Colorectal Cancer Flashcards
most common site of bowel affected by colorectal Ca?
rectum
single biggest RF for colorectal Ca?
age
RFs for colorectal Ca?
increasing AGE
FH-lifetime risk 1 in 10 if 1 first degree relative diagnosed under the age of 45
inherited conditions-FAP and HNPCC, FAP-mutated APC gene, predisposition to multiple benign polyp development in the large bowel, mutation arises sporadically in 25% of cases.
HNPCC (Lynch syndrome)-increased risk of bowel Ca, uterine Ca, ovarian Ca, stomach Ca, pancreatic Ca, bile duct and bladder Cas. ?FH of Ca at a young age.
other polyposis syndromes
BRCA 1 gene faults in women under 50yrs
IBD-UC more so
previous bowel Ca
previous Ca-prostate, lung, endometrial, lymphoma
other medical conditions-DM, acromegaly, gallstones
infections-H pylori, HPV
radiation exposure
diet-rich in red meat and fat, low in fibre-prolonged gut transit time-increase time bowel epithelium exposed to carcinogens in stool (?and irritation to bowel mucosa impacted stools increase cell turnover), folate and calcium
obesity, smoking, high alcohol
what is FAP?
familial adenomatous polyposis
autosomal dominant inherited condition responsible for 1% of all colorectal cancer
APC gene mutation (a TSG) on chromosome 5
prophylactic colectomy offered in teenage years as all patients will develop CR cancer by age of 40
also susceptible to polyps elsewhere e.g. cystic gland polyps in the duodeum, proximal stomach, and extraintestinal lesions e.g. osteomas, epidermoid cysts and desmoid tumours.
most common cause of death in colectomized patients=dudoenal Ca
genetics underlying HNPCC?
autosomal dominant inheritence
microsatellite instability-naturally occuring highly repeated short DNA sequences are shorter or longer than normal
mutated DNA mismatch-repair genes e.g. hMSH2 and hMLH1.
role of MRI scanning in rectal cancer?
used to stage rectal cancer by looking for local invasion and nodal disease, and determine if need for radiotherapy pre-op.
what is Gardners syndrome?
now considered variant of FAP
autosomal dominant inheritence
due to APC mutation on chromosome 5 causing multiple colonic polyps AND extra colonic diseases-skull osteoma, thyroid Ca, epidermoid cysts (often called sebaceous cysts-central punctum from sebum)
how does a colorectal Ca evolve from a polyp?
develops over a 10 year period from polyp to invasive cancer
polyp=areas of cells proliferating more quickly than the rest of the bowel mucosa, increased number of cell turnover cycles increases likelihood of something going wrong-mutations developing, and over time mutations accumulate in sequence, and multiple mutations responsible for cancer development
e.g. p53, deletion of colorectal gene (DCC), K-Ras and APC.
risk of adenoma malignant transformation increases with their size, how long been present, and more likely with sessile or flat polyps.
what is the role of aspirin in reducing risk of CR cancer?
been shown to have a protective effect due to inhibitory effect on COX-2 which is found in high concentrations in colorectal tissue and promotes polyp growth.
why is surgical removal of primary disease even in the case of metastatic disease still considered?
to reduce risk of bowel perforation and obstruction.
how is neoadjuvant radiotherapy used in bowel Ca treatment?
used before surgery in rectal cancer to limit pelvic recurrence for low rectal tumours.
why is radiotherapy ONLY used in rectal cancers and NOT colon cancers?
radiotherapy for colon would irradiate the small bowel aswell, causing enteritis and fistulae.
current guidelines on bowel cancer screening?
FOB testing used for all men and women aged between 60 and 74, every 2 years. if 3+ blood then colonoscopy if 2+ discuss colonoscopy if 1+ rpt FOB if 0+ rpt in 2 years
also at age 55, everyone offered a flexible sigmoidoscopy, 1/3 of those with Ca will be picked up.
investigations in secondary care for suspected colorectal cancer in order to make the diagnosis?
colonoscopy=gold standard
if patients have major comorbidity, can 1st offer flexible sigmoidoscopy then barium enema-apple core stricture
must biopsy any suspicious lesions
consider CT colonography (part. Elderly) as alternative to colonoscopy or flexi sig if local radiology has competence in this technique. This is an effective and safe way of detecting abnormalities using double contrast (gastrograffin), with no need for IV contrast, bowel prep or mobility on the table. However, may get false +ves, and if suspicious lesion should then offer colonoscopy with biospy to confirm diagnosis unless contraindicated.
which tumour marker can be monitored in patients with CR Ca to help predict relapse?
CEA-elevated pre-treatment levels have -ve prognostic significance
and can be monitored to help predict relapse in patients after surgery suitable for further resection.
