Chapter 17. Congenital Disorders of the Stomach Flashcards
1
Q
Disorders of the stomach are a frequent cause of clinical disease, with _______________ lesions being common.
A
inflammatory and neoplastic lesions
2
Q
Diseases of the stomach account for nearly _____ of all heath care spending on GI diseases.
A
1/3
3
Q
What are the 4 anatomic regions of the stomach?
A
- Cardia
- Fundus
- Body
- Antrum
4
Q
RECAP:
- ACh and Histamine => parietal cell => _____________
- Prostaglandins => parietal cells => ________________
- Parietal cells are mostly found in ______ and ____ of stomach, not the _____.
A
- ACh and Histamine: ↑ acid production
- Prostaglandins: ↓ acid production
- Parietal cells are found in fundus and body, not antrum
5
Q
What is gastrin?
Released by what?
A
-
Gastrin is a hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach
- Released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
6
Q
The ______ and _____ are lined by mucin-secreting foveolar cells that form small glands.
A
- Cardia
-
Antrum
- However, also contains endocrine cells, like G-cells, => release gastrin that stimulate parietal cells in fundus and body to secrete acid.
7
Q
Glands in the ______ and ________ have chief cells, which produce and secrete digestive enzymes like pepsin.
A
body
fundus
8
Q
What is the difference between erosion and an ulcer?
A
- Erosion: loss of epithelial layer that extends into the muscularis mucosa.
- Ulcer: Loss of the mucosal layer that can extend into [submucosa and muscular layer], are usually focal and mostly occur in the stomach and duodenum.
9
Q
What is gastritis?
A
Inflammation of the mucosa that is often generalized
10
Q
What differentiates Acute Gastritis from Gastropathy?
Causes of each?
A
- Acute gastritis: neutrophils are present
- Causes: Autoimmune or H.pylori
- Gastropathy: gastric mucosal disorder with minimal to no inflammation (no inflammatory cells are present)
- Causes: NSAIDs, EtOH, Bile, Stress
11
Q
Can gastropathy and acute gastritis be distinguished clinically?
A
No
Both cause epigastric pain, N/V. If severe, mucosal erosion, ulceration, hemtaemesis, melena.
12
Q
What mechanisms protect the gastric mucosa?
A
- Surface mucus secretion
- HCO3- secretion into mucus
- Mucosal blood flow
- Epithelial barrier
- Epithelial regeneration
- Prostaglandins
13
Q
What NL mechanisms damage the gastric mucosa?
A
- Gastric acidity
- Peptic enzymes
14
Q
What causes injury to the gastric mucosa?
A
- H. pylori
- NSAIDS
- Tobacco and alochol
- Gastric hyperacidity
- Duodenal-gastric reflux
- Ischemia and shock
15
Q
Ulcers associated with acute and chronic gastritis may include layers of what type of injury? (hint: mnemonic to remember layers)
A
- Necrotic debris
- Inflammation
- Granulation tissue
- Scar (fibrosis)
*NIGS
16
Q
What are causes of acute gastritis?
A
- NSAIDS
- alcohol
- chemo
- H. Pylori
17
Q
NSAIDs contribute to gastritis how?
A
Inhibit synthesis of prostaglandin E2 and I2 by COX => inhibit mucus/bicarb/phospholipid secretion/ mucosal BF, epithelial restitution, => increase acid production.
18
Q
Why are older adults more prone to gastritis?
A
↓ mucin and bicarb
19
Q
What is the morphology seen in acute gastritis?
A
- Surface epithelium is intact
- Foveolar cell hyperplasia that look like corkscrews
- Epithelial proliferation
20
Q
Presence of _________ above the BM in direct contact w/ epithelial cells is abnormal in all parts of the GI tract and signifies active inflammation (acute/chronic gastritis)
A
Neutrophils
21
Q
Concurrent erosion and hemorrhage is called ________.
A
acute erosive hemorrhagic gastritis
22
Q
How is the response to PPI’s different if the patient is suffering from NSAID-induced gastropathy vs. pain associated w/ bile reflux?
