GI 3 - cancers, infections + drugs. Flashcards
give 3 bacterial causes of infective diarrhoea
C difficile - e.g. hx of abx use (rest are travel).
shigella, salmonella, campylobacter, aeromonas, vibrio cholera.
E coli
what would you test the stool for, when investigating infective diarrhoea?
MC&S, ova cysts, parasites, C diff toxin.
give 2 viral causes of infective diarrhoea
norovirus - cruise ships etc.
rotavirus.
give 2 protozoal causes of infective diarrhoea
Giardia intestinalis
Entamoeba histolytica
Cryptosporidium parvum
Cyclospora cayetanensis
describe the pathogen that causes cholera
Vibrio cholera.
gram -ve curved flagellated motile vibrating/swarming rod.
faecal-oral spread.
describe the clinical features of cholera
profuse (1L/h) rice water stools, fever, vomiting, rapid dehydration.
how would you treat cholera?
tetracycline.
oral rehydration sachets.
how would you treat infective diarrhoea caused by salmonella, shigella or campylobacter?
ciprofloxacin oral/IV
describe the clinical features of bacillary dysentery.
abdo pain and bloody diarrhoea ± sudden fever and headache
what organism causes bacillary dysentery? how would you treat it?
shigella.
ciprofloxacin + avoid antidiarrhoeal drugs.
what type of tumours can arise from the oesophagus and where?
adenocarcinoma - lower third.
squamous carcinoma - upper 2 thirds.
name 2 risk factors for oesophageal carcinoma
smoking, alcohol, Barrett’s/GORD, obesity, achalasia, low vitamin A/C, nitrosamine exposure
give 3 symptoms of an oesophageal tumour
progressive dysphagia (initially for solids, then liquids too).
cough, weight loss, anorexia, retrosternal chest pain, dyspepsia
what would be your investigations of choice for diagnosis of oesophageal cancer, and then for staging?
endoscopic ultrasound with fine needle aspiration/biopsy of tumour.
CT for staging.
given most oesophageal cancers present late, what kind of treatment would you consider?
palliative - soft diet, oesophageal stent, analgesia - chemo/radiotherapy can be used palliatively.
what AIDS defining illness affects the oesophagus?
Kaposi’s sarcoma - found in mouth, oesophagus and hypopharynx
give 2 signs that indicate an oesophageal carcinoma is in the upper 1/3rd of the oesophagus
hoarseness and cough
give 2 differential diagnoses of oesophageal cancer
those of dysphagia
oesophagitis, diffuse oesophageal spasm, achalasia, benign oesophageal stricture
how are oesophageal cancers staged?
TNM system. T1 = invading lamina propria T2 = muscularis propria T3 = adventitia T4 = invasion of adjacent structures
what curative treatment might you attempt in a patient who has presented with early (local T1/T2) oesophageal carcinoma?
radical curative oesophagectomy + pre-op chemo with cisplatin
what is the main type of carcinoma affecting the stomach?
adenocarcinoma
give 3 things associated with gastric adenocarcinoma
pernicious anaemia, blood group A, H pylori, atrophic gastritis, adenomatous polyps, lower social class, smoking.
diet - high nitrates, salt, pickling, low vit C
what main lymph node is infiltrated in gastric tumours?
Virchow’s node (neck)
give 2 symptoms of gastric adenocarcinoma
epigastric pain relieved by food and antacids nausea vomiting anorexia weight loss dyspepsia dysphagia
give 2 signs of gastric adenocarcinoma
anaemia, jaundice, palpable epigastric mass with tenderness, Virchow’s node infiltration, dermatomyositis, acanthosis nigricans
in which part of the stomach do adenocarcinomas most commonly occur?
antrum
what makes up the Borrmann classification of gastric adenocarcinomas?
i. polypoid
ii. excavating
iii. ulcerating and raised
iv. diffusely infiltrative
how might gastric adenocarcinomas spread?
locally, lymphatics, blood borne (haematogenous), transcoelomic
what investigations would you perform in gastric adenocarcinoma?
gastroscopy + multiple ulcer edge biopsies.
endoscopic ultrasound.
