Colorectal Cancer Flashcards
Certain genetic mutations have been implicated in predisposing individuals to colorectal cancer, such as what?
Adenomatous polyposis coli (APC)
Hereditary nonpolyposis colorectal cancer (HNPCC)
Risk factors for colorectal cancer
Increasing age
Male
Family history
IBD
Low fibre diet
High processed meat intake
Smoking
Excess alcohol
Approximately 75% of colorectal cancers are sporadic, developing in people with no specific risk factors.
What is Adenomatous polyposis coli (APC)
A tumour suppressor gene, mutation of the APC gene results in growth of adenomatous tissue, such as Familial Adenomatous Polyposis (FAP)
Genetic predisposition to colorectal cancer
What is Hereditary nonpolyposis colorectal cancer (HNPCC)
A DNA mismatch repair gene, mutation to HNPCC leads to defects in DNA repair, such as Lynch syndrome
Common clinical features of colorectal cancer
Change in bowel habit
Rectal bleeding
Weight loss
Abdominal pain
Symptoms of (iron-deficiency) anaemia.
Right-sided colon cancers – clinical features
Abdominal pain
Iron-deficiency anaemia
Palpable mass in right iliac fossa
Often present late
Left-sided colon cancers – clinical features
Left-sided colon cancers
Rectal bleeding
Change in bowel habit
Tenesmus
Palpable mass in left iliac fossa or on PR exam
Which sided colon cancer is tenesmus more typical of?
Left sided
Which sided colon cancer is rectal bleeding more typical of?
Left sided
Which sided colon cancer is more likely to present late?
Right sided
When does NICE guidance recommend that patients should be referred for urgent investigation of suspected bowel cancer?
≥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
Rectal or abdominal mass
Aged under 50 with rectal bleeding AND any of the following unexplained symptoms:
Abdominal pain
Change in bowel habit
Weight loss
Iron-deficiency anaemia
Upper vs lower GI cancer - weight loss
As opposed to upper GI malignancies, progressive weight loss is usually only present in colorectal cancer cases with associated metastasis (or rarely in sub-acute bowel obstruction)
Main differentials when considering ?colorectal cancer and how they may differ
Inflammatory bowel disease – The average age of onset of inflammatory bowel disease is younger (20-40yrs) than with colorectal cancer and typically presents with diarrhoea containing blood and mucus
Haemorrhoids – Bright red rectal bleeding on the pan or surface of the stool but rarely presents with abdominal discomfort or pain, altered bowel habits, or weight loss
How often is FIT offered and for who?
In England and Wales, screening is offered every 2 years to men and women aged 60-74 years
For most of the UK a faecal immunochemistry test (FIT) is used
Consequence of a positive FIT?
If any of the samples are positive, patients are offered an appointment with a specialist nurse and further investigation via colonoscopy
Investigations in colorectal cancer
Routine bloods: FBCs (may show microcytic anaemia (iron def)), LFTs, clotting
Carcinoembryonic Antigen (CEA) - used to monitor disease progression and should be conducted both pre- and post-treatment, screening for recurrence.
Colonoscopy with biopsy + removal of any polyps seen(CT colonography considered if not suitable) - GOLD STANDARD INITIAL INVESTIGATION
Staging following initial diagnosis: CT scan/MRI rectum/Endo-anal ultrasound
Staging investigations in colorectal cancer?
CT scan (Chest/Abdomen/Pelvis) to look for distant metastases and local invasion
MRI rectum (for rectal cancers only) to assess the depth of invasion and potential need for pre-operative chemotherapy
Endo-anal ultrasound (for early rectal cancers, T1 or T2 only) to assess suitability for trans-anal resection
Biopsy samples being sent for histology will be assessed using TNM staging, histological subtyping, grading, and assessment of lymphatic, perineural, and venous invasion.
Role of biopsy in colorectal cancer
Biopsy samples being sent for histology will be assessed using TNM staging, histological subtyping, grading, and assessment of lymphatic, perineural, and venous invasion.
Increasingly, samples are also routinely being assessed for varying tumour-based markers (including mismatch-repair testing), to aid in the identification of Lynch syndrome and to optimise potential chemotherapy regimes.
Dukes Stage A colorectal cancer
A Confined beneath the muscularis - limited to the bowel wall
Dukes Stage B colorectal cancer
Extension through the muscularis propria - extending through the bowel wall
Dukes Stage C colorectal cancer?
Involvement of regional lymph nodes
Dukes Stage D colorectal cancer?
Distant metastasis
General principles of management in colorectal cancer?
All patients should be discussed with the multidisciplinary team (MDT).
The only definitive curative option is surgery, although chemotherapy and radiotherapy have an important role as neoadjuvant and adjuvant treatments, alongside their role in palliation.
Mainstay of curative management of colorectal cancer?
Surgery is the mainstay of curative management for localised bowel cancer. The general plan in most surgical management plans is suitable regional colectomy, to ensure the removal of the primary tumour with adequate margins and lymphatic drainage, followed either by primary anastomosis or formation of a stoma
When is colorectal cancer managed with right hemicolectomy or extended right hemicolectomy
Caecal tumours or ascending colon tumours
What does a right hemicolectomy involve?
