Gastric cancer / dumping syndrome / carcinoid syndrome

Background

• Gastric cancer is a malignancy arising from the stomach
• Gastric adenocarcinoma is the most common type of gastric cancer (90%)
• This condition can be divided into intestinal and diffuse gastric cancer types
• Intestinal gastric tumors are bulky and have glandular structures (most commonly found on the lesser curvature of the stomach)
• Diffuse gastric tumors are infiltration tumors and are composed of signet ring cells (stiffening of the gastric wall; also called linitis plastica is also found)

Version 2

Definition: Gastric cancer is a malignant neoplasm arising from the epithelial cells of the stomach lining.

Epidemiology:

• ★ Most common type: Gastric adenocarcinoma (90-95% of all gastric cancers)
• Incidence: ~1 million new cases annually worldwide
• ★ Most common location: Eastern Asia (Japan, Korea, China) and Eastern Europe
• ★ Most common age: 60-70 years (median age at diagnosis: 68 years)
• ★ Gender predilection: Male:Female ratio = 2:1
• ★ Most common site in stomach: Lesser curvature (40%), followed by cardia (35%)

Pathophysiology:

• Chronic inflammation → intestinal metaplasia → dysplasia → carcinoma (Correa cascade)
• Two main histologic types per Lauren classification:
  • Intestinal type (54%): Well-differentiated, glandular structures, better prognosis
  • Diffuse type (32%): Poorly differentiated, signet ring cells, worse prognosis

TYPES/CLASSIFICATION - was not included in the first version

Risk factor

• Gastric cancer is more common in Japan and Eastern Europe
• Helicobacter pylori (results in chronic gastritis secondary to increased production of proinflammatory proteins)
• Epstein-Barr virus (a rare cause of gastric adenocarcinoma)
• Nitrosamine exposure
• High salt intake
• Smoking tobacco
• Excessive alcohol use

Version 2

Major Risk Factors:

• Infectious:
  • H. pylori (★ most important modifiable risk factor)
  • Epstein-Barr virus (10% of gastric cancers)
• Dietary:
  • High salt intake
  • Smoked/preserved foods (nitrosamines)
  • Low fruit and vegetable intake
• Environmental:
  • Tobacco smoking (1.5-fold increased risk)
  • Excessive alcohol use
• Medical conditions:
  • Chronic atrophic gastritis
  • Pernicious anemia
  • Prior gastric surgery (15-20 years post-op)
  • Gastric polyps (adenomatous)
• Genetic:
  • Family history (3-fold increased risk)
  • Lynch syndrome
  • Li-Fraumeni syndrome

Clinical features

• Symptoms
  • Early satiety
  • Leser-Trelat signal sudden development of seborrheic keratoses
  • Acanthosis nigricans
  • Dysphagia (gastric adenocarcinoma arise proximal)
  • Persistent abdominal pain (commonly epigastric)
• Physical examination
  • Unintentional weight loss (secondary to reduced caloric intake)

Version 2

★ Most common symptoms (in order):

1. Weight loss (60-70%)
2. Abdominal pain (50-60%) - typically epigastric
3. Early satiety (40-50%)
4. Nausea/vomiting (30-40%)
5. Dysphagia (25%) - if proximal/GE junction involved

Physical Examination Findings:

• ★ Most common finding: Epigastric tenderness
• Advanced disease signs:
  • Virchow node (left supraclavicular lymphadenopathy)
  • Sister Mary Joseph nodule (periumbilical nodule)
  • Blumer shelf (palpable mass on rectal exam)
  • Krukenberg tumor (bilateral ovarian metastases)

Paraneoplastic Syndromes:

• Leser-Trélat sign: Sudden eruption of multiple seborrheic keratoses
• Acanthosis nigricans: Hyperpigmented, velvety skin changes
• Trousseau syndrome: Migratory thrombophlebitis

Diagnosis

• Endoscopy and biopsy (findings include signet ring cells)
• Barium studies (it may be superior to endoscopy in detecting linitis plastica)
• PET scan and CT scan for staging

Version 2

Diagnostic Workup:

1. Upper endoscopy with biopsy (★ gold standard)
   • Multiple biopsies (minimum 6-8)
   • Target suspicious areas and normal-appearing mucosa
2. Histopathology findings:
   • Intestinal type: Glandular structures
   • Diffuse type: Signet ring cells (>50% of tumor cells)
3. Staging studies:
   • CT chest/abdomen/pelvis (initial staging)
   • EUS (T and N staging)
   • PET/CT (detect occult metastases)
   • Diagnostic laparoscopy (detect peritoneal carcinomatosis)

