Gastro COPY Flashcards
What does maltase do?
cleaves disaccharide maltose to glucose + glucose
What does sucrose do?
cleaves sucrose to fructose and glucose
what does galactose do?
cleaves disaccharide lactose to glucose + galactose
What is the source/stimulus/actions of gastrin?
G cells in antrum of the stomach
Stimulated by:
Distension of stomach, vagus nerves (mediated by gastrin-releasing peptide), luminal peptides/amino acids
Inhibited by:
• low antral pH • somatostatin
↑ HCL= Increases acid secretion by gastric parietal cells, pepsinogen and IF secretion, increases gastric motility, stimulates parietal cell maturation
What is the source/stimulus/actions of CCK?
I cells in upper small intestine
Stimulated by:
Partially digested proteins and triglycerides
↑ secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, ↓ gastric emptying, trophic effect on pancreatic acinar cells, induces satiety
what is the source/stimulus/actions of secretin?
S cells in upper small intestine
Stimulated by:
Acidic chyme, fatty acids
↑ secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, ↓ gastric acid secretion, trophic effect on pancreatic acinar cells
what is the source/stimulus/action of VIP?
Small intestine / pancreas
Stimulated by:
Neural
Stimulates secretion by pancreas and intestines, inhibits acid and pepsinogen secretion
what is the source/stimulus/action of somatostatin?
D cells in the pancreas & stomach
Stimulated by:
Fat, bile salts and glucose in the intestinal lumen
↓ acid and pepsin secretion, ↓ gastrin secretion, ↓ pancreatic enzyme secretion, ↓ insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates gastric mucous production
what are the 3 principle mediators of acid secretion?
Principle mediators of acid secretion
• Gastrin
• Vagal stimulation
• Histamine
what are 4 factors that will increase acid secretion?
Factors increasing acid secretion
• Gastrinoma
• Small bowel resection (removal of inhibition)
• Systemic mastocytosis (elevated histamine levels)
• Basophilia
what are 2 factors that will decrease acid secretion?
Factors decreasing acid secretion
• Drugs: H2-antagonists, PPIs
• Hormones: secretin, VIP, GIP, CCK
What is a pharyngeal pouch?
–where is this situated anatomically?
-who is this most commonly found in?
Pharyngeal Pouch is a posteromedial diverticulum or herniation through Killian’s dehiscence.
Killian’s dehiscence is a triangular area in the wall of the pharynx between the thyropharyngeus and cricopharyngeus muscles.
It is more common in older patients and is 5 times more common in men
what are 5 features of pharyngeal pouch?
Features
• Dysphagia
• Regurgitation
• Aspiration
• Neck swelling which gurgles on palpation
• Halitosis (noticeably unpleasant odors exhaled in breathing)
what is travellers diarrhoea?
Travellers’ diarrhea may be defined as at least 3 loose to watery stools in 24 hours with or without one or more of abdominal cramps, fever, nausea, vomiting or blood in the stool.
what is the most common cause of travellers diarrhoea?
-what are the clinical features?
-what is the incubation period?
The most common cause is Escherichia coli
Watery stools
Abdominal cramps and nausea
12-48hours
what is ‘acute food poisoning’? and what are the typical causes?
Another pattern of illness is ‘acute food poisoning’. This describes the sudden onset of nausea, vomiting and diarrhea after the ingestion of a toxin. Acute food poisoning is typically caused by Staphylococcus aureus, Bacillus cereus or Clostridium perfringens.
which pathogen causes Prolonged, non-bloody diarrhea?
what should be found in stool?
what is the treatment?
Giardiasis
Diagnosis – look for cysts or parasites in stool
Treatment – metronidazole
which pathogen causes Profuse, watery diarrhea?
what is this commonly assoc with?
Cholera
toxin mediated disease often associated with outbreaks – refugee camps
uncommon
which pathogen causes bloody diarrhoea?
-what are other features?
-what is the incubation period?
Shigella
Vomiting and abdominal pain
48-72 hours
which pathogen causes severe vomiting?
-what is the incubation period?
-what foods are assoc?
Staph. Aureus
short incubation
Foods that have been frequently implicated in SFD are meat and meat products, poultry and egg products, milk and dairy products, salads, bakery products, especially cream-filled pastries and cakes, and sandwich fillings
which pathogen causes a flu-like prodrome
followed by crampy abdominal pains
fever and diarrhoea which may be bloody?
-what syndrome is assoc with this?
-is this common?
-what is the incubation period?
Campylobacter
complications included guillian barre
most common cause in the UK
48-72 hrs
which pathogen causes 2 types illness:
vomiting within 6 hours
diarrhoeal illness occurring after 6 hours
-what food assoc exists?
-what is the incubation period?
Bacillus cereus
-Bacillus cereus infection most commonly results from reheated rice
-1-6hrs
which pathogen causes Gradual onset bloody diarrhea abdominal pain and tenderness may last for several weeks?
-what seen on stool microscopy?
-what is treatment with?
-what can this disease also cause?
Amoebiasis
-stool microscopy may show trophozoites if examined within 15 minutes or kept warm (known as a ‘hot stool’)
-Treatment is with metronidazole
-Treatment for invasive amoebiasis should be followed by a luminal amoebicide to eradicate the cystic stage which is resistant to metronidazole and tinidazole (which are used against the invasive stage).
-Amoebiasis also causes liver and colonic abscesses.
describe the liver abscesses caused by amoebiasis?
-where abouts is this found?
-what 2 clinical features are seen?
-what investigations can be done?
usually a single mass in the right lobe (may be multiple). The contents are often described as ‘anchovy sauce’
features: fever, RUQ pain
serology is positive in > 90%
what type of organism is c. diff?
