Peptic duodenal ulcer

History (1)
Diocles

of Carystos (350 b.c.) - melancholic gassy

illness originating in the stomach (Yamada et al.)

Marcello

Donati first gastric ulcer (1586)

1975

China - 60 year old man with prepiloric

perforated ulcer (167 b.c.)
1688 - Muralto first ulcer description
1727 C. Rawlison first gastric perforation
1746

G. Hamberger - first duodenal perforation

History (2)
1881

Rydigier first gastric resection for

ulcer
1884

Mikulicz first attempt of suturing a

peptic ulcer perforation

1912

Bircher vagotomy in ulcer

surgery

1943

- L. Dragsted and H. Owens

troncular vagotomy

Definition
A breach,

mostly circumscribed of the

gastric or duodenal wall beyond
muscularis mucosae.

Erosion

mucosa

a breach limited only to the

Classification
Gastric
Duodenal:
Bulbar
Postbulbar

Anastomotic
Stress

ulcer (Curling or Cushing ulcers, in

sepsis)

Endocrine

ulcer (Zollinger-Ellison)

Classification
Histology

Acute
Chronic

Classification of benign gastric

ulcers (after Johnson, 1957)
Acute superficial:
Single or multiple ('erosions')
Chronic:
Type I, usually lesser curve
Type II, combined with duodenal ulcer
Type III, prepyloric

Type IV, proximal stomach <2 cm from oesophageal junction

Epidemiology 1
5-10%

in western world (300.000 new

cases in USA)
The 1-year point prevalence of active
gastric and duodenal ulcer in the United
States is approximately 1.8%
In 1998, it was estimated that there were
6.8 million cases of PUD in the United
States, representing a prevalence rate of
2490 cases per 100,000 persons.

Epidemiology 2
Duodenal/gastric

ulcer ratio is variable

Male:Female ratio=2-1 (clasically 4(6)-1)
More than 75% of patients with PUD are
of working age (18 to 65 years)

Stomach, gross and histology

From http://www.training.seer.cancer.gov

Anatomy

Vascularization

Nyhus et al.

Vagus nerve
into the
abdomen Testut

Inervation

Nyhus et al.

Lymphatics

Nyhus et al.

Gastric secretion

Gastric secretion regulation

Gastric secretion regulation

Nyhus et al.

Ohne magensaft kein peptisches geschwr K. Schwartz, 1911

Pathogenesis (1)
Gastric

secretion changes in peptic ulcer

patients
Increased BAO (normal: 0-10 mmol/hr)
Nocturnal increase of gastric output
Increased PCM
Exagerated response to stimuli (hystamine),

hypoglicemia, mechanical stimuli

Hypervagotony
Anomalous gastric secretion inhibition (secretin)

Pathogenesis (2)
Gastric

secretion regulation changes:

High output of gastrin as a response to

different stimuli
Anomalous negative feed-back of gastric

secretion gastrin-mediated
Somatostatin secretion inhibition

Pathogenesis (3)
Duodenal

mucosa changes in peptic ulcer

patients:
Prostaglandins deficit
Bicarbonate deficit
Diminished duodenal mucus
Helicobacter pylori (metaplasia)

Pathogenesis (4)

Genetics

Environment
NSAID
Smoking
Stress
Drugs (cocaine, crack)

Helicobacter pylori

Alimentary (alcohol etc.)

Helicobacter pylori
1975 - Howard Steer
1989 - J. R. Warren, B. J. Marshall
In 40-60% of western population
100% in tropics and the third world
More frequent in urban aria

Helicobacter pylori
Coco-bacil

Gram negative with multiple

enzymes
50%

are producing Vac A

cag A

higher virulence

Helicobacter pylori - genome

S SUERBAUM, M.D.,P MICHETTI, M.D. - N Engl J Med, Vol. 347, No. 15,2002

Click to edit Master text styles

Second level
Third level
Fourth level
Fifth level

H. pylori
interaction
S SUERBAUM, M.D.,P
MICHETTI, M.D. - N Engl J
Med, Vol. 347, No. 15,2002

Helicobacter pylori

Cliodna A M McNulty, Judith I Wyatt - Helicobacter pylori J Clin Pathol 1999;52:338-344

