Peptic Ulcer Disease in Adults

SECTION 1: Clinical Overview

1.1 Summary

Peptic ulcer disease (PUD) is a distinct break in the mucosal lining of the stomach (gastric ulcer) or the first portion of the small intestine (duodenal ulcer). This breach occurs when the normal mucosal defensive factors are overwhelmed by aggressive factors such as gastric acid and pepsin. Historically, PUD was considered a chronic, life-altering condition of stress and diet, but the paradigm shifted with the discovery of Helicobacter pylori by Marshall and Warren in 1984, revolutionizing treatment from "acid control" to "infection control." [1,2] The widespread use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) represents the other major etiological factor. [3] Globally, PUD affects approximately 4 million people annually, with a lifetime prevalence of 5-10% in the general population, though incidence has declined significantly in developed nations due to successful H. pylori eradication programs and reduced prevalence of infection. [4,5] The classification is primarily based on anatomical location (gastric vs duodenal) and etiology, with H. pylori-positive (60-90% of duodenal ulcers, 70-90% of gastric ulcers), NSAID-induced (20-30%), and idiopathic ulcers (less than 10%) being the primary categories. [6] Clinical significance is paramount due to the risk of life-threatening complications, including gastrointestinal hemorrhage (15-20% of cases), perforation (2-10%), and gastric outlet obstruction (1-2%). [7,8] Management has evolved from radical surgery (vagotomy/antrectomy) to highly effective medical therapy centered on H. pylori eradication and potent acid suppression with Proton Pump Inhibitors (PPIs). With modern triple or quadruple eradication therapy, cure rates exceed 85-90%, though antibiotic resistance is an emerging challenge. [9,10] The prognosis is excellent for uncomplicated PUD, with recurrence rates less than 5% after successful H. pylori eradication, compared to 60-90% without treatment. [11]

1.2 Key Facts

• Definition: A mucosal defect ≥5 mm in diameter extending through the muscularis mucosae of the stomach or duodenum, distinct from erosions which are superficial and do not penetrate the muscularis mucosae.
• Incidence: Approximately 0.1 to 0.3 per 1,000 person-years in Western countries, with declining trends over the past 30 years. [12,13]
• Prevalence: 5-10% lifetime risk; however, prevalence is declining in developed nations due to H. pylori eradication and decreasing infection rates among younger cohorts.
• Global Burden: H. pylori infects approximately 50% of the global population, with higher rates (> 60%) in developing countries and lower rates (20-30%) in developed nations. [14]
• Mortality: Overall 30-day mortality for bleeding ulcers is 5-10%; for perforation, mortality ranges from 10-40% depending on age and comorbidities. [15,16]
• Morbidity: Major cause of work absenteeism, reduced quality of life, and healthcare costs exceeding $10 billion annually in the United States.
• Peak Age: Duodenal ulcers peak between 30-50 years; gastric ulcers peak over age 60, reflecting the age distribution of NSAID use and H. pylori acquisition patterns.
• Sex Distribution: Historically 2:1 (M:F) for duodenal ulcers, but now approaching 1:1 due to increased NSAID use and smoking in women. [17]
• Pathognomonic Feature: Nocturnal pain (classically waking at 1-3 AM) relieved by food or antacids is characteristic of duodenal ulcers, while gastric ulcer pain is often exacerbated by food.
• Gold Standard Investigation: Esophagogastroduodenoscopy (EGD) with biopsy for H. pylori testing (rapid urease test, histology) and malignancy exclusion (gastric ulcers). Sensitivity and specificity both exceed 95%. [18]
• First-line Treatment: High-dose PPI-based triple therapy (PPI + clarithromycin + amoxicillin) for 14 days in areas with low clarithromycin resistance (less than 15%). [9]
• Second-line Treatment: Bismuth-based quadruple therapy (PPI + bismuth + tetracycline + metronidazole) for resistant H. pylori or as first-line in high-resistance areas. [19]
• Key Complication: Upper gastrointestinal bleeding (UGIB), occurring in 15-20% of patients, with re-bleeding rates of 10-15% despite endoscopic therapy. [20]
• Malignancy Risk: Gastric ulcers have a 3-5% risk of harboring adenocarcinoma; all gastric ulcers require multiple biopsies and follow-up endoscopy to confirm healing. [21]

1.3 Clinical Pearls

Diagnostic Pearl: "The Food-Pain Relationship" Gastric ulcer pain is often exacerbated by food (leading to weight loss), whereas duodenal ulcer pain is classically relieved by food (leading to weight gain). This distinction helps localize the lesion before endoscopy.

Examination Pearl: "Epigastric Tenderness" While non-specific, localized epigastric tenderness without guarding is the most common finding. The presence of "succussion splash" suggests gastric outlet obstruction, a late complication of chronic scarring.

Treatment Pearl: "The PPI Timing" Advise patients to take PPIs 30-60 minutes before the first meal of the day. This is crucial because PPIs only bind to actively secreting proton pumps, which are maximally stimulated by meal ingestion.

Pitfall Warning: "The Malignant Gastric Ulcer" Never assume a gastric ulcer is benign. Unlike duodenal ulcers, which are rarely malignant, all gastric ulcers require biopsy at index EGD and follow-up EGD to confirm healing and exclude gastric adenocarcinoma.

Mnemonic: "The 4 H's of PUD" H. pylori (most common cause), Hyperacidity (Zollinger-Ellison), Hard drugs (NSAIDs/Steroids), and Habitual smoking (impairs healing).

Emergency Pearl: "The Silent Perforation" In elderly patients or those on chronic steroids, the classic "board-like" abdomen may be absent. Maintain a high index of suspicion for perforation in any elderly patient with sudden onset vague abdominal pain.

Exam Pearl: "Forrest Classification" Examiners frequently ask about the Forrest classification for bleeding ulcers. Class Ia (spurting) and Ib (oozing) require immediate endoscopic intervention and have the highest re-bleed risk.

1.4 Why This Matters Clinically

• Patient outcomes: Failure to diagnose PUD or eradicate H. pylori leads to a 60-90% recurrence rate within one year. Mismanagement of a bleeding ulcer carries a significant risk of exsanguination and death.
• Healthcare burden: PUD remains one of the most expensive GI conditions due to emergency admissions for bleeding and the high cost of long-term PPI therapy and surveillance.
• Medico-legal: Failure to biopsy a gastric ulcer that later proves to be cancer is a common source of litigation. Similarly, failure to provide gastroprotection for high-risk NSAID users is a preventable error.
• Training relevance: PUD is a "bread and butter" topic for internal medicine and surgery boards, testing knowledge of physiology, microbiology, and emergency management.

SECTION 2: Epidemiology

2.1 Incidence & Prevalence

• Incidence: 0.1% per year in the general population (PMID: 26302443).
• Prevalence: Global prevalence of H. pylori is approximately 50%, though only 10-15% of those infected develop PUD.
• Lifetime Risk: 1 in 10 adults in Western societies will develop an ulcer.
• Trend: Decreasing incidence of H. pylori ulcers, but stable or increasing incidence of NSAID-related ulcers due to an aging population.
• Geographic Variation: Higher prevalence in developing nations (Africa, SE Asia) where H. pylori colonization occurs in early childhood.
• Temporal Patterns: Some studies suggest a slight increase in complications during winter months, possibly linked to NSAID use for viral illnesses.
• Healthcare Burden: Accounts for over 1 million hospitalizations annually in the United States alone.

2.2 Demographics Table

2.3 Risk Factors Tables

Non-Modifiable Risk Factors:

Modifiable Risk Factors:

2.4 Protective Factors

• Factor 1: PPI Co-therapy (RR 0.20): Potent acid suppression prevents NSAID-induced mucosal damage.
• Factor 2: High Fiber Diet (RR 0.60): May buffer bile acids and slow gastric emptying.
• Factor 3: Vitamin A intake (RR 0.70): Enhances mucus production and epithelial integrity.

SECTION 3: Pathophysiology

3.1 Step 1: Initiating Event/Trigger

H. pylori-Induced Ulceration:

The initiation of H. pylori-associated PUD involves a complex interplay of bacterial virulence factors and host immune responses.

Bacterial Virulence Factors:

• Urease Enzyme: The bacteria produce abundant urease, which hydrolyzes gastric urea to ammonia (NH3) and carbon dioxide (CO2). [22] The ammonia creates a local alkaline microenvironment (pH 6-7) surrounding the bacteria, protecting them from gastric acid (pH 1-3) and allowing survival in the hostile gastric lumen.
• CagA (Cytotoxin-Associated Gene A): Present in 60-70% of H. pylori strains, CagA is translocated into gastric epithelial cells via a Type IV secretion system. [23,24] Once inside, CagA undergoes tyrosine phosphorylation and activates multiple signaling pathways (ERK/MAPK, PI3K/AKT), leading to cytoskeletal rearrangement, disruption of tight junctions, and increased cell proliferation. CagA-positive strains are associated with a 2-3 fold increased risk of peptic ulceration and gastric cancer.
• VacA (Vacuolating Cytotoxin A): This pore-forming toxin induces vacuolation of epithelial cells, increases membrane permeability, and triggers apoptosis. [25] VacA also impairs T-cell function, contributing to chronic infection by evading immune clearance.
• Bacterial Adhesins: BabA (Blood group antigen-binding adhesin) binds to Lewis B antigens on gastric epithelial cells, particularly in individuals with blood group O, explaining the 1.3-fold increased risk in this population. [26] SabA (Sialic acid-binding adhesin) binds to inflamed mucosa, facilitating persistent colonization.

Molecular Mechanisms:

• Toll-like Receptor Activation: Bacterial lipopolysaccharide (LPS) and other PAMPs (pathogen-associated molecular patterns) activate TLR4 and TLR2 on gastric epithelial cells and immune cells.
• NF-κB Pathway: Activation leads to nuclear translocation of NF-κB, inducing transcription of pro-inflammatory cytokines (IL-8, IL-1β, TNF-α). [27]
• Disruption of Acid Regulation: In antral-predominant gastritis, H. pylori suppresses D-cell somatostatin secretion, removing the inhibitory "brake" on G-cell gastrin release. This leads to hypergastrinemia and increased parietal cell acid secretion, creating a high acid load in the duodenum that promotes duodenal ulceration. [28]

Cellular Response:

• Primary Cells Affected: Gastric epithelial cells (mucus-secreting and parietal cells), D-cells (somatostatin), G-cells (gastrin), and immune cells (neutrophils, macrophages, T-cells).
• Initial Changes: Within hours of infection, neutrophil recruitment causes acute inflammation. Over weeks to months, chronic active gastritis develops with lymphoplasmacytic infiltration.
• Time Course: Colonization occurs within days of exposure; chronic active gastritis develops over weeks; ulceration typically requires months to years of persistent infection and inflammation.

NSAID-Induced Ulceration:

NSAID-induced mucosal injury occurs through distinct topical and systemic mechanisms.

Primary Trigger - COX Inhibition:

• Systemic Mechanism: NSAIDs non-selectively inhibit both Cyclooxygenase-1 (COX-1, constitutive) and COX-2 (inducible), preventing the conversion of arachidonic acid to prostaglandins. [29,30]
• Loss of Prostaglandin E2 (PGE2): PGE2 is critical for gastric mucosal defense. It stimulates: (1) mucus and bicarbonate secretion, (2) mucosal blood flow, (3) epithelial cell proliferation and repair, and (4) inhibition of parietal cell acid secretion. Loss of PGE2 disrupts all these protective mechanisms.
• Topical Injury: NSAIDs are weak acids that become trapped in gastric epithelial cells (ion trapping), causing direct mitochondrial injury and oxidative stress. [31]

Microvascular Injury:

• Neutrophil-Endothelial Interactions: NSAIDs promote neutrophil adherence to gastric vascular endothelium via upregulation of adhesion molecules (ICAM-1, P-selectin). [32]
• Ischemia: Neutrophil-mediated microvascular occlusion reduces mucosal blood flow by 30-50%, impairing bicarbonate delivery and waste removal.
• Oxidative Stress: Neutrophil activation releases reactive oxygen species (ROS) and proteases that damage the epithelium.

Molecular Basis:

• Receptor Interaction: NSAIDs bind to the active site of COX enzymes, blocking substrate access.
• Dose-Response: Risk increases with higher NSAID doses, with relative risks of 2-4 for low-dose NSAIDs and 4-8 for high-dose therapy. [33]
• COX-2 Selective Inhibitors: Reduce but do not eliminate GI risk (RR 0.5-0.6 vs non-selective NSAIDs), as COX-2 also plays a role in mucosal healing.

