Prevalence of neurodegenerative/demyelinating disorders in patients with achalasia.

Introduction: Esophageal achalasia is a primary motility disorder. Although the exact pathogenesis is unknown, autoimmune, and neurodegenerative processes seem to be involved similarly to neurodegenerative and/or demyelinating disorders (NDDs). We hypothesized that the prevalence of NDD may be higher among patients with achalasia and vice versa as the background pathogenetic mechanisms are similar. Methods: This was a prospective, comparative questionnaire-based study. Patients with achalasia and patients with NDD were enrolled. Selected patients with achalasia were thoroughly examined by a neurologist and selected patients with NDD were examined by a gastroenterologist to confirm or rule out NDD or achalasia. We assessed the prevalence of both achalasia and NDD and compared them with their prevalence in general population. Results: A total of 150 patients with achalasia and 112 patients with NDD were enrolled. We observed an increased prevalence of NDD among patients with achalasia (6.0% (9/150); 95% CI (confidence interval): 3.1-11.2%) as compared to the estimated 2.0% prevalence in general population (p = 0.003). Although 32 out of 112 patients (28.6%) with NDD reported dysphagia, we did not observe significantly increased prevalence of achalasia in these patients (1.8% (2/112) vs 0.8% in general population, p = 0.226). Conclusion: The prevalence of NDD was significantly higher among patients with achalasia (6.0%) compared to general population (2.0%), suggesting an association of these disorders. Large-volume studies are necessary to confirm this finding.

Esophageal Motility Patterns After Peroral Endoscopic Myotomy in Patients With Achalasia.

BACKGROUND/AIMS: Several studies have reported partial recovery of peristalsis in patients with achalasia after myotomy. The aim of our study is to analyze esophageal motility patterns after peroral endoscopic myotomy (POEM) and to assess the potential predictors and clinical impact of peristaltic recovery. METHODS: We performed a retrospective analysis of prospectively collected data of consecutive patients with achalasia undergoing POEM at a tertiary center. High-resolution manometry (HRM) studies prior to and after POEM were reviewed and the Chicago classification was applied. RESULTS: A total of 237 patients were analyzed. The initial HRM diagnoses were achalasia type I, 42 (17.7%); type II, 173 (73.0%); and type III, 22 (9.3%). Before POEM, peristaltic fragments were present in 23 (9.7%) patients. After POEM the Chicago classification diagnoses were: 112 absent contractility, 42 type I achalasia, 15 type II, 11 type III, 26 ineffective esophageal motility, 18 esophagogastric junction outflow obstruction, 10 fragmented peristalsis, and 3 distal esophageal spasm. Altogether 68 patients (28.7%) had signs of contractile activity, but the contractions newly appeared in 47 patients (47/214, 22.0%). Type II achalasia showed a trend for appearance of contractions (P = 0.097). Logistic regression analysis did not identify any predictors of peristaltic recovery. The post-POEM Eckardt score did not differ between patients with and without contractions nor did the parameters of timed barium esophagogram. CONCLUSIONS: More than 20% of achalasia patients have signs of partial recovery of esophageal peristalsis after POEM. It occurs predominantly in type II achalasia but the clinical relevance seems to be negligible.

Confocal Laser Endomicroscopy vs Biopsies in the Assessment of Persistent or Recurrent Intestinal Metaplasia/Neoplasia after Endoscopic Treatment of Barrett's Esophagus related Neoplasia.

BACKGROUND AND AIMS: Patients after endoscopic treatment of Barrett's esophagus (BE) related neoplasia (BORN) should enter endoscopic surveillance with biopsies to detect persistent or recurrent neoplasia or intestinal metaplasia (IM). Probe-based confocal laser endomicroscopy (pCLE) serves as a virtual biopsy and could replace standard biopsies. However, the role of pCLE in patients after endoscopic treatment of BORN has not been systematically assessed. The aim of this study was to compare pCLE with biopsies in detecting persistent/recurrent IM/neoplasia. METHODS: A single center, prospective and pathologist-blinded study was performed. Patients after endoscopic treatment of BORN (endoscopic resection or dissection, radiofrequency ablation) underwent surveillance endoscopy with pCLE followed by biopsies. RESULTS: A total of 56 patients were enrolled: initial diagnoses were low-grade dysplasia (LGD) in 24 patients (43%), high-grade dysplasia (HGD) in 12 patients (21%) and early adenocarcinoma (EAC) in 20 patients (36%). Only one patient (2%) experienced recurrent neoplasia (LGD), which was diagnosed by pCLE only. Twenty patients (35.7%) experienced persistent/recurrent IM, diagnosed by both pCLE and biopsies in 17 patients (17/30, 85%) and by pCLE only in 3 pts (3/30, 15%). Sensitivity, specificity, positive and negative predictive values to diagnose recurrent/persistent IM did not differ significantly between pCLE and biopsies; diagnostic accuracy was 100% (95%CI 93.6-100) for pCLE and 94.6 (95%CI 85.1-98.9%) for biopsies, p=0.25. In patients with IM detected by both tested methods, pCLE detected significantly more goblet cells (median 43 per patient) than biopsies (median 12 per patient), p=0.01. CONCLUSION: pCLE is at least as effective as standard biopsies in the detection of persistent/recurrent IM after endoscopic treatment of BORN.

