NEWS & VIEWS
further clinical investigation and manage‑
ment. In symptomatic children, small-bowel
biopsy can be omitted if anti-TG2 antibody
levels are more than 10 times the upper limit
of normal for the assay used and if anti-
EMA and HLA-DQ2 and/or HLA-DQ8
testing shows a positive response. In symp‑
tomatic patients who do not fulfill these
criteria and in asymptomatic children, an
endoscopic examination of the upper small
intestine is recommended. This procedure
can include mucosal biopsies from the duo‑
denal bulb and the second or third portion
of the duodenum to confirm a diagnosis
of celiac disease. In addition, it can also
identify children with non­continuous duo‑
denal enteropathy or only bulbar lesions.
Furthermore, Husby et al.5 propose a simple
scoring system for the diagnosis of celiac
disease that includes the following para­
meters: symptoms, celiac-disease-specific
antibody levels, HLA-typing and findings
from small-bowel histology.
Presentation of these guidelines at the
annual ESPGHAN meeting in Sorrento,
Italy, May 2011, gave rise to lively discus‑
sion in the audience, in which the idea of a
diagnostic procedure without small-bowel
biopsy was questioned. In view of the fact
that reliable serological tests that are specific
to celiac disease are now available and that
limited health-care resources should be used
rationally, the guidelines proposed seem
reasonable. They rest on a solid basis, con‑
sidering the thorough review of the literature
presented by Husby and co-workers.5 These
new ESPGHAN guidelines will certainly
have an influence on the diagnostic work-up
of children with suspected celiac disease.
Fewer small-bowel biopsy procedures will
reduce health-care costs and the burden to
the patient and clinician. However, as the
authors rightly emphasize, this new diagnos‑
tic procedure should be carefully followed-up
in future prospective studies. These studies
should preferably be carried out with inter‑
national cooperation between national
childhood celiac disease working groups.10
Department of Pediatrics, Linköping University,
Norrköping Hospital, Norrköping, SE 601 82,
Sweden (L. Högberg, L. Stenhammar).
Correspondence: L. Stenhammar
larsstenhammar@yahoo.com
Competing interests
The authors declare no competing interests.
1. Di Sabatino, A. & Corazza, G. R. Coeliac
disease. Lancet 373, 1480–1493 (2009).
2. Zawahir, S., Safta, A. & Fasano, A. Pediatric
celiac disease. Curr. Opin. Pediatr. 21,
655–660 (2009).
128 | MARCH 2012 | VOLUME 9  www.nature.com/nrgastro
3. Mustalahti, K. et al. The prevalence of celiac
disease in Europe: Results of a centralized,
international mass screening project. Ann.
Med. 42, 587–595 (2010).
4. Myléus, A. et al. Celiac disease revealed in 3%
of Swedish 12‑year‑olds born during an
epidemic. J. Pediatr. Gastroenterol. Nutr. 49,
170–176 (2009).
5. Husby, S. et al. European Society for Pediatric
Gastroenterology, Hepatology, and Nutrition
guidelines for the diagnosis of coeliac disease.
J. Pediatr. Gastroenterol. Nutr. 54, 136–160
(2012).
6. Meeuwisse, G. W. Diagnostic criteria in coeliac
disease. Acta Paediatr. Scand. 59, 461–463
(1970).
CLINICAL GUIDELINES
Secondary prevention of gastric
cancer
Massimo Rugge, Matteo Fassan and David Y. Graham
The natural history of ‘epidemic’ intestinal-type gastric cancer provides
consistent data that enable clinicians to design multidisciplinary
strategies for secondary prevention. A recent paper by Dinis-Ribeiro et al.
reports guidelines for the management of patients with precancerous
stomach lesions.
Rugge, M. et al. Nat. Rev. Gastroenterol. Hepatol. 9, 128–129 (2012); published online 14 February 2012;
doi:10.1038/nrgastro.2012.19
The second half of the 20th century saw the
elucidation of the gastric oncogenic cascade,
which culminates in gastric cancer.1 Culture
of Helicobacter pylori established that this
bacterium was the most common cause of
active chronic gastritis, peptic ulcer and
gastric cancer.2 Although environmental
factors seem to be the main causes of these
diseases, host-related immunological mech‑
anisms could have a role in modulating the
severity of the gastric disease.3,4 This clini‑
cobiological information has been slow to
diffuse into the medical community, and it
has only just begun to have a major effect on
the daily practice of clinicians and patholo‑
gists. However, a number of conclusions
have been reached that can, and should,
directly affect clinical practice.
Most intestinal-type (so-called epidemic)
gastric cancers develop in a cancerization
field consisting of mucosal inflammation
and atrophy (that is, atrophic gastritis).1
In theory, categorizing patients in terms
of their risk of developing gastric cancer
should enable clinicians to provide the
most appropriate patient care. As gastritis,
particularly H. pylori-associated gastritis,
is a progressive disease, it is important to
stratify risk in terms of its reversibility or
© 2012 Macmillan Publishers Limited. All rights reserved
7. [No authors listed]. Revised criteria for
diagnosis of coeliac disease. Report of Working
Group of European Society of Paediatric
Gastroenterology and Nutrition. Arch. Dis. Child.
65, 909–911 (1990).
8. Wolters, V. M. et al. Is gluten challenge really
necessary for the diagnosis of coeliac disease
in children younger than age 2 years? J. Pediatr.
Gastroenterol. Nutr. 48, 566–579 (2009).
9. Högberg, L. & Stenhammar, L. Celiac disease.
Diagnosis criteria in young children. Nat. Rev.
Gastroenterol. Hepatol. 6, 447–448 (2009).
10. Ivarsson, A., Högberg, L. & Stenhammar, L. The
Swedish Childhood Coeliac Disease Working
Group after 20 years: history and future. Acta
Paediatr. 99, 1429–1431 (2010).
stabilization. In addition, cancer risk par‑
allels the degree and extent of atrophy. 3,4
A recent paper by Dinis-Ribeiro and col‑
leagues5 has addressed the secondary pre‑
vention of gastric cancer and the ‘what to
do’ problems in patient management.
Chronic gastric mucosal inflamma‑
tion triggers a combination of molecular
and phenotypic derangements that might
result in an absolute loss of resident glands
and/or the development of a new gland
phenotype (that is, metaplastic glands),6
which results in atrophy. In a subsequent
step, meta­plastic epithelia might undergo
dedifferentiation, resulting in a new cell
population that exhibits histologically
unequivocal neo­plastic transformation but
with no evidence of stromal invasion, which
is termed intraepithelial neoplasia (IEN).6
Upon acquisition of the capacity for stromal
intrusion, IEN results in cancer.
Depending on the nature of the glands
undergoing metaplasia, their transforma­
tion gives rise to different metaplastic
pheno­t ypes. 6 Pseudo-pyloric metaplasia
arises in oxyntic (corpus) glands, the origi‑
nal morphology of which changes into a
mucosecreting phenotype (corpus mucosa
antralization). Intestinal metaplasia might