CT for staging.
describe the treatment options for gastric adenocarcinoma
partial/total gastrectomy.
chemo - epirubicin, cisplatin, 5-fluorouracil.
surgical palliation - for obstruction, pain or haemorrage.
give 2 cell types that gastrointestinal stromal tumours (GIST)s could be
leiomyomas, leiomyosarcomas, leiomyoblastomas, Schwannomas
what are the treatment options for gastrointestinal stromal tumours?
1st line - surgical resection
2nd line - imatinib.
what is gastric lymphoma?
arises from mucosal areas from mucosa-associated lymphoid tissue - MALToma.
how would you treat a gastric lymphoma?
most are associated with H pylori - eradication.
surgery or chemo ± radiotherapy
which type of gastric polyp is pre-malginant?
adenomatous polyps.
hyperplastic polyps aren’t malignant, but can be accompanied by pre-malignant atrophic gastritis.
which types of gastric polyps are benign?
cystic gland, inflammatory fibroid polyps, hyperplastic polyps
where are adenocarcinomas and lymphomas found in the small intestine?
adenocarcinoma - duodenum and jejunum.
lymphoma - ileum.
what are the different types of lymphoma that can arise in the intestine?
Non-Hodgkin’s.
B cell, arising from MALT - polypoid masses in distal/terminal ileum.
T cell - ulcerated/strictures in proximal ileum.
what AIDS defining lymphoma can occur in the small intestine and where?
Burkitt’s lymphoma - terminal ileum of children
how might malignant small intestinal tumours be treated?
surgical excision ± chemo/radiotherapy
what autosomal dominant condition can cause benign small bowel tumours?
Peutz-Jeghers syndrome - mucocutaneous pigmentation and hamartomatous GI polyps - can undergo malignant change.
what type of cells do carcinoid tumours arise from and where in the small intestine are they found?
enterochromaffin cells, in appendix, ileum and rectum
what is carcinoid syndrome?
only occurs with liver mets, spontaneous red-blue flushing mainly on face and neck (kinins), pulmonary stenosis/tricuspid incompetence (5-HT), hepatomegaly.
tumours secrete serotonin, bradykinin, histamine, prostaglandins.
how would you treat carcinoid tumours?
somatostatin analogues - ocreotide and lanreotide.
what is a polyp? what type of lesion are most colonic polyps?
abnormal growth of tissue projecting into the intestinal lumen from the normally flat mucosal surface.
usually adenomas.
what is the clinical significance of colonic polyps?
they’re the precursor lesions of most colorectal cancer
list 3 features of an adenomatous polyp that increases the risk of malignant change
size >1cm. sessile polys (attached to colon wall directly) > pedunculated polyps (mucosal stalk between polyp and wall). severe dysplasia (>mild) villous histology > tubular. multiple polyps > singular.
what is HNPCC?
hereditary nonpolyposis colorectal cancer.
DNA mismatch repair genes are mutated.
what is the pathway of developing a colorectal cancer from a polyp?
normal epithelium => adenoma (polyp) => colorectal adenocarcinoma
how is colorectal cancer risk increased in patients HNPCC?
accelerated progression from polyps to CRC - doesn’t increase no. polyps, just speeds up their progression to malignancy.
what gene is mutated in familial adenomatous polyposis?
APC gene
how does FAP increase risk of colorectal cancer?
patient develops loads and loads of colorectal polyps in teenage years - increased risk of extracolonic malignancies.
