Seminar 10 - Colorectal Cancer Flashcards
What is the seed-soil hypothesis (relating to tumour cell tropism)
The ability of tumour cells from one site to adapt to a foreign environment may be limited to certain tissue types (e.g. if the soil is unfavorable)
Need the right conditions for the seed of cancer to grow
E.g., metastasis to skeletal muscle and spleen are rare despite a rich vascular supply -> “unfavorable soil”?.
The grading system for colorectal cancer can only be used for classic adenocarcinoma - true or false
True
This is because some histological variants may appear as poorly differentiated but act as well differentiated tumours
What is the most common cause of infective colitis in the West
Bacteria
In developing countries – parasites/fungal more common
What is the most common emergency surgery performed in paediatric patients
Appendectomy for appendicitis
Colonic adenomas are common in the older population - true or false
True
30% of adults in the western world will have them by age 60 so surveillance is carried out beginning at age 45/50
Describe the normal pathogenesis of colorectal adenocarcinomas
Most develop through normal mucosa progressing to colonic adenomas (precursor)
Then to invasive carcinoma through the adenoma-carcinoma sequence
How would you differentiate between a large bowel obstruction and toxic megacolon
Diagnosis may be apparent from clinical picture
Plain abdominal x-ray may show “thumb printing” or intraluminal soft tissue mass (pseudopolyps) if toxic megacolon
Further tests required
What is the normal treatment for FAP
Sigmoidoscopy is carried out from around age 12
A prophylactic colectomy is standard treatment. - usually before the age of 25
List the macroscopic features of pseudomembranous colitis
Yellow-white mucosal plaques:
Adherent but easily dislodged
Comprised of fibrin, mucin, neutrophils and cellular debris
May resemble polyps
May have a hyperaemic mucosal surface
White/ yellow/ green exudate over large areas of mucosal surface
What causes tumour cell interactions to loosen up in the metastatic cascade
E-cadherin function lost due to mutations
This dissolves intra-tumour cell connections
How long do the surface epithelial cells of the colon mucosa last
They are replaced around every 6 days, with the old cells sloughed off into the lumen
What is the precursor lesion to colorectal adenocarcinoma
colonic adenoma
Do hyperplastic polyps have malignant potential
No
however may occur in response to an adjacent or underlying inflammatory lesion or other mass
This is a non-specific reaction
What determines the likelihood of metastasis in solid malignant cancer
It correlates with other features of malignancy including lack of differentiation, aggressive local invasion, rapid growth, and large size.
However, there are numerous exceptions - small, well-differentiated, slow-growing lesions sometimes metastasize widely; some rapidly growing, large lesions remain localised for years
Which ethnicities have the highest incidence of colorectal cancer
African Americans have higher incidence of and mortality rate form colorectal adenocarcinoma than Caucasians
24% higher incidence in African American men and 19% higher incidence in African American
Can sarcomas spread via the lymphatics
Yes
How are high grade dysplastic lesions in the colon managed
They are managed with colectomy as tends to be associated with invasive carcinoma at that site or a distant one
Describe a pedunculated polyp
As the polyp proliferates, a stalk can form
This occurs due to enlargement and proliferation of the cells
List causes of infective colitis
Ingestion of pre-formed toxins
Infection by toxigenic organisms
Infection by enteroinvasive organisms (invade and destroy mucosal epithelium)
Infection by viral organisms
Can also be fungal, parasitic, mycobacterial
How are IBD patients monitored for colorectal cancer
They get routine colonoscopy and biopsy looking for dysplastic lesions from 8 yrs following diagnosis
What happens if small bowel obstruction is left untreated
Obstruction progresses to intestinal necrosis, perforation, sepsis, and multi-organ failure
You may get partial passage of flatus and sometimes stool in which type of small bowel obstruction
Partial bowel obstruction
Describe the muscular features of the colon
The large bowel has 3 strips of longitudinal muscle running across the surface which are the teniae coli.
Also has the haustra which are formed when the bowel muscles contract.
