Chapter 17 Flashcards
Presentation of congenital abnormalities in the GI tract
Regurgitation during feeding
How treat congenital abnormalities
Surgery
Globus
Feeling of something stuck int he back of the throat that cant be swallowed
Developmental abnormalities of the esophagus are often associated with what
Congenital heart defectsGU malformations
Neurological disorders
What is esophageal atresia
Thin, noncanalized cord replaces a segment of the structure creating a mechanical obstruction
Where is esophageal atresia common
Tracheal bifurcation
What is esophageal atresia associated with
A fistula connecting the upper and lower esophageal pouches to a bronchus or the trachea
Most commonly a clindamycin upper segment in esophageal atresia is associated with a fistula connecting what
The lower segment to the trachea
Immperforate anus: intestinal atresia is less common than esophageal atresia but frequently involves the ___
Duodenum
__ __ is the most common form of congenital intestinal atresia
Imperforate anus
What causes imperforate anus
Failure of cloacal membrane to involuted during development
Fistula
Connection between the esophagus and the trachea/bronchi
What happens when u have a fistula
Swallowed material or gastric fluids can enter the respiratory tract
Clinical fistula
Aspiration, suffocation, pneumonia, severe fluid/electrolyte imbalance
Stenosis
Incompeteform of atresia in which the lumen is markedly reduced in caliber via a fibrous thickening of the wall causing partial of complete obstruction
Causes of stenosis
Congenital or acquired as a consequence of inflammatory scarring int he setting of GERD, irradiation, systemic sclerosis (scleroderma), or caustic injury
Where is stenosis msot common
Esophagus and small intestine
Diaphragmatic hernia
Incomplete formation of the diaphragm allows cephalad displacement of the abdominal viscera
What can diaphragmatic hernia cause
Pulmonary hypoplasia which is incompatible with postnatal life
Omphalocele
Abdominal musculatureis incomplete and viscera herniate into the ventral membranous sac
How can you fix omphalocele
Surgery
_% of infants with omphalocele have another birth defect
40
Gastroschisis
Similar to an omphalocele but all layers of the abdominal wall fail to develop, from the peritoneum to the skin
What are ectopic tissues
Developmental rests
Where is most common gastric mucosa
Upper 1/3 of the esophagus (referred as an inlet patch)
Clinical ectopic pancreatic tissue
Asymptomatic, but can release gastric acid and lead to dysphagia, esophagitis, Barrett’s esophagus, or rarely adenocarcinoma
Where is ectopic pancreatic tissue found
Stomach or esophagus
Clinical ectopic pancreatic tissue
Nodules are usually asymptomatic, but can produce local damage and inflammation in some instances
If present in the pylorus->inflammation and scarring may lead to obstruction
What is gastric heteropia and how does it present
Small patches of ectopic gastric mucosa in the small bowel or colon can present with occult blood loss due to peptic ulceration of adjacent mucosa
True diverticulum
Blind pouch leading of the alimentary tract that communicates with the lumen
*lined by mucosa and ALL THREE LAYERS OF THE BOWEL WALL ARE PRESENT: MUCOSA, SUBMUCOSA, MUSCULARIS PROPORIA
What is the most common true diverticulum
Meckel diverticulum
Where does meckel diverticulum occur
Ileum
Why get meckel diverticulum
Persistence of the vitelline duct which connects lumen of the developing gut to the yolk sac
Meckel diverticulum extends from the __-__ side of the bowel
Anti mesenteric
Issues with meckel diverticulum
Mucosal lining may resemble normal small intestine but ectopic pancreatic or gastric tissue may be present (and functional)
Acid secretion can cause ulceration of adjacent mucosa can lead to occult bleeding or abdominal pain that looks like appendicitis
What is the rule of 2s for meckels diverticulum
2% of population
Occur within 2 feet of the ileocecal valve
2 inches long
2x more common in males
Symptomatic be age 2 (only4% are ever symptomatic)
Acquired diverticula most commonly occur in the __ __
Sigmoid colon
Acquired diverticula lack __ __ or have an attenuated __ ___
Muscularis propria
What causes congenital hypertrophic pyloric stenosis
Hyperplasia of the pylorus muscularis propria which obstructs the gastric outflow tract
What is congenital hypertrophic pyloric stenosis associated with
3-5x more likely in males
Turner syndrome and trisomy 18(Edward)
Erythromycin/azithromycin exposure (either orally or through maternal milk) in the first 2 weeks of like
Genetic component of congenital hypertrophic pyloric stenosis
Yup high concordance in monozygotic twins
Clinical congenital hypertrophic pyloric ctenosis
Regurgitation and new onset regurgitation, projectile, nonbillous vomiting after feeding with frequent demands for refeeding
Antecedent visible hyperperistalsis
Palpable firm, 1-2 cm ovoid abdominal mass
Signs and symptoms onset: between 3rd and 6th weeks of life
Treatment of congenital hypertrophic pyloric stenosis
Surgical splitting of the muscularis (myotome) is curative
Why do people get acquired pyloric stenonosis
Adults as a result of antral gastritis or peptic ulcers near the pylorus
Or
Carcinomas of the distal stomach and pancreas may also narrow the pyloric channel due to fibrosis or malignant infiltration
Hirschsprung disease
Congenital anganglionic megacolon (both plexuses are absent “anglionosis”
What causes hirschsprung disease
Arrested migration of NCC into the gut (neurocristopathy)
In hirschsprung disease NCC fail to migrate from the _ to the _ or ganglion cells undergo __ __
Cecum
Rectum
Premature death
In hirschsprung, what is absent in distal segments
Submucosal plexus (miessner) and myenteric plexus (of auerbach)
Describe the effect of having an aganglionic segment in hirschsprung disease
It lacks coordinating peristaltic contractions
Get functional obstruction
What happens to the normally innervated proximal colon in hirschsprung
Undergo progressive dilation and become massively distended-> may stretch and thin the colonic wall to the point of rupture (occurs most frequently near the cecum)
In hirschsprung the rectum is always affected, but what happens if only a few cm of the rectum is involved
Occasional passage of stool may occur and obscure the diagnosis
10% of hirschsprung disease cases occur in kid with __ __
Down syndrome
In 5% of hirschsprung disease 5% present with __ ___
Neurologic abnormalities
Genetics of hirschsprung disease
Mainly heterozygous loss-of-function mutations in RET (RTK) accounts for majority of familial causes and 15% of sporadic
Or
Sex linked factors -more likely in males, when present in females have longer aganlionic segments
Genetic and environmental modifiers
Clinical presentation of hirschsprung disease
Failure to pass meconium in the immediate post natal period
Obstruction or constipation, with visible, ineffective peristalsis
May progress to bilious vomiting or abdominal distension
At risk for perforation, peritonitis, and enterocolitis with fluid/electrolyte imbalance/ derangement
How diagnose hirschsprung
Requires documentation of the absence of ganglion cells in the affected segment
Confirm via intraoperative frozen section analysis
Can stain for the ganglion cells with H/E and immune staining for acetylcholinesterase
Treat hirschsprung
Surgical resection of aganglionic segment with anastomoses of the noramal proximal colon to the rectum
May require years to attain normal bowel function and continence
Acquired megacolon can occur at any age due to what
Associated with loss of ganglion cells (chagas disease)
Or not associated with loss of ganglion cells
- obstruction by neoplasm or inflammatory stricture
- toxic megacolon complicating ulcerative colitis
- visceral myopathy
- psychosomatic disorders
The upper 12 of the esophagus is supplied by what
Inferior thyroid artery
What supplies the middle 1/3 of the esophagus
Thoracic aorta branches
What supplies the lower 1.3 of the esophagus
Left gastric artery
Normal histology esophagus
Stratified squamous epithelium
Inner circular muscle+ outer longitudinal muscle
What does the esophagus develop from
Cranial portion of the foregut
Esophageal dysmotility
Structural obstruction
Functional obstruction:disruption of coordinated peristaltic contractions following swallowing
