Tumors of the Tumors of the StomachStomach

Dr. Gerry FraserDr. Gerry Fraser

Department of GastroenterologyDepartment of GastroenterologyRabin Medical CenterRabin Medical Center

Beilinson CampusBeilinson Campus

Case HistoryCase 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 Case History

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

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

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

Clinical ApproachClinical Approach

History and Physical Examination

Probably not serious Alarm Symptoms

Differential Diagnosis

Investigations? Urgency?

Treatment

Differential Diagnosis

Urgent InvestigationBlood Tests

Imaging

Tissue Diagnosis

Treatment

Differential DiagnosisDifferential DiagnosisBenign DiseaseBenign Disease

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

duodenal ulcer

• Hepatobiliary disease– Gallstone disease

• Pancreatic disease– Pancreatitis – acute, chronic,

Differential DiagnosisDifferential DiagnosisMalignant DiseaseMalignant 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 SymptomsAlarm Symptoms• Age >50y• Increasing abdominal pain, • Wakes at night • Anorexia, Weight loss• Early satiety• Anemia• Conclusion: Urgent Investigation

Histopathologic Types of Histopathologic Types of Malignant Gastric Tumors Malignant Gastric Tumors

(%)(%)

Glandular adenocarcinoma Signet ring adenocarcinomaLymphoma GISTUndifferentiated carcinoma LeiomyosarcomaUnclassified tumors

Type No. %

Glandular adenocarcinoma 99 47.60

Signet ring adenocarcinoma 43 20.66

Lymphoma 40 19.23

GIST 12 5.77

Undifferentiated carcinoma 6 2.88

Leiomyosarcoma 4 1.93

Unclassified tumors 4 1.93

Total 208 100.00

Histopathologic Types of Histopathologic Types of Malignant Gastric Tumors –Malignant Gastric Tumors –

208 cases208 cases

Epidemiology of Gastric Epidemiology of Gastric AdenocarcinomaAdenocarcinoma

Gastric Adenocarcinoma-Gastric Adenocarcinoma-EpidemiologyEpidemiology

• 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 Pathogenesis of Gastric CancerCancer

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)

• Familia adenomatous polyposis (FAP)

• Hereditary nonpolyposis colorectal cancer (HNPCC)

• E-cadherin mutations, • IL1β poymorphism• Blood group A

Multistep Pathway in the Multistep Pathway in the Pathogenesis of Gastric Cancer Pathogenesis of Gastric Cancer

Helicobacter and Gastric Helicobacter and Gastric CancerCancer

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

Gastric Cancer - DiagnosisGastric Cancer - Diagnosis

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

Normal Barium StudyNormal Barium Study

Gastric fundus

Gastric body

Gastric antrumPylorus

Duodenal cap

Duodenum-2nd part

Accuracy of Upper GI SeriesAccuracy 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

Barium Contrast Upper GI Series Barium Contrast Upper GI Series Gastric Cancer - Intestinal TypeGastric Cancer - Intestinal Type

Gastric antrum

Tumor

Gastric Cancer – Linitis PlasticaGastric Cancer – Linitis Plastica

Gastric antrum

Tumor

EndoscopyEndoscopy• 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 GastroscopyNormal Gastroscopy

Gastric antrum

Gastric body

Pylorus

Gastric fundus

Gastric CancerGastric 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

PathologyPathology

Diffuse Type Intestinal Type

Signet Ring CellsSignet Ring Cells

CTCT

• 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 UltrasoundEndoscopic Ultrasound

• Early vs advanced - 90% to 99% accurate

• EUS is comparable to CT detecting perigastric nodes– accuracy ranging around 50%

to 80%

Clinical Stage-TNM SystemClinical 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 Staging: Nodes and Metastases (TNM)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

TreatmentTreatment

• Surgery – only hope of cure• Chemotherapy• Radiotherapy

Gastric Cancer - PrognosisGastric Cancer - Prognosis

1-5-year relative survival rates for gastrectomy patients

LymphomaLymphoma

• 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 LymphomaGastric 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

MaltomaMaltoma• 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

ClinicalClinical• Epigastric pain• Dypepsia

MaltomaMaltoma

Low Grade MALToma Low Grade MALToma TreatmentTreatment

• 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 LymphomaDiffuse Large B-cell LymphomaClinicalClinical

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

Lymphoma - Upper GI seriesLymphoma - Upper GI series

Tumor

Lymphoma - GastroscopyLymphoma - Gastroscopy

Gastric Lymphoma Maltoma

CT - Gastric Lymphoma

Low Grade Malt Lymphoma

High Grade Malt Lymphoma

Diffuse Large B-cell LymphomaDiffuse Large B-cell Lymphoma Treatment Treatment

• Chemotherapy• Radiotherapy• Surgery

CarcinoidCarcinoid• 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 TractCarcinoids 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

• In most cases, carcinoid syndrome is associated with tumors of the midgut and foregut

• Hindgut tumors seldom produce such symptoms; those that do usually signal distant metastatic disease

Gastric Carcinoid - TypesGastric 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

HypergastrinemiaHypergastrinemia

Gastrin Causes ECL Hyperplasia

CarcinoidCarcinoid

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

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

Treatment Treatment • Type 1

Spontaneous resolution Endoscopic polypectomy Antrectomy Total gastrectomyHydrochloric acid

• Type 2/3– Surgery

Gastric Carcinoid - PrognosisGastric Carcinoid - Prognosis

Models of the Gastric Models of the Gastric Carcinogenic PathwayCarcinogenic Pathway

Intestinal Type• H. pylori infection induces:

– Chronic superficial gastritis– Atrophic gastritis– Inflammation and regeneration

cause intestinal metaplasia. – Inappropriate activation of a

series of genetic events

Models of the Gastric Models of the Gastric Carcinogenic PathwayCarcinogenic Pathway

Diffuse type • Defects in E-cadherin function

– Important in cell-cell adhesion– Tight association of epithelial cells– Mucosal integrity– Suppressor of epithelial cell invasion– E-cadherin (CDH1) mutations

• Hereditary diffuse gastric cancer (HDGC)