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COLORECTAL CANCER Flashcards

1
Q

Whats the incidence of colorectal cancer?

A

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

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2
Q

What is the adenoma-carcinoma sequence?

A

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

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3
Q

What genetic mutations are associated with colorectal cancer?

A

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

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4
Q

Is colorectal cancer inherited?

A

Only 5% of cases are truly inherited
The vast majority occur spontaneously

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5
Q

What are adenomas?

A

a benign, dysplastic tumour of columnar cells or glandular tissue.

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6
Q

What are the hereditary syndromes that increase the risk of colorectal cancer?

A

Hereditary non polyposis colorectal cancer (lynch syndrome)
Familial adenomatous polyposis
MYH-associated polyposis
Serrated polyposis syndrome
Peutz-jeghers syndrome
Juvenile polyposis syndrome

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7
Q

What is HNPCC? What proportion of cases of colorectal cancer is it responsible for?

A

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%

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8
Q

What is FAP? What proportion will develop colorectal cancer?

A

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.

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9
Q

What screening is done for FAP?

A

Annual colonoscopies from age 12-14
Prophylactic surgical resection can be offered if anything is found

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10
Q

What is Gardner’s syndrome?

A

A form of FAP
It can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin

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11
Q

What is MYH-associated polyposis?

A

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.

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12
Q

What are serrated polyps?

A

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

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13
Q

What is peutz-jeghers syndrome? Whats the risk of colorectal cancer?

A

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.

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14
Q

What is juvenile polyposis syndrome?

A

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

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15
Q

Whats the onset of cancer in lynch syndrome?

A

40-50 or younger (earlier than in sporadic cases!)

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16
Q

Whats the mean age of adenoma development in FAP? Whats the average age at which colorectal cancer develops?

A

16 years
39 years

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17
Q

How should FAP be managed?

A

Affected individuals should be offered a prophylactic colectomy

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18
Q

What is attenuated FAP?

A

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

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19
Q

What proportion of colorectal cancers originate from serrated polyps?

A

30%

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20
Q

What are the risk factors of colorectal cancer?

A

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

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21
Q

What are the protective factors for colorectal cancer?

A

Regular physical exercise
Dietary fibre
Non-starchy vegetables
Pulses
High calcium intake
Garlic

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22
Q

What proportion of cases of colorectal cancer have a positive family history?

A

10-20%

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23
Q

What are the most common sites for colorectal cancer to develop?

A

Rectum 40%
Sigmoid colon 30%
Caecum 15%
Transverse colon 10%
Descending colon 5%
(2/3rds occur distal to splenic flexure)

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24
Q

What proportion of colorectal cancers have metastatic spread at diagnosis?

A

25%

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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
26
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
27
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
28
How does colorectal cancer present?
Change in bowel habit Rectal bleeding Unexplained weight loss (when associated with metastasis) Abdominal pain Symptoms of anaemia
29
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
30
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
31
What does it suggest if someone with colorectal cancer has had unexplained weight loss?
Metastatic disease
32
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
33
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)
34
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
35
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
36
When did the national bowel cancer screening programme start?
2006
37
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
38
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
39
What will happen to the pt in who an adenoma is found during colorectal cancer screening?
They will undergo subsequent colonoscopic surveillance
40
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
41
Whats the old staging tool for colorectal cancer?
Dukes staging
42
What staging is done for colorectal cancer?
TNM staging
43
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
44
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
45
Whats the curative treatment for colorectal cancer?
Surgery often in combination with chemotherapy Radiotherapy for rectal cancers only
46
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
47
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
48
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)
49
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)
50
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)
51
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
52
What proportion of pt with colorectal carcinoma undergo surgery?
About 80%
53
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
54
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
55
What surgery is used for removing colorectal cancer that is a Nyerere but the rectum?
Segmental resection
56
When is chemotherapy indicated for colorectal cancer?
For patients who have undergone potentially curative surgery but are at high risk of developing recurrent disease
57
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
58
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
59
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
60
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.
61
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
62
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
63
How can some early rectal cancers be treated?
Trans anal surgery
64
How can early polyp cancers be treated?
Endoscopic polypectomy
65
Is metastatic colorectal cancer treatable?
Yes!
66
How is metastatic colorectal cancer treated?
Liver and lung metastases can be respected Up to 40% 5 year survival for pt undergoing liver resection
67
how can colorectal cancer present as an emergency?
Obstruction Perforation Bleeding
68
What is FOLFOX?
FOLinic acid, Fluorouracil and OXaliplatin - adjuvant therapy for colorectal cancer
69
What is CAPOX?
CAPecitabine and OXaliplatin - adjuvant therapy for colorectal cancer
70
What are the complications of colorectal cancer?
Bowel obstruction Metastasis IDA Jaundice Perforation
71
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
72
Why may a pt need palliative treatment for colorectal cancer?
Inoperable metastases Pt isnt fit enough
73
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
74
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
75
When does colorectal cancer tend to recur?
Early - within first 2-3 years after initial treatment (so pt are followed up for 5 years!)
76
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.
77
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)
78
What does a FIT test do?
It tests for microscopic blood in the stool
79
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
80
What are the 3 types of colorectal cancer and what are their proportions?
Sporadic 95% HNPCC 5% FAP <1%
81
What are pt with HNPCC at higher risk for?
Colorectal cancer Endometrial cancer
82
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) 1. At least 3 relatives with an associated cancer, 1 of whom is a first degree relative of the other 2 (FAP should be excluded) 2. At least 2 successive generations involved 3. At least 1 should be a first degree relative of the other 2 4. 1 or more relatives diagnosed before age of 50
83
What are the 3 technical factors for an anastomosis to heal?
Adequate blood supply Mucosal apposition No tissue tension
84
What type of resection is done when the cancer is in the caecum, ascending or proximal transverse colon?
Right hemicolectomy with a ileocolic anastomosis
85
What type of resection is done when the cancer is in the distal transverse or descending colon?
Left hemicolectomy with a colo-colon anastomosis
86
What type of resection is done when the cancer is in the sigmoid colon?
High anterior resection with a colo-rectal anastomosis
87
What type of resection is done when the cancer is in the upper rectum?
Anterior resection with a colo-rectal anstomosis
88
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
89
What type of resection is done when the cancer is in the anal verge?
Abdominal-perineal excision of the rectum
90
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)
91
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
92
What are the most common metastatic sites?
Liver via portal venous system Pulmonary seedlings Rarer - skin, brain, bone
93
What is the apple core sign?
A sign of colon cancers that narrow the bowel lumen
94
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
95
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!

GI AND SURGERY (31 decks)

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