Gastroenterology & Hepatology

Key Facts

Barrett oesophagus is a premalignant condition where the normal stratified squamous epithelium of the distal oesophagus is replaced by specialised intestinal metaplasia (columnar epithelium with goblet cells). It is the major risk factor for oesophageal adenocarcinoma.

Epidemiology

Barrett oesophagus affects 1-2% of the general population but is found in 3-5% of patients undergoing OGD for GORD. Male predominance (3:1). Mean age at diagnosis is 55-65 years. Prevalence is increasing in parallel with rising GORD and obesity rates. Oesophageal adenocarcinoma incidence has increased 6-fold over the past 40 years in the UK.

Aetiology

• Chronic GORD (>5 years): most important risk factor
• Central obesity: independently increases risk (visceral fat, intra-abdominal pressure)
• Male sex: 3:1 predominance
• Smoking: ~2x risk
• Family history: 7-10x risk if first-degree relative with Barrett/adenocarcinoma
• Protective factors: H. pylori infection (reduces acid output), aspirin/NSAIDs (anti-inflammatory)

Pathophysiology

Typical Presentation

• Often discovered incidentally at OGD for GORD symptoms
• Chronic heartburn and regurgitation (>5 years)
• May be completely asymptomatic
• Barrett itself does not cause specific symptoms - symptoms relate to underlying GORD

Findings at OGD

• Salmon-pink tongues or circumferential segments of columnar mucosa extending above the gastro-oesophageal junction
• Described using Prague classification (C and M measurements)

Red Flags

• Progressive dysphagia (stricture or malignancy)
• Weight loss (adenocarcinoma)
• GI bleeding (ulceration within Barrett segment)
• Iron deficiency anaemia
• Nodularity or irregularity within Barrett segment (possible dysplasia/cancer)

Bedside

• OGD with systematic biopsies: gold standard diagnosis
  • Seattle protocol: 4-quadrant biopsies every 2 cm in non-dysplastic Barrett, every 1 cm if dysplasia suspected
  • Prague classification: record C (circumferential) and M (maximal) extent
• High-resolution endoscopy with NBI/chromoendoscopy: improved dysplasia detection

Bloods

• FBC: iron deficiency anaemia (chronic blood loss)
• LFTs, U&Es: baseline

Imaging

• CT thorax/abdomen: staging if adenocarcinoma diagnosed
• Endoscopic ultrasound (EUS): T-staging of early cancers, lymph node assessment
• PET-CT: M-staging for oesophageal adenocarcinoma

Special Tests

• Histopathology: presence of goblet cells (intestinal metaplasia) confirms Barrett oesophagus in UK
• Dysplasia grading: must be confirmed by two expert GI pathologists
• Cytosponge (TFF3 test): emerging non-endoscopic screening tool - swallowed sponge collects cells; TFF3 positivity detects Barrett with ~80% sensitivity (BEST3 trial)

Non-pharmacological

• Endoscopic surveillance programme (BSG guideline):
  • No dysplasia, <3 cm: OGD every 5 years
  • No dysplasia, ≥3 cm: OGD every 3 years
  • Low-grade dysplasia (confirmed): endoscopic ablation (preferred) OR 6-monthly surveillance
  • High-grade dysplasia: endoscopic treatment (RFA, EMR/ESD)
• Lifestyle measures: weight loss, GORD management as above

Pharmacological

• Lifelong PPI: all Barrett patients should be on once-daily PPI (e.g. omeprazole 20 mg OD) regardless of symptoms - may reduce progression risk
• Aspirin: emerging chemopreventive evidence (AspECT trial - combination of high-dose PPI + aspirin reduced composite endpoint of mortality, cancer, and HGD in Barrett); not yet standard of care

Surgical/Interventional

• Radiofrequency ablation (RFA): first-line treatment for flat dysplastic Barrett (LGD and HGD); eradicates Barrett epithelium; ~90% complete eradication of dysplasia
• Endoscopic mucosal resection (EMR): for visible lesions/nodularity within Barrett segment; allows histological assessment and treatment
• Endoscopic submucosal dissection (ESD): for larger early lesions; en-bloc resection
• Oesophagectomy: for invasive adenocarcinoma (T1b+) or when endoscopic treatment not feasible
• Cryotherapy: emerging alternative ablative technique

Referral Criteria

• All Barrett oesophagus to gastroenterology for surveillance programme entry
• Dysplasia to specialist Barrett centre for MDT discussion and endoscopic treatment
• Adenocarcinoma to upper GI cancer MDT

Non-dysplastic Barrett carries a 0.3-0.5% annual risk of progression to adenocarcinoma. LGD has ~0.7% annual progression risk but is over-diagnosed (up to 70% downgraded on expert review). HGD has ~10% annual cancer risk and warrants treatment. After successful RFA, recurrence of intestinal metaplasia occurs in ~10% per year, necessitating ongoing surveillance. Overall, most Barrett patients die of causes unrelated to oesophageal cancer.

BSG Barrett Surveillance Schedule

Dysplasia-Carcinoma Sequence

Key Facts

Oesophageal cancer is a highly aggressive malignancy with poor prognosis. The epidemiological shift from squamous cell carcinoma to adenocarcinoma in Western countries parallels the rise in GORD and obesity.

Epidemiology

Approximately 9,300 new cases per year in the UK. The UK has one of the highest incidence rates of oesophageal adenocarcinoma worldwide. Male:female ratio is 2:1 (higher for adenocarcinoma - up to 7:1). Peak incidence is 60-80 years. 5-year survival is approximately 15% overall; ~40-50% for those undergoing curative resection.

Aetiology

Adenocarcinoma (distal/GOJ):

• Barrett oesophagus (30-60x risk)
• Chronic GORD
• Central obesity
• Smoking
• Male sex, Caucasian

Squamous cell carcinoma (mid-oesophagus):

• Smoking (5x risk) + alcohol (5x risk) - synergistic (25x combined)
• Achalasia
• Plummer-Vinson syndrome (iron deficiency + oesophageal web)
• Caustic stricture
• Tylosis (genetic - very high risk)
• HPV (types 16/18)
• Hot beverages (some evidence)

Pathophysiology

Adenocarcinoma arises through the metaplasia-dysplasia-carcinoma sequence in Barrett oesophagus, driven by chronic acid/bile exposure. Key molecular events include TP53 mutation, CDKN2A loss, and HER2 amplification (targetable with trastuzumab). SCC develops from squamous epithelium via dysplasia, driven by carcinogen exposure (tobacco, alcohol metabolites). Both types spread locally (mediastinal invasion), lymphatically (extensive submucosal lymphatic network), and haematogenously (liver, lungs, bone).

Typical Presentation

• Progressive dysphagia: initially solids, then liquids (>70% at presentation)
• Weight loss: often significant (>10% body weight)
• Odynophagia: painful swallowing
• Retrosternal discomfort/pain
• Regurgitation of undigested food

Late Features

• Hoarseness (recurrent laryngeal nerve invasion)
• Chronic cough (tracheo-oesophageal fistula)
• Cervical lymphadenopathy (Virchow's node - left supraclavicular)
• Hepatomegaly (liver metastases)
• Bone pain (skeletal metastases)

Red Flags

• Any progressive dysphagia (urgent OGD regardless of age)
• Dyspepsia with weight loss, anaemia, or vomiting in ≥55 years
• New dysphagia in known Barrett oesophagus
• Aspiration pneumonia (tracheo-oesophageal fistula)

Bedside

• OGD + biopsy: diagnostic - visualise tumour, obtain histology, assess location and length
• Nutritional assessment: weight loss, BMI, albumin

Bloods

• FBC: iron deficiency anaemia
• LFTs: liver metastases
• Albumin: nutritional status
• U&Es, clotting: pre-operative baseline
• HER2 status: on biopsy (adenocarcinoma - if positive, trastuzumab eligible)
• PD-L1 (CPS): immunotherapy eligibility

Imaging

• CT thorax/abdomen/pelvis with contrast: initial staging - local extent, lymphadenopathy, distant metastases
• PET-CT: detects occult metastases, changes management in ~15-20%
• Endoscopic ultrasound (EUS): T and N staging - most accurate for local invasion depth and regional nodes
• Staging laparoscopy: for GOJ/Siewert type II-III tumours to exclude peritoneal disease

Special Tests

• Barium swallow: if OGD not possible; shows shouldering, irregular narrowing
• Bronchoscopy: if tracheo-oesophageal fistula or airway invasion suspected
• Molecular testing: HER2, PD-L1 CPS, MSI status - guide systemic therapy

Non-pharmacological

• MDT discussion: all cases - upper GI cancer MDT (surgeon, oncologist, radiologist, pathologist, CNS, dietitian)
• Nutritional support: dietitian assessment; consider NG tube, PEG/RIG, or parenteral nutrition
• Smoking/alcohol cessation
• Pre-habilitation: exercise and nutrition optimisation before surgery

Pharmacological

• Neoadjuvant chemotherapy (adenocarcinoma):
  • FLOT regimen (5-FU, leucovorin, oxaliplatin, docetaxel): 4 cycles pre-op + 4 cycles post-op - current standard (FLOT4 trial)
  • OR ECF/ECX/EOF/EOX (MAGIC trial - perioperative chemotherapy)
• Neoadjuvant chemoradiotherapy (SCC preferred): carboplatin/paclitaxel + 41.4 Gy (CROSS trial - improved median survival from 24 to 49 months)
• Palliative chemotherapy: FOLFOX, capecitabine/oxaliplatin; median survival ~10 months
• Trastuzumab: add to chemotherapy if HER2-positive adenocarcinoma (ToGA trial)
• Nivolumab/pembrolizumab: checkpoint inhibitors for PD-L1 positive or MSI-high; adjuvant nivolumab post-neoadjuvant chemoRT (CheckMate 577)

Surgical/Interventional

• Oesophagectomy: curative intent for T1-T3 N0-N2 M0 (after neoadjuvant therapy)
  • Ivor Lewis (right thoracotomy + laparotomy): most common for distal/GOJ
  • McKeown (3-stage): for mid/upper oesophageal tumours
  • Minimally invasive (MIO): laparoscopic/thoracoscopic - reduced morbidity
• Endoscopic resection: EMR/ESD for T1a (mucosal) tumours; curative if clear margins and no poor prognostic features
• Oesophageal stenting (SEMS): palliative for dysphagia in inoperable disease
• Palliative radiotherapy: for dysphagia, bleeding, pain

Referral Criteria

• Urgent 2-week wait OGD for dysphagia or alarm symptoms (NICE NG12)
• All confirmed oesophageal cancers to upper GI cancer MDT
• Specialist oesophagogastric cancer centre for surgery (centralised services)

Overall 5-year survival is approximately 15%. Stage-dependent: Stage I ~60-80%, Stage II ~30-40%, Stage III ~15-25%, Stage IV <5%. Neoadjuvant chemo(radio)therapy + surgery gives best outcomes for locally advanced disease. The CROSS trial showed 49-month median survival with neoadjuvant chemoRT vs 24 months with surgery alone for SCC. Complete pathological response to neoadjuvant therapy occurs in ~15-30% and is associated with improved survival. Palliative treatment provides median survival of 6-12 months.

TNM Staging Summary (8th Edition)

Siewert Classification (GOJ Tumours)

Key Trials

Key Facts

Achalasia is a primary oesophageal motility disorder characterised by impaired LOS relaxation and absent oesophageal peristalsis, leading to progressive dysphagia and food stasis in the oesophagus.

Epidemiology

Incidence is approximately 1.6 per 100,000 per year with a prevalence of ~10 per 100,000. Equal sex distribution. Can occur at any age but peak incidence is 30-60 years. No clear ethnic predisposition.

Aetiology

• Primary (idiopathic): vast majority; likely autoimmune destruction of inhibitory neurones
• Secondary (pseudo-achalasia): malignancy at GOJ (mimics achalasia - important to exclude in older patients with short symptom duration), Chagas disease (Trypanosoma cruzi - South America)
• Genetic: rare familial forms; association with Allgrove syndrome (achalasia, alacrima, adrenal insufficiency - triple A syndrome)

Pathophysiology

Selective loss of inhibitory neurones (producing nitric oxide and VIP) in the myenteric plexus, with relative preservation of excitatory cholinergic neurones. This results in:

1. Failure of LOS relaxation: persistent tonic contraction of the LOS
2. Absent peristalsis: loss of sequential contraction in the oesophageal body
3. Progressive oesophageal dilatation: food stasis, fermentation, aspiration risk

The aetiology of neuronal loss is unclear - likely autoimmune (CD3+ T-cell infiltration in myenteric plexus), possibly triggered by viral infection (HSV-1) in genetically susceptible individuals.

Typical Presentation

• Progressive dysphagia to solids AND liquids (key differentiator from mechanical obstruction)
• Regurgitation of undigested food (often hours after eating, or nocturnal)
• Chest pain/discomfort (particularly Type III achalasia)
• Weight loss (variable, usually gradual)
• Nocturnal cough (aspiration of retained food)

Manometric Subtypes

• Type I (classic): minimal oesophageal pressurisation, dilated oesophagus
• Type II (with compression): panesophageal pressurisation in >20% of swallows - best treatment response
• Type III (spastic): premature/spastic contractions - worst prognosis, most symptomatic

Red Flags

• Rapid onset in elderly (>55 years) with weight loss → exclude pseudo-achalasia (GOJ malignancy)
• Haematemesis (oesophageal ulceration from stasis)
• Recurrent aspiration pneumonia
• Rapidly progressive symptoms (<6 months duration - pseudo-achalasia more likely)

Bedside

• OGD: first investigation to exclude malignancy - oesophageal dilatation, retained food/fluid, puckered LOS that "pops" open; must biopsy GOJ

Bloods

• FBC: anaemia (nutritional deficiency)
• Albumin: nutritional status
• Trypanosoma cruzi serology: if travel to South America

Imaging

• Barium swallow: classic bird-beak appearance (smooth tapering at LOS), dilated oesophagus, absent peristalsis on fluoroscopy, air-fluid level
• CT thorax/abdomen: exclude GOJ mass (pseudo-achalasia), assess oesophageal dilatation

Special Tests

• High-resolution manometry (HRM): gold standard diagnostic test
  • Elevated integrated relaxation pressure (IRP) >15 mmHg
  • Absent peristalsis (100% failed swallows in Type I/II)
  • Chicago Classification v4.0 subtyping (I, II, III)
• Timed barium swallow: functional assessment; measures oesophageal emptying at 1, 2, and 5 minutes; useful for monitoring treatment response
• EndoFLIP (functional lumen imaging probe): measures distensibility of GOJ; increasingly used intra-operatively

Non-pharmacological

• Dietary advice: eat slowly, chew thoroughly, drink water with meals, eat upright, avoid eating before bed
• Elevate head of bed: reduce nocturnal aspiration risk

Pharmacological

• Medical therapy (bridge to definitive treatment or for those unfit for intervention):
  • Nifedipine 10-20 mg SL 30 minutes before meals (reduces LOS pressure by ~30%)
  • Isosorbide dinitrate 5-10 mg SL 15 minutes before meals
  • Sildenafil 50 mg (NO-mediated LOS relaxation - off-label)
• Medical therapy has limited long-term efficacy (~50% symptom improvement, diminishes over time)

Surgical/Interventional

• Laparoscopic Heller myotomy + partial fundoplication (Dor anterior 180°): ~90% success; lower re-intervention rate than single dilatation; preferred for younger patients and Type III achalasia
• Peroral endoscopic myotomy (POEM): endoscopic alternative to Heller; ~90% success; higher rate of post-procedure GORD (up to 40-60%) as no fundoplication; increasingly popular
• Botulinum toxin injection (Botox 100 units into LOS): temporary relief (3-12 months); for patients unfit for dilatation/surgery
• Oesophagectomy: end-stage achalasia with megaoesophagus (>sigmoid oesophagus) not amenable to myotomy

Referral Criteria

• All suspected achalasia to gastroenterology for manometry
• Specialist oesophageal motility centre for definitive treatment
• Upper GI surgery for Heller myotomy or POEM
• Urgent investigation if pseudo-achalasia suspected

Both pneumatic dilatation and Heller myotomy provide good long-term symptom control in >80% at 5 years (European Achalasia Trial showed equivalence at 5 years). Type II achalasia has the best treatment response (~95%). Type III has the poorest response (~70%). POEM has excellent short-term results but higher GORD rates. Long-term achalasia is associated with a small increased risk of oesophageal squamous cell carcinoma (~3% lifetime risk) - some centres offer surveillance OGD every 3-5 years after 15 years of disease.

Chicago Classification v4.0 - Achalasia Subtypes

Treatment Comparison

Key Facts

Oesophageal varices are dilated portosystemic collateral veins in the submucosa of the oesophagus, developing as a consequence of portal hypertension. Variceal haemorrhage is one of the most serious complications of cirrhosis.

Epidemiology

Varices are present in approximately 50% of patients with cirrhosis at diagnosis - 40% in compensated cirrhosis, 60% in decompensated. Annual rate of new variceal development is ~5-8% per year. First variceal bleeding occurs at a rate of ~15% per year for large varices. Mortality per bleeding episode is 15-20% with current management.

