Measurement of oro-caecal transit time by magnetic resonance imaging.

OBJECTIVES: To assess prospectively the agreement of orocaecal transit time (OCTT) measurements by lactulose hydrogen breath test (LHBT) and magnetic resonance imaging (MRI) in healthy subjects. METHODS: Volunteers underwent abdominal 1.5-T MRI using axial and coronal single-shot fast-spin-echo T2-weighted sequences, having fasted and after lactulose ingestion (10 g/125 mL). Imaging and H2 excretion gas-chromatography were performed concurrently every 15 min up to 180 min. MR images were analyzed using semiautomatic segmentation to calculate small bowel gas volume (SBGV) and visually to detect bolus arrival in the caecum. Agreement between MRI- and LHBT-OCTT was assessed. RESULTS: Twenty-eight subjects (17 men/11 women; mean age ± standard deviation 30 ± 8 years) were evaluated. Two H2 non-producers on LHBT were excluded. OCTT measured by MRI and LHBT was concordant in 18/26 (69 %) subjects (excellent agreement, k = 0.924). Median SBGV was 49.0 mL (interquartile interval 44.1 - 51.6 mL). In 8/26 (31 %) subjects, MRI showed that the lactulose bolus was in the terminal ileum and not the caecum when H2E increased on LHBT. Median OCTT measured by MRI was significantly longer than OCTT measured by LHBT [135 min (120 - 150 min) vs. 127.5 min (105 - 150 min); p = 0.008]. Above baseline levels, correlation between [H2] and SBGV was significant (r = 0.964; p < 0.001). CONCLUSIONS: MRI provides valid measurements of OCTT and gas production in the small bowel. KEY POINTS: • MRI is a valid technique to measure OCTT. • Excellent agreement between MRI and LHBT was found. • Measuring gas production using MRI may provide evidence of small bowel fermentation.

Narrow-band imaging with magnifying endoscopy is accurate for detecting gastric intestinal metaplasia.

AIM: To investigate the predictive value of narrow-band imaging with magnifying endoscopy (NBI-ME) for identifying gastric intestinal metaplasia (GIM) in unselected patients. METHODS: We prospectively evaluated consecutive patients undergoing upper endoscopy for various indications, such as epigastric discomfort/pain, anaemia, gastro-oesophageal reflux disease, suspicion of peptic ulcer disease, or chronic liver diseases. Patients underwent NBI-ME, which was performed by three blinded, experienced endoscopists. In addition, five biopsies (2 antrum, 1 angulus, and 2 corpus) were taken and examined by two pathologists unaware of the endoscopic findings to determine the presence or absence of GIM. The correlation between light blue crest (LBC) appearance and histology was measured. Moreover, we quantified the degree of LBC appearance as less than 20% (+), 20%-80% (++) and more than 80% (+++) of an image field, and the semiquantitative evaluation of LBC appearance was correlated with IM percentage from the histological findings. RESULTS: We enrolled 100 (58 F/42 M) patients who were mainly referred for gastro-esophageal reflux disease/dyspepsia (46%), cancer screening/anaemia (34%), chronic liver disease (9%), and suspected celiac disease (6%); the remaining patients were referred for other indications. The prevalence of Helicobacter pylori (H. pylori) infection detected from the biopsies was 31%, while 67% of the patients used proton pump inhibitors. LBCs were found in the antrum of 33 patients (33%); 20 of the cases were classified as LBC+, 9 as LBC++, and 4 as LBC+++. LBCs were found in the gastric body of 6 patients (6%), with 5 of them also having LBCs in the antrum. The correlation between the appearance of LBCs and histological GIM was good, with a sensitivity of 80% (95%CI: 67-92), a specificity of 96% (95%CI: 93-99), a positive predictive value of 84% (95%CI: 73-96), a negative predictive value of 95% (95%CI: 92-98), and an accuracy of 93% (95%CI: 90-97). The NBI-ME examination overlooked GIM in 8 cases, but the GIM was less than 5% in 7 of the cases. Moreover, in the 6 false positive cases, the histological examination showed the presence of reactive gastropathy (4 cases) or H. pylori active chronic gastritis (2 cases). The semiquantitative correlation between the rate of LBC appearance and the percentage of GIM was 79% (P < 0.01). CONCLUSION: NBI-ME achieved good sensitivity and specificity in recognising GIM in an unselected population. In routine clinical practice, this technique can reliably target gastric biopsies.

