INFLAMMATIONS OF THE STOMACHINFLAMMATIONS OF THE STOMACH CHRONIC AUTOIMMUNE GASTRITISCHRONIC AUTOIMMUNE GASTRITIS Extensive multifocal atrophy (atrophic gastritis)Extensive multifocal atrophy (atrophic gastritis) Endemic in some parts of the world, e.g. JapanEndemic in some parts of the world, e.g. Japan Pathogenesis:Pathogenesis:

– Autoantibodies to gastric glands parietal cellsAutoantibodies to gastric glands parietal cells– Gland destruction & mucosal atrophyGland destruction & mucosal atrophy– Loss of acid & IF production (pernicious anemia)Loss of acid & IF production (pernicious anemia)

Pathology: variable gland loss, atrophy & intestinal Pathology: variable gland loss, atrophy & intestinal metaplasia; dysplasia of metaplastic epitheliummetaplasia; dysplasia of metaplastic epithelium

If severe parietal cell loss: hypo- or achlorhydria & If severe parietal cell loss: hypo- or achlorhydria & hypergastrinemiahypergastrinemia

Px:Px: 2 - 4% risk of developing gastric carcinoma 2 - 4% risk of developing gastric carcinoma

PATHOLOGY OF THE STOMACHPATHOLOGY OF THE STOMACH

HYPEPTROPHIC GASTRITISHYPEPTROPHIC GASTRITIS Group of uncommon conditions characterized by Group of uncommon conditions characterized by

enlargement of rugal folds of gastric mucosaenlargement of rugal folds of gastric mucosa Three main variants:Three main variants:

– MenetrierMenetrier’’s disease: rare idiopathic disease; may be s disease: rare idiopathic disease; may be asymptomatic or produces pain, nausea, vomiting & asymptomatic or produces pain, nausea, vomiting & bleeding; protein-losing gastroenteropathybleeding; protein-losing gastroenteropathy

– Hypersecretory gastropathy: associated with Hypersecretory gastropathy: associated with hyperplasia of parietal and chief cellshyperplasia of parietal and chief cells

– Gastric gland hyperplasia: secondary to excessive Gastric gland hyperplasia: secondary to excessive gastrin secretion by a gastrinoma (Zollinger-Ellison gastrin secretion by a gastrinoma (Zollinger-Ellison syndrome)syndrome)

Radiologically or endoscopically may mimic carcinomaRadiologically or endoscopically may mimic carcinoma

PATHOLOGY OF THE STOMACHPATHOLOGY OF THE STOMACH GASTRIC EROSIONS & ULCERATIONSGASTRIC EROSIONS & ULCERATIONS

Erosion: loss of superficial epithelium of Erosion: loss of superficial epithelium of mucosamucosa– May heal within daysMay heal within days

Ulcer: breach in the mucosa, which extends Ulcer: breach in the mucosa, which extends through the muscularis mucosa into the through the muscularis mucosa into the submucosa or deepersubmucosa or deeper– Needs longer time to healNeeds longer time to heal

Main types:Main types:– Acute gastric erosions & ulcerationsAcute gastric erosions & ulcerations– Peptic ulcersPeptic ulcers

GASTRIC ULCERATIONSGASTRIC ULCERATIONS

PEPTIC ULCERPEPTIC ULCER Chronic, most often solitary, lesions that occur in any Chronic, most often solitary, lesions that occur in any

part of GIT exposed to aggressive action of acid-part of GIT exposed to aggressive action of acid-peptic juicespeptic juices

Sites: 98% occur in either the duodenum or stomach Sites: 98% occur in either the duodenum or stomach (4:1 ratio)(4:1 ratio)

Patients: common in industrialized countries: 1-2% of Patients: common in industrialized countries: 1-2% of population have active disease; autopsy studies: 6-population have active disease; autopsy studies: 6-14% for men, 2-6% women14% for men, 2-6% women

Remitting-relapsing lesions, mostly in middle-aged to Remitting-relapsing lesions, mostly in middle-aged to older adultsolder adults

