Dr Sapna M

NORMAL ANATOMY/ HISTOLOGY

Stomach - Normal

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The normal gastric mucosa

Cardia – mainly mucus-secreting cells

Fundus (body) – acid producing parietal cells, pepsin producing chief cells

Pylorus – hormone (gastrin) production

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Stomach - Normal

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Stomach

Functions

◦ Mix food

◦ Reservoir

◦ Start digestion of

Protein

Nucleic acids

Fats

◦ Activates some enzymes

◦ Destroy some bacteria

◦ Makes intrinsic factor –B 12 absorption

◦ Destroys some bacteria

◦ Absorbs

Alcohol

Water

Lipophilic acid

B 12

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Bezoar

A bezoar is a mass found trapped in the gastrointestinal system (usually the stomach), though it can occur in other locations.

A pseudobezoar is an indigestible object introduced intentionally into the digestive system.

There are several varieties of bezoar, some of which have inorganicconstituents and others organic.

Stomach pathology

Congenital anomaly – pyloric stenosis

Inflammatory conditions – gastritis,

peptic ulcers

Tumors

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Pyloric stenosis

In 95% of infants with pyloric stenosis

the age at presentation is between 3

and 12 weeks of life, typically between

3 and 8 weeks.

Pyloric stenosis has been reported in

neonates within the first day of life.

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etiology

3 in 1,000 live births

more commonly in males

30 percent of cases occur in firstborn

genetic predisposition

Sibling has 5 times more incidence

environmental factors

Neonatal hypergastrinemia and gastric

hyperacidity may have a role

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CLINICAL MANIFESTATIONS

The classic presentation of IHPS is the three- to six-week-old baby who develops immediate postprandial, non-bilious, often

projectile VOMITING and demands to be re-fed soon afterwards

(a "hungry vomiter").

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Palpable mass

The mass is most easily felt

immediately after emesis because it

may otherwise be obscured by a

distended antrum and/or tensed

abdominal muscles

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Pancreatic heterotopia

Pancreatic tissue outside boundaries

of pancreas without anatomic or

vascular connections to pancreas

● Also called ectopic pancreas

● Present in 0.5% to 14% of autopsies

● Due to displacement of pancreatic

tissue during embryonic development

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Inflammatory

Disease of Stomach

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Definition

The term gastritis is used to denote inflammation associated with mucosal injury.

.

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PathophysiologyThe mechanisms of mucosal injury in gastritis is thought to be an imbalance of

aggressive factors

acid production or pepsin

and

defensive factors

mucus production

bicarbonate

and blood flow

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Protective factors vs. hostile factors

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Gastritis

Acute Chronic

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Classification of gastritis

Acute Chronic

•H pylori gastritis

•Other infective gastritis – bacteria,

virus, fungi, parasite

•Acute non infective gastritis

•Type A- autoimmune

•Type B- h pylori related

•Type AB- environmental

•Chemical – reflux gastritis

•Uncommon forms

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Acute & Chronic Difference

◦ Acute refers to short term inflammation

◦ Acute refering to neurophilic infiltrate

◦ Chronic referring to long standing forms

◦ Chronic referring to mononuclear cell

infiltrate especially lymphocyte and

macrophages

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Acute Gastritis

Definition

◦ An acute mucosal inflammatory

process, with neutrophilic infiltrate,

that is usually transient.

◦ There may be hemorrhage into the

mucosa or sloughing of the mucosa.

◦ Severe erosive form is an important

cause of severe GI bleeding

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Etiology◦ Frequently associated with, among others:

heavy use of NSAIDS, especially aspirin

excessive alcohol consumption

heavy smoking

severe stress e.g. trauma, burns, surgery

Ischemia

Systemic infection

◦ Often, idiopathic

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NSAIDs

NSAIDs and aspirin also

interfere with the protective

mucus layer by inhibiting

mucosal cyclooxygenase

activity, reducing levels of

mucosal prostaglandins

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Smoking

Promotes gastritis & ulcer occurrence

Increases the likelihood of

ulcer complications

Mechanisms

◦ Stimulate gastric acid secretion

◦ Stimulate bile salt reflux

◦ Causes alteration in mucosal blood flow

◦ Decrease mucus secretion

◦ Reduces prostaglandin synthesis

◦ Decrease pancreatic bicarbonate secretion

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Acute Gastritis - Pathogenesis

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All above Factor Acid secretion

+ back diffusion+ Bicarbonate

buffer

+

Blood flow

Disruption

of

Mucus layer +

Direct

Mucosal

Injury

Acute Gastritis

Stages of Acute Gastritis

Acute superficial gastritis

Inflammation of superficial

gastric mucosa.

