1 esophagus and stomach_learn

8/7/2019 1 ESOPHAGUS AND STOMACH_Learn

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ESOPHAGUS AND STOMACH


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Review Polyp: Any bump on the gut that sticks up above the inner surface into the lumen.

Hernia: Presence of a portion of an organ in a body space where it doesn't belong. Incarcerated hernia: One that can't be reduced, i.e., put back in its proper place.

Strangulated hernia: Where venous drainage is compromised and infarction is

imminent / present.

Erosion: A portion of the epithelium mucosa has been lost due to necrosis, butthere has been no lossofthe underlying connective tissue. In the stomach, as theterm is generally used, there may be loss of some connective tissue but sparing themuscularis mucosae.

Ulcer: A portion of the epithelium andsome ofthe underlying connective tissuehas been lost due to necrosis. In the stomach, an "ulcer" is typically diagnosed onlyif the muscularis mucosae is lost.

Diverticulum: An outpouching ofall the layersof the wall of a hollow organ.

Pseudo-diverticulum: Outpouching ofmucosa through a defect in the muscularispropria.

Paracrine / endocrine cells ("enterochromaffin, formerly "APUD" cells) are foundindividually all along the gut, and various ones produce various peptide hormonesof known and unknown significance.


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Strangulated umbilical hernia


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Review Reflux leads to fibrosis (scarring, shortening, perhaps narrowing) of

the esophagus, difficulty on swallowing ("dysphagia"), pain inswallowing ("odynophagia"), retrosternal pain ("heartburn") and/orslow GI bleeding leading to iron-deficiency. In severe cases, massiveGI bleeding (hematemesis, melena) can occur.

Other noteworthy causes of esophagitis include candida, CMV,

herpes, radiation, generalized diseases of stratified squamousepithelium or keeping a stomach tube down for more than a fewminutes. All the above can give some nasty ulcers.

You also remember the esophageal changes ("rubber hose") inscleroderma.

Drinking lye or some other caustic substance leads to corrosiveesophagitis, strictures, etc., etc.

The common cancers of the GI tract are carcinomas. Often the firstphysical finding is Virchow's sentinel lymph node, where the thoracicduct joins the left internal jugular vein.


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Norma

gastroesophageal

junction

This is a normal esophagus with the usual white to tan

smooth mucosa seen at the left. The gastroesophageal

junction (not an anatomic sphincter) is at the center,and the stomach is at the right. The upper GI

endoscopic view of the transition from tan squamous

mucosa to pink columnar mucosa is seen to the right.


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normal esophageal squamous mucosa

This is normal esophageal squamous mucosa at the left, with

underlying submucosa containing mucus glands and a duct

surrounded by lymphoid tissue. The muscularis is at the right.


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Candida Esophagitis

Left: In this necrotic debris, non-branching pseudohyphae and blastocysts arepresent.

Right: Multiple yellow plaques in the midesophagus are shown. In some areas, theplaque material becomes confluent. The surrounding uninvolved mucosa is normalwith a normal vascular pattern.


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Candida esophagitis

*Scrapes off,

unlike glycogen

acanthosis*


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Candida esophagitis


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Herpetic Esophagus

Left: Multiple well-circumscribed ulcers in the midesophagus are shown. Some

of the ulcers have become confluent, resulting in serpiginous shallowulcerations. The intervening mucosa is normal.

Right: The squamous epithelial cells exhibit multinucleation and prominentintranuclear inclusions. The inclusions have a mauve 'ground glass' appearance.


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Herpes of the esophagus


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herpes simplex

The lower esophagus here shows

sharply demarcated ulcerations that

have a brown-red base, contrasted

with the normal pale white

esophageal mucosa at the far left.Such "punched out" ulcers are

suggestive of herpes simplex

infection.


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Cytomegalovirus Infection

of Esophagus


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ESOPHAGUS

The "gullet" begins at the cricophagyngeus (the short "upper esophagealsphincter" starts here) and ends at the diaphragmatic hiatus orthereabouts ("lower esophageal sphincter").

Solid food may hang up at either site, or where the esophagus passesbehind the left main-stem bronchus or between enlarged hilar nodes.N

either sphincter is fool-proof (or even anatomic). Considerable coordination is required for a proper swallow (the big word

for "swallowing" is "deglutition"). Most of the time, the esophagusperforms its simple but important task well.

You remember that the upper esophagus (i.e., the first inch or so) hasmostly skeletal muscle (and is thus subject to diseases of nerve andskeletal muscle), the middle esophagus (i.e., maybe another inch) has bothskeletal and smooth muscle, and the distal esophagus (i.e., most of theesophagus) has mostly smooth muscle.

Unlike most of the rest of the gut, the esophagus has noserosa to helplimit the spreadofripsor cancers.


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Esophagus Birth Defects

Agenesis of some or all of the esophagus isuncommon.

Atresia of the esophagus, as elsewhere, is

failure of a normally-hollow organ to developits lumen. An atretic esophagus is represented, over part or

all of its length, by a fibromuscular cord without alumen. Less severely, portions of the esophagusmay be congenitally stenotic (i.e., too narrow).


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Atresia

The diagnosis of esophageal atresia is

suspected when, in the presence of

polyhydramnios (usually after 25 weeks),

repeated ultrasonographic examinations fail to

demonstrate the fetal stomach.


