1. Acute Gastritis

1.1 Epidemiology

• Acute gastritis is relatively common, often transient, and can arise in response to various offending agents or conditions.
• There is a poor correlation between endoscopic appearances (e.g. erythema, erosions) and the histological definition of gastritis.

1.2 Aetiology

Acute gastritis involves acute inflammation of the gastric mucosa.

Possible causes include:

1. Drugs
   • NSAIDs: Reduced prostaglandin-mediated mucosal protection.
   • Other irritants (e.g. certain chemotherapeutic agents).
2. Alcohol
   • Direct mucosal irritant effect.
3. Physiological Stress
   • Severe burns, intensive care settings (shock, multi-organ failure), or prolonged severe illness.
4. Bile Reflux (post-gastrectomy)
   • Bile salts injure the remnant stomach’s mucosa if pylorus is bypassed or incompetent.
5. Infections
   • Occasionally, acute Helicobacter pylori infection.
   • Rare viral causes (CMV, HSV) in immunocompromised states.

1.3 Pathogenesis

1. Balance of Defence vs. Injury
   • The gastric mucosa is protected by a mucin-bicarbonate layer, adequate mucosal blood flow, and epithelial renewal.
   • Acid and pepsin, along with noxious stimuli (e.g. NSAIDs, alcohol), can overwhelm these defences if they become excessive or if protective mechanisms are compromised.
2. Mechanisms Leading to Acute Inflammation
   • NSAIDs: Inhibit prostaglandin synthesis → less mucous and less bicarbonate → mucosal damage.
   • Alcohol or chemical irritants: Direct chemical injury to surface epithelium → local inflammation.
   • Stress-related: Reduced mucosal perfusion under shock/burn conditions → ischaemic injury → superficial erosions or ulcers.
3. Neutrophilic Infiltration
   • Hallmark of acute inflammation.
   • Mild injury leads to superficial involvement (erosions), whereas severe or prolonged injury can reach deeper layers, causing more pronounced ulceration or bleeding.

1.4 Risk Factors

• Excessive alcohol intake.
• Chronic or high-dose NSAID therapy without gastroprotection.
• Severe physiological stress (burns, major surgery, ICU admissions).
• Post-gastrectomy bile reflux.
• Rarely, viral infections in immunocompromised patients.

1.5 Clinical Features

• Often asymptomatic or mild dyspepsia.
• Epigastric pain/discomfort (may be diffuse).
• Nausea, vomiting, or haematemesis in more severe cases with erosions.
• Typically short-lived if the offending agent is removed.

1.6 Diagnostic Approach

• Clinical suspicion based on risk factors (e.g. NSAID use, alcohol).
• Endoscopy: May show erythema, superficial erosions; findings are not always reliable for diagnosing true histological “gastritis”.
• Histology (biopsy) provides definitive evidence of acute inflammatory changes (neutrophilic infiltration).
• Other tests:
  • Evaluate for H. pylori if suspicion of concurrent infection.
  • Check for anaemia if bleeding is suspected (full blood count, iron studies).

1.7 Management

1. Remove or Reduce Offending Causes
   • Discontinue or minimise NSAIDs or other irritant drugs if possible.
   • Advise limiting alcohol.
   • Provide supportive care in ICU settings for stress ulcer prophylaxis.
2. Acid Suppression
   • Proton pump inhibitors (PPIs) (e.g. omeprazole) or H2 receptor antagonists (e.g. ranitidine) to reduce acid-induced injury.
   • Antacids or sucralfate for symptomatic relief or mild cases.
3. Symptomatic Measures
   • Antiemetics for severe nausea/vomiting.
   • Adequate hydration and electrolyte balance if vomiting/bleeding significant.

1.8 Prognosis / Complications

• Most episodes of acute gastritis are self-limiting if the causative factor is removed.
• Potential complications if severe or prolonged:
• Superficial erosions progressing to more severe ulceration or bleeding.
• Acute haemorrhage in stress-related mucosal damage (stress ulcers).
• Typically, resolution occurs with appropriate intervention and withdrawal of offending agents.