100% lifetime risk of CRC, onset in young adults.
how can colorectal cancer be prevented in people with FAP?
regular screening from age of 12, prophylactic total colectomy at 20.
what other cancers, apart from CRC, are associated with FAP?
thyroid, pancreatic and hepatoblastomas.
give 3 risk factors of colorectal carcinoma
increasing age, obesity, IBS, diabetes, obesity, alcohol, FHx, colorectal polyps, low fibre diet, genetic predisposition (FAP. HNPCC), smoking, UC and Crohn’s
explain the different clinical features of right and left sided colorectal carcinomas
left - PR bleeding/mucus, obstruction, tenesmus, PR mass.
right - weight loss, anaemia, abdo pain, usually asymptomatic.
either - abdo mass, perforation, haemorrhage, fistula
what is the gold standard investigation in colorectal carcinoma?
colonoscopy with biopsy
describe the UK bowel cancer screening programme
all >60yrs has faecal occult blood testing every 2yrs - positive result = endoscopy.
which parts of the colon/rectum are most commonly affected by colorectal cancer?
rectum - 27%.
sigmoid colon - 20%.
caecum - 14%
what are the urgent referral criteria for bowel cancer?
1) over 40 with PR bleeding and change in bowel habit
2) any age with R lower abdo mass
3) palpable rectal mass
4) men/non-menstruating women with unexplained iron deficiency anaemia
explain the Dukes’ criteria system for staging colorectal carcinoma
A - limited to muscularis mucosae
B - extension through muscularis mucosae
C - involvement of regional lymph nodes
D - distant metastases
what is generally the treatment for colorectal carcinoma?
surgical resection followed by post-op chemo/radiotherapy.
are most liver tumours primary or secondary?
90% are secondary.
list some common origins of secondary liver tumours
men - stomach, lung, colon.
women - breast, colon, stomach, uterus.
what are the 5 types of primary malignant liver tumours?
hepatocellular carcinoma (HCC). cholangiocarcinoma angiosarcoma hepatoblastoma fibrosarcoma and hepatic GIST
list the 5 types of primary benign liver tumours
cysts, haemangioma, focal nodular hyperplasia, fibroma, benign GIST
list 3 symptoms of liver tumours
fever, malaise, anorexia, weight loss, RUQ pain.
jaundice - late, apart from in cholangiocarcinoma.
list 3 signs of liver tumours
hepatomegaly - smooth, or hard and irregular (mets, cirrhosis, HCC). signs of chronic liver disease. jaundice/ascites. abdo mass. bruit over liver = HCC.
how would you investigate liver cancer?
bloods.
US guided biopsy / MRI.
what protein is raised in serum in HCC?
alpha fetoprotein
how would you treat liver metastases? what is the prognosis?
mostly palliative treatment - prognosis is often less than 6/12
list 3 causes of HCC
*HBV.
HCV, autoimmune hepatitis, cirrhosis, non-alcoholic fatty liver, aflatoxin, clonorchis sinesis, anabolic steroids.
how would you diagnose HCC?
4 phase liver CT.
MRI.
biopsy.
how might HCC be treated?
resect solitary tumours.
liver transplant.
percutaneous ablation, tumour embolisation and sorafenib.
give 3 causes of cholangiocarcinoma
flukes, primary sclerosing cholangitis, HBV, HCV, diabetes mellitus.
what breakdown product is raised in the serum of those with cholangiocarcinoma?
bilirubin
how might cholangiocarcinoma be managed?
precutaneous (or via ERCP) stenting of obstruction.
surgery not an option.
what is the usual prognosis of cholangiocarcinoma?
5 months
what is the most common benign liver tumour? should it be biopsied?
haemangiomas.
incidental finding on US/CT - DON’T biopsy.
what are hepatic adenomas associated with? when is surgical resection indicated?
oral contraceptives, anabolic steroids.
only if symptomatic.
list some risk factors for pancreatic carcinoma
male >60yo smoking alcohol carcinogens diabetes mellitus chronic pancreatitis central adiposity diet high in fat + red/processed meat
what is the genetic association seen in pancreatic carcinoma?
