Outcomes of pneumatic dilation in achalasia: Extended follow-up of more than 25 years with a focus on manometric subtypes.

BACKGROUND AND AIM: Pneumatic dilation (PD) is the most popular nonsurgical treatment for achalasia. This study investigated predicting factors, including manometric subtypes for symptom recurrence in the long term, in patients with achalasia treated with a single PD. METHODS: Between 1983 and 2013, a total of 107 patients were treated initially with a single PD and included in this longitudinal cohort study. Outcomes were correlated with demographics, symptoms (Eckardt score), and esophagographic and manometric features. Manometric tracings were retrospectively classified according to the three subtypes of the Chicago classification. RESULTS: Ninety-one (85%) patients were successfully treated after the first PD. The median follow-up was 13.8 years (interquartile range 7-20). During follow-up, 54% of the patients experienced a clinical relapse. The overall cumulative success rates at 2, 5, 10, 15, 20, and 25 years were 64%, 53%, 49%, 42%, 36%, and 36%, respectively. Age < 40 years, lower esophageal sphincter pressure > 15 mmHg, a cardia width < 5 mm, and an esophageal barium column height > 1 cm 4 to 12 weeks post-dilation significantly correlated with symptom recurrence, whereas achalasia subtypes did not significantly correlate with the treatment results. CONCLUSION: Pneumatic dilation in achalasia is an effective therapy in the short term, but its effect wanes in the very long term. Young age at presentation, a high lower esophageal sphincter pressure, a narrow cardia, and an esophageal barium column of > 1 cm after PD are predictive factors for the need of repeated treatment.

Murine genetic deficiency of neuronal nitric oxide synthase (nNOS(-/-) ) and interstitial cells of Cajal (W/W(v) ): Implications for achalasia?

BACKGROUND AND AIM: Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice. METHODS: Esophageal manometry was performed with a micro-sized transducer catheter to quantify LES pressure, swallow evoked LES relaxation, and esophageal body motility. The LES morphology was examined by semiquantitative analysis of the immunoreactivity (reduction grade I-IV) of neuronal NOS (nNOS), ICC-IM, and VIP and their correlation with esophageal function. RESULTS: nNOS(-/-) in comparison to WT mice showed a significantly higher LES mean resting pressure with an impaired swallow induced relaxation, whereas W/W(v) mice had a hypotensive LES with decreased relaxation. W/W(v) and nNOS(-/-) mice demonstrated differing degrees of tubular esophageal dysfunction. The reduced immunoreactivity of nNOS correlated with an increased LES pressure and decreased LES relaxation, respectively. Cajal-cell reduction correlated with impaired LES relaxation, whereas VIP reduction revealed no correlation with esophageal function. CONCLUSIONS: The reduction of ICC-IM and nNOS can cause dysfunction of the LES and esophageal peristalsis, whereas VIP reduction seems to have no effect. ICC-IM and nNOS deficiency might be independent relevant causes of esophageal dysfunction similar to that seen in human achalasia.

Prospective evaluation of the routine use of a nasopharyngeal airway (Wendl Tube) during endoscopic propofol-based sedation.

BACKGROUND/AIMS: Insertion of a nasopharyngeal airway (NPA) during endoscopic sedation is only recommended in the event of respiratory problems. We evaluated the safety and efficacy of routine insertion of an NPA during sedation in gastrointestinal (GI) endoscopy. METHODS: Between July 2009 and April 2012, patients with colonoscopy or expected longer-lasting or therapeutic upper GI endoscopy were pseudo-randomized in a weekly alternating fashion to perform sedation (midazolam in combination with propofol) with or without NPA insertion. The primary outcome measure was respiratory depression (oxygen saturation <90%). Secondary measures included hypotension (systolic blood pressure <90 mm Hg), bradycardia (heart rate <40 beats/min) or nasopharyngeal damage after NPA insertion. RESULTS: 216 (106 females, mean age 60.7 ± 9.65 years) were enrolled. Colonoscopy was performed in 131 patients and upper endoscopy in 85 patients. In 105 patients an NPA was used (intervention group). Five (4.7%) of those patients showed minor nasopharyngeal injury. Respiratory depression (13.5 vs. 1.9%, p = 0.002) and hypotension (11 vs. 5%, p = 0.09) occurred more frequently in the control than in the intervention group. CONCLUSION: The routine placement of an NPA can reduce the frequency of hypoxemic events during endoscopic sedation with minor risks for nasopharyngeal injury.