A
- NSAID-induced: asymptomatic or have persistent epigastric pain that responds to antacids or PPI’s
- Bile reflux is typically unresponsive and may have occasional bilious vomiting
23
Q
Severe acute gastritis can result in _______.
A
Acute gastric ulcerations
24
Q
Stress-related mucosal diseases occur in patients with severe trauma, burn, incranial diseases, surgery, etc.
Stress ulcers are most common in individuals with what 3 things?
How are they caused?
Common in ______ patients.
A
1) Shock
2) Sepsis
3) Severe trauma
- => decreased mucosal perfusion, causing loss of protective barrier of mucus and bicarb.
- Common among critically ill patients.
- Like Curlings ulcers => all ICU pts are given prophylactic therapy includes PPIs (pantaprazole, omeprazole, etc)
25
_Stress-related mucosal diseases occur in patients with severe trauma, burn, incranial diseases, surgery, etc._
**Ulcers** in the **prox. duodenum** and occur in patients with **burns** or **trauma** are called?
* **Curling ulcers (Think curling irons will burn you!)**
* Loss of skin =\> decrease plasma volume =\> dehydration =\> hypotension to stomach/ mucosa =\> damage mucosa). Result: acute gastritis and ulcers
* Give PPIs to any pt that comes in w burns
26
_Stress-related mucosal diseases occur in patients with severe trauma, burn, incranial diseases, surgery, etc._
## Footnote
**Gastric**, **duodenal**, and **esophageal ulcers** that occur in persons w/ ↑ _intracranial pressure (tumor or hemorrhage)_ are termed?
What causes them?
Increase risk of?
1. **Cushing ulcers**
2. Increased intracranial pressure =\> **Direct stimulation of vagal nuclei =\>** increase ACh to stomach =\> hypersecretion of gastric acid =\> gastritis and ulcers
3. **\*Perforation**
27
The pathogenesis of **stress-related gastric mucosal injury** is most often due to what?
Hypotension, hypoxia or stressed-induced splanchnic vasoconstriction that cause **[local ischemia].**
28
What determines **acute** vs **chronic gastritis**?
**_Types of infiltrates that are seen._**
* **Acute gastritis** = neutrophil infiltration
* Often due to mucosal damage from acids
* **Chronic gastritis** = lymphocytes, plasma cells and MO
* 2 common causes: AI or H.pylori
29
Symptoms of **gastritis**
* **Dyspepsia** (N, V, loss of appetite, abdominal or epigastric pain)
* Worse w/ food because they cause more acid (H+) secretion.
30
What are the causes of ischemia seen in **stress-related gastric mucosal injury**?
1. **Systemic hypotension**
2. Stress-induced splanchnic vasoconstriction =\> ⬇︎ blood flow
3. ↑ of inducible NOS
4. ↑ release of vasoconstictor endothelin-1
31
What is the morphology of the **acute** **ulcers** seen in **stress-related mucosal diseases?**
* Sharply demarcated, multiple ulcers less than 1 cm in diamater, found anywhere in the stomach.
* Base of the ulcer is brown (blood) and the adjacent mucosa is NL.
32
How are **acute ulcers** in stress-related gastric mucosal injury different from **chronic peptic ulcers**?
1. **Multiple** and **located anywhere** in the stomach
2. **Scaring** and **thickining of BV** is **NOT** present
33
Most critically ill patients admitted to ICU have evidence of what damage?
**Damage to the gastric mucosa**
34
In critcally ill patients admitted to the ICU, what is the most important determinant of clinical outcome?
**_- Ability to correct the underlying condition-_**
Removal of the injurous factor normally causes healing with complete re-repithlialization.
35
What are the 2 **non-stress related** causes of **gastric bleeding**?
* 1. **Dielafoy lesions**
* 2. **GAVE** (gastric antral vascular ectasia)
36
What is a **Dieylafoy lesion?**
**Non-stress** related cause of gastric bleeding where there is erosion over a submucosal artery has improper branching of w/i wall of stomach, forming a LARGE mucosal artery.
