gastritis
Korstanje, A.
Citation
Korstanje, A. (2006, June 26). The serological gastric biopsy in primary care : studies on atrophic gastritis. Retrieved from https://hdl.handle.net/1887/4443
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Chapter V I I
Beauty is in the eye of the beholder.
Chapter VII
Short-term proton pump inhibitor administration in the non-inv asiv e diag nosis of the g rade of atrophic
c orpus g astritis
A. Korstanje 1, S .v an E ed en2, G .J .A.O fferh au s2, G .d en H artog3, I . B iem ond 4, C .B .H .W . L am ers 4
Keywords: A tro phic c o rpu s g as tritis , P ro to n pu m p in hib ito r s tim u latio n tes t, P eps in o g en , G as trin
A b s t r a c t
B a c k g rou n d: P roton p u m p inh ib itor ( P P I ) ad m inistration is k now n to b e a p o- tent p ep sinog en- releasing stim u lu s in h ealth y v olu nteers. P ep sinog en A lev el d ec reases in p atients w ith atrop h ic c h ang es in th e g astric c orp u s. A d ec reased seru m p ep sino- g en A resp ons to P P I, as a m ark er of an im p aired ox y ntic c h ief c ell fu nc tion, m ay b e u sed as a refined atrop h y test of th e ox y ntic m u c osa.
A im : T o v erify th e h y p oth esis th at in p atients w ith atrop h ic c orp u s g astritis P P I- in- d u c ed inc rease of p ep sinog en A is inv ersely c orrelated w ith th e g rad e of atrop h y .
P a t ien t s: S tu d y su b jec ts w ere 25 p rim ary c are p atients w ith serolog ic al atrop h ic c orp u s g astritis ( 12 M , 13 F , m ean ag e 6 7 y ears, rang e 31- 9 3) , ou tc om e of a c om m u - nity b ased ex p lorativ e stu d y .
M et h ods: After ob taining p re- treatm ent fasting sera and b iop sy sp ec im ens v ia u p - p er end osc op y , esom ep raz ole w as ad m inistered to all 25 p atients d u ring 2 w eek s, 40 m g d aily . T h e g rad e of atrop h y in th e b iop sy tissu e sp ec im ens w as assessed ac c ord ing to th e u p d ated S y d ney sy stem . An after- treatm ent fasting b lood sam p le w as c ollec ted for ev alu ation of seru m p ep sinog ens and g astrin lev els. F inally , th e seru m p ep sinog en A- resp ons to P P I w as related to th e h istolog y of eac h p atient.
R esu lt s: At p re- treatm ent testing , 20 of th e 25 p atients ag ain fu lfilled th e c riteria of
1G eneral p rac tic e ’s- G rav enp old er, T h e N eth erland s
2D ep artm ent of P ath olog y , Ac ad em ic M ed ic al C entre, Am sterd am , T h e N eth erland s
3D ep artm ent of G astroenterolog y , R ijnstate H osp ital Arnh em , T h e N eth erland s
4D ep artm ent of G astroenterolog y , L eid en, U niv ersity M ed ic al C entre, T h e N eth erland s
serological atrophic corpus gastritis. Pre-treatment histological examination of corpus biopsies of the whole group revealed 13 patients with severe, 6 with moderate and 1 pa- tient with mild gastric body atrophy. One patient had no corpus biopsies. After 2 weeks PPI-administration the 19 patients with moderate to severe atrophic body gastritis showed negligible increase in pepsinogen A serum level (mean preentry level 4.7 µg/l and post-PPI 4.9 µg/l, p > 0.05) and 1 patient with mild atrophy showed slight in- crease in pepsinogen A concentration (preentry 16, vs post-PPI 26). Post-PPI serum gas- trin levels had no additional diagnostic value in grading gastric body atrophy. As ex- pected, 4 patients with normal serum profile showed in the biopsies no gastric corpus atrophy. After PPI-administration they had significant, three- to fourfold, increase of the concentrations of pepsinogen A and a marked increase of serum gastrin from nor- mal baseline (p < 0.05).
Conclusion: PPI-stimulated increase of pepsinogen A in patients with atrophic corpus gastritis has an inverse relation with the grade of atrophy (r = - 0.79, p < 0.001).
