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
What happens if CDK inhibitors are defective
Cells with damaged DNA are able to divide
This creates mutated daughter cells that are at risk for malignant transformation.
How can regional nodes act as barriers against further dissemination of the tumour
The tumour cells can be arrested within the node
After arrest within the node, the cells may be destroyed by a tumour-specific immune response.
This response may lead hyperplasia of the nodes.
Therefore, enlarged lymph nodes do not always harbour metastases
Requires microscopy for definitive assessment.
Describe the natural history of colorectal adenocarcinoma
The precursor adenomas may be present for a decade before becoming malignant
The timeline for progression from premalignant lesion to malignant cancer has been said to range from 10-20yrs
What are the 3 types of surgery to treat large bowel obstruction
Right hemicolectomy
Hartmann’s procedure
Total colectomy
What is the most common pathway in CR cancer and why
The APC/b-catenin pathway because its activated in the classic adenoma-carcinoma sequence
What is the median age of presentation in Peutz-Jegher’s syndrome
11
Metastases are much more likely to migrate as multicellular aggregates - true or false
True
More likely than single cells
Describe the epidemiology of colonic adenomas
Develop in around 30% of Western adults by age 60.
Less common in Asia but increasing as Western diet/lifestyle becomes more prevalent.
How should you investigate pseudomembranous colitis
Stool sample checked for presence of enterotoxins
What is the normal role of the APC gene and what effect does it’s mutation have (APC/B-catenin pathway)
APC normally binds B-catenin to cause its breakdown
It’s deficiency (caused by mutation) allows B-catenin accumulation that will relocate to the nucleus to form complexes with DNA binding factor TCF and activates transcription of genes such as MYC and cyclin D1
These genes promote cell proliferation
p53 regulates which parts of the cell cycle
It regulates both the G1/S and G2/M checkpoints
How is small bowel obstruction classified
By the nature of the obstruction
Can be either simple or complicated
Or by degree of obstruction
Can be partial or complete
What determines whether the cell proliferates or is quiescent
The balance between cyclins and CDK and the inhibitors
Which factors influence the recurrence of rectal adenocarcinoma
Surgeon variability
Grade and stage of tumour
Location of the primary – low rectal cancers have highest recurrence rates
The ability to obtain negative margins during surgery
List some differentials for infective colitis
IBD
Pseudomembranous colitis
Ischaemic colitis
How does a sigmoid volvulus present on CT
A characteristic ‘coffee bean’ appearance
List the macroscopic features of hyperplastic polyps
Typically found in the left colon - often on crests of mucosal folds
Usually less than 5mm in diameter.
Can be a single but more commonly appear in multiples (particularly in sigmoid colon and rectum)
Smooth, nodular protrusions in the mucosa
List risk factors for small bowel obstruction
Previous abdominal surgery - main one!
Crohn’s
Hernia
Which type of colectomy is performed on transverse colon tumours
extended right hemicolectomy
How might sub-acute appendicitis present
With an appendicular mass
What are bowel polyps
Small growths on the lining of the colon or rectum
How common are bowel polyps
Very!
Around 1/4 of the over 50s will be affected by them
Which histological sign is associated with haematogenous mets
Histological evidence of penetration of small vessels at site of primary neoplasm
Ominous feature
List indicators of bowel perforation following a large bowel obstruction
Progression from cramping to more focal and constant pain - indicates localized peritoneal irritation due to a microperforation
Alternatively, a large intestinal perforation may cause a sudden relief of pain due to the nerves in the bowel wall no longer being stretched, but then it’s usually followed by progressive worsening of pain, as generalizedperitonitissets in.
What type of polyp is seen in Peutz-Jegher’s syndrome
Harmartomatous - will get multiple
What treatment is offered to juvenile polyp patients who get chronic or severe haemorrhage
Colectomy
Invasion of the ECM in the metastatic cascade is an active process - true or false
True
Where does cancer usually develop in HNPCC cases
The resulting colorectal cancer is commonly seen in the right colon.
What is the main long-term consequence of small bowel obstruction
Short bowel syndrome
Risk is low
Can metastatic sites of a tumour be predicted
For many it can - based on the location of the primary tumour
Most arrest in the first capillary bed (blood/lymphatic) they encounter
The lung and liver are most common sites
However there are many exceptions
Which sex is colorectal cancer more prevalent in
It is relatively equal between men and women
How does age affect the incidence of colorectal cancer
It increases as age does
<20% of cases occur <50yrs
Peak incidence between 60-70yrs
Median age of diagnosis is 67yrs
However the incidence of colorectal adenocarcinoma below 40yrs has been increasing and it is possible to see it in individuals as young as 20 if linked to causative syndromes such as FAP or HPNCC
The location of the colorectal cancer effects presentation to an extent - true or false
True
List some of the complications of palliative endoluminal stenting
Perforation
Migration
Incontinence
Cant be sued for low rectal tumours as causes intractable tenesmus
What gene is responsible for HNPCC
This syndrome is caused by mutations in DNA mismatch repair gene which produce the proteins responsible for the detection, excision and repair of errors that occur in DNA replication.
There are 5 main mismatch repair genes but the most common ones affected are MSH2 and MSH1
How does a caecal volvulus present on CT
Often described as having a foetal appearance
Describe how chemotherapy is utilised is colorectal adenocarcinoma
Used for advanced disease both neoadjuvantly and adjuvantly
Adjuvant chemo is standard for stage 3 tumours and can potentially be used in stage 2
What is meant by “altered cellular metabolism” in relation to cancer cells
Tumour cells undergo a metabolic switch to aerobic glycolysis (call the Warburg effect), which enables the synthesis of the macromolecules and organelles that are needed for rapid cell growth
What is meant by tumour dormancy
This is when metastatic cells take root and survive within distant tissues but fail to grow
Most colorectal cancers are picked up before they are symptomatic - true or false
True
Due to the awareness of the insidious onset of the condition, the frequency of the cancer and the presence of the precursor adenomas in 30% of over 60s, screening programmes are now in place from age 45/50
After mitosis, what stage of the cell cycle do cells go into
They can enter G1 after completing a round of mitosis (continuously replicating cells), or they can enter from G0
What is meant by an incarcerated hernia
The tissue cannot move back into the correct place and gets trapped
If incarceration persists, strangulation and ultimately infarction occurs
Define a complete bowel obstruction
Blockage of the intestine completely obstructs the lumen of the intestine, resulting in failure to pass flatus and stool
Generally associated with peritonitis
It’s a surgical emergency - often will not respond to anything other than surgery (some rare Crohn’s cases are the exception)
Why is retinoblastoma rare in the general population
Probability of 2 genetic hits is low
What is meant by “self-sufficiency in growth signals” in relation to cancer cells
Tumours have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation.
