Gastric adenocarcinoma and precursor states

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Chronic H pylori inflammation can progress to multifocal atrophy and intestinal metaplasia, reducing acid-producing glands and creating a field at risk of dysplasia. Autoimmune gastritis preferentially affects the body and fundus, causing iron deficiency early and B12 deficiency later. Dysplasia is neoplastic epithelium confined above the basement membrane; invasion through it establishes adenocarcinoma.

Symptoms are often late and non-specific. Persistent epigastric discomfort, anorexia, early satiety, anaemia, melaena or vomiting must be interpreted with age and trajectory. Diffuse infiltrative linitis plastica may stiffen the stomach without a prominent ulcer and superficial forceps biopsies can be falsely negative, requiring repeat deeper assessment.

Endoscopy and histology make the diagnosis. The UK Sydney scheme takes five samples across antrum, incisura and corpus; MAPS III uses two antrum/incisura and two corpus fragments in separately labelled vials, with a separate incisura sample optional. For extensive or advanced change, including both antrum and corpus or OLGA/OLGIM III–IV, the usual surveillance interval is three years. Discuss expected benefit and whether the person is likely to remain fit for endoscopic treatment at the next examination. MAPS III suggests discontinuing screening/surveillance, or not starting it, in asymptomatic people over 80; this does not exclude investigating new symptoms. Mild or moderate antral-only change without extensive endoscopic disease or additional risk factors needs no routine surveillance. For single-site intestinal metaplasia with a family history of gastric cancer, incomplete metaplasia or persistent H pylori, consider three-year surveillance. Extensive/advanced change plus a first-degree relative with gastric cancer may justify a shorter one- to two-year interval.

Key points

Most gastric cancers are adenocarcinomas developing through chronic inflammation, gland loss, intestinal metaplasia and dysplasia, although diffuse cancers may not form a discrete precursor field.
Helicobacter pylori is a major modifiable carcinogenic driver; autoimmune gastritis creates corpus-predominant atrophy, achlorhydria and B12 deficiency.
For suspected advanced gastric adenocarcinoma obtain at least eight viable biopsies; take only one or two targeted biopsies from a potentially endoscopically resectable lesion, and at least ten bite-on-bite samples when linitis plastica is suspected.
Established gastric cancer considered for radical gastrectomy needs whole-body staging and laparoscopy for occult peritoneal disease; a superficial lesion suitable for endoscopic resection does not routinely need CT, EUS, MRI or PET-CT before that resection.
Endoscopic resection is reserved for carefully staged superficial low-risk lesions that permit complete en-bloc pathological assessment.
Resectable more advanced adenocarcinoma usually needs perioperative systemic treatment and gastrectomy with appropriate lymphadenectomy in a specialist centre.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Helicobacter-driven inflammation

Persistent Helicobacter pylori gastritis can progress through glandular atrophy, intestinal metaplasia and dysplasia before intestinal-type gastric adenocarcinoma develops.

Autoimmune corpus gastritis

Autoimmune destruction of corpus parietal cells produces achlorhydria, hypergastrinaemia, iron and vitamin B12 deficiency, and a chronic field at risk of neoplasia.

Inherited or environmental susceptibility

Family history, smoking, high-salt preserved foods and inherited syndromes such as CDH1-associated diffuse gastric cancer modify an individual patient’s risk.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Intestinal pathway
Sustained mucosal inflammation favours metaplastic and dysplastic epithelial clones that accumulate alterations and ultimately invade through the basement membrane into gastric wall.
2
Diffuse pathway
Poorly cohesive cells infiltrate the wall and stiffen the stomach without always forming an exophytic mass.
3
Peritoneal dissemination
Once tumour penetrates the serosa, malignant cells can disseminate across peritoneal surfaces and form deposits that remain below routine CT resolution.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Occult chronic loss

Iron-deficiency anaemia or melaena may reflect an ulcerated cancer even without severe pain.

Reduced gastric capacity

Early satiety and weight loss can result from infiltrative wall thickening or outlet narrowing.

Atrophic precursor field

Extensive antral and corpus intestinal metaplasia carries more risk than a small focal change.

Diffuse infiltrationRed flag

Poor distension, thickened folds and a rigid stomach suggest linitis plastica despite limited surface ulceration.

Metastatic clues

Ascites, a left supraclavicular node, umbilical deposit or ovarian mass can indicate advanced spread.

