CH 26: STOMACH - Left gastric artery

ANATOMY o Consistently the largest artery to the stomach

Anatomic Relationships and Gross Morphology o Arises directly from the celiac trunk
- Most proximal abdominal organ of the digestive tract o Divides into an ascending and descending branch along the lesser gastric curvature.
- Cardia o Approximately 20% of the time, the left gastric artery supplies an aberrant vessel that
o The part of the stomach attached to the esophagus travels in the gastrohepatic ligament (lesser omentum) to the left side of the liver.
- Lower esophageal sphincter § Rarely, this is the only arterial blood supply to this part of the liver (replaced
o Proximal to the cardia at the GE junction left hepatic artery), and inadvertent ligation may lead to clinically significant
- Pyloric sphincter hepatic ischemia.
o Distal end § The more common smaller accessory left hepatic artery may be ligated
o Connects the stomach to the proximal without significant consequences
duodenum - Right gastroepiploic
- Majority of the stomach is quite mobile: o Second largest artery to the stomach
o Shorter lesser curvature on the right o Consistently arises from the gastroduodenal artery behind the first portion of the
o Longer greater curvature on the left duodenum.
- Fundus - Left gastroepiploic artery
o The superior- most distensible part of the stomach o Arises from the splenic artery, and together with the right gastroepiploic artery, forms the
o Boundaries: rich gastroepiploic arcade along the greater curvature.
§ Superior à diaphragm - Right gastric artery
§ Lateral à spleen o Usually arises from the hepatic artery near the pylorus and hepatoduodenal ligament
o Angle of His and runs proximally along the distal stomach
§ Where the fundus meets the left side of the GE junction - In the fundus along the proximal greater curvature, the short gastric arteries and veins arise from
o Inferior extent of the fundus the splenic circulation.
§ Considered to be the horizontal plane of the GE junction, where the body - There also may be additional vascular branches to the proximal stomach from the phrenic and
(corpus) of the stomach begins splenic circulation.
- Body of the stomach
o Contains most of the parietal (oxyntic) cells Veins draining the stomach
§ Some of which are also present in the cardia and fundus - Generally parallel the arteries.
- At the angularis incisura: - Left gastric (coronary vein) and right gastric veins
o The lesser curvature turns rather abruptly to the right, marking the anatomic beginning o Usually drain into the portal vein
of the antrum à comprises the distal 25% to 30% of the stomach o Occasionally the coronary vein drains into the splenic vein
- Liver, colon, spleen, pancreas, and occasionally the kidney, abut the stomach - Right gastroepiploic vein
o The left lateral segment of the liver usually obscures part of the anterior stomach. o Drains into the superior mesenteric vein near the inferior border of the pancreatic neck
o Inferiorly, the stomach is attached to the transverse colon by the gastrocolic omentum. - Left gastroepiploic vein
o The lesser curvature is tethered to the liver by the hepatogastric ligament o Drains into the splenic vein
§ Also referred to as the lesser omentum or pars flaccida
o Posterior to the stomach is the lesser omental bursa and the pancreas The richness of the gastric blood supply and its many anastomotic connections have important clinical
implications.
Arterial and Venous Blood Supply - At least two of the four named gastric arteries may be occluded or ligated without inducing gastric
ischemia.
o This is done routinely when the stomach is mobilized and pedicled on the right gastric
and right gastroepiploic vessels to reach into the neck as an esophageal replacement or
during sleeve gastrectomy for weight loss when the gastroepiploic arcade is interrupted
proximally and distally prior to gastric resection
- Following radical subtotal gastrectomy during which the right and left gastric arteries and both
gastroepiploic arteries are all ligated:
o The gastric remnant is adequately supplied by short gastric arteries as long as the
splenic artery is patent and intact.
- Angiographic control of gastric bleeding from a deep ulcer or tumor often requires embolization of
more than one feeding artery.
- Because of the rich venous interconnections in the stomach, a transjugular intrahepatic
portosystemic shunt (TIPSS) can effectively decompress esophagogastric varices in patients with
portal hypertension.

Lymphatic Drainage
- Gastric lymphatics parallel the blood vessels (Fig. 26-4)
- The stomach is the most richly vascularized portion of the alimentary tube with ample blood Part Drainage
flow and a dense intramural vascular anastomotic network Cardia and medial half of the corpus Left gastric and celiac axis
- The large majority of the gastric blood supply à from the celiac axis via four named arteries: Lesser curvature side of the antrum Right gastric and pyloric nodes
o Left and right gastric arteries Greater curvature half of the distal stomach Nodes along the right gastroepiploic chain
§ Form an anastomotic arcade along the lesser gastric curvature Proximal greater curvature side of the stomach Nodes along the left gastroepiploic or splenic hilum
o Right and left gastroepiploic arteries
Nodes along both the greater and lesser curvature Celiac nodal basin
§ Form an arcade along the greater gastric curvature
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 - Tumor arising in the distal stomach
o May give rise to positive lymph nodes in the splenic hilum
- The rich intramural plexus of lymphatics and veins
o Accounts for the fact that there can be microscopic evidence of malignant cells in the
gastric wall at a resection margin that is several centimeters away from palpable
malignant tumor.
o Also helps explain the not infrequent finding of positive lymph nodes, which may be many
centimeters away from the primary tumor, with closer nodes that are uninvolved.
- Lymphadenectomy à important part of an operation for gastric cancer
o Postganglionic sympathetic nerves then travel from the celiac ganglion to the stomach
along the blood vessels.
- Intrinsic nervous system of the stomach
o Made up of the neurons in the myenteric and submucosal plexuses
o There may be more intrinsic gastric neurons than extrinsic neurons, but their function is
poorly understood.
o The characterization of the vagus as the cholinergic system and the sympathetic system
as the adrenergic system of innervation is a misleading oversimplification.
o Although acetylcholine is an important neurotransmitter mediating vagal function, and
epinephrine is important in the sympathetic nerves, both systems (as well as the intrinsic
neurons) have various and diverse neurotransmitters, including cholinergic, adrenergic,
and peptidergic (e.g., substance P and somatostatin).

Histology
- Four distinct layers of the gastric wall: mucosa, submucosa, muscularis propria, and serosa
- Mucosa à inner layer made up of: epithelium, lamina propria, muscularis mucosa
Epithelium Columnar glandular
Lamina propria Beneath the basement of the epithelial cells
Contains connective tissue, blood vessels,
nerve fibers and inflammatory cells
Innervation Muscularis mucosa Thin muscle layer beneath the lamina propria
- Vagus nerves Deep boundary of the mucosal layer of the gut
o Provide the extrinsic parasympathetic innervation to the stomach - Scanning electron micrographs show a smooth mucosal carpet punctuated by the openings of the
- Acetylcholine gastric glands or units.
o The most important neurotransmitter o The gastric glands are lined with different types of epithelial cells, depending upon their
- Path of vagus nerve: location in the stomach
o From the vagal nucleus in the floor of the fourth cerebral ventricle, the vagus
traverses the neck in the carotid sheath and enters the mediastinum, where it gives off
the recurrent laryngeal nerve and divides into several branches around the esophagus.
o These branches come together again above the esophageal hiatus and form the left
(anterior) and right (posterior) vagal trunks (mnemonic LARP).
o Near the GE junction:
§ The anterior vagus sends a branch
(or branches) to the liver in the
gastrohepatic ligament, and
continues along the lesser curvature
as the anterior nerve of Latarjet
§ Posterior vagus sends branches to
the celiac plexus and continues
along the posterior lesser curvature
- The nerves of Latarjet
o Send segmental branches to the body of the
stomach before they terminate near the
angularis incisura as the “crow’s foot,”
sending branches to the antropyloric region. - There are also endocrine cells present in the gastric glands.
o There may be additional branches to the distal stomach and pylorus that travel near the - Progenitor or stem cells in the isthmus and base of the glands
right gastric and/or gastroepiploic arteries. o Differentiate and replenish sloughed cells on a regular basis.
- In 50% of patients, there are more than two vagal nerves at the esophageal hiatus. - Genetic studies show that there are several different subpopulations of stem cells in the gastric
o Branch that the posterior vagus sends to the posterior fundus à criminal nerve of glands and that during conditions of stress even chief cells exhibit the plasticity required to
Grassi. regenerate other types of gastric epithelial cells.
§ This branch typically arises above the esophageal hiatus and is easily - Throughout the stomach, the luminal carpet:
missed during truncal or highly selective vagotomy (HSV) o Consists primarily of mucus-secreting surface epithelial cells (SECs) that extend
- Vagal fibers originating in the brain synapse with neurons in Auerbach’s myenteric plexus and down into the gland pits for variable distances.
Meissner’s submucosal plexus. o These cells also secrete bicarbonate and play an important role in protecting the
- In the stomach, the vagus nerves affect secretion (including acid), motor function, and mucosal stomach from injury due to acid, pepsin, and/or ingested irritants.
bloodflow and cytoprotection. o In fact, all epithelial cells of the stomach (except the endocrine cells) contain carbonic
o Also has a role in appetite control and perhaps even mucosal immunity and inflammation anhydrase and are capable of producing bicarbonate.
- Most of the axons contained in the vagal trunks: afferent (i.e., carrying stimuli from the viscera to - In the cardia:
the brain). o Gastric glands are branched and secrete primarily mucus and bicarbonate, and little acid
- The extrinsic sympathetic nerve supply to the stomach - In the fundus and body:
o Originates at spinal levels T5 through T10 and travels in the splanchnic nerves to the o Glands are more tubular, and the pits are deep.
celiac ganglion. o Parietal and chief cells are common in these glands