Aetiology

• Cirrhosis (>90% of cases in UK): alcohol-related liver disease, NAFLD/MASLD, hepatitis B/C, autoimmune
• Pre-hepatic portal hypertension: portal vein thrombosis, splenic vein thrombosis
• Post-hepatic: Budd-Chiari syndrome, right heart failure, constrictive pericarditis
• Non-cirrhotic portal hypertension: schistosomiasis, sarcoidosis, nodular regenerative hyperplasia

Pathophysiology

Portal hypertension develops when resistance to portal blood flow increases (intrahepatic - cirrhotic nodules compressing sinusoids + activated stellate cells; or pre/post-hepatic). When HVPG exceeds 10 mmHg, portosystemic collaterals develop at sites of portal-systemic anastomosis. The oesophageal submucosal veins are thin-walled and become progressively dilated. Bleeding occurs when wall tension exceeds wall strength (LaPlace's law) - larger varices, higher portal pressure, and thinner walls increase rupture risk.

Acute Variceal Bleeding

• Massive haematemesis (bright red or coffee-ground)
• Melaena (may have fresh PR bleeding if massive)
• Haemodynamic compromise: tachycardia, hypotension, cool peripheries
• Signs of chronic liver disease: jaundice, spider naevi, palmar erythema, ascites, hepatosplenomegaly
• Hepatic encephalopathy: may be precipitated by GI bleed

Unruptured Varices

• Usually asymptomatic - discovered at screening OGD
• Features of underlying liver disease

Red Flags

• Haematemesis in a patient with known/suspected liver disease - assume variceal until proven otherwise
• Rapidly falling Hb with haemodynamic instability
• Signs of coagulopathy (bruising, prolonged bleeding)
• Encephalopathy developing after GI bleed

Bedside

• ABG/VBG: lactate, Hb (may take hours to drop)
• Observations: pulse, BP, RR, SpO₂, urine output
• GCS: encephalopathy assessment

Bloods

• FBC: Hb (may be falsely normal initially), platelets (often low in cirrhosis)
• Coagulation (INR/PT): often deranged in cirrhosis
• U&Es: AKI (hepatorenal syndrome), urea rises with GI bleed
• LFTs: bilirubin, albumin (prognostic - Child-Pugh/MELD scoring)
• Group and crossmatch: at least 4 units packed red cells
• Blood cultures: if sepsis suspected

Imaging

• OGD (oesophagogastroduodenoscopy): diagnostic and therapeutic - within 12 hours of presentation (after resuscitation)
  • Variceal grading: small (<5 mm), medium/large (>5 mm)
  • Red signs: cherry red spots, red wale markings (increased bleed risk)
• Doppler ultrasound: portal vein patency, flow direction, spleen size
• CT abdomen with portal phase: portal vein thrombosis, hepatocellular carcinoma screening

Special Tests

• HVPG measurement: gold standard for portal hypertension quantification (>10 mmHg = clinically significant); mainly research/specialist centres
• Transient elastography (FibroScan): liver stiffness >20 kPa suggests clinically significant portal hypertension; platelet count <150 also predictive (Baveno VII criteria)

Non-pharmacological

• Acute resuscitation: A-E approach; large-bore IV access; target Hb 70-80 g/L (over-transfusion increases portal pressure); correct coagulopathy with caution (target INR-based factor replacement is debated)
• Airway protection: intubation if GCS <8, massive haematemesis, or high aspiration risk
• Sengstaken-Blakemore tube: temporary tamponade (max 24 hours) as bridge to definitive treatment if endoscopy unavailable or failed; Danis stent as alternative

Pharmacological

• Acute bleed:
  • Terlipressin 2 mg IV stat then 1-2 mg every 4-6 hours for up to 5 days - reduces portal pressure; ONLY vasoactive drug licensed for variceal bleeding in UK
  • Prophylactic antibiotics: ceftriaxone 1 g IV OD (or ciprofloxacin 500 mg BD PO) for 5-7 days - reduces mortality and rebleeding
  • PPI: omeprazole 40 mg IV if ulcer co-exists; avoid routine use in variceal bleeding
• Primary prophylaxis (medium/large varices, no prior bleed):
  • NSBB: propranolol 40 mg BD (titrate to HR 55-60 bpm) OR carvedilol 6.25-12.5 mg OD (may be superior - reduces HVPG more)
  • OR VBL (variceal band ligation) every 2-4 weeks until eradicated
  • Baveno VII: patients with compensated cirrhosis, LSM <20 kPa and platelets >150 can avoid screening OGD
• Secondary prophylaxis (after first bleed):
  • Combination VBL + NSBB (most effective)
  • VBL every 2-4 weeks until eradication, then surveillance OGD

Surgical/Interventional

• OGD band ligation: first-line endoscopic treatment for acute variceal bleed; apply bands from GOJ upwards
• TIPSS (transjugular intrahepatic portosystemic shunt): for refractory/recurrent bleeding despite endoscopic + pharmacological therapy; early TIPSS (<72 hours) in high-risk patients (Child C <14 or Child B with active bleed) reduces mortality
• Balloon-occluded retrograde transvenous obliteration (BRTO): for gastric varices
• Liver transplantation: definitive treatment for underlying cirrhosis

Referral Criteria

• Emergency GI/hepatology referral for acute variceal bleeding
• Hepatology referral for all cirrhotic patients (variceal screening)
• Interventional radiology for TIPSS
• Transplant assessment if appropriate

First variceal bleed mortality is 15-20% per episode (down from >40% with modern management). 6-week mortality after first bleed is ~20%. Rebleeding rate without secondary prophylaxis is ~60% within 1 year. With combination VBL + NSBB, rebleeding rate is ~20-30%. Early TIPSS in high-risk patients reduces 1-year mortality. Child-Pugh C patients have worst prognosis (~50% 6-week mortality after variceal bleed). Liver transplantation offers definitive cure of portal hypertension.

Acute Variceal Bleed Protocol

Child-Pugh Score

Key Facts

Peptic ulcer disease (PUD) refers to ulceration of the gastric or duodenal mucosa, extending through the muscularis mucosae. It remains a significant cause of morbidity despite declining incidence due to H. pylori eradication and PPI use.

Epidemiology

Lifetime prevalence is approximately 5-10%. Incidence has declined significantly over the past 30 years due to H. pylori eradication and reduced NSAID use. However, PUD remains the commonest cause of upper GI bleeding. Duodenal ulcers are 4x more common than gastric ulcers. Male predominance (2:1). Peak incidence is 30-50 years for duodenal ulcers and 50-70 years for gastric ulcers.

Aetiology

• H. pylori infection: ~60% of gastric ulcers, ~90% of duodenal ulcers

• Smoking: 2x risk, impairs ulcer healing
• Physiological stress: Curling ulcer (burns), Cushing ulcer (raised ICP)
• Zollinger-Ellison syndrome: gastrinoma → massive acid hypersecretion
• Other: corticosteroids (synergistic with NSAIDs), alcohol, crack cocaine

Pathophysiology

PUD results from an imbalance between mucosal defence factors (mucus-bicarbonate barrier, prostaglandins, mucosal blood flow, epithelial cell renewal) and aggressive factors (gastric acid, pepsin, H. pylori, NSAIDs). H. pylori colonises the gastric antrum, producing urease (generates ammonia → alkaline microenvironment), CagA, and VacA toxins that cause chronic inflammation and disrupt the mucosal barrier. NSAIDs inhibit COX-1, reducing mucosal prostaglandin synthesis and compromising the mucus-bicarbonate barrier.

Duodenal Ulcer

• Epigastric pain relieved by food and antacids ("hunger pain")
• Pain worse at night/early morning (empty stomach)
• May have periods of remission and relapse

Gastric Ulcer

• Epigastric pain worsened by eating
• Nausea, early satiety
• Weight loss (may occur due to food avoidance)

Complications

• Bleeding: haematemesis, melaena, iron deficiency anaemia
• Perforation: sudden severe epigastric pain → peritonitis; free air on erect CXR
• Gastric outlet obstruction: persistent vomiting, succussion splash, metabolic alkalosis

Red Flags

• Haematemesis/melaena (bleeding ulcer)
• Acute severe abdominal pain with peritonism (perforation)
• Persistent vomiting with weight loss (outlet obstruction or malignancy)
• Age ≥55 with new dyspepsia (exclude malignancy - NICE NG12)
• Symptoms not responding to PPI + H. pylori eradication

Bedside

• H. pylori testing: urea breath test (¹³C-UBT) - first-line; OR stool antigen test. Stop PPI ≥2 weeks and antibiotics ≥4 weeks before testing
• Observations: if GI bleeding suspected

Bloods

• FBC: iron deficiency anaemia (chronic blood loss)
• U&Es: urea disproportionately raised with upper GI bleed
• LFTs, amylase/lipase: exclude biliary/pancreatic cause
• Group and save/crossmatch: if bleeding
• Fasting gastrin: if Zollinger-Ellison suspected (multiple/refractory ulcers)

Imaging

• OGD: gold standard - visualise ulcer, take biopsies (ALL gastric ulcers must be biopsied to exclude malignancy; duodenal ulcers rarely malignant), CLO test for H. pylori
• Erect CXR: free air under diaphragm if perforation suspected
• CT abdomen: if perforation suspected and CXR equivocal; staging if malignancy found

Special Tests

• CLO test (rapid urease test): biopsy placed in urea medium - colour change if H. pylori present
• Histology: Sydney protocol biopsies for H. pylori and dysplasia
• Repeat OGD: all gastric ulcers should have repeat OGD at 6-8 weeks to confirm healing and exclude malignancy

Non-pharmacological

• Stop NSAIDs/aspirin if possible; if essential, co-prescribe PPI
• Smoking cessation: impairs ulcer healing
• Dietary: no specific diet proven effective; avoid foods that worsen symptoms
• Reduce alcohol intake

Pharmacological

• H. pylori eradication (if positive):
  • First-line: PPI (omeprazole 20 mg BD or lansoprazole 30 mg BD) + amoxicillin 1 g BD + clarithromycin 500 mg BD for 7 days
  • Penicillin allergy: PPI + metronidazole 400 mg BD + clarithromycin 500 mg BD for 7 days
  • Second-line (if first-line fails): PPI + amoxicillin 1 g BD + metronidazole 400 mg BD for 7 days; or bismuth quadruple therapy
  • Confirm eradication: UBT or stool antigen ≥4 weeks after completing treatment
• PPI for ulcer healing: omeprazole 20 mg OD (duodenal - 4 weeks) or 20-40 mg OD (gastric - 8 weeks)
• Gastroprotection with NSAID use: PPI co-prescription (omeprazole 20 mg OD); consider switching to COX-2 inhibitor (celecoxib)

Surgical/Interventional

• Endoscopic haemostasis: for bleeding ulcers - adrenaline injection (1:10,000) + thermal coagulation or clips; repeat OGD if rebleed
• Interventional radiology: selective arterial embolisation for failed endoscopic haemostasis
• Surgery: for perforation (omental patch/Graham patch repair), uncontrolled bleeding (under-running of ulcer), and gastric outlet obstruction
• Highly selective vagotomy: historical; rarely performed now

Referral Criteria

• Urgent 2WW OGD: alarm features or age ≥55 with new dyspepsia (NICE NG12)
• Urgent surgical referral: perforation, uncontrolled bleeding
• Gastroenterology: refractory ulcers, suspected Zollinger-Ellison syndrome

H. pylori eradication cures >95% of H. pylori-associated duodenal ulcers and >80% of gastric ulcers. Reinfection rate in UK is <1% per year after successful eradication. NSAID-associated ulcers heal in >90% with PPI if NSAID stopped. Upper GI bleeding from peptic ulcers has an overall mortality of 5-10%. Perforation mortality is 5-10% with prompt surgical treatment (higher in elderly/delayed presentation). Rockall score >8 is associated with >40% mortality.

Rockall Score (Post-OGD)

Glasgow-Blatchford Score (Pre-OGD)

• Uses Hb, urea, SBP, pulse, melaena, syncope, liver disease, heart failure
• Score 0 = very low risk - may be suitable for outpatient management
• Score ≥6 = high risk - requires inpatient management + urgent OGD

Key Facts

Helicobacter pylori is one of the most common chronic bacterial infections worldwide, affecting approximately half the global population. In the UK, prevalence is ~30% and falling. It is the major aetiological factor in peptic ulcer disease and gastric cancer.

Epidemiology

Global prevalence is approximately 50% but varies enormously by country and socioeconomic status. UK prevalence is ~30% overall, higher in older adults (birth cohort effect - declining prevalence). Prevalence is higher in lower socioeconomic groups, crowded living conditions, and among immigrants from high-prevalence countries. Infection is usually acquired in childhood and persists unless treated.

Aetiology

Transmission is person-to-person via oral-oral, faecal-oral, or gastro-oral routes. Childhood acquisition is most common, associated with household crowding. The bacterium has evolved sophisticated mechanisms to colonise the hostile gastric environment.

Pathophysiology

H. pylori colonises the gastric antral mucosa beneath the mucus layer. Key virulence factors:

• Urease: converts urea to ammonia + CO₂, creating an alkaline microenvironment protecting the organism; ammonia itself damages epithelium
• CagA (cytotoxin-associated gene A): injected into epithelial cells via type IV secretion system; disrupts cell signalling, promotes inflammation and carcinogenesis
• VacA (vacuolating cytotoxin A): induces apoptosis and immune evasion
• Flagella: motility through mucus layer

Chronic infection causes:

1. MALT lymphoma: chronic antigenic stimulation of gastric lymphoid tissue

Asymptomatic

• Most H. pylori infections are asymptomatic (~80%)
• Incidental finding on testing for dyspepsia

Symptomatic

• Dyspepsia (epigastric pain, bloating, nausea)
• Peptic ulcer disease symptoms (see PUD entry)
• Iron deficiency anaemia (unexplained - H. pylori impairs iron absorption)
• Idiopathic thrombocytopaenic purpura (ITP) - association recognised

Red Flags

• Alarm symptoms (dysphagia, weight loss, GI bleeding, anaemia) - require OGD
• Symptoms persisting despite H. pylori eradication - consider alternative diagnosis
• Family history of gastric cancer in H. pylori-positive patient

Bedside

• ¹³C-Urea breath test (UBT): first-line non-invasive test; sensitivity/specificity >95%; must stop PPI ≥2 weeks, antibiotics ≥4 weeks before testing
• Stool antigen test (monoclonal): alternative first-line; sensitivity/specificity ~95%; same preparation requirements

Bloods

• H. pylori serology (IgG): indicates exposure but NOT active infection - does not distinguish current from past infection; NOT recommended for diagnosis or eradication confirmation
• FBC: iron deficiency anaemia

Imaging

• OGD: not first-line for H. pylori testing alone; indicated if alarm features or age ≥55 with new dyspepsia

Special Tests

• CLO test (rapid urease test): performed on gastric biopsy at OGD; results within 1-24 hours
• Histology: Sydney protocol biopsies - identifies H. pylori organisms, gastritis pattern, atrophy, intestinal metaplasia
• Culture and sensitivity: for antibiotic resistance testing (mainly research; increasingly used for clarithromycin resistance)
• PCR: emerging for resistance gene detection

Non-pharmacological

• Test-and-treat strategy (NICE CG184): for patients with dyspepsia without alarm features and age <55
• Test and treat: if positive, eradicate; retest to confirm eradication

Pharmacological

• First-line eradication (7 days):
  • PPI (omeprazole 20 mg BD or lansoprazole 30 mg BD) + amoxicillin 1 g BD + clarithromycin 500 mg BD
  • If penicillin allergic: PPI + clarithromycin 500 mg BD + metronidazole 400 mg BD
• Second-line (if first-line fails - 7 days):
  • PPI + amoxicillin 1 g BD + metronidazole 400 mg BD
  • OR bismuth quadruple therapy: PPI + bismuth subsalicylate 524 mg QDS + metronidazole 400 mg TDS + tetracycline 500 mg QDS for 14 days
• Third-line: guided by culture and sensitivity if available
• Confirm eradication: UBT or stool antigen ≥4 weeks after completing eradication and ≥2 weeks off PPI
• Gastric MALT lymphoma: H. pylori eradication alone achieves complete remission in >75% of early-stage gastric MALT lymphoma

Surgical/Interventional

• Not applicable for H. pylori infection itself
• Surgery for complications (perforation, bleeding, malignancy)

Referral Criteria

• Gastroenterology referral for eradication failure after 2 courses
• OGD for alarm symptoms or age ≥55 with new dyspepsia
• Gastric cancer MDT if malignancy detected
• Consider screening first-degree relatives of gastric cancer patients

Eradication success rate is ~85% with first-line triple therapy, ~90%+ with bismuth quadruple therapy. Clarithromycin resistance is rising in the UK (~15-20%) and is the main cause of treatment failure. Successful eradication cures >95% of H. pylori-associated duodenal ulcers. Reinfection rate in the UK is <1% per year. H. pylori eradication reduces gastric cancer risk by approximately 30-40% in infected individuals. Early-stage gastric MALT lymphoma has >75% complete remission with eradication alone.

