Acta Chirurgica Belgica

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Current Status of Proximal Gastric Vagotomy, One

Hundred Years after Pavlov: is it Finally History?

W. Mistiaen*, R. Van Hee & H. Bortier*

To cite this article: W. Mistiaen*, R. Van Hee & H. Bortier* (2005) Current Status of Proximal
Gastric Vagotomy, One Hundred Years after Pavlov: is it Finally History?, Acta Chirurgica Belgica,
105:2, 121-126, DOI: 10.1080/00015458.2005.11679684

To link to this article: https://doi.org/10.1080/00015458.2005.11679684

Published online: 11 Mar 2016.

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Review papers

Acta chir belg, 2005, 105, 121-126

Current Status of Proximal Gastric Vagotomy, One Hundred Years after Pavlov :
is it Finally History ?
W. Mistiaen*, R. Van Hee**, H. Bortier*
Laboratory for Human Anatomy and Embryology*, University of Antwerp, Belgium ; Dept of Surgery**, General
hospital Stuivenberg, Antwerp, Belgium.

Key words. Gastric ulcer ; gastric acid ; Helicobacter pylori ; vagotomy ; antibiotics ; resistance.

Abstract. One hundred years ago, the role of the vagal nerve in gastric acid production was established. After the sec-
ond World War, this paradigm served as the basis of treatment of peptic ulcer disease by pharmacological or surgical
means. A remarkable parallelism between the developments of both approaches was observed in the 1970s. On the one
hand, medication with less side effects became available. On the other hand, vagotomies were becoming more physio-
logic in nature and produced less postoperative symptoms. The elusive nature of peptic ulcer disease and the inability
to cure this by medication were acknowledged. Very few investigators, however, had reported on a possible infectious
origin of peptic ulcer disease and those reports were old. After 1984, the role of Helicobacter pylori in the disease was
discovered. With this shift in paradigm, the treatment of peptic ulcer disease changed radically, despite attempts in the
surgical community to develop simplified operations. This illustrates that neither the most powerful acid reducing drugs
on their own, nor the most physiological and least invasive surgical techniques stand the test of time if the underlying
paradigm changes. It also illustrates that old ideas should not be overlooked.

Introduction responsible for the formation of peptic ulcers were

One hundred years ago Pavlov delivered his lecture as
laureate for the Nobel Prize in Physiology and
Medicine. He showed that the nervous system played a
dominant role in the regulation of digestive processes.
He stated : “So the stimulation effected by the act of eat-
ing reaches the gastric glands by means of the nerve
fibers that are contained in the vagus nerves” (1). This
was the advent of modern physiology of digestion and
has added to the paradigm “no acid – no ulcer”. Its prin-
ciples also served as a basis for vagotomy as surgical
treatment of peptic ulcer disease. A parallelism between
the surgical and pharmacological acid reducing
approach could be observed. With the discovery of the
role of Helicobacter pylori in peptic ulcer disease, the
importance of a shift in paradigm on the therapeutic
approach of peptic ulcer disease is highlighted.
The causal model of peptic ulcer
It was stated that, without active gastric secretion, no
peptic ulcer would occur. An imbalance between the
defense – the gastric mucosa – and the aggression – the
gastric acid – was proposed as a mechanism. An
overview of available treatments for peptic ulcer in 1960
showed that most researchers focused their attention on
the defensive mechanisms (2). The mechanisms held
a) spasms of small arteries in the gastric wall with
decreased mucosal defense, b) increased gastric acid
production in patients with a duodenal ulcer,
c) increased stress after trauma or major surgery, d) neu-
rological stimuli causing pyloric spasms and retention of
gastric acid and e) infections. The latter, with primary
foci in the dental region and haematogenic dissemina-
tion to the gastic mucosa was already proposed in 1916,
after elaborate experiments with streptococci (3). The
role of gastroduodenal mucosal inflammation in relation
to infection as a precondition for ulceration was investi-
gated as early as 1923 (4). The production of gastric acid
played the most important role in the causal model of
this disease. This thinking had a profound influence on
the medical and surgical approach. In both fields,
research was stimulated towards reduction of gastric
acid secretion with emphasis on the reduction of the side
effects of the existing treatments.
Development of highly selective (or parietal cell or
proximal gastric) vagotomy
Despite the statement of Pavlov, surgical treatment of
peptic ulcer disease in the first decades of the twentieth
century was mainly gastro-enterostomy. Ulcer recur-
rence after this procedure, however, was unacceptably
high. Gastric resection was another operative treatment
122
for peptic ulcer. Its side effects, dumping, diarrhoea,
poor gastric emptying and weight loss served as a stim-
ulus for further research by LATARJET (5) and other sur-
geons. The modern era of this research began with
Lester DRAGSTEDT, who applied truncal vagotomy in
peptic ulcer patients (6). A drainage procedure was
added to prevent gastric stasis (5). The procedure was
considered to be easy, with an acceptable safety record.
