Seminar 10 - Colorectal Cancer Flashcards

Question

How do you manage infective colitis

Answer 1

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

Answer 2

Asian ethnicities followed by Hispanics

Answer 3

YES | Some tumours invade early and rarely met - one does not determine the other

Answer 4

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

Answer 5

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

Answer 6

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.

Answer 7

The obstruction causes distal interruption of faecal flow | Constipation will be absolute

Answer 8

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

Answer 9

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

Answer 10

``` Radiation Chemotherapy Chemoradiation Radioembolisation Intraoperative radiotherapy ```

Answer 11

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

Answer 12

False | Does not exclude

Answer 13

lined by simple columnar intestinal epithelium

Answer 14

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'

Answer 15

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)

Answer 16

False Sigmoid volvulus is more usually seen in frail or older patients Caecal volvulus is even rarer and more commonly seen in younger patients

Answer 17

Left | The symptoms are most obvious (bleeding/bowel habits) so often presents earlier

Answer 18

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

Answer 19

Wound infection | However, risk is minimised with laparoscopic surgery and prophylactic Abx

Answer 20

Managed with increased surveillance OR Colectomy - if multiple foci of flat dysplasia, in extensive or long standing disease or in older patients

Answer 21

It will lead to cancer

Answer 22

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)

Answer 23

Tumours are resistant to programmed cell death

Answer 24

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

Answer 25

Increased amylase and lipase from bloods | CT scan shows inflamed pancreas

Answer 26

Typically invasive, infiltrative and destroys surrounding normal tissues

Answer 27

A triad of symptoms seen in appendicitis | RIF pain, nausea and vomiting, low-grade fever

Answer 28

Cyclin B-CDK1

Answer 29

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

Answer 30

Called juvenile because the majority occur in children under the age of 5 Can present in older children too

Answer 31

Most common in adolescence and early adulthood (<40 y.o.)

Answer 32

YES | However, some do very infrequently (BCC and gliomas)

Answer 33

True | Can occur within polyps

Answer 34

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

Answer 35

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

Answer 36

Colicky abdominal pain - can be severe Vomiting Absolute constipation Diarrhoea in acute cases

Answer 37

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

Answer 38

True | Most are benign, and the majority do not progress.

Answer 39

The dentate line

Answer 40

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

Answer 41

Classed as this when the cancer cells form in the tissue of the rectum

Answer 42

G1 (pre-synthetic) S (DNA synthesis) G2 (pre-mitotic) M (mitotic) phases Quiescent cells are in a physiologic state called G0.

Answer 43

1- invasion of the ECM | 2- vascular dissemination, tissue homing & colonisation

Answer 44

TGFRBR2 gene - mutation results in uncontrolled cell growth Pore apoptotic protein BAX- causing enhanced survival of genetically abnormal clones

Answer 45

There are various checkpoint - G1-S, G2-M

Answer 46

Sessile serrated adenomas can appear histologically like hyperplastic Important to differentiate between them as cancer risk is very different

Answer 47

It creates a tissue plane that makes the tumour discrete, readily palpable, movable (nonfixed), and easily excisable by surgical enucleation

Answer 48

Genomic instability Cancer-promoting inflammation These are considered enabling characteristics since they promote cellular transformation and subsequent tumour progression

Answer 49

``` 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 ```

Answer 50

Colorectal carcinomas are more more likely to metastasise to liver since it is the first organ downstream of the primary tumour

Answer 51

True | They often go undetected for a long time as a result

Answer 52

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

Answer 53

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

Answer 54

The sequence of events that result in cell proliferation

Answer 55

High risk dysplasia is associated with a higher malignancy risk Only in that individual polyp, not in patient as a whole.

Answer 56

They are not at increased risk for other forms of cancer

Answer 57

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

Answer 58

If left untreated it can progress to intestinal necrosis, perforation, sepsis, and multi-organ failure

Answer 59

Same risk factors/causes as colorectal (other card) | High alcohol consumption has a greater effect though

Answer 60

NO Symptoms vary depending on causative organism, but may mimic each other and this alone should not the basis for determining the pathogen

Answer 61

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

Answer 62

Also at risk of developing adenomas at other sites such as the Ampulla of Vater and the stomach.

Answer 63

Underlying pathogenesis is still uncertain | Likely due to decreased cell turnover and delayed shedding which leads to an accumulation of cells

Answer 64

Men - just | slightly elevated M:F ratio (1.4:1)

Answer 65

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.

