Article pp.141-144 du Vol.16 n°3 (1986)

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l ditorial

L'histoire du Campylobacter pyloridis

G . N . G . TYTGAT, E.A.J. RAUWS, M.L. L A N G E N B E R G

D i v i s i o n o f G a s t r o e n t e r o l o g y a n d M i c r o b i o l o g y , A c a d e m i c M e d i c a l Centre, A m s t e r d a m ( T h e N e t h e r l a n d s )

The Campylobacter

Depuis la mise en 6vidence il y a quelques ann6es, par Warren [1] et Marshall [2] de micro- organismes flagell6s et spirill6s au niveau de la muqueuse gastrique, un int6r6t croissant et consi- d6rable s'est d6velopp6 dans le monde h propos de la signification de ces germes particuliers. Peu apr6s la description de Marshall, un programme a 6t6 entrepris sur une large 6chelle h Amsterdam afin d'6tudier les caract6ristiques et la signification de ces micro-organismes. Un fait saillant d6couvert au Laboratoire de microbiologie rut la d6monstra- tion d'une activit6 ur6ase positive permettant d'identifier ce germe comme 6tant le Campylobac- ter pyloridis ou des micro-organismes Campylobac- ter-like (MGCL). Depuis le d6but de nos 6tudes, des centaines de patients ont 6t6 suivis et 6tudi6s en fonction de la pr6sence Campylobacter pyloridis, particuli6rement au niveau de la muqueuse gastrique antrale. De nombreux r6sultats des 6tu- des en cours n'ont pas encore 6t6 publi6s in extenso [4]. C'est pourquoi nous allons limiter la pr6sente revue ~ certaines remarques g6n6rales relatives h nos r6sultats ou h ceux publi6s darts la litt6rature.

Comme d'autres observateurs, nous avons observ6 h Amsterdam, que le Campylobacter pyloridis est virtuellement pr6sent dans toutes les cultures de biopsies antrales obtenues chez des patients porteurs d'un ulc6re gastrique ou duod6- nah Les cultures obtenues h partir de biopsies antrales de patients souffrant de dyspepsie non- ulc6reuse furent, elles aussi, souvent positives, ce qui contraste avec une pr6valence de Campylobac- ter gastrique sur des biopsies antrales dans moins de 30 % d'un groupe de sujets contr61es v6ritable- ment asymptomatiques. Ce qui para~t plus important encore, c'est la relation 6troite entre la pr6- sence de ces micro-organismes et la pr6sence de signes histologiques non 6quivoques de gastrite. La gastrite antrale est sp6cialement caract6ris6e par la pr6sence de micro-6rosions h ia surface de l'6pi- th61ium et par une augmentation significative d'infiltrats h cellules polynucl6aires, non seulement dans la lamina propria, mais au niveau des cellules 6pith61iales. La gastrite est habitueilement absente chez les individus dont les cultures sont n6gatives.

Au cours du suivi de nos patients, lequel porte

Pyloridis stow

pr6sent sur plus de deux ans, il est devenu 6vident qu'une culture positive ie demeure quel que soit le nombre d'endoscopies-biopsies accomplies, alors qu'une personne porteuse de culture n6gative le reste 6galement pendant toute la dur6e de la p6riode d'observation.

Le Campylobacter pyloridis pr6sente une affinit6 61ective pour la couche de mucus rev6tant la surface de l'6pith61ium sp6cialement au niveau de I'antre, bien que ies biopsies pr61ev6es au niveau fundique puissent 6galement 6tre positives. Le micro-climat propre h cette couche de mucus semble favoriser la pullulation de ces micro-organismes, peut-6tre parce que le pH y est moins acide que celui de la lumi~re gastrique correspon- dante. Le suc gastrique ne parah pas ~tre le milieu id6al pour la croissance de cette bact6rie. I1 faut 6galement noter que la majorit6 sinon la totalit6 des patients porteurs de biopsies antrales positives sont porteurs d'anti-corps s6riques directs contre Campylobacter pyloridis. Les 6tudes pr61i- minaires conduisent h I'impression que le titre s6rique de ces anticorps varie en fonction du degr6 de coionisation des biopsies antrales.

