Postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance can link PPI-responsive heartburn to reflux better than acid exposure time.

BACKGROUND: Acid exposure time (AET) is considered the most useful parameter to predict response of reflux-related heartburn to medical or surgical treatment. However, recent studies showed high rates of heartburn response to proton pump inhibitor (PPI) therapy in patients with normal AET. We aimed to compare the efficacy of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) with AET in linking PPI-responsive heartburn to reflux. METHODS: Off-therapy impedance-pH tracings from 425 patients, 317 with PPI-responsive and 108 with PPI-refractory heartburn were blindly re-analyzed. Demographic and endoscopic characteristics, conventional impedance-pH variables, PSPW index, and MNBI were assessed with multivariate logistic regression to identify factors independently associated with PPI responsiveness. Prediction models were developed to assess the strength of reflux linkage with factors independently associated with PPI responsiveness by calculating the area under the curve (AUC) at receiver-operating-characteristic (ROC) analysis. KEY RESULTS: At multivariate logistic regression analysis, AET, MNBI, and PSPW index were the only factors independently associated with PPI responsiveness, abnormal values found in 60%, 76%, and 92% of PPI-responsive cases (P<.017). At ROC analysis, PSPW index (AUC:.794, P=.002) and MNBI (AUC: 0.742, P=.003), both separately and combined (AUC: 0.811, P<.001) linked reflux with PPI-responsiveness better than AET (AUC: 0.687). CONCLUSIONS & INFERENCES: AET, PSPW index, and MNBI are independently associated with PPI-responsive heartburn. PSPW index and MNBI can link PPI-responsive heartburn to reflux better than AET and should become part of the standard analysis of impedance-pH tracings.

The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring.

BACKGROUND: On-therapy impedance-pH monitoring in proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) yielded conflicting results. We aimed to assess the diagnostic value of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) in PPI-refractory heartburn. METHODS: On-therapy impedance-pH tracings from 189 consecutive patients with PPI-refractory heartburn were blindly reviewed. Patients were subdivided into refractory reflux esophagitis (RRE), healed reflux esophagitis (HRE), non-erosive reflux disease (NERD), and functional heartburn (FH) according to endoscopic and conventional impedance-pH findings. The diagnostic accuracy of PSPW index and MNBI in separating NERD from FH was assessed with receiver-operating-characteristic (ROC) analysis. Objectively documented persistent reflux remission at 3-year follow-up in 53 patients who underwent laparoscopic fundoplication served to evaluate PSPW index and MNBI as independent predictors of PPI-refractory GERD confirmed by positive surgical outcome. KEY RESULTS: Median PSPW index and MNBI values were significantly lower in 39 RRE (16%; 1145 Ω) than in 41 HRE (25%; 1741 Ω) and in 68 NERD (29%; 2374 Ω) patients, and in all three GERD subgroups compared to 41 FH cases (67%; 3488 Ω) (P<.008). At ROC analysis, comparing NERD to FH the area under the curve was 0.886 with PSPW index and 0.677 with MNBI (P=.005). PSPW index was an independent predictor of PPI-refractory GERD (odds ratio 0.6983, P=.012). CONCLUSIONS & INFERENCES: At on-therapy impedance-pH monitoring, PSPW index and MNBI efficiently distinguish PPI-refractory NERD from FH. The PSPW index represents an independent predictor of PPI-refractory GERD.

Vigor of peristalsis during multiple rapid swallows is inversely correlated with acid exposure time in patients with NERD.

