Plasminogen Activator Inhibitor-1 as a Marker of Esophageal Functional Changes in Pediatric Eosinophilic Esophagitis.

BACKGROUND & AIMS: Esophageal remodeling in eosinophilic esophagitis (EoE) can lead to esophageal rigidity with eventual luminal compromise and stenoses. Gauging esophageal functional alterations in EoE is challenging. An epithelial marker of functional remodeling would impact EoE management. METHODS: Esophageal biopsy specimens from children with and without EoE and primary human esophageal epithelial cells were used for PAI-1 immunohistochemistry, and cell proliferation experiments. PAI-1 immunostaining and basal cell hyperplasia were assessed in the context of concurrently obtained esophageal compliance measures on endoscopic functional lumen imaging probe (EndoFLIP). RESULTS: EndoFLIPs were performed in 45 children (32 with and 13 without EoE). Epithelial PAI-1 was increased in patients with active EoE versus inactive or control patients (P < .01). Esophageal compliance was lower in EoE patients versus controls, particularly in the proximal esophagus (P < .001). Proximal compliance was the strongest predictor of EoE (AUROC 0.88, 95% CI 0.77, 0.98) with esophageal compliance of less than 2.6%mL/mmHg demonstrating 82% sensitivity and 84% specificity for EoE. PAI-1 inhibition significantly diminished esophageal epithelial cell proliferation, suggesting PAI-1 could trigger basal cell hyperplasia. A composite mid-esophageal BZH + PAI-1 score was the strongest predictor of altered compliance (P = .02, AUROC 0.89 (95% CI 0.80, 0.99). CONCLUSIONS: PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.

Compartmentalized pressurization is a novel prognostic factor for hypercontractile esophagus.

BACKGROUND: Hypercontractile esophagus (HE) is a disorder of increased esophageal body contractile strength on high-resolution esophageal manometry (HREM). Compartmentalized pressurization (CP) is a pattern with an isobaric contour of >30 mmHg extending from the contractile front to the lower esophageal sphincter on HREM. The relevance of CP to HE has yet to be explored. METHODS: A retrospective review was performed on 830 HREM studies of patients to identify HE. HE patients' CP status and symptoms by Eckardt score (ES) were reviewed. Diagnoses were made using Chicago Classification (CC) v4.0. KEY RESULTS: Forty-seven patients (5.6%) were identified as having HE by CCv3, 30 (3.6%) of which had HE by CCv4. 11/30 HE patients had CP, and 19/30 did not. CP was associated with chronic opioid use (36.4% vs. 5.3% p = 0.047). Presenting ES was greater for HE patients with CP (7 vs. 4). Seven HE patients with CP and 11 without CP were managed medically. ES after medical therapy was higher in HE patients with CP compared to those without CP (9 vs. 0). No HE patients with CP responded to medical therapy. Kaplan-Meier analysis demonstrated significance of this association over time. 83% of all HE patients had all-cause symptom remission. CONCLUSIONS & INFERENCES: HE patients with CP are associated with a higher presenting ES. HE patients with CP do not respond to medical therapy, while HE patients without CP frequently do respond. CP in HE may have prognostic value in determination of treatment strategy for patients with HE.

Utilizing Esophageal Motility Tests in Diagnosing and Evaluating Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP's emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD's underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches.

Major mixed motility disorders: An important subset of esophagogastric junction outflow obstruction.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility disorder characterized by a lack of relaxation of the esophagogastric junction (EGJ), with preserved esophageal body peristalsis. We propose new terminology for the coexistence of EGJOO with hypercontractile esophagus and distal esophageal spasm as a major mixed motility disorder (MMMD), and normal peristalsis or a minor disorder of peristalsis such as ineffective esophageal motility with EGJOO as isolated or ineffective EGJOO (IEGJOO). METHODS: We reviewed prior diagnoses of EGJOO, stratified diagnoses as IEGJOO or MMMD, and compared their symptomatic presentations, high-resolution manometry (HRM) and endoluminal functional lumen imaging probe (EndoFLIP) metrics, and treatment responses at 2-6 months of follow-up. RESULTS: Out of a total of 821 patients, 142 met CCv3 criteria for EGJOO. Twenty-two were confirmed by CCv4 and EndoFLIP as having EGJOO and were clinically managed. Thirteen had MMMD, and nine had IEGJOO. Groups had no difference in demographic data or presenting symptoms by Eckardt score (ES). HRM showed MMMD had greater distal contractile integral, frequency of hypercontractile swallows, and frequency of spastic swallows, and greater DI by EndoFLIP. Patients with MMMD showed greater reduction in symptoms after LES-directed intervention when measured by ES compared with IEGJOO (7.2 vs. 4.0). CONCLUSION: Patients with MMMD and IEGJOO present similarly. Detectable differences in HRM portend different responses to endoscopic therapy. Because patients with MMMD have greater short-term prognosis, they should be considered a different diagnostic classification to guide therapy.

Successful D-POEM after failed surgical myotomy and diverticulectomy.

Video 1Case series showing 2 patients with prior failed Heller myotomy and diverticulectomy, with subsequent success with POEM, diverticulotomy, and closure with endoscopic suturing. Case 1 also depicts closure of an esophagopleural fistula.

Surgical management of esophageal achalasia: Evolution of an institutional approach to minimally invasive repair.

BACKGROUND: Surgical management of esophageal achalasia (EA) in children has transitioned over the past 2 decades to predominantly involve laparoscopic Heller myotomy (LHM) or minimally invasive surgery (MIS). More recently, peroral endoscopic myotomy (POEM) has been utilized to treat achalasia in children. Since the overall experience with surgical management of EA is contingent upon disease incidence and surgeon experience, the aim of this study is to report a single institutional contemporary experience for outcomes of surgical treatment of EA by LHM and POEM, with regards to other comparable series in children. METHODS: An IRB approved retrospective review of all patients with EA who underwent treatment by a surgical approach at a tertiary US children's hospital from 2006 to 2015. Data including demographics, operative approach, Eckardt scores pre- and postoperatively, complications, outcomes, and follow-up were analyzed. RESULTS: A total of 33 patients underwent 35 operative procedures to treat achalasia. Of these operations; 25 patients underwent laparoscopic Heller myotomy (LHM) with Dor fundoplication; 4 patients underwent LHM alone; 2 patients underwent LHM with Thal fundoplication; 2 patients underwent primary POEM; 2 patients who had had LHM with Dor fundoplication underwent redo LHM with takedown of Dor fundoplication. Intraoperative complications included 2 mucosal perforations (6%), 1 aspiration, 1 pneumothorax (1 POEM patient). Follow ranged from 8months to 7years (8-84months). There were no deaths and no conversions to open operations. Five patients required intervention after surgical treatment of achalasia for recurrent dysphagia including 3 who underwent between 1 and 3 pneumatic dilations; and 2 who had redo LHM with takedown of Dor fundoplication with all patients achieving complete resolution of symptoms. CONCLUSIONS: Esophageal achalasia in children occurs at a much lower incidence than in adults as documented by published series describing the surgical treatment in children. We believe the MIS surgical approach remains the standard of care for this condition in children and describe the surgical outcomes and complications for LHM, as well as, the introduction of the POEM technique in our center for treating achalasia. Our institutional experience described herein represents the largest in the "MIS era" with excellent results. We will refer to alterations in our practice that have included the use of flexible endoscopy in 100% of LHM cases and use of the endoscopic functional lumen imaging probe (EndoFLIP) in both LHM and POEM cases which we believe enables adequate Heller myotomy.