Special Surgery 8. Malignant Diseases of the Stomach: Symptoms, Diagnosis, Treatment

I. Types, Etiology and Pathology

Main Types

1. Adenocarcinoma
2. MALT lymphoma
3. Gastrointestinal stromal tumor (GIST)
4. Other: gastric neuroendocrine tumor

Gastric Adenocarcinoma

• Most common gastric malignancy: about 90-95%
• Often diagnosed late because early symptoms are nonspecific
• Origin: gastric glandular epithelium

Etiology / Risk Factors

• H. pylori infection → chronic gastritis → atrophy → intestinal metaplasia → dysplasia → carcinoma
• Gastric conditions: chronic atrophic gastritis, intestinal metaplasia, peptic ulcer on H. pylori background, adenomatous polyps
• Diet: nitrosamine-rich smoked/preserved food, excess salt, low fruit/vegetable intake
• Smoking, alcohol
• Previous gastric surgery, especially gastric stump cancer after Billroth II with long latency
• Genetic/familial: blood group A association, positive family history, CDH1 mutation, Lynch/FAP/Peutz-Jeghers syndromes

Lauren Subtypes

• Intestinal type: expansive growth, gland formation, better differentiated, linked to H. pylori/environmental factors, better prognosis
• Diffuse type: infiltrative growth, poorly differentiated, signet-ring cells, no gland formation, may cause linitis plastica, worse prognosis

MALT Lymphoma

• Mucosa-associated lymphoid tissue lymphoma
• Usually extranodal marginal zone B-cell non-Hodgkin lymphoma
• Often associated with chronic H. pylori infection
• Can occur at younger age than adenocarcinoma
• Better prognosis than gastric adenocarcinoma

GIST

• Gastrointestinal stromal tumor: malignant-potential mesenchymal tumor
• Derived from interstitial cells of Cajal
• Most common location: stomach
• Often KIT/CD117 or PDGFRA mutation
• Risk depends on size, mitotic index, site and tumor rupture

II. Symptoms, Spread and Staging

Clinical Features

• Early stage: often asymptomatic or nonspecific dyspepsia
• Epigastric discomfort/pain, bloating, nausea, early satiety
• Weight loss, anorexia, cachexia
• Persistent vomiting: antral/pyloric tumor → gastric outlet obstruction
• Dysphagia: cardia / gastroesophageal junction involvement
• Bleeding → hematemesis, melena, iron-deficiency anemia, weakness
• Palpable epigastric mass: advanced local disease

Metastatic and Paraneoplastic Signs

• Virchow node: left supraclavicular lymph node metastasis
• Sister Mary Joseph nodule: umbilical metastasis
• Krukenberg tumor: ovarian metastasis, often signet-ring carcinoma
• Blumer shelf: metastatic deposit palpable on rectal examination / pouch of Douglas
• Ascites, enlarged liver, jaundice: peritoneal or hepatic metastasis
• Paraneoplastic signs:

• Acanthosis nigricans
• Leser-Trelat sign: sudden diffuse seborrheic keratoses
• Trousseau syndrome: migratory thrombophlebitis

Routes of Spread

• Direct invasion: pancreas, transverse colon, liver, diaphragm, spleen
• Lymphatic: perigastric nodes, celiac nodes, Virchow node
• Hematogenous through portal vein: liver most common; also lung, bone, brain
• Peritoneal seeding: omentum/peritoneum, Douglas pouch, Krukenberg tumor, malignant ascites

TNM Staging of Gastric Adenocarcinoma

1. T: Tumor Depth

• Tis: carcinoma in situ / high-grade dysplasia
• T1a: lamina propria or muscularis mucosae
• T1b: submucosa
• T2: muscularis propria
• T3: subserosa
• T4a: serosa / visceral peritoneum
• T4b: adjacent organ invasion

2. N: Regional Lymph Nodes

• N0: no regional lymph node metastasis
• N1: 1-2 positive nodes
• N2: 3-6 positive nodes
• N3: 7 or more positive nodes

3. M: Distant Metastasis

• M0: no distant metastasis
• M1: distant metastasis
• Peritoneal metastasis or positive peritoneal cytology → metastatic disease in treatment planning

III. Diagnosis

Endoscopy and Histology

• Upper GI endoscopy / gastroscopy: gold standard
• Direct visualization + multiple biopsies from suspicious ulcer/mass
• Biopsy confirms tumor type, grade and histology
• Always biopsy gastric ulcers suspicious for malignancy
• Histology:

• Adenocarcinoma: intestinal vs diffuse/signet-ring features
• MALT lymphoma: immunohistochemistry and hematology classification
• GIST: KIT/CD117, DOG1, mutation testing when needed