BACKGROUND: Multiple rapid swallowing (MRS) during high-resolution manometry (HRM) is increasingly utilized as provocative test to assess esophageal peristaltic reserve. The aim of this study was to evaluate the correlation between MRS response and impedance and pH (MII-pH) parameters in endoscopy negative heartburn (ENH) patients. METHODS: We enrolled consecutive ENH patients, who underwent HRM and MII-pH study, with a selected MII-pH profile: abnormal MII-pH (pH+/MII+); normal MII-pH (pH-/MII-). HRM was performed with 10 wet swallows (WS) and one MRS. Mean distal contractile integral (DCI) during WS and MRS were calculated. MII-pH parameters including acid exposure time (AET), reflux events, baseline impedance levels (BI) and the efficacy of chemical clearance evaluated with the postreflux swallow-induced peristaltic wave (PSPW) index were measured. KEY RESULTS: We analyzed 103 patients: 49 MII+/pH+ (27 male), and 54 MII-/pH- (19 male). Mean age was similar between the two groups. As expected, mean AET and number of refluxes were higher in pH+/MII+ (p < 0.05). HRM was normal in all selected patients. Mean DCI-WS was similar between two groups (p = n.s.). Mean DCI-MRS- was higher in MII-/pH- vs MII+/pH+ (p < 0.05). The increase in DCI-MRS was inversely correlated with AET (-0.699; p < 0.001) and directly correlated with BI values (0.631; p < 0.001) and PSPW index (0.626; p < 0.001). CONCLUSIONS & INFERENCES: Following MRS, patients with abnormal impedance-pH test showed suboptimal contraction response as compared with those with normal impedance-pH test. Moreover, MRS response was inversely correlated with AET and directly correlated with BI values and PSPW index.

Neoplastic progression in short-segment Barrett's oesophagus is associated with impairment of chemical clearance, but not inadequate acid suppression by proton pump inhibitor therapy.

BACKGROUND: Pathophysiological mechanisms associated with neoplastic progression in patients with short-segment Barrett's oesophagus (SSBO), who represent the vast majority of the Barrett population, have not been defined. AIM: To evaluate pathophysiological characteristics of patients with SSBO and dysplasia detected at 3-year surveillance endoscopy (incident dysplasia). METHODS: Patients with SSBO underwent impedance-pH monitoring during heartburn-suppressing PPI therapy. Fifteen patients (12 males, median age 62 years) with incident dysplasia and 50 patients (43 males, median age 59 years) without dysplasia were compared. Impedance-pH parameters, including chemical clearance assessed by the post-reflux swallow-induced peristaltic wave (PSPW) index, were evaluated. RESULTS: All patients declared persisting heartburn suppression on maintenance PPI therapy at 3-year follow-up, 58/65 (89%) with standard dosages. The median gastric and oesophageal acid exposure time (GAET and OAET) did not differ between patients with and without incident dysplasia at the time of surveillance (36% and 0.6% vs. 33% and 0.5%) or index endoscopy (33% and 0.3% vs. 41% and 0.5%) (P > 0.05). Contrastingly, the median PSPW index was significantly lower in patients with than in patients without incident dysplasia at the time of surveillance (15%, vs. 32%) and index endoscopy (12% vs. 30%) (P = 0.001). The PSPW index, the GAET and the OAET did not vary over time (P > 0.05). A PSPW index <26% was predictive of incident dysplasia with a 75% accuracy. CONCLUSIONS: Neoplastic progression in SSBO is associated with impairment of chemical clearance, but not inadequate acid suppression by PPI therapy. Neoplastic progression in SSBO can be predicted by a low PSPW index.

Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn.

