tumors of the stomach dr. gerry fraser department of gastroenterology rabin medical center beilinson...
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Tumors of the Tumors of the StomachStomach
Dr. Gerry FraserDr. Gerry Fraser
Department of GastroenterologyDepartment of GastroenterologyRabin Medical CenterRabin Medical Center
Beilinson CampusBeilinson Campus
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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
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Case History 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 FindingsObjective Findings
• Physical examination: – fullness and tenderness in the
epigastrium
• Lab– Hemoglobin 11.6 g/dl, MCV 68, Fe 26
(low)
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Doc – What’s wrong with me?Doc – What’s wrong with me?(Have I got Cancer?)(Have I got Cancer?)
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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
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Differential DiagnosisDifferential DiagnosisBenign DiseaseBenign Disease
• Peptic Ulcer Disease– Gastritis, gastric ulcer, duodenitis,
duodenal ulcer
• Hepatobiliary disease– Gallstone disease
• Pancreatic disease– Pancreatitis – acute, chronic,
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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
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Alarm SymptomsAlarm Symptoms• Age >50y• Increasing abdominal pain, • Wakes at night • Anorexia, Weight loss• Early satiety• Anemia• Conclusion: Urgent Investigation
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Histopathologic Types of Histopathologic Types of Malignant Gastric Tumors Malignant Gastric Tumors
(%)(%)
Glandular adenocarcinoma Signet ring adenocarcinomaLymphoma GISTUndifferentiated carcinoma LeiomyosarcomaUnclassified tumors
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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
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Epidemiology of Gastric Epidemiology of Gastric AdenocarcinomaAdenocarcinoma
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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
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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
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Multistep Pathway in the Multistep Pathway in the Pathogenesis of Gastric Cancer Pathogenesis of Gastric Cancer
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Helicobacter and Gastric Helicobacter and Gastric CancerCancer
36/1246 H. pylori positive 0/280 negative patients developed gastric cancer
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Gastric Cancer - DiagnosisGastric Cancer - Diagnosis
Investigations• Barium studies• Upper gastrointestinal gastroscopy• CT scan• Endoscopic ultrasound (EUS)• Tumor markers - blood
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Normal Barium StudyNormal Barium Study
Gastric fundus
Gastric body
Gastric antrumPylorus
Duodenal cap
Duodenum-2nd part
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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
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Barium Contrast Upper GI Series Barium Contrast Upper GI Series Gastric Cancer - Intestinal TypeGastric Cancer - Intestinal Type
Gastric antrum
Tumor
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Gastric Cancer – Linitis PlasticaGastric Cancer – Linitis Plastica
Gastric antrum
Tumor
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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
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Normal GastroscopyNormal Gastroscopy
Gastric antrum
Gastric body
Pylorus
Gastric fundus
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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
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PathologyPathology
Diffuse Type Intestinal Type
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Signet Ring CellsSignet Ring Cells
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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
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Endoscopic UltrasoundEndoscopic Ultrasound
• 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 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
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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
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TreatmentTreatment
• Surgery – only hope of cure• Chemotherapy• Radiotherapy
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Gastric Cancer - PrognosisGastric Cancer - Prognosis
1-5-year relative survival rates for gastrectomy patients
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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%)
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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
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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
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ClinicalClinical• Epigastric pain• Dypepsia
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MaltomaMaltoma
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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
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Diffuse Large B-cell LymphomaDiffuse Large B-cell LymphomaClinicalClinical
• Pain• Nausea• Vomiting• Anorexia, weight loss• Fever• Night sweats• Diarrhea
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Lymphoma - Upper GI seriesLymphoma - Upper GI series
Tumor
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Lymphoma - GastroscopyLymphoma - 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 LymphomaDiffuse Large B-cell Lymphoma Treatment Treatment
• Chemotherapy• Radiotherapy• Surgery
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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
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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
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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
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HypergastrinemiaHypergastrinemia
Gastrin Causes ECL Hyperplasia
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CarcinoidCarcinoid
• 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 Treatment • Type 1
Spontaneous resolution Endoscopic polypectomy Antrectomy Total gastrectomyHydrochloric acid
• Type 2/3– Surgery
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Gastric Carcinoid - PrognosisGastric Carcinoid - Prognosis
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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
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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)