There were also side effects, such as dumping, diarrhoea
and gall stone formation. As a response to the postoper-
ative symptoms, partial or proximal gastric vagotomy
was experimentally developed in 1957 by GRIFFITH and
HARKINS (8). In this operation, the antral innervation was
preserved and no drainage procedure was added. This
procedure became widely known and applied as parietal
cell vagotomy or highly selective vagotomy from 1969
on (9, 10). In 1976, it was concluded that this operation
had the lowest morbidity and mortality of any operation
used at that time as treatment for peptic ulcer dis-
ease (11). This was attributed to an almost normal gas-
tric emptying, which was confirmed in gastric emptying
studies using radio labeled liquid and solid test meals in
peptic ulcer patients who had undergone highly selective
vagotomy without a drainage procedure (12, 13). Highly
selective vagotomy promised to become as effective as
truncal vagotomy.
Developments of the pharmacological approach and
the response of surgeons
Some parallellism with the pharmacological approach in
peptic ulcer patients could be made. In 1960, the med-
ical treatment was bed rest, a diet based on milk and
milk products for at least 6 weeks, antacids and anti-
cholinergics. The aim was comparable to that of
surgery : reduction or neutralisation of an increased
secretion of gastric acid. The pharmacological vagotomy
also had side effects, including a decreased gastric emp-
tying rate. Interestingly, when highly selective vagotomy
was clinically applied, histamine receptor 2 antagonists
also became available. These drugs also had fewer side
effects and replaced anticholinergics completely.
Surgical and pharmacological approaches were both
very succesful in their attempts to reduce the side effects
in gastric acid reduction. The year 1989 seemed a pivotal
moment for several reasons : powerful proton pump
inhibitors became available and the surgical community
had to redefine the guidelines for ulcer surgery (14). On
the one hand, it was stated that none of the available
drugs were able to alter ulcer diathesis, that it was not
known if they were protective and that no reduction in
ulcer mortality rate was found despite the prescription of
vast amounts of histamin-2 receptor antagonists (15).
On the other hand, vagotomy might offer some protec-
tion : although ulcers did recur after surgery, these rarely
W. Mistiaen et al.
bled or perforated. Therefore, surgery was recommend-
ed for those who relapsed frequently or early during or
after several courses of histamin-2 receptor antago-
nists (14). Highly selective vagotomy has been the sub-
ject of extensive investigation for its effects on gastric
acid secretion and other digestive functions (16). The
safety and the low number of postoperative side effects
were confirmed. Although the underlying principle –
reduction of gastric acid output - was the same for both
surgery and the pharmacological approach, the question
was raised if a cure of peptic ulcer disease was feasible,
since no permanent reduction of gastric acid secretion
could be achieved with pharmacological methods (14).
This could be attributed to the fact that the cause of pep-
tic ulcer disease was still not clear.
At the same time, the number of patients eligible for
surgery had diminished, so the expertise of the individ-
ual surgeon was expected to decline. A simplified pro-
cedure, with a steeper learning curve, could solve the
problem. This was becoming important, since the main
criticism for highly selective vagotomy and its variants
was the incidence of recurrent ulcer. The hope of reach-
ing an ever-improving record of clinical results at that
time was based on the hope that results could be
improved by experience (17-19) and on the relative ease
of the treatment of the recurrent ulcer (16). Even as
recently as 1998, postoperative results seemed to justify
some hope (20).
The complexity of this operation, which was consid-
ered as tedious and time consuming, served as the stimu-
lus for further research. Results of anatomical and physi-
ological investigations between 1970 and 1980 made it
possible to sever the posterior vagal trunk in the perfor-
mance of a vagotomy without drainage and the first clin-
ical results were published a few years later (21-23).
Reduction of gastric acid secretion was adequate and gas-
tric emptying rate was not altered significantly.
Seromyotomy of the gastric wall along the lesser curve
was developed in the same period (24). Both procedures
were combined, resulting in a simple operation for chron-
ic duodenal ulcer, called posterior truncal vagotomy with
anterior wall seromyotomy (25). The clinical results were
also encouraging. As an alternative to the seromyotomy, a
stapling procedure was proposed, as an attempt to avoid
unrecognised incomplete vagotomy or gastric wall perfo-
ration. It also resulted in a satisfactory reduction in gas-
tric acid output, with a limited or temporary effect on gas-
tric emptying (26-29). An acceptable degree of exocrine
pancreatic function was preserved (30).
