Esophageal motility disorder - has Chicago classification v4.0 simplified our management?

REVIEW PURPOSE: Addressing dysphagia is vital due to its prevalence and impact on healthcare expenditure. While high resolution manometry (HRM) effectively evaluates esophageal dysphagia, its role in oropharyngeal dysphagia and upper esophageal sphincter (UES) dysfunction remains debated. The fourth iteration of the Chicago classification (CC) offers an algorithmic approach for diagnosing abnormal motor patterns via HRM. This review assesses the CC's impact on dysphagia management. RECENT INSIGHTS: The Chicago classification version 4.0 emphasizes auxiliary and provocative techniques when the algorithm falls short of a conclusive diagnosis. It introduces stricter criteria for previously ambiguous conditions like ineffective motility and esophagogastric junction outflow obstruction. This version also introduces the concept of conclusive and inconclusive classifications based on symptoms, provocation maneuvers, and supportive testing minimizing ambiguity. SUMMARY: The Chicago classification v4.0 remains a useful tool for the diagnosis of well characterized esophageal motility disorders. However, major limitations include reliance on HRM and a focus on distal esophagus contractile characteristics without considering proximal esophagus or upper esophageal sphincter, both of which can sometimes be the only evident abnormality in patients with dysphagia. Despite efforts to reduce ambiguity, diagnostic challenges persist. These limitations can be addressed in future updates.

Development and modification of a dysphagia question prompt list to improve patient-physician communication: Incorporating both esophageal expert and patient perspectives.

BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions, intended to encourage question-asking by patients and enhance patient-physician communication. To date, a dysphagia-specific QPL has not been developed for patients with esophageal dysphagia symptoms. We aim to develop a dysphagia-specific QPL incorporating both esophageal expert and patient perspectives, applying rigorous methodology. METHODS: The QPL content was generated applying a two-round modified Delphi (RAND/UCLA) method among 11 experts. In round one, experts provided five answers to the prompts: "What general questions should patients ask when being seen for dysphagia?" and "What questions do I not hear patients asking but, given my experience, I believe they should be asking?" In round two, experts rated proposed questions on a 5-point Likert scale. Responses rated as "essential" or "important", determined by an a priori median threshold of ≥4.0, were accepted for inclusion. Subsequently, 20 patients from Stanford Health Care were enrolled to modify the preliminary QPL, to incorporate their perspectives and opinions. Patients independently rated questions applying the same 5-point Likert scale. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking "Are there questions we didn't ask, that you think we should?" KEY RESULTS: Eleven experts participated in both voting rounds. Of 85 questions generated from round one, 60 (70.6%) were accepted for inclusion, meeting a median value of ≥4.0. Questions were combined to reduce redundancy, narrowing down to 44 questions. Questions were categorized into the following six themes: 1. "What is causing my dysphagia?"; 2. "Associated symptoms"; 3. "Testing for dysphagia"; 4. "Lifestyle modifications"; 5. "Treatment for dysphagia"; and 6. "Prognosis". The largest number of questions covered "What is causing my dysphagia" (27.3%). Twenty patients participated and modified the QPL. Of the 44 questions experts agreed were important, only 30 questions (68.2%) were accepted for inclusion. Six patients proposed 10 additional questions and after incorporating the suggested questions, the final dysphagia-specific QPL created by esophageal experts and modified by patients consisted of 40 questions. CONCLUSIONS & INFERENCES: Incorporating expert and patient perspectives, we developed a dysphagia-specific QPL to enhance patient-physician communication. Our study highlights importance of incorporating patient perspective when developing such a communication tool. Further studies will measure the impact of this communication tool on patient engagement.

Development of a Preliminary Question Prompt List as a Communication Tool for Adults With Achalasia: A Modified Delphi Study.

BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions that enhance patient-physician communication by encouraging patients to ask questions during consultations. AIM: The aim of this study was to develop a preliminary achalasia-specific QPL created by esophageal experts. METHODS: The QPL content was derived through a modified Delphi method consisting of 2 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of achalasia" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" In round 2, experts rated questions on a 5-point Likert scale. Questions considered "essential" or "important" were accepted into the QPL. Feedback regarding the QPL was obtained in a pilot study wherein patients received the QPL before their consultation and completed surveys afterwards. RESULTS: Nineteen esophageal experts participated in both rounds. Of 148 questions from round 1, 124 (83.8%) were accepted into the QPL. These were further reduced to 56 questions to minimize redundancy. Questions were categorized into 6 themes: "What is achalasia," "Risks with achalasia," "Symptom management in achalasia," "Treatment of achalasia," "Risk of reflux after treatment," and "Follow-up after treatment." Nineteen patients participated in the pilot, most of whom agreed that the QPL was helpful (84.2%) and recommended its wider use (84.2%). CONCLUSIONS: This is the first QPL developed specifically for adults with achalasia. Although well-received in a small pilot, follow-up studies will incorporate additional patient feedback to further refine the QPL content and assess its usability, acceptability, and feasibility.

Clinical Improvement With Pyridostigmine in a Patient With Acetylcholine Receptor Antibody-Associated Autoimmune Gastrointestinal Dysmotility.

Autoimmune gastrointestinal dysmotility (AGID) is a rare form of limited autoimmune dysautonomia caused by autoantibodies against the enteric nervous system. Our patient was a 53-year-old man with 1 year of bloating, intolerance of oral intake, and recurrent ileus. Esophageal manometry showed aperistalsis and hypotensive lower sphincter, consistent with scleroderma esophagus. However, because the patient had no other sequelae of this disease, AGID was considered. Serologic evaluation revealed ganglionic acetylcholine receptor autoantibodies. Treatment with pyridostigmine led to resolution of symptoms. Early recognition of AGID should be considered when manometry shows scleroderma esophagus in patients without other evidence of systemic sclerosis.

Small Intestinal Bacterial Overgrowth Syndrome: A Guide for the Appropriate Use of Breath Testing.

The increased availability of noninvasive breath tests, each with limitations, has led to widespread testing for small intestinal bacterial overgrowth (SIBO) in patients with non-specific gastrointestinal complaints. The lactulose breath test (LBT) is based upon an incorrect premise and therefore incorrect interpretations which has resulted in the over-diagnosis of SIBO and the excessive use of antibiotics in clinical practice. Despite limitations, the glucose breath test (GBT) should be exclusively employed when considering SIBO in appropriately chosen patients. This review suggests guidelines for the optimal use and appropriate interpretation of the GBT for suspected SIBO. The LBT should be discarded from future use, and the literature based upon the LBT should be discounted accordingly.

Esophageal hypercontractility is abolished by cholinergic blockade.

BACKGROUND: Esophageal hypercontractility (EHC) is considered a major esophageal motor disorder of unclear etiology. Different mechanisms have been proposed, including an imbalance in inhibitory and excitatory esophageal innervation. We hypothesized that patients with EHC suffer from cholinergic hyperactivity. AIM: To interrogate the excitatory and inhibitory neurotransmission in EHC by assessing the esophageal motor response to atropine (ATR) and cholecystokinin (CCK), respectively, in EHC patients. METHOD: We retrospectively reviewed patients who underwent high-resolution manometry (HRM) with pharmacologic challenge in a tertiary referral center between 2007 and 2017. We identified 49 EHC patients who were categorized based on frequency of hypercontractile peristaltic sequence into "frequent" and "infrequent" and motility diagnosis groups. Deglutitive pressure metrics and esophageal motor responses to ATR (12 mcg/kg iv) and CCK (40 ng/kg iv) were analyzed across groups. RESULTS: Atropine abolished hypercontractility across all groups studied, converting nearly half of patients to a motor pattern of ineffective esophageal motility. Abnormal CCK responses primarily occurred in the patient groups with concomitant outflow obstruction. CONCLUSIONS: Hypercontractility is cholinergically mediated in all esophageal motor disorders. Most patients with isolated EHC appear to have excessive cholinergic drive, rather than loss of inhibitory innervation, and might be candidates for treatment with anticholinergic agents.

Clinical Functional Lumen Imaging Probe Testing in Esophageal Disorders: A Need for Better Quality Evidence.

In their article "Use of the Functional Lumen Imaging Probe in Clinical Esophagology," Savarino et al. report the outcomes of a Grading of Recommendations Assessment, Development, and Evaluation analysis performed by experts in the use of functional lumen imaging probe (FLIP) evaluation of esophageal disorders. For essentially all clinical indications, the recommendation for use was conditional with a very low quality of evidence. FLIP is an expensive, invasive technology examining limited aspects of esophageal function. Its role in complementing or replacing existing technology is uncertain, particularly when compared with manometric testing with additional provocative studies. Performing properly designed studies to demonstrate FLIP's true effectiveness and cost-effectiveness will be costly.