-what syndrome does this cause?
gram +ve rod
It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis.
what is the cause of c. diff?
Clindamycin is historically associated with causing Clostridium difficile but the aetiology has evolved significantly over the past 10 years. Second and third generation cephalosporins (e.g ciprofloxacin) are now the leading cause.
describe the clinical features of c. diff?
Features:
• Diarrhea
• Abdominal pain
• If severe, toxic dilatation
• Sometimes seen in nosocomial outbreaks
what is the diagnosis of c. diff?
Diagnosis is made by detecting Clostridium difficile TOXIN (CDT) in the stool
what is included in the management of c. diff?
Management:
• ORAL metronidazole for 10-14 days
• If severe or not responding to metronidazole then ORAL vancomycin may be used.
• For life-threatening infections a combination of oral vancomycin and intravenous metronidazole
should be used
fidaxomicin may also be used for patients who are not responding , particularly those with multiple co-morbidities
Other therapies
bezlotoxumab is a monoclonal antibody which targets Clostridium difficile toxin B - it is not in widespread use
what is small bowel overgrowth syndrome?
-what are the clinical features?
Small bowel bacterial overgrowth syndrome (SBBOS) is a disorder characterised by excessive amounts of bacteria in the small bowel resulting in gastrointestinal symptoms.
It should be noted that many of the features overlap with irritable bowel syndrome:
chronic diarrhoea bloating, flatulence abdominal pain
what are the risk factors for SBOS?
Risk factors for SBBOS
-neonates with congenital gastrointestinal abnormalities
-scleroderma
-diabetes mellitus
Important association: Systemic sclerosis, diverticulae and blind loop.
what are the investigations for SBOS?
Diagnosis
-hydrogen breath test
-small bowel aspiration and culture: this is used less often as invasive and results are often difficult to reproduce
clinicians may sometimes give a course of antibiotics as a diagnostic trial
what exotoxin does diphtheria release?
-what does this cause?
Diphtheria toxin commonly causes a ‘diphtheric membrane’ on tonsils caused by necrotic mucosal cells.
Systemic distribution may produce necrosis of myocardial, neural and renal tissue.
what exotoxin does e coli release?
-what does this cause?
Staph. aureus exotoxins lead to acute gastroenteritis, toxic shock syndrome and Staphylococcal scalded
skin syndrome
what is the treatment for SBOS?
Management
correction of underlying disorder antibiotic therapy: rifaximin is now the treatment of choice due to relatively low resistance. Co-amoxiclav or metronidazole are also effective in the majority of patients.
What exotoxin leads to lockjaw?
Lockjaw is caused by Clostridium tetani neurotoxin (tetanospasmin)
what does cholera toxin cause?
Cholera toxin causes activation of adenylate cyclase leading to ↑ in cAMP levels, which in turn leads to ↑ chloride secretion.
describe the acute treatment of eosophageal varices
-what should be done ideally prior to endoscopy?
-what agents can be used - how do these work?
-what can help to decrease mortality in patients with liver cirrhosis?
-can be used in uncontrolled haemorrhage?
-if all else fails what can be used?
Acute treatment of variceal hemorrhage
• ABC: patients should ideally be resuscitated prior to endoscopy
• Correct clotting: FFP, vitamin K
• Vasoactive agents: terlipressin is currently the only licensed vasoactive agent. It has been shown to be of benefit in initial hemostasis and preventing rebleeding. It acts by Constriction of the splanchnic vessels (contraindicated in
IHD, use Octreotide as alternative)
• Prophylactic antibiotics have been shown in multiple meta-analyses to ↓ mortality in patients
with liver cirrhosis
• Endoscopy: endoscopic variceal band ligation is superior to endoscopic sclerotherapy
• Sengstaken-blakemore tube if uncontrolled hemorrhage (in urgent setting when endoscopy is not ready)
• Transjugular intrahepatic portosystemic shunt (TIPSS) if above measures fail
What is used and done in the prophylaxis of variceal haemorrhage?
Prophylaxis of variceal hemorrhage
• Propranolol: ↓ rebleeding and mortality compared to placebo
• Endoscopic variceal band ligation (EVL) is superior to endoscopic sclerotherapy. It should be
performed at two-weekly intervals until all varices have been eradicated. Proton pump inhibitor cover is given to prevent EVL-induced ulceration
Describe the pathology of barretts oesophagus?
-what does this increase the risk of?
-how can is barretts oesophagus classed?
Barrett’s Esophagus refers to the metaplasia of the lower esophageal mucosa, with the usual squamous epithelium being replaced by columnar epithelium. There is ↑ risk of esophageal adenocarcinoma, estimated at 50-100 folds.
Barrett’s can be subdivided into short (<3cm) and long (>3cm). The length of the affected segment correlates strongly with the chances of identifying metaplasia.
describe the histological features of the columnar epithelium in barretts oesophagus?
Histological features: the columnar epithelium may resemble that of either the cardiac region of the stomach or that of the small intestine (e.g. with goblet cells, brush border)
describe the management of barretts oesophagus?
Management
• Endoscopic surveillance with biopsies
-for patients with metaplasia (but not dysplasia) endoscopy is recommended every 3-5 years
If dysplasia of any grade is identified endoscopic intervention is offered. Options include:
endoscopic mucosal resection
radiofrequency ablation
what are indications for OGD in GORD?
Indications for upper GI endoscopy:
• Age > 55 years
• Symptoms > 4 weeks or persistent symptoms despite treatment
• Dysphagia
• Relapsing symptoms
• Weight loss
Usually there is poor correlation between symptoms and endoscopy appearance
what is the gold standard investigation in GORD?