Laboratory Studies:

• CBC (iron deficiency anemia in 40%)
• CEA, CA 19-9 (prognostic, not diagnostic)
• H. pylori testing

Differential diagnosis

• Gastric lymphoma (associated with mucosa-associated lymphoid tissue)
• Gastric stromal cancer
• Neuroendocrine (carcinoid) tumor

Version 2

Tumor staging

Treatment

• Tumor confined to mucosa (endoscopic resection)
• Gastrectomy with lymphadenectomy (for more extensive disease)
• Metastatic (palliative chemotherapy and radiation, surgery performed for cases of obstruction)

Version 2

Treatment by Stage:

1. Early gastric cancer (T1a, well-differentiated, <2cm):

   • First-line: Endoscopic mucosal resection (EMR) or ESD
   • Criteria: No lymphovascular invasion, <2cm, well-differentiated

2. Localized disease (T1b-T4a, N0-N3, M0):

   • First-line: Gastrectomy with D2 lymphadenectomy
   • Perioperative chemotherapy: FLOT regimen (5-FU, leucovorin, oxaliplatin, docetaxel)
   • Alternative: MAGIC regimen (epirubicin, cisplatin, 5-FU)

3. Metastatic disease (M1):

   • First-line chemotherapy:
     • HER2-negative: FOLFOX or CAPOX
     • HER2-positive: Trastuzumab + chemotherapy
   • Second-line: Ramucirumab ± paclitaxel
   • Third-line: Immunotherapy (pembrolizumab if MSI-H)

Complications

• Virchow note (left supraclavicular node involvement is secondary to metastasis)
• Krukenberg tumor (metastasis to both ovaries)
• Sister Mary Joseph nodule (periumbilical metastasis)
• Dumping syndrome (gastrectomy complications)

Version 2

★ Most common complications:

1. Gastric outlet obstruction (25-35%)
2. Bleeding (20-30%)
3. Perforation (1-2%)

Metastatic patterns:

• ★ Most common site: Liver (48%)
• Peritoneal carcinomatosis (35%)
• Lung (15%)
• Bone (10%)

Special metastatic sites:

• Virchow node: Left supraclavicular (via thoracic duct)
• Krukenberg tumor: Bilateral ovarian metastases (signet ring cells)
• Sister Mary Joseph nodule: Periumbilical metastasis

DUMPING SYNDROME

BACKGROUND

Definition: Dumping syndrome is a constellation of gastrointestinal and vasomotor symptoms resulting from rapid gastric emptying of hyperosmolar contents into the small intestine.

Epidemiology:

• ★ Most common cause: Post-gastric surgery (10-40% incidence)
• ★ Most common surgery associated: Roux-en-Y gastric bypass
• Onset: Can occur immediately post-op or years later

TYPES/CLASSIFICATION

CLINICAL FEATURES

Early Dumping Symptoms:

• GI symptoms (★ most common):
  • Abdominal cramping
  • Nausea
  • Explosive diarrhea
  • Bloating
• Vasomotor symptoms:
  • Palpitations
  • Diaphoresis
  • Flushing
  • Dizziness
  • Syncope

Late Dumping Symptoms:

• Diaphoresis
• Tremor
• Confusion
• Hunger
• Weakness
• Syncope

DIAGNOSIS

Diagnostic Tests:

1. Clinical diagnosis (usually sufficient)

   • Characteristic symptoms
   • Temporal relationship to meals
   • History of gastric surgery

2. Oral glucose tolerance test:

   • 50g glucose load
   • Positive if: HR increase ≥10 bpm within 60 minutes (early dumping)
   • Late dumping: Hypoglycemia at 2-3 hours

3. Gastric emptying study:

   • Shows accelerated emptying

   • 70% emptied at 30 minutes (normal <40%)

TREATMENT

First-line Management (Dietary Modifications):

• Small, frequent meals (6 small meals/day)
• Avoid simple sugars and high-osmolar foods
• Separate liquids from solids (drink 30-60 min after meals)
• Increase protein and fat intake
• Add soluble fiber (slows gastric emptying)
• Lie down after meals (delays gastric emptying)

Second-line (Pharmacologic):

• Octreotide (50-100 μg SC before meals)
  • Mechanism: Delays gastric emptying, inhibits insulin release
  • Reserved for refractory cases
• Acarbose (25-100 mg with meals)
  • For late dumping/reactive hypoglycemia
  • Delays carbohydrate absorption

Third-line (Surgical):

• Rarely needed (<1% of cases)
• Options: Pyloric reconstruction, conversion to Roux-en-Y
• Reserved for severe, refractory symptoms

CARCINOID SYNDROME

BACKGROUND

Definition: Carcinoid syndrome is a paraneoplastic syndrome caused by systemic release of vasoactive substances (primarily serotonin) from well-differentiated neuroendocrine tumors (NETs).