BACKGROUND: Recently, it has been suggested that low esophageal basal impedance may reflect impaired mucosal integrity and increased acid sensitivity. We aimed to compare baseline impedance levels in patients with heartburn and pathophysiological characteristics related to functional heartburn (FH) divided into two groups on the basis of symptom relief after proton pump inhibitors (PPIs). METHODS: Patients with heartburn and negative endoscopy were treated with esomeprazole or pantoprazole 40 mg daily for 8 weeks. According to MII-pH (off therapy) analysis, patients with normal acid exposure time (AET), normal reflux number, and lack of association between symptoms and refluxes were selected; of whom 30 patients with a symptom relief higher than 50% after PPIs composed Group A, and 30 patients, matched for sex and age, without symptom relief composed Group B. A group of 20 healthy volunteers (HVs) was enrolled. For each patient and HV, we evaluated the baseline impedance levels at channel 3, during the overnight rest, at three different times. KEY RESULTS: Group A (vs Group B) showed an increase in the following parameters: mean AET (1.4 ± 0.8% vs 0.5 ± 0.6%), mean reflux number (30.4 ± 8.7 vs 24 ± 6.9), proximal reflux number (11.1 ± 5.2 vs 8.2 ± 3.6), acid reflux number (17.9 ± 6.1 vs 10.7 ± 6.9). Baseline impedance levels were lower in Group A than in Group B and in HVs (p < 0.001). CONCLUSIONS & INFERENCES: Evaluating baseline impedance levels in patients with heartburn and normal AET could achieve a better understanding of pathophysiology in reflux disease patients, and could improve the distinction between FH and hypersensitive esophagus.

Esophageal chemical clearance is impaired in gastro-esophageal reflux disease--a 24-h impedance-pH monitoring assessment.

BACKGROUND: Impedance-pH monitoring allows assessment of retrograde and antegrade intra-esophageal movement of fluids and gas. Reflux is followed by volume clearance and chemical clearance, elicited by secondary and swallow-induced peristalsis, respectively. We aimed to assess whether chemical clearance is impaired in gastro-esophageal reflux disease (GERD). METHODS: Blinded retrospective review of impedance-pH tracings from patients with erosive reflux disease (ERD) and non-erosive reflux disease (NERD), and from proton pump inhibitor (PPI)-refractory patients before and after laparoscopic fundoplication. The number of refluxes followed within 30 s by swallow-induced peristaltic waves was divided by the number of total refluxes to obtain a parameter representing chemical clearance namely the postreflux swallow-induced peristaltic wave (PSPW) index. KEY RESULTS: The PSPW index was significantly lower in 31 ERD (15%) and in 44 NERD (33%) off-PPI patients than in 30 controls (75%), as well as in 18 ERD (16%) and in 48 NERD (31%) on-PPI patients than in 26 on-PPI functional heartburn (FH) cases (67%) (P < 0.05 for all comparisons). In 29 PPI-refractory patients, the median PSPW index was unaltered by otherwise effective antireflux surgery (20% postoperatively, 21% preoperatively). The overall sensitivity, specificity, positive, and negative predictive values of the PSPW index in identifying GERD patients were 97%, 89%, 96%, and 93%. CONCLUSIONS & INFERENCES: Impairment of chemical clearance is a primary pathophysiological mechanism specific to GERD: it is unaffected by medical/surgical therapy, is not found in FH, and is more pronounced in ERD than in NERD. Using the PSPW index could improve the diagnostic efficacy of impedance-pH monitoring.

The added value of quantitative analysis of on-therapy impedance-pH parameters in distinguishing refractory non-erosive reflux disease from functional heartburn.

BACKGROUND: By analysis of symptom-reflux association, endoscopy-negative refractory heartburn can be related to acid/non-acid refluxes with impedance-pH monitoring. Unfortunately, patients frequently do not report symptoms during the test. We aimed to assess the contribution of quantitative analysis of impedance-pH parameters added to symptom-reflux association in evaluating patients with endoscopy-negative heartburn refractory to high-dose proton pump inhibitor therapy. METHODS: The symptom association probability (SAP), the symptom index (SI), the esophageal acid exposure time and the number of distal and proximal refluxes were assessed at on-therapy impedance-pH monitoring. Relationships with hiatal hernia and manometric findings were also evaluated. KEY RESULTS: Eighty patients were prospectively studied. Refractory heartburn was more frequently related to reflux by a positive SAP/SI and/or abnormal impedance-pH parameters (52/80 cases) (65%) than by a positive SAP/SI only (38/80 cases) (47%) (P = 0.038). In patients with refractory non-erosive reflux disease (NERD) defined by a positive SAP/SI and/or abnormal impedance-pH parameters, the prevalence of hiatal hernia was significantly higher (56%vs 21%, P = 0.007) and the mean lower esophageal sphincter tone was significantly lower (18.7 vs 25.8 mmHg, P = 0.005) than in those (35%) with reflux-unrelated, i.e., functional heartburn (FH). On the contrary, no significant difference was observed subdividing patients according to a positive SAP/SI only. CONCLUSIONS & INFERENCES: Quantitative analysis of impedance-pH parameters added to symptom-reflux association allows a subdivision of refractory-heartburn patients into refractory NERD and FH which is substantiated by pathophysiological findings and which restricts the diagnosis of FH to one third of cases.

Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD.

BACKGROUND: EsophyX is a novel transoral incisionless fundoplication device developed to mimic surgical fundoplication. EsophyX fundoplication improves acid reflux parameters in proton pump inhibitor (PPI)-responsive GERD patients but its efficacy in refractory GERD has been scarcely studied. AIM: To assess reflux parameters before and after EsophyX or laparoscopic fundoplication and their relationship with symptoms in refractory GERD. METHODS: In an open-label study, we enrolled prospectively patients with heartburn/regurgitation persisting despite high-dose PPI therapy. Impedance-pH monitoring was performed on PPI therapy before intervention and off PPI therapy 3 months after intervention. RESULTS: Ten patients chose to undergo EsophyX (EndoGastric Solutions, Redmond, WA, USA) fundoplication while ten chose laparoscopic fundoplication, and the baseline characteristics were comparable. Distal and proximal refluxes were significantly reduced post-operatively in the surgical but not in the endoscopic group and the median values were significantly lower in the former than in the latter. The oesophageal acid exposure time was normal in 50% of cases after EsophyX and in 100% of cases after surgery (P=0.033); the number of distal refluxes was normal in 20% and 90% of cases (P=0.005) and the number of proximal refluxes was normal in 40% and 100% of cases (P=0.011), respectively. A positive persisting symptom-reflux association was found post-operatively in 6/10 patients in the EsophyX group and in 0/10 patients in the surgical group (P=0.011). CONCLUSIONS: In patients with refractory GERD, EsophyX fundoplication is significantly less effective than laparoscopic fundoplication in improving reflux parameters and accordingly, in inducing symptom remission.

Weakly acidic refluxes have a major role in the pathogenesis of proton pump inhibitor-resistant reflux oesophagitis.

BACKGROUND: In patients with heartburn that persists despite proton pump inhibitor (PPI) therapy, reflux oesophagitis is found rarely, and its pathogenesis has been scarcely studied. AIM: To assess reflux parameters by impedance-pH monitoring in PPI-resistant reflux oesophagitis. METHODS: Impedance-pH monitoring was performed on PPI therapy in patients with symptomatic reflux oesophagitis detected despite standard or high-dose PPI therapy of at least 8-week duration. RESULTS: Twenty patients, ten on once daily and ten on twice daily PPI regimens, were studied. The gastric acid exposure time (per cent time pH <4) ranged from 10% to 81% and was >30% in 70% of cases, but the oesophageal acid exposure time (per cent time pH <4) was abnormal in 20% of patients only. The number of acid, weakly acidic and weakly alkaline refluxes was abnormal in 25%, 100% and 15% of patients, respectively. CONCLUSIONS: Weakly acidic refluxes were above the normal range in all cases, whereas acid reflux parameters and weakly alkaline refluxes were normal in the vast majority of cases. Gastric acid secretion, with consequent intra-gastric pepsins activation, persists despite ongoing PPI therapy and activated pepsins may well be present in weakly acidic refluxes. As activated pepsins maintain their proteolytic activity in a weakly acidic environment, they may be responsible for mucosal damage. We conclude that weakly acidic refluxes have a major role in the pathogenesis of PPI-resistant reflux oesophagitis. Therapeutic interventions in patients with PPI-resistant reflux oesophagitis should be tailored on the basis of impedance-pH-monitoring results.

