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Unit 10 PBL cases > Colorectal cancer > Flashcards

Colorectal cancer Flashcards

1
Q

What causes colorectal cancer and how does it develop?

A

Genomic instability leads to DNA damage
Defects in DNA repair mechanisms gives rise to mutations including APC
- APC is inactivated forming a truncated protein or mutation
- This regulates destruction complex - APC cannot bind to B-catenin
- B-catenin cannot be degraded and acts a transcription factor for proliferation genes - even in the absence of Wnt signalling
- Cell proliferation continues
- Cells don’t undergo apoptosis
- Gives rise to polyps
- Polyps left untreated eventually become malignant after accumulation of mutations
- Angiogenesis and metastasis

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2
Q

What is Wnt signalling in the proliferation of intestinal stem cells?

A

Wnt = secreted glycoprotein from stromal cells at base of colonic crypts
> Wnt binds to transmembrane protein receptor - Frizzled - Fz
> Activation of Wnt-Fz complex requires LRP5/6 receptor > Wnt signalling
> Activates Dsh
> Dsh causes Axon recruitment (part of the destruction complex)
> causes B-catenin release which translocates to nucleus and acts as TF for proliferation genes

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3
Q

What occurs in the absence of Wnt signaling?

A

Destruction complex stays together
GSK3 phosphorylates B-catenin
B-catenin undergoes ubiutination (ub) and subsequent proteasomal degradation
Results in inhibition of proliferation signal

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4
Q

What are the types of bowel cancer?

A

Adenocarcinoma: starts in gland cells in epithelial cells
Rare types:
- Squamous cell tumours: skin cells and gland cells
- Carcinoid tumours: neuroendocrine tumour
- Sarcoma: in the smooth muscle
- Lymphomas: cancers of lymphatic system
- Melanoma: in the rectum/anus

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5
Q

What is the grading of bowel cancer?

A

Low grade: similar to healthy tissue
- Grade 1 - cells look normal
- Grade 2 - moderately differentiated
High grade: very different to healthy tissue
- Grade 3 - poorly differentiated
- Grade 4 - undifferentiated - completely different from normal

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6
Q

How are bowel cancers staged?

A

TNM staging system
T - Primary tumour: T0 cannot be found, TX cannot be measured, T1,2,3,4
N - regional lymph nodes: NX cancer near LN cannot be measured, N0 no cancer LN, N1,2,3,4 - location and number of lymph nodes
M - MX cannot be measured, M0 not spread, M1 has spread

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7
Q

Numerical number staging system

A

Stage 0 - CIS
Stage 1 - cancer growth through inner lining
Stage 2 - local spread no lymph nodes
Stage 3 - lymph node involvement
Stage 4 - cancer spread to other organs and tissues

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8
Q

Adenoma

A

Neoplastic polyps
Precursor lesions to colorectal adenocarcinomas
Precancerous

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9
Q

Neoplasm

A

Rapid and autonomous growth

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10
Q

Polyp

A

Small non-cancerous growth protruding from tissue surface
Adenomas are therefore a type of polyp

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11
Q

Hyperchromasia

A

Increased staining nucleus - due to increased replications and growth

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12
Q

Dysplasia

A

Abnormal cellular growth and maturation

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13
Q

What are the two types of polyp shape?

A

Pedunculated:
- Stalk, slender, fibromuscular
- Prominent blood vessels from submucosa
- Lower risk to becoming cancerous
Sessile:
- Flat but slightly raised
- Broad and firmly attached to membrane
- No stalk
- Slightly higher risk of becoming cancerous

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14
Q

What are the different classification of adenomas?

A

Tubular: small, pedunculated polyps. Composed of small, rounded, or tubular glands
Villous: larger, sessile, covered by slender villi
Tubulovillous: some tubular, some villous, non-cancerous polyp, precancerous growth > adenocarcinoma.

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15
Q

What are the histological appearance of colonic adenomas?