2. Chronic Gastritis

2.1 Epidemiology

• Chronic gastritis encompasses long-standing inflammation of the gastric mucosa.
• Helicobacter pylori infection is by far the most common global cause.
• Autoimmune gastritis is less common overall, but significant in certain populations.
• Additional causes include CMV, TB, Crohn’s disease, and systemic diseases (sarcoid, graft-versus-host disease, granulomatous gastritis).

2.2 Aetiology

Chronic gastritis can be classified by aetiological factors:

1. Helicobacter pylori Gastritis
   • Primary cause worldwide (dominant cause in ~90% of chronic gastritis cases).
   • Typically affects the antrum (though can involve body).
2. Autoimmune Gastritis
   • Targets parietal cells (body/fundus-located).
   • Associated with circulating antiparietal cell or intrinsic factor antibodies.
3. Others
   • Infections: CMV, TB in immunocompromised or high-prevalence areas.
   • Systemic/Inflammatory: Crohn’s disease, sarcoidosis, graft-versus-host disease.
   • Granulomatous forms (rare).

2.3 Pathogenesis

2.3.1 H. pylori Gastritis

1. Bacterial Colonisation
   • H. pylori colonises gastric mucosa (often the antrum).
   • Bacteria produce ureases (converting urea to ammonia) and proteases that disrupt the mucous layer.
2. Host Inflammatory Response
   • This leads to acute on chronic inflammation dominated by lymphocytes and plasma cells.
   • Inflammatory mediators weaken the mucosal defences → predisposition to acid injury.
3. Consequences
   • Antral-predominant gastritis → risk of duodenal ulcer.
   • Body-predominant gastritis → risk of gastric ulcer.
   • Long-term: Intestinal metaplasia, increasing risk of gastric adenocarcinoma and MALT lymphoma.

2.3.2 Autoimmune Gastritis

1. Autoimmune Destruction
   • Immunological attack (type IV hypersensitivity) against parietal cells in the fundus/body of the stomach.
   • Antibodies (anti-parietal cell/intrinsic factor) are diagnostic markers but the underlying pathology is T-cell mediated.
2. Functional Loss
   • Atrophy of specialised mucosa: loss of acid secretion (achlorhydria) and intrinsic factor.
   • Consequent hypergastrinaemia (G-cell hyperplasia in the antrum) and risk of pernicious anaemia(vitamin B12 deficiency).
3. Progression
   • Chronic atrophic changes lead to intestinal metaplasia in some patients.
   • Increased risk of gastric adenocarcinoma (intestinal type).

2.3.3 Other Causes

• Chronic Infectious (CMV, TB) or Granulomatous forms:
  • Similar infiltration of inflammatory cells, but driven by specific pathogens/systemic conditions.
  • Chronic insults lead to mucosal damage, possible atrophy, or rarely strictures/fistulas if severe (e.g. Crohn’s).

2.4 Risk Factors

• H. pylori exposure (faecal-oral, oral-oral transmission).
• Genetic predisposition in autoimmune gastritis.
• Immunosuppression (CMV infection).
• Geographical prevalence: H. pylori is more common in certain regions; TB-related gastritis in high TB-burden areas.

2.5 Clinical Features

• Typically asymptomatic or mild.
• Can present with non-specific dyspepsia, anorexia.
• Autoimmune form: may lead to achlorhydria and pernicious anaemia (fatigue, glossitis, neurological signs if B12 deficiency is advanced).

2.6 Diagnostic Approach

1. Endoscopy
   • Mucosal changes not always specific; biopsy is essential for histological confirmation (lymphoplasmacytic infiltration, atrophy, metaplasia).
2. H. pylori Testing
   • Urea breath test, stool antigen test, or biopsy-based (rapid urease/histology).
3. Autoimmune Work-up
   • Serum vitamin B12 levels.
   • Anti-parietal cell or intrinsic factor antibodies.
4. Further investigations for other causes (CMV, TB) if indicated by clinical setting.