24hr esophageal pH monitoring is gold standard investigation in GORD
If endoscopy is negative consider 24-hr oesophageal pH monitoring (the gold standard test for diagnosis)
Pain on swallowing (odynophagia) is a typical of esophageal candidiasis - what is this a well documented complication of?
inhaled steroid therapy
Oesophageal Ca is a cause of dysphagia - what is this commonly assoc with? what may past history include?
-associated with weight loss, anorexia or vomiting during eating
-Past history may include Barrett’s esophagus, GERD, excessive smoking or alcohol use
Oesophagitis is a cause of dysphagia - what clinical features is assoc with this?
-May be history of heartburn
-Odynophagia but no weight loss and systemically well
oesophageal candidiasis is a cause of dysphagia - what may there be a history of?
There may be a history of HIV or other risk factors such as steroid inhaler use
Achalasia is a cause of dysphagia - what are three clinical features assoc. with this?
-Dysphagia of both liquids and solids from the start
-Heartburn
-Regurgitation of food - may lead to cough, aspiration pneumonia etc
Pharyngeal pouch is a cause of dysphagia:
-who is this more common in?
-what are the clinical features?
More common in older men
-Represents a posteromedial herniation between thyropharyngeus and cricopharyngeus muscles
-Usually not seen but if large then a midline lump in the neck that gurgles on palpation
-Typical symptoms are dysphagia, regurgitation, aspiration and chronic cough. Halitosis may occasionally be seen
Systemic sclerosis is a cause of dysphagia:
-what are the other features of CREST?
Other features of CREST syndrome may be present, namely Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
Myaesthenia gravis is a cause of dysphagia
-what are other clinical features that may be seen
Other symptoms may include extraocular muscle weakness or ptosis Dysphagia with liquids as well as solids
Globus hystericus
Globus hystericus is a cause of dysphagia:
-what other clinical features may be seen?
May be history of anxiety Symptoms are often intermittent
Achalasia is a cause of dysphagia:
-what is this?
-when does this normally present?
Failure of esophageal peristalsis and of relaxation of lower esophageal sphincter (LOS) due to degenerative loss of ganglia from Auerbach’s plexus i.e. LOS contracted, esophagus above dilated. Achalasia typically presents in middle-age and is more common in women
Name 6 clinical features of achalasia?
• Dysphagia of BOTH liquids and solids
• Typically variation in severity of symptoms
• Heartburn
• Regurgitation of food - may lead to cough, aspiration pneumonia etc
• Malignant change in small number of patients
• 7% ↑ in risk of squamous cell carcinoma
what is the gold standad for achalasia?
- what other investigations would be relevant?
The gold standard test for achalasia is esophageal manometry
• Barium swallow shows grossly expanded esophagus, fluid level
• CXR: wide mediastinum, fluid leve
what manometry finding would be found in achalasia?
Loss of peristalsis in distal esophagus, failure of LOS to relax during swallowing and (i.e ↑ residual relaxing pressure
what manometry finding would be found in scleroderma?
Loss of peristalsis in distal esophagus BUT ↓ resting LOS pressure
describe the treatment of achalasia?
• Intra-sphincteric injection of botulinum toxin
• Heller cardiomyotomy
• Balloon dilation
• Drug therapy has a role but is limited
by side-effects
what is Boerhaave’s syndrome?
Complete transmural (full-thickness) laceration or perforation of the esophagus, distinct from Mallory-Weiss syndrome, a nontransmural esophageal tear also associated with vomiting.
Boerhaave’s syndrome:
-where is perforation almost always found?
-what would be found on pleural fluid aspirate?
-more common in men or women?
-what ages does this effect?
-what other clinical features may be found?
• Perforation is almost always on Left side of Lower esophagus.
• Gastric contents enter the mediastinum and pleural cavity, if one were to perform a pleural fluid
aspirate; one is likely to aspirate gastric contents!
• ♂ > ♀ and typically between 50-70 years old
• Other clinical features that may suggest the diagnosis include odynophagia and surgical
emphysema in the neck
What are the different causes for boerhaaves syndrome?
• Vomiting (against a closed glottis) in eating disorders such as bulimia
• Rarely: Extremely forceful coughing - Obstruction by food
Iatrogenic perforation, accounts for 85-90% of cases of esophageal rupture, typically as a complication of an endoscopic procedure, feeding tube, or unrelated surgery.
what are the investigation findings in boerhaaves syndrome?
• Radiographs show mediastinal gas, effusion, and later pneumothorax.
Esophagram is used to confirm leak, first with water-soluble contrast, then barium if no leak demonstrated.
what is the management for boerhaaves syndrome?
Early operation after appropriate resuscitation offers the best chance of survival.
what drugs can causes dyspepsia?
Causes
• NSAIDs
• Bisphosphonates • Steroids
The following drugs may cause reflux by reducing lower esophageal sphincter (LOS) pressure
• Calcium channel blockers*
• Nitrates*
• Theophyllines
*calcium channel blockers and nitrates are occasionally used in the management of achalasia, itself a cause of dyspepsia, because of their effect on the LOS.
What are 7 ‘alarm’ signs in dyspepsia?
• Chronic gastrointestinal bleeding
• Progressive unintentional weight loss
• Progressive difficulty swallowing
• Persistent vomiting
• Iron deficiency anemia
• Epigastric mass
• Suspicious barium meal
when do patients need an urgent referral with dyspepsia?
Urgent referral (within 2 weeks) is indicated for patients with any alarm signs irrespective of age.
