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

I. Types, Etiology and Pathology

Main Types

Adenocarcinoma
Gastric lymphoma, especially MALT lymphoma
Gastrointestinal stromal tumor (GIST)
Neuroendocrine tumor

1. Gastric Adenocarcinoma

Most common malignant tumor of the stomach, about 90-95%
Arises from gastric glandular epithelium
Often diagnosed late because early symptoms are nonspecific

Risk Factors

H. pylori infection
Chronic atrophic gastritis
Intestinal metaplasia and dysplasia
Gastric ulcer on background of H. pylori gastritis
Adenomatous gastric polyps
Diet:

Nitrosamine-rich smoked/preserved food
High salt intake
Low fresh fruit/vegetable intake

Smoking
Obesity, especially cardia cancer
Previous gastric surgery, especially Billroth II stump carcinoma after long latency
Genetic/familial factors:

Positive family history
Blood group A association in classical teaching
CDH1 mutation → hereditary diffuse gastric cancer
Lynch syndrome, FAP, Peutz-Jeghers syndrome

Lauren Classification

Subtype	Features	Prognosis
Intestinal type	Expansive growth, gland formation, better differentiated, linked to H. pylori / atrophy / intestinal metaplasia and environmental factors	Better than diffuse type
Diffuse type	Infiltrative growth, poorly differentiated, signet ring cells, no gland formation, can cause linitis plastica	Worse; earlier spread, difficult margin assessment

2. MALT Lymphoma

Mucosa-associated lymphoid tissue lymphoma
Usually extranodal marginal zone B-cell non-Hodgkin lymphoma
Strongly associated with chronic H. pylori infection
Can occur at younger age than adenocarcinoma
Often better prognosis than gastric adenocarcinoma
Early low-grade disease may regress after H. pylori eradication

3. GIST

Gastrointestinal stromal tumor
Mesenchymal tumor derived from interstitial cells of Cajal
Most common site: stomach
Often KIT (CD117) or PDGFRA mutation
Malignant potential depends mainly on size, mitotic index, site and rupture
Can present as submucosal mass, bleeding or rupture

4. Gastric Neuroendocrine Tumors

Arise from neuroendocrine cells
May be associated with chronic atrophic gastritis and hypergastrinemia
Can be small/multiple and indolent or sporadic/aggressive depending on type
Treatment depends on size, invasion depth, grade and metastasis

II. Symptoms, Spread and Staging

Clinical Features

Early Disease

Often asymptomatic
Nonspecific dyspepsia
Epigastric discomfort or pain
Bloating, early satiety
Mild nausea
Mild weight loss

Advanced Disease

Significant weight loss, anorexia, cachexia
Persistent epigastric pain
Nausea and vomiting
Persistent vomiting → pyloric/antral obstruction
Dysphagia → cardia / gastroesophageal junction involvement
Bleeding:

Hematemesis
Melena
Iron-deficiency anemia
Weakness, fatigue

Palpable epigastric mass in advanced local disease
Ascites, jaundice or hepatomegaly in metastatic disease

Metastatic Signs

Virchow node: left supraclavicular lymph node metastasis
Sister Mary Joseph nodule: umbilical metastasis
Krukenberg tumor: ovarian metastasis, usually bilateral signet-ring metastasis
Blumer shelf: metastatic deposit palpable on rectal examination / pouch of Douglas
Ascites from peritoneal carcinomatosis
Enlarged liver from hepatic metastases

Routes of Spread

Direct local invasion: pancreas, transverse colon, liver, diaphragm, spleen
Lymphatic spread:

Perigastric lymph nodes
Celiac axis nodes
Virchow node in advanced disease

Hematogenous spread through portal circulation:

Liver most common
Lung, bone, brain can occur

Peritoneal seeding:

Omentum, peritoneum, pouch of Douglas
Krukenberg tumor
Malignant ascites

Paraneoplastic Signs

Acanthosis nigricans
Leser-Trelat sign: sudden seborrheic keratoses
Trousseau syndrome: migratory thrombophlebitis
Microangiopathic hemolytic anemia can occur rarely

