Gastric cancer

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

Gastric adenocarcinoma is commonly divided into intestinal and diffuse patterns. Intestinal-type cancer often follows H pylori-related atrophy, metaplasia and dysplasia and forms a focal glandular lesion. Diffuse signet-ring cancer infiltrates through the wall because cell adhesion is lost, producing a rigid non-distensible stomach and early peritoneal spread. Proximal and junctional tumours share aspects of oesophageal adenocarcinoma; precise epicentre classification determines staging and treatment protocol.

Endoscopy provides diagnosis and must describe location, size, ulceration and obstruction. Multiple biopsies reduce sampling error, but linitis may spare superficial epithelium, requiring deeper, EUS-guided or laparoscopic tissue. CT assesses distant and nodal burden. EUS is most valuable when T depth changes endoscopic versus surgical treatment. PET-CT is less reliable in diffuse and mucinous cancer. Staging laparoscopy detects small peritoneal implants and positive washings that prevent a non-beneficial gastrectomy.

Curative treatment ranges from endoscopic submucosal dissection for strictly favourable intramucosal disease to perioperative systemic treatment and gastrectomy for more advanced cancer. Distal tumours may permit subtotal resection, preserving more reservoir; proximal or diffuse disease often needs total gastrectomy. D2 lymphadenectomy removes defined perigastric and arterial nodal stations in experienced hands. Pathology reports margins, depth, nodes, regression, lymphovascular and perineural invasion and biomarkers.

Advanced treatment combines fluoropyrimidine and platinum-based therapy with HER2-directed or immune treatment when criteria are met. Local interventions treat bleeding and obstruction. Nutrition remains an oncological intervention: prehabilitation improves treatment fitness, and after gastrectomy patients need small energy-dense meals, dietetic follow-up and lifelong replacement monitoring. Refeeding risk, dumping, pancreatic insufficiency, bacterial overgrowth and recurrence can all cause weight loss and should not be collapsed into poor appetite.

Key points

Gastric adenocarcinoma often presents late with weight loss, epigastric discomfort, early satiety, anaemia or vomiting; a normal abdominal examination does not exclude it.
First-line diagnosis is high-quality upper-GI endoscopy with at least six biopsies from a suspicious lesion and separate mapping when premalignant background or linitis is considered.
Repeat deeper or bite-on-bite sampling, EUS-guided core or laparoscopic tissue when diffuse infiltrative cancer is suspected despite superficial non-diagnostic biopsies.
Contrast CT chest, abdomen and pelvis is the first staging overview. Use EUS for selected local staging, PET-CT selectively because diffuse and mucinous disease may be non-avid, and laparoscopy for occult peritoneal spread before radical treatment.
Staging laparoscopy with peritoneal cytology is a key reference step for potentially curable locally advanced gastric or junctional adenocarcinoma at peritoneal risk.
Very early low-risk mucosal cancer can be treated by expert endoscopic submucosal dissection when pathological criteria for negligible nodal risk are met.
Resectable disease usually receives perioperative chemotherapy and subtotal or total gastrectomy with an oncological D2 lymphadenectomy in a specialist centre.
Do not equate D2 lymphadenectomy with routine removal of pancreas and spleen; preserve uninvolved organs to reduce morbidity.
Advanced disease treatment depends on performance, HER2, PD-L1 and mismatch-repair or microsatellite status, prior treatment and the current funded indication.
Outlet obstruction can be relieved by endoscopic stent or gastrojejunostomy according to fitness, anatomy and expected duration; nutrition and aspiration control begin immediately.
After total gastrectomy, lifelong vitamin B12 replacement is required, with continuing iron, folate, calcium, vitamin D, bone and weight surveillance.
Dumping improves with small frequent meals, separating drinks from meals and reducing rapidly absorbed carbohydrate; severe symptoms require specialist dietary and medical treatment.
Eradicate H pylori when present and offer surveillance for appropriately staged extensive atrophy, metaplasia or hereditary risk through the dedicated premalignant pathway.

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

Helicobacter pylori inflammation

Chronic H pylori gastritis can progress through atrophy, intestinal metaplasia and dysplasia to intestinal-type adenocarcinoma, with risk modified by strain, host and environment.

Autoimmune and premalignant stomach

Autoimmune atrophic gastritis, pernicious anaemia, extensive metaplasia, adenomatous polyps and previous partial gastrectomy increase adenocarcinoma or neuroendocrine tumour risk.

Dietary and behavioural exposure

Smoking, high salt intake and preserved or smoked foods increase risk, while fresh produce and H pylori prevention reduce part of the population burden.

Inherited and viral susceptibility

Germline CDH1 causes hereditary diffuse gastric cancer, while Lynch, FAP, GAPPS and EBV-associated tumour biology define smaller clinically important groups.