Answer 66

Stable cells include hepatocytes and lymphocytes They are quiescent but can re-enter the cell cycle Enter G0 but can leave on appropriate stimulus

Answer 67

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.

Answer 68

This is usually a late sign of the disease due to the tumour invading/ compressing the nerve trunks

Answer 69

``` Change in bowel habit Rectal bleeding/ lower GI bleeding Weight loss Abdominal pain Pallor/weakness/ fatigue ```

Answer 70

Locomotion propels tumour cells through the degraded BMs and zones of matrix proteolysis

Answer 71

Highest in North America - US accounts for 10% of all CA cases Australia, New Zealand, Europe and Japan are additional areas of high incidence

Answer 72

True | Not limited to adenocarcinomas

Answer 73

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

Answer 74

They form few glands Other poorly differentiated ones may produce abundant mucin that will accumulate in the intestinal wall - giving a poor prognosis

Answer 75

PA malformations | Polyps in the stomach/small bowel

Answer 76

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

Answer 77

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.

Answer 78

It can stop the cell cycle for DNA repair or induce apoptosis if the damage is beyond repair

Answer 79

``` Other GI pathology Ectopic pregnancy UTI PID Renal stones ```

Answer 80

True | Only in rare cases though

Answer 81

Labile tissues include epidermis, bone marrow and the GIT | They may cycle continuously - never enter G0, constant division with a condensed G1

Answer 82

They are at increased risk of osteosarcoma + other soft tissue sarcomas. As well as the 10000x increased risk of the retinoblastoma

Answer 83

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

Answer 84

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.

Answer 85

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%.

Answer 86

A mechanical disruption in the patency of the GI tract, resulting in a combination of emesis, constipation, and abdominal pain.

Answer 87

They deliver mitogenic signals to the cell continuously, even in the absence of growth factor in the environment

Answer 88

Used to control symptoms and slow growth | Involves chemo, radio and surgery

Answer 89

Because the RB gene (which is responsible) was the first tumour suppressor gene discovered

Answer 90

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.

Answer 91

Small intestine | It's frequently involved because of its narrow lumen

Answer 92

Haematogenous spread Prefer to grow within large veins so can invade the branches of the renal vein > renal vein > IVC > right side of heart

Answer 93

C.diff - causes pseudomembranous colitis | Estimated 500,000 infections per year

Answer 94

full blood count (FBC) electrolytes C-reactive protein

Answer 95

``` Occult bleeding Changes in bowel habit Cramping and LLQ discomfort Bowel obstruction Tenesmus Mass in LIF or on PR exam ```

Answer 96

Defined as being more than 5cm from the anus Do an anterior resection (leaves the rectal sphincter intact)

Answer 97

It can result in failure of growth inhibition and uncontrolled cell proliferation.

Answer 98

Adenocarcinoma - accounts for 95% of cases

Answer 99

Ascending and descending colon | Rectum

Answer 100

General signs of inflammation – oedema, hyperaemia, ulceration Grossly, may mimic IBD

Answer 101

"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

Answer 102

Usually presents with non specific symptoms like fatigue and weight loss

Answer 103

40% lifetime cancer risk Increased risk of many different types of tumours Monitoring is therefore recommended

Answer 104

Cyclin A-CDK2 and cyclin A-CDK1

Answer 105

Urine or serum beta–HCG -> ?pregnancy Urinalysis -> ?infection ?DKA ECG -> ?arrhythmia MRI

Answer 106

Liver Regional lymph nodes Lung Bones

Answer 107

Normal cellular genes whose products promote cell proliferation

Answer 108

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

Answer 109

The tumour capsule | It keeps the cells together and prevents it penetrating surrounding tissues

Answer 110

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.

Answer 111

``` Intermittent abdominal pain Abdominal distention Nausea Vomiting Presence of risk factors Tenesmus ```

Answer 112

Proximal dilation of the bowel together with peristalsis | Can become severe

Answer 113

Invasiveness | In general only malignant ones invade

Answer 114

Supportive care Nasogastric decompression Correction of underlying cause using medical therapy e.g. Crohns

Answer 115

It indicates poor tissue perfusion | It is not diagnostic for intestinal ischaemia but can indicate

Answer 116

No predominant site in colon

Answer 117

True | Also requires activation of necessary factors

Answer 118

Benign epithelial proliferations with in the bowel

Answer 119

It is a rare autosomal dominant syndrome mainly caused by germline mutations in the STK11 gene This gene is a tumour suppressor

Answer 120

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

Answer 121

trans-anal excision or trans-anal endoscopic microsurgery

Answer 122

Juvenile polyps and Peutz-Jegher's syndrome

Answer 123

The ones produced by oncogenes | are usually active by default and thereby relieve cells of their dependency on growth factors and control by checkpoints

Answer 124

Tumours have unrestricted proliferative capacity, a stem cell-like property that permits tumour cells to avoid cellular senescence and mitotic catastrophe.