What are the three principle forms of esophageal dysmotility
Nutcracker esophagus
Diffuse esophageal spasm
Hypertensive lower esophageal sphincter
Esophageal dysmotility mimics __ pain
MI
Clinical esophageal dysmotility
Dysphagia+odynophagia+globus (feels like something’s is stuck in the back of the throat)
Regurgitation
Nutcracker esophagus (jackhammer esophagus)
High amplitude contractions of the distal esophagus
Due to loss of normal coordination between the inner circulat and outer longitudinal smooth muscle contractions
Diffuse esophageal spasm
Repetitive, simultaneous contractions of the distal esophageal smooth muscle
When swallowing cold food=chest pain
Hypertensive lower esophageal sphincter
Lower esophageal sphincter abnormality int he absence of altered contraction patterns -achalasia includes reduced esophageal peristaltic contractions
-achlasia is not a hypertensive lower esophageal sphincter
High resting pressure or incomplete relaxation is absent -seen in nutcracker esophagus and diffuse esophageal spasm
CREST syndrome
Calcinosis Raynaud phenomenon Esophageal dysmotility Sclerodactyly Telangiectasia
Zenker diverticulum (pharyngoesophageal diverticulum)
Functional obstruction==maintain weight and appetite
Sequelae of zenker diverticulum
Increased pressure within the distal pharynx due to impaired relaxation and spasm of the cricopharyngeus muscle after swallowing
Location of zenker diverticulum
Immediately above the upper esophageal sphincter
Who gets zenker diverticulum
Patients after 50
Clinical zenker diverticulum
Accumulate significant amounts of food
Can lead to regurgitation and halitosis
Mechanical esophageal obstruction cause
Strictures or cancer
Benign stricture-maintain weight and appetite
Malignant stricture-weight loss
Clinical mechanical esophageal obstruction
Progressive dysphagia
Initial onset of inability to swallow solids which then progresses to inability to swallow liquids
Patients may subconsciously modify their diet to favor soft food and liquid until the obstruction is nearly complete
Generally maintain their weight
Benign esophageal stenosis cause
Generally caused by fibrous thickening of the submucosa due to inflammation and scarring from chronic GERD, irradiation, or caustic injury
What is benign esophageal stenosis associated with
Atrophy of the muscularis proporia as well as secondary epithelial damage
What are esophageal mucosal webs
Uncommon, idiopathic ledge-like protrusions of mucosa that may cause obstruction
Semi circumferential lesions that protrude less than 5 mm are 2-4 mm thick, and are composed of a fibrovascular connective tissue and overlying epithelium
Who gets esophageal mucosal webs
Females over 40
Seen in paterson-brown-Kelly or Plummer-Vinson syndrome
What is esophageal mucosal web associated with
GERD, chronic graft-versus host disease, or blistering skin diseases
Main symptoms esophageal mucosal webs
Nonprogressive dysphagia with incompletely chewed food
Patterson brown Kelly (Plummer vinson) syndrome
Upper esophageal mucosal webs associated with
- iron deficient anemia
- glossitis(inflammation of the tongue)
- Cheilosis (corners of the mouth cracked)
Esophageal rings (schatzki rings)
Circumferential, including the mucosa, submucosa and (sometimes) hypertrophic muscularis proporia
Webs are semi-circumferential, thinner, and do not include the mucosa and submucosa
Esophageal rings involve what layers of the esophagus
All layers, usually distal
Esophageal rings: A rings
In distal esophagus above the gastro-esophageal jucntion; covered with squamous mucosa
Esophageal rings : B rings
At the squamocolumnar jucntion of the lower esophagus; may have gastric cardia-type mucosa
Diagnose esophageal rings
Barium swallow
Achalasia
Increased tone fo the lower esophageal sphincter as a result of impaired smooth muscle relaxation and an important cause of esophageal obstruction
Triad of achlasia
Incomplete lower esophageal sphincter (LES) relaxation (lack of NO and vasoactive intestinal polypeptide)
Increased LES tone tone (cholinergic signaling)
Lack of peristalsis of the esophagus
Signs and symptoms of achalasia
Dysphagia for solids and liquids
Difficulty belching
Chest pain
Bird beak sign on barium swallow
Should u do surveillance endoscopy for achlasia patients
Nah risk of esophageal cancer is too low
Primary achalasia causes
Idiopathic
Result of distal esophageal inhibitory neuronal degeneration-hirschsprung of the esophagus(failure of distal esophageal neurons to induce LES relaxation during swallowing
Signs of primary achalasia
Increase in tone, inability to relax LES and esophageal aperistalsis
Secondary achalasia cause
Chagas’ disease (trypanosoma cruzi)
- cause estruction of the myenteric plexus of auerbach, failure of peristalsis and esophageal dilation
- duodenal, colonic and ureteric myenteric plexuses may also be effected
Other systemic disease that can lead to achlasia-like disease
Diabetic autonomic neuropathy Malignancy Amyloidosis Sarcoidosis Sarcoidosis Lesions of dorsal motor nuclei (polio, surgical ablation) Down syndrome Allgrove (triple A) syndrome Immune mediated destruction of inhibitory esophageal neurons
Allgrove (triple A) syndrome
AR
Achalasia
Alacrima
Adrenocorticocotrophic hormone-resistant adrenal insufficiency
Immune mediated destruction of inhibitory esophageal neurons
Associated with HSV1
Occasionally coexistence with Sjögren’s syndrome or autoimmune thyroid disease
Achlasia treatment
Need to overcome the mechanical obstruction
Laparoscopic myotome
Pneumatic balloon dilation
Botox injections to inhibit LES cholinergic neurons
Mallory Weiss tears
Longitudinal lacerations of the mucosa near the gastroesophageal junction that usually cross the gastroesophageal function
What are Mallory Weiss tears associated with
Severe retching secondary to acute alcohol intoxication
What happens when you have Mallory Weiss tears
Prolonged vomiting
Why is there prolonged vomiting with Mallory Weiss tears
Reflex fails and allows for refluxing gastric contents to overwhelm the gastric inlet which leads to esophageal stretching and tearing ->hematemesis
Normally reflex relaxation of the LES usually precedes anti-peristaltic waves
Are Mallory Weiss tears fatal
No you get prompt healing without surgical intervention
Boerhaave syndrome
Much less common but much more severe
Characterization of Mallory Weiss tears
Transmural tearing and rupture of the distal esophagus
Severe mediastinitis
Presentation of boerhaave syndrome
Presents like a heart attack-severe chest pain , tachypnea and shock
Boerhaave causes __ sign: due to pneumoperitoneum in the mediastinum
Hamman
Treatment boerhaave syndrome
Surgical intervention
What is chemical and infectious esophagitis
Stratified squamous epithelial damage leading to dysphagia and pain+/- hemorrhage, stricture, or perforation
Odynophagia=pain on swallowing
Causes of chemical and infectious esophagitis
Induced by alcohol, corrosive acids/askalisis, hot fluids, heavy smoking or pharmalogical agents
Kids:accidental ingestion of household cleaning products
Adults: more severe damage following attempted suicide
Pill induced esophagitis
Less severe chemical injury to the esophageal mucosa can occur when medicinal pills lodge and dissolve int he esophagus rather than passing into the stomach intact
Iatrogenic chemical and infectious esophagitis
Irradiation, chemotherapy, graft vs host disease
What systemic desquamative disorders can cause chemical and infectious esophagitis
Bullous pemphigoid
Epidermolysis bullosa
Can crohns cause chemical and infectious esophagitis
Yup
Infectious causes of chemical and infectious esophagitis
Healthy: HSV
Immunosuppressed: HSV, CMV, or fungal (candida, mucormycosis, or aspergillosis)
Morphology chemical and infectious esophagitis
Commonly with dense neutrophilic infiltrates +/- necrosis
Granulation tissue leads to fibrosis
How does radiation causechemical and infectious esophagitis
Intimate proliferation and luminal narrowing of submucosal and mural blooms vessels which takes years to develop interstitial fibrosis following radiation therapy
How do pathogenic bugs causechemical and infectious esophagitis
Invade the laminae propria and cause necrosis of overlying mucosa
Candidiasis morphology in esophagitis
Grey white pseudomembranes of hyphae and inflammatory cells