Helicobacter pylori

Helicobacter pylori
Produces

hypergastrinemia and
hyperacidity (hypotheses):
Inhibitory protein synthesis acting on gastrin

releasing cells
Direct inhibition of somatostatin

Helicobacter pylori

Direct disruption of mucosa and influencing

cytokines or of the phospholipase

Activating the macrophages, TNF (Tumor

Necrosis Factor), IL1 synthesis, and oxygen
free radicals;

Autoantibodies production

Ulcer equation
NS AID
Ge ne tic
fac to rs

H. pylo ri

S tre s s

Cirrho s is

S mo king

S mo king

Mucus

MEN

Epithelium

Clorhidro-peptic
secretion

Bicarbonate secretion
Vascularization

ulcer

Click to edit Master text styles

Second level
Third level
Fourth level
Fifth level

H. pylori infection natural history - S SUERBAUM, M.D.,P MICHETTI, M.D. - N Engl J

Med, Vol. 347,No. 15,2002

Morfopatholoy
Microscopy

(Askanazy) 4 strata

Exudative - detritus, fibrin, germs or even

yeasts
Necrosis (fibrinoid) with inflammatory

infiltrate (active region)

Granulation strata
Fibrosis

Pathology (1)

Pathology (2)

Clinical signs
Pain
Periodicity
Aching

(with meals and seasonal)

pain

Vomiting
Habitus

Essentials of diagnosis
Epigastric

pain relieved by food or antacids.

Epigastric

tenderness.

Normal

or increased gastric acid secretion.

Signs

of ulcer disease on upper

gastrointestinal x-rays or endoscopy.

Evidence

of Helicobacter pylori infection.

Lab&explorations
Laboratory
Gastrin in serum (normal < 100 pg/mL) over

200 pg/mL in Zollinger-Ellison syndrome

Secretory tests (no longer in use)

Lab&explorations
Endoscopy

is the principal method of

diagnosis, as it enables biopsies to be
taken to exclude malignancy in gastric
ulcers, and to do a rapid urease test or
histological examination for Helicobacter.

Endoscopy
On open-access endoscopy for 'dyspepsia',
about 12% per cent of patients have
duodenal ulcer and 3% gastric ulcer, but the
numbers and ratios vary with age.
Every gastric ulcer should be suspected of
being malignant until proved benign by
multiple biopsies and complete endoscopic
healing.

Radiology

Radiographic studies
Deformities

and an ulcer niche.

Inflammatory

swelling and scarring may

lead to distortion of the duodenal bulb,
eccentricity of the pyloric channel, or
pseudodiverticulum formation.

The

ulcer itself may be seen either in

profile or, more commonly, en face.

Helicobacter pylori testing

Noninvasive
14C breath test
Serology
Stool antigen determination

Endoscopy
Direct examination and test
Cultures
Cliodna A M McNulty, Judith I Wyatt
- Helicobacter pylori J Clin Pathol
1999;52:338-344

Cliodna A M McNulty, Judith I Wyatt - Helicobacter pylori J Clin Pathol

1999;52:338-344

Cliodna A M McNulty, Judith I Wyatt - Helicobacter pylori J Clin Pathol

1999;52:338-344

Detection and Treatment of Helicobacter pylori

Infection in Adult Patients

Peptic ulcer evolution

Recurrence
Complications
Hemorrhage
Perforation
Penetration
Stenosis
Malignancy (only for gastric ulcers)

Zollinger-Elison syndrome
Zollinger

and Ellison defined the syndrome that

now bears their names 1955

Triad

of

severe ulcer disease,

gastric acid hypersecretion, and
non-beta islet cell tumors of the pancreas

0.1

to 1% of patients with peptic ulcer disease

Gastrinomas: Origin and

Classification
One

third (15% to 77% in different studies) of patients

with gastrinomas have multiple endocrine neoplasia
type 1 (MEN-1)

MEN-1

is an autosomal dominant genetic disorder

associated with a high degree of penetrance

Patients

with MEN-1 may have involvement of all three

organs (parathyroids, pancreatic islets, and pituitary)

Zollinger-Elison syndrome
The

tumor may be single or multiple and

can range in size for less than 1 cm to
more than 3 cm.

