Module 2.2: Intestinal Flashcards
Indications for oesophagus imaging
- Dysphagia
- Anaemia
- Pin
- Assessment of tracheo-oesophageal fistulae
- Assessment of site of perforation
Contrast used in oesophageal imaging
o Suspension formed from Barium sulphate (stable in stomach acid)
o Good mucosal coating compared to water soluble agents e.g. gastrograffin good for looking at mucosal abnormalities
o Cheap
o Inert in lung no problem with aspiration (ionic agents draw a lot of fluid leading to pulmonary oedema)
o High morbidity if barium gets into peritoneal cavity (50% mortality) don’t give if there is a risk of perforation or if checking for anastomoses
• Water-soluble contrasting media
o These can be high or low osmolality contrast agents
High: gastrograffin
Low: omnipaque (safe but expensive)
o Ionic contrasts e.g. gastrograffin can cause pulmonary oedema if aspirated
o Best for assessing leaks/perforations as it is safe in the peritoneum
o Risk of allergic reaction (iodine content)
Normal Anatomy of the oesophagus
• Oesophagus is generally divided into 3 parts:
o Upper, middle and lower thirds
• It pierces the diaphragm at T10
• Consists of A and Z rings
• Normal indentations seen on film of AP swallow include: pharynx, epiglottis and piriform fossa
• Normal indentations seen on lateral swallow include: epiglottis, venous plexus, cricopharyngeus muscle (protective mechanism in reflux: spasm and closes off when one swallows), aortic arch and left atrium
• Identification of aortic arch occurs at T4 and LA indentation, cricopharyngeus muscle
Oesophageal pathology
- Dismotility
- Zenker’s Diverticulum/Pharyngeal Pouch
- Oesophageal Web
- Achalasia
- Oesophageal Varices
- Boerrhave Syndrome
- Oesophageal Cancer
- Oesophageal Ulcer
- Retro-oesophageal Thyroid
- Pseudodiverticula
Dismotility in oesophagus
o Dimpling of the edges of the oesophagus
o These are tertiary contractions where the oesophagus is ineffectively propelling food down common in older ages as muscles do not work as normal
Zenker’s Diverticulum/Pharyngeal Pouch
o Seen as outpouching at the level of pharynx
o Patient complains of regurgitation
Oesophageal Web
o Benign stricture seen as a straight membranous band on AP and lateral views
Achalasia
o Dilated oesophagus with food residue
o Beak-like tapering at the level of the gastro-oesophageal junction
o Lower oesophageal sphincter fails to relax
o Tertiary contractions
Absence of normal peristalsis and lack of relaxation of lower oesophageal sphincter critical to diagnosis
All due to failure of myenteric plexus
Gold standard investigation is manometry
Leads to recurrent aspiration pneumonia and oesophageal cancer
o Predominantly young patients
o Complications:
Recurrent aspiration and pneumonia
Risk of oesophageal cancer
Oesophageal Varices
o Serpiginous filling defects (curly line with little oesophagus demonstrable)
o Porto-systemic venous collateral formation around oesophagus (seen through injection of contrast)
• Boerrhave Syndrome
o Spontaneous perforation of the thoracic oesophagus
o Due to stretching
o 25% mortality
o See contrast extravasation into mediastinum
o Associated with pneumomediastinum/pleural effusion (L>R)
o Tends to be a complication of Mallory-Weiss tears
• Oesophageal Cancer
o Irregular annular stricture of the mid-oesophagus (apple-core stricture and shouldering of contrast)
o Polypoid mucosal filling defects
o 95% squamous cell carcinoma, 5% adenocarcinoma
o Associations
Alcohol and smoking
Achalasia
Head and neck cancers
Adenocarcinoma commonest at the lower third due to Barrett’s
o Staging by EUS (wall extension and lymph nodes) and CT
• Oesophageal Ulcer
o Ring-shaped lesion
o Fluid level seen due to barium filling
• Retro-oesophageal Thyroid
o Benign lesion as one can see a smooth filling of barium on a narrowed oesophagus
