GASTRIC PATHOLOGY

GASTRITIS
ü Gastritis – a symptomatic or asymptomatic condition caused by various etiological agents,
characterized by inflammation of the gastric mucosa
ü Gastropathy – epithelial and / or vascular changes, without inflammation

Clinical –may be manifested by dyspeptic syndrome (dyspepsia = pain / discomfort in the upper abdominal
region , persistent / recurrent)
Endoscopic – macroscopic changes in the mucosa can be seen
Histopathological-the presence of inflammation confirms the diagnosis

Classification
¢ Acute gastritis: transient evolution, defined histologically by the presence of an acute inflammatory
infiltrate, occurring in a characteristic clinical context
¢ Chronic gastritis: the most common forms, characterized by a long evolution, defined histologically by
the presence of chronic inflammatory infiltrate

Sydney Classification of Gastritis (revised in 1994) -integrates clinical, endoscopic and histopathological
features

Sydney classification
 From an endoscopic point of view, it has been described:
- erythematous-exudative gastritis
- maculo-erosive gastritis
- papulo-erosive gastritis
- atrophic gastritis
- hemorrhagic gastritis
- gastritis of entero-gastric reflux
– gastritis with hypertrophic folds

 Topographically, 3 types of gastritis are described:

o antral gastritis
o gastritis of the gastric body
o pangastritis

Histologically, the following criteria are described

Chronic inflammation Predominence of lymphopllasmacytic infiltrate

Acute inflammation PMNs predominate over lymphocytes

Activity PMN infiltrate into the lamina propria, crypts,

surface epithelium, in the presence of chronic
inflammation
Atrophy Loss of specialized glands in the body / gastric
cavity
Intestinal metaplasia Subtypes of intestinal metaplasia of the foveolar and
superficial epithelium
H pylori infection Presence of H pylori in surface epielium
The etiological classification refers to:
Pathogen agent
Bacteria H pylori
H heimannii
Α-hemolytic streptococcus Staphylococcus Clostridium welchii
E. Coli
Proteus
Bacil Koch
Treponema pallidum
Viruses Herpes-virus
Cytomegalovirus
Fungous Candida
Histoplasm capsulatum Cryptococcus
Parasites and nematodes Toxoplasma
Strongiloids Cryptosporidium

Etiologicsl classification:

Patogen agent
Drugs Aspirin, NSAIDs
Associated conditions Alcohol
Liver cirrhosis
Stress gastritis
Stomach resected
Gastric localization in chronic diseases of Crohn's disease
the digestive tract Eosinophilic gastritis
Autoimmune causes Atrophic gastritis
Lymphocytic gastritis

Clinical picture
Ø Asymptomatic – common
Ø Dyspeptic manifestations
Ø Anemia
Ø Upper gastrointestinal bleeding

Treatment
- Hygienic diet
- Elimination of the etiological agent
Ø Stop alcohol
Ø NSAIDs
Ø Eradicate H pylori
- Drugs:
¢ Protectors of the gastric mucosa (Sucralfate)
¢ Antacids (Maalox, Gaviscon)
¢ Antisecretory (anti-H2, PPI)
 ACUTE GASTRITIS

Classification:
v Acute erosive and hemorrhagic gastritis:
- lesions occurring shortly after the contact of the gastric mucosa with various substances or after
decreased mucosal blood flow
- endoscopy - antral lesions in the etiology of NSAIDs, fornix and gastric body in stress gastritis; eroded
spots, bloody crusts, bleeding spots, cloths
- etio-pathogenesis: etiological factors act directly / indirectly on the gastric mucosa by decreasing the
level of prostaglandins or mucosal ischemia characterized by short-term lesions
- causes: aspirin / NSAIDs, alcohol, particular clinical situations - stress gastritis
v Acute H pylori positive gastritis - frequently acquired at a young age; In the absence of treatment, it
progresses slowly to the stage of chronic atrophic gastritis, with loss of antral glandular structures,
gastric body or extended to the entire stomach
v Acute phlegmonous and suppurative gastritis

Classification:
¢ Atrophic gastritis - characterized by a reduction in the number of glands and replacement of the gastric
epithelium with another type of epithelium (metaplasia). There are 2 main types of atrophic gastritis
¢ atrophic gastritis of the gastric body (autoimmune, type A) -predominantly antral
¢ atrophic gastritis (caused by environmental factors, type B)
¢ Chronic gastritis H pylori +
¢ Lymphocytic gastritis - uncertain pathogenesis, but there are arguments in favor of the involvement of H
pylori; the endoscopic appearance is papulo-erosive gastritis, located in the body. The diagnosis is
established histologically, after taking biopsies
¢ Eosinophilic gastritis

