Approximately one-third of the U.S. population is currently infected with Helicobacter pylori. Because of the organism’s wide spectrum of disease manifestations and its associated morbidity and mortality, considerable attention is focused on the diagnosis and treatment of this infection. This article summarizes our current understanding of H. pyloriand its radiologic implications.
is a senior medical student at the University of Pennsylvania
School of Medicine and
is Chief of the Gastrointestinal Radiology section in the
Department of Radiology at the Hospital of the University of
Pensylvania in Philadelphia, PA.
is arguably among the most prevalent infectious organisms of the
twentieth century. Since its discovery in 1983 by Warren and
this spiral, gram-negative rod has been implicated in numerous
disease processes, including gastritis, peptic ulcer disease, and
Because of the organism's wide spectrum of disease manifestations
and the associated morbidity and mortality, considerable attention
has been focused on the diagnosis and treatment of this infection.
This article will summarize our current understanding of
and its radiologic implications.
H. pylori gastritis
Approximately one-third of the U.S. population is currently
The prevalence of infection increases with age: More than 50% of
Americans over the age of 60 are
Nevertheless, the majority of infected persons are asymptomatic.
Infection is more common among lower socioeconomic groups.
Transmission is thought to be fecal-oral, oral-oral, or both.
Despite the high prevalence of
, infection rates in developed countries appear to be declining,
possibly because of improved sanitary conditions and better
infects the stomach, the organism colonizes and adheres to the
gastric epithelium but does not invade the mucosa.
Infection usually is confined to the gastric antrum but can also
involve the body or fundus, or even the entire stomach.
The ensuing gastritis is manifested histologically by early
neutrophilic infiltration, with subsequent predominance of plasma
cells and lymphoid nodules.
The acute inflammatory process is associated with parietal cell
failure and achlorhydria, presenting clinically as a mild vomiting
illness that quickly resolves.
In most cases, the organism subsequently colonizes the distal
stomach and duodenal bulb, while the proximal stomach returns to a
state of normal or even high acid output, placing the patient at
increased risk for peptic ulcer disease.
Other patients may develop a pangastritis that causes progressive
mucosal atrophy and intestinal metaplasia, decreasing the risk of
ulcers but increasing the risk of cancer.
usually can be eradicated from the stomach by a treatment regimen
consisting of antimicrobial agents (clarithromycin plus
metronidazole or amoxicillin) and a proton pump inhibitor (such as
However, in view of the high prevalence of
in the adult population, as well as the potential costs and side
effects associated with treating all
-positive persons, treatment is not currently recommended for
asymptomatic individuals with this infection. It is less clear
whether the large number of patients with dyspepsia who have no
endoscopic evidence of ulcers or tumor (so-called non-ulcer, or
functional, dyspepsia) should be treated with antimicrobial
therapy. In 1994, the NIH issued a consensus report stating that
there was not enough evidence to justify administration of
antimicrobial agents to
-positive patients with non-ulcer dyspepsia.
In 1997, however, another consensus statement from Europe supported
the use of antimicrobial therapy in these patients.
Two recent studies investigating the role of antimicrobial
-positive patients with non-ulcer dyspepsia also have yielded
conflicting data. McColl et al
found a statistically significant difference in the response of
-positive patients to antimicrobial therapy in comparison to
controls and concluded that all
-positive patients with non-ulcer dyspepsia should be treated with
antimicrobial as well as antisecretory agents. In contrast, Blum et
found no significant difference in the response of
-positive patients and controls to treatment with antimicrobial
therapy and concluded that eradication of
in these patients does not have a major role in improving symptoms.
Clearly, the controversy surrounding this organism and its role in
the development of non-ulcer dyspepsia is far from resolved.
H. pylori and peptic ulcer disease
is thought to have a major role in the development of peptic ulcers
not caused by nonsteroidal anti-inflammatory agents,
Zollinger-Ellison syndrome, or other hypersecretory states.
In various studies,
has been found to have a prevalence of 60 to 80% in patients with
gastric ulcers and 95 to 100% in those with duodenal ulcers.
The mechanism of ulcer formation is uncertain, but in the case
of duodenal ulcers,
gastritis may lead to increased gastrin production and subsequent
gastric metaplasia in the duodenum.
Such patients are more susceptible to colonization of the duodenum
, resulting in a weaker mucus barrier and a higher frequency of
ulcers in the metaplastic epithelium.