2.7 Management

1. H. pylori Gastritis
   • Eradication therapy (triple therapy: PPI + clarithromycin + amoxicillin/metronidazole).
   • Reduces risk of ulcer and some evidence of reversing precancerous changes if early.
2. Autoimmune Gastritis
   • Correct anaemia (vitamin B12 supplementation).
   • Monitor for other autoimmune disorders.
   • Regular surveillance if atrophic changes are significant (cancer risk).
3. Others
   • Address the underlying cause (e.g. TB, CMV, Crohn’s).
   • Supportive measures, acid suppression if symptomatic dyspepsia or ulcers.

2.8 Prognosis / Complications

• H. pylori:
  • Potential progression to peptic ulcer disease, gastric adenocarcinoma, or MALT lymphoma.
  • Eradication significantly lowers ulcer risk and can induce regression of MALT lymphoma.
• Autoimmune:
  • May develop pernicious anaemia, requiring lifelong B12 supplementation.
  • Higher risk of gastric carcinoma (intestinal type) due to chronic atrophic gastritis and metaplasia.
• Other:
  • Depends on the specific infection or systemic disorder. Chronic inflammation can lead to atrophy, rare malignant transformation.

3. Peptic Ulcer Disease

3.1 Epidemiology

• Peptic ulcer disease (PUD) encompasses gastric and duodenal ulcers, which are diagnosed at ~2 per 1000 patient years in developed countries.
• Incidence increases with age and is influenced heavily by environmental factors: Helicobacter pyloriprevalence, use of NSAIDs, and lifestyle (smoking, alcohol).
• H. pylori eradication has led to a decline in peptic ulcer frequency in many developed regions.

3.2 Aetiology

Peptic ulcers result from imbalance between luminal acid/pepsin and mucosal defences:

1. H. pylori (dominant cause worldwide):
   • Infects the gastric antrum, leading to increased acid and local mucosal damage.
2. NSAIDs
   • Decrease prostaglandin synthesis, compromising mucus and bicarbonate secretion, undermining mucosal defence.
3. Acid Hypersecretion
   • Rare states (e.g. Zollinger–Ellison syndrome) or antral H. pylori infection can result in excessive acid output.
4. Other Factors
   • Smoking, alcohol: Diminish mucosal defences.
   • Physiological stress: Tends to cause erosive gastritis but can contribute to ulcers in certain critical care scenarios.

3.3 Pathophysiology

1. Acid-Pepsin Aggression
   • Parietal cells secrete HCl (pH ~1) and chief cells secrete pepsinogen.
   • Under normal circumstances, the gastric/duodenal mucosa is safeguarded by unstirred mucus layer with bicarbonate (maintaining a local pH near 7).
   • Prostaglandins and good mucosal blood flow support this protective layer.
2. Defence Breakdown
   • H. pylori: Produces ureases (generating ammonia), proteases, and triggers inflammation. These factors weaken the mucus-bicarbonate layer and can increase acid production (especially in duodenal ulcers).
   • NSAIDs: Reduced prostaglandin synthesis leads to diminished mucus/bicarbonate output, compromised mucosal integrity.
   • In duodenal ulcers, excessive acid can overflow into the duodenum, especially when H. pylori infection in the antrum lowers the threshold for acid hypersecretion.
   • In gastric ulcers, local mucosal defences are more directly impaired by H. pylori or NSAIDs, permitting acid/pepsin injury to the stomach lining.
3. Ulcer Formation
   • Full-thickness necrosis extending beyond the muscularis mucosae (distinguishing from superficial erosions).
   • Chronic ulcers exhibit submucosal fibrosis, whereas acute ulcers (often stress-related) may be more superficial or have less fibrotic reaction.