Chronic autoimmune atrophic gastritis

 autosomal dominant inherited disease
- is characterized by the presence of anti-intrinsic factor and anti-parietal cell antibodies, specifically
directed against the proton pump in the parietal cell
- loss of parietal cell mass causes hypochlorhydria, deficiency in intrinsic factor synthesis and
insufficient absorption of vitamin B12 and pernicious anemia
- clinically silent until vitamin B12 deficiency becomes apparent
- megaloblastic anemia with degenerative neurological phenomena (paresthesias and difficulty
walking)
 substitute treatment with vitamin B12 throughout life

Atrophic gastritis predominantly antral type B

- ubiquitous disease with increasing incidence with age- more common in people with low socio-
economic status
- histopathological - multiple, focal lesions, with predominantly antral damage; in the initial stages the
changes are located at the level of the gastric angle and the small curvature- extrinsic factors (microbial,
dietary, etc.) are involved in the pathogenesis, especially H pylori
- the symptoms are nonspecific; is frequently associated with gastric ulcer and gastric type cancer
- diagnosis: endoscopic + biopsies from the gastric angle, small curvature and antrum
Helicobacter pylori chronic gastritis
- Helicobacter pylori - Gram negative bacillus, spiral, flagellate, microaerophilic, urease producer, living in
the gastric mucosa
- transmission is fecal-oral, oral-oral, gastro-oral
- the harmful effect of H pylori is due to the direct and indirect action (immune-inflammatory)
- the natural history of chronic gastritis H pylori + is staged, progressive, from chronic non-atrophic gastritis
to chronic atrophic gastritis with intestinal metaplasia and predominantly antral localization
- clinical - most are asymptomatic; dyspeptic manifestations may occur
- positive diagnosis:
- gastric biopsy + histological examination
- rapid urease test (min 2 biopsies of the antrum and one biopsy of the gastric body)
- serological tests - not recommended for eradication
- fecal test - for diagnosis and verification of eradication
- carbon-urea respiratory test - for diagnosis and eradication verification
- bacterial cultures

Treatment (Maastricht V):

- triple therapy (first line): PPI standard dose x 2 / day + Amoxicillin 2x1000 mg / day + Metronidazole
2x500 mg / day or Clarithromycin 2x500 mg / day, 7 days
- quadruple therapy (2nd line): PPI + Metronidazole + Tetracycline + Colloidal Bismuth, 14 days
- sequential therapy: PPI + antibiotic, 7-10 days, then PPI + another antibiotic, 7-10 days
- rescue therapy: PPI + amoxicillin + quinolone (levo / moxifloxacin), 10-14 days

GASTRIC AND DUODENAL ULCER

Definition: limited loss of substance of the gastric or duodenal mucosa beyond the muscular mucosa,
surrounded by acute or chronic inflammatory infiltrate or by a process of fibrosis

- Duodenal ulcer (UD) - most common in the first part of the duodenum; surrounding mucosa appears
congested, edematous, bleeding or friable (duodenitis)
- Gastric ulcer (UG) - most commonly seen on the small curvature near the gastric angle, but can be
located in any part of the stomach
- UD affects about 10% of the adult population and is 2-3 times more common than UG
- There is a trend of a rapid decline in the rate of peptic ulcer in the young male population and an
increase in the elderly, especially in the case of women
- Both UD and UG are common in the elderly

Pathophysiology -> UG and UD occur as a result of an imbalance between:

Defense factors (low)

o Mucus and bicarbonate secretion
o Epithelial integrity
o Local prostaglandins
o Integrity of local microcirculation

Factori de agresiune (crescuți)

o Hydrochloric acid
o Pepsin
o Gastroduodenal reflux
Defense factors:
v Mucus:
- secreted by the mucous gastric epithelium and the Brunner glands of the duodenum
- slows down the H + backscatter and facilitates their buffering by bicarbonate
- Bicarbonate: contributes to the pH gradient between the gastric lumen and the surface of the
epithelium
- Gastric epithelium: tight interepithelial junctions cause impermeability to H + ions
- Local prostaglandins:
- maintain local blood flow and epithelial integrity
- stimulates mucus and bicarbonate secretion
- Local blood flow: maintains the mucosal barrier
Aggression factors:
Hydrochloric acid:
o produced by the oxyntic mucosa of the body and fundus region
o Most patients with UD - acid hypersecretion
o Patients with UG - normo or hypochlorhydria
Pepsin:
 Secreted inactive by parietal cells
 Requires acidic medium to activate pepsinogen
Duodeno-gastric reflux: bile acids, lysolecithin, pancreatic proteases can lead to reflux gastritis and ulcers