How can a small bowel obstruction lead to intra-abdominal abscess
It can lead to an intra-abdominal infection where abscesses can form
Requires open surgery or image-guided drainage
What is short bowel syndrome
characterised by the functional or anatomical loss of extensive segments of small intestine resulting in inadequate absorption of enteral nutrition
What is the most common pathway for initial dissemination of cancer cells
Lymphatic spread
How long is the large intestine
Around 1.5m
Which 3 factors determine the site of metastais
Location + vascular drainage of the primary tumour.
Tropism of particular kinds of tumour cells for specific tissues - certain adhesion molecules or chemokine receptors can guide cells
Escape from tumour dormancy
How does ovarian cancer seed in the abdomen
It often involves the omentum
Characteristically leaves a heavy cancerous coating on the surfaces it spreads to
Sometimes, mucus-secreting appendiceal carcinomas or ovarian carcinomas fill the peritoneal cavity with a gelatinous neoplastic mass (pseudomyxoma peritonei).
List complications of pseudomembranous colitis
Toxic megacolon - Occurs in approx. 3% of C. diff patients with a mortality rate of 30-50%
Perforation and peritonitis
Paralytic Ileus
What neoadjuvant therapy is used in rectal adenocarcinoma
Usually consists of a long course of radiotherapy with sensitisation followed by an 8 week break then surgical resection followed by adjuvant chemotherapy
A short course of chemo/radiotherapy could be used instead neoadjuvantly
If the cancer is locally advanced then neoadjuvant therapy consists of induction chemotherapy as well as radiation
List the properties of the C.diff bacteria
Gram +ive, anaerobic rods
Form spores
Produce toxins A and B
List some differentials for pseudomembranous colitis
Abx-associated diarrhoea
Infective colitis
IBD
Ischaemic colitis
Patients with recurrent C.diff infections which do not respond to antibiotics may respond to a Faecal Microbiota Transplant - true or false
True
This takes processed stool from a healthy donor and implants it into the patient
Attempts to normalize the gut microbiome
How do you treat sepsis in large bowel obstruction cases
Broad-spectrum antibiotics should be initiated after blood has been drawn for microbiological culture
Treat cause as well of course
How can a small bowel obstruction lead to sepsis
Patients who develop intestinal necrosis are at risk of developing intestinal perforation
This can lead to intrabdominal sepsis and multi-organ failure
This is a cause of death in many patients
Patients with small bowel obstructions that are treated in a timely manner have a very good prognosis- true or false
True
Are polyps seen in HNPCC
Despite the name, polyps are usually present but in much lower number than seen in FAP (less than 100 adenomas)
What is the most common presentation for rectal adenocarcinoma
Rectal bleeding
Occurs in 60% of cases
How many polyps are seen in patients with FAP
At least 100 polyps have to be present for a FAP diagnosis but some patients will have thousands!
How does the cell cycle progress/repeat in permanent cells
Permanent cells include neurones, RBCs and cardiac myocytes
They have lost the capacity to proliferate
They enter G0 but cannot leave
How can metastatic tumours overcome dormancy
It is theorised that tumour cells secrete cytokines, growth factors and ECM molecules that act on the resident stromal cells & make the metastatic site habitable for the cancer cells
List potential complications of appendicitis
Most complications associated with perforation:
Sepsis
Generalised peritonitis – pts may require exploratory laparotomy if pathology cannot be identified
Describe the surgical approach to treating colorectal adenocarcinoma
Can be performed in cancer up to stage 4 and is usually done laproscopically rather than openly
Mostly it involves a regional colectomy to remove the primary with adequate margins and surgical removal of any effected nodes followed by either a primary anastomosis or formation of a stoma
Different approaches to the surgery are done depending on tumour location
What is the first line antibiotic used in the treatment of pseudomembranous colitis
Metronidazole 500mg PO TDS for 10 days
What is the purpose of the G2-M checkpoint in the cell cycle
It : ensures there has been accurate genetic replication before the cell actually divides.
What is the usual mechanism of death from appendicitis
Septic shock secondary to suppurative peritonitis following appendix perforation
Right and left sided colonic adenocarcinoma has the same general microscopic characteristics - true or false
True
There are some microsatellite unstable colon cancers that don’t have mutations in DNA mismatch repair enzymes - true or false
True
They instead but demonstrate the CpG island hypermethylation phenotype (CIMP)
In these tumours the MLH1 promoter region is typically hypermethylated which reduces MLH1 expression and repair function
What is the role of an oncogene
They have multiple roles, but virtually all encode active oncoproteins involved in signalling pathways that drive cell proliferation
List some of the complications of colonoscopy
Perforation
Bleeding
Post polypectomy electrocoagulation syndrome
Infection
Anaphylaxis/ resp distress from anaesthetic
What is meant by “ability to invade and metastasise” in relation to cancer cells
Tumour metastases are the cause of the vast majority of cancer deaths and arise from the interplay of processes that are intrinsic to tumour cells and signals that are initiated by the tissue environment
How do you treat sub-acute appendicitis
Initially treated conservatively – if symptoms resolve, appendectomy not indicated
How is metastatic colorectal carcinoma managed palliatively
Managed with chemo over surgery
However liver mets may be managed with surgery or cry/radio ablation if not surgically suitable
Radiotherapy is only given palliatively for mets to brain and bone
Define a complex bowel obstruction
Obstruction has progressed to ischaemia/gangrene and/or perforation - this is LIFE THREATENING
Requires urgent resuscitation and surgical intervention - Surgical emergency!
