Flashcards in Module 2: GI: Barretts and Esophageal Cancers and Non-Neoplastic Stomach Lesions Deck (41):
The last non neoplastic condition of the esophagus is Barrett's Esophagus, what is the etiology for this?
Long standing acid reflux esophagitis --- GERD
--what causes GERD?
2. limited scleroderma (CREST syndrome--calcinosis, Raynaud's phenomenon, esophageal dysmotility (GERD) , sclerodactyly, telangectasia)
3. Anti-centromere positive
4. Hiatal Hernia (sliding)
What is the presentation for Barrett's Esophagus?
2. Waterbrush (bad metallic taste of acid in the mouth)
4. Epigastric pain
5. Substernal discomfort relieved with antacids
(more common in whites)
The definitive diagnosis for Barrett's Esophagus is an upper GI endoscopy with biopsy, what would the findings be?
Normal Epithelium: stratified squamous non-keratinized
Intestinal Metaplasia: Tall columnar with goblet cells as a protective mechanism
Endoscopy: normal pearly white esophageal squamous mucosa --- velvety pink columnar mucosa (serpiginuos salmon colored patch)
What is the pathogenesis for Barrett's Esophagus?
Decreased tone in the LES --- genetic reprogramming of stem cells in the lower 1/3rd of the esophagus
What are the complications for Barrett's Esophagus?
#1 risk factor for intestinal dysplasia ---- adenocarcinoma of the esophagus (always due to Barrett's)
---most common in the US -- almost always distal 1/3rd of esophagus and preceded by chronic acid reflux
--globally SCC of esophagus is more common
Progressive dysphagia and odynophagia -- difficulty and painful swallowing
Melena --- iron deficiency anemia
There are two neoplasms of the esophagus, Squamous Cell Carcinoma (SCC) and Adenocarcinoma. First we will discuss SCC. What is the etiology for SCC?
Plummer-Vinson Syndrome (Patterson Brown Kelly Syndrome)
p16,p53 and Rb mutations (tumor suppressor genes)
What is the pathogenesis for SCC?
Usually in upper 2/3rd of esophagus (middle 1/3rd to be specific)
--growth pattern: exophytic, excavated and infiltrative
What is the presentation for SCC?
Progressive dysphagia (initially solids than liquids due to gradual luminal narrowing)
Fatigue (due to melena and iron deficiency anemia)
What demographic of the population presents with SCC?
Black and Asian Males greater than 50
--highest incidence in central Asia and Northern China
What are the two investigations done for SCC?
Barium Swallow: shows obstruction or narrowing of lumen (however need a Upper GI scope to confirm)
GI endoscopy w/Biopsy: malignant squamous cells invading into the submucosa and muscularis propria
In regards to SCC, explain the two histological slides 5c
Pic on left: Malignant squamous cells invading into the submucosa and muscularis propria. without keratin pearls so a worse dx
Pic on right: squamous cell whirls of keratin (Better prognosis because its well differentiated in function)
What is a complication of SCC?
1. Obstruct --- regurgitation ---- aspiration pneumonia
2. Bleeding --- melena ---- iron deficiency anemia
3. Form a TE fistula (food can get into the lungs --aspiration pneumonia ---- lung abscess)
4. Can spread to cervical, mediastinal, paratracheal, tracheobronchial, gastric and celiac nodes depending on site of tumor
Now moving onto the next malignancy of the esophagus is Adenocarcinoma. What is the etiology for this?
Barrett Esophagus (due to chronic GERD) is the precursor lesion
--risk varies from 30 fold to 100 fold
--more common than SCC
What is the pathogenesis for Adenocarcinoma?
Usually in the lower 1/3rd of the esophagus
--growth pattern: multistep process through dysplasia
What is the presentation for Adenocarcinoma?
Fatigue (due to melena --- iron deficiency anemia)
--commonly seen in white males
What investigations are done for Adenocarcinoma?
Barium Swallow: shows obstruction of lumen (need to confirm with scope)
GI endoscopy with biopsy: malignant glandular epithelium invading into the submucosa and muscularis propria
What are the complications of Adenocarcinoma?
Can obstruct (melena), perforate (mediastinitis) or form a TE fistula (food can get into lungs -- aspiration pneumonia --- lung abscess)
--can spread to gastric and celiac nodes
Now moving onto stomach lesions there are non neoplastic, neoplastic benign and neoplastic malignant. The first condition to discuss is a non neoplastic condition called pyloric stenosis, describe the features of the congenital condition.
Congenital: genetic pre-disposition
--more common in the first male child
--pathology: concentric hypertrophy of the circular muscle layer
--clinically: regurgitation, projectile vomiting, palpable epigastric olive like mass, visible peristalsis
What are some features of acquired pyloric stenosis?
Chronic Antral Gastritis
Moving onto the next non-neoplastic lesion of the stomach is gastritis, chronic and acute. First lets start with acute, what is acute gastritis?
Acute/transient inflammation and injury of mucosa
What are the predisposing factors for acute gastritis?
NSAIDS (inhibit PG synthesis)
Heavy smoking (impairs mucosal blood flow)
Severe stress (burns, surgery)
What is the presentation for acute gastritis?
May be asymptomatic
-may have epigastric pain, nausea, vomiting, hematemesis and melena
What is the pathogenesis for Acute gastritis?