What is the cancer risk associated with juvenile polyps
The polyposis syndrome is associated with dysplasia
Either within the polyps or via separate adenomas
30-50% of patients will develop colonic adenocarcinoma by age 50
How do you manage infective colitis
Many cases are self-limiting and only require supportive treatment e.g. oral rehydration
There is some argument as to the efficacy of antibiotic use in all pts – usually reserved for pts with persistent symptoms
Which ethnicities have the lowest incidence of colorectal cancer
Asian ethnicities followed by Hispanics
Are the properties of invasiveness and metastasis are separable in malignant tumours
YES
Some tumours invade early and rarely met - one does not determine the other
How can large bowel obstruction lead to sepsis
It is a frequent complication owing to bacterial translocation from the obstructed colon
Sepsis and septic shock are likely to follow colonic perforation without surgical intervention
Describe the different subtypes of colonic adenoma
Tubular - small and pedunculated with round/tubular glands
Villous - larger and sessile, covered in slim villi (more likely to become cancer but may be related to size)
Tubulovillous is a mix between the 2
Partial bowel obstructions tend to respond to non-operative therapy - true or false
True
Which factors stimulate the migration process in the metastatic cascade
Tumour cell-derived cytokines which act as autocrine motility factors
Cleavage products of matrix components (collagen, laminin)
Stromal cell-derived paracrine factors which stimulate motility.
What causes the constipation seen in small bowel obstruction
The obstruction causes distal interruption of faecal flow
Constipation will be absolute
Describe the specific pathogenesis of large bowel obstruction caused by a volvulus
Colonic volvulus arises following axial rotation of the colon on its mesenteric attachments
The sigmoid colon is the most frequently affected segment (76%), then the caecum (22%)
Once the volvulus has a 360° twist, then a closed loop obstruction is produced
Fluid and electrolyte shifts result from fluid secretion into the closed loop producing an increase in pressure and tension on the colonic wall that will eventually impair colonic blood supply
This results in ischaemia, necrosis, and perforation
What causes juvenile polyps
Several mutations associated with this condition, with some yet to be identified.
Most common mutation is in SMAD4 which is involved in the TGF-B pathway (regulates cellular growth)
Responsible for more than half of all cases
Which techniques are used for adjuvant therapy in rectal adenocarcinoma
Radiation Chemotherapy Chemoradiation Radioembolisation Intraoperative radiotherapy
How do right sided colorectal cancers present
Most often present with solely fatigue and weakness from iron deficiency anaemia
May also show abdo pain, RIF mass and diarrhoea
Includes those in the caecum
The absence of a STK11 mutation excludes a diagnosis of Peutz-Jegher’s syndrome - true or false
False
Does not exclude
What type of epithelium lines the small intestine
lined bysimple columnar intestinal epithelium
List the microscopic features of hyperplastic polyps
Composed of mature goblet and absorptive cells
Have a serrated surface - hallmark
Serrated appearance is caused by cellular overcrowding, so they are pushed up into ‘tufts’
Rectal mets may avoid the liver - true or false
True
Only the upper 1/3 of the rectum is drained portally so tumours from the bottom 2/3 may avoid the liver (drained systemically)
A caecal volvulus is more common in frail, elderly patients - true or false
False
Sigmoid volvulus is more usually seen in frail or older patients
Caecal volvulus is even rarer and more commonly seen in younger patients
Colorectal cancers on which side tend to present first
Left
The symptoms are most obvious (bleeding/bowel habits) so often presents earlier
When would you suspect HNPCC
If a patient has 3 or more relatives (at least one immediate) from 2 successive generations that have been affected by HNPCC associated cancers.
One of whom must have developed cancer under the age of 50
What imaging tests would you order for suspected large bowel obstruction
CT
AXR
What is a possible complication of an appendectomy
Wound infection
However, risk is minimised with laparoscopic surgery and prophylactic Abx
How are low grade dysplastic lesions in the colon managed
Managed with increased surveillance
OR
Colectomy - if multiple foci of flat dysplasia, in extensive or long standing disease or in older patients
What happens if an tumour suppressor gene loses function or has increased inhibition
It will lead to cancer
Which part of DNA is most affected by the mutations in HNPCC
The microsatellites - short repeating sequences in the DNA
Microsatellites are prone to expansion and can become unstable due to mutation accumulation – increased cancer risk
Mutations occur at much higher rates than usual (up to 1000x more than normal)
What is meant by “evasion of apoptosis” in relation to cancer cells
Tumours are resistant to programmed cell death
How do you manage a large bowel obstruction
Suspected impending perforation means there is no time to waste!