Stimulated pepsinogen A response to PPI can therefore be used as a marker for the severity of atrophic body gastritis.
I n t ro d u c t i o n
Since the recognition of gastric atrophy in 1870 – in post-mortem samples from a patient w ith pernicious anaemia – much attention and research hav e been d ev oted to d ecipher its und erlying pathophysiology( 1). T he biological back ground of the d ev elopment of gastric atrophy is still incompletely und erstood . Chronic atrophic gastritis is a multifactorial cond ition, caused by the interplay betw een a genetic set- up, gastric bacterial infection, and env ironmental factors( 2 -6 ). Atrophic gastritis is consid ered to be a preneoplastic lesion( 7-9 )and therefore reliably d iagnosing and grad ing of gastritis and mucosal atrophy is an important health issue.
Gastric end oscopy w ith biopsy is the typical d iagnostic method to d etermine at- rophic gastritis, but this is not d one routinely in patients w ithout gastric cancer.
Its principal use is to rule out the presence of cancer rather than to d etermine the presence and ex tent of atrophic gastritis.
Serum pepsinogen A and C hav e become popular as ind icators of atrophic bod y gastritis in epid emiological stud ies because these d eterminations are more simple and less inv asiv e than end oscopy w ith biopsy. A comparison betw een the histolog- ical find ings of atrophic gastritis and the serum pepsinogen lev els has alread y been mad e in the 80-s of the last century( 10).
Serum pepsinogen assays id entify the majority of patients w ith atrophic cor- pus gastritis, although they are less useful in assessing the d egree of atrophy in d e- tail. It is reported that the agreement of the ex tent of atrophic gastritis, assessing by end oscopic ex amination and by serum pepsinogen lev els, w as 5 7% , and agreement of the presence of atrophic gastritis w as 79 % ( 11). D epend ing on the population,
pepsinogens often have a high specificity but low sensitivity for the diagnosis of atrophic gastritis, whereas antibodies against Helicobacter pylori or CagA have a high sensitivity but low specificity (12,13 ). Serological techniq ues, in fact, suffer from an intrinsic limitation related to their low sensitivity for the mild forms of atrophic gastritis(11). This can be deduced from the fact that most of the commonly used as- says are based on the determination of more than one parameter to compensate for this limitation, and often it is clearly indicated that their use is confined to the assessment of " moderate-severe" or " advanced" forms of atrophy(14 -16).
The histological diagnosis remains the gold standard in the assessment of gas- tric atrophic pathology. H owever, even the histological diagnosis of chronic at- rophic gastritis is sometimes q uestionable, particularly in the context of active in- flammation(17,18). Also the patchy distribution of atrophic disorders may be responsible for false-negative results because biopsies might be taken from areas not involved by the disease. This may be of great conseq uence because atrophic gastritis is an important risk factor for gastric cancer(19,20).
To tackle the problem of the poor diagnostic performance of serological and histological methods for the diagnosis of fundic atrophic gastritis, complementary tests are mandatory. R ecently a novel device for gastric juice analysis, measuring ammonium concentration and pH during endoscopy, seems to be a promising tool for overcoming this diagnostic deficiency(21).
H owever, considering the physiological concept that secretory behaviour re- flects trophic condition and that secretory stimulation is a well-known diagnostic test to investigate integrity of functional cell mass, it is reasonable to assume that re- duced secretion of pepsinogen after stimulation might be a refined diagnostic marker of atrophy of the gastric corpus. Proton pump inhibitor (PPI) administra- tion is known to be a potent pepsinogen-releasing stimulus in healthy volunteers(22-
24 ). O ur premise is that in patients with atrophic corpus gastritis with loss of chief cell- mass, PPI-stimulation has a more or less rising effect on the level of serum pepsinogen, depending on the severity and extent of cell-reduction. In case of mild atrophy one could expect a modest increase in serum pepsinogen level after stim- ulation; in case of advanced atrophy there will be no relevant pepsinogen increase.
Therefore, a non-invasive PPI-stimulation test might give clearness in the troph- ical darkness of the gastric mucosa and may circumvent the problem of invasiveness of endoscopy and gastric juice analysis.