3.4 Risk Factors

• H. pylori infection (antral or body colonisation).
• NSAID or steroid use (especially combined with H. pylori).
• Smoking (impairs mucosal healing).
• Alcohol (possible direct mucosal irritation).
• Chronic illness or stress (less commonly leads to ulcers, more so erosions).
• Rare conditions causing gastric acid hypersecretion (Zollinger–Ellison).

3.5 Clinical Features

Peptic ulcer disease typically presents with epigastric pain.

Differences include:

1. Duodenal Ulcer
   • Pain: Occurs hours after meals or nocturnally, often relieved by eating or antacids.
   • Younger demographic (<40 years old), ~4:1 male:female.
   • Weight/appetite typically normal.
   • Increased acid secretion is common.
2. Gastric Ulcer
   • Pain: Occurs soon after eating, can cause anorexia or weight loss.
   • Elderly predisposition, ~2:1 male:female.
   • Normal acid secretion levels (or reduced).
   • Potential for malignancy, so endoscopic biopsy is essential.

3.6 Diagnostic Approach

1. Endoscopy
   • Key investigation: Direct visualisation and biopsy.
   • For gastric ulcers, repeat endoscopy at 8–12 weeks to confirm healing and rule out malignancy.
2. Testing for H. pylori
   • Biopsy-based urease tests, stool antigen, or urea breath tests.
   • Eradication is mandatory if present.
3. Imaging
   • Usually not mandatory beyond endoscopy, except if complications or suspicion of other pathology.

3.7 Management

1. H. pylori Eradication
   • If H. pylori positive, triple therapy (PPI + clarithromycin + amoxicillin/metronidazole).
   • Prevents recurrence in ~50% of cases if not eradicated.
2. Acid Suppression
   • Proton pump inhibitors (PPIs) for 4–8 weeks (depending on DU or GU).
   • H2 receptor antagonists are second-line alternatives.
3. Lifestyle / Drug Modification
   • Smoking cessation, reduce alcohol.
   • Discontinue NSAIDs if possible.
   • Address risk factors (e.g. steroid-sparing approach).
4. Maintenance Therapy
   • In high-risk scenarios (recurrent ulcers, bleeding episodes), consider long-term PPI.
5. Surgical Intervention
   • Rarely needed; indicated if bleeding, perforation, obstruction, or non-healing under medical treatment (e.g. partial gastrectomy, Billroth procedure).

3.8 Prognosis / Complications

• Uncomplicated PUD: Usually good prognosis with eradication of H. pylori and PPI therapy.
• Gastric Ulcer: Must exclude malignancy; endoscopic biopsy critical.
• Complications:
  • Haemorrhage (25% of peptic ulcer cases) → can present with haematemesis or melaena.
  • Perforation (10% in some series) → acute abdomen, free air under diaphragm.
  • Gastric Outlet Obstruction from scarring or oedema around the pylorus.
  • Mortality is primarily linked to complications (bleeding, perforation) and comorbidities.

4. Zollinger-Ellison Syndrome

4.1 Epidemiology

• Zollinger–Ellison syndrome (ZES) is rare but may occur in >1% of patients with peptic ulcer disease.
• Characterised by a triad:
  1. Severe or recurrent peptic ulceration (often multiple, possibly involving distal duodenum or beyond).
  2. Increased gastric acid secretion.
  3. Hypergastrinaemia due to a non-beta islet cell tumour (gastrinoma), usually in the pancreas.
• Approximately 60% of gastrinomas are malignant (though often slow-growing).
• 50% of tumours can be multiple, and 25% may be associated with other endocrine tumours in MEN1 (multiple endocrine neoplasia type I).

4.2 Aetiology

• Gastrinoma secretes excessive gastrin from the pancreas (non-beta islet cells) or occasionally from the duodenum/stomach.
• Hypergastrinaemia leads to marked acid production, driving persistent or atypical peptic ulcer disease.
• Up to 25% of ZES cases occur with MEN1, involving parathyroid/pituitary tumours as well.

