Achalasia in pregnancy.

Achalasia is characterised by incomplete relaxation of the lower oesophageal sphincter and aberrant oesophageal peristaltic activity resulting in impaired oesophageal emptying. This rare condition in pregnancy is unique as both the disease and its treatment are associated with fetomaternal risks and complications. A woman in her early 30s, gravida 3 para 2 at 35 weeks' pregnancy with suspected oesophageal achalasia, presented with shortness of breath, cough and fever following frequent bouts of vomiting and fluid regurgitation. She was diagnosed with aspiration pneumonia complicated by severe metabolic acidosis, malnutrition syndrome and fetal growth restriction. Following stabilisation of the acute clinical problems, delivery was expedited via caesarean section. Postpartum endoscopy confirmed the diagnosis of achalasia as per initial suspicion. Definitive surgery was performed several months later after optimisation of the patient's nutritional status. This case illustrates the life-threatening complications of achalasia in pregnancy.

Effect of esophageal body recoil on clinical outcomes in non-spastic achalasia.

BACKGROUND: Despite the established efficacy of achalasia treatments on symptomatic outcomes, there are limited data evaluating the treatment effect on esophageal dilatation. This study aimed to assess the effect achalasia treatment on esophageal dilatation and the effect of esophageal width reduction ("recoil") on clinical outcomes. METHODS: Patients with type I or type II achalasia that completed high-resolution manometry (HRM), functional lumen imaging probe (FLIP), and timed barium esophagram (TBE) pre and post treatment were included. Esophageal width was measured using TBE. Focused subgroup analysis was performed on patients with normal posttreatment EGJ opening on FLIP. Good clinical outcomes were defined as barium column height of <5 cm at 5 min and Eckardt Score ≤3. KEY RESULTS: Sixty-nine patients (41% type I and 59% type II) were included. Esophageal width decreased from pre to post treatment mean (SD) 4.2 (1.3) cm-2.8 (1.2) cm; p < 0.01. In the normal post treatment EGJ opening subgroup, esophageal width was less in patients with good TBE outcome compared to poor outcome mean (SD) 2.2 (0.7) cm versus 3.2 (1.4) cm (p < 0.01), but did not differ in good versus poor symptomatic outcome groups. Esophageal width recoil >25% posttreatment was associated with a greater rate of good TBE outcome (71% vs. 50%, p = 0.04) and good symptomatic outcome (88% vs. 50%; p = 0.04). CONCLUSIONS AND INFERENCES: Esophageal recoil was associated with good achalasia treatment outcome in patients without posttreatment EGJ obstruction. This suggests that mechanical properties of the esophageal wall, likely associated with tissue remodeling, play a role in clinical outcomes following achalasia treatment.

Peroral endoscopic myotomy provides effective palliation in type III achalasia.

BACKGROUND: Type III achalasia outcomes have historically been met with limited success after conventional laparoscopic Heller myotomy (LHM) and pneumatic dilation. Peroral endoscopic myotomy (POEM) has emerged as a promising alterative for a multitude of reasons. Our objective was to investigate POEM outcomes in palliating type III achalasia. METHODS: A retrospective analysis of a prospectively maintained database was conducted in a tertiary care institution between April 2014 and July 2019. The primary outcome was postoperative Eckardt score. We also explored the effect of lower esophageal sphincter (LES) integrated resting pressure (IRP) on manometry, barium column height and width, and complications. Standard statistical methods were applied using R. RESULTS: A total of 518 patients in the achalasia database were identified, with 308 patients undergoing LHM and 210 undergoing POEM during the study period. POEM was used for type III achalasia in 36 patients (median age, 60 years; 61.7% male), with a median operative time of 85 minutes (interquartile range [IQR], 71-115 minutes) and follow-up of 1 year (IQR, 0.16-2.25 years). Within the POEM group, 11 patients (33%) had previous interventions, including Botox injections to the LES (n = 7), pneumatic dilation (n = 1), and LHM (n = 3). A significant decrease in median Eckardt score was observed (7 preoperatively [IQR, 6-8.75] vs 0 postoperatively [IQR, 0-1]; P < .01). Similar improvements after POEM were noted in median LES IRPs (25.5 mmHg vs 4.5 mmgHg; P < .01), 1-minute barium column height (10 cm vs 0 cm; P < .01), and 1-minute barium column width (2 cm vs 0 cm; P < .01). Patients reported a return to activities of daily living in a median of 7 days (IQR, 3-7 days). Three patients experienced complications, including mucosal perforation resolving with conservative management (n = 1), readmission for bleeding duodenal ulcer responding to proton pump inhibitors (n = 1), and readmission for dysphagia and rehydration (n = 1). Postoperative esophageal pH studies were conducted in 21 patients (62%), demonstrating a Demeester score of >14.72 in 13 patients (62%). CONCLUSIONS: POEM provides effective and durable palliation for type III achalasia, as demonstrated by symptom relief, esophageal manometry, and radiographic measurement. Considering its low morbidity profile, POEM should be considered as first-line therapy in this challenging disease subtype.