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

1
Intestinal sequence follows metaplasia
Longstanding inflammation causes gland loss, intestinalisation, dysplasia and a cohesive gland-forming carcinoma that often produces a focal ulcer or mass.
2
Diffuse cancer loses cell adhesion
E-cadherin dysfunction permits discohesive signet-ring cells to infiltrate widely through the wall, creating stiffness and linitis without a discrete mucosal mass.
3
Regional spread follows gastric drainage
Submucosal and lymphatic invasion reaches perigastric and coeliac nodal stations, making an adequate D2 lymphadenectomy important for staging and local control.
4
Peritoneal dissemination can be occult
Serosal penetration sheds cells across peritoneum and ovaries, so small-volume metastasis or positive washings may be invisible on CT and PET.
5
Resection changes digestion permanently
Loss of reservoir, pyloric control, acid and intrinsic factor causes early satiety, dumping, malabsorption and B12, iron, calcium and vitamin-D problems after gastrectomy.

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

Early non-specific disease

Persistent dyspepsia, epigastric discomfort, appetite change or iron deficiency may be the only clue and needs age- and alarm-based endoscopy.

Outlet pattern

Early satiety, postprandial fullness, non-bilious vomiting, weight loss and succussion splash suggests distal gastric narrowing and retention.

Linitis plastica

Poor gastric distension, wall thickening, rapid satiety and diffuse signet-ring histology suggests infiltrative disease often under-sampled by mucosal biopsy.

Metastatic signs

Left supraclavicular node, umbilical nodule, ascites, hepatomegaly or ovarian mass indicates lymphatic, haematogenous or transcoelomic spread.

Major haemorrhage or perforationRed flag

Shock, haematemesis, melaena or a rigid peritonitic abdomen requires immediate resuscitation and endoscopic or surgical source control.

Post-gastrectomy syndrome

Postprandial cramps, palpitations, diarrhoea or later hypoglycaemia suggests early or late dumping rather than cancer recurrence alone.

Red flags requiring action

Unintentional weight loss with upper abdominal pain, reflux, dyspepsia or nausea requires urgent upper-GI cancer assessment under the age- and feature-specific pathway.
Progressive early satiety, recurrent vomiting, succussion splash or dehydration suggests malignant gastric outlet obstruction.
Melaena, haematemesis, iron-deficiency anaemia, syncope or haemodynamic change indicates overt or occult tumour bleeding.
A rigid abdomen, severe sudden epigastric pain, fever or free air suggests perforation and needs immediate surgical care.
Virchow node, umbilical nodule, ascites, pelvic mass or peritoneal thickening suggests disseminated lymphatic or transcoelomic disease.
Rapidly progressive diffuse wall thickening with poor distension can be linitis plastica despite repeated superficial negative biopsies.

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
First-line upper-GI endoscopy with multiple biopsiesFirst stepFirst line
Why
Visualise and localise tumour, assess obstruction and obtain sufficient tissue for histology and biomarkers.
Interpretation and limitations
Take at least six targeted samples from a suspicious lesion, document distance and anatomy and repeat with deeper methods when linitis or lymphoma remains plausible.
02
First-line contrast CT chest abdomen and pelvisFirst line
Why
Stage gastric wall relationships, regional nodes, liver, lung, peritoneum and other distant disease and identify biopsy sites.
Interpretation and limitations
A CT without visible peritoneal disease does not exclude small implants or malignant washings in a locally advanced diffuse or serosal tumour.
03
Selective EUS and PET-CT
Why
Resolve depth and nodes for early-treatment selection and identify additional metabolically active disease when histology is likely avid.
Interpretation and limitations
EUS is useful for T1 versus deeper disease; PET can be falsely negative in diffuse, signet-ring and mucinous cancer and should not replace laparoscopy.
04
Reference staging laparoscopy and cytology
Why
Detect occult peritoneal implants and free malignant cells before perioperative treatment or radical gastrectomy.
Interpretation and limitations
Positive implants or cytology indicate metastatic biology even when CT is negative and usually change intent away from immediate curative resection.
05
Advanced-disease biomarker panel
Why
Select HER2-directed and immune therapy and identify inherited mismatch-repair implications where appropriate.
Interpretation and limitations
Use validated HER2 scoring, PD-L1 combined positive score and MMR or MSI testing; account for heterogeneity and obtain adequate viable tumour.
06
Nutrition and deficiency assessment
Why
Quantify pre-treatment sarcopenia and post-resection micronutrient, dumping and malabsorptive problems.
Interpretation and limitations
Track weight and intake plus FBC, ferritin, B12, folate, calcium, vitamin D and bone health; investigate steatorrhoea and hypoglycaemic symptoms specifically.