The new model of ulcer treatment and the place of
surgery
In 1984, 68 years after Rosenows suggestion of an infec-
tious origin of peptic ulcer disease, MARSHALL and
Is Vagotomy Finally History ?
WARREN pointed to a relationship between peptic ulcer
disease and Campylobacter pyloridis, which is now
called Helicobacter pylori, but its role remained unclear
for some years (31, 32). However, an explosion of inter-
est in the role of this germ followed, which has contin-
ued up to the present time. Between 1992 and 2002,
more than 1,000 clinical trials appeared and more than
16,000 articles were written (33). This approach has
resulted in a dramatic benefit for patients with peptic
ulcer disease and a possible lifelong cure (34).
Interestingly, an effect of dental care on the occur-
rence of peptic ulcer was observed long before the dis-
covery of the role of Helicobacter pylori (2). This bac-
terium was directly observed in dental plaques and was
significantly associated with the presence of the organ-
ism in the stomach (35, 36). Helicobacter pylori colo-
nizes the human stomach and areas of gastric metaplasia
in the duodenum, but only a minority of those patients
that were infected develop peptic ulcers. This observa-
tion could explain why it was so difficult to make the
connection between Helicobacter pylori and peptic ulcer
disease. The paradigm of “no acid – no ulcer” needed
replacement by “treatment of pH but also of Hp”, since
Helicobacter pylori was an important pathogen in
gastroduodenal inflammation and ulceration. A down-
regulated immune response could play a role in the
development of duodenal ulcers (37). A connection
between an inflammatory activity in gastric mucosa and
a Helicobacter pylori infection was established. but this
was not straight forward. An increase of a counter-
inflammatory response, which might dampen the
inflammatory and cytotoxic effects also occurred (38). It
seemed possible that inflammation modified the secre-
tion of gastric acid, through cytokines and inter-
leukines (39). This effect could also serve as explanation
as to why the therapeutic measures were directed only
towards acid reduction : before the establishement of the
role of Helicobacter pylori in peptic ulcer disease, this
was the only phenomenon that could be tackled by med-
ication or by surgery. Vagotomy in whatever form had
the advantage that the obtained gastric acid reduction
had a more definitive character, but no definitive cure
seemed possible by acid reduction alone.
This new approach could be considered as a shift in
paradigm, with a profound effect on the therapeutic
approach of peptic ulcer disease. Prospects for a cure of
peptic ulcer disease would alter the therapeutic approach
forever. Nevertheless, some problems remained. A sin-
gle antibiotic with a proton pump inhibitor did not
always result in optimal eradication rates. Adding a sec-
ond antibiotic was more satisfactory (40). Despite its
effectiveness, there were problems including increasing
resistance of Helicobacter pylori to antibiotics, compli-
cated therapeutic regimens, side effects, patient compli-
ance and re-infection.
123
The problem of resistance is still growing and has
made complete eradication difficult until today (41).
Eradication rates under 90% were probably common
and considered as problematic (42). This problem is
nowadays worldwide and affects mostly Metronidazole,
but also other antibiotic agents. Rescue therapy with
several other antibiotic agents failed in approximately
20% of the patients (43, 44). In a series of patients with
two failed eradication attempts, even a third and compli-
cated course was frequently unsuccessful. Closely relat-
ed to the problem of resistance of Helicobacter pylori
was patient compliance. This was hampered by the com-
plicated regimens and by side-effects (45, 46). Shorter
and simpler regimens could result in better compli-
ance (47). Nevertheless, in one series, the eradication
rate in “good compliers” was less than 70% ! Bacterial
resistance and poor compliance could only account for
40% of the failures (46). Annual reinfection varied from
3% to 35% (47). With it, ulcer relapse could occur.
However, ulcer relapse could also be as recrudescence or
occur in H pylori negative patients (48). An ulcer recur-
rence with bleeding might occur occasionally in patients
cured of H pylori, even if acid output was normal (49).
Economical costs were also an important factor. The
main determinant of overall cost of treatment of peptic
ulcer was (and still is) the rate of eradication of
Helicobacter pylori (45). Eradication of Helicobacter
pylori prevented the relapse of peptic ulcer disease and
was cost-effective compared with maintenance acid sup-
pressive therapy (51, 52). In one study, after successful
eradication, half of the patients still used acid reducing
medication after one year. After 3 years, this was one
quarter. This seemed due to persisting symptoms (52).
A recent survey revealed that most surgeons in the
UK no longer performed vagotomy for duodenal ulcer
complication. More than 80% prescribed a Helicobacter
pylori eradication treatment : however, fewer than 60%
routinely tested their patients (53).