Three-year results of a multicenter prospective study of transoral incisionless fundoplication.

BACKGROUND: To date, there are no long-term data on the use of transoral incisionless fundoplication (TIF) for the treatment of chronic gastroesophageal reflux disease (GERD). We sought to prospectively evaluate the long-term safety and durability of TIF in a multi-center setting. METHODS: A longitudinal per protocol (PP) and a modified intention-to-treat (mITT) analysis at 1 and 3 years consisted of symptom evaluation using the GERD health-related quality of life (GERD-HRQL) questionnaire, medication use, upper gastrointestinal endoscopy, and pH-metry. RESULTS: Of 79 patients previously reported at 1 year, 12 were lost to follow-up, and 1 died from an unrelated cause. The remaining 66 patients were followed up and analyzed (mITT). Of 66 patients, 12 underwent revisional procedures, leaving 54 patients for PP analysis at a median of 3.1 years (range = 2.9-3.6). No adverse events related to TIF were reported at 2- or 3-year follow-up. On PP analysis, median GERD-HRQL score off proton pump inhibitors (PPIs) improved significantly to 4 (range 0-32) from both off (25 [13-38], P < .0001) and on (9 [0-22], P < .0001) PPIs. Discontinuation of daily PPIs was sustained in 61% (mITT) and 74% (PP) of patients. Of 11 patients with pH data at 3 years (PP), 9 (82%) remained normal. Based on mITT analysis, 9/23 (39%) remained normal at 3 years. CONCLUSIONS: The clinical outcomes at 3 years following TIF, patient satisfaction, healing of erosive esophagitis, and cessation of PPI medication support long-term safety and durability of the TIF procedure for those with initial treatment success. Although complete normalization of pH studies occurred in a minority of patients, successful cases showed long-term durability.

Clinical and manometric course of nonspecific esophageal motility disorders.

BACKGROUND AND AIMS: The evolution of nonspecific esophageal motility disorders remains unclear. The aim of this study was to investigate whether nonspecific esophageal motility disorders progress into specific motility disorders and whether such progression is predictable. METHODS: Seventy-six symptomatic patients (49 males, 27 females, mean age 57 ± 16 years) with newly diagnosed nonspecific esophageal motility disorders were prospectively registered and followed-up. Follow-up visits, with structured interviews and manometric re-evaluation, were recommended biannually and whenever symptoms exacerbated. RESULTS: Forty-three patients were followed for up to 4 years, symptoms worsened in 30% of patients, resolved in 26%, improved in 14% and were unchanged in 30%. Twenty-eight patients agreed to undergo manometric re-evaluation. Fifteen (53.6%) of these patients showed a progression to achalasia. The remaining patients continued to display features of nonspecific esophageal motility disorders (32%) or had normal motility (11%). The only significant association could be determined between age and progression to achalasia reaching nearly 100% in patients' ≤46 years of age. In contrast, none of the patients' ≥68 years progressed. CONCLUSION: More than half of the patients in our cohort with nonspecific esophageal motility disorders showed a transition into achalasia. Neither manometric nor clinical findings predicted the progression of nonspecific esophageal motility disorders. However, young patients were more likely to progress to achalasia.

Editorial: Cancer surveillance in achalasia: better late than never?

Patients with achalasia have an increased risk for the development of esophageal squamous cell cancer. Endoscopic surveillance in long-standing achalasia has been advocated by some, but the most recent American Society of Gastrointesinal Endoscopy guidelines regard current data as insufficient to support such an approach. In this issue of the American Journal of Gastroenterology, Leeuwenburgh and colleagues report on the results of a long-term prospective study with fixed surveillance intervals. The authors confirm earlier observations of an increased cancer risk after 10 years of symptomatic achalasia. Despite some limitations, this study and earlier data suggest that it might be worthwhile to consider endoscopic surveillance in patients with long-standing achalasia.