37
Where does a **Dieufaloy lesion** most commonly occur and what causes it?
- Along the **lesser curvature,** near the GE junction.
- **Erosion** due to **NSAIDS**
38
What is responsible for 4% of non-variceal **upper GI bleeding?**
**GAVE (gastric antral vascular ectasia)**
39
**Gastric antral vascular ectasia (GAVE)** can be recognized endoscopically how?
Alternating longitudinal stripes of **edematous red mucosa** w/ **pale mucosa** that is less injured **("watermelon stomach")**
40
While often idiopathic, **gastric antral vascular ectasia (GAVE)** can be associated with what underlying pathologies?
Patients may present how?
- **Cirrhosis** and **Systemic Sclerosis**
- **Occult fecal blood** and **iron-deficiency anemia**
41
What are the 2 common causes of **chronic gastritis** (inflammation + mucosal atrophy, providing a template for dysplasia and cancer to arise)?
* **1. H. Pylori (90%)**
* 2. AI gastritis (10%)
42
How are the **symptoms** in chronic gastritis different than acute gastritis?
**Less severe, more persistant.**
N, V, upper abdominal pain, but hematemesis is NOT common.
43
What type of bacteria is **H. Pylori?**
**Gram (-) rod (baccillus); spiral-shaped**
44
What part of the stomach does H. Pylori and AI gastritis cause **chronic gastritis?**
* **H. Pylori:** antrum
* **AI gastritis:** body and fundus
45
How does **chronic gastritis** due to **H. pylori** progress?
* [Initial antral gastritis] can progress to involve **body** or **fundus**
* **Multifocal atrophic gastritis,** which is patchy mucosal atrophy and **⬇︎ acid production** due to ⬇︎ parietal cells,
* **Intestinal metaplasia** (increase risk of gastric adenocarcinoma)
46
How does **atrophic gastritis** caused by **H. pylori** differ from chronic gastritis?
Atrophic gastritis has a **MULTI-FOCAL pattern**, not diffuse.
47
Who is **H. pylori** most common in?
1. **Poverty**
2. **Household crowing**
3. **Decreased education**
4. **AA/Mexicans**
48
How does **H.pylori** cause **chronic gastritis**?
H.Pylori **does not invade** mucosa. It sits on top of epithelial cells and secretes a protective barrier to survive in the acidic stomach via urease
* (makes ammonia =\> protect the bacteria from stomach acid and forms ammonium chloride =\> damages stomach; **↑ pH** =\> **↑ gastrin** release and **↑ acid production**)
49
What are other **H. Pyrlori** VF?
* 1. **Flagella**
* 2. **Adhesins**
* 3. **Toxins (CagA)** that are involved in disease progression
50
Who is the primary carrier of **H. pylori** and how is it transmitted?
**- Humans**
**- Fecal-oral**
51
What 2 **malignancies** are associated with **H.pylori**?
* 1. **Gastric adenocarcinoma**
* 2. **MALT lymphoma** (B-cell cancer that occurs in stomach and HIGHLY assx with H.pylori infection)
52
When inflammation caused by **H. pylori** is limited to the **antrum** there is an increased risk of?
**Duodenal peptic ulcer**
53
Which virulence factor of H. pylori is associated w/ **elevated gastric cancer risk** and allows for **colonization of gastric body** causing multifocal atrophic gastritis?
**CagA** gene
54
Polymorphisms of which immunologic mediators are associated w/ development of **pangastritis**, **atrophy**, and **gastric cancer** associated w/ H. pylori?
* **Increased**: TNF and IL-1β
* **Decreased**: IL-10 (anti-inflammatory)
55
Which vitamin deficiency is a risk factor for **H.pylori-associated gastric cancer**?
**Iron**
56
What inflammatory infiltrate are characteristic of **H. pylori chronic gastritis?**
* Gastrin?
* Acid production?
* Other lesions?