4.3 Pathophysiology

1. Excessive Gastrin Production
   • Gastrin normally stimulates parietal cells to secrete acid.
   • In ZES, the gastrinoma produces unregulated high levels of gastrin.
2. Mucosal Damage
   • Profound acid hypersecretion overwhelms the normal defences in the stomach, duodenum, or even more distal small bowel.
   • This results in multiple, refractory peptic ulcers and complications like bleeding or perforation.
3. Malabsorption
   • Diarrhoea and steatorrhoea can occur because the excess acid inactivates pancreatic enzymes and injures the intestinal mucosa, reducing nutrient absorption.
4. Metastatic Potential
   • Many gastrinomas are malignant (60%), though progression can be slower than typical pancreatic cancers.
   • Hepatic metastases greatly worsen prognosis.

4.4 Risk Factors

• Familial predisposition in MEN1.
• Pancreatic or duodenal tumour location.
• Multiple endocrine tumours (parathyroid, pituitary) if MEN1 is involved.

4.5 Clinical Features

• Severe, recurrent peptic ulcers often resistant to conventional therapy; may present in unusual sites (e.g. jejunum).
• Abdominal pain, dyspepsia from ulcers.
• Diarrhoea, steatorrhoea (due to acid inactivation of lipase and other enzymes).
• 50% tumours are multiple; ~60% malignant.
• In MEN1: may co-exist with parathyroid or pituitary tumours.

4.6 Diagnostic Approach

1. Gastric Acid Secretion
   • Basal acid output is grossly elevated, with minimal further increase upon pentagastrin injection.
2. Serum Gastrin
   • Significantly elevated.
   • Hypergastrinaemia in the context of high acid output is suggestive of ZES.
3. Localisation of Tumour
   • Endoscopic ultrasound or Octreoscan (radiolabelled somatostatin receptor scan) to locate the gastrinoma in the pancreas or duodenum.

4.7 Management

1. Surgical Resection
   • About 30% are resectable (single, small, localised).
   • Tumour removal or debulking if possible.
2. Medical Therapy
   • High-dose proton pump inhibitors (PPIs) for acid control, typically lifelong.
   • Octreotide (somatostatin analogue) may reduce gastrin secretion and help symptomatically.

4.8 Prognosis / Complications

• Hepatic metastasis is the main determinant of survival.
• 5-year survival across all ZES patients: 62–75%.
• With hepatic metastases, 5-year survival ~20%, 10-year ~10%.
• Persistent hyperacidity leads to recurrent ulcer complications (bleeding, perforation) and malabsorption if not controlled.

5.1 Epidemiology

• Gastric carcinoma is historically the commonest cause of cancer death worldwide, especially in China and Japan.
• Incidence has fallen in many Western countries but remains significant.
• In the UK (2011 data), there were 15 new cases per 100,000 males and 8 per 100,000 females.
• Occurs more often in men, typically over 50 years old.

5.2 Aetiology

1. Chronic H. pylori Infection (especially cagA strain)
   • Responsible for around two-thirds of cases.
   • Induces chronic atrophic gastritis → intestinal metaplasia → malignant transformation.
2. Familial and Genetic Factors
   • Blood group A association.
   • Rare gastric cancer families (e.g. E-cadherin mutation in New Zealand Māori).
   • Syndromes: Familial adenomatous polyposis, Peutz–Jegher’s.
3. Dietary and Environmental
   • High N-nitrosamines (pickled, smoked foods).
   • Low fruit/vegetable intake.
   • Smoking and alcohol.
4. Organic Disorders
   • Menetrier’s disease, previous partial gastrectomy (risk for stump carcinoma decades later).

