Anathomy • The gastrointestinal tract possess

a broadly similar structure throughout its length

- an innermost epithelium- a subepithelial lamina propria- two muscle layers, an inner

circular and an outer longitudinal layer, between which lies the myenteric plexus, the intrinsic neural control system of the musculature

• While this description most accurately describes the small intestine, the other organs of the gastrointestinal tract differ only subtly from this stereotype.

• The anatomy of the stomach differs from the intestine, possessing:

- an additional oblique muscular layer

- at either end a sphincter—specialized musculature designed to act as a unidirectional valve to control the flow of luminal contents

• the sphincter between the oesophagus and stomach (the lower oesophageal sphincter) lies at the level of the diaphragm

• the sphincter between the stomach and small intestine is known as the pylorus.

Proceeding from the surface epithelium into the pits, the mucosal cells considered in detail in the following subsections include the following:- mucous cells andmucous neck cells, which line the surface and extend into the pits, respectively;- parietal cells, which secrete hydrochloric acid and intrinsic factor; - endocrine cells,which secrete a variety of mediators;- toward the base of the pits, chief cells, which secrete pepsinogens Mucous cells.

•The acid-secreting parietal cell is located in the oxyntic gland, adjacentto ECL cell, D cell, important in thegastric secretory process

•This unique cell also secretes intrinsic factor (IF).

•The parietal cell expresses receptors for severalstimulants of acid secretion including histamine (H2), gastrin (cholecystokininB/gastrin receptor), and acetylcholine (muscarinic, M3)-Each of these are G protein–linked-Binding of histamine to the H2 receptor leads to activation of adenylate cyclase and an increase in cyclic AMP. -Activation of the gastrin and muscarinic receptors results in activation of the proteinkinaseC/phosphoinositide signaling pathway.-Each of these signaling pathways in turn regulates a series of downstream kinase cascades, which control the acid-secreting pump, H, K-ATPase.

•Parietal cells also express receptors for ligands that inhibit acid production (prostaglandins,somatostatin, and EGF).

•The duodenum (so named because it is 12 fingers' breadth in length) •retroperitoneal•possess on its medial aspect the ampulla of Vater which connects the pancreatic and common bile ducts to the duodenal lumen

Duodenal juice• an alkaline protein-containing fluid of

weak digestive power that is secreted by the duodenum

• contains invertase, maltase, lactase, erepsin, and enterokinase

• the chyme passes out of the stomach with an acid reaction, and its undigested constituents are at once subjected to a second process of digestion in the duodenum by an alkaline fluid, which is a mixture of the pancreatic juice, the bile, and the enteric juice.

• the pancreatic juice converts the remaining starch into sugars, and the remaining proteids into peptones, leucin, tyrosin, and fatty acids

• the bile it partly emulsifies and partly saponifies the fats

• the sugars are converted into lactic acid and butyric acid, possibly in part by the succus entericus, which is also amylolytic.

Defensive mechanisms

• The properties of the surface epithelial cells that provide the second line of gastroduodenal defensive factors include restitution, epithelial cell metabolism (e.g., transmembrane, transcellular resistances), acid-base transporters that maintain intracellular pH, and mucus secretion.

• The key subepithelial process that prevents mucosal injury is adequate mucosal blood flow.

Common symptoms

• Dyspepsia• Nausea• Vomiting • Bloating• Fast enough

Indigestion

Bloating

Pain in EpigastricRegion

Patients may speak of:

• indigestion (to describe any low-grade upper abdominal discomfort)

• sickness (to describe either nausea or vomiting)

Dyspepsia

• upper abdominal or lower chest discomfort or pain related to eating which may be described by the patient as a burning, a heaviness, or an aching

• often accompanied by other symptoms such as nausea, fullness in the upper abdomen, or belching

• the symptoms of upper gastrointestinal disease are imprecise and non-specific - the clinical history will often facilitate making the correct diagnosis quickly and limit unnecessary investigation

Functional dyspepsia

• previously called non-ulcer dyspepsia

• dyspepsia "without evidence of an organic disease that is likely to explain the symptoms“

• is estimated to affect about 15% of the general population in western countries

Nausea

• the term nausea should be restricted to the feeling of being about to vomit.

• acute nausea is usually accompanied by hypersalivation.

• caused by labyrinthine stimulation (as in motion sickness), distension of hollow viscera, or any severe somatic pain and by some drugs, especially opiates and those used in chemotherapy for malignant conditions

Vomiting • forceful ejection of gastric contents through the mouth by the co-ordinated contraction

of abdominal and gastric muscles with relaxation of the lower oesophageal sphincter. • non-productive vomiting is called retching.

- Vomiting occurs with peptic ulceration, especially when there is delayed gastric emptying (pyloric stenosis), and with advanced gastric cancer.

- It occurs with disorders of the biliary tree (especially as a result of gallstones) and with acute pancreatitis (in which it is a prime symptom).

- It is an important symptom of intestinal obstruction, especially with lesions above the ileocaecal valve, and it may occur with any cause of peritoneal inflammation such as appendicitis.