Lactulose breath test to assess oro-cecal transit delay and estimate esophageal dysmotility in scleroderma patients.

OBJECTIVES: To assess the correlation between delayed oro-cecal transit time (OCTT) and esophageal motility abnormalities in a cohort of systemic sclerosis (SSc) patients. METHODS: We prospectively enrolled 50 consecutive SSc patients and 60 healthy volunteers (HVs) as controls. Both groups underwent glucose breath test (GBT) to exclude small intestine bacterial overgrowth, lactulose hydrogen, and octanoic acid breath tests (LHBT and OBT) to measure OCTT and gastric emptying (GE), respectively, and manometry to assess esophageal motility. RESULTS: Thirty-one (63%) SSc patients presented ineffective esophageal motility (IEM) compared with 3 HVs (5%; P<0.01), 37 (74%) had an abnormal OCTT compared with 4 HVs (7%; P <0.01), and 16 (32%) had an altered GE compared with 4 HVs (7%; P <0.01). The median OCTT and gastric t½ were longer in SSc than in HVs (165 min vs. 101 min and 125 min vs. 78 min, respectively; P <0.01). A delayed GE was present in 12/37 (32%), whereas IEM in 27/37 (73%) SSc patients with prolonged OCTT. The prevalence of IEM increased in parallel with the prolongation of OCTT (31% when OCTT<150 min, 73% when OCTT≥150 min, and up to 85% when OCTT>180 min, P<0.01). CONCLUSIONS: Abnormalities of both esophageal and small intestine motility are frequent in SSc patients and esophageal motility is altered in most cases with small bowel involvement. Delayed GE plays a limited role in prolonging OCTT. LHBT is a non-invasive, cheap, well-tolerated diagnostic tool that may be useful to estimate intestinal involvement and also to estimate a higher risk of esophageal hypomotility in SSc patients.

Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn.

BACKGROUND: Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH). METHODS: Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n = 5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was >0.35. RESULTS: The prevalence of ME was higher (p < 0.0001) in EE (95 %), pH-POS (77 %), and HE (65 %) NERD patients than in FH patients (13 %) and HVs (15 %). Also, basal cell hyperplasia (p < 0.0023), DIS (p < 0.0001), and papillae elongation (p < 0.0002) showed similar rates of prevalence in the above populations (p < 0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p = 0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p < 0.0001 and p < 0.0001, respectively). CONCLUSIONS: The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy.

Reassessment of the role of methane production between irritable bowel syndrome and functional constipation.

BACKGROUND AND AIMS: Modifications of intestinal gas due to changes in microbiota may produce different symptoms. Our aim was to assess whether different patterns of hydrogen (H2) and methane (CH4) excretion were related to some intestinal disturbances. METHODS: Six hundred and twenty-nine consecutive patients underwent a 50 g-glucose breath test (GBT) on account of intestinal symptoms, which were evaluated by means of a questionnaire. "H2-producers" and "CH4-producers" were defined as with the presence of H2 peak >12 ppm more than the basal sample and mean CH4 excretion of 2 ppm, respectively. Forty healthy subjects were studied as controls. RESULTS: A small intestinal bacterial overgrowth was found in 45 cases (7.2%) and was associated with older age (p=0.0122). Methane production occurred in 32.3% of the study population. Methane excretion was strictly related to chronic constipation (p<0.001). Median CH4 excretion was higher in constipated patients compared with patients with normal daily stools (p=0.0406) and even more with patients complaining of diarrhea (p=0.0011). Different criteria for defining "methane-producers" provided similar results. Mean methane excretion of "methane producers" was 30.3 ppm in functional constipation and 21.5 ppm in constipation-irritable bowel syndrome (C-IBS) (p=0.0458). CONCLUSIONS: Methane excretion is clearly associated with alterations in intestinal motility, particularly favouring those with constipation. Mean methane excretion was higher in subjects suffering from functional constipation than C-IBS. Mean methane excretion ≥ 2 ppm appears to be an appropriate term to define "methane-producers".

