458 research outputs found
Proton pump inhibitor failure: why does it occur and how can it be managed?
No full textProton pump inhibitors (PPIs) are the best medical
therapy for patients with gastro-oesophageal reflux disease
(GORD), as they control symptoms and heal oesophagitis
in about 80% of the cases [1] . Despite this high
degree of efficacy, a substantial part of the patients remains
symptomatic on once-daily PPI, and this is particularly
true for those with non-erosive reflux disease
(NERD). Although there is no universal agreement on
the definition of PPI failure in terms of frequency and
severity of symptoms, an incomplete or unsatisfactory response
of them to a full course of PPIs can be empirically
accepted as ‘refractory GORD’
Pharmacodynamic studies on PPIs: look carefully at the country of origin.
No full textThe pharmacodynamic effect of proton pump inhibitors
(PPIs) given in single daily dose is characterised by a complete
control of gastric acid secretion during the daytime and
a relatively lower activity during the nighttime [1]. Doubling
and fractioning the standard dosage of PPIs is generally associated
with a more uniform and constant increase of gastric pH over the whole 24-h period [2,3]. Among the various
factors capable of affecting the pharmacodynamic profile of
PPIs, Helicobacter pylori infection harbouring in the stomach
has been documented as a cause of increased gastric pH
in many studies [4,5]. The mechanism is not clear, but the
production of ammonia buffering gastric acid as result of bacterial
urease activity seems to play the most important role [6].
In this issue of the journal, Shimatani et al. [7] have
evaluated, in a prospective cross-over study, 24 CYP2C19 extensive metaboliser individuals from Japan, who were
subdivided into 13 H. pylori-negative healthy volunteers
and 11 asymptomatic H. pylori-positive subjects. They were
administered sequentially placebo, rabeprazole 10 mg twice
daily and 20 mg twice daily for 7 days, in a randomised
manner, and underwent three 24-h intragastric pH measurements
on the 7th day of each treatment in order to assess
the influence of H. pylori infection on the acid-suppressant
effect of the two doses of PPI. The Authors selected a group
of extensive metabolisers to assimilate as much as possible
their study population to people living in Western countries.
It is well known that there is a genetic polymorphism of
CYP2C19 which allows us to subdivide subjects roughly
into two categories: extensive or rapid metabolisers and poor
or slow metabolisers. The latter group, however, is much
more frequent in Asian than in Caucasian populations [8]
and therefore the Authors excluded them from the study in
order to avoid a possible bias.
The results they obtained show that the two rabeprazole
dosages had a much greater acid suppressive effect than
placebo, without significant difference between them. As to
the status of H. pylori infection, intragastric pH was significantly
higher in infected than in non-infected subjects.
Accordingly, nocturnal acid breakthrough (NAB) occurred
less in the former group. The only difference between the
two dosages of rabeprazole was the lower number of NAB
episodes achieved with 20 mg than 10 mg twice daily in H.
pylori-negative subjects, although a statistical significance
was not reached. However, the clinical relevance of NAB
episodes has been overemphasised in the past, because most
patients with gastro-oesophageal reflux disease (GORD) do
not present this phenomenon and especially patients with Barrett’s
oesophagus are more likely to have acid reflux during
NAB [9].
The significantly higher acid inhibition of rabeprazole
than placebo and the increased intragastric pH in H. pyloripositive
compared with H. pylori-negative subjects are
expected according to the previous medical literature in this
field [1–6]. Moreover, the impact of H. pylori eradication in
the management of patients with acid-related diseases is only
marginal, because there is no need of PPI dose adjustment to
maintain the therapeutic benefit in GORD patients whose
infection has been eliminated [6,10]. Lastly, if we look at a
recent study also coming from Japan [11], it has been shown
that the presence of H. pylori infection potentiates the symptomatic
response of GORD patients to famotidine and not to
low-dose lansoprazole.
An important drawback of this study is that PPIs were
administered after meals, while it is well known that these
drugs achieve their maximal acid-lowering effect when
given approximately half an hour before breakfast [3,8,12].
Although the Authors quote some papers showing the lack
of influence by meals on the pharmacodynamic properties of
PPIs in Asiatic populations, many studies carried out inWestern
countries confirm that the antisecretory action of these
drugs is greatly affected by meals [13–15] and a once daily
morning dosage regimen is generally recommended in the
treatment of acid-related diseases. In addition, a very recent
paper [16] has also shown that more than 50% of patients taking
PPIs and referred for persistent GORD symptoms were
suboptimal dosers, in that the intake of the drug occurred
>60 min before meals, after meals, at bedtime or as needed.
Accordingly, the therapeutic successwas lower than expected
in these cases.