5.3 Pathophysiology

1. Intestinal Metaplasia and Atrophy
   • Chronic atrophic gastritis (often H. pylori-related) → patches of intestinal-type epithelium in the stomach.
   • Over time, dysplastic changes in these metaplastic foci can evolve into adenocarcinoma.
2. Morphological Spectrum
   • Polypoid lesions: Protruding into the lumen.
   • Diffuse infiltration (linitis plastica): Tumour infiltrates widely, thickening the stomach wall.
   • Early gastric cancer: Tumour confined to mucosa or submucosa. Early detection (e.g. in Japan) allows potential endoscopic cure.
3. Tumour Progression
   • Advanced lesions frequently invade deeper layers (muscularis propria, serosa).
   • Spreads via lymphatics and haematogenous routes; liver is a common metastasis site.

5.4 Risk Factors

• H. pylori (particularly cagA strain).
• Family history, blood group A, known gastric cancer families.
• Diet high in salted/pickled foods with nitrates.
• Smoking, alcohol.
• Menetrier’s disease, post-gastrectomy states.

5.5 Clinical Features

• Early disease often asymptomatic or only mild epigastric discomfort.
• Non-specific epigastric pain, not strongly meal-related; often relieved by acid suppressants.
• Weight loss, anorexia.
• Vomiting, haematemesis, or physical findings are usually late.
• Troisier’s sign: Left supraclavicular (Virchow’s) node.
• Trousseau’s sign (rare): Migratory thrombophlebitis.

5.6 Diagnostic Approach

1. Endoscopy
   • Key to visualise suspicious lesions; rolled, irregular-edged ulcers.
   • Multiple biopsies of ulcer edges to exclude malignancy.
2. Staging Investigations
   • Blood tests: Full blood count (anaemia), LFTs.
   • Chest X-ray, CT scan (thorax/abdomen) for metastatic workup.
   • Endoscopic ultrasound to assess depth of invasion.
   • Laparoscopy often required for definitive staging (peritoneal spread).

5.7 Management

1. Surgical Resection
   • Potentially curative but only feasible in a minority (many present with advanced or metastatic disease).
   • Resection (partial or total gastrectomy) plus lymph node dissection if localised disease is resectable.
2. Chemotherapy
   • Perioperative (neoadjuvant + adjuvant) may improve survival in resectable disease.
   • Palliative chemotherapy can be used for symptomatic control in advanced disease.
3. Palliation
   • If unresectable, palliative surgery or stenting for obstruction, analgesia, and nutritional support.

5.8 Prognosis / Complications

• Early gastric cancer (confined to mucosa/submucosa) has a 5-year survival ~90% if resected.
• Overall, prognosis is poor (~10% 5-year survival) due to late presentation.
• Metastatic disease (particularly hepatic) severely limits survival outcomes.
• Public awareness and earlier diagnosis (as in screening programmes in Japan) could improve outcomes.

6. Gastric Lymphoma

6.1 Epidemiology

• The stomach is the commonest extranodal site for non-Hodgkin’s lymphoma (NHL).
• Primary gastric lymphoma is rare (~1 per 100,000 per year), but the relative frequency is higher in older males (over 50), and the risk is increased in AIDS.
• These lymphomas are predominantly B-cell tumours:
  1. Aggressive large-cell lymphomas (majority).
  2. Low-grade MALT (mucosa-associated lymphoid tissue) lymphomas (minority).
• MALT lymphoma incidence in the stomach is ~0.5 per 100,000/year in Western countries and may be decreasing as H. pylori prevalence falls.

6.2 Aetiology

1. Primary Gastric Lymphoma
   • B-cell neoplasms arising from the gastric mucosa’s lymphoid tissue.
   • Infective/immunodeficient states (e.g. AIDS) increase relative risk.
2. MALT Lymphoma
   • Strongly associated with chronic H. pylori infection (particularly cagA strains).
   • Represents a distinct low-grade B-cell tumour triggered by ongoing immune stimulation from H. pylori.

