P. Cantù

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms.

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

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

Aliment Pharmacol Ther 31, 658–665

Relationship between motor function of the proximal stomach and transient lower oesophageal sphincter relaxation after morphine

Background: Morphine reduces the rate of transient lower oesophageal sphincter (LOS) relaxations but its site of action is presently unknown. There are no data available concerning its motor effects on the proximal stomach, an important site for triggering transient LOS relaxations. Aim: To evaluate the effect of morphine on the rate of transient LOS relaxations and motor function of the proximal stomach. Subjects and methods: In 19 healthy subjects, concurrent transient LOS relaxations with a sleeve sensor and motor function of the proximal stomach with a bag connected to an electronic barostat were recorded during pressure controlled (n = 9) and volume controlled (n = 10) gastric distensions after intravenous administration of placebo and morphine 100 μg/kg. Results: During pressure controlled distensions, intrabag volume was markedly decreased by morphine (median 189 ml (interquartile range 101–448) v 404 (265–868) after placebo; p<0.01) as was the rate of transient LOS relaxations (0.5/30 minutes (0.4–2) v 2.5 (2–4); p<0.01). When intrabag volume was kept constant (525 ml (490–600)) (that is, in volume controlled distensions), the rate of transient LOS relaxations was not affected by morphine (2/30 minutes (2–3) v 2.5 (2–3)). Gastric contractions decreased after morphine similarly during pressure controlled and volume controlled distensions (8.5/30 minutes (4–10) v 15.5 (9.5–20.5), p<0.02; and 6.5 (0–24) v 19.5 (12–22), p<0.05). Conclusions: The effect of morphine on transient LOS relaxations is dependent on the decrease in volume of the proximal stomach. Our data suggest that pharmacological interventions which decrease fundal volume should result in control of transient LOS relaxation mediated gastro-oesophageal reflux.

Multiple rapid swallowing in idiopathic achalasia: evidence for patients' heterogeneity.

Abstract  In order to evaluate the function of inhibitory neural pathways in achalasia, we compared the response of the oesophageal body and lower oesophageal sphincter (LOS) to single swallows (SS) and multiple rapid swallowing (MRS) in 20 consecutive patients with untreated idiopathic achalasia (10 men, aged 23–81 years) and in 20 control patients without dysphagia (nine men, aged 31–73 years), using sleeve manometry; 277 SS and 85 MRS were analysed. In the control group, MRS inhibited motor activity in the oesophageal body and induced a slightly lower (P < 0.05) nadir LOS pressure compared with SS. In the achalasia patients, MRS induced a variable response: eight patients had simultaneous motor activity during all MRS although onset was delayed compared with SS [median (interquartile range), 3.5 s (1.7–6.1) vs 1.4 s (0.8–3.9); P < 0.05], whereas eight patients showed motor inhibition which occurred during all MRS in four of them, and the remaining four had no motor activity both after SS and during MRS. Overall MRS did not decrease nadir LOS pressure compared with SS [12 mmHg (5–20) vs 16 mmHg (7–22); P > 0.1]; however, it induced complete LOS relaxation in three of the patients. MRS gives further evidence of functional heterogeneity among achalasia patients.

Gastro‐oesophageal reflux disease – pathophysiological issues of clinical relevance

Gastro‐oesophageal reflux disease is a multifactorial disorder in which the pathophysiological mechanisms are variably combined in different patients. Motor dysfunction of the lower oesophageal sphincter (LOS) and, possibly, the proximal stomach is a major cause of the increase in the number of reflux episodes. Transient LOS relaxation is the main mechanism of reflux in many patients with endoscopically negative disease, whereas a hypotensive LOS becomes relevant only in patients with oesophagitis. Alterations in primary and secondary peristalsis contribute to the increased oesophageal acid exposure by delaying clearance. The presence of a hiatus hernia, especially when voluminous and/or non‐reducible, increases the number of reflux episodes by mechanically weakening the oesophago‐gastric junction, and impairs oesophageal clearance. Hypersensitivity to acid is often present and contributes to the clinical manifestations of the disease, whereas oesophageal hypersensitivity, both to chemical and mechanical stimuli, plays a predominant role in a subset of patients. Increased concentrations of noxious compounds in the oesophageal refluxate may contribute to the development of anatomical lesions, but this is still a matter for debate. The clinical relevance of Helicobacter pylori infection and of mucosal defensive factors still needs to be fully elucidated.