Un autre motif de sp6culations s'est rapidement impos6 apr~s la d6couverte du r61e du Campylo- bacter pyloridis dans l'induction de la gastrite ou dans la diath6se ulc6reuse. Sur ce point, on ne peut avancer qu'une relation tout h fait hypoth6ti- que uniquement bas6e sur des suppositions qui n6cessitent des 6tudes ult6rieures afin de confirmer ou d'infirmer une pareille relation. I1 n'est pas difficile d'imaginer qu'une muqueuse gastrique d6jh inflammatoire soit plus vuln6rable vis-a-vis d'une agression acide h concentration normale ou vis-h-vis de substances nocives pr6sentes dans le suc gastrique. On pourrait donc envisager que l'inflammation de la muqueuse gastrique induise des modifications de motilit6 et des troubles de comp6tence pylorique, conduisant dans un second stade, ~ une perturbation de la vidange gastrique et peut-6tre h u n accroissement du reflux duo- d6no-gastrique,

On accepte en g6n6ral qu'une petite quantit6 de liquide bilieux intestinal suffit ~ irriter une muqueuse gastrique parce que le reflux am6ne un Tir6s-h-part : Prof. G.N,G. TYTGAT, Division of Gastroen-

terology-Hepatology, Academic Medical Centre, Academisch Ziekenhuis, Meibergdreef 9, 1105 AZ Amsterdam zuidoost (The Netherlands).

Mots-cl~s : bact6riologie, campylobacter pyloridis, duod6num, endoscopie, gastrite, ulc~re.

Key-words : bacteriology, campylobacter pyloridis, duode- num, endoscopy, gastritis, ulcus.

Acta Endoscopica Volume 16 - N~ 3 - 1986 141

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liquide c o n t e n a n t des sels biliaires d6shydroxyl6s et 6 v e n t u e l l e m e n t de la lysol6cithine. U n e telle action irritative sur ia m u q u e u s e gastrique est susceptible de r e n f o r c e r la perm6abilit6 de l'6pith6- lium m e m b r a n a i r e , de d i m i n u e r la p r o t e c t i o n de la barri6re 6pith61iale favorisant la r6trodiffusion de p r o t o n s d e p u i s le liquide gastrique vers la paroi de l'organe. Ces facteurs p e u v e n t pr6disposer la m u q u e u s e gastrique "~ la f o r m a t i o n d ' u n ulc6re.

N 6 a n m o i n s o n ne s'explique pas p o u r q u o i un ulc6re gastrique est h a b i t u e l l e m e n t solitaire et Iocalis6 le long de la petite c o u r b u r e dans une z o n e de transition e n t r e les m u q u e u s e s de type antral et f u n d i q u e , ces diverses particularit6s 6tant mal c o m p r i s e s et sujettes ~ discussion. C o m m e n t la pr6sence de C a m p y l o b a c t e r associ6e "~ l'inflam- m a t i o n , p a r t i c u l i 6 r e m e n t au niveau antral, peut- eile i n t e r v e n i r dans la gen6se d ' u n ulc6re duod6nal reste une relation e n c o r e plus difficile "~ com- p r e n d r e .

Nous avons 6galement tent6 d ' 6 v a l u e r l'efficacit6 de divers m 6 d i c a m e n t s employ6s dans la th6rapeu- tique de l'ulc6re p e p t i q u e ou d ' a n t i b i o t i q u e s qui paraissent actifs in vitro c o n t r e le C a m p y i o b a c t e r pyloridis, et ceci chez plusieurs centaines de patients. E n o u t r e , nous avons r6alis6 des essais en vue d ' a p p r 6 c i e r l'effet de ces d r o g u e s sur les alt6rations gastritiques. T o u s ces essais p h a r m a c o - logiques p e u v e n t se r 6 s u m e r de la facjon suivante - les anti-s6cr6toires de type H2 ( C i m e t i d i n e et R a n i t i d i n e ) , le sucralfate et les antibiotiques (Spi- r a m y c i n e ) n ' o n t aucun effet et n ' o n t jamais permis 1'6radication du m i c r o - o r g a n i s m e sur les biopsies antrales. J u s q u ' ~ pr6sent, deux m 6 d i c a m e n t s seule- m e n t paraissent utiles. Le subcitrate colloi'dal de bismuth ( D e N o l | p r o v o q u e la disparition de C a m p y l o b a c t e r pyloridis sur environ la moiti6 des cultures o b t e n u e s chez ces patients. Le t r a i t e m e n t par I'Amoxycilline p e r m e t l'6radication dans environ 70 % des cas. N 6 a n m o i n s la reprise de ces patients un mois apr6s l ' i n t e r r u p t i o n de I'essai t h 6 r a p e u t i q u e , m o n t r e que s e u l e m e n t 20 % des cultures de biopsies antrales sont rest6es n6gatives.