Synergistic Effects:

• NSAID + H. pylori: Concomitant infection and NSAID use have additive or synergistic effects, increasing ulcer risk 3-4 fold beyond either factor alone. [34]
• NSAID + Corticosteroids: Corticosteroids alone carry minimal ulcer risk (RR 1.1-1.5), but in combination with NSAIDs, risk increases 4-fold. [35]
• NSAID + Anticoagulants/Antiplatelets: Aspirin, clopidogrel, and anticoagulants dramatically increase bleeding risk (RR 6-13) without necessarily increasing ulcer incidence, reflecting impaired hemostasis rather than ulcerogenesis.

3.2 Step 2: Early Pathological Changes

Inflammatory Response: The presence of H. pylori or the loss of prostaglandins triggers a robust immune response.

• Cytokines: High levels of IL-8 (a potent neutrophil chemoattractant), IL-1β, and TNF-α.
• Complement: Activation of the alternative pathway occurs as bacterial proteins interact with serum.
• Acute Phase: Localized increase in vascular permeability and recruitment of leukocytes.

Cellular Infiltration:

• Neutrophils: These are the first responders, causing "active" gastritis. They release reactive oxygen species (ROS) and proteases that damage host tissue.
• Monocytes/Macrophages: Recruited to sustain the inflammatory milieu.

Tissue Changes:

• Microvascular Injury: NSAIDs cause neutrophil adherence to the vascular endothelium of the gastric microcirculation, leading to ischemia and reduced bicarbonate delivery.
• Edema: Submucosal edema develops as the epithelial barrier leaks.

3.3 Step 3: Established Disease Process

Progression of Pathology: As the aggressive factors (acid/pepsin) continue to assault the weakened mucosa, a focal area of necrosis develops.

• Tissue Remodeling: The body attempts to heal via granulation tissue, but persistent acid prevents epithelialization.
• Fibroblast Activation: Deep in the ulcer base, fibroblasts begin depositing collagen.

Histological Findings:

• Four Layers of Zenker: (1) Superficial zone of fibrinoid exudate, (2) Zone of necrotic tissue, (3) Zone of granulation tissue, (4) Zone of fibrous cicatrization (scarring).
• Pathognomonic: Finding H. pylori organisms in the mucus layer or within gastric pits.

Functional Consequences:

• Hyperchlorhydria: Specifically in duodenal ulcers, the high acid load enters the bulb, overwhelming the duodenal bicarbonate buffer.
• Gastric Metaplasia: The duodenum undergoes gastric metaplasia to protect itself, which ironically provides a niche for H. pylori to colonize the duodenum.

3.4 Step 4: Complications and Progression

Natural History: Without intervention, ulcers undergo cycles of partial healing and relapse. Chronic ulcers penetrate the muscularis propria.

• Penetration: The ulcer may erode into adjacent organs (e.g., the pancreas), leading to referred back pain and elevated amylase.

Local Effects:

• Vascular Erosion: If the ulcer erodes into a submucosal artery (e.g., gastroduodenal artery in posterior duodenal ulcers), massive hemorrhage occurs.
• Perforation: Full-thickness erosion into the peritoneal cavity, leading to chemical and then bacterial peritonitis.

Systemic Effects:

• Anemia: Chronic occult blood loss leads to iron deficiency anemia.
• Metabolic Alkalosis: Seen in gastric outlet obstruction due to persistent vomiting of hydrochloric acid.

3.5 Step 5: Resolution, Chronicity, or Death

Resolution/Healing: With PPI therapy, the pH is raised > 4.0, which inhibits pepsin activity and allows the epithelium to migrate across the granulation tissue base.

• Eradication: Removal of H. pylori allows the somatostatin-gastrin balance to normalize.

Scarring/Fibrosis:

• Pyloric Stenosis: Repeated ulceration and healing at the pylorus lead to a fixed, fibrous stricture, necessitating surgical or endoscopic intervention.

Outcomes:

• Cure: Achieved in > 95% of cases with successful H. pylori eradication and avoidance of NSAIDs.
• Death: Usually results from multi-organ failure following a major bleed or septic shock following perforation.

3.6 Classification/Staging

Johnson Classification (Gastric Ulcers):

3.7 Anatomical Considerations

• Duodenal Ulcers: 95% occur in the first portion (bulb), usually within 3 cm of the pylorus.
• Blood Supply: The gastroduodenal artery runs posterior to the first part of the duodenum; posterior ulcers are therefore high-risk for catastrophic bleeds.
• Nerve Supply: Vagus nerve (CN X) stimulates acid secretion; historically targeted by vagotomy.

3.8 Physiological Considerations

• Bicarbonate-Mucus Barrier: The "first line" of defense. Bicarbonate creates a pH gradient (pH 7 at the cell surface vs pH 2 in the lumen).
• Prostaglandins: Stimulate mucus and bicarbonate secretion, maintain mucosal blood flow, and inhibit parietal cell acid production.

SECTION 4: Clinical Presentation

4.1 Symptoms

Typical Presentation:

Atypical Presentations:

• Elderly: Often asymptomatic until complication (bleeding/perforation) occurs. May present with vague "failure to thrive" or confusion.
• NSAID Users: Frequently "silent" ulcers because NSAIDs mask the pain through their analgesic effect.
• Pregnancy: PUD symptoms often improve due to increased protective mucus and decreased acid during pregnancy.

4.2 Signs

General Examination:

• Vitals: Tachycardia and hypotension suggest hemorrhage or sepsis.
• Appearance: Pallor (anemia), cachexia (malignancy or obstruction).

System-Specific Signs:

4.3 Red Flags

[!CAUTION] RED FLAGS — Seek immediate help if:

• Hematemesis: Indicates active upper GI bleeding; high risk of shock.
• Melena: Black, tarry, foul-smelling stools indicate digested blood (at least 50-100cc).
• Sudden, Severe Pain: "Thunderclap" abdominal pain suggests acute perforation.
• Board-like Rigidity: Pathognomonic for peritonitis following perforation.
• Unexplained Weight Loss: Raises concern for gastric malignancy mimicking an ulcer.
• Persistent Vomiting: Suggests mechanical obstruction at the pylorus.
• New Onset Anemia: In an adult, must exclude GI blood loss (PUD or cancer).

4.4 Clinical Scoring

• Glasgow-Blatchford Score (GBS): Used in the ER to identify low-risk patients who can be safely discharged without inpatient endoscopy (Score 0-1 = low risk).
• Rockall Score: Used post-endoscopy to predict mortality and re-bleeding risk based on age, shock, and endoscopic findings.

SECTION 5: Clinical Examination

5.1 Structured Approach

ABCDE Approach (for Acute Presentation):

• A: Ensure airway is clear, especially if the patient is actively vomiting blood.
• B: Monitor respiratory rate; tachypnea may indicate metabolic acidosis (sepsis/shock).
• C: Two large-bore IVs (14-16G). Monitor BP and HR. Check capillary refill.
• D: Assess GCS; encephalopathy may occur in severe shock or hepatic overlap.
• E: Full abdominal exposure. Look for surgical scars (previous PUD surgery) and hernias.

5.2 Special Tests Table

5.3 Examination by Severity

• Mild: Normal vitals; mild epigastric tenderness; no guarding.
• Moderate: Mild tachycardia; orthostatic changes; persistent dyspepsia; occult blood in stool.
• Severe (Emergency): Hypotension; rigid abdomen; hematemesis; altered mental status.

SECTION 6: Investigations

6.1 Bedside Tests

6.2 Laboratory Tests

6.3 Imaging

6.4 Diagnostic Criteria

Endoscopic Diagnosis:

• Definitive Diagnosis: Direct endoscopic visualization of a mucosal defect in the gastric or duodenal mucosa ≥5 mm in diameter with visible depth extending through the muscularis mucosae into the submucosa or deeper layers. [36]
• Ulcer Characteristics: Well-demarcated crater with punched-out borders, often with a white or yellow fibrinous base, surrounded by edema and erythema.
• Differentiation from Erosions: Erosions are superficial mucosal breaks less than 5 mm that do not penetrate the muscularis mucosae and typically appear as multiple, shallow, linear or punctate lesions.

H. pylori Diagnostic Tests:

Invasive Tests (Require Endoscopy):

Non-Invasive Tests (No Endoscopy Required):

Optimal Testing Strategy:

• Pre-Endoscopy: In patients with uncomplicated dyspepsia less than 55 years without alarm features, "test-and-treat" with UBT or SAT is cost-effective in areas where H. pylori prevalence exceeds 10%. [44]
• During Endoscopy: Obtain ≥2 biopsies (one from antrum, one from corpus) for RUT and histology. In patients with recent PPI use or active bleeding, sensitivity of RUT decreases; rely on histology or defer testing. [45]
• Post-Eradication Confirmation: Perform UBT or SAT at least 4-6 weeks after completion of eradication therapy to confirm cure. Endoscopy is only indicated for post-eradication confirmation in gastric ulcers (to document healing and exclude malignancy). [46]

Forrest Classification for Bleeding Ulcers:

The Forrest classification stratifies bleeding ulcers based on endoscopic appearance and predicts re-bleeding risk and mortality. [47,48]

High-Risk Endoscopic Features:

• Ulcer size > 2 cm (RR 2.5 for re-bleeding)
• Posterior duodenal bulb location (proximity to gastroduodenal artery)
• High lesser curve gastric ulcers (proximity to left gastric artery)
• Forrest Ia, Ib, IIa lesions

Gastric Ulcer Malignancy Exclusion:

All gastric ulcers require malignancy exclusion due to 3-5% risk of gastric adenocarcinoma. [21,49]

Biopsy Protocol:

• Obtain 6-8 biopsies from the ulcer margin (4 quadrants, 2 from each quadrant)
• Additional biopsies from ulcer base if raised or nodular
• Separate biopsies from surrounding mucosa for H. pylori testing

High-Risk Features for Malignancy:

• Large ulcer size (> 3 cm)
• Irregular, raised, or rolled margins
• Nodular or friable ulcer base
• Location on greater curve or fundus (atypical for benign ulcers)
• Failure to improve with 2 weeks of PPI therapy

Follow-up Endoscopy:

• Mandatory at 8-12 weeks for all gastric ulcers to document complete healing
• Persistent ulceration or incomplete healing requires repeat biopsy
• Duodenal ulcers do not require follow-up endoscopy unless symptoms persist or malignancy is suspected (rare less than 0.5%)

Imaging for Perforation:

CT is preferred for:

• Elderly or immunosuppressed patients (may lack peritoneal signs)
• Atypical presentations
• Localized/sealed perforations
• Pre-operative planning and assessment of other pathology

SECTION 7: Management

⚠️ MANDATORY: ASCII MANAGEMENT ALGORITHM

┌─────────────────────────────────────────────────────────────┐
│             PEPTIC ULCER DISEASE MANAGEMENT                  │
└─────────────────────────────────────────────────────────────┘
                              │
                              ▼
              ┌───────────────────────────────┐
              │     INITIAL PRESENTATION      │
              │  • Assess ABCs / Vitals       │
              │  • Check for Red Flags        │
              └───────────────────────────────┘
                              │
              ┌───────────────┴───────────────┐
              ▼                               ▼
      [STABLE / CHRONIC]              [UNSTABLE / ACUTE]
      • Dyspepsia                     • Hematemesis/Melena
      • Epigastric pain               • Rigid Abdomen
              │                               │
              ▼                               ▼
      ┌─────────────────┐             ┌─────────────────┐
      │  INVESTIGATE    │             │   RESUSCITATE   │
      │ • H.pylori test │             │ • 2x L-bore IVs │
      │ • Referral EGD  │             │ • IVF / Blood   │
      └─────────────────┘             │ • IV PPI Bolus  │
              │                       └────────┬────────┘
              ▼                                │
      ┌─────────────────┐             ┌────────┴────────┐
      │      EGD        │             │   URGENT EGD    │
      │ • Biopsy (GU)   │             │ • Hemostasis    │
      │ • CLOtest       │             │ • Adrenaline/Clip│
      └────────┬────────┘             └────────┬────────┘
               │                               │
        ┌──────┴──────────────┬────────────────┴─────┐
        ▼                     ▼                      ▼
┌───────────────┐     ┌───────────────┐      ┌───────────────┐
│  H. PYLORI +  │     │  NSAID INDUCED│      │  PERFORATION  │
│               │     │               │      │               │
│ Eradication   │     │ Stop NSAID    │      │ NPO / NGT     │
│ Regimen       │     │ High-dose PPI │      │ Surgery Ref   │
└───────────────┘     └───────────────┘      └───────────────┘
        │                     │                      │
        ▼                     ▼                      ▼
┌───────────────┐     ┌───────────────┐      ┌───────────────┐
│ Confirm Cure  │     │ Maintenance   │      │ Post-Op Care  │
│ • UBT @ 4 wks │     │ • PPI if cont.│      │ • Abx / PPI   │
│ • EGD (if GU) │     │   NSAID       │      │ • H.pylori Rx │
└───────────────┘     └───────────────┘      └───────────────┘

7.1 Emergency/Acute Management

Immediate Actions (ABCDE approach):

1. Airway: If GCS less than 8 or massive hematemesis, consider intubation to prevent aspiration.
2. Breathing: Supplemental O2 to maintain SpO2 > 94%.
3. Circulation: 1-2L warmed crystalloid; activate massive transfusion protocol if shock persists. Target Hb > 7-8 g/dL (higher in CAD).
4. Disability: Monitor for hepatic encephalopathy if cirrhotic.
5. Exposure: Check for stigmata of chronic liver disease (spider naevi, caput medusae).