When

associated with MEN-1, studies

suggest that gastrinomas are usually
multiple and commonly found within the
duodenum and pancreas

Diagnostic
Difficult

to find

Serum gastrin over 200 pg/ml

Secretin provocative test
US
CT-scan
EUS
Angiography with sampling
MRI
Portal venous sampling for serum levels of gastrin
IOUS

Treatment
Medical
PPI large doses
BAO measuring

Surgical
Tumor excision, or
Total gastrectomy, and
Metastazis treatment

Upper digestive hemorrhage

Definition
Hematemesis vomiting blood
Melena the passage of black, tarry stools composed

largely of blood that has been acted on by gastric juices,

indicative of bleeding in the upper digestive tract.
Hemochezia red blood in stools
Rebleeding - hematemesis and/or melena with shock

(pulse>100b/min, CVP drop of 5 mm Hg or drop in HGB

level with 2g. Confirmation needs endoscopic
reevaluation

Upper digestive hemorrhage

Diagnostic

Ulcer

35-50

Erosions (ulcerations)

8-15

Esophagitis

5-15

Varices (gastroesophageal)
Mallory-Weiss syndrome

5-15
15

Malignancy

Vascular malformation

Rare

65
After British Society of Gastroenterology Gut 2002;51(suppl.
IV):iv1-iv6

Bleeding risk (endoscopic

assessment)
Sign

% of rebleed

Arterial bleeding

90

Visible vessel

50

Fresh clot in ulcer crater

25

Small bleeding without vessel

<20

Dark spot, red spot

<10

Freeman ML The current endoscopic diagnosis and intensive care unit management of
severe ulcer and non-variceal upper gastrointestinal hemorrhage Gastrintest Endosc Clin
North Am 1991, 1:229
66

Hemorrhagic ulcer

Forrest tip IIb

Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed.

Hemorrhagic ulcer

Ulcer perforation (1)

Brutal

debut

Severe

generalized abdominal pain

Shock
Loss

of bowel sounds

Board-like

rigidity of the abdominal wall

Feldman: Sleisenger & Fordtran's

Gastrointestinal and Liver Disease, 8th ed.

Ulcer perforation (2)

Diagnostic

(Mondor triad)

Pain (specific characteristics)

History for ulcer or dispepsia
Guarding or, more frequently abdominal wall

rigidity

Ulcer perforation (3)

Radiology (pneumoperitoneum) in 50-75% of

cases
Administration of oral soluble radiographic

contrast may demonstrate a leak.

Barium studies should be avoided when

perforation is suspected.
Endoscopy should not be performed.
In rare cases, urgent laparotomy is required to

make the diagnosis.

Pneumoperitoneum

Ecografie evideniind pneumoperitoneu

Stenosis (gastric outlet syndrome)

Gastric

outlet obstruction is the least common

complication of peptic (pyloric channel or duodenal)
ulcer disease (classically 1-3%).

Two

stages:

Functional (edema and inflammation surrounding an acute

ulcer, especially in the antrum or pyloric channel)

Organic (scarring with fibrosis and outlet narrowing)
Sistolic phase
Asistolic phase

Gastric outlet syndrome

Postprandial

epigastric fullness, early satiety,

and vomiting of materials ingested hours to
days previously.

Vomiting

may be worse toward the end of

the day.
If

gastric outlet obstruction is chronic,

patients may develop hypochloremic
alkalosis, tetany, weight loss, and, rarely,
aspiration pneumonia.

Gastric outlet syndrome

A succussion

splash may be audible on

physical examination.

The

diagnosis may be confirmed using

radiographic (barium), endoscopic, or
scintigraphic (gastric-emptying) studies

Gastric outlet syndrome treatment

Nasogastric

tube to fully evacuate the

stomach
Intravenous

replacement of fluid and

electrolytes is imperative

Intensive

antisecretory therapy with

intravenous H2RAs or proton-pump
inhibitors should be given to reduce
nasogastric fluid losses and to promote ulcer
healing

Gastric outlet syndrome treatment

Patients

with chronic obstruction and signs of malnutrition

should be given parenteral nutrition.

Upper

GI study using water-soluble contrast - after 72 hours

of gastric decompression.

About one-half to two-thirds of patients fail to improve after

5-7 days of gastric aspiration.

Up

to 90% of cases of gastric outlet obstruction will come to

either surgical or endoscopic dilatation within 1 year.