Whatever the pathogenesis, studies have shown that eradication
with antimicrobial and antisecretory therapy leads to more rapid
healing of both gastric and duodenal ulcers, as well as a lower
rate of ulcer recurrence and rebleeding when compared to
antisecretory therapy alone.
As a result, both the NIH and European consensus panels concluded
-positive patients with gastric or duodenal ulcers should be
treated with a combined regimen of antimicrobial and antisecretory
H. pylori and gastric cancer
Gastric carcinoma is the second most common malignant tumor in
the world, accounting for 750,000 deaths annually.
Recent data have strongly implicated
gastritis in the development of this cancer, particularly the
intestinal type of adenocarcinoma.
In one study, Parsonnet et al found that persons who were
were three times more likely to develop gastric carcinoma within 24
years than age-matched controls.
It has been postulated that childhood infection with
increases the risk of malignant transformation as a result of
decades of inflammation and long-term exposure of dividing stem
cells to various mutagens.
Considerable evidence exists demonstrating that chronic
infection initiates the sequence of events from atrophic gastritis
to intestinal metaplasia and dysplasia to, eventually, gastric
Despite the strong association between
and gastric cancer, fewer than 1% of those with
gastritis ever develop gastric carcinoma.
In view of the large number of infected persons who never develop
cancer, the cost and side effects of drug therapy, and the risk of
developing antibiotic-resistant strains of the organism, widespread
and eradication therapy do not appear to be warranted at the
In the future, a promising approach for eradication of
and prevention of gastric cancer might involve the development of
H. pylori and malt lymphoma
In 1983, Isaacson and Wright proposed the concept that low grade
B-cell gastric lymphomas arise from mucosa-associated lymphoid
There is now considerable evidence that these gastric MALT
lymphomas almost always occur in patients with underlying
Although the stomach is normally devoid of lymphoid tissue, chronic
antigenic stimulation by
infection may lead to the acquisition of organized lymphoid
follicles in the lamina propria of the gastric mucosa.
gastritis is then thought to trigger the development of these low
grade MALT lymphomas by causing autonomous proliferation of a
monoclonal population of plasma B-cells.
Because of the role of
in the pathogenesis of gastric MALT lymphomas, considerable
attention has recently been focused on the exciting possibility of
effecting a cure by
eradication rather than combinations of chemotherapy, radiation, or
surgery. In numerous studies, treatment of gastric MALT lymphoma
with various antibiotic regimens has led to complete regression of
these tumors, with success rates reported to be as high as 80%.
eradication is essential for cure, as untreated low grade MALT
lymphomas may undergo blastic transformation, eventually
progressing to aggressive, high grade gastric lymphomas.
i has therefore been advocated as the first line of treatment for
gastric MALT lymphoma.
Diagnosis of H. pylori gastritis
--Histologic examination of endoscopic biopsy specimens has been
considered the gold standard
for the diagnosis of
The organism can be demonstrated on biopsy specimens using
hematoxylin-eosin, Giemsa, and Warthin-Starry stains.
gastritis often has a multifocal distribution, it is important to
obtain multiple biopsy specimens from different areas of the
stomach in order to decrease the false-negative rate from sampling
Endoscopic biopsy specimens have a reported overall sensitivity
of 95% for the detection of
Alternatively, the organism's urease activity and ammonia
production can be used to identify
on tissue specimens via the rapid urease test, which has both a
sensitivity and specificity of 95% for detecting the organism.
Although tissue cultures have a sensitivity of 90% and a
specificity of 100%,
they are not routinely obtained because of the high cost and high
operator dependence of this technique.
--Noninvasive tests for
, such as the serologic
and urea breath tests, have increasingly been employed for routine
this infection. Advantages of these noninvasive tests include their
widespread availability, lower costs, and decreased procedural
risks when compared to endoscopy. Serologic techniques consist of
the rapid whole blood and ELISA tests; both of these tests have
sensitivities and specificities ranging from 90 to 95%.
However, serologic testing is less helpful after eradication
therapy, as anti-
IgG antibody levels cannot differentiate active from remote
infection and can take months to decline after the organism has
The urea breath test appears to be the best noninvasive
diagnostic test for
in terms of accuracy and cost. When
is present in the stomach, its urease activity causes hydrolysis of
C-13 or C-14 radiolabeled urea, which is excreted in exhaled breath
in the form of measurable quantities of radiolabeled CO
Although the NIH consensus conference reported the possibility of
false-negative results in patients receiving antibiotics or proton
pump inhibitors, the C-14 urea breath test is reported to have a
sensitivity and specificity of greater that 95%, making it
extremely suitable for clinical practice.
