Cardia

Fundus
Esophagus
Muscularis
externa Serosa
• Longitudinal layer
• Circular layer Body
• Oblique layer
Lesser Lumen
curvature Rugae of
mucosa

Greater
curvature
Pyloric Pyloric
Duodenum canal antrum
Pyloric sphincter
(a) (valve) at pylorus
Figure 23.14a
 Surface
epithelium

Mucosa

Lamina propria
Muscularis
mucosae
Submucosa
(contains submucosal
plexus) Oblique layer

Muscularis externa Circular layer

(contains myenteric
Longitudinal
plexus)
layer
Serosa
Stomach wall
(a) Layers of the stomach wall (l.s.)
 Stimulatory events Inhibitory events

Cephalic 1 Sight and thought Cerebral cortex Lack of Cerebral 1 Loss of

phase of food Conditioned reflex stimulatory cortex appetite,
impulses to depression
2 Stimulation of Hypothalamus Vagus parasym-
taste and smell and medulla nerve pathetic
receptors oblongata center

1 Stomach Vagovagal Medulla Vagus Gastrin G cells 1 Excessive

distension reflexes nerve secretion acidity
activates declines (pH <2)
stretch in stomach
Gastric receptors Local Overrides Sympathetic 2 Emotional
phase reflexes parasym- nervous upset
pathetic system
controls activation
2 Food chemicals G cells Gastrin
(especially peptides and release
caffeine) and rising pH to blood
activate chemoreceptors Stomach
secretory
activity
Entero- Local 1 Distension
gastric reflexes of duodenum;
1 Presence of low Intestinal reflex presence of
pH, partially digested fatty, acidic,
(enteric) Vagal
foods, fats, or hypertonic
gastrin nuclei
hypertonic solution Brief chyme, and/or
Intestinal release in medulla
in duodenum when effect irritants in
phase to blood
stomach begins to Pyloric the duodenum
empty sphincter

Release of intestinal 2 Distension;

hormones (secretin, presence of
cholecystokinin, vasoactive fatty, acidic,
intestinal peptide) partially
digested food
Stimulate
in the
Inhibit duodenum
PEPTIC ULCER DISEASE
•A peptic ulcer is defined as disruption of the
mucosal integrity of the stomach and/or duodenum
leading to a local defect or excavation due to active
inflammation

•Symptom complex:
• Epigastric pain exacerbated by fasting
and improved with meals
• >90% patients with this symptom
complex (dyspepsia) do not have ulcers
• majority of patients may be
asymptomatic

•Epidemiology (US)
• 4 million individuals (new cases and
recurrences) affected per year
• Lifetime prevalence is ~12% in men and
10% in women

•PUD significantly affects quality of life by impairing

overall patient well-being and contributing
substantially to work absenteeism

• an estimated 15,000 deaths per year occur as a

consequence of complicated PUD.
PEPTIC ULCER DISEASE: Etiology

1. Helicobacter pylori-associated
2. NSAID-associated
3. Stress ulcer
4. Acid Hypersecretion
Gastrinoma
Antral G cell hyperfunction/hyperplasia
5. Infections
Viral - HSV Type 1, CMV
6. Others
Epidemiology
DUODENAL ULCERS
• occur in 6–15% of the
Western population
• incidence declined steadily
from 1960 to 1980 and
has remained stable
• death rates, need for
surgery, and physician
visits have decreased by
>50% over the past 30
years.
GASTRIC ULCERS
•GUs tend to occur later in
life with a peak incidence
reported in the sixth decade
•> 1/2 occur in males and are
less common than Dus;
higher likelihood of GUs
being silent and presenting
only after a complication
develops
•Autopsy studies suggest a
similar incidence of DUs and
GUs.
Pathology
DUODENAL ULCERS
• occur most often in the first portion of
the duodenum (>95%)
• usually ≤1 cm in diameter but can
occasionally reach 3–6 cm (giant ulcer)
• sharply demarcated, with depth at
times reaching the muscularis propria
• base of the ulcer often consists of a
zone of eosinophilic necrosis with
surrounding fibrosis.
• malignant DUs are extremely rare
GASTRIC ULCERS
• Malignant GUs
– should be biopsied upon discovery
• Benign GUs
– are most often found distal to the
junction between the antrum and the
acid secretory mucosa.
– quite rare in the gastric fundus and are
histologically similar to DUs
– Benign GUs associated with H. pylori
are also associated with antral gastritis
– NSAID-related GUs have evidence of
a chemical gastropathy, typified by
foveolar hyperplasia, edema of the
lamina propria, and epithelial
regeneration in the absence o H. pylori
Pathophysiology
DUODENAL ULCERS
• H. pylori and NSAID-induced
injury
• increased basal and nocturnal
gastric acid secretion
• decreased bicarbonate secretion
GASTRIC ULCERS
• H. pylori or NSAID-induced mucosal damage
• GUs in the prepyloric area or those in the body
associated with a DU or a duodenal scar are
similar in pathogenesis to DUs
• normal to decreased gastric acid output
(basal and stimulated)
• in the presence of minimal acid levels, impairment
of mucosal defense factors may be present
• classified based on their location:
 Type I occur in the gastric body and tend to be
associated with low gastric acid production
 Type II occur in the antrum and gastric acid can vary
from low to normal
 Type III occur within 3 cm of the pylorus and are
commonly accompanied by DUs and normal or high
gastric acid production
 Type IV are found in the cardia and are associated
with low gastric acid production
PEPTIC ULCER DISEASE: Symptoms