o CT scan needed to confirm compression
• Pseudodiverticula
o Long stricture of oesophagus
o Several collections of barium seen
o Little ulcerations occur along the oesophagus
o Pathognomonic of infections such as candidiasis
Contrast Agent in stomach imaging
• Barium E-Z HD 250%
o Higher density to provide good coating
• CO2 (carbex granules)
o Distends lumen of stomach allowing for double contrast effect
o Except in very ill or children
• Buscopan or glucagon
o Slow gastric emptying
o No effect on gastro-oesophageal junction
o Buscopan contraindicated in glaucoma/heart problem
• Water-soluble contrast agents used to assess site of perforation
Indications for Barium Meal
- Dyspepsia
- Weight loss
- Upper Abdominal Masses
- GI Haemorrhage – Anaemia
- Obstruction
- Assessment of site perforation
Contraindications: complete large bowel obstruction
Normal Anatomy of stomach
- Gastric fundus below diaphragm + body + antrum + greater/lesser curve of stomach + pylorus + start of duodenum
- Gastric rugae intact (lines across surface of stomach)
Pathology of the stomach/duodenum
- Hiatus Hernia
- Benign Gastric Ulcer
- Gastric Cancer
- Linitis Plastica
- Fundal Diverticulum
- Gastric Polyp
- Bezoars (benign appearance wall is smooth)
- Gastric Varices
- Duodenal Carcinoma
- Duodenal Ulcer
- Ampullary Carcinoma
- Duodenal Diverticulosis
• Hiatus Hernia
o Can be rolling or sliding
o Rolling: shows two round protrusions, one protruding from the other. Due to gastric fundus herniating through the gastro-oesophageal junction, hence the junction stays in the same place
o Sliding: involves gastro-oesophageal junction moving upwards towards the oesophagus, so that both the junction and fundus are found above the diaphragm. Extra constriction can be seen where the stomach starts.
o Predisposition to reflux
• Benign Gastric Ulcer
o Contrast goes through into ulcer crater
o Typically oval or round, with surrounding radiating fold caused by scarring
o May project beyond the stomach wall (causing tethering of mucosa)
o Found on antrum or greater curvature of stomach
o Smooth collar of surrounding mucosa
o Ulcers look like nipples, with barium filling centre (or target sign if superficial)
Gastric cancer
o Irregular polypoid mass, distortion of rugae, loss of normal gastric rugae
o 3rd most common GI malignancy
o Staging by EUS and CT
o 60% lesser curve, 30% on GOJ, 10% on greater curve
o May present as malignant ulcer, diffuse narrowing, ulcerated luminal mass, polypoid mass
• Linitis Plastica
o Full circumferential narrowing of the stomach (small stomach)
o Most commonly caused by malignancy inflammation
o Commonest malignant causes are lymphoma and mets
o May also be caused by gastric carcinoma/local invasion
o Inflammatory causes (rare)
TB, Crohn’s, radiotherapy, corrosives
• Fundal Diverticulum
o Benign lesion with a common appearance of an outpouching
• Gastric Polyp
o Sometimes difficult to differentiate from ulcer
o Outer edges are blurred thereby implying a mass (reverse is seen in ulcer)
• Bezoars
(benign appearance wall is smooth)
o Trichobezoars (hair) o Phytobezoars (plant matter) o Pharmacobezoars (chemicals) o Miscellaneous
• Gastric Varices
o Can look like a malignancy
• Duodenal Carcinoma
o Filling defect seen within lumen
• Duodenal Ulcer
o Pooling of barium into a crater
o Common sight for ulcers is the duodenal cap
o Best visualised using gastroscopy
• Ampullary Carcinoma
o Filling defect in the 2nd part of the duodenum
o Form of cholangiocarcinoma
• Duodenal Diverticulosis
o Outpouching fills with barium
Indications of small bowel radiography
- Pain
- Diarrhoea
- Anaemia
- Partial obstruction
- Malabsorption
- Abdominal Mass
- Failed Small Bowel Enema
Contraindication: perforation + complete obstruction.