PATHOGENESIS -> 2 etiopathogenic factors involved :

H pylori:
o ulcer infection rate = 90-95%
o H pylori-induced gastritis affects the antrum in patients with associated UD and extends into the oxyntic
region in those with UG
o decreases the resistance of inflamed gastric mucosa to the effect of HCl -> UG
o colonization of the duodenum with islands of gastric mucosa and local H pylori infection -> UD
NSAIDs consumption:
o Local mechanisms: NSAID interaction with surface phospholipids;
o direct toxic effect by capturing intracellular NSAIDs: depletion of ATP by blocking oxidative
phosphorylation, decreasing local intracellular ATP reserves -> increasing mucosal permeability by
altering intercellular junctions and facilitating the effect of aggression factors
o Systemic mechanism: vascular ischemia -> inhibition of COX 1 -> decrease in prostaglandins with
vasodilating effect
Other contributing factors:
Ø smoking:
- increases chlorhydropeptic secretion
- decreases the synthesis of mucus, bicarbonate and prostaglandins
- decreases local blood flow
Ø genetic factor: DU – more common in patients' relatives
Ø stress and nutrition :coffee, alcohol, excitatory foods can exacerbate ulcers; stress can make painful
outbursts worse

CLINICAL PICTURE
§ Epigastric pain (burning / tingling / gnawing / epigastric fullness), characterized by:
§ rhythmicity - in UD, improves after ingestion of food, reappears late postprandial, at 1.5-3 h, or at night;
in UG, it appears early postprandial
§ periodicity - painful periods lasting days or weeks, separated by asymptomatic periods seasonal
§ character - shoots appear more frequently in spring and autumn
 § Accompanying symptoms: nausea, vomiting, weight loss, heartburn or regurgitation in patients with
hyperacidity
POSITIVE DIAGNOSIS
¢ Clinical signs + symptoms
¢ laboratory explorations

INVESTIGATIONS

Upper digestive endoscopy

- Examination of choice in establishing the diagnosis
- Visualize ulcer, bleeding stigmas, guide malignancy / benign, allow biopsy sampling, document healing,
and allow diagnosis of H pylori by antral and body biopsy
- UD has the endoscopic appearance of a small lesion, sometimes in the mirror (kissing ulcer); no biopsy
required
- UG requires multiple biopsies (4-8)

Bening GU malignant GU
Round / oval base, white Irregular appearance Neighboring mucosa with erosions
Smooth, regular edges Nodular edges, irregularly colored
Convergent folds to the base Convergent folds to the base

Barium swallow
v It has been replaced in importance by EDS
v Niche - extra filling on the contour of the stomach or duodenum
v Duodenal niche - small size, more common on the stomach lining
v Gastric niche - more often on the small curvature in the vertical part; Benign UG has small base,
protruding outline, perilesional halo and symmetrical folds, converging to the niche

Evaluation of gastric secretory status –useful in Zollinger-Ellison sd (hyperchlorhydria and gastrinemia)

Evaluation of H pylori infection :

- rapid urease test (min 2 biopsies of the antrum and one biopsy of the gastric body)
- serological tests
- fecal test
- carbon-urea respiratory test
- bacterial cultures

DIFFERENTIAL DIAGNOSIS
¢ Gastric cancer
¢ Non-ulcer dyspepsia
¢ Gastritis, gastropathy
¢ GERD
¢ Irritable bowel syndrome
¢ Gallbladder / bile duct disorders
¢ Chronic pancreatitis
¢ Zollinger-Ellison syndrome - presents as UG or UD, solitary, with severe evolution and lack of
response to treatment
COMPLICATIONS

Bleeding:
¢ the most common complication occurs in 15-50% of ulcers, sometimes as the first manifestation
¢ precipitated consumption of NSAIDs
¢ manifests as hematemesis, melena or hematochezia + signs of anemia (pallor, lipothymia, cold sweats,
thirst, nausea, hypotension, tachycardia) diagnosis: rectal cough, nasogastric aspiration, endoscopy
Perforation:
¢ the most serious complication
¢ occurs in 2-10% of cases
Ulcer related stenosis:
¢ occurs in 2% of all ulcers, juxtapylar or duodenal
¢ it is manifested by daily vomiting, early satiety or abdominal distension
Penetration:
- rare complication in the case of old ulcers
- posterior ulcers penetrate more frequently
- smoking, anti-inflammatory promotes the appearance of penetration

THERAPEUTIC PRINCIPLES

v Objectives:
- Improving symptom
-Healing the ulcerative lesion
- Changing natural history
- Prevention and treatment of complications
v Therapeutic means
- Hygienic diet
- Pharmaceutical treatment
- Endoscopic treatment
- Surgical treatment