Pathogenesis:Pathogenesis: unclear, but 2 key facts are known: unclear, but 2 key facts are known:– 1) Mucosal exposure to gastric acid & pepsin is a 1) Mucosal exposure to gastric acid & pepsin is a

requisite (requisite (““no acid, no ulcerno acid, no ulcer””))– 2) Strong causal relationship with 2) Strong causal relationship with H. pyloriH. pylori infection infection

PATHOGENESIS OF PATHOGENESIS OF

PEPTIC ULCERPEPTIC ULCER 1) Impaired host defense mechanisms play an essential 1) Impaired host defense mechanisms play an essential

role in gastric ulcers. role in gastric ulcers. Host mechanisms include:Host mechanisms include:

– Surface epithelial mucus secretionSurface epithelial mucus secretion– Bicarbonate secretion into mucus (buffered Bicarbonate secretion into mucus (buffered

environment)environment)– Apical surface membrane transport of acid & pepsinApical surface membrane transport of acid & pepsin– Rapid epithelial regenerative capacityRapid epithelial regenerative capacity– Mucosal blood flow (to remove back-diffused HMucosal blood flow (to remove back-diffused H++

– Mucosal elaboration of prostaglandinsMucosal elaboration of prostaglandins

PATHOGENESIS OF PATHOGENESIS OF

PEPTIC ULCERPEPTIC ULCER 2) 2) Helicobacter pyloriHelicobacter pylori infection: mechanisms: infection: mechanisms:

– Secretion of urease, protease & phospholipasesSecretion of urease, protease & phospholipases– Attracted PMNs release myeloperoxidase, which produces Attracted PMNs release myeloperoxidase, which produces

hypochlorous acid, & monochloramine (in the presence of hypochlorous acid, & monochloramine (in the presence of ammonia)ammonia)

– Colonization & direct damage of mucosal epithelial cells & Colonization & direct damage of mucosal epithelial cells & lamina propria endothelial cells by release of bacterial lamina propria endothelial cells by release of bacterial enzymes & other factors e.g. LPSenzymes & other factors e.g. LPS

– Leakage of tissue nutrients into surface sustaining bacillusLeakage of tissue nutrients into surface sustaining bacillus– Thrombotic occlusion of surface blood vessels by bacterial Thrombotic occlusion of surface blood vessels by bacterial

PAFPAF– Only 10-20% of infected individuals develop PUDOnly 10-20% of infected individuals develop PUD

PATHOGENESIS OFPATHOGENESIS OF

PEPTIC ULCERPEPTIC ULCER Other factors have been associated with PUD:Other factors have been associated with PUD:

– Zollinger-Ellison syndrome: excess gastrin secretion Zollinger-Ellison syndrome: excess gastrin secretion by tumor leading to excess acid productionby tumor leading to excess acid production

– Chronic use of NSAIDs & aspirin suppresses mucosal Chronic use of NSAIDs & aspirin suppresses mucosal PG synthesisPG synthesis

– Cigarette smoking: impairs mucosal blood flow & Cigarette smoking: impairs mucosal blood flow & healinghealing

– Alcohol: unproven direct cause; alcoholic cirrhosisAlcohol: unproven direct cause; alcoholic cirrhosis– Repeated use of high doses of corticosteroidsRepeated use of high doses of corticosteroids– Personality & psycological stressPersonality & psycological stress

PATHOLOGY OF PATHOLOGY OF

PEPTIC ULCERPEPTIC ULCER Usually round sharply punched-out craters 2-4 cmUsually round sharply punched-out craters 2-4 cm Sites:Sites:

– Duodenum: ant. & post. walls of first partDuodenum: ant. & post. walls of first part– Stomach: Lesser curvatureStomach: Lesser curvature

Associated chronic gastritis (DU 85-100%;GU 65%)Associated chronic gastritis (DU 85-100%;GU 65%) Histology: 4 zones: Histology: 4 zones:

– 1) base of thin necrotic fibrinoid debris 1) base of thin necrotic fibrinoid debris – 2) active nonspecific inflammation, underlied by 2) active nonspecific inflammation, underlied by – 3) granulation tissue & 3) granulation tissue & – 4) fibrous collagenous scar4) fibrous collagenous scar