HSV morphology esophagitis
Punched out ulcers with viral inclusions and a rim of epithelial cells
CMV morphology esophagitis
Shallow ulceration with nuclear and cytoplasmic inclusions
GVHD morphology esophagitis
Basal epithelial apoptosis, mucosal atrophy and submucosal fibrosis without significant acute inflammatory infiltrates
Reflux esophagitis GERD
Mucosal injury due to reflux of gastric juices-stratified squamous epithelium is resistant to abrasion from foods, but is sensitive to acid (gastric juice)
Most common cause of esophagitis and most common outpatient GI diagnosis
Reflux esophagitis GERD
Most common cause of GERD
Transient lower esophageal sphincter relaxation mediated by vagal pathways and can be triggered by gastric distension
What do submucosalglands in proximal and distal esophagus secrete
Mucin and HCO3
What does LES tone normally do
Prevent reflux of acidic gastric contents and decreased LES tone
What does decreased LES tone and/or increased abdominal pressure cause (GERD)
Reflux
- abdominal contents are under positive pressure
- thoracic contents are under negative pressure
What may exacerbate reflux disease GERD
Alcohol, tobacco, obesity, CNS depressants, pregnancy, hiatal hernia, delayed gastric emptying or increasedgastric volume
Reflux of gastric juices is central to the development of __ injury
Mucosal
Severe cases of GERD
Reflux of bile from the duodenum may exacerbate the damage
Morphology GERD
Hyperemia(redness)+edema
Basal zone hyperplasia
Thinning of superficial epithelial layers
Neutrophil and/or eosinophils infiltration
Clinical GERD who gets is
Most common in patients over 40
Symptoms of GERD
Heartburn, dysphagia, regurgitation of sour tasting contents, increased saliva
Is severity of GERD related to the histological damage
Nope histological damage does increase with disease duration
Kids with GERD symptoms
Fail to eat, failure to thrive, recurrent pneumonia’s
Complications GERD
Ulceration, hematemesis, melena, stricture, or barret esophagus
Treat GERD
Symptomatic relief with PPIs (omeprazole)
Which have replaced H2 histamine receptor blockers (cimetidine) to reduce gastric acidity
Hiatal hernia
Characterized by separation of the diaphragmatic courage and protrusion of the stomach into the thorax
Hiatal hernia symptoms
Symptomatic in fewer than 10%
Heartburn and regurgitation of gastric juices
May cause lower esophageal sphincter incompetence
Eosinophilia esophagitis
Incidence has increased
Large numbers of intraepithelial eosinophils, particularly superficially
What differentiates eosinophilia esophagitis from GERD, crohns and other causes of esophagitis
Large numbers of intraepithelial eosinophils , particularly superficially
Symptoms of eosinophilic esophagitis
Adults:food impaction+dysphagia
Children: feeding intolerance+GERD like signs and symptoms
-acid reflux is not prominent **
Eosinophilic esophagitis is associated with what
Atopic disorders-atopic dermatitis, allergic rhinitis, asthma, peripheral eosinophilia
Treat eosinophilic esophagitis
Dietary resection +/- topical or systemic corticosteroids
Do PPI help with eosinophilic esophagitis
Not provide relief nope nope
Esophageal varicose
Distention of subepithelial and submucosal venous vessels within the distal esophagus and proximal stomach
Varices=tortuous dilated veins within the submucosa
What causes esophageal varices
Portal HTN can result in the development of collateral channels at sites where the portal and canal system communicate->portal canal anastomoses
_% of patients with cirrhosis livers have __ __
Esophageal varices
What is the second most common cause of esophageal varices
Hepatic schistosomiasis (snail liver) is the second most common cause of varices worldwide
Pathogenesis esophageal varices
- collateral channel between the portal and canal circulations is established in severe portal HTN
- subepithelial and submucosal veins in the distal esophagus become congested
- most commonly associated with alcoholic cirrhosis and schistomiasis
Morphology esophageal varices
Tortuous, dilated veins in the distal esophageal and proximal gastric submucosa
Irregular luminal protrusion of overlying mucosa with superficial ulceration, inflammation or adherent blood clots
Clinical esophageal varices
Clinically silent until they rupture with catastrophic hematemesis (30% or more patients with varices hemorrhage die as a direct consequence of hemorrhage such as hypokalemia shock, hepatic coma, or other complications
Rupture may be due to inflammatory erosion, increased venous pressure, or increased hydrostatic pressure from vomiting
Treat esophageal varices
Splanchnic vasoconstriction, sclerotherapy (injection of thrombotic drugs), balloon tamponade, or band ligation
50% of people with esophageal varices die when
The first bleed (exsanguination or hepatic coma)
But also >50% chance of recurrence within 1 year with the same mortality rate
Patients with esophageal varices have a high risk of ____ (lage varices, elevated hepatic venous presssure gradient, previous bleeding, and advanced liver disease)
Hemorrhage
How treat esophageal varices propholactically
Treated prophylactically with beta blockers to reduce portal blood flow and with endoscopic varices ligation
Barret esophagus
Complication of chronic GERD
Intestinal metaplasia within the esophageal squamous mucosa
Stratified squamous epithelium->columnar epithelium
-columnar metaplasia of the esophageal squamous mucosa(names for what it turns into)
What percent of people with GERD have barret esophagus
10%
What color is mucous in Barrett’s esophagus
Salmon
Who gets Barrett esophagus
White males 40-60
People with Barrett’s esophagus have an increased risk of what
Esophageal adenocarcinoma
S-barrettt esophagus is a precursor lesion
Most don’t bet esophageal tumours
Shared mutations common when dysplasia is present
Morphology Barrett
Patches of red, velvety mucosa extend cephalad from the gastroesophageal jucntion
Metaplastic mucosa alternates with residual smooth, pale squamous (esophageal) mucosa and interfaces with light brown columnar (gastric) mucosa distally-obliterates the Z line
Subclassifications of Barrett esophagus
Long segment >_3cm
Short segment <3cm
Risk of dysplasia in barrett correlates with what
Length of esophagus affected
Gland architecture in barrett
Abnormal and characterized by budding, irregular shapes and cellular crowding
What can Barrett’s progress to
Intramucosal carcinoma, if there is neoplastic cel invasion of the lamina propria
Diagnosis Barrett’s
- identified only with endoscopy and biopsy, prompted by GERC signs and symptoms
- diagnosis requires intestinal-type columnar epithelium (mucin secreting goblet cells)
- there are mucous vacuoles that stain light blue in the shape of a wine-goblet with H/E
Clinical barrett
Esophagitis like heartburn, regurgitation, dysphagia
Not all patients will develop cancer, but no way to predict
Treatment barrett
Periodic endoscopy with biopsy for dysplasia surveillance
Therapeutic intervention with carcinoma including surgical resection, esophagectomy, photodynamic therapy, laser ablation and endoscopic mucosectomy
Esophageal tumors
Most are squamous cell carcinoma or adenocarcinoma
Other esophageal malignancies are less common
Benign:mesenchymal origin (leiomyomas are most common)
Risk factors for esophageal adenocarcinoma
Most arise from barretts or obesity related GERD Tobacco, radiation exposure H pylori Caucasian Males 7x more likely
How does helicobacter cause esophageal adenocarcinoma
H pylori-.gastric atrophy->decrease acid secretion->decreased GERD->decreased barret esophagus
Reduced rates of H pylori may also be a factor in the increasing indecency of esophageal adenocarcinoma
Esophageal adenocarcinoma accounts for _% of all esophageal cancers in the USA
> 50
Genetics esophageal adenocarcinoma
Stepwise accu,Latino of genetic and epigenetic alterations from barret esophagus
Early mutations of esophageal adenocarcinoma
TP53, CDKN2A (p16/INK4a)
Late mutations that cause esophageal adenocarcinoma
EGFR, ERBB2, met, cyclin D1, cyclin E
Morphology esophageal adenocarcinoma
Range from exophytic nodules to excavated, deeply infiltrating masses
Mostly in distal 1/3 of esophagus and can invade the adjacent cardia
Tumors produce mucin and form glands
Clinical esophageal adenocarcinoma-how discovered