Emergency Medications:

• PPI Bolus: Pantoprazole 80mg IV bolus followed by 8mg/hr infusion (PMID: 20439516).
• Prokinetics: Erythromycin 250mg IV 30-60 mins before EGD to clear the stomach of blood.
• Antibiotics: Ceftriaxone 1g IV if cirrhosis/variceal bleed suspected.

7.2 Conservative Management

Lifestyle Modifications:

• Smoking Cessation: Essential; smoking stimulates acid and reduces mucosal blood flow.
• Alcohol: Limit intake; avoid spirits which are directly caustic.
• Diet: No specific "ulcer diet" exists, but avoid triggers (spicy, caffeine, late-night meals).
• Stress: While not a primary cause, stress management improves symptom perception.
• NSAID avoidance: Switch to Acetaminophen (Paracetamol) or selective COX-2 inhibitors with PPI.

7.3 Medical Management

H. pylori Eradication Therapy:

The choice of eradication regimen depends on local antibiotic resistance patterns, prior antibiotic exposure, penicillin allergy, and treatment history. [9,19,52]

First-Line Regimens:

Standard Triple Therapy (Areas with less than 15% Clarithromycin Resistance):

Efficacy: 70-85% eradication in intention-to-treat (ITT) analysis; declining due to increasing clarithromycin resistance (now > 15-20% in many regions). [53]

Bismuth Quadruple Therapy (First-line in High-Resistance Areas or Second-line After Triple Therapy Failure):

Efficacy: 85-95% eradication; effective even with clarithromycin or metronidazole resistance; increasing availability of single-capsule formulations improves compliance. [54,55]

Concomitant (Non-Bismuth) Quadruple Therapy:

Efficacy: 85-90%; superior to standard triple therapy in areas with moderate clarithromycin resistance (15-40%). [56]

Sequential Therapy (Alternative First-line):

• Days 1-5: PPI + Amoxicillin 1g BD
• Days 6-10: PPI + Clarithromycin 500mg BD + Metronidazole 500mg BD

Efficacy: 80-90%; may be inferior to concomitant or bismuth quadruple therapy in high-resistance regions; compliance issues with changing regimens. [57]

Rescue/Salvage Regimens (After 2+ Failed Eradication Attempts):

Levofloxacin Triple Therapy:

Efficacy: 70-85%; fluoroquinolone resistance increasing in some regions (10-20%); risk of tendinopathy and C. difficile infection. [58]

High-Dose Dual PPI-Amoxicillin Therapy (Vonoprazan-based):

Efficacy: 85-90%; vonoprazan (potassium-competitive acid blocker) achieves more potent and consistent acid suppression than PPIs; effective even with antibiotic resistance; approved in Japan, under investigation elsewhere. [59,60]

Antibiotic Resistance Patterns:

Strategies to Optimize Eradication:

1. High-dose PPI: Use double-dose PPIs (e.g., omeprazole 40mg BD) to achieve intragastric pH > 6, optimal for antibiotic efficacy. [62]
2. Extended Duration: 14-day regimens superior to 7-10 day regimens (absolute benefit 5-10%). [63]
3. Adjunctive Probiotics: Addition of Lactobacillus and Saccharomyces species may increase eradication rates by 5-10% and reduce antibiotic-associated diarrhea. [64]
4. Culture and Sensitivity: In areas with high resistance or after multiple failures, culture-directed therapy (if available) improves success rates to > 90%.
5. Patient Education: Emphasize adherence; missed doses reduce eradication rates by 15-20%.

Acid Suppression Therapy (For Ulcer Healing):

Proton Pump Inhibitors (First-line):

Duration:

• Uncomplicated duodenal ulcers: 4-6 weeks
• Uncomplicated gastric ulcers: 8-12 weeks
• Giant ulcers (> 3 cm): 12-16 weeks

IV PPI for Acute Bleeding:

• Loading dose: Pantoprazole or esomeprazole 80mg IV bolus
• Infusion: 8mg/hour continuous infusion for 72 hours post-endoscopy
• Evidence: Reduces re-bleeding rates from 20% to 10% and need for surgery from 10% to 5%. [65,66]

H2-Receptor Antagonists (Second-line, Now Rarely Used):

Mucosal Protective Agents:

NSAID-Related Ulcer Prevention:

Risk Stratification for GI Complications:

Gastroprotection Strategies:

Special Considerations:

• Aspirin for cardiovascular prophylaxis: Even low-dose aspirin (75-100mg) increases ulcer and bleeding risk 2-4 fold. Co-prescribe PPI in high-risk patients. [68]
• Dual antiplatelet therapy (DAPT): Aspirin + clopidogrel increases bleeding risk 6-13 fold. PPI co-therapy essential; use PPIs with minimal CYP2C19 interaction (pantoprazole) to avoid clopidogrel attenuation concerns (clinical significance debated). [69]

7.4 Surgical Management

Indications for Surgery:

1. Perforation: Acute surgical emergency (Graham Patch repair).
2. Obstruction: If endoscopic dilation fails.
3. Uncontrolled Bleeding: Failure of two endoscopic attempts.
4. Suspected Malignancy: Non-healing gastric ulcer despite therapy.
5. Intractability: Rare in the PPI era.

Procedure Description:

• Laparoscopic Graham Patch: Omentum is placed over the perforation and sutured.
• Partial Gastrectomy (Billroth I/II): Removal of the ulcer-bearing area.
• Highly Selective Vagotomy: Denervating parietal cells to reduce acid (rarely performed now).

7.5 Disposition

Admission Criteria:

1. Hemodynamic instability (shock/tachycardia).
2. Active hematemesis or melena.
3. High-risk endoscopic stigmata (Forrest I or IIa/b).
4. Evidence of perforation or obstruction.
5. Severe comorbidities (CHF, Cirrhosis).

Discharge Criteria:

1. GBS score 0-1 (pre-EGD).
2. Clean-based ulcer (Forrest III).
3. Hemodynamically stable for > 24 hours.
4. Able to tolerate oral intake and medications.

SECTION 8: Complications

8.1 Immediate Complications

Upper Gastrointestinal Bleeding (UGIB):

Bleeding occurs in 15-20% of PUD patients and represents the most common life-threatening complication. [20,70]

Endoscopic Hemostasis Techniques:

Combination therapy (epinephrine injection + second modality) is superior to epinephrine monotherapy, reducing re-bleeding from 20% to 10%. [73,74]

Angiographic Embolization:

• Indication: Failed endoscopic hemostasis (after 2 attempts) or inability to identify bleeding source endoscopically
• Technique: Selective catheterization of gastroduodenal, left gastric, or right gastric artery with coil or gelfoam embolization
• Efficacy: 75-90% immediate hemostasis; re-bleeding in 10-20%
• Complications: Intestinal ischemia (1-5%), hepatic injury (less than 1%)

Surgical Hemostasis:

• Indication: Hemodynamic instability despite resuscitation, failed endoscopic and angiographic hemostasis, perforation
• Procedures:
  • "Duodenal ulcer: Oversewing of bleeding vessel + vagotomy and pyloroplasty/gastrojejunostomy (historical) or oversewing alone (modern)"
  • "Gastric ulcer: Wedge resection (if lesser curve), Billroth I partial gastrectomy (if large/malignant)"
• Mortality: 10-30%; significantly higher than medical/endoscopic management due to patient selection (older, sicker, delayed presentation) [75]

Perforation:

Free perforation occurs in 2-10% of PUD patients, creating a surgical emergency. [76,77]

Perforation Management:

Non-Operative Management (Selected Cases):

• Indication: less than 24h from symptom onset, hemodynamically stable, minimal free fluid on CT, no signs of sepsis, ability for close monitoring
• Criteria: Localized peritoneal signs, sealed perforation on imaging, contrast study showing no leak
• Treatment: NPO, NG decompression, IV PPI, broad-spectrum antibiotics (pip-tazo or carbapenem + metronidazole), serial abdominal exams
• Success Rate: 70-80% in highly selected patients; 20-30% require delayed surgery [79]

Operative Management (Majority):

Post-operative Management:

• Broad-spectrum antibiotics for 5-7 days (or until afebrile 24-48h)
• High-dose PPI (IV then oral) for 8-12 weeks
• H. pylori eradication therapy (once NPO status resolved)
• Follow-up to confirm eradication and ulcer healing

Penetration (Posterior Ulcers):

Gastric Outlet Obstruction (GOO):

8.2 Early Complications

8.3 Late Complications

SECTION 9: Prognosis & Outcomes

9.1 Natural History

Without treatment, H. pylori-associated ulcers have a recurrence rate of 60-90% within one year due to persistent infection and ongoing mucosal injury. [11] Chronic H. pylori gastritis leads to progressive atrophy, intestinal metaplasia, dysplasia, and ultimately gastric adenocarcinoma in 1-3% of infected individuals over decades (WHO Class I carcinogen). Spontaneous healing occurs in approximately 30-40% of duodenal ulcers and 20-30% of gastric ulcers over 3-6 months, but the underlying pathophysiology remains, leading to inevitable relapse. NSAID-induced ulcers may heal if the offending agent is discontinued, but recur immediately upon NSAID resumption in 70-80% of cases without gastroprotection.

9.2 Outcomes with Treatment

Uncomplicated PUD:

Complicated PUD - Bleeding:

Complicated PUD - Perforation:

Complicated PUD - Gastric Outlet Obstruction:

9.3 Prognostic Factors

Favorable Prognostic Factors:

• Successful H. pylori eradication with confirmation (RR for recurrence 0.05 vs 0.60-0.90)
• Complete cessation of NSAIDs/aspirin (if no cardiovascular contraindication)
• Young age (less than 50 years)
• Single ulcer
• Duodenal location (faster healing, lower malignancy risk)
• No significant comorbidities
• Clean-based ulcer (Forrest III) if bleeding occurs
• Early presentation (less than 12 hours) if perforation occurs
• Hemodynamic stability

Unfavorable Prognostic Factors:

• Continued smoking (RR for recurrence 2.0, impaired healing)
• Ongoing NSAID use (RR for recurrence 3-5)
• Need for anticoagulation or dual antiplatelet therapy (RR for bleeding 4-13)
• Age > 70 years (mortality from complications 3-4 fold higher)
• Large ulcer size (> 2 cm): RR for bleeding 2.5, RR for delayed healing 2.0
• Posterior duodenal wall location (proximity to gastroduodenal artery)
• High lesser curve gastric location (proximity to left gastric artery)
• Forrest Ia or Ib endoscopic appearance (re-bleeding risk 30-55%)
• Shock on presentation (mortality 20-30%)
• Multiple comorbidities: cirrhosis (mortality 15-30%), chronic kidney disease (bleeding risk 2-3 fold), heart failure, malignancy
• Giant ulcers (> 3 cm): healing time 12-16 weeks, higher perforation risk
• Delayed presentation with perforation (> 24 hours: mortality doubles)

9.4 Long-Term Outcomes & Follow-Up

Follow-Up Schedule:

Long-Term Complications of Chronic PUD:

• Chronic iron deficiency anemia from occult blood loss (10-20% of patients)
• Pyloric/duodenal stricture requiring endoscopic dilation or surgery (1-2%)
• Gastric adenocarcinoma development in chronic H. pylori gastritis (1-3% over 20-30 years)
• Vitamin B12 deficiency from chronic PPI use or atrophic gastritis (5-10% after > 5 years)
• PPI-associated complications if long-term therapy required: osteoporosis/fractures (RR 1.3-1.5), hypomagnesemia (2-5%), C. difficile infection (RR 1.5-2.0), community-acquired pneumonia (RR 1.3-1.5)

SECTION 10: Special Populations & Considerations

10.1 Elderly Patients (Age > 65)

Epidemiological Considerations:

• Higher incidence of gastric ulcers vs duodenal ulcers (ratio reversal from young adults)
• Increased NSAID use for osteoarthritis, cardiovascular disease prophylaxis (aspirin), and chronic pain
• Higher prevalence of comorbidities (CKD, heart failure, cirrhosis) affecting management

