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Aims Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia. Methods One hundred and twenty-one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aβ plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined. Results The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, P < 0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs ( P = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden ( P = 0.02), particularly in the neocortical frontal, parietal and temporal regions. Conclusions High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele. [ABSTRACT FROM AUTHOR]

Background Transient lower esophageal sphincter relaxation ( TLESR) is a vagally mediated reflex that occurs most frequently after a meal. Cardiac vagal tone ( CVT) decreases after a meal, and correlates with changes in gastric electrical activity. Furthermore, decreased CVT has been reported in patients with gastro-esophageal reflux disease. We therefore aimed to characterize the association between postprandial changes in CVT and the occurrence of TLESR and reflux. Methods Ten healthy volunteers underwent simultaneous autonomic nervous system, gastric myoelectric activity, lower esophageal-sphincter pressure, and reflux monitoring for 30 min in the fasting state, followed by a standard meal, and a further 4 h postprandially. Results are in mean ± SEM. Key Results The number of TLESRs (P < 0.0001) and reflux episodes (P < 0.0001) increased after the meal, while CVT decreased (P < 0.01). Cardiac sensitivity to baroreceptor reflex ( CSB) showed similar time course changes to CVT (P = 0.06). During the first postprandial hour there was a strong correlation between the number of TLESRs and reflux episodes with CVT (R2 = 0.51 and R2 = 0.50, respectively; P < 0.05). There was also an increase in the dominant power and power ratio on electrogastrography (P < 0.05) after the meal. Conclusions & Inferences In healthy volunteers, the increase in the number of TLESRs and reflux episodes after a meal occurred mostly at a time of reduced CVT. Further studies should explore whether modulation of CVT can modify frequency of TLESRs and also this relationship should be further explored in patients with reflux disease. [ABSTRACT FROM AUTHOR]

I. Marinoni, M. Lee, S. Mountford, A. Perren, I. Bravi, L. Jennen, A. Feuchtinger, J. Drouin, F. Roncaroli and N. S. Pellegata (2013) Neuropathology and Applied Neurobiology 39, 256-269 Characterization of MENX-associated pituitary tumours Aims: The aim of this study is to evaluate the pathological features, serum hormone levels and ex vivo cultures of pituitary adenomas that occur in rats affected by MENX syndrome. MENX is multiple endocrine neoplasia syndrome caused by a germline mutation in the cell cycle inhibitor p27. Characterization of MENX adenomas is a prerequisite to exploit this animal model for molecular and translational studies of pituitary adenomas. Methods: We investigated MENX pituitary adenomas with immunohistochemistry, double immunofluorescence, electron microscopy, reverse transcription polymerase chain reaction (RT-PCR), measurement of serum hormone levels and ex vivo cultures. Results: Adenomas in MENX rats belong to the gonadotroph lineage. They start from 4 months of age as multiple neoplastic nodules and progress to become large lesions that efface the gland. Adenomas are composed of chromophobic cells predominantly expressing the glycoprotein alpha-subunit (αGSU). They show mitotic activity and high Ki67 labelling. A few neoplastic cells co-express gonadotropins and the transcription factor steroidogenic factor 1, together with growth hormone or prolactin and Pit-1, suggesting that they are not fully committed to one cell lineage. Ex vivo cultures show features similar to the primary tumour. Conclusions: Our results suggest that p27 function is critical to regulate gonadotroph cells growth. The MENX syndrome represents a unique model to elucidate the physiological and molecular mechanisms mediating the pathogenesis of gonadotroph adenomas. [ABSTRACT FROM AUTHOR]

Background Few data are available comparing intragastric pH measured with the traditional catheter-based and the more recent wireless system (Bravo), and also comparing intraesophageal and intragastric pH during reflux events. Aims of our study were to elucidate these points. Methods Eleven subjects with functional dyspepsia underwent placement of a Bravo capsule 9 cm below the squamo-columnar junction (SCJ) and of a dual-electrode catheter, so that the distal electrode was located 9 cm below and the proximal one 6 cm above the SCJ. Key Results The wireless system showed lower intragastric pH than the traditional catheter in the postprandial period (median 2.2 wireless vs 2.7 catheter, P < 0.05) but not in the whole 24 h. Moreover, during the 24 h, minimum intraesophageal pH during reflux events was lower than the simultaneous pH in the gastric body recorded using the catheter (2.2 vs 2.4, P < 0.01) and in the postprandial period lower than the one recorded using both techniques (2.3 vs 2.8 wireless and 3.2 catheter, P < 0.001). Conclusions & Inferences (i) after meals, in the 1st 2 h postprandial pH in the gastric body is significantly lower when measured with the wireless capsule than with the traditional catheter, presumably because of less buffering by food in proximity of the mucosa, (ii) during reflux events intraesophageal pH is lower than pH in the gastric body, in accordance with the notion of greater intragastric acidity in the subcardial region. [ABSTRACT FROM AUTHOR]