Acute erosive gastritis

Destruction of multiple small

zones of superficial mucosa.

Acute Gastric Ulceration

Destruction of full thickness of mucosa31

Mucosal congestion ,edema

inflammation & ulceration

ACUTE GASTRITIS -

MORPHOLOGY

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Acute Gastritis - MorphologyRanges from edema with neutrophil infiltration, vascular congestion,&

an intact epithelium, to erosion (mucosal defect that does not cross

the muscularis mucosa) and hemorrhage.

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Acute Gastritis

Gastric mucosa

demonstrates

infiltration by

Neutrophils

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Acute Gastritis

diffusely hyperemic

gastric mucosa

causes for acute

gastritis

◦ alcoholism

◦ drugs

◦ infections, etc.

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Complications:

Malignancy

Hemorrhage

Perforation

Obstruction

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Chronic Gastritis

Definition

◦ Chronic mucosal inflammatory changes

leading to atrophy and metaplasia

(usually without erosions)

Dysplasia and ultimate neoplasia are

complications.

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Chronic Gastritis

Type B

Antral Gastritis

Type A

Autoimmune gastritis

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Type B (Antral Gastritis)

◦ 90% of patients with antral chronic gastritis: Helicobacter pylori infected

Motile, gram negative curvilinear rods that elaborate urease (buffers gastric acid) & toxins and have adhesins to bind to the epithelium.

Pathogenesis◦ H. pylori (urease NH4

+ + toxins) + Host (acid + peptic enzymes) Chronic Inflammation

◦ Antibodies Gland destruction + Mucosal atrophy acid intrinsic factor (which can lead to pernicious anemia)

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Helicobacter pylori infection

H. pylori – silver stain

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H. pylori – giemsa stain

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H. pylori – H & E stain

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Pathogenetic qualities of H.pylori;

Adheres to gastric epithelium

Lives within mucous gel layer overlying gastric epithelium

Penetrates intercellular junctions

Invades gastric glands and canaliculi of parietal cells

Secretes urease to produce ammonia, which protects it from

gastric acid

Produces cytotoxins that may play role in pathogenicity

Induces epithelial cytolysis and disrupts intercellular

junctions

Increases permeability of mucous layer to hydrogen ions

and pepsin

Enables gastric acid and pepsin to create ulcer craters

Evades host immune defenses

Damages tissue.

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Noninvasive

Urea Breath Test (UBT) Blood test

Invasive

Biopsy Urease TestHistology

Culture

Stool antigen test

Upper gastrointestinal (upper GI) X-ray

Other tests

Endoscopy

Helicobacter gastritis

2 patterns of infection

◦ Diffuse involvement of body and antrum

(“pan gastritis” associated with

diminishing acid output)

◦ Infection confined to antrum (antral

gastritis, associate with increased acid

output)

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Type A (Auto immune)

Etiology

◦ Autoimmune - antibodies to parietal cells,

gastrin receptor, intrinsic factor, and H+,K+

ATPase

<10% of cases of chronic gastritis

Possible autosomal dominant inheritance

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Morphology of chronic gastritis

Chronic inflammatory cell

infiltration

Mucosal atrophy

Intestinal (goblet cell)

metaplasia

Seen in Helicobacter and

autoimmune gastritis (not

chemical)

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Autoimmune gastritis

Autoimmune gastritis -

pernicious anemia

Chronic atrophic

gastritis is associated

with Ab’s

- intrinsic factor

- patietal cell

bright green IF- in the

parietal cells of the

gastric mucosa.

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Autoimmune Gastritis -Morphology

PJ Goldblatt, MD

Diffuse mucosal damage of the body and fundic

mucosa. Antrum less involved.