Mechanoreceptors of the proximal stomach and perception of gastric distension

OBJECTIVES:To assess the role of tension receptors in gastric perception by pharmacologically modifying gastric contractile activity during isovolumetric distensions of the proximal stomach with the hypothesis that relaxation decreased perception and contraction increased it.METHODS:Fourteen healthy subjects underwent two 30-min isovolumetric (75% of the threshold volume for discomfort) distensions using a barostat. During the second distension, either gastric relaxation was induced by intravenous (i.v.) glucagon 4.8 μg/kg bolus plus 9.6 μg/kg per h or contraction by i.v. erythromycin 3 mg/kg. Hunger and fullness were assessed with a 100-mm analog scale before and at 15 and 30 min during each distension.RESULTS:Glucagon decreased baseline intrabag pressure (8.4 ± 1.0 vs 10.7 ± 1.3 mmHg; p < 0.05) and abolished the pressure waves (0 vs 16.7 ± 2.3) when compared with placebo, whereas erythromycin increased baseline pressure (13.2 ± 1.0 vs 11.9 ± 0.9 mmHg; p < 0.05) and the rate of pressure waves (31.7 ± 5.4 vs 20.5 ± 3.1; p < 0.05). Fullness increased (p < 0.05) during distension, but it was unaffected by either of the drugs: Δ score (i.e., score during distension− baseline score) of 38 ± 10 mm (glucagon) versus 22 ± 10 (placebo) and 24 ± 17 mm (erythromycin) versus 36 ± 14 (placebo) at 15 min. Similar observation were made at 30 min. Hunger was influenced neither by distension nor by any of the two drugs consistently.CONCLUSIONS:Our data do not support a prominent role of tension receptors of the proximal stomach on perception of fullness, suggesting that stretch, that is, volume, is the more relevant stimulus.

Long-term effects of pneumatic dilatation on symptoms and lower oesophageal sphincter pressure in achalasia.

Background: Pneumatic dilatation is an effective treatment for achalasia. Although follow-up studies have shown that its clinical benefit persists for years, it is still unknown whether the decrease in lower oesophageal sphincter (LOS) pressure is maintained over time. Our aim is to assess the long-term effects of pneumatic dilatation on symptoms and LOS pressure in patients with idiopathic achalasia. Methods: Eleven consecutive patients with achalasia (7 men) underwent 1 ( n = 5) or 2 ( n = 6) pneumatic dilatations (Rigiflex dilator) in order to achieve a stable (> 1 year) clinical remission. Clinical scores (0-12, with scores of h 3 indicating remission) and LOS pressure (sleeve manometry) were determined before treatment, after 3 and 12 months, and then every year for 6 years. Results: No operative complications occurred. The patients showed a marked clinical improvement (2.0 (2.0-2.0), median (IQ range), after 3 months versus 8.0 (7.2-9.0) before treatment; P < 0.001), which was maintained throughout the follow-up period. Concurrently, there was a marked decrease in LOS pressure (5.0 (4.0-7.0) mmHg after 3 months versus 25.0 (20.0-36.2) before treatment; P < 0.001), which also remained stable over time. Conclusions: One or two pneumatic dilatations induce stable clinical remission and a decrease in LOS pressure that remains unchanged over time. Our data further support the use of dilatations as first-line treatment of achalasia.