What type of cancer is seen in FAP
Type of cancer is adenocarcinoma - can form tubular, villous or typical forms
Why do some patients with colorectal adenocarcinoma die from CVD
It commonly affects older adults - higher risk of CVD
Also associated with obesity, smoking, high alcohol and poor diet - all risk factors for CVD
List clinical features of rectal adenocarcinoma
Rectal bleeding Change in bowel habit – often in the form of diarrhoea but also tenesmus or the feeling of incomplete evacuation Occult bleeding detected by FAT Abdominal pain – usually colicky and may be assoc. with bloating Urinary symptoms Nack/pelvic pain Malaise Jaundice - liver mets Peritonitis if they perforate
Describe the natural history of rectal adenocarcinomas
The main point regarding Nx is the rectal adenocarcinoma has a much higher risk of pelvic recurrence than the colonic form and the local recurrences tend to give a poor prognosis
Can metastasise - liver, nodes, lung, bone
It is common for metastatic tumour cells to invade the 1st venous capillary bed they encounter - true or false
True
However it is not always the case
Why are malignant tumours often harder to remove surgically
Because they usually lack a well-defined capsule and cleavage plane
This is why surgeons will excise with a margin
What happens if an oncogene becomes functional or is no longer inhibited
It will lead to cancer
What is meant by “Insensitivity to growth-inhibitory signals” in relation to cancer cells
Tumours may not respond to molecules that inhibit the proliferation of normal cells, usually because of inactivation of tumour suppressor genes that encode components of growth inhibitory pathways.
Which extra-intestinal manifestations are associated with FAP
Congenital hypertrophy of the retinal pigment epithelium
Can be used as early screening
What is the widest part of the lower GI tract
The caecum
What is the most common cause of small bowel obstruction in children
Intussusception
Abnormal peristalsis forces one segment of intestine is into the immediately distal one (telescopes)
It pulls all of the mesenteric vessels along with it which can cut off blood supply as well as causing obstruction.
List common symptoms of pseudomembranous colitis
Fever
Diffuse abdominal pain and watery diarrhoea (+/- blood)
Has a distinctive smell
Vomiting is rare
How can bowel polyps be typed
By appearance - sessile or pedunculated
Classed as either neoplastic or non-neoplastic
What is meant by “ability to evade host immune response” in relation to cancer cells
The cells of the adaptive and innate immune system can recognise and eliminate cells displaying abnormal antigens (e.g., a mutated oncoprotein). Cancer cells exhibit a no. of alterations that allow them to evade the host immune response.
Tumour cells are more likely to possess cells with stem cell-like properties - true or false
True
This contributes to metastatic cells but also the ‘plasticity’ required to adapt to growth in a new microenvironment
For enterocolitis that’s caused by ingestion of pre formed toxins how is the bacteria spread and what is a big cause of this subtype
Faecal oral spread of disease
Cholera is a big cause i
Which sex is more commonly affected by bowel polyps
Slightly more common in men
Which organs are considered part of the lower GI Tract
From the caecum to anus
Caecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum and anus
Large bowel obstruction is a common symptom of colorectal cancer - true or false
True
Has an incidence range of 15% to 29%
List common growth factor receptor oncoproteins that are activated in cancer
RAS
PI3K
MYC
D cyclins
What treatment is offered for patients with colonic adenomas
Regular monitoring via colonoscopy
Polyp removal
This aims reduce incidence of cancer by preventing progression
What is the most common neoplastic polyp
Colonic adenoma
Describe the pathogenesis of large bowel obstruction
Colon proximal to obstruction dilates and the build up of gas and stool causes an increase in pressure
This reduces mesenteric blood flow producing mucosal oedema
Wall becomes oedematous and stops absorbing fluids and water which leads to dehydration and metabolic imbalances
With progression, the arterial blood supply becomes jeopardised with mucosal ulceration, full thickness wall necrosis, and eventual perforation
This provides conditions for bacterial translocation, which can produce septic complications.
Aside from the polyps, which other symptom is seen in Peutz-Jegher’s syndrome
Mucosal hyperpigmentation
Seen in lips, nostrils, buccal mucosa, palms, genitals and perianal area
Look like freckles but differentiated by buccal presentation
Can you tell which colonic adenomas are likely to progress to cancer
No
There are some suggestive signs like size and severity of dysplasia but not a perfect system
What are the key diagnostic factors for small bowel obstruction
- Constipation/failure to pass gas or stool
- Presence of risk factors
- Intermittent abdominal pain
- Vomiting
Others include - pyrexia, nausea, tachycardia, groin swelling
How can you differentiate between a small bowel obstruction and acute appendicitis
Ultrasound and CT confirm diagnosis of appendicitis in most cases
High alcohol consumption has a slightly higher risk of causing rectal adenocarcinoma than colonic adenocarcinoma - true or false
True
Give an example of tropism in cancer metastasis
CD44 adhesion molecules expressed on normal T-lymphocytes is used by these cells to migrate to selective sites in lymphoid tissues.
Solid tumours also often express CD44 which appears to enhance their spread to lymph nodes and other metastatic sites.
Right sided cancers tend to effect older individuals - true or false
False
Right sided cancers tend to effect younger individuals with left sided ones more commonly effecting older individuals
How do you diagnose colorectal cancer
Gold standard – colonoscopy and biopsy
Flexible sigmoidoscopy or CT colonography can be done if co-morbidities or frailty contradict colonoscopy an biopsy
What is the role of the WnT pathway
WnT has a major role in controlling cellular growth and differentiation during embryological development
Which part of the GI tract is the appendix attached to
The caecum
What is the MSI pathway of CR cancer associated with
Defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome
How can a small bowel obstruction lead to necrosis and infarction
As obstruction progresses, intestinal perfusion decreases, resulting in infarction and necrosis of tissue
This is accelerated by the simultaneous onset of peritonitis, leukocytosis, dehydration, and pre-renal acute kidney injury
List the microscopic features of infective colitis
Inflammation may be confined to lamina propria
Seen as hyperaemic mucosa with some neutrophilic exudate
Normal crypt architecture will remain intact
Cryptitis – Epithelial injury as a result of neutrophil activity
In severe cases, may see crypt abscesses, haemorrhage, or necrosis
Which mutations occur in the APC/B-catenin pathway
Mutations in both copies of APC - resulting pathway promotes cell proliferation
KRAS activating mutations - a late event in the process which promotes cell growth and prevents apoptosis,
LOF mutations in tumour suppressors SMAD2/4 allowing unrestrained cell growth
TP53 mutations
What is the distinguishing feature of the duodenum
Brunner’s glands
What is the main cause of C.diff infection
Use of broad spectrum antibiotics
Most often involved – cephalosporins, clindamycin, penicillin’s (amoxicillin/ ampicillin)
List factors which promote tumour cell dissemination in the metastatic cascade
Clumping of tumour cells in the blood
Travelling as multi-cellular aggregates
Presence of stem-cell like properties which allow them to adapt to growth in a new microenvironment.
