GI - Colorectal cancer Flashcards
CRC
Epidemiology
Typical sites
Modes of metastasis
Epidemiology:
- > 90% of CRC occurs in patients age ≥ 50
- M: F ratio = 1.3: 1
- Commonest cancer in Hong Kong
- 2nd leading cause of cancer death in both males and females
Typical sites: Majority of CRC are left-sided cancer
- Ascending colon = 25%
- Transverse colon = 10%
- Descending colon = 15%
- Sigmoid = 20%
- Rectum = 30%
Modes of metastasis: Hematogenous/ Lymphatic/ Contiguous/ Transperitoneal
- Liver is usually the first site of metastasis since the venous drainage of intestinal tract
is via the portal venous system
- Lung can be the first site of metastasis for tumours in distal rectum since inferior rectal veins drains into IVC rather than portal venous system
CRC
Risk factors
Non-modifiable:
- Asian or Ashkenazi Jews
- Old age
Past medical history (PMH)
- Previous colorectal cancer (CRC)
- Colonic adenomatous polyps
- Hereditary colorectal cancer syndrome
* Familial adenomatous polyposis (FAP)
* Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch syndrome)
* Familial juvenile polyposis
* MYH-associated polyposis
* Hamartoma polyposis
- Inflammatory bowel disease
- Obesity
- Diabetes mellitus (DM)
Family history:
- Colorectal cancer (4x risk)
- Colonic adenomatous polyps
Social history:
- Smoking
- Alcoholism
- Lack of physical exercise
- Dietary lifestyle
* Red and processed meat
* Lack of dietary fibers
* High temperature cooking
Familial adenomatous polyposis (FAP)
Inheritance
Variants
Genetic cause
Disease course
Inheritance:
- Autosomal dominant (AD) syndrome
- Up to 25% present without other affected family members
Variants:
- Gardner’s syndrome = FAP associated with extracolonic manifestation
- Turcot’s syndrome = FAP associated with CNS tumours
- Attenuated FAP = < 100 adenomatous colorectal polyps at presentation
Genetics:
- germline mutations in adenomatous polyposis coli (APC) gene on chromosome 5
- APC gene is a tumour suppressor gene
Disease course:
- Polyp and symptoms appear at an average age of 16 (2nd – 3rd decades of life)
- Colorectal cancer occurs in 90% of untreated individuals at the age of 45 and approaches ~100% by 50 years old
- > 100 adenomatous colorectal polyps
- Adenomatous polyps do NOT have high malignant potential individually
- Increased risk of CRC due to vast number of adenomatous polyps
Familial adenomatous polyposis (FAP)
Extracolonic manifestations
Familial adenomatous polyposis (FAP)
Investigations
Investigation: Mainly by colonoscopy
- Colonoscopy showing > 100 polyps in addition to extra-colonic tumours of duodenum and
pancreas (ampullary carcinoma)
Genetic testing:
- APC genetics testing of at-risk family members
Surveillance:
- Flexible sigmoidoscopy every 1 year (annual) starting at age 12
- OGD every 1 – 3 years starting at age 25: for adenocarinoma in any part of GIT especially duodenum
Familial adenomatous polyposis (FAP)
Treatment options
Surgical treatment:
Total proctocolectomy with end ileostomy
Total proctocolectomy with ileal-pouch anal anastomosis (IPAA):
- Indicated for profuse polyposis without rectal sparing/ >10 rectal adenomas
- Indicated for mesenteric desmoid tumours (cannot convert IRA to IPAA later due to shortened mesentery)
- Higher risk of bleeding and infertility in women
Total abdominal colectomy with ileorectal anastomosis (IRA)
- Indicated if rectal sparing/ <10 rectal adenoma + all polyps managed endoscopically by colonoscopic snare excision
- May progress to severe rectal polyposis and require a secondary proctectomy
Hereditary non-polyposis colorectal cancer (HNPCC)
Inheritance
Genetic cause
Disease course
Inheritance:
- Autosomal dominant (AD) syndrome
Genetic cause: Amsterdam criteria for Lynch syndrome
- patients and family with a germline mutation in one of the DNA mismatch repair (MMR) genes: MLH1 (90%), MSH2, MSH6 (10%), EPCAM gene
Disease course:
- 70 – 80% of affected individuals will develop CRC
- Mean age of colorectal cancer at age 40 – 45 with some presenting in their 20s
Hereditary non-polyposis colorectal cancer (HNPCC)
Clinical manifestations
Diagnostic criteria
CRC:
- Predominant right sided
- Arise from large/ flat/ dysplastic adenomas
- Rapid progression from adenomas
Extra-colonic manifestation
o GI: Gastric/ Pancreas/ Biliary/ Small intestine
o Gyn: Endometrial/ Ovarian
o Uro: Renal/ Ureter
o CNS: Brain (glioma)
o Others: Sebaceous gland
Amsterdam criteria: 3-2-1 rule
- 3 or more relatives with Lynch syndrome associated cancer
- 2 or more successive generations should be affected
- 1 or more cancers were diagnosed before age of 50
- Familial adenomatous polyposis should be excluded in CRC
- Tumour should be verified by pathological examination
Hereditary non-polyposis colorectal cancer (HNPCC)
Investigations and surveillance
Management