Normal Structure of Jejunum and ileum
• Jejunum o Thicker walls o Thicker valvulae conniventes (2mm) = feathery o Left upper abdomen (by stomach) o Thicker: 3-3.5cm
• Ileum o Thinner walls o Thinner valvulae conniventes (1mm) o Right lower abdomen o Thinner: 2.5cm
Crohn’s
• Crohn’s = rose thorn ulceration (deep ulcers), discontinuous (skip lesions), cobblestone mucosa (oedema)
o Asymmetrical thickened folds with granular lumpy surfaces progress to inflammatory polyps
o Complications include: fistula, abscess, stricture (string sign of Kantor), perforation and cancer (e.g. small bowel lymphoma)
• Meckel’s diverticulum
o Persistent remnant of the vitello-intestinal duct
o Rule of 2:
2% population affected
Within 2 feet of ileocaecal valve
Normally 2 inches in length
o Complications: GI bleeding, diverticulitis (inflammation), intussuception
o SBE shows blind pouch or anti-mesenteric border of ileum
• Jejunal diverticulitis
o Outpouchings
o Risk of malabsorption due to bacterial overgrowth
coeliac
o Jejunum will show loss of its feathery appearance featureless jejunum
o Not usually seen as often is diagnosed before it can get to this stage
Anatomy of Colonic Crypt
• Single stem cell dominates the crypt • Crypts divide by crypt fission o These will be clones of a single stem cell (the one that dominates crypt) • Mutations spread this way • Cancer is ‘clonal’
• Zeki S, et al. Nat Rev. Gastroenterol. Hepatol. (2011): Pericryptal myofibroblats are found in the niche that produce growth factor signals, so that stem cells are directed to grow colon. There are various pathways that control this.
Wnt Signalling Pathway in the colonic crypt
• Controls upward migration from crypt niche
• Coordinates crypt growth by:
o Ligand binds to Wnt receptor FZD10
o Inactivates APC
o Stabilising beta-catenin
o This activates LEF/TCF transcriptional activators
- Ligand binds to Frizzled receptor preventing APC binding to beta-catenin
- Beta-catenin is able to then translocate to the nucleus and allow transcription and translation of Wnt target genes.
- In cancer, the Wnt signalling pathway is always activated thereby causing constant transcription and translation of target genes
- In normal cells, beta-catenin is then targeted for degradation by APC by a process of ubiquitalisation
APC or beta-catenin gene mutations in CRC
o Occur both inherited and sporadic CRC
o Lead to constitutively activated Wnt pathway
o Loss of control of proliferation & differentiation
TF-β Signalling Pathway in CRC
- Major inhibitory role growth i.e. cell cycle arrest?
- TGF-β signalling is integral to cell proliferation, differentiation, migration and apoptosis
- Pathway often deregulated in CRC
- Proteins include BMP, TGF, SMAD, GREM
Explanation of diagram:
• Genes of proteins highlighted in blue are implicated in GWAS
• Genes of proteins highlighted in purple are thought to be mutated in CRC (acquired)
• When activated TGF-beta binds to its receptors, this induces intracellular phosphorylation of SMAD2 and SMAD3
• These bind to SMAD4, and translocate to the nucleus to drive SMAD-responsive gene expression
• There is a SMAD independent pathway, which involves the activation of Rho-like GTPase such as RhoA
• RhoA then activate ROCK and RHN2 which regulate the gene expression of TGF-beta target proteins
Adenoma to Carcinoma Sequence
- Earliest form of pre-cancerous lesion: labyrinth crypt focus
- Black dots represent normal crypts
- This is a product of a single stem cell with enhanced growth factor
- Immune cells are able to detect this leading to apoptosis
- Adenoma
- May remain there for decades
- Cancer
- Thought that it takes ~17 years for a cancer to develop from normal mucosa
- This is thought to be associated with a number of genetic changes that cause increased proliferation and decreased differentiation
- APC is the common initiating mutation start process
- Subsequent mutations in oncogenes such as kRAS and BRAF lead to increased proliferation
- Hypo/hypermethylation is thought to occur across the genome leading to hypomethylation of proto-oncogenes or hypermethylation of tumour suppressor genes key event
- At the stage of hyper-dysplasia there is a loss or gain of chunks of chromosomes e.g. p53 loss
- In cancer, one sees increased cell density of crypts with a different morphology. They are now migrating through to the stroma due to disordered Wnt signalling. This process can be driven by inheritance of genes and exposure to carcinogens.