Simultaneous Examination of Eosinophil Infiltration in Esophageal Mucosa and Muscle in Patients with Achalasia: Direct Biopsy of the Esophageal Muscle at Per-oral Endoscopic Myotomy.

BACKGROUND: The relationship between eosinophilic esophagitis (EoE) and achalasia is not completely understood. There have been reports of eosinophilic infiltration of all esophageal layers in patients with achalasia. However, a routine endoscopic biopsy of the muscular layer is usually not feasible. We evaluate the safety and efficacy of muscle layer biopsy during per-oral endoscopic myotomy (POEM) as well as the prevalence of eosinophilic infiltration of the esophageal mucosa and muscular layer in patients with achalasia. PATIENTS AND METHODS: All enrolled patients had diagnosed achalasia and had simultaneous biopsies of the muscular layer at the middle esophagus and distal esophageal sphincter as well as the mucosal layer of the proximal and distal esophagus during POEM. All POEM procedures took place from August 2018 to December 2018 or September 2019 to November 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. Eosinophilic infiltration in the biopsy specimen was examined. KEY RESULTS: Twenty consecutive patients (65% female, age range: 21-84) with a pre-procedure Eckardt score of >6 were enrolled during the study period, with the duration of their achalasia ranging from 1 to 32 years. Eighteen patients had clinical symptomatic improvement after POEM, as defined by an Eckardt score <3. Endoscopic examination did not reveal any signs of eosinophilic esophagitis. Pathologic examination of biopsies revealed eosinophilic infiltration in three of 20 patients (15%) in the distal esophageal mucosa (all <15 eosinophils/HPF) and none in the proximal esophageal mucosa. There was no eosinophilic infiltration in the distal esophageal sphincter and the middle esophageal muscle. No complication was noted due to muscle biopsy. CONCLUSIONS AND INFERENCES: Submucosal tunneling during POEM provides a safe access for direct esophageal muscle biopsy. This is the first report of the simultaneous biopsy of the esophageal mucosa and muscle in patients with achalasia. Contrary to all previously published studies, the association of esophageal eosinophilic infiltration and achalasia was not observed in this small sample study. Based on our findings, immune or autoimmune reaction rather than direct eosinophilic infiltration in the muscle is more likely the cause of achalasia.

Use of the functional luminal imaging probe in pediatrics: A comparison study of patients with achalasia before and after endoscopic dilation and non-achalasia controls.

BACKGROUND: Achalasia is an esophageal motility disorder characterized by esophagogastric junction (EGJ) dysfunction and impaired esophageal peristalsis with significant impact on quality of life. While the functional luminal imaging probe (FLIP) has been used to assess EGJ distensibility in achalasia, its clinical utility in pediatrics is limited due to absence of normative values and correlations with clinical outcomes in children. Thus, we sought to evaluate FLIP's use in a pediatric achalasia cohort undergoing dilations and non-achalasia controls. METHODS: We conducted a retrospective study of pediatric patients with achalasia who underwent FLIP before and immediately after balloon dilations and compared to a non-achalasia cohort. KEY RESULTS: Thirty patients with achalasia (mean age, 15.2 years; 40% female), including fourteen treatment-naïve and thirteen controls (mean age, 7.9 years; 61% female) were identified. Median EGJ distensibility index (EGJ-DI) 2.07 mm2  mmHg-1 and diameter (9.23 mm) in treatment-naïve patients were significantly lower compared to controls (EGJ-DI 6.8 mm2  mmHg-1 ; diameter 18.61 mm; (p < 0.001). Balloon dilations resulted in a significant increase in EGJ-DI immediately after the dilation, particularly in treatment-naïve patients (p < 0.001), and a significant improvement in Eckardt scores (p < 0.001). CONCLUSIONS & INFERENCES: Functional luminal imaging probe measurements of EGJ-DI in pediatric patients with achalasia are mostly consistent with adult findings. However, normal EGJ-DI is seen in symptomatic patients, including treatment-naive, highlighting the need for pediatric reference data. Balloon dilations achieve a significant increase in EGJ-DI with improvement in Eckardt scores, confirming the therapeutic value of dilations in achalasia management.