 epigastric pain
hunger-pain-food-relief pattern
relief w/ antacids
 pain/discomfort centered in upper abdomen
 night distress, anorexia, nausea, vomiting,
 bloating, belching, fullness
PEPTIC ULCER DISEASE: Diagnosis

1. Hx and PE
2. Laboratory evaluation
CBC, liver function tests, creatinine, calcium
serum gastrin, serum salicylate, serum group I pepsinogen
3. H. pylori testing
biopsy urease test, histology, urea breath test, serology
4. Acid secretion
BAO, MAO
5. Upper GI radiography
6. Endoscopy
PEPTIC ULCER DISEASE: Differential Diagnosis

1. Functional disorders
2. Gastric CA
3. Drug-induced gastritis/dyspepsia
4. Infiltrative or granulamotous disorders
5. Infectious diseases
6. Biliary tract disease
7. Acute pancreatitis
8. Intestinal ischemia
PEPTIC ULCER DISEASE: Management

1. Acid suppressive agents

PPIs, H2 receptor antagonists,, sucralfate, antacids

2. H. pylori treatment
Clarithromycin, Amoxycillin, Metronidazole

3. Surgery
complications of peptic ulcers
 DRUGS THAT REDUCE GASTRIC ACID SECRETION
DRUG CATEGORY EXAMPLE DAILY DOSE ROUTE OF
ADMINISTRATION

Proton pump inhibitors Omeprazole 20 - 40 mg

Oral, IV
Lansoprazole 15 - 30 mg
Oral
Pantoprazole 20 - 40mg Oral
Receptor antagonists
H2 Cimetidine 800 mg Oral, IV
Ranitidine 300 mg Oral, IV
Nizatidine 300 mg Oral, IV
Famotidine 40 mg Oral, IV
Oral
M3 Atropine/related Varies w/ drug
drugs
M1 Pirenzipine
CCK B L 365, 260/ others

Receptor agonists
PGE agonist Misoprostol 600 - 800 ug Oral
> 100 ug IV
Somatostatin agonist Octreotide
DRUGS THAT REDUCE GASTRIC ACID SECRETION

DRUG CATEGORY EXAMPLE ROUTE OF

ADMINISTR-
Mucosal protective ATION
Agents
Sucralfate Sucralfate p.o.
PG analogues Misoprostol p.o.
Bismuth compounds Bismuth subsalicylate p.o.

Antacids Maalox p.o.

Mg-Al(OH)3 Novaluzid p.o.
Kremil-S p.o.
PEPTIC ULCER DISEASE: Complications

1. Upper GI bleeding
Mgt: endoscopic methods, surgery
2. Gastric outlet obstruction
SSx: early satiety, bloating, epigastric pain, vomiting,
weight loss, nausea
3. Perforation
30-50% NSAID-associated, usually elderly patients
4. Penetration 20%
site: pancreas, gastrohepatic omentum, biliary tract, liver,
greater omentum, mesocolon, colon, vascular structures
ENDOSCOPIC MANAGEMENT

• Injection sclerotherapy
• Endoscopic hemoclipping
• Thermal probe
• Argon Plasma Coagulation
• Others
Helicobacter Pylori
• Prevalence:
• developing parts of the world 80%
• industrialized countries: 20-50%