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Esophagus Birth Defects

Tracheo-esophageal fistulas of severalvarieties are common neonatal surgicalproblems.

The proximal esophagus may enter the trachea orbronchus, producing coughing upon feeding.

The proximal esophagus may end blindly and thedistal esophagus arise from a large airway,preventing feeding and causing the stomach to fill

with air (the most common version). Or there may simply be a window between the

two organs.


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Tracheo-esophageal

fistulas Left: The probe enters the

larynx and trachea andpasses through the fistula tothe esophagus.

Right: Barium of fistula


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Globus hystericus ("globus syndrome",

"globus pharyngeus")

A "lump in the throat", is spasm of the back of thethroat and perhaps the upper esophagus.

It creates the feeling of a mass in the hypopharynx.Sometimes the cause is organic (i.e., a reflex fromsomething wrong nearby, perhaps reflux from theesophagus spilling into the larynx); often it'spsychosomatic.

Psychiatrists attribute it to "swallowed tears", and

the cure is to cry. (D

espite its banal nature, thesensation of a mass may frighten a patient.Spontaneous cures of non-biopsy-proven throatcancer" sound like globus.)


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Zenker's "pulsion" diverticulum

Adjacent to the cricophagyngeus muscle. A

hiding-place for last week's spaghetti and last

month's pills (so that's why they didn't work....)

The smell alone may create a serious social

problem.

A Zenker's can be a true or pseudodiverticulum


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Zenker's "pulsion"

diverticulum

Left: The diverticulum is on theright and the true esophageallumen is on the left. They areseparated by a "bridge" oftissue.


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Zenkers pulsion diverticulum

*Adjacent to the cricophagyngeus muscle;

can be a true or pseudodiverticulum.


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Achalasia

Means "failure of a sphincter to relax when it should".U

sually, this meansthe lower esophageal sphincter.

In the U.S., the problem is usually idiopathic failure of the lower sphincterto relax. The cause is usually inflammation of the myenteric plexus, witheventual nerve damage, but nobody knows why this happens. In othercases, the ganglion cells are simply lost instead.

The esophagus remains filled with food. The patient (typically a youngadult) will notice regurgitation and bad breath. The situation may becomereally nasty as more and more food accumulates in a mega-esophagus.Fortunately, most patients are cured by a single endoscopic dilatation ofthe sphincter; there's also "botox", or laparoscopic myotomy and partialfundoplication for the hard cases

Untreated, achalasia is a life-threatening problem (carcinoma, aspiration

pneumonia). You remember that Chagas' disease (T. cruzi) is an important cause of

mega-esophagus worldwide.


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Esophageal Achalasia Failure of a sphincter to relax when it should, usually the lower

Usually caused by inflammation of the Myenteric plexus

Can be treated with botox

Birds beak sign on barium swallow


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Achalasia


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Glycogen plaques

These are acanthotic (i.e., thick spiny layer)

epithelium with extra glycogen.

The most common lesion of the esophagus, byfar, and exactly as serious as freckles.


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Webs

These are contracted, localized fibrous scars thatform little shelves ("ledges") that may obstruct thelumen.

They are most common in the upper esophagus, andmost common in women. Their etiology is usually

obscure; some are congenital, some result fromreflux, graft-vs-host disease, and pemphigus.

No one knows quite what to make of a supposedassociation between upper esophageal webs, irondeficiency anemia, and a risk for squamous cellcarcinoma in the proximal esophagus. Whether ornot this really exists, it's called "Plummer-Vinson

syndrome Shown Right.


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Schatzki's ring

This is a washer-shaped partially-obstructing fibrous ring atthe squamo-columnar junctionjust above thegastroesophageal junction. It is a radiologist's delight and maybe seen in any adult; long a mystery, cases that occur in the

absence of reflux may be due to pill enlodgement. A-ring is the same, at the gastro-esophageal junction.

A big chunk of solid food (i.e., poorly-chewed beef) may hangup on a web or ring. In bad cases, softer food may havetrouble negotiating the obstruction.


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Schatzkis ring

A washer-shaped partially-obstructing fibrous ring at thesquamo-columnar junction just above the gastroesophagealjunction


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Schatzki's ring


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Hiatus hernia

This is said to be present whenever a portion

of the stomach pooches up through the

diaphragmatic hiatus.

Present in up to 10% of adults (typically the

overweight), they are most often sub-clinical.


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Hiatus hernia The stomach herniates

upwards into theoesophagus


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Sliding hiatus hernia

A sliding hiatus hernia (the usual kind) is presentwhen a short esophagus (congenital, fibrous scarringfrom years of reflux, diaphragm pulled low byobesity) pulls the proximal stomach into the chest.

As the esophagus contracts during swallowing,radiologists watch the stomach slide further upthrough the diaphragm.

As with "reflux esophagitis", the distal esophagus is

likely to become inflamed and damaged as a result ofexposure to pepsin and acid.


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Para-esophageal ("rolling") hiatus hernia

Para-esophageal ("rolling") hiatus hernia (the lesscommon kind) is present when a portion of thestomach rolls up through the diaphragm alongside anesophagusofnormal length.

This is typically a non-problem, but the herniatedportion of stomach may become strangulated.

Future pathologists: Don't expect to see either type

of hernia (or, for that matter, a Schatzki's ring, or anintestinal hernia) after death, when the muscles ofthe body relax / go into rigor mortis.