Answer 125

Familial In sporadic cases almost always only 1 eye affected

Answer 126

Most common in the colon and rectum but can also occur earlier in GI tract

Answer 127

Usually under 3cm in diameter. Pedunculated with a smooth, reddish surface. Cystic spaces often dilating the crypts - characteristic signs

Answer 128

Alongside palliative care biological therapy can be given

Answer 129

Suggests constriction of the colonic lumen | Often due to a ring-shaped colon cancer

Answer 130

Most commonly involves the peritoneal cavity but can also incl. pleural, pericardial, subarachnoid & joint spaces

Answer 131

True | This is compounded if lymph node mets are also present

Answer 132

The development of tumours or neoplasms from normal cells

Answer 133

Accounts for less than 1% of all cases of colorectal cancer

Answer 134

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

Answer 135

No strong risk factors Smoking and a low fibre diet are thought to elevate the risk slightly

Answer 136

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.

Answer 137

It usually develops in the first year following surgery and can be local, distant or both

Answer 138

sex chord tumours in testes

Answer 139

Watery diarrhoea

Answer 140

False | 75% of cases are sporadic

Answer 141

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

Answer 142

True | Half of these deaths are in the under 5s

Answer 143

low rectal cancers have highest recurrence rates

Answer 144

Mucosa Submucosa Mucularis propria Serosa

Answer 145

``` Bleeding DVT and PE Infection Injury to small bowel and bladder Anastomotic leaks May require permanent stoma ```

Answer 146

Methylation-induced gene silencing

Answer 147

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.

Answer 148

They detect DNA or chromosomal damage and ensure that cells with genetic imperfections do not complete replication

Answer 149

Most commonly seen in those in their 60s or 70s

Answer 150

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

Answer 151

No | Rectum is macroscopically distinct from the colon for that reason

Answer 152

It causes quiescence or permanent cell cycle arrest | This is due to the action of tumour suppressor genes

Answer 153

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

Answer 154

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

Answer 155

``` Frequent/ repeated antibiotic use Immunosuppression Advanced age Hospitalisation or nursing home residence Potentially PPI use ```

Answer 156

if the tumour has invaded or is compressing the bladder

Answer 157

Clostridium difficile

Answer 158

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

Answer 159

Yes | Monoclonal antibodies and targeted genetic therapy can be used in specific cases

Answer 160

Small veins - due to their thinner walls However, some cancers prefer to grow within large veins, such as renal cell carcinoma or HCC

Answer 161

Most grow as cohesive, expansile masses that develop a surrounding rim of condensed connective tissue (capsule).

Answer 162

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

Answer 163

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

Answer 164

If there is persistent tachycardia, fever, and/or abdominal pain and tenderness

Answer 165

``` Acute colonic pseudo-obstruction Chronic idiopathic megacolon Toxic megacolon Endometriosis Pseudomembranous colitis ```

Answer 166

Prophase Metaphase Anaphase Telophase This is followed by cytokinesis

Answer 167

The caecum This is because it has the largest diameter and is where the bowel wall is thinnest This is regardless of underlying cause

Answer 168

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)

Answer 169

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

Answer 170

Dominant Patients inherit one mutated allele and one normal. The normal one is usually lost via further mutation or epigenetic silencing

Answer 171

colorectal adenomas or polyps current or previous malignancy inflammatory bowel disease diverticular disease

Answer 172

``` 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 ```

Answer 173

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.

Answer 174

Around 40% The remaining 60% are sporadic

Answer 175

Hyperplastic Inflammatory Harmartomatous

Answer 176

Lung | Liver

Answer 177

Peyer’s patches

Answer 178

Cells with damaged DNA are able to divide | This creates mutated daughter cells that are at risk for malignant transformation.

Answer 179

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.

Answer 180

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

Answer 181

Right hemicolectomy Hartmann’s procedure Total colectomy

Answer 182

The APC/b-catenin pathway because its activated in the classic adenoma-carcinoma sequence

Answer 183

True | More likely than single cells

Answer 184

Develop in around 30% of Western adults by age 60. | Less common in Asia but increasing as Western diet/lifestyle becomes more prevalent.