• Predisposing factors:
• poor socioeconomic status
• low education attainment

• Other risk factors for H. pylori infection:

(1) birth or residence in a developing country
(2) domestic crowding
(3) unsanitary living conditions
(4) unclean food or water
(5) exposure to gastric contents of an infected
individual

• Transmission: person to person following an oral-oral

or fecal-oral route.
Acute Gastritis
H. pylori infection
• acute gastritis.
• chronic gastritis

Bacterial infection of the stomach or phlegmonous

gastritis
• rare, potentially life-threatening disorder
characterized by marked and diffuse acute
inflammatory infiltrates of the entire gastric
wall, at times accompanied by necrosis.
• Elderly individuals, alcoholics, and AIDS
patients may be affected.
• Potential iatrogenic causes: polypectomy and
mucosal injection with India ink
• Organisms: streptococci, staphylococci,
Escherichia coli, Proteus, and Haemophilus
species.
• Mgt: antibiotic Rx; gastrectomy

Other types of infectious gastritis

• may occur in immunocompro-mised
individuals such as AIDS patients.
• herpetic (herpes simplex) or CMV gastritis
• histologic finding of intra- nuclear
inclusions(CMV)
CHRONIC GASTRITIS

•inflammatory cell infiltrate consisting primarily of • Intestinal metaplasia denotes the

lymphocytes and plasma cells, with very scant neutrophil conversion of gastric glands to a small
involvement. intestinal phenotype with small-bowel
mucosal glands containing goblet cells

•Endoscopic and serologic markers of severity

• gross inspection
• classification of mucosal abnormalities during
standard endoscopy, magnification endoscopy,
endoscopy with narrow band imaging and/or
autofluorescence imaging
•Measurement of several serum biomarkers including
pepsinogen I and II levels, gastrin-17, and anti-H. pylori
serologies
• Intestinal metaplasia is an important
predisposing factor for gastric cancer
• Treatment in chronic gastritis is aimed at
the sequelae and not the underlying
inflammation.
• Patients with pernicious anemia will require
parenteral vitamin B supplementation on a
12

long-term basis.

•Phases:
• Eradication of H. pylori is often recommended
• superficial gastritis even if PUD or a low-grade MALT lymphoma is
not present.
• atrophic gastritis.
• gastric atrophy
TYPE A GASTRITIS (Autoimmune)

• less common
• involves primarily the fundus and body, with antral sparing
• associated with pernicious anemia in the presence of
circulating
antibodies against parietal cells and IF
•Antibodies to parietal cells :
• >90% of patients with pernicious anemia
• up to 50% of patients with type A gastritis

• Antibodies to thyroid antigens :

• ½ of patients with PA
• 30% of patients with thyroid disease have circulating
• antiparietal cell antibodies

•Anti-IF antibodies :
• more specific than parietal cell antibodies for type A gastritis
• ~40% of patients with pernicious anemia.
TYPE B GASTRITIS

• Type B, or antral-predominant, gastritis

• more common form of chronic gastritis
•Etio:H. pylori infection
•Increases with age,:age> 70 100%
•Histology improves after H. pylori eradication.
•Multifocal atrophic gastritis, gastric atrophy
with subsequent metaplasia
• Gastric adenoCA, low-grade B cell lymphoma,
MALT lymphoma
•H. pylori infection is now considered an
independent risk factor for gastric cancer
Recommendations for Rx of NSAID-Induced Gastritis

Clinical Setting Recommendation

Active ulcer

NSAID discontinued H2 receptor antagonist or PPI

NSAID continued PPI

Prophylactic therapy Misoprostol

PPI

Selective COX-2 inhibitor

Eradication if active ulcer present or there is a

H. pylori infection
past history of peptic ulcer disease
Guide to NSAID Therapy

No/Low NSAID NSAID GI Risk

GI Risk

No CV Risk Traditional NSAID Coxib or

(no aspirin) Traditional NSAID + PPI
or misoprostol

Consider non-NSAID therapy

CV Risk Traditional NSAID + PPI A gastroprotective agent must

(consider aspirin) or misoprostol if GI risk be added if a traditional NSAID
warrants gastroprotection must be prescribed