Staging Investigations

• CT chest/abdomen/pelvis: local spread, lymph nodes, liver/lung metastasis, ascites/peritoneal disease if visible
• EUS: tumor depth and perigastric nodes; useful especially for early tumors/endoscopic resection decision
• PET-CT: selected cases for distant metastasis; diffuse/signet-ring tumors may be less FDG-avid
• Staging laparoscopy: detects occult peritoneal metastasis before curative surgery in locally advanced disease
• Peritoneal lavage cytology may be taken during staging laparoscopy
• Upper GI barium series: less used; can show filling defect, ulcerated mass, linitis plastica or obstruction, but cannot biopsy

Laboratory Tests and Biomarkers

• CBC: iron-deficiency anemia / bleeding
• Electrolytes, renal function: vomiting, dehydration, preoperative risk
• Liver function tests: liver metastasis or biliary obstruction
• Albumin/nutritional assessment: operative risk and prehabilitation need
• CEA and CA 19-9: not diagnostic; useful for follow-up if elevated initially
• Advanced adenocarcinoma biomarkers: HER2, PD-L1, MSI/MMR, sometimes CLDN18.2 depending on local protocol

IV. Treatment

Adenocarcinoma: General Principles

• Treatment depends on stage, location, histology, biomarkers and patient fitness
• Onco-team decision: surgery + oncology + radiology + pathology + gastroenterology + dietetics
• Only curative options: complete endoscopic resection in selected early cancer or R0 gastrectomy with lymphadenectomy
• Distant metastasis/peritoneal dissemination → usually palliative systemic treatment

Early Gastric Cancer

• Tis / selected T1a mucosal cancer → endoscopic resection if lymph node metastasis risk is very low
• EMR: endoscopic mucosal resection
• ESD: endoscopic submucosal dissection, allows en bloc resection of larger superficial lesions
• Gastrectomy if T1b submucosal invasion, poor differentiation, lymphovascular invasion, positive margin or nodal suspicion

Resectable Adenocarcinoma

• T2 or higher and/or N+ locally advanced disease → perioperative/neoadjuvant chemotherapy in fit patients
• Common European regimen: FLOT-type chemotherapy
• Sequence: staging → staging laparoscopy when indicated → neoadjuvant chemotherapy → restaging → radical gastrectomy + lymphadenectomy → postoperative chemotherapy if fit
• D2 lymphadenectomy: standard in experienced gastric cancer surgery
• Adjuvant chemotherapy/chemoradiotherapy: if perioperative therapy was not given, margins positive, lymphadenectomy inadequate or local protocol indicates

Surgical Procedures

1. Distal / Subtotal Gastrectomy

• For antral, pyloric or distal body tumor if adequate proximal margin is possible
• Reconstruction:

• Billroth I: gastroduodenostomy
• Billroth II: gastrojejunostomy
• Roux-en-Y gastrojejunostomy

2. Total Gastrectomy

• For proximal, diffuse, poorly differentiated, multicentric or extensive tumors
• Reconstruction: Roux-en-Y esophagojejunostomy
• Needs lifelong vitamin B12 replacement and nutritional follow-up

3. Lymphadenectomy

• D1: perigastric nodes
• D2: perigastric + named arterial station nodes along left gastric, common hepatic, celiac and splenic artery regions
• Splenectomy/pancreatectomy only if directly invaded, not routine

T4 / Unresectable / Palliative Disease

• T4a serosal invasion can still be resectable if R0 is possible and no metastasis
• T4b adjacent organ invasion: multivisceral resection only in selected fit patients if R0 possible
• Unresectable/metastatic disease → systemic chemotherapy ± targeted/immunotherapy
• HER2-positive advanced adenocarcinoma → trastuzumab with chemotherapy if appropriate
• Obstruction palliation: endoscopic stent, gastrojejunostomy bypass, feeding jejunostomy/nutritional support
• Bleeding palliation: endoscopic hemostasis, radiotherapy, embolization or selected palliative surgery
• Palliative gastrectomy is not routine; reserve for uncontrolled bleeding, perforation or obstruction in selected patients

MALT Lymphoma Treatment

• Localized low-grade H. pylori-positive disease → H. pylori eradication first-line
• Regression can take months → follow with repeat endoscopy/biopsy
• Persistent localized disease or H. pylori-negative selected cases → radiotherapy
• Disseminated/high-grade transformation → systemic immunochemotherapy
• Surgery is rare; mainly for complications not controlled otherwise

GIST Treatment

• Localized resectable GIST → complete surgical resection without tumor rupture
• Usually wedge/local gastric resection is enough
• Formal lymphadenectomy is not routine because nodal spread is rare
• Imatinib: neoadjuvant for selected large/borderline tumors, adjuvant for high-risk tumors, systemic treatment for metastatic/unresectable GIST

Prognosis

• Depends mainly on stage at diagnosis
• Early gastric cancer: excellent prognosis after complete treatment, often >90% 5-year survival
• Advanced/metastatic adenocarcinoma: poor prognosis, often diagnosed late
• Bad prognostic factors: diffuse/signet-ring type, positive nodes, positive margin, peritoneal spread, poor fitness/malnutrition
• MALT lymphoma usually has better prognosis than adenocarcinoma
• GIST prognosis depends on size, mitotic index, site, rupture and mutation