TNM Staging of Gastric Adenocarcinoma

1. T: Tumor Depth

Tis: carcinoma in situ / high-grade dysplasia
T1: lamina propria, muscularis mucosae or submucosa

T1a: lamina propria or muscularis mucosae
T1b: submucosa

T2: muscularis propria
T3: subserosa
T4a: serosa / visceral peritoneum
T4b: adjacent organs or structures

2. N: Regional Lymph Nodes

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

3. M: Distant Metastasis

M0: no distant metastasis
M1: distant metastasis
Peritoneal metastasis / positive peritoneal cytology counts as metastatic disease in practical oncological decision-making

III. Diagnosis

Upper GI Endoscopy / Gastroscopy

Gold standard diagnostic test
Direct visualization of tumor
Biopsy confirms histology and grade
Multiple biopsies from suspicious ulcer or mass
Describes exact location: cardia, fundus, body, antrum, pylorus, lesser/greater curvature
Assesses bleeding, obstruction and synchronous lesions

Histopathology and Biomarkers

Confirms tumor type:

Adenocarcinoma: intestinal vs diffuse/signet ring features
Lymphoma: immunohistochemistry and hematology classification
GIST: KIT/CD117, DOG1, mutation testing when needed
Neuroendocrine tumor: grade, Ki-67 index, synaptophysin/chromogranin

For advanced adenocarcinoma, treatment biomarkers can include:

HER2
PD-L1
MSI/MMR status
CLDN18.2 where available/local protocol uses it

Imaging and Staging

CT chest, abdomen and pelvis:

Local extension, lymph nodes, liver/lung metastases
Ascites, peritoneal disease if visible
Relation to adjacent organs

Endoscopic ultrasound (EUS):

Useful for early tumors when endoscopic treatment is considered
Assesses depth of invasion and perigastric nodes
Less useful if stenotic bulky tumor prevents passage

PET-CT:

Can detect distant metastasis in selected cases
Diffuse/signet-ring tumors may be less FDG-avid

Staging laparoscopy:

Important before curative surgery in locally advanced gastric cancer
Detects occult peritoneal metastasis not seen on CT
Peritoneal washing cytology can be taken

Upper GI contrast series:

Less used today
Can show linitis plastica, filling defect, ulcerated mass or obstruction
Cannot replace biopsy

Laboratory Tests

CBC: iron-deficiency anemia, bleeding
Electrolytes and renal function: vomiting/dehydration, preoperative risk
Liver function tests: liver metastasis or biliary obstruction
Albumin/nutritional markers: operative risk
Tumor markers:

CEA and CA 19-9 are not diagnostic
Can help follow selected patients if elevated at baseline

Preoperative Assessment

Performance status and frailty
Nutritional assessment and prehabilitation
Cardiopulmonary fitness for gastrectomy
Onco-team decision: surgeon, oncologist, radiotherapist, gastroenterologist, radiologist, pathologist, dietitian
Separate operability of patient from resectability of tumor

IV. Treatment

Gastric Adenocarcinoma: General Principles

Treatment depends on tumor stage, location, histology, biomarkers and patient fitness
Only curative treatment is complete R0 resection or curative endoscopic resection in selected early cancers
Most locally advanced tumors need multimodal treatment
Distant metastasis or peritoneal dissemination usually means palliative systemic therapy

1. Early Gastric Cancer

Early gastric cancer = tumor limited to mucosa/submucosa regardless of lymph node status
Endoscopic treatment possible only when lymph node metastasis risk is very low
Endoscopic mucosal resection (EMR)
Endoscopic submucosal dissection (ESD)
Typical criteria:

Tis or T1a mucosal lesion
Differentiated histology
Small size and no ulceration in strict classical criteria
No lymphovascular invasion
En bloc complete resection possible

Gastrectomy if submucosal invasion, poor differentiation, lymphovascular invasion, positive deep margin or nodal suspicion