In evaluation of GERD or surveillance of barrett
Presentation symptoms of clinical esophageal adenocarcinoma
Dysphagia, progressive weight loss, hematemesis, chest pain and vomiting
Prognosis esophageal adenocarcinoma
By the time symptoms appear, the tumor has likely spread to submucosal lymphatic vessels-advanced stage
5 year survival <35%, 80% if limited to the mucosa or submucosa
Risk factors for esophageal squamous call carcinoma
Patients greater than 45
Males 4:1
8x increased risk in african American vs white
Alcohol and tobacco synergy, caustic esophageal injury, achalasia, Plummer Vinson syndrome, scalding beverages, tylosis (AKA howel-Evans syndrome) (RHBDF2 mutation)
Nutritional defiency (poverty), polycyclic hydrocarbons, nitrosamines, other mutagens
What geographies have increased incidence os esophageal squamous cell carcinoma
Iran, central china, Hong Kong, Brazil, South Africa, and western Kenya (consumption of a fermented milk, called mursik, which contains acetaldehyde)
Genetics of esophageal squamous cell carcinoma
HPV infection in high risk areas
SOX2 amplification-believed to be involved in cancer stem cell self renewal and survival
Cyclin D1 overexpression
Tumor suppressor TP53, E cadherine, NOTch1 loss of function
How does squamous cell carcinoma begin
Begins as a squamous dysplasia (in situation lesion same as intraepithelial neoplasia or carcinoma in situation elsewhere)
Morphology of early squamous cell carcinoma esophagus
Small, gray white plaque like mucosal thickening
Lesions of squamous cell carcinoma esophagus may expand as __ ___, ulcerate, or become diffusely infiltrating with wall thickening and luminal stenosis/obstruction
Exophytic lesions
___ network allows circumferential and longitudinal spread in squamous cellcarcinoma
Lymphatic
What happens when there is deep invasion of squamous cell carcinoma into adjacent structures
Can lead to PNA or exsanguination form invasion into the aorta
Most squamous cell carcinoma esophagus are moderately well differentiated-prognosis implication
Not terrible
Half of squamous cell carcinoma occur in the ___ of the esophagus in contract to adenocarcinoma
Middle 1/3
Where does esophageal squamous cell carcinoma spread from the upper third (poor prognosis0
Cervical lymph nodes
Where does esophageal squamous cell carcinoma spread from the middle third of the esophagus (poor prognosis)
Mediastinal, paratracheal, and tracheobronchial lymph nodes
Where does esophageal squamous cell carcinoma spread from the lower third of the esophagus (poor prognosis)
Gastric and celiac lymph nodes
Clinical esophageal squamous cell carcinoma
Insidious onset of dysphagia, odynophagia (painful swallowing) or obstruction
Diet is subconsciously altered to soft food and liquid which contributes to nutritional defiency and weight loss in addition to the systemic effects of the tumor itself
Hemorrhage, iron defiency, sepsis due to ulceration
Tracheoesophageal fistula (risk for aspiration)
Prognosis esophageal squamous cell carcinoma
Early detection (still superficial) : 75% 5 year survival
USA prognosis<20% 5 year survival
Variable based on tumor stage and and patient age, race, and gender
What does the cardia/antrum of stomach consist of
Lined with mucin secreting foveolar cells that form small glands
Endocrine cells (G cells) that relase gastrin and stimulate luminal acid secretion via parietal cells in the fundus and body
What does the body and fundus of the stomach consist of
Well-developed glands and chief cells that produce and secrete digestive enzymes (pepsinogen)
Parietal cells secrete HCL
Gastritis
Mucosal inflammatory process
Acute gastritis
When neutrophils are present
Gastroparesis
When inflammatory cells are rare or absent
Gastritis symptoms
May be asymptomatic or have persistent epigastric pain
Billious vomiting is possible with bile reflux
Gastritis respond to PPI
Maybe maybe not
Can you distinguish gastrophy from gastritis based on clinical grounds
No
Gatropathy
When inflammatory cells are rare or absent
Acute gastritis
Transient mucosal inflammatory process involving neutrophils
Self limiting with neutrophils on biopsy
Hyperemia and no blood loss
May be transient or cause variable degrees of epigastric pain, nausea, and vomiting
What can severe acute gastritis lead to
Mucosal erosion, ulceration, hemorrhage, hemtemesis, melena, and massive blood loss
Gastropathy
Mucosal inflammation with scant inflammatory cells
What may cause gastropathy
NSAIDS, alcohol, bile, stress induced injury, portal HTN
Symptoms gastropathy
May be transient or cause variable degrees of epigastric pain, nausea, and vomiting
What can severe gastropathy lead to
Mucosal erosion, ulceration, hemorrhage, hematemesis, melena, and massive blood loss
How do NSAIDS damage gastric mucosa
NSAIDS reduce bicarbonate production and interfere with muco/cyto-protective prostagladins which inhibit acid production, promote mucin synthesis and increase vascular perfusion
How is gastric mucosa damaged by h pylori and in uremic patients
Inhibition of gastric bicarbonate transporters by ammonium ions in urease secreting h pylori and uremic patients
How do damaged gastric mucosal cells damage in old people
Reduce secretion of mucin and bicarbonate
How else can gastric mucosa be damaged
Decreased O2 at high altitudes
Ingestion of harsh chemicals (alcohol smoking)
Ischemia and shock
Gastric mucosa protection by foveolar cells
Mucin secretion prevents food from directly touching the epithelium
How often is the gastric mucosa replaced
3-7 days
Gastric mucosa protection epithelial cell
Physician barrier; beneath the mucus
Gastric mucosa protectionL limits back diffusion of acid and luminal materials (pepsin) into the __ __
Lamina propria
Gastric mucosa protection: any back diffused material is washed away by ____ ___
Mucosal vasculature
In acid secreting parts of the stomach, a capillary ____ is generated as parietal cells secrete hydrochloride acid into the gastric lumen and bicarbonate into the vessels
Alkaline tide
__ Into the lumen, __ into the vessels
Acid
Bicarbonate
COX dependent synthesis of ___
Prostagladins E2 and I2
__ plays a larger role that __, but both isoenzymes contribute to mucosal protection
COX1 COX2
Gastrophy and acute gastritis morphology
Moderate edema and slight vascular congestion
Surface epithelium is intact
Foveolar cell hyperplasia and characteristic corkscrew profiles and epithelial proliferation
Presence of neutrophils above the basement membrane in direct contact with epithelial cells is abnormal in all parts of the GI tract and signifies active inflammation (gastritis not gastropathy)
Erosion==loss of epithelium; superficial mucosal defect
-accompanied by a pronounced neutrophilic infiltrate and a fibrincontaining pursuant exudate in the lumen, hemorrhage may occur and cause dark, punctae in hyperemic mucosa
Concurrent erosion and hemorrhage==acute erosive hemorrhagic gastritis
When erosions extend deeply, they may progress to ulcers
Stress related mucosal disease cause
Due to severe trauma, extensive burns, intracranial disease, major surgery, physiologic stress
Often related to localized ischemia
For stress related mucosal disease, endoscopically visibile lesions tend to appear in the first _ days of illness
3
Stress ulcers
Occur in individuals with shock, sepsis or severe trauma
-1-4% of critically ill patients admitted to intensive care units show histological evidence of gastric mucosal damage and will require transfusion
Curling ulcer
Occur in the proximal duodenum; associated with severe burns or trauma (like from a curling iron0
Cushing ulcers
Associated with increased intracranial pressure (Cushing reflex)
- direct stimulation of vagal nuclei leads to hypersecretion of gastric acid
- damage to parasympathetic component of vagus nerve
- may occur in several GI regions: gastric, duodenal and esophageal
- high incidence of perforation
Pathogenesis stress related mucosal disease
- often related to local ischemia (hypotension or reduced flow from splanchnic vasoconstriction)
- upregulation of inducing BO synthase
- increased release of endothelin1 (vasoconstrictor)
- COX2 upregulation is protective (nonselective NSAIDS will block COX1 and COX2)
- intracranial injury->direct stimulation of vagal nuclei->hypersecretion of gastric acid
- systemic acidosis->lowers intracellular pH of mucosal cells->mucosal injury