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Para-esophageal

("rolling") hiatushernia


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Traction diverticula

These probably result from scar contraction in

the mediastinum (i.e., TB).

They are uncommon.


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Traction diverticula

Arrows point to the small, wide mouth pouch

located at the tracheal bifurcation


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Gastroesophageal reflux (GERD, formerly,

"peptic esophagitis") Common esophagal problem; result of an incompetent lower esophageal sphincter.

Everyone has probably experienced sudden, unexpected reappearance of a little bitof lunch in the back of the mouth. But sustained or frequent reflux starts a viciouscycle that becomes a major threat to the health of the esophagus and lungs.

The sphincter is inflamed, scars, and becomes further damaged. The epitheliumkeeps getting digested and regrowing, with much more opportunity to select formutated cells.

The correlation between clinical symptoms and endoscopy is remarkably poor. Onlyabout half of the patients with severe "GERD" on endoscopy even have heartburn.

The cause of common "reflux" remains obscure. Mechanical problems (includingoverweight and sliding hiatus hernia) must contribute, and the problem is moresevere if there's "excess stomach acid / pepsin / bile" or the gastric contents staysfor some reason within the esophagus. Other things that irritate the esophagus(swallowing spicy food, alcohol, very hot beverages, and/or tobacco juice) will nothelp either. Pregnancy, benzodiazepines, intubation, and tobacco use are allimplicated as well. Lying flat makes matters worse (tip: try propping the head of thebed up on cinder blocks).

The diagnosis of GERD is made clinically on endoscopy, but pathology may beobtained for confirmation.


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GERD


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GERD

Pathologists diagnose reflux based on the following criteria: More than 20% of the thickness of the epithelium is taken up by

basal cells (i.e., cuboidal ones with scanty cytoplasm, i.e., nuclei atleast half the diameter of the cells. Why the thickness of the basal cell layer? In reflux, the surface cells get

digested and the basal cells are multiplying overtime to replace them.

papillae with visible cores more than 2/3 of the way up theepithelium;

eosinophils in the epithelium (we used to teach that this is moresensitive and specific than it really is, but it's still a fairly goodmarker:

polys in the epithelium (this just means there's an ulcer, which iswhat you'd expect if reflux is severe)

balloon cells (hydropic change in injured cells)

Future pathologists: Be sure you've got that specimenproperly oriented, and consider asking the clinician to send

it up on cardboard


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GERD


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Gastroesophageal reflux

THE common esophageal problem, the

result of an incompetent lower

esophageal sphincter.


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Reflux


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esophageal acute ulcer

An esophageal acute ulcer is shown here in which the squamous

mucosa has been lost. In the ulcer base are inflammatory cells

and fibrin.


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Barrett's

Esophagus If replacement of the normal squamous epithelium by a columnar epithelium has

occurred, you may have a Barrett's esophagus.

Today's definitions of Barrett's usually require goblet cells, and for the truly hardcore,the non-goblet cells are both absorptive and secretory. Older definitions of Barrett'sallowed any columnar epithelium type.

Ignore hamartomas of gastric-type mucosa; cancer probably only occurs if there ismetaplasia w/goblet cells, so perhaps one day Barrett's will be redefined to this.

There are at least 2 million "Barrett's" patients in the U.S. In Sweden, 1.6% of thepopulation is affected, with alcohol and tobacco being risk factors.

As you'd expect ("Nowell's law triumphant"), finding a Barrett's esophagus meansthere's been some hits on the genome, and the genetically damaged cells have had achance to overgrow the area because of repeated healing from reflux. This is a fertilebreeding ground for adenocarcinoma of the esophagus.

You'll look at dysplasias from Barrett's biopsies frequently, and there are likely to befurther refinements that will help you let the surgeons know when to operate (laser,scrape, etc). All Barrett's have some hyperchromasia of the nuclei in the lower portionsof the glands. Low-grade dysplasia features loss of mucus production, stratified nuclei inthe crypts, and elongated nuclei in parallel. High-grade dysplasia features stratificationon the surface, branching glands, and/or cribriform stuff in the crypts. Be careful aboutcalling "severe dysplasia" if there is inflammation; it might be better to treat the refluxand repeat the biopsy. One major criterion that says "operate" is loss of the basalorientation of the nuclei, i.e., this is more than just the kind of atypia that one finds in

an adenomatous polyp.


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Barrett's

Esophagus


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Barretts esophagus

Pre-cancer A: normal, stratified squamous epithelium

B: Intestinal metaplasia of epithelium with

chronic inflammation


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Barrett's

esophagus

Another cause for inflammation is a so-called

"Barrett's esophagus" in which there is gastric-

type mucosa above the gastroesophageal

junction.Note the columnar epithelium to the

left and the squamous epithelium at the right.

This is "typical" Barrett's mucosa, because

there is intestinal metaplasia as well (note the

goblet cells in the columnar mucosa).

Metaplasia of the normal

esophageal squamous mucosa

has occurred here, with the

appearance of gastric typecolumnar mucosa.


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Barrett's esophagus


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Perforated esophagus

Perforated esophagus can result from

swallowing the wrong thing. Chicken bones

are infamous these can pierce the heart or

cause other dreadful problems.


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Perforated esophagus

Left: (1)Perforated esophagus with (2) intraluminalhematoma

Right: Histopathology reveals transmural acute and chronicinflammation with extensive ulceration and necrosis of theesophagus.