* **Intraepithelial neutrophils** and **subepithelial plasma cells**
* **Gastrin:** NL to ↓
* **Acid production:** ↑ or slightly ↓
* **Other lesions:** Hyperplastic/inflammatory polyps
57
**Build-up of neutrophils in lumen of gastric pits** often seen with H. pylori gastritis can form what?
**Pit abcesses**
58
What **serology** are characteristic of **H. pylori chronic gastritis?**
* **Sequelae?**
* **MC in?**
* AB to H. Pylori
* Peptic ulcer, adenocarcinoma, MALToma
* Low SES, poverty, rural areas
59
**H. pylori** displays trophism for which cells and part of stomach?
**Gastric epithelia** --\> **antrum**
60
Intense **H. pylori infection** can lead to inflammatory infiltrates producing what finding that mimics **appearance of early cancer**?
**Thickened rugal folds**
61
**Lymphoid aggregates**, some with **germinal centers** are frequently present in **H. pylori gastritis** and represent an induced form of?
Potential to transform into?
* Induced form of **MALT**
* **Lymphoma**
62
**H. pylori** can be stained with?
**Warthin-Starry silver stain**
63
Which tests can be used in the **diagnosis** of H. pylori infection?
1. anti-H.pylori Abs test
2. Fecal bacterial detection
3. Urease breath test
64
Effective treatment for **H. pylori infection** includes combinations of?
**Triple therapy** for 7-10 days
* **1. PPI**
* **2. Clarithromycin**
* **3. Amoxicillin/metroniazide**
65
_**Autoimmune gastritis** can cause chronic gastritis._
* - Location
* - Inflammatory infiltrate
* - Gastrin
* **Body** of the stomach
* **Lymphocytes** (CD4+ T cells) and **MO**
* **↑ gastrin** (hypergastrinemia)
66
How does **AI gastritis** cause chronic gastritis?
**AI gastritis (pernicious anemia);**
1. **CD4+ T cells** destroy parietal cells
2. Cytoxicity of parietal cells and atrophy of gastric body onxytic glands =\>
1. ↓ gastric acid secretion (achlorhydia) =\> **hypergastrinemia** and **antral G-cell hyperplasia**
2. **↓ of secretion of intrinsic factor**, which is needed for B12 absorption in the terminal ileum.
1. =\> **B12 deficienc**y =\> **pernicious anemia.**
3. Lead to *chronic inflammation* in the body
67
**Autoimmune gastritis** is characterized by 5 findings (i.e., Abs and deficiencies)?
1. Abs to parietal cells and IF
2. ↓ serum pepsinogen I
3. Endocrine cell hyperplasia
4. Vit B12 def
5. Defective gastric acid secretion (achlorydia) =\> hypergastrinemia
68
**_AI gastritis - associated chronic gastritis;_**
* Acid production
* Other lesions
* Serology
* Sequelae
**Acid production:** decreased
**Other lesions:** Neuroendocrine hyperplasia
**Serology**: AB to parietal cells (H, K, ATPase, IF)
**Sequelae**: atrophy, pernicious anemia, adenocarcinoma, carcinoid tumor
69
What autoimmune disorders cause AI gastritis?
1. **AI disease**
2. **Thyroiditis**
3. **DM**
4. **Graves**
70
How is the atrophy of autoimmune gastritis different from that of H. pylori-mediated?
**DIFFUSE** atrophy = achlorhydria
## Footnote
- H. pylori causes mulitfocal (patchy) = NO achlorhy
71
Autoantibodies to which parietal cell components are most prominently seen in **autoimmune gastritis?**
Do they cause damage?
1. H+, K+-ATPase
2. Proton pumps
3. IF
\***Not pathogenic,** because neither secreted IF or proton pumps are accessible to circulating antibodies
72
**AI gastritis** is characterized by WHAT?
**Diffuse** mucosal damage of the oxyntic (acid-producing) mucosa within the **body** and **fundus** of the stomach
73
What are some of the characteristic findings morphologically in **autoimmune gastritis?**
i.e., mucosa, inflammatory rxn, suface changes, and presence of which cells?