With healing, crater fills with granulation tissue, with With healing, crater fills with granulation tissue, with re-epithelialization from margins, nearly restoring re-epithelialization from margins, nearly restoring normal architecture with a fibrous scar remainingnormal architecture with a fibrous scar remaining

CLINICAL FEATURES OF CLINICAL FEATURES OF

PEPTIC ULCERPEPTIC ULCER Chronic remitting & relapsing diseaseChronic remitting & relapsing disease c/o epigastric pain, worse at nights, 1-3 hrs after c/o epigastric pain, worse at nights, 1-3 hrs after

meals, may be relieved by alkalis or food; meals, may be relieved by alkalis or food; nausea, vomiting, bloating, belching, weight loss nausea, vomiting, bloating, belching, weight loss

May present with complications: May present with complications: – hemorrhage: minimal to massivehemorrhage: minimal to massive– Perforation:uncommon but serious; peritonitis Perforation:uncommon but serious; peritonitis – Pyloric channel obstruction: rarePyloric channel obstruction: rare– Malignant Malignant ““transformationtransformation””: gastric ulcers: gastric ulcers

Rx: medical & surgicalRx: medical & surgical

PEPTIC ULCERPEPTIC ULCERGASTRIC ULCERGASTRIC ULCER DUODENAL ULCERDUODENAL ULCER M:F= 1.5-2:1M:F= 1.5-2:1 Genetics plays no roleGenetics plays no role Low-to-normal acid outputLow-to-normal acid output Major cause: decreased Major cause: decreased

mucosal resistance mucosal resistance against acid & pepsinagainst acid & pepsin

H. pyloriH. pylori present in 70% present in 70% Pain within 30 min. after Pain within 30 min. after

meal, not relieved by meal, not relieved by eatingeating

Associated with malignant Associated with malignant ““transformationtransformation””

M:F=3:1M:F=3:1 Genetics play important roleGenetics play important role Higher acid outputHigher acid output Major cause: Exposure of Major cause: Exposure of

mucosa to excessive mucosa to excessive amounts of acid & pepsin amounts of acid & pepsin

H. pyloriH. pylori present in all cases present in all cases Pain 1.5-3 hrs after meal, Pain 1.5-3 hrs after meal,

relieved by ingestion of milk relieved by ingestion of milk or foodor food

Malignant transformation is Malignant transformation is unknownunknown

PATHOLOGY OF THE STOMACHPATHOLOGY OF THE STOMACH ACUTE GASTRIC ULCERSACUTE GASTRIC ULCERS

Acute stress erosions & ulcers: focal gastric mucosal Acute stress erosions & ulcers: focal gastric mucosal defects that develop acutely after severe stress: defects that develop acutely after severe stress: – shock shock – extensive burns (Curlingextensive burns (Curling’’s ulcers)s ulcers)– severe trauma, including major surgery, sepsis ..severe trauma, including major surgery, sepsis ..– conditions with increased intracranial pressure, e.g. conditions with increased intracranial pressure, e.g.

hemorrhage, trauma, surgery, tumor (Cushinghemorrhage, trauma, surgery, tumor (Cushing’’s ulcers). s ulcers). Pathogenesis: Gastric acid hypersecretion, systemic Pathogenesis: Gastric acid hypersecretion, systemic

acidosis, vagal stimulation, gastric mucosal hypoxia, acidosis, vagal stimulation, gastric mucosal hypoxia, exogenous ulcerogenic agents (alcohol, smoking, caffeine, exogenous ulcerogenic agents (alcohol, smoking, caffeine, aspirin..) may potentiate appearance of stress ulcersaspirin..) may potentiate appearance of stress ulcers

Pathology: Small, one/multiple, variable depth, no gastritisPathology: Small, one/multiple, variable depth, no gastritis

STOMACHSTOMACH

TUMORSTUMORS Benign gastric tumors are more common than Benign gastric tumors are more common than

malignant tumors, but infrequently cause clinical malignant tumors, but infrequently cause clinical problems; reported in 5-25% of autopsiesproblems; reported in 5-25% of autopsies