The present study was undertaken to test the hypothesis that patients with cor- pus mucosal atrophy show abnormally low pepsinogen responses to PPI-adminis- tration. Therefore, we have measured serum pepsinogen levels in patients with serological body atrophy before and after 2 weeks course of esomepraz ol 4 0 mg daily. In addition we have compared this individual pepsinogen response to PPI with the histological data of the biopsy specimens of each patient. To the best of our knowledge, this is the first report on the diagnostic performance of short course PPI to determine the severity of atrophic body gastritis and possibly the increased
Short-term proton pump inhibitor
risk for gastric cancer. Our study premise is that PPI-induced increase of pepsino- gen A in patients with gastric body atrophy has an inversely graded relation with at- rophy.
S u b j e c t s a n d m e t h o d s
Study Population
The study was performed in a group of 25 patients with serological gastric body atrophy. They were selected from 997 adult subjects, consecutively entering the pri- mary health care system because of common medical problems, who volunteered in a serological screening study for atrophic body gastritis. Subjects younger than 18 years, pregnant women, patients with gastric resection, renal insufficiency and those using antisecretory agents were excluded. All 25 study subjects, 12 men and 13 women, mean age 67 years, range 31-93, were indigenous Dutch citizens, born in The N etherlands. N obody of this group of 25 had used acid suppressant medication before the study.
The study was performed in the family practice in ’s-Gravenpolder, a rural vil- lage in the province Z eeland in The N etherlands.
Informed consent was obtained from all subjects, and the protocol was ap- proved by the E thics Committee of the L eiden U niversity M edical Center.
PPI - c h oic e , dos ag e r e g im e n and te s ting s c h e m e
E someprazole 40 mg, was administered orally, once daily for 14 days. The choice for esomeprazole, the modern S-isomer of omeprazole, was made by the literature based outstanding sustained gastric acid control with reduced interpatient vari- ability(25-27). A dosis of 40 mg daily appears to be the dosis for optimal and safe acid suppression. B efore and after the 2 weeks esomeprazole course venous blood sam- ples were collected from all subjects for the assessment of fasting serum pepsinogen and gastrin.
Se r olog ic al e x am ination
All sera samples were tested by well-validated radio-immunoassays for levels of pepsinogen A, pepsinogen C and gastrin(28). Our validated criteria for advanced serological atrophic corpus gastritis, corresponding to pentagastrine refractory achlorhydria or severe hypochlorhydria (PAO < 5 mmol/hr), expressed in the level of the serum markers, were a serum concentration of pepsinogen A < 17 µg/l, a pepsinogen A/C ratio < 1.6 and an accompanying serum concentration of gastrin
> 100 ng/l (28).
E ndos c opy and b iops y s am pling
B efore the start of the PPI-administration all individuals underwent endoscopy in
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the usual manner, using an Olympus video - endo sc o py eq uipment. S tandardiz ed b io psy sampling fo r histo lo gic al ex aminatio n w as perfo rmed w ith 4 b io psies fro m the anterio r and po sterio r w all o f the mid antrum and also 4 b io psies fro m the an- terio r and po sterio r w all o f the mid c o rpus, respec tively ab o ut 2 c m pre- pylo ric and ab o ut 5 c m distal o f the o eso phagus- c ardia junc tio n. B io psies fo r histo lo gy w ere fix ed in 1 0 % b uffered fo rmalin.
Histological examination
I n b rief, 5 mic ro n sec tio ns w ere hemato x ylin and eo sin stained and ex amined ac c o rding to the updated S ydney c lassific atio n system( 2 9 - 3 1 ). A tro phy w as defined as lo ss o f the deeper spec ializ ed glands, i.e. in the gastric b o dy the parietal c ells and sec o ndly the c hief c ells, in the antrum the gastrin pro duc ing G - c ells. I ntestinal metaplasia ( IM ) is the replac ement o f gastric muc o sa b y small intestine- lik e muc o sa.
I M c o ntrib utes to atro phy w hen ex tending deeply into the muc o sa to invo lve the gland c o mpartment. A ll histo patho lo gic al issues w ere semi- q uantitatively graded as ab sent, mild, mo derate o r severe.