Flip Technology for Assessing Esophageal Structural and Motor Disorders: a Skeptic's View.

PURPOSE OF REVIEW: Functional lumen impedance (FLIP) technology has become commercially available to assess structural and motor abnormalities of the esophagus. Increasing numbers of papers have described novel findings with this technology. This review examines the validity of the FLIP technique, how it compares with existing diagnostic modalities, and evidence to date on diagnostic accuracy. RECENT FINDINGS: FLIP studies require deep sedation at the time of endoscopy to complete. They assess a simulated state of esophageal obstruction in only a distal part of the esophagus rather than deglutitive motor function of the entire esophagus. The available normative dataset is small and not matched to the older age of patients typically being evaluated. The test-retest agreement in health and disease is unknown, as is the operator dependence on performing and interpreting findings. Studies to date have largely excluded patients with structural disorders, which FLIP cannot reliably distinguish from motor disorders. FLIP is an expensive technology that has been made clinically available without its true utility being established. For FLIP to be deemed a device ready for widespread clinical use, additional studies on validity, diagnostic accuracy, and outcomes need to be performed. Prospective clinical studies need to include all patients and assess the incremental cost-effectiveness of FLIP over more innovative use of existing technology, such as high-resolution manometry with provocative challenges.

Diagnostic differences in the pharmacologic response to cholecystokinin and amyl nitrite in patients with absent contractility vs type I Achalasia.

BACKGROUND: Absent esophageal contractility (AC) is distinguished from type 1 achalasia (ACH1) during high-resolution manometry (HRM) on the basis of normal or elevated deglutitive integrated relaxation pressure (IRP) values. However, IRP measurements are subject to pressure recording error. We hypothesized that distinctive responses to pharmacologic provocation using amyl nitrite (AN) and cholecystokinin (CCK) could reliably distinguish AC patients from those with ACH1. AIM: To compare esophageal response with AN and CCK in a well-defined cohort of ACH1 and AC patients. METHOD: All available clinical, radiographic, endoscopic, and manometric information in 34 patients with aperistalsis was reviewed to determine the final diagnosis of ACH1 and AC. The differences in response to provocative challenges with the rapid drink challenge (RDC) test and administration of AN and CCK were compared between these two groups. RESULTS: Eighteen patients were diagnosed with ACH1 and sixteen with AC. While IRP values were significantly higher in ACH1, the standard criterion value misclassified four AC patients as having ACH1 and five ACH1 patients as having AC. IRP values on the RDC did not accurately segregate AC from ACH1, but we were able to identify AN and CCK esophageal motor response criteria that allowed correct classification of ACH1 and AC patients. CONCLUSIONS: Nearly a quarter of AC and ACH1 patients may be misdiagnosed based on manometric IRP criteria alone. Differences in the esophageal motor responses to AN and CCK have the potential to facilitate the correct diagnosis in these challenging patients.

Motility Patterns Following Esophageal Pharmacologic Provocation With Amyl Nitrite or Cholecystokinin During High-Resolution Manometry Distinguish Idiopathic vs Opioid-Induced Type 3 Achalasia.

BACKGROUND & AIMS: In some patients, the type 3 achalasia (A3) motor pattern may be an effect of chronic use of high-dose opioids. No motor findings have been identified to differentiate opioid-induced A3 (OA3) from idiopathic A3 (IA3). We investigated whether OA3 could be distinguished from IA3 on the basis of differences in esophageal motor responses to amyl nitrite, cholecystokinin, or atropine. METHODS: We performed a retrospective study of patients who received pharmacologic provocation during esophageal high-resolution manometry from 2007 through 2017 at a tertiary referral center. We identified 26 patients with IA3 (9 women; mean age, 68 ± 13 years) and 24 patients with OA3 (15 women; mean age, 59 ± 10 years). We compared pressure topography metrics during deglutition and after administration of amyl nitrite, cholecystokinin, or atropine between patients with OA3 vs IA3. RESULTS: Amyl nitrite induced a similar relaxation response in both groups, but the rebound contraction of the lower esophageal sphincter during amyl nitrite recovery, and the paradoxical esophageal contraction during the first phase of cholecystokinin response, were both significantly attenuated in patients with OA3. The second phase of cholecystokinin response in patients with OA3 was 100% relaxation, when present, in contrast to only 26% of patients with IA3. There was no significant difference between groups in inhibition of lower esophageal sphincter tone or esophageal body contractility by cholinergic receptor blockade. CONCLUSIONS: Nearly half of patients with an A3 pattern of dysmotility are chronic, daily users of opioids with manometry patterns indistinguishable from those of patients with IA3. Patients with OA3 differ from patients with IA3 in responses to amyl nitrite and cholecystokinin. These findings might be used to identify patients with dysmotility resulting from opioid use.