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Chronic Gastritis

Clinical Features

◦ Usually only a few symptoms: nausea, vomiting, upper abdominal discomfort

◦ Autoimmune

Hypo to achlorhydria (severe loss of parietal glands)

Hypergastrinemia

10% have pernicious anemia

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Clinical Complications

◦ Autoimmune:

Often seen in association with other

autoimmune disorders (Hashimoto

thyroiditis, Addison disease, and type I

diabetes)

Significant risk for the development of

gastric carcinoma (2-4%) and

endocrine tumors (carcinoid tumor)

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Chronic GastritisMorphology

◦ Varying degrees of mucosal damage possible

◦ Mucosal lesions are reddened, with thickened rugae

◦ Atrophied rugae in long-standing cases

◦ Lymphocytes and plasma cell infiltrate; neutrophils indicate “active” inflammation (may or may not be present)

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◦ Regeneration - constant feature

◦ Metaplasia - mucosa of antral and body-fundic regions converts to columnar absorptive cells and goblet cells (intestinal metaplasia)

◦ Atrophy - marked loss of glands

◦ Dysplasia – precursor lesion to gastric cancer in atrophic gastritis

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Sydney System of

Grading Chronic Gastritis

1. Site: Antral, Corporal mucosa

2. Grading of: (Mild, Moderate, Marked)

H-Pylori

Chronic inflammation

Activity

Atrophy

Intestinal metaplasia

*Normal lymphocytes & plasma cells in lamina propria = up to

5/HPF

*No Neutrophils in lamina propria

Peptic Ulcer Disease

Peptic Ulcer Disease

Condition characterized by

◦ Erosion of GI mucosa resulting from

digestive action of HCl and pepsin

Peptic Ulcer Disease

Ulcer development

◦ Lower esophagus

◦ Stomach

◦ Duodenum

◦ 10% of men, 4% of women

Types

Acute

◦ Superficial erosion

◦ Minimal erosion

Chronic

◦ Muscular wall erosion with formation of

fibrous tissue

◦ Present continuously for many months or

intermittently

Peptic Ulcer Disease Etiology and Pathophysiology

Develop only in presence of acid environment

Excess of gastric acid not necessary for ulcer development

Person with a gastric ulcer has normal to less than normal gastric acidity compared with person with a duodenal ulcer

Peptic Ulcer Size – variable; 0.3 – 4 cm in

diameter

Shape - round to oval

Sharply demarcated, clean-cut,

punched-out area with clean base

Margins are usually level with

surrounding mucosa or slightly

elevated due to edema; the mucosa

is undermined at the edges

Radiating mucosal rugae

80% are solitary, 80% occur in the

duodenum, of which 90% in the

first part of the duodenum on the

anterior wall’ within a few

centimeter of the pyloric ring.

19% occur in the stomach(usually at

the lesser curvature at the border of

the body and antrum.

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Gastric Ulcer- Endoscopic Appearance

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Gastric Ulcer- Gross Appearance

Sharply punched-out

Large, mucosal defect or ulcer

Radiating mucosal folds

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Acute Gastric Ulcer

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Giant gastric ulcer

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Duodenal Peptic Ulcers- Gross

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Microscopy:

Overhanging gastric

mucosal margins (A)

Necrotic fibrinoid

debris (B)

Acute inflammatory

infiltrate (C)

Granulation tissue

(D)

Fibrotic scarred

base (E)

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A

B

C, D

E

Ulcer Base

Superficial thin layer of

necrotic fibrinoid debris

Zone of inflammatory

infiltrate with neutrophils

Zone of granulation

tissue with dilated blood

vessels and lymphocytes

Zone of fibrous scarring

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Gastric ulcerDuodenal Ulcer

middle age 50-60Any age specially 30-40Age

More in maleMore in maleSex

SameStress job eg. ManagerOccupation

Epi. Can radiate to

back

Epigastric , discomfortPain

Immediately after

eating

2-3 hours after eating &

midnight

Onset

EatingHungerAgg.by

Gastric ulcerDuodenal UlcerLying down or vomitingEatingRelived by

Few weeks1-2 monthsDuration

Common(to relieve the

pain)

UncommonVomiting

Pt. afraid to eatGoodAppetite

Avoid fried foodGood , eat to relieve the painDiet

wt. Loss No wt. lossWeight

60%40%Hematemesis

40%60%Melena

GASTRIC TUMORS

BENIGN:

POLYPS (HYPERPLASTIC vs. ADENOMATOUS)

LEIOMYOMAS (Same gross and micro as sm. muscle)

LIPOMAS (Same gross and micro as adipose tissue)

MALIGNANT

(ADENO)Carcinoma

LYMPHOMA

POTENTIALLY MALIGNANT

G.I.S.T. (Gastro-Intestinal “Stromal” Tumor)

CARCINOID (NEUROENDOCRINE)

WHO GASTRIC NEOPLASMS

Epithelial Tumors:

Adenomatous polyps

Adenocarcinoma (papillary, tubular, mucinous, signet

ring, adenosquamous, unclassified),

Small cell, Carcinoid (neuroendocrine)

Nonepithelial Tumors: Leiomyooma, Leimyosarcoma,

Schwannoma, GIST, Granular Cell Tumor, Kaposi

sarcoma

Malignant Lymphomas:

What is gastric cancer?