S tatistical analy sis
S tatistic al analysis o f the differenc es b efo re and after eso mepraz o l administratio n w as perfo rmed b y applying the paired S tudent’s t- test and c o rrelatio ns w ere studied b y standard statistic al metho ds.
R e s u l t s
R etesting S er ological atr op h ic cor p u s gastr itis b efor e P P I - A d ministr ation B ased upo n the pretreatment testing o f the b io mark ers, 2 0 patients, o f the gro up o f 2 5 , again fulfilled the c riteria o f sero lo gic al atro phic c o rpus gastritis, w hile 5 par- tic ipants did no t.
T he 5 " dro p- o uts" sub jec ts sho w ed the fo llo w ing sero lo gic al c harac teristic s.
One sub jec t ( no . 8 ) had after retesting no rmal gastrin w ith lo w pepsino gen A and lo w ratio A :C , thus no lo nger fulfilling the c riteria o f sero lo gic al gastric b o dy at- ro phy. T he remaining 4 sub jec ts sho w ed after retesting no rmal serum pro file, o f w ho m 2 perso ns ( no s. 3 and 1 4 ) had b o rderline test results in the first ro und and the o ther 2 perso ns ( no s. 6 and 1 5 ) had an unex plained c o nversio n to no rmal levels o f the serum mark ers. R etesting is mandato ry in c ase o f b o rderline test results.
P r etr eatment h istological examination of oxy ntic and antr al M u cosa
T he presenc e o r ab senc e o f atro phic gastritis and the grade o f atro phy w as assessed direc tly b efo re starting P P I - administratio n.
A s sho w n in table 1, histo lo gic al atro phic b o dy gastritis w as fo und in 2 0 pa- tients, o f w ho m 1 sub jec t sc o red mild, 6 perso ns mo derate and 1 3 severe b o dy at-
rophy. One patient (no. 4) with serological atrophic corpus gastritis had only antrum biopsies and no corpus biopsy specimens. Nine patients showed histological antral atrophy, 5 mild, 2 moderate and 2 severe atrophy. One patient had no antral biop- sies (no.15).
F our patients (nos. 3, 6, 14 and 15) showed only chronic aspecific inflammation and no atrophy.
Serum pepsinogen A concentration before and after PPI-stimulation
The individual measurements of pepsinogen A before and after the 14-day course of oral esomeprazole are shown in table 1 and figure 1.
In the 4 non-atrophic patients (patient nos. 3, 6, 14, 15), mean age 65 years (range 49-77), a marked increase in the pepsinogen A level occurred: mean pepsino- gen pre-entry level 17 µ g/l, mean post-PPI concentration 59 µ g/l, p < 0.05.
The 19 patients with moderate and severe histological atrophic corpus gastritis, mean age 58 years (range 31-93) showed negligible increase in serum pepsinogen A level. The mean preentry level of pepsinogen A was 4.7 µ g/l and the mean post-PPI concentration was 4.9 µ g/l, p > 0.05 vs. preentry. There was no difference in stimu- lated pepsinogen levels between patients with moderate and advanced atrophy.
Also patient no. 4, without corpus biopsy specimens, had a negligible change in pepsinogen A level, pointing to severe corpus atrophy.
One patient (patient no. 8), age 74 years, with a borderline pepsinogen A level of 16 µ g/l, showed a modest pepsinogen increase, from 16 to 26 µ g/l. He appeared to have mild corpus atrophy.
Serum gastrin concentration before and after PPI-stimulation
Serum gastrin levels measured before and after esomeprazole administration are shown in table 1 and figure 2.
Basal serum gastrin concentrations ranged from 59 to 134 ng/l in patients with normal antral and corpus mucosa (patients nos. 3,6,14 ). Oral PPI-stimulation in- creased their gastrin very clearly with a range from 602 to 1531 ng/l , p < 0.05. One patient (no. 15) had no antrum biopsies but only corpus biopsies; the corpus biop- sies showed no atrophy. The gastrin behaviour (preentry 77, post-PPI 760) points to normal antral function.
The group with antral atrophy showed a preentry gastrin range from 68 to 1284 ng/l. The post-PPI range was 122 to 731 ng/l. The presence or absence of corpus at- rophy determines in the nature of things also the preentry level of gastrin.