Surgery in ulcer complications
The major complications of peptic ulcer disease were
perforation, uncontrollable bleeding and gastric outlet
obstruction. The question still remained : do patients
who need closure of a perforation or suture of a bleed-
ing ulcer also need a definitive procedure, such as a
vagotomy ? Some observed with the decrease of surgery
for uncomplicated duodenal ulcer an increase in surgery
for bleeding ulcers (54). In patients at risk for re-bleed-
ing and death, surgery decreased mortality if performed
before shock developed. Proximal gastric vagotomy for
bleeding ulcers could be selected in good risk
patients (55) but few surgeons have experience with this
procedure in such conditions. Suturing followed by a
medical treatment seemed safer. Referral to a centre
124
with expertise could be advocated (56). Vagotomy or its
simplified variants seemed more often required for
bleeding ulcers in patients from low socio- economic
levels, in whom medical treatment and its surveillance
were unaffordable (57).
Closure of perforated duodenal ulcer with vagotomy
was recommended due to a low mortality and minimal
stress (58). Some even considered proximal gastric
vagotomy a “gold standard” treatment of perforated
ulcer in the absence of risk factors (59). There was lower
ulcer recurrence in experienced hands and there was no
harm in those (unidentifiable) patients that might not
have benefited from definitive surgery (60). Patients
with significant symptoms for more than 3 months prior
to the perforation did well after closure with proximal
gastric vagotomy. Vagotomy in the presence of general-
ized peritonitis after ulcer perforation was not warrant-
ed (61). Treatment of Helicobacter pylori infection was
seen as an adjunct following surgical treatment of
gastroduodenal disease (62).
Elective surgery for duodenal ulcer still has its pro-
ponents. According to some, proximal gastric vagotomy
should be offered to patients with a duodenal ulcer,
refractory to all forms of medical therapy (63), in
patients with a persistent ulcer that is not Helicobacter
pylori positive or in patients in whom H pylori cannot be
eliminated. It may be needed again if Helicobacter
pylori becomes resistant to a whole series of antibio-
tics (56). With this evolution, it might be possible that
the introduction of the simplified techniques through the
laparoscope could revive surgical treatment of peptic
ulcer to some degree. Reports appeared in the last
decade of the twentieth century, concerning the laparo-
scopic approach of peptic ulcer disease as elective
surgery. It was considered as cost effective compared to
a life long pharmacological treatment (64-66). There
was a shorter hospital stay, reduced costs, less morbidi-
ty and improved comfort (67, 68). A more accurate
approach seemed possible, due to better visualization of
the small vagal connections to the parietal cells (69). In
patients with a perforated or bleeding ulcer, laparoscop-
ic vagotomy proved to be a low morbidity surgical
option only in the absence of risk factors, which was
also the case for open surgery (70-72).
Laparoscopy had renewed interest in vagotomy as a
treatment for duodenal ulcers, with an indication of
operation, which should be based on therapy resistant
symptoms (66). Nevertheless this approach did not
change the recurrence rate of peptic ulcer after vagoto-
my and was therefore assumed not to alter the indication
for surgery (73).
The simplified procedures through the laparoscope
proved to be equally efficacious in experimental reduc-
tion of acid output and compared favourably with trun-
cal vagotomy with pyloroplasty (74). Gastric emptying
W. Mistiaen et al.
rate was preserved (75). These procedures were even
considered as “gold standard” for their simplicity and
effectiveness in intractable duodenal ulcer disease and
could be used in patients who could not take long-term
medication. Very precise performance was enabled
through the laparoscope (76, 77).
Guidelines can be obtained from randomized con-
trolled trials, but these are few. Some recommendations
can be made, however.
In perforated ulcers, a laparoscopic approach seems
preferable to conventional surgery since postoperative
morbidity is lower (78, 79), but immediate acid reducing
surgery is not warranted in the presence of generalized
peritonitis (61).
In bleeding ulcers, endoscopic treatment had lower
direct costs of medical care (80) but early surgery was
effective if a high risk for rebleeding was present. A sub-
group of patients who received re-endoscopic treatment
still required surgery (81). Massive bleeding, uncontrol-
lable by endoscopy needs urgent surgery (82).
Vagotomy in complicated peptic ulcers can only be
performed if there are no other risk factors (70-72) and
if the surgeon has an expertise with this type of opera-
tion.
Conclusion
The history of treatment of peptic ulcer disease revealed
that a profound understanding of the nature of a disease
is necessary for proper treatment. At the beginning of the
twentieth century, Pavlov documented the importance of
the role of the nervus vagus in the control of gastric acid
production. It was also clear that in many patients with
a peptic ulcer, gastric acid production had increased.