95% have mutations in KRA52
what are the clinical features of carcinoma of the head of pancreas?
painless obstructive jaundice (pain late on, radiates to back).
pruritus, Courvoisier’s sign (enlarged, palpable gallbladder), central abdo mass, hepatomegaly
what are the clinical features of carcinoma of the body/tail of pancreas?
abdo pain, weight loss, anorexia, dull ache radiating to back, relieved when sitting forward.
polyarthritis, skin nodules
what investigations would you carry out in pancreatic carcinoma?
transabdominal ultrasound.
CT.
bloods - Ca19-9 antigen - not specific, but good marker for monitoring progress.
how would you manage a patient with pancreatic carcinoma? what is their prognosis like?
surgical resection with post-op chemo or palliative endoscopic stents.
opiates/radiotherapy for pain.
mean survival less than 6/12.
name 2 PPIs
lansoprazole, omeprazole, pantoprazole
how do PPIs work?
reduce gastric acid secretion by irreversibly inhibiting H+/K+ ATPase in gastric parietal cells - this is the proton pump responsible for secreting H+.
suppresses gastric acid production almost completely.
give an example of an H2 receptor antagonist
ranitidine
why are H2 receptor antagonists not as good at suppressing gastric acid secretion as PPIs?
blocking the H2 receptor reduces the activation of the proton pump - but the pump can be activated by other pathways, so does not completely suppress secretion like PPIs do.
how does loperamide work?
agnoist of the opioid mu-receptors in GI tract - increases non-propulsive contractions of the gut smooth muscle, but reduces peristaltic contractions.
transit of bowel content is thus slowed, and anal sphincter tone is increased - more water absorbed from faeces as there’s more time for this, so stools are hardened.
give 2 examples of aminosalicylates - what are they used for?
mesalazine - UC.
sulfasalazine - UC + RA.
how do aminosalicylates work to treat UC?
release 5-ASA, which has anti-inflammatory and immunosuppressive effects and acts topically on the gut.
name an antimuscarinic with a GI use - what disease is used to treat and why?
hyoscine butylbromide - first line for IBS, used for their antispasmodic effects.
how do antimuscarinics work in the gut?
bind to muscarinic ACh receptor and competitively inhibit ACh - increase in peristaltic contraction and reduction in smooth muscle tone, and reduced gut secretions - opposite to parasympathetic rest and digest effects.
name an acetylcholinesterase inhibitor with a GI indication and what it is used for?
neostigmine - used for pseudoobstruction of the colon.
how does neostigmine work?
it is a reversible acetylcholinesterase inhibitor - increases about of ACh available to stimulate both nicotinic and muscarinic receptors - produces muscle contraction to restore bowel motility.
how does ursodeoxycholic acid work?
reduces cholesterol absorption and is used to dissolve cholesterol gallstones.
it’s a bile acid that is present in the body anyway.
how does cholestyramine work?
binds bile in GI tract to prevent its reabsorption by forming insoluble complexes with bile acids, which are then excreted in the faeces.
useful for pruritus in primary biliary cirrhosis/liver failure.
also reduces plasma cholesterol levels.
vasoconstrictors such as terlipressin are used to medically manage bleeding oesophageal varices, how do they stop the bleeding?
analogue of vaopressin, which itself causes vasoconstriction - reduced blood flow to the area.
imatinib is used when surgery isn’t an option for treatment of gastric stromal tumours - how does it work? what haematological disorder is it the principal treatment for?
it’s a tyrosine kinase inhibitor, so blocks the transfer of a phosphate group from ATP to a protein in a cell.
cell cannot proliferate.
also used to treat CML.
why are somatostatin analogues used to treat carcinoid syndrome?
carcinoid tumours release hormones including serotonin, bradykinin etc.
somatostatin analoges inhibit the release and action of these hormones.
which types of oesophageal cancer occur in the upper 2/3rd and lower 2/3rd?
upper 2/3rd - squamous carcinoma
lower 1/3rd - adenocarcinoma