Impedance-pH reflux patterns can differentiate non-erosive reflux disease from functional heartburn patients.

INTRODUCTION: Symptom association is important to distinguish non-erosive reflux disease [NERD; abnormal oesophageal acid exposure time (AET) and/or positive symptom association] from functional heartburn (FH; normal AET and negative symptom association). Asymptomatic patients during reflux monitoring are challenging as symptom association cannot be assessed. AIM: To evaluate whether impedance-pH reflux patterns are useful to differentiate NERD from FH. METHODS: Endoscopy-negative reflux patients underwent impedance-pH off-therapy. Oesophageal AET, characteristics of reflux episodes and symptom association probability (SAP) were measured. Twenty patients asymptomatic during the first test repeated a second examination. RESULTS: Of 329 patients, 130 (40%) were pH-POS, 120 (36%) pH-NEG/SAP+ (hypersensitive oesophagus = HO) and 79 (24%) pH-NEG/SAP- (FH). Total and acid reflux episodes were significantly higher (p < 0.01) in pH-POS compared to pH-NEG/SAP+, pH-NEG/SAP- and healthy volunteers (HVs). Patients pH-NEG/SAP+ had a significantly increased number of weakly acidic reflux episodes compared to pH-POS, pH-NEG/SAP- and HVs (p < 0.01). The rate of proximal reflux episodes in pH-POS (50%) and pH-NEG/SAP+ (47%) was higher (p < 0.01) than in pH-NEG/SAP- (33%) and HVs (33%). Measuring AET, number of reflux episodes and percentage of proximal reflux events permits to identify FH in 70% of cases and HO in 80% of cases who repeated the examination. CONCLUSION: In patients with normal AET and SAP+, increased number of weakly acidic reflux and higher rate of proximal reflux are the main discriminant features. There is large overlap between FH and HVs. These differences can be of help in diagnosing patients with normal oesophageal acid exposure who fail to have symptoms during MII-pH testing.

Overweight is a risk factor for both erosive and non-erosive reflux disease.

INTRODUCTION: Studies have reported that the association between overweight and erosive oesophagitis is very strong, whilst seeming less consistent with non-erosive reflux disease. AIM: We have hypothesized that this difference may be due to the heterogeneity of endoscopy-negative population. METHODS: We studied 81 patients with erosive oesophagitis, 48 controls and 295 endoscopy-negative patients classified by impedance-pH-testing as: (1) pH-POS (abnormal acid exposure); (2) hypersensitive oesophagus (normal acid exposure/SAP+); (3) functional heartburn (normal acid exposure/SAP-). Body mass index was also calculated. RESULTS: Mean body mass index was significantly higher (p<0.05) in erosive oesophagitis than in endoscopy-negative patients as a whole and controls [27 (18-40) vs. 25 (16-48) vs. 23 (16-34)]. However, the separation of endoscopy-negative patients showed that mean body mass index was higher (p<0.05) in those with increased acid exposure time [26 (18-45)] than in hypersensitive oesophagus [24 (16-48)]. The former subgroup was similar to erosive oesophagitis, whilst the latter one to both functional heartburn [23 (16-34)] and controls (p=ns). Increased body mass index represented a risk factor for erosive oesophagitis (odds ratio 1.4; 95% confidence interval, 1.2-1.6) and non-erosive reflux disease pH-POS subgroup (odds ratio 1.35; 95% confidence interval, 1.2-1.5). CONCLUSION: Our study shows that overweight represents an important risk factor for erosive oesophagitis and pH-POS non-erosive reflux disease and not for hypersensitive oesophagus and functional heartburn. This provides an explanation for the previously reported lesser role of this variable in non-erosive reflux disease population.

Achalasia with dense eosinophilic infiltrate responds to steroid therapy.