Classification of benign tumors:Classification of benign tumors:– PolypsPolyps– GI Stromal tumors (GIST): spindle cell tumorsGI Stromal tumors (GIST): spindle cell tumors– Lipomas, hemangiomas, granular cell tumors, Lipomas, hemangiomas, granular cell tumors,

heterotopic pancreatic restsheterotopic pancreatic rests Classification of malignant tumors:Classification of malignant tumors:

– CarcinomasCarcinomas– LymphomasLymphomas– Sarcomas (malignant GI stromal tumors)Sarcomas (malignant GI stromal tumors)

TUMORS OF THE STOMACHTUMORS OF THE STOMACH

GASTRIC POLYPSGASTRIC POLYPS Nodule projecting above level of surrounding mucosaNodule projecting above level of surrounding mucosa 2-6% of patients undergoing endoscopy; 0.5% of 2-6% of patients undergoing endoscopy; 0.5% of

autopsiesautopsies Classification: Classification:

– 1) Hyperplastic (inflammatory) polyps [85%] & 1) Hyperplastic (inflammatory) polyps [85%] & fundic gland polyps [10%]; no malignant fundic gland polyps [10%]; no malignant transformationtransformation

– 2) Multiple hamartomatous polyps (Peutz-Jeghers 2) Multiple hamartomatous polyps (Peutz-Jeghers syndrome): raresyndrome): rare

– 3) Neoplastic polyps (tubular adenoma or villous 3) Neoplastic polyps (tubular adenoma or villous adenoma) [5%]: contain dysplastic epithelium, 50% adenoma) [5%]: contain dysplastic epithelium, 50% chance of malignant transformationchance of malignant transformation

TUMORS OF THE STOMACHTUMORS OF THE STOMACH

GASTRIC CARCINOMAGASTRIC CARCINOMA Approximately 90% of gastric malignant tumorsApproximately 90% of gastric malignant tumors Variable geographic distribution: Japan, Latin America ..Variable geographic distribution: Japan, Latin America .. 3% of all cancer; dismally poor px: 5 yr survival 5-15%3% of all cancer; dismally poor px: 5 yr survival 5-15% Histologic types of gastric adenocarcinoma:Histologic types of gastric adenocarcinoma:

– 1) Intestinal type1) Intestinal type– 2) Gastric diffuse type2) Gastric diffuse type

Risk factors (for intestinal type):Risk factors (for intestinal type):– Diet: nitrites, smoked & pickled food, salt, ...Diet: nitrites, smoked & pickled food, salt, ...– Gastric disease: H. pylori, intestinal metaplasia, ...Gastric disease: H. pylori, intestinal metaplasia, ...– Altered anatomy: post-subtotal gastrectomyAltered anatomy: post-subtotal gastrectomy

Table 17-5. Factors Associated with Increased Incidence of Gastric Carcinoma

Environmental FactorsInfection by H. pylori

•Present in most cases of intestinal-type carcinoma

Diet

•Nitrites derived from nitrates (water, preserved food) •Smoked and salted foods, pickled vegetables, chili peppers •Lack of fresh fruit and vegetables

Low socioeconomic statusCigarette smoking

Host FactorsChronic gastritis

•Hypochlorhydria: favors colonization with H. pylori •Intestinal metaplasia is a precursor lesion

Partial gastrectomy

•Favors reflux of bilious, alkaline intestinal fluid

Gastric adenomas

•40% harbor cancer at time of diagnosis •30% have adjacent cancer at time of diagnosis

Barrett esophagus

•Increased risk of gastroesophageal junction tumors

Genetic Factors

Slightly increased risk with blood group A

Family history of gastric cancer

Hereditary nonpolyposis colon cancer syndrome

Familial gastric carcinoma syndrome (E-cadherin mutation

GASTRIC ADNENOCARCINOMAGASTRIC ADNENOCARCINOMA

INTESTINAL TYPE DIFFUSE TYPEINTESTINAL TYPE DIFFUSE TYPE Arise from gastric Arise from gastric

mucous cells that have mucous cells that have undergone intestinal undergone intestinal metaplasiametaplasia