Supportive + emergency surgery
If there is time for investigations and the cause can be determined then the treatment will vary depending on the cause
How can you differentiate between a small bowel obstruction and acute pancreatitis
Increased amylase and lipase from bloods
CT scan shows inflamed pancreas
How do malignant tumours typically grow
Typically invasive, infiltrative and destroys surrounding normal tissues
What is Murphy’s triad
A triad of symptoms seen in appendicitis
RIF pain, nausea and vomiting, low-grade fever
Which cyclins and CDKs are essential for the G2-M transition
Cyclin B-CDK1
Which mutations increase the risk of colorectal cancer
APC mutations – tumour suppressor gene whose mutation leads to growth of adenomatous tissue
Linked to FAP
HPNCC mutations – DNA mismatch repair gene with mutations leading to defects in DNA repair
Linked to HPNCC
Who gets juvenile polyps
Called juvenile because the majority occur in children under the age of 5
Can present in older children too
At which age is appendicitis most common
Most common in adolescence and early adulthood (<40 y.o.)
Can all malignant tumour metastasise
YES
However, some do very infrequently (BCC and gliomas)
Invasive adenocarcinomas have potential for spread - true or false
True
Can occur within polyps
What makes up the tumour capsule in benign tumours
It consists of ECM deposited by stromal cells such as fibroblasts
These cells are activated by hypoxic damage resulting from pressure of the expanding tumour
List the macroscopic features of colorectal cancers in the distal cancer
Carcinomas are usually annular lesions producing ‘napkin ring’ constrictions and luminal narrowing occasionally causing obstruction
It will grow into the bowel wall over time
They characteristically are firm
List symptoms of small bowel obstruction
Colicky abdominal pain - can be severe
Vomiting
Absolute constipation
Diarrhoea in acute cases
Which factors determine 5-year survival in colorectal adenocarcinoma
Geography -
US – overall 5yr survival = 65%
Japan, Europe and Australia = from 60% to 40%
China, India, Philippines, Thailand and Gambia = 30-42% ( 4% in Gambia)
Stage:
Localised disease = 90.2%
Regional disease = 71.8%
Distant disease = 14.3%
Metastasis
Most colonic adenomas will not progress to cancer - true or false
True
Most are benign, and the majority do not progress.
The mucosa of the large intestine is completely devoid of villi - true or false
True
At what point does the rectum become the anus
The dentate line
What causes the tumour cells to attach to ‘remodelled’ ECM component in the metastatic cascade
There is a loss of adhesion cells and the signals which promote cell survival
And the ECM itself is modified - cleavage of BM proteins generates novel sites for receptors to bind tumour cells
Within colorectal adenocarcinoma, how is rectal carcinoma specifically classed
Classed as this when the cancer cells form in the tissue of the rectum
List the stages of the cell cycle
G1 (pre-synthetic)
S (DNA synthesis)
G2 (pre-mitotic)
M (mitotic) phases
Quiescent cells are in a physiologic state called G0.
What are the two phases of the metastatic cascade
1- invasion of the ECM
2- vascular dissemination, tissue homing & colonisation
Which specific genes are affected in the MSI pathway and what are the effects
TGFRBR2 gene - mutation results in uncontrolled cell growth
Pore apoptotic protein BAX- causing enhanced survival of genetically abnormal clones
List inhibitors of the cell cycle
There are various checkpoint - G1-S, G2-M
Which type of adenoma can be confused with a hyperplastic polyp
Sessile serrated adenomas can appear histologically like hyperplastic
Important to differentiate between them as cancer risk is very different
What is the benefit of encapsulation in benign
It creates a tissue plane that makes the tumour discrete, readily palpable, movable (nonfixed), and easily excisable by surgical enucleation
What can accelerate the genetic and epigenetic alterations that confer the hallmarks of cancer
Genomic instability
Cancer-promoting inflammation
These are considered enabling characteristics since they promote cellular transformation and subsequent tumour progression
List some of the complications of a stoma
Parastomal hernia Stomal blockage = perforation, skin irritation around stoma Fistula connecting stoma to skin Stoma retraction, Stoma prolapse Stoma stricture = blockage and perforation Stoma leak into peritoneum = peritonitis Stomal ischemia
Where is colorectal carcinoma most likely to metastasise to and why
Colorectal carcinomas are more more likely to metastasise to liver since it is the first organ downstream of the primary tumour
Its important to consider malignancy in all patients who present with large bowel obstruction - true or false
true
Colorectal cancers tend to develop insidiously - true or false
True
They often go undetected for a long time as a result
What does metastasis involve
Involves invasion of lymphatics, blood vessels, or body cavities by tumour followed by spread of the tumour to sites physically discontinuous with the primary tumour
Which bacterial virulence factors can contribute to infective colitis
Adherence to epithelial cells via fimbriae or pili - causes destruction of the brush border
Enterotoxins - they enter cells and stimulate electrolyte secretion
Invasion factors - invade by endocytosis and cause intracellular proliferation and then cell lysis
Cytotoxicity
What is the cell cycle
The sequence of events that result in cell proliferation
How does level of dysplasia affect cancer risk in neoplastic polyps
High risk dysplasia is associated with a higher malignancy risk
Only in that individual polyp, not in patient as a whole.