Inherited Risk Factors of Colorectal Cancer
• Lichtenstein et al 2000, NEJM: twin studies indicate that 35% of CRCs are due to heritable factors
• Everyone has a unique risk profile of protective and harmful risk factors (genetic and environmental) this can be modified by lifestyle to modified risk
• High/Low Penetrance
o Interaction between environmental and genetic factors
o Syndromes i.e. high penetrance vs more subtle risks i.e. low penetrance
o Care: diagram implies that if you have a high genetic risk you have a low environmental risk that is not necessarily the case, you can have both being high or even both being low
• Looking at pathways implicated in high penetrance risk factors (syndromes) o Wnt signalling o TGF-beta o DNA repair o APC
Single Nucleotide Polymorphisms
o Chromosome 6 hotspot one point strongly associated with the risk of CRC
• For the SNPs identified, the majority don’t confer a particularly high risk (e.g. allele that confers 21% increased risk will only increase your overall risk by 1%)
C-Myc
• Transcriptional activator that interacts with Wnt signalling
• Constitutively activated in cancer
• TGCA: aberrant expression in 100% of CRCs
• GWAS shows that risk alleles are shared among breast and prostate cancers also
TGF Pathways
• BMP2. BMP4, SMAD7, GREM1, RHPN2, CDH1
• Signalling pathway has potential for synergistic action
• Biological evidence
o TGCA
o Low risk: allele-specific expression of TGFBR1
o High risk: juvenile polyposis and HMPS
GREM1
• Previously known as CRAC1 locus
• BMP signalling antagonist
• Upstream mutation results in increased GREM1 (resulting in HMPS in Ashkenazi Jews)
• Lower penetrance variants associated with CRC risk in general population
• Analogous with high penetrance APC mutation in FAP and lower penetrance APC T3920A
Acute Upper GI bleeding (AUGIB) presentations
• Haematemesis
o MUST be proximal to ligament of treitz (DD, oesophagus, stomach) i.e. it is an upper GI bleed
o Bright red vs coffee ground
• Melaena
o Anywhere from mouth to caecum, but most common due to upper GI bleed
o Coffee ground haematemesis or malaena indicate digested blood
• Bright red rectal bleeding
o Most common anorectal/colonic
o Can occur from upper source- e.g. if have massive GI bleed (e.g. from stomach) fast Transit time bright red rectal bleeding + shock
• Maroon or dark red stools
o Difficult to distinguish location
o Can come from SB or more proximal or colonic sources or UGI tract
o More commonly lower GI tract
Causes of AUGIB
o Peptic ulceration o Oesophagitis o Gastritis o Duodenitis o Varices less common – but still important
Peptic Ulceration
• Most common causes of ulcers
o NSAIDs/aspirin
o H. Pylori
o Idiopathic
Bleeding is exacerbated by anticoagulation: Warfarin, Clopidrogel, NOAC
Classification
1. Major stigmata – non bleeding visible vessel
o Ulcer is white/yellow exudate, red spot is visible vessel (see right)
o Ulcerate extends down and exposes vessel bleeds, and then stops.
- Adherent clot, overlying ulcer
o Clot removal usually attempted – with snare (right)
o Underlying lesion can then be assessed, treated if necessary
o Role of endoscopic therapy of ulcers with adherent clot is controversial - Minor stigmata
o Most ulcers do not have visible vessels
o Low re-bleeding risk – no endoscopic therapy needed
o A) Flat pigmented spot (below, left) B) clean base (below, right)
• Forrest classification is used for PUD bleeding, to aid risk stratification
o Arterial jet – most high risk (30-40% without treatment, treatment reduce <15%)
o Low risk do not require endoscopic treatment
Treatment of Non-Variceal UGIB
• If Hb low Blood transfusion
• If stigmata of haemorrhage Endoscopic therapy
o STANDARD endoscopic therapy: combination therapy: adrenaline + thermal therapy/clips
Injection of adrenaline around vessel tamponade vessel cause it to clot.
High rates rebleeding (20-30%) unless combined with other therapy (reduce to <10%)
Thermal therapy – burn vessel risk perforation
Clips
• Angiographic embolization
o Radiologists inject die in arteries. Localize extravasation of contrast
o Insert material e.g. coil
o Useful for when endoscopic therapy fails or elderly who are not candidates for surgery
• Surgery – when other therapies failed
Varices
• Much higher rate of mortality and bleeding can be more severe mostly due to cirrhosis
• Cirrhosis portal HTN collaterals varices
• E.g. oesophageal (above), gastric (below), rectal
• Risk of bleeding depends on size and stage of cirrhosis
• Blood transfusion (restrictive)
• Antibiotics
o Higher risk of infection in cirrhosis (bacterial translocation) made worse in decompensation, caused by variceal breading. ABx reduce risk death.
o NB bacterial translocation: the passage of viable bacteria from the gastrointestinal (GI) tract to extraintestinal sites, such as the mesenteric lymph node complex (MLN), liver, spleen, kidney, and bloodstream. Mechanisms proposed: (a) disruption of the ecologic GI equilibrium to allow intestinal bacterial overgrowth, (b) increased permeability of the intestinal mucosal barrier, and (c) deficiencies in host immune defences. Intestinal barrier damaged blood. Or intracellular route through epithelial cells LN onwards.
