Gastric and Duodenal Disorders

Peptic Ulcers

estimated prevalence in US 4 million and growing; men more at risk than women

4x more duodenal ulcers than gastric ulcers, but GU is increasing; gastric ulcers most common in antrum

incidence of DU increases until age 60 and plateaus (males > females); GU is rare before age 40, peaks 55-65 yrs (equal sex distribution)

ulceration occurs when mucosal defenses are overwhelmed by gastric acid and pepsin

mucosa is breached to the submucosal level or deeper

pepsin and acids are requisite for ulceration, but hyperacidity is not a prerequisite; ulceration more likely occurs when the mucosal defenses are broken down by acid in concert with other factors

Zollinger-Ellison syndrome: extreme hypersecretion of acid Þ usually predisposes to ulcers (but does not always lead to ulcers)

DU is often preceded by GU ulcer in the antrum

differential diagnosis inlcudes cancer

Benign	Malignant
mostly pylorus	found anywhere
small (<3 cm)	larger
flat margin	raised nodular mass
Straight walls	poorly definded walls
Clean base	dirty base
Punched out appearnce	lumpy, bumpy appearance

Risk Factors for Peptic Ulcers

(1) NSAIDs and salicylates

steroid use without NSAID use is not a risk factor; risk factors for NSAID users: age>60, disease duration>20 yrs, chronic disability, corticosteroid use

two mechanisms: locally with alteration of cell membrane permeability and systemic inhibition of PG synthesis

inhibit cyclooxygenase and thereby decrease levels of prostaglandins which play a role mucosal protection

PGs normally increase bicarb and mucous production; enhance mucosal bloodflow; inhibit acid production; increase cell renewal and repair

analgesic effect may mask pain of an ulcer and contribute to later diagnosis Þ present with bleeding or perforation

if heavy NSAIDs must be used, a prophylactic drug should be used to prevent ulcers (PGE analogs, H₂ antagonists); NSAIDs associated with 3-6 fold increased risk of bleeding or death from peptic ulcer disease

(2) Helicobacter pylori

colonize only gastric-type mucosa; gastric metaplasia and metaplastic tissue in duodenum adjacent to ulcer sites

associated with Ý gastric secretion; lead to antibodies which cross-react with gastric mucosa

leads to development of mucosa-associated lymphoid tissue (MALT) in the stomach Þ lymphoma

H. pylori associated with: chronic gastritis; peptic ulcer disease; adenocarcinoma; malignant lymphoma of stomach

gram negative spiral rods present in 90% of DU patients and 70% of GU patients – in antrum

however, also present in 20-55% of normal population Þ H. pylori contributes to ulcers, but is not itself causative

higher prevalence in developing countries; higher prevalence among aged; fecal-oral transmission

non-invasive, live in mucous layer above the epithelium

pathogenesis: enzyme urease breaks urea into ammonia which is toxic; also cagA and vacA toxins Þ gastritis; resulting inflammation from toxins are damaging

therapy to kill H. pylori results in healing of ulcers and fewer recurrent ulcers than with other treatments

(3) Smoking and Alcohol

decreased PG and bicarb secretion; increased acid secretion; altered mucosal blood flow

smoking is associated with slower healing and greater risk of recurrent ulcers and Ý risk of complications

(4) Stress

can be related to physical stress (ischemia/reperfusion)
psychological stress has also been cited but no conclusive evidence

Treatment for Peptic Ulcers

anti-ulcer drugs are the first step (H₂ receptor antagonists)

upper endoscopy or upper GI series should be performed if symptoms are not alleviated

endoscopy can also be employed to spot and repair complications

hemorrhage: very common complication
stricture and obstruction: dilate with a balloon
perforation: hole in GI tract lead to GI emptying into peritoneum and peritonitis

requires emergency surgery

surgery:

The only reasons to do surgery on ulcers:

(1) hemorrhage
(2) perforation
(3) obstruction
(4) intractability
(5) recurrence after surgery

vagotomy: cut vagus to reduce acid secretion

Historical note: Surgeons used to cut the vagal nerve innervating the whole stomach. Though this solved the acid problem it also caused 15% of all patients to get the Dumping Syndrome (whereby all stomach contents get directly dumped into the duodenum). It was later realized that vagal innervation of the antrum had nothing to do with acidity but rather motility. By only cutting the branches in the upper parts of the stomach this problem was resolved.
side effects are: early satiety; decreased gastric peristalsis; rapid dumping of liquids; indigestible solids may accumulate in the stomach

antrumectomy: remove antrum and thereby remove most G-cells

reduced gastrin production Þ reduce acid

Billroth I (gastroduodenectomy): attach duodenum directly to stomach

Billroth II (gastrojejunostomy): close the end of the duodenum and attach the stomach to the jejunum

Gastritis

Acute

caused by chemicals and drugs or mucosal ischemia resulting from stress or shock
major characteristic is diffuse mucosal hemorrhages; also edema, ulceration, erosion

Chronic

much more common than acute gastritis

multifocal atrophic gastritis

most common form of gastritis in the world

often follows a cleared H. pylori infection

metaplastic change to mucous cells is common and may lead to adenocarcinoma

has components of both chronic (eosinophils, lymphocytes) and acute (neutrophils) inflammation

Þ chronic active inflammation

found primarily in antrum and body/fundus

autoimmune gastritis

result of autoantibodies to parietal cells
histologically similar to MAG
found primarily in body/fundus

hypertrophic gastritis

result of gastrin-producing tumors

Þ hyperplasia of mucosa Þ intense mucosal folding

Gastric Cancers

benign tumors: leiomyomas (neoplasm involving smooth muscle tissue) are the most common

most common in antrum and lesser curvature

malignant tumors may be polypoid, ulcerative, or infiltrative (limitus plastica)

infiltrative are impossible to diagnose with a surface biopsy Þ problematic

signet ring cells are characteristic

higher incidence in Japan and China than US

diet, H. pylori predispose, ulcers and antacids do not (except that antacids may promote H. pylori growth)

presents with pain, bleeding, obstruction, but often asymptomatic until late stages

metastasis through direct extension; lymphatics Þ Virchow’s node in left neck; hematogenous Þ liver; peritoneal seeding Þ Krukenberg tumor (ovarian)

tumors are often diagnosed at late stages and resection is necessary