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Case History
66 year old man complains of: • Epigastric pain which has gradually increased
for the past two months• Loss of appetite (anorexia)• Early satiety• Weight loss of 5 kilos• Vomited twice in the past week
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Case History
• Black bowel movements for 2 days three weeks previously (melena)
• Wakes at night with pain• Took aspirin for pain• Weak
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Objective Findings
• Physical examination: – fullness and tenderness in the
epigastrium• Lab
– Hemoglobin 11.6 g/dl, MCV 68, Fe 26 (low)
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Clinical Approach
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Differential DiagnosisBenign Disease
• Peptic Ulcer Disease– Gastritis, gastric ulcer, duodenitis,
duodenal ulcer• Hepatobiliary disease
– Gallstone disease• Pancreatic disease
– Pancreatitis – acute, chronic,
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Differential DiagnosisMalignant Disease
• Gastric tumor – Adenocarcinoma, lymphoma, Gastrointestinal Stromal
Tumors (GIST), leiomyosarcoma, neuroendocrine • Liver and bile ducts
– Primary, secondary liver tumors, cholangiocarcinoma, gallbladder cancer
• Pancreas– Adenocarcinoma solid (>80%) or cystic (5%),
neuroendocrine
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Alarm Symptoms• Age >50y• Increasing abdominal pain, • Wakes at night • Anorexia, Weight loss• Early satiety• Anemia• Conclusion: Urgent
Investigation
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Gastric Tumors5 main types: • Adenocarcinoma: This is the most common type of
stomach cancer, 90 to 95 percent of stomach cancer cases, and develops in the glandular tissues.
• Lymphoma: Develops in lymphatic tissue of the stomach wall – about 5% of tumors.
• Carcinoid Tumors: Develops in the hormone-producing tissues of the stomach. Most of these tumors do not spread to other organs – 3%.
• Gastrointestinal Stomal Tumors (GIST): Develops in the stomach wall tissues that contain a specific type of cell called intestinal cells of Cajal. Gastrointestinal stomal tumors are a rare form of cancer and can occur anywhere in the gastrointestinal tract. However the majority of GIST cases occur in stomach – 2%.
• Leiomyosarcoma: Develops in the stomach muscle layer 1%.
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Epidemiology of Gastric Adenocarcinoma
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Gastric Carcinoma Epidemiology
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Gastric Adenocarcinoma-Epidemiology
• Incidence and mortality decreasing
• Risk greater in lower socioeconomic classes
• Migrants from high to low-incidence nations maintain their susceptibility to gastric cancer
• Migrant offspring approximates that of the new homeland
• Environmental exposure early in life
• Dietary carcinogens
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Pathogenesis of Gastric Cancer
Environmental(intestinal type)
• Helicobacter pylori• Diet
– High concentrations of nitrates in dried, smoked, and salted foods
• Smoking• Surgery to control benign
peptic ulcer disease• Adenomatous polyps• Ménétrier's disease
Genetic(diffuse type)
• Familial adenomatous polyposis (FAP)
• Hereditary nonpolyposis colorectal cancer (HNPCC)
• E-cadherin mutations, • IL1β poymorphism• Blood group A
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Multistep Pathway in the Pathogenesis of Gastric Cancer
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Helicobacter and Gastric Cancer
36/1246 H. pylori positive 0/280 negative patients developed gastric cancer
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Gastric Cancer - Diagnosis
Investigations• Barium studies• Upper gastrointestinal gastroscopy• CT scan• Endoscopic ultrasound (EUS)• Tumor markers - blood
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Normal Barium Study
Gastric fundus
Gastric body
Gastric antrumPylorus
Duodenal cap
Duodenum-2nd part
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Barium Contrast Upper GI Series Gastric Cancer - Intestinal Type
Gastric antrum
Tumor
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Gastric Cancer – Linitis Plastica
Gastric antrum
Tumor
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Accuracy of Upper GI Series
Concern about missing gastric cancer • Double-contrast upper GI studies - sensitivity
of more than 95% • Anatomical shifting of cancer toward the
proximal stomach– carcinomas of the cardia and fundus now
comprise 30% to 40% – difficult to evaluate by barium studies
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Endoscopy• Procedure of choice• Sensitivity – 95% for advanced
gastric cancer• Ability to take biopsies• Perform on any patient with dypepsia
>45y• Perform on any patient with alarm
symptoms
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Normal Gastroscopy
Gastric antrum
Gastric body
Pylorus
Gastric fundus
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Gastric Cancer
• Diffuse type 30 - 40% • Younger patients• Genetic mutations • “Linitis plastica"-type tumour• H. pylori not important
• Intestinal type 60-70%• Older age, more men• Environmental causes• Discrete tumour • H.pylori important
Lauren classification
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Pathology
