Asymmetrical elevation of esophagogastric junction pressure suggests hiatal repair contributes to antireflux surgery dysphagia.

The radial distribution of esophago-gastric junction (EGJ) pressures with regard to troublesome dysphagia (TDysph) after antireflux surgery is poorly understood. Before and after antireflux surgery, end-expiratory and peak-inspiratory EGJ pressures were measured at eight angles of 45° radial separation in patients with reflux disease. All 34 patients underwent posterior crural repair, then either 90° anterior (N = 13) or 360° fundoplication (N = 21). Dysphagia was assessed prospectively using a validated questionnaire (score range 0-45) and TDysph defined as a dysphagia score that was ≥5 above pre-op baseline. Compared with before surgery, for 90° fundoplication, end-expiratory EGJ pressures were highest in the left-anterolateral sectors, the position of the partial fundoplication. In other sectors, pressures were uniformly elevated. Compared with 90° fundoplication, radial pressures after 360° fundoplication were higher circumferentially (P = 0.004), with a posterior peak. Nine patients developed TDysph after surgery with a greater increase in end-expiratory and peak-inspiratory EGJ pressures (P = 0.03 and 0.03, respectively) and significantly higher inspiratory pressure at the point of maximal radial pressure asymmetry (P = 0.048), compared with 25 patients without TDysph. Circumferential elevation of end-expiratory EGJ pressure after 90° and 360° fundoplication suggests hiatal repair elevates EGJ pressure by extrinsic compression. The highly localized focal point of elevated EGJ pressure upon inspiration in patients with TDysph after surgery is indicative of a restrictive diaphragmatic hiatus in the presence of a fundoplication.

Endoscopic dilatation improves long-term dysphagia following head and neck cancer therapies: a randomized control trial.

Long-term pharyngeal dysphagia is a common complication following head and neck cancer (HNC) therapies. High-level evidence for pharyngoesophageal junction (POJ) dilatation as a treatment in this population is lacking. We aimed to evaluate the safety and efficacy of POJ dilatation in dysphagic HNC survivors. This single-center, single-blind, placebo-controlled trial (St George Hospital, Sydney, Australia) randomly assigned (1:1) HNC survivors with long-term dysphagia (≥12 months postcompleted HNC therapies) to receive either graded endoscopic dilatations or sham dilatation (placebo). Patients were blinded to intervention types. Two strata were used for permuted randomization: (1) HNC therapies (total laryngectomy vs. chemoradiation alone); (2) Prior POJ dilatation (nil vs. previous dilatation). The primary endpoint was a short-term clinical response in swallowing function (3 months), defined as (1) a decrease in Sydney Swallow Questionnaire score by ≥200 or a score ≤ ULN; and (2) satisfactory global clinical assessment. The secondary endpoints were dysphagia relapse and serious adverse events. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000707369). Between 13 January 2013 and 16 January 2017, 41 patients were randomly assigned to endoscopic dilatation (n = 21) or placebo (n = 20). The short-term response rate in the endoscopic dilatation group was 76% (n = 16), compared with 5% (n = 1) in the placebo group (P < 0.001). There were no serious adverse events. The finding of a mucosal tear postdilatation was associated strongly with clinical response (OR 13.4, 95% CI [2.4, 74.9], P = 0.003). Kaplan-Meier estimate of dysphagia relapse is 50% by 9.6 months (95% CI [6.0, 19.2]) from completion of dilatation. Endoscopic dilatation of the POJ is a safe and efficacious therapy for the treatment of long-term dysphagia in HNC survivors. Close follow-up and repeat dilatation are necessary given the high dysphagia relapse rate.

Novel Intra-Procedural Distensibility Measurement Accurately Predicts Immediate Outcome of Pneumatic Dilatation for Idiopathic Achalasia.