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Lacerated esophagus

Lacerated esophagus usually results from heavy-dutyvomiting during which the esophagus fails to relax(alcohol abuse, pregnancy, post-anesthesia;"Mallory-Weisssyndrome").

Endoscopists and pathologists see little longitudinaltears, usually in the distal esophagus. They are aproblem only if bleeding is massive, or if theesophagus actually ruptures ("Boerhaave'ssyndrome"; at these sites of rupture, the muscularis

mucosae is apparently absent:


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Lacerated esophagus

A large bird with laceration Only good gross pic. Its

Nasty!


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Mallory-Weiss syndrome

Lacerated esophagus usually results from heavy-duty

vomiting during which the esophagus fails to relax.


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Esophageal varices

Esophageal varices are dilatations of the esophago-gastric venous plexus. These result from portal veinhypertension from any cause, as the blood from thestomach and intestines seeks the low-pressurepathway back to the heart.

You won't know varices are there until they bleed.And they bleed massively when their attenuatedoverlying mucosa is rubbed away, or they just pop

from pressure. This is the fast way out of life formany problem drinkers.


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Esophageal varices


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Esophageal VaricesDilations of the esophago-

gastric venous plexus as a

result of portal vein

hypertension.

* Prone to rupture*

Blue arrows: gastroesophageal junction

Black arrows: varices


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Portal hypertension

Portal hypertension patients will also

commonly exhibit hemorrhoids and dilated

veins around the umbilicus ("caput medusae")

Remember that portal hypertension will

greatly accelerate GI bleeding from non-

variceal causes (gastritis, peptic esophagitis,

ulcer, Mallory-Weiss) as well.


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The causes of portal hypertension....

Pre-hepatic Thrombosis of the portal vein

Hypercoagulability

Polycythemia vera, sickle cell, others

Invasion by tumor (usually hepatocellular carcinoma)

Tumor compressing the portal vein

Intra-hepatic Cirrhosis from any cause

Other obstructive disease Bad alcoholic liver disease without cirrhosis

Schistosomiasis without cirrhosis

Central hyaline sclerosis in alcoholism

Various birth defects Post-hepatic

Budd-Chiari (thrombosis of hepatic veins) Causes as for thrombosis of portal vein


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Tumors of the Esophagus

Benign tumors of the esophagus: Banal, and

relatively uncommon. For example,

fibrovascular hamartomas.

Carcinoma of the esophagus strikes around

8000 people each years and kills most of

them.


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Squamous cell carcinoma

Squamous cell carcinoma has historically been the most common esophagealcancer in the United States, but is becoming less common.

Most patients are males (more than 4:1), black men are at higher risk thanothers, and in the U.S., the large majority are both smokers (cigarets, cigars)anddrinkers.

Old lye strictures are also frequent sites for esophageal cancer, as is the Chagas-disease ridden mega-esophagus.

The epidemic of highly-aggressive squamous cell carcinoma in Mainland Chinahas been attributed to aspergillus fungus contamination, nitrosamines, vitamindeficiency, zinc deficiency, molybdenum deficiency, ethnic teas, and ethnicdelicacies that are pickled (i.e., rendered rich in certain fungi).

Any portion of the esophagus can be involved; the middle third is slightly more

common than the others. Like most squamous cell carcinomas, esophageal cancer arises in squamous

dysplasia, is often multifocal, grows as a fungating lesion (less often, just anulcer), and produces symptoms (dysphagia, food "sticking") only late. Becauseof its location, the later stages of this disease are particularly cruel.


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Squamous cell

carcinoma

The whorled structuresrepresent keratin pearls andindicate that this tumor isdifferentiating into structuresrecognizable as being of

squamous origin


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Squamous Cell Carcinoma of Esopohagus

Most patients are males who

smoke and drink


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SCC of

esophagus

At the upper left is a remnant of

squamous esophageal mucosa

that has been undermined by an

infiltrating squamous cell

carcinoma of the mid-esophagus.

Solid nests of neoplastic cells are

infiltrating down through the

submucosa at the right.

Esophageal cancers often spread

to surrounding structures, making

surgical removal difficult.

At high power, these infiltrating nests

of neoplastic cells have abundant pink

cytoplasm and distinct cell borders

typical for squamous cell carcinoma.

Esophageal carcinomas are not usually

detected early and, therefore, have a

very poor prognosis.


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Adenocarcinoma

Adenocarcinoma is now almost as common as squamous cellcarcinoma, and is probably increasing in frequency. It arises mostoften arising in a Barrett's esophagus. Again, the malepredominance is marked (more than 6:1) and as you'd expect,symptomatic reflux is a strong risk factor.

Tobacco and obesity are risk factors, alcohol consumption is not. It'sbasically the same lesion as cancer of the gastric cardia.

The longer the Barrett's region, the higher the risk, and smoking alsoincreases risk.

Most of the current work on esophageal carcinoma focuses on early,

accurate diagnosis and surgical treatment. This will be of specialinterest to those of you who do primary care in rural areas; you arelikely to do your own endoscopy.

Both types of cancers often arise multifocally. Since normalesophageal epithelium contains glycogen, you can help demarcate

dysplastic squamous epithelium using Lugol's iodine solution.