GC is not far from us……

Napoleon‘s gastric cancer：tumor found on the lesser curvature of

the stomach: What cause? How to treat?

Ambition is never content, even on the summit of greatness.

He conquered the larger part of Europe, but he could not conquer gastric cancer

How to diagnose

What is epidemiology and etilogy

What is the pathology

How to treat

Content

How to diagnose

What is epidemiology and etilogy

What is the pathology

How to treat

Content

GC Worldwide incidence

Male 16.4Female 8.2

Male 36.3Female 16.9

Male 77.9Female 33.3

Male 10.8Female 4.9

Male 43.6Female 19.0

Male 5.9Female 2.6

Male 11.5Female 4.3

Male 18.6Female 13.3

Male 8.4Female 4.0

Eastern Europe

Japan

Australia/New Zealand

China

Northern Africa

Southern Africa

Central America

WesternEurope

NorthAmerica

In terms of geographic distribution, high rates apply to Japan, China and Eastern Europe and low rates to North America.

Almost 40% of cases occur in China .

Pazdur R et al. Cancer management: A multidisciplinary approach. edition,2002

Gastric

Cancer

H. pylori

Precancerouschanges

Genetic factors

Diet

Etiological Factors of GC

Precancerous changes

precancerous diseases

chronic atrophic gastritis

gastric ulcer

gastric polyps

gastric remnant

precancerous lesion

atypical hyperplasia

“The new study suggest he was chronically infected with the bacteria Helicobacter pylori.”

“full of salt-preserved foods but sparse in fruits and vegetables--common fare for long military”

H. pylori

Genetic factors“his father had also died of stomach cancer which led to the theory that he had inherited the disease.”

Diet

Precancerouschanges

Why Napoleon died of GC

chronic atrophic gastritis?

How to diagnose

What is epidemiology and etilogy

What is the pathology

How to treat

Content

Early gastric cancer

Defined as a tumor confined to the mucosal or submucosal

layer, with or without lymph node metastasis

Advanced gastric cancer

invasion depth beyond submucosal layer

Morphology

SITE - Favoured location is the

lesser curvature of the antropyloric region

Gastric carcinoma is classified on the basis of

- depth of invasion

- macroscopic growth pattern

- histologic subtype

ADENOCARCINOMA

GROWTH PATTERNS

Gross: Linitis

plastica carcinoma

diffusely infiltrates

the entire gastric

wall without forming

an intraluminal

mass. The wall of

the stomach is

typically thickened

to about 2-3 cm.

and has a leathery,

inelastic

consistency.

Lauren classification

Intestinal type

--- associated with most

environmental risk factors

--- carries a better prognosis

--- shows no familial history

Diffuse type--- consists of scattered cell

clusters with poor prognosis

Intestinal type gland

formation by malignant

cells,

Gastric carcinoma.

Diffuse type demonstrating

signet-ring carcinoma cells.

Bormann classifications

Gross classification

phymatoid type

ulcerative type

infiltrative ulcerative

diffuse infiltrative type

Histology classification

Adenocarcinoma occupy 95%

Lymphomas 2%

Carcinoids 1%

Adenocathomas 1%

Squamous cell 1%

TNM classification ——T

Primary tumor:

depth of tumor invasion

Tx- cannot be assessed

T0- no evidence

Tis- carcinoma in situ, no invasion of lamina

T1- invades lamina propria or submucosa

T2- invades muscularis or subserosa

T3- penetrates serosa, no adjacent structure

T4- invades adjacent structures

T:Primary tumor

Direct extension into omentum, pancreas,

diaphragm, transverse colon, and

duodenum.

If lesion extends beyond wall to a free

peritoneal surface, peritoneal involvement

is frequent.