--In recent years, various radiographic features of
gastritis have been documented on double-contrast upper
gastrointestinal examinations. In the largest retrospective study
to date, Sohn et al
found that a significantly greater percentage of patients with
gastritis had thickened gastric folds (i.e., greater than 5 mm in
diameter) than controls (figure 1). Thickened folds were most
common in the antrum but were also found in the proximal stomach or
the entire stomach. Although thickened folds are a nonspecific
finding that can be associated with a variety of inflammatory or
even neoplastic conditions, Sohn et al concluded that this was the
single most useful criterion for identifying
Although less common, polypoid gastritis with markedly
thickened, lobulated folds also was found in a significantly
greater percentage of patients with
than controls and was considered to be another useful sign of
gastritis (figure 2).
However, polypoid folds can also be found in patients with lymphoma
or other neoplasms. In such cases, endoscopy and biopsy are
required to confirm the presence of
and rule out a malignant tumor as the cause of this finding.
Additionally, Sohn et al found enlarged areae gastricae (i.e., 3
mm or greater in diameter) to be another sign of
gastritis (figure 3). In fact, it was suggested that the
combination of thickened folds and enlarged areae gastricae has the
greatest diagnostic yield for this infection.
In another review, by Gelfand and Ott, gastric erosions, antral
narrowing, and inflammatory polyps were considered to be findings
These authors also suggested that
duodenitis may be manifested by thickened folds (greater than 4 mm
in diameter), nodules, or erosions in the duodenum. When
infection is suspected on the basis of any of these findings, it is
the responsibility of the radiologist to inform the primary care
provider of the possibility of
in the final report.
Recent data suggest that low grade gastric MALT lymphomas
sometimes are manifested by characteristic findings on
double-contrast studies. Levine et al reported a patient with
gastric MALT lymphoma in whom a barium study revealed innumerable
tiny nodules throughout the stomach.
Subsequently, Yoo et al reported four patients with MALT lymphomas
manifested by multiple, rounded, often confluent nodules varying
from 2 to 7 mm in diameter (figure 4).
A similar appearance could be caused by severe gastritis with
enlarged areae gastricae, leukemic infiltration, or even a
polyposis syndrome. Nevertheless, this radiographic finding should
raise concern about the possibility of gastric MALT lymphoma.
Because it is a curable disease, endoscopic biopsy specimens should
be obtained whenever MALT lymphoma is suspected on barium
Given the variety of options currently available for the
gastritis, we are no longer limited to endoscopy, an expensive,
inconvenient, and invasive test for evaluating an extremely common
clinical problem. In today's managed care environment, less costly
and less invasive procedures such as the urea breath test and
serologic testing have increasingly been employed to detect this
infection, making routine endoscopy for dyspepsia unnecessary. The
double-contrast upper gastrointestinal examination also is a useful
test in these patients, particularly when performed in conjunction
with other noninvasive tests for
The following is one possible scenario for evaluating patients
with dyspepsia in the future. A patient with recent onset of
symptoms that are unresponsive to empirical medical therapy could
undergo a double-contrast upper gastrointestinal examination. If a
benign-appearing gastric or duodenal ulcer is demonstrated at
fluoroscopy, the barium study can be followed by a noninvasive test
. If positive, the patient could then be treated with a regimen
that includes antimicrobial and antisecretory agents. If the barium
study reveals gastritis or duodenitis without evidence of ulcer
disease, the patient is presumed to have non-ulcer dyspepsia, a
condition which is not currently thought to warrant treatment with
antimicrobial agents. In this case, no further testing for
would be required. Finally, if the barium study reveals polypoid
gastritis, malignant-appearing ulcers, or any suspicious findings,
endoscopy and biopsy should be performed to rule out malignant
tumor. Such an approach would allow treatment of dyspepsia with the
least amount of discomfort, inconvenience, and risk to the patient.
In the future, further investigation hopefully will allow us to
better define appropriate management of patients with non-ulcer
dyspepsia who are infected with
. Such trials may ultimately show that eradication of
is warranted in all symptomatic patients with this infection. As
the role of
in the development of gastric carcinoma also is better clarified,
it may eventually be deemed cost effective to prophylax all
-positive persons with antibiotics or even a vaccine against this
potentially fatal illness. Despite the recent information explosion
, much is still unknown. However, it seems likely that the
importance of and our curiosity about this unique organism will
carry us well into the next millennium.
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