- Metabolic causes of vomiting include diabetic ketoacidosis, hypoadrenalism, and uraemia. - Drugs which cause vomiting include opiates, some antibiotics (for example erythromycin),

and chemotherapeutic agents. - Alcoholism, raised intracranial pressure, and pregnancy are important causes of early

morning vomiting.

Effortless vomiting

• without a definable cause may be psychogenic- this is usually a disorder of young women many of whom

have suffered psychological trauma (such as sexual abuse)- it is not related to the vomiting of bulimia, a condition that

is part of the anorexia nervosa syndrome

• Rumination is the repetitive regurgitation of gastric contents into the mouth after meals, the regurgitated material then being reswallowed. It is not associated with nausea, heartburn, or discomfort and often appears to be simply an acquired habit.

Abdominal pain

• Pain in the upper abdomen has been considered under the heading dyspepsia. Upper abdominal discomfort is so common that its presence alone is of no value in distinguishing between those patients with organic disease and those with a functional disorder.

• Symptoms are rarely specific but should be reinterpreted in the light of screening investigations (such as the blood count, a straight radiograph of the abdomen, and assessment of serum markers of inflammatory disease).

Investigations

• Upper GI endoscopy

• Investigation for Helicobacter pylori

• Find medication-related dyspepsia

PEPTIC ULCER

•A gastrointestinal ulcer is defined as a breach in the epithelium that penetrates the muscularis mucosae. •If the muscularis is not breached it is called an erosion.•Duodenal ulcers and gastric ulcers are often considered together as peptic ulcers but differ considerably with regard to epidemiology, pathogenesis, presentation, andmanagement

Epidemiology

• Developed countries: 1980-1999 – DU 8-10% and annual incidence of 0,2%– GU 3 times more rare– Decrease in incidence since 1970– Decrease of DU principally in men M/F 3-4/1 la 2/1

and even 1/1– GU no significant modifications in incidence.– Decreased incidence principally in young and

middle aged men; is becoming a disease of old age.

International prevalence (Place)

Etiopathogenesis • Aggressive factors implicated in ulcer– Acid hypersecretion

• Increase in parietal cell mass• Increase in vagus tone• Increase in parietal cellular sensibility to gastrin• Antral G cells hyper function• Nocturnal acid hypersecretion• Deterioration in inhibitory mechanism of acid secretions• Motility disturbances: Duodenal ulcer-rapid gastric emptying,

gastric ulcer- gastric hypomotility– Pepsin hypersecretion

• Hiperpepsinogenemia I- Helicobacter pylori – Duodenogastric reflux

• Biliary acids, lisolecitin and proteolytic enzymes.

Etiopathogenesis• Factors of defense – Pre-epithelial factors• Bicarbonate and mucus barriers• Tensioactive phospholipids

– Epithelial factors• Cellular resistance (normal cellular metabolism)• Intra-cellular PH maintenance• Growth factors (epithelial growth factors,

Prostaglandins, NO)• Mechanism of repair of epithelial lesions

– Post-epithelial factors• Abnormal mucous blood flow

Etiopathogenesis• Individual factors– Genetic factors: group 0 & A, Lewis and non-

secretory factor (a-b-)– Familial Hyperpepsinogenemia type I– Studies: 39% genetic factors and 61% average

predisposing factors– Associated diseases : ZE syndrome, MEN I,

systemic mastocytosis, alfa 1 antitrypsin deficiency, hepatic cirrhosis, chronic pancreatitis, Crohn’s disease, COPD, polycythemia vera, basophilic leukemia, amyloidosis

– Personality changes : anxiety, neuralgia

Etiopathogenesis

• Average risk factors– smoking– NSAID– Corticotherapy

( controversial)– Stress

Ulcerous disease

• chronic disease with multiple complain (dyspeptic syndrome) characterized anatomo-pathologically by the presence of ulcerous crater which crosses the muscularis mucosa, with gastric and /or duodenal localization

Etiology/Classification

• Helicobacter Pylori + ulcer• NSAID (aspirin) induced ulcer • Stress induced ulcer• Ulcer which accompanies genetic diseases and

syndromes• Helicobacter pylory - ulcer.

How it happens …

• Peptic ulcers happen when the acids that help you digest food, damage the walls of the stomach or duodenum.

• The most common cause is infection with a bacterium called Helicobacter pylori.

• Another cause is the long-term use of nonsteroidal anti-inflammatory medicines (NSAIDs) such as aspirin and ibuprofen.

• Stress and spicy foods do not cause ulcers, but can make them worse.

Gastric ulcers

• GUs tend to occur later in life than duodenal lesions, with a peak incidence reported in the sixth decade.

• More than half of GUs occur in males and are less common than DUs, perhaps due to the higher likelihood of GUs being silent and presenting only after a complication develops.

• Autopsy studies suggest a similar incidence of DUs and GUs.

Gastric ulcer

• can represent a malignancy.• Benign GUs are most often found distal to the junction

between the antrum and the acid secretory mucosa. This junction is variable, but in general the antral mucosa extends about two-thirds of the distance of the lesser curvature and one-third the way up the greater curvature.