It is also reasonable to think that the unusual administration
time of PPIs in this study may be responsible for
the surprising finding of a similar acid inhibition by the two
different dosages of rabeprazole. Many studies have clearly
shown a dose-dependent effect of PPIs [17,18] and this is
the reason for which doubling the dosage of PPIs can be the
simplest and most convenient measure to transform a therapeutic
failure with standard doses into a success [19,20]. It
cannot be excluded, however, that the similar pharmacodynamic
profiles of the two doses of rabeprazole, 10 mg and
20 mg twice daily, are due to the well known lower gastric
acid secretion of Asian than Caucasian populations [21] and
this reduced acid output can be adequately controlled even
by the smaller dose of PPI.
In conclusion, the study by Shimatani et al. is well done
from a methodological point of view and the Authors must be
congratulated for choosing Japanese patients with a genetic
polymorphism of CYP2C19 which is similar to that found
in Western populations. However, on one hand, the results
they achieved confirm previous studies on the influence of
H. pylori infection on the antisecretory effect of PPIs and,
on the other hand, seem to be greatly affected by the peculiar
physiologic background of Asian people. Therefore, their
findings cannot be easily extrapolated to ourWestern patients
and it must be acknowledged that the Authors themselves
have emphasised this point by making clear in the title of
the paper that the study was performed in Japanese subjects
Functional heartburn and non-erosive reflux disease.
No full textAbstract: Gastroesophageal reflux disease ( GERD) is a common disorder in Western countries. For many years our attention has been focused on patients with erosive esophagitis, but in recent times we have realized that endoscopy-negative reflux disease is the most common presentation of this illness, affecting up to 70% of these individuals. Patients with the non-erosive form (NERD) are a heterogeneous group including various subpopulations with different mechanisms for their main symptom of heartburn: reflux of acidic and non-acidic gastric contents, mucosal hypersensitivity, intra-esophageal distension by gas, intraduodenal infusion of fat, muscle contractions and psychological abnormalities. As to esophageal acid exposure, patients with NERD can be subdivided into those with abnormal and normal pH testing. The latter group includes patients with a positive correlation between symptoms and reflux events, in whom heartburn can be controlled by proton pump inhibitor ( PPI) therapy. According to the recent Rome III criteria, they are still in the realm of GERD. An additional group is called functional heartburn, because this typical symptom is associated neither with an abnormal pH test nor with a positive symptom index. Their response to PPIs is very disappointing. Therefore, there is an increasing consensus on the fact that they do not have GERD and should be treated with drugs other than PPIs
Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease
No full textINTRODUCTION: Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. AIM: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). METHODS: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. RESULTS: Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p<0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. CONCLUSION: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux
Prevention of postoperative recurrence of Crohn's disease by Adalimumab: a case series.
No full textAbstract: Adalimumab, an anti-TNF-alpha monoclonal antibody, was found to be effective for the treatment of luminal Crohn's disease (CD), but its efficacy for the prevention of postoperative recurrence of CD is still unknown. Here, we present a case series of six patients who underwent resection for an ileocecal stricture caused by CD. Surgery removed the involved ileocolon, and pathology confirmed the presence of a fibrotic stricture. Two weeks after the operation, they were given Adalimumab at the dose of 160/80/40mg every 2 weeks and were followed up. Since then, they have been disease-free for similar to 3 years after surgery on clinical, radiological, and endoscopic/histological grounds (Crohn's Disease Activity Index <= 110 in all occasions). Up to now, they have had no anemia, no increase in inflammatory indices, and no abnormal blood tests. These are the first cases, to our knowledge, in which Adalimumab has been successfully used to prevent the postsurgical recurrence of CD, an event so far considered to be mandatory. Further large placebo-controlled studies are necessary to show the therapeutic advantage and the economic implications of these observations
The role of Acid in functional dyspepsia.
No full textTo The Editor:
We read the recent study by Xiao et al. (1) with interest. The authors evaluated 24-h pH monitoring and response to rabeprazole (10 mg b.i.d.) for 4 weeks in 186 consecutive Functional Dyspepsia (FD) patients identified using the validated Rome III criteria (2). Subdividing FD patients on the basis of their predominant symptom, they found that those complaining of epigastric burning had the highest prevalence of abnormal reflux and the greatest response to anti-secretive therapy. These results are in keeping with those observed in a study we have recently published (3) evaluating the overlap between FD and Non-Erosive Reflux Disease (NERD) in a large population of endoscopy-negative patients. We investigated 200 patients with NERD using impedance-pH monitoring off-PPI therapy in order to clearly identify the different subgroups of patients collected under the NERD umbrella (4). Moreover we prospectively used a validated dyspepsia questionnaire to evaluate presence and severity of dyspeptic symptoms (5). We observed that NERD patients with abnormal pH (% time pH 4,2%) more frequently complained of symptoms such as epigastric pain and epigastric burning (Epigastric Pain Syndrome, EPS), while patients with functional heartburn (normal pH and negative symptom association; FH) referred more frequently nausea, early satiety, postprandial fullness and bloating (Post-prandial Distress Syndrome, PDS). Moreover, in the same study we found that patients with abnormal-pH and overlapping EPS symptoms responded better to anti-secretive therapy (72%) than patients with hypersensitive esophagus (normal pH and positive symptom association) and FH (53% and 29%, respectively), although in our study the information about therapeutic response was retrospectively obtained.
