The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Evaluation of outcome after cardiomyotomy for achalasia using the Chicago classification.

BACKGROUND: Achalasia can be subdivided into manometric subtypes according to the Chicago classification. These subtypes are proposed to predict outcome after treatment. This hypothesis was tested using a database of patients who underwent laparoscopic Heller's cardiomyotomy with anterior fundoplication. METHODS: All patients who underwent Heller's cardiomyotomy for achalasia between June 1993 and March 2015 were identified from an institutional database. Manometry tracings were retrieved and re-reported according the Chicago classification. Outcome was assessed by a postal questionnaire, and designated a success if the modified Eckardt score was 3 or less, and the patient had not undergone subsequent surgery or pneumatic dilatation. Difference in outcome after cardiomyotomy was analysed with a mixed-effects logistic regression model. RESULTS: Sixty, 111 and 24 patients had type I, II and II achalasia respectively. Patients with type III achalasia were more likely to be older than those with type I or II (mean age 63 versus 50 and 49 years respectively; P = 0·001). Some 176 of 195 patients returned questionnaires after surgery. Type III achalasia was less likely to have a successful outcome than type II (odds ratio (OR) 0·38, 95 per cent c.i. 0·15 to 0·94; P = 0·035). There was no significant difference in outcome between types I and II achalasia (II versus I: OR 0·87, 0·47 to 1·60; P 0·663). The success rate at 3-year follow-up was 69 per cent (22 of 32) for type I, 66 per cent (33 of 50) for type II and 31 per cent (4 of 13) for type III. CONCLUSION: Type III achalasia is a predictor of poor outcome after cardiomyotomy. There was no difference in outcome between types I and II achalasia.

Intra-bolus pressure and esophagogastric gradient, assessed with high-resolution manometry, are associated with acid exposure and proximal migration of refluxate.

Trans-sphincteric pressure gradient (TSPG) seems to play a relevant role in eliciting refluxes during transient lower esophageal sphincter relaxations (TLESRs). Intra-bolus pressure (IBP) is considered to be correlated to esophageal wall tone. We aimed to evaluate the relationship between IBP, TSPG during TLESRs and the dynamic properties of refluxate in gastroesophageal reflux disease. Sixteen non-erosive reflux disease (NERD), 10 erosive disease (ERD) patients and 12 healthy volunteers (HVs), underwent 24-hour impedance-pH monitoring and combined high-resolution manometry-impedance before and 60 minutes. After a meal, ERD patients presented a significantly lower mean IBP (4.7 ± 1.6 mmHg) respect to NERD patients (8.9 ± 2.8 mmHg) and HVs (9.2 ± 3.2 mmHg). NERD patients with physiological abnormal acid exposure time showed a mean IBP (10.4 ± 3.1 mmHg) significantly higher than that in NERD with pathological abnormal acid exposure time (5.1 ± 1.5 mmHg). The TSPG value was significantly higher during TLESRs accompanied by reflux than during TLESRs not associated with reflux, both in patients and in HVs. A significant direct correlation was found between IBP, TSPG and proximal spread of refluxes in patients and in HVs. Gastroesophageal reflux disease patients display different degrees of esophageal distension. An increased compliance of the distal esophagus may accommodate larger volumes of refluxate and likely facilitates the injuries development. Higher TSPG values appear to facilitate the occurrence of refluxes during TLESRs. In patients with NERD, higher TSPG and IBP values favor proximal spread of refluxate and hence may play a relevant role in symptom generation.