Morphology stress related mucosal disease
Multiple shallow ulcers found anywhere int he stomach
Base is brown (blood)
Adjacent mucosa is normal
There is no scarring and blood vessel thickening that characteristic chronic peptic ulcers
Clinical stress related mucosal disease
Healing takes days to weeks once the stimulus has ended
Most important determinant of prognosis: ability to correct underlying conditions
Stress related mucosal disease if corrected , ___ is normal
Re-epithelialization
1-4% of critically ill patients with stress related gastric mucosa admitted to the ICU show histological evidence of what
Gastric mucosal damage and will require transfusion
_% of stress related gastric mucosa perforate
5%
Dieulafoy lesion
Rare, improperly branched submucosal artery within the wall of the stomach
Diameter of dieulafoy lesion
10x greater than a mucosal capillary
Where are dieulafoy lesions found
Along lesser curvature , near gastroesophageal junction
Why do dieulafoy lesions bleed
Gastric bleeding can occur secondary to erosion of overlying epithelium
Treat dieulafoy lesion
Self limited, but can be copious
What are dieulfaoy lesions associated with
NSAIDS, often recurrent
Gastric antral ectasia (GAVE)
Longitudinal stripes of edematous erythematous mucosa alternating with less severely injured, paler mucosa
What causes gastric antral vascular ecstasia
Due to ecstatic mucosal vessels producing stripes of edematous erythematous mucosa alternating with less severely injured pale mucosa
Why get erythematous stripes with gastric antral vascular ecstasia
Ecstatic mucosal vessels
Nickname for gastric antral vascular ectasia
Watermelon stomach
Gastric antral vascular ecstasia morphology
Antral mucosa has reactive gastropathy with dilated capillaries containing fibrin thrombi
Cause of gastric antral vascular ecstasia
Idiopathic or associated with cirrhosis or systemic sclerosis
Presentation gastric antral vascular ecstasia
May present with occult fecal blood or iron deficient anemia
Chronic gastritis
Ongoing mucosal inflammation with mucosal atrophy
What is the most common cause of chronic gastritis
Helicobacter pylori
Most common cause of diffuse atrophic gastritis
Autoimmune
Autoimmune etiologies make up less than 10% of chronic gastritis cases but is the most common form of chronic gastritis in patients without _____
H pylori
Symptoms chronic gastritis
Nausea, vomiting, upper abdominal pain
Prognosis chronic gastritis
Less severe than acute gastritis, but more persistent signs and symptoms
Hematemesis is rare
Helicobacter pylori
Spiral or curved bacilli
Almost all patients with duodenal ulcers, gastric ulcers, or chronic gastritis have __
H pylori
Most patients with H pylori are asymptomatic. When do they seek help
When chronic gastritis is causing problems
What is h pylori associated with
Poverty, household crowding, decreased education, rural, mexican
Spreading of h pylori
Fecal oral
How does h pylori present
Antral gastritis with normal or increased acid production
H pylori causes increased __ production, but ___ is uncommon
Gastrin
Hypergastrinemia
Pathogenesis h pylori
Interplay of gastroduodenal mucosal defenses, inflammatory responses and bacteria virluence factors
Multifocal atrophic gastritis
Gastritis that progresses to involve the gastric body and fundus: associated with patchy mucosal atrophy , reduced parietal cell mass and acid secretion, intestinal metaplasia, and increased risk of adenocarcinoma
Inverse relationship between duodenal peptic ulcer and gastric adenocarcinoma that correlated with pattern of gastritis
?
What are the virluence factors of H pylori
Flagella: motility
Urease: generates ammonia from endogenous urea and elevates local gastric pH; enhances bacterial survival
Adhesions:bind surface of foveolar cells
CagA associated with increased risk of gastric gander
CagA expressing strains of h pylori can effectively colonize the gastric body and cause __ ___ ___
Multifocal atrophic gastritis
Risk factors associated with pangastritis, atrophy and gastric cancer with h pylori
Overexpression of TNF, IL-1B
Decreased IL10
Iron defiency
H pylori are concentrated where
Superficial mucus overlying surface and neck epithelium ant typically infect the antrum
Morphology H pylori infection
Infected mucosa is erythematous and coarse to nodular
Variable numbers of intra epithelium and luminal neutrophils forming pit abscesses
Lamina propria with abundant plasma cells, macrophages and lymphocytes
Chronic h pylori morphology
Diffuse mucosal atrophy with prominent lymphoid aggregates (occasional germinal centers) and is associated with increased risk of gastric adenocarcinoma
Look for helicobacter pylori with a _____ stain
Warthrin starry
How diagnose h pylori
Serologic test for antibodies
Fecal bacteria detection
Urea breath test (ammonia production)
Biopsies *GOLD STANDARD
Treat h pylori
Antibiotic+PPI
Patients usually improve after treat but relapses can occur after incomplete eradication or reinfection
Prophylactic and therapeutic vaccines are still at an early stage non development
Location of h pylori vs autoimmune
H p-antrum
Autoimmune -body
Inflammatory infiltrate h pylori vs autoimmune
Hp-neutrophils, subepithelial plasma cells
Autoimmune-lymphocytes,macrophages
Acid production h pylori vs autoimmune
Hp-increased to slightly decreased
Autoimmmune-decreased
Gastrin h pylori vs autoimmune
Hp-normal to decreased
Autoimmune-increased
Other lesions h pylori vs autoimmunes
Hp-hyperplastic/inflammatory polyps
Autoimmune-neuroendocrine hyperplasia
Serology h pylori vs autoimmune
Hp-antibodies to h pylori
Autoimmune-antibodies to parietal cells (H, K-ATPase, IF)
Associations h pylori vs autoimmune
Hp-peptic ulcer, adenocarcinoma, MALToma
Autoimmune0autoimmune disease, thyroiditis, DM, Graves’ disease
Distribution h pylori vs autoimmune
Hp-multifocal, leaves patches of residual parietal and chief cells (hypochlorhydria)
Autoimmune-diffuse, knocks out all the parietal cells and alt he chief cells (achlorhydria)
Autoimmune gastritis
Antibodies to parietal cells and IF leading to loss of gastrin and IF in serum and gastric acid secretions
What is spared in autoimmune gastritis
Antrum
Autoimmune gastritis is associated with hyper____
Gastrinemia
Why get hypergastrinemia with autoimmune gastritis
Loss of negative feedback
Symptoms of autoimmune gastritis
Antibodies to parietal cells and intrinsic factors detectable in serum and gastric secretions
Decreased serum pepsinogen I concentration—chief cells are collateral damage
B12 (cobalmin) defiency and associated megaloblastaic pernicious anemia
-also see hyper-segmented neutrophils
Defective gastric acid (achlorhydria)
-h pylori may cause hypochlorhydria, but not achlorhydria
In autoimmune gastritis, __T cells destroy patietal cells, including H/K ATPase
CD4
In autoimmune gastritis, what does loss of parietal cells result in
Loss of gastric acid (HCL and IF) production
Chief cells and autoimmune gastritis
They are collateral damage
Can you get repopulation in autoimmune gastritis
If immunosuppression is sufficient, gastric stem cells survive and differentiate
Diagnosis autoimmune gastritis
Autoantibodies important but not pathogenic bc they cant access the target
Morphology autoimmune gastritis
Diffuse atrophy
Rugal folds lost
Diffuse mucosal damage of oxyntic (acid producing) mucosa in the body and fundus, but there may be regions of oxyntic mucosa that is still intact that looks like polyps or nodules
- inflammatory infiltrate of lymphocytes, macrophages, and plasma cells
- CAN SEE THE BLOOD VESSELS BECASEU THE MUCOSA IS SO THIN
What do we see with lost of rugal folds in autoimmune gastritis
Smooth appearance seen in autoimmune gastritis
Are rugal folds lost in h pylori
Nope
Presentation autoimmune gastritis
Early detection of autoantibodies to parietal cells and IF
Anemia in a few
20% of individuals with pernicious anemia have autoimmune gastritis, although may be asymptomatic
Autoimmune gastritis progresses to __ _ over 20-30 years
Gastric atrophy
Age of diagnosis of autoimmune gastritis
60
Autoimmune gastritis is associated with _ defiency
B12
Genetics autoimmune gastritis
Familial/genetic predisposition
-little evidence of linkage to specific HLA alleles
What happens to the spinal cord with B12 defiency
Subacute degeneration!