Consider non-NSAID therapy Consider non-NSAID therapy

Refractory Ulcers
• Poor compliance
• Persistent Hp infection
• NSAID use
• Cigarette smoking
• Gastric acid hypersecretory
states (e.g. ZES)
• The majority (>90%) of GUs and DUs heal with
the conventional therapy
•
A GU that fails to heal after 12 weeks and a DU
that does not heal after 8 weeks of therapy
should be considered refractory.
• Once poor compliance and persistent H. pylori
infection have been excluded, NSAID use,
either inadvertent or surreptitious, must be
excluded.
• Cigarette smoking must be eliminated
• For a GU, malignancy must be meticulously
•
excluded.
Consideration should be given to a gastric acid
hypersecretory state :
• ZES or the idiopathic form, which can
be excluded with gastric acid analysis.
• Although a subset of patients have
gastric acid hypersecretion of unclear
etiology as a contributing factor to
refractory ulcers
• , ZES should be excluded with a fasting
gastrin or secretin stimulation test
Refractory Ulcers: Management
• More than 90% of refractory
ulcers (either DUs or GUs) heal
after 8 weeks of treatment with
higher doses of PPI (omeprazole,
40 mg/d; lansoprazole 30–60
mg/d).
• Higher doses of PPI • Surgical intervention may be a
consideration
• R/O rare causes: • Other rare causes of refractory
ulcers must be excluded before
recommending surgery.
• Consider surgery • Rare etiologies of refractory ulcers
that may be diagnosed by gastric
or duodenal biopsies include :

ischemia, Crohn’s disease,

amyloidosis, sarcoidosis,
lymphoma, eosinophilic
gastroenteritis, smoking crack
cocaine or infection
(cytomegalovirus [CMV],
tuberculosis, or syphilis).
SURGERY: Indications

• Refractory ulcers
• Hemorrhage not responding to
endoscopic treatment
• Gastric outlet obstruction
• Perforation/ penetration
• Malignancy
Specific Operations for Duodenal
Ulcers
Surgical treatment was originally designed to decrease
gastric acid secretion.

Operations most commonly performed include

(1) vagotomy and drainage (by pyloroplasty,

gastroduodenostomy, or gastrojejunostomy),

(2) highly selective vagotomy (which does not require a

drainage procedure)

(3) vagotomy with antrectomy.

The specific procedure performed is dictated by the

underlying circumstances:
• elective versus emergency
• degree and extent of duodenal ulceration
• etiology of the ulcer (H. pylori, NSAIDs, malignancy)
• expertise of the surgeon.
Specific Operations for GUs

•The location and the presence of a concomitant DU

dictate the operative procedure performed for a GU.

•Antrectomy (including the ulcer) with a Billroth I

anastomosis
• treatment of choice for an antral ulcer.

•Vagotomy is
• performed only if a DU is present.
• Although ulcer excision with vagotomy and
drainage procedure has been proposed, the
higher incidence of ulcer recurrence makes
this a less desirable approach.

•Subtotal gastrectomy w/ a Roux-en-Y

esophagogastrojejunostomy (Csendes’ procedure)
• For Ulcers located near the esophagogastric
junction may require a more radical approach,

•Antrectomy, intraoperative ulcer biopsy, and vagotomy

(Kelling-Madlener procedure)
• may be indicated in fragile patients with a
high GU.
• Less aggressive approach
• Ulcer recurrence approaches 30% with this
procedure.
Complications
Immediate
• Bleeding
• Gastric retention
• Dysphagia
• Leakage of duodenal stump
• Obstruction of the stoma
• Acute pancreatitis
Late
• Dumping syndrome
• Diarrhea
• Steatorrhea
• Enterogastric reflux
• Recurrent ulceration
• Iron deficiency anemia
• Risk of colorectal and
gastric tumors
• Weight loss
• Megaloblastic anemia
• Osteomalacia
• Anastomotic ulcer
• Gastro-jejunocolic fistula
AFFERENT LOOP SYNDROME

Rarely seen today as a result of the decrease in the performance of Billroth II

anastomosis

Two types of afferent loop syndrome:

A. Bacterial overgrowth in the afferent limb secondary to stasis.

• more common
• Patients may experience postprandial abdominal pain,
• bloating, and diarrhea with concomitant malabsorption
• of fats and vitamin B .
12

• Cases refractory to antibiotics may require surgical revision of the loop.

