Peptic ulcer disease

An ulcer is "a defect in gastric or intestinal mucosae that extends through the muscularis mucosae"

i.e. extends into submucosal layer

Epidemiology

Declining incidence in developed countries
Declining progression to complicated PUD
Ulcers are rare before the age of 40, and peak incidence is 55-65

Aetiology - MINT

Medications
- NSAIDs/aspirin
  - Increased COX-1 inhibition leads to decreased prostaglandins and therefore impaired mucosal protection
  - Normally, prostaglandins protects gastric and duodenal mucosa from luminal acid and pepsin via increased mucin and bicarbonate secretion and increased mucosal endothelium blood flow and promoting epithelial cell proliferation and migration to the luminal surface
  - Risk for mucosal injury is roughly proportionate to the anti-inflammatory effect associated with each NSAID
  - Ulcers are more often found in the stomach (anywhere in stomach)
  - Not typically associated with gastritis
  - Ulcers do not usually recur when NSAIDs are discontinued
- Steroids
Infections
- H . Pylori
  - Separate topic
- Syphilis
- CMV - multiple round, erythematous, raised lesions in body and antrum, often with 'halo' pattern
Neoplasms
- Neoplastic - ZES
  - Separate topic
- Malignancy
  - Extremely rare with duodenal ulcers, but consider for gastric ulcers (either gastric adenocarcinoma or metastatic melanoma/breast/lung cancer)
Trauma
- Smoking
- Physiological stress
- Cocaine/methamphetamine
  - Causes ischaemia
Prior gastric surgery

Pathophysiology

Decreased defensive factors
- Mucosal bicarbonate secretion
- Mucus production
- Adequate blood flow
- Growth factors
- Cell renewal
- Endogenous prostaglandins
Increased damaging factors
- Hydrochloric acid secretion (gastric acid is normally protective, but ulcerogenic in the presence of a mucosal injury)
- Pepsins
- Chronic alcohol intake
- Smoking
- Duodenal bile reflux
- Ischaemia
- NSAIDs/corticosteroids
- Hypoxia
- H . Pylori

Anatomy

Modified Johnson anatomic classification
Historically used to guide aetiology based on location
Not as relevant now that we know the majority of ulcers are caused by H. pylori, but can be used to define what operation should be performed for each ulcer
60% of ulcers occur on the lesser curvature - most occur within 1.5cm of the histologic transition point between fundal and antral mucosa

Clinical manifestations:

Dyspepsia (epigastric discomfort) (present in 80%)
- Usually mid-epigastric pain which is quite well localised
- CLASSICALLY occurs 2-5 hours post-prandially, when acid secretion is maximal, and no food is present
- Frequently relieved shortly after food/antacid ingestion
- Constant pain suggests deeper penetration of the ulcer - radiating to back implies posterior penetration, possibly through to pancreas
- May have non-specific food-provoked symptoms
  - Nausea/vomiting, early satiety, belching, fatty food intolerance, reflux in 45%
Asymptomatic
- About 70%
- More likely to be asymptomatic in older patients, those on NSAIDs
Can't differentiate between gastric and duodenal ulcers clinically
Symptoms related to complications
- Bleeding
- Gastric outlet obstruction
- Perforation
Alarm features (in dyspepsia)
- Unintentional weight loss
- Progressive dysphagia
- Odynophagia
- Unexplained iron deficiency anaemia
- Persistent vomiting
- Palpable mass or lymphadenopathy
- Family history of upper GI cancer

Investigation

Endoscopy
- Indications:
  - Any patient with gastric ulceration on imaging (can be deferred up to 12 weeks post imaging)
  - Any patient with duodenal ulceration on imaging and 'alarm features' above
- Sensitivity ~90%
CT can be used to diagnose
Barium radiography
- Look for barium within the ulcer crater
- Can miss subtle ulcers
- Misses 50% of duodenal ulcers
- Can't biopsy

Differential diagnosis

Gastric malignancy
- 1/3 of ulcers >2cm harbour malignancy
- Ulcers not healing at 12 weeks should also raise suspicion
- Look for ulcers with irregular or heaped-up edges
Coeliac disease
Chronic pancreatitis
Biliary disease
Drug-induced dyspepsia