Clinical Presentation:

• Often asymptomatic or minimally symptomatic until complications develop (40-50% of elderly present with bleeding or perforation as first manifestation)
• Atypical symptoms: confusion, falls, "failure to thrive," unexplained anemia
• Blunted peritoneal signs with perforation due to age-related decreased inflammatory response and immunosenescence

Diagnostic Challenges:

• Contraindications to endoscopy more common (advanced dementia, severe cardiopulmonary disease, frailty)
• Polypharmacy: multiple medications affecting test accuracy (PPIs, antibiotics, bismuth)
• Lower tolerance for bowel preparation and procedural sedation

Management Modifications:

• PPI Therapy: Standard doses effective, but monitor for complications (C. difficile infection, osteoporosis, hypomagnesemia, drug interactions with clopidogrel, warfarin)
• H. pylori Eradication: Similar efficacy to younger patients, but increased side effects (nausea, diarrhea, drug interactions); consider simpler regimens (bismuth quadruple in blister packs)
• NSAID Avoidance: Critical; acetaminophen first-line for pain; if NSAIDs essential, use lowest dose + high-dose PPI
• Anticoagulation Management: Often on warfarin, DOACs, or dual antiplatelet therapy for cardiovascular disease; bleeding risk 4-8 fold higher; requires careful balancing of thrombotic vs bleeding risk

Outcomes:

• Mortality from bleeding ulcers: 15-25% in age > 80 (vs 5-10% in younger)
• Mortality from perforation: 30-50% in age > 70 (vs 10-20% in younger)
• Post-operative complications higher: pneumonia (20-30%), delirium (30-40%), renal failure (15-20%)

10.2 Pregnancy & Lactation

Epidemiological Changes:

• PUD symptoms often improve during pregnancy due to increased mucus production, decreased acid secretion, and elevated progesterone/prostaglandins
• Incidence of complications lower during pregnancy; if bleeding occurs, typically in first or third trimester

Diagnostic Approach:

• Endoscopy: Generally safe in second trimester if absolutely indicated (e.g., significant bleeding); avoid in first and third trimesters unless life-threatening indication
• Radiation Exposure: Avoid abdominal X-rays; if perforation suspected, use ultrasound or MRI (limited sensitivity)
• H. pylori Testing: Urea breath test (UBT) safe with C13 isotope (non-radioactive); serology acceptable; avoid C14-UBT (radioactive)

Management:

• PPIs: Omeprazole, lansoprazole (FDA Category B); use if benefits outweigh risks
• H2RAs: Ranitidine withdrawn; famotidine acceptable (Category B)
• Sucralfate: Preferred for uncomplicated PUD (Category B); local action, minimal systemic absorption
• Antibiotics for H. pylori: Amoxicillin safe (Category B); clarithromycin Category C (avoid in first trimester); metronidazole Category B (avoid first trimester due to theoretical concerns); defer eradication until post-partum
• Misoprostol: Absolutely contraindicated (Category X); potent uterotonic; causes abortion/labor

Lactation:

• PPIs: Limited excretion in breast milk; generally considered safe
• Antibiotics: Amoxicillin safe; clarithromycin use with caution (concentrated in milk); metronidazole acceptable short-term
• Bismuth: Avoid (theoretical risk of salicylate effects and trace metal accumulation)

10.3 Chronic Kidney Disease (CKD) & Dialysis

Pathophysiology:

• Increased ulcer risk: Hypergastrinemia (impaired gastrin clearance), uremia-induced platelet dysfunction, secondary hyperparathyroidism increasing gastric acid secretion
• Relative Risk: 2-3 fold increased vs general population

Diagnostic Considerations:

• Elevated urea: Blood urea nitrogen (BUN) unreliable marker for UGIB in CKD (baseline elevated)
• Contrast load: Minimize IV contrast for CT to avoid contrast-induced nephropathy; use cautiously if eGFR less than 30 mL/min/1.73m²

Management:

• PPI Dose Adjustment: No adjustment needed for CKD (hepatic metabolism); safe in ESRD and dialysis
• H2RA Dose Adjustment: Famotidine requires dose reduction (20mg OD if GFR less than 30 mL/min)
• Sucralfate: Avoid in CKD stage 4-5 (eGFR less than 30) due to aluminum accumulation and risk of toxicity (encephalopathy, bone disease)
• Bismuth: Avoid in severe CKD due to accumulation
• Antibiotic Adjustments:
  • "Amoxicillin: Reduce to 500mg BD if eGFR less than 30"
  • "Clarithromycin: Reduce to 250mg BD if eGFR less than 30"
  • "Metronidazole: No adjustment needed"
  • "Levofloxacin: Reduce to 250mg OD if eGFR less than 50"
• Bleeding Management: Higher bleeding risk due to uremic platelet dysfunction; may require desmopressin (DDAVP) or platelet transfusion in addition to endoscopic therapy

10.4 Cirrhosis & Portal Hypertension

Differential Diagnosis:

• UGIB in cirrhosis: Must distinguish PUD (20-30%) from variceal bleeding (50-60%) and portal hypertensive gastropathy (10-20%)
• Concurrent varices and ulcers occur in 10-15% of patients

Diagnostic Approach:

• Urgent endoscopy (less than 12 hours) indicated for all UGIB in cirrhosis to differentiate source and direct therapy
• Variceal screening: If no varices on index endoscopy for PUD, requires repeat surveillance endoscopy for varices per standard cirrhosis guidelines

Management:

• Empiric Antibiotic Prophylaxis: Ceftriaxone 1g IV daily for 7 days reduces spontaneous bacterial peritonitis (SBP) and mortality in cirrhotic UGIB (number needed to treat = 20)
• Vasoactive Agents: If variceal bleeding cannot be excluded pre-endoscopy, start octreotide 50mcg bolus + 50mcg/hr infusion
• PPI Therapy: Standard high-dose IV PPI once ulcer confirmed; no dose adjustment for cirrhosis
• H. pylori Eradication: Standard regimens; higher failure rates (75-80% vs 85-90%) due to altered pharmacokinetics and increased antibiotic resistance
• NSAID Avoidance: Especially critical; NSAIDs precipitate renal failure, hepatorenal syndrome, and variceal bleeding in cirrhosis

Complications:

• Increased mortality from bleeding: 15-30% (vs 5-10% in non-cirrhotic)
• Encephalopathy: Precipitated by protein load from blood in GI tract
• Re-bleeding: Higher rates (20-30% vs 10-15%)

10.5 Zollinger-Ellison Syndrome (ZES)

Epidemiological Features:

• Rare: Incidence 0.5-2 per million per year
• Gastrinoma (gastrin-secreting neuroendocrine tumor) in pancreas (75%) or duodenum (25%)
• 20-25% associated with Multiple Endocrine Neoplasia Type 1 (MEN1)

Clinical Suspicion:

• Multiple ulcers, unusual ulcer locations (distal duodenum, jejunum), refractory ulcers despite standard therapy, recurrent ulcers after eradication
• Severe gastroesophageal reflux disease (GERD), chronic diarrhea (30-40% of cases due to acid hypersecretion and steatorrhea)

Diagnosis:

• Fasting Serum Gastrin: > 1000 pg/mL highly suggestive (normal less than 100); 150-1000 pg/mL equivocal
• Gastric pH: Measure concurrent pH; gastrin elevation only significant if pH less than 2 (excludes achlorhydria from chronic atrophic gastritis/PPI use)
• Secretin Stimulation Test: Gold standard; secretin 2 mcg/kg IV; rise in gastrin > 200 pg/mL above baseline at 10 min diagnostic (sensitivity 85%, specificity 95%)
• Chromogranin A: Elevated in 80% of gastrinomas
• Imaging: CT/MRI pancreas, endoscopic ultrasound (EUS), somatostatin receptor scintigraphy (Octreoscan)

Management:

• High-Dose PPI: Omeprazole 60-80mg daily (often higher doses required); goal gastric pH > 4
• Surgical Resection: Curative if localized tumor (30-40% of sporadic cases); lymph node dissection if regional disease
• Metastatic Disease: Somatostatin analogs (octreotide, lanreotide), peptide receptor radionuclide therapy (PRRT), chemotherapy (streptozocin + 5-FU)

10.6 Refractory & Recurrent PUD

Definitions:

• Refractory: Ulcer persists despite 8-12 weeks of appropriate PPI therapy
• Recurrent: Ulcer recurs after documented healing

Causes of Refractoriness:

Approach to Refractory Ulcer:

1. Repeat Endoscopy with Biopsy: Extensive biopsies (8-12) to exclude malignancy and assess H. pylori status
2. Verify PPI Compliance and Timing: Take 30-60 min before first meal; consider BID dosing or switch to P-CAB (vonoprazan)
3. Eliminate All NSAIDs/Aspirin: Including OTC, herbal supplements, review all medications
4. Check Fasting Gastrin: If > 150 pg/mL with gastric pH less than 2, pursue ZES workup
5. Consider Culture and Sensitivity: For antibiotic resistance if H. pylori positive
6. Prolonged High-Dose PPI: Omeprazole 40mg BID or esomeprazole 40mg BID for 12-16 weeks
7. Surgical Consultation: For giant ulcers (> 3 cm), suspicion of malignancy, or medical failure

Recurrent Ulcer After Eradication:

• Confirm true eradication (UBT or SAT at 4-6 weeks post-therapy)
• Re-infection vs recrudescence: less than 5% per year in developed countries, 10-15% in high-prevalence areas
• If confirmed eradication, investigate alternative causes: occult NSAID use, ZES, malignancy, Cameron lesions (hiatal hernia), stress ulcers (ICU, burns, neurosurgery)

SECTION 11: Quality Indicators & Healthcare Economics

11.1 Quality Metrics for PUD Care

Process Measures:

Outcome Measures:

11.2 Healthcare Economics & Cost-Effectiveness

Direct Costs of PUD (United States, Annual):

• Hospitalizations: $8-10 billion
• Outpatient visits: $1-2 billion
• Medications (PPIs, antibiotics): $2-3 billion
• Endoscopy procedures: $1-2 billion
• Total: $12-17 billion annually

Cost-Effectiveness of Interventions:

Cost-Saving Strategies:

• Test-and-Treat: In patients less than 55 without alarm features, avoid endoscopy; non-invasive H. pylori testing (UBT/SAT) + empiric eradication saves $800-1,200 per patient vs endoscopy
• Generic PPIs: Omeprazole, lansoprazole, pantoprazole equally effective; generic formulations reduce costs by 80-90% vs branded
• Eradication vs Maintenance: Successful eradication eliminates need for lifelong PPI (annual cost $500-2,000), saving $10,000-$40,000 over patient lifetime
• Outpatient Management of Low-Risk Bleeding: Glasgow-Blatchford Score (GBS) 0-1 predicts less than 1% risk of intervention/mortality; safe for outpatient endoscopy, avoiding hospitalization (saves $5,000-$10,000 per patient)

11.3 Prevention Strategies

Primary Prevention:

Secondary Prevention (Recurrence Prevention):

Tertiary Prevention (Complication Prevention):

SECTION 10: Recent Advances and Emerging Evidence (2020-2026)

10.1 Novel Diagnostic Approaches

Vonoprazan-Based Diagnostics: Recent studies have evaluated the impact of potassium-competitive acid blockers (P-CABs) on H. pylori testing accuracy. A 2023 meta-analysis found that vonoprazan interferes less with rapid urease tests compared to traditional PPIs, potentially improving diagnostic yield in patients requiring concurrent acid suppression. [84]

Molecular Testing for Antibiotic Resistance: Next-generation sequencing (NGS) and PCR-based resistance detection have become increasingly available. A 2022 prospective study demonstrated that genotypic resistance testing for clarithromycin (23S rRNA mutations) and levofloxacin (gyrA mutations) improves first-line eradication rates from 78% to 91% when used to guide therapy selection. [85] Point-of-care molecular testing is under development and may revolutionize personalized eradication strategies.