H. Pylori Eradication Regimens Summary

Testing Summary

Key Facts

Gastric cancer is a major global health burden. Despite declining incidence in the UK, it remains a leading cause of cancer-related death due to late presentation.

Epidemiology

Approximately 6,700 new cases per year in the UK. Male:female ratio 2:1. Incidence increases with age (peak 70-80 years). Strong geographic variation - highest rates in East Asia, Eastern Europe, South America. UK incidence has halved over the past 40 years (declining H. pylori prevalence, better food preservation). However, proximal/GOJ tumours are increasing.

Aetiology

• H. pylori infection: most important risk factor for non-cardia gastric cancer (3-6x risk)
• Dietary: high salt intake, nitrosamines (processed meats), smoked foods; protective factors include fresh fruit and vegetables
• Smoking: 1.5-2x risk
• Pernicious anaemia: autoimmune atrophic gastritis → 3-6x risk
• Previous partial gastrectomy: stump carcinoma (20-30 year latency)
• Genetic: CDH1 mutation (hereditary diffuse gastric cancer - prophylactic gastrectomy indicated), Lynch syndrome, FAP, Li-Fraumeni
• Blood group A: 20% increased risk

Pathophysiology

Diffuse type (including signet ring cell/linitis plastica): loss of E-cadherin (CDH1 gene) causes loss of cell-cell adhesion, allowing tumour cells to infiltrate diffusely through the gastric wall. More common in younger patients and has a worse prognosis.

Early Disease

• Often asymptomatic or non-specific dyspepsia
• May be detected incidentally at OGD

Advanced Disease

• Weight loss (most common presenting symptom - up to 60%)
• Dyspepsia/epigastric pain (50%)
• Dysphagia (proximal/GOJ tumours)
• Nausea and vomiting (especially pyloric tumours)
• Early satiety (linitis plastica - reduced gastric distensibility)
• GI bleeding: haematemesis, melaena, iron deficiency anaemia

Metastatic Disease

• Virchow's node (left supraclavicular lymphadenopathy - Troisier's sign)
• Sister Mary Joseph nodule (periumbilical metastasis)
• Krukenberg tumour (ovarian metastasis - particularly signet ring cell)
• Blumer's shelf (palpable rectal shelf on DRE - peritoneal deposit in pouch of Douglas)
• Ascites (peritoneal carcinomatosis)
• Hepatomegaly (liver metastases)

Red Flags

• Any dysphagia (urgent OGD regardless of age)
• Age ≥55 with weight loss + upper abdominal pain/reflux/dyspepsia → urgent 2WW referral
• Palpable epigastric mass
• Unexplained iron deficiency anaemia

Bedside

• OGD + multiple biopsies: diagnostic - minimum 8 biopsies from ulcer rim and base
• Nutritional assessment: weight, BMI, albumin

Bloods

• FBC: iron deficiency anaemia
• LFTs: liver metastases
• U&Es, albumin: nutritional/renal status
• CEA, CA19-9, CA72-4: tumour markers (limited sensitivity; useful for monitoring)
• HER2 status: on biopsy specimen (if positive - trastuzumab eligible)
• PD-L1 CPS, MSI/dMMR: immunotherapy eligibility

Imaging

• CT thorax/abdomen/pelvis with contrast: initial staging
• PET-CT: assess for distant metastases, response to neoadjuvant therapy
• Endoscopic ultrasound (EUS): T-staging and lymph node assessment
• Staging laparoscopy + peritoneal washings: essential before curative surgery - detects occult peritoneal disease in ~20% with normal CT

Special Tests

• Molecular profiling: HER2, PD-L1, MSI, FGFR2, Claudin 18.2 - guide targeted therapy
• Hereditary cancer gene testing: CDH1 if diffuse gastric cancer <50 years or family history

Non-pharmacological

• Upper GI cancer MDT discussion: all cases
• Nutritional support: dietitian, NG/NJ feeding or parenteral nutrition if needed
• Pre-habilitation: exercise and nutritional optimisation before surgery
• Psychological support: cancer nurse specialist

Pharmacological

• Perioperative chemotherapy (curative intent):
  • FLOT (5-FU, leucovorin, oxaliplatin, docetaxel): 4 cycles pre-op + 4 cycles post-op - current standard (FLOT4 trial)
  • Previously ECF/ECX (MAGIC trial)
• Trastuzumab: add to chemotherapy if HER2-positive (IHC 3+ or FISH+) - ToGA trial
• Nivolumab + chemotherapy: first-line for advanced/metastatic with CPS ≥5 (CheckMate 649)
• Palliative chemotherapy: FOLFOX, capecitabine + oxaliplatin; median survival ~10-12 months
• Ramucirumab (anti-VEGFR2): second-line ± paclitaxel (RAINBOW trial)

Surgical/Interventional

• Subtotal gastrectomy: distal tumours (antrum/body) with 5 cm proximal margin
• Total gastrectomy: proximal tumours, linitis plastica, diffuse type
• D2 lymphadenectomy: standard of care (≥16 lymph nodes for adequate staging)
• Endoscopic resection (EMR/ESD): for early gastric cancer (T1a, well-differentiated, <2 cm, no ulceration)
• Palliative stenting: for GOJ obstruction
• Palliative bypass/jejunostomy: for gastric outlet obstruction

Referral Criteria

• 2WW referral: alarm features per NICE NG12
• All confirmed gastric cancers to upper GI cancer MDT
• Genetics referral if diffuse gastric cancer <50 years or family history (CDH1 testing)

Overall 5-year survival is approximately 20%. Stage-dependent: Stage IA ~70-80%, Stage IB ~50-60%, Stage II ~30-40%, Stage III ~10-20%, Stage IV <5%. FLOT perioperative chemotherapy improved median overall survival from 35 to 50 months compared to ECF/ECX. Complete pathological response to neoadjuvant chemotherapy occurs in ~15-20%. Linitis plastica/signet ring cell histology carries a particularly poor prognosis. Hereditary diffuse gastric cancer (CDH1 mutation carriers) has lifetime gastric cancer risk of ~70% - prophylactic total gastrectomy recommended.

Gastric Cancer Staging (Simplified TNM 8th Edition)

Key Trials

Key Facts

Coeliac disease is a systemic autoimmune disorder triggered by ingestion of gluten (found in wheat, barley, rye) in genetically susceptible individuals. It causes inflammation and villous atrophy in the small intestine, leading to malabsorption.

Epidemiology

Prevalence is approximately 1% in the UK (1 in 100), but up to 75% remain undiagnosed ("coeliac iceberg"). Female:male ratio is 2:1. Can present at any age - bimodal distribution with peaks in childhood (after weaning) and 40-60 years. First-degree relatives have 10% prevalence. More common in Northern European populations.

Aetiology

• Genetic: HLA-DQ2 (present in ~95% of coeliac patients) and HLA-DQ8 (~5%). These are necessary but not sufficient - 30-40% of the general population carry HLA-DQ2/DQ8 but only 1% develop coeliac disease
• Environmental trigger: gluten (gliadin peptides from wheat, secalins from rye, hordeins from barley). Oats are tolerated by most coeliacs unless contaminated
• Other factors: early childhood infections, timing of gluten introduction, gut microbiome

Pathophysiology

Gliadin peptides resist complete enzymatic digestion. Deamidated gliadin peptides are presented by HLA-DQ2/DQ8 on antigen-presenting cells to CD4+ T cells. This triggers a Th1-mediated immune response causing:

1. Intraepithelial lymphocyte (IEL) infiltration: CD8+ T cells causing epithelial damage
2. Crypt hyperplasia: compensatory proliferation
3. Villous atrophy: progressive destruction of villi → reduced absorptive surface area
4. Autoantibody production: anti-tTG and anti-endomysial antibodies (markers used for diagnosis)

The resulting malabsorption affects multiple nutrients: iron (duodenum), folate (jejunum), fat-soluble vitamins (A, D, E, K), calcium, and B12 (terminal ileum if extensive disease).

Classical Presentation

• Chronic diarrhoea (pale, bulky, malodorous - steatorrhoea)
• Bloating and abdominal distension
• Weight loss/failure to thrive (children)
• Fatigue

Non-classical/Atypical Presentation (increasingly recognised)

• Iron deficiency anaemia (most common presenting feature in adults)
• Unexplained fatigue
• Osteoporosis/osteomalacia (vitamin D/calcium malabsorption)
• Mouth ulcers (aphthous stomatitis)
• Elevated liver enzymes (unexplained transaminitis)
• Infertility/recurrent miscarriage
• Peripheral neuropathy
• Depression

Dermatitis Herpetiformis

• Intensely itchy vesicular rash on extensor surfaces (elbows, knees, buttocks)
• "Skin manifestation" of coeliac disease
• Granular IgA deposits on skin biopsy (dermal papillae)

Red Flags

• Unintentional weight loss despite GFD (non-responsive coeliac - consider lymphoma)
• New abdominal pain/obstruction in known coeliac (EATL)
• Persistent symptoms despite strict GFD >12 months (refractory coeliac disease)
• Severe malnutrition or hypoalbuminaemia

Bedside

• Ensure patient is eating gluten: must have consumed gluten-containing food for ≥6 weeks before testing (ideally ≥1 portion/day)

Bloods

• tTG-IgA: first-line serological test - sensitivity/specificity >95%
• Total IgA: 2-3% of coeliacs have IgA deficiency (false-negative tTG-IgA)
• If IgA deficient: request IgG-based tests (tTG-IgG, deamidated gliadin peptide IgG - DGP-IgG)
• Endomysial antibodies (EMA-IgA): confirmatory test - very high specificity (~99%)
• FBC: iron deficiency anaemia, folate deficiency (macrocytosis), mixed picture
• Ferritin, folate, B12: nutritional deficiency assessment
• Calcium, vitamin D, PTH: bone metabolism
• LFTs: unexplained transaminitis (resolves with GFD)
• Thyroid function: associated autoimmune thyroiditis
• HLA-DQ2/DQ8: negative result virtually excludes coeliac disease (useful in diagnostic uncertainty, patients already on GFD)

Imaging

• Not routinely required for diagnosis
• DEXA scan: baseline bone density at diagnosis (osteoporosis screening)

Special Tests

• OGD with duodenal biopsies: gold standard - ≥4 biopsies from D2 + ≥1 from D1 (bulb)

• Coeliac UK serology pathway: in adults with strongly positive tTG-IgA (≥10x ULN) + positive EMA, diagnosis may be made without biopsy (ESPGHAN criteria increasingly adopted in adults)

Non-pharmacological

• Lifelong strict gluten-free diet (GFD): exclude wheat, barley, rye; oats tolerated by most if uncontaminated. Expert dietitian essential
• Coeliac UK membership: food labelling guidance, GF prescription products
• Gluten-free prescriptions: available on NHS for staple items (bread, pasta, flour)
• Nutritional supplementation: iron, folate, calcium, vitamin D as needed
• Pneumococcal vaccination: functional hyposplenism in coeliac disease
• Annual review: symptoms, adherence, tTG-IgA (should normalise), FBC, ferritin, folate, B12, calcium, vitamin D, LFTs, thyroid function

Pharmacological

• Correct nutritional deficiencies: ferrous sulphate 200 mg BD/TDS, folic acid 5 mg OD, calcium/vitamin D, B12 injections if deficient
• Dapsone 50-100 mg OD: for dermatitis herpetiformis (with GFD)
• Refractory coeliac disease (RCD): type I - budesonide 9 mg OD, azathioprine; type II - consider cladribine or autologous stem cell transplant (specialist centres)

Surgical/Interventional

• Not routinely indicated
• Surgery may be needed for EATL or small bowel lymphoma complicating coeliac disease

Referral Criteria

• Gastroenterology referral for all new diagnoses for biopsy confirmation and GFD education
• Specialist dietitian referral at diagnosis (essential)
• DEXA scan: at diagnosis and repeat if abnormal
• Suspect refractory coeliac disease if persistent symptoms despite strict GFD >12 months → specialist centre referral

Most patients achieve complete symptomatic and histological remission on a strict GFD. Villous atrophy typically resolves within 6-24 months. Serological markers normalise within 6-12 months. Untreated coeliac disease increases risk of: enteropathy-associated T-cell lymphoma (EATL - 6-10x risk, but absolute risk still low), small bowel adenocarcinoma, osteoporotic fractures, and adverse pregnancy outcomes. Strict GFD adherence reduces cancer risk to near-population levels. Refractory coeliac disease type II has a 50% 5-year risk of progression to EATL.

Marsh Classification

Conditions Warranting Coeliac Screening (NICE NG20)

Key Facts

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI) characterised by chronic abdominal pain associated with altered bowel habit, without identifiable organic pathology. It is one of the commonest conditions in primary care.

Epidemiology

IBS affects 10-15% of the UK adult population. Female:male ratio is approximately 2:1. Peak onset is 20-40 years. It accounts for 25-50% of gastroenterology outpatient referrals. Only ~30% of sufferers consult a doctor. IBS significantly impairs quality of life - comparable to IBD and depression in impact.

Aetiology

IBS is multifactorial:

• Gut-brain axis dysfunction: altered central processing of visceral signals (visceral hypersensitivity)
• Post-infectious: 10-15% develop post-infectious IBS after gastroenteritis (Campylobacter, Salmonella, norovirus)
• Psychological factors: anxiety, depression, childhood adversity, stress (bidirectional gut-brain interaction)
• Gut microbiome alteration: dysbiosis, small intestinal bacterial overgrowth
• Dietary triggers: FODMAPs (fermentable oligo-, di-, monosaccharides and polyols), lactose, caffeine, alcohol
• Genetic: modest familial aggregation

Pathophysiology

• Visceral hypersensitivity: lowered pain threshold in the gut - rectal balloon distension studies show pain at lower volumes
• Altered motility: accelerated transit in IBS-D, delayed transit in IBS-C
• Mucosal immune activation: increased mast cells, T lymphocytes in mucosa (especially post-infectious IBS)
• Serotonin (5-HT) dysregulation: 95% of body serotonin is in the gut - increased 5-HT in IBS-D, decreased in IBS-C
• Central sensitisation: altered brain processing of gut signals (fMRI studies show increased activation of pain processing areas)

Typical Presentation

• Recurrent abdominal pain/discomfort: often lower abdominal, colicky; related to defaecation (may improve or worsen)
• Altered bowel habit: diarrhoea, constipation, or alternating; urgency; incomplete evacuation
• Bloating/abdominal distension: common, often worse through the day
• **Symptoms often triggered by food, stress, or menstruation

Subtypes (Rome IV)

• IBS-C: hard/lumpy stools ≥25% of bowel movements; loose stools <25%
• IBS-D: loose/watery stools ≥25%; hard stools <25%
• IBS-M: both hard and loose stools ≥25% each

Red Flags (Not IBS - Investigate Further)

• Age >50 with new symptoms
• Unexplained weight loss
• Rectal bleeding
• Family history of bowel/ovarian cancer
• Anaemia
• Nocturnal symptoms waking from sleep
• Palpable abdominal/rectal mass
• Raised inflammatory markers (CRP, calprotectin)

Bedside

• History: Rome IV criteria assessment, dietary triggers, psychological comorbidity, medication review
• Examination: usually normal; mild abdominal tenderness; check for mass, organomegaly

Bloods

• FBC: exclude anaemia
• CRP/ESR: normal in IBS (raised suggests IBD/other organic disease)
• tTG-IgA + total IgA: exclude coeliac disease (NICE CG61)
• TFTs: if clinical suspicion of thyroid disease
• CA-125: if ovarian cancer considered (women >50 with bloating)

Stool Tests

• Faecal calprotectin: <100 μg/g effectively excludes IBD (NPV >95%); key investigation in distinguishing IBS from IBD (NICE DG11)
• FIT (faecal immunochemical test): if colorectal cancer concern
• Stool cultures: if infective/post-infective aetiology

Imaging/Endoscopy

• NOT routinely required for IBS diagnosis in young patients without red flags
• Colonoscopy: if red flags, age >50, raised calprotectin, failed empirical treatment

Special Tests

• SeHCAT scan: bile acid malabsorption (especially IBS-D)
• Hydrogen breath tests: lactose intolerance, SIBO
• Anorectal physiology: if constipation with suspected pelvic floor dyssynergia

Non-pharmacological

• Lifestyle: regular meals, adequate hydration (8 cups/day), regular exercise, stress management
• Dietary advice (first-line):
  • General: reduce caffeine, alcohol, fizzy drinks, high-fat foods, limit fresh fruit to 3 portions/day
  • Low FODMAP diet: supervised by dietitian; elimination for 4-8 weeks then staged reintroduction; evidence of benefit in ~50-75% (Staudacher et al., 2017)
  • Fibre: soluble fibre (ispaghula husk) may help IBS-C; insoluble fibre (bran) often worsens symptoms
• Psychological therapy: CBT (face-to-face or digital), gut-directed hypnotherapy (evidence from Manchester group), mindfulness - effective for refractory IBS

Pharmacological

• IBS-C:
  • Ispaghula husk (Fybogel) 1 sachet BD
  • Linaclotide 290 mcg OD (guanylate cyclase-C agonist - NICE TA)
  • Lubiprostone 8 mcg BD (if linaclotide ineffective)
  • PEG laxatives (macrogol) - less evidence specifically for IBS-C
• IBS-D:
  • Loperamide 2-4 mg PRN (max 16 mg/day)
  • Cholestyramine 4 g BD-QDS trial (bile acid malabsorption)
  • Eluxadoline 100 mg BD (mixed opioid agonist/antagonist - limited UK use)
• Pain/global symptoms:
  • Antispasmodics: mebeverine 135 mg TDS, hyoscine butylbromide 10 mg TDS, peppermint oil capsules 187 mg TDS
  • TCAs (first-line for refractory pain per NICE): amitriptyline 10-30 mg ON - start low, increase slowly; NNT ~4 for IBS
  • SSRIs: fluoxetine 20 mg OD, citalopram 10-20 mg OD - for IBS-D with anxiety/depression; less evidence than TCAs for pain

Surgical/Interventional

• Not indicated for IBS
• Biofeedback for pelvic floor dyssynergia (if contributing to IBS-C)

Referral Criteria

• Gastroenterology: red flags, diagnostic uncertainty, refractory symptoms despite treatment
• Dietitian: FODMAP diet guidance
• Psychological services: CBT, gut-directed hypnotherapy for refractory IBS

IBS is a chronic relapsing condition. Most patients have ongoing symptoms over many years, although severity fluctuates. Approximately 50% of patients improve over time. IBS does not increase mortality or risk of IBD/cancer. Quality of life is significantly impaired - work absenteeism, social isolation, healthcare utilisation are substantial. Low FODMAP diet improves symptoms in 50-75%. TCAs improve global IBS symptoms in ~60% (NNT 4). Psychological therapies have durable benefit.