General practitioners' knowledge of and attitudes to inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease requiring long-term management. General practitioners (GPs) are often the first point of contact for initial symptoms and flares. Thus we assessed GPs' attitudes to and knowledge of IBD. METHODS: A state-wide postal survey of GPs was performed collecting demographic details, practice and attitudes in IBD-specific management and knowledge. RESULTS: Of 1800 GPs surveyed in South Australia, 409 responded; 58% were male, 80% Australian trained and 73% practised in metropolitan areas. Most GPs (92%) reported seeing zero to five IBD patients per month. Overall, 37% of the GPs reported being generally 'uncomfortable' with IBD management. Specifically, they were only somewhat comfortable in providing/using maintenance therapy, steroid therapy or unspecified therapy for an acute flare. They were uncomfortable with the use of immunomodulators and biologicals (71 and 91% respectively). No GP reported never referring, referring sometimes (12%), often (34%) or always (55%). Most (87%) GPs rated their communication with private specialists positively; while only 32% were satisfied with support from public hospitals. Of concern, most (70%) monitored patients on immunosuppression on a case-by-case basis rather than by protocol. In multivariable analyses, GPs' IBD-specific knowledge did not influence comfort with overall management, nor did knowledge influence GP comfort with any particular therapy. CONCLUSION: Individual GPs care for few IBD patients and have variable attitudes in their practice. Whether improvement can realistically be achieved given individual GP's paucity of patients is questionable. These data support the provision of better support and specific action plans for IBD patients.

The treatment of achalasia patients with esophageal varices: an international study.

Background: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk. Methods: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group. Results: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 ± 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller's myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p < 0.0001) at 6 months follow-up, with treatment outcomes resembling those of 20 non-cirrhotic achalasia patients who underwent similar therapy. No patients had recorded complications of bleeding or perforation. Conclusion: This study shows an excellent short-term symptomatic response in patients with esophageal achalasia and varices and demonstrates that the therapeutic outcomes and complications, other than transient encephalopathy in both patients who had a portosystemic shunt, did not differ to disease-matched patients without varices.

Gastric feed intolerance is not increased in critically ill patients with type II diabetes mellitus.

OBJECTIVE: To examine the occurrence of feed intolerance in critically ill patients with previously diagnosed type II diabetes mellitus (DM) who received prolonged gastric feeding. DESIGN AND SETTING: Retrospective study in a level 3 mixed ICU. PATIENTS: All mechanically ventilated, enterally fed patients (n = 649), with (n = 118) and without type II DM (n = 531) admitted between January 2003 and July 2005. INTERVENTIONS: Patients with at least 72 h of gastric feeding were identified by review of case notes and ICU charts. The proportion that developed feed intolerance was determined. All patient received insulin therapy. RESULTS: The proportion of patients requiring gastric feeding for at least 72 h was similar between patients with and without DM (42%, 50/118, vs. 42%, 222/531). Data from patients with DM were also compared with a group of 50 patients matched for age, sex and APACHE II score, selected from the total non-diabetic group. The occurrence of feed intolerance (DM 52% vs. matched non-DM 50% vs. unselected non-diabetic 58%) and the time taken to develop feed intolerance (DM 62.6 +/- 43.8 h vs. matched non-DM 45.3 +/- 54.6 vs. unselected non-diabetic 50.6 +/- 59.5) were similar amongst the three groups. Feed intolerance was associated with a greater use of morphine/midazolam and vasopressor support, a lower feeding rate and a longer ICU length of stay. CONCLUSIONS: In critically ill patients who require prolonged enteral nutrition, a prior history of DM type II does not appear to be a further risk factor for feed intolerance.

Functional association between proximal and distal gastric motility during fasting and duodenal nutrient stimulation in humans.

A functional integration exists between proximal and distal gastric motor activity in dogs but has not been demonstrated in humans. To determine the relationship between proximal and distal gastric motor activity in humans. Concurrent proximal (barostat) and distal (antro-pyloro-duodenal (APD) manometry) gastric motility were recorded in 10 healthy volunteers (28 +/- 3 years) during (i) fasting and (ii) two 60-min duodenal infusions of Ensure((R)) (1 and 2 kcal min(-1)) in random order. Proximal and APD motor activity and the association between fundic and propagated antral waves (PAWs) were determined. During fasting, 32% of fundic waves (FWs) were followed by a PAW. In a dose-dependent fashion, duodenal nutrients (i) increased proximal gastric volume, (ii) reduced fundic and antral wave (total and propagated) activity, and (iii) increased pyloric contractions. The proportion of FWs followed by a distal PAW was similar between both infusions and did not differ from fasting. During nutrient infusion, nearly all PAWs were antegrade, propagated over a shorter distance and less likely to traverse the pylorus, compared with fasting. In humans, a functional association exists between proximal and distal gastric motility during fasting and duodenal nutrient stimulation. This may have a role in optimizing intra-gastric meal distribution.