However, the hypothesis concerning the infectious ori-
gin of peptic ulcer disease was completely neglected.
This resulted in a treatment directed to the reduction of
gastric acid by surgical and pharmacological means.
Both approaches underwent a remarkable process of
refining and improving. This resulted in a major
decrease of side effects, but the problem of ulcer relapse
was never fully solved.
The discovery of the role of Helicobacter pylori in
peptic ulcer disease resulted in a completely different
approach to peptic ulcer disease. It also resulted in the
almost complete disappearance of a very thoroughly
investigated surgical treatment, despite the preservation
of physiological motility and the development of a min-
imally invasive approach through the laparoscope. Only
in some patients with complicated ulcers, a form of
highly selective vagotomy could be added to the closure
of the perforation or the haemostatic procedure. This
approach, however, required that the procedure be
performed by a surgeon with expertise. A simplified
procedure could avoid a long learning curve and a
Is Vagotomy Finally History ?
laparoscopic approach could avoid significant morbi-
dity.
References
1. http://www.nobel.se/medicine/laureates/1904/Pavlov-lecture.html.
2. Nederlands leerboek der interne geneeskunde. Eds : Van Buchem
FSP, Scheltema & Holkema, Amsterdam, The Netherlands, 1960
pp. 28-53 (FE Revers).
3. ROSENOW C. E. The causation of gastric and duodenal ulcer by
streptococci. J Infect Dis, 1916, 333-385.
4. KONJETNY G. E. Die chronische gastritis des ulcusmagens.
Zentralblatt für Chirurgie, 1923, 26 : 1026-1028.
5. LATARJET A. Resection des nerfs de l’estomac : technique opera-
toire. Bull Acad Med Paris, 1922, 87 : 681.
6. DRAGSTEDT L. R., OWENS F. M. Jr. Supra-diaphragmatic section of
the vagus nerves in the treatment of duodenal ulcer. Proc Soc Exp
Biol Med, 1943, 53 : 152.
7. DRAGSTEDT L. R., SCHAFER P. W. Removal of the vagus innervation
of the stomach in gastroduodenal ulcer. Surgery, 1945, 17 : 742-9.
8. GRIFFITH C. A., HARKINS H. N. Partial gastric vagotomy : an exper-
imental study. Gastro-enterology, 1957, 32 : 96-102
9. AMDRUP E., JENSEN H. E. Selective vagotomy of the parietal cell
mass preserving innervation of the undrained antrum. Gastro-
enterology, 1970, 59 : 522-7.
10. JOHNSTON D., WILKINSON A. Highly selective vagotomy without a
drainage procedure in the treatment for duodenal ulcer. Br J Surg,
1970, 57 : 289-96.
11. JORDAN P. H. Jr. Current status of parietal cell vagotomy. Ann Surg,
1976, 184 : 659-71.
12. VAN HEE R., MISTIAEN W., BLOCKX P. Gastric emptying of liquids
after highly selective vagotomy for duodenal ulcer. Hepatogastro-
enterology, 1989, 36 : 92-6.
13. MISTIAEN W., VAN HEE R., BLOCKX P., HUBENS A. Gastric emptying
for solids in patients with duodenal ulcer before and after highly
selective vagotomy. Dig Dis Sci, 1990, 35 : 310-6.
14. TAYLOR T. V. Current indications for elective peptic ulcer surgery.
Br J Surg, 1989, 76 : 427-8.
15. FLETCHER D. R. Peptic disease : can we afford current manage-
ment ? Aust NZ J Surg, 1997, 67 : 75-80.
16. SCHIRMER B. D. Current status of parietal cell vagotomy. Ann Surg,
1989, 209 : 131-48.
17. JOHNSTON D., GOLIGHER J. C. The influence of the individual
surgeon and the type of vagotomy upon the insulin test after
vagotomy. Gut, 1971, 12 : 963-7.
18. Editorial. Recurrent ulcer after vagotomy : just a matter of
technique ? Lancet, 1976, 2 : 1005-7.
19. BLACKET R. L., JOHNSTON D. Recurrent ulcer after highly selective
vagotomy for duodenal ulcer. Br J Surg, 1981, 68 : 705-10.
20. LINDSETMO R. O., JOHNSEN R., REVHAUG A. Abdominal and dys-
peptic symptoms in patients with peptic ulcer treated medically or
surgically. Br J Surg, 1998, 85 : 845-9.
21. BRIZZI E., SERANTONI C., CRANI P. A., ORBANDINI A., PERNICE L. The
distribution of the vagus nerves in the stomach. Chir Gastro-
enterol, 1973, 7 : 17-34.