Hygienic diet
¢ Quitting smoking, alcohol, avoiding spices - promotes healing
¢ Avoid fried foods, citrus fruits, fruit juices, carbonated drinks
¢ Avoiding NSAIDs

DRUGS
Antacids
Ø Fast effect, low effectiveness
Ø It is administered 6-7 times / day
Ø Antacid substances contain aluminum and magnesium hydroxide, calcium carbonate and baking soda
Ø Most products combine the laxative effect of Mg with the constipating effect of Al
Ø Ex. Maalox, Almagel
Mucoasal protectors
- action at the level of protective and antisecretory factors
- Forms a protective barrier on the surface with the ulcer lasting 12 hours Inhibits pepsin and blocks the
harmful effects of bile salts
- Prostaglandin secretion increases
- Ex. Sucralfate 1 gx4 / day - rarely on its own
Antisecretories
H2 receptor antagonists– competitively inhibits H2 receptors in the parietal cell membrane; ex. Ranitidine,
Famotidine etc
Proton pomp inhibitors PPIs:
¢ the strongest inhibitors of acid secretion;
¢ blocks the final stage of H-synthesis by the parietal cell nocturnal secretory rebound effect (nocturnal
loss of acid secretion inhibitory effect)
¢ Side effects: long-term administration increases the risk of infections, hypomagnesaemia, osteoporosis
¢ Ex. Omeprazole, Esomeprazole, Rabeprazole, Lansoprazole, Pantoprazole
¢ It is given in standard doses for 4 weeks in the UD and 8 weeks in the UG, respectively
¢ Antibiotic treatment - to eradicate H pylori infection

ENDOSCOPIC TREATMENT
- It addresses complications
Ø Endoscopic hemostasis in upper GI bleeding
Injecting 1 / 10,000 adrenaline solution will be used in combination with another method of endoscopic
treatment
Ø The clips or thermocoagulation can be used alone or in combination with the injection of adrenaline
solution
Ø Endoscopic dilation of pyloric stenosis -
Ø with pneumatic balloon under direct or fluoroscopic control
Ø Endoscopic mucosectomy ( ESD)
Ø for gastric ulcerated lesions with dysplasia
Ø for gastric cancer "in situ" in carefully selected cases

SURGICAL TREATMENT
¢ Absolute indications: perforation, penetration
¢ GU with operative indication
¢ Forms refractory to correct treatment after 2 months
¢ Life-threatening bleeding that cannot be treated endoscopically
¢ Biopsied ulcers with malignant cells
¢ DU with operative indication
¢ Life-threatening bleeding that cannot be treated endoscopically
¢ Pyloric stenoses that cannot be dilated endoscopically

MONITORING
¢ At 4-6-8 weeks
¢ Clinical, endoscopic
¢ DU does not require endoscopic reassessment
¢ GU requires repeat EDS + multiple biopsy sampling
 GASTRIC CANCER
INCIDENCE
¢ The third leading cause of cancer death in the world
¢ 90% of cases – ADK
¢ The incidence among men is twice as high as among women
¢ the incidence of gastric cancer increases with age (maximum incidence 50-70 years) and is rarely seen
below the age of 30 years.
¢ High mortality - Japan, Costa Rica, Chile, China, former USSR countries
¢ Low mortality - Western Europe, North America

ETIOPATHOGENIC FACTORS
 H pylori infection - first order carcinogen
 Diet rich in canned / salted foods and low in vitamin C, beta-carotene and fresh
fruit; A high-salt diet is likely to increase the risk of developing gastric cancer.
 Food nitrates can be converted to nitrosamines by bacteria at neutral pH;
Nitrosamines are present in the stomach in patients with achlorhydria, who are
at increased risk of developing cancer.
 Smoking increases the risk of gastric cancer Genetic and hereditary factors
 Precancerous conditions (adenomatous polyps, resected stomach)

CLASSIFICATION
Ø Depending on the depth of the invasion:
- early gastric cancer, affecting only the mucosa, with / without involvement of the submucosa, with / without
lymph node involvement
- advanced gastric cancer, which exceeds the submucosa

Histologically, 2 forms are described:

- Diffuse type
- Intestinal type

Clasificarea Lauren a cancerului gastric

Criteria Intestinal type Diffuse type
Grade of differentiation Well differentiated (gland Undifferentiated (isolated malignant cells,
formation) solitary or in nests)
Association with yes No
intestinal metaplasia
macroscopic Well circumscribed (polypoid or Indistinct edges (plastic dash)
appereance ulcerated)
Dissemination Early hepatic Early peritoneal
Epidemiology It is common in areas with a high Equal frequency in high-incidence and low-
incidence, in males and the elderly incidence areas, more common in young people
and females
Prognosis Better than the diffuse type infaust