1. Oxyntic mucosa of the body is thin and loss of rugal folds
2. Deeper inflammatory rxn and centered on the gastric glands
3. No superficial lamina propria cells seen in H. pylori.
4. no parietal and chief cells
5. intestinal metaplasia ( goblet cells and columnar absorptive cells)
74
Which stain can allow for visualization of **endocrine hyperplasia** associated w/ autoimmune gastritis?
Immunostains for **chromogrannin A**
75
What is the progression of **autoimmune gastritis** like and what is the median age of diagnosis?
Which sex is more affected?
- Progression to gastric atrophy occurs over **20-30 years**
- Median age = **60 yo**
- Slightly more **women** affected (as w/ most autoimmune dz)
76
What is the clinical presentation of **AI gastritis?**
Linked to sxs of anemia
1. **Atrophic glossitis** (smooth and beefy red tongue)
2. **Megaloblastosis of RBC and epithelial cells**
3. Malabsorptive diarrhea
4. **Peripheral neuropathy:** paresthesias + bilateral symmetrical numbness in LE =\> can progress to spastic tingling =\> complete paraplegia
5. **Spinal cord lesions** --\> Subacute combined degeneration of SC (loss of dorsal/lateral spinal tracts)
77
What can be corrected in regards to B12 deficiency thru **B12 replacement therapy?**
**ONLY anemia sx,** however once complete paraplegia has developed, recovery is poor.
78
Why can both forms of chronic gastritis lead to **gastric adenocarcinoma**?
* Chronic inflammation can lead to **metaplastic atrophic gastritis** =\> intestinal metaplasia (stomach tissue changes to intestinal tissue)
* HY: key path finding is goblet cells in the stomach and inflammatory cells in the lamina propria
79
**Eosinophilic gastritis** most commonly affects what part of stomach?
Increased serum levels of?
Associated w/ allergic rxns in children to what?
* Antral or pylorus
* IgE
* Cows milk, soy protein, immune disorders, parasites, H. pylori.
80
**Lymphocytic gastritis** (Varioliform Gastritis) is sometimes associated w/ what underlying disease?
Most often in which **gender** presenting with what sx's?
* **Celiacs disease**
* **F,** with non-specific abdominal sx
81
What is the most common specific cause of **Granulomatous Gastritis** in Western populations?
Other causes?
* Crohns disease
* Sarcoidosis, infection
82
Usually, patients with **peptic ulcer disease (PUD)** develop in _____ ulcer. 90% occur in\_\_\_\_\_\_\_\_ and 10% occur in the \_\_\_\_\_.
* **Solitary**
* 90% = **proximal duodenum**
* 10%= **antrum**
83
What are the **risk factors** for PUD (10 of them from table)?
1. **H.pylori**
2. **Cigarette use (synergizes w/ H.pylori )**
3. **NSAIDS (potentiated by steroids**
4. Illicit drugs
5. - Alcoholic cirrhosis
6. - Psychological stress
7. - Endocrine cell hyperplasia
8. - ZE syndrome
9. - Viral infection (CMV, herpes simplex)
84
Nearly all **peptic ulcers** are associated w/ what 3 risk factors?
1. H. pylori
2. Smoking
3. NSAIDS
85
Most common form of **peptic ulcer disease** occurs where and is associated with what?
Levels of what will be ↑ and ↓?
Antrum or duodenum as result of **chronic H. pylori-induced antral gastritis & resulting hyperchlorhydria.**
* ↑ gastric acid secretion
* ↓ duodenal HCO3- secretion
86
A new group of **duodenal PUD patients \>60 yo** have emerged recently as a result of what?
Presence of what can increase risk?
- **↑ NSAID use**
* Especially when combined w low-dose aspirin (for CV benefit)
- Facilitated if **concurrent H. pylori** infection is also present
87
How can **cigarette use** and **CV disease** contribute to **PUD**?
↓ mucosal BF, oxygenation and healing
88
Where are most **duodonal ulcers** located?