A high preentry gastrin level, pointing to functional intact antral mucosa and an advanced corpus atrophy, remained high after PPI-stimulation with unpredictable increase or decrease.
Patient no. 8 had antral atrophy with metaplasia (preentry gastrin 68, stimu- lated gastrin 102) and mild corpus atrophy (preentry pepsinogen A 16 and stimu- lated pepsinogen 102).
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Table 1.Serological and histological characteristics in gastric atrophy in 25 primary healthcare patients b ef ore and af ter 2 w eek s P P I-administration
= no corpus biopsy
= no antrum biopsy
P P I = proton pump inh ibitor P g A = pe psinog e n A P g C = pe psinog e n C
A /C rat = pe psinog e n A to C ratio
S e rol G B A = se rolog ic al g astric bod y atroph y H istol G B A = h istolog ic al g astric bod y atroph y H istol G A A = h istolog ic al g astric antrum atroph y – = abse nt, + = mild , + + = mod e rate , + + + = se v e re
pre–PPI serology post–PPI serology histology
patnr P g A P g C A /C G astrin S e rol P g A P g C A /C G astrin H istol H istol
ratio G B A ratio G B A G A A
1 1 4 0 .3 1 6 6 4 + 2 4 0 .6 1 5 3 1 + + + –
2 2 9 0 .2 1 2 6 9 + 1 8 0 .2 1 4 9 0 + + + –
3 1 7 6 2 .7 8 6 – 5 8 1 7 3 .5 8 0 2 – –
4 1 4 0 .3 2 2 1 2 + 2 6 0 .4 2 0 3 1 –
5 3 7 0 .4 1 2 3 + 3 4 0 .8 3 4 2 + + + –
6 2 5 1 5 1 .7 1 3 4 – 6 2 2 3 2 .7 1 5 3 1 – –
7 8 9 0 .9 9 3 3 + 5 8 0 .7 1 0 2 3 + + + –
8 1 6 2 3 0 .7 6 8 – 2 6 2 2 1 .2 1 0 2 + +
9 1 1 7 0 .1 7 6 4 + 1 1 8 0 .1 6 5 6 + + + –
1 0 2 1 2 0 .2 5 3 4 + 2 9 0 .2 6 4 2 + + + –
1 1 0 7 0 .1 2 0 8 6 + 1 6 0 .1 2 0 0 0 + + + –
1 2 1 2 0 .4 1 3 5 2 + 1 3 0 .3 1 4 5 6 + + + +
1 3 3 1 1 0 .3 1 7 9 1 + 3 9 0 .3 1 3 8 5 + + –
1 4 1 7 5 3 .5 5 9 – 9 1 2 6 3 .5 6 0 2 – –
1 5 9 2 5 .3 7 7 – 2 4 5 4 .3 7 6 0 –
1 6 3 5 0 .7 1 1 6 + 7 1 2 0 .6 1 2 2 + + + + + +
1 7 9 1 1 0 .8 6 2 8 + 9 1 6 0 .5 1 5 5 9 + + + –
1 8 3 4 0 .7 5 5 2 + 5 5 0 .9 1 2 5 4 + + +
1 9 5 1 6 0 .3 4 5 9 + 8 1 1 0 .7 4 0 3 + + +
2 0 6 4 1 .3 1 4 6 + 8 6 1 .4 4 8 2 + + –
2 1 1 4 0 .3 2 2 5 7 + 1 5 0 .2 1 6 7 0 + + + –
2 2 1 4 1 8 0 .8 1 1 7 9 + 1 2 7 1 .9 1 0 9 2 + + +
2 3 4 1 2 0 .3 1 5 9 + 7 9 0 .8 2 6 1 + + + +
2 4 6 1 1 0 .5 1 2 8 4 + 7 1 1 0 .6 7 3 1 + + + + +
2 5 1 1 1 4 0 .8 2 8 4 + 1 4 8 1 .7 2 6 2 + + + + + +
Overall, there were marked differences in the gastrin PPI-response without uni- form correlation with the grade of atrophy .