Trainee participation during screening colonoscopy does not affect ADR at subsequent surveillance, but may result in early follow-up.

Background and study aims Training future endoscopists is essential to meet rising demands for screening and surveillance colonoscopies. Studies have shown conflicting results regarding the influence of trainees on adenoma detection rates (ADR). It is unclear whether trainee participation during screening adversely affects ADR at subsequent surveillance and whether it alters surveillance recommendations. Patients and methods A retrospective analysis of average-risk screening colonoscopies and surveillance exams over a subsequent 10-year period was performed. The initial inclusion criteria were met by 5208 screening and 2285 surveillance exams. Patients with poor preparation were excluded. The final analysis included 7106 procedures, including 4922 screening colonoscopies and 2184 surveillance exams. Data were collected from pathology and endoscopy electronic databases. The primary outcome was the ADR with and without trainee participation. Surveillance recommendations were analyzed as a secondary outcome. Results Trainees participated in 1131 (23 %) screening and in 232 (11 %) surveillance exams. ADR did not significantly differ ( P  = 0.19) for screening exams with trainee participation (19.5 %) or those without (21.4 %). ADRs were higher at surveillance exams with (22.4 %) and without (27.5 %) trainee participation. ADR at surveillance was not adversely affected by trainee participation during the previous colonoscopy. Shorter surveillance intervals were given more frequently if trainees participated during the initial screening procedure ( P  = 0.0001). Conclusions ADR did not significantly differ in screening or surveillance colonoscopies with or without trainee participation. ADR at surveillance was not adversely affected by trainee participation during the previous screening exam. However, trainee participation may result in shorter surveillance recommendations.

Does trainee participation during colonoscopy affect adenoma detection rates?

INTRODUCTION: Training future endoscopists is essential to meeting the increasing demands for colonoscopy. It remains unknown whether adenoma detection rates are adversely affected by trainee participation. METHODS: This is a single-center, prospective study. The primary aim of this study was to investigate whether adenoma detection rates differed between procedures with or without trainee involvement. A total of 368 consecutive patients entered the analysis (181 with trainee participation and 187 without). RESULTS: Adenomas were detected in 19.3% of experienced physician-only procedures and in 14.9% of procedures with trainee participation. Advanced adenomas were detected in 8.6% of experienced physicians' procedures vs. 4.9% of trainee procedures. Polyp detection was nearly identical in both groups (32% for experienced physicians; 33% for trainees). Trainee participation delayed the procedure by a mean of seven minutes. CONCLUSION: Adenoma detection rates did not differ significantly, whether there was trainee involvement or not. A trend toward finding more adenomas or advanced adenomas in the absence of a trainee was observed, but it was lower than previously reported interobserver variability among experienced physicians. The small difference in adenoma detection was not observed for polyp detection, which may be explained by the more frequent removal of hyperplastic polyps by trainees.

Comprehensive epidemiological and genotype-phenotype analyses in a large European sample with idiopathic achalasia.

BACKGROUND AND AIM: Although an eight-residue insertion in HLA-DQß1 has been recently identified as a genetic risk factor for idiopathic achalasia, other risk factors are still unknown. In the present study, we carried out an epidemiological survey and a genotype-phenotype (G×P) analysis to gain further insights into the etiology of achalasia. METHODS: We obtained medical data from 696 achalasia patients and 410 controls, as well as their first-degree relatives (2543 of patients and 1497 of controls). For the G×P analysis, we stratified the patients into HLA-DQß1 insertion carriers and noncarriers. RESULTS: Our data show that patients are more often affected by viral infections before achalasia onset (P<0.0001, most significantly for varicella zoster virus infections). In addition, allergic (P=0.0005) and autoimmune disorders (P=0.0007, most significantly for psoriasis and Sjögren's syndrome) represent comorbid disease conditions. First-degree relatives of patients also show higher prevalence rates of allergic disorders (P=0.0007) and psoriasis (P=0.016) compared with control relatives. Moreover, the G×P analysis reveals that achalasia is triggered by pregnancies in female HLA-DQß1 insertion carriers (P=0.031). CONCLUSION: Our data point to a role of viral infections in the development of achalasia. In addition, they provide evidence for a relationship between achalasia and allergic, as well as autoimmune, disorders. Furthermore, pregnancy seems to be a disease-triggering factor in female HLA-DQß1 insertion carriers, which points to hormonal and/or immunosuppressive factors influencing disease development.

