Massimo Pierluigi Di Simone

Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia.

Abstract OBJECTIVE: We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia. METHODS: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean ± SE) of nitrinergic neurons per section was visually quantified in each specimen. RESULTS: In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 ± 0.1) and the gastric component (2 ± 0.6) of the LES as compared to those in controls (15 ± 5 and 12 ± 4, respectively; p CONCLUSIONS: Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease.

Functional outcome in handsewn versus stapled ileal pouch-anal anastomosis

Eighty-eight of 119 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were evaluated. Forty patients had a handsewn anastomosis (Hs) with mucosectomy, and 48 had a stapled anastomosis (St). In each patient, we evaluated operative, morphologic, functional, and manometric features. The results in the Hs and St groups were similar when the anastomosis was within 1 cm of the dentate line. In particular, there was no correlation between the type of anastomosis and the number of bowel movements in a 24-hour period, the presence of the urge to defecate, and the use of antidiarrheal drugs. Leakage was significantly higher in the Hs group, even when the anastomosis was less than 1 cm from the dentate line. Pouchitis was more frequent in the Hs group, and, within this group, among those with a short distance between the anastomosis and the dentate line. No correlations were found between the presence of columnar epithelium or active colitis in the mucosa below the anastomosis, the functional outcomes, and the incidence of pouchitis.

Onset timing of delayed complications and criteria of follow-up after operation for esophageal achalasia

BACKGROUND The purpose of this study was to define the length of follow-up necessary to obtain definitive results of the Heller myotomy for the therapy of esophageal achalasia and the modalities of long-term follow-up. Insufficient myotomy, periesophageal scarring, and gastroesophageal reflux esophagitis are the most common late complications of operation for achalasia. Columnar-lined esophagus with or without dysplasia and cancer can further complicate postoperative reflux esophagitis. Because progressive worsening of results with time has been reported, we assessed the timing of appearance of these complications. METHODS Since 1973, 129 patients submitted to Heller myotomy were clinically and objectively followed up. Mean follow-up was 97.4 months (range, 12 to 268 months). Of 129 patients, 42 were followed up for less than 5 years (17 voluntary drop outs, 10 reoperations, 3 deaths, 12 in follow-up), 47 more than 5 years, 26 more than 10 years, 12 more than 15 years, and 2 more than 20 years. The timing of onset of symptoms and complications related to the myotomy were evaluated as was the development of dysplasia and cancer. RESULTS In 11 patients, severe dysphagia due to insufficient myotomy reappeared a mean of 12.4 months after the operation (range, 3 to 30 months). In 7 patients with periesophageal scarring, dysphagia recurred a mean of 18.8 months (range, 6 to 28 months) after the operation. Postoperative reflux esophagitis appeared in 22 patients a mean of 76.5 months (range 21 to 168 months) after the operation. Columnar-lined esophagus was detected in 8 patients a mean of 143.1 months (range, 85 to 230 months) after the operation. Mild to moderate dysplasia was found in 5 of 8 patients with columnar-lined esophagus a mean of 191.6 months after the operation (range, 152 to 287 months), and intramucosal adenocarcinoma was found in 1 patient with columnar-lined esophagus after 8 years. CONCLUSIONS Dysphagia secondary to insufficient myotomy and periesophageal scarring recurs early, not later than 3 years. Conversely, abnormal gastroesophageal reflux with related complications can appear more than 10 years postoperatively. Five years after the operation the follow-up should be primarily endoscopic and histologic. Results should withstand a follow-up of at least 10 years.

Fungal dysbiosis in mucosa-associated microbiota of Crohn’s disease patients

BACKGROUND AND AIMS Gut microbiota is involved in many physiological functions and its imbalance is associated with several diseases, particularly with inflammatory bowel diseases. Mucosa-associated microbiota could have a key role in induction of host immunity and in inflammatory process. Although the role of fungi has been suggested in inflammatory disease pathogenesis, the fungal microbiota has not yet been deeply explored. Here we analysed the bacterial and fungal composition of the mucosa-associated microbiota of Crohns disease patients and healthy subjects. METHODS Our prospective, observational study evaluated bacterial and fungal composition of mucosa-associated microbiota of 23 Crohns disease patients [16 in flare, 7 in remission] and 10 healthy subjects, using 16S [MiSeq] and ITS2 [pyrosequencing] sequencing, respectively. Global fungal load was assessed by real time quantitative polymerase chain reaction. RESULTS Bacterial microbiota in Crohns disease patients was characterised by a restriction in biodiversity. with an increase of Proteobacteria and Fusobacteria. Global fungus load was significantly increased in Crohns disease flare compared with healthy subjects [p < 0.05]. In both groups, the colonic mucosa-associated fungal microbiota was dominated by Basidiomycota and Ascomycota phyla. Cystofilobasidiaceae family and Candida glabrata species were overrepresented in Crohns disease. Saccharomyces cerevisiae and Filobasidium uniguttulatum species were associated with non-inflamed mucosa, whereas Xylariales order was associated with inflamed mucosa. CONCLUSIONS Our study confirms the alteration of the bacterial microbiota and is the first demonstration of the existence of an altered fungal microbiota in Crohns disease patients, suggesting that fungi may play a role in pathogenesis.

Clinical and surgical relevance of the progressive phases of intrathoracic migration of the gastroesophageal junction in gastroesophageal reflux disease

OBJECTIVE The pathophysiologic influence of progressive intrathoracic migration of the gastroesophageal junction axial to the esophagus on gastroesophageal reflux disease was investigated. METHODS A radiologic-manometric study was performed on hiatal insufficiency, concentric hiatus hernia, and short esophagus, the three radiologic steps of intrathoracic gastroesophageal junction migration, and on healthy volunteers. The distances between inferior and superior margins of the lower esophageal sphincter and the diaphragm were measured. Endoscopic, manometric, and pH-metric evaluations were performed after barium swallow in 38 patients with severe gastroesophageal reflux disease and sliding hiatus hernia with intraabdominally reducible gastroesophageal junction, in 35 patients with hiatal insufficiency, in 40 with concentric hiatus hernia, and in 19 with short esophagus. RESULTS The distance from the lower esophageal sphincter inferior margin to the diaphragm was different in healthy volunteers (-2.6 +/- 0.9 cm [standard deviation]) versus that in patients with hiatal insufficiency (-1.0 +/- 0.7 cm; p = 0.02), concentric hiatus hernia (-0.8 +/- 1.0 cm; p = 0.02), and short esophagus (4.0 +/- 2.5 cm; p = 0.0002), and in patients with short esophagus versus hiatal insufficiency (p = 0.0002) and concentric hiatus hernia (p = 0.0002). Lower esophageal sphincter tone was reduced between healthy volunteers (19 +/- 9.1 mm Hg [standard deviation]) and patients with sliding hiatus hernia (12 +/- 7.2 mm Hg;p = 0.02), hiatal insufficiency (10 +/- 5.9 mm Hg; p = 0.0001), concentric hiatus hernia (7 +/- 3.1 mm Hg; p = 0.00002), and short esophagus (7 +/- 3.7 mm Hg; p = 0.00003) and between concentric hiatus hernia versus sliding hiatus hernia (p = 0.007). Acid gastroesophageal reflux total time percent was increased between healthy volunteers (2.4% +/- 1.8% [standard deviation]) and patients with sliding hiatus hernia (12.8% +/- 7.8%;p = 0.02), hiatal insufficiency (17.2% +/- 15.8%; p = 0.0001), concentric hiatus hernia (24.0% +/- 19.6%;p = 0.00002), and short esophagus (26.1% +/- 19.6%;p = 0.00002) and between sliding hiatus hernia versus concentric hiatus hernia (p = 0.002) and short esophagus (p = 0.01). CONCLUSIONS Permanent gastroesophageal junction orad migration axial to the esophagus has greater pathophysiologic relevance on gastroesophageal reflux disease than sliding hiatus hernia with an intraabdominally reducible gastroesophgeal junction. Hiatal insufficiency, concentric hiatus hernia, and short esophagus are markers of progressively increasing irreversible cardial incontinence and therefore indications for surgical therapy.

Hiatus hernia and intrathoracic migration of esophagogastric junction in gastroesophageal reflux disease.

The prevalence and clinical presentation of reducible and irreducible hiatus hernia were investigated within a gastro-esophageal reflux disease patient population. Reflux symptoms and esophagitis data were collected on 791 patients. The barium swallow was used to assess the esophagogastric junction. Clinical and endoscopic findings were tested to predict radiographic findings. The esophagogastric junction was normal in 17% of patients, 53% had a sliding hiatus hernia with a reducible esophagogastric junction; in 23% it was irreducible although axial, and 8% had massive incarcerated hiatus hernia. The presence of reducible sliding hiatus hernia did not influence clinical presentation. Axial irreducibility presented with long-standing severe symptoms and esophagitis in 80% of cases. Clinical and endoscopic findings predicted axial irreducibility in 52% of cases. In conclusion, sliding hiatus hernia with an reducible esophagogastric junction does not influence the severity of gastroesophageal reflux disease. An irreducible esophagogastric junction is associated with long-standing severe gastroesophageal reflux disease. Clinical and endoscopic findings may only be indicative of axial esophagogastric junction irreducibility; thus barium swallow should be part of the work-up.

Obscure gastrointestinal bleeding: single centre experience of capsule endoscopy

The advent of capsule endoscopy (CE) has resulted in a paradigm shift in the approach to the diagnosis and management of patients with obscure gastrointestinal bleeding (OGIB). With increasing global availability of this diagnostic tool, it has now become an integral part of the diagnostic algorithm for OGIB in most parts of the world. However, there is scant data on optimum timing of CE for maximizing diagnostic yield. OGIB continues to be a challenge because of delay in diagnosis and consequent morbidity and mortality. We evaluated the diagnostic yield of CE in identifying the source of bleeding in patients with OGIB. We identified patients who underwent CE at our institution from May 2006 to May 2011. The patients’ medical records were reviewed to determine the type of OGIB (occult, overt), CE results and complications, and timing of CE with respect to onset of bleeding. Out of 346 patients investigated for OGIB, 246 (71.1%) had some lesion detected by CE. In 206 patients (59.5%), definite lesions were detected that could unequivocally explain the OGIB. Small bowel angiodysplasia, ulcer/erosions secondary to Crohn’s disease, non-steroidal anti-inflammatory agent use, and neoplasms were the commonest lesions detected. Visualization of the entire small bowel was achieved in 311 (89.9%) of cases. Capsule retention was noted in five patients (1.4%). In this study, CE was proven to be a safe, comfortable, and effective, with a high rate of accuracy for diagnosing OGIB.

The frequency of true short oesophagus in type II–IV hiatal hernia

OBJECTIVES The misdiagnosis of short oesophagus may occur on recurrence of the hernia after surgery for type II-IV hiatal hernia (HH). The frequency of short oesophagus in type II-IV hernia is undefined. The aim of this study was to assess the frequency of true short oesophagus in patients undergoing surgery for type II-IV hernia. METHODS Thirty-four patients with type II-IV hernia underwent minimally invasive surgery. After full isolation of the oesophago-gastric junction, the position of the gastric folds was localized endoscopically and two clips were applied in correspondence. The distance between the clips and the diaphragm (intra-abdominal oesophageal length) was measured. When the intra-abdominal oesophagus was <1.5 cm after oesophageal mobilization, the Collis procedure was performed. After surgery, patients underwent a follow-up, comprehensive of barium swallow and endoscopy. RESULTS After mediastinal mobilization (median 10 cm), the intra-abdominal oesophageal length was >1.5 cm in 17 patients (4 type II, 11 type III and 2 type IV) and ≤ 1.5 cm in 17 patients (13 type III and 4 type IV hernia). No statistically significant differences were found between patients with intra-abdominal oesophageal length > or ≤ 1.5 cm with respect to symptoms duration and severity. Global results (median follow-up 48 months) were excellent in 44% of patients, good in 50%, fair in 3% and poor in 3%. HH relapse occurred in 3%. CONCLUSIONS True short oesophagus is present in 57% of type III-IV and in none of type II HHs. The intraoperative measurement of the submerged intra-abdominal oesophagus is an objective method for recognizing these patients.

Barrier effect of Esoxx(®) on esophageal mucosal damage: experimental study on ex-vivo swine model.

The aim of the present study was to assess the potential barrier effect of Esoxx®, a new nonprescription medication under development for the relief of gastroesophageal reflux symptoms. Esoxx is based on a mixture of hyaluronic acid and chondroitin sulfate in a bioadhesive suspension of Lutrol® F 127 polymer (poloxamer 407) which facilitates the product adhesion on the esophageal mucosa. The mucosal damage was induced by 15 to 90 minutes of perfusion with an acidic solution (HCl, pH 1.47) with or without pepsin (2000 U/mL, acidified to pH 2; Sigma-Aldrich). Mucosal esophageal specimens were histologically evaluated and Evans blue dye solution was used to assess the permeability of the swine mucosa after the chemical injury. The results show that: (1) esophageal mucosal damage is related to the perfusion time and to the presence of pepsin, (2) mucosal damage is associated with an increased permeability, documented by an evident Evans blue staining, (3) perfusion with Esoxx is able to reduce the permeability of the injured mucosa, even after saline washing of the swine esophagus. These preliminary results support further clinical studies of Esoxx in the topical treatment of gastroesophageal reflux symptoms.

Prepouch Ileitis After Ileal Pouch-anal Anastomosis: Patterns of Presentation and Risk Factors for Failure of Treatment

Background and Aims There is a lack in the literature about prepouch ileitis [PI], in particular regarding risk factors associated with failure of the medical treatment. Aim of the study is to analyse the characteristics of PI patients and to compare those who required surgery with those who were successfully treated with conservative therapy. Methods All cases presenting a diagnosis of PI were included and analysed. Patients eventually requiring surgery were compared with those who were managed conservatively, for symptoms of presentation, endoscopic characteristics, and rate of response to medical treatment. A sub-analysis of outcomes based on the final histology was performed. Results The overall incidence of PI among 1286 patients was 4.4% [57], after a median of 6.8 years from pouch surgery. Symptoms included increased frequency [26.4%], outlet obstruction [21%], and bleeding [15.8%]. Afferent limb stenosis affected 49.1% of patients. The comparison showed that patients requiring surgery had a higher rate of Crohns disease and indeterminate colitis [42.1 vs 0% and 15.8 vs 2.6%, p < 0.0001], outlet obstruction as main symptom [47.4 vs 7.9%, p = 0.0023], and afferent limb stenosis [73.7 vs 36.8%, p = 0.008] at endoscopy. Rate of failure of medical treatment at 5 years was 8.2% in patients with ulcerative colitis and 75% in the presence of both indeterminate colitis and Crohns disease [p < 0.0001]. Conclusions Crohns disease, indeterminate colitis, and stenosis with outlet obstruction are risk factors for failure of treatment after diagnosis of PI. Early aggressive therapy and surgery should be considered in these cases.