A

Tubular adenoma: Long thin tube shaped glands, enlarged hyperchromatic nuclei
Villous adenoma: cells connect to each other to form long villi. Enlarged, hyperchromatic nuclei

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16
Q

What is the process of the defecation reflex?

A

Peristalsis moves stool towards rectum by mass movement and haustral contraction
Stool collects in the rectum and activates stretch receptors > urge to defecate begins
Intrinsic pathway activates the myenteric plexus and imitates local peristalsis
Extrinsic pathway activates parasympathetic input further stimulates peristalsis and causes internal and external anal sphincter relaxation
If defecation is not desired, voluntary contraction of external sphincter can delay it
If defecation is appropriate, series of reflexes:
- relaxation of external sphincter
- contraction of abdominal wall muscles
- relaxation of pelvis wall muscles

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17
Q

What is the difference between internal and external anal sphincter?

A

Internal anal sphincter:
- smooth muscle
- Parasympathetic control
- relax involuntarily
External anal sphincter:
- Skeletal muscle
- Somatic nerve supply (voluntary)
- Innervated by pedundal nerve

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18
Q

How can a patient reduce risk of CRC?

A
  • Increase fruit and veg intake: increase fibre and folic acid
  • Stop smoking
  • Reduce alcohol
  • Healthy weight
  • Be physically active
  • Participate in bowel cancer screening
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18
Q

What are the non-modifiable risk factors for CRC?

A

Family history: HNPCC (MLH1 gene), FAP (APC gene)
Condition: IBD or other chronic GI conditions increases risk over time
Age: 9 in 10 cases are 60+, accumulation of mutations over time

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18
Q

What are the modifiable risk factors for CRC?

A

Weight: estimated 20% cases are caused by obesity. Adipokines and hormones released from adipocytes involved in pathogenesis of CRC
Diet: Lots of alcohol, red/processed meat
Exercise: insulin levels affect pathway in pathogenesis of CRC
Alcohol and smoking: increases damage to DNA, accumulation of mutations

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19
Q

What are the three main symptoms of CRC?

A

Blood in stools
Change in bowel habits
Abdominal pain

19
Q

What are the other symptoms of CRC?

A

Cachexia
weakness and faitgue
Bloating
Weight gain
Incomplete evacuation/tenesmus

20
Q

What causes blood in stools in CRC?

A

Small tumours may bleed due to abnormal angiogenesis
Endothelial cells do not form a continuous, uniform monolayer = leaky and inefficient
In larger tumours, may grow into blood vessels and cause larger bleeds

21
Q

What is melena?