B: Afferent loop syndrome can present with severe abdominal pain and bloating
• less common; occur 20-60 min
• pain is often followed by nausea and vomiting of bile-containing material.
• pain and bloating may improve after emesis
• cause of this clinical picture is theorized to be incomplete drainage of bile and
pancreatic secretions from an afferent loop that is partially obstructed
• cases refractory to dietary measures may need surgical revision or conversion
of the Billroth II anastomosis to a Roux-en-Y gastrojejunostomy.
 DUMPING SYNDROME
series of vasomotor and GI signs and symptoms and occurs in patients who have
undergone vagotomy and drainage (especially Billroth procedures)

Early dumping Late dumping

• takes place 15–30 min after meals • typically occurs 90 min to
• consists of crampy abdominal discomfort, 3 h after meals.
nausea, diarrhea, belching, tachycardia, • Vasomotor symptoms (light-
palpitations, diaphoresis, light-headedness, headedness, diaphoresis,
and, rarely, syncope. palpi- tations, tachycardia,
• arise from the rapid emptying of hyper- and syncope) predominate
osmolar gastric contents into the small during this phase.
intestine, resulting in a fluid shift into the gut •thought to be secondary to
lumen with plasma volume contraction and hypogl cemia from excessive
acute intestinal distention. insulin release.
• Release of vasoactive GI hormones
(vasoactive intestinal polypeptide,
neurotensin, motilin) is also theorized to
play a role in early dumping.
ZOLLINGER-ELLISON SYNDROME

Epidemiology Clinical Manifestations

•0.1 to 1% of individuals presenting with PUD •Peptic ulcer: i>90% of gastri- noma patients.
•Females > males • ulcers in unusual locations (second part of the
• majority of patients are diagnosed between ages 30 and 50. duodenum and beyond),
•Gastrinomas are classified into: • ulcers refractory to stan- dard medical therapy,
• sporadic tumors (80%) • ulcer recurrence after acid-reducing surgery,
• associated with multiple endocrine neoplasia • ulcers presenting with frank complications
• (MEN) type 1 (bleeding, obstruction, and perforation), or ulcers in
the absence of H. pylori or NSAID ingestion
Pathophysiology .
• Hypergastrinemia originating from an autonomous neoplasm is •Symptoms of esophageal : up to two-thirds of patients
the driving force responsible for the clinical man- ifestations in • mild esophagitis to frank ulceration with stricture
ZES. and Barrett’s mucosa.
•The increased gastric acid output leads to peptic ulcer diath-
esis, erosive esophagitis, and diarrhea. •Diarrhea: up to 50% of patients.
• Etiology of the diarrhea is multifactorial, .
Tumor Distribution • Epithelial damage can lead to a mild degree of
•Pancreas: 80%. maldigestion and malabsorption of nutrients.
•Duodenal tumors : 50-75%. • The diarrhea may also have a secretory component
•Extrapancreatic sites include: due to the direct stimulatory effect of gastrin on
• stomach, bones, ovaries, heart, liver, and lymph enterocytes or the co-secretion of additional
nodes. hormones from the tumor such as vasoactive
intestinal peptide.
Prognosis:
•More than 60% of tumors are considered malignant, •MEN 1 syndrome in ~25% of patients.
•Up to 30–50% of patients having multiple lesions or metastatic • This autosomal dominant disorder involves primarily
disease at presentation. three organ sites:
• the parathyroid glands (80–90%), pancreas (40–
Histologically, 80%), and pituitary gland (30–60%).
•gastrin-producing cells appear well-differentiated, expressing • The syn-drome is caused by inactivating mutations
markers typically found in endocrine neoplasms (chromogranin, of the MEN1 tumor sup- pressor gene found on the
neuron-specific enolase). long arm of chromosome 11q13. The gene encodes
for Menin, which has an important role in DNA
replication
ZOLLINGER-ELLISON SYNDROME
Diagnosis Treatment
Fasting gastrin levels: usually <150 pg/mL.
Aims:
• All gastrinoma patients will have a gastrin level >150–200
• ameliorating the signs and symptoms related to
pg/mL. Gastric
hormone overproduction,
Gastric pH:
• curative resection of the neoplasm
• pH <3 is suggestive of a gastrinoma
• control tumor growth in metastatic disease.
• Gastric secretory studies:
• BAO:
Medical Rx:
• Normal BAO in nongastric surgery patients is
•PPIs
typically <5 meq/h.
• are the treatment of choice
• A BAO >15 meq/h in the presence of
• Initial PPI doses tend to be higher than those used
hypergastrinemia is considered pathognomonic of
for treatment of GERD or PUD.
ZES,
•Octreotide or lanreotide
• but up to 12% of patients with common PUD may
• may be considered as adjunctive therapy to the PPI
have elevated BAO to a lesser degree that can
in patients with tumors that express somatostatin
• overlap with levels seen in ZES patients,
receptors and have peptic symptoms that are
• BAO/ MAO ratio using pentagastrin infusion
difficult to control with high-dose PPI.
• BAO/MAO ratio >0.6 being highly suggestive of
Surgery
ZES.
• Sporadic gastrinomas:
Gastrin provocative tests:
• provide a definitive cure
• Secretin test
• immediate cure rates as high as 33% with
• most sensitive and specific gastrin provocative test
10-year disease-free inte vals as high as
for the diagnosis of gastrinoma is the secretin
95% in sporadic gastrinoma patients
study.
undergoing surgery.
• An increase in gastrin of ≥120 pg within 15 min of
• Surgical therapy of gastrinoma patients with MEN 1
secretin injection has a sensitivity and specificity of
• remains controversial because of the
>90% for ZES.
difficulty in rendering these patients
• PPI-induced hypochlorhydria or achlorhydria may
disease-free with surgery
lead to a false-positive secretin test; thus, this agent
• only 6% of MEN 1 patients are disease-free
must be stopped for 1 week before testing.
5 years after an operation.
• Calcium infusion study
• the clinical course of MEN 1 patients is
• less sensitive and specific than the secretin test
benign and rarely leads to disease-related
• clinical characteristics are highly sug- gestive of
mortality, recommending that early surgery
ZES but the secretin stimulation is inconclusive.
be deferred
WHEN TO OBTAIN A FASTING SERUM GASTRIN LEVEL