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Adenocarcinoma Risk Factors:

Male Barretts Esophagus

Tobacco

Obesity

Reflux

Alcohol is not a risk factor

Esophagus


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Stomach Review Healthy mucosa:

Surface, pits ("crypts" / "foveolae") in all areas... Tall surface mucous cells (make "neutral mucus") Deep in pits, all areas... Neck cells (reserve cells for both above and below; "the proliferative zone")

Cardiac glands... More neck-type cells

Gastric glands... Parietal cells (eosinophilic, packed with mitochondria; make acid and intrinsicfactor); Chief cells (pale,granular)

Pyloric glands...Neck-type cells; G-cells (gastrin producers)

Dieulafoy's malformation is an extra-large artery running along the mucosa of the lesser curvature. It

can cause severe bleeding, even into the chest. Intestinal metaplasia: A common finding. Most often it's caused by helicobacter; you might see it in

autoimmune atrophic gastritis with achlorhydria (perhaps due to the associated bacterial colonization);bile reflux and previous radiation.

An experienced endoscopistcan spot areas of intestinal metaplasia by their slightly morewhitish color.

Intestinal metaplasia is clearly the precursor lesion for "intestinal type" stomach cancer.

Any kind of stomach cancer can harbor any kind of mucin. In case somebody (not me) asks: Sulfomucin... Very acid... Intestine; if in stomach, the epithelium is atrophic-metaplastic and is likely

to turn nasty

Carboxymucin... Acid... Intestine (also called "acid sialomucin")

Neutral mucin,,, Neutral... Stomach (also called "neutral sialomucin").

Future pathologists: Use alcian blue to stain the acid mucins!

l


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Normal

Stomach

This is the normal appearance of thestomach, which has been opened along

the greater curvature. The esophagus is

at the left. In the fundus can be seen the

lesser curvature. Just beyond the antrum

is the pylorus emptying into the first

portion of duodenum is at the lower right.The normal appearance of the gastric

fundus on upper GI endoscopy is shown

below at the left, with the normal

duodenal appearance at the right.

This is the normal appearance of

the gastric antrum extending to

the pylorus at the right of center.

The first portion of the duodenum(duodenal bulb) is at the far right.

Di h iIn this case, the diaphragmatic dome is missing


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Diaphragmatic

hernias

result from failure of the

diaphragm to form properly.

Portions of stomach,

intestines, and other organs

end up in the chest.

on the left, allowing herniation of the abdominal

contents into the chest cavity. The metal probe in

the photograph is behind the left lung, which has

been displaced by the stomach. Below the

stomach is a dark spleen (at the white arrow).The white arrow overlies the left lobe of liver

which is extending upward.


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Stomach Birth Defects

Congenital pyloric stenosis isprobably a hereditary defect ofvariable penetrance in which thepylorus of the stomach ishypertrophic, and the gastric outletmay become fully obstructed,

typically at the endofthe firstmonth oflife.

The infant experiences projectilevomiting, and the surgeon feels amass in the upper abdomen. Surgicalsplitting of the pylorus effects acure.

It is more common in boys, andTurner's XO is also a risk.


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Pyloric Stenosis

More common inmales and TurnersXO

Infant experiencesprojectile vomiting


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pyloric stenosis

This is pyloric stenosis. Note the prominent hypertrophied muscle with elongation and

narrowing of the pylorus at the gastric outlet on the left. Pyloric stenosis is uncommon,

but is a cause for "projectile" vomiting in an infant about 3 to 6 weeks of age. Males areaffected more than females. The overall incidence is approximately 3 per 1000 livebirths.

The "pacemaker" interstitial cells of Cajal (ICC) regulate motility, and contain the enzyme

heme oxygenase-2 which generates carbon monoxide (CO) as a neurotransmitter to

cause relaxation in adjacent smooth muscle cells. The lack of ICCs in pyloric stenosis

results in deficient CO production leading to motility dysfunction.


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Dilated stomach

Often impressive.

Causes include beer chug-a-lugging, bowel obstruction, misplacedendotracheal tubes, gastroparesis (think of diabetic autonomicneuropathy), and (in the dead) inept CPR attempts. (Amateursfirst blow air into the stomach, then rupture it by pressing in the

wrong place.


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Bezoars

These are swallowed goodies that remainpermanently in the stomach.

Hairballs (trichobezoars) are seen in people whoenjoy nibbling their long hair ("Rapunzel

syndrome"). Or ask a pet cat.


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Phytobezoars

May be chunks of ill-chewed vegetable matter, or (worst) persimmonremnants. The latter contain a substance that, complexed with acid, turnsinto cementand may require surgery.

Treating a gastric phytobezoar with meat tenderizer.

Things that interfere with gastric emptying (diabetes, other dysautonomias,post-vagotomy, anti-cholinergic medicines) enhance one's ability topersonally experience a bezoar.


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gastroparesis


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Acute gastritis

Acute damage to the gastric mucosa from any cause.

Pathologists define this to be neutrophils in the epitheliumabove the basement membrane.

If there is necrosis of any epithelial cells, it is "erosivegastritis" -- you remember that an erosion is inflammationplus necrosis of an epithelium without necrosis of theunderlying connective tissue (at least not yet).

Pathogenetic mechanisms include: compromise of the mucosal defenses

killing of epithelial cells

increased acid production / decreased bicarbonate production ischemic injury


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Acute Gastritis Important causes:

alcohol consumption

aspirin use (remember this one; even the "minidose aspirin" that is supposed to be sogood for you gives about half of users gastric erosions

caffeine use

chemotherapy for cancer

food allergy (it's for real, and endoscopy is much more accurate than skin-tests or RAST.Probably causes at least some of the cases of the mysterious "eosinophilicgastroenteritis".