• Benign GUs are quite rare in the gastric fundus and are histologically similar to DUs. Benign GUs associated with H. pylori are associated with antral gastritis.

• In contrast, NSAID-related GUs are not accompanied by chronic active gastritis but may instead have evidence of a chemical gastropathy.

Gastric ulcer

• the majority of GUs can be attributed to either H. pylori or NSAID-induced mucosal damage.

• GUs that occur in the prepyloric area or those in the body associated with a DU or a duodenal scar are similar in pathogenesis to DUs.

• Gastric acid output (basal and stimulated) tends to be normal or decreased in GU patients.

• When GUs develop in the presence of minimal acid levels, impairment of mucosal defense factors may be present.

Macroscopic – gastric ulcer

Microscopic – gastric ulcer

Duodenal ulcer

• DUs are estimated to occur in 6 to• 15% of the western population. The incidence

of DUs declined steadily• from 1960 to 1980 and has remained stable

since then. The death rates,• need for surgery, and physician visits have

decreased by 50% over• the past 30 years.

Duodenal ulcer pathology• DUs occur most often in the first portion• of duodenum (95%), with 90% located within 3 cm of the

pylorus.• They are usually 1 cm in diameter but can occasionally reach 3 to• 6 cm (giant ulcer). Ulcers are sharply demarcated, with depth at

times• reaching the muscularis propria. The base of the ulcer often

consists• of a zone of eosinophilic necrosis with surrounding fibrosis.

Malignant• duodenal ulcers are extremely rare.

Duodenal ulcer• Many acid secretory abnormalities have been described• in DU patients. Of these, average basal and nocturnal gastric• acid secretion appear to be increased in DU patients as compared to• control; however, the level of overlap between DU patients and control• subjects is substantial. The reason for this altered secretory process is• unclear, but H. pylori infection may contribute to this finding. Accelerated• gastric emptying of liquids has been noted in some DU patients• but is not consistently observed; its role in DU formation, if any, is• unclear. Bicarbonate secretion is significantly decreased in the duodenal• bulb of patients with an active DU as compared to control subjects.• H. pylori infection may also play a role in this process.

Macroscopic –duodenal ulcer

A 49-year-old man was admitted with sudden onset of severe pain in the epigastrium. Recently, he had taken a course of a non-steroidal anti-inflammatory drug (NSAID). This had caused indigestion, which had worsened in the two days prior to his presentation. On examination, the patient was ill and had a rigid abdomen. The operative photograph shows a perforated duodenal ulcer.

Microscopic – duodenal ulcer

• Representative micrographs of duodenal mucosa stained by haematoxylin and eosin

Ulcer HP+

• 80-90% of ulcers after excluding AINS• Increased risk 4x duodenal ulcer and 3x gastric

ulcer• Decreased risk of recurence if eradication is

successful: 6% 1 yr and 17% > 1 yr, superior supraselective vagotomy.

UK Incidence & Prevalence (Person)

H. pylori infection• Incidence: 1-3% of adults p.a. (HPA)• Prevalence infection: 40% population (HPA: >50% of 50+yr

olds)

Ulceration•Incidence:

– DU in 30-50yrs old; higher incidence in men – GU in >60yr olds; higher incidence in women

•Low prevalence in younger age groups•Duodenal ulcer: up to 10% of population

Ulcer HP+

• Reversible gastrine hypersecretion predominant postprandial

• Increase in acid secretion if gastritis is antral• Hipersecretion of pepsinogen• Changes in adherent mucus• Changes in appearance of gastroduodenal

mucus.

Ulcer induced by NSAIDs

• Mucus, bicarbonate secretion, microcirculation (mucosal appearance depends upon PG (PGE)

• NSAIDs inhibits COX1 and COX2 by decreasing physiological and pathological prostaglandins (systemic effect )

• Some of NSAID (weak acids) have mucosal irritant effect (local effect )

• NSAID and HP are independent factors in ulcerogenesis but have additional effects (to eradicate HP before starting treatment with NSAID)

• Mucosal adaptation

Ulcer induced by NSAIDs

• Injury to the mucosa also occurs as a result of the topical encounter

• with NSAIDs. Aspirin and many NSAIDs are weak acids that remain

• in a nonionized lipophilic form when found within the acid environment

• of the stomach. Under these conditions, NSAIDs migrate across

• lipid membranes of epithelial cells, leading to cell injury once trapped

• intracellularly in an ionized form.

Endocrine Ulcer

• Zollinger Ellison Syndrome (gastrinoma) isolated or in association with MEN I (0,5%)

Stress Ulcer• Acid hypersecretion• Systemic arterial hypotension• Stress coagulopathy• Ischemic induced mucosal defects.

Clinical manifestations of ulcer disease

Symptoms Epigastric pain described as a burning or gnawing discomfort can

be present in both DU and GU.

GU• Discomfort may actually be

precipitated by food.• Nausea and weight loss

occur more commonly in GU patients.

DU• The typical pain pattern in

DU occurs 90 min to 3 h after a meal and is frequently relieved by antacids or food.