Those with sporadic retinoblastoma are at risk of which other cancers
They are not at increased risk for other forms of cancer
How can neoplastic polyps form invasive carcinomas
Can form invasive carcinomas if the dysplastic epithelial cells breach the basement membrane and enter the lamina propria, no met potential so polypectomy usually works
How can small bowel obstruction be fatal
If left untreated it can progress to intestinal necrosis, perforation, sepsis, and multi-organ failure
What causes rectal adenocarcinoma
Same risk factors/causes as colorectal (other card)
High alcohol consumption has a greater effect though
Can symptoms alone be used to determine the causative organism in infective colitis
NO
Symptoms vary depending on causative organism, but may mimic each other and this alone should not the basis for determining the pathogen
What criteria is used to determine HNPCC risk
Amsterdam criteria
3 or more relatives (at least one immediate) from 2 successive generations that have been affected
One must’ve had cancer before age 50
Aside from colon cancer, what types of cancer are seen in FAP
Also at risk of developing adenomas at other sites such as the Ampulla of Vater and the stomach.
What causes hyperplastic polyps
Underlying pathogenesis is still uncertain
Likely due to decreased cell turnover and delayed shedding which leads to an accumulation of cells
Which sex is more prone to appendicitis
Men - just
slightly elevated M:F ratio (1.4:1)
What is the likelihood of developing cancer in FAP cases
The adenomas present in these patients will undergo malignant transformation with 100% of FAP patients developing colorectal adenocarcinoma if untreated.
This usually occurs before the age of 30 but always by age 50.
How does the cell cycle progress/repeat in stable cells
Stable cells include hepatocytes and lymphocytes
They are quiescent but can re-enter the cell cycle
Enter G0 but can leave on appropriate stimulus
List potential causes of inflammatory polyps
May be seen as part of inflammatory processes such as UC or Crohn’s.
The example of a purely inflammatory polyp is solitary rectal ulcer syndrome.
When does rectal cancer cause back/pelvic pain
This is usually a late sign of the disease due to the tumour invading/ compressing the nerve trunks
List common clinical features of colorectal cancer
Change in bowel habit Rectal bleeding/ lower GI bleeding Weight loss Abdominal pain Pallor/weakness/ fatigue
If diagnosed and treated early, the rate of complications from appendicitis is relatively low - true or false
True
Describe how tumour cells migrate in the first phase of the metastatic cascade
Locomotion propels tumour cells through the degraded BMs and zones of matrix proteolysis
Which countries have the highest incidence of colorectal cancer
Highest in North America - US accounts for 10% of all CA cases
Australia, New Zealand, Europe and Japan are additional areas of high incidence
Any neoplastic lesion in the GI tract may produce a neoplastic polyp - true or false
True
Not limited to adenocarcinomas
Both host and invader factors influence metastasis - true or false
True
Describe the epidemiology of colorectal cancer in the UK
It is the 4th most common cause of cancer
Has the second highest mortality rate of all cancers
In the UK on average there are 40,000 new cases of colorectal cancer
Describe the microscopic features of poorly-differentiated colorectal adenocarcinomas
They form few glands
Other poorly differentiated ones may produce abundant mucin that will accumulate in the intestinal wall - giving a poor prognosis
List some of the extra-intestinal manifestations of juvenile polyps
PA malformations
Polyps in the stomach/small bowel
What screening is offered in HNPCC
Colonoscopy surveillance should be offered at least every 2 years from the ages of 25-75.