B12 defiency: spinal cord lesion
Demyelination of dorsal and lateral spinal tracts
B12 defiency: peripheral neuropathy
Paresthesia and numbness
B12 defiency cerebral dysfunction
Personality changes
B12 defiency: cerebral dysfunction
Persaonality changes
B12 defiency: memory
Memory loss to psychosis
Are neurological symptoms reversed with b12 replacement therapy
Nope
B12 defiency atrophic glossitis
Tongue becomes smooth and beefy red
B12 megaloblastisis of RBC and epithelial cells (rarely: pernicious anemia)
Ok
Diarrhea b12 defiency
Yup
Eosinophilic gastritis
Heavy eosinophilic infiltration of mucosa and muscularis in the antral or pyloric region
Eosinophilic gastritis has elevated ig_
E
Eosinophilic gastritis
May be infectious, due to allergy to ingested material (cows milk and soy protein are the most common in children), systemic sclerosis (scleroderma), polymyositis, parasitic infections and H pylori
Lymphocytic (varioliform) gastritis
Idiopathic, affecting females
40% of lymphocytic (varioliform) gastritis cases are associated with __ __ (implies immune mediated pathogenesis)
Celiac disase
Lymphocytic (varioform) gastritis has marked increase in the number of the intraepithelial DC_ T cells
8
Morphology lymphocytic (varioliform) gastritis
Distinctive endoscopic appearance: thickened folds covered by small nodules with central aphthous ulceration
What part of the stomach does lymphocytic (varioform) gastritis effect
Entire stomach
Granulomatous gastritis
Any gastritis that contains well formed granulomas or aggregates of epithelioid macrophages
Many idiopathic
Most common specific cause of granulomatous gastritis
Gastric involvement by Crohn’s disease
Also associated with sarcoidosis and infection (mycobacteria, fungi, CMV, H pylori)
In granulomatous gastritis, what mar occur secondary to transmural granulomatous inflammation
Narrowing and rigidity of the gastric antrum
Peptic ulcer disease
Chronic mucosal ulceration of the lesser curve of the stomach at junction of body and antrum (gastric peptic ulcers) or proximal duodenum
What is peptic ulcer disease associated with
H pylori infection, NSAIDS< or cigarette smoking
Increased gastric acid secretion and decreased duodenal bicarbonate secretion
Why has incidence of peptic ulcer disease decreased in developed countries
H pylori control
New group of patients getting PUD??
Older than 60 years has emerged with PUD due to prolonged NSAID
Pathogenesis peptic ulcer disease
Imbalance in mucosal defense mechanisms and damaging factors causing chronic gastritis
Decreased mucosal blood flow, oxygenation and healing
Develops on a background of chronic gastritis
What is peptic ulcer disease associated
Cigarettes and CV
Where are peptic ulcers most common
Proximal duodenum-usually solitary
Morphology peptic ulcer disease
Sharply punched out defect with over hanging mucosal borders and smooth, clean ulcer bases
-HEAPED UP PERIPHERAL MARGINS==MALIGNANC
Vessel walls within the affected area are commonly thickened and sometimes thrombosed. Bleeding can lead to life threatening hemorrhage
Does peptic ulcer disase transform to cancer
Not really
If peptic ulcer does transform to cancer, what is the sign
Heaped up peripheral margins=malignancy
Surrounding mucosa in peptic ulcer disease
Chronic gastritis, intestinal metaplasia develops in both forms of chronic gastritis and is a risk factor for gastric adenocarcinoma
Clinical presentation peptic ulcer disease
Epigastric burning or aching pain, which is worse at night and 1-3 hours after meals since food buffers the acid
Nausea, vomiting, bloating, belching and weight loss often occur
Pain of penetrating peptic ulcers may be referrred where
Back, LUQ or chest (misinterpret origin of pain)
What causes relief of peptic ulcer disease
Milk, alkali agents or food
Is peptic ulcer disease is perforation the first indication
No rarely the first indication
Treat peptic ulcer disease
H pylori eradication, neutralization of acid via PPI
Discontinue NSAIDS
Surgery is relegated for bleeding or perforated peptic ulcers because antibiotics are so effective
Mucosal atrophy and intestinal metaplasia
Long standing chronic gastritis of body and fundus leads to loss of parietal cell mass (oxyntic atrophy)
How do we recognize mucosal atrophy and intestinal metaplasia
Presence of goblet cells
Risk of mucosal atrophy and intestinal metaplasia
Risk of adenocarcinoma is greatest in autoimmune gastritis possibly because achlorhydria of gastric mucosal atrophy allows overgrowth go bacteria that produce nitrosamines
Mucosal atrophy and metaplasia h pylori
Less commonly occurs in chronic h pylori gastritis, but regresses after clearance of organism
Dysplasia
Pre invasive in situ lesion
Chronic gastritis exposes epithelium to inflammation related free radical damage and proliferate stimuli
Pathogenesis dysplasia
Chronic gastritis leads to accumulation of genetic alterations-> pre invasive in situ lesions->carcinoma
Morphology dysplasia
Variable epithelial size, shape and orientation with coarse chromatin texture, hyperchromasia and nuclear enlargement
Remain cytologically immature (vs regenerating epithelial cells which mature at surface)
-reactive epithelial cells mature as they reach the mucosal surface, while dysplastic lesions remain cytologically immature
Gastritis cystica
Exuberant epithelial proliferation with entrapment of epithelium lined cysts
Gastritis cystica submucosa
Gastritis cystica polyposa
Gastritis cysticadeep layers of gastric wall
Gastritis cystica profunda
What is gastritis cystica associated with
Chronic gastritis and partial gastrectomy
-presumed that gastritis cystica i trauma induced
Gastritis cystica may mimic what
Invasive adenocarcinoma
-regenerative epithelial changes can be prominent the entrapped epithelium
Hypertrophic gastropathies
Uncommon diseases characterized by giant cerebriform enlargement of the rugal folds due to epithelial hyperplasia without inflammation
Get excessive growth factor release
Examples of hypertrophic gastropathies
Menetrier disease
Zollinger Ellison syndrome
Menetrier disease
Rare, diffuse foveolar cell hyperplasia of the body and fundus
Pathology menetrier disease
Protein losing enteropathy leads to systemic hypoproteinemia
Due to overexpression of TGFa
Morphology menetrier disease
Irregular enlargement of gastric rugae in body and fundus
Hyperplasia of foveolar mucous cells
Glands are elongated with a corkscrew like appearance with cystic dilation
Only modest inflammation
Diffuse patchy hypoplasia of parietal and chief cells is common
Menetrier disease presentation
Weight loss, diarrhea, peripheral edema (hypoproteinemia)
Menetrier disease kids
Self limiting
Ofte follows a respiratory infection in children
Adults with menetrier disease have an increased risk of what
Increased risk of gastric adenocarcinoma in adults
Treat menetrier disease
IV albumin+parenteral nutrition (supportive)
TGFa blocking agents show promise
Severe:gastrctomy
Zollinger Ellison
Rare gastrinoma (gastrin secreting tumors) of the small intestine or pancreas
Increased gastrin levels in zollinger ellison
Proliferation of gastric parietal cells (up to 5x)
In zollinger ellison, there is hyperplasia of what
Mucus and neck cells
In zollinger ellison there is __ hyperproduction
Mucin
Characterization zollinger ellison
Doubling of the oxyntic mucosal thickness due to
- a fivefold increase in the number of parietal cells
- hyperplasia of mucous neck cells
- mucin hyperproduction-proliferation of endocrine cells within oxyntic mucosa
Presentation of zollinger ellison
Duodenal ulcers (excess aid production) and/or chronic diarrhea
Zollinger ellison increased risk of
Proliferation of gastric endocrine cells (may form small nodules or true carcinoid tumors)
Treat zollinger ellison
Block hypersecretion of acid via PPI
Allows peptic ulcers to heal
Prevents gastric perforation
Then begins to focus on the tumor, the main determinant of long term survival
Gastrinomas-what percent malignant
60-90% though slow growing
Gastrinomas-what percent sporadic
75%
Gastrinomas: what percent have MEN I (multiple endocrine neoplasia) aka warmer syndrome
25%
Treat gastrinomas
Somatostatin analogues
Menetrier disease-age, location, predominent cell, inflammatory infiltrate, signs and symptoms, risk factors, malignant transformation
30-69
Body and fundus
Mucosa
Limited, lymphocytic
Hypoproteinemia, weight loss, diarrhea, peripheral edema
None
Yes
Zollinger ellison - age, location, predominant cell, inflammatory infiltrate, sign and symptoms, risk factors, malignant transformation
50
Fundus
Parietal cells > mucous, endocrine
Neutrophilic
Peptic ulcers (duodenal)
MEN 1
No
Inflammatory and hyperplastic polyps-age, location, predominant cell, inflammatory infiltrate, signs and symptoms, risk factors, malignant transformation
50-60
Antrum>body
Mucous
Neutrophils and lymphocytes
Similar to chronic gastritis
Chronic gastritis, H pylori
Occasional
Gastrica cystica - age, location, predominent cell, inflammatory infiltrate, signs and symptoms , risk factors, malignant transformation to adenocarcinoma