• Pain that awakes the patient from sleep(between midnight and 3 A.M.) is the most discriminating symptom

The mechanism for development of abdominal pain in ulcer patients is unknown. Several possible explanations include acid-induced activation of chemical receptors in the duodenum, enhanced duodenal sensitivity to bile acids and pepsin, or altered gastroduodenal motility.

Diagnosis

• Endoscopy (>40yrs, first time). Capture all cases?• Faecal / breath tests for H. pylori• GI X-ray

False positive testsMissed cases? – risk of transmission / disease progression

Why are they important?

• HPA – “infectious disease” but main effects are from chronic burden

• Potential “medical emergency”• Chronic symptoms – health and economic costs• H. pylori also linked to:– Functional dypepsia– Cancer (2-6x more likely, though still rare)

• Differential clinical outcome - interaction between bacterial properties (phenotypic variation), genetics and environmental / behavioural factors

Emergency admission for perforation

Rates per million resident population. Three-year moving averages

Implications for care of older people

(Bardhan et al. 2004, Digestive & Liver Disease 36(9), 577-588)

Endoscopy

• endoscopy provides the most sensitive and specific approach for examining the upper gastrointestinal tract

• facilitates photographic documentation of a mucosal defect and tissue biopsy to rule out malignancy (GU) or H. pylori

• endoscopic examination is particularly helpful in identifying lesions too small to detect by radiographic examination, for evaluation of atypical radiographic abnormalities, or to determine if an ulcer is a source of blood loss.

• Endoscope is passed through the mouth, to the stomach, examining the lining of the stomach

• Many endoscopes are equipped with a small clipper with which tissue samples can be taken (endoscopic biopsy)

• Endoscopes can also be used for treatment.

Endoscopy

Endoscopy

Benign gastric ulcer

Benign gastric ulcer

Endoscopy:

Duodenal ulcer

Duodenal ulcer (a)

Duodenal ulcer (b)

Radiographic (barium study)• still commonly used as a first test for documenting an ulcer• the sensitivity of older single-contrast barium meals for detecting a DU is as

high as 80%, with a double-contrast study providing detection rates as high as 90%

• sensitivity for detection is decreased in small ulcers (0.5 cm), presence of previous scarring, or in postoperative patients

• DU appears as a well-demarcated crater, most often seen in the bulb• GU may represent benign or malignant disease• typically, a benign GU also appears as a discrete crater with radiating

mucosal folds originating from the ulcer margin• ulcers 3 cm in size or those associated with a mass are more often malignant• up to 8% of Gus that appear to be benign by radiographic appearance are

malignant by endoscopy or surgery. Radiographic studies that show a GU must be followed by endoscopy and biopsy.

Typical radiographic features of benign gastric ulcer (a)

Typical radiographic features of benign gastric ulcer (c)

Typical radiographic features of benign gastric ulcer (d)

Typical radiographic features of duodenal ulcer (b)

Diagnosis of H. pylori infection• Three methods can be used to detect H. pylori in gastric biopsies:1. The biopsy urease test depends on the the ability of the bacterium to generate

alkali.2. H. pylori bacteria are readily detected histiologically using special stains.3. Bacterial culture allows the antibiotic sensitivity of the patient's strain to be

determined.

• Two tests allow H. pylori to be diagnosed without endoscopy:1. Serology is accurate and convenient but remains positive for several months after

successful eradication, and is not useful for determining whether eradication has been successful.

2. The urea breath test. The patient drinks a solution of urea containing carbon atoms labelled with 13C or 14C. Labelled CO2, generated by bacterial urease, can be detected in the breath by mass spectroscopy or radioactive counting if the infection is present. This test is ideal for testing the success of eradication, if this is required.

Prognosis • Recurrence of H. pylori-related duodenal ulceration is uncommon

after successful eradication. • The rate of reinfection with H. pylori is about 0.7 per cent per

annum in Western adults. Higher rates of reinfection have been reported in developing countries but this is not universal and the reinfection rate is 1 per cent per annum in China. Apparent reinfection in the West is often actually persistence of the initial infection.

• Recurrent ulceration in the absence of H. pylori may be due to NSAIDs, Crohn's disease, or the Zollinger–Ellison syndrome. In some patients recurrent ulceration after eradication of H. pylori is associated with persistent high acid output in the absence of a gastrinoma.

COMPLICATIONS

• Acute:– bleeding (hematemesis, melena)– perforations

• Chronic:– piloric stenosis– Cancer??????????

Gastrointestinal bleeding • Haemorrhage remains a challenging problem and is the main cause of death

from peptic ulcers. • Blood loss may be slow and present as unexplained anaemia but more typically

presents acutely with haematemesis or melaena or both with varying degrees of hypovolaemic shock.

• Older patients need particular attention because they are much more vulnerable to the effects of hypovolaemia.

• Endoscopy is performed, preferably after the patient's condition has stabilized, to define the source of bleeding and to apply endoscopic treatments. Ulcers which are actively bleeding or show stigmata, such as adherent clot or a visible vessel, which make further bleeding likely can be treated with lasers, heater probes, or local injection of adrenaline.