A specific diagnostic pattern of stimulated gastrin is only visib le in patients with non-atrophic gastritis of b ody and antral mucosa.
Correlation between PPI-test and histology
S timulated pepsinogen A appears to have a reliab le predictive value in the grade of atrophic corpus gastritis. S timulated gastrin shows in the nature of things er- ratic movements and has no decisive role in the diagnosis of atrophic b ody gastri- tis.
One patient had no corpus b iopsies, so that in our study in 9 6 % ( 2 4 / 2 5 pa- tients) PPI-stimulated pepsinogen A and histology matched a similar diagnosis.
PPI-stimulated increase of pepsinogen A in patients with atrophic corpus gas- tritis has an inverse relation with the grade of atrophy ( r = - 0 .7 9 , p < 0 .0 0 1 ) .
A n ab normally low pepsinogen A respons to PPI points to severe mucosal at- rophy of the ox y ntic mucosa.
pre post pre post
T w o w eek s trea tm en t w ith 4 0 m g sid esom epra z ole
H istolog ic a l a troph ic c orpu s g a stritis p < 0.05
serum pepsinogen A (μg/l)
-v e + v e 00
0
0
0
0
5 0
4 0
0
0
0
0
Figure 1.
D i s c u s s i o n
Proton pump inhibitors (PPIs) are highly effective drugs that have revolutionized the management of acid- pepsin disorders over the last tw o decades. T he design of an effective therapy may be useful not only in treatment but also in identifying causes of disease. T he selectivity of PPIs is so accurate that this q uality can be uti- lized to identify acid- related disorders, such as gastroesophageal reflux disease(3 2 -
3 5 ). U sing the " cause- and- effect" respons to a PPI in acid hypersecretion it might be
conceivable, from a scientific point of view , to use this respons also in acid hy- posecretion of the gastric mucosa. A cid hyposecretion, hypochlorhydria, reflects a degree of atrophy of the stomach and is as a rule asymptomatic. T he " cause and effect" response to PPI in gastric atrophic conditions should therefore be considered as a biochemical respons. Preferably non- invasive diagnostic tools are w elcome in the often tough diagnosis of atrophic gastritis.
T his present w ork is the first report on the diagnostic approach of atrophic gas- tritis w ith PPI- stimulated pepsinogen and gastrin. T he main findings in our PPI- atrophy study in patients w ith atrophic body gastritis are as follow s:
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pre post pre post T w o w eek s trea tm en t w ith 4 0 m g sid esom epra z ole
H istolog ic a l a troph ic c orpu s g a stritis p < 0.05
serum gastrin (ng/l)
-v e + v e 2 5 00
2 000
1 5 00
1 000
5 00
0
F ig ure 2 .
[1] increase in PPI-stimulated serum pepsinogen A has an inverse relation with the grade of mucosal b ody atrophy , [2 ] gastrin respons to PPI adds no decisive information ab out the grade of atrophy of the gastric corpus [3 ] reduced gastrin respons to PPI might b e usefull in the case of predominant antral atrophic gastritis ( patient no. 8 ) . T he results of the 2 5 patients, enrolled in this study , indicate that measurement of PPI-stimulated serum pepsinogen A in patients, suspected of having atrophic b ody gastritis, can b e used as a non-invasive mark er of the presence and severity of mucosal corpus atrophy . An ab normally low serum pesinogen A respons to PPI-ad- ministration supports strongly the diagnosis of severe b ody atrophy .
T he 14 -day course was selected b ecause it is the period req uired to achieve high- est levels of pepsinogen A in a study in 8 healthy volunteers with omepraz ole 3 0 mg daily b y F esten e.a.( 2 2 ).
T he mechanism of the effect of PPIs on serum pepsinogens remains speculative.
O mepraz ole( 3 6 )and somatostatin( 3 7 )inhib it pepsinogen-secretion into the gastric lumen. In vitro ex periments with isolated gastric glands show that the sum of ex - ocrine and endocrine secretion of pepsinogen A increases after omepraz ole( 3 8 ). T he comb ination of these data suggests that inhib ition of ex ocrine secretion followed b y increased storage and release of pepsinogen A into the circulation is prob ab ly re- sponsib le for the effect of omepraz ole on serum pepsinogen A levels.