Characteristics of gastro-esophageal reflux episodes in Barrett's esophagus, erosive esophagitis and healthy volunteers.

BACKGROUND: 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.

Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy.

BACKGROUND: In short-segment Barrett's oesophagus (SSBO) heartburn may be absent and oesophageal acid exposure time (OAET) assessed with pH-only monitoring may be normal. By detecting reflux episodes independently of their acidity, multichannel intraluminal impedance-pH (MII-pH) monitoring allows a comprehensive characterization of reflux events, either off or on proton pump inhibitor (PPI) therapy. AIM: To assess reflux parameters by MII-pH monitoring in newly diagnosed SSBO, at baseline and as modified with PPI therapy. METHODS: Short-segment Barrett's oesophagus was defined by oesophageal intestinal metaplasia up to 3 cm in length. 24-h MII-pH monitoring was performed before and during PPI therapy. RESULTS: Fifty patients were studied prospectively. Normal OAET was found at baseline in 15 patients (30%), 8 and 2 of whom with a higher than normal number of acid and weakly acidic refluxes, respectively. Overall, abnormal reflux parameters were detected by MII-pH monitoring in 90% of patients. Reflux events were prevalent in the upright period. On PPI therapy, acid refluxes decreased and a correspondent increase in weakly acidic refluxes was observed (median from 48.5 to 9 and from 16 to 57.5, respectively) (P < 0.001). CONCLUSIONS: Acid refluxes, mainly in the upright period, characterize SSBO. PPI therapy transforms acid refluxes into weakly acidic refluxes.

Efficacy in intra-oesophageal acid suppression may decrease after 2-year continuous treatment with proton pump inhibitors.

BACKGROUND: Long-term intra-oesophageal acid suppression with proton pump inhibitors represents a management option for Barrett's oesophagus and severe reflux oesophagitis, but its stability over time has not been adequately assessed. AIM: Our aim was to evaluate prospectively the efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity after 2-year continuous treatment. METHODS: Forty-five patients with Barrett's oesophagus or severe reflux oesophagitis on a proton pump inhibitor regimen (once or twice daily) that normalised the total percentage acid exposure time were re-evaluated by means of 24-h oesophageal pH-monitoring after 2-year of continuous unmodified treatment. RESULTS: A significant rise in the total percentage acid exposure time was observed at 2-year follow-up (P=0.029), owing to an increased value in 27 (60%) cases (9 on a twice daily regimen), higher than normal in 10 of them (22% of the whole group) (3 on a twice daily regimen). In 18 patients (40%) the total percentage acid exposure time was stable or decreased. Heartburn remained efficiently suppressed in all patients. CONCLUSIONS: The efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity during continuous treatment may decrease over time, up to abnormal levels of oesophageal acid exposure in a minority of cases. This may occur without heartburn recurrence and with both once and twice daily regimens.

Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?

BACKGROUND: The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed. AIM: To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations. METHODS: Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period. RESULTS: Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls. CONCLUSIONS: In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.

Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole.

BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.

Pathophysiological characteristics of patients with non-erosive reflux disease differ from those of patients with functional heartburn.

BACKGROUND: Patients with endoscopy-negative heartburn can be subdivided into non-erosive reflux disease and functional heartburn on the basis of abnormal and normal, respectively, oesophageal acid exposure. Different pathophysiological characteristics could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn. AIM: To assess if non-erosive reflux disease and functional heartburn are pathophysiologically distinguishable. METHODS: Oesophageal manometry and pH-monitoring were performed in 145 patients with endoscopy-negative heartburn, in 72 patients with erosive reflux disease, in 58 patients with complicated reflux disease, and in 60 controls. RESULTS: Patients with non-erosive reflux disease (84 cases) and functional heartburn (61 cases) differed with regard to the prevalence of hiatal hernia (49% vs. 31%, P = 0.008), the mean lower oesophageal sphincter tone (18.5 vs. 28.4 mmHg, P < 0.05), and the number of upright diurnal acid refluxes lasting more than 5 min (3.6 vs. 0.37, P < 0.05). The results were very close in thenon-erosive reflux disease, erosive reflux disease and complicated reflux disease groups, whilst patients with functional heartburn were indistinguishable from controls. CONCLUSIONS: Pathophysiological characteristics typical of gastro-oesophageal reflux disease are found in patients with non-erosive reflux disease but not in patients with functional heartburn. This could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn and suggests considering different management strategies.