Multiple ulcers

Ulcers in unusual locations; associated with severe esophagitis; resistant to therapy with frequent recurrences; in
the absence of nonsteroidal anti-inflammatory drug ingestion or H. pylori infection

Ulcer patients awaiting surgery

Extensive family history for peptic ulcer disease

Postoperative ulcer recurrence

Basal hyperchlorhydria

Unexplained diarrhea or steatorrhea

Hypercalcemia

Family history of pancreatic islet, pituitary, or parathyroid tumor

Ménétrier’s disease (MD)

•average age of onset of 40–60 years with a male Diagnosis:

predominance; very rare
• Differential diagnosis (large gastric folds :
ZES, malignancy (lymphoma, infiltrating carcinoma),
infectious etiologies (CMV, histoplasmosis, syphilis,
tuberculosis), gastritis polyposa profunda, and infiltrative
disorders such as sarcoidosis.
•Histologically:
•massive foveolar hyperplasia (hyperplasia of surface
and glandular mucous cells) and a marked reduction in
oxyntic glands and parietal cells and chief cells
• Etiology :
•children - often CMV
•adults - unknown.
Overexpression of the growth factor TGF-α
results in overstimulation of the epidermal growth
•Gastric acid: usually reduced or absent
•Barium studies
•Endoscopy with deep mucosal biopsy, preferably full thickness
with a snare technique,
•Surgically obtained full-thickness biopsy to exclude malignancy.
•Complete blood count, serum gastrin, serum albumin, CMV and
H. pylori serology, and pH testing of gastric aspirate during
endoscopy should be included as part of the initial evaluation of
patients with large gastric folds.
Management:
Medical therapy
•anticholinergic agents, prostaglandins, PPIs, prednisone,
somatostatin analogues (octreotide) and H receptor
2

factor receptor (EGFR) pathway and increased antagonists :yields varying results.
proliferation of mucus cells,
•Standard therapy for Ulcers
resulting in the observed foveolar hyperplasia.
•Clinical presentation :
•Cetuximab
•usually insidious and progre ssive • EGF inhibitory antibody
• Epigastric pain, nausea, vomiting, anorexia, peripheral • considered the first-line treatment for MD
edema, weight loss Surgery
•Occult GI bleeding • severe disease with persistent and substantial protein
•protein-losing gastropathy due to hypersecretion of loss despite therapy
gastric mucus accompanied by hypoalbuminemia and •Total gastrectomy
edema (20-100%)