Answer 185

Stool sample checked for presence of enterotoxins

Answer 186

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

Answer 187

It regulates both the G1/S and G2/M checkpoints

Answer 188

By the nature of the obstruction Can be either simple or complicated Or by degree of obstruction Can be partial or complete

Answer 189

The balance between cyclins and CDK and the inhibitors

Answer 190

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

Answer 191

IBD Pseudomembranous colitis Ischaemic colitis

Answer 192

A characteristic ‘coffee bean’ appearance

Answer 193

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

Answer 194

Previous abdominal surgery - main one! Crohn’s Hernia

Answer 195

extended right hemicolectomy

Answer 196

With an appendicular mass

Answer 197

Small growths on the lining of the colon or rectum

Answer 198

Very! | Around 1/4 of the over 50s will be affected by them

Answer 199

Histological evidence of penetration of small vessels at site of primary neoplasm Ominous feature

Answer 200

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 generalized peritonitis sets in.

Answer 201

Harmartomatous - will get multiple

Answer 202

The resulting colorectal cancer is commonly seen in the right colon.

Answer 203

Short bowel syndrome | Risk is low

Answer 204

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

Answer 205

It is relatively equal between men and women

Answer 206

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

Answer 207

Perforation Migration Incontinence Cant be sued for low rectal tumours as causes intractable tenesmus

Answer 208

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

Answer 209

Often described as having a foetal appearance

Answer 210

Used for advanced disease both neoadjuvantly and adjuvantly | Adjuvant chemo is standard for stage 3 tumours and can potentially be used in stage 2

Answer 211

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

Answer 212

This is when metastatic cells take root and survive within distant tissues but fail to grow

Answer 213

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

Answer 214

They can enter G1 after completing a round of mitosis (continuously replicating cells), or they can enter from G0

Answer 215

The tissue cannot move back into the correct place and gets trapped If incarceration persists, strangulation and ultimately infarction occurs

Answer 216

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)

Answer 217

Probability of 2 genetic hits is low

Answer 218

Tumours have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation.

Answer 219

It can lead to an intra-abdominal infection where abscesses can form Requires open surgery or image-guided drainage

Answer 220

characterised by the functional or anatomical loss of extensive segments of small intestine resulting in inadequate absorption of enteral nutrition

Answer 221

Lymphatic spread

Answer 222

Around 1.5m

Answer 223

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

Answer 224

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).

Answer 225

Toxic megacolon - Occurs in approx. 3% of C. diff patients with a mortality rate of 30-50% Perforation and peritonitis Paralytic Ileus

Answer 226

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

Answer 227

Gram +ive, anaerobic rods Form spores Produce toxins A and B

Answer 228

Abx-associated diarrhoea Infective colitis IBD Ischaemic colitis

Answer 229

True This takes processed stool from a healthy donor and implants it into the patient Attempts to normalize the gut microbiome

Answer 230

Broad-spectrum antibiotics should be initiated after blood has been drawn for microbiological culture Treat cause as well of course

Answer 231

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

Answer 232

Despite the name, polyps are usually present but in much lower number than seen in FAP (less than 100 adenomas)

Answer 233

Rectal bleeding | Occurs in 60% of cases

Answer 234

At least 100 polyps have to be present for a FAP diagnosis but some patients will have thousands!

Answer 235

Permanent cells include neurones, RBCs and cardiac myocytes They have lost the capacity to proliferate They enter G0 but cannot leave

Answer 236

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

Answer 237

Most complications associated with perforation: Sepsis Generalised peritonitis – pts may require exploratory laparotomy if pathology cannot be identified

Answer 238

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

Answer 239

Metronidazole 500mg PO TDS for 10 days

Answer 240

It : ensures there has been accurate genetic replication before the cell actually divides.

Answer 241

Septic shock secondary to suppurative peritonitis following appendix perforation

Answer 242

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

Answer 243

They have multiple roles, but virtually all encode active oncoproteins involved in signalling pathways that drive cell proliferation

Answer 244

Perforation Bleeding Post polypectomy electrocoagulation syndrome Infection Anaphylaxis/ resp distress from anaesthetic

Answer 245

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

Answer 246

Initially treated conservatively – if symptoms resolve, appendectomy not indicated

Answer 247

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

Answer 248

Obstruction has progressed to ischaemia/gangrene and/or perforation - this is LIFE THREATENING Requires urgent resuscitation and surgical intervention - Surgical emergency!