Physiological and pathological roles of the accommodation response in lower esophageal sphincter relaxation during wet swallows.

The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1-11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, - 0.6-6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5-44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18-28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice.

Ultrasound, electromyography, and balloon guidance for injecting botulinum toxin for cricopharyngeal achalasia: A case report.

INTRODUCTION: Botulinum toxin (BTX) injection is a widely used treatment option for dysphagia associated with cricopharyngeal (CP) muscle achalasia, but uniform standards and protocols for administration techniques and injection sites are still lacking. This case study suggests that a unique administration technique involving a combination of ultrasound, electromyography, and balloon guidance for injecting the CP muscle can reduce inadvertent migration of BTX to non-injected tissues and increase the effectiveness and safety of BTX treatment. PATIENT CONCERNS: We describe the case of a 74-year-old man who could not swallow food or saliva for 8 months. DIAGNOSIS: The patient showed signs of true bulbar paralysis, including dizziness, hoarseness, and dysphagia. The fiberoptic endoscopic evaluation of swallowing showed massive mucilage secretion and residual materials in the postcricoid region and aspiration when swallowing 1 ml of yogurt. The video fluoroscopic swallowing study showed profoundly limited epiglottic folding and CP muscle non-relaxation, despite several unsuccessful swallow attempts. INTERVENTIONS: To manage insufficient relaxation opening of the CP muscle, BTX injection was performed using ultrasound, electromyography, and balloon catheter guidance. The narrow CP muscle situated above the balloon was identified as the target of injection by ultrasound. OUTCOMES: The patient was able to eat a soft diet. The follow-up fibrotic endoscopic swallowing study demonstrated a reduction in the amount of pharyngeal residue. The video fluoroscopic swallowing study showed that CP muscle relaxation was significantly enhanced and no penetration was shown. CONCLUSION: The unique administration technique with triple guidance holds several advantages, suggesting that it may be a promising treatment for CP muscle achalasia.

Cardiovascular dysautonomia in Achalasia Patients: Blood pressure and heart rate variability alterations.

Achalasia is a disease characterized by the inability to relax the esophageal sphincter due to a degeneration of the parasympathetic ganglion cells located in the wall of the thoracic esophagus. Achalasia has been associated with extraesophageal dysmotility, suggesting alterations of the autonomic nervous system (ANS) that extend beyond the esophagus. The purpose of the present contribution is to investigate whether achalasia may be interpreted as the esophageal manifestation of a more generalized disturbance of the ANS which includes alterations of heart rate and/or blood pressure. Therefore simultaneous non-invasive records of the heart inter-beat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) of 14 patients (9 female, 5 male) with achalasia were compared with the records of 34 rigorously screened healthy control subjects (17 female, 17 male) in three different conditions: supine, standing up, and controlled breathing at 0.1 Hz, using a variety of measures in the time and spectral domains. Significant differences in heart rate variability (HRV) and blood pressure variability (BPV) were observed which seem to be due to cardiovagal damage to the heart, i.e., a failure of the ANS, as expected according to our hypothesis. This non-invasive methodology can be employed as an auxiliary clinical protocol to study etiology and evolution of achalasia, and other pathologies that damage ANS.

Estimation of mechanical work done to open the esophagogastric junction using functional lumen imaging probe panometry.

In this study, we quantify the work done by the esophagus to open the esophagogastric junction (EGJ) and create a passage for bolus flow into the stomach. Work done on the EGJ was computed using functional lumen imaging probe (FLIP) panometry. Eighty-five individuals underwent FLIP panometry with a 16-cm catheter during sedated endoscopy including asymptomatic controls (n = 14), 45 patients with achalasia (n = 15 each, three subtypes), those with gastroesophageal reflux disease (GERD; n = 13), those with eosinophilic esophagitis (EoE; n = 8), and those with systemic sclerosis (SSc; n = 5). Luminal cross-sectional area (CSA) and pressure were measured by the FLIP catheter positioned across the EGJ. Work done on the EGJ (EGJW) was computed (millijoules, mJ) at 40-mL distension. Additionally, a separate method was developed to estimate the "work required" to fully open the EGJ (EGJROW) when it did not open during the procedure. EGJW for controls had a median [interquartile range (IQR)] value of 75 (56-141) mJ. All achalasia subtypes showed low EGJW compared with controls (P < 0.001). Subjects with GERD and EoE had EGJW 54.1 (6.9-96.3) and 65.9 (10.8-102.3) mJ, similar to controls (P < 0.08 and P < 0.4, respectively). The scleroderma group showed low values of EGJW, 12 mJ (P < 0.001). For patients with achalasia, EGJROW was the greatest and had a value of 210.4 (115.2-375.4) mJ. Disease groups with minimal or absent EGJ opening showed low values of EGJW. For patients with achalasia, EGJROW significantly exceeded EGJW values of all other groups, highlighting its unique pathophysiology. Balancing the relationship between EGJW and EGJROW is potentially useful for calibrating achalasia treatments and evaluating treatment response.NEW & NOTEWORTHY Changes in pressure and diameter occur at the EGJ during esophageal emptying. Similar changes can be observed during FLIP panometry. Data from healthy and diseased individuals were used to estimate the mechanical work done on the EGJ during distension-induced relaxation or, in instances of failed opening, work required to open the EGJ. Quantifying these parameters is potentially valuable to calibrate treatments and gauge treatment efficacy for subjects with disorders of EGJ function, especially achalasia.