2. Resectable Locally Advanced Adenocarcinoma

Usually T2 or higher and/or node-positive disease
European-style standard for fit patients: perioperative chemotherapy, commonly FLOT-type regimen
Sequence:

Diagnosis and staging
Staging laparoscopy if indicated
Neoadjuvant/perioperative chemotherapy
Restaging
Radical gastrectomy + lymphadenectomy
Postoperative chemotherapy if patient recovers and protocol allows

Adjuvant chemotherapy or chemoradiotherapy can be used when perioperative therapy was not given, lymphadenectomy was inadequate, margins are positive or local protocol indicates

3. Surgical Procedures

Distal / Subtotal Gastrectomy

For antral, pyloric and distal body tumors when adequate proximal margin is possible
Removes distal stomach + omentum + regional lymph nodes
Reconstruction:

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

Total Gastrectomy

For proximal, diffuse, multicentric or extensive tumors
Required for linitis plastica / diffuse involvement
Reconstruction: Roux-en-Y esophagojejunostomy
Requires lifelong vitamin B12 replacement and nutritional follow-up

Proximal Gastrectomy

Selected proximal tumors in specialized practice
Higher reflux risk than total gastrectomy depending on reconstruction
Not used for diffuse or extensive disease

Lymphadenectomy

D1: perigastric nodes only
D2: perigastric + named arterial station nodes along left gastric, common hepatic, celiac and splenic artery regions
D2 lymphadenectomy is standard in experienced high-volume gastric cancer surgery
Splenectomy/pancreatectomy not routine unless directly invaded
Goal: R0 resection + adequate nodal staging/clearance

4. T4 / Borderline or Unresectable Local Disease

T4a serosal invasion can still be resectable if no metastasis and R0 is possible
T4b adjacent organ invasion may need multivisceral resection in selected fit patients if R0 possible
Unresectable if major vascular invasion, diffuse peritoneal disease, distant metastasis or impossible R0 resection
Conversion surgery after systemic therapy can be considered only in highly selected responders

5. Metastatic / Palliative Treatment

Goals: symptom control, nutrition, bleeding/obstruction relief, prolong survival
Systemic therapy:

Platinum/fluoropyrimidine-based chemotherapy backbone
Trastuzumab for HER2-positive advanced adenocarcinoma
Immunotherapy depending on PD-L1/MSI/MMR status and local protocol
Other targeted therapy based on biomarkers where available

Obstruction palliation:

Endoscopic stent for selected outlet/cardia obstruction
Gastrojejunostomy bypass for distal obstruction if expected survival and fitness justify
Feeding jejunostomy or nutritional support when oral intake is inadequate

Bleeding palliation:

Endoscopic hemostasis if possible
Radiotherapy for tumor bleeding
Angioembolization or palliative surgery in selected severe cases

Palliative gastrectomy is not routine; consider only for uncontrolled bleeding/perforation/obstruction in selected patients

MALT Lymphoma Treatment

Stage and histology by endoscopy/biopsy, CT and hematology workup
H. pylori eradication is first-line for localized low-grade H. pylori-positive MALT lymphoma
Regression can take months; follow with repeat endoscopy/biopsy
Radiotherapy for persistent localized disease or H. pylori-negative selected cases
Systemic immunochemotherapy for disseminated/high-grade transformation
Surgery is rarely used, mainly for complications such as bleeding/perforation not otherwise controlled

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
Do not rupture tumor capsule → peritoneal recurrence risk
Imatinib:

Neoadjuvant for large/borderline resectable tumors to reduce morbidity
Adjuvant for high-risk tumors depending on mutation and risk
Systemic treatment for metastatic/unresectable GIST

Prognosis

Depends mainly on stage at diagnosis
Early gastric cancer has excellent prognosis if completely treated
Advanced/metastatic gastric adenocarcinoma has poor prognosis
Diffuse/signet-ring type, positive nodes, positive margins and peritoneal spread worsen prognosis
MALT lymphoma usually has better prognosis than adenocarcinoma
GIST prognosis depends on size, mitotic index, site, rupture and mutation