The Role of Psychological Factors in Noncardiac Chest Pain of Esophageal Origin.

Background/Aims: Noncardiac chest pain (NCCP) of esophageal origin is a challenging clinical problem of diverse etiology that affects more than 80 million Americans yearly. We assess the prevalence and impact of psychological disorders on NCCP of esophageal origin, describe possible mechanisms associated with this condition, and review psychological therapy options. Methods: Online search using PubMed and Medline from January 1, 1966, to April 30, 2023. Results: Psychological disorders have been reported in up to 79% of patients with NCCP of esophageal origin. Several psychological disturbances have been identified with this condition, including depression, anxiety, panic disorder, phobias, and obsessive-compulsive and somatoform disorders. It is unclear whether the psychological disorders trigger the chest pain or vice versa. Multiple psychological mechanisms have been linked to chest pain and may contribute to its pathogenesis and severity. These mechanisms include cardiophobia, poor coping strategies, negative social problem solving, stress and perceived control, hypervigilance to cardiopulmonary sensations, altered pain perception, and alexithymia. Psychological therapies for NCCP of esophageal origin include cognitive behavioral therapy, hypnotherapy, physical and relaxation training, breathing retraining, and alternative medicine. Among the therapeutic options, cognitive behavioral therapy has been shown to be an effective treatment for NCCP of esophageal origin. Conclusion: This review raises awareness about the high prevalence of psychological disorders in NCCP of esophageal origin and highlights the need for clinical trials and trained therapists to address the management of this taxing clinical problem.

Diagnostic differences in high-resolution esophageal motility in a large Mexican cohort based on geographic distribution.

High-resolution esophageal manometry [HRM] has become the gold standard for the evaluation of esophageal motility disorders. It is unclear whether there are HRM differences in diagnostic outcome based on regional or geographic distribution. The diagnostic outcome of HRM in a diverse geographical population of Mexico was compared and determined if there is variability in diagnostic results among referral centers. Consecutive patients referred for HRM during 2016-2020 were included. Four major referral centers in Mexico participated in the study: northeastern, southeastern, and central (Mexico City, two centers). All studies were interpreted by experienced investigators using Chicago Classification 3 and the same technology. A total of 2293 consecutive patients were included. More abnormal studies were found in the center (61.3%) versus south (45.8%) or north (45.2%) P < 0.001. Higher prevalence of achalasia was noted in the south (21.5%) versus center (12.4%) versus north (9.5%) P < 0.001. Hypercontractile disorders were more common in the north (11.0%) versus the south (5.2%) or the center (3.6%) P.001. A higher frequency of weak peristalsis occurred in the center (76.8%) versus the north (74.2%) or the south (69.2%) P < 0.033. Gastroesophageal junction obstruction was diagnosed in (7.2%) in the center versus the (5.3%) in the north and (4.2%) in the south p.141 (ns). This is the first study to address the diagnostic outcome of HRM in diverse geographical regions of Mexico. We identified several significant diagnostic differences across geographical centers. Our study provides the basis for further analysis of the causes contributing to these differences.

Jackhammer Esophagus: Current Concepts and Dilemmas.

Jackhammer esophagus (JE) is a recently recognized esophageal motility disorder that is characterized by hypercontractile peristalsis. More than 500 cases have been reported in the literature. Among patients referred for esophageal motility disorders, the prevalence of JE ranges from 0.42% to 9%, with most series describing a prevalence of 2% to 4%. Most cases are women (60.5%). The mean reported age of patients with JE is 65.2 years, and patients commonly have dysphagia (62.8%). Reflux symptoms occur in ∼40% of patients, and chest pain affects more than one-third of patients (36.4%). JE is a heterogenous disorder that is associated with several conditions, including obesity, opioid use, lung transplantation, eosinophilic infiltration of the esophagus, neoplasia, and systemic diseases. The cause and pathogenesis remain unknown, but several observations suggest that it is the result of multiple conditions that likely precipitate increased excitation and abnormal inhibition of neuromuscular function. The natural course of JE also is unknown, but progression to achalasia has been observed in a few patients. Treatment is challenging, in part because of the insufficient understanding of the disorder's underlying mechanisms. Various therapeutic modalities have been used, ranging from observation only to pharmacologic and endoscopic interventions (eg, botulinum toxin injection) to peroral endoscopic myotomy. Treatment efficacy remains largely anecdotal and insufficiently studied.

Effects of Race and Sex on Features of Eosinophilic Esophagitis.

