Colorectal and Anal Cancer Flashcards
What is a polyp?
-Excrescence of mucosal lining
-Does not formally indicate nature of the lesion
Classification of large bowel polyps
-Neoplastic
-Hamartomata’s
-Inflammatory
-Unclassified
Neoplastic polyps
-Solitary= adenoma (tubular, tubulovillous, villous architecture)
-Multiple= familial adenomatous polyposis
Hamartomata’s polyps
-Solitary= juvenile polyp/ Peutz-Jeghers
-Multiple= juvenile polyposis/ Peutz-Jeghers syndrome/ Cronkhite-Canada syndrome/ Cowden’s disease
Inflammatory polyps
-Solitary= Benign lymphoid polyp/ pseudo-polyp
-Multiple= Benign lymphoid polyposis/ pseudo-polyposis (UC)
Unclassified polyps
-Solitary= metaplastic/ hyperplastic lipoma/ neurofibroma
-Multiple= Multiple metaplastic polyps/ MAP (MYTH associated polyposis)
Chance of malignant potential conversion with colorectal adenomas
-Size
=<1cm: 1%
=1-2cm: 9.5%
=>2cm: 50%
-Type
=Tubular: 5%
=Tubulo-villous: 22%
=Villous: 40%
-Dysplasia
=<1cm no dysplasia: 1%
=>1cm with dysplasia 27%
Molecular events in colorectal carcinogenesis
-Normal epithelium suffers Wnt signalling aberrations (APC/ b catenin mutations)
-Aberrant crypt foci
-Early adenoma then has K-ras mutation/ TGFb-R2 inactivation
-Intermediate adenoma then has loss of 18q genes
-Late adenoma
=SEQUENTIAL ACCUMULATION OF GENETIC MUTATION- HYPOMETHYLATION
-p53 mutation/ stabilisation= carcinoma= metastasis
Colorectal cancer aetiology
-Age
-Western diet
=High fat, red meat, total energy, low fibre, hight stool pH
-Lifestyle: smoking, lack of exercise, beer in rectal
-IBD: pan UC and Crohn’s
-Sporadic 95%
-Genetic predisposition
=35% overall contribution
=Dominant gene disorders: HNPCC (hereditary nonpolyposis colorectal cancer 5%), FAP (familial adenomatous polyposis) <1%
Overview of Lynch syndrome
-HNPCC
-Autosomal dominant
-Most common form of inherited colon cancer
-Around 70-80% of patients develop cancers, often of the proximal colon, which are usually poorly differentiated and highly aggressive
-Most common genes involved: MSH2 (60%), MLH1 (30%)
Patients with HNPCC are also at a higher risk of other cancers, with endometrial cancer being the next most common association, after colon cancer
-HNPCC family may be better served with a panproctocolectomy rather than segmental resection
Pragmatic Amsterdam criteria for HNPCC
->3 family member with histologically proven CC
-1 relative a 1st first degree
->2 generations affected
-Age at onset <50 years in at least one member
-Uterine cancer in 1> relatives acceptable as part of 3 members
Overview of FAP
-Rare autosomal dominant condition
-Formation of hundreds of polyps be age 30-40
=Carcinoma inevitably
-Mutation in tumour suppressor gene (APC) chromosome 5
-Genetic testing from DNA white blood cells
-Risk from duodenal tumours
-A variant of FAP called Gardner’s syndrome can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin
-Total proctocolectomy with ileal pouch anal anastomosis (IPAA) formation in their twenties.
Emergency clinical presentations of CC
-Obstruction: abdo pain, nausea, vomiting
-Perforation
-Bleeding
-Localised pain
Elective clinical presentations of CC
-Altered bowel habit: diarrhoea/ constipation/ urgency/ frequency
-Rectal bleeding: bright red or melena
-Colicky pain: obstruction/inflammation
-Unexplained anaemia
-Anorexia/ weight loss/ malaise: chronic bleeding
-Flatulence
Topographical distribution of CC
- 35% = Rectum
- 26%= Sigmoid
- 22% = Caecum
- 12%= Splenic flexure
- 5%= Transverse
rectal: 40%
sigmoid: 30%
descending colon: 5%
transverse colon: 10%
ascending colon and caecum: 15%
Investigation of symptomatic individuals
-Colonoscopy
-CT colonography (virtual colonoscopy)
-Emergency operation (20-25%)
Screening of colorectal cancer
most cancers develop from adenomatous polyps. Screening for colorectal cancer has been shown to reduce mortality by 16%
the NHS offers home-based, Faecal Immunochemical Test (FIT) screening to older adults
a one-off flexible sigmoidoscopy at the age of 55 years was trialled in England but was abandoned in 2021
=this mainly due to an inability to recruit enough clinical endoscopist, exacerbated by the covid-19 pandemic
=the trial, partly funded by Cancer Research UK, had shown promising early results and it remains to be seen whether flexible sigmoidoscopy will be used as part of a future bowel screening programme
Describe a FIT test
-the NHS now has a national screening programme offering screening every 2 years to all men and women aged 60 to 74 years in England, 50 to 74 years in Scotland. Patients aged over 74 years may request screening
-eligible patients are sent Faecal Immunochemical Test (FIT) tests through the post
-a type of faecal occult blood (FOB) test which uses antibodies that specifically recognise human haemoglobin (Hb)
-used to detect, and can quantify, the amount of human blood in a single stool sample
-advantages over conventional FOB tests is that it only detects human haemoglobin, as opposed to animal haemoglobin ingested through diet
-only one faecal sample is needed compared to the 2-3 for conventional FOB tests
-whilst a numerical value is generated, this is not reported to the patient or GP, who will instead be informed if the test is normal or abnormal
-patients with abnormal results are offered a colonoscopy
NICE recommendations for FIT in guiding referral
with an abdominal mass, or
with a change in bowel habit, or
with iron-deficiency anaemia, or
aged 40 and over with unexplained weight loss and abdominal pain, or
aged under 50 with rectal bleeding and either of the following unexplained symptoms:
abdominal pain
weight loss, or
aged 50 and over with any of the following unexplained symptoms:
rectal bleeding
abdominal pain
weight loss, or
aged 60 and over with anaemia even in the absence of iron deficiency
What is under surveillance for CC?