Probe-based confocal laser endomicroscopy versus biopsies in the diagnostics of oesophageal and gastric lesions: A prospective, pathologist-blinded study.

BACKGROUND AND AIM: Probe-based confocal laser endomicroscopy (pCLE) provides real-time microscopic visualisation. Our aim was to compare the diagnostic accuracy of pCLE with standard biopsies in patients with visible oesophageal or gastric lesions. METHODS: This was a single-centre, prospective, pathologist-blinded study. Patients underwent high-resolution endoscopy, and lesions were examined by pCLE followed by standard biopsies. A definitive diagnosis was determined from resection specimen. Main outcomes were overall diagnostic accuracy, sensitivity, specificity and positive and negative predictive values. RESULTS: We examined 74 lesions in 67 patients. Definitive diagnoses revealed 34 malignant and 40 non-malignant lesions. pCLE diagnosis was correct in 89.2% (66/74), while diagnosis based on biopsy was correct in 85% (57/67; p = 0.6). The overall diagnostic accuracy of biopsies was 85% (76-94%) and that of pCLE was 89% (79-96%). pCLE correctly diagnosed malignant lesions, comprising oesophageal adenocarcinoma, oesophageal squamous-cell cancer or gastric adenocarcinoma, in 88.2% (30/34) of cases, while biopsy was correctly diagnosed in 75.9% (22/29; p = 0.3). Sensitivity and specificity to diagnose a malignant lesion were 75.9% (95% confidence interval (CI) 56-89%) and 100% (95% CI 90-100%) for biopsies and 88.2% (95% CI 72-97%) and 92% (95% CI 79-98%) for pCLE. No differences between biopsies and pCLE were found with regard to sensitivity, specificity to diagnose dysplastic and benign lesions (p > 0.2). CONCLUSION: pCLE provides satisfactory diagnostic accuracy comparable with standard biopsies in patients with oesophageal or gastric lesions. ClinicalTrials.gov identifier: NCT0292049).

Radiofrequency Ablation in Patients with Barrett's Esophagus- related Neoplasia - Long-Term Outcomes in the Czech National Database.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) with/without endoscopic resection (ER) is the standard endoscopic treatment modality for Barrett's esophagus (BE) related neoplasia (BORN). The main aim of this study was to assess the long-term outcomes of RFA in patients with BORN. METHODS: We retrospectively analyzed the prospectively collected data from the Czech national database. Main outcomes were: complete remission of neoplasia (CR-N), complete remission of intestinal metaplasia (CR-IM), recurrence of both neoplasia and IM, and safety. RESULTS: From a total of 170 patients with BORN treated with RFA, 136 patients were analyzed. They were followed up for a median of 27.5 months. Fifty-six patients (41%) had low-grade intraepithelial neoplasia (LGIN), 46 (34%) had high-grade intraepithelial neoplasia (HGIN) and 34 (25%) had early adenocarcinoma (EAC). RFA was combined with previous ER in 65 patients (48%). CR-IM and CR-N were achieved in 77.9% (95% CI 70.0-84.6%) and 98.5% (95% CI 94.8-99.8%). Among 30 patients without CR-IM, 22 (73%) did not have macroscopic signs of BE. Recurrent neoplasia was detected in 4.5% of patients (6/134) and 15% (16/106) experienced a recurrence of IM at the level of the neo-Z-line. Diagnosis of cancer was an independent risk factor for recurrent IM after RFA (OR 7.0, 95% CI 1.6-30.9, p<0.0005). CONCLUSION: RFA is highly effective in achieving remission in patients with BORN. A significant proportion of patients did not achieve CR-IM or had a recurrence of IM despite macroscopically absent BE. Recurrence of neoplasia was infrequent but not negligible, thus, patients after successful RFA still require endoscopic surveillance.