BACKGROUND & AIMS: Clinical and endoscopic features of eosinophilic esophagitis (EoE) differ between children and adults and among racial backgrounds. We investigated whether there were any associations between race or sex and clinical presentation, endoscopic features, and histologic findings from patients with EoE of various racial backgrounds. METHODS: We performed a retrospective, multicenter, cross-sectional analysis of 793 patients with EoE (476 adults and 317 children; mean age, 26 years; range, 0.1-84 years; 72% male) from clinical registries at 5 tertiary care centers in the United States. EoE was defined per consensus guidelines. Data with predetermined variables were extracted from clinical registries at each participating institution. RESULTS: Of the study cohort, 660 patients were white (83%), 77 were African American (10%), and 56 were of other races (7%). A significantly larger proportion of white persons than African Americans or other races had dysphagia (74%, 56%, and 53%, respectively; P < .001), food impaction (35%, 13%, and 13%, respectively; P < .001), and features of EoE that included rings (46%, 25%, and 18%, respectively; P < .001) or furrows (70%, 58%, and 55%, respectively; P = .012). Males and females had similar clinical presentations, histories of atopy, findings from endoscopy, and histologic characteristics. A higher proportion of males than females had strictures (17% vs 11%; P = .038). CONCLUSIONS: Race, and to a smaller degree sex, are associated with features of EoE. African Americans have different clinical symptoms and fewer endoscopic features of EoE than white persons. EoE should be considered in African Americans even without typical findings.

Early Comparison of Inflammatory vs. Fibrostenotic Phenotype in Eosinophilic Esophagitis in a Multicenter Longitudinal Study.

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that causes esophageal remodeling and stricture formation. We compared the clinical course of symptoms, endoscopic findings, histology, and changes in phenotype over time in EoE patients with inflammatory and fibrostenotic phenotypes. METHODS: Data were obtained from EoE patients from three medical centers and followed prospectively. Endoscopic features and histology from index and follow-up endoscopies were recorded. Behavior was classified as inflammatory if endoscopic findings demonstrated furrows or white plaques and as fibrostenotic if endoscopic findings included fixed rings or strictures. RESULTS: Two hundred and fifty-six EoE patients were included in the analysis. The mean age was 32±18 years, 25% of patients were <18 years, 89% of patients were Caucasians, and 74% of patients were male. The mean duration of symptoms before diagnosis was 6.8±7.2 years with a follow-up of 1.7±1.9 years (maximum follow-up of 12 years). Fifty-four percent of patients presented with fibrostenotic EoE, whereas 46% presented with inflammatory EoE. Patients with inflammatory disease were younger than those with fibrostenotic disease (24±19 vs. 39±15 years, P<0.001). Patients with fibrostenotic disease had a longer duration of symptoms than those with inflammatory disease (8.1±7.7 vs. 5.3±6.3 years, P=0.002). Over the study period, 47 (18%) had remission of inflammatory EoE, 68 (27%) continued to have inflammatory disease, 74 (29%) continued to have fibrostenotic disease, 65 (25%) fibrostenotic patients had regression of fibrosis, and 2 patients (1%) progressed from inflammatory disease to fibrostenotic disease. Patients who had regression from their fibrostenosis were more likely than patients who continued to demonstrate fibrostenosis to have a decrease in proximal (54% vs. 32%, P<0.001) and distal (70% vs. 38%, P<0.001) eosinophilia. CONCLUSIONS: Most EoE patients maintained their phenotype or had an improvement with <1% progressing from inflammatory to fibrostenosis. This suggests that early therapeutic strategies aimed at controlling inflammation may interrupt, decrease, or prevent the remodeling fibrosis in EoE.

Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

BACKGROUND: Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. AIM: Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. METHODS: Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. RESULTS: Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. CONCLUSIONS: Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

Gastroesophageal reflux disease and the elderly.

Gastroesophageal reflux disease is a common disorder in all patients but a particular problem in the elderly, for whom the disease often presents with advanced mucosal damage and other complications. Symptoms are also not as reliable an indication of disease severity in older patients. Likewise, therapy is more difficult because of potential side effects and drug interactions.

Hepatic Portal Venous Gas: An Unusual Complication Following Upper Endoscopy and Dilation.

Hepatic portal venous gas (HPVG), a rare condition in which gas accumulates in the portal venous circulation, is often associated with a significant underlying pathology, such as intestinal ischemia, sepsis, and trauma. HPVG after endoscopy or dilation is an unusual complication. We report a case of HPVG following upper endoscopy and dilation for an esophageal stricture in a 34-year-old patient with eosinophilic esophagitis (EoE). The patient was treated conservatively, and his symptoms resolved. Follow-up computed tomography (CT) scan showed resolution of HPVG. This case highlights a rare and potentially ominous complication of upper endoscopy and dilation and underscores the role of conservative management.

Nonspecific motility disorders, irritable esophagus, and chest pain.

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic- and gender-based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high-resolution manometry in noncardiac chest pain; whether pH-impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain.

Causes, evaluation, and consequences of eosinophilic esophagitis.

This paper presents commentaries on whether eosinophilic esophagitis is a food allergy; inflammation in the context of eosinophilic esophagitis; whether eosinophilic esophagitis a cause of noncardiac chest pain; the role of endoscopy in the evaluation of eosinophilic esophagitis; and whether response to proton pump inhibitor therapy can distinguish eosinophilic esophagitis from gastroesophageal reflux disease.

Distal esophageal spasm: an update.

Distal esophageal spasm (DES) is an esophageal motility disorder that presents clinically with chest pain and/or dysphagia and is defined manometrically as simultaneous contractions in the distal (smooth muscle) esophagus in ≥20% of wet swallows (and amplitude contraction of ≥30 mmHg) alternating with normal peristalsis. With the introduction of high resolution esophageal pressure topography (EPT) in 2000, the definition of DES was modified. The Chicago classification proposed that the defining criteria for DES using EPT should be the presence of at least two premature contractions (distal latency<4.5 s) in a context of normal EGJ relaxation. The etiology of DES remains insufficiently understood, but evidence links nitric oxide (NO) deficiency as a culprit resulting in a disordered neural inhibition. GERD frequently coexists in DES, and its role in the pathogenesis of symptoms needs further evaluation. There is some evidence from small series that DES can progress to achalasia. Treatment remains challenging due in part to lack of randomized placebo-controlled trials. Current treatment agents include nitrates (both short and long acting), calcium-channel blockers, anticholinergic agents, 5-phosphodiesterase inhibitors, visceral analgesics (tricyclic agents or SSRI), and esophageal dilation. Acid suppression therapy is frequently used, but clinical outcome trials to support this approach are not available. Injection of botulinum toxin in the distal esophagus may be effective, but further data regarding the development of post-injection gastroesophageal reflux need to be assessed. Heller myotomy combined with fundoplication remains an alternative for the rare refractory patient. Preliminary studies suggest that the newly developed endoscopic technique of per oral endoscopic myotomy (POEM) may also be an alternative treatment modality.

Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system.

OBJECTIVE: Abnormalities are commonly identified during endoscopy in eosinophilic oesophagitis (EoE). There is no standardised classification to describe these features. This study aimed to evaluate the interobserver agreement of a grading system for the oesophageal features of EoE. METHOD: The proposed system incorporated the grading of four major oesophageal features (rings, furrows, exudates, oedema) and the presence of additional features of narrow calibre oesophagus, feline oesophagus, stricture and crepe paper oesophagus. Endoscopic videos from 25 patients with EoE and controls were reviewed by 21 gastroenterologists. Interobserver agreement was assessed by estimating multi-rater κ and the proportion of pairwise agreement. RESULTS: Using the original grading system, agreement for rings, furrows and exudates was moderate (κ=0.38-0.46, 56-65% agreement) but poor for oedema (κ=0.23, 51% agreement). Identification of narrow calibre oesophagus had fair agreement (κ=0.30, 74% agreement) while feline oesophagus had poor agreement (κ=0.15, 68% agreement). After collapsing the severity grading for oedema and furrows and eliminating poorly performing features of feline oesophagus and narrow calibre oesophagus, a modified grading system demonstrated good agreement for the four major features of EoE (κ=0.40-0.54, 71-81% agreement) and additional features of stricture and crepe paper oesophagus (κ=0.52 and 0.58, 79% and 92% agreement). CONCLUSIONS: The proposed system for endoscopically-identified oesophageal features of EoE defines common nomenclature and severity scores for the assessment of EoE disease activity. The system has good interobserver agreement among practising and academic gastroenterologists.

A comprehensive review of eosinophilic esophagitis in adults.

Eosinophilic esophagitis is a recently described disease characterized by the presence of upper gastrointestinal tract symptoms in association with a dense esophageal eosinophilic infiltrate. The awareness and interest of physicians and researchers in this disease has been increasing as reflected by the number of publications on this topic in the last 5 years. The aim of this review is to summarize the latest evidence with regard to epidemiology, pathogenesis, diagnostic, and management of eosinophilic esophagitis, primarily in adults and selected areas in children.

Noncardiac chest pain: epidemiology, natural course and pathogenesis.

Noncardiac chest pain is defined as recurrent chest pain that is indistinguishable from ischemic heart pain after a reasonable workup has excluded a cardiac cause. Noncardiac chest pain is a prevalent disorder resulting in high healthcare utilization and significant work absenteeism. However, despite its chronic nature, noncardiac chest pain has no impact on patients' mortality. The main underlying mechanisms include gastroesophageal reflux, esophageal dysmotility and esophageal hypersensitivity. Gastroesophageal reflux disease is likely the most common cause of noncardiac chest pain. Esophageal dysmotility affects only the minority of noncardiac chest pain patients. Esophageal hypersensitivity may be present in non-GERD-related noncardiac chest pain patients regardless if esophageal dysmotility is present or absent. Psychological co-morbidities such as panic disorder, anxiety, and depression are also common in noncardiac chest pain patients and often modulate patients' perception of disease severity.