Helicobacter (see below)

radiation injury

reflux of lysed lecithin ("lysolecithin") from the duodenal bile

shock

spicy foods

staph food poisoning

"stress" (maybe)

tobacco use

viruses (Norwalk calicivirus winter "stomach 'flu", others; all about viral gastroenteritis

You can figure out for yourself what the mechanisms might be in each case.Anatomically, you may see anything from mild edema and a few polys to bloodysloughing of chunks of the upper mucosa, and symptoms can range from "upsetstomach to vomiting blood by the pint.

Autoimmune ("fundic", "chronic active",


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Autoimmune ( fundic , chronic active ,

"diffuse atrophic", "type A") chronic

gastritis An autoimmune process that attacks primarily the fundic glands. You'll see loss of mucous secretion, striking shortening of the glands,

and usually loss of the parietal cells.

Patients usually (60+%) have autoantibodies against parietal cellH+/K+ ATPase (and usually others against intrinsic factor).

This is the usual cause of the achlorhydria (i.e., greatly diminished orno stomach acid) and Addisonian pernicious anemia.

Around 10% of these patients go on to develop stomach cancer.

Many of these patients have other autoimmune endocrine diseasesas well. The three to remember are Addison'sdisease oftheadrenals, Hashimoto'sdisease ofthe thyroid and insulin-dependentdiabetes.

Future pathologists: Since there is no acid and no feedback, the G-cells undergo hyperplasia in the antrum. They are a single layer ofclear cells. This is a breeding-ground for carcinoids supposedly.

Work on autoimmune gastritis is overshadowed nowadays byhelicobacter, but the finding of anti-parietal cells seems solid.

Perhaps those lacking the antibody were really helicobacter-inducedatrophy (see below). And helicobacter itself can supposedly triggerthe autoantibodies.


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Acute Gastritis

Neutrophils in the epithelium above the basement

membrane


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acute gastritis

At high power, gastric mucosademonstrates infiltration by neutrophils.

This is a more typical acute gastritis

with a diffusely hyperemic gastric

mucosa. There are many causes for

acute gastritis: alcoholism, drugs,

infections, etc.

Eosinop i ic


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allergic

gastroenteritis

H li b t t iti


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Helicobacter gastritis The vast majority of the old "unexplained chronic gastritis" ("type B gastritis") cases are caused by

helicobacter.

You'll have no trouble recognizing the familiar wiggly creatures on the surface of (often obviouslydamaged) gastric mucosa.

Giemsa, immune, or silver stains show them to advantage.

Helicobacter flourishes in the stomach because it cleaves urea to ammonia under acid conditions.

Helicobacter's virulence factor, CagA protein, actually gets inoculated into the stomach cells.

Nobody knows yet exactly what it does to cells after it enters, though it deregulates at least one growthcontrol gene. The other virulence factor, VacA (vacuolizing cytotoxin A) is even more mysterious.

There's a chronic infiltrate with both lymphocytes and neutrophils. Lymphoidfollicles in the mucosa

suggest "Helicobacter". Pyloric metaplasia advances from the antral area into the fundus, perhaps decreasing acid production,

and the fundic glands may atrophy as well. You may see intestinal metaplasia, especially near any ulcersthat may be present. Acid production may be increased, decreased, or normal.

When the fundus is involved, the fundic glands become shallow ("patchy atrophic gastritis", to bedistinguished from autoimmune atrophic gastritis), and typically exhibit intestinal metaplasia (i.e.,enterocytes, goblet cells; it's especially pre-malignant -- type III -- when they are filled with "acidmucus/sulfomucus" as in the real intestine) and/or antral metaplasia (neck cells, G-cells). In advanced

autoimmune gastritis only, the parietal cells are completely gone. In any portion, the rugae are likely to flatten and vanish. The process begins at the surface and work

downward into the glands. Lesions of various stages are present simultaneously in different parts of thestomach. Eventually, the surface will come to exhibit at least some intestinal metaplasia and probablysome degree of dysplasia.

Helicobacter gastritis involving most of the stomach is the precursor lesion to the epidemic stomachcancers seen in much of the world.

Removing Helicobacter cures this illnes. Most people with significant duodenitis (i.e., polys) have

Helicobacter gastritis


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Helicobacter

gastritis


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Helicobacter Pylori Helicobacter gastritis involving most of

the stomach is the precursor lesion tothe epidemic stomach cancers seen inmuch of the world

Lymphoid follicles in the mucosa suggestHelicobacter


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Menetrier's disease ("idiopathic


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( p

hypertrophic gastritis"; "enlarged fold

gastitis) Idiopathic hyperplasia of

the surface mucous cells,with correspondingatrophy of the glands.Makes for some big folds,and a lot of protein loss inthe excessive mucus.

Menetrier's is caused (at

least sometimes) byHelicobacter, and resolveswhen you clear thebacteria.


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Menetriers disease

Idiopathic hyperplasia

of the surface mucous

cells, with

corresponding atrophyof the glands

Menetriers


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Menetrier s

disease


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Zollinger-Ellison syndrome

Gastrinoma (often in the pancreas) causing

hyperplasia of the gastric glands. Makes for a

very upset, ulcerated stomach.