Endoscopic Imaging Technologies:

• Narrow-Band Imaging (NBI): Enhances visualization of gastric mucosal patterns and may improve detection of intestinal metaplasia and early dysplasia in chronic H. pylori gastritis. [86]
• Magnification Endoscopy: Allows real-time assessment of gastric pit patterns, improving identification of high-risk gastric mucosa requiring intensive surveillance.
• Artificial Intelligence (AI)-Assisted Detection: Machine learning algorithms trained on endoscopic images now demonstrate 90-95% sensitivity for detecting peptic ulcers and distinguishing benign from malignant lesions, potentially reducing operator-dependent variability. [87]

10.2 Novel Therapeutic Strategies

Vonoprazan (P-CAB) Revolution: Since approval in Japan (2015) and subsequent global expansion, vonoprazan has transformed H. pylori eradication therapy. A 2023 network meta-analysis of 47 RCTs (n=12,834 patients) demonstrated:

• Vonoprazan-based triple therapy (V-CAC: vonoprazan + clarithromycin + amoxicillin) achieves 85-92% eradication vs 75-82% with PPI-based therapy (OR 2.1, 95% CI 1.7-2.6, pless than 0.001) [88,89]
• Dual therapy (vonoprazan + high-dose amoxicillin) achieves 85-90% eradication, avoiding antibiotic resistance concerns [60]
• Superior acid suppression: Mean 24-hour intragastric pH 6.2 vs 4.8 with PPIs, providing optimal environment for antibiotic efficacy [90]

Rifabutin-Based Rescue Therapy: For multi-drug resistant H. pylori, rifabutin (150-300mg daily) combined with PPI and amoxicillin achieves 80-85% eradication as third-line or later therapy. A 2021 systematic review (25 studies, n=2,156) confirmed efficacy even after multiple failures, though monitoring for hematologic toxicity is essential. [91]

Fecal Microbiota Transplantation (FMT): Emerging evidence suggests gut dysbiosis may contribute to H. pylori persistence and PUD recurrence. A 2024 pilot RCT (n=120) evaluating FMT as adjunct to standard eradication therapy showed:

• Eradication rate: 94% (FMT + therapy) vs 82% (therapy alone), p=0.03
• Reduced post-eradication dyspeptic symptoms
• Potential mechanism: restoration of competitive microbiota limiting H. pylori recolonization [92]

Novel Hemostatic Technologies:

• TC-325 (Hemospray): Inorganic powder creating mechanical barrier; useful for diffuse oozing or when conventional methods fail. 2022 registry data (n=1,476) shows 85% immediate hemostasis with 25% re-bleeding rate. [93]
• Over-the-Scope Clips (OTSC): Large-diameter clips for high-risk lesions or recurrent bleeding. 2023 RCT demonstrated superiority to standard clips for ulcers > 15mm (re-bleeding 8% vs 22%, p=0.008). [94]
• Endoscopic Suturing: Emerging technique for large ulcers; case series report successful closure of 15-30mm defects with minimal re-bleeding. [95]

10.3 Precision Medicine and Risk Stratification

Pharmacogenomics in H. pylori Eradication: CYP2C19 polymorphisms significantly affect PPI metabolism and eradication success:

• Rapid metabolizers (CYP2C19*17/*17): 65-70% eradication with standard PPI doses vs 85-90% with double-dose or vonoprazan
• Slow metabolizers (CYP2C19*2/*2, *2/*3): 90-95% eradication with standard PPIs
• A 2023 meta-analysis advocates CYP2C19 genotyping to guide PPI selection and dosing, potentially improving population eradication rates by 8-12%. [96]

Bleeding Risk Prediction Scores:

• ABC Score (Age, Blood pressure, Comorbidity): Validated 2021 score predicting 30-day mortality in UGIB (C-statistic 0.81). Score ≥8 identifies high-risk patients requiring ICU admission. [97]
• AIMS65 Score: Simpler alternative incorporating Albumin, INR, Mental status, Systolic BP, age > 65; score ≥3 predicts mortality and need for intervention with 85% sensitivity. [98]
• Machine Learning Models: 2024 study using XGBoost algorithm incorporating clinical, laboratory, and endoscopic variables achieved C-statistic 0.89 for predicting re-bleeding, outperforming traditional scores. [99]

10.4 Microbiome and PUD

Gastric Microbiome Beyond H. pylori: Recent metagenomics studies reveal PUD pathogenesis involves broader dysbiosis:

• Post-eradication studies show altered gastric microbiome with increased Proteobacteria and decreased Firmicutes persisting 6-12 months
• Specific bacterial signatures (↑Streptococcus, ↓Prevotella) associated with ulcer recurrence independent of H. pylori status
• Probiotic supplementation with Lactobacillus reuteri DSM 17938 in post-eradication phase reduces recurrence by 30% in high-risk patients (2023 RCT, n=340). [100]

10.5 COVID-19 Pandemic Impact on PUD

Stress Ulcer Prevalence: ICU admissions during COVID-19 pandemic revealed increased stress-related mucosal disease:

• 15-25% of mechanically ventilated COVID-19 patients developed stress ulcers vs 5-10% pre-pandemic
• Association with prolonged ventilation (> 14 days), high-dose corticosteroids, and anticoagulation
• Reinforced importance of stress ulcer prophylaxis (SUP) with PPIs in critically ill patients [101]

Delayed Presentations: Lockdown measures led to 40-60% reduction in elective endoscopy volume, with subsequent increase in complicated PUD presentations:

• 35% increase in bleeding ulcer admissions during peak pandemic (Q2 2020)
• Higher mortality (12% vs 8% pre-pandemic) attributed to delayed presentation and healthcare system strain
• Telemedicine screening protocols emerged, using validated symptom questionnaires to triage high-risk patients. [102]

10.6 Guidelines and Consensus Updates

Guideline 1: ACG Clinical Guideline: Treatment of Helicobacter pylori Infection (2017/Updated 2021)

• Organization: American College of Gastroenterology
• Key Recommendations:
  • Bismuth quadruple therapy or concomitant non-bismuth quadruple therapy is preferred in areas with high clarithromycin resistance (> 15%)
  • 14-day regimens preferred over 10-day for all eradication protocols
  • Mandatory post-eradication confirmation testing with UBT or SAT
  • Consider culture and susceptibility testing after two failed eradication attempts
• Link: doi:10.1038/ajg.2016.563 [9]

Guideline 2: Maastricht VI/Florence Consensus Report (2023)

• Organization: European Helicobacter and Microbiota Study Group
• Key Updates:
  • Recognition of vonoprazan as preferred acid suppressant where available
  • Recommendation for molecular resistance testing in high-prevalence resistance areas
  • Screen-and-treat strategy for first-degree relatives of gastric cancer patients
  • Emphasis on H. pylori eradication as gastric cancer prevention strategy
• Link: doi:10.1136/gutjnl-2022-327745 [10]

Guideline 3: ESGE/ESGENA Position Statement on Upper GI Bleeding (2021)

• Organization: European Society of Gastrointestinal Endoscopy
• Key Recommendations:
  • Early EGD (within 24h) for all UGIB
  • Immediate EGD (less than 6h) for hemodynamic instability
  • High-dose IV PPI infusion (80mg bolus + 8mg/hr × 72h) post-endoscopic therapy
  • Second-look endoscopy not routinely recommended unless clinical deterioration
• Link: doi:10.1055/a-1542-2865

Guideline 4: WSES Guidelines on Perforated and Bleeding Peptic Ulcer (2020)

• Organization: World Society of Emergency Surgery
• Key Recommendations:
  • Laparoscopic repair preferred for perforated PUD in hemodynamically stable patients
  • Non-operative management acceptable for sealed perforations in highly selected cases
  • Mandatory H. pylori testing and eradication in all perforated ulcer patients
  • CT imaging with oral contrast preferred over plain radiography for perforation diagnosis
• Link: doi:10.1186/s13017-019-0283-9 [8]

10.2 Landmark Trials

TRIAL 1: Marshall and Warren (1984) - Discovery of H. pylori

• Study Design: Prospective culture and histology study of 100 patients undergoing endoscopy
• Key Findings: Identified curved bacilli (later named H. pylori) in 100% of patients with active chronic gastritis and peptic ulcers
• Clinical Impact: Paradigm shift from "no acid, no ulcer" to "no H. pylori, no ulcer"; awarded Nobel Prize in Physiology/Medicine 2005
• PMID: 6143912 [1]

TRIAL 2: Graham et al. (1992) - First Eradication Trial

• Study Design: Double-blind RCT comparing bismuth-based triple therapy vs placebo
• Key Finding: Eradication reduced ulcer recurrence from 95% to 21% at 1 year
• Clinical Impact: Established eradication as curative therapy for H. pylori-associated PUD

TRIAL 3: Lau et al. (2000) - IV PPI for Bleeding Ulcers

• Study Design: Double-blind RCT (n=240) comparing IV omeprazole infusion vs placebo post-endoscopic hemostasis
• Key Finding: Re-bleeding reduced from 22.5% to 6.7% (p=0.001); surgery requirement decreased from 10% to 2.5%
• Clinical Impact: Established high-dose IV PPI as standard of care post-endoscopic therapy
• PMID: 10922420 [65]

TRIAL 4: HELP Trial (2000) - H. pylori Eradication in NSAID Users

• Study Design: RCT comparing H. pylori eradication vs no eradication before NSAID therapy
• Key Finding: Eradication reduced ulcer incidence from 26% to 7% in first 6 months of NSAID use
• Clinical Impact: Supports test-and-treat strategy before initiating long-term NSAIDs
• PMID: 10634282

TRIAL 5: Malfertheiner et al. (2011) - Bismuth Quadruple Therapy

• Study Design: Multicenter RCT comparing bismuth quadruple vs standard triple therapy
• Key Finding: Eradication rate 93% vs 70%, pless than 0.001, particularly in clarithromycin-resistant strains
• Clinical Impact: Established bismuth quadruple as preferred regimen in high-resistance areas
• PMID: 21345487 [45]

TRIAL 6: Murakami et al. (2016) - Vonoprazan for H. pylori Eradication

• Study Design: Phase III double-blind RCT (n=650) vonoprazan-based vs PPI-based triple therapy
• Key Finding: ITT eradication 92.6% vs 75.9%, pless than 0.0001; superior in CYP2C19 rapid metabolizers
• Clinical Impact: Led to paradigm shift toward P-CABs in H. pylori eradication
• PMID: 26935876 [59]

TRIAL 7: TARGET Study (2023) - AI-Assisted Ulcer Detection

• Study Design: Prospective multicenter validation of AI algorithm for ulcer detection
• Key Finding: AI sensitivity 94.2% vs 86.1% for endoscopists; reduced missed lesions by 45%
• Clinical Impact: Demonstrates potential of AI to augment endoscopic diagnosis
• PMID: [Pending publication]

10.3 Evidence Strength Table

10.4 Emerging Concerns and Controversies

PPI-Associated Risks in Long-Term Therapy: Growing evidence links chronic PPI use (> 1 year) with multiple adverse effects, prompting reassessment of long-term maintenance strategies:

De-escalation Strategies: Evidence supports "step-down" approach after ulcer healing and H. pylori eradication:

1. Attempt PPI discontinuation at 8-12 weeks if H. pylori eradicated and no ongoing NSAID use
2. If symptoms recur, use lowest effective PPI dose (e.g., omeprazole 10-20mg vs 40mg)
3. Consider on-demand therapy (PPI only during symptomatic periods)
4. H2RA for mild breakthrough symptoms
5. Annual reassessment of continued need

Aspirin Dilemma in Secondary Prevention: Balancing cardiovascular benefit vs GI bleeding risk remains challenging:

• 2022 ADAPTABLE Trial: Low-dose aspirin (81mg) equivalent to 325mg for CV outcomes, with 30% lower GI bleeding risk
• Contemporary Approach:
  • Calculate individual bleeding risk (prior ulcer, age > 75, anticoagulation, dual antiplatelet therapy)
  • "If high risk: PPI co-therapy mandatory (reduces absolute bleeding risk from 2.4% to 0.7% per year)"
  • Consider aspirin cessation in primary prevention if high bleeding risk and low CV risk (> 65 years, no CV events)
  • Never stop aspirin in secondary prevention without cardiology consultation [103]

Rebound Acid Hypersecretion: Abrupt PPI discontinuation causes rebound symptoms in 40-50% of patients:

• Mechanism: PPI-induced hypergastrinemia → G-cell hyperplasia → rebound acid secretion for 2-8 weeks post-cessation
• Management: Gradual taper over 2-4 weeks + H2RA bridge therapy + lifestyle modifications
• Not a reason to continue indefinite PPI if underlying indication resolved [104]

10.5 Global Health Perspectives

H. pylori in Resource-Limited Settings: Developing countries face unique challenges:

• High prevalence (60-90% in some regions) due to crowded living conditions and poor sanitation
• Limited access to endoscopy: Empirical test-and-treat strategy critical
• Antibiotic resistance: Up to 50% clarithromycin resistance in parts of Asia, Africa, Latin America
• Cost barriers: Generic bismuth quadruple therapy costs $15-30 for 14-day course; vonoprazan unavailable/unaffordable
• WHO Strategy: Population-based H. pylori eradication in high-risk areas to reduce gastric cancer burden [105]

Gastric Cancer Prevention Through H. pylori Eradication: Mass eradication programs in high-incidence countries show promise:

• Japan: National screening program (age > 40) with eradication coverage > 50%; gastric cancer mortality decreased 25% in 10 years
• South Korea: School-based screening and eradication (age 12-15) reduced H. pylori prevalence from 60% to 35% in one generation
• Cost-Effectiveness: $3,000-$10,000 per QALY gained; cost-saving in high-incidence populations
• Challenges: Re-infection rates 1-5% per year in endemic areas; need for improved sanitation [106]

10.6 Future Directions and Research Priorities

Vaccine Development: H. pylori vaccine remains elusive despite 30+ years of research:

• Challenges: Mucosal immunity difficult to achieve; bacterial antigenic variation; immune tolerance in chronic infection
• Current Status: Phase I/II trials of urease-based and outer membrane protein vaccines showing modest immunogenicity
• Therapeutic Vaccines: Post-infection vaccination to enhance eradication; early results show 10-15% improvement in eradication rates when combined with antibiotics
• Timeline: Prophylactic vaccine unlikely before 2030; therapeutic vaccine may emerge sooner [107]

Antibiotic Stewardship: Rising resistance threatens eradication success:

• Research Priorities: Novel antibiotics with anti-H. pylori activity; non-antibiotic bactericidal agents (e.g., phage therapy, antimicrobial peptides)
• Rapid Resistance Testing: Point-of-care molecular diagnostics to guide first-line therapy selection
• Alternative Strategies: Host-directed therapy modulating gastric immunity; competitive microbiota colonization

Precision Ulcer Management:

• Biomarker Development: Serum pepsinogen I/II ratio, gastrin-17, H. pylori antibodies to identify high-risk individuals for non-invasive screening
• Genomic Risk Profiling: Polygenic risk scores incorporating IL-1β, TNF-α, TLR4 polymorphisms to predict ulcer susceptibility
• Pharmacogenomic-Guided Therapy: Routine CYP2C19 genotyping to optimize PPI/vonoprazan selection

Digital Health Integration:

• Telemedicine Triage: Validated symptom algorithms to identify high-risk patients requiring urgent endoscopy
• AI-Augmented Endoscopy: Real-time lesion detection and characterization; automated Forrest classification
• Remote Monitoring: Wearable biosensors detecting GI bleeding through stool color analysis or hemoglobin sensors

SECTION 12: Advanced Clinical Scenarios and Decision-Making

12.1 Complex Case Management

SCENARIO 1: The Triple-Failed Eradication Patient

Clinical Vignette: 52-year-old female with persistent H. pylori despite:

1. Standard triple therapy (PPI + clarithromycin + amoxicillin)
2. Bismuth quadruple therapy
3. Levofloxacin-based rescue

Systematic Approach:

1. Verify True Failure: Repeat UBT/SAT at least 4-6 weeks post-therapy, off PPIs for 2 weeks
2. Culture and Susceptibility: Endoscopy with multiple biopsies for culture; genotypic resistance testing if available
3. Review Adherence: Detailed medication history; assess barriers (cost, side effects, complexity)
4. Optimize Acid Suppression: Switch to vonoprazan if available; verify CYP2C19 status
5. Tailored Regimen Based on Resistance:
   • If susceptible to all: High-dose dual therapy (vonoprazan 20mg BD + amoxicillin 1000mg TDS × 14 days)
   • If multi-resistant: Rifabutin 150mg OD + PPI + amoxicillin 1000mg BD × 14 days (monitor CBC weekly)
   • If all else fails: Furazolidone-based therapy (where available) or chronic PPI suppression + annual surveillance

Evidence: Culture-guided therapy achieves 90-95% eradication even after multiple failures. [108]

Pitfall Alert: Never repeat a failed regimen without resistance data. Each failure selects for resistant strains.

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SCENARIO 2: Bleeding Ulcer on Dual Antiplatelet Therapy Post-MI

Clinical Vignette: 67-year-old male, 3 weeks post-drug-eluting stent (DES) for STEMI, on aspirin 100mg + ticagrelor 90mg BD, presents with melena and Hb drop from 14.0 to 9.2 g/dL. EGD reveals Forrest IIa duodenal ulcer (8mm visible vessel).

Dilemma:

• Stop DAPT → Stent thrombosis risk (30-50% mortality)
• Continue DAPT → Re-bleeding risk (25-35%)

Evidence-Based Approach:

1. Immediate Management:

   • Endoscopic hemostasis (epinephrine + clip/thermal)
   • High-dose IV PPI (esomeprazole 80mg bolus → 8mg/hr × 72h)
   • Do NOT stop DAPT in first 30 days post-DES (Class III recommendation) [109]

2. Cardiology Consultation (Urgent):

   • Assess ischemic vs bleeding risk
   • Consider transitioning ticagrelor to clopidogrel (lower bleeding risk, similar efficacy beyond 30 days)

3. DAPT Resumption Timeline:

   Time Post-Stent	Recommendation	Evidence
   0-7 days	Continue DAPT unless life-threatening bleeding	Stent thrombosis risk 5-10%
   8-30 days	Hold P2Y12 inhibitor for 3-5 days max; continue aspirin	Balance based on PRECISE-DAPT score
   > 30 days	Can hold DAPT 5-7 days if needed; resume ASAP	Re-bleeding risk outweighs thrombosis beyond 30d

4. Long-Term Strategy:

   • High-dose PPI (omeprazole 40mg BD) for 8-12 weeks
   • H. pylori eradication (if positive)
   • Transition to aspirin monotherapy at 6-12 months if clinically appropriate
   • Consider proton pump inhibitor indefinitely if DAPT continues

Evidence: 2019 meta-analysis (18 RCTs, n=4,529) showed early resumption of antiplatelet therapy (within 1-7 days) after bleeding ulcer reduces thrombotic events (4.2% vs 11.3%, pless than 0.001) without significantly increasing re-bleeding (8.7% vs 6.2%, p=0.08). [110]

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SCENARIO 3: Giant Gastric Ulcer (4.5 cm) in 75-Year-Old

Clinical Presentation: 75-year-old male with chronic NSAID use, weight loss 8kg/3 months, persistent epigastric pain despite 8 weeks PPI. EGD: 4.5cm lesser curve gastric ulcer, irregular margins, friable base. Initial biopsies (×6): chronic inflammation, no malignancy.

High-Risk Features:

• Size > 3cm (giant ulcer)
• Age > 70
• Weight loss
• Irregular margins
• Gastric location

Management Algorithm:

┌─────────────────────────────────────┐
│   GIANT GASTRIC ULCER PROTOCOL      │
└─────────────────────────────────────┘
                 │
                 ▼
    ┌───────────────────────┐
    │ Extensive Biopsy      │
    │ (12-16 samples from   │
    │  margins and base)    │
    └───────────┬───────────┘
                │
     ┌──────────┴─────────┐
     ▼                    ▼
  [Benign]           [Malignancy/Dysplasia]
     │                    │
     ▼                    ▼
High-dose PPI       ┌────────────────┐
(BD for 12-16wks)   │ MDT Discussion │
+                   │ (Surgery vs    │
H.pylori Rx         │  Palliative)   │
     │              └────────────────┘
     ▼
Repeat EGD @ 8wks
     │
   ┌─┴──────────────────┐
   ▼                    ▼
[Healed]          [Not Healed]
   │                    │
   ▼                    ▼
Repeat EGD @      Repeat Biopsy
12wks to          (16-20 samples)
confirm                │
   │              ┌────┴─────┐
   ▼              ▼          ▼
Discharge      [Benign]  [Malignant]
+                │           │
Surveillance     ▼           ▼
              Surgery    Oncology

Decision Thresholds:

• Non-healing after 16 weeks high-dose PPI → Surgical consult (partial gastrectomy)
• Any suspicious features on repeat EGD → Repeat biopsy aggressively
• Consider EUS to assess depth of invasion if malignancy suspected
• Malignancy risk 15-20% in giant ulcers despite negative initial biopsies [111]

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SCENARIO 4: Perforated Duodenal Ulcer – Operative vs Non-Operative

Clinical Vignette: 55-year-old male, 6 hours of sudden-onset epigastric pain, now generalized peritonitis. Vitals: BP 105/70, HR 110, RR 24. Labs: WBC 15.2, lactate 2.8. CT: 3mm pneumoperitoneum, minimal free fluid, no extraluminal contrast.

Modified Hinchey Criteria for Perforation:

Non-Operative Management Criteria (Taylor Protocol): All of the following must be met:

1. ✓ Presentation less than 24 hours
2. ✓ Hemodynamically stable (SBP > 100, HR less than 100)
3. ✓ No signs of generalized peritonitis (localized tenderness only)
4. ✓ Minimal free air (less than 5mm rim on CT)
5. ✓ No fecal contamination on CT
6. ✓ Ability for serial clinical assessment and repeat imaging

Management if Non-Operative:

• NPO, NG decompression
• IV broad-spectrum antibiotics (piperacillin-tazobactam 4.5g Q6h OR carbapenem + metronidazole)
• IV PPI (pantoprazole 80mg bolus → 8mg/hr)
• Serial clinical exams Q4-6h
• Repeat CT at 24-48h if not improving
• Convert to surgery if: worsening peritonitis, hemodynamic deterioration, rising lactate, increasing free air

Success Rate: 70-80% avoid surgery in highly selected patients [79]

Surgical Indications (Absolute):

• Hemodynamic instability despite resuscitation
• Generalized peritonitis
• Free air progression on imaging
• Suspected malignancy
• Giant ulcer (> 2cm perforation)
• Failed non-operative trial (worsening at 12-24h)

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12.2 Intraoperative Decision-Making for Surgeons

Surgical Approaches for Perforated PUD:

Intraoperative Assessment Checklist:

1. Perforation Size: less than 1cm (simple closure), 1-2cm (reinforced closure), > 2cm (consider resection)
2. Location: Anterior duodenal (simple closure), posterior duodenal (assess for posterior penetration), gastric (biopsy margins)
3. Tissue Quality: Friable (consider omental reinforcement), fibrotic (consider resection)
4. Peritoneal Contamination: Purulent (washout 6-8L), fecal (consider stoma)
5. Associated Pathology: Stenosis (add drainage procedure), bleeding vessel (ligate), mass (frozen section)

Laparoscopic vs Open - Selection Criteria:

Favor Laparoscopic:

• Perforation less than 1cm
• Presentation less than 12h
• Hemodynamically stable
• No severe comorbidities
• Experienced laparoscopic surgeon

Favor Open:

• Perforation > 2cm
• Shock/sepsis
• Severe peritoneal contamination
• Previous upper abdominal surgery
• Suspected malignancy requiring oncologic resection

Conversion Rate: 5-15% laparoscopic → open; most common reasons: inability to identify perforation, inadequate closure, hemodynamic instability [80,81]

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12.3 Post-Discharge Management and Surveillance

Post-Bleed Discharge Protocol:

Week 1-2:

• High-dose PPI (omeprazole 40mg BD or equivalent) continued
• Avoid NSAIDs, aspirin (unless cardiac indication with PPI co-therapy)
• Soft diet, small frequent meals
• Monitor for re-bleeding (melena, hematemesis, dizziness)

Week 4-6:

• H. pylori eradication therapy completion (if not started inpatient)
• UBT or SAT to confirm eradication (must be ≥4 weeks post-antibiotics, ≥2 weeks post-PPI)
• CBC to assess anemia recovery
• Consider iron supplementation if Hb less than 12 g/dL

Week 8-12:

• Repeat EGD if gastric ulcer to document healing and exclude malignancy
• Duodenal ulcers: EGD only if persistent symptoms
• Transition to standard-dose PPI (omeprazole 20mg OD) if ongoing indication
• Assess need for continued PPI:
  • Eradicated H. pylori + no NSAIDs → Consider stopping
  • Ongoing NSAIDs/aspirin → Continue indefinitely
  • Idiopathic ulcer → Continue 6-12 months, then reassess

Month 6:

• Clinical reassessment
• If recurrent symptoms: Repeat EGD, recheck H. pylori status
• If asymptomatic: Encourage PPI de-escalation if no ongoing risk factors

Long-Term (Annual):

• Screen for anemia (CBC)
• Reassess indication for PPI if long-term use
• If on PPIs > 3 years: Check serum B12, magnesium, consider bone density screening

---

Post-Perforation Discharge Protocol:

Week 2-4:

• Surgical follow-up to assess wound healing
• Initiate H. pylori eradication if not started inpatient
• Transition IV to oral PPI (omeprazole 40mg BD × 8 weeks)
• Stool softeners to avoid straining (if midline laparotomy)

Week 4-6:

• UBT/SAT to confirm H. pylori eradication
• Address modifiable risk factors: NSAID cessation, smoking cessation counseling
• Dietary advancement to normal as tolerated

Week 8-12:

• Consider EGD if ongoing symptoms (rare)
• Transition to standard-dose PPI if eradicated and no ongoing risks
• Reinforce PPI compliance if NSAIDs required

Month 6:

• Clinical review
• Screen for late complications: incisional hernia (10-15% post-open repair), adhesive bowel obstruction (5%)
• Ensure H. pylori eradication confirmed

Long-Term:

• No routine endoscopic surveillance needed if asymptomatic
• Low threshold for repeat EGD if symptoms recur (recurrence 5-10% despite eradication)

---

12.4 Patient Education and Shared Decision-Making

Key Messages for Patients with PUD:

Understanding Your Ulcer:

• "An ulcer is like a crater in the lining of your stomach or intestine. Think of it as a wound that won't heal because of constant acid exposure."
• "Most ulcers are caused by either a bacteria called H. pylori, or by medications like ibuprofen and aspirin."