OBJECTIVES: Often 2-3 graduated pneumatic dilatations (PD) are required to treat achalasia as there is no current intra-procedural predictor of clinical response. Distensibility measurements using functional lumen imaging probe (FLIP) may provide an intra-procedural predictor of outcome. Our aim was to determine the optimal criterion for esophagogastric junction (EGJ) distensibility measurements during PD that predicts immediate clinical response. METHODS: EGJ distensibility was prospectively measured using FLIP immediately pre- and post-PD. The EGJ distensibility index (EGJ-DI) was defined as a ratio of the narrowest cross-sectional area and the corresponding intra-bag pressure at 40 ml distension. Immediate and short-term clinical responses were defined as Eckardt score ≤3 assessed 2 weeks Post-PD and at 3-month follow-up, respectively. RESULTS: In 54 patients, we performed thirty-seven 30 mm; twenty 35 mm and six 40 mm PDs. The short-term response rate to the graded PD was 93% (27/29) in newly diagnosed achalasia; 87% (13/15) and 70% (7/10) in those who had relapsed after previous PD and Heller's Myotomy, respectively. Among those demonstrating an immediate response, EGJ-DI increased by an average of 4.5 mm2/mmHg (95% CI (3.5, 5.5) (P<0.001). Within-subject Δ EGJ-DI was highly predictive of immediate clinical response with AUROC of 0.89 (95% CI [0.80, 0.98], P<0.001). An increment in EGJ-DI of 1.8 mm2/mmHg after a single PD predicts an immediate response with an accuracy of 87%. CONCLUSIONS: FLIP-measured Δ EGJ-DI is a novel intra-procedural tool that accurately predicts immediate clinical response to PD in achalasia. This technique may potentially dictate an immediate mechanism to "step-up" dilator size within a single endoscopy session.

Correlation of esophageal pressure-flow analysis findings with bolus transit patterns on videofluoroscopy.

Pressure-flow analysis quantifies the interactions between bolus transport and pressure generation. We undertook a pilot study to assess the interrelationships between pressure-flow metrics and fluoroscopically determined bolus clearance and bolus transport across the esophagogastric junction (EGJ). We hypothesized that findings of abnormal pressure-flow metrics would correlate with impaired bolus clearance and reduced flow across the EGJ. Videofluoroscopic images, impedance, and pressure were recorded simultaneously in nine patients with dysphagia (62-82 years, seven male) tested with liquid barium boluses. A 3.6 mm diameter solid-state catheter with 25 × 1 cm pressure/12 × 2 cm impedance was utilized. Swallowed bolus clearance was assessed using a validated 7-point radiological bolus transport scale. The cumulative period of bolus flow across the EGJ was also fluoroscopically measured (EGJ flow time). Pressure only parameters included the length of breaks in the 20 mmHg iso-contour and the 4 second integrated EGJ relaxation pressure (IRP4s). Pressure-flow metrics were calculated for the distal esophagus, these were: time from nadir impedance to peak pressure (TNadImp to PeakP) to quantify bolus flow timing; pressure flow index (PFI) to integrate bolus pressurization and flow timing; and impedance ratio (IR) to assess bolus clearance. When compared with controls, patients had longer peristaltic breaks, higher IRs, and higher residual EGJ relaxation pressures (break length of 8 [2, 13] vs. 2 [0, 2] cm, P = 0.027; IR 0.5 ± 0.1 vs. 0.3 ± 0.0, P = 0.019; IRP4s 11 ± 2 vs. 6 ± 1 mmHg, P = 0.070). There was a significant positive correlation between higher bolus transport scores and longer peristaltic breaks (Spearman correlation r = 0.895, P < 0.001) and with higher IRs (r = 0.661, P < 0.05). Diminished EGJ flow times correlated with a shorter TNadImp to PeakP (r = -0.733, P < 0.05) and a higher IR (r = -0.750, P < 0.05). Longer peristaltic breaks and higher IR correlate with failed bolus clearance on videofluoroscopy. The metric TNadImp to PeakP appears to be a marker of the period of time over which the bolus flows across the EGJ.

Osteonecrosis of the jaw: surgical treatment results before and during the COVID-19 pandemic in one of the reference hospitals in Poland.

OBJECTIVE: The COVID-19 pandemic has had a huge impact not only on everyday life but, above all, on the functioning of medical entities. During its duration, there were problems with access to health care, including maxillofacial surgery departments. The aim of the study is to analyze how the pandemic affected the surgical results of the treatment of osteonecrosis of the jaws at the Clinic of Maxillofacial Surgery in Poznan which delivers services in maxillofacial surgery for almost 4.5 million inhabitants in Poland. PATIENTS AND METHODS: We conducted a retrospective analysis of patients' medical records before and during the pandemic restrictions. The data was obtained by entering the appropriate passwords and ICD-10 diagnoses (e.g., M87) in the hospital's IT system. The obtained information was subjected to statistical analysis. RESULTS: The number of patients before and during the pandemic did not differ significantly. During the COVID-19 pandemic, the waiting time of patients after admission to the hospital for surgery and the total time of hospitalization were shortened. The number of complications was similar in both groups. However, the waiting time for a follow-up visit was longer during restriction time. CONCLUSIONS: The COVID-19 pandemic had an impact on the course of surgical treatment in patients with osteonecrosis of the jaws. The outcomes of the medical procedure remained consistent with the ones observed before the implementation of restrictions. This is likely due to the urgency of the illness. Despite the pandemic, a critical condition called osteonecrosis of the jaw was treated promptly.

Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation in patients with slow-transit constipation.

BACKGROUND: Sacral nerve stimulation (SNS) is emerging as a potential treatment for patients with constipation. Although SNS can elicit an increase in colonic propagating sequences (PSs), the optimal stimulus parameters for this response remain unknown. This study evaluated the colonic motor response to subsensory and suprasensory SNS in patients with slow-transit constipation. METHODS: Patients with confirmed slow-transit constipation were studied. Either a water-perfused manometry catheter or a high-resolution fibre-optic manometry catheter was positioned colonoscopically to the caecum. A temporary electrode was implanted transcutaneously in the S3 sacral nerve foramen. In the fasted state, three conditions were evaluated in a double-blind randomized fashion: sham, subsensory and suprasensory stimulation. Each 2-h treatment period was preceded by a 2-h basal period. The delta (Δ) value was calculated as the frequency of the event during stimulation minus that during the basal period. RESULTS: Nine patients had readings taken with a water-perfused catheter and six with a fibre-optic catheter. Compared with sham stimulation, suprasensory stimulation caused a significant increase in the frequency of PSs (mean(s.d.) Δ value - 1·1(7·2) versus 6·1(4·0) PSs per 2 h; P = 0·004). No motor response was recorded in response to subsensory stimulation compared with sham stimulation. Compared with subsensory stimulation, stimulation at suprasensory levels caused a significant increase in the frequency of PSs (P = 0·006). CONCLUSION: In patients with slow-transit constipation, suprasensory SNS increased the frequency of colonic PSs, whereas subsensory SNS stimulation did not. This has implications for the design of therapeutic trials and the clinical application of the device.

In-vivo demonstration of a high resolution optical fiber manometry catheter for diagnosis of gastrointestinal motility disorders.

Fiber optic catheters for the diagnosis of gastrointestinal motility disorders are demonstrated in-vitro and in-vivo. Single element catheters have been verified against existing solid state catheters and a multi-element catheter has been demonstrated for localized and full esophageal monitoring. The multi-element catheter consists of a series of closely spaced pressure sensors that pick up the peristaltic wave traveling along the gastrointestinal (GI) tract. The sensors are spaced on a 10 mm pitch allowing a full interpolated image of intraluminal pressure to be generated. Details are given of in-vivo trials of a 32-element catheter in the human oesophagus and the suitability of similar catheters for clinical evaluation in other regions of the human digestive tract is discussed. The fiber optic catheter is significantly smaller and more flexible than similar commercially available devices making intubation easier and improving patient tolerance during diagnostic procedures.

Ab initio study of the Br(2P)-HBr van der Waals complex.

This study reports an ab initio characterization of a prereactive van der Waals complex between an open-shell atom Br((2)P) and a closed shell molecule HBr. The three adiabatic potential surfaces 1 (2)A('), 2 (2)A('), and 1 (2)A("), which result from the splitting of degenerate P state of Br are obtained from coupled cluster calculations. The coupling between same-symmetry states is calculated by multireference configuration-interaction method. A transformation to a diabatic representation and inclusion of the spin-orbit coupling effects on the interactions are also discussed. Bound states are calculated using an adiabatic bender model. The global minimum on the lowest adiabatic potential surface corresponds to a T-shaped geometry and has a well depth of D(e)=762.5 cm(-1) at R(e)=3.22 A. A secondary minimum occurs for a hydrogen-bonded geometry with D(e)=445.3 cm(-1) at R(e)=4.24 A. Upon inclusion of spin-orbit coupling the hydrogen-bonded minimum remains at the same depth, but the T-shaped minimum washes out to less than half of its spin-free value. The lowest bound state is localized in the linear minimum. The spin-orbit coupling plays a very important role in shaping of the potential energy surfaces of Br-HBr.

The critical importance of pharyngeal contractile forces on the validity of intrabolus pressure as a predictor of impaired pharyngo-esophageal junction compliance.