Red flags requiring action

Iron-deficiency anaemia, early satiety, persistent vomiting, weight loss, dysphagia or a palpable epigastric mass requires prompt upper-GI assessment.
A gastric ulcer that appears benign still needs appropriate biopsy and follow-up to demonstrate healing and exclude an underlying cancer.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
High-quality gastroscopy with lesion samplingFirst step
Why
Inspect the entire stomach and establish cancer or precursor histology.
Interpretation and limitations
Take at least eight viable biopsies from advanced cancer, one or two targeted biopsies from a potentially resectable superficial lesion and at least ten bite-on-bite biopsies if linitis is suspected despite negative surface tissue.
02
Topographic precursor mapping
Why
Define the anatomical extent and histological stage of atrophy or intestinal metaplasia.
Interpretation and limitations
A UK Sydney set uses five sites across antrum, incisura and corpus. MAPS III requires two antrum/incisura and two corpus fragments in two labelled vials, with an optional separate incisura sample; report distribution rather than pooling it.
03
Helicobacter pylori testing and eradication check
Why
Identify and remove a treatable carcinogenic driver.
Interpretation and limitations
Account for test suppression. For eradication confirmation, wait at least 4 weeks after antibiotics or bismuth and stop a PPI for at least 2 weeks before a carbon-13 urea breath or validated stool-antigen test; for peptic ulcer, NICE schedules retesting 6 to 8 weeks after treatment begins.
04
Staging CT
Why
Assess local extension, nodes and distant metastases.
Interpretation and limitations
Use CT in the radical gastrectomy pathway. MAPS III advises against routine CT, EUS, MRI or PET-CT before endoscopic resection of an early gastric lesion unless features suggest deep invasion or it is not suitable for local treatment.
05
Staging laparoscopy with cytology
Why
Detect occult peritoneal or surface liver spread before laparotomy.
Interpretation and limitations
Positive peritoneal disease changes a curative resection plan even when cross-sectional imaging appears clear.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Benign peptic ulcer

Benign peptic ulcers can produce identical pain or bleeding, so gastric ulceration needs adequate edge biopsy and documented healing after treatment.

Gastric lymphoma

Gastric lymphoma may cause ulceration or diffuse wall thickening but has lymphoid histology, distinct staging requirements and treatment compared with adenocarcinoma.

Gastrointestinal stromal tumour

A gastrointestinal stromal tumour forms a subepithelial mesenchymal mass and requires tissue acquisition and risk assessment distinct from a mucosal adenocarcinoma pathway.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Potentially curable cancerExclude occult peritoneal spreadFirst stepBiopsy confirms gastric adenocarcinoma and CT shows no distant metastases.

1Review pathology, nutrition and performance status at the specialist MDT.
2Perform staging laparoscopy for potentially curable gastric disease and sample suspicious deposits or washings according to protocol.
3Choose perioperative therapy and gastrectomy extent from stage, site and fitness.
4Verify restaging, surgery date and postoperative pathology ownership after systemic treatment.

02Precursor mappingTurn distribution into a surveillance decisionA 64-year-old is expected to remain fit for endoscopic treatment over the next three years. Image-enhanced endoscopy finds no focal lesion; mapped biopsies show complete intestinal metaplasia in antrum and corpus, OLGIM III and H pylori. There is no first-degree family history of gastric cancer.

1Confirm that at least two antrum/incisura and two corpus fragments were examined in separate vials and review family history, metaplasia subtype and endoscopic extent.
2Treat H pylori after checking penicillin allergy and antibiotic exposure, then confirm eradication at least 4 weeks after antibiotics and after a 2-week PPI washout using a carbon-13 urea breath or validated stool-antigen test.
3Discuss the likely benefit of surveillance and the patient's preferences. Both-compartment OLGIM III disease, expected treatment fitness and no first-degree family-history modifier support a three-year interval; the patient agrees to recall. Extensive disease with an affected first-degree relative would prompt consideration of one- to two-year surveillance.
4Record treatment, eradication testing and the agreed three-year recall with ownership. Reassess fitness and benefit before the next examination rather than continuing automatic recall after major decline; the over-80 MAPS III advice concerns asymptomatic surveillance, not investigation of new alarm symptoms.

03Gastric ulcer reviewObtain tissue and prove healingA 2 cm gastric ulcer is seen during an admission, but active bleeding prevents safe biopsy.