The evaluation of the dilation-degree classification of esophageal achalasia patients from the viewpoint of esophageal clearance.

PURPOSE: To examine whether or not we could propose a more appropriate dilation-degree classification suitable for the pathological condition of patients with esophageal achalasia. METHODS: In accordance with the current dilation-degree classification, the maximum dilated diameter was measured based on the esophageal barium swallow. The relationship between the pathophysiology and dilation-degree classification was examined. Furthermore, the current dilatation-degree classification from the viewpoint of esophageal clearance was evaluated to examine whether or not a more appropriate dilatation-degree classification could be proposed. RESULTS: Because the clearance ratio tended to decrease at a maximum expansion diameter of 80 mm, when the maximum dilated diameter was divided into units of 10 mm, they were classified into two groups, with 80 mm as the boundary. As a result, the illness period was significantly prolonged (p = 0.0045) and the frequency of sigmoid type was high (p < 0.001) for lengths of ≥ 80 mm. With regard to the esophageal clearance rate, the clearance rate was significantly decreased in patients with a diameter of ≥ 80 mm at 5 min after taking barium (p = 0.0229). CONCLUSIONS: From the viewpoint of esophageal clearance, classification into 2 groups with a boundary of 80 mm may reflect the pathological condition.

Disorders of the enteric nervous system - a holistic view.

The enteric nervous system (ENS) is the largest division of the peripheral nervous system and closely resembles components and functions of the central nervous system. Although the central role of the ENS in congenital enteric neuropathic disorders, including Hirschsprung disease and inflammatory and functional bowel diseases, is well acknowledged, its role in systemic diseases is less understood. Evidence of a disordered ENS has accumulated in neurodegenerative diseases ranging from amyotrophic lateral sclerosis, Alzheimer disease and multiple sclerosis to Parkinson disease as well as neurodevelopmental disorders such as autism. The ENS is a key modulator of gut barrier function and a regulator of enteric homeostasis. A 'leaky gut' represents the gateway for bacterial and toxin translocation that might initiate downstream processes. Data indicate that changes in the gut microbiome acting in concert with the individual genetic background can modify the ENS, central nervous system and the immune system, impair barrier function, and contribute to various disorders such as irritable bowel syndrome, inflammatory bowel disease or neurodegeneration. Here, we summarize the current knowledge on the role of the ENS in gastrointestinal and systemic diseases, highlighting its interaction with various key players involved in shaping the phenotypes. Finally, current flaws and pitfalls related to ENS research in addition to future perspectives are also addressed.

Duration of symptoms and manometric parameters offer clues to diagnosis of pseudoachalasia.