Rome IV Diagnostic Criteria for IBS

Bristol Stool Chart and IBS Subtypes

Key Facts

Crohn's disease is a chronic, relapsing inflammatory bowel disease characterised by transmural, granulomatous inflammation that can affect any part of the GI tract. Along with ulcerative colitis, it constitutes the two main forms of IBD.

Epidemiology

UK prevalence is approximately 145 per 100,000 (rising). Incidence is ~7-10 per 100,000 per year. Peak onset 15-30 years (second smaller peak at 50-70 years). Slight female predominance. Higher incidence in Northern European and North American populations. Incidence is rising in previously low-incidence populations (Asia, Africa).

Aetiology

Multifactorial: genetic susceptibility + environmental triggers + immune dysregulation + altered microbiome:

• Genetics: >200 susceptibility loci identified; NOD2/CARD15 (chromosome 16) - first Crohn's gene identified; ATG16L1 (autophagy); IL23R
• Smoking: strongest modifiable risk factor (2x risk, doubles relapse rate)
• Appendicectomy: may increase risk (opposite to UC)
• Microbiome: reduced diversity (particularly Firmicutes); increased Enterobacteriaceae
• NSAIDs: may trigger flares

Pathophysiology

Genetically determined defects in innate immunity (NOD2 - pattern recognition receptor for muramyl dipeptide) and autophagy lead to impaired handling of intraluminal bacteria. This triggers an excessive adaptive immune response with Th1/Th17 polarisation, producing TNF-α, IL-12, IL-23, and IFN-γ. Transmural inflammation causes the hallmark features: deep ulceration, non-caseating granulomata, fibrosis (strictures), and sinus tract formation (fistulae).

Typical Presentation

• Chronic diarrhoea (usually non-bloody, unlike UC)
• Abdominal pain (often RIF - terminal ileal disease)
• Weight loss and malnutrition
• Fatigue
• Low-grade fever

Disease Location-Specific Features

• Ileal: RIF pain, diarrhoea, B12/bile acid malabsorption, risk of stricture/obstruction
• Colonic: diarrhoea (may be bloody), similar to UC but rectal sparing common
• Perianal: fistulae, abscesses, skin tags - present in 30-40%
• Upper GI: mouth ulcers, dysphagia, gastric outlet obstruction (rare)

Extra-Intestinal Manifestations

• Musculoskeletal: peripheral arthropathy (Type I - large joints, correlates with disease activity; Type II - small joints, independent), sacroiliitis, ankylosing spondylitis (HLA-B27)
• Skin: erythema nodosum (correlates with disease activity), pyoderma gangrenosum (independent)
• Eyes: anterior uveitis, episcleritis
• Hepatobiliary: PSC (rare - more common in UC), gallstones (bile acid malabsorption)
• Renal: oxalate stones (fat malabsorption → increased oxalate absorption)

Red Flags

• Acute abdominal pain with distension (obstruction/perforation)
• Perianal sepsis (abscess requiring drainage)
• Significant GI bleeding
• High-output fistula (dehydration, electrolyte derangement)
• Nutritional failure (BMI <18.5, hypoalbuminaemia)

Bedside

• Stool: faecal calprotectin (>200 μg/g strongly suggests IBD), stool cultures (exclude infection including C. difficile)
• Perianal examination: skin tags, fistula openings, abscess

Bloods

• FBC: anaemia (iron, B12, folate deficiency), raised platelets (inflammation)
• CRP/ESR: disease activity markers
• Albumin: nutritional status and disease severity
• U&Es, LFTs: baseline; LFTs for PSC screening
• Iron studies, B12, folate: nutritional deficiencies
• TPMT/NUDT15: before starting thiopurines (azathioprine/mercaptopurine)

Imaging

• MR enterography (MRE): gold standard for small bowel assessment - strictures, fistulae, inflammation, abscess
• Pelvic MRI: perianal disease assessment (fistula mapping)
• CT abdomen: if acute presentation (perforation, abscess, obstruction)
• Abdominal USS: thickened bowel wall, abscess detection

Special Tests

• Ileocolonoscopy + biopsies: gold standard for diagnosis - assess from terminal ileum to rectum
  • Findings: aphthous ulcers, deep serpiginous ulcers, cobblestoning, skip lesions, relative rectal sparing
  • Histology: non-caseating granulomata (30-50%), transmural inflammation, lymphoid aggregates
• Upper GI endoscopy: if upper GI symptoms
• Capsule endoscopy: small bowel assessment if MRE inconclusive (ensure no stricture first)
• Montreal classification: age at diagnosis (A1/A2/A3), location (L1-L4), behaviour (B1-B3 + p for perianal)

Non-pharmacological

• Smoking cessation: most important modifiable factor - doubles relapse rate if continues
• Nutritional support: dietitian involvement; correct deficiencies
• Exclusive enteral nutrition (EEN): first-line for inducing remission in children/adolescents (equal to steroids); used adjunctively in adults
• MDT approach: gastroenterologist, surgeon, dietitian, IBD nurse specialist, psychologist

Pharmacological

• Inducing remission:
  • Mild-moderate: budesonide 9 mg OD for 8 weeks (ileal/right-sided); oral prednisolone 40 mg OD tapering over 8 weeks (extensive/severe)
  • Moderate-severe/steroid-dependent: anti-TNF therapy (infliximab 5 mg/kg IV at 0, 2, 6 weeks then 8-weekly; OR adalimumab 160 mg then 80 mg then 40 mg EOW)
  • Refractory: vedolizumab (anti-α4β7 integrin), ustekinumab (anti-IL12/23), risankizumab (anti-IL23)
• Maintaining remission:
  • Thiopurines: azathioprine 2-2.5 mg/kg/day or mercaptopurine 1-1.5 mg/kg/day (check TPMT/NUDT15)
  • Methotrexate: 15-25 mg/week SC/IM (second-line maintenance)
  • Biologics: continued anti-TNF, vedolizumab, ustekinumab - most effective for maintaining remission
• Perianal disease: antibiotics (metronidazole 400 mg TDS + ciprofloxacin 500 mg BD), anti-TNF (infliximab most evidence), seton drainage
• 5-ASAs (mesalazine): limited role in Crohn's (unlike UC); may have modest benefit in mild colonic Crohn's

Surgical/Interventional

• Surgery needed in ~50% within 10 years of diagnosis
• Ileocaecal resection: for refractory ileal disease or stricture (LIR!C trial - comparable to infliximab for limited ileocaecal Crohn's)
• Stricturoplasty: bowel-preserving option for short strictures
• Abscess drainage: percutaneous or surgical
• Seton insertion: for perianal fistulae
• Defunctioning stoma: for severe perianal or colonic disease

Referral Criteria

• All IBD to gastroenterology for specialist management
• IBD nurse specialist for ongoing support
• Surgical referral for complications (stricture, abscess, fistula)
• Fertility/obstetric counselling before pregnancy (optimise disease control)

Crohn's disease is a lifelong condition with relapsing-remitting course. ~50% require surgery within 10 years of diagnosis. Post-operative recurrence is common (~50% endoscopic recurrence at 1 year). Smoking cessation reduces relapse by 50%. Biologics have significantly improved outcomes - reduced hospitalisation and surgery rates. Mortality is slightly increased compared to general population (standardised mortality ratio 1.2-1.5). Colorectal cancer risk is increased in Crohn's colitis (similar magnitude to UC - surveillance colonoscopy recommended).

Montreal Classification

Crohn's vs Ulcerative Colitis

Key Facts

Ulcerative colitis is a chronic relapsing-remitting inflammatory bowel disease characterised by diffuse mucosal inflammation of the colon, always involving the rectum and extending proximally in a continuous fashion.

Epidemiology

UK prevalence is approximately 240 per 100,000 (higher than Crohn's). Incidence is ~10-12 per 100,000 per year. Peak onset 15-25 years (second smaller peak at 55-65). Equal sex distribution. More common in non-smokers and ex-smokers (smoking is paradoxically protective). Higher in Northern European, North American, and Jewish populations.

Aetiology

• Genetics: >200 susceptibility loci; HLA-DRB1; IL-10; weaker genetic component than Crohn's
• Smoking: paradoxically PROTECTIVE; disease often presents/flares after smoking cessation
• Appendicectomy: protective effect (~70% reduced risk)
• Microbiome: reduced diversity, decreased Firmicutes
• Environmental: stress, NSAIDs, infections can trigger flares

Pathophysiology

UC involves a dysregulated mucosal immune response with Th2 polarisation (IL-5, IL-13 predominant). Epithelial barrier dysfunction allows bacterial translocation, triggering NF-κB-mediated inflammation. Unlike Crohn's, inflammation is confined to the mucosa and submucosa, with crypt abscesses and goblet cell depletion being characteristic histological findings. Continuous inflammation from the rectum proximally (no skip lesions) distinguishes UC from Crohn's colitis.

Mild UC

• <4 bloody stools/day
• No systemic features
• Normal inflammatory markers

Moderate UC

• 4-6 bloody stools/day
• Mild systemic features
• Mildly raised CRP

Acute Severe UC (Truelove & Witts Criteria)

• ≥6 bloody stools/day PLUS ≥1 of:
  • Pulse >90 bpm
  • Temperature >37.8°C
  • Hb <105 g/L
  • ESR >30 mm/hr or CRP >30 mg/L
• Medical emergency - requires hospital admission

Extra-Intestinal Manifestations

• Similar to Crohn's but PSC is more common in UC (up to 5%)
• Erythema nodosum, pyoderma gangrenosum, anterior uveitis
• Peripheral arthropathy, sacroiliitis/AS
• VTE risk increased (especially during flares)

Red Flags

• Acute severe UC (Truelove & Witts criteria)
• Toxic megacolon (colonic dilatation >6 cm + systemic toxicity)
• Perforation (acute abdomen, free air)
• Massive haemorrhage

Bedside

• Stool: faecal calprotectin (>200 strongly suggests IBD), stool cultures + C. difficile toxin (exclude infective cause)
• Abdominal X-ray: if acute severe UC - assess for toxic megacolon (>6 cm), mucosal islands, free air

Bloods

• FBC: anaemia, raised platelets
• CRP/ESR: disease activity (raised CRP is poor prognostic marker in acute severe UC)
• Albumin: low in severe disease (prognostic)
• U&Es, LFTs: baseline; LFTs for PSC screening
• TPMT/NUDT15: before thiopurines

Imaging

• AXR: toxic megacolon assessment in acute severe UC
• CT abdomen: if complications suspected (perforation, abscess)

Special Tests

• Colonoscopy + biopsies: gold standard - continuous inflammation from rectum, loss of vascular pattern, mucosal erythema/friability, pseudopolyps
  • Histology: crypt abscesses, crypt architectural distortion, goblet cell depletion, chronic inflammatory infiltrate
• Flexible sigmoidoscopy: safer than full colonoscopy in acute severe UC
• Travis (Oxford) criteria: for predicting steroid failure in acute severe UC - day 3: stool frequency >8/day OR CRP >45 mg/L + stool frequency 3-8/day → 85% risk of colectomy

Non-pharmacological

• MDT approach: gastroenterologist, IBD nurse, dietitian, surgeon
• VTE prophylaxis: LMWH for all inpatients with active UC
• Nutritional support: iron replacement, dietitian review

Pharmacological

• Inducing remission (mild-moderate):
  • 5-ASA (mesalazine): topical (rectal foam/suppository) for proctitis; oral mesalazine 2.4-4.8 g/day for more extensive disease (NICE NG130)
  • If 5-ASA insufficient: oral prednisolone 40 mg/day tapering over 8 weeks
• Acute severe UC (inpatient):
  • IV hydrocortisone 100 mg QDS + VTE prophylaxis + stool chart + daily bloods
  • Assess response at day 3 (Travis/Oxford criteria)
  • If failing IV steroids: rescue therapy - infliximab 5 mg/kg IV (ACT 1/2 trials) OR ciclosporin 2 mg/kg/day IV (Lichtiger protocol)
  • If rescue fails: emergency subtotal colectomy
• Maintaining remission:
  • 5-ASA (mesalazine): first-line maintenance; oral ± topical
  • Thiopurines: azathioprine 2-2.5 mg/kg/day - if steroid-dependent or frequent relapse
  • Biologics: infliximab, adalimumab, vedolizumab (anti-α4β7), tofacitinib (JAK inhibitor), upadacitinib, ozanimod (S1P modulator) - for moderate-severe refractory UC

Surgical/Interventional

• Proctocolectomy + ileal pouch-anal anastomosis (IPAA/J-pouch): curative; gold standard elective surgery
• Subtotal colectomy + end ileostomy: emergency operation for toxic megacolon, perforation, or failed medical rescue
• Subsequent completion proctectomy ± IPAA
• Pouchitis: common complication of IPAA (up to 50%) - treat with metronidazole 400 mg TDS or ciprofloxacin 500 mg BD

Referral Criteria

• All IBD to gastroenterology
• Urgent surgical review: acute severe UC failing medical therapy, toxic megacolon
• Colorectal cancer surveillance from 8 years post-diagnosis

UC follows a relapsing-remitting course. ~50% are in remission at any time. 20% will require colectomy within 10 years of diagnosis. Acute severe UC carries ~1% mortality with modern management. Toxic megacolon has ~5-10% mortality. Colorectal cancer risk is increased after 8-10 years of extensive colitis (~1% per year cumulative risk in pancolitis). Regular surveillance colonoscopy reduces cancer mortality. Proctocolectomy is curative but IPAA-related complications (pouchitis, reduced fertility in women) must be considered.

Truelove & Witts Severity Classification

Acute Severe UC Management Timeline

Key Facts

Colorectal cancer (CRC) is one of the most common and deadly cancers in the UK, but outcomes are significantly better with early detection. The NHS bowel cancer screening programme and FIT-based triage have improved stage at diagnosis.

Epidemiology

CRC is the 3rd most common cancer in the UK (~42,900 cases/year) and the 2nd most common cause of cancer death (~16,800/year). Lifetime risk is approximately 1 in 15. Incidence increases sharply after age 50. Male:female ratio ~1.2:1. Incidence is rising in younger adults (<50 years) in the UK and globally.