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 Parietal cells
- Secrete acid and intrinsic factor into the gastric lumen, and bicarbonate
into the intercellular space.
- They have a characteristic ultrastructural appearance with secretory
canaliculi (deep invaginations of the surface membrane) and cytoplasmic
tubulovesicles containing the acid-producing apparatus H+/K+-ATPase
(proton pump)
- Most mitochondria-rich cell in the body
- When stimulated, the cytoplasmic tubulovesicles fuse with the membrane
of the secretory canaliculus; when acid production ceases, the process
is reversed.
- Produce the only truly essential substance made by the stomach (i.e.,
intrinsic factor)
- Tend to occupy the midportion of the gastric glands found in the corpus
Chief cells
- Also called zymogenic cells
- Secrete pepsinogen I, which is maximally activated at a pH of 2.5.
- They tend to be clustered toward the base of the gastric glands and
have a low columnar shape.
- Ultrastructurally, chief cells have the characteristics of protein-
synthesizing cells: basal granular endoplasmic reticulum, supranuclear
Golgi apparatus, and apical zymogen granules
- When stimulated, produce two immunologically distinct proenzyme forms
of pepsinogen: predominantly pepsinogen I and some pepsinogen
II, most of which is produced by SECs.
- These proenzymes are activated in an acidic luminal environment.
o Histamine-secreting enterochromaffin-like (ECL) cells and
o Somatostatin-secreting D cells are also found
- In the antrum:
o Gastric glands are again more branched and shallow, parietal cells are rare, and gastrin-
secreting G cells and somatostatin-secreting D cells are present.
- A variety of hormone-secreting cells are present in various proportions throughout the gastric
mucosa
- Histologic analysis suggests that in the normal stomach:
o 13% of the epithelial cells are oxyntic (parietal) cells
o 44% are chief (zymogenic) cells
o 40% are mucous cells
o 3% are endocrine cells
- In general, the antrum produces gastrin but not acid, and the proximal stomach produces acid but
not gastrin.
- The border between the corpus and antrum migrates proximally with age (especially on the lesser
curvature side of the stomach
- Submucosa
o Deep to the muscularis mucosa
o Rich in branching blood vessels, lymphatics, collagen, various inflammatory cells, and
nerve fibers and ganglion cells of Meissner’s autonomic submucosal plexus.
o The collagen-rich submucosa gives strength to GI anastomoses
- The mucosa and submucosa are folded into the grossly visible gastric rugae,
o Which tend to flatten out as the stomach becomes distended
- Muscularis propria/ muscularis externa
o Below the submucosa
o Consists of an incomplete inner oblique layer, a complete middle circular layer
(continuous with the esophageal circular muscle and the circular muscle of the pylorus),
and a complete outer longitudinal layer (continuous with the longitudinal layer of the
esophagus and duodenum)
o Within the muscularis propria is the rich network of autonomic ganglia and nerves that
make up Auerbach’s myenteric plexus.
o Specialized pacemaker cells, the interstitial cells of Cajal (ICC), also are present
- Serosa
o The outer layer of the stomach also known as the visceral peritoneum.
o This layer provides significant tensile strength to gastric anastomoses
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o When tumors originating in the mucosa penetrate and breach the serosa, microscopic
or gross peritoneal metastases are common, presumably from shedding of tumor cells
that would not have occurred if the serosa had not been penetrated
o In this way, the serosa may be thought of as an outer envelope of the stomach.
PHYSIOLOGY
- Stomach stores food and facilitates digestion through a variety of secretory and motor functions.
- Important secretory functions:
o Production of acid, pepsin, intrinsic factor, mucus, and a variety of GI hormones
- Important motor functions:
o Food storage (receptive relaxation and accommodation), grinding and mixing, controlled
emptying of ingested food, and periodic interprandial “housekeeping”
Acid Secretion
- Hydrochloric acid in the stomach
o Hastens both the physical and (with pepsin) the biochemical breakdown of ingested food.
- In an acidic environment:
o Pepsin and acid à facilitate proteolysis.
- Gastric acid also inhibits the proliferation of ingested pathogens, which protects against both
infectious gastroenteritis and intestinal bacterial overgrowth and helps to maintain a healthy
gastrointestinal microbiome.
- Long-term acid suppression with proton pump inhibitors (PPIs)
o Has been associated with an increased risk of community-acquired Clostridium difficile
colitis and other gastroenteritis, presumably because of the absence of this protective
germicidal barrier
Parietal Cell
- The parietal cell is stimulated to secrete acid when one or more of three membrane receptor types
is stimulated by acetylcholine (from vagally stimulated enteric neurons), gastrin (from G cells), or
histamine (from ECL cells).
- Enzyme H+/K+-ATPase
o Parietal cell proton pump
o Stored within the intracellular tubulovesicles
o Final common pathway for gastric acid secretion
- When the parietal cell is stimulated:
o There is a cytoskeletal rearrangement and fusion of the tubulovesicles with the apical
membrane of the secretory canaliculus.
o The heterodimer assembly of the enzyme subunits into the microvilli of the secretory
canaliculus à results in acid secretion
§ With extracellular potassium being exchanged for cytosolic hydrogen.
- Although electroneutral, this is an energy-requiring process because the hydrogen is secreted
against a gradient of at least 1 million-fold, which explains why the parietal cell is packed with energy
producing mitochondria.
- During acid production:
o Potassium and chloride are also secreted into the apical secretory canaliculus through
separate channels à providing potassium to exchange for H+ via the H+/K+-ATPase,
and chloride to accompany the secreted hydrogen.
- At the basolateral membrane, the combined activity of various cotransporters and ion exchangers
accomplishes intracellular pH regulation and electrolyte homeostasis
- The normal human stomach contains approximately 1 billion parietal cells
o Total gastric acid production is proportional to parietal cell mass
- Almost all of the parietal cells are in the proximal 2/3 stomach
o Though there are some parietal cells found in gastric antral glands
- Potent acid-suppressing PPI drugs
o Irreversibly interfere with the function of the H+/K+- ATPase molecule.
o These agents must be incorporated into the activated enzyme to be effective and thus
work best when taken before or during a meal (when the parietal cell is stimulated).
- When PPI therapy is stopped:
o Acid secretory capability gradually returns (within days) as new H+/K+-ATPase is
synthesized.
- Gastrin, acetylcholine, and histamine
o Stimulate the parietal cell to secrete hydrochloric acid
- Gastrin
o Bind to type B cholecystokinin (CCK2) receptors on ECL cells à stimulates ECL cell
histamine release à binds to H2 receptor on the parietal cell
3
 § This stimulates adenylatecyclase (via a G-protein–linked mechanism) and - Intestinal phase
increases cAMP à activates protein kinases à increased levels of o Thought to be mediated by a hormone released from the proximal small bowel mucosa
phosphoproteins and activation of the proton pump in response to luminal chyme.
o Also binds to CCK2 receptors on the parietal cell, but this is less important for acid o Starts when gastric emptying of ingested food begins, and it continues as long as
secretion than the gastrin effect on ECL cells nutrients remain in the proximal small intestine
- Acetylcholine from intrinsic neurons o Accounts for about 10% of meal-induced acid secretion
o Binds to M3 muscarinic receptors on the parietal cell, which (like gastrin binding to CCK2 - Interprandial basal acid secretion
receptors) à stimulates phospholipase C via a G-protein–linked mechanism o 2 to 5 mEq hydrochloric acid per hour
à leading to increased production of inositol trisphosphate from membrane bound o About 10% of maximal acid output (MAO)
phospholipids o Greater at night
- Inositol trisphosphate - Basal acid secretion
o Stimulates the release of calcium from intracellular stores à activation of protein kinases o Probably contributes to the relatively low bacterial counts found in the stomach.
and activation of H+/K+-ATPase o Reduced 75% to 90% by vagotomy or continuous H2-receptor blockade
- Somatostatin released from mucosal D cells in the antral and oxcyntic mucosa in response to luminal - The pivotal role that ECL cells play in the regulation of gastric acid secretion is emphasized in Fig.
acid 26-13.
o Binds to SSTR2 receptors on parietal cells and inhibits acid release directly. o The acid stimulatory effect of gastrin is largely mediated by histamine released from
o Also inhibits acid secretion in a paracrine fashion, binding to nearby ECL cells in the mucosal ECL cells.
oxcyntic mucosa and decreasing histamine release, and binding to nearby antral G cells o H2-receptor knockout mice do not secrete acid in response to gastrin.
to inhibit gastrin release § This explains why the H2-receptor antagonists (H2RAs) are effective
inhibitors of acid secretion, even though histamine is only one of three
Physiology of Acid Secretion parietal cell stimulants.
- Food ingestion is the physiologic stimulus for acid secretion o The mucosal D cell, which releases somatostatin, is also an important regulator of acid
- The acid secretory response that occurs after a meal is traditionally described in three phases: secretion.
cephalic, gastric, and intestinal § Somatostatin inhibits histamine release from ECL cells and gastrin release
- Cephalic/ vagal phase from antral G cells.
o Begins with the thought, sight, smell, o The function of D cells can be inhibited by Helicobacter pylori infection, resulting in an
and/or taste of food. exaggerated acid secretory response
o These stimuli activate several cortical - Proton pump inhibitors
and hypothalamic sites (e.g., tractus o Potent suppressors of gastric acid secretion.
solitarius, dorsal motor nucleus, and o This results in hypergastrinemia and consequent ECL stimulation
dorsal vagal complex), and signals are o In patients on long-term PPI (median 5.5 years), the degree of hypergastrinemia does
transmitted to the stomach by the vagal not appear to correlate with the length of treatment.
nerves which stimulate enteric o Chronic PPI use
submucosal neurons. § Has been associated with ECL hyperplasia and type 1 gastric
o Acetylcholine is released à stimulation neuroendocrine tumor, but so far there has been no evidence link in these
acid secretion from parietal cells agents to malignant gastric epithelial or neuroendocrine tumors
o Vagal stimulation à also leads to gastrin o Gastrin levels return to normal within a few days of PPI cessation, but during this time,
release from antral G cells via CGRP, some patients may experience gastric hyperacidity and dyspeptic symptoms, which may
and sensitizes ECL cells to gastrin. lead to difficulty in getting patients off the medication.
o Although the acid secreted per unit of § This is less likely to occur with short-term PPI use and may be ameliorated
time in the cephalic phase is greater than by PPI dose tapering and/or initiation of H2 blockers prior to PPI cessation
in the other two phases, the cephalic
phase is shorter. Pepsinogen Secretion
§ Thus, the cephalic phase - Food ingestion: the most potent physiologic stimulus for pepsinogen secretion from chief cells
accounts for no more than - Acetylcholine ß the most important mediator
30% of total acid secretion in response to a meal - Somatostatin inhibits pepsinogen secretion.
o Sham feeding (chewing and spitting) stimulates gastric acid secretion only via the - Pepsinogen I
cephalic phase àresults in acid secretion that is about half of that seen in response to o Produced by chief cells in acid producing glands
IV pentagastrin or histamine - Pepsinogen II
o Produced by chief cells and by SECs in both acid producing and gastrin producing (i.e.,
- Gastric phase antral) glands
o Begins when the food reaches the stomach - Pepsinogen is cleaved to the active pepsin enzyme in an acidic environment and is maximally
o Lasts until the stomach is empty active at pH 2.5, and inactive at pH >5, although pepsinogen II may be activated over a wider pH
o Accounts for about 60% of the total acid secretion in response to a meal range than pepsinogen I.
o Has several components: - Pepsin catalyzes the hydrolysis of proteins and is denatured at alkaline pH
§ Amino acids and small peptides directly stimulate antral G cells to secrete - Serum levels of pepsinogen I and II are increased in helicobacter gastritis, so elevated pepsinogen
gastrin, which is carried in the bloodstream to the ECL and parietal cells à I and II levels and positive helicobacter serology are presumptive evidence of active helicobacter
stimulating acid secretion in an endocrine fashion. infection.
§ Proximal gastric distention stimulates acid secretion via a vagovagal reflex - Longstanding helicobacter infection may lead to atrophic gastritis, suggested by decreased
arc, which is mitigated by truncal or highly selective vagotomy (HSV) pepsinogen I/II ratio (from chief cell loss) and hypergastrinemia (from parietal cell loss and
§ Antral distention also stimulates antral gastrin secretion. hypochlorhydria
§ Ongoing cephalic vagal input stimulates gastrin release, which in turn
stimulates histamine release from ECL cells and acid secretion
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Intrinsic Factor
- Activated parietal cells secrete intrinsic factor in addition to hydrochloric acid.
o Presumably the stimulants are similar, but acid secretion and intrinsic factor secretion
may not be linked.
- Intrinsic factor binds to luminal vitamin B12, and the complex is absorbed in the terminal ileum via
mucosal receptors.
- Vitamin B12 deficiency can be life threatening, and patients with total gastrectomy or pernicious
anemia (i.e., patients with no parietal cells) require B12 supplementation by a nonenteric route.
- Some patients develop vitamin B12 deficiency following gastric bypass, presumably because there
is insufficient intrinsic factor present in the small proximal gastric pouch and oral B12 intake may be
decreased.
- Under normal conditions, a significant excess of intrinsic factor is secreted, and acid-suppressive
medication does not appear to inhibit intrinsic factor production and release.
Gastric Mucosal Barrier
- Important elements of gastric barrier function and cytoprotection are listed below:
- When these defenses break down, ulceration occurs.
- A variety of factors are important in maintaining an intact gastric mucosal layer.
o The mucus and bicarbonate secreted by SECs form an unstirred mucous gel with a
favorable pH gradient.
o Cell membranes and tight junctions prevent hydrogen ions from gaining access to the
interstitial space.
o Hydrogen ions that do break through are buffered by the alkaline tide created by
basolateral bicarbonate secretion from stimulated parietal cells.
o Any sloughed or denuded SECs are rapidly replaced by migration of adjacent cells, a
process known as restitution.
- Mucosal blood flow plays a crucial role in maintaining a healthy mucosa, providing nutrients and
oxygen for the cellular functions involved in cytoprotection.
o During acid secretion, there is a tremendous gradient favoring the movement of
hydrogen ions from the lumen to the interstitium.
o This “back-diffused” hydrogen is buffered and rapidly removed by the rich blood supply.
o When “barrier breakers” such as bile or aspirin lead to increased back-diffusion of
hydrogen ions from the lumen into the lamina propria and submucosa, there is a
protective increase in mucosal blood flow.
o If this protective response is blocked, gross ulceration can occur.
- Important mediators of these protective mechanisms include:
o Prostaglandins, nitric oxide, intrinsic nerves, and peptides (e.g., calcitonin gene-related
peptide, gastrin- releasing peptide [GRP], gastrin, and heat shock proteins).
- Sucralfate acts locally to enhance mucosal defenses.
- Protective reflexes involve afferent sensory neurons, and they can be blocked by the application of
topical anesthetics to the gastric mucosa, or the experimental destruction of the afferent sensory
nerves.
- In addition to these local defenses, there are important protective factors in saliva, duodenal
secretions, and pancreatic or biliary secretions
GASTRIC HORMONES
- The stomach is the source of important peptides which work in an autocrine (EGF and surface
epithelial cells, TGF and parietal cells), paracrine (somatostatin), endocrine (gastrin), and/or
neurocrine (ghrelin) fashion
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Gastrin
- Produced by antral G cells and is the major hormonal stimulant of acid secretion during the
gastric phase predominantly via an endocrine effect on histamine generating ECL cells and to a
lesser extent via a direct effect on parietal cells.
- A variety of molecular forms exist:
o Big gastrin (34 amino acids; G34), little gastrin (17 amino acids; G17), and mini-gastrin
(14 amino acids; G14)
- The large majority of gastrin released by the human antrum is G17.
- The biologically active pentapeptide sequence at the C-terminal end of gastrin is identical to that of
CCK.
- Luminal peptides and amino acids ß most potent stimulants of gastrin release
- Luminal acid ß most potent inhibitor of gastrin secretion
o Predominantly mediated in a paracrine fashion by somatostatin released from antral D
cells
- Gastrin-stimulated acid secretion is significantly blocked by H2 antagonists, suggesting that the
principal mediator of gastrin-stimulated acid production is histamine from mucosal ECL cells
and not direct stimulation of parietal cell by gastrin (see Fig. 26-13).
- In fact, chronic hypergastrinemia is associated with hyperplasia of gastric ECL cells and, rarely,
gastric type I gastric neuroendocrine tumors (type I gastric carcinoid).
- Gastrin is trophic to gastric parietal cells and to other GI mucosal cells including gastric stem cells.
- It also is a regulator of gastric cellular proliferation, migration, invasion, apoptosis and angiogenesis
- Mucosal biopsies of the gastric body from patients with gastrinoma show a thick mucosa with excess
parietal cells, while similar biopsies in patients years after antrectomy (i.e., low gastrin state) show
thin mucosa and decreased parietal cells.
o In animal studies, gastrin administration has been shown to stimulate the growth of
established colon cancers and to cause pancreatic acinar cell hyperplasia.
- Important causes of hypergastrinemia:
o Pernicious anemia, acid-suppressive medication, gastrinoma, retained antrum following
distal gastrectomy and Billroth II surgery, and vagotomy.
o
Ghrelin
- Small peptide that is produced mainly in the stomach
- Produced by specialized P/D1 endocrine cells in gastric oxyntic glands.
- 90% of the body’s ghrelin stores:
o Stomach
o Duodenum
- Potent secretagogue à pituitary growth hormone
- Weak secretogogue à ACTH and prolactin
- Appears to be a major orexigenic regulator of appetite
- Crosses the blood brain barrier and stimulates appetite via hypothalamic receptors
- Also stimulates appetite peripherally by stimulating vagal afferent fibers in the gastric wall
- When elevated: appetite is stimulate
- When surpressed: appetite is decreased.
- Levels are elevated before a meal and decreased postprandially.
o Levels are high during starvation and decreased during hyperglycemia.
- Obesity and insulin resistance à associated with low ghrelin levels, but resection of the primary
source of this hormone (i.e., the stomach) may partly account for the anorexia and weight loss seen
in some patients following gastric resection including sleeve gastrectomy
- The effect of RYGBP on ghrelin physiology is controversial.
o This very effective weight loss procedure has been shown by some investigators to be
associated with suppression of plasma ghrelin levels (and appetite) in humans
- Other groups have failed to show a significant decrease in ghrelin levels following gastric bypass but
have found such decreases following sleeve gastrectomy, another effective weight loss operation
- Possibly, subtle differences in operative technique, patient selection, or experimental (including
assay) conditions account for the disparate results of studies on the effect of bariatric surgery on
ghrelin levels in obese patients.
- Interestingly the two common metabolites of ghrelin have different physiologic effects: acyl-ghrelin
increases gastric emptying and appetite while deacyl ghrelin decreases gastric emptying and
induces satiety
- Obviously appetite control is complex with redundant and overlapping orexigenic and anorexigenic
pathways and signals.
5
Somatostatin
! Somatostatin is produced by D cells located throughout the gastric mucosa
! The predominant form in humans is somatostatin 14, though somatostatin 28 is present as well.
! The major stimulus for somatostatin release is antral acidification
! Acetylcholine from vagal nerve fibers inhibits its release
! Somatostatin inhibits acid secretion from parietal cells and gastrin release from G cells
! It also decreases histamine release from ECL cells
! The proximity of the D cells to these target cells suggests that the primary effect of somatostatin is
mediated in a paracrine fashion, but an endocrine (i.e., blood- stream) effect also is possible.
Gastrin-Releasing Peptide
! GRP is the mammalian equivalent of bombesin, a hormone discovered more than two decades ago
in an extract of skin from a frog.
! In the antrum, GRP stimulates both gastrin and somatostatin release by binding to receptors on
the G and D cells.
! There are nerve terminals ending near the mucosa in the gastric body and antrum, which are rich in
GRP immunoreactivity.
! When GRP is given peripherally, it stimulates acid secretion, but when it is given centrally into
the cerebral ventricles of animals, it inhibits acid secretion, apparently via a pathway involving
the sympathetic nervous system.
Leptin
! Leptin is a protein primarily synthesized in adipocytes.
! It is also made by chief cells in the stomach, the main source of leptin in the GI tract.
! Leptin works at least in part via vagally mediated pathways to decrease food intake in animals.
! Not surprisingly, leptin, a satiety signal hormone, and ghrelin, a hunger signal hormone, are both
synthesized in the stomach, an organ increasingly recognized as central to the mechanisms of
appetite control.
Autocrine Proteins
! Gastric surface epithelial cells secrete a variety of proteins that are important regulators of SEC
health, including trefoil factor family proteins and heat shock proteins.
! Parietal cells may also be influenced by molecules they secrete including transforming growth factor-
α.
GASTRIC MOTILITY AND EMPTYING
! Gastric motor function has several purposes.
! Interprandial motor activity
○ Clears the stomach of undigested debris, sloughed cells, and mucus.
! When feeding begins, the stomach relaxes to accommodate the meal.
! Regulated motor activity then breaks down the food into small particles and controls the output into
the duodenum.
! The stomach accomplishes these functions by coordinated smooth muscle relaxation and
contraction of the various gastric segments (proximal, distal, and pyloric).
! Smooth muscle myoelectric potentials are translated into muscular activity, which is modulated by
extrinsic and intrinsic innervation and hormones.
! The mechanisms by which gastric distention is translated into a neurohormonal satiety signal have
only been partially elucidated.
Intrinsic Gastric Innervation
! The intrinsic innervation
○ consists of ganglia and nerves that constitute the enteric nervous system
! There are a variety of neurotransmitters that effect gastric smooth muscle
○ excitatory (augment muscular activity)
○ inhibitory (decrease muscular activity)
! Important excitatory neurotransmitters include:
○ acetylcholine, the tachykinins, substance P, and neurokinin A
! Important inhibitory neurotransmitters include:
○ nitric oxide (NO) and vasoactive intestinal peptide (VIP)
! Serotonin has been shown to modulate both contraction and relaxation.
! A variety of other molecules affect motility, including GRP, histamine, neuropeptide Y,
norepinephrine, and endogenous opioids.
! Specialized cells in the muscularis propria also are important modulators of GI motility.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
○ These cells, called interstitial cells of Cajal, are distinguishable histologically from
neurons and myocytes and appear to amplify both cholinergic excitatory and nitrergic
inhibitory input to the smooth muscle of the stom- ach and intestine.
○ They are thought to be the cell of origin for gastrointestinal stromal tumors (GISTs),
which are the most common mesenchymal neoplasms in the GI tract.
Segmental Gastric Motility
! Proximal stomach
○ serves a short-term food storage function
○ helps regulate basal intragastric tone
○ consists of slow tonic contractions and relaxations, lasting up to 5 minutes
■ This activity is the main determinant of basal intra- gastric pressure, an
important determinant of liquid emptying
■ Rapid phasic contractions may be superimposed on the slower tonic motor
activity
○ When food is ingested, intragastric pressure falls as the proximal stomach relaxes
○ This proximal relaxation is mediated by two important vagovagal reflexes: receptive
relaxation and gastric accommodation.
■ Receptive relaxation
! Refers to the reduction in gastric tone associated with the act of
swallowing
! This occurs before the food reaches the stomach and can be
reproduced by mechanical stimulation of the pharynx or
esophagus
■ Gastric accommodation
! Refers to the proximal gastric relaxation associated with
distention of the stomach
! Mediated through stretch receptors in the gastric wall and does
not require esophageal or pharyngeal stimulation
○ Initially, as the meal enters the stomach, there is a drop in intragastric pressure mediated
by nitric oxide.
○ As the meal progresses, the intragastric pressure rises, parallel with the onset of satiety.
○ Interestingly, satiety does not seem to be associated with any specific level of intragastric
pressure.
○ Obese patients have a delayed onset of satiety, so an obvious hypothesis to be tested
is that a pharmacologic-induced increase in gastric tone leads to increased satiety and
decreased food intake in this patient group.
○ Because receptive relaxation and accommodation are mediated by afferent and efferent
vagal fibers, they are significantly altered by truncal and highly selective vagotomy.
■ Both these operations result in decreased gastric compliance, shifting the
volume/pressure curve to the left.
■ Presumably for any given amount of food ingested, the intragastric pressure
is higher, and perhaps in some patients the onset of satiety is sooner.
■ This may be one explanation for weight loss associated with vagotomy, and
it also helps explain accelerated liquid gastric emptying postvagotomy, which
likely contributes to dumping symptoms in some patients.
○ NO and VIP
■ Principal mediators of proximal ga tric relaxation
○ But a variety of other agents increase proximal gastric relaxation and compliance,
including dopamine, gastrin, CCK, secretin, GRP, and glucagon.
○ Proximal gastric tone also is decreased by duodenal distention, colonic distention, and
ileal perfusion with glucose (ileal brake).
! Distal stomach
○ mixes and grinds the food
○ The pylorus helps the process when closed, facilitating retropulsion of the solid food
bolus back into the body of the stomach for additional breakdown
○ The pylorus opens intermittently to allow metered emptying of liquids and small solid
particles into the duodenum.
○ The distal stomach breaks up solid food and is the main determinant of gastric
emptying of solids
○ Slow waves of myoelectric depolarization sweep down the distal stomach at a rate of
about three per minute.
○ These waves originate from the proximal gastric pacemaker, high on the greater
curvature.
6
 ○ The pacing cells appear to be the interstitial cells of Cajal, which have been shown to
have a similar function in the small intestine and colon.
○ Most of these myoelectric waves are below the threshold for smooth muscle contraction
in the quiescent state and thus are associated with negligible changes in pressure
○ Neural and/or hormonal input, which increases the plateau phase of the action potential,
can trigger muscle contraction, resulting in a peristaltic wave associated with the
electrical slow wave and of the same frequency (three per minute)
○ There are measurable abnormalities in gastric slow wave activity in disorders of gastric
motility such as gastroparesis, but reliable elec- trogastrogaphy to aid in the diagnosis
and management of these problems is not yet a clinical reality.
○ It is likely that implantable gastric pacemakers benefit some patients with gastroparesis
by favorably impacting this myoelectric coupling, normalizing gastric slow wave patterns.
! Migrating motor complex (MMC)
○ Controls distal gastric motor activity during fasting
○ “gastrointestinal housekeeper”
○ Purported function: To sweep along any undigested food, debris, sloughed cells, and
mucus after the fed phase of digestion is complete
○ Lasts approximately 100 minutes (longer at night, shorter during daytime) and is divided
into four phases
■ Phase I
! About half the length of the entire cycle
! Period of relative motor inactivity
! High-amplitude muscular contractions do not occur in phase I of
the MMC
■ Phase II
! About 25% of the entire MMC cycle
! Consists of some irregular, high-amplitude, generally
nonpropulsive contractions
■ Phase III
! Period of intense, regular (about three per minute), propulsive
contractions, only lasts about 5 to 10 minutes
! Most phase III complexes of the GI MMC begin in the stomach,
and the frequency approximates that of the myoelectric gastric
slow wave
■ Phase IV is a transition period.
○ Neurohormonal control of the MMC is poorly understood, but it appears that different
phases are regulated by different mechanisms.
■ For example, vagotomy abolishes phase II of the gastric MMC but has little
influence on phase III that persists even in the autotransplanted stomach,
totally devoid of extrinsic neural input
■ This suggests that phase III is regulated by intrinsic nerves and/or hormones.
■ Indeed, the initiation of phase III of the MMC in the distal stomach
corresponds temporally to elevation in serum levels of motilin, a hormone
produced in the duodenal mucosa.
■ Resection of the duodenum abolishes distal gastric phase III in dogs,
and resection of the duodenum in humans (e.g., with
pancreaticoduodenectomy, the Whipple procedure) commonly results in
early postoperative delayed gastric emptying.
■ There are clearly motilin receptors on gastric smooth muscle and nerves.
■ Other modulators of gastric MMC activity include NO, endogenous opioids,
intrinsic cholinergic and adrenergic nerves, and duodenal pH.
■ The onset of MMC phase III signals the return of hunger in humans, but oddly
ghrelin, a major orexigenic hormone, appears to have little to do with phase
III.
○ Feeding abolishes the MMC and leads to the fed motor pattern.
■ The fed motor pattern of gastric activity starts within 10 minutes of food
ingestion and persists until all the food has left the stomach.
■ The neurohormonal initiator of this change is unknown, but CCK and the
vagus appear to play some role since sham feeding transiently induces
antral motor activity resembling the fed motor pattern which is blocked by the
CCK receptor antagonist loxiglumide.
■ Gastric motility during the fed pattern resembles phase II of the MMC, with
irregular but continuous phasic contractions of the distal stomach.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
■ During the fed state, about half of the myoelectric slow waves are associated
with strong higher frequency distal gastric contractions.
■ Some are prograde and some are retrograde, serving to mix and grind the
solid components of the meal.
■ The magnitude of gastric contractions and the duration of the pattern are
influenced by the consistency and composition of the meal.
! The pylorus functions as an effective regulator of gastric emptying and an effective barrier to
duodenogastric reflux.
! Bypass, transection, or resection of the pylorus may lead to uncontrolled gastric emptying of food
and the dumping syndrome
! Pyloric dysfunction or disruption may also result in uncontrolled entry of duodenal contents into the
stomach.
! Perfusion of the duodenum with lipids, glucose, amino acids, hypertonic saline, or hydrochloric acid
results in closure of the pylorus and decreased transpyloric flow.
! Ileal perfusion with fat has the same effect.
! A variety of neurohumoral pathways are involved with these physiologic responses, and there is
evidence that different pathways may be involved for different stimuli.
! The pylorus is readily apparent grossly as a thick ring of muscle and connective tissue.
! The density of nerve tissue in the pyloric smooth muscle is several folds higher than in the antrum,
with increased numbers of neurons staining positive for substance P, neuropeptide Y, VIP, and
galanin.
! Interstitial cells of Cajal are closely associated with pyloric myocytes, and the myoelectric slow wave
of the pylorus has the same frequency as that seen in the distal stomach.
! The motor activity of the pylorus is both tonic and phasic.
! During phase III of the MMC, the pylorus is open as gastric contents are swept into the duodenum.
! During the fed phase, the pylorus is closed most of the time.
! It relaxes intermittently, usually in synchronization with lower- amplitude, minor antral contractions.
! The higher-amplitude, more major antral contractions are usually met with a closed pylorus,
facilitating retropulsion and further grinding of food.