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Stress ulcers

(the usual "acute erosions")

small (less than 1 cm) areas of loss of some (or all) the mucosa.Note thatnobody really knows where "acute gastritis" leaves off and "stress ulcers"begin; probably they're part and parcel of the same reaction pattern.

If the patient has burns, they are "Curling's ulcers" (* think of a hotcurling iron). If the patient has intracranial trauma, they are "Cushing'sulcers" (attributed to vagal stimulation of gastric acid secretion, named forfamous neurosurgeon Harvey Cushing).

Their pathogenesis constitutes a major mystery of medicine. Except inCushing's ulcers, hyperacidity does not seem to be the problem. Most ofthe factors that produce "acute gastritis" can also help produce stressulcers. Some workers now favor catecholamine effect (i.e., ischemia)

and/or some glucocorticoid effect. Pre-pyloric erosions are due to stress


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Stress Ulcers

Small (


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Curling Ulcers

Peptic Ulcers


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Peptic Ulcers Ulcers resulting from the digestive actionofacid-pepsin ("no acid, no ulcer") on the gastric

mucosa. A common problem,somewhat more common in men, usually subclinical, prone to

remit and relapse ("once an ulcer, always an ulcer"). "U

lcers can occur anywhere along theGI tract. Frequency: 80% duodenum 19% stomach 1% elsewhere

The early wisdom was that almost all patients with either gastric or duodenal ulcer patientshave Helicobacter on board, and eliminating the creature eliminates the disease. Of coursethat was an exaggeration; a large minority of stomach ulcer patients are helicobacter-negative.

Other risk factors for ulcer include being under physical or emotional stress, smoking, takingaspirin or NSAID's, boozing, a family history, blood type O (* blood group factors, notablyLewis B, mediate attachment of Helicobacter:; a factor BabA binds to blood group O), havinga job that requires you to be physically active, * non-secretor status (ask a blood banker orcriminologist, these people keep Lewis B on board), hypercalcemia from any cause (enhancesgastrin secretion), cirrhosis and emphysema (make life stressful), and having a stomach tubedown.None of these are overwhelmingly powerful. (You will get an ulcer, and probablyseveral, if you develop a gastrinoma.)

Those with duodenal ulcers tend to secrete acid too abundantly when stimulated, and to

empty their stomachs too readily. Gastric ulcer types tend to have low-normal levels of acid, and tend either to have chronic

gastritis or take lots of aspirin or other substances noxious to the stomach. People withlongstanding gastric ulcers almost all have "chronicgastritis" in the antrum, and intestinalmetaplasia near the ulcer.


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Peptic Ulcers

Most (almost all) patients with duodenal ulcers, and a majority of those with gastric ulcers,now are known to have Helicobacteron board, and the bug is thought to be an importantpart of the pathogenesis.

In the duodenum, there appears to be a vicious cycle between Helicobacter infection andantral metaplasia that permits the bugs to thrive. This is not surprising, considering theabrupt appearance and disappearance of ulcers. Antral metaplasia is a common finding innormal duodenum, and perhaps this how duodenal ulcers begin.

The rare Helicobacter-negative duodenal ulcer patient may have Crohn's, Zollinger-E

llison,taking steroids or NSAID's, or just be unlucky.

Peptic ulcers are usually single, and most are less then 3 cm across. They look sharplypunched-out (as you'd expect, rolled borders suggest malignancy). However, they maypenetrate deeply. The base is always keep clean by digestive juice.

Gastric ulcers are usually on the lesser curvature, and the favorite site is near or in theantrum. Duodenal ulcers are usually in the first portion, but may be anywhere. As scarcontracts, the mucosal folds radiate from the ulcer.

Peptic ulcers may cause pain (relieved when food or antacid neutralizes stomach acid,recurring after a meal stimulates stomach acid), hemorrhage, perforate (call the surgeon!)and/or cause fibrosis leading to obstruction (notably of the pylorus).

We believe they do not undergo malignant transformation ("cancers often ulcerate, butulcers seldom/never cancerate").

Future surgeons: You may "CHOP" out the ulcer if it is chronic, hemorrhaging uncontrollably,obstructing the gastric outlet, or perforated.

Peptic Ulcers


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Peptic Ulcers


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Peptic Ulcers


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Hyperplastic ("inflammatory") polyps

Extremely common and thought to result fromexuberant regeneration of the mucosalepithelium.

They usually look like multiple little rice grains,but may be larger. Microscopically, they arecomposed ofdilated glands lined with pit-typecells.

The big ones (over 1.5 cm) can turn cancerous


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Hyperplastic polyps of stomach Extremely common and thought to

result from exuberant regenerationof the mucosal epithelium

Microscopically: dilated glands linedwith pit-type cells

Stomach

Adenomatous polyps


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Adenomatous polyps

("neoplastic polyps", "adenomas")

Tend to be pedunculated, with villi and/or

crypts, and the current definitions require

some dysplasia. They are premalignant, there

is a link to syndromes and a familial tendency,and maybe half would turn into cancer if left

alone (but who wants to do that study?)


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Adenomatouspolyps

adenomatous


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adenomatous

polyp

The concept of differentiation is

demonstrated by this smalladenomatous polyp (tubular adenoma)

of the colon. Note the difference in

staining quality between the epithelial

cells of the adenoma at the top and the

normal glandular epithelium of the

colonic mucosa below.

i i bl


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Gastric Leiomyoblastoma

This unusual smooth muscle tumor showsa velvetty red mucosa over its surface.