D ' a p r 6 s les r6sultats de ces 6tudes, il semble tr6s difficile d ' o b t e n i r par m o n o t h 6 r a p i e , unc 6radica- tion c o m p l b t e des micro-organismes sur les biopsies antrales. A u d6part de l'analysc d6taill6e de la c o m p o s i t i o n du D N A de ces micro-organismes o b t e n u s chez diff6rents individus, il a 6t6 possible de m o n t r e r q u e les germes r6apparus ont la m6me c o m p o s i t i o n en D N A que celle des micro-organismes objectiv6s avant le t r a i t e m e n t chez un m 6 m e individu. II s'agirait donc p r o b a b l e m e n t d ' u n e r e c r u d e s c e n c e plut6t que d ' u n e v6ritable r6cidive via une r6infection du tissu antral. En utilisant une m o n o t h 6 r a p i e , le m 6 d i c a m e n t p6n6trc v r a i s e m b l a b l e m e n t de fa~on insuffisante la couche de mucus, o u bien ii est incapable d ' 6 r a d i q u e r c o m p l 6 t e m e n t le micro-organisme en cause. Cer- tains g e r m e s survivent ~t I'agression m6dicamcn- teuse et pullulent "~ n o u v e a u apr6s l ' i n t e r r u p t i o n de la t h 6 r a p e u t i q u e . Si on utilise une th6rapeuti- q u e c o m b i n 6 e associant subcitrate et bismuth colloidal ( D e N o i | et Amoxycilline, un plus haut

p o u r c e n t a g e d'6radications peut 6tre o b t e n u . On ne sait pas j u s q u ' h pr6sent quelle est la p r o p o r t i o n de patients qui p e u v e n t rester e x e m p t s de bact6- ries du fait que les 6tudes relatives "~ ce p r o b l 6 m e sont e n c o r e en cours.

Nous avons 6t6 particuli~rement intrigu6s par les r6sultats o b t e n u s avec le subcitrate de bismuth colloidal et ce, p o u r plusieurs raisons. I1 a 6t6 montr6 jusqu'~t pr6sent et cela au moins dans 10 essais t h 6 r a p e u t i q u e s relatifs 'h I'ulc6re duod6nal et dans 5 relatifs '~ l'ulc6re gastrique, que le D e N o l | non s e u l e m e n t a p p o r t e un haut taux de cicatrisa- tion mais q u ' e n o u t r e un ulc6re trait6 par le D e N o l | a une m o i n d r e tendance "~ la r6cidive.

Ceci est vrai h la fois p o u r l'ulcbre duod6nal et pour les ulc6res gastriques. P o u r q u o i un ulc6re trait6 par le D e N o l | manifeste-t-il une m o i n d r e tendance "~ ia r6cidive par rapport "~ d ' a u t r e s th6- rapeutiques reste une question a c t u e l l e m e n t sans r6ponse. Ce d6calage des taux de r6cidives apr6s traitement au D e N o i | pourrait 6tre en r a p p o r t avec la capacit6 du subcitrate de bismuth colloidal de s u p p r i m e r ou 6 r a d i q u e r le C a m p y l o b a c t e r pyloridis, t o u j o u r s pr6sent chez les patients atteints de maladie ulc6reuse. N o u s nous d e m a n d o n s si l'am6- lioration 6vidente de la gastrite apr6s 6radication du C a m p y l o b a c t e r pyloridis suite au t r a i t e m e n t p a r le subcitrate de bismuth colloidal, n'est pas l'expli- cation de la r6sistance a p p a r e m m e n t meilleure de la m u q u e u s e g a s t r o d u o d 6 n a l e contre une agression r6cidivante et la f o r m a t i o n de I'ulc6re. En fait une telle am61ioration de l'image histologique gastrique n'a jamais 6t6 o b s e r v 6 e par nous apr6s d ' a u t r e s types de t r a i t e m e n t par m6dicaments anti-ulc6reux.

I1 faut souligner q u ' a u cours de toutes ces 6tudes, il para~t possible p o u r la premi6re fois, d'am61iorer par des m 6 d i c a m e n t s une image histoiogique de gastrite. D e plus, l'am61ioration de Finflammation apr6s arr6t du m 6 d i c a m e n t et la r6apparition de ia gastrite avec r e c r u d e s c e n c e de la prolif6ration des micro-organismes, r e s t e n t des arguments p r o b a n t s en faveur de leur r61e v6ritablement pathog6ne.