! Modulation of pyloric motor activity is complex.
○ There is evidence for both inhibitory and excitatory vagal pathways.
○ Some contractile vagal effects are mediated by opioid pathways because they are
blocked by naloxone.
○ Electrical stimulation of the duodenum causes the pylorus to contract, whereas
electrical stimulation of the antrum causes pyloric relaxation.
○ Nitric oxide is an important mediator of pyloric relaxation.
○ Other molecules that may play a physiologic role in controlling pyloric smooth muscle
include serotonin, VIP, prostaglandin E1, and galanin (pyloric relaxation); and histamine,
CCK, and secretin (pyloric contraction).
Gastric Emptying
! The control of gastric emptying is complex.
! In general, liquid emptying is faster than solid emptying.
! Osmolarity, acidity, caloric content, nutrient composition, and particle size are important modulators
of gastric emptying.
! Stimulation of duodenal osmoreceptors, glucoreceptors, and pH receptors clearly inhibits gastric
emptying by a variety of neurohumoral mechanisms. CCK has been consistently shown to inhibit
gastric emptying at physiologic doses
! Recently, it has been noted that the anorexigenic hormone leptin, secreted largely by fat but also by
gastric mucosa, inhibits gastric emptying, perhaps through the same pathway as CCK (which also
has properties of a satiety hormone).
! The orexigenic hormone ghrelin has the opposite effect.
Liquid Emptying
! The gastric emptying of water or isotonic saline follows first-order kinetics, with a half emptying
time around 12 minutes.
! Thus, if one drinks 200 mL of water, about 100 mL enters the duodenum by 12 minutes, whereas if
one drinks 400 mL of water, about 200 mL enters the duodenum by 12 minutes.
! This emptying pattern of liquids is modified considerably as the caloric density, osmolarity, and
nutrient composition of the liquid changes
! Up to an osmolarity of about 1 M, liquid emptying occurs at a rate of about 200 kcal per hour.
! Duodenal osmoreceptors and hormones (e.g., secretin and VIP) are important modulators of liquid
gastric emptying.
! Generally, liquid emptying is delayed in the supine position.
7
 ! Traditionally, liquid emptying has been attributed to the activity of the proximal stomach, but it is
probably more complicated than previously thought.
! Clearly, receptive relaxation and gastric accommodation play a role in gastric emptying of liquids.
! Patients with a denervated (e.g., vagotomized), resected, or plicated (e.g., fundoplication) proximal
stomach have decreased gastric compliance and may show accelerated gastric emptying of liquids.
! Some observations suggest an active role for the distal stomach in liquid emptying.
! For instance, even if the proximal intragastric pressure is lower than duodenal pressure, normal
gastric emptying of liquids can occur.
! Also, diabetic patients may have normal proximal gastric motor function and profoundly delayed
gastric emptying of liquids.
! Indeed, antral contractile activity does correlate with liquid gastric emptying, and this distal gastric
activity appears to vary with the nutrient composition and caloric content of the liquid meal.
Diagnostic Tests
! Depending on the circumstances, distal gastric motor activity can promote or inhibit gastric emptying
! Esophagogastroduodenoscopy
of liquids.
○ Esophagogastroduodenoscopy (EGD) is a safe and accurate outpatient procedure
! Distal gastrectomy and pyloric stenting both obviously interfere with distal gastric motor activity, and
performed under conscious sedation.
both accelerate the initial rapid phase of liquid gastric emptying.
○ Smaller flexible scopes with excellent optics and a working channel are easily passed
Solid Emptying
transnasally in the unsedated patient.
! Normally, the half-time of solid gastric emptying is less than 2 hours.
○ Following an 8-hour fast, the flexible scope is advanced under direct vision into the
! Unlike liquids, which display an initial rapid phase followed by a slower linear phase of emptying,
esophagus, stomach, and duodenum.
solids have an initial lag phase during which little emptying of solids occurs.
○ The fundus and GE junction are inspected by retroflexing the scope.
○ It is during this phase that much of the grinding and mixing occurs.
○ To rule out cancer with a high degree of accuracy, all patients with gastric ulcer
! A linear emptying phase follows, during which the smaller particles are metered out to the
diagnosed on upper GI series or found at EGD should have multiple biopsy specimens
duodenum.
of the base and rim of the lesion.
! Solid gastric emptying is a function of meal particle size, caloric content, and composition (especially
○ Brush cytology also should be considered.
fat).
○ Gastritis should be biopsied both for histologic examination and assessment and for a
! When liquids and solids are ingested together, the liquids empty first.
tissue urease test and histologic evaluation to rule out the presence of H pylori.
! Solids are stored in the fundus and delivered to the distal stomach at constant rates for grinding.
○ If Helicobacter infection is detected, it should be treated because of the etiologic
! Liquids also are sequestered in the fundus, but they appear to be readily delivered to the distal
association with peptic ulcers, mucosa-associated lymphoid tissue (MALT), and gastric
stomach for early emptying.
cancer; in addition, eradication may ameliorate symptoms.
! The larger the solid component of the meal, the slower the liquid emptying.
○ The most serious complications of EGD are perforation (which is rare, but can occur
! Patients bothered by dumping syndrome are advised to limit the amount of liquid consumed with the
anywhere from the cervical esophagus to the duodenum), aspiration, and respiratory
solid meal, taking advantage of this effect.
depression from excessive sedation.
! Three prokinetic (metoclopramide, erythromycin, domperidone) may be used to treat delayed
○ Although EGD is a more sensitive test than double-contrast upper GI series, these
gastric emptying.
modalities should be considered complementary rather than mutually exclusive.
! Barium Upper GI Study
○ Plain abdominal X-rays may be helpful in the diagnosis of gastric perforation
(pneumoperitoneum) or delayed gastric emptying (large air-fluid level).
○ Double-contrast upper GI series may be better than EGD at elucidating gastric
diverticula, fistula, tortuosity, stricture location, and size or morphology of hiatal hernia.
○ Although there are radiologic characteristics of ulcers that suggest the presence or
absence of malignancy, gastric ulcers always require adequate biopsy.
! Computed Tomographic Scanning and Magnetic Resonance Imaging
○ Usually, significant gastric disease can be diagnosed without these sophisticated
imaging studies.
○ However, one or the other should be part of the routine staging work-up for patients with
a malignant gastric tumor.
○ Magnetic resonance imaging (MRI) may prove clinically useful as a quantitative test
DIAGNOSIS OF GASTRIC DISEASE for gastric emptying, and it may even hold some promise for the analysis of myoelectric
Signs and Symptoms derangements in patients with gastroparesis.
! The most common symptoms of gastric disease are pain, weight loss, early satiety, and anorexia. ○ Virtual gastroscopy using multi detector CT scan or MRI is not yet widely used, but these
! Nausea, vomiting, bloating, and anemia also are frequent complaints. techniques may prove useful for screening and staging of gastric disease
! Several of these symptoms (pain, bloating, nausea, and early satiety) are often described by ○ CTA or MRA
physicians as dyspepsia, synonymous with the common nonmedical term indigestion. ■ Useful in evaluating the blood supply to the stomach after endovascular
! Common causes of dyspepsia include: treatment of aortic and/or visceral arterial disease or in patients with previous
○ gastroesophageal reflux disease (GERD), helicobacter gastritis, and other disorders of upper abdominal operation in whom gastric conduit construction is
the stomach, gallbladder, and pancreas contemplated, e.g., with esophagectomy.
! Although none of the aforementioned symptoms alone is specific for gastric disease, when elicited ○ Arteriography
in the context of a careful history and physical examination, they point to a differential diagnosis, ■ Can be helpful in the occasional poor-risk patient with exsanguinating gastric
which can be refined with certain tests hemorrhage, in the patient with occult gastric bleeding, or when CTA or MRA
! Early endoscopy should be considered in patients presenting with recent onset of alarm symptoms is inconclusive in delineating vascular anatomy.
(weight loss, anemia, dysphagia, vomiting) particularly those over 55 years of age
! Endoscopic Ultrasound
○ Useful in the evaluation and management of gastric mass lesions
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 8
 ○ Local staging of gastric adenocarcinoma with EUS is quite accurate, and this modality
can be used to plan therapy.
○ At many centers, patients with transmural and/or node positive adenocarcinoma of the
stomach are considered for preoperative (neoadjuvant) chemoradiation therapy.
○ EUS is the best way to clinically stage these patients locoregionally.
○ Suspicious nodes can be sampled with EUS-guided endoscopic needle biopsy.
○ Malignant tumors that are confined to the mucosa on EUS may be amenable to
endoscopic mucosal resection (EMR).
○ EUS also can be used to assess tumor response to chemotherapy.
○ Submucosal masses are commonly discovered during routine EGD.
■ Large submucosal masses should be resected unless benign pathology is a
certainty, but observation may be appropriate for some small submucosal
masses (e.g., lipoma or leiomyoma).
○ There are endoscopic characteristics of benign and malignant mesenchymal tumors, and
thus, EUS can provide reassurance, but no guarantee, that small lesions under
observation are probably benign.
○ Thus, EUS-guided needle biopsy should be considered.
○ Submucosal varices also can be assessed by EUS.
! Gastric Secretory Analysis
○ Analysis of gastric acid output requires gastric intubation, and it is performed infrequently
nowadays.
○ This test may be useful in the evaluation of patients with hypergastrinemia, including the
Zollinger-Ellison syndrome (ZES), patients with refractory ulcer or GERD, and patients
with recurrent ulcer after operation.
○ Historically, gastric analysis was performed most commonly to test for the adequacy of
vagotomy in postoperative patients with recurrent or persistent ulcer.
○ Now this can be done by assessing peripheral pancreatic polypeptide levels in response
to sham feeding.
○ A 50% increase in pancreatic polypeptide within 30 minutes of sham feeding suggests
intact vagal function.
○ Normal basal acid output (BAO) is greater than 5 mEq/h.
○ MAO is the average of the two final stimulated 15-minute periods and is usually 10 to 15
mEq/h.
○ Peak acid output is defined as the highest of the four stimulated periods.
○ Patients with a gastrinoma commonly have a high BAO, often above 30 mEq/h, but
consistently above 15 mEq/h unless there has been previous vagotomy or gastric
resection.
○ In patients with gastrinoma, the ratio of BAO to MAO exceeds 0.6.
○ Normal acid output in the patient prescribed acid-suppressive medication usually means
that the patient is noncompliant.
○ To assess acid-secretory capacity in the absence of medication effect, H2 blockers and
PPIs should be withheld for several days before gastric analysis.
! Scintigraphy
○ The standard scintigraphic evaluation of gastric emptying involves the ingestion of a test
meal with one or two isotopes and scanning the patient under a gamma camera.
○ A curve for gastric emptying is plotted, and the half-time is calculated.
○ Normal standards exist at each facility.
○ Duodenogastric reflux can be quantitated by the IV administration of hepato- biliary
iminodiacetic acid (HIDA scan), which is concentrated and excreted by the liver into the
duodenum.
○ Software allows a semiquantitative assessment of how much of the isotope refluxes into
the stomach.
○ Positron emission tomography (PET) scan or CT/PET scan is useful in staging certain
patients with gastric malignancy.
! Tests for Helicobacter pylori
○ A variety of tests can help the clinician to determine whether the patient has active H
pylori infection.
○ The predictive value (positive and negative) of any of these tests when used as a
screening tool depends on the prevalence of H pylori infection in the screened
population.
○ A positive test is quite accurate in predicting H pylori infection, but a negative test can
be unreliable.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
○ Thus, in the appropriate clinical setting, treatment for H pylori should be initiated on the
basis of a positive test, but not necessarily withheld if the test is negative.
○ Helicobacter infection should be treated when the diagnosis is made and eradication is
confirmed.
○ A positive serologic test is presumptive evidence of active infection if the patient has
never been treated for H pylori.
○ Histologic examination of gastric mucosal biopsy using special stains is the gold
standard test for helicobacter infection.
○ Other sensitive tests include commercially available rapid urease tests, which assay for
the presence of urease in mucosal biopsy specimens (strong presumptive evidence of
infection).
○ Urease is an omnipresent enzyme in H pylori strains that colonize the gastric mucosa.
○ The carbon labeled urea breath test has become the standard test to confirm eradication
of H pylori following appropriate treatment.
○ In this test, the patient ingests urea labeled with nonradioactive 13C or 14C.
○ The labeled urea is acted upon by the urease present in the H pylori and converted into
ammonia and carbon dioxide.
○ The radiolabeled carbon dioxide is excreted from the lungs and can be detected in the
expired air (Fig. 26-22). It also can be detected in a blood sample.
○ The fecal antigen test also is quite sensitive and specific for active H pylori infection and
may also be used to confirm cure after treatment. Helicobacter culture may be useful to
assess antimicrobial resistance in persistently recalcitrant cases.
! Antroduodenal Motility Testing and Electrogastrography
○ Antroduodenal motility testing and electrogastrography (EGG) are performed in
specialized centers and may be useful in the evaluation of the occasional patient with
dyspeptic symptoms.
○ EGG consists of the transcutaneous recording of gastric myoelectric activity.
○ Antroduodenal motility testing is done with a tube placed transnasally or transorally into
the distal duodenum.
○ There are pressure-recording sensors extending from the stom- ach to the distal
duodenum.
○ The combination of these two tests together with scintigraphy provides a thorough
assessment of gastric motility.
HELICOBACTER PYLORI INFECTION
! Over 50% of people worldwide are infected with Helicobacter pylori.
! Infection with H pylori is a chronic disease and does not resolve spontaneously without specific
treatment.
! Worldwide, H pylori–induced gastritis accounts for 80% to 90% of all gastritis.
! Chronic gastritis associated with H pylori is the most important risk factor for peptic ulcer and
gastric adenocarcinoma.
! Successful H pylori treatment largely eliminates recurrent peptic ulcer in infected patients, and
eradication of H pylori worldwide would eliminate most cases of gastric adenocarcinoma, a major
cause of cancer death worldwide.
! Helicobacter pylori infection is also associated with MALT lymphoma, dyspepsia, hyperplastic gastric
polyps, and even immune thrombocytopenic purpura.
! Human beings are the only reservoir for H pylori.
! Infection is presumed to occur by oral ingestion of the bacterium, which dramatically alters the gastric
microbiome.
! In helicobacter- infected individuals, 90% of gastric bacteria are helicobacter, whereas in
helicobacter-negative patients 90% of gastric bacteria are a combination of firmicutes,
actinobacteria, bacteroidetes, proteobacteria, and fusobacteria.
! The prevalence of H pylori infection varies among populations and is strongly correlated with
socioeconomic conditions.
! In developing countries, H pylori infection usually occurs in childhood, and over 80% of adults are
infected.
! Reinfection after curative treatment is common.
! Infection rates are lower in industrialized countries, and the prevalence of infection in the United
States has been declining since the second half of the 19th century as hygiene and sanitation have
improved.
! Nonetheless, H pylori infection is predicted to remain endemic in the United States for the next
century.
! Family members of infected individuals and healthcare workers are at increased risk of infection.
9
 ! With specialized flagella and a rich supply of urease, H pylori is uniquely equipped for survival in the
hostile environment of the stomach.
! Helicobacter strains that lack either flagella or urease are nonpathogenic.
! The pathogenesis of helicobacter infection involves:
○ survival in the acidic gastric lumen
○ flagellated movement from the lumen across the mucus layer to the surface epithelial
cell
○ adhesion to the surface epithelial cell
○ toxin production
! Up to 15% of the protein in a Helicobacter organism is composed of cytoplasmic urease that converts
periplasmic urea into CO2 and ammonia.
○ This buffers the surrounding acid, allowing the bacteria to survive the inimical luminal
environment until it can burrow deeply into the surface mucus, propelled by its flagella
! H pylori typically does not invade the surface epithelial cell layer.
! Rather, it triggers a host immune response by attaching to gastric epithelial cells.
! Important Helicobacter adhesins mediating surface cell injury include:
○ neutrophil activating protein A
○ heat shock protein 60
○ sialic acid–binding adhesin
! Helicobacter-produced toxins include vacuolating cytotoxin A and cag A (cytotoxin-associated gene
A).
! The initial inflammatory response to Helicobacter infection is characterized by recruitment of
neutrophils, followed sequentially by T and B lympho- cytes, plasma cells, and macrophages
! The resultant chronic gastric inflammation in affected individuals is characterized by enhanced
mucosal expression of multiple cytokines and the presence of reactive oxygen and nitrogen species,
and long-term infection is associated with mucosal cell DNA damage and chromosomal instability
and increased apoptosis
! The net effect is a weakening of mucosal defenses.
! The mechanism by which the helicobacter organism avoids recognition and destruction by the
mucosal immune system is a topic of interest and active research.
! Acute H pylori infection causes a nonerosive pangastritis that is invariably followed by the
development of chronic gastritis.
! Chronic antral gastritis with sparing of the proximal stomach occurs in about 10% of infected patients,
and this predisposes to peptic ulcer disease (PUD).
! The other 90% of Helicobacter-infected patients develop chronic inflammation of the proximal
stomach (corpus dominant gastritis), which can lead to gastric cancer in about 1% to 3% of this
group.
! H pylori infection is the major cause of peptic ulceration.
! Patients with H pylori infection and antral gastritis are three and one-half times more likely to develop
PUD than patients without H pylori infection.
! Up to 90% of patients with duodenal ulcers, and at least 70% of patients with gastric ulcers, have H
pylori infection.
! It is clear from multiple randomized prospective studies that curing H pylori infection dramatically
alters the natural history of PUD, decreasing the recurrent ulcer rate from more than 75% in patients
treated with a course of acid- suppressive therapy alone (in whom H pylori is not eradicated) to less
than 20% in patients treated with a course of antibacterial therapy.
! In patients with duodenal ulcer caused by helicobacter, the associated antral gastritis leads to
relative hypergastrinemia by depleting antral somatostatin, the primary inhibitor of antral gastrin
release.
! H pylori infection is associated with decreased levels of somatostatin, decreased somatostatin
messenger RNA production, and fewer somatostatin-producing D cells.
! The mechanism of decreased antral somatostatin synthesis and release may be related to:
○ (a) antral alkalinization due to helicobacter urease (acid in the antrum releases
somatostatin)
○ (b) toxic cytokine effect on antral D cells
○ (c) Helicobacter production of N-α-methylhistamine, an H3 receptor agonist, which binds
H3 receptors on the antral D cell and decreases somatostatin release
! Since the gastritis does not involve the oxcyntic mucosa, hypergastrinemia leads to hyperacidity and
parietal cell hyperplasia.
! The acid hypersecretion and the antral gastritis are thought to lead to antral epithelial metaplasia in
the postpyloric duodenum.
! This duodenal metaplasia allows H pylori to colonize the duodenal mucosa, and this is where the
duodenal ulcer occurs.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
! In fact, in patients with gastric metaplasia of the duodenum, the risk of developing a duodenal ulcer
increases 50-fold.
! When H pylori colonizes the duodenum, there is a significant decrease in acid-stimulated duodenal
bicarbonate release.
! When H pylori infection is successfully treated, acid secretory physiology tends to normalize.
! Relapse of duodenal ulcer after eradication of H pylori may signal reinfection of the gastric mucosa
by the organism.
! Many patients with antral dominant helicobacter gastritis never develop duodenal ulcer, and some
patients with peptic ulcer do not have Helicobacter.
○ This obviously suggests that there are other important pathogenetic factors involved in
peptic ulcer.
! And even in the presence of active H pylori infection, strong acid suppression usually heals peptic
ulcer, an observation consistent with the old dictum “no acid, no ulcer.”
! But successful helicobacter treatment eliminates ulcer recurrence and the need for long-term PPI.
! And long-term PPI in patients with active Helicobacter infection may lead to corpus predominant
gastritis, which leads to atrophic gastritis and increases the risk of gastric cancer.
! Thus, Helicobacter infection should be treated and eradication confirmed.
! Testing for H pylori infection should be performed in patients with peptic ulcer, gastritis, significant
dyspepsia, MALT lymphoma, and early gastric cancer.
! Noninvasive methods for diagnosis of H pylori infection include:
○ the urea breath test
■ has a sensitivity and specificity of greater than 90% and is useful for initial
diagnosis of infection and for follow-up after eradication therapy since it is
positive only in the presence of active infection
○ serology
■ Because H pylori induces a strong immunologic response, serological testing
is useful but may not be as accurate as the urea breath test or the stool
antigen test, and a positive serology persists after eradication of H pylori
infection, so serology is not useful to confirm successful treatment of
Helicobacter infection.
○ detection of stool antigen
■ another noninvasive test to detect active H pylori infection, but it is
recommended that only locally validated tests be used
! H pylori infection can also be diagnosed by histologic evaluation of gastric biopsies and/or the rapid
urease test on fresh biopsies.
! Culture of H pylori is not routine and is usually reserved for recurrent infection and for antibiotic
sensitivity testing when second-line therapy has failed.
! All tests for H pylori have a false negative rate.
! Empiric Helicobacter treatment can be considered despite negative tests if clinical likelihood of
infection is high, e.g., a compliant nonsmoking, non–NSAID-consuming patient facing operation for
nonhealing peptic ulcer or a patient with unexplained gastritis.
! Patients with a positive test should be treated and eradication confirmed.
! Spontaneous cure without treatment is very rare.
! It is important to note that none of the therapeutic regimens reported to date cure H pylori infection
in 100% of patients.
! To be effective, antimicrobial drugs must be combined with gas- tric acid secretion inhibitors or
bismuth salts.
! The Maastricht V/Florence Consensus Report provides current recommenda- tions for diagnosis
and treatment of H pylori infection in various clinical scenarios, including recommendations for areas
with high metronidazole and clarithromycin resistance.
○ Ideally, a treatment regimen is chosen with 90% effectiveness.
○ Treatment failure requires an alternative course of therapy.
○ Failure to eradicate infection after two tries should prompt Helicobacter culture and
sensitivity testing and referral to a specialist.
! With assiduous treatment, Helicobacter eradication can be achieved in nearly every patient.
! Patients with atrophic gastritis require endoscopic surveillance because the same sequence of
inflammation to metaplasia to dysplasia to carcinoma, that is well known to occur in the esophagus
from reflux-induced inflammation (and in the colon from inflammatory bowel disease), is now
increasingly well recognized to occur in the stomach with Helicobacter- induced gastritis.
! Helicobacter also clearly has an etiologic role in the development of gastric lymphoma.
10
PEPTIC ULCER DISEASE • A variety of other diseases are known to cause peptic ulcer, including ZES (gastrinoma),
• Peptic ulcers are focal defects in the gastric or duodenal mucosa that extend into the submucosa antral G-cell hyperfunction and/or hyperplasia, systemic mastocytosis, trauma, burns, and
or deeper. major physiologic stress. Other causative agents include drugs (all NSAIDs, aspirin, and
• They may be acute or chronic and, ultimately, are caused by an imbalance between mucosal cocaine), smoking, and psychologic stress.
defenses and acid/peptic injury. • In the United States, probably more than 90% of serious peptic ulcer complications can be attributed
to H. pylori infection, NSAID use, and/or cigarette smoking.
Epidemiology (US-based)
• Peptic ulcer remains a common ACID SECRETION AND PEPTIC ULCER
outpatient diagnosis, but the number of Duodenal Ulcer
physician visits, hospital admissions, • A variety of abnormalities related to mucosal acid exposure have been described in patients
and elective operations for PUD has with duodenal ulcer (Fig. 26-29).
decreased steadily and dramatically with • Although duodenal ulcer patients as a group have a higher mean basal acid output (BAO) and mean
the widespread use of acid suppression, maximal acid output (MAO) compared to normal controls, many duodenal ulcer patients have basal
or highly selective vagotomy. and peak acid outputs in the normal range, and there is no correlation between acid secretion and
o The incidence of emergency surgery the severity of the ulcer disease.
and the death rate associated with o As a group, duodenal ulcer patients produce more acid than normal controls in response to
peptic ulcers has not decreased nearly any known acid secretory stimulus. Although they usually have normal fasting serum gastrin levels,
so dramatically. DU patients often produce more gastric acid at any given dose of gastrin than controls.
o These epidemiologic changes probably o Considering that many duodenal ulcer patients do produce excessive gastric acid, it has been argued
represent the net effect of several factors, including (beneficially) decreased prevalence of H. pylori that a “normal” fasting gastrin level in these patients is inappropriately high, and that there is an
infection, better medical therapy, and increased outpatient management and (detrimentally) the use impaired feedback mechanism, especially in light of the apparently increased sensitivity of the
of NSAIDs and aspirin (with and without ulcer prophylaxis) in an aging population with multiple risk parietal cell mass to gastrin.
factors. • Some patients with duodenal ulcer also have increased rates of gastric emptying that deliver
• PUD is one of the most common GI disorders in the United States with a prevalence of about 2%, an increased acid load per unit of time to the duodenum.
and a lifetime cumulative prevalence of about 10%, peaking around age 70 years. The costs of • Finally, the buffering capacity of the duodenum in many patients with duodenal ulcer is
PUD, including lost work time and productivity, are estimated to be above $8 billion per year in the compromised due to decreased duodenal bicarbonate secretion and duodenal gastric
United States. metaplasia.
• Recent studies have shown an increase in the rates of hospitalization and mortality in elderly
patients for the peptic ulcer complications of bleeding and perforation. Gastric Ulcer
o This may be due in part to the increasingly common use of NSAIDs and aspirin in this elderly • In patients with gastric ulcer, acid secretion is
cohort, many of whom also have H. pylori infection. variable. Currently, five types of gastric ulcer are
described, although the original Johnson
PATHOPHYSIOLOGY AND ETIOLOGY classification contained three types.
o The most common, Johnson type I gastric ulcer,
is typically located near the angularis incisura on
the lesser curvature, close to the border between
antral and corpus mucosa.
§ Patients with type I gastric ulcer usually
have normal or decreased acid secretion.
o Type II gastric ulcer is associated with active or
quiescent duodenal ulcer disease, and type III
gastric ulcer is prepyloric ulcer disease.
§ Both type II and type III gastric ulcers are
associated with normal or increased
gastric acid secretion and surgically are
treated similar to duodenal ulcer.
o Type IV gastric ulcers occur near the GE
junction, and acid secretion is normal or below
normal.
• A variety of factors may contribute to the development of PUD. Although it is now recognized that
o Type V gastric ulcers are medication induced and
the large majority of duodenal and gastric ulcers are caused by H pylori infection and/or
may occur anywhere in the stomach.
NSAID use, the final common pathway to ulcer formation is acid-peptic injury of the
• Patients with gastric ulcers may have weak
gastroduodenal mucosal barrier.
mucosal defenses that permit an abnormal
• Acid suppression heals both duodenal and gastric ulcers and prevents recurrence if continued.
amount of injurious acid backdiffusion into the
mucosa.
• In general, H. pylori predisposes to ulceration, both by acid hypersecretion and by compromise
• Duodenogastric reflux may play a role in
of mucosal defense mechanisms.
weakening the gastric mucosal defenses, and a
• NSAID use causes ulcers predominantly by compromise of mucosal defenses.
variety of components in duodenal juice, including
• Weakened mucosal defenses play a role in both duodenal and gastric ulcers, and acid
bile, lysolecithin, and pancreatic juice, have been shown to cause injury and inflammation in the
hypersecretion may result in a duodenal or gastric ulcer in the setting of normal mucosal
gastric mucosa.
defenses.
• NSAIDs and aspirin have similar effects.
• Elimination of H. pylori infection or NSAID use is important for optimal ulcer healing, and perhaps
• Although chronic gastric ulcer usually is associated with surrounding gastritis, it is unproven that the
is even more important in preventing ulcer recurrence and/or complications.
latter leads to the former.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 11
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN PEPTIC ULCER DISEASE • In 1842, Curling described duodenal ulcer and/or duodenitis in burn patients. Decades later,
• Chronic use of NSAIDs (including aspirin) increases the risk of peptic ulcer disease about Cushing described the appearance of acute peptic ulceration in patients with head trauma
fivefold and upper GI bleeding at least twofold. Complications of PUD (specifically hemorrhage (Cushing’s ulcer).
and perforation) are much more common in patients taking NSAIDs. • Even the ancients recognized the undeniable links between PUD and stress. Patients still present
o More than half of patients who present with peptic ulcer hemorrhage or perforation report the recent with ulcer complications (bleeding, perforation, and obstruction) that are seemingly exacerbated by
use of NSAIDs, including aspirin. Many of these patients remain asymptomatic until they develop stressful life events (Robbin’s: Stress ulcer).
these life-threatening complications. • The use of crack cocaine has been linked to juxtapyloric peptic ulcers with a propensity to perforate.
• The overall risk of significant serious adverse GI events in patients taking NSAIDs is more than Alcohol is commonly mentioned as a risk factor for PUD, but confirmatory data are lacking.
three times that of controls (Table 26-6).
• In elderly patients taking NSAIDs: CLINICAL MANIFESTATIONS
o the likelihood that they will require an operation related to a GI complication is 10 times • More than 90% of patients with PUD complain of abdominal pain.
that of the control group, and the risk that they will die from a GI cause is about four and o The pain is typically nonradiating, burning in quality, and located in the epigastrium. The mechanism
one-half times higher. of the pain is unclear.
o higher hospitalization rate for serious GI events than those who do not. • A history of PUD, use of NSAIDs, over-the-counter antacids, or antisecretory drugs is suggestive
of the diagnosis.
• Other signs and symptoms include nausea, bloating, weight loss, stool positive for occult blood, and
anemia.
DUODENAL ULCER GASTRIC ULCER
o Often experience pain 2 to 3
hours after a meal and at night. o More commonly occurs with
o Two-thirds of patients with eating and is less likely to
Pain
duodenal ulcers will complain awaken the patient at night.
of pain that awakens them
from sleep.
• Incidence of gastric ulcer is
similar in men and women.
• Twice as common in men • On average, gastric ulcer
compared to women patients are older
Epidemiology
• Duodenal ulcer patients • The incidence is increasing in
younger. the elderly, perhaps because
of increasing NSAID and
aspirin.