22. DANIEL E. E., SARNA S. K. Distribution of excitatory vagal fibers
in canine gastric wall to control motility. Gastro-enterology, 1976,
71 : 608-13.
23. HILL G. L., BARKER M. C. J. Anterior highly selective vagotomy
with posterior truncal vagotomy : a simple technique for dener-
vating the parietal cell mass. Br J Surg, 1978, 65 : 702-5.
24. TAYLOR T. V. Lesser curve superficial seromyotomy : an operation
for chronic duodenal ulcer. Br J Surg, 1979, 66 : 733-7.
25. TAYLOR T. V., GUNN A. A., MC LEOD D. A. D., MCLENNAN I.
Anterior lesser curve seromyotomy and posterior truncal vagoto-
my in the treatment of chronic duodenal ulcer. Lancet, 1982, II
846-9.
26. HENDRICKX L., VAN HEE R., VAN DER KELFT E., HUBENS A. Anterior
gastric wall stapling combined with posterior truncal vagotomy :
an experimental technique for gastric acid reduction. Eur Surg
Res, 1987, 19 : 225-32.
125
27. MISTIAEN W., VAN HEE R., BLOCKX P. Comparison of the effect of
conventional highly selective vagotomy and anterior gastric wall
stapling with posterior truncal vagotomy on the gastric emptying
rate for solid meals in beagle dogs. Eur Surg Res, 1994, 26 : 28-34.
28. VAN HEE R., MISTIAEN W., HENDRICKX L., BLOCKX P. Anterior gas-
tric wall stapling combined with posterior truncal vagotomy in the
treatment of duodenal ulcer. Br J Surg, 1995, 82 : 934-7.
29. MISTIAEN W., VAN HEE R., BLOCKX P. Gastric emptying rate of liq-
uid meals after anterior gastric stapling and posterior truncal vago-
tomy in beagle dogs : discrepancy with results for solid food.
Hepatogastroenterol, 1998, 45 : 286-92.
30. MISTIAEN W., VAN HEE R., BAO S. H. Pancreatic secretion after
anterior gastric wall stapling with posterior truncal vagotomy in
dogs. Eur Surg Res, 1996, 28 : 154-61
31. MARSHALL B. J., WARREN J. R. Unidentified curved bacilli in the
stomach of patients with gastritis and peptic ulceration. Lancet,
1984, 1 (8390) : 1311-5.
32. PRICE A. B., LEVI J., BOLBY J. M. et al. Campylobacter pyloridis in
peptic ulcer disease : microbiology, pathology and scanning elec-
tron microscopy. Gut, 1985, 26 : 1183-8.
33. MALHOTRA S., PANDHI P. Eradication of helicobacter pylori : cur-
rent perspectives. Expert Opin Pharmacother, 2002, 3 : 1031-8.
34. MALFERTHEINER P., LEODOLTER A., PEITZ U. Cure of helicobacter
pylori-associated ulcer disease through eradication. Bailleres Best
Pract Res Clin Gastro-enterol, 2000, 14 : 119-32.
35. YOUNG K. A., ALLAKER R. P., HARDIE J. M. Morphological analy-
sis of Helicobacyer pylori from gastric biopsies and dental plaque
by scanning electron microscopy. Oral Microbiol Immunnol,
2001, 16 (3) : 178-81.)
36. WATTS T. Management of Helicobacter pylori infection : dental
plaque is a potential reservoir for Helicobacter pylori. BMJ, 2002,
324 (7337) : 614-5.)
37. STROMBERG E., EDEBO A., SVENNERHOLM A. M., LINDHOLM C.
Decreased epithelial cytokine responses in the duodenal mucosa
of Helicobacter pylori-infected duodenal ulcer patients. Clin-
Diagn-Lab-Immunol, 2003 Jan, 10 (1) : 116-24
38. HOLCK S., NORGAARD A., BENNEDSEN M., PERMIN H., NORN S.,
ANDERSEN L. P. Gastric mucosal cytokine responses in Helico-
bacter pylori-infected patients with gastritis and peptic ulcers.
Association with inflammatory parameters and bacteria load.
FEMS-Immunol-Med-Microbiol, 2003 May 25, 36 (3) : 175-80
39. YAKABI K., MIMURA H., IWABUCHI H. et al. Neutrophil-derived
hydroxyl radicals mediate interleukin-8-induced increases in
tetragastrin-stimulated acid secretion in rats. Dig-Dis-Sci, 2003
Jun, 48 (6) : 1081-7
40. HOFFMAN J. S. Pharmacological therapy of Helicobacter pylori
infection. Seminars in gastro-intestinal disease, 1997, 8 : 156-63.