Routine endoscopic investigation of patients of any age, presenting with dyspepsia and without alarm signs is not necessary, however patients aged 55 years and over should be referred urgently for endoscopy if dyspepsia symptoms are:
• Recent in onset rather than recurrent and
• Unexplained (e.g. New symptoms which cannot be explained by precipitants such as NSAIDs)
and
• Persistent: continuing beyond a period that would normally be associated with self-limiting
problems (e.g. Up to four to six weeks, depending on the severity of signs and symptoms)
How do you manage patients who have dyspepsia but do not meet referral criteria - ‘undiagnosed dyspepsia’?
This can be summarised at a step-wise approach
• Review medications for possible causes of dyspepsia
• Lifestyle advice
• Trial of full-dose PPI for one month*
• ‘Test and treat’ using carbon-13 urea breath test
*it is unclear from studies whether a trial of a PPI or a ‘test and treat’ should be used first
what kind of bacteria is h. pylori?
Helicobacter pylori is a Gram negative bacteria
what diseases is h pylori associated with?
Associations
• Peptic ulcer disease (95% of duodenal ulcers, 75% of gastric ulcers)
• Gastric cancer
• B cell lymphoma of MALT tissue (eradication of H pylori 80% causes regression)
• Atrophic gastritis
Is there a role for eradicating H pylori in GORD?
The role of H pylori in Gastresophageal reflux disease (GERD) is unclear - there is currently no role of eradication of H pylori in GERD.
what are the 6 different tests that exist for h. pylori?
-Urea breath test
-Rapid urease test (e.g. CLO test)
-Serum antibody
-Culture of gastric biopsy
-Gastric biopsy
-Stool antigen test
Urea breath test:
-what should be stopped prior to test?
-how does it work?
-what is it used for in addition to diagnosis?
-sensitive?specific?
• Patients consume a drink containing carbon isotope 13 (13C) enriched urea
• Urea is broken down by H. pylori urease
• After 30 mins patient exhale into a glass tube
• Mass spectrometry analysis calculates the amount of 13C CO2
• Sensitivity 95-98%, specificity 97-98%
• Used to confirm eradication
• Should not be performed within 4 weeks of treatment with an antibacterial or within 2 weeks of an antisecretory drug (e.g. a proton pump inhibitor)
Rapid Urease Test: CLO
-how does this work?
-sensitive/specific?
• Biopsy sample is mixed with urea and pH indicator
• Color change if H pylori urease activity
• Sensitivity 90-95%, specificity 95-98%
Serum antibody test for H pylori
-what is the con for this?
-sensitivity/specificity?
• Remains positive after eradication
• Sensitivity 85%, specificity 80%
Culture of gastric biopsy in h. pylori
-what does this provide information on?
-sensitive/specific?
• Provide information on antibiotic sensitivity
• Sensitivity 70%, specificity 100%
Gastric biopsy in h. pylori
-what does this provide information on?
-sensitive/specific?
• Histological evaluation alone, no culture
• Sensitivity 95-99%, specificity 95-99%
how sensitive/specific is a stool antigen test in h.pylori
• Sensitivity 90%, specificity 95%
what is peutz-jeghers syndrome?
-how is this inherited?
-what is this characterised by?
Peutz-Jeghers syndrome is an autosomal dominant condition characterized by numerous hamartomatous polyps in the gastrointestinal tract.
what is the mortality of peutz-jeghers syndrome?
Around 50% of patients will have died from a gastrointestinal tract cancer by the age of 60 years.
How is peutz-jeghers syndrome inherited?
-what does the responsible gene encode?
• Autosomal dominant
• Responsible gene encodes serine threonine
kinase LKB1 or STK11
Describe the features of peutz-jeghers syndrome?
• Hamartomatous polyps in GI tract (mainly small bowel)
• Pigmented lesions on lips, oral mucosa, face, palms and soles
• classical histological appearance of smooth muscle “arborisation”
• Intestinal obstruction e.g. Intussusception
• Gastrointestinal bleeding
what is the management of peutz-jeghers syndrome?
• Conservative unless complications develop
what is oesophageal cancer most commonly due to?
-what conditions are associated with this?
-where are the majority of tumours anatomically?
Until recent time esophageal cancer was most commonly due to a squamous cell carcinoma but the incidence of adenocarcinoma is rising rapidly. Adenocarcinoma is now (since 2010) the most common type of oesophageal cancer and is more likely to develop in patients with a history of gastro-esophageal reflux disease (GERD) or Barrett’s.
The majority of tumours are in the middle third of the esophagus.
is anything protective against oesophageal ca?
Helicobacter pylori may actually be protective against esophageal cancer
what are the risk factors for squamous cell carcinoma of the oesophagus?
• Smoking
• Alcohol
• Achalasia
• Plummer-vinson syndrome
• Rare: coeliac disease, scleroderma
• Sensetive to radiotherapy
what are the risk factors for adenocarcinoma of the oesophagus?
• GERD
• Barrett’s esophagus
what cells are seen in gastric adenocarcinoma?
signet ring cells
signet ring cells may be seen in gastric cancer. They contain a large vacuole of mucin which displaces the nucleus to one side. Higher numbers of signet ring cells are associated with a worse prognosis
Gastric Ca
-peak age
-countries affected?
-males or females?
pidemiology
• Overall incidence is decreasing, but incidence of tumors arising from the cardia is increasing
• Peak age = 70-80 years
• More common in Japan, China, Finland and Columbia than the west
• More common in ♂s, 2:1
what are 7 associations with gastric ca?
• H. pylori infection (although it is protective against esophageal cancer)
• Blood group A: gAstric cAncer
• Gastric adenomatous polyps
• Pernicious anemia
• Smoking
• Diet: salty, spicy, nitrates
• May be negatively associated with duodenal ulcer
what is the diagnosis of gastric ca?