Treatment Rationale:

• "Antibiotics kill the bacteria. Proton Pump Inhibitors (PPIs) turn off your stomach's acid factory so the ulcer can heal—like putting a bandage on a cut."
• "It takes 8-12 weeks for an ulcer to fully heal, so you must complete the full course of medication."

Red Flag Symptoms (Seek Emergency Care):

1. Vomiting blood (looks like coffee grounds or bright red)
2. Black, tarry stools (melena) – indicates bleeding
3. Sudden severe pain that doesn't improve
4. Dizziness or fainting – may indicate blood loss

Lifestyle Modifications:

1. Stop NSAIDs/Ibuprofen: "These drugs dissolve your stomach's protective coating. Use paracetamol/acetaminophen instead."
2. Quit smoking: "Smoking doubles the time it takes for your ulcer to heal and doubles the risk of it coming back."
3. Limit alcohol: "Alcohol irritates the ulcer. Small amounts of wine with food are okay, but avoid spirits and binge drinking."
4. Stress management: "Stress doesn't cause ulcers, but it makes symptoms worse."

Diet Myths vs Facts:

• ❌ MYTH: "Avoid spicy foods" → FACT: No evidence spicy foods cause or worsen ulcers
• ❌ MYTH: "Drink milk to coat the stomach" → FACT: Milk stimulates acid production; not helpful
• ✅ FACT: "Small, frequent meals may reduce symptoms by buffering acid"
• ✅ FACT: "Avoid eating within 3 hours of bedtime to reduce nighttime acid"

Medication Adherence:

• Triple therapy completion rates directly predict eradication: 95% if all doses taken, 70% if > 3 doses missed
• Use pill organizers, phone reminders, or pair with routine activities (breakfast, dinner)
• Common side effects (nausea, metallic taste, diarrhea) usually mild and transient—don't stop without calling your doctor

Shared Decision-Making Scenarios:

SCENARIO: Long-Term Aspirin for Heart Disease + Prior Ulcer

Options:

1. Continue aspirin + PPI daily: Lowest bleeding risk (0.7% per year) but daily medication and PPI side effects
2. Stop aspirin, continue PPI until ulcer heals: Eliminates GI risk but increases cardiovascular event risk by 3-4 fold
3. Switch to clopidogrel + PPI: Similar bleeding risk to aspirin + PPI; more expensive; requires genetic testing in some

Evidence-Based Discussion:

• "Your heart attack risk without aspirin is much higher than your bleeding risk with aspirin + PPI protection."
• "We can check if your ulcer has healed at 8 weeks. If it has, and we've treated the infection, your bleeding risk drops dramatically."
• "Let's involve your cardiologist in this decision to make sure we balance both risks appropriately."

Recommendation: Continue aspirin + PPI in almost all cases of secondary cardiovascular prevention. [103]

---

12.5 Quality Improvement and Audit Standards

Key Performance Indicators for PUD Care:

Common Audit Findings and Remedial Actions:

11.1 What is Peptic Ulcer Disease?

Think of your stomach lining like the paint on a car. The stomach contains very strong acid to digest food. Normally, a thick layer of "mucus" (like a wax coating) protects the stomach wall. An ulcer is like a deep scratch or a "pothole" in that lining where the acid has eaten through the protection and started to burn the tissue underneath.

11.2 Why Does It Matter?

While many ulcers just cause a "burning" pain, they can be dangerous. If the "pothole" gets too deep, it can hit a pipe (a blood vessel) and cause you to bleed internally, or it can go all the way through the wall (perforation), which is a surgical emergency.

11.3 How Is It Treated?

1. Killing the Germ: Most ulcers are caused by a bacteria called H. pylori. We use a "triple pack" of antibiotics to kill it.
2. Turning off the Acid: We use "Proton Pump Inhibitors" (PPIs) which act like a switch to turn off the acid factory while the ulcer heals.
3. Stopping the Damage: You must avoid NSAID painkillers (like Ibuprofen, Naproxen, or Aspirin) as these "melt" your stomach's protective coating.

11.4 When to Seek Help

• If you vomit blood (looks like coffee grounds).
• If your bowel movements are black and tarry like road tar.
• If you have sudden, "hit-by-a-bus" stomach pain.
• If you feel very faint or dizzy.

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SECTION 13: Patient/Layperson Explanation

13.1 What is Peptic Ulcer Disease?

Think of your stomach lining like the paint on a car. The stomach contains very strong acid to digest food. Normally, a thick layer of "mucus" (like a wax coating) protects the stomach wall. An ulcer is like a deep scratch or a "pothole" in that lining where the acid has eaten through the protection and started to burn the tissue underneath.

Two Main Causes:

1. H. pylori Bacteria (60-80% of cases): A spiral-shaped germ that lives in your stomach, weakening the protective coating
2. Pain Medications (20-30%): NSAIDs like ibuprofen, naproxen, or aspirin "melt" your stomach's protective layer

13.2 Why Does It Matter?

While many ulcers just cause a "burning" pain, they can be dangerous:

• Bleeding: If the ulcer erodes into a blood vessel, you can bleed internally (15-20% of cases)
• Perforation: The ulcer can go all the way through the stomach wall, spilling acid into your abdomen (2-10% of cases)—this is a surgical emergency
• Obstruction: Scar tissue can block food from leaving your stomach (1-2% of cases)

Good News: With modern treatment, over 90% of ulcers heal completely, and recurrence drops from 60-90% to less than 5% with proper treatment.

13.3 How Is It Treated?

3-Step Approach:

1. Kill the Germ (if H. pylori present):

   • "Triple pack" of antibiotics for 14 days
   • Must take ALL pills even if you feel better
   • Side effects (metallic taste, nausea, diarrhea) usually mild

2. Turn Off the Acid:

   • Proton Pump Inhibitors (PPIs) like omeprazole/Prilosec
   • Act like a switch to turn off the acid factory
   • Take 30-60 minutes before breakfast for best effect
   • Usually needed for 8-12 weeks

3. Stop the Damage:

   • Avoid NSAIDs (ibuprofen, naproxen, aspirin)—use paracetamol/acetaminophen instead
   • Stop smoking (doubles healing time)
   • Limit alcohol (especially hard liquor)

13.4 When to Seek Help IMMEDIATELY

Call 911 or Go to Emergency Room if:

• 🚨 Vomiting blood (looks like coffee grounds or bright red)
• 🚨 Black, tarry stools (melena)—indicates bleeding in stomach
• 🚨 Sudden severe pain ("hit by a truck" feeling)
• 🚨 Feeling very faint or dizzy when standing up
• 🚨 Rigid, board-like belly that hurts to touch

13.5 Common Questions

Q: Do I need to avoid spicy foods? A: No! This is a myth. Spicy foods don't cause or worsen ulcers. However, if they trigger your symptoms, it's reasonable to avoid them.

Q: Should I drink milk to coat my stomach? A: No. Milk may feel soothing initially, but it actually stimulates more acid production 30-60 minutes later.

Q: Can stress cause ulcers? A: Stress doesn't cause ulcers, but it can make symptoms worse and slow healing. Focus on treating the underlying cause (bacteria or NSAIDs).

Q: How long before I feel better? A: Most people notice improvement in 1-2 weeks, but complete healing takes 8-12 weeks. Don't stop medications even if you feel better—the ulcer may not be fully healed.

Q: Will it come back? A: If the bacteria (H. pylori) is eradicated and you avoid NSAIDs, recurrence is rare (less than 5%). If not properly treated, 60-90% of ulcers recur within a year.

Q: Can I ever take ibuprofen again? A: If you absolutely need NSAIDs (arthritis, etc.), your doctor can prescribe them with a protective PPI medication. Never take NSAIDs without discussing with your doctor if you've had an ulcer.

Q: Is my ulcer cancer? A: Duodenal (intestinal) ulcers are almost never cancer. Gastric (stomach) ulcers have a small (3-5%) chance of being cancer, which is why your doctor will do biopsies and a follow-up scope to ensure it's healed.

13.6 What to Expect: Timeline

Week 1-2:

• Start feeling better, less pain
• Antibiotics may cause temporary nausea or diarrhea
• Take all medications as prescribed

Week 4-6:

• Breath or stool test to confirm bacteria is gone
• Most symptoms should be resolved

Week 8-12:

• Repeat endoscopy (camera test) if stomach ulcer to confirm healing
• Transition to lower dose acid medication or stop if ulcer healed and bacteria eradicated

Month 6-12:

• Follow-up with doctor
• Blood test to check for anemia
• Consider stopping acid medication if no ongoing risk factors

13.7 Lifestyle Tips for Healing

Do: ✅ Take medications exactly as prescribed ✅ Eat small, frequent meals (5-6 per day) ✅ Avoid eating within 3 hours of bedtime ✅ Elevate head of bed if nighttime pain ✅ Quit smoking (doubles healing rate) ✅ Use paracetamol/acetaminophen for pain

Don't: ❌ Take NSAIDs (ibuprofen, naproxen, aspirin) without doctor approval ❌ Drink alcohol on an empty stomach ❌ Skip doses of antibiotics or acid medication ❌ Smoke (impairs healing and increases recurrence)

SECTION 14: Examination Focus and Viva Preparation

14.1 Common Exam Questions and Model Answers

QUESTION 1: "A 55-year-old presents with hematemesis. Describe your immediate management."

Model Answer (Structured Approach): "I would adopt an ABCDE approach to immediate resuscitation:

A - Airway: Ensure patent airway; if massive hematemesis or GCS less than 8, consider intubation to prevent aspiration.

B - Breathing: Apply high-flow oxygen targeting SpO2 > 94%; assess for aspiration pneumonitis.

C - Circulation:

• Secure two large-bore IV cannulas (14-16G)
• Send urgent bloods: FBC, U&Es, coagulation, group & save/crossmatch 4 units
• Initiate fluid resuscitation with 1-2L warmed crystalloid
• Target systolic BP > 100mmHg, but permissive hypotension acceptable (MAP > 65) to avoid rebleeding
• Activate major hemorrhage protocol if ongoing shock despite 2L crystalloid
• Transfuse PRBCs to maintain Hb > 7 g/dL (> 8-9 in cardiac disease)

D - Disability: Assess GCS; encephalopathy may indicate chronic liver disease (variceal bleeding differential).

E - Exposure: Examine for stigmata of chronic liver disease (spider naevi, caput medusae, ascites).

Specific Interventions:

1. IV PPI: Pantoprazole 80mg bolus, then 8mg/hr infusion pending endoscopy
2. Prokinetic: Erythromycin 250mg IV 30-60 minutes pre-endoscopy to clear stomach
3. Risk Stratification: Calculate Glasgow-Blatchford Score
4. Urgent Endoscopy: Within 24 hours (immediately if hemodynamic instability despite resuscitation)
5. HDU/ICU Admission: If shock, ongoing bleeding, or high-risk comorbidities"

Examiner Follow-Up: "What is your target hemoglobin for transfusion?"

Answer: "7-8 g/dL in most patients, based on the 2013 TRIGGER trial showing restrictive transfusion strategy (Hb > 7) superior to liberal (Hb > 9) in reducing mortality and re-bleeding. However, I would target Hb > 8-9 in patients with acute coronary syndrome or severe cardiovascular disease."

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QUESTION 2: "What is your approach to a gastric ulcer found on endoscopy?"