Workup for cause

Careful history - ask about all risk factors above
Perform at least two tests for H. pylori while off PPIs and antibiotics
Consider urine salicylate levels for surreptitious aspirin use
Biopsy ulcer for malignancy
Fasting serum gastrin level (off PPI)

Medical management

Uncomplicated PUD (also needed for all other situations below):

- H . Pylori eradication
  - HP7 - see separate topic
- Avoid NSAIDs/steroids
  - Will need 8 weeks of PPI, and consider maintenance PPI if need to stay on NSAIDs long-term
- Stop smoking
- Restrict EtOH to one per day
- Antacids
  - See description under 'GORD' topic
  - Mostly replaced by antisecretory therapy in modern times, but can be used for symptom control
- Sucralfate
  - See 'GORD' topic
  - Not clearly established to benefit PUD
- Histamine antagonists
  - See 'GORD'
  - Despite differences in potency, RCTs have demonstrated that all H2-receptor antagonists result in healing rates of 70-80% after 4 weeks and 80-90% after 8 weeks
- PPIs
  - See 'GORD'
  - Most potent anti-secretory agent
  - Healing rate 85% at 4 weeks and 96% at 8 weeks

Uncomplicated gastric ulcers:

Complicated gastric ulcers:

- PPI 8 weeks (often needs repeat endoscopy to confirm healing before ceasing therapy)

Uncomplicated duodenal ulcers:

- PPI 14 days
- Abx
- If asymptomatic post-treatment, no further PPI/Abx needed, and can confirm eradication

Complicated duodenal ulcers:

- PPI 8 weeks

Ulcers secondary to H. pylori

- See separate topic

Ulcers secondary to NSAIDs

- PPI (6 weeks if <1cm, 8 weeks if >1cm)
- Cease NSAIDs
- Lifelong PPI if:
  - Persistent ulcer on repeat scope
  - >2cm ulcer and age >50 or multiple comorbidities
  - Recurrent peptic ulcers
  - Condition requiring long-term NSAID use

Ulcers not associated with NSAIDs or H. pylori:

- PPI 4 weeks for duodenal ulcer, 8 weeks for gastric ulcer
- Repeat endoscopy, especially for gastric ulcers
- See above workup
- If workup negative, probably needs lifelong PPI

Persistent ulcers at repeat scope

- Biopsy for malignancy
- Consider medications, H pylori, smoking, alcohol
- Consider ZES

Prognosis

>90% heal with eradication of h. pylori
Acid-reducing procedures e.g. vagotomy probably not helpful - adds risk without improving outcomes

Complications

Common approach to treatment

- NBM
- IVF
- PPI (80mg BD either esomeprazole/pantoprazole)
  - Reduce to 40mg BD when tolerating PO intake
  - Then reduce to 40mg daily after 1/12
- ?H. pylori - however can't really test while bleeding or on PPIs
- Cease NSAIDs/aspirin if possible - if not possible, eternal PPI

Perforation (9%)

- 60% are duodenal, 20% antral, 20% gastric
  - Gastric more likely (10%) to contain malignancy
  - Most gastric perforations occur along the anterior aspect of the lesser curvature
- Presentation:
  - Phase 1 (0-2 hours)
    - Sudden onset epigastric pain, becoming more generalised
    - Local chemical peritonitis - doesn't want to move
    - Presyncope/syncope, weak pulse, cool extremities, tachycardia
  - Phase 2 (2-12 hours)
    - Pain may improve, but generalised, worse with movement
    - Peritonitic, rigid, tympanitic over liver, ileum
  - Phase 3 (>12 hours)
    - Hypotension, CV collapse
- Investigation
  - CXR - free gas in 65%
  - Typical history and CXR could technically be enough to operate
  - CT if any doubt, preferably with oral contrast
- Scores
  - Boey
  - PULP (Peptic ULcer Perforation score)
- Management:
  - 2x peripheral canulas, NBM + NGT, IVF, IDC, IV PPI, Abx (cover enteric gram negative rods, anaerobes, mouth flora - i.e. cef/met or piptaz, add in antifungal if sick), ?ICU, goals of care
  - Medical
    - 'Herman Taylor regimen' from a paper in 1946
    - Can sometimes be used in patients <70yo, well, early presentation
    - Only consider in patients with localised symptoms, in stable condition, and with a contrast study confirming a sealed leak
    - Close monitoring, serial exams, NPO + NGT, Abx and PPI
    - Perc drainage PRN
    - Short-term mortality in patients who need surgery but are not operative candidates is 30-60%
  - Surgical
    - Indications
      - Required in almost all patients
      - Delay to surgery increases mortality
      - Be aware that free gas without peritonism can sometimes be managed non-operatively
    - Technique
      - Open
        Upper midline laparotomy
        
