Cortical Lewy bodies and Aß burden are associated with prevalence and timing of dementia in Lewy body diseases.

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), Aß 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 Aß 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 Aß 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.

Postprandial cardiac vagal tone and transient lower esophageal sphincter relaxation (TLESR).

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 (R(2)  = 0.51 and R(2)  = 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.

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.

Traditional vs wireless intragastric pH monitoring: are the two techniques comparable?

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.

Role of symptoms, trend of liver tests, and endotherapy in management of post-cholecystectomy biliary leak.

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.

A pneumatic dilation strategy in achalasia: prospective outcome and effects on oesophageal motor function in the long term.

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.

Multiple rapid swallowing: a complementary test during standard oesophageal manometry.

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.

Central nervous system tissue heterotopia of the nose: case report and review of the literature.

The authors present a case of heterotopic central nervous system tissue observed in an 81-year-old male in the form of an ethmoidal polyp. A review of the literature indicates that this is a rare condition characterised by a connective tissue lesion with astrocytic and oligodendrocytic glial cells, which may be located outside the nasal pyramid in some cases and inside the nasal cavity in others. The most important diagnostic aspect involves differentiating these from meningoencephalocele, which maintains an anatomical connection with central nervous system tissue. Contrast-enhanced imaging is essential for diagnosis, as in cases of heterotopic central nervous system tissue, it will demonstrate that there are no connections with intra-cranial tissue. Endoscopic excision is the treatment of choice.

Thymoma arising in the wall of a thymic cyst.

A 54-year-old male, non smoker, began to suffer from persistent dyspnoea and fever. X-ray and CT scan showed a cystic lesion located in the left anterior mediastinum. This lesion was removed instead of the initially scheduled surgical resection with video-assisted thoracoscopic surgery (VATS) preceded by fine needle aspiration (FNA). A diagnosis of thymoma arising in the wall of thymic cyst was made. Such a rare tumour should be taken into consideration in treating patients with a cystic mediastinal lesion, before VATS and FNA.

Wireless pH monitoring: better tolerability and lower impact on daily habits.

BACKGROUND: Twenty-four hours oesophageal pH monitoring is considered the reference-standard for the diagnosis of gastro-oesophageal reflux disease, but it is limited by catheter discomfort and limitations of daily habits. AIM: We evaluated tolerability and impact on food intake and daily activities of catheter-based compared to wireless pH monitoring. PATIENTS: One-hundred and thirty-three consecutive patients with suspected gastro-oesophageal reflux disease were enrolled. METHODS: Seventy-eight patients (36 M, 53+/-2 years) underwent the 24 h catheter-based and 55 patients (25 M, 44+/-3 years) the 48 h wireless pH monitoring. Discomfort at placement and during the test was evaluated by 100 mm visual analogue scales. Limitations of food intake and of daily activities were evaluated by standardized questionnaires (score 0 to 3). RESULTS: Discomfort (mean+/-standard error of the mean) at placement and during the test was 32+/-3 versus 29+/-4 (p=ns) and 37+/-3 versus 22+/-3 (p<0.001) for the catheter-based versus wireless techniques. Limitation of food intake and of daily activities (mean+/-standard error of the mean) were 0.9+/-0.1 versus 0.4+/-0.1 (p<0.05) and 1.2+/-0.1 versus 0.2+/-0.1 (p<0.0001), respectively. CONCLUSIONS: The wireless pH monitoring is better tolerated and has minor impact on daily habits compared to the traditional technique. Whether this translates into better diagnostic accuracy remains to be evaluated.