Different patterns of oesophageal acid exposure distinguish complicated reflux disease from either erosive reflux oesophagitis or non-erosive reflux disease.

BACKGROUND: The reason why less than one-half of patients with gastro-oesophageal reflux disease develop complicated reflux disease (ulcerative oesophagitis, oesophageal strictures and Barrett's oesophagus) and erosive reflux oesophagitis is not fully understood. Supine nocturnal oesophageal acid reflux is considered to be critically involved in this phenomenon, but reliable data are lacking. AIM: To clarify whether high levels of supine nocturnal oesophageal acid exposure are associated with complicated reflux disease. METHODS: Ambulatory 24-h oesophageal pH monitoring was performed in 220 patients with gastro-oesophageal reflux disease (56 with complicated reflux disease, 76 with erosive reflux oesophagitis and 88 with non-erosive reflux disease). The total, supine nocturnal and upright diurnal percentage acid reflux times were calculated. RESULTS: The total percentage acid reflux time was significantly greater in complicated reflux disease than in either erosive reflux oesophagitis (P = 0.024) or non-erosive reflux disease (P = 0.000). These differences were entirely due to a greater supine nocturnal percentage acid reflux time (P = 0.038 and P = 0.000, respectively), whereas no difference was observed in the upright diurnal percentage acid reflux time. CONCLUSIONS: Complicated reflux disease is characterized by high levels of supine nocturnal percentage acid reflux time. Prospective studies would be appropriate to clarify whether the normalization of this parameter is relevant to the effective management of this subset of patients with gastro-oesophageal reflux disease.

Effective intra-oesophageal acid suppression in patients with gastro-oesophageal reflux disease: lansoprazole vs. pantoprazole.

BACKGROUND: : Effective intra-oesophageal acid suppression is an important therapeutic goal in complicated and atypical gastro-oesophageal reflux disease. AIM: : To compare the efficacy of lansoprazole and pantoprazole in normalizing oesophageal acid exposure. METHODS: : Fifty patients with complicated or atypical gastro-oesophageal reflux disease were randomly assigned to receive 30 mg lansoprazole (n = 26) or 40 mg pantoprazole (n = 24) once daily. Three to four weeks after the start of treatment, patients underwent 24-h oesophageal pH monitoring whilst on therapy. If the results were improved but still abnormal, the dosage was doubled and pH monitoring was repeated. If oesophageal acid exposure was not improved, the patient was shifted to the alternative drug regimen. RESULTS: : Oesophageal acid exposure was normalized in all 26 patients treated with lansoprazole (in 35% of cases with a double daily dosage), whereas in six of the 24 (25%) patients treated with pantoprazole it was neither normalized nor lowered (P = 0.008). Accordingly, the mean percentage acid reflux time was significantly lower for the lansoprazole group (2.1) than for the pantoprazole group (5.8) (P = 0.032). CONCLUSIONS: : Effective intra-oesophageal acid suppression can be accomplished more reliably with lansoprazole than with pantoprazole in patients with complicated and atypical gastro-oesophageal reflux disease.

Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra-oesophageal acid suppression.