**Anterior** part of the **proximal duodenum** (near pyloric valve)
89
What are complications of **duodenal ulcers?**
* **Upper GI bleeding,** more likely when located posteriorly because can erode gastroduodenal artery.
* **Pancreatitis**
* **Perforation**
90
Grossly how does the classic **peptic ulcer** appear?
**Sharply punched-out** w/ hemorrhage and fibrosis
\*Is virtually diagnostic
91
Perforation of a **peptic ulce**r into the **\_\_\_\_\_\_\_\_\_\_\_** is considered a surgical emergency.
How may this be detected clinically?
**- peritoneal cavity**
- Free air under the diaphragm on upright XR of abomen
92
What is the most frequent complication associated with **PUD**?
**Bleeding**
\*May be **first** indication of an ulcer
93
Which complication of PUD is most often associated w/ **chronic ulcers** and more often assoicated w/ **pyloric channel ulcers**?
Causes what symptoms?
- **Obstruction** due to **edema** or **scarring**
- Incapacitating, crampy abdominal pain
94
Which complication associated w/ PUD accounts for **2/3 of ulcer deaths**?
**Perforations**
95
What are the major clinical signs and symptoms of **PUD**?
- **Epigastric burning** or **pain**
* Worse at night
* Relieved by alkali foods
96
How does a meal affect the experience of pain in someone with a **gastric ulcer** vs. **duodenal ulcer**?
- **Gastric** --\> pain is worse 1-3 hrs after meal bc stimulates acid release.
- **Duodenal** --\> pain improves w/ meal bc stim bicarb secretion
97
**Penetrating ulcers** in **PUD** may cause pain to be referred where and can be misinterpreted as?
**Back, LUQ or chest**
Can be misinterpreted as **cardiac** in origin
98
What are the current mainstays of **treatment** for **PUD**?
1. Treat H. pylori
2. PPI's to neutralize gastric acid
3. \*Important to withdraw agents such as NSAIDs and selective COX-2 inhibitors
99
Which glands are affected in **autoimmune gastritis?**
**Gastric body oxyntic glands**
100
Oxyntic atrophy may be associated with **intestinal metaplasia**, recognized by the presence of \_\_\_\_\_\_\_\_\_\_\_\_\_.
**Goblet cells**
101
\_\_\_\_\_\_\_\_\_ of peptic ulcers RARELY occur.
**Malignant transformation**
102
Peptic ulcer are sharply punched out. What is more characteristic of cancers?
**Heaped up margins**
103
Some patients with PUD may present with what complications others than epigastric burning or aching pain (i.e., more serious complications)?
1. - Iron deficiency anemia
2. - Hemorrhage
3. - Perforation
104
Where are **gastric ulcers** most commonly located?
Rupture will cause what?
* **Lesser curvature of the stomach.**
* **Rupture** =\> bleeding due to **L. gastric artery**
105
What are causes of **gastric ulcers?**
* 1. **70%** are due to **H. pylori**
* 2. **Adenocarcinoma**, thus, they MUST be **biopsied**,
106
**Long-standing chronic gastritis** can lead to what?
1. Loss of parietal cells
2. Intestinal metaplasia
3. Increased risk for adenocarcinoma
107
The risk for **gastric adenocarcinoma** is greatest with:
_H. Pylori_ or _AI gastritis?_
**AI gastritis**
108
\_\_\_\_\_\_\_\_\_\_ due to parietal cell deficiency can **predispose to cancer** by allowing bacterial overgrowth and producing carcinogens nitrosamines.
**Achlorhydria** (no HCl in gastric secretions)
109
What happens to **intestinal metaplasia i**n H. pylori gastritis when the organism is cleared?
**It can regress**
110
What is **hypertrophic gastropathy** and what are the 2 most common?
Rare diseases that cause by **large rugal folds** due to **epithelial hyperplasia (not inflammation)** due to too much GF release.
* 1. Menetrier Disease
* 2. Zollinger- Ellison syndrome
111
**Menetrier disease** is associated with excess?
Characterized by?
Anatomicaly where is it seen?
Sx?