Mucosal erosion --- loss of surface epithelium
Erosions with hemorrhage --- acute erosive gastritis
Edema and congestion of lamina propria
Neutrophils in surface epithelium and glands
Before we move onto chronic gastritis, what are diseases caused by H. pylori?
1. Chronic Gastritis
2. Extranodal Marginal Lymphoma of MALT type (MALToma) ---present with abdominal pain, nausea, vomiting and weight loss. tx--with abx if no response tx with chemotherapy/rituximab
3. Chronic Gastric Ulcer -- has malignant potential
4. Intestinal Gastric Adenocarcinoma
5. Most common = Duodenal Ulcers (never become malignant and pain is relieved after eating)
6. Affects the antro--pyloric region at the lesser curvature
The next non-neoplastic syndrome we will discuss will be chronic gastritis: What is the etiology for chronic gastritis and most common location?
Etiology: Chronic infection with H.pylori
Location: at the antro-pyloric region of the lesser curvature.
What is the pathogenesis for H.pylori in chronic gastritis?
H. pylori produces urease ( cleaves urea and turns into ammonia to neutralize the acid) and phospholipase (destroys the phospholipid bilayer in the mucosa of the stomach)
---diffuse effacement of the mucosa by the lymphocytes this gives you chronic gastritis/peptic ulcers
--takes place in the antrum and pylorus because G cells are located here and H. pylori loves to destroy the G cells
--G cells make gastrin so therefore patients end up with hypogastrinemia (aka low gastrin levels because no G cells)
What do you see on histology for chronic gastritis (slide 6a)?
Lymphoid Aggregates (can eventually lead to a MALTOMA which is b cell lymphoma in the mucosa)
--chronic inflammatory infiltrate (lymphocytes, plasma cells) in the lamina propria
--H. pylori is gram negative and non invasive so therefore thats why gastritis stays in the mucosa
--Addition of neutrophils when acute on chronic happens
What investigations are done for chronic gastritis?
1. Endoscopic biopsy with silvers stain: H. pylori appears black (slide 6a) with H and E (6a) cant see H. pylori (best investigation) (mainly see plasma cells, b cells and PMNS)
2. Urea Breath Test and Stool Antigen: these are the best investigations if H.pylori is causing recurrent infections.
What are complications for chronic gastritis?
1. Chronic inflammation -- intestinal metaplasia ---- dysplasia ---- intestinal gastric adenocarcinoma (in antrum and pylorus)
2. Lymphoid aggregates --- uncontrolled proliferation of B cells --- MALTOMA (Gastric lymphoma) due to b cell aggregates in the mucosa
Now we move onto autoimmune chronic gastritis which is a type II HSR at the fundus and body. What is the pathogenesis?
Body and Fundus is the location of parietal cells so damaging the parietal cells means no more negative feedback so constantly in a state of G cell hyperplasia (hypergastrinemia) and enterochromaffin (neuroendocrine) hyperplasia. no parietal cells means no acid which is why G cells are trying to produce more and more gastrin.
--no relief with antiacids
--etiology is autoimmune destruction by anti-parietal cell Ab
What are the complications?
1. Atrophic gastritis: fundus/body becomes antralized (aka no acid)
2. Intestinal metaplasia -- dysplasia ---intestinal gastric adenocarcinoma (in fundus and body)
3. G cell hyperplasia --- increased gastrin and enterochromaffin levels -- dysplasia --- type I gastric carcinoid
4. Pernicious Anemia (decreased intrinsic factor, decreased vit B12 and increased methylmalonic acid)
Next topic are acute gastric ulcers, what is the etiology?
1. Extensive Burns (curling ulcers)
2. Head Injuries (cushing ulcers)
(other causes: NSAIDs, alcohol, and stress)
What is the pathogenesis for acute gastric ulcers?
Systemic acidosis and hypoxia with burns
Vagal stimulation in head injuries
What is the histology for acute gastric ulcers?
Multiple, small and circular ulcers with no indurated bases
Gastric rugae are normal
Now moving onto chronic gastric ulcers (peptic ulcers). What describe the gross image on slide 6b
Punched out ulcer with sharp and raised margin
--Rugae radiates like the spokes of the wheel due to fibrosis
(key signs it is chronic)
What is the etiology for chronic gastric ulcers (peptic)?
H. pylori most common of the lesser curvature
--more common in lesser curvature but if happens in the greater curvature then there is a higher chance of malignancy
In a chronic gastric ulcer ,describe the inflammation seen.
Inflammation extends beyond the mucosa
What is the presentation for gastric ulcer?
Epigastric pain that worsens shortly after eating (So therefore these patients have weight loss)
The more common location for an ulcer is the duodenal ulcer, what are the signs for duodenal ulcer?
1. Etiology: H. pylori
2. Pain gets better after eating
--dont avoid eating and hence dont lose weight unlike a gastric ulcer
3. Acid is not entering the duodenum
5. No risk of malignancy
The best investigation for a gastric ulcer is an upper GI scope with biopsy, what would you see on biopsy?
Starting from the most superficial down
N: necrotic debris
I: inflammatory cells (lymphocytes, plasma cells, neutrophils if acute on chronic--patients who take NSAIDs)
G: granulation tissue (Angiogenesis + type III collagen)
S: scar (type I collagen)