6.3 Pathophysiology

1. Aggressive Large-Cell Gastric Lymphoma
   • High-grade malignant transformation of B-lymphocytes in the gastric wall.
   • Often infiltrates beyond the mucosa, can be transmural, forming bulky tumours.
   • Tends to present similarly to gastric adenocarcinoma (mass effect, ulcerative lesions).
2. MALT Lymphoma
   • Chronic antigenic stimulation by H. pylori fosters lymphoid aggregates in the stomach.
   • Over time, these reactive B-cells can acquire mutations → neoplastic clones.
   • Characterised by lymphoepithelial lesions and “reactive” germinal centres (follicles).
   • Early/low-grade disease may regress if antigenic (H. pylori) stimulus is removed (i.e. eradication).
3. Progression
   • High-grade or advanced lymphoma may necessitate more aggressive treatments.
   • Deep infiltration can involve submucosa, muscularis, or beyond, with potential nodal/ distant spread.

6.4 Risk Factors

• Chronic H. pylori infection (especially cagA strains) for MALT-type.
• Immunodeficiency (e.g. HIV/AIDS).
• Older age, male preponderance.
• Possible additional factors: diet, environment (less well-defined for lymphoma than for carcinoma).

6.5 Clinical Features

• Often indistinguishable from gastric adenocarcinoma:
  • Epigastric pain, anorexia, weight loss.
  • Possible upper GI bleeding (haematemesis), or chronic GI blood loss → anaemia.
• Systemic ‘B’ symptoms (in advanced disease): fevers, night sweats, weight loss (common in aggressive lymphoma).
• MALT lymphoma tends to be low-grade, often discovered incidentally or through mild dyspepsia symptoms.

6.6 Diagnostic Approach

1. Histology (gold standard):
   • Endoscopic biopsies (deep mucosal samples) or laparoscopic tissue for definitive diagnosis.
   • Large-cell lymphoma vs. low-grade MALT typed by immunohistochemistry.
2. Endoscopic Ultrasound / CT
   • Assess local infiltration depth, nodal involvement.
   • Abdominal CT for staging/assessment of spread.
3. H. pylori Testing
   • Particularly in suspected MALT lymphoma (urea breath test, stool antigen, biopsy-based tests).

6.7 Management

6.7.1 Primary Gastric Lymphoma (Large-Cell / Aggressive)

• Early disease: Surgical resection may be feasible (~minority of cases).
• Advanced disease: Combined chemotherapy ± radiotherapy is the mainstay.
• Prognosis: 5-year survival ~50% overall, better in younger/low stage disease.

6.7.2 MALT Lymphoma

• H. pylori eradication leads to remission in ~75% of cases.
• For refractory disease or high-grade transformation:
  • Endoscopic mucosal resection (rarely needed if localised).
  • Chemoradiotherapy.
  • Surgical resection only in select cases.
• Long-term endoscopic follow-up essential; recurrence can appear years later.
• Prognosis: Excellent if low-grade, with a 10-year survival of ~95%.

6.8 Prognosis / Complications

• Overall 5-year survival in primary gastric lymphoma ~50%.
• MALT lymphoma has a much better outlook (10-year survival ~95% if low-grade).
• The presence of hepatic metastasis or extensive spread significantly worsens survival in aggressive forms.
• Some cases may remain indolent for years, especially MALT subtypes responding to H. pylori therapy.

7. Other Gastric Tumours

7.1 Epidemiology

7.1.1 Gastrointestinal Stromal Tumours (GISTs)

• Rare tumours (~1 per 100,000 annually).
• Occur throughout the GI tract: 60% in the stomach, 30% in the small intestine.
• Originates from interstitial cells of Cajal.

7.1.2 Gastric Polyps

• Hyperplastic or cystic fundal polyps are relatively common, usually benign and of no clinical significance, often found incidentally.
• Adenomatous polyps are rare but premalignant and can co-exist with colonic polyps (e.g. familial polyposis syndromes).