Women may also be offered screening tests for womb cancer from the age of 35
List the blood supply to the lower GI tract
Blood supply comes from the branches of the SMA, IMA, internal iliac artery and the internal pudendal artery.
SMA through its ileocolic, right colic, and middle colic branches
IMA through its left colic, sigmoid, and superior rectal (hemorrhoidal) branches
Internal iliac artery through its middle rectal and inferior rectal (branch of internal pudendal) branches
Marginal artery of Drummond connects the branches to form a collateral system.
What is the role of p53
It can stop the cell cycle for DNA repair or induce apoptosis if the damage is beyond repair
List some differentials for appendicitis cases
Other GI pathology Ectopic pregnancy UTI PID Renal stones
Colorectal adenocarcinoma can be made of signet ring cells similar to those of gastric cancer - true or false
True
Only in rare cases though
How does the cell cycle progress/repeat in cells from labile tissues
Labile tissues include epidermis, bone marrow and the GIT
They may cycle continuously - never enter G0, constant division with a condensed G1
Those with familial retinoblastoma are at risk of which other cancers
They are at increased risk of osteosarcoma + other soft tissue sarcomas.
As well as the 10000x increased risk of the retinoblastoma
Is genetic testing available for the families of HNPCC patients
Yes
It’s a blood test that looks for common mutations
Can also look for microsatellite instability or immunohistochemical signs– can lead onto genetic test
If gene negative may still be offered screening
Describe the structure of the mucosa of the colon
It lines the lumen of the colon
Made up of absorptive, columnar epithelium with many associated goblet cells which secrete mucus
It also has associated endocrine cells and basal stem cells
Backed by a lamina propria (connective tissue with macrophages, plasma cells and other immune cells) and muscularis mucosa.
The majority of small bowel obstruction occur in which patient group
Those who have had previous abdominal surgery
Account for 60% of cases
In patients with Crohn’s disease, the incidence may be upwards of 25%.
What is the definition of small bowel obstruction
A mechanical disruption in the patency of the GI tract, resulting in a combination of emesis, constipation, and abdominal pain.
How do mutated growth factor receptors contribute to cancer development
They deliver mitogenic signals to the cell continuously, even in the absence of growth factor in the environment
What is the role of palliative care in advanced colorectal cancer
Used to control symptoms and slow growth
Involves chemo, radio and surgery
Why are so many tumour suppressor studies based on retinoblastoma
Because the RB gene (which is responsible) was the first tumour suppressor gene discovered
List the main differences between colonic adenomas and dysplastic polyps
CA is neoplastic but HP is not
CA more common in the right colon but HP in left
In CA the serrated architecture will be seen throughout the full length of the involved gland, including the crypt, crypt base (leads to crypt dilation and lateral growth)
In HP the serration is restricted to the upper 1/3 of the involved surface.
Obstruction is most common in which part of the GI tract
Small intestine
It’s frequently involved because of its narrow lumen
How does renal cell carcinoma spread
Haematogenous spread
Prefer to grow within large veins so can invade the branches of the renal vein > renal vein > IVC > right side of heart
What is the leading cause of healthcare acquired infection in the US
C.diff - causes pseudomembranous colitis
Estimated 500,000 infections per year
What non-imaging tests would you order for suspected large bowel obstruction
full blood count (FBC)
electrolytes
C-reactive protein
How do left sided colorectal cancers present
Occult bleeding Changes in bowel habit Cramping and LLQ discomfort Bowel obstruction Tenesmus Mass in LIF or on PR exam
Which type of colectomy is performed on high rectal tumours
Defined as being more than 5cm from the anus
Do an anterior resection (leaves the rectal sphincter intact)
What happens when tumour suppressor genes are abnormal
It can result in failure of growth inhibition and uncontrolled cell proliferation.