What is the purpose of cell proliferation
It is fundamental to organism development, to maintenance of steady-state tissue homeostasis and to replacement of dead or damaged cells
List risk factors for sporadic colorectal carcinoma
Increasing age, Family history IBD Low fibre diet High processed meat/ refined carbs and fat intake Obesity Sedentary lifestyle Smoking High alcohol intake
What causes solitary rectal ulcer syndrome
Impaired relaxation of the anorectal sphincter which creates a sharp angle anteriorly
This leads to recurrent abrasion and ulceration on the anterior rectal wall
The polyp can form as a result of recurrent injury/healing cycles
What is a harmartomatous polyp
A subtype of polyp which is typically associated with genetic or acquired syndromes.
List the main sphincter sparing procedures performed in rectal cancer
Low anterior resection and abdominal perineal resection
These are preferred as better for patient QoL
What is a tumour suppressor gene
A protein or gene that opposes any of the various hallmarks of cancer
They can stop cell cycle progression and DNA replication
But they also have many other mechanisms
Do harmartomatous polyps have a risk of cancer
Yes some of them do
Depends on the underlying mutation/cause
At what point does the sigmoid colon become the rectum
Level of S3
How does hepatocellular cancer spread
Haematogenous spread
They penetrate the portal and hepatic radicals and then grow into the main venous channels
What is the most common site for distant metastasis in colorectal adenocarcinoma
The liver
This is due to the portal drainage of the colon
Which mutation is found in 15-20% of all human tumours
RAS mutations
In some cancers the frequency is even higher - 90% of pancreatic adenocarcinoma
What potentially fatal condition can be caused by polyps in Peutz-Jegher’s syndrome
Intussusception
Which type of colectomy is performed on low rectal tumours
Defined as being less than 5cm from the anus
Do an abdominoperineal resection (removes the distal colon, rectum and anal sphincter resulting in permanent colostomy)
What is the biggest risk factor for colonic adenomas containing invasive cancer at time of diagnosis
Large size - 40% of >4cm adenomas contain invasive cancer
Dysplasia within the adenoma is another risk
Once the cell passes G1 it is obligated to go into mitosis - true or false
True
A patient over 40 presents with an appendicular mass, how should they be managed
All pts >40 y.o. should be investigated for colon malignancy
Surgery for a large bowel obstruction carries an appreciable risk - true or false
True
List the microscopic features of appendicitis
Hallmark feature is neutrophilic infiltration of the muscularis propria
May progress onto focal ulceration
May see abscess with neutrophilic exudate
Where the tissue has become infarcted, areas of gangrenous necrosis may be found
What is the histological hallmark of hyperplastic polyps
The serrated surface
Which surgical procedure is used to treat a colon obstruction or perforation
Hartmans Procedure
This involves complete resection of the recto-sigmoid colon resulting in the requirement for closure of the rectal stump and formation of an end colostomy
Emergency surgery
IBD patients are at increased risk of colorectal carcinomas - true or false
True
Also at increased risk of colonic adenoma which is the precursor lesion to colorectal adenocarcinoma
What are the 2 major pathways which cause in colorectal cancer
The APC/B-catenin pathway - activated in the classic adenoma-carcinoma sequence
AND
The MSI pathway
Both pathways require a stepwise accumulation of mutations and have epigenetic events that enhance progression
Which type of colectomy is performed on caecal and ascending colon tumours
right hemicolectomy
Describe the path of the large intestine/colon
Tract begins with the caecum in the lower right abdominal quadrant
The colon ascends to the base of the liver (ascending colon) before turning at the hepatic/right colic flexure and becoming the transverse colon. (travels from right to left side of abdomen. The transverse colon takes another right angled turn below the spleen (splenic/left colic flexure) and becomes the descending colon.
This becomes the sigmoid colon in the LLQ
The secondary spontaneous Rb mutations is inevitable in familial cases - true or false
True - in a small number of cases only though!
Presents like autosomal dominant inheritance
List the macroscopic features of polyps in FAP
Vast numbers of small polyps present – from 100 up to the thousands!
May have a dominant polyp which is larger.
What is the purpose of tumour cells clumping in the blood
Believed to enhance cell survival in circulation
List some of the rarer cancer types that can affect the rectum
Lymphomas (1.3%),
Carcinoid tumours ( 0.4%)
Sarcomas (0.3%)
Is acute appendicitis a surgical emergency
Yes
It can take the appendix as little as 48-72 hours from symptom onset to rupture so must be treated as an emergency
Which type of cancer commonly spreads haematologically
Typical of sarcomas but also seen with carcinomas
List the venous drainage of the lower GI tract
Venous drainage, matches the named arterial supply (e.g., superior and inferior mesenteric veins) which all eventually drain into the hepatic portal vein
How many polyps are typically seen in autosomal dominant cases of Juvenile Polyps
Polyp numbers range from 3 up to 100s
May also have extra-intestinal manifestations
What are the 2 main prognostic factors for colorectal adenocarcinoma
Depth of invasion and the presence or absence of lymph node mets
What is the most important feature distinguishing a benign tumour from malignant
Ability to metastasise
What is the main clinical consequence of the adherence virulence factor of the bacteria in enterocolitis
Issues with food absorption
This is because the bacteria sticks to the gut wall and destroys the brush border
What determines the prognosis of small bowel obstruction in those who have not had previous abdominal surgery
The underlying cause and their response to the treatment of it
They may have an underlying malignancy, inguinal hernia, congenital band, or Crohn’s disease as the cause of the obstruction
What is the similarity and difference between the 2 pathways that lead to CR cancer
Both involve a stepwise accumulation of multiple mutations
They will differ and the genes involved and the mechanism by which mutation occurs
What screening is offered to family members of those with FAP
Should be offered a sigmoidoscopy every 1-2 years from age 12-35. Ages 35+ get one every 3 years instead.