DIAGNOSIS
• In the young patient with dyspepsia and without alarm symptoms, it may be appropriate to
initiate empirical PPI therapy for PUD without upper endoscopy or upper GI series.
• NSAIDs and aspirin should be stopped if the patient is taking these drugs, and Helicobacter should
be ruled out with testing and treated if present.

• Factors that clearly put patients at increased risk for NSAID-induced GI complications include age
>60, prior GI event, high NSAID dose, concurrent steroid intake, and concurrent anticoagulant
intake. Proton pump inhibitors have been shown to significantly decrease upper GI bleeding risk in
patients on chronic warfarin, low dose aspirin, and/or antiplatelet agents.
• ANY patient taking NSAIDs or aspirin who has one or more of these risk factors should
receive concomitant acid suppressive medication, preferably PPI (Table 26-7). High-dose H2
blockers have been shown to be somewhat less effective than PPIs in preventing GI
complications in these high-risk patients on antiplatelet therapy, but clearly, they are better than no
acid suppression.

SMOKING, STRESS, AND OTHER FACTORS

• Smokers are about twice as likely to develop PUD as nonsmokers.
• Smoking increases gastric acid secretion and duodenogastric reflux. Smoking decreases both
gastroduodenal prostaglandin production and pancreaticoduodenal bicarbonate production.
These observations may be related, and any or all could explain the observed association
between smoking and PUD.
• Although difficult to measure, both physiologic and psychologic stress undoubtedly play a role
in the development of peptic ulcer in some patients.
• It is prudent to discuss with the patient the small possibility of an alternative diagnosis, including
malignancy, even if symptoms improve with the initiation of empiric therapy.
• Patients with persistent dyspepsia, and those who cannot stop NSAIDs or aspirin for health
reasons should have an upper endoscopy, and all patients, regardless of age, should have
this study if any alarm symptoms (Table 26-5) are present. A double-contrast upper GI X-ray
study may be useful.

BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 12

 o Shock, hematemesis, transfusion requirement exceeding four units in 24 hours, and certain
endoscopic stigmata (active bleeding or visible vessel) define this high-risk group.

Risk stratification tools: Proven useful in predicting rebleeding and death, and in identifying a low risk cohort.
o As can be seen in Table 26-9, the maximal Blatchford score is 23, and the maximal Rockall score
is 11.
o Studies have shown that a BLATCHFORD SCORE of 1 or less, or a ROCKALL SCORE of 2 or
less, identifies patients who are very unlikely to be suffering from life-threatening upper GI
bleeding.
o Blatchford Score: does not use endoscopic criteria and may be better in identifying the low
risk cohort.
o The shorter modified Blatchford score may be just as useful (BUN, Hgb, pulse, BP; maximal score
16).
§ High-risk patients benefit from endoscopic therapy to stop the bleeding
§ Low-risk patients with low-risk lesions can be promptly discharged and treated as
outpatients.

• Once an ulcer has been confirmed endoscopically or radiologically, obvious possible causes
(Helicobacter, NSAIDs, gastrinoma, cancer) should always be considered.
• All gastric ulcers should be adequately biopsied, and any sites of gastritis should be
biopsied to rule out H pylori, and for histologic evaluation.
o Additional testing for H pylori may be indicated. It is reasonable to test all peptic ulcer patients
and those with nonulcer dyspepsia for H. pylori (Table 26-8).
• If the peptic ulcer is unusual (distal duodenal or jejunal) or if the patient is Helicobacter and NSAID
negative:
o Consider baseline serum gastrin level to rule out gastrinoma should be considered

COMPLICATIONS
• The three most common
complications of PUD, in
decreasing order of frequency, are
bleeding, perforation, and
obstruction.

Bleeding
• Most peptic ulcer–related deaths in
the United States are due to
bleeding.
• Inhospital mortality and length of
stay can be predicted by the
AIMS65 score, with a score of 0
predicting negligible mortality and a score of 5 predicting a 30% inhospital mortality.
• Bleeding peptic ulcers are by far the most common cause of upper GI bleeding in patients
admitted to a hospital (Fig. 26-31).

Clinical Manifestations and Diagnosis:

• Patients with a bleeding peptic ulcer typically present with melena and/or hematemesis. Naso-
gastric aspiration is usually confirmatory of upper GI bleeding.
• Abdominal pain is quite uncommon. Shock may be present, necessitating aggressive
resuscitation and blood transfusion.
• Early endoscopy is important to diagnose the cause of the bleeding and to assess the need
for hemostatic therapy.

Risk Stratification and Management:

• Three-fourths of the patients who come to the hospital with bleeding peptic ulcer will stop bleeding
if given acid suppression and nothing by mouth.
• One fourth will continue to bleed or will rebleed after an initial quiescent period, and virtually
all the mortalities (and all the operations for bleeding) occur in this group.
o This group can be fairly well delineated based on clinical factors related to the magnitude of the
hemorrhage, comorbidities, age, and endoscopic findings.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 13
 • The most common endoscopic hemostatic modalities used are injection with epinephrine and
electrocautery.
• In a case with exposed vessel, mechanical hemostasis using clips is useful to control the
bleeding.
o Biopsy should be performed to evaluate for H pylori infection.
• Persistent bleeding or rebleeding after endoscopic therapy is an indication for repeat endoscopic
treatment.
o After two endoscopic failures: Consider surgery
o Elderly patients and patients with multiple comorbidities do not tolerate repeated episodes of
hemodynamically significant hemorrhage, and they may benefit from early elective operation
after initially successful endoscopic treatment, especially if they have a high-risk ulcer.
• Deep bleeding ulcers on the posterior duodenal bulb or lesser gastric curvature are high-risk
lesions because they often erode large arteries less amenable to nonoperative treatment, and early
operation should be considered.
Perforation
Clinical Manifestations and Diagnosis::
• Perforated peptic ulcer usually presents as an acute abdomen. The patient can often give the exact
time of onset of the excruciating abdominal pain. Initially, a chemical peritonitis develops from the
gastric and/or duodenal secretions, but within hours a bacterial peritonitis supervenes.
• The patient is in obvious distress, and the abdominal examination shows peritoneal signs. Usually,
marked involuntary guarding and rebound tenderness is evoked by a gentle examination.
• Upright chest X-ray shows free air in about 80% of patients.
2. Cessation of Risk Factors
• Peptic ulcer patients should stop smoking and avoid alcohol and NSAIDs (including aspirin).
• Patients who require NSAIDs or aspirin to treat other medical conditions: should always take
concomitant PPIs or high dose H2 receptor blockers.
3. Helicobacter pylori therapies
• Testing for H. pylori infection is performed, and if it is found, it should be treated with one of several
acceptable regimens (Table 26-10).
• If initial H. pylori testing is negative and ulcer symptoms persist, an empirical trial of anti–H
pylori therapy is reasonable since false-negative H. pylori tests are not uncommon.
• Generally, acid suppression can be stopped after 3 months if the ulcerogenic stimulus (e.g., H
pylori, NSAIDs, or aspirin) has been removed. However, long-term maintenance PPI therapy
should be considered in:
o all patients admitted to hospital with ulcer complications,
o all high-risk patients on NSAIDs or aspirin (the elderly or debilitated), and
o all patients requiring anticoagulation or antiplatelet agents or those with a history of
recurrent ulcer or bleeding.
• Consideration should also be given to maintenance PPI therapy in refractory smokers with a history
of peptic ulcer.
4. Sucralfate
• Sucralfate acts locally on mucosal defects and is well tolerated, and occasionally it is useful
as a supplement to acid suppression.

Management:
• Once the diagnosis has been made, the patient is given analgesia and antibiotics, resuscitated
with isotonic fluid, and taken to the operating room.
• Fluid sequestration into the third space of the inflamed peritoneum can be impressive, so
preoperative fluid resuscitation is mandatory.
• Sometimes, the perforation has sealed spontaneously by the time of presentation, and surgery can
be avoided if the patient is doing well.
• Nonoperative management is appropriate only if there is objective evidence that the leak has
sealed (i.e., radiologic contrast study), and in the absence of clinical peritonitis.

Obstruction
Clinical Manifestation:
• Gastric outlet obstruction occurs in no more than 5% of patients with PUD.
• It is usually due to duodenal or prepyloric ulcer disease, and it may be acute (from inflammatory
swelling and peristaltic dysfunction) or chronic (from cicatrix).
• Patients typically present with nonbilious vomiting and may have profound hypokalemic
hypochloremic metabolic alkalosis and dehydration. Pain or discomfort is common.
• Weight loss may be prominent, depending on the duration of symptoms.
• A succussion splash may be audible with stethoscope placed in the epigastrium.

Diagnosis and Management:

• Initial treatment is nasogastric suction, IV hydration and electrolyte repletion, and acid
suppression.
• The diagnosis is confirmed by endoscopy.
• Most patients admitted to the hospital nowadays with obstructing ulcer disease require
intervention, either balloon dilation or operation.
• Cancer must be ruled out because most patients who present with the symptoms of gastric
outlet obstruction will have a pancreatic, gastric, or duodenal malignancy.

MEDICAL TREATMENT OF PEPTIC ULCER DISEASE

1. Proton-Pump Inhibitors
SURGICAL TREATMENT OF PEPTIC ULCER DISEASE
• PPIs are the mainstay of medical therapy for PUD, but highdose H2-receptor antagonists (H2RAs)
• The indications for surgery in PUD are (in order of decreasing frequency) perforation, obstruction,
and sucralfate are also quite effective.
bleeding, and intractability or nonhealing. (See Choice of Operation for Peptic Ulcer, Table 26-
• Patients hospitalized for ulcer complications: should receive high-dose intravenous PPI and,
12)
when discharged, should be considered for lifelong PPIs unless the definitive cause is eliminated
• Gastric cancer must always be considered in patients with gastric ulcer or gastric outlet obstruction.
or a definitive operation performed.
• Today, most patients undergoing emergent operation have simple patch of a perforated ulcer or
oversewing of a bleeding ulcer.

BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 14

 • Simultaneous performance of vagotomy either truncal or highly selective is increasingly • During truncal vagotomy (Fig. 26-34), care must be
uncommon, probably due to surgeon unfamiliarity with the procedure and reliance on postoperative taken not to perforate the esophagus, a potentially
PPIs to decrease acid secretion. lethal complication. Intraoperative frozen section
o Vagotomy may improve outcomes in emergency ulcer surgery. confirmation of at least two vagal trunks is prudent;
o Before denying the stable low-risk patient a highly selective vagotomy or truncal vagotomy and additional vagal trunks are common.
drainage as an adjunct to simple patch or oversew, the surgeon should consider that many • Unlike HSV, V + D is widely accepted as a
patients having emergency operation for successful definitive operation for complicated
peptic ulcer will not take long-term PPI, PUD.
do not have Helicobacter, or will continue • It has been described as a useful part of the operative
to smoke or take NSAIDs. treatment for bleeding duodenal and gastric ulcer,
o The large majority of these excellent studies perforated duodenal and gastric ulcer, and
were done in the pre-PPI, pre-Helicobacter, obstructing duodenal and gastric (types II and III)
pre-NSAID era, and focused on elective ulcer.
operation for intractable disease, an unusual • When applied to gastric ulcer, the ulcer should be
indication for operation nowadays. Thus, excised or biopsied.
today’s surgeon should take great care in
applying this literature to inform surgical Truncal Vagotomy
decision making. • Truncal vagotomy denervates the antropyloric mechanism, and therefore, some sort of procedure
• Traditionally, the vast majority of peptic ulcers is necessary to ablate or bypass the pylorus.
were treated by a variant of one of the three o Gastrojejunostomy is a good choice in patients with gastric outlet obstruction or a severely diseased
basic operations: proximal duodenum.
§ parietal cell vagotomy, also called § The anastomosis is done between the proximal jejunum and the most dependent portion of
highly selective vagotomy (HSV) or the greater gastric curvature, in either an antecolic or retrocolic fashion (Fig. 26-35).
proximal gastric vagotomy,
§ vagotomy and drainage (V+D), and
§ vagotomy and distal gastrectomy.
o Recurrence rates are lowest but morbidity
highest with the latter procedure, while the
opposite is true for HSV (Table 26-11).

Parietal Cell Vagotomy or Highly Selective Vagotomy:

• HSV severs the vagal nerve supply to the
proximal two-thirds of the stomach, where
essentially all the parietal cells are located, and
preserves the vagal innervation to the antrum § Marginal ulceration is a potential complication.
and pylorus and the remaining abdominal viscera § Mechanical complications are also possible such as afferent or efferent loop obstruction,
(Fig. 26-33). internal hernia, and intussusception.
• Thus, the operation decreases total gastric acid
secretion by about 75%, and GI side effects are rare. o Pyloroplasty is useful in patients who
• Elective HSV has largely been supplanted by long- require a pyloroduodenotomy to deal with
term PPI treatment, but the operation, which has a the ulcer complication (e.g., posterior
learning curve, may still be useful in the patient bleeding duodenal ulcer), in those with
(elective or emergent) who is noncompliant with, limited or focal scarring in the pyloric
intolerant of, or cannot afford medical treatment. region, or when gastrojejunostomy is
• Historically, HSV has not performed particularly well technically difficult.
for type II (gastric and duodenal) and type III § The most commonly performed
(prepyloric) gastric ulcer, perhaps because of pyloroplasty is the Heineke-
hypergastrinemia caused by gastric outlet Mikulicz type (Fig. 26-36).
obstruction and persistent antral stasis. § Other occasionally useful
techniques include the Finney
Taylor Procedure (Fig. 26-37) and the Jaboulay
• The Taylor procedure, a straightforward laparoscopic operation, consists of a posterior truncal pyloroplasties (Fig. 26-38).
vagotomy and anterior seromyotomy (but anterior HSV is probably equivalent), and it is an attractive § These more extensive
and simple alternative to HSV with similar results. pyloroplasty techniques may
make subsequent distal gastric
Vagotomy + Drainage (V + D): Truncal Vagotomy and Pyloroplasty/ Gastrojejunostomy resection more difficult and/or
• Truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy are the hazardous.
paradigmatic vagotomy and drainage procedures.
• HSV may be substituted for truncal vagotomy.
• The advantage of V + D is that it can be performed safely and quickly by the experienced surgeon.
The main disadvantages are the side effect profile (10% of patients have significant dumping and/or
diarrhea).
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 15
 Distal Gastrectomy Without Vagotomy
• Distal gastrectomy without vagotomy (usually about a 50% gastrectomy to include the ulcer)
has traditionally been the procedure of choice for type I gastric ulcer.
• The addition of vagotomy should be considered for type II and III gastric ulcers (because the
pathophysiology is more analogous to duodenal ulcer), or if the patient is believed to be at increased
risk for recurrent ulcer, or perhaps even if Billroth II reconstruction is contemplated (to decrease the
chance of marginal ulcer).
• Subtotal gastrectomy (75% distal gastrectomy) without vagotomy is rarely used to treat PUD
today, although it was the most popular ulcer operation at the middle of the last century.

Pylorus Preserving Gastrectomy (PPG)

• Pylorus preserving gastrectomy (PPG) was first reported as a surgical option for gastric ulcer
that could minimize both dumping and duodenogastric reflux.
• Though not widely adopted for this indication, in some centers PPG is considered a good minimally
invasive surgical option for early gastric cancer.

Choice of Operation for Peptic Ulcer

Vagotomy and Antrectomy (V + A)

• Although vagotomy and antrectomy (V + A) is associated
with a very low ulcer recurrence rate and is applicable to
many patients with complicated PUD (e.g., bleeding duodenal
and gastric ulcer, obstructing peptic ulcer, nonhealing gastric
ulcer, and recurrent ulcer), V + A has a higher operative
mortality risk (compared with HSV or V + D), and is
irreversible.
• Following antrectomy, GI continuity may be reestablished
with a Billroth I gastroduodenostomy (Fig. 26-39) or a
Billroth II loop gastrojejunostomy (Fig. 26-40).
• Since antrectomy routinely leaves a 60% to 70% gastric
remnant, routine reconstruction as a Roux-en-Y
gastrojejunostomy should be avoided (Fig. 26-41).
o Although the Roux-en-Y operation is an excellent procedure
for keeping duodenal contents out of the stomach and
esophagus, in the presence of a large gastric remnant, this
reconstruction will predispose to marginal ulceration and/or
gastric stasis.

Contraindications:
• V + A should be avoided in hemodynamically unstable
patients, and in patients with extensive inflammation and/or scarring of the proximal duodenum,
because secure anastomosis (Billroth I) or duodenal closure (Billroth II) may be difficult.
• The choice of operation for the individual patient with PUD depends on a variety of factors, including
the type of ulcer (duodenal, gastric, recurrent, or marginal), the indication for operation, and the
condition of the patient.
• Other important considerations are intra-abdominal factors (duodenal scarring/inflammation,
adhesions, or difficult exposure), the ulcer diathesis status of the patient, the surgeon’s experience
and personal preference, whether H pylori infection is present, the need for NSAID therapy,
previous treatment, and the likelihood of future compliance with treatment.
• Table 26-12 shows the surgical options for managing various aspects of PUD.
• In general, resective procedures have a lower ulcer recurrence rate, but a higher morbidity
and mortality rate (see Table 26-11) compared to nonresective ulcer operations.
• H. pylori and/or NSAIDs:
o Because ulcer recurrence often is related to, the case is usually managed adequately without
reoperation.
o Thus, gastric resection to minimize recurrence in duodenal ulcer disease is usually not justified
• Gastric ulcer:
o resection for gastric ulcer remains the standard because of the risk of cancer.
o Clearly, the modern trend in peptic ulcer operation could be described as “less is more.”

BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 16

BLEEDING PEPTIC ULCER
• Bleeding is the most common cause of ulcer-related death, but only rarely do patients with bleeding
gastric or duodenal ulcer require operation today.
• The success of endoscopic treatment and medical therapy for bleeding PUD has resulted in the
selection of a small subgroup of high-risk patients for today’s surgeon. It is likely that patients
currently coming to operation for bleeding PUD are at higher risk for a poor outcome than ever
before.
• The surgical options for treating bleeding PUD include:
§ suture ligation of the bleeder;
§ suture ligation and definitive nonresective ulcer operation (HSV or V + D); and
§ gastric resection (usually, including vagotomy and ulcer excision).
o Gastric ulcer requires biopsy if not resected.
Operation for Bleeding Peptic Ulcer
• The management of bleeding peptic ulcer is summarized in the algorithm provided in Fig. 26-42.
• All patients admitted to the hospital with bleeding peptic ulcer should be adequately
resuscitated and started on IV PPI.
• Most patients will stop bleeding with these measures alone, but about 25% will continue to bleed
or will rebleed in hospital.
• It is important to identify this high-risk group early with clinical and endoscopic parameters because,
essentially, all the deaths from bleeding ulcer occur in this group.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
• Surgical consultation is mandatory, and endoscopic hemostatic therapy (cautery, epinephrine
injection, clipping) is indicated and usually successful in these high-risk patients.
• Indications for operation include:
o massive hemorrhage unresponsive to initial endoscopic control,
o recurrent hemorrhage requiring multiple transfusions after two attempts at endoscopic control,
o ongoing hemorrhage and transfusion with limited availability of blood for transfusion or lack of
availability of a therapeutic endoscopist,
o early rehospitalization for bleeding ulcer, and
o concurrent indications for surgery such as perforation or obstruction.
• Patients with massive bleeding from high-risk lesions (e.g., posterior duodenal ulcer with
erosion of gastroduodenalartery, or lesser curvature gastric ulcer with erosion of left gastric artery
or branch) should be considered for operation as should those presenting in shock, those
requiring more than four units of blood in 24 hours or eight units of blood in 48 hours, and those
with ulcers >2 cm in diameter.
• The mortality rate for surgery for bleeding peptic ulcer is around 20%.
• Angiography and embolization may be useful in some patients.
! The two operations most commonly used for bleeding duodenal ulcer are:
○ Oversewing of the ulcer with or without vagotomy
○ Drainage, or V + A
! Oversewing alone compared to definitive operations results in:
○ Higher rebleeding rate
○ Lower operative mortality
! When the mortality for reoperation for rebleeding is considered, the overall mortality is probably
comparable for the two approaches
! Patients who are in shock or medically unstable should not have gastric resection
! An initial pyloromyotomy incision allows access to the bleeding posterior duodenal ulcer
! An expeditious Kocher maneuver allows the surgeon to control the hemorrhage with the left hand
if necessary
! Heavy suture material on a stout needle is used to place figure-of-eight sutures or a U-stitch to
secure the bleeding vessel at the base of the posterior duodenal ulcer
○ Multiple sutures are usually necessary
17
 ! Once the surgeon is unequivocally convinced that hemostasis is secure → pyloroplasty can be ! Occasionally nonsurgical treatment can be used in the stable patient without peritonitis in whom
performed radiologic studies document a sealed perforation
! If the patient is stable, surgeon is experienced, and vagotomy is straightforward → vagotomy may ! Patients with acute perforation and GI blood loss (either chronic or acute) should be suspected of
be considered having a second ulcer or a GI cancer
! If the patient is not a high operative risk and V + A is selected ! The options for surgical treatment of perforated duodenal ulcer are
○ Smaller duodenal ulcers are resected with the specimen ○ Simple patch closure
○ Larger bleeding duodenal ulcers must often be left behind in the duodenal stump ○ Patch closure and HSV
○ Suture hemostasis must be attained and a secure duodenal closure accomplished ○ Patch closure and V + D
■ The anterior wall of the open duodenum can be sutured to either the proximal ! Simple patch closure
or distal lip of the posterior ulcer once the bleeding vessel has been sutured ○ Currently the most commonly performed operation for perforated peptic ulcer
■ The duodenal closure can be buttressed with omentum and the duodenum ○ Procedure of choice in patients with hemodynamic instability and/or exudative peritonitis
should be decompressed, either with a lateral duodenostomy or retrograde signifying a perforation >24 hours old
tube via the proximal jejunum or well secured nasogastric tube secured with ! Addition of HSV should be considered:
tip well into afferent limb ○ In stable patients without longstanding perforation, particularly those with chronic
○ Right upper quadrant closed suction peritoneal drainage is important symptoms or failure of medical treatment
○ Use of a feeding jejunostomy is also considered ! Vagotomy and drainage
○ A Billroth II anastomosis reestablishes gastrointestinal continuity ○ Also an acceptable definitive operation for perforated duodenal ulcer, but occasionally
! The initial management of bleeding gastric ulcers and the indications for operation are similar to side effects are disabling
those for bleeding duodenal ulcer ○ If gastrojejunostomy has been performed, marginal ulcer can be life-threatening
! These lesions tend to occur in older and/or medically complicated patients, and this fact may ! Distal gastric resection
increase the operative risk ○ Best treatment for perforated gastric ulcer in the stable patient without multiple operative
○ But planned surgery in a resuscitated patient results in a better operative survival rate risk factors
than emergent operation in a patient who has rebled and is in shock ! Vagotomy is usually added for type II and III gastric ulcers
! Distal gastric resection to include the bleeding ulcer is the procedure of choice for bleeding ! Alternative options in an unstable or high-risk patient, or in a patient with a perforation in an
gastric ulcer inopportune location:
! Second best is V + D with oversewing and biopsy of the ulcer to rule out cancer ○ Patch closure with biopsy
! Oversewing of the bleeder and biopsy followed by long term acid suppression is a reasonable ○ Local excision and closure
alternative in high-risk or unstable patients ○ Biopsy, closure, truncal vagotomy, and drainage
! All perforated gastric ulcers, even those in the prepyloric position, should be biopsied if they are
Perforated Peptic Ulcer not removed at surgery

Obstructing Peptic Ulcer

! Acute ulcers associated with obstruction due to edema and/or motor dysfunction → may
respond to intensive antisecretory therapy and nasogastric suction
! Most patients with significant obstruction from chronic ulceration
○ Require some sort of more substantial intervention
○ Endoscopic balloon dilation can often transiently improve obstructive symptoms, but
many of these patients ultimately fail and come to operation
! The standard operation for obstructing PUD is vagotomy and antrectomy
○ Alternatively, vagotomy and gastrojejunostomy should be considered if a difficult
duodenal stump is anticipated with resection
! HSV and gastrojejunostomy
○ May be comparable to V + A for obstructing ulcer disease
○ Is appealing because it can be done laparoscopically and does not complicate future
resection, if needed
○ However, potentially curable gastric or duodenal cancers can be missed with this
approach

Intractable or Nonhealing Peptic Ulcer

! Intractability should be an unusual indication for peptic ulcer operation
! The patient referred for surgical evaluation because of intractable PUD should raise red flags for
the surgeon:
○ Maybe the patient has a missed cancer
○ Maybe the patient is noncompliant (not taking prescribed PPI, still taking NSAIDs, still
smoking)
○ Maybe the patient has Helicobacter despite the presence of a negative test or previous
treatment
! The surgeon should review the differential diagnosis of nonhealing ulcer before any consideration of
operative treatment (considering acid secretion can be totally blocked and H pylori eradicated with
! Perforation is the second most common complication of peptic ulcer
modern medication, so the question remains: “Why does the patient have a persistent ulcer
! It is a much more common indication for operation than bleeding
diathesis?”)
! NSAID and/or aspirin use have been inextricably linked with perforated PUD, especially in the
elderly population
! Surgery is almost always indicated for ulcer perforation
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 18
 Zollinger-Ellison Syndrome
! Surgical treatment should be considered in patients with nonhealing or intractable PUD who have:
○ Multiple recurrences
○ Large ulcers (>2 cm)
○ Complications (obstruction, perforation, or hemorrhage)
○ Suspected malignancy
! Definitive operation, particularly gastric resection, should be considered most cautiously in the thin
or marginally nourished individual
! The surgeon should not fall into the trap of performing a large, irreversible operation on these
patients, based on the unproven theory that if all other methods have failed to heal the ulcer, a large
operation is required
○ One argument: current medical care has healed the typical peptic ulcers, and patients
presenting with true intractability or nonhealing will be more difficult to treat and are likely
to have chronic problems after a major ulcer operation
! If surgery is necessary, a lesser operation may be preferable
○ Avoid truncal vagotomy and/or distal gastrectomy as the initial elective operation for
intractable peptic ulcer in the thin or asthenic patient
○ Alternatives for intractable duodenal ulcer include HSV with or without gastrojejunostomy
(reversible drainage operation)
○ In thin or frail patients with nonhealing gastric ulcer, wedge resection with HSV should
be considered
○ Otherwise, distal gastrectomy (to include the ulcer) is recommended
! It is unnecessary to add a vagotomy in patients with type I or type IV (juxta-esophageal) gastric
ulcers because they are usually associated with acid hyposecretion
! Type IV gastric ulcers may be difficult to resect as part of a distal gastrectomy, and other surgical
techniques have been described to treat these more proximal lesions
! ^ Operations for gastric ulcer
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
! ZES is caused by the hypersecretion of gastrin, typically by a duodenal or pancreatic
neuroendocrine tumor (i.e., gastrinoma)
! Most cases (80%) are sporadic, but 20% are inherited
! The inherited or familial form of gastrinoma is associated with multiple endocrine neoplasia type
I (MEN I)
○ Characterized by parathyroid, pituitary, and pancreatic (or duodenal) tumors
○ Gastrinoma is the most common islet cell tumor in patients with MEN I
○ Patients with MEN I usually have multiple gastrinomas, and surgical cure is usually not
achievable
■ Vs. sporadic gastrinomas → more often solitary and are more often
amenable to surgical cure
○ 50% to 60% of gastrinomas → malignant, with lymph node, liver, or other distant
metastases at operation
■ 5-year survival in patients with metastatic disease is 40%
■ > 90% of patients with sporadic, completely resected gastrinoma will be
cured
! The most common symptoms of ZES are:
○ Epigastric pain
○ GERD
○ Diarrhea
! > 90% of patients with gastrinoma have peptic ulcers
○ Most ulcers are in a typical location (proximal duodenum)
○ Atypical ulcer location (distal duodenum, jejunum, or multiple ulcers) should prompt an
evaluation for gastrinoma
! Gastrinoma also should be considered in the differential diagnosis of recurrent or refractory peptic
ulcer, secretory diarrhea, gastric rugal hypertrophy, esophagitis with stricture, bleeding or perforated
ulcer, familial ulcer, peptic ulcer with hypercalcemia, and gastric neuroendocrine tumor (carcinoid)
! The majority of patients with ZES have been symptomatic for several years before definitive
diagnosis and
! Patients with ZES and MEN1 are diagnosed in their 20s and 30s
! Patients with sporadic ZES more typically are diagnosed in their 40s and 50s
! ZES is an important element in the differential diagnosis of hypergastrinemia
19
 ○ All patients with gastrinoma have an elevated gastrin level
○ Hypergastrinemia in the presence of elevated BAO strongly suggests gastrinoma
■ Patients with gastrinoma usually have a BAO >15 mEq/h or >5 mEq/h if they
have had a previous procedure for peptic ulcer
○ Acid secretory medications should be held for several days before gastrin measurement,
because acid suppression may falsely elevate gastrin levels
! Causes of hypergastrinemia can be divided into those associated with hyperacidity and those
associated with hypoacidity
! The diagnosis of ZES is confirmed by the secretin stimulation test
○ An IV bolus of secretin (2 U/kg) is given, and gastrin
levels are checked before and after injection
○ An increase in serum gastrin of 200 pg/mL or greater
suggests the presence of gastrinoma
! Patients with gastrinoma should have serum calcium and
parathyroid hormone levels determined to rule out MEN1
○ If present, parathyroidectomy should be considered
before resection of gastrinoma
! About 80% of primary tumors are found in the gastrinoma
triangle
○ Many tumors are small (<1 cm), making preoperative
localization difficult
! Transabdominal ultrasound is quite specific, but not very
sensitive
! CT will detect most lesions >2 cm in size, and MRI is comparable
! EUS
○ More sensitive than noninvasive imaging tests
○ It still misses many smaller lesions or lesions in inaccessible locations (e.g., the
pancreatic tail)
! Somatostatin receptor scintigraphy (the octreotide scan) or Gallium-68 dotatate PET/CT
○ Sensitive and specific when the pretest probability of gastrinoma is high
○ May identify sites of regional or distant metastatic disease
! Angiographic localization studies
○ Are infrequently performed for gastrinoma
○ Both diagnostic angiography and transhepatic selective venous sampling of the portal
system have been supplanted by selective arterial secretin infusion, which helps to
localize the tumor as inside or outside the gastrinoma triangle
○ This study is rarely performed given increasing availability of endoscopic
ultrasonography and accurate nuclear medicine imaging
! All patients with sporadic (nonfamilial) gastrinoma should be considered for surgical exploration
○ The lesions can be located in over 90% of patients, and a majority are cured by
extirpation of the gastrinoma
○ A thorough intraoperative exploration of the gastrinoma triangle and pancreas is
essential
○ Other sites (i.e., liver, stomach, small bowel, mesentery, and pelvis) should be evaluated
as part of a thorough intra-abdominal evaluation to find the primary tumor
■ Primary tumor is most often solitary and in the duodenal wall
○ The duodenum and pancreatic head should be extensively mobilized and intraoperative
ultrasound should be utilized
○ Intraoperative EGD with transillumination may be considered
○ If the tumor cannot be located, longitudinal duodenotomy with inspection and palpation
of the duodenal wall is performed
○ Lymph nodes from the portal, peripancreatic, and celiac drainage basins should be
removed
○ Ablation or resection of hepatic metastases when identified should be considered
! The management of gastrinoma in patients with MEN I is controversial because patients are
infrequently cured by operation
○ Acid hypersecretion in patients with gastrinoma can always be managed with high-
dose PPIs
○ Highly selective vagotomy
■ May make management easier in some patients
■ Should be considered in those with surgically untreatable or unresectable
gastrinoma
! Gastrectomy for ZES is not indicated
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
STRESS GASTRITIS AND STRESS ULCER
! Stress gastritis has all but disappeared from the clinical (if not endoscopic) lexicon, largely due to
better critical care and acid suppression or cytoprotective agents (e.g., sucralfate) in the ICU
! Stress gastritis and stress ulcer are probably due to inadequate gastric mucosal blood flow during
periods of intense physiologic stress
○ Adequate mucosal blood flow is important to maintain the mucosal barrier and to buffer
any back-diffused hydrogen ions
○ When blood flow is inadequate, these processes fail and mucosal breakdown occurs
○ Modern intensive care, with emphasis on adequate tissue perfusion and oxygenation,
has decreased the severity of gastric mucosal injury seen in the ICU
! Although it is still common to see small mucosal erosions when performing upper endoscopy in the
ICU, it is rare for these lesions to coalesce into the larger bleeding erosions
! Routine acid suppression in the ICU → less mucosal injury will be caused in the potentially weakened
gastric mucosa if there is less luminal acid
! Some studies suggest: routine acid suppression → leads to overgrowth of gastric bacteria →
increases the incidence and/or severity of aspiration pneumonia in the ICU
○ Nevertheless, acid suppression, particularly in the severely ill patient, remains an
important part of clinical pathways in most ICUs
! In the extraordinarily rare patient requiring operation today for hemorrhagic stress gastritis, the
surgical options include:
○ V + D with oversewing of the major bleeding lesions
○ Near total gastrectomy
○ Angiographic embolization and endoscopic hemostatic treatment also be considered
ATROPHIC GASTRITIS
! Atrophic gastritis is characterized by:
○ Atrophy
○ Disappearance of gastric glands and loss of parietal and chief cells
! The most common cause is chronic H pylori infection, particularly in the corporal distribution
○ Vs. the antral distribution which is more typically associated with peptic ulcer disease
! Can also result in atrophic gastritis:
○ Autoimmune destruction of cells (pernicious anemia)
○ Chemical irritation (e.g., bile reflux)
! Some patients with atrophic gastritis develop intestinal metaplasia in the gastric mucosa that may
progress to dysplasia and then to gastric cancer
! Numerous cofactors have been implicated, including diet, altered gastric microbiome, genetics, and
hypergastrinemia
! Patients with atrophic gastritis are at risk for gastric cancer and should undergo periodic
endoscopic surveillance
○ Markers for increased risk for gastric cancer:
■ Metaplastic atrophic gastritis
■ Dysplastic atrophic gastritis
! Patients with high grade dysplasia may benefit from gastrectomy
! Cancer risk is related to the extent of the atrophic gastritis and intestinal metaplasia
! Grading systems have been developed to stratify cancer risk based on endoscopic findings → two
such systems are the
○ Operative link on gastritis assessment (OLGA)
○ Operative link on gastric intestinal metaplasia (OLGIM) assessment
■ May be more useful in stratifying gastric cancer risk (since pathologists agree
more on the histological diagnosis of intestinal metaplasia than atrophic
gastritis)
! These systems define the severity (“stage”) of atrophic gastritis based on the histologic grading of
at least five gastric biopsies (lesser and greater curve antrum; lesser and greater curve corpus;
angularis incisura)
! May benefit from surveillance endoscopy every 3 years:
○ Patients stratified as stage 3 or 4 gastritis
○ Those with pernicious anemia
! Serum markers are also useful in helping to identify patients with atrophic gastritis who usually
have:
○ Increased serum gastrin and iron deficiency due to parietal cell loss and hypochlorhydria
or achlorhydria
○ Decreased pepsinogen I levels due to chief cell loss
○ B12 deficiency due to parietal cell loss and concomitant loss of intrinsic factor
20
MALIGNANT NEOPLASMS OF THE STOMACH ○ Environmental factors appear to be more important in the pathogenesis of the intestinal
! The most common primary malignant gastric neoplasm is adenocarcinoma (95%) form of gastric cancer compared to the diffuse form
○ Lymphoma and GIST account for most of the remaining cases
Diet and Drugs
! A diet high in pickled, salted, or smoked food is found in many regions of high gastric cancer risk
! Dietary nitrates have been implicated as a possible cause of gastric cancer
○ Gastric bacteria (more abundant in the achlorhydric stomach of patients with atrophic
gastritis, a risk factor for gastric cancer) convert nitrate into nitrite, a known carcinogen
○ The reduced consumption of nitrate-rich preserved foods seen with the widespread
availability of refrigeration has been suggested as a cause of the dramatic decrease in
gastric cancer
! A diet high in fresh fruits and vegetables and rich in vitamin C and E has been shown to
decrease the risk of gastric cancer
! Tobacco use probably increases the risk of stomach cancer
! Alcohol use probably has no effect
○ ! Regular aspirin use may be protective
! Other rare primary malignancies include neuroendocrine tumor, angiosarcoma, carcinosarcoma,
and squamous cell carcinoma
Helicobacter pylori
! Occasionally the stomach is a site of hematogenous metastasis from other sites (e.g., melanoma or
breast cancer)
! Malignant tumors from adjacent organs may also invade the stomach by:
○ Direct extension (e.g., colon or pancreas)
○ Peritoneal dissemination (e.g., ovary or appendiceal)

Adenocarcinoma
Epidemiology
! Gastric cancer is the fourth most common cancer type and the second leading cause of cancer
death worldwide
! Western industrialised countries: There has been a dramatic decrease in the incidence of gastric
cancer, largely in the intestinal form rather than in the diffuse form of gastric cancer
! Asia and Eastern Europe: gastric cancer remains a leading cause of cancer death
! United States: The estimated 5-year survival rate is 27%, up from about 15% in 1975
! In general, gastric cancer is a disease of the elderly, and it is twice as common in blacks as in
whites
! In younger patients
○ Tumors are more often of the diffuse variety ! The risk of gastric cancer in patients with chronic H pylori infection is increased about threefold
○ Tend to be large, aggressive, and poorly differentiated, sometimes involving the entire ! Compared to uninfected patients
stomach (linitis plastic) ○ Patients with a history of gastric ulcers are more likely to develop gastric cancer
! Gastric cancer has a higher incidence in groups of lower socioeconomic status ○ Patients with a history of duodenal ulcers are at decreased risk for gastric cancer
Etiology ! This may be due to the fact that some patients develop antral-predominant disease (predisposing
! Gastric cancer is more common in patients with to duodenal ulcer and somehow protecting against gastric cancer)
○ Pernicious anemia ! Other patients develop corpus-predominant gastritis, resulting in hypochlorhydria and somehow
○ Blood group A predisposing to gastric ulcer and gastric cancer
○ Family history of gastric cance ! It has been demonstrated that bone marrow-derived stem cells play a key role in the pathogenesis
of gastric adenocarcinoma in patients with chronic H pylori infection

! When patients migrate from a high-incidence region to a low-incidence region, the risk of gastric
cancer decreases in the subsequent generations born in the new region
○ This strongly suggests an environmental influence on the development of gastric cancer ! ^ theoretical sequence for development of gastric adenocarcinoma
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 21
 ! It must be recognized that gastric adenocarcinoma is a multifactorial disease
○ Not all patients with gastric cancer have H pylori
○ There are some geographic areas with a high prevalence of chronic H pylori infection
and a low prevalence of gastric cancer (the “African enigma”)
! H pylori–infected patients seem to be at decreased risk for the development of adenocarcinoma of
the distal esophagus and cardia region
○ Perhaps corporeal gastritis decreases acid secretion, creating a less damaging refluxate
and thus reducing the risk for Barrett’s esophagus, the precursor lesion for these tumors

Epstein-Barr Virus
! About 10% of gastric adenocarcinomas carry the EBV virus
! It has been suggested that EBV infection is a late step in gastric carcinogenesis, since EBV
transcripts are present in cancer cells but not in the metaplastic cells of precursor epithelium

Genetic Factors
! Most gastric cancers are aneuploid
! The most common genetic abnormalities in sporadic gastric cancer affect the p53 and COX-2
genes
○ > 2/3 of gastric cancers have deletion or suppression of the important tumor-
suppressor gene p53
○ Approximately the same proportion have overexpression of COX-2
■ In the colon, tumors with upregulation of this gene have suppressed
apoptosis, more angiogenesis, and higher metastatic potential
■ Gastric tumors that overexpress COX-2 are more aggressive
! A germline mutation in the CDH1 gene encoding E-cadherin
○ Was shown to be associated with hereditary diffuse gastric cancer
○ Prophylactic total gastrectomy should be considered in patients with these mutations

Polyps
! Benign gastric polyps are classified as
○ Neoplastic (adenoma and fundic gland polyps)
○ Nonneoplastic (hyperplastic polyp, inflammatory polyp, hamartomatous polyp)
! Inflammatory and hamartomatous polyps have little or no malignant potential
! Fundic gland polyps
○ Commonly seen in patients on long-term PPI therapy
○ Are not premalignant
○ But in patients with familial adenomatous polyposis (FAP), dysplasia in these lesions is
not uncommon, gastric cancer has been reported to arise in a background of fundic gland
polyposis in this setting
! Hyperplastic polyps
○ Usually occur in the setting of chronic inflammation
○ Large hyperplastic polyps (>2 cm) may harbor dysplasia or carcinoma in situ, and gastric
cancer may develop remote from the hyperplastic polyp in an area of associated chronic
inflammation
! ! Gastric adenomas
○ Are premalignant
Premalignant Conditions of the Stomach
○ Patients with familial adenomatous polyposis (FAP) have a high prevalence of gastric
! The most common precancerous lesion is atrophic gastritis
adenomatous polyps (about 50%), and are 10 times more likely to develop
! There is a growing appreciation of the important influence of the chronic inflammatory milieu on the
adenocarcinoma of the stomach than the general population
genome of mucosal cells
○ Screening EGD is indicated in these families
! Chronic inflammation leads to both genetic and epigenetic changes in mucosal cells, which in the
○ Patients with hereditary nonpolyposis colorectal cancer may also be at risk for gastric
stomach leads to the development of gastritis-associated cancer
cancer

BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 22

 Atrophic gastritis o Surgery should be conducted with the aim of complete extirpation of the stomach to squamous
- Chronic atrophic gastritis is by far the most common precursor for gastric cancer, particularly the lined esophagus proximally and normal duodenal mucosa distally.
intestinal subtype. o Mutation-carrying females are also at increased risk of breast cancer, most often lobular
- The prevalence is higher in older age groups, carcinomas, and should be carefully monitored.
o but it is also common in younger people in areas with a high incidence of gastric cancer. - Up to 10% of gastric cancer cases appear to be familial without a clear-cut genetic diagnosis.
- In many patients, H pylori is critical in the pathogenesis of atrophic gastritis. o First-degree relatives of patients with gastric cancer have a two- to threefold increased risk of
- Correa described three distinct patterns of chronic atrophic gastritis: developing the disease.
o autoimmune (involves the acid-secreting proximal stomach), o Patients with hereditary nonpolyposis colorectal cancer have a 10% risk of developing gastric
o hypersecretory (Involving the distal stomach) cancer, predominantly the intestinal subtype.
o environmental (involving multiple random areas at the junction of the oxyntic and antral mucosa). o The mucous cell hyperplasia of Ménétrier’s disease is generally considered to carry a 5% to
10% risk of adenocarcinoma.
Intestinal metaplasia o Periodic surveillance EGD is prudent in all the aforementioned conditions. The glandular
- Gastric carcinoma often occurs in an area of intestinal metaplasia, and the risk of gastric cancer is hyperplasia associated with gastrinoma is not premalignant, but ECL hyperplasia and/or carcinoid
proportional to the extent of intestinal metaplasia of the gastric mucosa. tumors can occur.
o These observations suggest that intestinal metaplasia is a precursor lesion to gastric cancer.
- There are different pathologic subtypes of intestinal metaplasia in the stomach, based upon the histologic PATHOLOGY
and biochemical characteristics of the changed mucosal glands. Dysplasia
o In the complete type of intestinal metaplasia - It is generally accepted that gastric dysplasia is the universal precursor to gastric adenocarcinoma.
§ the glands are lined with goblet cells and intestinal absorptive cells - Patients with severe dysplasia should be considered for gastric resection if the abnormality is widespread
§ These cells are indistinguishable histologically and biochemically from their small bowel or multifocal, or EMR if the severe dysplasia is localized.
counterparts. - Patients with mild dysplasia should be followed with endoscopic biopsy surveillance, and Helicobacter
- There is evidence that eradication of H pylori infection leads to significant regression of intestinal metaplasia eradication.
and improvement in atrophic gastritis.
o Treatment of H pylori is mandatory for patients with these pathologic findings and H pylori Early gastric cancer
infection. - Early gastric cancer is defined as adenocarcinoma
limited to the mucosa (T1a) and submucosa
Benign gastric ulcer (T1b) of the stomach.
- Although once considered a premalignant condition, it is likely that the older literature addressing gastric - The entity is common in Asia, where the higher
ulcers was confounded by the inclusion of inadequately biopsied ulcers s as “benign,” when, in fact, they frequency of gastric cancer justified adoption of
were malignant. aggressive surveillance programs.
- Regardless, all gastric ulcers should be viewed as malignant until proven otherwise with adequate biopsy - Approximately 10% of patients clinically staged with
and follow-up. early gastric cancer will have lymph node
metastases.
Gastric remnant cancer - There are several subtypes of early gastric cancer
- It has long been recognized that stomach cancer can develop in the gastric remnant following subtotal o Approximately 70% of early gastric cancers
gastrectomy. are well differentiated
- The extent of risk is controversial, but the phenomenon is real. o 30% are poorly differentiated.
- Most tumors develop >10 years following the initial operation - The overall cure rate with adequate gastric resection
- usually arise in an area of chronic gastritis, metaplasia, and dysplasia. and lymphadenectomy is 95%.
o This is often near the anastomosis, but many of these tumors are quite large at presentation. - In some Japanese centers, 50% of the gastric
- Bile or alkali reflux gastritis has been implicated as a precursor, and the greatest number of cases have cancers treated are early stage (compared to less
been reported following Billroth II gastroenterostomy where some transit of pancreatic and biliary than 20% of resected gastric adenocarcinomas in
secretions through the stomach is obligate. the United States).
- Although Roux-en-Y anastomosis has been suggested to be protective, this hypothesis remains unproven. - Selected patients with early gastric cancer can be
- Stage for stage, the prognosis for gastric stump cancer is similar to that of other proximal gastric treated with endoscopic resection.
cancers. - Gross morphology and histologic subtypes: Gastric
cancer has been subdivided into four morphologic
Other premalignant states subtypes:
- hereditary diffuse gastric cancer (HDGC). o Polypoid - are not ulcerated
o associated with Mutations in the E-cadherin gene (CDH1) o Fungating - are predominantly intraluminal
o HDGC is an autosomal dominant trait with a high degree of penetrance. with ulceration.
o the lifetime risk of gastric cancer in individuals with pathogenic germline mutations is 70% (in men) o Ulcerative - are self-descriptive.
and 56% (in women). o scirrhous. - infiltrate the entire thickness of
o CDH1 is a tumor-suppressor gene and a second somatic hit is required for tumorigenesis. the stomach and cover a very large surface
o The median age at diagnosis of gastric cancer is 38 years. area, commonly involve the entire stomach
o Presentation with clinically significant gastric cancer in this setting is associated with a grave and have a particularly poor prognosis.
prognosis. - The first two are characterized by a largely
o Increasing recognition of HDGC has afforded the opportunity for early recognition of pathogenic intraluminal mass.
mutations in relatives of individuals with index cases and utilization of prophylactic or early total - In the latter two gross subtypes, the bulk of the tumor
gastrectomy. mass is confined to the wall of the stomach.
- Multifocal intramucosal carcinoma - Although these latter lesions may be technically resectable with total gastrectomy, it is common for both the
o is a frequent finding on putative prophylactic gastrectomy specimens, even in patients without a esophageal and duodenal margins of resection to show microscopic evidence of tumor infiltration; distant
preoperative diagnosis of carcinoma, affirming the role of early intervention. metastasis, overt or occult, is frequent and death from recurrent disease within 6 months is common.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 23
- Palliative chemotherapy may prolong median survival. CLINICAL MANIFESTATIONS
- The location of the primary tumor in the stomach is essential in planning an operation. - Most patients who are diagnosed with gastric cancer in the United States have advanced stage III or IV
o Several decades ago, the large majority of gastric cancers were in the distal stomach. disease at the time of diagnosis.
o Recently, there has been a proximal migration of tumors, so currently, the distribution is closer to - The most common symptoms are weight loss and decreased food intake due to anorexia and early
40% distal, 30% middle, and 30% proximal. satiety.
- Abdominal pain (usually not severe and often ignored) is also common.
Histology - Other symptoms include nausea, vomiting, and bloating.
- The most important prognostic indicators in gastric cancer are both histologic: - Acute GI bleeding is somewhat unusual (5%), but chronic occult blood loss is common and manifests as
o lymph node involvement iron deficiency anemia and heme-positive stool.
o depth of tumor invasion. - Dysphagia is common if the tumor involves the cardia of the stomach.
- Tumor grade (degree of differentiation: well, - Paraneoplastic syndromes such as Trousseau’s syndrome (thrombophlebitis), acanthosis nigricans
moderately, or poorly) is also important (hyperpigmentation of the axilla and groin), or peripheral neuropathy are rarely present.
prognostically. - Physical examination typically is normal.
- There are several histologic classifications of - Other than signs of weight loss, specific positive physical findings usually indicate incurability.
gastric cancer. - A focused examination in a patient in whom gastric cancer is a likely part of the differential diagnosis should
- The World Health Organization recognizes several include an examination of the neck, chest, abdomen, and rectum. Cervical, supraclavicular (on the left
histologic types. referred to as Virchow’s node), and axillary lymph nodes may be enlarged, and can be sampled with fine-
- The commonly used Lauren classification needle aspiration cytology.
separates gastric cancers into: o Malignant pleural effusions or ascites, or aspiration pneumonitis may be present.
o intestinal type (53%) - An abdominal mass may indicate a large (usually T4) primary tumor, liver metastases, or carcinomatosis
§ associated with chronic atrophic (including Krukenberg’s tumor of the ovary).
gastritis, severe intestinal - A palpable umbilical nodule (Sister Joseph’s nodule) is pathognomonic of advanced disease.
metaplasia, and dysplasia, - Rectal exam may reveal heme-positive stool and hard nodularity extraluminally and anteriorly, indicating
§ tends to be less aggressive than the so-called drop metastases, or rectal shelf of Blumer in the pouch of Douglas.
diffuse type.
o diffuse type (33%) DIAGNOSTIC EVALUATION
§ more likely to be poorly differentiated - Distinguishing between peptic ulcer and gastric cancer on clinical grounds alone can be difficult.
§ associated with younger patients and - Patients over the age of 55 years who have new-onset dyspepsia as well as all patients with dyspepsia
proximal tumors. and alarm symptoms (weight loss, recurrent vomiting, dysphagia, evidence of GI bleeding, or anemia) or
o unclassified (14%). with a family history of gastric cancer should undergo prompt upper endoscopy and biopsy if a mucosal
- The Ming classification also is useful and easy to lesion is noted.
remember, with only two types—expanding (67%) and - Essentially, all patients in whom gastric cancer is part of the differential diagnosis should have endoscopy
infiltrative (33%). and biopsy.
- Recently, the significance of human epidermal growth - If suspicion for cancer is high and the biopsy is negative, the patient should be reendoscoped and more
factor receptor-2 (HER2) was reported in patients with aggressively biopsied.
gastric cancer. - In some patients with gastric tumors, upper GI series can be helpful in planning treatment.
o In breast cancer, overexpression of HER2 has - Although a good double-contrast barium upper GI examination is sensitive for gastric tumors (up to 75%
been reported in 15% to 25% of cases, and it is sensitive), in most centers, endoscopy has become the gold standard for the diagnosis of gastric
well recognized as an unfavorable prognostic malignancy.
factor. o In addition, recent advances in endoscopy have contributed to the earlier diagnosis of gastric
o The development of molecular targeted agents cancer.
such as trastuzumab has improved the survival - Magnifying endoscopy with narrow-band imaging (NBI) has undergone technological improvements and
of HER2-positive patients. can observe the microvascular architecture of the mucosa and microsurface pattern of the lesion.
o Likewise, in gastric cancer, HER2 o has been reported to be accurate and reliable in the diagnosis of early gastric cancer.
overexpression has been reported in 13% to - Preoperative staging of gastric cancer is best accomplished with abdominal/pelvic CT scanning with
30% of patients. IV and oral contrast.
o HER2 targeting with trastuzumab resulted in o MRI is probably comparable.
improved survival in patients with stage IV - The best way to stage the tumor locally is via EUS,
gastric cancer, and immunohistochemistry (IHC) o which gives fairly accurate (80%) information about the depth of tumor penetration into the gastric
staining for HER2 should be performed in wall,
recurrent or metastatic cases. o and can usually show enlarged (>5 mm) perigastric and celiac lymph nodes.
- Expression of other growth receptors in gastric cancer o However, there are limitations to tumor staging with EUS.
have been characterized as well, including HER1 § It is highly operator dependent and may underestimate lymph node involvement because
(epidermal growth factor rector) and HER3. The latter is normal-sized nodes (<5 mm) can harbor metastases.
associated with poor prognosis, but efforts to target these o EUS is most accurate in distinguishing early gastric cancer (T1) from more advanced tumors.
receptors for therapeutic benefit are still exploratory.
1. Positron emission tomography scanning
Pathologic staging - Whole-body PET scanning derives its power from the preferential accumulation of positron-emitting 18F-
- Ultimately, prognosis is related to pathologic stage. fluorodeoxy glucose in tumor compared to nontumor cells.
- The most widespread system for staging of gastric cancer - It is most useful in the evaluation of distant metastasis in gastric cancer, but it can also be useful in
is the tumor-node-metastasis (TNM) staging system locoregional staging.
- PET scan is accurate when combined with spiral CT (PET-CT) and should be considered before major
surgery in patients with particularly high-risk or locally advanced tumors.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 24