• Rebleeding is an indication for surgery.• After the acute episode, it is important to attend to the cause of the ulcer.

Eradication of H. pylori, if it is present, greatly diminishes the frequency of further episodes of bleeding in future, but this is a measure that is frequently overlooked.

Hematemesis

• "hema“ - blood + "emesis“ - vomit = bloody vomit

• red• coffee ground vomitus - occurs when blood is

in contact with gastric acid for at least 1 hour.

Hematemesis/HemoptisisWhere is it from?

GI TRACT RESPIRATORY TRACT

Dark red or brownIn clumpsMixed with foodAcidic pHStomachache, abdominal discomfortNausea, retching before and after episode

Bright redFoamy, runnyMixed with mucousAlkaline pHChest pain, warmth or gurgling over the chestPersistent cough

Melena

• the passage of dark black, liquid, tarry, metallic-smelling stools

• melenic stools usually indicate bleeding proximal to the right side of the colon

• it usually indicates that hemorrhage has remained for > 8hrs in the GI tract

Hematochesis

• the passage of bright red stools

• is usually indicative of bleeding from the rectum & anus, however 50% are due to proximal lesions (mainly in the colon) that are profuse enough that they avoid remaining in the gut for 8hrs & are not expressed as blood intermixed with stools

Causes of GI bleeding

• duodenal ulcer hemorrhage (25%)• gastric ulcer hemorrhage (20%)• mucosal tears of the esophagus or fundus (Mallory-

Weiss tear)• esophageal varices• erosive gastritis, erosive esophagitis• Dieulafoy lesion• gastric varices• gastric cancer• ulcerated gastric leiomyoma

Upper gastrointestinal bleeding

Stigmata of recent hemorrhage (a)

Stigmata of recent hemorrhage (b)

Stigmata of recent hemorrhage (c)

Stigmata of recent hemorrhage (d)

Stigmata of recent hemorrhage (e)

Stigmata of recent hemorrhage (f)

Stigmata of recent hemorrhage (g)

Stigmata of recent hemorrhage (h)

Penetration

• sudden onset or worsening of pain with considerable abdominal tenderness followed by the onset of peritonitis with board-like rigidity, rebound tenderness, and loss of bowel sounds

• gas in the peritoneum may lead to loss of liver dullness to percussion, and is usually visible beneath the diaphragm on erect chest radiograph

• the differential diagnosis includes acute pancreatitis, acute cholecystitis and other causes of an acute abdomen such as gut infarction or perforation of other organs

Perforated peptic ulcer

Acute peritoneal syndrome

Pyloric stenosis• repeated duodenal ulceration• the main symptom is vomiting which may contain food eaten

the previous day• typical symptoms of duodenal ulceration may or may not

precede the onset of vomiting• patients rapidly become dehydrated and develop

hypokalaemia with a metabolic acidosis, they may also be malnourished

• a succussion splash, which is normally present up to 4 h after a meal, is present at other times

• barium radiology or upper endoscopy show a distended stomach containing retained food and secretions and with a narrowed pyloric canal

• the differential diagnosis includes cancer of the distal stomach

Pyloric outlet obstruction and peripyloric ulcer disease (b)

Pyloric outlet obstruction and peripyloric ulcer disease (c)

Pyloric outlet obstruction and peripyloric ulcer disease (d)

Piloric stenosis – Investigations

Piloric stenosis

Differential diagnosis

• Nonulcer Dyspepsia =abdominal pain or discomfort that occurs in the upper abdomen without the presence of an ulcer, is a major complaint that affects about 15% of the population annually, most of whom do not seek medical care

• Other Gastrointestinal Diseases GI diseases that mimic PUD include upper GI neoplasms (i.e., gastric and pancreatic cancer), mesenteric ischemia, which is sometimes referred to as abdominal angina, and pancreatitis or cholecystitis. Gastric or duodenal involvement with Crohn’s disease or with typical and atypical strains of Mycobacterium tuberculosis can produce gastric retention and ulcer-type symptoms

STOMACH CANCER

Epidemiology

– More common in man than in women

– More frequent in China, Japan, Chile, former USSR, Est Europe; low in India, Africa

– Dramatic decline in incidence in past 20-30 years

Incidence

• gastric cancer is the second most common cause of cancer mortality, after lung cancer, worldwide. It is estimated that gastric cancer causes more than 620,000 deaths per year worldwide. In the United States, approximately 21,500 new cases of gastric cancer were diagnosed in 2000 and 13,000 patients died of this disease the same year.

• most gastric tumors are adenocarcinomas• other less common gastric malignant diseases:

lymphoma, stromal tumor and gastric polyps

Malignant gastric neoplasms

Risc factors

– diet: high carbohidrates and salt preserved foods, deficiet in fruits and vegetable

– high dietary intake of nitrates (preservation food)

– Helicobacter pylori

– atrophic gastritis (pernitious anemia)

– partial gastrectomy (more than 15 years)

Patological features

• Adenocarcinoma accounts for 95% of the stomach cancers, whereas squamous cell carcinoma, carcinoid tumors, leiomyosarcoma, and lymphoma constitute the rest of the gastric tumors.