-what is the staging?
• Diagnosis: endoscopy with biopsy
• Staging:
-CT or endoscopic ultrasound - endoscopic ultrasound has recently been shown to be
superior to CT
(CT scanning of the chest abdomen and pelvis is the routine first line staging investigation in most centres.
Laparoscopy to identify occult peritoneal disease
PET CT (particularly for junctional tumours))
what are the clinical features of gastric Ca?
dyspepsia
nausea and vomiting
anorexia and weight loss
dysphagia
what are the 3 different types of tumours of the gastro-oesophageal junction?
Type 1 True oesophageal cancers and may be associated with Barrett’s oesophagus.
Type 2 Carcinoma of the cardia, arising from cardiac type epithelium
or short segments with intestinal metaplasia at the oesophagogastric junction.
Type 3 Sub cardial cancers that spread across the junction. Involve similar nodal stations to gastric cancer.
what is the treatment for gastric ca:
-proximally sited disease
-if tumour <5cm OG junction
-type 2 junctional tumours
-lymph nodes
-additional chemo/radio?
Proximally sited disease greater than 5-10cm from the OG junction may be treated by sub total gastrectomy
Total gastrectomy if tumour is <5cm from OG junction For type 2 junctional tumours (extending into oesophagus) oesophagogastrectomy is usual Endoscopic sub mucosal resection may play a role in early gastric cancer confined to the mucosa and perhaps the sub mucosa (this is debated) Lymphadenectomy should be performed. A D2 lymphadenectomy is widely advocated by the Japanese, the survival advantages of extended lymphadenectomy have been debated. However, the overall recommendation is that a D2 nodal dissection be undertaken. Most patients will receive chemotherapy either pre or post operatively.
colorectal cancer screening:
-why is this done?
-what are the main techniques being evaluated?
-which technique can reduce mortality?
-what is the role of CEA?
Screening:
• Most cancers develop from adenomatous polyps therefore a screening program could theoretically ↓ mortality
• Main techniques being evaluated are faecal occult blood (FOB) testing, sigmoidoscopy and colonoscopy
• Fecal occult blood testing is the only method to have been proven to ↓ mortality (by about 20%) in trials. Sensitivity can be ↑ by DNA analysis for the APC gene
• Trials looking at screening using flexible sigmoidoscopy are currently underway
• Carcinoembryonic antigen may be used to monitor for recurrence in patients post- operatively or to assess response to treatment in patients with metastatic disease. The CEA-scan study is a nuclear medicine procedure — that uses a small dose of radioactive isotope to image tumors sometimes invisible to other diagnostic tests. That isotope is guided to tumors via antibody fragments engineered to seek out and attach to any tissue that expresses carcinoembryonic antigen (CEA), a protein found on virtually all colorectal tumors. CEA blood tests attempt to detect this same protein in blood, but often fail to do so, due to lack of
sensitivity.
what are 4 different causes of a positive faecal occult blood test?
Causes for a positive fecal occult blood testing are:
• 2-10%: cancer (colorectal cancer, gastric cancer)
• 20-30% adenoma or polyps
• Bleeding peptic ulcer
• Angiodysplasia of the colon
what is the national screening programme in the UK for colorectal ca?
-who gets it?
-how is this sent?
-how does it work?
-what is the advantage over conventional FOB tests?
-if this is abnormal what happens?
-the NHS now has a national screening programme offering screening every 2 years to all men and women aged 60 to 74 years in England, 50 to 74 years in Scotland. Patients aged over 74 years may request screening
-eligible patients are sent Faecal Immunochemical Test (FIT) tests through the post
-a type of faecal occult blood (FOB) test which uses antibodies that specifically recognise human haemoglobin (Hb)
-used to detect, and can quantify, the amount of human blood in a single stool sample
-advantages over conventional FOB tests is that it only detects human haemoglobin, as opposed to animal haemoglobin ingested through diet
-only one faecal sample is needed compared to the 2-3 for conventional FOB tests
-whilst a numerical value is generated, this is not reported to the patient or GP, who will instead be informed if the test is normal or abnormal
-patients with abnormal results are offered a colonoscopy
if patients have an abnormal FIT test:
-how many will have a normal exam?
-how many will have polyps?
-how many will have cancer?
5 out of 10 patients will have a normal exam
4 out of 10 patients will be found to have polyps which may be removed due to their premalignant potential
1 out of 10 patients will be found to have cancer
what is ‘bowel scope screening’?
-who can get this?
-what is this?
screening for bowel cancer using sigmoidoscopy is being rolled out as part of the NHS screening program
the aim (other than to detect asymptomatic cancers) is to allow the detection and treatment of polyps, reducing the future risk of colorectal cancer
this is being offered to people who are 55-years-old
NHS patient information leaflets refer to this as ‘bowel scope screening’
patients can self-refer for bowel screening with sigmoidoscopy up to the age of 60, if the offer of routine one-off screening at age 55 had not been taken up
Describe ‘Dukes Staging’ in colorectal cancer?
• The Dukes staging system is widely employed for classifying colorectal cancers and is a useful predictor of survival. Tumour grade and depth of penetration are also important:
• Duke A (Stage I) defines a tumour confined to the bowel wall (i.e. mucosa and submucosa).
• Duke B (Stage II) invades through the muscle wall.
• Duke C (Stage III) involves lymph nodes.
• After this the patient presents with metastatic disease at distant sites (Stage IV).
what are 5 prognostic indicators post complete resection in colorectal ca?
• Poorly differentiated histological type.
• Tumour adherence to adjacent organs.