Current endoscopic ultrasound-guided approach to incidental subepithelial lesions: optimal or optional?

Subepithelial lesions (SEL) are identified during endoscopic procedures on a regular basis. They can occur anywhere in the gastrointestinal (GI) tract and are located beneath the normal epithelial layer, which explains why a tissue diagnosis is difficult to obtain with routine biopsies. Endoscopic ultrasound (EUS) is used to further characterize these lesions. EUS can distinguish intramural lesion from extramural compression. Furthermore, it allows allocation of intramural lesions to a specific layer of the GI wall and offers additional information as to whether a lesion could be benign or malignant. EUS also assists in choosing the optimal means of tissue acquisition. The choice of tissue acquisition is based on a number of factors, such as tumor size, EUS features, and location within the GI tract or within a specific layer of the GI wall. Furthermore, local expertise and patient factors should be considered when deciding whether tissue acquisition, surgical intervention or follow up is recommended. In this review we offer an EUS-guided approach to the evaluation of incidental SEL based on current evidence and point out areas of uncertainty, which explain why the proposed algorithmic approach may be optional rather than optimal.

Surgical therapy of primary intestinal lymphangiectasia in adults.

Primary intestinal lymphangiectasia (PIL) is a rare disorder, especially in adults. It causes a local disruption of chylus transport and is part of the exudative gastroenteropathies. Conservative therapy includes dietary measures or somatostatin medication. Taking the differential diagnosis of PIL into consideration is a major challenge, since patients suffering from PIL may present with diarrhoea and lymphedema or chylous ascites. This can be explained by the chronic lymphedema of the bowel leading to dilation of the vessels (intraluminal loss) and sometimes even to a rupture (peritoneal loss). Push-pull enteroscopy and capsule endoscopy are the proper interventional diagnostic tools to discover PIL. Exploratory laparoscopy may be useful in unclear cases. Surgical resection of the altered intestine has been described with positive results. Exploratory laparoscopy may even be a diagnostic tool in unclear cases. Resection of the altered intestine is a treatment option in symptomatic and treatment-refractory cases.

Oculopharyngeal muscular dystrophy as a rare cause of dysphagia.

Oculopharyngeal muscular dystrophy (OPMD) is a rare cause for late-onset dysphagia. OPMD normally follows an autosomal dominant inheritance. Herein we describe a rare case of an autosomal recessive inheritance of OPMD. An 80-year-old male presented with progressive dysphagia, frequent aspiration and change of voice getting inarticulate and hoarse. Physical examination showed ptosis of the right eyelid. Endoscopic and manometric investigation revealed a nonspecific motility disorder with hypopharyngeal esophageal hypotension. The severity of dysphagia became apparent when significant aspiration occurred during a barium swallow. Magnetic resonance imaging of the head ruled out a malignant or cerebral ischemic process. Based on the neurological examination, neurogenic muscular dystrophy was suspected and DNA analysis was performed. The analysis confirmed the extremely rare diagnosis of an autosomal recessive inheritance pattern of OPMD with homozygous (GCN)6(GCN)4(GCN) expansion of the poly-(A) binding protein nuclear 1 gene. As OPMD normally follows an autosomal dominant inheritance, consanguinity of the patient's parents was suspected.

Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia.

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQß1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P=1.73×10(-19)). In addition, two amino acid substitutions in the extracellular domain of HLA-DQα1 at position 41 (lysine encoded by HLA-DQA1*01:03; P=5.60×10(-10)) and of HLA-DQß1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P=1.20×10(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia.