Butterfly Wings Effect on High Resolution Manometry in A Patient with Esophageal Achalasia.

A 57-year-old man presented with dysphagia in solids and liquids deteriorating in the last months and weight loss of 3 kg. A thoracic CT revealed a limit dilatation of the lower esophagus with food residue. An upper endoscopy was performed revealing bubble content and a contraction of the Lower Esophageal Sphincter (LES). A barium esophagogram demonstrated deceleration of esophageal emptying and a bird beak sign indicative of esophageal achalasia (Figure A). High resolution esophageal manometry was performed to evaluate the subtype of achalasia. The catheter could not be intubated into the stomach because of LES spasticity, it folded back cephalad at this level, producing a mirror image, the characteristic "butterfly wings" appearance of a folded manometry catheter (Figure B).

Chronic constipation in Parkinson's disease: clinical features and molecular insights on the intestinal epithelial barrier.

Background: Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods: Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results: PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion: Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities.

Graded pneumatic dilation in subtype I and II achalasia: long-term experience in a single center.

BACKGROUND: The efficacy of pneumatic dilation (PD) in the management of achalasia has yielded variable results. The availability of high-resolution manometry led to the identification of 3 clinically relevant subtypes of achalasia, revealing the poor efficacy of PD in subtype III. Furthermore, PD showed a lower response rate in patients with subtype III compared to laparoscopic Heller myotomy and peroral endoscopic myotomy. This study aimed to investigate the short- and long-term efficacy, safety profile and side effects of PD with a "graded approach" in subtypes I and II achalasia. METHODS: We enrolled 141 patients (male 67, mean age=66±16.26 years) with achalasia (n=27 subtype I, n=74 subtype II and n=40 subtype III) between January 2010 and July 2020 at St. Orsola University Hospital, Bologna, Italy. We analyzed the data of patients with subtypes I and II, who underwent a graded-protocol PD. Short- and long-term clinical efficacy, complications and gastroesophageal reflux disease (GERD) were recorded. RESULTS: One month after graded protocol PD, 100% subtype I and 96.2% subtype II achalasia patients showed clinical remission. The PD procedure was completed without major complications in all patients. In the long-term follow up (median time: 56 months), 95.5% subtype I and 90% subtype II achalasia patients had an Eckardt score ≤3. GERD occurred in 27.7% of all patients. CONCLUSION: A graded-protocol PD applied in the appropriate achalasia subtypes was shown to be a safe and highly effective approach, in both the short- and long-term.

Accreditation program for gastrointestinal endoscopes reprocessing in Italy: An on-site survey.

Background and study aims Endoscope reprocessing has been associated with a variable failure rate. Our aim was to present an overview on current practices for reprocessing in Italian facilities and discuss the principle critical points. Methods In 2014 the Italian Society for Digestive Diseases implemented an accreditation program in collaboration with an independent organization for certification and with the Italian Association for Endoscopy Technical Operators. During a 1-day site visit of the endoscopy center, two endoscopists, one nurse, and the representative of the certification body evaluated the endoscope reprocessing. Results As of July 1, 2020, 28 endoscopy centers had been accredited. Ten centers are completing the measures to correct deficiencies found at the visit. Three centers withdrew from the program. The accreditation program has found variations between the various centers, confirming the poor compliance with guidelines. Major deviations from the standards, established by the model before the site visit according to national and international guidelines, concerned instrument cleaning (44.7 % of the centers), instrument storage (23.7 %), and microbiological tests (31.6 %). Conclusions Our overview demonstrated the lack of many reprocessing phases, which are important to prevent endoscopy-associated infections. Accreditation can achieve a transformation in quality and safety of reprocessing with the Italian centrally-led approach.

Incidence of Gastroesophageal Reflux in Dogs Undergoing Orthopaedic Surgery or Endoscopic Evaluation of the Upper Gastrointestinal Tract.

Gastroesophageal reflux (GER) is a common event during general anaesthesia but is often underdiagnosed in veterinary medicine. The oesophageal pH in anaesthetised dogs undergoing endoscopic evaluation of the upper gastrointestinal tract (END group; n = 12) or orthopaedic surgery (ORT group; n = 12) was measured using an oesophageal probe. The dogs were sedated with acepromazine or with methadone or butorphanol, and anaesthesia was induced with propofol and maintained with isoflurane. Of the 24 dogs in this study, 21 (87.5%) had an episode of GER during anaesthesia. The incidence of GER, as well as the first, the minimum, and the maximum pH values, did not differ significantly between the groups. The mean maximum difference versus the first pH value was higher for dogs in the END group (-2.6 ± 3.5) as compared with those in the ORT group (-0.7 ± 2.5), although they were not statistically significant (p = 0.25). The administration of methadone or butorphanol had no significant effect on the development of acidic reflux or biliary reflux. In the acepromazine-sedated dogs, the incidence of GER did not differ significantly between patients undergoing an endoscopic procedure and those undergoing orthopaedic surgery; however, during endoscopy, fluctuations in the oesophageal pH can be expected, even without any clinical signs of GER.

The Italian Society for Digestive Endoscopy (SIED) accreditation and quality improving project based on international standards.

Background and study aims Accreditation of endoscopy services, using valid quality indicators, may address failures to comply with quality standards between endoscopy services. The aim of this work was to present the Italian Society for Digestive Endoscopy (SIED) accreditation model and its effectiveness. Methods A team of eight endoscopists identified quality indicators derived from international guidelines and assessed them in each center voluntarily requesting accreditation. During a 1-day site visit, two expert endoscopists, the representative of the independent and international administrative certification body and a professional nurse evaluated the endoscopy center, by direct observation of the endoscopy team and examination of the medical records Results In all centers we noted shortcomings in instrument reprocessing. In 30 of 40 centers (75 %) the information in the nursing charts was incomplete. Sampling for Helicobacter pylori had not been done in 12 of 40 centers (30 %). In six of 40 centers (15 %) the adenoma detection rate for each endoscopist had not been evaluated. Post-polypectomy intervals were inappropriate in 12 of 40 centers (30 %). We noted a statistically significant difference ( P  < 0.001) between the answers to the SIED checklist of indicators submitted to the inspection team for accreditation before the site visit and the situation found for colonoscopy on site. As of June 30, 2018, 18 endoscopy centers had been accredited and 10 centers had not yet being accredited because they had not completed the measures to correct points raised at the visits. Conclusions Numerous Italian endoscopy centers fail to meet important quality indicators. Our accreditation program can provide means for detecting these problems and correcting them by implementing SIED standards.

Chronic non-allergic rhinitis with neutrophils is associated with higher acid exposure time: A pH-impedance monitoring study.

BACKGROUND & AIM: Chronic rhinitis, a diffuse disease with a prevalence of 40%, can be classified in allergic (AR) and non-allergic rhinitis (NAR). Nasal cytology allows for the identification of different NAR sub-types according to the inflammatory cell infiltrate. NAR etiopathogenesis is not well clarified and, for NARNE (non-allergic rhinitis with neutrophils) subtype, gastroesophageal reflux disease (GERD) has been suggested as one of the etiopathogenetic factors. Aim of this study is to evaluate the role of GERD in patients with NARNE. METHODS: Fifty-one consecutive patients referred to our Ear, Nose and Throat (ENT) unit with nasal symptoms and cytology suggestive for NAR, were enrolled in the study. All the patients performed a gastroenterological evaluation, high resolution esophageal manometry and a 24-h pH-Impedance monitoring. RESULTS: Twenty-five (49%) patients tested positive at nasal cytology for NARNE. A pathologic pH-impedance was identified in seven patients (28%) with NARNE, as opposed to only one (4%) with different NAR subtypes. Statistical analysis showed that higher acid exposure time (AET) and weaker post nasal drainage were more common in NARNE vs. other NAR patients. CONCLUSIONS: NARNE strongly correlates with higher AET and refluxes number; thus, NARNE patients should be tested with pH-impedance monitoring in addition to nasal cytology.

A new mechanism of gastroesophageal reflux in hiatal hernia documented by high-resolution impedance manometry: a case report.

Gastroesophageal reflux disease (GERD) is recognized to be a multifactorial disease and several mechanisms leading to reflux have been described, nevertheless its pathophysiology has not been fully clarified. Hiatus hernia is a known risk factor for GERD since it impairs the esophagogastric junction, leading to: reduction in lower esophageal sphincter pressure; increase in the frequency of the transient lower esophageal sphincter relaxation; and impairment of esophageal clearance. Last generation diagnostic techniques have improved the understanding of these mechanisms. A 72-year-old woman with hiatus hernia and GERD underwent a high resolution impedance manometry (HRIM) after a partial response to treatment with pantoprazole. None of the proposed pathophysiological mechanisms for GERD could explain the presence of reflux: HRIM showed normal lower esophageal sphincter (LES) pressure and contractile integral, complete bolus clearance in all test swallows, and absence of transient LES relaxation. However, after the end of each peristaltic wave, as the LES pressure returned to resting values, a gastroesophageal reflux was detected until the following swallow. We describe an interesting case of a patient with a sliding hiatus hernia, with symptoms suggestive of GERD, in which HRIM revealed a new possible mechanism through which hiatus hernia may lead to GERD.

Prucalopride exerts neuroprotection in human enteric neurons.

Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT4 receptors are known to mediate intestinal peristalsis and recent data in experimental animals have shown their role in neuronal maintenance and neurogenesis. This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H2O2 as shown by increased survival (73.5 ± 0.1% of neuronal survival vs. 33.3 ± 0.1%, respectively; P < 0.0001) and a significant reduction of proapoptotic caspase-3 and caspase-9 activation in all neurons tested. The protective effect of prucalopride was reversed by the specific 5-HT4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well-known enterokinetic effect.

Treatment of achalasia in the era of high-resolution manometry.

Esophageal achalasia is a primary motility disorder characterized by impaired lower esophageal sphincter relaxation and absence of esophageal peristalsis leading to impaired bolus transit, manifested with symptoms such as dysphagia, regurgitation, retrosternal pain, and weight loss. The standard diagnostic tool is esophageal manometry which demonstrates incomplete relaxation of the lower esophageal sphincter and impaired esophageal peristalsis. Recently, a new advanced technique, high-resolution manometry (HRM) with the addition of pressure topography plotting, using multiple sensors to capture the manometric data as a spatial continuum, allows a detailed pressure recording of the esophageal motility. This technique, currently the gold standard for the diagnosis of achalasia, has led to a subclassification of three manometric types that seem to have different responsiveness to treatment. Because its pathogenesis is as yet unknown, achalasia treatment options are not curative. Type II achalasia patients respond better to treatment compared to those with types I and III. Low-risk patients with type I or II achalasia have good outcome with both graded pneumatic dilatations and laparoscopic Heller myotomy, while type III achalasia patients respond better to laparoscopic Heller myotomy. Although, type III achalasia patients responds less in comparison to types I and II to laparoscopic Heller myotomy. Peroral endoscopic myotomy is a promising new technique but long-term follow-up studies for its safety and efficacy must be performed. This article reviews the current therapeutic options, highlighting the impact of HRM to predict the outcome and the new insights for the treatment of achalasia.

Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough: a comparison between two different daily doses of lansoprazole.

AIM: To compare two different daily doses of lansoprazole given for 12 weeks and to assess the role of gastrointestinal (GI) investigations as criteria for selecting patients. METHODS: Out of 45 patients referred for unexplained chronic persistent cough, 36 had at least one of the GI investigations (endoscopy, 24-h esophageal pH-metry and a 4-week trial of proton pump inhibitor (PPI) therapy) positive and were randomly assigned to receive either 30 mg lansoprazole o.d. or 30 mg lansoprazole b.i.d. for 12 weeks. Symptoms were evaluated at baseline (visit 1) after the PPI test (visit 2) and after the 12-week lansoprazole treatment period (visit 3). RESULTS: Thirty-five patients completed the study protocol. Twenty-one patients (60.0%) reported complete relief from their cough with no difference between the two treatment groups (58.8% and 61.1% had no cough in 30 mg lansoprazole and 60 mg lansoprazole groups, respectively). More than 80% of the patients who had complete relief from their cough at the end of the treatment showed a positive response to the PPI test. CONCLUSION: Twelve weeks of lansoprazole treatment even at a standard daily dose, is effective in patients with chronic persistent cough. A positive response to an initial PPI test seems to be the best criterion for selecting patients who respond to therapy.

The role of ultrasound in biliary and pancreatic diseases.

The possibilities and the limits of transabdominal ultrasonography (US) in the diagnosis of bilio-pancreatic diseases are reviewed here in the light of the last 10 years' research. US remains the method of choice for the diagnosis of gallstones and is generally accepted as an initial imaging technique in gallstone complications, such as acute cholecystitis. Moreover the method can be useful for the detection of the biliary complications after laparoscopic cholecystectomy and after liver transplantation. US is still considered the first diagnostic procedure when stones are suspected in the common bile duct. The use of color Doppler can provide a differential diagnosis of gallbladder cancer with respect to other benign inflammatory or polypoid lesions. Color Doppler US allows to detect vascular complications of acute pancreatitis such as pseudoaneurysms. US is still considered useful for the initial screening of the pancreatic cancer. However, for staging other imaging techniques must be employed. With US useful informations are obtained in the diagnosis of cystic tumors of the pancreas and of pancreatic metastases. US is generally of little use for the diagnosis of endocrine tumors.