List the microscopic features of polyps in Peutz-Jegher’s syndrome
Branching networks of connective tissue, smooth muscle, lamina propria and glands lined with normal intestinal epithelium
Which second line tests might you order to determine the cause of large bowel obstruction
beta-HCG -> ?pregnancy
Urinalysis -> ?UTI
Electrocardiogram -> ?arrhythmia
water-soluble contrast study
List the 5 main causes of small bowel obstruction in adults
Previous surgery -with the formation of intra-abdominal adhesions
Inguinal hernia with incarceration - most common cause of intestinal obstruction worldwide
Crohn’s disease - causing strictures or adhesions due to the chronic inflammation
Intestinal malignancy
Appendicitis
What is pseudomembranous colitis also known as
Clostridium Difficile-Associated Colitis
What is the only definitive treatment for colorectal adenocarcinoma - true or false
True
Although chemo and radiotherapy are also used
What is involved in total colectomy
Removal of a large portion of the bowel
An ileosigmoid or ileorectal anastomosis can be fashioned if subtotal and the patient is well enough.
Alternatively, an end ileostomy can be formed and the rectal stump oversewn
List common differentials for small bowel obstruction
Ileus Infectious gastroenteritis Large bowel obstruction Intestinal pseudo obstruction Acute appendicitis Acute pancreatitis UTI
List common complications of large bowel obstruction
Bowel perforation
Sepsis
Death
List common mechanisms of death in colorectal adenocarcinoma
Mets - leading to liver failure or pulmonary effects
Risk of GI Haemorrhage, perforation and obstruction all which can be fatal
CVD - due to association with poor lifestyle
What promotes the clumping of tumour cells in blood
It is promoted by interactions between blood and tumour components (esp. platelets and polyphosphate)
Polyphosphate activates factor XII which causes fibrin deposition + stabilisation of tumour emboli
This may enhance ability of cells to arrest en-masse within capillary beds.
Which other conditions is associated with SMAD4 mutations (seen in juvenile polyps)
SMAD4 is also associated with hereditary haemorrhagic telangiectasia so patients may have both
How are dysplastic lesions in the colon classified
As either low or high grade
How do you treat complete or complicated small bowel obstruction
Supportive care
Nasogastric decompression – removes upper GI contents
Emergency surgery and correction of underlying cause
What is the most common type of cancer in the rectum
Adenocarcinoma - 98% of cases
Falls under colorectal adenocarcinoma
What can stop RAS activation
GTPase-activating proteins (GAPs) apply brakes to RAS activation
What are cyclins
Regulatory proteins whose concentrations rise and fall during the cell cycle
What is the most common hereditary cause of colorectal cancer
HNPCC
Accounts for 2-4% of cases
What is the precursor lesion to most colonic adenocarcinoma
Colonic adenomas
What type of gene is HPNCC and how does its mutation potentially lead to CR cancer
A DNA mismatch repair gene and so mutation leads to defects in DNA repair
What type of cancer is seen in HNPCC
Adenocarcinomas,
Can be sessile serrated or mucinous
How would the Gi tract be divided according to embryology
Upper portion derived from the foregut (mouth to major papilla of duodenum)
Middle derived from midgut (papilla to middle of the transverse colon)
Lower derived from the hindgut (mid transverse to anus)
What is the most common treatment for rectal adenocarcinoma
Most commonly treated through radical resection of the rectum including removal of local lymph nodes ( at least 10)
How would you differentiate between a large bowel obstruction and chronic idiopathic megacolon
V difficult to differentiate, specialist studies required!
Are the local nodes ever bypassed in metastatic spread
Yes - called skip metastasis Possibly due to microscopic mets or variation in normal lymphatic drainage
Which symptoms can bowel polyps cause
Typically asymptomatic - picked up on bowel screenings
May present with mucus/blood in stool, changes to bowel habit or abdominal pain if large
How do you manage appendicitis
Definitive treatment is laparoscopic appendectomy – all patients with suspected or confirmed appendicitis should be referred within 24 hrs
All pts should be given a prophylactic pre-op dose of antibiotics – course should be continued post-operatively in pts with perforation or abscess formation
What is apoptosis
A type of programmed cell death that serves to eliminate unwanted and irreparably damaged cells, with the least possible host reaction
Both copies of the APC gene need to be inactivated to form colonic adenomas - true or false
True
This can occur through genetic mutations or epigenetic events
What causes degradation of the ECM in the metastatic cascade
Tumour cells secrete proteolytic enzymes (MMPs, cathepsins) or induce stromal cells to do so to break it down
These proteases are often over-expressed in tumours
What happens if the polyp in solitary rectal ulcer syndrome gets trapped in the faecal stream
Can result in mucosal prolapse
How would you differentiate between a large bowel obstruction and endometriosis
Ultrasonography (transabdominal and transvaginal) would show endometriotic cysts, but has a limited role in detecting endometrial implants
What are adhesions
Fibrous bands of scar tissue that causes organs to attach to the surgical site or to other organs
This causes the lumen of the bowel to get kinked or pinched in certain spots - obstruction
Which surgical procedures can be used for palliative treatment in colorectal cancer
Endoluminal stenting to relive acute obstruction
Stoma formation for acute obstruction
Resection of mets alongside adjuvant chemo, mainly in the liver
What is the lifetime risk of colorectal cancer in HNPCC patients
Up to 80%
List activators of the cell cycle
cyclins and CDKs chaperon cell cycle progression
What stimulates cell proliferation
A combination of soluble growth factors and ECM signals transmitted via integrins
What is the main risk factor for developing colonic adenomas
A family history of colorectal adenocarcinoma.
Describe the genetic basis of FAP
Autosomal dominant condition caused by mutations in the APC gene which is a key part of the WnT pathway
APC gene is a tumour suppressor
Specific APC mutations are associated with other extra-intestinal manifestations and are now named variants (e.g. Gardner’s syndrome).
How does size affect cancer risk in neoplastic polyps
Size does correlate to risk of progression to cancer
Very rare if under 1cm but 40% of those over 4cm will become cancerous.
The development of colorectal adenocarcinoma includes both genetic and epigenetic alterations - true or false
True
Obstruction of the GI tract can occur at any level - true or false
True
Describe how radiotherapy is utilised is colorectal adenocarcinoma
Only really used for rectal cancer and rarely given for cancer in the colon due to the risk of small intestine damage
Its usually given neoadjuvantly and rarely adjuvantly
Its particularly useful if on MRI the rectal cancer appears to have threatened circumferential resection
In metastatic disease radiotherapy is only given palliatively for mets to brain and bone
Which type of colectomy is performed on descending colon tumours
left hemicolectomy
How is rectal adenocarcinoma recurrence managed
Usually managed with surgical abdoperineal resection or pelvic exenteration
Most colonic adenomas will progress to colonic adenocarcinoma - true or false
False
Only 10% will
List the parts of the large intestine
Made of the caecum, colon, rectum, anal canal and anus
List the macroscopic features of appendicitis
May appear grossly normal
Lumen may contain frank blood and pus
May be obvious rupture
Cause of obstruction may be found on autopsy e.g. faecalith
May see yellow-tan fibrinopurulent exudate
Ulceration in the mucosa
How can you confirm a clinical diagnosis of small bowel obstruction
CT
Bowel polyps always occur in multiples - true or false
False
Patient’s may have a single polyp or multiple – it depends on the type/cause
Can you be an asymptomatic carrier of C.diff
Yes
Among general population, 3-5% of adults are colonised and are asymptomatic carriers
Which type of mutations commonly affect the tumour suppressor genes in the APC/B-catenin pathway
Usually caused by chromosomal deletions - chromosomal instability is a hallmark of this pathway.
Alternatively they can be silenced by methylation of CpG rich zones or CpG islands within the 5’ region of genes
Describe the process of small bowel obstruction
Obstruction occurs
Causes proximal dilatation and interruption of faecal flow
In acute cases, there can be hyperperistalsis distal to the obstruction, leading to diarrhoea
Obstructed bowel will, over time, prevent appropriate venous drainage with the possible result of decreased arterial perfusion
Untreated patients will develop progressive intestinal ischaemia, necrosis, and perforation.
List clinical features of rectal adenocarcinoma
Rectal bleeding Change in bowel habit – often in the form of diarrhoea but also tenesmus or the feeling of incomplete evacuation Occult bleeding detected by FAT Abdominal pain – usually colicky and may be assoc. with bloating Urinary symptoms Nack/pelvic pain Malaise Jaundice - liver mets Peritonitis if they perforate
May be asymptomatic
Which parts of the lower GI tract are intraperitoneal
The transverse and sigmoid colon
Have associated mesenteries
How does advanced stage colorectal cancer present
This displays more abdominal tenderness, macroscopic rectal bleeds, palpable abdominal masses and hepatomegaly and ascites
What is the major cause of death in colorectal adenocarcinoma
Metastasis
Most frequently through liver mets causing failure but could also be through pulmonary mets = haemorrhage or infection
What is the role of PTEN
phosphatase and tensin homologue
It applies the breaks to PI3K activation
Which type of colectomy is performed on sigmoid colon tumours
Sigmoidcolectomy
How do you diagnose appendicitis
Diagnosis is usually made clinically, but can be difficult to establish pre-operatively
Look for rebound tenderness, Rovsing’s sign, the psoas sign and obturator sign on physical exam
Bloods may show elevated CRP, leukocytosis with neutrophilia
Which cyclins and CDKs regulate the G1-S transition
Cyclin D-CDK2, cyclin D-CDK4, cyclin D-CDK6, and cyclin E-CDK2
They do so by phosphorylating the Rb protein
Which investigations should be done for infective colitis
Stool cultures
Colonoscopy with mucosal biopsy
What is involved in Hartmann’s procedure
Involves the removal of the sigmoid colon with formation of a left iliac fossa colostomy.
The rectal stump is closed.
Theoretically reversible, but many patients opt not to undergo another major abdominal operation and, instead, keep their colostomy
What are the most common familial causes of colorectal cancer
FAP and HPNCC
What is the purpose of the G1-S checkpoint in the cell cycle
It monitors DNA integrity before irreversibly wasting cellular resources to DNA replication.
How does a low fibre diet contribute to colorectal cancer
Poorly understood
Thought that it leads to reduced stool bulk/movement and altered intestinal microbiota
This leads to increased synthesis of potentially toxic reactive oxidative by-products from bacterial metabolism
They remain in contact with the mucosa causing damage for prolonged periods of time due to reduced stool movement.
What happens to the cell cycle when checkpoint activation occurs in the cell cycle
This occurs when DNA irregularity is detected
It delays cell cycle progression & triggers DNA repair.
What is paralytic ileus
Decreased GI motility without mechanical obstruction
List the microscopic features of a colonic adenoma
Epithelial dysplasia (nuclear hyperchromasia, elongation and stratification) which is mostly seen near the surface. This is often accompanied by prominent nucleoli, eosinophilic cytoplasm and a reduction in goblet cells.
What determines the mortality and survival from a large bowel obstruction
Determined by underlying disease process
List the key elements of cell proliferation
Accurate DNA replication
Coordinated synthesis of other cellular components
Equal apportionment of DNA and organelles to daughter cells via mitoses and cytokinesis
These are
How can rectal tumours be picked up if they have no symptoms
PR examination
Occult bleeding can be picked up by FAT
List the macroscopic features of polyps in Peutz-Jegher’s syndrome
Large and pedunculated polyp with a lobulated surface
List some of the complications of cryotherapy for liver mets
Liver cracking
Thrombocytopenia
DIC
What is toxic megacolon
Colonic distension associated with systemic toxicity
What is meant by direct seeding of body cavities or surfaces in relation to metastasis
When a malignant neoplasm penetrates an “open field” (no physical barriers).
Which patients are most likely to get a recurrence of small bowel obstruction
Patients with previous surgery
This is because the likely cause is adhesions and they are therefore at risk of recurrent adhesions despite adequate adhesiolysis
What are CDKs
Cyclin-dependent kinases
They are protein kinases that are activated after binding with their specific cyclins
When does cancer usually develop in HNPCC cases
Typically develop at a younger age than sporadic cancers.
When is surgery used for pseudomembranous colitis and what procedure is performed
In severe cases which do not respond to medical management
Typically do a subtotal colectomy with preservation of the rectum
Intestinal obstruction is a common surgical emergency - true or false
True
It accounts for up to 20% of admissions with acute abdominal pain
Harmartomatous polyp syndromes can cause non-sporadic colorectal cancer - true or false
True
Includes syndromes like juvenile polyposis and Peutz-Jegher’s syndrome
Which tumours are termed MSI-High
Tumours that originate through the MSI pathway
They have high levels of microsatellite instability as this is where the mutation occurs
List the microscopic features of juvenile polyps
Cystic spaces are filled with mucin and inflammatory debris.