Answer 249

Type of cancer is adenocarcinoma - can form tubular, villous or typical forms

Answer 250

It commonly affects older adults - higher risk of CVD Also associated with obesity, smoking, high alcohol and poor diet - all risk factors for CVD

Answer 251

``` 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 ```

Answer 252

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

Answer 253

True | However it is not always the case

Answer 254

Because they usually lack a well-defined capsule and cleavage plane This is why surgeons will excise with a margin

Answer 255

It will lead to cancer

Answer 256

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.

Answer 257

Congenital hypertrophy of the retinal pigment epithelium | Can be used as early screening

Answer 258

The caecum

Answer 259

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.

Answer 260

Fever Diffuse abdominal pain and watery diarrhoea (+/- blood) Has a distinctive smell Vomiting is rare

Answer 261

By appearance - sessile or pedunculated | Classed as either neoplastic or non-neoplastic

Answer 262

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.

Answer 263

True | This contributes to metastatic cells but also the ‘plasticity’ required to adapt to growth in a new microenvironment

Answer 264

Faecal oral spread of disease | Cholera is a big cause i

Answer 265

Slightly more common in men

Answer 266

From the caecum to anus | Caecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum and anus

Answer 267

True | Has an incidence range of 15% to 29%

Answer 268

RAS PI3K MYC D cyclins

Answer 269

Regular monitoring via colonoscopy Polyp removal This aims reduce incidence of cancer by preventing progression

Answer 270

Colonic adenoma

Answer 271

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.

Answer 272

Mucosal hyperpigmentation Seen in lips, nostrils, buccal mucosa, palms, genitals and perianal area Look like freckles but differentiated by buccal presentation

Answer 273

No | There are some suggestive signs like size and severity of dysplasia but not a perfect system

Answer 274

1. Constipation/failure to pass gas or stool 2. Presence of risk factors 3. Intermittent abdominal pain 4. Vomiting Others include - pyrexia, nausea, tachycardia, groin swelling

Answer 275

Ultrasound and CT confirm diagnosis of appendicitis in most cases

Answer 276

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.

Answer 277

False | Right sided cancers tend to effect younger individuals with left sided ones more commonly effecting older individuals

Answer 278

Gold standard – colonoscopy and biopsy Flexible sigmoidoscopy or CT colonography can be done if co-morbidities or frailty contradict colonoscopy an biopsy

Answer 279

WnT has a major role in controlling cellular growth and differentiation during embryological development

Answer 280

The caecum

Answer 281

Defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome

Answer 282

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

Answer 283

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

Answer 284

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

Answer 285

Brunner’s glands

Answer 286

Use of broad spectrum antibiotics | Most often involved – cephalosporins, clindamycin, penicillin's (amoxicillin/ ampicillin)

Answer 287

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.

Answer 288

It is fundamental to organism development, to maintenance of steady-state tissue homeostasis and to replacement of dead or damaged cells

Answer 289

``` Increasing age, Family history IBD Low fibre diet High processed meat/ refined carbs and fat intake Obesity Sedentary lifestyle Smoking High alcohol intake ```

Answer 290

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

Answer 291

A subtype of polyp which is typically associated with genetic or acquired syndromes.

Answer 292

Low anterior resection and abdominal perineal resection | These are preferred as better for patient QoL

Answer 293

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

Answer 294

Yes some of them do | Depends on the underlying mutation/cause

Answer 295

Level of S3

Answer 296

Haematogenous spread They penetrate the portal and hepatic radicals and then grow into the main venous channels

Answer 297

The liver | This is due to the portal drainage of the colon

Answer 298

RAS mutations | In some cancers the frequency is even higher - 90% of pancreatic adenocarcinoma

Answer 299

Intussusception

Answer 300

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)

Answer 301

Large size - 40% of >4cm adenomas contain invasive cancer Dysplasia within the adenoma is another risk

Answer 302

All pts >40 y.o. should be investigated for colon malignancy

Answer 303

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

Answer 304

The serrated surface

Answer 305

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

Answer 306

True | Also at increased risk of colonic adenoma which is the precursor lesion to colorectal adenocarcinoma

Answer 307

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

Answer 308

right hemicolectomy

Answer 309

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

Answer 310

True - in a small number of cases only though! | Presents like autosomal dominant inheritance

Answer 311

Vast numbers of small polyps present – from 100 up to the thousands! May have a dominant polyp which is larger.