Diffuse Type Intestinal Type
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Signet Ring Cells
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CT
• 65% to 90% sensitivity for advanced gastric cancer
• 50% for early gastric cancers
• CT has trouble discerning metastases less than 5 mm in size
• CT is mainly for the detection of distant metastases and as a complement to EUS for assessing regional lymph node involvement
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Endoscopic UltrasoundStaging
• Early vs advanced - 90% to 99% accurate
• EUS is comparable to CT detecting perigastric nodes– accuracy ranging around
50% to 80%
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Clinical Stage-TNM System
Tis: Carcinoma in situ: intraepithelial tumor without invasion of the lamina propriaT1: Tumor invades lamina propria or submucosaT2: Tumor invades the muscularis propria or the subserosaT3: Tumor penetrates the serosa (visceral peritoneum) without invading adjacent structuresT4: Tumor invades adjacent structures
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Staging: Nodes and Metastases (TNM)
Regional Lymph Nodes (N)• N0: No regional lymph node metastasis • N1: Metastasis in 1 to 6 regional lymph nodes • N2: Metastasis in 7 to 15 regional lymph nodes • N3: Metastasis in more than 15 regional lymph nodes
Distant metastasis (M) • MX: Distant metastasis cannot be assessed• M0: No distant metastasis• M1: Distant metastasis
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Treatment
• Surgery – only hope of cure• Chemotherapy• Radiotherapy
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Gastric Cancer - Prognosis
1-5-year relative survival rates for gastrectomy patients
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Lymphoma
• Malignancies of the lymphatic system• Hodgkin’s and Non-Hodgkin’s lymphoma
(NHL)• GI lymphomas (Ly) are almost always NHL• GI tract may be involved as part of the
general involvement or the only site (secondary or primary)
• May be B cell (85%) or T-cell (15%)
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Gastric Lymphoma• Stomach can be the primary site • The stomach can be secondarily involved
in disseminated nodal disease • 20% of all gastric tumors• 90% are B-cell Lymphomas• 40% low grade mucosa-associated
lymphoid tissue or MALT• 50% diffuse large B-cell lymphoma
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Maltoma• Normal gastric tissue does not have
lymphoid tissue• Chronic antigenic stimulation by H pylori
may be the initiating event in the pathogenesis of gastric MALT lymphoma
• H. pylori infection causes gastritis which leads to lymphoid aggregates, lymphoid hyperplasia, clonal expansion
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Clinical• Epigastric pain• Dypepsia
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Maltoma
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Low Grade MALToma Treatment
• Early stage low grade and Helicobacter pylori positive – 95% of maltomas – eradication
• 60-80% respond• Complete regression may take >12 m• Endoscopic and EUS follow-up required• Advanced - chemotherapy
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Diffuse Large B-cell LymphomaClinical
• Pain• Nausea• Vomiting• Anorexia, weight loss• Fever• Night sweats• Diarrhea
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Lymphoma - Upper GI series
Tumor
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Lymphoma - Gastroscopy
Gastric Lymphoma Maltoma
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CT - Gastric Lymphoma
Low Grade Malt Lymphoma
High Grade Malt Lymphoma
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Diffuse Large B-cell Lymphoma Treatment
• Chemotherapy• Radiotherapy• Surgery
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Carcinoid• Neuroendocrine tumors• Enterochromaffin cells (EC) of the
gastrointestinal tract• Stain with potassium chromate
(chromaffin), a feature of cells that contain serotonin
• The clinical characteristics of carcinoid tumors vary with the location of the tumor
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Carcinoids of the GI Tract
Carcinoid malignancies originating from 3 areas:
• Foregut– esophagus, stomach and the bronchial tree of the lungs;
• Midgut– pancreas, duodenum, ilium and appendix; and
• Hindgut– ascending, descending and transverse colons and rectum
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Gastric Carcinoid - Types
• Type 1 - Hypergastrinemia – Pernicious anemia and chronic atrophic
gastritis– usually multiple, small and benign,
• Type 2 - Hypergastrinemia– multiple endocrine neoplasia type
1 (MEN1) combined with Zollinger-Ellison syndrome
– Small, multiple and can metastasize• Type 3 No hypergastrinaemia
– Highly malignant and metastasize
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Hypergastrinemia
Gastrin Causes ECL Hyperplasia
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Carcinoid
• Average at diagnosis – 62y• Male = Female• Usually asymptomatic – incidental
finding at gastroscopy• EUS helps define invasion• Biopsies stain for chromogranin
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Treatment • Type 1
Spontaneous resolution Endoscopic polypectomy Antrectomy Total gastrectomyHydrochloric acid
• Type 2/3– Surgery
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Gastric Carcinoid - Prognosis