Radiofrequency ablation for Barrett's esophagus-related neoplasia.

Barrett's esophagus (BE) is a premalignant condition associated with increased risk of developing esophageal adenocarcinoma. In the past, BE patients with high-grade intraepithelial neoplasia (IEN) or early adenocarcinoma (EAC) were indicated for esophagectomy. With the recent advance in endoscopy, endoscopic techniques have surpassed esophagectomy in the treatment of Barrett's esophagus-related neoplasia and minimized the treatment-related morbidity. Patients with IEN are candidates for endoscopic treatment - endoscopic mucosal resection (ER) of visible lesions and/or ablation therapy of flat Barrett's mucosa. ER combined with radiofrequency ablation (RFA) is now considered as a gold standard for treatment of patients with early Barrett's cancer. RFA is currently the most effective method of ablation used in the treatment of low-grade intraepithelial neoplasia/high-grade intraepithelial neoplasia without visible lesions and for ablation of residual Barrett's mucosa following ER/ESD of EAC or HGIN aiming to achieve complete eradication of Barrett's surface and thus, decreasing the risk of recurrent dysplasia or cancer. The rates of complete remission of neoplasia and metaplasia after completion of endoscopic treatment are 81-92.6% and 75-88.2%, respectively. The aim of this article is to review the principles, techniques, indications, efficacy and safety of this ablative method and surveillance of patients after successful treatment with RFA.

Role of confocal laser endomicroscopy in patients with early esophageal neoplasia.

Probe-based confocal laser endomicroscopy (pCLE) enables real-time histopathological assessment during endoscopic procedures to evaluate epithelial and subepithelial structures with a 1000x magnification. It may be used in various localizations not only in the digestive tract, but its role in clinical practice is still a matter of discussion. The main advantages of pCLE compared to standard biopsies may be: 1) real-time diagnosis; 2) which may be done by the endoscopist; and 3) a larger evaluated area compared to standard biopsies. In theory, pCLE has the potential to eliminate the need for biopsy. However, pCLE cannot replace standard biopsies at this time, among others, standard forceps biopsies are presently more cost-effective. pCLE may be used to enhance the diagnostic arsenal and improve mucosal visualization and evaluation in patients with Barrett's esophagus (BE), with visible esophageal lesions and in patients undergoing surveillance endoscopy after endoscopic treatment of BE related neoplasia. pCLE requires sufficient training and use of validated classifications systems. At present, the majority of endoscopic centers do not use pCLE routinely and no guidelines recommend its routine use for patients with different esophageal diseases, although pCLE is (in selected indications) reimbursed in some countries. This article describes the principle and performance of pCLE and reviews its use in patients with BE and early esophageal neoplasia.

Erratum to: Per-oral endoscopic myotomy (POEM): mid-term efficacy and safety.

The Given Names and Family Names were all inadvertently inverted. The correct order is: Jan Martinek, Hana Svecova, Zuzana Vackova, Radek Dolezel, Ondrej Ngo, Jana Krajciova, Eva Kieslichova, Radim Janousek, Alexander Pazdro, Tomas Harustiak, Lucie Zdrhova, Pavla Loudova, Petr Stirand, Julius Spicak. The original article was corrected.