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

Benign peptic ulcer

H pylori and NSAIDs cause ulceration and bleeding, but every suspicious gastric ulcer requires adequate biopsy and documented healing because malignant ulcers can look benign.

Gastric lymphoma

MALT and diffuse large B-cell lymphoma can cause thickening, ulcer or mass and need deep biopsies, immunophenotyping and a haematological rather than gastrectomy-first pathway.

Gastrointestinal stromal tumour

A subepithelial muscularis-propria mass may ulcerate and bleed; EUS-guided tissue and KIT or DOG1 pathology distinguish it from epithelial adenocarcinoma.

Pancreatic or extrinsic disease

Pancreatic, duodenal, biliary, ovarian and nodal malignancy can compress outlet or invade stomach and requires cross-sectional imaging and lineage-specific tissue.

Functional or benign obstruction

Gastroparesis, bezoar, peptic stenosis and postsurgical dysmotility cause retention and vomiting without malignant histology, though endoscopy still excludes a structural lesion.

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

01Suspected cancerEndoscope and biopsy without delayFirst stepAlarm dyspepsia, weight loss, anaemia, vomiting, early satiety or bleeding suggests a gastric lesion.

1Assess bleeding, obstruction, perforation, hydration, aspiration and nutrition and stabilise emergencies before or alongside urgent endoscopy.
2Perform a complete high-quality examination with multiple targeted biopsies and obtain deeper or image-guided tissue if diffuse infiltration, lymphoma or subepithelial tumour remains possible.
3Complete CT staging, pathology and dietetic assessment and refer to the specialist oesophago-gastric MDT rather than arranging isolated surgery from endoscopic appearance.

02Curative stagingLook for invisible peritoneal diseaseHistology confirms adenocarcinoma and CT shows no definite distant spread or unresectability.

1Use EUS for an early local-depth decision and selective PET-CT for additional disease according to histology and junctional anatomy.
2Perform staging laparoscopy with washings in a locally advanced, diffuse, signet-ring, serosal or otherwise peritoneal-risk tumour before committing to radical resection.
3Assess cardiopulmonary, frailty, nutrition and patient goals and choose endoscopic resection, perioperative chemotherapy with gastrectomy or another curative protocol in the MDT.

03Resectable diseaseCombine perioperative therapy and oncological surgeryStaging confirms resectable non-metastatic disease suitable for major treatment.

1Deliver the agreed preoperative systemic cycles with response, marrow, neuropathy, nutrition and organ monitoring and reassess resectability before operation.
2Perform subtotal or total gastrectomy with adequate margins and pancreas- and spleen-preserving D2 lymphadenectomy unless direct involvement requires additional resection.
3Review pathological stage and response and resume postoperative therapy when recovery permits, while starting lifelong nutritional and B12 planning after total gastrectomy.

04Advanced diseaseMatch systemic treatment to biomarkers and goalsPeritoneal, distant or unresectable disease is confirmed or radical treatment is unsuitable.

1Review performance, symptoms, organ function, HER2, PD-L1 and MMR or MSI and prior treatment and select the current funded systemic combination.
2Control bleeding with endoscopy, radiotherapy or embolisation and obstruction with stent or bypass according to expected durability, surgical fitness and anatomy.
3PreferredReassess early for clinical benefit and toxicity and integrate nutrition, analgesia, ascites, antiemesis, palliative care and preferred-place discussions from diagnosis.

05After gastrectomyReplace nutrients and retrain intakeSubtotal or total gastrectomy has changed reservoir, transit and absorption.

1Use small frequent energy- and protein-dense meals, separate most fluids from food and involve an upper-GI dietitian before severe weight loss develops.
2Provide lifelong intramuscular B12 after total gastrectomy and monitor iron, folate, calcium, vitamin D, bone, weight and symptoms at defined intervals.
3Investigate persistent diarrhoea, steatorrhoea, vomiting or hypoglycaemia for dumping, pancreatic insufficiency, bacterial overgrowth, stricture and recurrence and treat the specific mechanism.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Reduces micrometastatic relapse and improves outcomes around gastrectomy in fit patients with suitable resectable gastric or junctional adenocarcinoma.

FLOT perioperative chemotherapy

Every 2 weeks, a specialist FLOT cycle commonly uses intravenous docetaxel 50 mg/m², oxaliplatin 85 mg/m² and leucovorin 200 mg/m² followed by fluorouracil 2,600 mg/m² over 24 hours, usually for four preoperative and four postoperative cycles.

Confirm DPD status and monitor blood counts, sepsis, mucositis, diarrhoea, neuropathy, thrombosis, nutrition and renal and hepatic function; postoperative complications may require delay, reduction or omission.

Targets amplified or overexpressed HER2 in eligible advanced gastric or gastro-oesophageal-junction adenocarcinoma.

