemotherapy - mainstay!!
Palliative radiotherapy
What postoperative surveillance should be done for colorectal cancer?
Total colonoscopy before surgery to look for additional lesions.
If not achieved then a second ‘clearance’ colonoscopy within 6 months of surgery is essential
Pt with stage 2 or 3 disease should be followed up with regular colonoscopy and CEA measurements
Annual CT scans of chest and abdomen to detect operable liver metastases should be performed for up to 3 years post surgery
When does colorectal cancer tend to recur?
Early - within first 2-3 years after initial treatment (so pt are followed up for 5 years!)
Whats the prognosis for colorectal cancer?
Following diagnosis with CRC:
78% survive one year
58% survive five years or more
Around 70% of those 15-39 survive 5 years compared to around 40% of those aged over 80.
Interestingly survival is also higher in those aged 60-69 - this may be related to the screening programme.
1 year survival is around 98% if diagnosed at stage 1, compared to 44% in those with stage 4 disease.
How can colorectal cancer be prevented?
Healthy balanced diet, avoiding processed/red meats
Smoking cessation and limiting alcohol consumption
Maintaining a healthy weight
Cacium supplementation but this increases risk of prostate cancer in men
Aspirin in those with lynch syndrome (daily aspirin taken for >2 years)
What does a FIT test do?
It tests for microscopic blood in the stool
What does a FOB test do? Why is the FIT test better?
Faecal occult blood test - checks for occult blood
The FIT test only detects human haemoglobin whereas FOB test can detect animal haemoglobin ingested through diet
Only 1 faecal sample is needed for a FIT test compared to 2-3 for FOB tests
What are the 3 types of colorectal cancer and what are their proportions?
Sporadic 95%
HNPCC 5%
FAP <1%
What are pt with HNPCC at higher risk for?
Colorectal cancer
Endometrial cancer
What are the Amsterdam criteria?
a set of diagnostic criteria used by doctors to help identify families which are likely to have Lynch syndrome (HNPCC)
- At least 3 relatives with an associated cancer, 1 of whom is a first degree relative of the other 2 (FAP should be excluded)
- At least 2 successive generations involved
- At least 1 should be a first degree relative of the other 2
- 1 or more relatives diagnosed before age of 50
What are the 3 technical factors for an anastomosis to heal?
Adequate blood supply
Mucosal apposition
No tissue tension
What type of resection is done when the cancer is in the caecum, ascending or proximal transverse colon?
Right hemicolectomy with a ileocolic anastomosis
What type of resection is done when the cancer is in the distal transverse or descending colon?
Left hemicolectomy with a colo-colon anastomosis
What type of resection is done when the cancer is in the sigmoid colon?
High anterior resection with a colo-rectal anastomosis
What type of resection is done when the cancer is in the upper rectum?
Anterior resection with a colo-rectal anstomosis
What type of resection is done when the cancer is in the low rectum?
Anterior resection (low TME) with a colo-rectal anastomosis +/- defunctioning stoma
What type of resection is done when the cancer is in the anal verge?
Abdominal-perineal excision of the rectum
What are the differences between right and left sided colorectal tumours?
L side - presents with bleeding/mucous PR, altered bowel habit, obstruction, tenesmus and mass PR
R side - weight loss, anaemia, abdo pain and obstruction is less likely
Right side more likely flat polyps
Right side Ed tumours more likely to develop in pt with a genetic predisposition to colorectal cancer
Right sided colon cancers tend to be diagnosed much later than left sided as they only produce symptoms when relatively advances (stool is liquid here so pain/cramps/obstruction symptoms tend not to occur)
Why is it thought that colorectal cancer is due largely to dietary factors?
As Otis more common in westernised populations e.g. Europe’s, USA, japan having higher rates than Africa and Asia
What are the most common metastatic sites?
Liver via portal venous system
Pulmonary seedlings
Rarer - skin, brain, bone
What is the apple core sign?
A sign of colon cancers that narrow the bowel lumen
What may be seen on the CT with colorectal cancer?
Bulky irregular mass
Subtle thickening of the wall
Apple core lesion
Dilated colon into a mass
What screening for colorectal cancer was introduced but stopped in 2021?
One off screening flexible sigmoidoscopy to people in their 55th year - this reduces the indicidence by 33% and mortality by 43%
It was not seen as a priority after the covid19 pandemic!