TNM classification ——N

Regional Lymph NodesNX- cannot be assessed

N0- no nodes

N1- mets in 1-6 regional

nodes

N2- mets in 7-15 regional

nodes

N3- mets in more than 15

regional nodes

TNM classification ——M

Distant metastasisMX- cannot be assessed

M0- no distant metastases

M1-distant metastases

Spread Patterns

Direct invasion

Lymph node dissemination

Blood spread

Intraperitoneal colonization

Special term

Blumer shelf

A shelf palpable by reactal examination, due to

metastatic tumor cells gravitating from an abdominal

cancer and growing in the rectovesical or rectouterine

pouch

Krukenberg tumor

A tumor in the ovary by the spread of stomach cancer

What is the classification for Napoleon,GC

“The scientists suggest that Napoleon died

from a T3N1M0 (stage IIIA)gastric cancer. This means the tumour (T3) had spread to some local lymph nodes (N1) near the stomach, but had not spread or metastased (M0) to other organs. The prognosis for such tumours is known to be very poor. ”

How to diagnose

What is epidemiology and etilogy

What is the pathology

How to treat

Content

Clinical manifestation

Early Gastric Cancer

Asymptomatic or silent 80%

Peptic ulcer symptoms 10%

Nausea or vomiting 8%

Anorexia 8%

Early satiety 5%

Abdominal pain 2%

Gastrointestinal blood loss <2%

Weight loss <2%

Dysphagia <1%

Clinical manifestation

Advanced Gastric Cancer

Weight loss 60%

Abdominal pain 50%

Nausea or vomiting 30%

Anorexia 30%

Dysphagia 25%

Gastrointestinal blood loss 20%

Early satiety 20%

Peptic ulcer symptoms 20%

Abdominal mass or fullness 5%

Asymptomatic or silent <5%

Special signs

Linitis plastica:

--- diffusely infiltrating with a rigid stomach

Virchow’s node:

--- left supraclavicular lymph node

Sister Mary Joseph’s node:

--- umbilical lymph node

prerectal pouch mass (Blumer shelf)--- seeding metastasis

Sister Mary Joseph’s node

Laboratory tests

Assists in determining optimal therapy.

CBC identifies anemia, with may be caused by bleeding,

liver dysfunction, or poor nutrition.

30% have anemia.

Tumor markers

CEA:carcino-embryonic antigen

CA19-9:carbohydrate antigen

CA724:carbohydrate antigen

Imaging Studies

Endoscopic diagnosis

--- biopsy needed for definitive diagnosis

Endoscopic screening--- general population or high risk persons

How to diagnose Napoleon,GC

Endoscopic diagnosis?

Endoscopic Ultrasonography?

CT scan? Preoperative staging

......

Why?

How to diagnose

What is epidemiology and etilogy

What is the pathology

How to treat

Content

G.I.S.T. TUMORS Can behave and/or look benign or malignant

Usually look like smooth muscle, i.e., “stroma”

Are usually POSITIVE for

c-KIT (CD117), i.e., express this antigen on immunochemical staining, the tumor cells are derived from the interstitial cells, of Cajal, a “neural” type of cell

G.I.S.T. TUMORS

c-KIT (receptor for stem cell factor)

mutations

platelet-derived growth factor

receptor-a. (PDGFRA) mutations

tyrosine kinase inhibitor (STIS71) has

been shown to be effective in

treatment

GIST

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CARCINOID TUMOR

arise from the diffuse components of the

endocrine system

majority are found in the GI tract, and more

than 40% occur in the small intestine

tracheobronchial tree and lungs

Gastric carcinoids

release peptide and nonpeptide

hormones to coordinate gut function

carcinoids are intramural or

submucosal masses that create small

polypoid lesions

Carcinoid tumor

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The most important prognostic factor for GI carcinoid

tumors is location

Foregut carcinoid tumors

rarely metastasize and are generally cured by resection

Midgut carcinoid tumors

Aggressive, greater depth of local invasion, increased size, and presence of

necrosis and mitosis are associated with poor outcome

Hindgut carcinoids occur in appendix & rectum

in appendix almost uniformly benign < 2cm

Rectal carcinoid rarely metastsize

GASTRIC LYMPHOMA

Primary :

Mucosa (gut)-associated lymphoid tissue tumor

Previously called

MALToma, MALT-type lymphoma, or MALT lymphoma,

Now called

Extranodal marginal zone B-cell lymphoma of MALT type

lymphoepithelial lesion (LEL) is a hallmark

Secondary

spread from adjacent lymph nodes

Peptic ulcers

Gastric carcinoma

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