This is stomach mucosa.

i i l l


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Gastrointestinal stromal tumors

The common spindle-cell neoplasms of the

stomach, bearing a trademark c-kit mutation

and stainable antigen, and responding to

Gleevic(imatinib). They range from totallybenign to highly malignant.


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Gastrointestinal

stromal tumors

G i i id


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Gastric carcinoid

High levels of gastrin causes enterochromaffin

cell hyperplasia, and most people who get

gastric carcinoid have high gastrin levels

(atrophic gastritis or Zollinger-Ellison). Andrats actually get such tumors after lifetime

omeprazole.


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Gastric carcinoid

G t i d i


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Gastric adenocarcinoma

While its prevalence in the U.S. has decreased strikingly in recent decades, thiscontinues to be an important cancer killer in every country. Around 15,000 peopleper year die of stomach cancer in the U.S. Rates in the rest of the world are alsodeclining.

Risk factors include: diet -- smoked food, ethnic pickled delicacies, lack of green vegetables, liking your meat

well-done, lack of meat / animal fat, nitrates/nitrites (obviously alot of this is junk

science) status post partial gastrectomy (the old ulcer operation)

helicobacter

blood groups A and AB

Diet and environment are evidently much more important than ethnicbackground. First-generation immigrants have the risk of their home countries;second-generation immigrants the risk of their new countries

There are two major types of gastric adenocarcinoma, with different cells of origin: (1) Diffuse infiltrative gastric adenocarcinoma

(2) Intestinal type gastric adenocarcinoma.

G t i d i


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G t i d i


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Gastric


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adenocarcinoma

This is a signet ring cell pattern of

adenocarcinoma in which the cells arefilled with mucin vacuoles that push the

nucleus to one side, as shown at the arrow.

Diff i filt ti t i d i


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Diffuse infiltrative gastric adenocarcinoma

Arises from the neck cell.

It exhibits small glands made of polyhedralcells with round, tame-looking nuclei, or cells

infiltrating singly. It is the most commonsubtype of signet-ring cancers.

Helicobacter, autoimmune gastritis, andintestinal metaplasia are not risk factors.

The frequency of this cancer is actuallyincreasing dramatically in the US.

Diffuse infiltrative


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Diffuse infiltrative

gastric

adenocarcinoma

I t ti l t t i d i


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Intestinal type gastric adenocarcinoma

Typically arises in the setting oflongstanding

"atrophic gastritis" or other "chronic gastritis",

usually in the presence of helicobacter and/or

autoimmune gastritis and/or intestinal metaplasia

and/or bile reflux.

It features large glands made oftall cells with rod-

shaped nuclei (as in the more common, more

familiar primary carcinomas of the colon). This is thecommon type of stomach cancer in the high-risk

countries

Intestinal type


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Intestinal type

gastricadenocarcinoma

Stomach Cancers


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Stomach Cancers The gross is the usual for a cancer (a cauliflower, an ulcer, or diffuse invasion). The histology

is what you'd expect. In either case, you may see invasive glands, papillae, signet-ring cells,mucus lakes, desmoplasia, and most anything else, though when you see signet ring cellinvasion, it is usually the "diffuse" type rather than the "intestinal" type. Terms: linitisplastica: "leather bottle stomach from a diffusely-infiltrating, desmoplastic cancer.Krukenberg tumor: Drop-metastases causing enlargement of the ovaries. Sister MaryJoseph's node: metastasis to the umbilicus (named for the Mayo brothers' scrub nurse).Rectal shelf ("of Blumer"): Drop-metastases to the lowest place on the peritoneum(remember the "pouch ofDouglas"?)

Symptoms are also what you'd expect -- nausea, vomiting, early satiety, GI bleeding. Asyou'd also expect, there are usually no symptoms until it's too late. (If you have an extracauliflower in you stomach, you'd never know it.)

There is so much stomach cancer in Japan that people get endoscoped routinely in search ofit, and there are many cures (unlike in the US). (For some reason that no one understands,the Japanese have a tremendously high rate of atrophic gastritis, conceivably from the localstrains of helicobacter, and this is where most of these cancers arise. Biopsy all stomach

ulcers you see --even a cancer may shrink on a regimen of H2-blockers and antacids. Most gastric adenocarcinomas are probably preceded by high-grade carcinoma-in-

situ/dysplasia; dysplasia usually invades the mucosa soon, and until it penetrates themuscularis propria, it's called "early gastric cancer" (EGC). It can stay in the mucosa for a longtime.

Some diffuse-infiltrating cancers may start de novo, without dysplasia

Detected late (and it still usually is), stomach cancer has a generally poor prognosis.

The mainstay of therapy for stomach cancer is surgery.

Lymphomas


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Lymphomas

Stomach lymphomas (and other GI lymphomas) are

less common than carcinomas but have a better

prognosis. Since they tend to be bulky, patients

present with obstruction.

Western ("American") lymphomas are usually

familiar B-cell lymphomas. Helicobacter seems to be

the big risk factor. (no surprise, since Helicobacter

makes lymphoid follicles grow). However, manygastric lymphomas are helicobacter-negative and

different genetically.


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Lymphomas

Stomach Lymphoma


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Stomach Lymphoma

Stomach

Less common than carcinomasb h b

1 esophagus and stomach_learn

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