Aetiology

Sporadic (~75%):

• Age >50, adenomatous polyps, obesity, physical inactivity, processed/red meat, smoking, alcohol, diabetes

Hereditary (~5-10%):

• Lynch syndrome (HNPCC): ~3-5% of CRC; autosomal dominant; mutations in MMR genes (MLH1, MSH2, MSH6, PMS2); lifetime CRC risk ~50-80%
• Familial adenomatous polyposis (FAP): APC gene; >100 adenomas; near 100% CRC risk by age 40 without surgery
• MUTYH-associated polyposis (MAP): autosomal recessive
• Peutz-Jeghers, juvenile polyposis: hamartomatous polyposis syndromes

Inflammatory (~1%):

• Ulcerative colitis/Crohn's colitis (>8-10 years of extensive disease)

Pathophysiology

Right-Sided (Caecum/Ascending Colon)

• Iron deficiency anaemia (often the only finding)
• Vague abdominal pain (RIF)
• Palpable RIF mass
• Weight loss
• Occult bleeding (rarely overt PR bleeding)

Left-Sided (Descending/Sigmoid Colon)

• Change in bowel habit (usually increased frequency/looser stools)
• Rectal bleeding (often mixed with stool)
• Colicky abdominal pain
• Tenesmus
• May present acutely with large bowel obstruction

Rectal Cancer

• Rectal bleeding (bright red, on/mixed with stool)
• Mucus PR
• Tenesmus and urgency
• Sensation of incomplete evacuation

Red Flags (NICE NG12 - 2WW Referral)

• Age ≥40 with unexplained weight loss + abdominal pain
• Age ≥50 with unexplained rectal bleeding
• Age ≥60 with change in bowel habit or iron deficiency anaemia
• Rectal/abdominal mass
• FIT ≥10 μg Hb/g in symptomatic patients

Bedside

• DRE: palpable rectal mass (~40% of rectal cancers within reach)
• FIT (faecal immunochemical test): ≥10 μg Hb/g in symptomatic patients triggers referral; ≥120 μg Hb/g in screening

Bloods

• FBC: iron deficiency anaemia
• LFTs: liver metastases
• CEA (carcinoembryonic antigen): baseline for post-operative monitoring (not diagnostic)
• U&Es: baseline

Imaging

• CT thorax/abdomen/pelvis: staging (TNM)
• MRI pelvis: essential for rectal cancer - local staging (T and N), mesorectal fascia involvement, EMVI status
• PET-CT: if oligometastatic disease being considered for resection
• CT colonography: alternative to colonoscopy if incomplete or contraindicated

Special Tests

• Colonoscopy + biopsy: gold standard diagnostic investigation
• Molecular profiling: RAS/BRAF mutation, MSI/dMMR status - guide targeted therapy and immunotherapy
• Lynch syndrome screening: IHC for MMR proteins on all CRC specimens (universal screening recommended); germline testing if deficient
• CT liver: detailed assessment if hepatic metastases for potential resection

Non-pharmacological

• Colorectal cancer MDT: all cases - surgeon, oncologist, radiologist, pathologist, CNS
• Enhanced recovery after surgery (ERAS): pre-habilitation, early mobilisation, early nutrition
• Stoma counselling: if stoma likely

Pharmacological

• Adjuvant chemotherapy (Stage III - node-positive):
  • FOLFOX (5-FU, leucovorin, oxaliplatin) × 3-6 months - reduces recurrence by ~20% (MOSAIC trial)
  • Capecitabine monotherapy if oxaliplatin not tolerated (X-ACT trial)
  • Stage II: selective adjuvant chemo if high-risk features (T4, <12 nodes examined, poorly differentiated, LVI, perforation)
• Neoadjuvant for rectal cancer:
  • Long-course chemoradiotherapy (capecitabine + 45 Gy) for threatened mesorectal fascia
  • Short-course radiotherapy (25 Gy in 5 fractions) followed by surgery
  • Total neoadjuvant therapy (TNT): emerging - chemotherapy + radiotherapy before surgery (RAPIDO trial)
• Metastatic CRC:
  • FOLFOX/FOLFIRI ± bevacizumab (anti-VEGF) or cetuximab/panitumumab (anti-EGFR - RAS wild-type only)
  • Immunotherapy: pembrolizumab for MSI-high/dMMR CRC (KEYNOTE-177 trial)

Surgical/Interventional

• Right hemicolectomy: caecal/ascending colon tumours
• Left hemicolectomy: descending colon
• Sigmoid colectomy: sigmoid tumours
• Anterior resection: upper/mid rectal cancer (sphincter-preserving)
• Abdominoperineal resection (APR): low rectal cancer with permanent colostomy
• TME (total mesorectal excision): standard for rectal cancer - reduces local recurrence
• Laparoscopic/robotic surgery: standard of care where available
• Liver resection: for resectable hepatic metastases (20-40% 5-year survival)
• Emergency surgery: obstruction (stenting as bridge to surgery or Hartmann's procedure), perforation

Referral Criteria

• 2WW referral per NICE NG12 criteria (see red flags above)
• All confirmed CRC to colorectal cancer MDT
• Genetics referral if Lynch syndrome, FAP, or CRC <50 years
• Hepatobiliary MDT for liver metastases

Overall 5-year survival is approximately 55%. Stage-dependent: Stage I ~90%, Stage II ~80%, Stage III ~65%, Stage IV ~10-15%. Screen-detected CRC has significantly better stage distribution and outcomes. Adjuvant FOLFOX improves 5-year DFS from ~60% to ~73% in stage III. MSI-high/dMMR CRC has better prognosis in early stages but poorer response to 5-FU alone; responds well to immunotherapy in advanced disease. Local recurrence after TME for rectal cancer is <5%. Rising incidence in under-50s is a concern.

Dukes/TNM Staging Correlation

Key Trials

Key Facts

Colorectal polyps are abnormal growths projecting from the colonic or rectal mucosa. They are extremely common, found in ~25-30% of screening colonoscopies. While most are benign, adenomatous and sessile serrated polyps are premalignant and their detection and removal is the basis of colorectal cancer prevention.

Epidemiology

Prevalence increases with age: ~25-30% of adults >50 years have adenomatous polyps. Male predominance (1.5:1). Adenomas are found in ~40% of NHS bowel cancer screening colonoscopies. The transition from adenoma to carcinoma takes approximately 10 years in most cases.

Aetiology

• Sporadic adenomas: age, obesity, red/processed meat, smoking, alcohol, physical inactivity
• Hereditary syndromes: FAP (APC gene - AD), attenuated FAP, MUTYH-associated polyposis (AR), Lynch syndrome (MMR genes), Peutz-Jeghers (STK11 - hamartomatous), juvenile polyposis (SMAD4/BMPR1A)
• Protective factors: aspirin/NSAIDs, calcium, folate, physical activity, high-fibre diet

Pathophysiology

Adenoma-carcinoma sequence (chromosomal instability pathway - ~80% of CRC):

• KRAS activation → adenoma growth
• SMAD4/DCC loss → advanced adenoma
• TP53 loss → carcinoma

Serrated neoplasia pathway (~20% of CRC):

• Sessile serrated lesions (flat, right colon) are harder to detect endoscopically
• Account for many "interval cancers" (cancers arising between surveillance colonoscopies)

Asymptomatic (Most Common)

• Discovered incidentally at screening or diagnostic colonoscopy
• FIT-positive on bowel cancer screening

Symptomatic

• Rectal bleeding (usually occult; rarely overt)
• Iron deficiency anaemia
• Change in bowel habit (rare unless large/multiple)
• Mucous discharge (villous adenomas - may cause hypokalaemia from secretory diarrhoea)
• Rarely: intussusception (pedunculated polyps), prolapse through anus

Red Flags

• Large polyp with malignant features (hard, fixed, ulcerated)
• Multiple polyps (>10 - consider polyposis syndrome)
• Young patient (<50) with adenomas (hereditary syndrome)
• Polyp with high-grade dysplasia or invasive cancer on histology

Bedside

• DRE: may detect low rectal polyps
• FIT: may be positive (screening or symptomatic investigation)

Bloods

• FBC: iron deficiency anaemia (occult blood loss)
• U&Es: hypokalaemia (rare - secretory villous adenoma)

Imaging

• CT colonography: alternative to colonoscopy; detects polyps >6 mm with >90% sensitivity; polyps found require colonoscopic polypectomy

Special Tests

• Colonoscopy: gold standard - allows visualisation, biopsy, and polypectomy
  • Assess: number, size, morphology (Paris classification: pedunculated Ip, sessile Is, flat IIa/IIb/IIc)
  • Polypectomy: snare removal with diathermy; EMR for sessile polyps >10 mm; ESD for large flat lesions
• Histopathology: type (adenoma, serrated, hyperplastic), grade of dysplasia, completeness of excision, presence of invasive cancer
  • Haggitt classification (pedunculated malignant polyps): levels 1-4 invasion
  • Kikuchi classification (sessile malignant polyps): sm1-sm3 submucosal invasion depth
• Genetic testing: if ≥10 adenomas, or family history suggesting polyposis syndrome; APC, MUTYH, MLH1/MSH2/MSH6/PMS2

Non-pharmacological

• Polypectomy at colonoscopy: curative for most benign polyps
  • Cold snare: preferred for polyps <10 mm
  • Hot snare: for polyps 10-20 mm
  • EMR: piecemeal or en-bloc for sessile polyps >20 mm
  • ESD: en-bloc resection of large flat/early cancerous lesions at specialist centres
• Surveillance colonoscopy (BSG 2020 guideline):
  • Low risk (1-2 adenomas, <10 mm, no HGD): no surveillance or colonoscopy at 10 years
  • Intermediate risk (3-4 small adenomas OR ≥1 adenoma 10-19 mm): colonoscopy at 3 years
  • High risk (≥5 adenomas OR ≥1 adenoma ≥20 mm OR HGD): colonoscopy at 3 years; if high risk again, repeat at 3 years; if clear, extend to 5 years
  • Serrated lesions: SSL ≥10 mm or with dysplasia - surveillance at 3 years

Pharmacological

• Aspirin: chemopreventive evidence (reduces adenoma recurrence and CRC risk); routine use for prevention not currently recommended outside Lynch syndrome
• Celecoxib: reduces polyp burden in FAP but cardiovascular risk limits use

Surgical/Interventional

• Surgical resection: for polyps not amenable to endoscopic removal (size, location, suspicion of invasive cancer)
• Malignant polyp management: if T1 CRC in polyp - assess completeness of excision, invasion depth (sm level), differentiation, LVI; if high-risk features → segmental colectomy
• Prophylactic colectomy: FAP (typically ileal pouch-anal anastomosis at ~20 years of age)

Referral Criteria

• Polyposis syndrome suspected (>10 adenomas) → genetics + specialist centre
• Large complex polyps (>20 mm) → specialist EMR/ESD centre
• Malignant polyp with high-risk features → CRC MDT
• Family history meeting criteria for genetic testing

Most adenomatous polyps are cured by polypectomy. Without removal, ~5-10% of adenomas progress to cancer over ~10 years. Cancer risk increases with polyp size (0.3% for <10 mm, 5% for 10-20 mm, ~15% for >20 mm), villous histology, and high-grade dysplasia. FAP without colectomy has near 100% CRC risk by age 40. Surveillance colonoscopy after polypectomy reduces CRC incidence by ~75-90%. Malignant polyps with favourable features (sm1, well-differentiated, no LVI, complete excision) have <3% lymph node metastasis risk - polypectomy alone may be curative.

BSG Post-Polypectomy Surveillance (2020)

Hereditary Polyposis Syndromes

Key Facts

Bowel cancer screening aims to detect colorectal cancer at an earlier, more treatable stage and to prevent CRC by detecting and removing premalignant adenomatous polyps. The NHS BCSP is one of the most established cancer screening programmes in the UK.

Epidemiology

CRC screening is offered because: CRC is common (~42,900 cases/year), has a long premalignant phase (adenoma-carcinoma sequence ~10 years), effective screening tests exist, and early detection dramatically improves survival (stage I 5-year survival >90% vs stage IV ~10%). Uptake of bowel cancer screening in England is approximately 65-70% - lower in men, younger age groups, and deprived populations.

Aetiology

Screening is offered to the average-risk population. Higher-risk groups have separate surveillance pathways:

• Family history: first-degree relative with CRC <50 or 2+ first-degree relatives → earlier/more frequent colonoscopy
• Lynch syndrome: colonoscopy every 2 years from age 25
• FAP: annual sigmoidoscopy/colonoscopy from age 12-14
• IBD: surveillance colonoscopy from 8 years after onset of extensive colitis

Pathophysiology

Screening exploits the biology of the adenoma-carcinoma sequence:

• Adenomas take ~10 years to progress to cancer - screening interval of 2 years provides multiple opportunities for detection
• Adenomas and cancers bleed intermittently - FIT detects haemoglobin in stool
• Polypectomy at screening colonoscopy interrupts the adenoma-carcinoma sequence, preventing cancer development
• Earlier stage detection at screening → better prognosis and less intensive treatment needed

Screening Pathway

• Invitation: automatic letter with FIT kit sent to home address; ages 56-74 every 2 years
• FIT completion: collect small stool sample at home; return by post
• Results: within 2 weeks; normal (<120 μg Hb/g) - routine recall in 2 years; abnormal (≥120 μg Hb/g) - invitation for screening colonoscopy
• Specialist screening practitioner (SSP) consultation: pre-colonoscopy assessment

Screening Colonoscopy Outcomes

• No abnormality: return to routine screening
• Adenomatous polyps: polypectomy + enter surveillance programme
• Cancer detected: staging and MDT referral
• Incomplete colonoscopy: CT colonography offered

Red Flags (Outside Screening)

• Symptomatic patients should NOT wait for screening - investigate per NICE NG12
• FIT can be used as a triage tool in symptomatic patients (threshold ≥10 μg Hb/g - NICE DG30)
• Screening is for asymptomatic average-risk population only

Bedside

• FIT (faecal immunochemical test): quantitative measurement of human haemoglobin; specific to lower GI bleeding (unlike guaiac which detected any haem)
• Advantages over guaiac FOBt: single sample, no dietary restrictions, automated analysis, quantitative result, higher sensitivity for CRC (~95% vs ~60%)

Bloods

• FBC: iron deficiency anaemia (in symptomatic patients)
• CEA: not used for screening - used for monitoring after treatment

Imaging

• CT colonography: alternative if colonoscopy incomplete, contraindicated, or patient preference; detects polyps >6 mm with >90% sensitivity

Special Tests

• Colonoscopy: gold standard investigation following positive FIT; allows biopsy and polypectomy
• Flexible sigmoidoscopy: previously used in bowel scope screening (one-off at age 55); being phased out
• Capsule endoscopy: for complete colonic assessment if colonoscopy not possible (emerging role)
• ctDNA (circulating tumour DNA): emerging blood-based screening technology under investigation (e.g. multi-cancer early detection tests)

Non-pharmacological

• Population-level screening: FIT every 2 years, ages 56-74 (extending to 50-74)
• Informed choice: screening information leaflet with invitation; consent required
• Quality assurance: BCSP has rigorous QA standards for colonoscopy (caecal intubation rate >95%, adenoma detection rate >25%, polyp retrieval rate >90%)
• Address health inequalities: targeted interventions to improve uptake in underserved populations (GP endorsement, text reminders, translated materials)

Pharmacological

• Aspirin chemoprevention: evidence of CRC risk reduction (~20% with regular aspirin use); not currently recommended as primary prevention for average-risk population but considered in Lynch syndrome (CaPP2 trial - aspirin 600 mg/day reduced CRC in Lynch syndrome)

Surgical/Interventional

• Polypectomy: at screening colonoscopy - curative for adenomas
• Surgery: if screen-detected cancer (see CRC management)
• Post-polypectomy surveillance: per BSG guideline based on risk stratification

Referral Criteria

• Positive screening FIT → automatic referral to screening centre for colonoscopy
• Symptomatic patients with FIT ≥10 → 2WW referral per NICE NG12
• High-risk family history → genetics/high-risk surveillance programme
• Lynch syndrome → 2-yearly colonoscopy from age 25

Bowel cancer screening reduces CRC mortality by approximately 25% in participants. The UK Flexible Sigmoidoscopy Trial showed 30% reduction in CRC incidence and 35% reduction in CRC mortality with one-off sigmoidoscopy at 55. Screen-detected cancers have significantly better stage distribution: >70% Dukes A/B vs ~50% in symptomatic presentation. 5-year survival for screen-detected CRC is approximately 75-80% vs ~55% overall. National uptake of ~65-70% means significant numbers are not benefiting - improving uptake is a key public health priority.

NHS BCSP Key Parameters

High-Risk Surveillance Pathways

Wilson & Jungner Screening Criteria Applied to CRC

Key Facts

Diverticular disease is one of the most common conditions of the large intestine in Western populations. The vast majority of people with diverticula remain asymptomatic (diverticulosis). A minority develop symptomatic disease or complications.

Epidemiology

Prevalence increases with age: <5% under 40, ~30% aged 40-60, >50% over 70. Equal sex distribution. Western populations have much higher prevalence than African and Asian populations (attributed to low-fibre diet). Complications requiring hospitalisation are increasing.