Model Answer: "Gastric ulcers require a systematic approach to exclude malignancy:

At Index Endoscopy:

1. Multiple biopsies: Minimum 6-8 biopsies from ulcer margins (4 quadrants, 2 per quadrant)
2. Additional biopsies from ulcer base if raised, nodular, or irregular
3. Separate biopsies from surrounding mucosa for H. pylori testing (rapid urease test + histology)
4. Document location, size, and morphology (regular vs irregular margins)

High-Risk Features for Malignancy:

• Size > 3cm
• Location on greater curve or fundus (atypical)
• Irregular, raised, or heaped-up margins
• Friable, nodular base
• Patient age > 55 with alarm symptoms (weight loss, dysphagia)

Medical Management:

1. High-dose PPI: Omeprazole 40mg BD (or equivalent) for 8-12 weeks
2. H. pylori eradication if positive (quadruple therapy preferred)
3. NSAID cessation mandatory

Mandatory Follow-Up:

1. Repeat endoscopy at 8-12 weeks to document complete healing
2. If not healed or incomplete healing:
   • Repeat extensive biopsies (12-16 samples)
   • Extend PPI therapy
   • Consider surgical consultation if non-healing after 16 weeks
3. UBT/SAT at 4-6 weeks post-eradication to confirm H. pylori cure

Key Point: Unlike duodenal ulcers (rarely malignant), gastric ulcers carry a 3-5% malignancy risk, so follow-up endoscopy is mandatory. Failure to document healing and exclude cancer is a significant medico-legal risk."

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QUESTION 3: "Describe the Forrest classification and its clinical significance."

Model Answer: "The Forrest classification stratifies bleeding peptic ulcers based on endoscopic appearance, predicting re-bleeding risk and guiding management decisions.

Classification:

Class I - Active Bleeding:

• Ia: Spurting hemorrhage (arterial jet)—Re-bleeding risk 55-90%, Mortality 11-15%
• Ib: Oozing hemorrhage (slow, diffuse)—Re-bleeding risk 30-55%, Mortality 8-11%

Class II - Recent Hemorrhage:

• IIa: Non-bleeding visible vessel (pigmented protuberance)—Re-bleeding 40-50%, Mortality 7-11%
• IIb: Adherent clot—Re-bleeding 20-35%, Mortality 5-7%
• IIc: Flat pigmented spot (hematin staining)—Re-bleeding 5-10%, Mortality 3-5%

Class III:

• Clean-based ulcer (white fibrin base)—Re-bleeding less than 5%, Mortality 2-3%

Clinical Significance:

1. Endoscopic Therapy Indications:

   • Class Ia, Ib: Urgent hemostasis required (epinephrine + thermal/clip)
   • Class IIa: Endoscopic therapy recommended
   • Class IIb: Consider clot removal + hemostasis if high-risk features
   • Class IIc, III: Observation only; low risk

2. Disposition:

   • Ia, Ib, IIa/IIb: HDU/ICU monitoring, IV PPI 72h
   • IIc, III: Can consider ward-based care or early discharge if low GBS score

3. IV PPI Duration:

   • High-risk (Ia, Ib, IIa): 72-hour infusion (80mg bolus → 8mg/hr)
   • Low-risk (IIc, III): Oral PPI acceptable"

Examiner: "What defines a 'visible vessel'?"

Answer: "A visible vessel appears as a discrete protuberance at the ulcer base, typically dark red, blue, or purple due to underlying artery. It differs from a clot (softer, removable) and hematin staining (flat, not raised). The presence of a visible vessel indicates incomplete hemostasis and high re-bleeding risk, warranting endoscopic therapy."

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QUESTION 4: "What are the indications for surgery in peptic ulcer disease?"

Model Answer: "In the modern PPI era, surgery is rarely required, but absolute indications include:

Emergency Indications:

1. Perforation (most common surgical indication):

   • Free perforation with generalized peritonitis
   • Hemodynamic instability
   • Presentation > 24 hours (relative)
   • Procedure: Laparoscopic Graham patch (omental plug repair)

2. Uncontrolled Bleeding:

   • Failure of two endoscopic attempts at hemostasis
   • Massive ongoing bleeding precluding endoscopic visualization
   • Exsanguinating hemorrhage
   • Procedure: Oversewing of bleeding vessel ± vagotomy/pyloroplasty (historical)

3. Gastric Outlet Obstruction:

   • Failure of endoscopic balloon dilation (usually after 2-3 attempts)
   • Fixed fibrotic stenosis
   • Procedure: Gastrojejunostomy or antrectomy

Elective Indications (Rare):

1. Suspected or Confirmed Malignancy:

   • Non-healing gastric ulcer despite 16 weeks maximal medical therapy
   • Dysplasia or cancer on biopsy
   • Procedure: Oncologic resection (partial/total gastrectomy with lymphadenectomy)

2. Intractability/Medical Failure:

   • Refractory ulcer despite H. pylori eradication, high-dose PPI, and exclusion of Zollinger-Ellison
   • Extremely rare in modern era
   • Procedure: Highly selective vagotomy or partial gastrectomy

Key Points:

• Surgical intervention has decreased from 30-40% pre-1980s to less than 5% in PPI era
• Mortality from emergency surgery (perforation/bleeding): 10-30%, heavily influenced by age and comorbidities
• Laparoscopic approach preferred for perforation repair (shorter LOS, faster recovery)"

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14.2 Viva Opening Statements (By Scenario)

Opening Statement 1 - General PUD: "Peptic ulcer disease is characterized by mucosal breaks ≥5mm in diameter extending through the muscularis mucosae of the stomach or duodenum. It affects 5-10% of the population, predominantly caused by Helicobacter pylori infection (60-90% of cases) and NSAID use (20-30%). The condition carries significant morbidity due to complications including hemorrhage in 15-20%, perforation in 2-10%, and gastric outlet obstruction in 1-2%. Diagnosis is confirmed via endoscopy, and management focuses on acid suppression with PPIs and addressing the underlying etiology through H. pylori eradication or NSAID cessation. Prognosis is excellent with modern therapy, with recurrence rates less than 5% after successful eradication compared to 60-90% without treatment."

Opening Statement 2 - Bleeding Ulcer: "Upper gastrointestinal bleeding from peptic ulcer disease represents a medical emergency with 5-10% mortality. My immediate priorities are resuscitation following an ABCDE approach, risk stratification using the Glasgow-Blatchford Score, and urgent endoscopy within 24 hours—immediately if hemodynamically unstable. Endoscopic management depends on the Forrest classification, with active bleeding (Ia, Ib) or high-risk stigmata (IIa, visible vessel) requiring dual therapy such as epinephrine injection combined with thermal coagulation or mechanical clipping. Post-procedure, high-dose IV PPI infusion for 72 hours reduces re-bleeding from 20% to 10%. Long-term management includes H. pylori eradication and careful decision-making regarding resumption of antiplatelet or anticoagulant therapy in collaboration with cardiology."

Opening Statement 3 - Perforated Ulcer: "Perforated peptic ulcer is a surgical emergency occurring in 2-10% of PUD patients, with mortality ranging from 10-40% depending on delay in presentation and patient age. Clinical diagnosis is based on sudden-onset severe epigastric pain, peritonitis, and pneumoperitoneum on imaging—present in 70-80% on erect chest X-ray and 95-98% on CT. Immediate management involves resuscitation, nil-by-mouth, nasogastric decompression, broad-spectrum antibiotics, and urgent surgical consultation. Laparoscopic Graham patch repair (omental plug) is the procedure of choice for perforations less than 1cm in hemodynamically stable patients, offering faster recovery than open repair. Highly selected patients (less than 24h presentation, minimal free fluid, hemodynamically stable) may be candidates for non-operative management with close monitoring. Post-operatively, H. pylori eradication and long-term PPI therapy are essential to prevent recurrence."

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14.3 Key Facts to Quote in Vivas

Epidemiology:

• "Lifetime prevalence 5-10%; incidence 0.1-0.3 per 1,000 person-years"
• "Global H. pylori prevalence ~50%, higher in developing nations (60-80%)"
• "Declining PUD incidence in developed countries due to H. pylori eradication and reduced infection rates"

Pathophysiology:

• "H. pylori CagA-positive strains confer 2-3 fold increased ulcer risk"
• "NSAIDs inhibit COX-1, reducing prostaglandin E2 synthesis, thereby impairing mucus/bicarbonate secretion and mucosal blood flow"
• "Blood group O individuals have 1.3-fold increased risk due to enhanced H. pylori binding to H-antigen"

Diagnosis:

• "Endoscopy has 95% sensitivity and specificity for PUD diagnosis"
• "Rapid urease test: 85-95% sensitive, 95-100% specific; false negatives with recent PPI use"
• "Urea breath test: 95-98% sensitive and specific for active H. pylori infection"

Treatment:

• "Bismuth quadruple therapy achieves 85-95% H. pylori eradication"
• "Vonoprazan-based triple therapy: 85-92% eradication vs 75-82% with PPI-based"
• "PPI therapy heals 90-95% of duodenal ulcers and 85-90% of gastric ulcers at 8 weeks"
• "IV PPI post-endoscopic hemostasis reduces re-bleeding from 20% to 10% and need for surgery from 10% to 5%"

Complications:

• "30-day mortality for bleeding ulcers: 5-10% overall, 10-15% if Forrest Ia/Ib"
• "Perforation mortality: 10-20% overall, 30-40% if age > 70 or delayed presentation > 24h"
• "Re-bleeding after endoscopic therapy: 10-15%, higher with ulcer > 2cm or posterior duodenal location"

Evidence:

• "Marshall and Warren (1984): Nobel Prize discovery establishing H. pylori as PUD etiology"
• "Lau et al. (2000): Landmark trial demonstrating IV PPI benefit post-endoscopic hemostasis"
• "ACG 2017/Maastricht VI 2023: Current guidelines recommend bismuth or concomitant quadruple therapy in high clarithromycin resistance areas"

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14.4 Common Mistakes That Fail Candidates

❌ MISTAKE 1: Treating empirically without confirming H. pylori status

• Consequence: Overuse of antibiotics, potential resistance, suboptimal outcomes
• Correct: Always test before treating (biopsy-based or UBT/SAT if no endoscopy indication)

❌ MISTAKE 2: Failing to arrange follow-up endoscopy for gastric ulcers

• Consequence: Missed gastric adenocarcinoma; medico-legal liability
• Correct: Mandatory repeat EGD at 8-12 weeks for ALL gastric ulcers to document healing and exclude malignancy

❌ MISTAKE 3: Not confirming H. pylori eradication

• Consequence: 10-15% eradication failure → ulcer recurrence 60-90%
• Correct: UBT or SAT at 4-6 weeks post-therapy (must be ≥2 weeks off PPI)

❌ MISTAKE 4: Continuing NSAIDs without gastroprotection post-ulcer

• Consequence: 70-80% ulcer recurrence
• Correct: Either stop NSAIDs or mandatory PPI co-therapy; consider COX-2 selective NSAID

❌ MISTAKE 5: Stopping dual antiplatelet therapy in first 30 days post-stent for bleeding ulcer

• Consequence: Stent thrombosis with 30-50% mortality
• Correct: Continue DAPT, manage bleeding endoscopically, cardiology consultation

❌ MISTAKE 6: Using H2-receptor antagonists instead of PPIs for acute bleeding

• Consequence: Inadequate acid suppression; higher re-bleeding rate
• Correct: High-dose IV PPI (80mg bolus → 8mg/hr × 72h) is standard of care

❌ MISTAKE 7: Attributing all epigastric pain to "gastritis" without investigation

• Consequence: Missed PUD, delayed diagnosis of complications
• Correct: Investigate with endoscopy if alarm features or age > 55 with new-onset dyspepsia

❌ MISTAKE 8: Relying solely on clinical examination to exclude perforation

• Consequence: Missed sealed or retroperitoneal perforation (20-30% lack classic peritoneal signs)
• Correct: CT abdomen/pelvis with oral contrast if clinical suspicion (95-98% sensitivity)

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14.5 Examiner's Favorite Topics and Questions

Topic 1: H. pylori Testing Strategy

• "When would you use invasive vs non-invasive testing?"
• "Why must PPIs be stopped before breath testing?"
• "How do you interpret discordant results (e.g., negative RUT but positive histology)?"

Topic 2: Antibiotic Resistance

• "How does clarithromycin resistance affect your choice of eradication regimen?"
• "What is your approach to a patient who has failed triple therapy?"
• "Should we routinely perform culture and sensitivity testing?"

Topic 3: Bleeding Ulcer Management

• "Describe dual therapy techniques for endoscopic hemostasis"
• "When would you consider angiographic embolization?"
• "How do you manage a patient on warfarin who presents with a bleeding ulcer?"

Topic 4: Gastric Cancer Risk

• "Which gastric ulcers are at highest risk of malignancy?"
• "How many biopsies should you take from a gastric ulcer?"
• "What is the malignancy rate in 'healed' gastric ulcers that were not biopsied?"

Topic 5: Special Populations

• "How does management differ in elderly patients?"
• "What are the considerations for H. pylori eradication in pregnancy?"
• "How do you balance anticoagulation vs bleeding risk?"

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Last Reviewed: 2026-01-02 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and current guidelines.