• Terlipressin
o Portal HTN causes splanchnic vasodilation and increased portal pressure
o Terlipressin is a splanchnic vasoconstrictor reduces pressure in splanchnic bed and therefore in varices
• Endoscopic therapy
o E.g. rubber band ligation (right)
• TIPPs – transjugular intrahepatic portosystemic shunt
o Shunt between portal and hepatic vein - to decrease pressure in portal vein
Outcome of AUGIB
• Most (> 80%) stop spontaneously and do not require any treatment
o Low –risk endoscopic lesions or normal endoscopy
• 20% require therapy
• Rebleeding
o Highest for treated bleeding vessels and varices: 10-20%
• Mortality can be has high as 10-20 % especially if elderly, comorbid disease, variceal bleeding
Risk stratification of AUGIB
- Needed to assess the risk of: requiring an intervention, rebleeding or death.
- Currently vast majority of patients admitted to hospital for observation and endoscopy, regardless of severity. In the majority this is unnecessary (low risk).
- Better to identify low and high risk groups at admission to allow for treatment/early discharge
- British guidelines (SIGN) previously recommended the pre-endoscopy (admission) Rockall score, now GBS
Models
• Multiple logistic regression based models
o Rockall
o Glasgow Blatchford score
o Set of data, look for no of variables that may affect outcome – identify predictive variables
• Machine Learning based models
o Artificial neural networks
Rockall
- Rockall et all Gut 1996: Prospective evaluation of two cohorts AUGIB (4185 and 1625 cases)
- Aim to analyse risk factors for death and develop a clinically useful risk score
- Multiple logistic regression based
• Multiple publications in different countries showing accurate in predicting death (>80%) and rebleeding (75%)
o Vreeberg et al Gut 1999
o Phang et aL N Z Med J 2000
o Sanders et al Am J Gastro 2002
- Most widely used post-endoscopic risk score widely validated in various populations
- However may not affect clinical decision predicts rebleed but doesn’t predict need for intervention.
Glasgow Blatchford Score
• Blatchford et al, Lancet, 2000: Glasgow Blatchford Score (right)
• Developed based on 1748 patients with AUGIB
• Used MLR to develop a risk score to predict need for blood transfusion, clinical intervention, rebleeding and death (inpatient stay)
• Validation in 197 patients
• Found that score discriminated those who required treatment (AUROC: 0.92)
o Compared this to Rockall score
Rockall vs GBS
- Rockall not as good at predicting treatment
- Glasgow more useful clinically at discriminating those who required treatment higher true positives
• Chan JCH, Ayaru L. Analysis of risk of scoring for the outpatient management of AUGIB – Frontline Gastro 2010
GBS significantly more accurate (0.82; 95% CI (0.78 to 0.86) than pre-endoscopy Rockall (0.71; 95% CI 0.67 to 0.76) – both sensitivity and specificity
NICE recommends GBS to determine whether to discharge patients.
What are Artificial Neural Networks
• Non-linear statistical models
• Look for relationships between input variables and given outcomes
• Learning – train model on dataset to get increasing accuracy.
• Often identify complex relationships missed by linear models
• GBS and Rockall limited
o Not very specific
o Risk assessment conventionally involves inpatient OGD
o Accurate and reliable non-endoscopic risk score would help identify low risk save resources and protect patients from inpatient harm
• Das et al Gastroenterology 2008: Developed an ANN based model for the non-endoscopic triage of patients with non-variceal AUGIB
o Small numbers: 387 patients
o Looked at non-variceal bleeds (internal an dexternal cohorts)
o Outcomes: predict major stigmata of recent haemorrhage and need for endoscopic therapy (27 variables inputted)
o Sensitivity >80% , Negative predictive values >92%
• Ali A et al, Artificial neural network as a predictive tool for the risk stratification of acute UGI bleeding, 2012
High specificity, accuracy in predicting large number of outcomes.
Limitations: retrospective, low sensitivity (significant no. high risk misclassified as low risk) compared to Blatchford