Assessment of oesophageal motor function using combined perfusion manometry and multi-channel intra-luminal impedance measurement in normal subjects.

Multichannel intraluminal impedance (MII) is being used increasingly to assess oesophageal bolus clearance. However, there is no good standardization of the impedance parameters that define 'effective bolus clearance'. The aim of this study was to define these important impedance parameters and to determine their normal values. Concurrent perfusion manometry and MII were performed in 42 healthy volunteers. Ten, 5-mL liquid (saline) boluses and then, 10x5-mL low impedance viscous boluses were tested in each subject in the right-lateral position. Normal values for bolus presence time (BPT) at each site and total bolus transit time (TBTT) were determined from either 'normal' peristaltic responses (amplitude>or=30 mmHg in distal oesophagus) or 'super-normal' peristaltic responses (amplitudes>or=50 mmHg at all sites). The relationship between BPT and TBTT within a response and per-individual performance was determined. A total of 840 swallows of liquids and viscous responses were analysed. BPT and TBTT of viscous swallows were longer than those for liquids. Non-peristaltic responses were significantly more likely not to clear a viscous than a liquid bolus. Within a response, the number of sites with prolonged BPT strongly predicted the incidence of prolonged TBTT. Using impedance criteria, normal oesophageal bolus clearance is defined when an individual completely clears at least 70% of liquid responses and at least 60% of viscous responses. This study provides normal values for impedance measurement of bolus clearance when combined with perfusion manometry. These values will allow standardization of impedance application in oesophageal function testing, in both research and clinical setting.

Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease.

This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour ambulatory manometry and pH recording. In the 3-hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 +/- 23 s and 41 +/- 5 s, respectively, P < 0.001). In the 24-hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.

Effects of ranitidine and of cimetidine on pentagastrin-stimulated gastric acid secretion.

We compared the effect of oral and intravenous ranitidine, a new H2-receptor antagonist, with that of cimetidine on pentagastrin-stimulated gastric acid secretion in normal subjects. Ranitidine in intravenous doses of 20, 60, and 100 mg and oral doses of 100, 150, and 200 mg inhibited acid secretion. Only the 100 mg iv ranitidine dose was substantially more effective than cimetidine. Comparable dose-related decreases in gastric secretory volume were observed. Acid inhibition correlated strongly (r = 0.90) with plasma ranitidine concentration, with the estimated plasma concentration producing 50% inhibition (IC50) being 95 ng/ml. Maximal acid inhibition achieved was 87.3%. We conclude that ranitidine is a potent inhibitor of gastric acid secretion and should be a valuable addition to the medical treatment of acid-peptic disease.

Systemic pharmacomodulation of transient lower esophageal sphincter relaxations.

Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism of reflux in patients with gastroesophageal reflux disease. They are therefore attractive targets for pharmacotherapy. During the past 5 years, there has been a burgeoning interest in the neural pathways that control these events and in the pharmacologic receptors involved in these pathways. Several agents have been shown to reduce the rate of TLESRs, including cholecystokinin-A antagonists, anticholinergic agents, nitric oxide synthase inhibitors, morphine, somatostatin, serotonin type 3-receptor antagonists, and gamma-aminobutyric acid-B (GABA(B)) agonists. Their predominant site of action appears to be on either the afferent pathways and/or the central integrative mechanisms within the dorsal vagal complex in the brainstem. Most of the agents tested are unsuitable for clinical use either because of side effects or because of the lack of an orally effective formulation. The most promising agents identified to date are the GABA(B) agonists. Baclofen, the prototype GABA(B) agonist, inhibits the rate of TLESRs by more than 50%. Control of TLESRs is a major new approach to the treatment of reflux disease. It is likely to be applicable to the majority of patients, particularly those without macroscopic mucosal lesions or only mild erosive disease. Further development of more effective agents will depend both on a better understanding of the neural pathways and receptors involved in the control of TLESRs, as well as on investigation of other novel agents. At present, inhibition of TLESRs is at the threshold of transition from concept to practical use. Whether it makes the final leap into the mainstream of therapy will depend on the development of new, novel, and well-targeted pharmacologic agents.

Esophageal body motor response to reflux events: secondary peristalsis.

The esophageal body is a major component of the antireflux mechanism. Disruption of esophageal peristalsis affects both volume clearance and delivery of swallowed saliva to the distal esophageal body. The esophageal body responds to reflux by an increase in primary peristalsis through stimulation of swallowing and secondary peristalsis through esophageal distension. Primary peristalsis is the most common motor event after reflux and accounts for up to 90% of initial and subsequent motor activity. Secondary peristalsis is uncommon but may be important during sleep when swallowing is relatively suppressed. Some patients with reflux disease, particularly those with severe esophagitis, exhibit impaired esophageal responses to reflux. It is likely that this impairment prolongs acid clearance and may also influence the proximal extent of the refluxate within the esophageal body.

Physiological variations in blood glucose concentration affect oesophageal motility and sensation in normal subjects.

BACKGROUND/AIMS: A marked elevation in the blood glucose concentration (approximately 15 mmol L-1) slows oesophageal peristalsis. Recent studies indicate that changes in blood glucose within the normal postprandial range affect gastric motility and emptying. The aim of this study was to investigate whether such alterations in blood glucose also affect oesophageal motility. METHODS: In eight healthy subjects oesophageal motility and sensation to balloon distension were measured on two separate days while blood glucose concentrations were stabilized with an insulin-glucose clamp at 4 mmol L-1 and 8 mmol L-1. RESULTS: Peristaltic velocity in the proximal oesophagus and over the oesophagus as a whole was faster at a plasma glucose concentration of 8 mmol L-1 compared with those at 4 mmol L-1 (proximal 3.3 +/- 0.3 cm s-1 vs 2.6 +/- 0.2 cm s-1, P < 0.05, total 3.1 +/- 0.2 cm s-1 vs 2.7 +/- 0.2 cm s-1, P < 0.005) but there were no differences in wave amplitude or duration, or basal lower oesophageal sphincter pressure (LOSP). The threshold for initial perception of oesophageal distension was lower at a plasma glucose of 8 mmol L-1 (2.9 +/- 0.5 mL vs 4.9 +/- 1.0 mL, P < 0.05). CONCLUSIONS: physiological variations in plasma glucose concentration influence oesophageal motility and sensation. These observations suggest that in order to minimize effects of varying plasma glucose levels on oesophageal motility, manometry should be performed under the same fasting or fed conditions when oesophageal motor function is evaluated.

Mechanisms of gastro-oesophageal reflux in the ferret.

