Lecture 28

Question 1

What is cholelithiasis?

Answer 1

Gallstones.

Question 2

Gallstones are present in how many people?

Answer 2

10-20% of adults. 80% of gallstones are “silent”.

Question 3

What are the types of gallstones?

Answer 3

1) Cholesterol stones - 80% of gallstones contain crystalline cholesterol monohydrate.
2) Pigment stones - Bilirubin and calcium salts. See in patients with ongoing homolysis and increase breakdown of haemoglobin producing bilirubin.

Question 4

What is the pathogenesis of cholesterol stones?

Answer 4

Bile becomes supersaturated with cholesterol.
Conditions (stasis) favour crystal formation.
Cholesterol crystals remain in gallbladder long enough for stones to form e.g. stasis; and to increase in size.

Question 5

What are the risk factors for cholelithiasis?

Answer 5

1) The incidence rises with age and is greater in women.
2) Estrogenic influences (oral contraceptives, pregnancy), obesity and rapid weight loss favour stone formation.
3) Gallbladder stasis favours stone formation.
4) A family history of gallstones.
5) Rare in under developed or developing societies.

Question 6

What are the risk factors for pigment stones?

Answer 6

1) Disorders that favour the formation of bilirubin stones: chronic haemolytic syndromes and bacterial infection of the biliary tree.
2) Pigment stones are predominant in non-Western populations, because of infections and parasites.

Question 7

What are the clinical consequences of gallstones?

Answer 7

1) May be asymptomatic (no symptoms) - 70-80% asymptomatic lifetime.
2) Symptomatic 1-3% per year:
Cholecystitis - acute/chronic.
Biliary colic - due to cholecoholithisasis.
Complications of above e.g. cholagitis, obstructive cholestasis, pancreatitis.

Question 8

What is acute cholecystitis?

Answer 8

Acute inflammation of the gallbladder. Most cases are precipitated by gallstones. Where there is obstruction of the neck of the gallbaldder/cystic duct. Chemical irritation appears to be the major factor with bacterial infection later.

Question 9

What are the clinical features of cholecystitis?

Answer 9

1) RUQ abdominal pain and tenderness.
2) Febrile.
3) Laboratory: neutrophil leucocytosis, raised bilirubin, ALP and GGT if stone in the common bile duct.
4) Imaging - ultrasound of gallbladder.

Question 10

What is Chronic Cholecystitis?

Answer 10

It is a result from long-term association of gallstones and low-grade inflammation. Some cases have a history of repeated attacks of mild acute cholecystitis.

Question 11

Describe the pathology of chronic cholecystitis?

Answer 11

The pathology is variable. The wall is thickened, and the gallbladder is often contracted but may be normal size or enlarged.

Question 12

How do you manage cholecystitis?

Answer 12

1) Initial acute event: many settle with conservative therapy (IV fluids, pain relief) and up to 25% may require acute surgical intervention.
2) Longer term: cholecystectomy - most now laparoscopic.

Question 13

What is choledocholithisais?

Answer 13

The presence of gallstones within the biliary tree.

Question 14

What are the complications of choledocholithisasis?

Answer 14

1) Biliary obstruction - colicky abdominal pain.
2) Obstructive jaundice.
3) Pancreatitis.
4) Cholangitis.

Question 15

What are the cancers of the biliary system?

Answer 15

1) Carcinoma of the gall bladder.

2) Carcinoma of the extrahepatic ducts.

Question 16

Describe the pathology for carcinoma of the gallbladder?

Answer 16

1) Most are adenocarcinomas.
2) Most hav invaded the liver by the time of diagnosis.
3) Seen on older patients.
4) Poor prognosis - 5 year Overall Survival Rate is 1%.

Question 17

Describe the incidence of tumours of the colon and rectum?

Answer 17

Cancers of colon are a major health problem in NZ. They’re the most common cancer in NZ, second cause of cancer death (in NZ) after lung cancer.

Question 18

What are the two categories of colon and rectum cancer?

Answer 18

1) Benign tumours - present as polyps.

2) Malignant tumours - mainly adenocarcinomas (rolled edges and ulcerated).

Question 19

What are polyps?

Answer 19

Circumscribed growth or tumour (benign) which projects above the surrounding mucosa.

Question 20

What are the types of polyps?