Trastuzumab for HER2-positive advanced adenocarcinoma

A standard three-weekly intravenous schedule uses trastuzumab 8 mg/kg as a loading dose then 6 mg/kg every 3 weeks with the selected fluoropyrimidine and platinum regimen under the licensed indication.

Confirm gastric-specific HER2 scoring and monitor left-ventricular function, infusion reactions and pregnancy; heterogeneity can produce false-negative small biopsies and treatment should follow current funding criteria.

Replaces vitamin B12 when loss of parietal cells and intrinsic factor prevents adequate absorption after total gastrectomy.

Hydroxocobalamin after total gastrectomy

Give hydroxocobalamin 1 mg intramuscularly every 2 to 3 months lifelong after the initial replacement course, using more frequent neurological loading if a symptomatic deficiency is present.

Check the complete anaemia and neurological differential, including iron and folate, and do not give folate alone before excluding B12 deficiency because neurological injury may progress.

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

Bleeding and perforation

Ulcerated tumour causes chronic anaemia or major haemorrhage, while transmural necrosis can perforate and produce peritonitis and sepsis.

Outlet obstruction and aspiration

Antral or pyloric narrowing causes retained food, vomiting, hypochloraemic alkalosis, dehydration, aspiration and inability to tolerate systemic treatment.

Peritoneal and metastatic disease

Ascites, bowel obstruction, ovarian Krukenberg deposits, liver metastases and distant nodes produce pain, jaundice, malnutrition and loss of function.

Post-gastrectomy syndromes

Anastomotic leak, dumping, bile reflux, small-stomach intake, weight loss and micronutrient deficiencies require lifelong nutritional surveillance.

Treatment-related organ toxicity

Perioperative and advanced regimens cause marrow suppression, infection, neuropathy, diarrhoea, mucositis, thrombosis, cardiac dysfunction and immune-mediated disease.

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

During perioperative treatment, review blood counts, organ function, neuropathy, infection, thrombosis, weight, muscle and ability to proceed to surgery rather than completing cycles automatically.
After gastrectomy, monitor leak, bleeding, chest infection, anastomotic function and intake early and weight, dumping, reflux and micronutrients long term.
Measure FBC, ferritin, B12, folate, calcium, vitamin D and renal and liver function on a planned schedule and use DEXA according to bone risk.
During HER2 or immune treatment, monitor cardiac or organ-specific immune toxicity and investigate new respiratory, bowel, endocrine, renal, skin or neurological symptoms promptly.
Use interval CT and symptom review for advanced treatment, distinguishing ascites, obstruction and nutritional decline from stable measurable target lesions.
After endoscopic resection, follow the pathology-defined scar and background-mucosa surveillance plan and eradicate H pylori with proof of clearance.
Provide rapid access for recurrent vomiting, bleeding, dysphagia, peritonitic pain, jaundice or new nodal and abdominal findings.

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

Linitis can hide beneath mucosa

Diffuse signet-ring infiltration may leave superficial epithelium deceptively bland, requiring deep sampling or laparoscopic confirmation when the stomach is rigid.

CT cannot clear the peritoneum

Small implants and free malignant cells lie below cross-sectional resolution, which is why laparoscopy prevents some futile gastrectomies.

D2 does not mean routine organ sacrifice

Modern oncological lymphadenectomy removes defined nodal stations while preserving uninvolved spleen and pancreas to reduce operative morbidity.

A gastric ulcer needs closure

Adequate biopsy and documented healing are necessary because symptom improvement with acid suppression does not exclude ulcerated malignancy.

Weight loss has multiple mechanisms

Small reservoir, dumping, pancreatic insufficiency, stricture, depression and recurrence require different treatment and should not be labelled cachexia without assessment.

B12 replacement is lifelong

After total gastrectomy oral dietary B12 cannot overcome loss of intrinsic-factor physiology reliably, so scheduled parenteral replacement must survive transitions of care.

11Common pitfallsFrequent interpretation and management errors.

01
Treating alarm dyspepsia or iron-deficiency anaemia repeatedly without endoscopy.
02
Accepting superficial negative biopsies when linitis plastica remains clinically and radiologically likely.
03
Assuming a negative CT excludes peritoneal metastasis before radical gastrectomy.
04
Using PET-CT as the decisive exclusion test for diffuse or signet-ring cancer.
05
Removing spleen or pancreas routinely as a misunderstood component of D2 surgery.
06
Starting perioperative chemotherapy without nutrition, DPD and organ-fitness assessment.
07
Calling all postoperative weight loss cancer cachexia and missing dumping, stricture or pancreatic insufficiency.
08
Failing to prescribe lifelong B12 and defined iron, calcium, vitamin-D and bone monitoring after total gastrectomy.
09
Selecting HER2 or immune treatment from an outdated or inadequate specimen without validated biomarker review.