Aim: Biliary leaks are widely reported complications of cholecystectomy, but standard management remains undecided. The objective of our study was to report the role of symptoms, biochemical tests, and ERCP in patients with a leak.Materials and Methods: Twenty-one patients (8 M, 26-77 years) with suspected post-cholecystectomy biliary leak were retrospectively studied. Symptoms and liver tests (LTs) after surgery were monitored. Trends of LTs were considered positive if increases at >48 h were seen. ERCP was performed in all patients. Findings at endoscopy and treatments were reported. Outcome results were obtained for all patients.Results: Seventeen of 21 patients had persistent biliary leak at ERCP, because of direct injury (n = 10), accessory duct (n = 4), or cystic duct stump (n = 3). Eleven of 17 patients (six without symptoms), had distal obstruction because of surgical injury (n = 8), stone (n = 2), or cholangiocarcinoma (n = 1) and underwent stenting (n = 4), naso-biliary drainage, NBD (n = 3), or surgery (n = 4). Among the six patients without obstruction (four without symptoms), stenting was performed in two and NBD in four. The four patients without apparent leak underwent NBD. Impairment of LTs was present in ten out of eleven (91%) patients with obstruction versus six of ten (60%) without obstruction. No complications occurred after ERCP. During a median follow-up of 33 months (cholangiocarcinoma excluded) all but one remained asymptomatic.Conclusions: Symptoms and trend of LTs were not predictive of biliary obstruction in patients with a leak after cholecystectomy. Both endotherapy and surgery had favorable outcomes. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 658–665 Background Long-term follow-up studies of achalasia after pneumatic dilation, mostly retrospective, have shown variable results. Aim To examine the outcome of achalasia after pneumatic dilation using a prospective follow-up programme. Methods One or two dilations (first dilation treatment) in 77 patients to achieve stable (>1 year) remission and patients followed up with yearly clinical and manometric assessments. Endoscopy, pH monitoring and barium swallow were also performed. Results A total of 69 patients achieved stable remission and were followed up for 5.6 years (3–10.7) [median (IQ range)], whereas six patients underwent cardiomyotomy and two experienced a perforation. Twelve of the 69 patients relapsed after 2.6 years (1.7–5.1): nine of 12 underwent one to two further dilations. Six-year remission rate (by Kaplan–Meyer estimates) was 82% after first dilation treatment and 96% after all dilations. Continuous antisecretory treatment was clinically needed in 16%, oesophagitis present in 7% and reflux pathological in 28% of the patients. Beneficial effects of dilation on oesophageal motility and on diameter of the oesophageal body at barium swallow were maintained during follow-up. Conclusions A management strategy including sessions of pneumatic dilation until stable remission and a standardized follow-up is highly successful in the long term. Gastro-oesophageal reflux is clinically relevant in a minority of patients. [ABSTRACT FROM AUTHOR]