1Document why tissue was not obtained and assess the appropriateness of cancer exclusion with the patient. When it remains appropriate, arrange repeat endoscopy within two weeks; age or comorbidity should inform that discussion rather than allow an unbiopsied ulcer to be assumed benign.
2At repeat endoscopy obtain at least six biopsies from edge and base, increasing to at least eight when malignant features are present, and test for H pylori.
3Treat ulcer disease and plan healing reassessment in the context of age, comorbidity, preferences and whether a result would change care. For an H pylori-positive gastric ulcer, NICE specifies 6–8 weeks after treatment begins; the BSG/JAG standard advises repeat within 12 weeks of diagnosis, with further biopsies when appropriate. This healing review does not replace the earlier repeat after omitted biopsy.
4Verify histology, H pylori result and complete healing; if cancer is found or healing fails, transfer promptly to the specialist cancer pathway.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

Combines acid suppression with two antibiotics to eradicate H pylori in the local protocol; choose another current local or national branch when allergy or previous antimicrobial exposure makes this combination unsuitable.

One current local first-line H pylori regimen: omeprazole, amoxicillin and metronidazole

For a confirmed infection in an adult weighing at least 40 kg with normal hepatic function, GFR above 30 mL/min, no penicillin allergy and no metronidazole use in the previous year, one March 2026 NHS Somerset example is omeprazole 20 mg orally twice daily, amoxicillin 1 g orally twice daily and metronidazole 400 mg orally twice daily for 7 days. With the cited omeprazole 10 mg gastro-resistant tablets, each 20 mg dose is two tablets; swallow whole without chewing or crushing.

Exclude penicillin/severe immediate beta-lactam hypersensitivity and nitroimidazole allergy. At GFR 10–30 mL/min the amoxicillin product limit is 500 mg twice daily; below 10 it is 500 mg daily. At GFR 30 or below, obtain an individually adjusted eradication regimen before prescribing rather than using this full-dose example. Hepatic impairment also requires an individual regimen/dose review: do not default to 20 mg omeprazole twice daily or full-dose metronidazole in severe disease. Omeprazole is contraindicated with nelfinavir; avoid combining it with clopidogrel and ask the prescriber/pharmacist to select a suitable acid-suppression alternative without stopping clopidogrel automatically. Take metronidazole with or after food, avoid alcohol during treatment and for 48 hours afterwards, and review warfarin/INR, lithium, methotrexate and other interactions. Check adherence and the eradication result when indicated before selecting treatment after failure.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Gastric outlet obstruction

Antral, pyloric or proximal small-bowel narrowing retains gastric contents, causing persistent vomiting, chloride and potassium loss, dehydration, aspiration and weight loss.

Tumour haemorrhage

Friable neoplastic vessels cause chronic occult iron loss or overt haematemesis and melaena, and major bleeding can compound anaemia and physiological instability.

Peritoneal carcinomatosis

Peritoneal surface spread produces ascites, multifocal intestinal obstruction, pain and nutritional decline and usually removes the option of curative gastrectomy.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track haemoglobin, iron status, weight, intake and vomiting while diagnosis proceeds.
Record the exact H pylori regimen, prior-antibiotic and allergy checks, adherence and appropriately timed eradication result.
Before recalling a person for precursor surveillance, review expected benefit, preferences and likely fitness for endoscopic treatment at that examination. Extensive/advanced disease usually has a three-year interval; extensive/advanced change plus a first-degree family history may justify one to two years. Consider three years for single-site metaplasia with family history, incomplete subtype or persistent H pylori. Otherwise low-risk antral-only disease needs no routine surveillance; MAPS III suggests stopping or not starting asymptomatic surveillance over 80. New symptoms are assessed on their own merits.
After gastrectomy, monitor nutrition, B12, iron, calcium, vitamin D and dumping symptoms.
Escalate new ascites, obstruction, bleeding or rapid functional decline without waiting for routine review.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Background mucosa matters

Cancer treatment addresses the lesion; mapping identifies the remaining field at risk.

CT cannot clear the peritoneum

Small serosal or peritoneal deposits are the reason staging laparoscopy remains important in potentially curable gastric cancer.

Linitis can evade forceps

Diffuse submucosal infiltration may need repeated targeted or deeper tissue when the stomach is rigid but surface biopsies are negative.

Eradication modifies future risk

Treating H pylori is useful in precursor disease but does not erase established extensive metaplasia.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every gastric erosion a benign explanation for iron deficiency.
02
Pooling mapping biopsies so anatomical extent cannot be reconstructed.
03
Proceeding to gastrectomy without staging laparoscopy in a potentially curable gastric cancer.
04
Stopping follow-up of a non-healing ulcer after one superficial benign biopsy set.

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