Proliferation of well Proliferation of well formed glandsformed glands

Expanding growthExpanding growth Well or moderately Well or moderately

differentiateddifferentiated Associated with risk Associated with risk

factorsfactors Usually >50 yrs; M>FUsually >50 yrs; M>F DecreasingDecreasing in frequencyin frequency

Arise de novo Arise de novo from native from native gastric mucous gastric mucous cells cells

Proliferation of Proliferation of ““signet-ringsignet-ring”” cells cells

Infiltrative growthInfiltrative growth Poorly differentiatedPoorly differentiated Undefined risk Undefined risk

factorsfactors Usually <50 yrs; M=F Usually <50 yrs; M=F Increasing in Increasing in

frequencyfrequency

PATHOLOGY PATHOLOGY

GASTRIC CARCINOMAGASTRIC CARCINOMA Sites: Pylorus & antrum 50-60%, cardia 25%, body Sites: Pylorus & antrum 50-60%, cardia 25%, body

& fundus 15-25%; lesser 40% & greater curvature & fundus 15-25%; lesser 40% & greater curvature 12%12%

Gross appearance: Gross appearance: »1) Exophytic 1) Exophytic »2) Flat or depressed (focal effacement of 2) Flat or depressed (focal effacement of

mucosa or linitis plastica) mucosa or linitis plastica) »3) Excavated (ulcer-like)3) Excavated (ulcer-like)

Histology: Dysplasia carcinoma in situHistology: Dysplasia carcinoma in situ Depth of invasion (stage):Depth of invasion (stage):

»Early gastric carcinoma: confined to mucosa Early gastric carcinoma: confined to mucosa & submucosa regardless of LN status& submucosa regardless of LN status

»Advanced gastric carcinoma: extended Advanced gastric carcinoma: extended beyond submucosabeyond submucosa

CLINICAL FEATURES OF CLINICAL FEATURES OF

GASTRIC CARCINOMAGASTRIC CARCINOMA Early gastric carcinoma is generally Early gastric carcinoma is generally

asymptomatic; usually discovered by endoscopy asymptomatic; usually discovered by endoscopy while screening persons at high risk; excellent while screening persons at high risk; excellent prognosisprognosis

Advanced carcinoma may be asymptomatic; may Advanced carcinoma may be asymptomatic; may cause abdominal discomfort, weight loss, or cause abdominal discomfort, weight loss, or obstructive symptoms; dismal prognosisobstructive symptoms; dismal prognosis

Spread to regional & distant lymph nodes; earliest Spread to regional & distant lymph nodes; earliest lymph node metastasis may be to supraclavicular lymph node metastasis may be to supraclavicular (Virchow(Virchow’’s) LNs) LN

Krukenberg tumor: intraperitoneal spread of Krukenberg tumor: intraperitoneal spread of gastric carcinoma to both ovariesgastric carcinoma to both ovaries

TUMORS OF THE STOMACHTUMORS OF THE STOMACH

GASTRIC LYMPHOMAGASTRIC LYMPHOMA May be primary or secondaryMay be primary or secondary GL represent 5% of all gastric malignaciesGL represent 5% of all gastric malignacies Classification similar to nodal lymphoma; mostly B-cell Classification similar to nodal lymphoma; mostly B-cell

typetype Stomach is the most common site of extranodal Stomach is the most common site of extranodal

lymphomas (20%)lymphomas (20%) Patients: middle aged & elderly; clinical features depend Patients: middle aged & elderly; clinical features depend

on type, grade and stage of lymphomaon type, grade and stage of lymphoma MALT (mucosa-associated lymphoid tissue) lymphomas MALT (mucosa-associated lymphoid tissue) lymphomas

(MALToma) are most common: (MALToma) are most common: – low grade, limited to mucosa or submucosalow grade, limited to mucosa or submucosa– lymphoepithelial lesions are characteristiclymphoepithelial lesions are characteristic– hypothesized to be related to hypothesized to be related to H. pyloriH. pylori gastritis, with gastritis, with

chronic antigenic stimulation giving rise to one or more chronic antigenic stimulation giving rise to one or more clones of lymphoid cellsclones of lymphoid cells

– Px: relatively good;Rx: antibiotics, surgery, chemoPx: relatively good;Rx: antibiotics, surgery, chemo