41. CRESPO A., SUH B. Helicobacter pylori infection : epidemiology,
pathophysiology and therapy. Arch Pharm Res, 2001, 24 : 485-98.
42. TRUST T. J., ALM R. A., PAPPO L. Helicobacter pylori : today’s treat-
ment and possible future treatment. Eur J Surg Suppl, 2001, 586 :
82-8.
43. GRAHAM D. Y., RAKEL R. E., FENDRICK A. M. et al. Practical advice
on eradicating Helicobacter pylori infection. Postgrad Med, 1999,
105 : 137-40.
44. VICENTE R., SILICIA B., GALLEGO S., REVILLO M. J., DUCONS J.,
GOMOLLON F. Helicobacter pylori eradication in patients with pep-
tic ulcer after two treatment failures : a prospective culture guided
study. Gastro-enterol Hepatol, 2002, 25 : 438-42.
45. GODSHALL C. J. treatment of Helicobacter pylori infection in
patients with peptic ulcer disease. Am J Surg, 2002, 183 : 2-3.
46. WERMEILLE J., CUNNINGHAM M., DEDERING J. P. et al. Failure of
Helicobacter pylori eradication : is poor compliance the main
cause ? Gastro-enterol Clin Biol, 2002, 26 : 216-9.
47. DOBRILLA G. Peptic ulcer, functional dyspepsia, Helicobacter
pylori : a, 1998 stock-taking on the topic of their correlation and
therapeutic strategies. Recent Prog Med, 1999, 90 : 347-54.
48. DIXON J. S. Helicobacter pylori eradication : unravelling the facts.
Scand J Gastro-enterol Suppl, 1995, 212 : 48-62.
49. CAPURSO G., ANNIBALE B., OSBORN J., D’AMBRARTINO G.,
LAHNER E., DELLE-FAVE G. Occurrence and relapse of bleeding
from duodenal ulcer : respective roles of acid secretion and Helico-
bacter pylori infection. Alimet Pharmacol Thet, 2001, 15 : 821-9.
126
50. RAUWS E. A., VAN DER HULST R. W. Current guidelines for the
eradication of Helicobacter pylori in peptic ulcer disease. Drugs,
1995, 50 : 984-90.
51. VAKIL N., FENNERTY M. B. Cost-effectiveness of treatment regi-
mens for the eradicatiion of Helicobacter pylori in duodenal ulcer.
Am J Gastro-enterol, 1996, 91 : 239-45.
52. KHAN Z., NAIR P., O’SHEA C., SPIERS N., PLAYFORD R. F., WICKS A.
C. Does Helicobacter pylori eradication reduce the long-term
requirements for acid suppressants in patients with a history of
peptic ulcer disease in general practice ? Results from a four-year
longitudinal study. Scand J Gastro-enterol, 2002, 37 : 144-7.
53. GILLIAM A. D., SPEAKE W. J., LOBO D. N., BECKINGHAM I. J. Current
practice of emergency vagotomy and Helicobacter pylori eradica-
tion for complicated ulcer in the United Kingdom. Br J Surg,
2003, 90 : 88-90.
54. KATKHOUDA N. Peptic ulcer surgery in, 1994. Endosc Surg Allied
Technol, 1994, 2 : 87-90.
55. LEGRAND M. J., JACQUET N. Surgical approach in severe bleeding
peptic ulcer. Acta Chir Belg, 1996, 59 : 240-4.
56. JOHNSON A. G. Proximal gastric vagotomy : does it have a place in
the future management of peptic ulcer ? World J Surg, 2000, 24 :
259-63.
57. BALAFREJ S., ECHARRAB E. M., EL OUNANI M. et al. Treatment of
bleeding duodenal ulcer. A study of mortality and indication of
surgical treatment. J Chir Paris, 1997, 134 : 406-9.
58. TSUGAWA K., KOYANAGI N., HASHIZUME M. et al. The therapeutic
strategies in performing emergency surgery for gastroduodenal
ulcer perforation in 130 patients over 70 years of age.
Hepatogastro-enterology, 2001, 48 : 156-62.
59. SUTER M. Surgical treatment of perforated peptic ulcer. Is there a
need for change ? Acta Chir Belg, 1993, 93 : 83-7.
60. JORDAN P. H. Jr., THORNBY J. Perforated pyloroduodenal ulcers.
Long-term results with omental patch closure and parietal cell
vagotomy. Ann Surg, 1995, 221 : 479-88.
61. NG E. K., LAM Y. H., SUNG J. J. et al. Eradication of H pylori pre-
vents recurrence of ulcer after simple closure of duodenal ulcer
perforation. Ann Surg, 2000, 231 : 153-8.