Introduction Many patients attending GI physiology units for assessment of dysphagia and GORD also complain of postprandial bloating and/or belching. Excessive fasting aerophagia has been recently described in patients with severe continuous bloating and belching. Exaggerated air swallowing might be more relevant for postprandial symptoms but, thus far, objective assessment of prandial aerophagia and normal values are lacking. Oesophageal impedance can detect air swallowing. We aimed to quantify aerophagia during meals in asymptomatic subjects and patients with postprandial bloating and belching. Methods We assessed aerophagia during meals using ambulatory impedance-pH monitoring in 39 healthy, asymptomatic controls (from the US-Belgian MII-pH Normal value study, Shay . 2004; mean age in original study 39, range 22–62) to establish normal 95% confidence intervals. We identified 38 patients (mean age 43, range 17–74) with postprandial bloating and/or belching who attended the GI physiology unit for assessment of dysphagia or GORD as primary symptoms. Mealtime air swallows were visually identified when swallows were associated with antegrade flow and fast impedance increase (at least 3000 Ω from baseline) in the most distal recording segment. A score of air swallows/10 min mealtime was calculated for each subject. In patients with mealtime exaggerated air swallowing (above 95th percentile of normal values) we examined for evidence of concomitant fasting aerophagia. Results The 95% percentile range of mealtime aerophagia in normal subjects was 6.8 to 9.4 episodes/10 min, mean 8.1. Patients had significantly higher mealtime air swallowing rates than controls (mean 11.8 episodes/10 min, SEM 1.0, p = ). There was no significant difference between predominant bloating and belching subgroups. Only 4 of 23 patients with exaggerated mealtime air swallowing had concomitant fasting aerophagia. OC-054 Prandial aerophagia in normal controls and patients with belching and bloating Conclusion We established normal values of mealtime air swallowing using oesophageal impedance. Patients with postprandial bloating and/or belching exhibit increased aerophagia during meals. Most of these patients do not have fasting aerophagia. Exaggerated air swallowing during meals can now be objectively detected and biofeedback techniques can be attempted to modify such behaviour as a potential therapeutic strategy for these patients with functional GI symptoms. [ABSTRACT FROM PUBLISHER]

Introduction Persistent reflux symptoms occur in a subgroup of patients following antireflux surgery. These symptoms can be due failure of the antireflux barrier. GI physiology studies are performed to evaluate the OGJ function and anatomy in these patients. Recent studies with high resolution manometry (HRM) have shown the presence of a dual high pressure zone (HPZ) at the OGJ as an expression of persistent hiatus hernia. However, the relation between dual high pressure zone, oesophageal hypomotility and persistent symptoms is unclear. The aim of this study was to evaluate reflux parameters and oesophageal motility patterns with HRM in a group of symptomatic patients after fundoplication. Methods Ten patients (5 male, 5 female; mean age 55 years) were selected based on the presence of persistent typical reflux symptoms post-Nissen fundoplication. The patients underwent HRM and impedance-pH monitoring ‘off’ PPI. The existence of dual HPZ, oesophageal hypomotility and amplitude of the after-contraction post multiple rapid swallowing (MRS) were evaluated together with acid and non-acid reflux parameters. Increased number of reflux events (post Nissen) was considered if >30/24 h. Results Six out of ten patients had a dual HPZ on HRM. Acid exposure time and number of acid reflux events in these patients was significantly higher than those with a single HPZ (12.7% vs 0.5%, p=0.01). The patients with a dual HPZ more commonly exhibited oesophageal hypomotility and poor response to MRS compared to the patients with a single HPZ (4/6 vs 1/4). In addition more of the patients with a dual HPZ showed impaired acid reflux clearance compared to patients with single HPZ (5/5 vs 1/3). Conclusion HRM and impedance-pH measurement allows a precise assessment of patients with symptoms postfundoplication. Our study suggests that the presence of a dual HPZ on oesophageal HRM is associated with impairment of oesophageal motility and impaired oesophageal acid clearance, and hence may be important in the persistence of GORD symptoms postoperatively. [ABSTRACT FROM PUBLISHER]

Multiple rapid swallowing (MRS) stimulates neural inhibition resulting in abolition of contractions in the oesophageal body (OB) and complete lower oesophageal sphincter (LOS) relaxation which is followed by peristalsis and LOS contraction. The aim of this study was to evaluate the yield of MRS to detect abnormalities in inhibitory or excitatory oesophageal mechanisms in patients with oesophageal symptoms and either normal standard manometry or ineffective oesophageal motility (IOM). MRS (five water swallows, 2 mL, separated by 2–3 s) was evaluated in 23 healthy subjects, 109 symptomatic patients with normal standard sleeve manometry and in 48 patients with IOM. Healthy subjects had complete inhibition of OB motility during MRS and a strong motor response after MRS, i.e. amplitude of OB contractions in the oesophageal body and LOS tone being higher than after single swallows. Almost 70% of patients with oesophageal symptoms and normal manometry had abnormal MRS, mainly consistent on inability to increase amplitude of OB contractions after MRS. Nearly, half of the patients with IOM were able to normalize OB contractions after MRS. MRS is a simple complementary test that can be added to standard oesophageal manometry. Two-thirds of patients with normal manometry show abnormal MRS that could potentially underlie their symptoms. A normal response to MRS in patients with severe IOM might be used to predict response to prokinetic treatment. [ABSTRACT FROM AUTHOR]