Macroscopic • gastric cancers can be broadly categorized by their location and

appearances• proximal (cardia) versus distal (including body and antrum) cancers -

major etiologic significance- distal cancers are more common in areas with a high gastric cancer

incidence- cardia cancers are more prevalent in whites from populations with a low

background incidence of gastric cancer

• the former may be closely related to chronic H pylori infection, whereas the latter is often the consequence of chronic gastroesophageal reflux disease and Barrett esophagus

• the incidence of gastroesophageal junction carcinomas is increasing in the United States 4 and in many other developed countries

There are several different forms of gastric cancer; this slide shows an infiltrating type. Here, malignant cells in groups or lines tend to infiltrate the wall of the stomach, causing it to become thicker, and rigid. It comes to resemble a “leather bottle” used to carry wine. It is also known as linitis plastica (linitis originally referred to linen or cloth) and this was thought to be due to inflammation (“itis”), but the inflammatory-appearing cells have been shown to be cancer cells. Mucin stains are sometimes helpful in differentiating cancer cells from chronic inflammatory cells.

Microscopic • Microscopically, several histological classifications of gastric cancer are used. • The most widely used classification, proposed by Lauren, 87 broadly divides

gastric cancer into diffuse and intestinal types, with contrasting epidemiology, etiology, and prognosis

• The intestinal type is characterized by cohesive neoplastic cells forming glandular tubular structures, is more common in the distal stomach and is often preceded by preneoplastic stages such as intestinal metaplasia. It is more prevalent in regions with a high background incidence of gastric cancer and is generally associated with a better surgical outcome than the diffuse type

• The diffuse type is characterized by its biologic behavior, shows sheets of epithelial cells or cells scattered in a stromal matrix without evidence of gland formation; may contain signet-ring cells.

• Approximately 5% to 10% of tumors remain unclassified, and they are called mixed-type tumors

Cascade of gastric carcinogenesis• Based on extensive observational

studies in populations with high gastric cancer incidences, gastric cancer is generally believed to be a multistep progression from chronic gastritis, atrophy, and intestinal metaplasia ultimately to dysplasia and cancer.

• This paradigm of gastric carcinogenesis has been coined the Correa cascade, which was subsequently modified to incorporate H pylori in the initial stage of the sequence.

H&E appearance of intestinal type gastric cancer.

H&E appearance of diffuse type gastric cancer.

Symptoms • Early gastric cancer typically produces no symptoms. Only patients with

advanced disease will notice any discomfort.

- The most frequent symptoms and signs patients experience are weight loss and abdominal pain.

- Persistent vomiting can occur in antral tumors obstructing the gastric outlet. - Dysphagia may be present when tumors obstruct the gastroesophageal

junction.- Early satiety, although not a common presentation of gastric cancer, may

suggest a diffusely infiltrative tumor resulting in loss of distensibility of the stomach.

- Gastrointestinal bleeding has been reported in about 10% to 15% of patients, but frank bleeding is rare. Overt massive upper gastrointestinal bleeding may be more common in gastric stromal tumors.

Signs • Physical signs are usually absent in patients with gastric carcinomas,

except in metastatic disease.

• A palpable abdominal mass is rare before regional extension of the tumor.

• Metastasis to the left supraclavicular lymph node produces the so-called Virchow node, along the peritoneal surfaces may result in a periumbilical nodule ( Sister Mary Joseph node), ovarian mass ( Krukenberg tumor), or tumor mass in the cul-de-sac ( Blumer shelf); peritoneal seeding of tumor may produce malignant ascites

• Paraneoplastic syndromes: acanthosis nigricans, membranous glomerulonephritis, microangiographic hemolytic anemia, arterial and venous thrombi (Trousseau syndrome), seborrheic dermatitis ( Leser-Trélat sign) and dermatomyositis.

Diagnosis • Because of the silent nature of the disease, timely diagnosis of gastric cancer is

difficult.

• Conventionally, radiologic imaging played a major role in the initial diagnosis of gastric cancer; with the use of double-contrast techniques - false-negative rates of up to 25% have been reported in lesions between 5 and 10 mm in diameter

• Upper gastrointestinal endoscopy and biopsy have been the standards for the diagnosis of gastric cancer

• CT scanning defines the spread of the primary tumour and gross lymphatic and metastatic disease

• MRI scanning• Endoscopic ultrasound is useful in the local staging of gastric carcinoma.• Laparoscopy may be necessary to confirm the presence of peritoneal metastases• Ultrasonography will identify hepatic metastases

• Biochemical markers

Biochemical markers

• low serum pepsinogen I• elevated gastrin level • H. pylori antibody testing

Laboratory anemia -iron deficiencyhypoalbuminemia- poor nutritionabnormal liver chemistry - hepatic involvement

STAGING• The clinical and pathological

staging of gastric carcinoma is of paramount importance in the management of the patient.

• The depth of the tumor invasion (T), the involvement of lymph nodes (N), and the presence of metastasis to other organs (M) are the major considerations.

• This TNM staging system has been extensively used in the evaluation of gastric cancer.