During the procedure the ileocolic, right colic, and right branch of the middle colic vessels (branches of the SMA) are divided and removed with their mesenteries
When is colorectal cancer managed with an extended right hemicolectomy
Transverse colon tumour
What surgical approach may be used to manage a caecal tumour?
Right hemicolectomy
What surgical approach may be used to manage an ascending colon tumour?
Right hemicolectomy
What surgical approach may be used to manage a transverse colon tumour?
Extended right hemicolectomy
When is colorectal cancer managed with a left hemicolectomy
Descending colon tumour
What surgical approach may be used to manage an descending colon tumour?
Left hemicolectomy
When is colorectal cancer managed with a Sigmoidcolectomy?
Sigmoid tumour
What surgical approach may be used to manage a sigmoid tumour?
Sigmoidcolectomy
What does a left hemicolectomy involve?
The left branch of the middle colic vessels (branch of SMA/SMV), the inferior mesenteric vein, and the left colic vessels (branches of the IMA/IMV) are divided and removed with their mesenteries
What does a sigmoidcolectomy involve?
In this instance, the IMA is fully dissected out with the tumour in order to ensure adequate margins are obtained.
What surgical approach may be used to manage a high rectal tumour >5cm from the anus?
Anterior Resection
When might a anterior resection be used?
high rectal tumour >5cm from the anus
What does an anterior resection involve?
This approach is favoured as leaves the rectal sphincter intact if an anastomosis is performed (unlike AP resections). Often a defunctioning loop ileostomy is performed to protect the anastomosis and reduce complications in the event of an anastomotic leak, which can then be reversed electively four to six months later
What does an Abdominoperineal (AP) Resection involve?
This technique involves excision of the distal colon, rectum and anal sphincters, resulting in a permanent colostomy
What surgical approach may be used to manage a low rectal tumour <5cm from the anus?
Abdominoperineal (AP) Resection
When might an abdominoperineal resection be performed?
Low rectal tumour <5cm from the anus
When is a Hartman’s procedure performed?
This procedure is used in emergency bowel surgery, such as bowel obstruction or perforation.
This involves a complete resection of the recto-sigmoid colon with the formation of an end colostomy and the closure of the rectal stump
What does a Hartman’s procedure involve?
This involves a complete resection of the recto-sigmoid colon with the formation of an end colostomy and the closure of the rectal stump
Colorectal cancer presenting with bowel obstruction can be relieved how?
A decompressing colostomy or endoscopic stenting, after which staging and patient status can be optimised
Role of chemotherapy in colorectal cancer?
Chemotherapy is indicated typically in patients with advanced disease (adjuvant chemotherapy in Dukes’ C colorectal cancer has been found to reduce mortality by 25%). Systemic therapy for metastatic colorectal cancer is tailored with patient-specific and disease-specific predictive markers.
An example chemotherapy regime for patients with metastatic colorectal cancer is FOLFOX, comprised of Folinic acid, Fluorouracil (5-FU), and Oxaliplatin, which has been demonstrated to significantly improvement in 3-year disease-free survival for patients with advanced colon cancer.
Newer biologic agents or immunotherapies are being developed and used to growing success.
What is the FOLFOX chemotherapy regime for patients with metastatic colorectal cancer?
Folinic acid, Fluorouracil (5-FU), and Oxaliplatin
Role of radiotherapy in colorectal cancer management?
Radiotherapy can be used in rectal cancer (it is rarely given in colon cancer due to the risk of damage to the small bowel), most often as neo-adjuvant treatment, and can be given alongside chemotherapy.
It is of particular use in patients with rectal cancers which look on MRI to have a “threatened” circumferential resection (i.e. within 1mm). They can undergo pre-operative long-course chemo-radiotherapy to shrink the tumour, thereby increasing the chance of complete resection and cure; time interval to surgery is then approximately 8-10 weeks.
Due to certain cases achieving complete response with chemo-radiotherapy, some patients with rectal cancer will opt for a rectal preserving treatment approaches, where a “watch-and-wait” strategy is employed with the omission of radical surgery and close surveillance.
Is radiotherapy used more often in rectal or colon cancer? Why?
Radiotherapy can be used in rectal cancer (it is rarely given in colon cancer due to the risk of damage to the small bowel), most often as neo-adjuvant treatment, and can be given alongside chemotherapy.
Strong risk factors of colorectal cancer?
Increasing age
Heridiatry syndromes (FAP, Lynch syndrome, juvenile polyposis, Peutz-Jeghers syndrome)
Increased alcohol intake
Smoking tabacco
Processed meat
Obesity
Previous exposure to radiation
IBD
Hereditary syndromes which increase the risk of colorectal cancer?
Familial adenomatous polyposis
Hereditary nonpolyposis colorectal cancer
(Lynch Syndrome)
Juvenile polyposis
Peutz-Jeghers syndrome
Weak risk factors for colorectal cancer?