Per-oral endoscopic myotomy (POEM): mid-term efficacy and safety.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) is becoming a standard treatment for achalasia. Long-term efficacy and the rate of post-POEM reflux should be further investigated. The main aim of this study was to analyze safety and mid-term (12 and 24 months) clinical outcomes of POEM. METHODS: Data on single tertiary center procedures were collected prospectively. The primary outcome was treatment success defined as an Eckardt score < 3 at 12 and 24 months. A total of 155 consecutive patients with achalasia underwent POEM; 133 patients were included into the analysis (22 patients will be analyzed separately as part of a multicenter randomized clinical trial). RESULTS: POEM was successfully completed in 132 (99.2%) patients, and the mean length of the procedure was 69.8 min (range 31-136). One patient underwent a drainage for pleural effusion; no other serious adverse events occurred. Treatment success at 3, 12, and 24 months was observed in 95.5% (CI 89.6-98.1), 93.4% (86.5-96.8), and 84.0% (71.4-91.4) of patients, respectively. A total of 11 patients (8.3%) reported initial treatment failure (n = 5) or later recurrence (n = 6). The majority of relapses occurred in patients with achalasia type I (16.7 vs. 1.1% achalasia type II vs. 0% achalasia type III; p<0.05). At 12 months, post-POEM reflux symptoms were present in 29.7% of patients. At 3 months, mild reflux esophagitis was diagnosed in 37.6% of patients, and pathological gastroesophageal reflux was detected in 41.5% of patients. A total of 37.8% of patients had been treated with a proton pump inhibitor. CONCLUSION: POEM resulted in greater than 90% treatment success at 12 months which tends to decrease to 84% after 2 years. More than one-third of the patients had mild reflux symptoms and/or mild esophagitis.

Long-Term Loss of Response in Proton Pump Inhibitor-Responsive Esophageal Eosinophilia Is Uncommon and Influenced by CYP2C19 Genotype and Rhinoconjunctivitis.

OBJECTIVES: Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is diagnosed in at least one-third of patients with suspected eosinophilic esophagitis (EoE). We aimed to evaluate the durability and factors influencing long-term efficacy of PPI therapy. METHODS: Retrospective multicenter cohort study of patients with PPI-REE who had at least 12 months of follow-up. PPI therapy was tapered to the lowest dose, which maintained clinical remission. Primary outcomes were the proportion of patients with loss of histological response (<15 eos/HPF) and predictors of loss of response. CYP2C19 polymorphisms were determined from blood samples in a subset of patients. RESULTS: Seventy-five PPI-REE patients were included (mean follow-up 26 months (12-85)), of whom fifty-five (73%) had sustained histological remission on low-dose PPI therapy. Loss of response was significantly higher in those patients with a CYP2C19 rapid metabolizer genotype (36% vs. 6%, P = 0.01) and with rhinoconjunctivitis (40% vs. 13%, P = 0.007). On the multivariate analysis, a CYP2C19 rapid metabolizer genotype (odds ratio (OR) 12.5; 95% confidence interval (CI): 1.3-115.9) and rhinoconjunctivitis (OR 8.6; 95% CI: 1.5-48.7) were independent predictors of loss of response. Among relapsing patients, eosinophilia was limited to the distal esophagus in 14/20 (70%). Nine of ten relapsers, with distal eosinophilia, all showing a CYP2C19 rapid metabolizer genotype, regained histological remission after PPI dose intensification. CONCLUSIONS: Most PPI-REE patients remain in long-term remission on low-dose PPI therapy. CYP2C19 rapid metabolizer genotypes and rhinoconjunctivitis were independent predictors of loss of response to PPI, but patients frequently responded to PPI dose escalation.

Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's esophagus.

AIM: To assess the sampling quality of four different forceps (three large capacity and one jumbo) in patients with Barrett's esophagus. METHODS: This was a prospective, single-blind study. A total of 37 patients with Barrett's esophagus were enrolled. Targeted or random biopsies with all four forceps were obtained from each patient using a diagnostic endoscope during a single endoscopy. The following forceps were tested: A: FB-220K disposable large capacity; B: BI01-D3-23 reusable large capacity; C: GBF-02-23-180 disposable large capacity; and jumbo: disposable Radial Jaw 4 jumbo. The primary outcome measurement was specimen adequacy, defined as a well-oriented biopsy sample 2 mm or greater with the presence of muscularis mucosa. RESULTS: A total of 436 biopsy samples were analyzed. We found a significantly higher proportion of adequate biopsy samples with jumbo forceps (71%) (P < 0.001 vs forceps A: 26%, forceps B: 17%, and forceps C: 18%). Biopsies with jumbo forceps had the largest diameter (median 2.4 mm) (P < 0.001 vs forceps A: 2 mm, forceps B: 1.6 mm, and forceps C: 2mm). There was a trend for higher diagnostic yield per biopsy with jumbo forceps (forceps A: 0.20, forceps B: 0.22, forceps C: 0.27, and jumbo: 0.28). No complications related to specimen sampling were observed with any of the four tested forceps. CONCLUSION: Jumbo biopsy forceps, when used with a diagnostic endoscope, provide more adequate specimens as compared to large-capacity forceps in patients with Barrett's esophagus.