Answer 312

Believed to enhance cell survival in circulation

Answer 313

Lymphomas (1.3%), Carcinoid tumours ( 0.4%) Sarcomas (0.3%)

Answer 314

Yes | It can take the appendix as little as 48-72 hours from symptom onset to rupture so must be treated as an emergency

Answer 315

Typical of sarcomas but also seen with carcinomas

Answer 316

Venous drainage, matches the named arterial supply (e.g., superior and inferior mesenteric veins) which all eventually drain into the hepatic portal vein

Answer 317

Polyp numbers range from 3 up to 100s | May also have extra-intestinal manifestations

Answer 318

Depth of invasion and the presence or absence of lymph node mets

Answer 319

Ability to metastasise

Answer 320

Issues with food absorption | This is because the bacteria sticks to the gut wall and destroys the brush border

Answer 321

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

Answer 322

Both involve a stepwise accumulation of multiple mutations | They will differ and the genes involved and the mechanism by which mutation occurs

Answer 323

Should be offered a sigmoidoscopy every 1-2 years from age 12-35. Ages 35+ get one every 3 years instead.

Answer 324

Branching networks of connective tissue, smooth muscle, lamina propria and glands lined with normal intestinal epithelium

Answer 325

beta-HCG -> ?pregnancy Urinalysis -> ?UTI Electrocardiogram -> ?arrhythmia water-soluble contrast study

Answer 326

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

Answer 327

Clostridium Difficile-Associated Colitis

Answer 328

True | Although chemo and radiotherapy are also used

Answer 329

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

Answer 330

``` Ileus Infectious gastroenteritis Large bowel obstruction Intestinal pseudo obstruction Acute appendicitis Acute pancreatitis UTI ```

Answer 331

Bowel perforation Sepsis Death

Answer 332

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

Answer 333

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.

Answer 334

SMAD4 is also associated with hereditary haemorrhagic telangiectasia so patients may have both

Answer 335

As either low or high grade

Answer 336

Supportive care Nasogastric decompression – removes upper GI contents Emergency surgery and correction of underlying cause

Answer 337

Adenocarcinoma - 98% of cases | Falls under colorectal adenocarcinoma

Answer 338

GTPase-activating proteins (GAPs) apply brakes to RAS activation

Answer 339

Regulatory proteins whose concentrations rise and fall during the cell cycle

Answer 340

HNPCC | Accounts for 2-4% of cases

Answer 341

Colonic adenomas

Answer 342

A DNA mismatch repair gene and so mutation leads to defects in DNA repair

Answer 343

Adenocarcinomas, | Can be sessile serrated or mucinous

Answer 344

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)

Answer 345

Most commonly treated through radical resection of the rectum including removal of local lymph nodes ( at least 10)

Answer 346

V difficult to differentiate, specialist studies required!

Answer 347

Yes - called skip metastasis Possibly due to microscopic mets or variation in normal lymphatic drainage

Answer 348

Typically asymptomatic - picked up on bowel screenings | May present with mucus/blood in stool, changes to bowel habit or abdominal pain if large

Answer 349

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

Answer 350

A type of programmed cell death that serves to eliminate unwanted and irreparably damaged cells, with the least possible host reaction

Answer 351

True | This can occur through genetic mutations or epigenetic events

Answer 352

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

Answer 353

Can result in mucosal prolapse

Answer 354

Ultrasonography (transabdominal and transvaginal) would show endometriotic cysts, but has a limited role in detecting endometrial implants

Answer 355

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

Answer 356

Endoluminal stenting to relive acute obstruction Stoma formation for acute obstruction Resection of mets alongside adjuvant chemo, mainly in the liver

Answer 357

cyclins and CDKs chaperon cell cycle progression

Answer 358

A combination of soluble growth factors and ECM signals transmitted via integrins

Answer 359

A family history of colorectal adenocarcinoma.

Answer 360

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).

Answer 361

Size does correlate to risk of progression to cancer | Very rare if under 1cm but 40% of those over 4cm will become cancerous.

Answer 362

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

Answer 363

left hemicolectomy

Answer 364

Usually managed with surgical abdoperineal resection or pelvic exenteration

Answer 365

False | Only 10% will

Answer 366

Made of the caecum, colon, rectum, anal canal and anus

Answer 367

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

Answer 368

False | Patient’s may have a single polyp or multiple – it depends on the type/cause

Answer 369

Yes | Among general population, 3-5% of adults are colonised and are asymptomatic carriers

Answer 370

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

Answer 371

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.

Answer 372