Lack of dietary fibre
Limited physical activity
Asbestos exposure
Red meat (non-processed)
TNM staging of colorectal : T
Tis - carcinoma in situ/intramucosal cancer
T1 - extends through the mucosa into the submucosa
T2 - extends though the submucosa into the muscularis
T3 - Extends through the muscularis into the subserosa
T4 - extends into neighbouring organs or tissues
TNM staging of colorectal : N
N0 - no regional lymph node involvement
N1 - metastasis to 1-3 regional lymph nodes
N2 - metastasis to 4 or more regional lymph nodes
TNM staging of colorectal : M
M0 - no distant mets
M1 - distant mets
Patients with Duke’s stage C or stage III (T1-4, N1-2, M0) colon cancer benefit from what management?
Adjuvant chemotherapy and surgical rescetion
fColorectal cancer patients without lymph node involvement but with high risk features (such as vascular or perineural invasion) also show improved survival with what additional management?
Adjuvant chemotherapy
What does FIT stand for?
Faecal immunochemical test
When might it be useful to request a faecal occult sample ?
Aged > 50 with either:
Unexplained abdominal pain
Unexplained weight loss weight loss
Aged > 60 with any form of anaemia
Aged under 60 with:
Changes in their bowel habit
Iron-deficiency anaemia
In what situations may someone come to the attention of oncology services with colorectal cancer?
Positive faecal occult sample requested (due to >50 - unexplained abdominal pain or weight loss, >60 any for of anaemia, under 60 with iron def aneamia or changes in bowel habit)
Other symptoms may include tenesmus, change in stool form (thin, small stools) and abdominal distension.
Patients may also be identified by the current bowel screening programme which offers a faecal immunochemical test (FIT) every 2 years to all men and women aged 60 – 74.
More rarely, patients may present as a clinical emergency as a consequence of carcinoma, such as large bowel obstruction.
Colon cancer: Stage 1-4 disease management (assuming pt suitable for surgery)
Surgical resection ± post-operative chemotherapy
+ STAGE IV (mets): pre-operative chemotherapy may also be performed.
The staged colectomy and resection of metastatic disease is performed after pre-operative chemotherapy.
Management of rectal cancer (assuming pt suitable for surgery)
For patients with rectal cancer suitable for surgery: Anterior resection for tumours >8 cm from the anal canal or involving the proximal 2/3 of the rectum. Abdomino-perineal (AP) resection for tumours <8 cm from the anal canal or involving the distal 1/3 of the rectum.
Patients with stage III disease benefit from post-operative chemotherapy.
Patients with stage IV disease benefit from post-operative chemoradiotherapy
How might patients with colorectal not suitable for surgery be managed?
Management is with chemotherapy (FOLFOX or FOLFIRI i.e. oxaliplatin/irinotecan plus folinic acid plus fluorouracil are the preferred regimens).
New monoclonal antibody therapies are becoming available. Note that NICE concluded that cetuximab (anti-EGFR), is cost effective
Stenting for obstructing tumours of the sigmoid colon or rectum
If the colorectal cancer patient presents with acute bowel obstruction, what interim measure might be used?
a Hartmann’s procedure may be required as an interim measure (resection of the rectosigmoid colon with formation of a temporary end colostomy and anorectal stump).
Familial adenomatous polyposis genetic abnormality + inheritance
Caused by a mutation in the adenomatous polyposis coli (APC) gene and has an autosomal dominant inheritance pattern.
How are patients with familial adenomatous polyposis managed and why?
Patients develop hundreds of adenomatous polyps in their teens and are virtually guaranteed to develop colorectal cancer by their 20s, unless they undergo prophylactic proctocolectomy.
Note that there is a high risk of developing duodenal cancer, so patients undergo regular endoscopic surveillance.
What is Gardener’s syndrome?
Gardener’s syndrome is a variant of FAP in which patients may also develop epidermal cysts, supernumerary teeth, osteomas, and thyroid tumours.
How is HNPCC/Lynch syndrome managed and why?
Patients have an 80% risk of developing colorectal cancer by their 30s.
There is increased risk of additional cancers such as gastric, endometrial, breast, and prostate cancer.
Patients are managed with regular endoscopic surveillance.
HNPCC/Lynch syndrome - genetic abnormality and inheritance?
Is caused by a mutation in the mismatch repair genes MLH1/MSH2 and has an autosomal dominant inheritance pattern.
Peutz-Jeghers syndrome genetic abnormality and inheritance?
Is caused by a mutation in the STK11 gene and has an autosomal dominant inheritance pattern.
How are patient with Peutz-Jeghers syndrome managed and why?
The risk of neoplastic transformation of hamartomatous polyps is low, but many polyps are present so patients are at increased risk of developing colorectal cancer.
They are managed with regular endoscopic surveillance.
How and when do patients with Peutz-Jeghers syndrome usually present?
Patients typically present in their teens with mucocutaneous pigmentaiton and hamartomatous polyps.
What genetic condition warrants prophylactic proctocolectomy?
Familial adenomatous polyposis (FAP) - mutation in the adenomatous polyposis coli gene, which otherwise virually guarentees development of colorectal cancer before the patient turns 20