Epidemiology:

• Occurs in 10% of patients with NETs
• ★ Most common primary site: Small intestine (45%), specifically ileum
• ★ Most common age: 50-60 years
• Prerequisite: Usually requires liver metastases (bypasses hepatic metabolism)

Pathophysiology:

• NETs produce serotonin, histamine, kallikrein, prostaglandins
• Normally metabolized by liver (first-pass effect)
• Liver metastases → systemic circulation → syndrome
• Exception: Bronchial NETs (direct systemic drainage)

CLINICAL FEATURES

★ Classic Triad:

1. Flushing (85-90%)
   • Face, neck, upper chest
   • Lasts 2-5 minutes
   • Triggered by: alcohol, stress, exercise, certain foods
2. Secretory diarrhea (70-80%)
   • Watery, non-bloody
   • 10-20 bowel movements/day
   • Associated with cramping
3. Bronchospasm/wheezing (15-20%)

Additional Features:

• Carcinoid heart disease (50% with syndrome)
  • ★ Most common valve affected: Tricuspid (regurgitation > stenosis)
  • Right-sided valvular fibrosis
  • Plaque-like deposits
• Pellagra (5%) - niacin deficiency (4 D's: Dermatitis, Diarrhea, Dementia, Death)
• Mesenteric fibrosis → bowel obstruction
• Telangiectasias (chronic vasodilation)

DIAGNOSIS

Laboratory Tests:

1. 24-hour urine 5-HIAA (★ gold standard)
   • Sensitivity: 90%, Specificity: 90%

   • 25 mg/24h (normal <10 mg/24h)

   • Avoid serotonin-rich foods 3 days prior
2. Plasma chromogranin A
   • Elevated in 80-90% of NETs
   • Non-specific (also elevated in PPI use, renal failure)
3. Plasma serotonin (less reliable than 5-HIAA)

Imaging:

1. CT/MRI abdomen - initial imaging
2. Ga-68 DOTATATE PET/CT - most sensitive for NETs
3. Echocardiogram - screen for carcinoid heart disease

Histopathology:

• Well-differentiated tumor cells
• "Salt-and-pepper" chromatin
• Positive for chromogranin A, synaptophysin
• Ki-67 index for grading

DIFFERENTIAL DIAGNOSIS

TREATMENT

Symptomatic Management:

1. First-line: Somatostatin analogues

   • Octreotide 100-500 μg SC TID or
   • Lanreotide 90-120 mg deep SC q4 weeks
   • Controls symptoms in 70-80%
   • May slow tumor growth

2. Refractory diarrhea:

   • Add telotristat 250 mg TID (tryptophan hydroxylase inhibitor)
   • Loperamide, diphenoxylate

3. Flushing:

   • Avoid triggers
   • H1/H2 blockers for histamine-secreting tumors

Tumor-Directed Therapy:

1. Localized disease: Surgical resection (curative intent)
2. Metastatic disease:
   • Peptide receptor radionuclide therapy (PRRT) with Lu-177 DOTATATE
   • Hepatic artery embolization for liver metastases
   • Everolimus (mTOR inhibitor)
   • Cytotoxic chemotherapy (poorly differentiated only)

Carcinoid Crisis Prevention:

• High-dose octreotide (500 μg/hr IV) perioperatively
• Avoid triggers: catecholamines, histamine-releasing drugs
• Have vasopressors ready (avoid epinephrine)

COMPLICATIONS

★ Most common complication: Carcinoid heart disease (50%)

• Tricuspid regurgitation/stenosis
• Pulmonary valve involvement (less common)
• Right heart failure
• Treatment: Valve replacement when symptomatic

★ Most life-threatening: Carcinoid crisis

• Profound flushing, bronchospasm, hypotension
• Triggered by anesthesia, surgery, tumor manipulation
• Treatment: High-dose IV octreotide

HIGH-YIELD EXAM FACTS