T here are no data on the b iochemical effect of PPIs on serum pepsinogens in gas- tric atrophy .
It is ob vious that with the progressive loss of specializ ed chief cells in the ox y nic mucosa and the parallel diminishing production of the pepsinogens, there is no storage of pepsinogen A for ex ocrine secretion and to release into the circulation, when gastric secretion is inhib ited.
T he mechanism of the effect of PPIs on serum gastrin seems to b e more natu- ral. Intragastric acidity regulates the gastrin release from the antral G -cells through a negative feedb ack mechanism: when the gastric juice pH falls due to high parietal cell secretion, the release of gastrin is inhib ited, whilst when the gastric juice pH rises, hy pergastrinaemia ensues to stimulate the parietal cell mass. G astrin, as a regulatory peptide, is secreted directly in the ciculation( 3 9 ,4 0 ). T herefore, it is com- prehensib le that gastric acid suppression increases circulating gastrin serum con- centrations( 4 1). In humans, serum gastrin levels may increase up to four-fold when treated with PPI( 4 1,4 2 ). H owever, in patients with advanced antral mucosal atrophy with low numb er of G -cells, gastrin levels will b e low and stimulation has less or no ef- fect ( patient nos. 16 and 2 5 in table 1).
T h e d ia g n o s is o f g a s tr ic a tr o p h y is u s u a lly m a d e b y e n d o s c o p y w ith h is to lo g i- c a l e x a m in a tio n o f b io p s ie s . H o w e v e r, a s to e n d o s c o p ic a l a n d h is to lo g ic a l fin d in g s th e r e is a w e ll- k n o w n d is c r e p a n c y b e tw e e n r o u tin e a n d " a c c u r a te " a n a ly s is o f a tr o p h ic g a s tr itis . A p r e - e n d o s c o p ic a l, r e lia b le p r e d ic tio n o f a tr o p h y , a m o r e a p p r o p r ia te b io p s y p la n a n d a n in fo r m e d s k ille d p a th o lo g is t im p r o v e th e id e n tific a tio n o f a tr o p h y s ig n ific a n tly a n d s h o w th a t th e p r e v a le n c e o f th is c o n d itio n is h ig h e r th a n u s u a lly
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diagnosed( 2 1 ). I t is in our opinion unacceptable that patients with preneoplastic conditions pass undiagnosed, even after an invasive diagnostic procedure.
I n this context measuring basal pepsinogen and in borderline test results P P I - stimulated pepsinogen might well represent a good solution.
The capability of predicting pre-endoscopically the atrophic mucosal status would permit the application of an appropriate biopsy plan, with a sufficient num- ber of biopsies, so as to limit the problem of the patchy distribution of the lesions and better characteriz e the histo-pathological aspects of conditions at risk of neo- plastic degeneration. F urthermore, the endoscopist and, more particularly, the pathologist could be alerted about the possible presence of atrophic and other im- portant disorders.
This study demonstrates that the P P I -atrophy test is a simple, accurate, and economic tool that allows refined detection of gastric atrophy and helps to determine the severity of atrophic gastritis. All this seems to imply that atrophic status could be assessed even in primary care setting and an optimal selective invasive diagnos- tic program could be achieved with cost reduction.
A limitation of our study is the relatively small number of patients studied, with, as a conseq uence, a low statistical power. However, the results of the present study demonstrate clearly the diagnostic potential of the P P I -stimulated pepsino- gen in the diagnosis of gastric body atrophy. F urther research in a larger group of patients has to give an answer on the q uestion if the P P I -atrophy test deserves a place in the diagnostic field of gastric atrophy.
In conclusion, the present study shows that the pepsinogen respons to short term P P I- administration is abnormally low in patients with low basal pepsinogen concen- tration due to atrophy of the oxyntic mucosa. The P P I -stimulated increase of pepsinogen A has an inverse relation with the grade of atrophy. Therefore, the serum pepsinogen respons to P P I can be used as a marker to determine the sever- ity of gastric corpus atrophy and to identify patients with body atrophy in case of borderline basal pepsinogen.
R e f e r e n c e s
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Short-term proton pump inhibitor