Noncardiac chest pain and fibromyalgia.

Fibromyalgia (FM) remains an enigmatic and challenging clinical entity to manage, given its far-reaching spectrum of symptoms, chronicity, associated psychopathology, and lack of clinically available diagnostic tests. However, recent insights into the pathophysiology of FM offer hope that this condition, as with all members of the central sensitization syndromes, can be more readily diagnosed, measured, and treated. This paper presents the epidemiology features and pathogenesis of FM in the context of evaluating NCCP as a prototype among central pain sensitization syndromes. Evidence for the multimodality approach to treatment of this condition is also presented.

Variation in Barrett's esophageal wall thickness: is it associated with histology or segment length?

GOALS: To measure esophageal wall thickness (EWT) with endoscopic ultrasound (EUS) in patients with and without Barrett's esophagus (BE). BACKGROUND: Segment length and histology are used to evaluate BE. The development of varying depths of ablation therapy has renewed interest in using EUS for BE. STUDY: In this prospective study, EWT measurements were taken from the balloon-mucosal interface to the outer most hyper-echoic line. These measurements were correlated with the highest grade of BE dysplasia and segment length, and then compared with the measurements from control group. RESULTS: Between 2004 to 2007, 76 BE patients (69 men, mean age 68 y, 4 ND, 14 low-grade dysplasia, 52 high-grade dysplasia, 6 carcinoma in situ) and 53 normal controls (18 men, mean age 60 y) underwent EUS. The mean EWT was 2.4 mm for controls, 3.1 mm for nondysplastic BE, 3.2 mm for low-grade dysplasia, 3.4 mm for high-grade dysplasia, and 3.9 mm for carcinoma in situ. In the control group of 53 patients, the mean EWT was 2.4 mm. Compared with normal controls, the mean EWT was significantly greater in all histologic subgroups of BE patients (P<0.001). No statistically significant correlation was seen between EWT and BE histology grade. There were no correlations between age, gender, or BE segment length and EWT (P=0.55). CONCLUSIONS: EWT is greater among patients with BE compared with control patients; however, there were no systematic differences in EWT were found among BE patients, based on histology and segment length.

Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults.

OBJECTIVES: The etiology of eosinophilic esophagitis (EoE) is not well understood. It has been proposed that eosinophils migrate to the esophagus in response to various ingested and inhaled allergens. Recent reports in children found an increased proportion of cases of EoE during months with higher outdoor aeroallergens. To our knowledge, this has not been evaluated in adults. We aimed to determine whether there is a seasonal distribution in the number of newly diagnosed cases of EoE in an adult population. METHODS: We conducted a retrospective review of consecutive adult cases newly diagnosed with EoE in 1 year. Cases were grouped based on the index month when the diagnosis was made at endoscopy. To test the consistency of the observations, a second cohort of consecutive cases of similar sample size diagnosed at a different period in time was also analyzed. RESULTS: In total, 41 patients were diagnosed with EoE at our center during the study period, providing an annual prevalence of 0.98%. More cases were diagnosed with EoE during the months of April and May than any other month (P<0.001). When patients were grouped seasonally, there was a significant increase of EoE cases in spring and summer months (n=28) when compared with the fall and winter months (n=13) (P=0.019). Analysis of the second cohort of cases (n=37) from 2002 to 2006 confirmed a similar seasonal diagnostic pattern for EoE during the outdoor seasons. CONCLUSIONS: Our data demonstrate that EoE has a seasonal prevalence in adults. The seasonal variation pattern found in newly diagnosed EoE cases in adults supports the potential role of aeroallergens in the pathogenesis of EoE.

Noncardiac chest pain-treatment approaches.

Treatment of noncardiac chest pain is often difficult because of the heterogeneous nature of the disorder. This condition can stem from gastroesophageal reflux, visceral hyperalgesia, esophageal motility disorders, psychiatric dysfunction, abnormal biomechanical properties of the esophageal wall, sustained esophageal contractions, abnormal cerebral processing of visceral stimulation, or disrupted autonomic activity. For a treatment to be successful, diagnosis of the underlying cause is essential. This article examines three decades of studies from around the world. It concludes that new research into additional mechanisms involved in visceral pain appears promising; but that future studies using improved selective adenosine receptor antagonists and other therapeutic interventions are needed.