N6anmoins jusqu'~, pr6sent, or/ n'est pas certain que ie C a m p y l o b a c t e r pyloridis soit impliqu6 dans la pathog6nie de l'ulc6re gastrique et 6ventuelle- ment de l'ulc6re duod6nal. De n o m b r e u s e s 6tudes s6quentielles sur d ' i m p o r t a n t s groupes de patients suivis sont n6cessaires afin de savoir v r a i m e n t quelle est la signification pathog6nique de ces micro-organismes. La seule observation qui puisse 6tre accept6e c o m m e un fait indiscutable est la relation e n t r e l'image histologique de gastrite et la pr6sence de ce type particulier de micro-organisme. P o u r le reste, on en est aux q u e s t i o n s "

quelle est l'influence ~ long t e r m e de l'6radication de ces m i c r o - o r g a n i s m e s sur les r6cidives de la maladie ulc6reuse ? Q u e l l e est la p r o v e n a n c e natu- relle de cette bact6rie ? Quelle est la source de la contamination ? Q u e l l e est la meilleure a p p r o c h e th6rapeutique afin d'61iminer le C a m p y l o b a c t e r pyloridis ? C e t t e 6radication du micro-organisme procure-t-elle l'arr6t de la progression de la gastrite aigu~ vers la gastrite c h r o n i q u e , et enfin la gastrite c h r o n i q u e a t r o p h i q u e ? L'infestation chro-

142 V o l u m e 16 - N " 3 - 1 9 8 6 A c t a E n d o s c o p i c a

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nique p a r le C a m p y l o b a c t e r est-elle la principale cause de l ' 6 v o l u t i o n c h r o n i q u e vers l ' a t r o p h i e de la m u q u e u s e g a s t r i q u e , laquelle ~t long t e r m e r6alise la c o n d i t i o n o p t i m a l e au d 6 v e l o p p e m e n t d ' u n e d6g6n6rescence m a l i g n e ? Existe-t-il des i m a g e s particuli~res de la gastrite a n t r a l e p a r infection C a m p y l o b a c t e r pyloridis ? P o u r q u o i certains individus sont-ils i n c a p a b l e s d'61iminer s p o n t a n 6 m e n t ce m i c r o - o r g a n i s m e ? Existe-t-il u n e pr6disposition g6n6tique ? Existe-t-il un d6ficit i m m u n i t a i r e expli- q u a n t la r6ceptivit6 individuelle ? P o u r q u o i ces m i c r o - o r g a n i s m e s sont-ils si difficiles h 61iminer ?

D e v o n s - n o u s d i s p o s e r de m 6 d i c a m e n t s s u s c e p t i b l e s de m i e u x p 6 n 6 t r e r la c o u c h e d e m u c u s et d e la d6truire en p a r t i e afin d ' e x p o s e r les m i c r o - o r g a - nismes h u n e a c t i o n bact6ricide plus efficace ? Ainsi p e u v e n t 6tre f o r m u l 6 e s de n o m b r e u s e s q u e s - tions qui n 6 c e s s i t e n t u n e r 6 p o n s e u r g e n t e . S e u l e u n e 6 v a l u a t i o n p r u d e n t e a v e c des m 6 t h o d e s de l a b o r a t o i r e m 6 t i c u l e u s e s , est susceptible de c o m - p r e n d r e l'histoire n a t u r e l l e du C a m p y l o b a c t e r pyloridis. Ce p r o b l ~ m e m6dicai constitue a c t u e l l e - m e n t un s u j e t de r e c h e r c h e fascinant.

RI~Ft~RENCES 1. WARREN J.R. - - Unidentified curved bacilli on gastric

epithelium in active chronic gastritis. Lancet, 1983, i, 1273.

2 . M A R S H A L L B . - - Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet, 1983, i, 1273- 1275.

3. LANGENBERG M.L., TYTGAT G.N.J., SCHIPPER M.E.I. - - Campylobacter-like organisms in the stomach of patients and healthy individuals. Lancet, t984, i, 1348.

4. TYTGAT G.N.J., LANGENBERG M.L., RAUWS E.A.J., RIETRA P.J.G.M. - - Campylobacter-like organisms (CLO) in the human stomach. Gastroenterology, 1985, 88 (5).

5. LANGENBERG M.L., RAUWS E.A.J., WIDJO.IOKU- SUMO A., TYTGAT G.N.J., ZANEN H.C. - - To be published, J. Clin. Microbiol., 1986.