Radiological findings• It may not be possible to

differentiate a benign from a malignant ulcer by barium studies

• A malignant ulcer typically has an asymmetric ulcer crater excentrically located in an irregular mass with distortion or obliteration of the normal mucosal fold surrounding the ulcer.

• Other features such as nodularity, clubbing, fusion, or amputation of radiating folds also suggested malignancy.

• The use of radiologic imaging has gradually been replaced by endoscopy.

Endoscopy

• Endoscopy is widely used in the initial diagnosis of gastric cancer and has generally replaced contrast radiologic studies in many centers.

Gastric carcinoma

Endoscopic view reveals presence of obviously ulcerated mass

CT

• (CT) scanning in the preoperative staging, its value remains disputable.

• One of the limitations of CT is the inability to differentiate between different layers of the gastric wall and hence the inability to define the T stage.

• The role of CT is confined to its ability to demonstrate invasion outside the stomach wall and the presence of distant metastasis.

MRI

• The role of magnetic resonance imaging (MRI) in the preoperative staging of gastric cancer is yet to be defined.

• MRI requires a longer scan time than CT and thus is easily subjected to artifact from respiration and bowel movement. The other limitation of MRI is the lack of a widely accepted oral contrast medium to distend the stomach.

• MRI is superior to CT in delineating the layered structure of the stomach wall, and it may be used in predicting the depth of tumor invasion (T staging).

Nuclear Medicine 87 year old woman with neoplastic meningitis from gastric cancer. FDG PET showed deoxyglucose uptake in the stomach and the head of the pancreas (A). No deoxyglucose uptake was apparent in the spinal canal on FDG PET (B).

Endoscopic ultrasonography (EUS)

• EUS provides an accurate assessment of T staging and is superior to other imaging modalities for the local staging of gastric cancer.

• The overall accuracy of EUS in T staging was estimated to be 78%. 152 The accuracy tends to be lower for T2 tumors because of the tendency to overstage these tumors as a result of poor differentiation between inflammation and infiltration.

• The overall accuracy of N staging was estimated to be 70%.

Endoscopic ultrasound confirms the depth of invasion

Carcinoma in the body of the stomach

Laparoscopy

• Often detects unexpected peritoneal or liver metastasis that may not be identified by other imaging techniques.

• The role of laparoscopy in preoperative staging is difficult to evaluate because most published series involved heterogeneous patient populations and gave inconsistent results.

• The overall rate of detecting peritoneal and liver metastases by laparoscopy ranged from 3% to 37% and 2% to 25%, respectively

Prognostic • The mortality of gastric cancer in many parts of the

world, with the exception of Japan, has not been changed over the past few decades.

• A review from the National Cancer Data Base revealed that the overall 5-year and 10-year survival rates of patients diagnosed with gastric cancer between 1985 and 1996 were 28% and 20%, respectively

• Men had a poorer prognosis than women• Proximal cancer was associated with worse prognosis

than distal cancer

GASTRIC TUMORS OTHER THAN ADENOCARCINOMAS

• Gastric Lymphoma• Gastrointestinal Stromal Cell Tumors• Gastric Carcinoid Tumors

GASTRIC POLYPS

Gastric Lymphoma• Although primary gastric lymphoma is a rare malignant disease

that accounts for less than 5% of all gastric malignancies, it is the most common form of gastrointestinal lymphoma.

• It is estimated that approximately 70% of primary extranodal lymphomas of the gastrointestinal tract arise from the stomach.

• Most (80%) of gastric lymphomas are B cell in origin.• The origin of this disease remains elusive, but many of these

tumors, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, are related to chronic inflammation attributed to H pylori infection. H heilmannii has also been linked to MALT lymphoma

Gastric Lymphoma

• Macroscopically, it may not be possible to differentiate gastric lymphoma from carcinoma.

• Gastric lymphoma can be polypoid, fungating, infiltrating, or even ulcerative in appearance. Most lymphoma spreads by submucosal infiltration, and the muscular layer is usually spared until a very late stage of the disease. Further spread to local and regional lymph nodes then follows.

• Microscopically, there is considerable heterogeneity among different classification systems.

Gastric Lymphoma

• Symptoms of gastric lymphoma are nonspecific: the most frequent symptoms are abdominal pain, weight loss, nausea, vomiting, and anorexia. Bleeding occurs in about 20% of cases.

• Upper gastrointestinal endoscopy is widely used in the diagnosis of gastric lymphoma that can provide histological proof.

• Multiple and deep gastric biopsies are usually required for histological diagnosis because tumors may develop in the submucosal lymphoid tissue covered by normal gastric mucosa.

Gastric lymphoma-prognosis

• The grading and staging of gastric lymphoma are the two decisive prognostic factors. In a review by the German-Austrian Gastrointestinal Lymphoma Study Group, the overall 2-year survival rates for low-grade lymphoma ranged from 89% to 96%.

• Patients with high-grade lymphoma fare much worse. • When surgery was performed, patients with

complete resection had significantly better survival than those with incomplete resection (2-year survival of 83% to 88% versus 53%).