• Bowel perforation.
• Colonic obstruction at the time of diagnosis.
• Venous invasion by the tumour.
describe the management of colorectal ca
-what is the main treatment
-when is adjuvant chemo warranted? what other drug can be added and what is its side effect?
-when is adjuvant radiotherapy used?
-when is adjuvant radiotherapy combined with chemo?
• Surgical excision of a colonic carcinoma is the main treatment
• Adjuvant chemotherapy (5-fluorouracil and folinic acid) is warranted in high-risk stage II colonic carcinomas and all stage III colonic carcinomas.
• The addition of oxaliplatin has been shown to improve survival in these patients in a large
multicentre trial (MOSAIC study), but the additional drug can cause a severe peripheral
neuropathy.
• Adjuvant radiotherapy is used in rectal carcinomas. This is combined with chemotherapy in
stage II and III rectal carcinomas to reduce the risk of local as well as metastatic relapse.
what are the three types of colon cancer genetically?
• Sporadic (95%)
• Hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
• Familial adenomatous polyposis (FAP, <1%)
what genetic mutations are implicated in sporadic colon ca?
Studies have shown that sporadic colon cancer may be due to a series of genetic mutations. For example, more than half of colon cancers show allelic loss of the adenomatous polyposis coli (APC) gene. It is believed a further series of gene abnormalities e.g. activation of the K-ras oncogene, deletion of p53 and DCC tumour suppressor genes lead to invasive carcinoma
HNPCC:
-how is this inherited?
-how many people will develop ca?
-what is the nature of the ca that develops?
-how many gene mutations have been identified?
HNPCC, an autosomal dominant condition, is the most common form of inherited colon cancer. Around 90% of patients develop cancers, often of the proximal colon, which are often poorly differentiated and highly aggressive. Currently four gene mutations have been identified (including in the hMLH1 and hMSH2 genes).
what criteria is used for HNPCC
-describe this
Amsterdam criteria for HNPCC
• At least 3 family members with colon cancer
• The cases span at least two generations
• At least one case diagnosed before the age of 50 years
what is involved in screening for HNPCC in high risk groups?
HNPCC screening for ↑ risk group:
• Colonoscopy every 2 years from 20 to 40 years age then annually
• Check mutation in DNA or mismatched repair gene.
what is FAP?
-how is this inherited?
-what does this lead to?
-other than colorectal ca what else are these patients higher risk for?
Familial Adenomatous Polyposis (FAP) is a rare autosomal dominant condition which leads to the formation of hundreds of polyps by the age of 30-40 years. Patients inevitably develop carcinoma.
Patients with FAP are also at risk from duodenal tumours which is important cause of death.
what is FAP due to?
-how is this tested?
It is due to a mutation in a tumour suppressor gene called adenomatous polyposis coli gene (APC), located on chromosome 5. Genetic testing can be done by analysing DNA from a patient’s white blood cell.
does FAP affect young or older people
Patients generally have a total colectomy with ileo-anal pouch formation in their twenties.
What is Gardner’s syndrome and what clinical features can this cause?
A variant of FAP called Gardner’s syndrome can also feature osteomas of the skull and mandible, can be identified based on oral findings, including multiple impacted and supernumerary teeth, multiple jaw osteomas which give a “cotton-wool” appearance to the jaws, as well as multiple odontomas, Congenital Hypertrophy of the Retinal Pigment Epithelium
(CHRPE), in addition to multiple adenomatous polyps of the colon, thyroid carcinoma and epidermoid cysts on the skin.
What warrants an urgent (within 2 weeks) referral to the colorectal service for investigations ?colon ca?
• Patients > 40 years old, reporting rectal bleeding with a change of bowel habit towards looser stools and/or ↑ stool frequency persisting for 6 weeks or more
• Patients > 60 years old, with rectal bleeding persisting for 6 weeks or more without a change in bowel habit and without anal symptoms
• Patients > 60 years old, with a change in bowel habit to looser stools and/or more frequent stools persisting for 6 weeks or more without rectal bleeding
• Any patient presenting with a right lower abdominal mass consistent with involvement of the large bowel
• Any patient with a palpable rectal mass
• Unexplained iron deficiency anemia in men or non-menstruating women (Hb < 11 g/dl in
men, < 10 g/dl in women)
what is zollinger-ellison syndrome caused by?
-what can this occur as part of?
is condition characterized by excessive levels of gastrin, usually from a gastrin secreting tumour usually of the duodenum or pancreas. Around 30% occur as part of MEN type I syndrome
what are the clinical features of zollinger ellison syndrome?
Zollinger-Ellison syndrome typically presents with multiple gastroduodenal ulcers causing abdominal pain, diarrhea and malabsorption. High-dose proton pump inhibitors are needed to control the symptoms.
what is the diagnosis of zollinger ellison syndrome?
• Fasting gastrin levels, the single best screen test: done in 3 different days as the gastrin secretion is pulsatile
• Secretin stimulation test: considered +ve if there is ↑ in gastrin >200 pg/mL after secretin injection (Normally Secretin supresses gastrin, but in ZE, it simply shows that the source of gastrin is not the stomach and it is somewhere else like pancresae)
what is the management of zollinger-ellison syndrome?
• If not mets, surgical resection is the cure
• Octreotide can be used to alleviate symptoms with interferon and chemotherapy to attempt cure
non respectable tumor
• PPI is used to control symptoms in acute stages
Gastric MALT lymphoma:
-what is this assoc with?
-prognosis?
-what does this respond to if low grade?
-what may be found in the blood?