What is the most common form of colorectal cancer
Adenocarcinoma - accounts for 95% of cases
Which parts of the lower GI tract are retroperitoneal
Ascending and descending colon
Rectum
List the macroscopic features of infective colitis
General signs of inflammation – oedema, hyperaemia, ulceration
Grossly, may mimic IBD
What are the steps of ECM invasion in metastasis
“Loosening up” of tumour cell-tumour cell interactions
Degradation of ECM
Attachment to ‘remodelled’ ECM component
Migration and invasion of tumour cells
This initial phase of metastasis culminates in penetration through the endothelial BM and transmigration into the vascular space
How does early stage colorectal cancer present
Usually presents with non specific symptoms like fatigue and weight loss
What is the risk of developing cancer in Peutz-Jegher’s syndrome
40% lifetime cancer risk
Increased risk of many different types of tumours
Monitoring is therefore recommended
Which cyclins and CDKs are active in the S phase
Cyclin A-CDK2 and cyclin A-CDK1
Which other investigations might you do (second line) to further investigate the cause of bowel obstruction
Urine or serum beta–HCG -> ?pregnancy
Urinalysis -> ?infection ?DKA
ECG -> ?arrhythmia
MRI
List common met sites for colorectal adenocarcinoma
Liver
Regional lymph nodes
Lung
Bones
What is a proto-oncogene
Normal cellular genes whose products promote cell proliferation
Describe the pathogenesis of pseudomembranous colitis
Broad spectrum antibiotics disrupt the normal bowel flora and allows C. diff overgrowth
Toxin produced by C.diff cause inflammatory response leading to epithelial disruption and the formation of raised pseudomembranous plaques
Exact mechanism poorly understood
What prevents a benign tumour from invading
The tumour capsule
It keeps the cells together and prevents it penetrating surrounding tissues
Describe the pathway by which breast cancer escapes dormancy when metastasising
The met to bone (tropism) and secrete PTH-related protein (PTHRP)
This stimulates osteoblasts to make RANKL which activates osteoclasts
This degrades the bone matrix and release growth factors embedded within it, like IGF and TGF-b
These factors bind to receptors on the cancer cells activating signalling pathways that support the growth and survival of the cancer cells.
What are the key diagnostic factors for a large bowel obstruction
Intermittent abdominal pain Abdominal distention Nausea Vomiting Presence of risk factors Tenesmus
What causes the colicky abdominal pain in small bowel obstruction
Proximal dilation of the bowel together with peristalsis
Can become severe
Aside from metastasis, what is the best discriminator of malignant and benign tumours
Invasiveness
In general only malignant ones invade
How do you treat incomplete or uncomplicated small bowel obstruction
Supportive care
Nasogastric decompression
Correction of underlying cause using medical therapy e.g. Crohns
In the context of bowel obstruction, what does an elevated lactate suggest
It indicates poor tissue perfusion
It is not diagnostic for intestinal ischaemia but can indicate
What is the predominant site for polyps in FAP patients
No predominant site in colon
Each stage of the cell cycle requires completion of the previous step - true or false
True
Also requires activation of necessary factors
What are hyperplastic polyps
Benign epithelial proliferations with in the bowel
What is the genetic basis of Peutz-Jegher’s syndrome
It is a rare autosomal dominant syndrome mainly caused by germline mutations in the STK11 gene
This gene is a tumour suppressor
Describe the pattern of mutation in familial cancers (in general)
Risk of cancer is inherited as an AD trait due to germline mutation in a tumour suppressor gene.
Tumours have second ‘hits’ in the sole normal TSG allele causing the disease
The same TSG is frequently mutated in sporadic tumours of the same type
Which treatment is reserved for specific patients with early stage rectal adenocarcinoma
trans-anal excision or trans-anal endoscopic microsurgery
List examples of conditions that cause harmartomatous polyps
Juvenile polyps and Peutz-Jegher’s syndrome
What is the major difference between the molecules produces by protooncogenes and those produced by oncogenes
The ones produced by oncogenes
are usually active by default and thereby relieve cells of their dependency on growth factors and control by checkpoints
What is meant by “limitless replicative potential (immortality)” in relation to cancer cells
Tumours have unrestricted proliferative capacity, a stem cell-like property that permits tumour cells to avoid cellular senescence and mitotic catastrophe.