``` 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

Answer 373

The transverse and sigmoid colon | Have associated mesenteries

Answer 374

This displays more abdominal tenderness, macroscopic rectal bleeds, palpable abdominal masses and hepatomegaly and ascites

Answer 375

Metastasis | Most frequently through liver mets causing failure but could also be through pulmonary mets = haemorrhage or infection

Answer 376

phosphatase and tensin homologue | It applies the breaks to PI3K activation

Answer 377

Sigmoidcolectomy

Answer 378

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

Answer 379

Cyclin D-CDK2, cyclin D-CDK4, cyclin D-CDK6, and cyclin E-CDK2 They do so by phosphorylating the Rb protein

Answer 380

Stool cultures | Colonoscopy with mucosal biopsy

Answer 381

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

Answer 382

FAP and HPNCC

Answer 383

It monitors DNA integrity before irreversibly wasting cellular resources to DNA replication.

Answer 384

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.

Answer 385

This occurs when DNA irregularity is detected | It delays cell cycle progression & triggers DNA repair.

Answer 386

Decreased GI motility without mechanical obstruction

Answer 387

``` 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. ```

Answer 388

Determined by underlying disease process

Answer 389

Accurate DNA replication Coordinated synthesis of other cellular components Equal apportionment of DNA and organelles to daughter cells via mitoses and cytokinesis These are

Answer 390

PR examination Occult bleeding can be picked up by FAT

Answer 391

Large and pedunculated polyp with a lobulated surface

Answer 392

Liver cracking Thrombocytopenia DIC

Answer 393

Colonic distension associated with systemic toxicity

Answer 394

When a malignant neoplasm penetrates an "open field" (no physical barriers).

Answer 395

Patients with previous surgery This is because the likely cause is adhesions and they are therefore at risk of recurrent adhesions despite adequate adhesiolysis

Answer 396

Cyclin-dependent kinases | They are protein kinases that are activated after binding with their specific cyclins

Answer 397

Typically develop at a younger age than sporadic cancers.

Answer 398

In severe cases which do not respond to medical management | Typically do a subtotal colectomy with preservation of the rectum

Answer 399

True | It accounts for up to 20% of admissions with acute abdominal pain

Answer 400

True | Includes syndromes like juvenile polyposis and Peutz-Jegher's syndrome

Answer 401

Tumours that originate through the MSI pathway | They have high levels of microsatellite instability as this is where the mutation occurs

Answer 402

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

Answer 403

Most common - adenocarcinoma Rarer carcinomas ; squamous cell, adenosqaumous, spindle cell, undifferentiated Rarer non-carcinomas; lymphoma, carcinoid tumours, sarcoma

Answer 404

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

Answer 405

False The sigmoid loop is usually thickened from recurrent episodes of volvulus SO the caecum is again at greatest risk

Answer 406

Associated with cancers at other sites too, including endometrium, stomach, ovaries, ureters, brain, small bowel, hepatobiliary tract pancreas and skin

Answer 407

Small, flatter elevations of the mucosa | Most polyps start out like this anyway

Answer 408

TRUE | It accounts for 12% to 16% of emergency surgery admissions and 20% of emergency laparotomies in the UK

Answer 409

Most commonly by normal or compacted stool (faecalith) Tumours Worms Gallstones Post-viral lymphatic hyperplasia (more common in children and teens)

Answer 410

A tumour suppressor gene | Mutation leads to growth of adenomatous tissue which can then become cancerous

Answer 411

Necrosis/infarction (risk: medium) Sepsis -> multi-organ failure (risk: medium) . Intra-abdominal abscess (risk: low)

Answer 412

colon cancers, also pancreatic, breast, lung, ovarian, and uterine

Answer 413

The epithelial cells lining the colon

Answer 414

Surveillance recommended from ages 45-50 or 10 years before youngest relative developed the cancer.

Answer 415

Duodenum - found in the epigastric region surrounding the head of the pancreas and is split into four parts jejunum - contains plicae circulares and villi which increase the absorption of products of digestion Ileum - important in absorbing vitamin B12 and bile acids

Answer 416

Starts as dull periumbilical pain - visceral Migration occurs as the inflammation progresses to involve the serosa, which irritates the parietal peritoneum - parietal pain

Answer 417

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

Answer 418

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

Answer 419

Travelling (“travellers’ diarrhoea”) Immunosuppression Extremes of age

Answer 420

Colonic adenomas

Answer 421

Dehydration -> Hypovolaemia and AKI Septic shock following a bowel perforation

Answer 422

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

Answer 423

Mixed inflammatory infiltrates, superficial erosions and epithelial proliferation. If associated with prolapse you also see smooth muscle hyperplasia within the lamina propria.

Answer 424

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.

Answer 425

The latter would have an elevated WBC count +++

Answer 426

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

Answer 427

An intestinal blockage with no peritonitis | It generally reflects early or partial obstruction and may respond to non-operative therapy

Answer 428

No | Can get sporadic ones

Answer 429

Via the faecal-oral route - healthcare worker hands, incorrectly cleaned bedpans or By contaminated surfaces

Answer 430

Lynch syndrome

Answer 431

In acute cases, there can be hyperperistalsis distal to the obstruction, leading to diarrhoea

Answer 432

growth factors, growth factor receptors, signal transducers, transcription factors, or cell cycle components

Answer 433

Sporadic usually leads to solitary polyps | In the syndrome numbers range from 3 up to 100s

Answer 434

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

Answer 435

Resection of distant tumour nodules

Answer 436

CT will reveal the level of obstruction in the bowel

Answer 437

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

Answer 438