• Associated with H. pylori infection in 95% of cases
• Good prognosis
• If low grade then 80% respond to H. pylori eradication
• Paraproteinemia may be present
What is angiodysplasia?
is a vascular deformity of the gastrointestinal tract which predisposes to bleeding and iron deficiency anemia
what condition is angiodysplasia associated with?
-what is thought to be caused by?
aortic stenosis
The association between angiodysplasia and aortic stenosis is thought to be caused by von Willebrand factor (vWF) being proteolysed in the turbulent blood flow around the aortic valve. vWF is most active in vascular beds with high shear stress, such as angiodysplasia, and deficiency of vWF increases the bleeding risk from such lesions
what is used in the diagnosis of angiodysplasia?
Diagnosis
• Colonoscopy
• Mesenteric angiography if acutely bleeding
what is the management for angiodysplasia?
Management
• Endoscopic cautery or argon plasma coagulation
• Antifibrinolytics e.g. Tranexamic acid
• Estrogens may also be used
list the causes of acute pancreatitis:
GETSMASHED
• Gallstones
• Ethanol
• Trauma
• Steroids
• Mumps (other viruses include Coxsackie B)
• Autoimmune (e.g. Polyarteritis nodosa), Ascaris infection
• Scorpion venom
• Hypertriglyceridemia, Hyperchylomicronemia**, Hypercalcemia, Hypothermia
• ERCP
• Drugs (azathioprine, mesalazine*, didanosine, bendroflumethiazide, furosemide, pentamidine,
steroids, sodium valproate)
• ↑ Degree burn of large skin area with significant inhalation injury
describe a rare association with acute pancreatitis seen in the eyes?
• Ischemic (Purtscher) retinopathy (cotton wool spots seen on fundoscopy) - may cause temporary or permanent blindness. This condition may be seen following head trauma and in conditions such as acute pancreatitis, fat embolisation, amniotic fluid embolisation, and vasculitic diseases.
what is the criteria used in acute pancreatitis for prognosis?
• Age > 55
• WBC > 16
• Urea > 16
• Glucose > 11
• Alb < 30
• ALT > 250
• Ca+ < 1
• LDH > 350
• PO2 < 8
• Hematocrit ↓ >10%
• Base deficit > 4
• Fluid loss > 6L
what can be used as a marker of severity in acute pancreatitis on intial assessment?
Clinical impression of severity
Body mass index >30
Pleural effusion
APACHE score >8
what can be used as a marker of severity in acute pancreatitis 24 hours after admission
Clinical impression of severity
APACHE II >8
Glasgow score of 3 or more
Persisting multiple organ failure
CRP>150
what can be used as a marker of severity in acute pancreatitis 48hours after admission?
Glasgow Score of >3
CRP >150
Persisting or progressive organ failure
what is the glasgow panc score?
PaO2< 7.9kPa
Age > 55 years
Neutrophils (WBC > 15)
Calcium < 2 mmol/L
Renal function: Urea > 16 mmol/L
Enzymes LDH > 600IU/L
Albumin < 32g/L (serum)
Sugar (blood glucose) > 10 mmol/L
what may acute pancreatitis be secondary to in the context of HIV infection?
Pancreatitis in the context of HIV infection may be secondary to anti- retroviral treatment (especially didanosine) or by opportunistic infections e.g. CMV
what are 6 causes of high amylase?
Acute pancreatitis
Pancreatic pseudocyst
Mesenteric infarct
Perforated viscus
Acute cholecystitis
Diabetic ketoacidosis
what tests are used in diagnosing acute pancreatitis?
Traditionally hyperamylasaemia has been utlilised with amylase being elevated three times the normal range.
However, amylase may give both false positive and negative results.
Serum lipase is both more sensitive and specific than serum amylase. It also has a longer half life.
Serum amylase levels do not correlate with disease severity
describe the management of acute pancreatitis:
-three main areas of management
Nutrition
-There is reasonable evidence to suggest that the use of enteral nutrition does not worsen the outcome in pancreatitis
-Most trials to date were underpowered to demonstrate a conclusive benefit.
-The rationale behind feeding is that it helps to prevent bacterial translocation from the gut, thereby contributing to the development of infected pancreatic necrosis.
Use of antibiotic therapy
-Many UK surgeons administer antibiotics to patients with acute pancreatitis.
-A recent Cochrane review highlights the potential benefits of administering Imipenem to patients with established pancreatic necrosis in the hope of averting the progression to infection.
-There are concerns that the administration of antibiotics in mild attacks of pancreatitis will not affect outcome and may contribute to antibiotic resistance and increase the risks of antibiotic associated diarrhoea.
Surgery
-Patients with acute pancreatitis due to gallstones should undergo early cholecystectomy.
-Patients with obstructed biliary system due to stones should undergo early ERCP.
-Patients who fail to settle with necrosis and have worsening organ dysfunction may require debridement, fine needle aspiration is still used by some.
-Patients with infected necrosis should undergo either radiological drainage or surgical necrosectomy. The choice of procedure depends upon local expertise.
what is chronic pancreatitis?
-what does this affect?
-what is this due to?
Chronic Pancreatitis is an inflammatory condition which can ultimately affect both the exocrine and endocrine functions of the pancreas. Around 80% of cases are due to alcohol excess with up to 20% of cases being unexplained.
describe 3 features of chronic pancreatitis?
• Pain is typically worse 15 to 30 minutes following a meal
• Steatorrhoea: symptoms of pancreatic insufficiency usually develop between 5 and 25 years
after the onset of pain
• Diabetes mellitus develops in the majority of patients. It typically occurs more than 20 years
after symptom begin
what are the 3 investigations used for chronic pancreatitis?