Aetiology

• Low-fibre diet: most important modifiable risk factor - reduces stool bulk, increases colonic transit time and intraluminal pressure
• Age: progressive weakening of colonic wall, loss of elastin
• Connective tissue disorders: Ehlers-Danlos, Marfan (diverticulosis at younger age)
• Medications: NSAIDs, corticosteroids, opioids (increase complication risk)

Pathophysiology

Symptomatic Diverticular Disease

• Intermittent LIF pain ("left-sided appendicitis")
• Altered bowel habit (constipation or diarrhoea)
• Bloating
• Often overlaps with IBS symptoms

Acute Diverticulitis (see separate entry)

• Constant LIF pain, fever, nausea
• LIF tenderness ± guarding

Diverticular Bleeding

• Sudden painless massive PR bleeding (maroon/bright red)
• Usually self-limiting (80%)
• Can cause haemodynamic instability if severe

Red Flags

• Peritonism (rigid abdomen - perforation)
• Pneumaturia/faecaluria (colovesical fistula)
• Large bowel obstruction symptoms (absolute constipation, distension, vomiting)
• Massive PR bleeding with haemodynamic instability

Bedside

• Observations: pulse, BP, temperature
• Abdominal examination: LIF tenderness, guarding, mass
• DRE: PR bleeding assessment

Bloods

• FBC: WCC (infection), Hb (bleeding)
• CRP: raised in diverticulitis
• U&Es, LFTs: baseline
• Lactate: if concern for ischaemia/sepsis
• Group and save/crossmatch: if significant bleeding

Imaging

• CT abdomen/pelvis with contrast: gold standard for acute diverticulitis - pericolic fat stranding, wall thickening, abscess, perforation
• Hinchey classification (CT-based staging of diverticulitis complications): I (pericolic abscess), II (pelvic/distant abscess), III (purulent peritonitis), IV (faecal peritonitis)
• Colonoscopy: NOT in acute phase (perforation risk); perform 6-8 weeks after acute episode to exclude malignancy
• CT colonography: alternative for excluding malignancy post-episode

Special Tests

• CT angiography/mesenteric angiography: for active diverticular bleeding if not self-limiting
• Capsule endoscopy: rarely needed; if diagnostic uncertainty

Non-pharmacological

• Asymptomatic diverticulosis: reassurance; high-fibre diet (30 g/day), adequate hydration, regular exercise
• Symptomatic diverticular disease: high-fibre diet (introduce gradually to minimise bloating), weight management

Pharmacological

• Symptomatic disease: bulk-forming laxatives (ispaghula husk) if constipation; antispasmodics (mebeverine) for pain
• Acute diverticulitis: see separate entry
• Diverticular bleeding: resuscitation (IV fluids, blood products), usually conservative; tranexamic acid 1 g IV if severe

Surgical/Interventional

• Diverticular bleeding: colonoscopic haemostasis (clipping, injection), mesenteric angiography + embolisation if ongoing, emergency colectomy if life-threatening
• Recurrent diverticulitis/complications: elective sigmoid colectomy (laparoscopic preferred); after 2+ episodes of uncomplicated diverticulitis or after 1 complicated episode
• Colovesical fistula: sigmoid colectomy with fistula repair
• Abscess drainage: percutaneous CT-guided drainage for Hinchey I-II abscesses ≥3 cm

Referral Criteria

• Surgical referral for complicated/recurrent diverticulitis
• Colonoscopy 6-8 weeks post-acute episode to exclude malignancy (especially first episode)
• Emergency surgical review for perforation/peritonitis

Most people with diverticulosis remain asymptomatic. ~20% develop symptomatic diverticular disease. ~4% of those with diverticulosis develop diverticulitis. After one episode of uncomplicated diverticulitis, recurrence rate is ~20-30% over 10 years. Complicated diverticulitis (abscess, perforation) carries higher morbidity and mortality. Diverticular bleeding is self-limiting in ~80% but recurrence rate is ~25%. Emergency surgery for perforation (Hinchey III-IV) carries mortality of 10-20%.

Hinchey Classification

Diverticular Bleeding vs Other Lower GI Bleed Causes

Key Facts

Acute diverticulitis is the most common complication of diverticular disease, occurring when a diverticulum becomes inflamed and/or infected. It ranges from mild pericolic inflammation to life-threatening perforation with faecal peritonitis.

Epidemiology

Approximately 10-25% of patients with diverticulosis will develop diverticulitis in their lifetime. Incidence is rising, particularly in younger patients (<50 years). Hospital admissions for diverticulitis have increased by ~50% over the past 20 years. Left-sided predominance in Western populations; right-sided more common in Asian populations.

Aetiology

Diverticulitis occurs when a diverticulum becomes obstructed by a faecalith (inspissated faecal material), leading to:

• Increased intraluminal pressure within the diverticulum
• Mucosal erosion and microperforation
• Bacterial translocation and local inflammation
• Pericolic abscess formation if contained; peritonitis if free perforation

Risk factors for developing diverticulitis: obesity, smoking, NSAIDs/corticosteroids, immunosuppression, sedentary lifestyle.

Pathophysiology

Uncomplicated Diverticulitis

• Constant LIF pain (may be suprapubic or generalised)
• Fever (low-grade)
• Nausea ± vomiting
• Change in bowel habit (constipation or diarrhoea)
• LIF tenderness, may have localised guarding
• Palpable LIF mass (phlegmon)

Complicated Diverticulitis

• Abscess: swinging fever, persistent pain, palpable tender mass
• Perforation: sudden severe pain, generalised peritonism, sepsis
• Fistula: pneumaturia, faecaluria, recurrent UTIs (colovesical); faeculent vaginal discharge (colovaginal)
• Obstruction: colicky pain, distension, absolute constipation, vomiting

Red Flags

• Generalised peritonism (rigid abdomen, rebound tenderness)
• Sepsis (tachycardia, hypotension, fever >38.5°C, raised lactate)
• Pneumoperitoneum on imaging
• Failure to improve after 48-72 hours of appropriate treatment

Bedside

• Observations: temperature, pulse, BP, RR (sepsis screen)
• Abdominal examination: tenderness, guarding, peritonism, mass
• Urinalysis: exclude UTI; pneumaturia suggests colovesical fistula
• Pregnancy test: in women of childbearing age

Bloods

• FBC: leucocytosis
• CRP: raised (correlates with severity)
• U&Es: AKI (sepsis, dehydration)
• Lactate: raised in sepsis/ischaemia
• Blood cultures: if septic

Imaging

• CT abdomen/pelvis with IV contrast: gold standard (sensitivity >95%)
  • Findings: pericolic fat stranding, colonic wall thickening (>4 mm), diverticula, abscess, extraluminal air (perforation), fistula
  • Hinchey staging guides management
• AXR: limited utility; may show ileus or free air but CT is far superior
• USS: may show pericolic collection; operator-dependent; useful in thin patients

Special Tests

• Colonoscopy: CONTRAINDICATED in acute phase (perforation risk); perform 6-8 weeks post-episode
• CT colonography: alternative post-episode imaging to exclude malignancy
• Contrast enema (water-soluble): rarely used now; replaced by CT

Non-pharmacological

• Uncomplicated (mild): may manage in community - clear fluids progressing to low-residue diet, analgesia (paracetamol - avoid NSAIDs/opioids)
• Hospital admission: if unable to tolerate oral intake, significant fever/sepsis, immunosuppressed, failed outpatient management
• Nil by mouth + IV fluids: if severe/complicated

Pharmacological

• Uncomplicated diverticulitis:
  • Antibiotics: co-amoxiclav 625 mg TDS PO for 5-7 days; OR ciprofloxacin 500 mg BD + metronidazole 400 mg TDS
  • DIABOLO trial: showed no benefit of antibiotics over conservative management for uncomplicated diverticulitis - practice shifting towards no antibiotics in mild cases
• Complicated/severe:
  • IV antibiotics: piperacillin-tazobactam 4.5 g TDS; OR meropenem 1 g TDS if severe sepsis
  • IV fluids, analgesia, VTE prophylaxis
• Analgesia: paracetamol 1 g QDS; avoid NSAIDs (perforation risk) and opioids (constipation, increased intraluminal pressure)

Surgical/Interventional

• Percutaneous abscess drainage: CT-guided for collections ≥3 cm (Hinchey I-II); with IV antibiotics
• Emergency surgery (Hinchey III-IV):
  • Hartmann's procedure: sigmoid resection + end colostomy + rectal stump closure; standard emergency operation; reversal in ~60% at 3-6 months
  • Primary anastomosis ± defunctioning loop ileostomy: increasingly preferred in selected patients (lower stoma rates)
  • Laparoscopic lavage: debated for Hinchey III - LOLA/SCANDIV/LADIES trials showed conflicting results
• Elective sigmoid colectomy: after recovery from complicated diverticulitis, or after 2+ uncomplicated episodes if significantly impacting quality of life (laparoscopic preferred)

Referral Criteria

• Emergency surgical review: peritonism, sepsis, failure of conservative management
• Outpatient surgical review: recurrent episodes, complicated disease, fistula, stricture
• Colonoscopy at 6-8 weeks: to exclude malignancy (mandatory after first episode)

Uncomplicated diverticulitis resolves in >95% with conservative/antibiotic management. After one episode, ~20-30% have recurrence over 10 years. Complicated diverticulitis (Hinchey III-IV) carries mortality of 10-20%. Emergency Hartmann's procedure has ~15% mortality. Elective laparoscopic sigmoid colectomy has <2% mortality with good long-term outcomes. Colovesical fistula repair has >90% success rate.

Acute Diverticulitis Management Algorithm

Key Trials

Key Facts

Acute appendicitis is the most common surgical emergency, accounting for >40,000 appendicectomies per year in the UK. Early diagnosis and treatment are essential to prevent perforation and peritonitis.

Epidemiology

Lifetime risk is approximately 7% (8.6% males, 6.7% females). Peak incidence is 10-30 years. Rare in under-2s and over-70s (but higher complication rates at extremes of age). Incidence is higher in Western countries.

Aetiology

• Luminal obstruction: faecolith (most common in adults), lymphoid hyperplasia (most common in children - often viral-triggered), foreign body, tumour (carcinoid, adenocarcinoma - rare), parasites

Pathophysiology

Luminal obstruction causes continued mucosal secretion against a closed loop, raising intraluminal pressure. This compresses mucosal veins, causing oedema, ischaemia, and bacterial translocation (E. coli, Bacteroides fragilis). Inflammation progresses from mucosal (catarrhal) to transmural (suppurative) to gangrenous to perforated. Perforation may be contained (appendix mass/phlegmon, peri-appendicular abscess) or free (generalised peritonitis). The progression from symptom onset to perforation typically takes 24-72 hours.

Classic Presentation

• Periumbilical pain (visceral, poorly localised - T10 dermatome) → migrates to RIF over 12-24 hours (somatic, well-localised as parietal peritoneum inflamed)
• Anorexia (almost universal - absence should prompt diagnostic reconsideration)
• Nausea ± vomiting (usually follows pain onset - important: pain precedes vomiting in appendicitis, opposite in gastroenteritis)
• Low-grade fever (37.5-38.5°C; higher suggests perforation)

Clinical Signs

• McBurney's point tenderness: 2/3 from umbilicus to ASIS
• Guarding and rebound tenderness (peritoneal irritation)
• Rovsing's sign: palpation of LIF causes RIF pain
• Psoas sign: pain on hip extension (retrocaecal appendix)
• Obturator sign: pain on internal rotation of flexed hip (pelvic appendix)

Atypical Presentations

• Retrocaecal (~65%): flank/back pain, less peritonism
• Pelvic: suprapubic pain, diarrhoea, urinary frequency
• Elderly: vague symptoms, delayed presentation → higher perforation rate
• Pregnancy: pain displaced superiorly by gravid uterus
• Children: less typical history, rapid progression to perforation

Red Flags

• Generalised peritonism (perforation)
• Sepsis (tachycardia, hypotension, fever >38.5°C)
• Palpable RIF mass (appendix mass - usually >48 hours symptoms)
• Very young (<5 years) or elderly - higher perforation rates

Bedside

• Observations: pulse, BP, temperature, RR
• Urinalysis: exclude UTI, haematuria (ureteric colic); sterile pyuria may occur with pelvic appendix adjacent to ureter
• Pregnancy test (β-hCG): mandatory in all women of childbearing age

Bloods

• FBC: leucocytosis (WCC >10 × 10⁹/L in ~80%; neutrophilia)
• CRP: raised (>10 in most; >100 suggests complicated appendicitis)
• U&Es: dehydration, baseline
• Lactate: if concern for sepsis

Imaging

• CT abdomen/pelvis with IV contrast: first-line in adults - sensitivity >95%, specificity >95%; shows appendiceal dilatation (>6 mm), wall thickening, periappendiceal fat stranding, appendicolith, abscess, free fluid
• USS abdomen: first-line in children and pregnant women; sensitivity ~85% (operator-dependent); non-compressible appendix >6 mm
• MRI: alternative in pregnancy if USS inconclusive

Special Tests

• Alvarado (MANTRELS) score: Migration, Anorexia, Nausea/vomiting, RIF Tenderness, Rebound, Elevated temperature, Leucocytosis, Shift to left; score 0-10; ≥7 = operate; 5-6 = CT; <5 = observe
• Appendicitis Inflammatory Response (AIR) score: alternative scoring system

Non-pharmacological

• NBM: preparation for potential surgery
• IV fluids: resuscitation
• Analgesia: IV paracetamol + IV morphine (do NOT withhold analgesia - historical practice of withholding is outdated and unethical)

Pharmacological

• IV antibiotics (pre-operative): co-amoxiclav 1.2 g IV or cefuroxime 1.5 g + metronidazole 500 mg IV; continue post-operatively for 5 days if complicated/perforated
• Antibiotic-only treatment: emerging option for uncomplicated appendicitis - CODA trial showed ~70% avoided surgery at 90 days with antibiotics alone; APPAC II - 7-day moxifloxacin course; ~25-30% eventually need appendicectomy within 5 years; appropriate discussion of options with patient

Surgical/Interventional

• Laparoscopic appendicectomy: gold standard; lower wound infection rate, faster recovery, better cosmesis than open; diagnostic advantage (can visualise pelvis/other pathology)
• Open appendicectomy: if laparoscopy unavailable or converted
• Appendix mass: if >48 hours symptoms with contained mass - initial conservative management (IV antibiotics) with interval appendicectomy at 6-8 weeks (debated - some centres now advocate early surgery)
• Peri-appendicular abscess: CT-guided drainage + IV antibiotics; interval appendicectomy

Referral Criteria

• All suspected appendicitis: urgent surgical review
• Diagnostic uncertainty: CT imaging
• Appendix mass/abscess: surgical team for conservative vs interventional management
• Histology: always send appendix specimen (carcinoid tumour found in ~1%)

Uncomplicated appendicitis treated with appendicectomy has near-zero mortality and <5% complication rate. Perforation rate is ~20% overall (higher in children <5 and elderly >70). Perforation increases morbidity (wound infection, abscess, ileus) but mortality remains <1% with modern care. Negative appendicectomy rate with CT usage is <5% (previously ~15-20% without imaging). After antibiotic-only treatment, ~25-30% require appendicectomy within 5 years. Incidental carcinoid tumour: if <10 mm and appendiceal, appendicectomy is curative.

Alvarado (MANTRELS) Score

Key Facts

Bowel obstruction is a common surgical emergency. The distinction between small and large bowel obstruction is important as aetiology, management, and prognosis differ significantly.

Epidemiology

SBO accounts for ~80% of all intestinal obstructions and is responsible for ~20% of emergency surgical admissions. LBO accounts for ~20%. Adhesional SBO is the commonest cause overall. Colorectal cancer is the commonest cause of LBO.

Aetiology

Small bowel obstruction:

• Adhesions from previous surgery (~60%) - commonest overall cause
• Hernias (~20% - inguinal, femoral, incisional, internal)
• Malignancy (small bowel tumours, peritoneal carcinomatosis)
• Crohn's disease (stricture)
• Intussusception (children - idiopathic; adults - lead point e.g. polyp/tumour)
• Gallstone ileus (large gallstone through cholecystoenteric fistula → impaction at ileocaecal valve)

Large bowel obstruction:

• Colorectal cancer (~60%)
• Volvulus (~20% - sigmoid > caecal)
• Diverticular stricture (~10%)
• Pseudo-obstruction (Ogilvie syndrome)

Pathophysiology

Small Bowel Obstruction

• Colicky central/periumbilical pain (5-10 minute cycles)
• Vomiting (early - bilious/faeculent if distal)
• Abdominal distension (moderate)
• Absolute constipation (late - initially may still pass flatus/stool)
• Tinkling/high-pitched bowel sounds → absent (late)

Large Bowel Obstruction

• Colicky lower abdominal pain
• Absolute constipation (early - no flatus or stool)
• Marked abdominal distension
• Vomiting (late - may be faeculent)

Red Flags (Strangulation/Ischaemia)

• Constant severe pain (rather than colicky)
• Tachycardia, hypotension, fever
• Peritonism (guarding, rebound)
• Irreducible tender hernia
• Raised lactate, leucocytosis
• Absent bowel sounds
• Rapidly worsening clinical state

Bedside

• Observations: pulse, BP, temperature, urine output (catheter if needed)
• NG tube: decompression (therapeutic and diagnostic - bilious aspirate)
• Hernia sites: examine ALL hernial orifices (inguinal, femoral, incisional, umbilical)

Bloods

• FBC: leucocytosis (strangulation/infection)
• U&Es: dehydration, hypokalaemia (vomiting), AKI
• Lactate: raised with ischaemia/strangulation
• LFTs, amylase/lipase: exclude biliary/pancreatic cause
• VBG: metabolic alkalosis (vomiting) or acidosis (ischaemia)
• Group and save: pre-operative

Imaging

• CT abdomen/pelvis with IV contrast: gold standard - identifies site of obstruction (transition point), cause, and complications (ischaemia, perforation, closed-loop)
  • SBO: dilated small bowel (>3 cm), collapsed distal, transition point
  • LBO: dilated colon (>6 cm; caecum >9 cm), obstructing lesion
• AXR: initial assessment - dilated loops (SBO: central, valvulae conniventes; LBO: peripheral, haustral folds); limited sensitivity/specificity
• Gastrograffin follow-through: for adhesional SBO - therapeutic (osmotic effect) and prognostic; passage to colon on 24-hour film predicts resolution without surgery

Special Tests

• CT angiography: if mesenteric ischaemia suspected
• Colonoscopy: therapeutic for sigmoid volvulus decompression; diagnostic for LBO cause

Non-pharmacological

• "Drip and suck": IV fluid resuscitation + NG decompression
• NBM: bowel rest
• Catheterisation: monitor urine output
• Thromboprophylaxis: LMWH
• Monitoring: serial examinations, bloods (lactate, WCC), repeat imaging if not improving

Pharmacological

• IV fluids: aggressive crystalloid resuscitation (Hartmann's or 0.9% saline with K+ replacement)
• Electrolyte correction: potassium, magnesium
• Analgesia: IV paracetamol + IV opioids (titrated)
• Anti-emetics: ondansetron 4-8 mg IV, cyclizine 50 mg IV
• Gastrograffin 100 mL oral/via NG tube: for adhesional SBO - safe if no strangulation; predict need for surgery (contrast in colon on 24h XR = likely to resolve)
• Neostigmine 2 mg IV (over 5 min with cardiac monitoring): for acute colonic pseudo-obstruction (Ogilvie syndrome) if caecal diameter >12 cm

Surgical/Interventional

• SBO - adhesional: conservative management resolves ~75% within 48-72 hours; surgery if strangulation, failed conservative (no improvement by 72 hours, or no contrast in colon on 24h Gastrograffin)
• SBO - hernia: emergency surgery if strangulated/irreducible
• LBO - cancer: emergency colonic stenting (as bridge to surgery) or emergency surgery (Hartmann's procedure or primary anastomosis ± defunctioning ileostomy)
• LBO - volvulus: see separate entry
• Laparoscopic/open adhesiolysis: for adhesional SBO
• Bowel resection: for ischaemic/gangrenous bowel (with or without anastomosis depending on contamination)

Referral Criteria

• All bowel obstruction: urgent surgical review
• Emergency theatre: strangulation, perforation, closed-loop obstruction
• Colorectal MDT: if LBO from malignancy
• Interventional radiology/endoscopy: colonic stenting

Adhesional SBO: ~75% resolve with conservative management. Mortality for uncomplicated SBO is <5%. Strangulated/ischaemic bowel increases mortality to 10-25%. LBO from colorectal cancer: emergency surgery mortality is 15-20% (vs 2-5% for elective resection). Closed-loop obstruction has the highest perforation risk. Recurrent adhesional SBO occurs in ~15-20% after adhesiolysis. Colonic stenting as bridge to surgery has lower stoma rates than emergency surgery.