Which type of retinoblastoma is often bilateral
Familial
In sporadic cases almost always only 1 eye affected
When are bowel polyps most commonly found
Most common in the colon and rectum but can also occur earlier in GI tract
List the macroscopic features of juvenile polyps
Usually under 3cm in diameter.
Pedunculated with a smooth, reddish surface.
Cystic spaces often dilating the crypts - characteristic signs
What treatment is used if the rectal adenocarcinoma is not surgically resectable and is metastatic
Alongside palliative care biological therapy can be given
An apple core sign on CT suggests what
Suggests constriction of the colonic lumen
Often due to a ring-shaped colon cancer
Which body cavities/surfaces are commonly affected by direct seeding
Most commonly involves the peritoneal cavity but can also incl. pleural, pericardial, subarachnoid & joint spaces
Invasion into the muscularis propria will significantly reduce survival in colorectal adenocarcinoma - true or false
True
This is compounded if lymph node mets are also present
What is oncogenesis
The development of tumours or neoplasms from normal cells
What proportion of colon cancer cases does FAP account for
Accounts for less than 1% of all cases of colorectal cancer
When would a subtotal/total colectomy be performed for a large bowel obstruction
Carried out for obstructing lesions in the descending or sigmoid colon when the caecum has torn.
For these lesions, it is not safe to just remove the obstruction, so subtotal colectomy is undertaken
What are the risk factors for appendicitis
No strong risk factors
Smoking and a low fibre diet are thought to elevate the risk slightly
List the microscopic features of polyps in FAP
FAP polyps are histologically the same as the sporadic adenomas - differentiated by number
May also see flat, depressed adenomas
Or microscopic adenomas which consist of only 1 or 2 dysplastic crypts.
When and where does recurrence of rectal adenocarcinoma typically occur
It usually develops in the first year following surgery and can be local, distant or both
Which tumours are seen in young children with Peutz-Jegher’s syndrome
sex chord tumours in testes
The electrocute secretion stimulated by enterotoxins causes which symptom of infective colitis
Watery diarrhoea
The majority of colorectal cancer is familial - true or false
False
75% of cases are sporadic
What are the first line investigations for small bowel obstruction
CT scan of the abdomen and pelvis- GOLD standard
Water-soluble contrast study
Arterial blood gases (including lactate)
Full blood count - can help to understand and manage the metabolic consequences
Annually, enterocolitis accounts for over 1 million deaths worldwide - true or false
True
Half of these deaths are in the under 5s
Rectal adenocarcinomas in which position are most likely to recur
low rectal cancers have highest recurrence rates
List the 4 layers of the Lower GI tract
Mucosa
Submucosa
Mucularis propria
Serosa
List some of the complications of colectomy
Bleeding DVT and PE Infection Injury to small bowel and bladder Anastomotic leaks May require permanent stoma
What is the most common epigenetic event that causes progression along the pathways to colorectal cancer
Methylation-induced gene silencing
List the macroscopic features of a colonic adenoma
Can range from small pedunculated polyps to large sessile lesions.
The surface texture is velvety or raspberry like.
Typically range from 0.3-10cm in diameter.
Can be subtyped based on architecture - tubular, tubulovillous and villous.