- Excess secretion of **TGF-α**
- **Diffuse hyperplasia** of the foveolar ****_m_**ucus cells** of the **_BODY_** and **_FUNDUS_**
* ↑ mucus secretion =\> achlorhydria (loss of acid)
* Protein loss
- **Hypoproteinemia**, **WL** and **diarrhea**
112
When does **Menetrier Disease** occur?
* **30-60s (Men)**
* If in kids, sxs and pathology are similar, but self limited and often follows respiratory infection.
113
**Zollinger-Ellison disease** is caused by?
Characterized by?
Anatomicaly where is it seen?
Sx?
- **Gastrin-secreting tumors (gastrinomas)** in SI or pancreas
- I**ncrease in number of parietal cells** =\> double the onxytic mucosal thickness (lesser extent, mucus and endocrine cells)
- **Fundus**
**- Duodenal ulcers** or **chronic diarrhea**
114
High levels of gastrin associated w/ **ZE syndrome** induces what changes?
1. Hyperplasia of mucous neck cells
2. Mucin hyperproduction
3. Proliferation of endocrine cells
115
**ZE** is most common in what ages?
**50s**
116
What inflammatory infiltrate is seen in the **hypertrophic gastropathies?**
* **Menetrier Disease:** limited (lymphocytes)
* **ZE:** Neutrophils
117
What risk factors are seen in the **hypertrophic gastropathies?**
* **Menetrier disease:** N/A
* **ZE:** MEN (multiple endocrine neoplasia)
118
Are Zollinger-Ellison syndrome and Menentrier Disease associated w/ increased risk for **adenocarcinoma?**
**ONLY** Menetrier Disease
119
How fast do **gastrinomas** grow and are they typically benign or malignant?
- **Slow** growing
- **60-90%** are malignant
120
**MEN-1** is associated with what tumor of the GI?
**Gastrinomas** ---\> Zollinger-Ellison syndrome
121
\_\_\_\_\_\_\_\_\_\_ that project above the level of the mucosa are ID'd in up to 5% of UGI endoscopy.
**Polyps**, **nodules** or **masses**
122
What are the 3 types of **gastric polyps (benign tumors)** and which are the most common?
1. **Inflammatory or hyperplastic polyps\*\*\* (75%)**
2. Fundic gland polyp
3. Gastric adenoma
123
Where do the 3 types of polyps occur and what cells are involved?
1. **Inflammatory and hyperplasia polyps**
* Antrum \> body
* mucus cells
2. **Fundic gland polyps**
* Body and fundus
* parietal and chief cells
3. **Gastric adenocarciomas**
* Antrum \> body
* dysplastic intestinal
124
I**nflammatory/hyperplastic polyps** are most common in what age group?
Develop in association with what underlying disorder?
**50-60s**
**Chronic gastritis** due to **H. pylori**
125
The risk of **dysplasia** associated with **inflammatory or hyperplastic polyps** is correlates with what?
Which polyps should be resected for further examination?
**Size**, polyps larger than 1.5 cm should be resected
126
What are the **symptoms** of inflammatory or hyperplastic polyps?
Similar to chronic gastritis.
127
**Fundic Gland Polyps** occur in what 2 ways?
Which is associated with a risk of cancer?
1. **Sporadic**
1. most often due to PPIs
2. **Syndromic**: pts with FAP (familial adenomatis polyposis) =\> dysplasia =\> adenocarcinomo
128
Why has the prevalence of **Fundic Gland Polyps** increased markedly in recent years?
**PPIs** =\> increase gastrin =\> onxytic gland growth
129
What are the symptoms of **fundic gland polyps?**
**None**, besides **nasaeu**
130
**Gastric adenomas** is most common in ____ YO and risk factors include ___________ (3)
* **Males 50-60YO**
* RF:
* **Chronic gastritis**
* **Atrophy**
* **Intestinal metaplasia**
* **FAP**
131
Are **gastric adenomas** associated with adenocarcinoma?