Variable
Body
Mucous, cyst-lining
Neutrophils and lymphocytes
Similar to chronic gastritis
Trauma, prior surgery
No
Fundus gland polyps-age, location, predominent cell, inflammatory infiltrate, signs and symptoms, risk factors, malignant transformation to adenocarcinoma
50
Body and fundus
Parietal and chief
None
None, nausea
PPIs, FAP
Syndromic (FAP)
Gastric adenomas-age, location, predominent cell, inflammatory infiltrate, signs and symptoms, risk factors, malignant transformation to adenocarcinomas
50-60
Antrum>body
Dysplastic intestinal
Variable
Similar to chronic gastritis
Chronic gastritis, atrophy, intestinal metaplasia
Frequent
What is the most common gastric polyp and tumor
Hyperplastic (inflammatory) polyp
75% of all gastric polyps
What are hyperplastic (inflammatory ) polyps associated with
Chronic gastritis (indicated the injury that leads to reactive hyperplasia and polyp growth)
Who gets hyperplastic polyps
50-60
In hyperplastic polyps, dysplasia is correlated with what
Polyp size
Morphology hyperplastic polyps
Multiple
Ovoid in shape with a smooth surface, though there may be superficial erosions/ulceration
Irregular, dilated, elongated foveolar glands
Lamina proporia is edematous with variable acute/chronic inflammation
Fundic gland polyps
Polyps that develop in the gastric body and fundus , can be single or multiple
Why get fundic gland polyps
Sporadically and in individuals with familial adenomatous polyposis (FAP)
Fundic gland polyps have increasaed incidence associated with what
With increased PPI use
Why do PPI cause fundic gland polyps
PPI inhibit acid production->increased gastrin secretion->tropic effect of oxyntic glands
Presentation of fundic gland polyps
Asymptomatic OR nausea, vomiting or epigastric pain
Morphology fundic gland polyps
Well circumscribed lesions with a smooth surface
Cystically dilated, irregular glands lined by flattened parietal and chief cells
Inflammation absent or minimal
Genetic fundic gland polyps
FAP mutation
Cancer risk of sporadic fundic gland polyps
Sporadic fundic polyps carry zero cancer risk
Cancer risk familial adenomatous polyposis (FAP) associated polyps
Dysplasia and cancer can follow
Gastric adenoma represent _% of gastric polyps
10
What are gastric adenoma associated with
FAP and chronic gastritis with atrophy and intestinal metaplasia (gastric adenomas are pre malignant neoplastic lesions)
Gastric adenoma risk of transformation
Risk of transformation to invasive cancer is much higher in gastric adenomas than intestinal adenomas
Males or females gastric adenoma
Males 3:1
Who gets gastric adenoma
50-60
Gastric adenoma single or multiple
Solitary
Where are gastric adenomas
<2cm, if greater be concerned
Antrum
Morphology gastric adenomas
Some degree of dysplasia of the intestinal type columnar epithelium
Enlargement, elongation, pseudostratification, hyperchormasia of nuclei, epithelial crowding
High grade: more atypia, glandular budding, gland within gland, or cribiform structures
Most common malignant of the stomach 905
Gastric adenocarcinoma
Where are gastric adenocarcinoma
Antrum
Who gets gastric adenocarcinoma
Japan, china, Costa Rica, Eastern Europe
Where should we use mass endoscopic screening for gastric adenocarcinoma
Effective in areas where incidence is high
Not cost effective in areas where incidence is low
Socioeconomic status and gastric adenocarcinoma
Most common in lower socioeconomic groups and individuals with multifocal mucosal atrophy and intestinal metaplasia—gastric dysplasia and adenomas are recognizable precursor lesion associated with gastric adenocarcinoma
Environmental factors gastric adenocarcinoma
H pylori cause of overall reduction in gastric cancer is most closely linked to decrease in h pylori prevelance
Dietary factors and gastric adenocarcinoma
Gastric cancer rates in second generation immigrants similar to those in their new country of residence
Nitroso compounds, benzoapyrene=increased
Antioxidants of fruit/vegetables, leafy greens=decreased
Partial gastrectomy (for PUD) allows bile reflux and development of chronic gastritis
Gastric adenocarcinoma precursor lesion
Gastric dysplasia and adenomas
Why is overall incidence of adenocarcinoma falling
Likely due to barrett esophagus , reflecting increased GERD and obesity
-gastric cardia cancer on the rise
Genetics gastric adenocarcinoma
TP53 mutation in both diffuse and intestinal gastric cancers
Metastases of gastric adenocarcinoma goes to where
- left supraclavicular sentinel lymph node (virchow node)
- periumbilical lymph nodes (sister Mary Joseph nodule)
- left axillary lymph node (Irish node)
- ovary (krukenberg tumor)
- pouch of Douglas (blunder shelf)
Diffuse type gastric adenocarcinoma
Infiltrates the wall diffuses, thickens it and is typically composed of signet ring cells
Genetics diffuse gastric adenocarcinomas
CDH1(tumor suppressor gene that encodes E cadherin) mutation, BRCA1
-loss of e cadherin is a key step in the development of diffuse gastric cancer
Diffuse type gastric adenocarcinoma morphology
- signet ring cells that are discohesive and do not form glands-discohesive as a result of loss of e cadherin
- large intracellular mucin vacuoles that push nucleus to the periphery=signet ring
- induce fibrous desmoplastic response
- no identified precursor lesion
- linitis plastica (leather bottle): appearance when there are large areas of infiltration, diffuse rugal flattening, and a rigid , thickened wall
Diffuse type gastric adenocarcinomas: epidemiology
Occurs uniformly across the globe
No gender preference
Clinical diffuse type gastric adenocarcinoma
- incidence is uniform across countries
- no identified precursor lesions
- no gender preference
- early satiety=gastric wall cant expand
Intestinal type gastric adenocarcinoma
Forms bulky masses
Intestinal type gastric adenocarcinoma genetics
Increased Wnt signaling
Loss of function mutations: APC, TGFb, BAX, CDKN2A (tumour suppressor genes…FAP patients carry germline APC mutations->increased risk of intestinal type gastric cancer)
-gain of function B catenin
Genetic variants of pro inflammatory and immune response genes, including those that encode IL-1B, TNF, IL10, IL8, and TLR4 are associated with elevated risk of gastric cancer when accompanied by H pylori infection (chronic inflammation accompanies gastric neoplasia)
Morphology intestinal type gastric adenocarcinoma
Tend to grow along broad cohesive fronts to form either an exophytic mass of an ulcerated tumor
Apical mucin vacuoles, abundant mucin may be present in gland lumina
Develop from precursor lesions including flat dysplasia and adenomas
Epidiomiology intestinal type gastric adenocarcinoma
55 years
Males 2:1
Occurs mostly in high risk areas
Decrease in gastric cancer incidence applies only to the intestinal type because intestinal type is more closely associated with atrophic gastritis and intestinal metaplasia
Clinical gastric adenocarcinoma
Early signs and symptoms resemble chronic gastritis and PUD
Dyspepsia, dysphagia, nausea
Often discovered locate with weight loss, anorexia, early satiety, anemia, and hemorrhage
Prognosis gastric adenocarcinoma
Depth of invasion and extend of nodal and distant metastases at time of diagnosis==most important
Local invasion of duodenum, pancreas and retoperitoneum
Metastases to virchow node , periumbilical nodes, axillary nodes, or pouch of Douglas
Treatment gastric adenocarcinoma
Surgical resection remains preferred
Survival gastric adenocarcinoma (local lymph node metastases)
5 year survival >90% even with lymph node metastases
Survival gastric adenocarcinoma (advanced)
<20% 5 year survival
Overall survival gastric adenocarcinoma
30% 5 year survival
Why is prognosis for gastric adenocarcinoma not great
Advanced stage that most gastric cancers are discovered
MALToma
Extranodal lymphoma that arises anywhere in the GI tract, but espicially in the stomach
What is the most common site of extranodal lymphoma
Stomach
What is the msot common site of EBV-positive B cell lymphoproliferations in allergenic hematopoietic stem cell and organ transplant recipients
Bowel
What percent of gastric malignancies are primary lymphomas
5
Induction of MALToma
Induced as a result of chronic inflammation (chronic gastritis: H pylori)
Most commonly raised sites of MALToma
Arises in sites normally devoid of organized lymphoid tissue
Induction of stomach MALT
Result of chronic gastritis
Most common induction of MALToma in stomach
H pylori most common inducer in the stomach
H pylori eradication results in durable remission with low rates of recurrence for MALToma. How treat h pylori
Combination antibiotic therapy results in long term remission—treat the underlying condition and cure the cancer
Peters patches MALToma
May also occur in areas of preexisting malt (Peyers patches)
Antibiotics MALToma
Induces tumor regression
Recurrence rate MALToma
Low rate of recurrence
Genetics MALToma-what are the three translocations?