• Abdominal x-ray shows pancreatic calcification in 30% of cases
• CT is more sensitive at detecting pancreatic calcification
• Functional tests: pancreolauryl and Lundh tests may be used to assess exocrine function if
imaging inconclusive
what is the management of chronic pancreatitis?
Management
• Pancreatic enzyme supplements
• Analgesia
• Antioxidants: limited evidence base - one study suggests benefit in early disease
what are 5 local complications in acute pancreatitis?
Peripancreatic fluid collections
Pseudocysts
Pancreatic necrosis
Pancreatic abscess
Haemorrhage
Peripancreatic fluid collections:
-how often do these occur?
-where are these usually located?
-what can these develop into?
-what is the treatment?
Occur in 25% cases
Located in or near the pancreas and lack a wall of granulation or fibrous tissue
May resolve or develop into pseudocysts or abscesses
Since most resolve aspiration and drainage is best avoided as it may precipitate infection
Pseudocysts in acute pancreatitis:
-how do these form? what is the nature of them?
-when do these usually occur?
-what are the investigations for these?
-when can these be diagnosed?
-what is the treatment?
-In acute pancreatitis result from organisation of peripancreatic fluid collection. They may or may not communicate with the ductal system.
-The collection is walled by fibrous or granulation tissue and typically occurs 4 weeks or more after an attack of acute pancreatitis
-Most are retrogastric
-75% are associated with persistent mild elevation of amylase
-Investigation is with CT, ERCP and MRI or endoscopic USS
-They cannot be diagnosed until more than 6 weeks after the acute attack
-Symptomatic cases may be observed for 12 weeks as up to 50% resolve
-Treatment is either with endoscopic or surgical cystogastrostomy or aspiration
Pancreatic necrosis in acute pancreatitis:
-what can this involve?
-what do complications from this link to?
-how are these managed?
Pancreatic necrosis may involve both the pancreatic parenchyma and surrounding fat
Complications are directly linked to extent of parenchymal necrosis and extent of necrosis overall
Early necrosectomy is associated with a high mortality rate (and should be avoided unless compelling indications for surgery exist)
Sterile necrosis should be managed conservatively (at least initially)
Some centres will perform fine-needle aspiration sampling of necrotic tissue if infection is suspected. False negatives may occur and the extent of sepsis and organ dysfunction may be a better guide to surgery
Pancreatic abscess in acute pancreatitis:
-what is this?
-what do these occur as a result of?
-what is the treatment?
Intraabdominal collection of pus associated with pancreas but in the absence of necrosis
Typically occur as a result of infected pseudocyst
Transgastric drainage is one method of treatment, endoscopic drainage is an alternative
Haemorrhage as a local complication of acute pancreatitis:
-how can this develop?
-what sign can develop?
Infected necrosis may involve vascular structures with resultant haemorrhage that may occur de novo or as a result of surgical necrosectomy.
When retroperitoneal haemorrhage occurs Grey Turner’s sign may be identified
What is the systemic complication of pancreatitis?
Acute respiratory distress syndrome
associated with a high-mortality rate of around 20%
what are the symptoms of pancreatic pseudocyst?
• Abdominal pain or a mass.
• Fever
• Persistently raised amylase and liver function tests
what are the two cystic tumours that can occur in the pancreas?
-are these benign/malignant
• Serous cystadenoma: benign and remain benign.
• Mucinous cystadenoma: this may be benign but has the potential to become malignant.
what are the investigations for cystic tumours in the pancreas?
-how to distinguish between serous cystadenoma and mucinoous cystadenoma?
• CT or MRI can distinguish between the two.
• Aspiration of the cyst for cytology and carcinogenic embryonic antigen
what is the management of:
-mucinous neoplasm
-serous cystadenoma or asymptomatic pseudocyst
• Mucinous neoplasm: most patients undergo limited surgery of the pancreatic cyst.
• Serous cystadenoma or aymptomatic pseudocyst: can also be associated with polycystic kidney disease and von Hippel–Lindau disease. Considerable debate exists as to whether follow up is necessary; in younger patients it may not be. Anyhow, guidelines generally recommend annual
review for a period of around 4 years.
pancreatic cancer:
-incidence
-more males or females?
-what is the 5 year survival rate
-what is the most common oncogene
-what is the commonest form of endocrine tumour
-which age is affected?
• Incidence in the West: 9 cases per 100 000 and it’s increasing over the last 20 years.
• 60% are ♂
• 5-year survival rate: 2%
• K-ras is the most common oncogene in this condition
• Insulinomas are the commonest form of endocrine tumours of the pancreas
• Majority of cases occur in patients over the age of 60
what are 9 assoc. with pancreatic ca?
• Smoking (with a twofold increase in incidence)
• Diabetes
• Chronic pancreatitis
• Hereditary pancreatitis
• Hereditary non-polyposis colorectal carcinoma
• Multiple endocrine neoplasia
• Peutz-jeghers syndrome
• BRCA2
• Dysplastic naevus syndrome
what is included in the investigation of pancreatic ca?
• Contrast CT is used for diagnosis and assessment of invasion
• ERCP restricted to palliative care
• CA 19-9
• U/S abdomen is less reliable when the tumor is in the body or tail
describe the management of pancreatic cancer?
• Surgical intervention represents the only chance of long-term survival with < 20% suitable for surgery at diagnosis. Eligibility for resection depend on:
“ Tumor size < 4cm
“ Invasion of superior mesenteric artery or portal vein
“ Presence of mets
• Radio and chemotherapy are ineffective
what is Cowden’s syndrome?
-what tumour suppressor gene is involved?
Cowden’s syndrome is an inherited condition resulting from a defect in the PTEN tumour suppressor gene.