BACKGROUND: Effective intra-oesophageal acid suppression can be achieved with lansoprazole. The daily dosage could be influenced by the presence of hiatal hernia. AIM: To assess the lansoprazole daily dosage required to normalize oesophageal acid exposure in patients with and without hiatal hernia. METHODS: Fifty patients with complications or atypical manifestations of gastro-oesophageal reflux disease were given lansoprazole, 30 mg once daily. Three to four weeks after the start of treatment, patients underwent oesophageal pH monitoring while on therapy. If the results were still abnormal, the lansoprazole dosage was doubled and 24-h pH-metry was repeated 20-30 days thereafter. RESULTS: A 30-mg daily dosage of lansoprazole normalized oesophageal acid exposure in 70% of cases, whilst a 60-mg daily dosage was necessary in the remainder: the two groups differed only in the presence of hiatal hernia (28% vs. 100%, respectively; P=0.000). Effective intra-oesophageal acid suppression was obtained in all 25 patients without hiatal hernia with the 30-mg daily dosage of lansoprazole. CONCLUSIONS: Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra-oesophageal acid suppression in complicated and atypical gastro-oesophageal reflux disease. High efficacy of a 30-mg daily dosage of lansoprazole can be predicted in the absence of hiatal hernia.

Laparoscopic fundoplication versus lansoprazole for gastro-oesophageal reflux disease. A pH-metric comparison.

BACKGROUND: Treatment strategies that abolish abnormal reflux could prevent long-term complications of gastro-oesophageal reflux disease. AIMS: To compare the efficacy of laparoscopic fundoplication and lansoprazole in abolishing abnormal reflux in patients with gastro-oesophageal reflux disease. PATIENTS: Study population comprised 130 patients referred for possible antireflux surgery and with heartburn as the dominant symptom. METHODS: After oesophageal manometric and pH-metric evaluation and detailed information 55 patients asked to undergo laparoscopic antireflux surgery while 75 chose a medical treatment regimen based on lansoprazole. Treatment efficacy was assessed by ambulatory oesophageal pH-monitoring. RESULTS: All 55 patients who underwent fundoplication became free of heartburn: oesophageal pH-monitoring gave normal results in 85%. In patients treated with lansoprazole, at individualized daily dosages titrated to abolish both heartburn and abnormal acid reflux, normal pH-metric results were obtained in 96% of cases (p<0.05 vs surgically treated patients). CONCLUSIONS: Lansoprazole at individualized dosages was significantly more effective than laparoscopic fundoplication, in the short-term, in abolishing abnormal reflux in gastro-oesophageal reflux disease patients.

Lansoprazole vs. omeprazole for gastro-oesophageal reflux disease: a pH-metric comparison.

BACKGROUND: Lansoprazole and omeprazole are widely used proton pump inhibitors for the management of gastro-oesophageal reflux. Normalization of oesophageal acid exposure is an important goal in the management of complicated and atypical gastro-oesophageal reflux disease. AIM: To compare the efficacy of lansoprazole and omeprazole in the abolition of abnormal reflux as assessed by oesophageal pH monitoring. METHODS: Seventy patients with complicated or atypical gastro-oesophageal reflux disease were randomly assigned to receive 30 mg lansoprazole or 20 mg omeprazole once daily. Three to four weeks after the start of treatment, patients underwent oesophageal pH monitoring while on therapy. If the results were still abnormal, the proton pump inhibitor dosage was doubled and 24-h pH-metry was repeated after 20-30 days. RESULTS: Thirty-six patients were randomized to receive lansoprazole and 34 patients to receive omeprazole. Ten of the 36 (29%) patients treated with 30 mg lansoprazole once daily and 23 of the 34 (68%) patients treated with 20 mg omeprazole once daily had persistently abnormal reflux at oesophageal pH monitoring (P < 0.001). In all such cases, repeat pH monitoring after doubling the proton pump inhibitor dosage gave normal results. CONCLUSIONS: At the currently marketed dosages of lansoprazole and omeprazole, normalization of oesophageal acid exposure in patients is accomplished more easily with lansoprazole.