Treatment
Drugs
Antiacids
Cytoprotective agents - Sucralfate is a complex sucrose salt in

which the hydroxyl groups have been substituted by aluminum

hydroxide and sulfate. This compound is insoluble in water and
becomes a viscous paste within the stomach and duodenum,
binding primarily to sites of active ulceration.

Adverse effects - chronic renal insufficiency to prevent aluminum-

induced neurotoxicity. Hypophosphatemia and gastric bezoar

formation have also been rarely reported. (1 g four times per day)

Anticholinergics

Designed to inhibit activation of the muscarinic

receptor in parietal cells, met with limited
success due to their relatively weak acidinhibiting effect and significant side effects (dry
eyes, dry mouth, urinary retention).

Bismuth-containing compounds
Colloidal

bismuth subcitrate (CBS) and

bismuth subsalicylate (BSS, PeptoBismol)

Long-term

usage with high doses,

especially with the avidly absorbed CBS,
may lead to neurotoxicity. These
compounds are commonly used as one of
the agents in an anti-H. pylori regimen

Prostaglandin analogues
Prostaglandin

analogues enhance mucous

bicarbonate secretion, stimulate mucosal
blood flow, and decrease mucosal cell
turnover.

Misoprostol

is contraindicated in women who

may be pregnant, and women of
childbearing age must be made clearly
aware of this potential drug toxicity. (200 ug
four times per day)

H2 receptor antagonist
Four

of these agents are presently

available (cimetidine, ranitidine,
famotidine, and nizatidine), and their
structures share homology with histamine.

Presently,

this class of drug is often used

for treatment of active ulcers (4 to 6
weeks) in combination with antibiotics
directed at eradicating H. pylori

Proton pomp inhibitors

Omeprazole,

esomeprazole,
lansoprazole, rabeprazole, and
pantoprazole are substituted
benzimidazole derivatives that covalently
bind and irreversibly inhibit H+,K+ATPase.

Treatment
Goal

- relief of symptoms (pain or

dyspepsia), promote ulcer healing, and
ultimately prevent ulcer recurrence and
complications.

PPI, proton pump

inhibitor; RBC,
ranitidine bismuth
citrate;
R, metronidazole 400
mg, used adequately
in many countries - P.
MALFERTHEINER et
al. consensus
Maastricht 2 i 3
2000 i 2005

Hemorrhagic ulcer therapy

Vasopressors
Endoscopy
Surgery

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Second level
Third level
Fourth level
Fifth level

Surgery
Absolute

indications

Major hemorrhage
Perforation
Stenosis

Treatment

Relative indications
Repeated hemorrhage
Penetration
Arterial hypertension in hemorrhagic ulcer patients
Portal hypertension
Postbulbar ulcer
Multiple ulcers
Zollinger-Ellison syndrome
Professional risk patients

Surgery - goals
Excision

of the lesion

Lowering

pH (obtain an hypoacid

stomach)
Redo

the continuity of the digestive tract

Vagotomia- variante
Vagus nerves anatomy and
vagotomy types
VP posterior vagus, VA
anterior vagus, R. H-B hepatobiliary r., R. C. celiac r., N.A.M.C.
Lesser curvature anterior nerve
(Latarjet),
N.P.M.C. great curvature
anterior nerve, VT troncular
vagotomy, VS selective
vagotomy, VSS parietal cell
vagotomy (limit - 5-7 cm)

Posterior troncular
vagotomy with
anterior seromiotomy
(Taylor)

Pyloroplasty

Nyhus et al.

Suturing a
perforated
duodenal ulcer

Nyhus et al.

Hemostasis in situ

Nyhus et al.

Gastric resection (R),

hemigastrectomy (H) and antrectomy
(A);
a. Gastroduodenoanstomy (PanBillroth I),
b. Gastrojejunostomy - Billroth II

Billroth II operation and some of its modifications. (From Soybel DI, Zinner MJ: Stomach and duodenum:
Operative procedures. In Zinner MJ, Schwartz SI, Ellis H [eds]: Maingot's Abdominal Operations, vol I, 10th
ed. Stamford, CT, Appleton & Lange, 1997.)

JA Myers, JW Millikan, TJ Saclarides - Common Surgical Diseases, Springer 2008