Surveillance
- Colonoscopy: Starting at age 20 every 1 year
- OGD with biopsy of gastric antrum: Starting at age 30 every 1 – 2 years
- USG kidney and bladder: Starting at age 30 every 1 – 2 years
- Pelvic examination, endometrial biopsy, ransabdominal/transvaginal USG and CA125: Starting at age 30 every 1 year
Treatment
* Total abdominal colectomy with ileorectal anastomosis (IRA)
* Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO)
Colon
Vascular supply and lymphatics
Rectum
Anatomical boundaries
Anatomical features
Divisions
Neurovascular and lymphatics
Anatomical: Measuring 12 – 15 cm long starting from rectosigmoid junction to dentate line
o Radiographic: Sacral promontory is the upper limit of rectum
o Endoscopic: 15 cm from anal verge is the upper limit of rectum
Anatomical: Absence of taeniae coli, epiploic appendices and haustration; NOT suspended by a true mesentery
Mesorectum: perirectal areolar tissue that is thicker posteriorly and contains terminal branches of IMA
Divisions:
- Upper 1/3 = Covered by peritoneum anteriorly and laterally
- Middle 1/3 = Covered by peritoneum anteriorly only
- Lower 1/3 = Completely extra-peritoneal lying below pelvic peritoneum
Anal canal
Anatomical boundaries
Neurovascular and lymphatic supply
Anatomical definition of rectal cancers
Anal canal
* Measuring 4 cm long from the anal verge
* Dentate (Pectinate) line divides upper 2/3 and lower 1/3 of anal canal
Location of rectal cancer
* Lower rectal cancer = 4 – 8 cm from anal verge
* Middle rectal cancer = 8 – 12 cm from anal verge
* Upper rectal cancer = 12 – 15 cm from anal verge
CRC
Pathogenesis pathways
Adenoma-carcinoma sequence (60 – 70% of sporadic cancer): Chromosomal instability pathway
- arise from adenomatous polyps (2/3 all polyps) by accumulation of mutations and transform into adenomas
- Progression from adenoma to carcinoma takes at least 10 years on average
- Villous adenomas are associated with highest malignancy risk: up to 40%
- Other adenomas e.g. tubular, hyperplastic, non-polypoid adenomas have lower risk of malignant change
- Associated genetic changes: Acitvation of K-ras oncogene, Inactivation of APC and p53 tumour suppressor genes, Mutation of MYH repair gene
Microsatellite instability pathway (MSI) (15% of sporadic cancer)
- Strongly associated with HNPCC
- Includes MSH2, MLH1, PMS1, PMS2, MSH6/GTBP
- Instability promotes mutation, genomic instability and ultimately to carcinogenesis
CRC
TNM staging
TNM:
- Stage I = Tumour that is invasive through the muscularis mucosae but are confined to the
submucosa (T1) or muscularis propria (T2) in the ABSENCE of nodal metastasis
- Stage II = Tumour that invades through bowel wall into Subserosa or non-peritonealized pericolic or perirectal tissues (T3) or into other organs or tissues or through the visceral peritoneum (T4) in the ABSENCE of nodal metastasis
- Stage III = Presence of nodal metastasis with any T stage
- Stage IV = Presence of distant metastasis
Duke’s staging (superceded by TNM)
- Duke’s A = Tumour within wall of the bowel
- Duke’s B = Tumour invades through the wall of bowel
- Duke’s C = Presence of regional LN metastasis
- Duke’s D = Presence of distant metastasis
Colorectal polyp
Types and malignant potential
- Inflammatory pseudopolyp: No malignant potential
- Inflammatory reaction to muscosal ulcersations and regenerations in Inflammatory bowel disease - Haramtomatous: No malignant potential
- Juvenile polyp: young onset, might require polypectomy
- Peutz-Jeghers polyps: Associated with the Peutz-Jeghers syndrome (PJS) due to STK11 mutations - Serrated:
- Hyperplastic (most common non-neoplastic polyp): no malignant potential except subtype hyperplastic polyposis
- Sessile serrated polyp/ adenoma (SSP/A): Malignant potential, precursor lesion to sporadic microsatellite
instability-high (MSI-H) colon cancer
- Traditional Serrated Adenoma (TSA): malignant potential, prevalent in rectocigmoid colon
Adenomatous polyp: Malignant potential
- Endoscopic types: Sessile, Flat, Depressed, Pedunculated
- Histological types: Tubular (80% CRC), Villous (5-15% CRC), Tubulovillous (5-15% CRC)
- Malignant potential: Sessile > Pedunculated; Villous > Tubular
Classification for malignant colorectal polyps
Haggitt classification (1985) of pedunculated malignant colorectal polyps
Kudo (Kikuchi) classification of sessile malignant colorectal polyps
High risk features of malignant colonic polyps
High risk feature:
- associated with an increased incidence of LN
metastasis and residual cancer
- need for radical resection
List:
* Poorly differentiated histology
* Lymphovascular invasion
* Inadequate endoscopic resection margin < 2 mm
* T1 lesion with invasion into the lower 1/3 of the submucosa (Sm-3)
* T2 lesion or above with invasion through the muscularis propria
CRC