**YES! Frequently**, especially if **\>2cm**
132
**Gastric adenomas** are ____________ neoplastic lesions
**PRE-MALIGNANT**
133
\_\_\_\_\_\_\_\_ develop in a background of chronic gastritis and are associated with intestinal metaplasia and mucosal (glandular atrophy).
**Gastric adenomas**
134
What are the morphological characteristics of **Gastric Adenomas?**
**Intestinal-type columnar epithelium** w/ varying degrees of **dysplasia**
135
Which 2 gastric polyp types are associated with **familial adenomatous polyposis (FAP)?**
1. **Fundic polyps**
2. **Gastric adenomas**
136
What are the **malignant tumors** of the stomach? (4)
1. **Gastric adenocarcinomas**
2. **Lymphoma**
3. **Carcinoid**
4. **GIST (gastrointestinal stromal tumor)**
137
What is the most common **malignancy** of the stomach?
**Gastric Adenocarcinoma (95%)**
138
What are the types of **gastric adenocarcinoma**?
* 1. **Intestinal type:** bulky mass that occurs due to intestinal metaplasia caused by H.pylori and AI gastritis
* 2. **Diffuse type:** stomach diffusely thickens and infilrates the wall, due to thickening of gastric mucosa cells (not intestinal metaplasia)
139
Early symptoms of **gastric adenocarcinoma?**
Late?
**Early**
* Resemble those of **chronic gastritis** and **PUD** (dyspepsia, dysphagia, N)
**Late**
* Weight loss (anorexia)
* Early satiety (mainly in DIFFUSE cancers)
* Anemia
* Hemorrhage
140
Because early symptoms of gastric adenocarcinoma resemble chronic gastritis and PUD, what does this mean?
Gastric adenocarcinoma is often **found LATE** in the disease stage
141
Which countries have a 20-fold higher incidence of **gastric adenocarcinomas?**
- **Japan**
- **Chile**
- **Costa Rica**
- **Eastern Europe**
\*More common in **low SES groups**
142
Gastric adenocarcinoma has often spread when found.
Where are the **most common sites of metastasis** for Gastric Adenocarcinoma?
1. **Supraclavicular LN** (Virchow node)
2. **Periumbilical LNs** (Sister Mary Joseph nodule)
3. **Left axillary LN** (Irish node)
4. **Ovary** (Krukenberg tumor)
5. **Recto-uterine pouch** (of Douglas)
143
What are recognizable precursor lesions seen with gastric adenocarcinoma?
**1. Gastric dysplasia**
**2. Gastric adenomas**
144
The cause of overall reduction in gastric cancer is most closely linked to what?
Other factors?
**Decreases in H. pylori** prevalence
145
Majority of gastric cancers are ___________ heriditary
not
146
**Familial gastric cancer** is strongly associated with what genetic mutation?
This gene encodes what?
**LOF** of **CDH1**, which encodes **E-cadherin**
147
What germline mutations are associated with the development of **diffuse gastric adenocarcinoma?**
Loss of **E-cadherin**
148
What germline mutations are associated with the development of **sporadic/FAP intestinal gastric adenocarcinoma?**
* Mutations that cause **increased signaling in Wnt pathway**
* **LOF in APC**
* ****TGFβ, BAX, or CDKN2A
* **GOF B-catenin**
149
Persons with **FAP** and what mutations have an increased risk for the **intestinal-type gastric cancer,** especially in high-risk areas such as Japan?
**APC**
150
What are precursor lesions to **intestinal type gastric adenocarcinoma?**
1. **Metaplasia**
2. **Atropgy**
3. **Dysplasia**
4. **Adenoma**
5. **Menetrier**
151
**Intestinal type** of **Gastric adenocarcinoma** is most common where?
Risk factors?
**Lesser curvature** of the stomach, where ulcers form.
RF: older men, smoking, EToH, nitrosamines/NMDA, Type A blood
152
What is the characteristic gross finding of **diffuse gastric adenocarcinoma?**
On biopsy?
- **Linitis plastica** (stomach looks like thick leather)
- **Signet ring cells:** mucin forms inside the cell and pushes the nucleus to the periphery.
153