The rest of the polyp is lamina propria expanded by mixed inflammatory infiltrates.
May have reduced mucularis mucosae - or can be normal
List types of cancer that can arise in the colon/rectum
Most common - adenocarcinoma
Rarer carcinomas ; squamous cell, adenosqaumous, spindle cell, undifferentiated
Rarer non-carcinomas; lymphoma, carcinoid tumours, sarcoma
Can malignant tumours have a capsule
Slowly expanding malignant tumours may develop an apparently enclosing fibrous capsule
However, histological examination of these ‘pseudo-encapsulated’ masses almost always show rows of tumour cells penetrating the margin & infiltrating adjacent structures - not a true capsule
In cases of large bowel obstruction caused by sigmoid volvulus, the sigmoid colon is the most common site of perforation - true or false
False
The sigmoid loop is usually thickened from recurrent episodes of volvulus
SO the caecum is again at greatest risk
Aside from colorectal, what cancers are seen in HNPCC
Associated with cancers at other sites too, including endometrium, stomach, ovaries, ureters, brain, small bowel, hepatobiliary tract pancreas and skin
Describe a sessile polyp
Small, flatter elevations of the mucosa
Most polyps start out like this anyway
Small bowel obstruction is a medical emergency - true or false
TRUE
It accounts for 12% to 16% of emergency surgery admissions and 20% of emergency laparotomies in the UK
List causes of luminal obstruction in the appendix
Most commonly by normal or compacted stool (faecalith)
Tumours
Worms
Gallstones
Post-viral lymphatic hyperplasia (more common in children and teens)
What type of gene is APC and why does its mutation lead to increased risk of CR cancer
A tumour suppressor gene
Mutation leads to growth of adenomatous tissue which can then become cancerous
List some of the short term complications of small bowel obstruction
Necrosis/infarction (risk: medium)
Sepsis -> multi-organ failure (risk: medium)
. Intra-abdominal abscess (risk: low)
Which tumours are seen in adults with Peutz-Jegher’s syndrome
colon cancers, also pancreatic, breast, lung, ovarian, and uterine
Which cells do colorectal cancers originate from
The epithelial cells lining the colon
What surveillance is recommended for those with a family history of neoplastic polyps/adenocarcinoma
Surveillance recommended from ages 45-50 or 10 years before youngest relative developed the cancer.
What are the 3 sections of the small intestine
Duodenum - found in theepigastric regionsurrounding thehead of the pancreasand is split intofour parts
jejunum- containsplicae circularesand villi which increase the absorption of products of digestion
Ileum - important in absorbingvitamin B12andbile acids
Why does pain migrate in appendicitis
Starts as dull periumbilical pain - visceral
Migration occurs as the inflammation progresses to involve the serosa, which irritates the parietal peritoneum - parietal pain
Which type growth factor receptor is the most important in cancer
Receptor tyrosine kinases are arguably the most important
They are activated in tumours by multiple mechanisms incl. point mutations, gene rearrangements and gene amplifications
They then activate several signalling pathways - RAS
What regulates CDKs
They are regulated by catabolism or by binding of CDK inhibitors (CDKIs).
CDKIs enforce cell cycle checkpoints - especially important at G1/S and G2/M
The inhibitors can stop progression of the cycle
List risk factors for infective enterocolitis
Travelling (“travellers’ diarrhoea”)
Immunosuppression
Extremes of age
List some examples of neoplastic polyps
Colonic adenomas
What are the common mechanisms of death from pseudomembranous colitis
Dehydration -> Hypovolaemia and AKI
Septic shock following a bowel perforation
List the macroscopic features of colorectal cancers in the proximal cancer
Tumours often grow as polypoid, exophytic masses extending along one wall of the ascending colon and large calibre caecum
Rare for them to cause obstruction
It will grow into the bowel wall over time
They characteristically are firm
List the microscopic features of inflammatory polyps (in reference to solitary rectal ulcer syndrome)
Mixed inflammatory infiltrates, superficial erosions and epithelial proliferation.
If associated with prolapse you also see smooth muscle hyperplasia within the lamina propria.
Is genetic testing available in families with FAP
Genetic screening can be used to eliminate family members if the specific mutation is known - e.g. if they have the APC mutation
If APC mutation not found genetic screening cannot be used and screening is offered instead.
How would you differentiate between a large bowel obstruction and pseudomembranous colitis
The latter would have an elevated WBC count +++
In the MSI pathway, where do mutations occur
The mutations accumulate in microsatellite repeats - called microsatellite instability
The microsatellite sequences are located in coding or promoter regions of genes involved in the regulation of cell growth
Define a simple bowel obstruction
An intestinal blockage with no peritonitis
It generally reflects early or partial obstruction and may respond to non-operative therapy
Are all harmartomatous polyps associated with a genetic condition
No
Can get sporadic ones
How is C.diff transmitted
Via the faecal-oral route - healthcare worker hands, incorrectly cleaned bedpans
or
By contaminated surfaces
What is the other name for HNPCC
Lynch syndrome
Why might you see diarrhoea in small bowel obstruction
In acute cases, there can be hyperperistalsis distal to the obstruction, leading to diarrhoea
What can a protooncogene encode
growth factors, growth factor receptors, signal transducers, transcription factors, or cell cycle components
Describe the difference between sporadic and syndromic Juvenile Polyps
Sporadic usually leads to solitary polyps
In the syndrome numbers range from 3 up to 100s
What are colonic adenomas
They are the precursor lesion to the majority of colorectal adenocarcinoma
They are epithelial neoplasm’s that range from small, often pedunculated, polyps to large sessile lesions
Which procedure can improve survival in colorectal adenocarcinoma patients with a small number of mets
Resection of distant tumour nodules
How can you differentiate between a small bowel obstruction and large bowel obstruction
CT will reveal the level of obstruction in the bowel
What is the incubation period for C.diff in pseudomembranous colitis
Typically 2-3 days
Symptoms usually present 5-10 days after antibiotics course started
However, symptoms can develop up to 8 wks after treatment discontinued
List common symptoms of infective colitis
Abdominal pain Watery diarrhoea (+/- blood) Vomiting Frequency and urgency Fever
What happens in the cell cycle when the genetic damage is too severe for repair
The cells undergo apoptosis or enter a non-replicative state called senescence
Primarily occurs via p53-dependent mechanisms
At which part of the colon are most of your adenocarcinomas found
They are found approximately equally distributed throughout the colon so there is no area they are predominantly found
What is the most common malignancy of the GI tract
Colorectal Adenocarcinoma
Significant cause of morbidity and mortality
What is an oncoprotein
A protein encoded by an oncogene that drives increased cancer cell proliferation
May result from a variety of aberrations
How are colorectal adenocarcinomas graded
Grading is based upon the gland formation within the tumour
Well differentiated adenocarcinoma = >95% of tumour is gland forming
Moderately differentiated adenocarcinoma = 50-95% of tumour is gland forming
Poorly differentiated adenocarcinoma = <50% of the tumour is gland forming
Describe the pattern of lymphatic spread in metastatic cancers
It follows the natural routes of lymph drainage from the affected organ
E.g., breast carcinoma in upper outer quadrant -> axillary nodes > infraclavicular & supraclavicular.