POSITIVE DIAGNOSIS
 Clinical examination + anamnesis
 Radiological examination
 Gastroscopy + biopsies / cytology by brushing
  ! The definite diagnosis is given by the histopathological examination

CLINICAL PICTURE
Asymptomatic (80% of cases)
Dyspeptic manifestations
In advanced forms may appear:
Upper abdominal discomfort with insidious onset, ranging from vague postprandial fullness to constant, severe
pain
Significant weight loss
Early satiety (plastic line),
nausea and vomiting in tumors affecting the pylorus
Dysphagia in tumors affecting the cardia
Sometimes selective anorexia (meat)
Sclerotegumentary pallor (occult bleeding, rarely hematemesis and / or melena)

Long-term evolution with regional extension - Palpable tumor mass in the epigastrium
Metastases:
¢ Lymph nodes: left supraclavicular lymphadenopathy (Virchow-Troisier)
¢ Peritoneal: Blumer's sign (palpable Douglas sac bottoms palpable on rectal or vaginal examination);
¢ neoplastic ascites, ovarian determinations (Krukenberg)
¢ Periumbilical region: Sister Mary Joseph's nodule
¢ Hepatic: irregular hard hepatomegaly, jaundice
Paraneoplastic syndromes:
migratory thrombophlebitis, microangiopathic haemolytic anemia, acanthosis nigricans, seborrheic dermatosis,
itchy skin

INVESTIGATIONS
Radiological examination
v May show tumors with diam. 5-10 mm
v Superior EDS in plastic linitis
v He can't give up early forms
v Appearance: vegetative
formation ulcer(giant niche)
infiltrative formation

Upper Endoscopy
v allows biopsies to be taken for histopathological examination up to 8-10 biopsies should be taken from
the suspected lesions
v Diffuse gastric cancer infiltrates the submucosa and muscularis propria and may remain undetected on
endoscopic examination, being useful to take multiple, deep biopsies
v advanced gastric cancer - vegetative / ulcerated / infiltrative appearance
v early gastric cancer - polypoid appearance / ulceration / mucosal discoloration

STAGING
CT scan of the chest and abdomen may show gastric wall thickening, lymphadenopathy, and metastatic
pulmonary and hepatic spread - limited ability to determine the depth of local tumor invasion
Endoscopic ultrasound
- useful for local tumor staging - highlights the depth of the tumor invasion at the level of the gastric wall
and the extension to the locoregional lymph nodes –
- is the most important investigation to confirm if the tumor is limited to the superficial mucosa, before
performing endoscopic resection
Laparoscopy may be considered in candidates for surgery to rule out peritoneal invasion
PET CT useful for further delimitation of the tumor
TNM classification is used for staging category
T (primary tumor) indicates the depth of tumor invasion category
N denotes the presence or absence of lymph node invasion category
M indicates the presence or absence of distant metastases
Depending on the TNM classification, steps 0-4 are described below

DIFFERENTIAL DIAGNOSIS
 Benign gastric ulcer (biopsies and endoscopic control)
 Malignant lymphoma
 Benign tumors (leiomyomas)
 Gastric polyps
 Menetrier gastritis
 Other cancers of the stomach (colon, pancreas)

SCREENING

It is recommended to screen the following categories considered at risk:

Chronic atrophic gastritis with intestinal metaplasia and pernicious anemia - EDS is recommended at min. 5
years + multiple biopsies
Gastric ulcer - is followed endoscopically (+ 6-8 biopsies) at 8 and 12 weeks; if left untreated after 12 weeks
of correct treatment (refractory ulcer) -> maximum dose of PPI is allowed for another 8 weeks or surgery
Stomach resected for gastric cancer - monitored by EDS year + biopsies
Stomach resected for benign diseases - is followed endoscopically at 15-20 years
Gastric adenomas - excision + EDS recommended annually

TREATMENT

- It involves a multidisciplinary team

Surgical treatment
- Healing role - in early or advanced lesions (total / subtotal gastrectomy)
- Palliative role - in advanced and complicated forms with stenosis / HDS
Endoscopic treatment
• Healing role - in early non-ulcerated lesions, limited to the mucosa (endoscopic mucosal resection or
submucosal endoscopic dissection)
• Palliative role - stent mounting in heart cancer or pyloric region; stopping HDS; endoscopic gastrostomy
Radio and chemotherapy - adjuvant or palliative