-HNPCC
-FAP
-IBD
-Prior cancer
Population screening for CC
-Implemented SE Scotland
-Immunological test
Overall investigations for CC
-History and clinical examination
-Digital rectal examination
-Rigid sigmoidoscopy and biopsy
-Colonoscopy/ CT colon
-All patients with proven CRC require entire colon assessed
-Abdominal CT scan (emergency)
Preoperative staging imaging
-CT scan- chest, abdo, pelvis
-MRI pelvis (rectal ca, tumours below peritoneal reflection)
-Ultrasound: transcutaneous liver, rectal endoluminous USS
-CT/PET scan- currently restricted to work-up for resection of liver, distant Mets or local recurrence
-CEA tumour markers
Emergency CC surgery
-Segmental excision and on-table colonic lavage (obstruction)
-Colectomy and ileectomy anastomosis
-Hartmann’s procedure
In the emergency setting where the bowel has perforated the risk of an anastomosis is much greater, particularly when the anastomosis is colon-colon. In this situation, an end colostomy is often safer and can be reversed later. When resection of the sigmoid colon is performed and an end colostomy is fashioned the operation is referred to as a Hartmann’s procedure. Whilst left-sided resections are more risky, ileo-colic anastomoses are relatively safe even in the emergency setting and do not need to be defunctioned.
Elective CC surgery
-Segmental resection
-Restorative rectal excision +/- colonic pouch
-Transanal excision of rectal cancer
-Colonscopic polypectomy
Resections for colorectal cancer
-Caecum/ascending/proximal transverse= right hemicolectomy, ileo-colic anastomosis
-Descending/ distal transverse= left hemicolectomy, colo-colon
-Sigmoid= high anterior resection colo-rectal
-Rectal= anterior resection, colo-rectal anastomosis
Duke’s staging of CC
A= no lymph nodes, limited to bowel wall
B= no lymph nodes, through full thickness bowel wall
C= lymph nodes involved, C1 regional lymph nodes involved, C2 apical lymph nodes involved
D= lymph nodes involved, metastatic disease
T in TNM staging
-Tx= Primary tumour cannot be assessed
-Tis= carcinoma in situ
-T1= cancer invades submucosa
-T2= cancer invades muscularis propria
-T3 cancer into subserosa or non-peritonealised pericolic or perirectal tissues
-T4= perforates viscous peritoneum or directly invades adjacent organs
N in TNM staging
-Nx= the regional lymph nodes cannot be assessed
-N0= no regional lymph nodes involved
-N1= Metastases in 1-3 pericolic or perirectal lymph nodes
-N2= Metastases in 4 or more pericolic or perirectal lymph nodes
-N3= Metastases in lymph node along the course of a major named blood vessel
M in TNM staging
-Mx= presence of distant metastases cannot be assessed
-M0= no distant metastases
-M1= Distant metastases
Pathological prognostic factors
-Tumour type (standard, signet cell, mucus producing, anaplastic)
-Extent of local spread/ peritoneal involvement
-Histological grading (degree of differentiation)
-Lymph node involvement
-Lymphatic invasion on microscopy
-Vascular invasion on microscopy
-Pushing vs infiltrating margin
-Host lymphocytic infiltration
Adjuvant chemotherapy
Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), particularly for metastatic disease
-5-fluorouracil based regimens (capecitabine)
-Combination therapy (CAPOX)
-Capecitabine (thymidylate synthase inhibitor) + oxaliplatin
-2nd line
=Cetuximab (to epidermal growth factor receptor)
=Bevacizumab (to vascular endothelial growth factor)
=Temozolomide
Neoadjuvant radiotherapy for rectal cancer
-Short course pre-op 25Gy over 5 days in week leading up to surgery
-Long course 52Gy over 3 months
=30% reduction in local recurrence rate
=No overall mortality reduction for any XRT regimen
=Down-staging inoperable to operable cancers
Aetiology of anal cancer
-Human papilloma virus 6, 11, 16
-Anoreceptive intercourse
-Immunosuppression (HIV)
Pathology of anal cancer
-AIN (anal intra-epithelial neoplasia)
-Squamous
-Adenocarcinoma
-Basiloid
-Small cell carcinoma
-Malignant melanoma
Clinical presentation of anal cancer
-Ulcer
-Wart lesion
-Pruritis
-Pain
-Bleeding
Treatment of anal cancer
-Local excision for invasive carcinoma T1/T2 tumours
-Combined chemo-radiation for invasive carcinoma
-Abdomino-perineal excision - salvage procedure