Overall, these results reinforce the role of acid not only in patients with gastroesophageal reflux disease but also in patients with EPS syndrome, in particular in case of epigastric burning, and suggest that in these patients antisecretory therapies should be considered as first choice more than in patients with PDS syndrome, where prokinetics seem to be more appropriate. At the same time therapies different from acid suppression (antidepressants? hypnotherapy?) should be considered in patients with FH in order to spare these patients from wasteful and protracted courses of years of acid suppression
Management strategy for patients with gastroesophageal reflux disease: A comparison between empirical treatment with esomeprazole and endoscopy-oriented treatment
No full textCharacteristics of gastro-esophageal reflux episodes in Barrett's esophagus, erosive esophagitis and healthy volunteers
No full textBACKGROUND: Gastro-esophageal reflux is considered a major culprit in the pathogenesis of Barrett's esophagus (BE). Still, there is controversy on the role of weakly acidic and weakly alkaline reflux in BE. To compare characteristics of reflux episodes patients with BE, erosive esophagitis (EE), and healthy volunteers (HV).
METHODS: One hundred consecutive patients with BE (75 short-segment BE, 25 long-segment BE), 50 with EE and 48 HV underwent multichannel intraluminal impedance-pH off-therapy. We quantified esophageal acid exposure, characteristics, and proximal extension of reflux episodes.
KEY RESULTS: Total and acid reflux episodes gradually increased from HV [28 (17.5-43) and 18 (8-31)] to EE [73.5 (54-96) and 52 (39-68)], short-segment BE (SSBE) [83 (73.2-131) and 65 (43.3-95)] and long-segment BE (LSBE) [105 (102-187) and 77 (75-107)]. Weakly acidic reflux episodes were significantly higher (P < 0.05) in LSBE [36 (27.5-50.5)] and SSBE [34 (18.5-41)] compared to EE [21.5 (15-37)] and HV [19 (14-25)]. No differences in terms of proportion of acid, weakly acidic and weakly alkaline reflux were found [HV (49%-49%-2%) vs EE (68%-32%-1%) vs SSBE (65%-34%-1%) vs LSBE (69%-30%-1%); P = ns]. In LSBE, a higher percentage of reflux episodes (P < 0.05) reached the proximal esophagus (59%) compared with SSBE (43%).
CONCLUSIONS & INFERENCES: Barrett esophagus patients have more severe reflux as shown by the number of acid and weakly acidic reflux episodes, re-reflux episodes and proximal migration. Given that PPI change only the pH of the refluxate, the role of weakly acidic reflux in Barrett's patients on acid suppressive therapy warrants further investigation
Cell proliferation of squamous epithelium in gastro-oesophageal reflux disease: correlations with clinical, endoscopic and morphological data
No full textBackground: The microscopic assessment of squamous epithelium lesions in gastro-oesophageal reflux disease (GERD) is subjective. The Ki67 nuclear antigen expressed by proliferating cells provides an objective measure of regeneration in the squamous epithelium. Aim: To evaluate Ki67 expression in GERD patients and controls, in comparison with histological lesions, pH-metry and endoscopic data.
Methods: Eighty-seven patients with GERD symptoms and 20 symptom-free controls underwent endoscopy and 24-h pH monitoring. Oesophageal biopsies (4 cm, 2 cm and Z-line) were stained with Ki67/MIB-1 antibodies; the Ki67-positive nuclear area was assessed with an image analysis system and expressed as percentage of the whole epithelial area (Ki67-%).
Results: Ki67-% was significantly higher in 32 patients with erosive oesophagitis, 44 endoscopy-negative GERD and 11 patients with functional heartburn than in controls (P = 0.0001). Both controls and patients showed a progressive increase in Ki67-% from 4 cm to the Z-line (P < 0.0001). Ki67-% showed a significant correlation with other conventional histological lesions (P ranged between 0.0151 and <0.0001).
Conclusions: Ki67 evaluation provides quantitative and objective data on squamous epithelium proliferative activity. This marker can be applied in the distinction of endoscopy-negative GERD from healthy controls
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