Clinical presentation
Clinical presentation:
- PR bleeding
- Melena
- Hematochezia
- Abdominal pain
* Partial or complete obstruction
* Peritoneal dissemination
* Intestinal perforation leading to generalized peritonitis
- Abdominal distention
- Change in bowel habit
- Tenesmus
- Diminished caliber of stool
- Lymphadenopathy
-Anemic symptoms - Pallor/ Palpitations/ Dyspnea
- Constitutional symptoms
- Nausea and vomiting
- Anorexia and weight loss
Extents of bowel resection
General rule: malignancy indicates ligation of vessels at their origin
- Segmental colectomy: cut descending colon with left colic branches
- Ileocecectomy: cut distal ileum and cecum with ileal branch of ileocolic artery
- Right hemicolectomy (benign): cut distal ileum, cecum, ascending colon, transverse colon to the right of middle colic artery + ileal and colic branches of ileocolic artery + right colic artery + branch of middle colic artery
- Right hemicolectomy (malignant): cut distal ileum, cecum and ascending colon, transverse colon to the right of middle colic artery + ORIGIN of ileocolic, right colic, middle colic artery and vein
- Extended right hemicolectomy: same as right hemocolectomy (malignant) + extend towards splenic flexure of transverse colon
- Transverse colectomy (usually do extended right hemicolectomy instead): cut from hepatic to splenic flexure of transverse colon, root of middle colic and left colic arteries
- Left hemicolectomy (benign): cut splenic flexure of transverse colon, descending colon and sigmoid colon above rectosigmoid junction + Branches of left colic artery + branches of sigmoid artery
- Left colectomy (malignant): cut splenic flexure of transverse colon, descending colon, and sigmoid colon below rectosigmoid junction + Origin of IMA and IMV
- Total colectomy: entire intraperitoneal colon from terminal ileum to below rectosigmoid junction with associated mesentery + All mesenteric vessels ligated close to origin
Compare open vs laparoscopic vs robotic colectomy
Laparoscopic colectomy:
- Uncomplicated localized colorectal
cancer
- No prior extensive abdominal surgery
Open colectomy:
- complicated colorectal cancer
Fecal immunochemical tests (FIT)
MoA
Sampling
Advantage and disadvantage
MoA:
- detect only human globin and thus do NOT detect upper GI bleeding since the globin is digested during the transit (more specific to lower GI bleeding)
- Food with peroxidase activity also do not produce a positive reaction
Sampling:
- Only 1 stool sample is required for automated analysis
- Sensitivity of test decreases with mailing, delayed processing after sampling and exposure to high ambient temperature due to Hb degradation
A
Fecal DNA test
MoA
Sampling
Advantage and disadvantage
MoA:
- Genetic mutations and epigenetic changes acquired during carcinogenesis can be detected in stool from DNA shed by colorectal neoplasm
Sampling:
- Individuals collect a full stool sample
- Optimal interval between screening fecal DNA test is every 3 years
Sigmoidoscopy for CRC screening
Testing procedure
Advantages and disadvantages
Testing:
- 60 cm sigmoidoscopy can reach to splenic flexure and can only identify leftsided colonic lesions
- paired with air-contrast barium enema to detect transverse and right-sided colonic lesions
Interval:
- Recommended every 5 years when performed alone or every 10 years if performed along with FOBT or fecal immunochemical test (FIT)
- Follow-up colonoscopy is indicated of multiple or large adenomas (≥ 1.0 cm) and for adenomas with villous histology
Colonoscopy for CRC screening
Testing procedure
Advantages and disadvantages
Testing:
- Definitive test for detection of advanced adenomas and colorectal cancer
- Used for screening, diagnostic and therapeutic purposes
Test procedures
- Aggressive bowel preparation is required
- Recommended to screen every 3-6 months for first 3 year
- Then every 6 months for 2 years
- CEA every 3-6 months
Rectal cancer
Local excision
Indication
Technique
Outcome
Rectal cancer
APR
Indication
Technique
Rectal cancer multivisceral resection
Indication
Technique
Outcome
Guaiac-based fecal occult blood test (gFOBT)
MoA
Specimen
Test performance
Advantage and disadvantage
MoA:
- Guaiac testing of stool samples identifies Hb by the presence of a peroxidase reaction which turns the guaiac-impregnated paper blue
- Guaiac reagents available on marker includes Hemoccult-SENSA (preferred)/ Hemoccult/ Hemoccult-II/ Hemoccult-R
Sample:
- Screening by gFOBT should be performed on 3 consecutive stool specimens
- Vitamin C should be restricted for at least 3 days prior to sampling (cause FN)
- Restrictive diet is NOT necessary as it decreases screening compliance
Test performance
- Hemoccult SENSA: Sensitivity = 64 – 80%; Specificity = 87 – 90%
- Hemoccult II: Sensitivity = 25 – 38%; Specificity = 98 – 99%