A patient presented with chronic substernal discomfort and intermittent dysphagia for solids. High-resolution impedance manometry (HRIM) of the esophagus showed that there was no peristalsis in the esophageal body but incomplete relaxation of the lower esophageal sphincter and incomplete bolus transit, so the patient was diagnosed with achalasia. Moreover, probably because of esophageal stasis, eosinophilic infiltration that mimicked a pattern of eosinophilic esophagitis was observed, on the basis of multiple biopsies of the esophagus. The patient was given 50 mg prednisolone once daily; the symptoms improved dramatically, and HRIM showed complete recovery of esophageal peristalsis, deeper relaxation of the lower esophageal sphincter, and complete bolus transit profile. HRIM can therefore be used to assess dysmotility abnormalities in patients with achalasia and eosinophilic-like esophagitis, and steroids relieve these symptoms. Treatment with a high dose of prednisolone resulted in a complete disappearance of dysphagia because of improved esophageal motility and reduced eosinophilic infiltrate. It is therefore important to control the inflammatory process in patients with idiopathic achalasia, which is likely to result from an autoimmune reaction.

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease.

INTRODUCTION: Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. AIM: To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. METHODS: Consecutive endoscopy-negative patients treated with proton pump inhibitors (n=219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. RESULTS: Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP-, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP-, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. CONCLUSION: Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients.

Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy.

OBJECTIVES: We sought to compare reflux and symptom association patterns in patients with nonerosive reflux disease (NERD), erosive esophagitis (EE), and in healthy volunteers (HVs). METHODS: Patients with EE and NERD underwent combined impedance-pH monitoring. Normal values were defined on the basis of previously collected data from 48 HVs. We evaluated distal esophageal acid exposure time (AET), number and type of reflux episodes (acid, nonacid), acid and bolus clearance times, proximal extension of reflux episodes, and symptom association probability (SAP). RESULTS: Distal AET (percentage time, pH<4) was higher (P<0.01) in 58 EE patients (median 7.4%, 25-75th percentile 4.2-9.9%) compared with 168 NERD patients (4.2% (1.2-6.4%)) and 48 HVs (0.7% (0.2-1.4%)). Patients with EE and NERD had a higher (P<0.01) number of acid reflux episodes compared with HVs (51 (37-66) vs. 34 (22-51) vs. 17 (8-31); P<0.05), but a similar number of nonacid reflux episodes (22 (15-39) vs. 23 (15-38) vs. 18 (14-26); P=NS). The percentage of reflux episodes reaching the proximal esophagus was higher (P<0.01) in EE patients (57% (45-73%)) than in NERD patients (45% (36-60%)) and HVs (33% (19-46%)). A positive SAP for heartburn or regurgitation was found in 161 of 168 (96%) NERD and 54 of 58 (93%) EE patients (P=NS). CONCLUSIONS: Acid reflux episodes, volume, and acid clearance are important factors in the pathogenesis of reflux-induced lesions. Nonacid reflux contributes less to esophageal mucosa damage, but is involved in the development of reflux symptoms in both NERD and EE patients.

[Possible connection between gastroesophageal reflux and interstitial pulmonary fibrosis in patients with systemic sclerosis]. / Correlazione tra reflusso gastroesofageo e fibrosi interstiziale polmonare in pazienti affetti da sclerosi sistemica.

Interstitial lung disease represents the main cause of morbidity and mortality in patients with systemic sclerosis. The mechanisms leading to interstitial lung disease are poorly understood and thus current strategies have little effect on this progressive and fatal disease. Therefore, it appears relevant the importance to assess the possible risk factors involved in its pathogenesis. Previous studies in vivo and in vitro suggested that pulmonary fibrosis can occur after repeated aspiration of small amounts of gastric contents over long periods of time. Recently, our group observed that patients with systemic sclerosis and pulmonary fibrosis have a more severe degree of gastroesophageal reflux with a greater number of reflux events and a higher percentage of reflux episodes reaching the proximal esophagus, causing an increasing risk of microaspiration, compared to patients with systemic sclerosis without lung involvement. Further larger controlled studies are necessary to evaluate whether or not the development of interstitial lung disease in systemic sclerosis patients can be prevented by treating gastroesophageal reflux.