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

Case History

• Black bowel movements for 2 days three weeks previously (melena)

• Wakes at night with pain• Took aspirin for pain• Weak

Objective Findings

• Physical examination: – fullness and tenderness in the

epigastrium• Lab

– Hemoglobin 11.6 g/dl, MCV 68, Fe 26 (low)

Doc – What’s wrong with me?(Have I got Cancer?)

Clinical Approach

Differential DiagnosisBenign Disease

• Peptic Ulcer Disease– Gastritis, gastric ulcer, duodenitis,

duodenal ulcer• Hepatobiliary disease

– Gallstone disease• Pancreatic disease

– Pancreatitis – acute, chronic,

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

Alarm Symptoms• Age >50y• Increasing abdominal pain, • Wakes at night • Anorexia, Weight loss• Early satiety• Anemia• Conclusion: Urgent

Investigation

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%.

Epidemiology of Gastric Adenocarcinoma

Gastric Carcinoma Epidemiology

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

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

Multistep Pathway in the Pathogenesis of Gastric Cancer

Helicobacter and Gastric Cancer

36/1246 H. pylori positive 0/280 negative patients developed gastric cancer

Gastric Cancer - Diagnosis

Investigations• Barium studies• Upper gastrointestinal gastroscopy• CT scan• Endoscopic ultrasound (EUS)• Tumor markers - blood

Normal Barium Study

Gastric fundus

Gastric body

Gastric antrumPylorus

Duodenal cap

Duodenum-2nd part

Barium Contrast Upper GI Series Gastric Cancer - Intestinal Type

Gastric antrum

Tumor

Gastric Cancer – Linitis Plastica

Gastric antrum

Tumor

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

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

Normal Gastroscopy

Gastric antrum

Gastric body

Pylorus

Gastric fundus

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

Pathology

Diffuse Type Intestinal Type

Signet Ring Cells

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

Endoscopic UltrasoundStaging

• Early vs advanced - 90% to 99% accurate

• EUS is comparable to CT detecting perigastric nodes– accuracy ranging around

50% to 80%

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

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

Treatment

• Surgery – only hope of cure• Chemotherapy• Radiotherapy

Gastric Cancer - Prognosis

1-5-year relative survival rates for gastrectomy patients

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%)

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

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

Clinical• Epigastric pain• Dypepsia

Maltoma

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

Diffuse Large B-cell LymphomaClinical

• Pain• Nausea• Vomiting• Anorexia, weight loss• Fever• Night sweats• Diarrhea

Lymphoma - Upper GI series

Tumor

Lymphoma - Gastroscopy

Gastric Lymphoma Maltoma

CT - Gastric Lymphoma

Low Grade Malt Lymphoma

High Grade Malt Lymphoma

Diffuse Large B-cell Lymphoma Treatment

• Chemotherapy• Radiotherapy• Surgery

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

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

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

Hypergastrinemia

Gastrin Causes ECL Hyperplasia

Carcinoid

• Average at diagnosis – 62y• Male = Female• Usually asymptomatic – incidental

finding at gastroscopy• EUS helps define invasion• Biopsies stain for chromogranin

Treatment • Type 1

Spontaneous resolution Endoscopic polypectomy Antrectomy Total gastrectomyHydrochloric acid

• Type 2/3– Surgery

Gastric Carcinoid - Prognosis