Pharmacologic interrogation of patients with esophagogastric junction outflow obstruction using amyl nitrite.

BACKGROUND: The Chicago Classification of esophageal motility includes a group of patients who show evidence of esophagogastric junction outflow obstruction (EGJOO) as demonstrated by elevated integrated relaxation pressure (IRP) and preserved peristalsis. Our aim is to classify EGJOO patients based on response to amyl nitrite (AN) during high-resolution manometry. METHODS: Patients were considered to have true EGJOO if elevated IRP during supine swallow persisted in the upright position and was associated with high intrabolus pressure. The EGJ response to AN was compared between patients with achalasia type 2 (A2) and normal esophageal motility. Based on the relaxation gain (deglutitive IRP-AN IRP) value that best discriminated these two groups (10 mm Hg), patients with true EGJOO were categorized as being in either the AN-responsive (AN-R) or AN-unresponsive (AN-U) subgroups. KEY RESULTS: In the group of 49 patients with true EGJOO, the AN response classified 27 patients (IRP = 25 ± 10 mm Hg) with AN-R and 22 patients (IRP = 20 ± 5 mm Hg) with AN-U (P = 0.2). In AN-R, AN produced a relaxation gain and rebound after-contraction response at the EGJ comparable to A2 patients. AN-U patients had an elevated IRP after AN and a relaxation gain similar to normal esophageal motility patients. AN-U patients were obese and had higher prevalence of sleep apnea (P < 0.05). CONCLUSIONS: Among patients with true EGJOO, only half have pharmacologic evidence of impaired LES relaxation. Pharmacologic interrogation of the EGJ is thus necessary to identify the subgroup of EGJOO patients who could be expected to benefit from LES ablative therapies.

Chronic daily opioid exposure is associated with dysphagia, esophageal outflow obstruction, and disordered peristalsis.

BACKGROUND: Opioid receptors are present in the esophagus, and chronic opioid therapy may be associated with esophageal dysfunction. Given the current opioid epidemic in the United States, the potential contribution of opioids to esophageal dysmotility is important from both public health and patient care perspectives. Therefore our aim is to investigate the potential contribution of opioids to dysphagia and the prevalence of major motor disorders in patients undergoing manometric evaluation. METHODS: The anonymized electronic medical records of patients linked to their de-identified high-resolution manometry (HRM) studies were reviewed. The patients were grouped based on their opioid exposure history at the time of HRM: opioid-naïve and chronic daily users. The oral morphine milligram equivalent daily dose (MMED) of opioids was computed. KEY RESULTS: 10% of patients referred for esophageal HRM were taking opioid analgesics on a chronic daily basis, and they had a significantly higher prevalence of dysphagia than their opioid-naïve counterparts. The chronic daily opioid users displayed a significantly higher prevalence of achalasia type 3 (ACH3) and esophagogastric junction outflow obstruction (EGJOO) motility phenotypes. The MMED of opioids was a significant predictor of esophageal pressure metrics and motility diagnoses (P < 0.0001). CONCLUSIONS: Chronic daily opioid intake is associated with impaired deglutitive LES relaxation and disorganized peristaltic sequence. While a minority of patients on chronic daily opioid therapy present with major esophageal motor disorders, they comprise nearly half of ACH3 and a third of EGJOO motility phenotypes.

Presence of Irritable Bowel Syndrome Symptoms in Quiescent Inflammatory Bowel Disease Is Associated with High Rate of Anxiety and Depression.