``` Abdominal pain Watery diarrhoea (+/- blood) Vomiting Frequency and urgency Fever ```

Answer 439

The cells undergo apoptosis or enter a non-replicative state called senescence Primarily occurs via p53-dependent mechanisms

Answer 440

They are found approximately equally distributed throughout the colon so there is no area they are predominantly found

Answer 441

Colorectal Adenocarcinoma | Significant cause of morbidity and mortality

Answer 442

A protein encoded by an oncogene that drives increased cancer cell proliferation May result from a variety of aberrations

Answer 443

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

Answer 444

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

Answer 445

Direct seeding of body cavities or surfaces Lymphatic spread Haematogenous spread

Answer 446

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

Answer 447

small intestine and gastric tumours

Answer 448

P21, p27 and p57 are a family which broadly inhibit (most) CDKs

Answer 449

South America, India, Africa and South Central Asia

Answer 450

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

Answer 451

Vancomycin can also be used alone or in conjunction with metronidazole in these cases

Answer 452

Most syndromes are associated with germline mutations in tumour-suppressor genes or pro-oncogenes

Answer 453

No | Dysplasia is rare in these cases

Answer 454

Melanomas, breast and prostate cancers

Answer 455

In the healthcare setting | Some estimates say that 30% of hospitalised adults will be colonised with C. diff, but most will remain disease-free

Answer 456

True | An incidence of around 0.1% to 5%

Answer 457

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

Answer 458

Colonic malignancy Approximately 30% of colorectal cancer patients initially present to an emergency care setting with obstruction

Answer 459

The high fat intake also enhances hepatic synthesis of cholesterol and bile acids which may then be converted to carcinogens by the intestinal bacteria

Answer 460

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

Answer 461

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

Answer 462

It can occur if tumour cells pass through pulmonary capillary beds/arteriovenous shunts or when lung cancers give rise to tumour emboli.

Answer 463

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

Answer 464

More prevalent in intensive care and internal medicine

Answer 465

No Instead it has deep crypts This is where the goblet and endocrine cells are

Answer 466

Around 70% | The remaining 30% are thought to be caused by de novo mutations

Answer 467

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

Answer 468

Sigmoid is kind of S shaped – curves from LLQ to the level of S3 vertebrae (kind of central) This section is particularly mobile

Answer 469

breast/prostate carcinomas | They preferentially met to bone due to organ tropism

Answer 470

More likely to present with abdominal pain | Less common for them to present with the red flag symptoms like bleeding, weight loss etc.

Answer 471

Abdominal CT scan will be negative for any intestinal obstruction Stool cultures may be positive for viruses or bacteria

Answer 472

``` 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. ```

Answer 473

CT or contrast enema confirms diagnosis and excludes mechanical causes of obstruction

Answer 474

CT scan will show passage of contrast throughout the small bowel and into the rectum

Answer 475

X-ray and CT may show dilated small or large bowel, which may be massively dilated No real obstruction

Answer 476

approx. 7%

Answer 477

Most common in the small intestine, but can be seen in the colon, stomach and less commonly in the bladder and even lungs

Seminar 10 - Colorectal Cancer Flashcards

(522 cards)