Subcardial 24-h Wireless pH Monitoring in Gastroesophageal Reflux Disease Patients With and Without Hiatal Hernia Compared With Healthy Subjects

OBJECTIVES:After meals, highly acidic gastric juice is present in the subcardial region, the so-called acid pocket. Patients with gastroesophageal reflux disease (GERD) have a higher frequency of acidic reflux. Our aim was to investigate the possible differences in subcardial pH in GERD over 24 h and the role of hiatal hernia (HH), using a wireless capsule.METHODS:A total of 14 healthy volunteers (4 men, 24–60 years), 10 GERD patients without HH (4 men, 25–68 years), and 11 GERD patients with HH ≥3 cm (2 men, 46–74 years) underwent 24-h wireless pH monitoring 2 cm below the squamocolumnar junction. All patients had increased 24-h acid reflux. A standardized lunch was given to all study subjects.RESULTS:No capsule detached during the 24-h recording. Median 24-h pH was similar in healthy subjects, and in patients without and with HH, median: 1.4 (interquartile range: 1.2 –1.9), 1.5 (1.3 –1.7), and 1.4 (1.3 –1.7), respectively. Similar results were seen in the supine period. Median pH after the standardized meal was often highly acidic, 2.7 (1.5 – 3.2), 1.9 (1.6 – 2.3), and 2.5 (1.6 – 3.2), respectively. The first minute with a median pH <2 occurred 14 min (4 – 49), 14 min (6 – 25), and 20 min (4 – 43), respectively, P=NS, after the end of the meal. Similar data were observed on pooling all meals together.CONCLUSIONS:Subcardial pH is confirmed to be highly acidic early after meals, but it is similar over 24 h in healthy subjects and GERD patients independent of the presence of HH.

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

Objective. A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. Material and methods. Twelve patients (7 M, age range 24–65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25–54 years). Results. In the patients’ group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)±6 (SEM) versus 86±6 and 232 min±16 versus 160±7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): −22 min (mean); −10 to −34 (95% CI) and −48 min; −10 to −85, respectively, decreased both percentage of time at pH < 4 (p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R2<0.005). Conclusion. The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.

ERCP and short-term stent-trial in patients with anastomotic biliary stricture following liver transplantation

BACKGROUND Anastomotic biliary stricture represents one of the possible factors leading to liver dysfunction after transplantation. PURPOSE Our aims were to evaluate the role of endoscopic retrograde cholangio-pancreatography and a short-term stenting (stent-trial) in assessment of the clinical relevance of the biliary stricture. MATERIALS AND METHODS Thirty transplanted patients for HCV (n=17) or non-HCV (n=13)-related cirrhosis (27M, median age 53 yr, range 24-67 yr) who developed persistently abnormal liver function tests and presented with an anastomotic biliary stricture suggested by non-invasive cholangiography, underwent endoscopic retrograde cholangio-pancreatography. If the stricture was confirmed, dilation was performed and a plastic stent was placed. Clinical and biochemical evaluation was done one and two months later. Resolution of symptoms and normalization or > 50% reduction of at least one liver function test were needed to consider the stricture as clinically relevant. Patients were followed up for a median of 19 months. RESULTS Endoscopic retrograde cholangio-pancreatography was successful in 29 patients and confirmed the anastomotic biliary stricture in 19 (66%); 14 patients underwent endoscopic dilation and stenting and five patients underwent surgery. The stent-trial suggested the stricture to be clinically relevant in 7 of 14 patients, confirmed by prolonged stenting and follow-up. A trend towards a higher likelihood of a clinically relevant stricture was observed in HCV-negative compared to HCV-positive patients (5 of 7, 71% vs 2 of 7, 29% , respectively; p=0.1). CONCLUSIONS Our data suggest that endoscopic retrograde cholangio-pancreatography is a valuable tool to evaluate the clinical relevance of an anastomotic stricture, when coupled with a short-term stent-trial.