SBO vs LBO Comparison

Normal vs Obstructed Bowel Diameters

Key Facts

Volvulus is a surgical emergency involving rotation of the bowel on its mesenteric axis, causing closed-loop obstruction and compromised blood supply. Sigmoid volvulus is the most common type in Western countries.

Epidemiology

Volvulus accounts for ~5% of large bowel obstruction in the UK and 20-50% in parts of Africa and Asia (the "volvulus belt"). Sigmoid volvulus: peak age 60-80 years, male predominance (3:1), associated with institutionalisation and neuropsychiatric disease. Caecal volvulus: younger patients (30-50 years), female predominance.

Aetiology

Sigmoid volvulus:

• Redundant sigmoid colon with a long, narrow mesenteric pedicle
• Chronic constipation → sigmoid megacolon
• Institutionalisation: nursing homes, psychiatric facilities (medication-related constipation: antipsychotics, opioids)
• Chagas disease (megacolon - South America)
• High-fibre/high-residue diet (African/Asian populations)

Caecal volvulus:

• Mobile caecum (congenital incomplete peritoneal fixation - ~10% of population)
• Previous surgery (adhesions altering caecal mobility)
• Pregnancy
• Marathon running (rare)

Pathophysiology

Rotation creates a closed-loop obstruction with progressive bowel dilatation proximal to the twist. Mesenteric vessel compression causes venous congestion, then arterial compromise, leading to ischaemia, gangrene, and perforation. Sigmoid volvulus typically twists anticlockwise. The closed-loop mechanism means that, unlike simple obstruction, decompression cannot occur proximally, and pressure rises rapidly - high perforation risk, especially if caecal diameter >12 cm.

Sigmoid Volvulus

• Elderly patient, often from care home
• Progressive abdominal distension (often massive)
• Colicky lower abdominal pain
• Absolute constipation
• Vomiting (late)
• History of chronic constipation, previous episodes
• On examination: massively distended abdomen, tympanic; rectum often empty on DRE

Caecal Volvulus

• Younger patient
• Acute onset colicky abdominal pain (often RIF initially)
• Distension
• Vomiting (earlier than sigmoid)
• May mimic SBO

Red Flags

• Peritonism (ischaemia/gangrene)
• Sepsis (fever, tachycardia, hypotension)
• Absent bowel sounds
• Bloody PR discharge (mucosal ischaemia)
• Raised lactate

Bedside

• AXR: often diagnostic
  • Sigmoid: coffee bean sign (inverted U), large dilated loop arising from pelvis, no haustral markings, overlap sign
  • Caecal: dilated caecum displaced to LUQ, SBO features
• Observations: sepsis screen

Bloods

• FBC: leucocytosis (strangulation)
• U&Es: dehydration, electrolyte disturbance
• Lactate: raised = ischaemia
• VBG: metabolic acidosis (ischaemia)

Imaging

• CT abdomen/pelvis: gold standard - whirl sign (twisted mesentery at the twist point), dilated bowel, transition point; identifies ischaemia (poor wall enhancement, pneumatosis) and perforation
• AXR: may be sufficient for classic sigmoid volvulus presentation in known patient

Special Tests

• Flexible sigmoidoscopy: diagnostic AND therapeutic for sigmoid volvulus - mucosal assessment for viability + flatus tube insertion
• Contrast enema (water-soluble): "bird's beak" at the twist point - rarely needed with CT availability

Non-pharmacological

• Sigmoid volvulus (no peritonitis): endoscopic decompression first-line
  • Rigid sigmoidoscope or flexible endoscope passed through twist → dramatic decompression of gas/liquid
  • Flatus tube inserted and left in situ for 24-48 hours (prevents early recurrence)
  • ~80% success rate for initial decompression
• NBM, IV fluids, NG decompression if SBO component

Pharmacological

• IV fluids: aggressive resuscitation
• IV antibiotics: if signs of ischaemia/perforation (piperacillin-tazobactam 4.5 g TDS)
• VTE prophylaxis
• Correct electrolyte imbalances

Surgical/Interventional

• Sigmoid volvulus - definitive:
  • Elective sigmoid colectomy: recommended after successful decompression (recurrence rate ~60% without surgery); laparoscopic preferred
  • If patient unfit for surgery: percutaneous endoscopic colostomy (PEC) - emerging option
• Sigmoid volvulus - emergency surgery: if gangrenous, perforated, or failed endoscopic decompression
  • Hartmann's procedure (sigmoid resection + end colostomy) - commonest emergency operation
  • Primary anastomosis ± defunctioning ileostomy in selected patients
• Caecal volvulus: endoscopic decompression usually unsuccessful (~10-20%)
  • Right hemicolectomy: definitive treatment
  • Caecopexy: alternative in selected cases (higher recurrence)

Referral Criteria

• Emergency surgical review for all volvulus
• Urgent endoscopy for sigmoid volvulus decompression
• Colorectal surgical review for definitive management after decompression

Sigmoid volvulus: endoscopic decompression successful in ~80%, but recurrence without surgery is ~60%. Elective sigmoid colectomy has <5% mortality. Emergency surgery for gangrenous sigmoid volvulus has 15-30% mortality. Caecal volvulus: emergency right hemicolectomy mortality is ~10-15%. Overall mortality for volvulus is ~10-15%, rising to 30-40% with gangrene/perforation.

Sigmoid vs Caecal Volvulus

Volvulus Management Algorithm

Key Facts

Acute pancreatitis is a common and potentially life-threatening condition. Early recognition, severity assessment, and supportive care are crucial. Gallstones and alcohol account for >75% of cases.

Epidemiology

Incidence is approximately 30-50 per 100,000 per year in the UK and is increasing. Hospital admissions for acute pancreatitis have doubled over 20 years. Gallstone pancreatitis is more common in women; alcoholic pancreatitis in men. Overall mortality is ~5% but rises to 30-50% in severe necrotising pancreatitis.

Aetiology

• Gallstones (~50%): stone migrating through/impacting at ampulla of Vater
• Alcohol (~25%): typically requires >5 years of heavy drinking (>80 g/day)
• Idiopathic (~15%): many likely microlithiasis or genetic
• Other: hypertriglyceridaemia (>11.3 mmol/L), hypercalcaemia, drugs, ERCP, autoimmune pancreatitis, pancreatic tumour, trauma, viral (mumps, CMV)

Pathophysiology

Premature activation of trypsinogen to trypsin within pancreatic acinar cells triggers an autodigestive cascade. In gallstone pancreatitis, transient biliary obstruction causes pancreatic duct hypertension. In alcoholic pancreatitis, toxic metabolites (fatty acid ethyl esters) damage acinar cells. Activated enzymes digest pancreatic tissue and peripancreatic fat (saponification). The systemic inflammatory response (SIRS) can lead to multi-organ dysfunction. Severe disease causes pancreatic necrosis, which may become secondarily infected (usually by gut bacteria, typically at day 7-21).

Typical Presentation

• Severe epigastric pain radiating straight through to the back
• Sudden onset, constant, worsened by eating, partially relieved by sitting forward
• Nausea and vomiting (>80%)
• Abdominal tenderness with guarding (often less peritonism than expected given severity - "silent abdomen")

Severe Disease Features

• Shock (tachycardia, hypotension)
• Respiratory distress (ARDS, pleural effusions - especially left-sided)
• Oliguria (AKI)
• Jaundice (if choledocholithiasis/biliary obstruction)

Rare Signs

• Grey Turner's sign: flank bruising (retroperitoneal haemorrhage)
• Cullen's sign: periumbilical bruising
• Both indicate haemorrhagic pancreatitis and are late signs

Red Flags

• Persistent organ failure >48 hours (severe pancreatitis)
• Rising CRP >150 mg/L at 48 hours
• Infected necrosis (fever, rising WCC after initial improvement at day 7-21)
• Cholangitis (Charcot's triad: fever, jaundice, RUQ pain) - needs urgent ERCP

Bedside

• Observations: pulse, BP, RR, SpO₂, temperature, urine output
• ABG/VBG: PaO₂ (ARDS risk), lactate, glucose

Bloods

• Serum lipase (preferred) or amylase: >3× ULN diagnostic; lipase is more sensitive and specific (remains elevated longer)
• FBC: leucocytosis
• CRP: key prognostic marker; >150 mg/L at 48 hours predicts severe disease
• U&Es: AKI, dehydration
• LFTs: raised ALT >2× ULN suggests gallstone aetiology; raised bilirubin/ALP suggests choledocholithiasis
• Calcium: low (saponification of peripancreatic fat - prognostic)
• Triglycerides: if >11.3 mmol/L, likely cause
• Glucose: hyperglycaemia (stress response, endocrine pancreatic damage)

Imaging

• USS abdomen: within 24 hours - assess for gallstones (aetiology); dilated CBD suggests choledocholithiasis
• CT abdomen/pelvis with IV contrast: NOT needed for diagnosis if clear clinically; indicated at 72-96 hours if severe/deteriorating - assess necrosis extent (CT severity index)
• MRCP: if CBD stones suspected but USS equivocal

Special Tests

• Modified Glasgow (Imrie) score at 48 hours: ≥3/8 = severe (PANCREAS mnemonic)
• APACHE II: at admission - ≥8 predicts severe
• CT severity index (Balthazar): grades A-E + necrosis percentage
• IgG4: if autoimmune pancreatitis suspected

Non-pharmacological

• Aggressive IV fluid resuscitation: Ringer's lactate 5-10 mL/kg/hr for first 12-24 hours, guided by urine output (target >0.5 mL/kg/hr) and haemodynamic parameters
• Early enteral nutrition: oral diet as tolerated (no need to wait for pain resolution or normalisation of enzymes); NG/NJ feeding if unable to eat; avoid TPN unless EN not possible
• HDU/ICU admission: if severe pancreatitis or organ failure
• VTE prophylaxis

Pharmacological

• Analgesia: IV paracetamol 1 g QDS + IV opioid (morphine/oxycodone - titrated); patient-controlled analgesia if needed; avoid NSAIDs in severe disease (renal risk)
• Anti-emetics: ondansetron 4-8 mg IV
• Antibiotics: NOT routinely indicated for acute pancreatitis or sterile necrosis; indicated for infected necrosis (meropenem 1 g TDS) or concurrent cholangitis

Surgical/Interventional

• ERCP: within 24 hours if concurrent cholangitis; within 72 hours if persistent biliary obstruction without cholangitis; NOT routinely for gallstone pancreatitis without obstruction
• Cholecystectomy: during index admission for mild gallstone pancreatitis (PONCHO trial - reduces recurrence from 17% to 5%); or within 2 weeks for severe
• Infected pancreatic necrosis: step-up approach (PANTER trial, TENSION trial)
  1. Percutaneous catheter drainage
  2. Endoscopic transluminal necrosectomy (if walled-off necrosis)
  3. Minimally invasive surgical necrosectomy (VARD)
  4. Open necrosectomy (last resort)
• Pseudocyst drainage: if symptomatic/infected; endoscopic (EUS-guided) preferred

Referral Criteria

• ICU/HDU: organ failure, severe disease (Glasgow ≥3)
• Hepatobiliary/pancreatic surgery: complicated pancreatitis, necrosectomy
• ERCP: concurrent cholangitis, persistent biliary obstruction
• Follow-up: identify and address cause; alcohol service if alcohol-related

Mild pancreatitis (~80%): mortality <1%, resolves within 1 week. Severe pancreatitis (~20%): mortality 15-30%. Infected necrosis: mortality 30-50% (reduced to ~15% with step-up approach). Overall mortality ~5%. Recurrence: 20-30% for gallstone pancreatitis if cholecystectomy not performed. Long-term complications include pseudocyst (10-20%), pancreatic exocrine/endocrine insufficiency, and chronic pancreatitis (especially alcohol-related).

Modified Glasgow (Imrie) Score - PANCREAS Mnemonic

Key Trials

Key Facts

Chronic pancreatitis is characterised by progressive, irreversible inflammatory changes leading to fibrosis and loss of exocrine and endocrine function. Pain management and nutritional support are central to care.

Epidemiology

Prevalence approximately 50 per 100,000 in the UK. Incidence 5-12 per 100,000 per year. Male predominance (3:1) - related to higher alcohol consumption. Mean age at diagnosis 35-55 years.

Aetiology

TIGAR-O classification:

• Toxic-metabolic: alcohol (~70% in UK), smoking (independent risk factor, doubles risk), hypercalcaemia, hypertriglyceridaemia
• Idiopathic: ~20% (early-onset <35 years and late-onset >55 years)
• Genetic: PRSS1 (hereditary pancreatitis - AD, high penetrance), SPINK1, CFTR mutations
• Autoimmune: type 1 (IgG4-related, associated with sclerosing cholangitis, sialoadenitis) and type 2 (duct-centric, associated with IBD)
• Recurrent acute pancreatitis: sentinel acute pancreatitis event (SAPE) hypothesis
• Obstructive: pancreas divisum, ampullary stenosis, pancreatic duct tumour

Pathophysiology

Pain

• Chronic epigastric pain radiating to the back
• Constant or episodic; worsened by eating and alcohol
• May "burn out" in late disease (fibrosis replaces functional tissue)
• Often requires opioid analgesia → risk of dependence

Exocrine Insufficiency

• Steatorrhoea: pale, bulky, offensive stools that are difficult to flush
• Weight loss, malnutrition
• Fat-soluble vitamin deficiency (A, D, E, K)

Endocrine Insufficiency

• Type 3c (pancreatogenic) diabetes mellitus: typically develops after years of chronic pancreatitis; both insulin and glucagon deficiency → brittle diabetes with hypoglycaemia risk

Red Flags

• New/worsening jaundice (bile duct stricture, pancreatic cancer)
• Rapid weight loss (pancreatic cancer)
• New diabetes in chronic pancreatitis (pancreatic cancer risk)
• GI bleeding (splenic vein thrombosis → gastric varices)
• Palpable abdominal mass (pseudocyst)

Bedside

• Faecal elastase-1: <200 μg/g = exocrine insufficiency; <100 = severe; simple stool test
• HbA1c/fasting glucose: diabetes screening

Bloods

• LFTs: raised ALP/bilirubin if bile duct stricture
• Amylase/lipase: may be normal in chronic pancreatitis (burnt-out pancreas)
• HbA1c, fasting glucose: diabetes
• Fat-soluble vitamins (A, D, E): deficiency assessment
• Nutritional markers: albumin, prealbumin, magnesium, zinc
• IgG4: if autoimmune pancreatitis suspected
• CA19-9: if malignancy suspected (limited specificity)
• Genetic testing: PRSS1, SPINK1, CFTR if hereditary/early-onset

Imaging

• CT abdomen: pancreatic calcifications (pathognomonic), duct dilatation, parenchymal atrophy, pseudocysts
• MRCP/secretin-MRCP: pancreatic and biliary duct assessment - sensitivity for early disease
• EUS: most sensitive test for early chronic pancreatitis - Rosemont criteria (parenchymal and ductal features)
• AXR: may show pancreatic calcifications