BACKGROUND: Pseudoachalasia manifests high-resolution manometry (HRM) findings of achalasia but results from a secondary process. We analyzed clinical and HRM characteristics of pseudoachalasia, including malignant and non-malignant subtypes. METHODS: High-resolution manometry was retrospectively reviewed in patients with confirmed pseudoachalasia, and corroborated with endoscopic and radiographic studies. A control cohort of idiopathic achalasia patients was identified. Clinical characteristics, Eckardt score, and HRM metrics were extracted from institutional records. Grouped data and medians (interquartile range) were compared between pseudoachalasia and idiopathic achalasia, and between malignant and non-malignant pseudoachalasia, using parametric and non-parametric statistical tests. KEY RESULTS: Of 28 pseudoachalasia patients (62.2 ± 2.5 years, 60.7% female), 18 (64.3%) had malignancy, and 10 (35.7%) had non-malignant obstruction. Although Eckardt score did not differentiate pseudoachalasia from 58 achalasia patients (55.9 ± 2.5 years, 53.4% female), weight loss was greater (median 9.1 [5.0-18.5] vs 3.6 [0-9.1] kg, P < .02) with shorter duration of symptoms (median 12.9 [8.0-38.6] vs 36.0 [25.7-45.0] weeks, P < .001] in pseudoachalasia. Esophagogastric junction (EGJ) metrics demonstrated lower mean IRP values and lower EGJ contractile integral in pseudoachalasia (P < .04 for each comparison with idiopathic achalasia). Type 1 pattern was more frequent in pseudoachalasia (39.3% vs 13.8%, P < .008). Pseudoachalasia demonstrated incomplete HRM patterns, with lower rates of lack of peristalsis (79.6%, vs 93.1% in achalasia, P < .05). Despite higher Eckardt scores in malignant vs non-malignant pseudoachalasia (median 8.0 [7.0-9.0] vs 6.0 [3.5-7.8], P < .03], no significant HRM differences were noted. CONCLUSIONS AND INFERENCES: Pseudoachalasia manifests with a shorter history, greater weight loss, and incomplete HRM achalasia patterns compared to achalasia.

Timed barium swallow for assessing long-term treatment response in patients with achalasia: Absolute cutoff versus percent change - A cross-sectional analytic study.

BACKGROUND: Timed barium swallow (TBS) assesses esophageal emptying before and after therapy in patients with achalasia. Our aim was to compare the accuracy of percent change in barium height with traditional absolute cutoff of <5 cm on post-treatment TBS. MATERIALS AND METHODS: Consecutive patients with treatment naïve achalasia treated with either PD, HM, or POEM between 1/2012 and 7/2017 were eligible for inclusion. The accuracy of percent change in pre- and post-treatment barium height at 5 minutes versus an absolute <5 cm cutoff for assessing treatment response was assessed using the receiver operating curve analysis (ROC). RESULTS: Eighty-one patients met the inclusion criteria. The median percent change in barium heights at five minutes in patients who did not improve was 6 percent increase (n = 10; mean 10.6) versus 78 percent decrease (n = 71; mean 64) in patients who improved (P = 0.0001). The AUC for percent change in TBS 5 minutes height was 76% (95% CI 48% to 90%), and a 3% decrease from baseline as a cutoff had a sensitivity of 60% and specificity of 99%. The AUC for post-treatment TBS 5 minutes height was 79% (95% CI 53% to 91%), and the 5 cm cutoff had a sensitivity of 70% and specificity of 75%. CONCLUSIONS: The results show that 3% percent improvement in pre- and post-treatment barium height at 5 minutes rather than absolute cutoff value of <5 cm on post-treatment TBS is a better indicator of treatment success in achalasia patients. These findings indicate the need for reassessment of tools to identify treatment response.

Achalasia subtypes can be identified with functional luminal imaging probe (FLIP) panometry using a supervised machine learning process.

BACKGROUND: Achalasia subtypes on high-resolution manometry (HRM) prognosticate treatment response and help direct management plan. We aimed to utilize parameters of distension-induced contractility and pressurization on functional luminal imaging probe (FLIP) panometry and machine learning to predict HRM achalasia subtypes. METHODS: One hundred eighty adult patients with treatment-naïve achalasia defined by HRM per Chicago Classification (40 type I, 99 type II, 41 type III achalasia) who underwent FLIP panometry were included: 140 patients were used as the training cohort and 40 patients as the test cohort. FLIP panometry studies performed with 16-cm FLIP assemblies were retrospectively analyzed to assess distensive pressure and distension-induced esophageal contractility. Correlation analysis, single tree, and random forest were adopted to develop classification trees to identify achalasia subtypes. KEY RESULTS: Intra-balloon pressure at 60 mL fill volume, and proportions of patients with absent contractile response, repetitive retrograde contractile pattern, occluding contractions, sustained occluding contractions (SOC), contraction-associated pressure changes >10 mm Hg all differed between HRM achalasia subtypes and were used to build the decision tree-based classification model. The model identified spastic (type III) vs non-spastic (types I and II) achalasia with 90% and 78% accuracy in the train and test cohorts, respectively. Achalasia subtypes I, II, and III were identified with 71% and 55% accuracy in the train and test cohorts, respectively. CONCLUSIONS AND INFERENCES: Using a supervised machine learning process, a preliminary model was developed that distinguished type III achalasia from non-spastic achalasia with FLIP panometry. Further refinement of the measurements and more experience (data) may improve its ability for clinically relevant application.

Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.