7.2 Aetiology

1. GISTs
   • Arise from mesenchymal cells (interstitial cells of Cajal).
   • Driven by mutations in c-kit (tyrosine kinase receptor) or related oncogenes.
2. Gastric Polyps
   • Hyperplastic/cystic: Possibly linked to local irritation or chronic gastritis.
   • Adenomatous: Reflect dysplastic changes with a background of familial or sporadic polyp formation.

7.3 Pathophysiology

7.3.1 Gastrointestinal Stromal Tumours

1. Tyrosine Kinase Oncogene Activation
   • Most GISTs show c-kit gene expression (CD117 positive), leading to continuous tyrosine kinase activity that drives tumour proliferation.
   • Tumours originate from muscularis propria and submucosa, forming submucosal bulges that can ulcerate into the lumen or expand extraluminally.
2. Malignant Potential
   • Determined by tumour size, mitotic rate, and c-kit oncogene expression.
   • Larger tumours with high mitotic activity carry increased risk of metastasis (commonly liver or peritoneum).

7.3.2 Gastric Polyps

1. Hyperplastic / Cystic Polyps
   • Represent a benign hyperproliferation of the mucosa or cystic glands.
   • Typically do not progress to malignancy.
2. Adenomatous Polyps
   • Neoplastic lesion with risk of malignant transformation (akin to colonic adenomas).
   • Arise due to dysplastic changes in the gastric epithelium, occasionally linked with familial polyp syndromes.

7.4 Risk Factors

• GISTs:
  • Age.
  • Family history of disease.
• Gastric Polyps:
  • Hyperplastic: Chronic gastritis or mucosal irritants.
  • Adenomatous: Possible link to familial adenomatous polyposis, or sporadic development.

7.5 Clinical Features

7.5.1 Gastrointestinal Stromal Tumours

• Often incidental discovery on endoscopy or imaging.
• May ulcerate → GI bleeding (haematemesis or melaena).
• Larger or malignant GISTs can cause mass effect, abdominal pain, or rarely metastases.

7.5.2 Gastric Polyps

• Usually asymptomatic; found incidentally.
• Rarely large adenomatous polyps might cause bleeding or obstructive symptoms.
• Key concern is differentiation from early gastric cancer.

7.6 Diagnostic Approach

1. GISTs
   • Endoscopy: Submucosal mass with possible overlying ulceration.
   • Biopsy: Often submucosal, may require deeper sampling or endoscopic ultrasound guidance.
   • Histology: Immunohistochemical staining positive for CD117 (c-KIT).
2. Gastric Polyps
   • Endoscopic detection.
   • Biopsy to rule out dysplasia/malignancy, particularly in suspicious or large polyps.
   • Colonoscopy if adenomatous polyp found (looking for colonic polyps).

7.7 Management

7.7.1 Gastrointestinal Stromal Tumours

• Surgical resection is the mainstay for localised disease.
• Chemoradiotherapy (traditional approach for advanced GISTs) has largely been replaced or supplemented by tyrosine kinase inhibitors:
  • Imatinib: A specific inhibitor of the c-kit receptor, has revolutionised malignant GIST treatment, extending median survival from <2 years to >5 years.
  • Sunitinib is an option in imatinib-resistant disease, further improving outcomes.

7.7.2 Gastric Polyps

• Hyperplastic/fundic: No specific treatment if small and asymptomatic; remove if suspicious or symptomatic.
• Adenomatous: Require resection (endoscopic removal if feasible) due to premalignant potential.
• Colonoscopy recommended to check for concomitant colonic polyps if adenomatous.

7.8 Prognosis / Complications

• GISTs:
  • Prognosis depends on tumour size, mitotic index, and resectability.
  • Metastatic GIST improved substantially with tyrosine kinase inhibitors (imatinib, sunitinib).
  • Long-term disease control is possible in advanced cases with targeted therapy.
• Gastric Polyps:
  • Hyperplastic polyps: generally benign, very low risk.
  • Adenomatous polyps: premalignant; timely resection prevents progression to gastric carcinoma.