        0-3cm perforation/easy: take full-thickness transversely-orientated (so as not to stricture the lumen) interrupted bites with 3/0 PDS, clipped on artery forceps but not tied. Fashion a pedicle of omentum and flip it into the defect, then loosely tie the sutures. Leak test. 5L wash and drain.
        If omentum is flimsy, can use mobilised falciform ligament or serosal patch
        
        This is termed a pedicled (Cellan-Jones) or free (Graham) patch
        
        >3cm perforation/difficult/unable to close with simple omentopexy: Choose between definitive procedure or damage control.
        Definitive procedure: Likely to be resection +/- diversion.
        Distal gastrectomy and a Bilroth II or Roux-en-Y reconstruction. See separate topic - 'distal gastrectomy'.
        
        Greater curvature - easier to wedge resect back to healthy stomach, may not need to divert
        
        A large lesser curvature or duodenal ulcer is notoriously difficult - likely to be distal/subtotal gastrectomy.
        
        Repair and diversion, instead of resection and diversion (I think this is a suboptimal option) - can form a Roux-en-Y bypass/Bilroth II and then either staple across the distal stomach with a non-cutting TA stapler, or tie a 1 PDS suture around the stomach to divert, which will be expected to eventually give way. Another option is to make a gastrotomy and then place a mucosal purse-string suture around the pylorus from internally.
        
        Damage control: If unable to perform a definitive procedure for patient factors or disease factors, will need to do a damage-control procedure - drain with Foley catheter, washout, transfer to UGIS unit. Better to do this than try a complicated resection and reconstruction on an unwell patient with limited UGIS experience.
        Tube duodenostomy - 16Fr Foley surrounded by a loose purse-string to support it, with additional peritoneal drainage and NGT
        
        Bring some omentum up to cover the defect too
        
        Triple-ostomy approach sits between damage control and definitive repair - drainage of the ulcer bed (maybe with a T-tube or IDC), stomach drainage through a PEG/NGT, and feeding jejunostomy, ideally with pyloric exclusion to prevent gastric contents contacting ulcer. If doing this, perhaps better just formally resecting.
      - Laparoscopic
        Less morbidity and wound complications
        
        Good option in stable and well-resuscitated patients with an easily-accessible perforation
      - Lavage with 5-10L N/S
      - Classically, leave a drain and NGT for two days then restart PO intake after 48 hours. Consider CT with PO contrast or methylene blue leak test prior.
      - Empiric antibiotics 3-5 days and H. pylori eradication once tolerating oral intake (may need longer courses of antibiotics with delayed intervention)
  - Endoscopic therapy is emerging
- Prognosis
  - 30% 90-day mortality
- Special situations
  - Perforation and bleeding
    - Might be a 'kissing' ulcer - can enlarge the perforation, suture-transfix the bleeding ulcer, then close the perforation

Bleeding (73%)

- See 'UGiB' for initial workup and management, including operative technique

Gastric outlet obstruction (3%)

- See separate topic

Penetration

- Refers to penetration through bowel wall without free perforation or leakage into the peritoneum
- i.e. fistula into another organ

Intractable PUD

- Truly intractable PUD is now rare
- Refer to workup table above
- Consider eventual treatment with a vagotomy +/- antrectomy

Elective surgery for PUD

Indications:
- H . Pylori cannot be eradicated
- Cannot be taken off NSAIDs
- Rarer cause of PUD that can't be fixed
- Patients non-compliant with antisecretory therapy (controversial)
See separate topic under 'UGIS operations'