Transient lower oesophageal sphincter (LOS) relaxation is the major mechanism of gastro-oesophageal reflux in humans--an event unassociated with swallowing. Mechanisms involved in triggering transient LOS relaxation are poorly understood, and their further study requires a small animal model. In this study we aimed to establish methods for prolonged ambulant oesophageal manometry in ferrets, and to determine motor events associated with reflux episodes and their triggering by different gastric nutrient loads. Forty-two studies were performed on nine ferrets with chronic cervical oesophagostomies, through which a manometric assembly was introduced and secured to a collar, which incorporated a microphone for detection of swallows. The assembly included a gastric feeding channel, one gastric and four oesophageal manometric sideholes, a 2.5-cm-long LOS sleeve sensor, and an oesophageal pH electrode. Intragastric infusions were given over 2 min, the first after a 30-min control recording period, and in 29/42 studies, a second infusion was given 60 min later. Infusions were either 25 mL 10% dextrose solution, pH 3.5 (22 studies), 25 mL triglyceride emulsion (Intralipid) pH 3.5 (11 studies), or 25 mL air (nine studies). Episodes of oesophageal acidification were absent before gastric infusions. After infusion, 2.1 +/- 0.2 episodes occurred over the first 30 min. After glucose infusion, 15/18 acidification episodes (83%) occurred during transient LOS relaxation, and 3/18 (17%) occurred after gradual (< 1 mmHg sec-1) downward drifts in basal LOSP to < 2 mmHg. After lipid infusion two acidification episodes occurred, both during transient LOS relaxation. Mean duration of transient LOS relaxation was 8.0 +/- 0.4 sec. All infusions increased occurrence of transient LOS relaxation to a similar extent, each of which ended with primary peristalsis. We conclude that gastric infusion of glucose, lipid and gas are all effective in provoking gastro-oesophageal reflux in ferrets. Reflux occurs through similar mechanisms to those seen in humans, i.e. increased triggering of transient LOS relaxation. The conscious ferret is therefore an appropriate model for future studies of manipulation of mechanisms giving rise to gastro-oesophageal reflux.

A comparison of micromanometric and standard manometric techniques for recording of oesophageal motility.

Perfused micromanometric assemblies with an outer diameter of 2 mm or less have been developed for use in premature infants and small laboratory animals. Such assemblies offer advantages with regard to subject comfort and low perfusion rates that make them attractive for use in adults. The aim of this study was to investigate the recording fidelity of micromanometric assemblies in the measurement of oesophageal peristalsis in adults. Two micromanometric assemblies with an outer diameter of 1.8-2.0 mm and a length suitable for use in adults (165 cm), and containing micromanometric lumina of 0.28-0.35 mm i.d. and a standard lumen of 0.6-0.75 mm i.d. were evaluated. Each assembly was tested by measurement of pressure rise rate in response to sudden occlusion, and in vivo during oesophageal peristalsis by simultaneous comparison with an intraluminal strain gauge. At perfusion rates of 0.01-0.15 mL min-1 microlumina achieved pressure rise rates of 21-430 mmHg sec-1 that were comparable to 37-390 mmHg sec-1 for the standard lumina perfused at 0.15-0.6 mL min-1. During oesophageal peristalsis, micromanometric lumina recorded the occurrence and timing of all pressure waves accurately when compared with standard lumina and the microtransducer. However, microlumina under-recorded pressure wave amplitude to varying degrees dependent upon perfusion rate although the performance of microlumina could be improved to that of the standard lumen by shortening their length to 70 cm. Micromanometric assemblies are suitable for recording oesophageal peristalsis in adults although there is some impairment of absolute manometric fidelity. Fidelity can be improved by minimizing total assembly length.

Motor events underlying gastro-oesophageal reflux in ambulant patients with reflux oesophagitis.

Information on the mechanism of gastro-oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis. Concurrent ambulatory oesophageal manometry and pH monitoring were performed in 11 ambulant patients with erosive oesophagitis. Lower oesophageal sphincter (LOS) pressure was monitored with a perfused sleeve sensor. Recordings were made for 90 min before and 180 min after a meal. At set times patients sat in a chair or walked. LOS pressure was < or = 2 mmHg at the time of reflux for 98% of reflux episodes. Transient LOS relaxation was the most common pattern overall and the predominant pattern in seven patients, whilst persistently absent basal LOS pressure was the most common pattern in four patients. The pattern of LOS pressure was not altered by the presence of hiatus hernia or by walking. Straining occurred at the onset of 31% of acid reflux episodes but often followed the development of an oesophageal common cavity. The occurrence of straining was not influenced by walking. In ambulant patients with reflux oesophagitis: (1) LOS pressure is almost always absent at the time of reflux, usually because of transient LOS relaxation, (2) persistently absent basal LOS pressure is an important mechanism of reflux in a few patients, (3) straining may help to induce acid reflux in a variable proportion of occasions and may in some instances be a response to gas reflux, and (4) walking does not influence the occurrence of reflux or its mechanisms.