Few exceptions - skip mets
List the 3 main routes of dissemination in cancer
Direct seeding of body cavities or surfaces
Lymphatic spread
Haematogenous spread
Define a partial/incomplete bowel obstruction
The blockage of the intestine is not complete, resulting in partial passage of flatus (gas) and occasionally stool
It is not a surgical emergency and can resolve with non-operative therapy
Which tumours are seen in late childhood with Peutz-Jegher’s syndrome
small intestine and gastric tumours
List the p proteins which broadly inhibit CDKs
P21, p27 and p57 are a family which broadly inhibit (most) CDKs
Which countries have the lowest incidence of colorectal cancer
South America, India, Africa and South Central Asia
How do patients with appendicitis typically present
Dull periumbilical pain which then migrates to McBurney’s point in RIF (right iliac fossa) and becomes sharp
Patients will complain of pain on deep palpation and rebound tenderness
Murphy’s triad – RIF pain, nausea and vomiting, low-grade fever
Which antibiotics are used for severe or resistant cases of pseudomembranous colitis
Vancomycin can also be used alone or in conjunction with metronidazole in these cases
Which type of mutation is the typical cause of harmartomatous polyps
Most syndromes are associated with germline mutations in tumour-suppressor genes or pro-oncogenes
In sporadic cases of juvenile polyps is cancer common
No
Dysplasia is rare in these cases
Which cancers often demonstrate tumour dormancy
Melanomas, breast and prostate cancers
Where is most c.diff infection acquired
In the healthcare setting
Some estimates say that 30% of hospitalised adults will be colonised with C. diff, but most will remain disease-free
Small bowel obstruction is uncommon in the general population - true or false
True
An incidence of around 0.1% to 5%
Adenocarcinomas are approximately equally distributed over the entre length of the colon - true or false
True
List the microscopic features of pseudomembranous colitis
Characteristic eruption of mucopurulent exudate from damaged crypts in a “volcano” or “mushroom cloud” pattern
Adjacent mucosa may be intact but overlayed by neutrophilic pseudomembrane
As disease progresses, crypts may become necrotic and ulcerated
What is the most common cause of large bowel obstruction in adults
Colonic malignancy
Approximately 30% of colorectal cancer patients initially present to an emergency care setting with obstruction
How does high fat intake increase the risk of CR cancer
The high fat intake also enhances hepatic synthesis of cholesterol and bile acids which may then be converted to carcinogens by the intestinal bacteria
What is the typical incubation period for infective enterocolitis
Incubation period depends on type of infection
Pre-formed toxins may cause symptoms within hours but toxigenic organisms may incubate for a number of days
Describe the microscopic features of most colorectal adenocarcinomas
Most tumours will be composed of tall columnar cells that look like the dysplastic epithelium found in adenomas
They are characteristically firm because their invasive component causes a strong desmoplastic response
How can arterial metastatic spread occur
It can occur if tumour cells pass through pulmonary capillary beds/arteriovenous shunts or when lung cancers give rise to tumour emboli.
What effect do oncogenes have on oncoproteins
They increase or alter the function of oncoproteins
They are usually active by default and resistant to control by external signals
This occurs via various mechanisms
In which wards is C.diff colitis more common
More prevalent in intensive care and internal medicine
Does the large intestine have villi
No
Instead it has deep crypts
This is where the goblet and endocrine cells are
What proportion of FAP cases are inherited
Around 70%
The remaining 30% are thought to be caused by de novo mutations
What’s the difference between the causes of enterocolitis that’s caused by ingestion of pre formed toxins and infection by toxigenic organisms
Ingestion of pre-formed - the organism has already formed the toxin before being ingested
The toxigenic organisms will form and release their toxins when they are inside the host itself
Describe the shape of the sigmoid colon
Sigmoid is kind of S shaped – curves from LLQ to the level of S3 vertebrae (kind of central)
This section is particularly mobile
Give an example of cancer that do not metastasise to the first site of vascular drainage (as expected)
breast/prostate carcinomas
They preferentially met to bone due to organ tropism
Which symptom of colorectal cancer do young people tend to present with
More likely to present with abdominal pain
Less common for them to present with the red flag symptoms like bleeding, weight loss etc.
How can you differentiate between a small bowel obstruction and infectious gastroenteritis
Abdominal CT scan will be negative for any intestinal obstruction
Stool cultures may be positive for viruses or bacteria
What are the 8 hallmarks of cancer
Self-sufficiency in growth signals. Ability to evade host immune response. Insensitivity to growth-inhibitory signals. Limitless replicative potential (immortality). Ability to invade and metastasise. Sustained angiogenesis. Evasion of apoptosis. Altered cellular metabolism.
How would you differentiate between a large bowel obstruction and acute colonic pseudo-obstruction
CT or contrast enema confirms diagnosis and excludes mechanical causes of obstruction
How can you differentiate between a small bowel obstruction and an ileus
CT scan will show passage of contrast throughout the small bowel and into the rectum
How can you differentiate between a small bowel obstruction and intestinal pseudo obstruction
X-ray and CT may show dilated small or large bowel, which may be massively dilated
No real obstruction
What is the overall lifetime risk of developing appendicitis
approx. 7%
Where do polyps develop in Peutz-Jegher’s syndrome
Most common in the small intestine, but can be seen in the colon, stomach and less commonly in the bladder and even lungs