Answer 20

1) Non neoplastic polyps.
2) Neoplastic polyps - adenoma.
To know what they are they need to be biopsied.

Question 21

What are the types of non neoplastic polyps?

Answer 21

1) Hyperplastic polyps:
Benign.
Usually asymptomatic.
Do not have malignant potential.
Small 3-6mm, common.
2) Inflammatory polyps:
Seen in IBD, overgrowth.
Benign (pesudopolyps).

Question 22

What are neoplastic polyps?

Answer 22

Known as adenomas.
Benign polyps with malignant potential. 
Most age >50, M=F.
Familial predisposition.
Epithelial proliferation with variable degrees of dysplasia.

Question 23

What are the types of neoplastic polyps (adenomas)?

Answer 23

1) Tubular adenomas: most common, mostly tubular glands.
2) Villous adenomas: villous projections, often large and sessile.
3) Tubulovillous adenomas: mixture of above.

Question 24

Describe the clinical features for polyps?

Answer 24

1) Most asymptomatic - may get picked up when screening for colon.
2) May bleed, mucosal discharge - if at distal end of bowel may associate with blood discharge in rectum.
3) If larger - altered bowel habit and bowel obstruction.

Question 25

Describe the adenoma to carcinoma sequence?

Answer 25

Adenomas start off as small and eventually expand and become carcinomas through molecular changes. This means if you do screening strategies, removal of the adenomas will reduce risk and incidence of patients developing carcinomas.

Question 26

Describe neoplastic polyps and the risk of transformation to carcinoma?

Answer 26

The polyps size - rare if 4cm.

Degree of dysplasia.

Question 27

Describe the pathology of the progression from adenoma to carcinoma?

Answer 27

1) Germ line (inherited) or somatic (acquired) mutations of cancer suppressor genes
(first hit). there is loss of APC locus on chromosome 5q.
2) Methylation abnormalities causes inactivation of normal alleles (second hit).
3) Protooncogene mutations - K-RAS at 12p12 (chromosome).
4) Homozygous loss of additional cancer suppression genes (p53) and over expression of COX-2.
5) Additional mutation, gross chromosomal alterations.

Question 28

Describe the incidence of colorectal cancer?

Answer 28

15% of all cancer deaths.

Peak age is 60-70, rare in age Females rectal cancers.

Question 29

What are the environmental risk factors for colorectal cancer?

Answer 29

1) Diet (high red meat, low fibre, which carb diet).
2) High incidence in developed countries e.g. NZ, Auz and US.
3) Protective effect of aspirin and NSAID.

Question 30

Describe the pathology of colon cancer?

Answer 30

1) Adenocarcinoma.
2) Variable differentiation.
3) Found caecum, ascending, transverse, descending, sigmoid colon and rectum.

Question 31

What is the staging of colorectal cancer?

Answer 31

T = extent of invasion of bowel wall.
N = number of lymph nodes involved.
M = metastatic disease present or not.
Prognosis determined by stage of tumour.

Question 32

What are the clinical features of colorectal cancer?

Answer 32

1) Abdominal pain, mucous discharge, PR bleeding, change in bowel habit, bowel obstruction.
2) Right sided tumours - may present with iron deficiency anaemia due to occult bleeding (not obvious).
3) Spread to regional nodes, liver, lungs, bones.
4) Constitutional symptoms e.g. weight loss, malaise.

Question 33

Describe Familial Polyposis Syndromes?

Answer 33

These are a group of inherited polyposis syndromes. It is an autosomal dominant inheritance disorder. There is predisposition to malignant transformation in the colon and other sites. There has been a study that has given clues to molecular pathology of colorectal cancer.

Question 34

Describe Familial Adenomatous Polyposis?

Answer 34

Multiple adenomas in the colon and elsewhere in the gut - most tubular adenomas.

1) Usually evident adolescent.
2) Transform into cancer.
3) APC gene on chromosome 5q21.
4) Autosomal dominant.
5) Prophylactic colectomy.

Question 35

Describe Hereditary Nonpolyposis Colorectal Cancer (HNPCC)?

Answer 35

1) Autosomal dominant inheritance.
2) 5% of all colorectal cancer cases.
3) Consider if family history or young age of onset of cancer.
4) Progress adenoma to carcinoma but no increase in polyps.
5) Due to inherited mutation in DNA mismatch pair gene.