Systematic review: relationships between sleep and gastro-oesophageal reflux.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep, but the mechanism remains unclear. AIM: To review the literature concerning gastro-oesophageal reflux during the sleep period, with particular reference to the sleep/awake state at reflux onset. METHODS: Studies identified by systematic literature searches were assessed. RESULTS: Overall patterns of reflux during the sleep period show consistently that oesophageal acid clearance is slower, and reflux frequency and oesophageal acid exposure are higher in patients with GERD than in healthy individuals. Of the 17 mechanistic studies identified by the searches, 15 reported that a minority of reflux episodes occurred during stable sleep, but the prevailing sleep state at the onset of reflux in these studies remains unclear owing to insufficient temporal resolution of recording or analysis methods. Two studies, in healthy individuals and patients with GERD, analysed sleep and pH with adequate resolution for temporal alignment of sleep state and the onset of reflux: all 232 sleep period reflux episodes evaluated occurred during arousals from sleep lasting less than 15 s or during longer duration awakenings. Six mechanistic studies found that transient lower oesophageal sphincter relaxations were the most common mechanism of sleep period reflux. CONCLUSIONS: Contrary to the prevailing view, subjective impairment of sleep in GERD is unlikely to be due to the occurrence of reflux during stable sleep, but could result from slow clearance of acid reflux that occurs during arousals or awakenings from sleep. Definitive studies are needed on the sleep/awake state at reflux onset across the full GERD spectrum.

Automated impedance-manometry analysis detects esophageal motor dysfunction in patients who have non-obstructive dysphagia with normal manometry.

BACKGROUND: Automated integrated analysis of impedance and pressure signals has been reported to identify patients at risk of developing dysphagia post fundoplication. This study aimed to investigate this analysis in the evaluation of patients with non-obstructive dysphagia (NOD) and normal manometry (NOD/NM). METHODS: Combined impedance-manometry was performed in 42 patients (27F : 15M; 56.2 ± 5.1 years) and compared with that of 24 healthy subjects (8F : 16M; 48.2 ± 2.9 years). Both liquid and viscous boluses were tested. MATLAB-based algorithms defined the median intrabolus pressure (IBP), IBP slope, peak pressure (PP), and timing of bolus flow relative to peak pressure (TNadImp-PP). An index of pressure and flow (PFI) in the distal esophagus was derived from these variables. KEY RESULTS: Diagnoses based on conventional manometric assessment: diffuse spasm (n = 5), non-specific motor disorders (n = 19), and normal (n = 11). Patients with achalasia (n = 7) were excluded from automated impedance-manometry (AIM) analysis. Only 2/11 (18%) patients with NOD/NM had evidence of flow abnormality on conventional impedance analysis. Several variables derived by integrated impedance-pressure analysis were significantly different in patients as compared with healthy: higher PNadImp (P < 0.01), IBP (P < 0.01) and IBP slope (P < 0.05), and shorter TNadImp_PP (P = 0.01). The PFI of NOD/NM patients was significantly higher than that in healthy (liquid: 6.7 vs 1.2, P = 0.02; viscous: 27.1 vs 5.7, P < 0.001) and 9/11 NOD/NM patients had abnormal PFI. Overall, the addition of AIM analysis provided diagnoses and/or a plausible explanation in 95% (40/42) of patients who presented with NOD. CONCLUSIONS & INFERENCES: Compared with conventional pressure-impedance assessment, integrated analysis is more sensitive in detecting subtle abnormalities in esophageal function in patients with NOD and normal manometry.