2. Staging laparoscopy and peritoneal cytology
- Laparoscopy has emerged as a valuable adjunct to gastric cancer staging, particularly in patients with
more substantial tumors.
o This modality allows for rapid identification of macrosopic peritoneal metastases.
- Peritoneal lavage identifies an additional subset of patients with microscopic dissemination.
o The prognostic significance of the latter has been established by several investigators.
o Gastrectomy should be deferred in patients with positive peritoneal cytology without obvious
peritoneal metastases.
o Patients with gastric cancer who undergo R0 resection (i.e., no gross residual disease) and are
found to have positive peritoneal cytology (no gross carcinomatosis) have a much poorer
prognosis than those with negative cytology (median survival 14.8 months vs. 98.5 months).
- Stand-alone laparoscopy may influence management in up to 36% of cases and is increasingly advocated
to allow appropriate initial treatment selection.
o The yield is likely highest in patients with:
§ T3 or T4 tumors, proximal tumors
§ evidence of regional nodal involvement
o such patients may benefit from neoadjuvant therapy, and laparoscopy should be offered prior to
initiation of treatment.
- Systemic therapy is the cornerstone of therapy for patients with Stage IV disease
o and surgery is generally reserved for palliation of symptoms (e.g., an obstructing distal tumor) in
patients with metastases identified during laparoscopy.
TREATMENT
- Surgical resection is the only potentially curative treatment for gastric cancer and most patients with
clinically resectable locoregional disease should undergo gastrectomy.
- The goals of curative surgical treatment are resection of all tumor (i.e., R0 resection and adequate
lymphadenectomy to afford accurate staging and provide locoregional control.
- Generally, the surgeon strives for a grossly negative margin of at least 5 cm, although an evidence base
for this is lacking and recent retrospective analyses have suggested that more conservative resections may
be adequate.
- Conversely, complete resection of diffuse tumors sometimes proves challenging, and wider gross margins
guided by frozen section are sometimes appropriate.
- Prior to extending the resection on the basis of a positive frozen section margin, the surgeon should
determine whether the microscopic tumor cells are within the wall or on the serosal.
o The latter may indicate incurable disseminated disease, rendering additional resection proximally
or distally moot, particularly when it makes the anastomosis or stump closure more difficult or
hazardous.
- More than 15 resected lymph nodes are required for adequate staging, a relevant marker of quality of
care.
- Therapeutic nihilism should be avoided, and in the low-risk patient, an aggressive attempt to resect all
tumor should be made.
- The primary tumor may be resected en bloc with adjacent involved organs (e.g., distal pancreas, transverse
colon, or spleen) during the course of curative gastrectomy.
- Palliative gastrectomy may be indicated in the rare patient with incurable disease, but most patients
presenting with stage IV gastric cancer can be managed without major operation.
1. Extent of gastrectomy
- The standard operation for gastric cancer is radical subtotal gastrectomy.
- Unless required for R0 resection, total gastrectomy confers no additional survival benefit and may have
adverse nutritional or quality-of-life consequences and higher perioperative morbidity and mortality.
- Subtotal gastric resection typically entails:
o ligation of the left and right gastric and gastroepiploic arteries at their origins
o the en bloc removal of the distal 2/3 of the stomach, including the pylorus and 2 cm of duodenum,
the greater and lesser omentum, and all associated lymphatic tissue
- In the absence of involvement by direct extension, the spleen and pancreatic tail are not removed.
- Reconstruction is usually by Billroth II gastrojejunostomy or Roux-en-Y gastrojejunostomy.
o The former is associated with shorter operative time and precludes roux limb stasis.
o The latter mitigates bile reflux and, therefore, may be associated with better quality of life long
term.
o In East Asia, especially Japan, Billroth-I gastroduodenostomy is frequently performed after distal
gastrectomy.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
§ Billroth-I gastroduodenostomy consists of one anastomosis (which is usually
straightforward and keeps the duodenum in the food stream).
o In the United States, traditional surgical teaching eschews gastroduodenostomy following gastric
cancer resection because of the possibility of anastomotic recurrence and obstruction.
o A risk of remnant carcinoma attributed to bile reflux has been invoked in support of Roux-en-Y
reconstruction over Billroth II or I. Strong evidence linking reconstruction approach to long-term
oncologic outcome is lacking.
- Total gastrectomy with Roux-en-Y esophagojejunostomy may be required for R0 resection and is
frequently the optimal operation for patients with proximal gastric adenocarcinoma.
- The construction of a jejunal pouch is associated with superior nutritional recovery in some but not all
reports, and is a consideration.
- Proximal subtotal gastric resection, a technically feasible alternative to total gastrectomy for some
proximal gastric tumors, requires esophagogastrostomy to a denervated distal gastric remnant, and
functional outcomes are generally poor.
o Pyloroplasty in this setting virtually guarantees bile esophagitis, and if the pylorus is left intact,
gastric emptying may be problematic.
o An isoperistaltic jejunal interosition (Henley loop) between the esophagus and antrum may
mitigate some of the adverse symptoms associated with this operation but adds additional
complexity.
2. Extent of lymphadenopathy
- The 3rd edition of Japanese classification of gastric carcinoma defines lymph node stations on the basis of
anatomic landmarks.
o Lymph node stations 1 to 12 and 14V are classified as regional and metastasis to any other lymph
nodal stations constitute distant disease.
o So-called D1 lymphadenectomy in distal gastrectomy requires the dissection of stations 1, 3,
4sb, 4d, 5, 6, and 7.
o Additional resection of stations 8a, 9, 11p, and 12a constitute D2 lymphadenectomy.
o D1 lymphadenectomy in total gastrectomy requires dissection of stations 1 through 7
o D2 lymphadenectomy includes stations 8a to 12a as well.
- The operation most commonly performed in the United States for gastric cancer is a D1 resection and
involves removal of the primary tumor with perigastric nodes.
- The standard operation for gastric cancer in Asia and specialized U.S. centers is D2 gastrectomy, which
involves a more extensive lymphadenectomy (removal of the D1 and D2 nodes).
o In addition to the tissue removed in a D1 resection, D2 gastrectomy includes the superior
peritoneum overlying the mesocolon and, selectively, the pancreas, as well as nodes along the
common hepatic and splenic arteries, and the celiac axis.
- Splenectomy and distal pancreatectomy are not routinely performed because this has been shown to
increase the morbidity and mortality of the operation.
- The purported survival advantage of D2 gastrectomy in gastric cancer is shows the 5-year survival rates for
gastric cancer stratified by pathologic stage for the United States and Japan.
- Randomized prospective trials have not confirmed this survival advantage.
- Two studies showed increased operative mortality with D2 gastrectomy, but the most recent study did not.
- With extended lymphadenectomy, much of the morbidity and mortality is attributable to performance of
splenectomy and distal pancreatectomy, which are no longer routinely included as part of the D2
gastrectomy
- Because D2 lymphadenectomy in total gastrectomy requires the dissection of station 10 (i.e., splenic hilar
lymph nodes) splenectomy is still selectively performed, particularly for locally advanced fundic tumors.
- Longer-term follow-up from the Dutch lymphdenectomy trial demonstrating a disease-specific survival
advantage with D2 dissection as well as recognition that pancreas and spleen preserving dissection can
be performed with low morbidity have provided momentum for increased utilization of D2 gastrectomy at
high-volume centers in the United States and Europe.
- Some experts have argued that the D2 operation affords better staging and informs more rational decision-
making regarding multimodality therapy.
- Without question, D2 provides a better yield of evaluable nodes.
- Given the frequent inadequacy of lymph node evaluation with gastrectomy in the United States and the
association with poorer outcomes, greater attention to the conduct of the operation and pathologic specimen
evaluation is clearly desirable.
- Whether better outcomes after more extensive dissection are an epiphenomenon of improved pathologic
staging, or a function of therapeutic benefit, remains unclear.
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 3. Chemotherapy and radiation for gastric cancer
- The actuarial 5-year survival rates for resected gastric adenocarcinoma stages I, II, and III in the United
States are approximately 75%, 50%, and 25%, respectively.
- Because most surgical patients have stage II disease or greater, adjuvant therapy is indicated in the
majority of patients who undergo initial resection.
o Adjuvant chemotherapy alone has not proven effective, at least in studies from Europe and the
United States.
o Several studies from Japan and Korea have indicated a survival advantage with adjuvant
chemotherapy after D2 gastrectomy.
o The discordance between outcomes in Asia and those from the United States and Europe have
been attributed to differences in disease biology or treatment approaches.
o Proponents of the latter suggest that D2 lymphadenectomy provides sufficient locoregional control
and that chemotherapy alone has efficacy after optimal surgery.
- A preferred adjuvant approach in the United states incorporates chemotherapy and radiation based on the
result of the intergroUp trial.
o This prospective randomized study of adjuvant treatment with chemotherapy (5-fluorouracil and
leucovorin) and radiation (4500 cGy) demonstrated a survival benefit in resected patients with
stage II and III adenocarcinoma of the stomach.
o Only 10% of patients entered in the study actually had D2 gastrectomy, and most (54%) had less
than an adequate D1 gastrectomy.
o Because adequacy of lymphadenectomy has been correlated with survival, particularly in patients
with stage III gastric cancer, it has been suggested that the benefits of adjuvant chemoradiation
shown in this study would be vitiated by a more extensive operation.
- Neoadjuvant chemotherapy has emerged as a viable alternative to adjuvant chemoradiotherapy in
Europe and the United States.
o Theoretical advantages of this approach include more consistent completion of multimodality
therapy, downstaging, earlier treatment of micrometastatic disease, and the ability to gauge
response at the in situ tumor.
o The MAGIC trial, a randomized controlled trial comparing perioperative epirubicin, cisplatin, and
5-flourouracil to surgery alone demonstrated a survival advantage and supported this approach in
patients with at least stage II disease.
o A subset of patients with very symptomatic tumors may not be eligible for this approach, and the
perception that systemic therapy is an ineffective detour for patients who require locoregional
control with surgery is sometimes hard to overcome.
o Regardless, neoadjuvant approaches are increasingly utilized, and even more rigorous regimens
incorporating radiotherapy or targeted agents have been explored, sometimes with promising
outcomes.
- Recent clinical trials from Asia suggest the potential benefit of adjuvant chemotherapy after D2
lymphadenectomy in patients with advanced gastric cancer.
o These trials compared surgery alone and surgery plus adjuvant chemotherapy including oral
fluoropyrimidines in resected advanced gastric cancer.
o A study from the Japan Clinical Oncology Group showed a 69% overall 5-year survival rate in
patients with clinically curable T2b, T3, and T4 gastric cancer, treated with D2 gastrectomy alone.
o A subsequent trial from Korea demonstrated a survival advantage with adjuvant capecitabine and
oxaliplatin after D2 gastrectomy compared to D2 gastrectomy alone.
o It is uncertain whether this approach can be translated to patients in the United States.
- Although the prognosis of metastatic or recurrent gastric cancer is poor, systemic chemotherapy provides
a significant survival benefit over the best supportive care.
- Agents that have shown activity against gastric cancer include 5-fluorouracil (5-FU), cisplatin, doxorubicin,
methotrexate, taxanes, and camptothecin.
- Until recently, 5-FU–based chemotherapy, especially in combination with platinums, played a key role in
the treatment for the unresectable gastric cancer as well as several types of cancer, such as colon and
lung.
- In the 1990s, the introduction of novel anticancer agents such as camptothecin, taxanes, third-
generation platinums, and new oral fluoropyrimidines, improved the prognosis of unresectable gastric
cancer.
- It is likely that targeted molecular agents will have an increasing role in treating gastric cancer.
o Recently, Trastuzumab, a humanized molecular antibody reactive against the extracellular
domain of HER2, increased the effectiveness of cytotoxic chemotherapy in patients with HER2
over-expressing advanced gastric cancer.
o Other large trials are ongoing. Determination of HER2 gene amplification status may have
prognostic significance.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
4. Endoscopic resection
- The short- and long-term morbidity associated with gastrectomy and the relatively infrequent dissemination
of superficial (i.e., T1) tumors to regional nodes have compelled exploration of endoscopic resection for
selected lesions.
- Numerous East Asian centers have demonstrated that some patients with early gastric cancer are
adequately treated with endoscopic mucosal resection (EMR).
- EMR is most appropriate for patients in whom the probability of lymph node metastasis is low.
- According to the Japanese treatment guidelines for gastric cancer, EMR is a standard treatment for well
differentiated gastric cancer confined to the mucosa (T1a), measuring less than 2 cm and without
signs of ulceration.
o Such lesions are associated with a negligible risk of lymph node metastasis.
- En bloc resection is required to evaluate margins for confirmation of complete resection.
- The development of endoscopic submucosal dissection (ESD) allows en bloc resection of larger tumors.
o This has increased the feasibility of endoscopic resection of larger lesions (<3 cm) at experienced
centers.
- If pathologic evaluation of the resected specimen does not demonstrate ulceration, penetration of the
muscularis mucosae, or lymphatic invasion, the risk of lymph node metastases is less than 1%.
- Even the occasional patient with higher risk stigmata may be managed endoscopically, particularly in the
presence of comorbidities that preclude safe operation.
SCREENING FOR GASTRIC CANCER
- In Japan, it clearly has been shown that patients participating in gastric cancer screening programs have a
significantly decreased risk of dying from gastric cancer.
o Thus, screening is effective in a high-risk population.
- Screening the general population in the United States (a low-risk country) is probably not justified, but
patients clearly at risk for gastric cancer probably should have periodic endoscopy and biopsy. This
includes:
o patients with familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, gastric
adenomas, Ménétrier’s disease, intestinal metaplasia or dysplasia, and remote gastrectomy or
gastrojejunostomy.
GASTRIC LYMPHOMA
- generally account for about 4% of gastric malignancies.
- Over half of patients with non-Hodgkin’s lymphoma have involvement of the GI tract.
- The stomach is the most common site of primary GI lymphoma, and over 95% are non-Hodgkin’s type.
- Most are B-cell type, thought to arise in mucosa associated lymphoid tissue (MALT), although most
high-grade gastric lymphomas are without any characteristics of the low-grade MALT neoplasm.
- About half of gastric lymphomas are histologically low grade, and about half are high grade.
- Interestingly, the normal stomach is relatively devoid of lymphoid tissue. However, in the setting of chronic
gastritis, the stomach acquires MALT, which can undergo malignant degeneration. Again, H pylori is
thought to be the culprit.
- In populations with a high incidence of gastric lymphoma, there is a high incidence of H pylori infection;
patients with gastric lymphoma also usually have H pylori infection.
- Low-grade MALT lymphoma, essentially a monoclonal proliferation of B cells, presumably arises from a
background of chronic gastritis associated with H pylori.
o These relatively innocuous tumors then undergo degeneration to high-grade lymphoma, which is
the usual variety seen by the surgeon.
o Remarkably, when the H pylori is eradicated and the gastritis improves, the low-grade MALT
lymphoma often disappears.
o Thus, low-grade MALT lymphoma is not a surgical lesion.
- Careful follow-up is necessary particularly in those lesions with a t(11:18) translocation, thought to be a
risk factor for a more aggressive MALT lesion.
- If low-grade lymphoma persists after H pylori eradication, radiation should be considered for disease
clinically confined to the stomach (stage I), while chemotherapy with or without radiation is used for
more advanced lesions.
- Patients with high-grade gastric lymphoma require aggressive oncologic treatment for cure and present
with many of the same symptoms as gastric cancer patients.
o However, systemic symptoms such as fever, weight loss, and night sweats occur in about 50% of
patients with gastric lymphoma.
o The tumors may bleed and/or obstruct.
o Lymphadenopathy and/or organomegaly suggest systemic disease.
o Diagnosis is by endoscopy and biopsy.
- Much of the tumor may be submucosal, and an assiduous attempt at biopsy is necessary.
26
- Primary lymphoma is usually nodular with enlarged gastric folds.
- A diffusely infiltrative process akin to linitis plastica is more suggestive of secondary gastric
involvement by lymphoma.
- A diligent search for extragastric disease is necessary before the diagnosis of localized primary gastric
lymphoma is made.
o This includes:
§ EUS
§ CT scanning of the chest, abdomen, and pelvis
§ bone marrow biopsy.
- Most patients with high-grade gastric lymphoma are currently treated with chemotherapy and radiation,
without surgical resection.
o Treatment-related perforation or bleeding is an unusual but recognized complication.
- For disease limited to the stomach and regional nodes, radical subtotal D2 gastrectomy may be
performed, especially for bulky tumors with bleeding and/or obstruction.
- Palliative gastrectomy for tumor complications also has a role. Certainly, a multidisciplinary team should
be involved in managing patients with primary gastric lymphoma.
GASTROINTESTINAL STROMAL TUMOR
- GISTs arise from interstitial cells of Cajal (ICC) and are distinct from leiomyoma and leiomyosarcoma,
which arise from smooth muscle.
- Prognosis in patients with GIST tumors depends on tumor size, location, and mitotic count.
- Metastasis, when it occurs, is typically by the hematogenous route.
- Virtually all GISTs should be resected along with a margin of normal tissue.
- Most GISTs (and almost no smooth muscle tumors) express c-KIT (CD117) or the related PDGF receptor
A, as well as CD34;
o almost all smooth muscle tumors (and almost no GISTs) express actin and desmin.
o These markers can often be detected on specimens obtained by fine-needle aspiration and are
useful in differentiating between GIST and smooth muscle tumor histopathologically.
- Lesions that are definitively leiomyoma by histopathologic criteria can be observed if small and
asymptomatic.
o Larger or symptomatic gastric leiomyomas are adequately treated by enucleation or wedge
resection.
- Lesions that are definitively GIST or leiomyosarcoma are best treated by resection with negative margins.
- Most equivocal lesions should be resected provided that the patient has a reasonable operative risk.
- Two-thirds of all GISTs occur in the stomach and have a more favorable prognosis than do GISTs
occurring in other locations.
- Epithelial cell stromal GIST is the most common cell type arising in the stomach,
o and cellular spindle type is the next most common.
- The glomus tumor type is seen only in the stomach.
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
- Smaller lesions are usually found incidentally, although they occasionally may ulcerate and cause bleeding.
- Larger lesions may produce symptoms of weight loss, abdominal pain, fullness, early satiety, and bleeding.
o An abdominal mass may be palpable.
- Metastasis is by the hematogenous route, most often to liver.
- Diagnosis is by endoscopy and biopsy, although the interpretation of the latter may be problematic.
o When performed, a transluminal (i.e., endoscopic) approach to biopsy is preferred to a
percutaneous one, to avoid to the potential for fragmentation and peritoneal seeding. A
nondiagnostic biopsy does not preclude resection of a suspicious appearing lesion.
- Metastatic workup entails CT of the abdomen, and pelvis (chest X-ray suffices in lieu of CT of the chest
for most patients).
- Most GISTs are solitary.
- Local resection with clear margins is adequate surgical treatment but is sometimes impractical for larger
prepyloric or pyloric channel tumors, or those near the GE junction.
- True invasion of adjacent structures by the primary tumor is occasionally seen with larger more aggressive
lesions. If safe, en bloc resection of involved surrounding organs is appropriate to remove all tumor.
- The risk of tumor recurrence or metastasis behavior has been stratified into four groups according to the
tumor size and mitotic count.
o Very low risk - defined by size <2 cm and<5 mitoses/50 HPF (high-power field).
o Low risk - defined by size 2 to 5 cm and <5 mitoses/50 cm.
o Intermediate risk - defined by size <5 cm and 6 to 10 mitoses/50 HPF or size 5 to 10 cm and >5
mitoses/50 HPF.
o High risk - defined by size >5 cm and >5 mitoses/50HPF, size >10 cm regardless of mitotic rate
or >10 mitoses/50 HPF regardless of size.
- As mentioned, stomach lesions are associated with lower risk than are tumors in other locations.
- Classification based on tumor location, size, and mitotic rate have been proposed to evaluate the risk of
recurrence and metastasis and role for adjuvant therapy.
- Mutations in the oncodriver c-kit and PDGFRA are present in a majority of GISTs.
o This has been exploited through the use of imatinib (Gleevec), a tyrosine kinase inhibitor.
o Several clinical trials in a metastatic disease setting demonstrated marked improvements in
median survival from 9 months to greater than 5 years.
o These striking results not only established imatinib as the primary therapy for metastatic GIST,
but they also compelled broader efforts to target solid tumors with small molecule inhibitors.
o Notably, up to 50% of treated patients develop resistance to imatinib by 2 years, and several
second-line agents have been utilized for patients with refractory disease, most notable sunitinib.
- efficacy of imatinib as adjuvant therapy for high risk GIST has been demonstrated in two randomized
clinical 8 trials, ACOSOG Z9001 and SSG XVIII.
o The former trial randomized patients to 1 year of adjuvant imatinib or placebo and showed an
improvement in recurrence-free survival with imatinib.
o The latter trial demonstrated an overall survival advantage with 3 years compared to 1 year of
therapy.
o Imatinib is now recommended in high risk groups as an adjuvant therapy, for three years or
longer.
o Preoperative therapy with imatinib may be indicated in selected patients with larger lesions that
may be more difficult to completely resect or require multivisceral resection.
o Molecular profiling has been embraced with growing recognition that specific tumor subtypes are
insensitive to imatinib.
§ Patients with PDGFRA D842V mutations, for example, do not respond to imatinib.
- Management of metastatic GIST is principally medical, but surgery has a selected role.
27
 GASTRIC NEUROENDOCRINE TUMORS BENIGN GASTRIC NEOPLASMS
- Compared to neuroendocrine tumors of the midgut and hind-gut, neuroendcorine tumors of the stomach Leiomyoma
are rare. - submucosal and firm
- Gastric neuroendocrine tumors comprise about 1% of all neuroendocrine tumors and less than 2% of gastric - If ulcerated
neoplasms. o umbilicated appearance and may bleed
- They arise from gastric enterochromaffin-like (ECL) cells and may have malignant potential. - Histologically
- The apparent incidence of gastric neuroendocrine tumors is increasing, perhaps related to increased o lesions appear to be of smooth muscle origin
detection or the increasing use of acid suppressive medication. - Lesions <2 cm
o The latter may cause hypergastrinemia, and gastrin has a recognized trophic effect on gastric o usually asymptomatic and benign
ECL cells. - Larger lesions
- Nomenclature remains a point of confusion; carcinoid and well-differentiated neuroendocrine tumor (NET) o may cause symptoms such as bleeding, obstruction, or pain
are synonymous according to WHO classification. - Asymptomatic lesions <2 cm
- Gastric neuroendocrine tumors are classified into one of three different types. o may be carefully observed or enucleated if fine-needle aspiration and immune markers
o Type I is the most common, accounting for about 75% of cases. confirm smooth muscle tumor; larger lesions and symptomatic lesions should be
§ Type I lesions occur in patients with chronic hypergastrinemia secondary to pernicious removed by wedge resection (often possible laparoscopically)
anemia or atrophic gastritis. - When lesions thought to be leiomyoma are observed rather than resected
§ These lesions occur more frequently in women, o the patient should be made aware of their presence and the small possibility for
§ are often multiple and small, and have low malignant potential (<5% metastasize). malignancy
§ The role of long-term acid suppression with resultant hypergastrinemia in the pathogenesis
of type I gastric carcinoids is unclear. Lipoma
o Type II gastric neuroendocrine tumors are associated with MEN1 and ZES. - benign submucosal fatty tumors that are usually asymptomatic, found incidentally on upper GI series
§ These lesions also tend to be small and multiple, or EGD
§ but they have a somewhat higher malignant potential than type I lesions (10% - Endoscopically,
metastasize). o have a characteristic appearance
§ are more common in the setting of MEN1; they are quite uncommon in patients with o there also is a characteristic appearance on EUS
sporadic ZES. - Excision is unnecessary unless the patient is symptomatic
§ The constellation of gastric acidity, hypergastrinemia, and gastric neuroendocrine tumors
suggests gastrinoma until proven otherwise. Gastroparesis
o Type III gastric neuroendocrine tumors are sporadic. - Gastric motility disorders
§ They are most often solitary (usually >2 cm) o delayed gastric emptying (gastroparesis)
§ occur more commonly in men. o rapid gastric emptying
§ They are not associated with hypergastrinemia. o motor and sensory abnormalities (e.g., functional
§ Most patients have regional nodal or distant metastases at the time of diagnosis, and dyspepsia)
some present with symptoms of carcinoid syndrome. - most surgically relevant primary disorder of gastric motility
- Gastric neuroendocrine tumors are usually diagnosed with endoscopy and biopsy. - Most patients present with nausea, vomiting, bloating, early
o Biopsy may be difficult because of the submucosal location, and EUS can be helpful in defining satiety, and/or abdominal pain
the size and depth of the lesion. - 80% of these paatients
- The type can be determined based upon clinical context, patient history, the presence or absence of o Women
atrophic gastric mucosa, gastric pH and gastrin level. o some are diabetic
- Some tumors are submucosal and may be quite small. - Postprandial vomiting
- They are often confused with heterotopic pancreas or small leiomyomas. o significantly complicates the management of blood
- Plasma chromogranin A levels are frequently elevated. glucose in the latter group, predisposing to
- CT scan and octreotide or gallium dotatate scans are useful for staging. hypoglycemia following preprandial insulin
- Type I and II patients with numerous diminutive lesions can be followed with serial endoscopy. - In patients with gastroparesis
o Small lesions confined to the mucosa (typically type I or type II lesions) less than 1 cm may be o important to rule out mechanical gastric outlet
treated endoscopically with EMR if there are only a few lesions (<5). obstruction, and small-bowel obstruction
o Occasionally a slightly larger lesion (1–2 cm) necessitate local surgical excision. - upper GI series
o Larger lesions and type III lesions should be removed by D1 or D2 gastrectomy. o may suggest slow gastric emptying and relative
- Antrectomy to mitigate gastric secretion in type I patients with refractory growing lesions was invoked as atony or it may be normal
a viable treatment strategy in the past, but it is rarely indicated. - EGD
- Survival is excellent for node-negative patients (>90% 5-year survival); node-positive patients have a o may show bezoars or retained food but is frequently
50% 5-year survival. normal
- Gastrinoma should be resected if located in patients with type II carcinoid. - Gastric emptying scintigraphy
- The 5-year survival for patients with type I gastric carcinoid is close to 100%; for patients with type III lesions, o shows delayed solid emptying, and often delayed
the 5-year survival is less than 50%. liquid emptying
- Somatostatin analogue therapy may delay progression of metastatic disease. - can be a manifestation of a variety of problems
- Surgical debulking may have a role in selected patients with limited metastatic disease. - Medical treatment
o includes promotility agents, antiemetics, and,
perhaps, botulinum injection into the pylorus
- If the the diabetic gastroparetic patient is not a candidate for pancreas transplant
o both gastrostomy (for decompression) and jejunostomy tubes (for feeding and
prevention of hypoglycemia) can be helpful in managing these patients
- Other surgical options
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 28
 o implantation of a gastric pacemaker - Mucosal lesions can usually be controlled with endoscopic hemotherapy and medical management
o pyloroplasty - Occasionally, arteriography can be helpful.
o peroral endoscopic pyloromyotmy (particularly in patients responsive to pyloric Botox
injection) Isolated Gastric Varices
o gastric resection - occur in the absence of esophageal varices and are classified as type I (fundic) or type II (distal to
§ should be done only after other therapeutic options have been exhausted fundus including proximal duodenum
- presence is usually associated with portal hypertension or splenic vein thrombosis
MASSIVE UPPER GASTROINTESTINAL BLEEDING - there is a significant bleeding risk from isolated gastric varices
- acute GI bleeding proximal to the ligament of Treitz, - on long-term follow-up, there is no indication for the routine application of prophylactic measures.
- requires blood transfusion - Patients with acute upper GI bleeding from isolated gastric varices
- stomach and proximal duodenum o should be considered high risk
o most common sources of pathology associated with this diagnosis - Although data are limited, octreotide and/or vasopressin infusion may decease bleeding, if
- most common causes of acute upper GI bleeding in emergency department or hospitalized patients tolerated
o peptic ulcer - Balloon tamponade with a Sengstaken- Blakemore tube
o gastritis o may provide temporary control of exsanguinating hemorrhage from type isolated gastric
o Mallory-Weiss syndrome varices
o esophagogastric varices o if this is used, endotracheal intubation for airway protection is prudent
- Less common causes - Endoscopic treatment with sclerotherapy or varix ligation
o benign or malignant neoplasm o less successful than in esophageal varices but should be considered
o angio- dysplasia - Interventional radiology
o Dieulafoy’s lesion o should be consulted and bal- loon-occluded retrograde transvenous obliteration
o portal gastropathy considered
o Ménétrier’s disease - transjugular intrahepatic portosystemic shunt (TIPSS)
o watermelon stomach o may be useful if there is nonsegmental portal hypertension
- Arterioenteric fistula - If patient has splenic vein thrombosis and left-sided (sinistral) or segmental portal