There is an explosive growth o f interest world- wide with respect to the significance o f a peculiar microorganism at the level o f the gastric mucosa since Warren [1] and Marshall [2] rediscovered a few years ago the presence o f a spirilled flagellated microorganism on the gastric mucosa. Soon after Marshall's description a large scale study program was also launched in Amsterdam to study the cha- racteristics and the significance o f this peculiar organism. Rather striking was the discovery in the Laboratory o f Microbiology o f the remarkably high urease activity o f this organism which provisionally received the name Campylobacter Pyloridis or Gas- tric Campylobacter-like organism ( G C L O ) . Since the beginning o f our studies several hundreds of patients have been screened and studied with res- pect to the presence o f Campylobacter Pyloridis especially on the mucosa o f the gastric antrum.

Many o f the results o f this ongoing study have not been published in extenso [4]. Therefore we will limit this survey to some general remarks and gene- ral impressions o f our results and those published in literature.

A s did other investigators, we too f o u n d in A m s - terdam that Campylobacter Pyloridis was present in virtually all cultures f r o m antral biopsies obtained in patients with gastric or duodenal ulcer. Cultures from antral biopsies o f patients with non-ulcer dys- pepsia were also very often positive, in contrast with a prevalance o f gastric Campylobacter in antral biopsies o f less than 30 % o f a group of truly asymptomatic control individuals. What appears even more important is the striking rela- tionship between the presence o f this microorganism and the presence o f unequivocal histological evi- dence o f gastritis. Such antral gastritis is especially characterized by the presence o f micro-erosions along the surface epithelium and a significant increase o f polynuclear cells, not only in the lamina propria, but also permeating between the epithelial cells. Gastritis was usually absent in those indivi- duals where the cultures were negative. During our

follow-up studies, extending n o w over two years, it became obvious that a positive culture remains positive no matter h o w often you repeat the endoscopy and biopsy, whereas a person with nega- tive cultures stays negative f o r the total length o f the observation period.

The Campylobacter Pyloridis organisms have the peculiar preference f o r the mucus gel layering the surface epithelium especially o f the antrum, although biopsies f r o m the corpus fundus area are usually positive too. The micro-climate in this mucus gel seems to favour the growth o f the micro- organism, perhaps because the p H is less acid in contrast with the gastric lumen. Gastric juice appears indeed not to be the ideal environment f o r the bacterium. It is also remarkable that most, if not all, patients with positive antral biopsies have serum antibodies direct against Campylobacter Pyloridis. Preliminary studies lead to the impres- sion that the serum titre o f these antibodies fluc- tuate with the degree o f colonisation o f the antral biopsies.

There has been a lot o f speculation, starting early after the rediscovery o f Campylobacter Pyloridis with respect to the induction o f gastritis and the diathesis towards peptic ulcer disease. A t this point it is fair to say that any relationship at present is only hypothetical, only based upon suppositions which need further study to confirm or deny such relationship. It is indeed not difficult to conceive that an already inflamed gastric mucosa is more vulnerable towards the normal acid peptic agression or noxious substances present within the gastric juice. One could also easily envisage that inflamma- tion o f the gastric mucosa could induce distur- bances o f motility and impairment o f pyloric com- petence, which might then lead to disturbed gastric emptying and perhaps increased duodenogastric reflux. It is generally accepted that bilious small intestinal content may irritate gastric mucosa upon reflux through the presence o f dihydroxy bile salts and perhaps the presence o f lysolecithin. Such irri-

Acta Endoscopica Volume 16 - N ~ 3 - 1986 143

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tation of the gastric mucosal lining would lead to enhanced permeabiliby o f the epithelial membrane, to disturbance o f the barrier function with impaired protection against back-diffusion o f protons from the gastric juice into the gastric wall. All these factors could predispose the gastric mucosa towards ulcer formation. However, why a gastric ulcer is usually solitary and usually located along the lesser curve in the area o f transition between antral and corpus fundic mucosa, remains poorly understood and speculative. H o w the presence of Campylobac- ter Pyloridis and inflammation, especially in the antrum, would lead to duodenal ulcer, is even more difficult to understand.

We also tried to evaluate the efficacy of various drugs as used in the therapy of peptic ulcer disease or antibiotics which appear active in vitro against Campylobacter Pyloridis in a few hundred patients.

In addition we tried to find out whether these drugs were of any influence upon the gastritic changes.

A l l these pharmacological trials can be summarized as f o l l o w s : He- receptor blockers (Cimetidin and Ranitidin), sucralphate and the antibiotic spiramy- cin are of no benefit as we never have seen eradica- tion of the microorganism from antral biopsies.

