CRC Flashcards
Most common colorectal cancer
95% adenocarcinoma
2/3 colon
1/3 rectal
How many cases of CRC are sporadic?
85%
10% familial risk
1% underlying IBD
Risk factors
Age Male 3:2 Female Previous adenoma/CRC Smoking Obesity Diabetes mellitus Diet - decreased fibre, fruit and veg, calcium, increased red meat and alcohol Streptococcus bovis bacteraemia IBD - ulcerative colitis > crohns Congenital Genetic
Predisposing inheritable factors for CRC
HNPCC (Lynch syndrome)
FAP
Which structures give rise to majority of CRCs?
Colorectal polyps
100s-1000s by FAP
Classification of colorectal polyps
Benign or malignant
Epithelial or mesenchymal
Define an adenoma
Benign, pre-malignant growth of epithelial origin
3 types of adenoma and rate of occurence
Tubular 75%
Tubuovillous (15%)
Villous 10%
Pedunculated or sessile - stalk or no stalk
What characterises a high risk adenoma
Size
Number
Degree of dysplasia
Villous architecture
An adenoma can progress to …
An invasive carcinoma
Describe the evolution of an adenoma to an invasive carcinoma
Activation of oncogene - kras, c-myc
Loss of tumour suppressor gene - APC, p53, DCC
Defective DNA Repair Pathway genes - microsatellite instability
3 processes in malignancy
Cell growth
Proliferation
Apoptosis
Oncogenes involved in CRC
K ras, c-myc
TSG lost in CRC
APC, p53, DCC
6 Aspects of Presentation
- Rectal bleeding (faecal occult blood)
- Altered bowel opening to loose stools for more than weeks
- Iron deficiency Anaemia
- Palpable rectal or Right lower abdominal mass
- Acute colonic obstruction (stenotic tumour)
- Systemic symptoms - weight loss, fatigue, anorexia
Investigation of CRC
Screening- faecal occult blood test Bloods - FBC for anaemia, CEA Colonoscopy Barium enema - apple core sign CT colonography CT abdo/pelvis
Staging investigations
CT chest/abdo/pelvis
MRI for rectal tumours
PET/rectal endoscopic US
Staging systems
TNM Dukes A-confined to muscularis mucosa B- extended beyond muscularis mucosa C- lymph nodes D- distant metastases
Treatment
Surgery
- Duke A and polyps - Endoscopic/ local resection
- Laparotomy
- Colostomy
- Hepatectomy for metastases
Conservative - macmillan nurse and patient education
Chemotherapy
- Dukes C and B, postive lymph node
- Agents - oxaliplatin, 5- FU (fluorouracil)
Radiotherapy - rectal cancer only
Palliative
Chemo, colonic stenting to prevent obstruction
Purpose of screening
Detect pre-malignancies
Modalities of screening
Faecal Occult Blood Test Faecal immunochemical test (FIT) Flexible sigmoidoscopy Colonoscopy CT colonography
Uses of colonoscopy
Biopsy
Polypectomy
Risks associated with colonsocopy
Perforation and Bleeding
Sedation and bowel prep needed
High Risk groups for CRC
HNPCC, FAP
IBD
Familial
Previous adenomas/CRC
What groups are offered CRC screening?
Ages 50-74
2 yearly FOBT
If positive offered colonoscopy
Which gene is mutated in Familial Adenomatous Polyposis
APC on chromosome 5
What is the inheritance pattern of FAP mutations?
Autosomal dominant
How does FAP present?
Multiple adenomas of the colon
50% by age of 15
95% by age 35
Extra-colonic manifestations
Desmoid Tumours
Congenital Retinal Hypertrophy of the Pigment Epithelia (CRHPE)
How often should someone with FAP be screened
Annually from age 10-12
Prophylaxis offered with FAP?
Proctocolectomy from 16-25
Extra-colonic manifestations of FAP
Benign gastric fundic cystic hyperplasia
Duodenal adenomas in 90%
Periampullary cancer 5%
Chemoprevention in FAP
NSAIDS
Sulindac
Reduces polyp number
Prevents recurrence of high grade adenomas in retained rectal segment
Pattern of inheritance of Hereditary Non-Polyposis Colorectal Cancer
Autosomal Dominant
What mutation occurs in HNPCC
DNA mismatch repair - MLH1, MSH2
Causes microsatellite instability
Presentation of CRC in HNPCC
Early onset
Right sided
Associated cancers with HNPCC
Genitourinary Endometrial Stomach Pancreas CNS- glioblastoma
Diagnostic Criteria for HNPCC
Amsterdam/Bethesda
Genetic testing
Screening for HNPCC
From age 25
2 yearly colonoscopy
Congenital risk factors for CRC
Juvenile Polyposis Syndrome - Autosomal dominant
Peutz-Jeghers - Autosomal dominant, melanosis of oral mucosa
Complications of CRC
Obstruction
Intussusception
Heavy bleeding
Metastasis
2 expressions of FAP
FAP coli -osteoma, epidermoid cysts, fibromas, desmoid tumours, lipomas, supernumeray teeth, periampullary cancers
Gardner Syndrome
Most common cancer syndrome
HNPCC lynch
Pathology of IBD –> CRC
Inflammation –> dyspasia –> carcinoma
Common subtypes of adenocarcinoma
Mucinous
Signet ring
Medullary
Site of CRC with increasing age
RHS
Age related change
Most present in sigmoid and rectum
Difference between left and right tumours
Right tend to be larger, more aggressive, distant metastases
Left - altered bowel habit, obstruction, hematochezia (fresh bleeding in anus)
Gold standard treatment
Endoscopy
Detection
Treatment of minor lesions - polypectomy, mucosal resection, submucosal dissection
Most common sites of distant metastases
Liver
Lung
Bone
What are Krukenberg’s tumours?
Present first as ovarian lesions
Tumours secondary to Colorectal or GI cancer
What plexus is within the submucosa?
Meissner’s
What plexus is withint the muscularis propria?
Auerbach’s
Which part of the rectum are lesions most likely to spread to the peritoneum?
Upper rectum
Majority is extraperitoneal
Fascia surrounding Mesorectal fascia
Waldeyer;s fascia- separate from sacrum posteriorly
Denonvillier’s fascia - separate from prostate anteriorly
Mesorectal fascia extends to which set of muscle?
Levator ani - puborectal sling