o always be considered in the patient who has an aortic graft or who has undergone repair hypertension
of a visceral artery aneurysm o splenectomy is quite effective in controlling bleeding from isolated gastric varices
- most important issues in the early hospital management of patients with acute upper GI bleeding o The operative mortality is 5%
o resuscitation and risk stratification - Liver transplantation
- Large-bore IV access and Foley catheterization is accomplished, and nasogastric intubation is o should always be considered in the cirrhotic patient.
considered
- Risk stratification is essentially accomplished by answering the following questions: Hypertrophic Gastropathy
o What is the magnitude and acuity of the hemorrhage? (Menetrier’s Disease)
§ Hypotension, tachycardia, oliguria, low hematocrit, pallor, altered mentation, - two clinical syndromes characterized by epithelial hyperplasia and giant gastric folds
and/or hematemesis suggest a large blood loss that has occurred over a o ZES
short period of time. This is a high-risk situation. o Ménétrier’s disease
o Does the patient have significant chronic disease, particularly lung, liver, kidney, and/or - is characteristically associated with protein-losing gastropathy and hypochlorhydria
heart disease, which com- promises physiologic reserve? - large rugal folds in the proximal stomach
§ If yes, this is a high-risk situation. - the antrum is usually spared
o Is the patient anticoagulated, or immunosuppressed? - Mucosal biopsy
§ If yes, this is a high-risk situation. o diffuse hyperplasia of the surface mucus-secreting cells and usually decreased parietal
o On endoscopy, is the patient bleeding from varices, or is there active bleeding, or is there cells
a visible vessel, or is there a deep ulcer overlying a large vessel (e.g., posterior duode- - caused by local overexpression of transforming growth factor-α in the gastric mucosa
nal ulcer overlying the gastroduodenal artery)? o which stimulates the epidermal growth factor receptor, a receptor tyrosine kinase, on
o Could the patient be bleeding from an arterio-enteric fistula? gastric SECs
§ If yes, this is a high-risk situation. - results in the selective expansion of surface mucous cells in the gastric body and fundus
- When judged to be low risk, most patients will stop bleedIng/ with supportive treatment and IV PPI. - few patients with this unusual disease have been successfully treated with the epidermal growth
- Selected patients may be discharged from the emergency department and managed on an factor receptor blocking monoclonal antibody cetuximab.
outpatient basis. - Most patients with Ménétrier’s disease are middle-aged men who present with epigastric pain,
- If the patient is deemed to be high risk based on one or more of the aforementioned questions, then weight loss, diarrhea, and hypoproteinemia
the following should be done immediately: - There may be an increased risk of gastric cancer
o Type and cross-match for transfusion of blood products. - Sometimes, the disease regresses spontaneously
o Admit to ICU or monitored bed in specialized unit. - Occasionally it is associated with H pylori infection, and the disease improves with helicobacter
o Consult surgeon eradication
o Consult gastroenterologist. - Total gastrectomy
o Start intravenous PPI. o may be indicated for bleeding, severe hypoproteinemia, or cancer
o Perform upper endoscopy within 12 hours, after resuscitation and correction of
coagulopathy Watermelon Stomach (Gastric Antral Vascular Ectasia)
o Endoscopic hemostasis - parallel red stripes atop the mucosal folds of the distal stomach give this rare entity its sobriquet.
§ should be considered in most high-risk patients with acute upper GI - Histologically
bleeding. o characterized by dilated mucosal blood vessels that often contain thrombi, in the
- Although the surgeon should be involved early in the hospital course of all high-risk patients with lamina propria
acute upper GI bleeding, most of these patients will be adequately managed without operation - Mucosal fibromuscular hyperplasia and hyalinization
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 29
 o often are present Foreign Bodies
- histologic appearance can resemble portal hypertensive gastropathy, but the latter usually affects - Ingested foreign bodies are usually asymptomatic
the proximal stomach, whereas watermelon stomach pre- dominantly affects the distal stomac - Small coins usually pass through the GI tract without difficulty
- β-Blockers and nitrates - Sharp or large objects in the stomach should be removed
o useful in the treatment of portal hypertensive gastropathy, are ineffective in patients with o This can usually be done endoscopically, with an overtube technique
gastric antral vascular ectasia - Recognized dangers
- Usually elderly women with chronic GI blood loss requiring transfusion o aspiration of the foreign body during removal and rupture of drug-containing bags in
- Most have an associated autoimmune connective tissue disorder, and at least 25% have chronic “body packers.”
liver disease o Both complications can be fatal
- Nonsurgical treatment options - Surgical removal
o Estrogen and progesterone o recommended in body packers who ingest drug parcels for smuggling and in patients
o endoscopic treatment with the neodymium yttrium-aluminum garnet (Nd:YAG) laser with large jagged objects that cannot be safely removed endoscopically
or argon plasma coagulator - Corrosive objects (i.e., batteries) should be removed promptly usually endoscopically
- Antrectomy - Ingested magnets should be removed unless they are small and singular and without other ingested
o may be required to control blood loss, and this operation is quite effective but carries metal objects
increased morbidity in this elderly patient group
- Patients with portal hypertension and antral vascular ectasia Mallory-Weiss Syndrome
o should be considered for transjugular intrahepatic portosystemic shunt (TIPSS) - longitudinal tear in the mucosa of the GE junction
- presumably caused by forceful vomiting and/or retching, and it is commonly seen in alcoholics
Dieulafoy’s Lesion - Ipresents with upper GI bleeding, often with hematemesis
- Congenital arteriovenous malformation characterized by an unusually large tortuous submucosal - Endoscopy confirms the diagnosis and may be useful in controlling the bleeding, but 90% of
artery patients stop bleeding spontaneously
- If this artery is eroded, impressive pulsatile bleeding may occur - Other options to control the bleeding
- To the endoscopist or surgeon, this appears as a stream of arterial blood emanating from what o balloon tamponade
appears grossly to be a normal gastric mucosa. o angiographic embolization
o lesion typically occurs in middle-aged or elderly men and may be more common in o selective infusion of vasopressin, systemic vasopressin, and operation
patients with liver disease - Surgical treatment consists of oversewing the bleeding lesion through a long gastrotomy.
- Patients typically present with upper GI bleeding, which may be intermittent, and endoscopy can
miss the lesion if it is not actively bleeding Volvulus
- Treatment options - twist of the stomach that usually occurs in association with a large hiatal hernia
o endoscopic hemostatic therapy, angiographic embolization, or operation - also can occur in patients with an unusually mobile stomach without hiatal hernia
- At surgery, the lesion may be oversewn or resected stomach twists along its long axis (organoaxial volvulus), and the greater curvature flips up
- If the stomach twists around the transverse axis, it is called mesenteroaxial rotation
Bezoars/Diverticula - Often, volvulus is a chronic condition that can be surprisingly asymptomatic
- Bezoars - In these instances, expectant nonoperative management is typically advised, especially in the elderly
o concretions of indigestible matter that accumulate in the stomach - The risk of strangulation and infarction has been overestimated in asymptomatic patients
- Trichobezoars - Symptomatic patients
o composed of swallowed hair o should be considered for operation, especially if the symptoms are severe and/or
- Phytobezoars are composed of vegetable matter and, in the United States, are usually seen in progressive
association with gastroparesis or gastric outlet obstruction - Patients may present with symptoms of pain and pressure related to the intermittently distending
- They also are associated with persimmon ingestion and poorly emptying twisted stomach
- Most commonly, bezoars produce obstructive symptoms, but they may cause ulceration and o Pressure on the lung may produce dyspnea
bleeding o pressure on the pericardium may produce palpitations
- Diagnosis is suggested by upper GI series and confirmed by endoscopy o pressure on the esophagus may produce dysphagia
- Treatment options - Symptoms are often relieved with vomiting or passage of a nasogastric tube
o enzyme therapy (papain, cellulase, or acetylcysteine) - Gastric infarction
o endoscopic disruption and removal o surgical emergency, and the patient can be moribund
o surgical removal. - Gastric necrosis may be extensive or focal
- Gastric diverticula - Elective operation for gastric volvulus usually involves reduction of the stomach and gastropexy
o usually solitary and may be congenital or acquired with or without repair of hiatal hernia
- Congenital diverticula - Gastropexy alone
o true diverticula and contain a full coat of muscularis propria o should be considered for high-risk patients since it can nearly always be performed
- acquired diverticula laparoscopically and may be surprisingly effective in relieving mechanical symptoms
o (perhaps caused by pulsion)
o usually have a negligible outer muscle layer GASTROSTOMY
o Most gastric diverticula occur in the posterior cardia or fundus and are usually - performed either for alimentation or for gastric drainage/decompression
asymptomatic. - may be done percutaneously, laparoscopically, or via open technique
o they can become inflamed and may produce pain or bleeding - percutaneous endoscopic gastrostomy
o Perforation is rare o most common method used
- Asymptomatic diverticula - open techniques
o do not require treatment, but symptomatic lesions should be removed o Stamm method
o can often be done laparoscopically § Most common surgical technique
§ Can be performed open or laparoscopically
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 - Some evidence that adding dietary fiber compounds at mealtime may improve the syndrome
- If dietary manipulation fails
o patient is started on octreotide, 100 μg subcutaneously twice daily
o can be increased up to 500 μg twice daily if necessary
o The long-acting depot octreotide preparation is useful
- Octreotide
o not only ameliorates the abnormal hormonal pattern seen in patients with dumping
symptoms, but it also promotes restoration of a fasting motility pattern in the small
intestine (i.e., restoration of the MMC)
- α-glucosidase inhibitor acarbose
o may be particularly helpful in ameliorating the symptoms of late dumping.
- Only a very small percentage of patients with dumping symptoms ultimately require surgery
- Most patients improve with time (months and even years), dietary management, and medication
o the surgeon should not rush to reoperate on the patient with dumping symptoms
- Multidisciplinary nonsurgical management must be optimized first
- Before reoperation
o a period of inhospital observation is useful to define the severity of the patient’s
symptoms and patient compliance with prescribed dietary and medical therapy.
o Witzel method
- results of remedial operation for dumping are variable and unpredictable
o Janeway method
- variety of surgical approaches
§ designed to create a permanent nondraining gastric stoma that can be
o none of which work consistently well
intermittently intubated, is more complicated than the other open techniques,
- there is not a great deal of experience reported in the literature with any of these methods and long-
and is rarely necessary
term follow-up is rare
- Complications of gastrostomy
- Patients with disabling refractory dumping after gastrojejunostomy
o Dislodgment
o can be considered for simple takedown of this anastomosis provided that the pyloric
o leakage with peritonitis
channel is patent
o aspiration pneumonia
- reversed intestinal segment is rarely used today—and rightly so
- Although gastrostomy tubes usually do prevent tense gastric dilatation
- operation interposes a 10-cm reversed segment of intestine between the stomach and the proximal
o they may not adequately drain the stomach, especially when the patient is bedridden,
small bowel
and they cannot always be relied upon to prevent pulmonary aspiration of gastric
o slows gastric emptying, but often leads to obstruction, requiring reoperation.
contents
Isoperistaltic interposition (Henley loop) has not been successful in ameliorating severe
dumping over the long term
POSTGASTRECTOMY PROBLEMS
Dumping Syndrome
Roux-en-Y gastrojejunostomy
- phenomenon caused by the destruction or bypass of the pyloric sphincter
- Associated with delayed gastric emptying, probably on the basis of disordered motility in the Roux
- other factors undoubtedly play a role because dumping can occur after operations that preserve the
limb
pylorus, such as parietal cell vagotomy
- Taking advantage of this disordered physiology, surgeons have used this operation successfully in
- appropriate stimulus may provoke dumping symptoms, even in some patients who have not
the management of the dumping syndrome
undergone surgery
- Although this is probably the procedure of choice in the small group of patients requiring operation
- Clinically significant dumping
for severe dumping following gastric resection, gastric stasis may result, particularly if a large gastric
o occurs in 5% to 10% of patients after pyloroplasty, pyloromyotomy, or gastrectomy, and
remnant is left
consists of a constellation of postprandial symptoms ranging in severity from annoying
- In the presence of significant gastric acid secretion, marginal ulceration is common after both
to disabling
jejunal interposition and Roux-en-Y procedures
- symptoms are thought to be the result of the abrupt delivery of a hyperosmolar load into the small
o concomitant vagotomy and hemigastrectomy should be considered
bowel due to ablation of the pylorus or decreased gastric compliance-
- theoretical possibility of treating postpyloroplasty dumping with a Roux-en-Y to the proximal
- 15 to 30 minutes after a meal
duodenum (the duodenal switch, a potentially reversible operation) has not yet been reported
o patient becomes dia- phoretic, weak, light-headed, and tachycardic
- Because pyloric ablation seems to be the dominant factor in the etiology of dumping
- These symptoms may be ameliorated by recumbence or saline infusion
o it is not surprising that conversion of Billroth II to Billroth I anastomosis has not been
- Crampy abdominal pain
successful in the treatment of dumping.
o not uncommon, and diarrhea often follows.
o early dumping
Diarrhea
o should be distinguished from postprandial (reactive) hypoglycemia, also called late
- may be the result of truncal vagotomy, dumping, or malabsorption
dumping, which usually occurs later (2–3 hours following a meal) and is relieved by
- Truncal vagotomy
the administration of sugar
o associated with clinically significant diarrhea in 5% to 10% of patients
- variety of hormonal aberrations have been observed in early dumping, including increased serum
o occurs soon after surgery
levels of VIP, CCK, neurotensin, peripheral hormone peptide YY, renin-angiotensin-aldosterone, and
o not associated with other symptoms, a fact that helps to distinguish it from dumping.
decreased atrial natriuretic peptid
- may be a daily occurrence, or there may be significant periods of relatively normal bowel function.
- Late dumping
The symptoms tend to improve over the months and years after the index operation
o associated with hypoglycemia and hyperinsulinemia.
- cause of postvagotomy diarrhea is unclear
- Medical therapy for the dumping syndrome
- Possible mechanisms
o dietary modification and somatostatin analogue (octreotide)
o intestinal dysmotility
- symptoms improve if the patient avoids liquids during meals
o accelerated transit
- Hyperosmolar liquids (e.g., milk shakes) may be particularly troublesome
o bile acid malabsorption
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 31
 o rapid gastric emptying
o bacterial overgrowth
§ is facilitated by decreased gastric acid secretion and (even small) blind loops.
§ can be confirmed with the hydrogen breath test, a simpler test is an empirical
trial of oral antibiotics
- Some patients with postvagotomy diarrhea respond to cholestyramine
o in others codeine or loperamide may be useful
- Octreotide should also be tried
- Another theoretical cause of diarrhea following gastric surgery is fat malabsorption due to acid
inactivation of pancreatic enzymes or poorly coordinated mixing of food and digestive juices
- can be confirmed with a qualitative test for fecal fat and treated with acid suppression
- Postvagotomy diarrhea
o usually does not respond to treatment with pancreatic enzymes
- In the rare patient who is debilitated by postvagotomy diarrhea unresponsive to medical
management
o operation might be considered, but outcomes can be problematic
o operation of choice
§ 10-cm reversed jejunal interposition placed in continuity 100 cm distal to
the ligament of Treitz
§ Another option is the onlay antiperistaltic distal ileal graft
§ Both operations can cause obstructivesymptoms and/or bacterial overgrowth
Gastric Stasis
- Following surgery on the stomach may be due to a problem with gastric motor function or caused
by an obstruction
- gastric motility abnormality could have been preexisting and unrecognized by the operating surgeon
- it may be secondary to deliberate or unintentional vagotomy, or resection of the dominant gastric
pacemaker
- An obstruction may be
o Mechanical
§ anastomotic stricture, efferent limb kink from adhesions or constricting
mesocolon, or a proximal small-bowel obstruction
o Functional
§ retrograde peristal- sis in a Roux limb
- presents with vomiting (often of undigested food), bloating, epigastric pain, and weight loss.
- evaluation of a patient with suspected postoperative gastric stasis includes EGD, upper GI and small
bowel series, gastric emptying scan, and gastric motor testing. Endoscopy shows gastritis and
retained food or bezoar
- anastomosis and efferent limb
o should be evaluated for stricture or narrowing
- dilated efferent limb
o suggests chronic stasis, either from a motor abnormality (e.g., Roux syndrome) or
mechanical small bowel obstruction (e.g., chronic adhesion)
- If the problem is thought to be primarily a disorder of intrinsic motor function
o newer techniques such as EGG and GI manometry should be considered, but chronic
distal mechanical obstruction may result in disordered motility in the proximal organ
confounding interpretation.
- Once mechanical obstruction has been ruled out, medical treatment is successful in most cases of
motor dysfunction following previous gastric surgery
o consists of dietary modification and promotility agents
- Intermittent oral antibiotic therapy
o may be helpful in treating bacterial overgrowth, with its attendant symptoms of bloating,
flatulence, and diarrhea
- Gastroparesis following V + D
o may be treated with subtotal gastrectomy but simple loop gastrojejunoctomy (GJ)
o should be tried if previous drainage was pyloroplasty
- Billroth II anastomosis with Braun enteroenterostomy
o may be preferable to Roux-en-Y reconstruction after subtotal gastrectomy for gastric
stasis, but bile reflux can still occur
- Initial operation for gastric stasis
o Often associated with persistent gastric empty- ing problems that may subsequently
require near-total or total gastrectomy, a nutritionally unattractive option
- Delayed gastric emptying following ulcer surgery (V + D or V + A)
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
o may represent an anastomotic stricture (often due to recurrent ulcer) or proximal small
bowel obstruction
- Recurrent ulcer
o may respond to medical therapy with PPI and abstinence from NSAIDs, aspirin, and
smoking
o if necessary, endoscopic dilation is occasionally helpful
o when associated with symptomatic gastric stasis
§ reoperation is often necessary
- Gastroparesis following subtotal gastric resection
o best treated with near-total (95%) or total gastric resection and Roux-en-Y
reconstruction
- If total gastrectomy is performed, a jejunal reservoir should be considered
- Gastric pacing
o promising, but it has not achieved widespread clinical usefulness in the treatment of
postoperative gastric atony
Bile Reflux Gastritis and Esophagitis
- Most patients who have undergone ablation or resection of the pylorus
o have bile in the stomach on endoscopic examination, along with some degree of gross
or microscopic gastric inflammation
- attributing postoperative symptoms to bile reflux is problematic because most asymptomatic patients
have bile reflux too
- it is generally accepted that a small subset of patients have bile reflux gastritis syndrome
o These patients present with nausea, bilious vomiting, and epigastric pain, and
quantitative evidence of excess enterogastric reflux.
o symptoms often develop months or years after the index operation
o differential diagnosis
§ includes afferent or efferent loop obstruction, gastric stasis, and small-bowel
obstruction
o Plain abdominal X-rays, upper endoscopy, upper GI series, abdominal CT scan, and
gastric emptying scans are helpful in evaluating these possibilities.
- Bile reflux
o may be quantified with gastric analysis or esophageal impedance testing or with
scintigraphy (bile reflux scan)
- enterogastric reflux is greatest after Billroth II gastrectomy or gastrojejunostomy, and least after
vagotomy and pyloroplasty, with Billroth I gastrectomy giving intermediate values
- Patients who are well into the abnormal range of bile reflux
o may be considered for remedial surgery if symptoms are severe
- Remedial surgery
o will eliminate the bile from the vomitus and may improve the patient’s pain, but it is quite
unusual to render these patients completely asymptomatic, especially if they are narcotic
dependent.
- Bile reflux gastritis after distal gastric resection may be treated by one of the following options:
o Roux-en-Y gastroje- junostomy
o interposition of a 40-cm isoperistaltic jejunal loop between the gastric remnant and the
duodenum (Henley loop)
o Billroth II gastro jejunostomy with Braun enteroenterostomy
o total gastrectomy with Roux esophagojejunostomy
- To minimize reflux of bile into the stomach or the esophagus
o the Roux limb should be at least 45 cm long (preferably 60 cm)
- Braun enteroenterostomy
o should be placed at a similar distance from the stomach
- Excessively long limbs may be associated with obstruction or malabsorption
- All of these operations can result in marginal ulceration on the jejunal side of the gastrojeju-
nostomy and thus are combined with a generous distal gastrectomy
- If this has already been done at a previous operation
o Roux or Braun operations may be attractively simple
- Whether truncal vagotomy should be considered to decrease the risk of marginal ulceration is
controversial because acid-suppressing medications may be equally effective
- In addition, the benefits of decreased acid secretion following vagotomy may be out- weighed by
problems with vagotomy-associated dysmotility in the gastric remnant
- The Roux operation may be associated with an increased risk of emptying problems compared to
the other two options, but controlled data are lacking
32
 - Patients with debilitating bile reflux after gastrojejunostomy
o can be considered for simple takedown of this anastomosis provided that the pyloric
channel is open.
- Primary bile reflux gastritis (i.e., no previous operation)
o Rare
o may be treated with the duodenal switch operation, essentially an end-to-end Roux-
en-Y to the proximal duodenum
o Achilles’ heel of this operation: marginal ulceration
o it should be combined with highly selective vagotomy, and/or long-term acid
suppressive medication.
- Bile gastritis or esophagitis
o Recognized complication after esophagogastrectomy with or without pyloroplasty
o can be effectively treated by division of the duodenum immediately distal to the pylorus
with drainage of the prepyloric antrum into a Roux limb
o Preservation of the right gastroepiploic pedical is important
- Proximal subtotal gastrectomy with esophago-antral anastomosis
o should be avoided, but when performed, the pylorus should be left intact.
Roux Syndrome
- A subset of patients who have had distal gastrectomy and Roux-en-Y gastrojejunostomy will have
great difficulty with gastric emptying in the absence of mechanical obstruction
- These patients present with vomiting, epigastric pain, and weight loss
- Endoscopy
o may show retained food or bezoars, dilation of the gastric remnant, and/or dilation of the
Roux limb
- Anastomotic inflammation and stricture from marginal ulceration
o confounding finding
- upper GI series confirms these findings and may show delayed gastric emptying
- This is better quantified by a gastric emptying scan, which always shows delayed solid emptying and
may show delayed liquid emptying as well.
- GI motility testing
o Shows with much of the propulsive activity toward, rather than away from, the stomach
- Gastric motility also may be abnormal
- Presumably the disordered motility in the Roux limb occurs in all patients with this operation
- Why only a subset develops the Roux syndrome is unclear
o Perhaps patients with disordered gastric motility are at most risk.
- Seems to be more common in patients with a generous gastric remnant
- Truncal vagotomy also implicated
- Medical treatment
o promotility agents
- Surgical treatment consists
o paring down the gastric remnant
- Care should be taken to preserve adequate blood supply to the new gastric pouch
- If the left gastric artery is intact, a vertically oriented lesser curvature based pouch (similar to gastric
bypass) with excision of the fundus can be considered
- If gastric motility is severely disordered, 95% gastrectomy or total gastrectomy should be
considered
- The Roux limb
o should be resected if it is dilated and flaccid, unless doing so puts patient at risk for short
bowel
Gallstones
- Gallstone formation following gastric surgery generally is thought to be secondary to vagal
denervation of the gallbladder with attendant gallbladder dysmotility and stasis
- Although prophylactic cholecystectomy is not justified with most gastric surgery, it should be
considered if the gallbladder appears abnormal, especially if subsequent cholecystectomy is likely
to be difficult
- If preoperative evaluation reveals sludge or gallstones, or if intraoperative evaluation reveals stone
o incidental cholecystectomy should be considered.
Weight Loss
- common in patients who have had a vagotomy and/or gastric resection
- The degree of weight loss tends to parallel the magnitude of the operation
BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021
- may be insignificant in the obese but devastating in the asthenic patient
- surgeon should always consider the possible nutritional consequences before performing a gastric
resection for benign disease in a thin patient
- causes of weight loss after gastric surgery generally fall into one of two categories:
o altered dietary intake
o malabsorption
- If a stool stain for fecal fat is negative
o it is likely that decreased caloric intake is the cause
§ most common cause of weight loss after gastric surgery
§ it may be due to small stomach syndrome, postoperative gastroparesis,
anorexia due to loss of ghrelin, or self-imposed dietary modifi- cation
because of dumping and/or diarrhea
- Consultation with an experienced dietitian may prove invaluable.
Anemia
- Iron absorption takes place primarily in the proximal GI tract, and it is facilitated by an acidic
environment
- Intrinsic factor
o essential for the enteric absorption of vitamin B12, is made by the parietal cells of the
stomach
- Vitamin B12 bioavailability
o is facilitated by an acidic environment
- Folate-rich vegetables
o may be poorly tolerated if gastric emptying is delayed or if gastric capacity is limited
- Since iron, B12, and folate play vital roles in hematopoiesis, it is easy to understand why patients
who have had a gastric operation are at risk for anemia.
- most common metabolic side effect in patients who have had a gastric bypass for morbid
obesity
- also occurs in up to one-third of patients who have had a vagotomy and/or gastric resection
- Iron deficiency is the most common cause, but vitamin B12 or folate deficiency also occurs, even
in patients who have not had total gastrectomy
- patients who have had a total gastrectomy will all develop B12 deficiency without some type of
regular nonenteral vitamin B12 administration
- Gastric bypass patients
o should be given oral iron supplements and monitored for iron, B12, and folate deficiency
- Patients who have had a vagotomy and/or gastrectomy
o should be similarly monitored with periodic determination of hematocrit, red blood cell
indices, iron and transferrin levels, B12, and folate levels
- Marginal nutrient status should be corrected
o with oral and/or parenteral supplementation
Bone Disease
- Gastric surgery sometimes disturbs calcium and vitamin D metabolism
- Calcium absorption occurs primarily in the duodenum, which is bypassed with gastrojejunostomy.
- Fat malabsorption
o may occur because of blind loop syndrome and bacterial overgrowth or because of
inefficient mixing of food and digestive enzymes
o can significantly affect the absorption of vitamin D, a fat-soluble vitamin
- Both abnormalities of calcium and vitamin D metabolism can contribute to metabolic bone disease
in patients following gastric surgery
- The problems usually manifest as pain and/or fractures many years after the index operation.
- Musculoskeletal symptoms should prompt a study of bone density.
- Dietary supplementation of calcium and vitamin D may be useful in preventing these complications.
- Routine skeletal monitoring of patients at high-risk (e.g., elderly males and females and
postmenopausal females) may prove useful in identifying skeletal deterioration that may be slowed
or stopped with appropriate treatment after gastric surgery
LAPAROSCOPIC GASTRIC OPERATIONS
- The most common laparoscopic gastric operations performed today are for GERD and obesity
- all conventional gastric operations can be performed with minimal access techniques
- Some are more technically challenging (e.g., partial or total gastric resection) are of debatable
advantage over conventional open approaches
- Certainly, highly selective vagotomy, vagotomy and gastrojejunostomy, and gastrostomy
o lend themselves to a minimal access approach
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 - Laparoscopic local excision is often feasible for GI stromal tumors, leiomyo- mas, or gastric
diverticula
- Difficult to access lesions near the GE junction or pylorus
o may be removed through an anterior gastrotomy
- more recent approaches utilizing transgastric ports or combined laparoscopic and endoscopic
approaches show promise in allowing removal of practically any small gastric lesion with limited
incisions.
- In Japan and Korea
o laparoscopic and robotic assisted approaches have been applied increasingly in the
management of gastric cancer
- Indeed, laparoscopic subtotal gastrectomy has supplanted the traditional open operation as the
preferred operation for patients with earlier stage tumors, and laparocopic total gastrectomy for
proximal tumors is performed with regularity and excellent outcomes
- The Asian experience has firmly established the feasibility of safe laparoscopic D2 gastrectomy.
o Translation of this experience to the United States, however, is not easily accomplished
- Studies from Asia suggest that expertise in the laparoscopic approach require upwards of 40
cases, a challenging baseline given the much lower incidence of gastric cancer in the United States
- more advanced spectrum of disease and higher mean BMI in Western countries are additional
barriers to widespread implementation of laparoscopic resection for gastric cancer.
- Notwithstanding, several high volume centers in the United States have reported excellent outcomes
after laparoscopic gastrectomy
- As robotic technology that facilitates dissection and anastomosis with articulated instrumentation
and enhanced visualization becomes increasingly ubiquitous, the pendulum will likely swing toward
increasing utilization of minimal access approaches for all gastric operations

BULLECER D&V, CARLOBOS, CHY, PRADO, SARENO, TANG 2021 34