Mucosa-Associated Lymphoid Tissue Lymphoma

• MALT lymphoma was first described in 1983 by Issacson and Wright 203 as a distinct pathological entity.

• They described that certain low-grade B-cell gastrointestinal lymphomas recapitulated the features of Peyer patches or MALT.

• MALT lymphoma is characterized by the presence of plasma cells, reactive follicles, and centrocyte-like cells that tend to invade mucosal epithelium and form characteristic lymphoepithelial lesions.

• Most are of B-cell origin, and the most frequent site of involvement is the stomach. These tumors tend to arise as polyclonal proliferation in chronic inflammatory tissues, either autoimmune or infectious

Gastrointestinal Stromal Cell Tumors

• Gastrointestinal stromal tumors (GISTs) encompass a heterogenous group of mesenchymal tumors

• Gastric stromal tumors with predominant smooth muscle differentiation are termed gastric smooth muscle were conventionally called leiomyomas and leiomyosarcomas.

• Gastric mesenchymal tumors of neural origin can be divided into four main groups depending on the origin: peripheral nerve (schwannoma, neurofibroma, and neuroma); sympathetic or chromaffin system (neuroblastoma, ganglioneuroma, and paraganglioma); gastrointestinal plexus (gastrointestinal autonomic nerve tumor) and undetermined.

• The precise cellular origin of GISTs has been proposed to be the interstitial cell of Cajal, an intestinal pacemaker cell

Gastrointestinal Stromal Cell Tumors

• Histologically, the distinction between benign and malignant tumors is difficult, and there is no unequivocal criterion to differentiate the two.

• Mitotic activity and tumor size appear to be more reliable in categorizing tumors as benign, borderline, and malignant, but there is no agreed cutoff point for these values.

• The use of EUS may also help in differentiating benign from malignant tumors.

• Tumors less than 30 mm in diameter with regular margins and with a homogenous echo pattern are usually benign.

Gastrointestinal Stromal Cell Tumors

• Patients can present with nausea, vomiting, abdominal pain, gastrointestinal bleeding, and even metastatic diseases.

• Bleeding is considered the most common presentation.• Malignant tumors can metastasize to the liver and

peritoneum and, rarely, to lymph nodes, bone, and lung.

• Accurate preoperative diagnosis can be difficult, and percutaneous biopsy carries a theoretical risk of peritoneal seeding and tumor rupture.

Gastric Carcinoid Tumors

• Gastric carcinoid tumors are rare, accounting for only about 3% of all carcinoids.

• Enterochromaffin-like cells are the main endocrine cell types in type 1 and type 2 disease

• Type 1 tumors tend to be small (<100 mm) and multiple. They are considered the most benign of the three forms of carcinoid tumors and have a relatively low frequency of metastasis, between 9% and 23%.

• Type 2 tumor is associated with the gastrin-producing neoplasms in Zollinger-Ellison syndrome as part of the multiple endocrine neoplasia syndrome type I. This type of carcinoid has intermediate metastatic potential

Gastric Carcinoid Tumors

• The clinical presentations of gastric carcinoids are usually nonspecific and variable including pain, vomiting, anemia, and bleeding, or they can be discoveredincidentally during endoscopy for other reasons.

• Presentation with the typical carcinoid syndrome of flushing, diarrhea, cutaneous edema, and bronchoconstriction is uncommon.

• This is more closely related to the secretion of histamine than to that of substance P, serotonin, or 5-hydroxyindoleacetic acid.

Gastric Carcinoid Tumors-prognosis

• The overall 5-year survival in patients with all types is 49%. However, patients with type 3 gastric carcinoids have a significantly worse prognosis than do those with type 1 and 2 lesions.

• Five-year survival of patients with localized gastric carcinoid is 64.3%, whereas survival in patients with distant metastases drops to 10%.

Gastric polyps

• uncommon• the estimated incidence is less than 1% in autopsy or

radiologic surveys• up to 50% of gastric polyps are discovered• incidentally during endoscopy for unrelated symptoms• they may be solitary or multiple• occasionally they are associated with other polyposis

syndromes (familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, and Cronkhite-Canada syndrome)

Gastric polyps

• One of the most important characteristics of gastric polyps is the potential for malignant transformation, particularly in adenomatous polyps.

• It is believed that the histological composition and size of the polyps may determine their malignant potential.

• The frequency of malignant transformation varies from 6% to 75% in the literature.

Adenomatous polyps

• Adenomatous polyps account for about 10% of gastric polyps and they are more prevalent in areas with a high incidence of gastric cancer.

• This type of polyp is associated with a higher risk of malignant transformation, and the risk is size dependent.

• Coexistence of adenoma with carcinoma is not uncommon.

Fundic gland polyps

• are also known as fundic gland hyperplasia or glandular cysts.

• They are recognized as the most frequent type of gastric polyp, accounting for nearly half of all gastric polyps

• They are located exclusively in the acid-producing mucosa and thus are not found in the antrum.

• The polyp may regress and may have no malignant potential.

• Gastric polyps occurring as part of the familial adenomatous polyposis syndrome are usually fundic gland polyps.