What is the function of the surveillance mechanisms in the cell cycle
They detect DNA or chromosomal damage and ensure that cells with genetic imperfections do not complete replication
Which group is most commonly affected by hyperplastic polyps
Most commonly seen in those in their 60s or 70s
Describe the pathogenesis of appendicitis
Lumen of the appendix is obstructed – most commonly by normal or compacted stool (faecalith)
Mucus continues to be produced, leading to distension and an increase in intraluminal pressure
Resident bacteria begin to multiply rapidly (most commonly Bacteroides fragilis and Escherichia coli), triggering a neutrophilic immune response
Appendix becomes engorged and congested. Small vessels are compressed as pressure continues to rise and the tissue becomes ischaemic, weakening the wall to the point of rupture
Does the rectum have teniae coli
No
Rectum is macroscopically distinct from the colon for that reason
What happens in normal cells when oncogenes are expressed
It causes quiescence or permanent cell cycle arrest
This is due to the action of tumour suppressor genes
The lymphatic vessels found around margins of invading cancers are sufficient for lymphatic spread - true or false
True
What is meant by “sustained angiogenesis” in relation to cancer cells
Tumour cells, like normal cells, are not able to grow without a vascular supply to bring nutrients and oxygen and remove waste products. Hence, tumours must induce angiogenesis. and sustain it for growth
How does tumour cell tropism affect site of metastasis
Tumours can express adhesion molecules whose ligands are found on the endothelial cells pf specific target organs
So even if it in not in line with the primary site’s drainage, the cells can migrate there - spread is enhanced
Chemokine receptors can guide the tumour cells to these tissues - similar to immune chemotaxis
List risk factors for pseudomembranous colitis
Frequent/ repeated antibiotic use Immunosuppression Advanced age Hospitalisation or nursing home residence Potentially PPI use
When does rectal cancer cause urinary symptoms
if the tumour has invaded or is compressing the bladder
What causes pseudomembranous colitis
Clostridium difficile
List potential causes of large bowel obstruction
Colorectal malignancy - most common (60% of cases)
Diverticular strictures - 20% of cases
Volvulus
Other, rarer causes include hernias, other abdominal or pelvic malignancies, or endometriosis
Can biological therapy be used in colorectal cancer
Yes
Monoclonal antibodies and targeted genetic therapy can be used in specific cases
Which type of vessel is typically involved in haematogenous spread
Small veins - due to their thinner walls
However, some cancers prefer to grow within large veins, such as renal cell carcinoma or HCC
How do benign tumours typically grow
Most grow as cohesive, expansile masses that develop a surrounding rim of condensed connective tissue (capsule).
What is the one exception to the rule of benign tumours not invading
Haemangiomas - benign neoplasms of tangled blood vessels)
This is because they are often unencapsulated and permeate the site in which they arise e.g., dermis of the skin or the liver
What drives cell cycle progression
It is driven by protein phosphorylation events involving cyclins and cyclin-dependent kinases (CDKs)
Different combinations of cyclins and CDKs are associated with each of the important transitions in the cell cycle
When would you consider perforation in a large bowel obstruction
If there is persistent tachycardia, fever, and/or abdominal pain and tenderness
List some potential differentials for large bowel obstruction
Acute colonic pseudo-obstruction Chronic idiopathic megacolon Toxic megacolon Endometriosis Pseudomembranous colitis
List the phases of mitosis
Prophase
Metaphase
Anaphase
Telophase
This is followed by cytokinesis
What is the usual site of rupture following large bowel obstruction and why
The caecum
This is because it has the largest diameter and is where the bowel wall is thinnest
This is regardless of underlying cause
Which features of IBD confer an increased risk of colorectal cancer
Longer duration of disease – risk spikes after 8-10yrs with disease
Larger extent of disease – patients with pancolitis are at greatest risk, Crohns patients without colonic involvement have no increased risk
Higher severity of inflammatory response – greater frequency and severity of inflammatory response gives an increased risk (neutrophil levels indicate severity)
What is involved in a right hemicolectomy
Includes any operation that removes the ileocaecal valve and the caecum.
The colonic resection can be limited to the caecum or extended to the descending colon
Is HNPCC autosomal dominant or recessive
Dominant
Patients inherit one mutated allele and one normal. The normal one is usually lost via further mutation or epigenetic silencing
List risk factors for large bowel obstruction
colorectal adenomas or polyps
current or previous malignancy
inflammatory bowel disease
diverticular disease
Using retinoblastoma as an example, describe the two-hit” hypothesis of oncogenesis
2 mutations (hits) involving both alleles of RB are required to produce retinoblastoma Can occur as one germline mutation and one spontaneous somatic mutation - familial cases Or as 2 separate somatic mutations - sporadic cases
What is an oncogene
Mutated or over-expressed versions of proto-oncogenes that function autonomously, having lost dependence on normal growth-promoting signals
They cause extensive cell growth, even in the absence of growth factors and other growth-promoting external signals.
What proportion of retinoblastoma is familial
Around 40%
The remaining 60% are sporadic
List some examples of non-neoplastic polyps
Hyperplastic
Inflammatory
Harmartomatous
Due to the fact that most cancer’s primary mets will occur first capillary bed downstream from the primary site, what are the most common sites of metastasis
Lung
Liver
What is the distinguishing feature of the Ileum
Peyer’s patches