Special Tests

• 72-hour faecal fat collection: >7 g/day confirms fat malabsorption (gold standard but impractical - faecal elastase preferred)
• DEXA scan: osteoporosis screening (vitamin D/calcium malabsorption)

Non-pharmacological

• Alcohol abstinence: most important - slows progression, reduces pain
• Smoking cessation: independent risk factor for progression
• Dietary: small frequent meals, low-fat diet, avoid large fatty meals; dietitian involvement essential
• Nutritional supplementation: fat-soluble vitamins, calcium, vitamin D
• Psychosocial support: addiction services, pain management teams, psychological support

Pharmacological

• PERT (pancreatic enzyme replacement therapy): CREON - 50,000 units lipase with main meals, 25,000 with snacks; adjust dose to stool output; take with food
  • Add PPI (omeprazole 20 mg OD) if suboptimal response (acid degrades enzymes)
• Pain management:
  • Step 1: paracetamol 1 g QDS ± low-dose NSAID (if renal function allows)
  • Step 2: weak opioid (codeine, tramadol)
  • Step 3: strong opioid (morphine, oxycodone - use with caution, addiction risk)
  • Adjuvants: pregabalin 75-300 mg BD, amitriptyline 10-50 mg ON, duloxetine 60 mg OD
  • Antioxidant therapy: some evidence for selenium, vitamin C, vitamin E combination
• Diabetes management: insulin (often required); metformin if mild; beware hypoglycaemia (glucagon deficiency)

Surgical/Interventional

• ERCP: pancreatic duct stenting, stone extraction, stricture dilatation
• ESWL (extracorporeal shockwave lithotripsy): for large pancreatic duct stones before ERCP
• EUS-guided coeliac plexus block: pain management (temporary effect - 3-6 months)
• Surgery for pain:
  • Frey procedure (lateral pancreaticojejunostomy + limited head excision): large duct disease
  • Beger procedure: duodenum-preserving pancreatic head resection
  • Total pancreatectomy with islet autotransplantation (TPIAT): selected centres, refractory pain
• Pseudocyst drainage: EUS-guided, endoscopic, or surgical if symptomatic/complicated

Referral Criteria

• Hepato-pancreatico-biliary (HPB) team referral for all
• Pain management service for refractory pain
• Diabetes team for pancreatogenic diabetes
• Genetics referral if hereditary pancreatitis suspected
• Addiction/alcohol services

Chronic pancreatitis is a progressive condition. Alcohol cessation slows but does not halt progression. Pain may improve in late-stage disease ("burn-out"). Exocrine insufficiency develops in ~60% over 10 years. Type 3c diabetes develops in ~30-50%. Pancreatic cancer risk is 5-10% lifetime (~15-fold increased risk). Mortality is increased: 10-year survival ~70% (primarily from comorbidities - cardiovascular, liver disease in alcohol-related). Quality of life is significantly impaired by chronic pain.

TIGAR-O Classification

PERT (CREON) Dosing Guide

Key Facts

Pancreatic cancer is one of the most lethal malignancies, with an overall 5-year survival of <10%. Late presentation, early metastasis, and resistance to chemotherapy contribute to the dismal prognosis.

Epidemiology

~10,500 new cases per year in the UK (10th most common cancer but 5th cause of cancer death). Incidence is rising. Median age at diagnosis 72 years. Slight male predominance. Lifetime risk ~1 in 70.

Aetiology

• Smoking: strongest modifiable risk factor (2x risk, 25% attributable fraction)
• Chronic pancreatitis: 15x risk (especially hereditary pancreatitis - 50x)
• New-onset diabetes: 1-2% of new diabetes >50 years will have pancreatic cancer within 3 years
• Obesity: 20% increased risk
• Family history: 5-10% have familial predisposition (BRCA2, PALB2, ATM, STK11/Peutz-Jeghers, Lynch syndrome, FAMMM)
• Chronic alcohol excess: via chronic pancreatitis rather than direct effect

Pathophysiology

PDAC arises from pancreatic intraepithelial neoplasia (PanIN) through stepwise genetic mutations: KRAS (>90%, earliest), CDKN2A/p16, TP53, SMAD4 (DPC4). The tumour creates a dense desmoplastic stroma (hypoxic, immunosuppressive microenvironment) that limits drug delivery and immune cell infiltration. Perineural invasion is characteristic and contributes to severe pain. Early lymphatic and haematogenous metastasis (liver, peritoneum, lungs) is common.

Head of Pancreas (60-70%)

• Painless progressive obstructive jaundice (dark urine, pale stools, pruritus)
• Courvoisier's sign: palpable, non-tender gallbladder + painless jaundice
• Weight loss

• New-onset diabetes

Body/Tail (30-40%)

• Epigastric pain radiating to back (often dull, constant, worse lying flat)
• Weight loss (often profound - >10% body weight)
• New-onset diabetes
• Present later → even poorer prognosis

Metastatic Disease

• Hepatomegaly, ascites (peritoneal carcinomatosis)
• Sister Mary Joseph nodule, Virchow's node
• Trousseau syndrome (migratory thrombophlebitis - paraneoplastic DVT)

Red Flags

• Painless jaundice in any age group
• New diabetes >50 years with weight loss
• Unexplained weight loss with back/epigastric pain
• Migratory thrombophlebitis (Trousseau syndrome)
• NICE NG12: urgent 2WW referral for ≥40 with jaundice, or CT within 2 weeks for upper abdominal mass

Bedside

• History: weight loss, jaundice, new diabetes, smoking/alcohol, family history
• Examination: jaundice, palpable gallbladder, hepatomegaly, ascites, Virchow's node

Bloods

• LFTs: obstructive pattern (raised ALP, GGT, conjugated bilirubin)
• CA19-9: raised in ~80% of PDAC; >37 U/mL; useful for monitoring treatment response; can be falsely raised in obstructive jaundice, cholangitis; falsely normal in Lewis antigen-negative patients (~10%)
• FBC: anaemia
• HbA1c: new diabetes screening
• Coagulation (INR): may be deranged (vitamin K malabsorption in obstructive jaundice)

Imaging

• CT thorax/abdomen/pelvis (pancreatic protocol): triple-phase (arterial, portal, delayed); gold standard for diagnosis and resectability assessment; assesses vascular involvement (SMA, coeliac, portal vein, SMV)
  • Resectability: resectable (no vascular involvement), borderline resectable (vascular contact <180°), locally advanced unresectable (>180° arterial encasement), metastatic
• MRCP: biliary and pancreatic duct assessment
• EUS ± FNA: tissue diagnosis (if CT inconclusive or tissue confirmation needed for oncological treatment); staging
• PET-CT: assess for occult metastases in borderline resectable disease
• Staging laparoscopy: identify occult peritoneal disease (changes management in ~15%)

Special Tests

• Molecular profiling: KRAS, BRCA1/2 (for olaparib eligibility - POLO trial), MSI/dMMR status
• Germline testing: BRCA2, PALB2 if family history or young onset
• Biliary stenting (ERCP): for palliation of jaundice or pre-operative biliary drainage (controversial - mainly if jaundice severe or delayed surgery)

Non-pharmacological

• HPB MDT discussion: all cases
• Nutritional support: dietitian, PERT (CREON), manage diabetes
• Biliary drainage: ERCP + metal stent for palliation of jaundice; plastic stent as temporary bridge in resectable disease
• Psychological support: cancer nurse specialist

Pharmacological

• Adjuvant (post-resection):
  • Modified FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin) × 12 cycles: current standard (PRODIGE 24/CCTG PA.6 trial - median DFS 21.6 vs 12.8 months)
  • Gemcitabine + capecitabine: alternative if FOLFIRINOX not tolerated (ESPAC-4 trial)
• Neoadjuvant: increasingly used for borderline resectable - FOLFIRINOX or gemcitabine/nab-paclitaxel; aims to downstage and improve R0 resection rate
• Palliative chemotherapy (advanced/metastatic):
  • FOLFIRINOX (fit patients - median OS 11.1 months, ACCORD 11 trial)
  • Gemcitabine + nab-paclitaxel (median OS 8.5 months, MPACT trial)
  • Gemcitabine monotherapy (if unfit)
• Targeted: olaparib maintenance for BRCA-mutated PDAC after platinum chemotherapy (POLO trial)
• Pain management: WHO analgesic ladder; pregabalin/amitriptyline as adjuvants; EUS-guided coeliac plexus neurolysis for severe pain

Surgical/Interventional

• Pancreaticoduodenectomy (Whipple): for head/uncinate tumours; ~5% perioperative mortality at high-volume centres
• Distal pancreatectomy + splenectomy: for body/tail tumours
• Total pancreatectomy: for multifocal disease or positive resection margin
• Vascular resection/reconstruction: in borderline resectable disease at specialist centres
• Palliative procedures: biliary stenting (ERCP/PTC), gastrojejunostomy (duodenal obstruction), coeliac plexus neurolysis (pain)

Referral Criteria

• 2WW referral per NICE NG12
• All confirmed cases to HPB MDT
• Specialist HPB centre for surgery (centralised service)
• Genetics referral if family history or BRCA/PALB2 mutation carriers
• Palliative care early involvement for advanced disease

Overall 5-year survival <10% (~7%). Resectable disease (15-20% at diagnosis): median survival 20-24 months with adjuvant mFOLFIRINOX; 5-year survival ~20-30% after R0 resection. Locally advanced unresectable: median survival ~12-15 months. Metastatic: median survival ~6-11 months. FOLFIRINOX improved outcomes significantly compared to gemcitabine alone. Perioperative mortality at high-volume centres is ~3-5%. Poor prognostic factors: positive margin (R1), node-positive, high CA19-9, poor differentiation.

Resectability Classification

Key Trials

Key Facts

Gallstones are extremely common and represent a significant burden on healthcare systems. While most remain asymptomatic, symptomatic stones can cause significant morbidity and life-threatening complications.

Epidemiology

Prevalence is 10-15% in UK adults. Female predominance (2:1). Increases with age - >25% of women >60 years. Annual incidence of symptoms in stone carriers is ~1-4%. Over 70,000 cholecystectomies are performed annually in England.

Aetiology

Cholesterol stones (80%):

• Supersaturation of bile with cholesterol (relative excess of cholesterol vs bile salts and phospholipids)
• Risk factors: obesity, oestrogen (female sex, OCP, pregnancy), rapid weight loss, fibrates, diabetes, Crohn's (bile acid malabsorption)

Pigment stones (20%):

• Black (haemolytic): chronic haemolysis (sickle cell, spherocytosis, thalassaemia), liver cirrhosis
• Brown (infection-related): biliary infection, parasites (Clonorchis, Ascaris), biliary stasis

Pathophysiology

Cholesterol stones form when bile becomes supersaturated with cholesterol. Gallbladder hypomotility (stasis) and nucleation factors promote crystal formation and stone growth. Stones may remain in the gallbladder (causing biliary colic if impacted in cystic duct) or migrate into the CBD (choledocholithiasis), causing obstructive jaundice, cholangitis, or pancreatitis.

Biliary Colic

• Constant RUQ/epigastric pain (misnomer "colic" - pain is steady, not intermittent)
• Duration 30 minutes to 6 hours (if >6 hours → suspect cholecystitis)
• Often post-prandial, especially fatty meals
• Radiation to right scapula/shoulder
• Nausea, vomiting
• Normal inflammatory markers, no fever

Complications

• Acute cholecystitis: persistent RUQ pain >6 hours, fever, Murphy's sign
• Choledocholithiasis: jaundice, dark urine, pale stools, raised ALP/bilirubin
• Ascending cholangitis: Charcot's triad (fever/rigors, jaundice, RUQ pain); Reynolds' pentad (+ confusion, hypotension = severe sepsis)
• Gallstone pancreatitis: epigastric pain radiating to back, raised lipase

Red Flags

• Fever with rigors and jaundice (cholangitis - septic emergency)
• Persistent severe RUQ pain with peritonism (perforated gallbladder/empyema)
• Painless jaundice (consider head of pancreas tumour, not just CBD stone)

Bedside

• Observations: temperature, pulse, BP
• Murphy's sign: positive in cholecystitis (inspiratory arrest on RUQ palpation during deep breath)

Bloods

• FBC: leucocytosis (cholecystitis, cholangitis)
• CRP: raised in cholecystitis/cholangitis
• LFTs: ALP/GGT raised (obstructive pattern) if CBD stones; ALT may be transiently raised (stone passage)
• Bilirubin: conjugated hyperbilirubinaemia in CBD stones
• Amylase/lipase: raised if gallstone pancreatitis
• Blood cultures: if cholangitis suspected

Imaging

• USS abdomen: first-line - gallbladder stones (>95% sensitivity), wall thickening (>3 mm suggests cholecystitis), pericholecystic fluid, CBD dilatation (>6 mm suggests choledocholithiasis)
• MRCP: gold standard for CBD stone detection - sensitivity >95%
• CT: for complications (perforation, abscess, pancreatitis)

Special Tests

• ERCP: diagnostic AND therapeutic for CBD stones - sphincterotomy + stone extraction; NOT for diagnosis alone (invasive, complication risk 5-10% including pancreatitis)
• EUS: highly sensitive for small CBD stones; alternative to MRCP
• HIDA scan (cholescintigraphy): if acalculous cholecystitis suspected or functional gallbladder disorder

Non-pharmacological

• Asymptomatic gallstones: no treatment - reassurance; "leave well alone" (annual risk of symptoms only 1-4%)
• Dietary: reduce fatty food intake (may reduce attacks but does not dissolve stones)

Pharmacological

• Biliary colic analgesia: diclofenac 75 mg IM (first-line - reduces pain AND reduces progression to cholecystitis); paracetamol, opioids if needed; buscopan (hyoscine butylbromide) 20 mg IV for spasm
• Ursodeoxycholic acid (UDCA): 8-12 mg/kg/day; dissolves small cholesterol stones (<10 mm) in functioning gallbladder; rarely used (slow, high recurrence); mainly for those unfit for surgery

Surgical/Interventional

• Laparoscopic cholecystectomy: gold standard for symptomatic gallstones; same-day or next-day surgery for uncomplicated biliary colic is safe; for cholecystitis - early (within 72 hours) preferred over delayed (ACDC trial, CHOCOLATE trial)
• ERCP + sphincterotomy: for CBD stones - before or during cholecystectomy
• Intraoperative cholangiogram (IOC): to identify CBD stones during cholecystectomy
• Cholecystostomy (percutaneous gallbladder drain): for acute cholecystitis if patient unfit for surgery (sepsis control; bridge to cholecystectomy)

Referral Criteria

• Surgical referral for all symptomatic gallstones (cholecystectomy)
• Emergency surgical review for cholecystitis, cholangitis, gallstone pancreatitis
• ERCP for CBD stones

Asymptomatic gallstones rarely cause problems - <4% become symptomatic per year. After first episode of biliary colic, ~70% have further episodes within 2 years. Laparoscopic cholecystectomy has <0.5% mortality and <5% complication rate. Post-cholecystectomy syndrome (persistent pain) occurs in ~10-15%. Bile duct injury during laparoscopic cholecystectomy occurs in ~0.3-0.5%. Gallstone pancreatitis: recurrence is 20-30% without cholecystectomy.

Gallstone Complication Summary

Key Facts

Acute cholecystitis is the most common complication of gallstone disease. Early surgical intervention has been shown to be superior to delayed surgery and is now the standard of care in most centres.

Epidemiology

Approximately 20% of patients with symptomatic gallstones develop acute cholecystitis. ~20,000 emergency cholecystectomies per year in England. Acalculous cholecystitis accounts for ~10% and is seen in critically ill patients.

Aetiology

• Acalculous (10%): gallbladder ischaemia/stasis - critical illness, major surgery, TPN, HIV, immunosuppression

Pathophysiology

Typical Presentation

• Persistent RUQ/epigastric pain (>6 hours - differentiates from biliary colic)
• Fever (38-39°C)
• Nausea, vomiting
• Positive Murphy's sign: inspiratory arrest on deep palpation of RUQ
• RUQ guarding, palpable gallbladder/mass in ~30%

Complications

• Empyema: swinging fevers, very tender gallbladder, systemic sepsis
• Gangrenous cholecystitis: may paradoxically have less pain (nerve death); high perforation risk
• Perforation: peritonitis, sepsis
• Mirizzi syndrome: common hepatic duct compression by impacted cystic duct stone → obstructive jaundice

Red Flags

• Sepsis (tachycardia, hypotension, fever >39°C)
• Generalised peritonitis (perforation)
• Jaundice (concomitant choledocholithiasis or Mirizzi)
• Palpable tense RUQ mass (empyema)

Bedside

• Murphy's sign: positive
• Observations: temperature, pulse, BP

Bloods

• FBC: leucocytosis (WCC >11 × 10⁹/L)
• CRP: raised
• LFTs: mildly raised ALP/GGT; if bilirubin raised → suspect CBD stone or Mirizzi
• Amylase/lipase: exclude pancreatitis
• Blood cultures: if septic