A

Black tarry stools, caused by bleeding in higher GI tract

22
What is haematochezia?
Fresh, red blood in stool
23
What may involve bowel changes in CRC?
Diarrhoea, constipation, change in frequency, narrower stoolsWhat
24
What causes change in bowel habit in CRC?
Diarrhoea: Secretory process from tumour Partial obstruction and overflow around tumour, fluid can't be absorbed - increases fluidity of stool Constipation: Tumours on external wall may compress colon contents > faecal compaction, reduce motility Tumours of mucosal lining can adhere to enteric neurons that innervate smooth muscles > reduces peristalsis, slows gut motility
25
What causes abdominal pain in CRC?
Tumours indirectly cause release of bradykinins and tryptase which stimulates nociceptors Tumours can compress nociceptors and initiate pain Pain usually present in later stages
26
What is cachexia?
Causes unintentional weight loss, loss of appetite, muscle wasting, fatigue Increased catabolism of muscle proteins Cytokines released supress appetite, increase energy expenditure
27
What causes weakness and fatigue on CRC?
Fatigue can be due to internal blood loss causing anaemia Only noticeable once metastasised to liver or bone marrow
28
What causes bloating in CRC?
Bowel obstruction, partial or complete - may reduce ability to pass wind
29
What causes weight gain in CRC?
May cause build up of fluid in legs or abdominal cavity - irritation may causes ascites
30
What causes incomplete evacuation or tenesmus in CRC?
Normally from tumours in rectum stimulating stretch receptors in the visceral wall, due to distention of wall
31
What are the differential diagnoses for symptoms of CRC?
IBD, diverticulitis, haemorrhoids - blood in stool IBS, IBD, coeliac disease - change in bowel habit, abdominal pain
32
How may CRC be diagnosed?
Colonoscopy: entire colon. highest sensitivity and specificity for diagnosis, can take biopsy during Flexible sigmoidoscopy: sigmoid colon. Stool tests: FIT and FOBT detect blood - FOBT is not specific to human blood Stool DNA test: can detect altered DNA CT colonography: assess for metastasis and lymph nodes Barium enema: barium liquid injected into rectum, coats lining of colon
33
What is the prep for a colonoscopy?
- Eat low-fibre diet 2-3 days before and increase fluid intake - Strong laxative day before to clear bowel - Can't eat anything on day, apart from 2 hours before
34
What can CT colonography and MRI show?
Increased wall thickness > tumoral infiltration > ill defined masses in liver
35
What is the physiology of Picolax?
Inhibits absorption of water and electrolytes > increases secretion into intestinal lumen Hydrolysed by colonic bacterial enzyme - sulphatase - to form active metabolite (BHPM) > acts directly on colonic mucosa and stimulates colonic peristalsis
36
When may Picolax be used?
To clear bowel before surgery, or colonoscopy Constipation
37
What are the side effects of Picolax?5
Diarrhoea GIT discomfort Dizziness Nausea Vomiting
38
What is the screening process for CRC?
available to everyone 60-74 every two years Bowel screening kit send home Faecal immunological test - Write date on sample bottle - Use container to catch poo - Use sample stick to transfer into bottle - Place sample bottle into pre paid envelope - Post
39
What are the possible results for bowel screening tests?
No further tests needed - no blood found, invited back in two years time Further tests needed - significant amount of blood found, follow up appointment to find cause > colonoscopy
40
What are different treatments for CRC?
Chemotherapy Radiotherapy Surgery Immunotherapy
41
What drugs are used in chemotherapy in treatment of CRC?
Fluorouracil (5-FU) Capecitabine Folinic acid Oxalipatin
42
What is the mechanism of fluorouracil 5-FU?
Fluorouracil mimics the structure of uracil and the cancer takes this up and incorporates it into its RNA This disrupts protein synthesis by having a non-functioning RNA As a result the cancer will not be able to produce to grow and maintain itself Overtime the cancer will die being unable to replace the cells that die
43
What are the side effects of 5-FU?
Nausea and vomiting Mucositis - inflammation of mucus membranes of the mouth and throat > dysphagia Hand foot syndrome - soles and palms = swollen, red, blistered Myelosuppression Fatigue Photosensitivity
44
What are the types of radiotherapy that may be used to treat CRC?
External radiation therapy Internal radiation therapy Preoperative (neoadjuvant) radiotherapy - before main treatment Postoperative (adjuvant) radiotherapy - if risk of relapse Palliative radiotherapy - when cure is not possible, alleviate symptoms
45
What are the types of surgery to manage CRC?
Local excision: removal of early stage tumour Resection of colon with anastomosis: part of colon is removed, remaining parts joined together Resection of colon with colostomy: if anastomosis not possible, colostomy bag used Proctocolectomy: removal of entire colon and rectum
46
Colostomy vs ileostomy vs urostomy
Colostomy: opening in large intestine through abdo wall - usually left iliac fossa Ileostomy: opening in ileum through abdo wall - usually right iliac fossa. Entire colon bypassed or removed Urostomy: ureters attached to resected section of ileum, through abdo wall
47
What are the complications of a stoma?
- Infection - Dehydration - Bowel obstruction - Skin damage around stoma - Stoma prolapse - Stoma retraction - Parastomal hernia
48
What reasons may explain delay behaviour?
Anxiety/embarrassment Fear of diagnosis Lack of awareness of symptoms Normalising symptoms Social and structural barriers Previous problematic doctor patient relationship

Unit 10 PBL cases (6 decks)

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