BACKGROUND: Inflammatory bowel disease (IBD; Crohn's disease, CD and Ulcerative colitis, UC) and irritable bowel syndrome (IBS) have overlapping symptoms. Few prevalence studies of IBS in quiescent IBD have used colonoscopy with histology to confirm inactive disease. The aims were (1) to determine the percentage of IBD patients in deep remission whose persistent IBS-like symptoms (IBD/IBS+) would cause them to be classified as having active disease, based on the calculation of Harvey Bradshaw Index (HBI) or UC disease activity index (UCDAI); (2) to identify demographic and disease characteristics that are associated with IBD/IBS+. METHODS: This was a prospective study at a single tertiary care IBD center. 96/112 patients with colonoscopy and histology confirmed quiescent disease consented and completed Rome III criteria for IBS Survey, and the hospital anxiety and depression scale (HADS). Other demographic and disease specific data were collected. RESULTS: 36% (28/77) and 37% (7/19) of CD and UC patients, respectively, met diagnostic criteria for IBS. Significantly higher HBI/UCDAI scores (p = 0.005) and low short inflammatory bowel disease questionnaire (SIBDQ) scores (p ≤ 0.0001) were seen in IBD/IBS+ patients. 29% of patients in deep remission were mis-categorized by HBI/UCDAI as having active disease when they fulfilled Rome III criteria for IBS. Psychiatric diagnosis (OR 3.53 95% CI 1.2-10.2) and earlier onset of IBD (OR 1.056 95% CI 1.015-1.096) were associated with IBD/IBS+. Patients fulfilling IBS criteria had higher hospital anxiety and depression scale (HADS). CONCLUSION: IBD/IBS+ affect scoring of IBD disease activity scales and become less useful in guiding treatment plans.

Clinical Conundrum: Killian-Jamieson Diverticulum with Paraesophageal Hernia.

Killian-Jamieson diverticulum is a outpouching of the lateral cervical esophageal wall adjacent to the insertion of the recurrent laryngeal to the larynx and is much less common in clinical practice than Zenkers Diverticulum. Surgical management of Killian-Jamieson diverticulum requires open transcervical diverticulectomy due to the proximity of the recurrent laryngeal nerve to the base of the pouch. We present a case of a Killian-Jamieson diverticulum associated with a concurrent large type III paraesophageal hernia causing significant solid-food dysphagia, post-prandial regurgitation of solid foods, and chronic cough managed with open transcervical diverticulectomy and laparoscopic paraesophageal hernia repair with Nissen fundoplication.

Scintigraphy Demonstrates High Rate of False-positive Results From Glucose Breath Tests for Small Bowel Bacterial Overgrowth.

BACKGROUND & AIMS: Breath tests for hydrogen and/or methane are used to detect small bowel bacterial overgrowth (SBBO), but false-positive results can arise from clinical conditions that accelerate small bowel transit and deliver unabsorbed glucose to the colon. We investigated the prevalence of false-positive results from glucose breath tests by also evaluating patients with scintigraphy. METHODS: In a retrospective study, we reviewed data from glucose breath tests performed with concurrent scintigraphy on 139 patients with suspected SBBO at the Medical College of Wisconsin from January 2003 through July 2013. Results from breath tests were considered abnormal (positive) if there was an increasing curve of hydrogen or methane by >15 parts per million above baseline within 90 minutes. Scintigraphy was used to determine whether this increase occurred before or after the glucose bolus arrived at the cecum. Data from a subset of 45 patients with prior upper gastrointestinal surgery were analyzed separately. RESULTS: Forty-six of the patients (33%) had abnormal results from breath tests. On the basis of scintigraphy findings, 22 of these patients (48%) had false-positive results, which were caused by colon fermentation of unabsorbed glucose. Colon fermentation caused false-positive results in 65% of patients who had undergone upper gastrointestinal surgery and 13% of patients without prior surgery. Patients with false-positive results caused by colonic fermentation had shorter mean oro-cecal transit times (18 minutes) compared with patients with positive breath-test results because of SBBO (79 minutes) or negative results (86 minutes). CONCLUSIONS: Almost half of positive results from glucose breath tests are false because of colonic fermentation. All patients with abnormal results from breath tests should be considered for confirmatory repeat breath testing with concurrent scintigraphy to distinguish SBBO from colonic fermentation. Most patients who have undergone upper gastrointestinal surgery have abnormal results from breath tests and should be assessed by using concurrent scintigraphy with the initial breath test.