T(11;18)(q21;q21) most common
T(1;4)(p22;q32)
T(14;18)(q32;q21)
Also h pylori can activate MLT/BCL10 pathway in MALTomas that lack these translocations
What do the translocations of MALTomas cause
Constitutive activation of NFKB-> B cell growth and proliferation
T(11;18)(q21;q21)
API2 (apoptosis inhibitor)-MLT (mutated in MALT lymphoma) fusion protein
T(1;4)(p22;q32)
Increased BCL-10
T(14;18)(q32;q21)
Increased expression of intact MALT1
Prognosis MALToma
Failure to eradicate leads to invasion of muscularis proporia and lymph node involvement
May transform to more aggressive diffuse, large B cell lymphomas
Associated with p53+/p16 mutations which makes them unresponsive to H pylori eradication
Morphology MALTomas
Dense infiltrate of atypical lymphocytes in lamina proporia
Neoplastic lymphocytes infiltrate the gastric glands vocally to create lymphoepithelial lesion (diagnostic)
May have B cell follicles or plasmacytic differentiation
Express CD19, 20-B cell markers
25% CD43+ve-unusual feature that may be diagnostic
Monoclonality may be demonstrated by restricted expression of either kappa or gamma light chains
Presentation MALToma
Dyspepsia+epigastric pain
Possible hematemesis, melena and constitutional signs and symptoms (weight loss)
MALToma may be difficult to distinguish from
H pylori gastritis
H pylori gastric and MALTOma may __
Coexist or have overlapping signs and symptoms and appearances on endoscopy
Treat MALToma
Combination antibiotic therapy results in long term remission
Carcinoid tumor (well differentiated neruoendocrine tumors)
More indolent course than a GI carcinoma
What are carcinoid tumors associated with
Endocrine cell hyperplasia, autoimmune chronic atrophic gastritis, MEN-I and zollinger ellison syndrome
- gastric endocrine cell hyperplasia has been linked to proton pump inhibitor therapy
- progression to a neuroendocrine neoplasm is extremely low
Where are carcinoid tumor
40% in the small intestine
Tracheobronchial tree and lungs-2nd most common
Carcinoid tumor morphology
Yellow-tan intramural or submucosal masses that create smal polypoid lesions
-typically arise within oxyntic mucosa when in the stomach
Firm due to intense desmoplastic response which can cause bowel obstruction
Range from islands to sheets of uniform cohesive cells with scant granular cytoplasm
Oval, stippled nuclei
Carcinoid tumors are are + for what
Neuroendocrine markers
When does carcinoid tumor present
Peak incidence in 6th decade
Signs and symptoms carcinoid tumors
Based on type of hormone being produced
Prognosis carcinoid tumor
Based on location
Prognosis foregut carcinoid tumor
Rarely metastasize and are generally cured by resection
Carcinoid midgut prognosis
Multiple and tend to be aggressive
Hindgut carcinoid prognosis
Almost always benign
Stomach -prevelance, secretory products, signs and symptoms, behavior, associations
<10%
Histamine, somatostatin, serotonin
Gastritis and ulcers
Variable
Atrophic gastritis, MEN-1
Proximal duodenum-prevelance, secretory products, signs and symptoms, behavior , associations
<10%
Gastrin, somatostatin, CCK
Peptic ulcers, biliary obstruction, abdominal pain
Variable
Zollinger ellison syndrome , NF-1
Jejunum and ileum -prevelance, secretory products, signs and symptoms , behavior,associations
> 40%
Serotonin, substance P, polypeptide YY
Obstruction, metastatic disease
Aggressive
Appendix-prevelance, secretory products,signs and symptoms, behavior, associations
<25%
Serotonin, polypeptide YY
Asymptomatic
Benign
Colorectal -prevelance, secretory products, signs and symptoms, behavior, associations
<25%
Serotonin, polypeptide YY
Abdominal pain, weight loss
Variable
Carcinoid syndrome
Ileal tumors that lead to cutaneous flushing+sweating
Bronchospasm
Diarrhea+colicky abdominal pain
Right sided cardiac valvular fibrosis
Due to vasoactive secretion of 5HT into systemic circulation
Associated with metastatic liver disease
Intestinal tumors that produce vasoactive substances have significant ‘first pass’ effect
—-no first pass if liver is burdened with disease
Gastrointestinal stromal tumor
Most common mesenchymal tumor of the abdomen
Mesenchymal tumor that arises from intestitial cells of cajal (pacemaker cells for gut peristalsis) or the GI muscularis propria
Where do gastrointestinal stromal tumor
1/2 in stomach
Precursor lesions gastrointestinal stromal tumor
Clinically silent with low mitosis index, lack pleomorphism
Age of gastrointestinal stromal tumor
60 years
Kids gastrointestinal stromal tumor
Carney triad (non hereditary syndrome of unknown etiology seen primary in young females that includes GIST, paraganglioma, and pulmonary chondroma)
Increased risk of gastrointestinal stromal tumors in who
Increased risk in patients with NF1
GIST genetics
KIT tyrosine kinase gain of function 80%
PDGFRA activating mutation 8%(overexpressed in stomach)
Deletion of chromosome 9p (CDKN2A), 14, and 22
Alterations in chromosome #
Mitochondrial succinate dehydrogenase complex (SDH-A, SDH-B, SDH-C, SDH-D) mutation
- loss of function of SDH inherited germline
- Carey-stratakis syndrome :increased for GIST and paraganglioma
Mutation of _ or _ (mutually exclusive) is an early even in sporadic GIST
KIT
PDGFRA
Morphology GIST
Solitary, well-circumscribed fleshy masses
Cut surface shows whorled appearance
Epithelioid: epithelial appearing cells
Spindle type:the elongated cells
Diagnostic markers for GIST
KIT in interstitial cells of cajal and 95% of gastric GIST
Clinical GIST
Signs and symptoms related to mass effects or blood loss (anemia)
Treat GIST
Surgical resection
KIT, PDGFRA GIST treat
Imatinib treatment (resistance due to secondary mutations)
What determines prognosis GIST
Tumor size, mitosis index, location
Gastric GIST are _ aggressive than intestinal GIST
Less
Recurrence is _ for GIST smaller than 5 cm but ___ for mitotically active tumors larger than 10 cm
Rare
Common