62. HATZ R., SCHILDBERG F. W. Helicobacter pylori infections – are
these diseases relevant for surgical treatment ? Langenbecks Arch
Surg, 2000, 385 : 75-83.
63. KAUFFMAN G. L. Jr. Duodenal ulcer disease : treatment by surgery,
antibiotics or both. Adv Surg, 2000, 35 : 121-35.
64. CASAS A. T., GADACZ T. R. Laparoscopic management of peptic
ulcer disease. Surg Clin North Am, 1996, 76 : 515-22.
65. MCCLOY R., NAIR R. Minimal access surgery – the renaissance of
gastric surgery ? Yale J Biol Med, 1994, 67 : 159-66.
66. FUCHS K. H., FREYS S. M., FEIN M., THIEDE A. Current aspects of
gastroduodenal disease : diagnosis of pathophysiologic back-
ground and indications for operative therapy. Endosc Surg Allied
Technol, 1994, 2 : 91-4.
67. ROYSTON C. M., BROUGH W. A. Laparoscopic surgery for hiatal
hernia and peptic ulceration. Eur J Gastro-enterol Hepatol, 1997,
9 : 756-60.
W. Mistiaen et al.
68. CADIERE G. B., BRUYNS J., HIMPENS J., VAN ALPHEN P.,
VERTRUYEN M. Laparoscopic highly selective vagotomy. Hepato-
gastro-enterology, 1999, 46 : 4500-6.
69. WETSCHER G. J., THEN P., PROFANTER C., BRUGGER M., HINDER R.
A., POINTNER R. Laparoscopic technique of proximal selective
vagotomy. Wien Jlin Wochenschr, 1996, 108 : 262-6.
70. GOH P., TEKANT Y. Endoscopic haemostasis of bleeding peptic
ulcers. Dig Dis, 1993, 11 : 216-27.
71. CADIERE G. B., HIMPENS J., BRUYNS J. Laparoscopic proximal
gastric vagotomy. Endosc Surg Allied Technol, 1994, 2 : 105-8.
72. KHOSROVANI C., KOHEN M., GUIBERTEAU B., LE NEEL J. C.
Perforations of duodenopyloric ulcers. Prognostic factors and
therapeutic choices. Retrospective study of 140 patients. Ann
Chir, 1994, 48 : 345-9.
73. BECKER H. D., JEHLE E., KREIS M. Evaluating elective surgical
procedures in ulcer surgery. Chirurg, 1996, 67 : 14-9.
74. BRODY F. J., TRAD K. S. Comparison of acid reduction in anti ulcer
operation. Surg Endosc, 1997, 11 : 123-5.
75. SCHNEIDER T. A. Jr, WITTGEN C. M., ANDRUS C. H., KAMINSKI D. L.
Comparison of minimally invasive methods of parietal cell
vagotomy in a porcine model. Surgery, 1992, 112 : 649-55.
76. CROCE E., AZZOLA M., GOLIA M. et al. Laparoscopic posterior trun-
cal vagotomy and anterior proximal gastric vagotomy. Endosc
Surg Allied Technol, 1994, 2 : 113-6.
77. LAWS H. L., MCKERNAN J. B. Endoscopic management of peptic
ulcer disease. Ann Surg, 1993, 217 : 548-56.
78. SIU W. T., LEONG H. T., LAW B. K. et al. Laparoscopic repair for
perforated peptic ulcer : a randomized controlled trial. Ann Surg,
2002, 235 : 313-9.
79. DRUART M. L., VAN HEE R., ETIENNE J. et al. Laparoscopic repair
of perforated duodenal ulcer. A prospective multi-centre trial.
Surg Endosc, 1997, 11 : 1017-20.
80. GRALNEK I. M., JENSEN D. M., KOVACS T. O. et al. An economic
analysis of patients with active arterial peptic ulcer haemorrhage
treated with endoscopic heater probe, injection sclerosis or
surgery in a prospective randomized trial. Gastro-intest Endosc,
1997, 46 : 105-12.
81. IMHOF M., OHMANN C., ROHER H. D., GLUTIG H. Endoscopic versus
operative treatment in high-risk ulcer bleeding patients – results of
a randomised study. Langenbecks Arch Surg, 2003, 387 : 327-36.
82. OHMANN C., IMHOF M., ROHER H. D. Trends in peptic ulcer
bleeding and surgical treatment. World J Surg, 2000, 24 : 284-93.
W. P. Mistiaen, M.D., Ph.D.
Laboratory for Human Anatomy and Embryology
University of Antwerp
Groenenborgerlaan 171
B-2020 Antwerp, Belgium
Tel. : 32 3 218 03 90
Fax : 30 3 218 03 98
E-mail : wilhelm.mistiaen@ua.ac.be