Only two drugs at present have appeared to be useful. Colloidal bismuth subcitrate (DeNol | leads to disappearance o f the Campylobacter Pylo- ridis from the cultures in approximately half of the patients. Treatment with amoxicillin led to eradica- tion in roughly 70 %. However, if one restudies those patients, one month after the end of the therapeutical trial, then only in roughly 20 % cul- tures of the antral biopsies are still negative. It would appear from these studies that it is very difficult with monotherapy to completely eradicate the microorganism from antral biopsies. Through detailed analysis o f the D N A composition of the microorganisms obtained in various individuals, it could be shown that the reoccurring microorganism has the same DNA-composition as was present before the therapy in a single individual. That would mean that we are probably dealing with recrudescence instead of true recurrence via reinfec- tion of the antral tissue. Probably when using monotherapy, the drugs either insufficiently pene- trate the mucus gel or anyhow appear incapable of fully eradicating the microorganisms. Some proba- bly survive this chemical attack and then regrow after stopping the therapy. I f one uses a combina- tion therapy, combining colloidal bismuth subcitrate (DeNol | and amoxicillin, a much higher percen- tage of eradication can be obtained at present.

Whether such patients stay free of regrowing bacte- ria is unknown at present, as these studies are being conducted now.

We have been particularly intrigued by the results obtained with colloidal bismuth subcitrate for the following reason. It has been shown by now, at least in some 10 duodenal ulcer trials, and some five gastric ulcer trails, that DeNol | not only leads to a very high healing rate, but that an ulcer, healed with DeNol | has a much slower tendency to recur. This is seen both for duodenal and for

gastric ulcer. Why an ulcer healed with DeNol | manifests a slower delayed chance of recurrence compared with other therapies, is fully unknown.

This delayed recurrence rate after heating with DeNol | may perhaps be related to the efficacy o f colloidal bismuth subcitrate in suppressing or eradi- cating Campylobacter Pyloridis, always present in patients with peptic ulcer disease. We wonder whe- ther the obvious improvement in gastritis which may be seen after eradicating o f Campylobacter Pyloridis after colloidal bismuth subcitrate therapy, is not the explanation for the apparent better resis- tance of the gastroduodenal mucosa against recur- rent damage and ulcer formation. Indeed, such improvement in gastric histology has never been observed in our hands after therapy with other peptic ulcer drugs. A point which needs to be stressed in all these studies is that it appears possi- ble for the first time to improve histologic gastritis with drugs. Moreover, the improvement of inflam- mation after suppression or eradication of the drug and the reappearance of gastritis with recrudescence of the microorganism appears strong indication to us that this microorganism has to be considered as a true pathogen.

Whether Campylobacter Pyloridis is indeed pathogenetically related to gastric ulcer and perhaps duodenal ulcer, is by no means certain at present.

Many more studies in large groups of sequentially followed up patients are necessary before we truly know the pathogenetic significance of this microor- ganism. The only observation which we can accept as a true fact is the relationship between histological gastritis and the presence of this peculiar microor- ganism. For the rest only questions remain : What is the long term influence o f eradication of this microorganism with respect to recurrent peptic ulcer disease ? What is the natural source of this bacte- rium ? What is the source o f contamination ? Which is the best therapeutical approach to eradi- cate this Campylobacter Pyloridis ? Will eradication o f this microorganism allow arrest of the progres- sion of acute gastritis towards chronic gastritis and ultimately chronic atrophic gastritic ? Is chronic investation with Campylobacter the main cause lea- ding to chronic atrophic changes in the gastric mucosa, which might create an optimal environ- ment to malignant degeneration in the long run ? Is there a peculiar endoscopic appearance of the antrum mucosa when infected with Campylobacter Pyloridis ? Why do some individuals appear inca- pable of eradicating this microorganism sponta- neously ? Is there a genetic predisposition ? Is there an underlying immune deficit explaining individual susceptibility ? Why does this organism appear so difficult to eradicate ? Do we need drugs that pene- trate better the mucus gel or that partially destroy the mucus gel to expose the microorganism better to the bacteriocidal drugs ? Obviously many more questions can be formulated which urgently need an answer. Only through careful evaluation with meti- culous laboratory techniques will be able to under- stand the Campylobacter story, at present a most fascinating medical problem.

144 V o l u m e 16 - N " 3 - 1 9 8 6 A c t a E n d o s c o p i c a