INTRODUCTION: Restrictive defects of the pharyngo-esophageal junction (PEJ) are common in both structural and neurological disorders and are amenable to therapies aiming to reduce outflow resistance. Intrabolus pressure (IBP) acquired with high-resolution manometry and impedance (HRMI) is an indicator of resistance and a marker of reduced PEJ compliance. Constraints and limitations of IBP as well as the optimal IBP parameter remain undefined. AIMS: To determine: (i) the impact of peak pharyngeal pressure (PeakP) on the diagnostic accuracy of IBP for the detection of a restrictive defect at the PEJ and (ii) the optimal IBP parameter for this purpose. METHODS: In 52 dysphagic patients previously treated for head and neck cancer. Five candidate IBP measures and PeakP were obtained with HRMI, as well as a presence of a stricture determined by a mucosal tear after endoscopic dilatation. Predictive values of IBP measures were evaluated by receiver operating characteristic (ROC) analysis for all patients and reiterated as patients with lowest PeakP were progressively removed from the cohort. RESULTS: All IBP parameters had fair to good accuracy at predicting strictures. Intrabolus pressure measured at a discrete point of maximum admittance 1 cm above the maximal excursion of the upper esophageal sphincter had highest sensitivity (0.76) and specificity (0.78). When PeakP was at least 57 mm Hg both sensitivity and specificity improved to 0.9. CONCLUSIONS: Pharyngeal propulsive force has substantial impact on the accuracy of IBP as a predictor of a PEJ stricture. When PeakP is ≥57 mm Hg, an elevated IBP is highly predictive of a restrictive defect at the PEJ.

Pathophysiology of swallowing following oropharyngeal surgery for obstructive sleep apnea syndrome.

BACKGROUND: Uvulopalatopharyngoplasty (UPPP) and coblation channeling of the tongue (CCT) are oropharyngeal surgeries used to treat obstructive sleep apnea syndrome. The extent to which UPPP and CCT affect pharyngeal swallow has not been determined. We therefore conducted a novel case series study employing high-resolution impedance manometry (HRIM) to quantify the swallowing-related biomechanics following UPPP and/or CCT surgery. METHODS: Twelve patients who underwent UPPP+CCT or CCT only were assessed an average 2.5 years postsurgery. Swallow function data were compared with ten healthy controls. All patients completed the Sydney swallow questionnaire (SSQ). Pharyngeal pressure-flow analysis of HRIM recordings captured key distension, contractility and pressure-flow timing swallow parameters testing 5, 10, and 20 mL volumes of thin and thick fluid consistencies. KEY RESULTS: Postoperative patients had more dysphagia symptoms with five returning abnormal SSQ scores. Swallowing was biomechanically altered compared to controls, consistent with diminished swallowing reserve, largely driven by elevated hypopharyngeal intrabolus pressure due to a reduced capacity to open the upper esophageal sphincter to accommodate larger volumes. CONCLUSIONS & INFERENCES: Patients who have undergone UPPP and/or CCT surgery appear to have a deficiency in normal modulation of the swallowing mechanism and a reduced swallowing functional reserve. We speculate that these changes may become relevant in later life with the onset of age-related stressors to the swallowing mechanism. This case series strikes a note of caution that further studies are needed to determine the role of preoperative swallow assessment in patients undergoing UPPP and/or CCT surgery.

Removal of tonic nitrergic inhibition is a potent stimulus for human proximal colonic propagating sequences.

Propagating sequences (PS) are important in colonic propulsion and defecation, yet the triggers of these motor patterns are not understood. Nonadrenergic noncholinergic neurones are believed to modulate smooth muscle in the gastrointestinal tract via the ubiquitous inhibitory neurotransmitter nitric oxide (NO). In the mouse colon periods of quiescence correlate with an increase in the release of NO. We investigated the colonic response to NO synthase inhibition in the conscious human subject. Intravenous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA; 3 or 6 mg kg(-1) h(-1)) occurred in random order in six healthy volunteers in whom a 5 m long nasocolonic manometry catheter was positioned such that 16 recording sites, at 7.5-cm intervals, spanned the terminal ileum and colon. L-NMMA infusion at 3 mg kg(-1) h(-1), but not 6 mg kg(-1) h(-1) significantly (P = 0.02) increased proximal colonic PS frequency (2.0 +/- 1.9 vs 11.7 +/- 7.0 PS h(-1)) and non-propagating motor activity (5,296 +/- 2,750 vs 6,362 +/- 1,275 mmHg s). We conclude that blockade of NO synthesis has a stimulatory effect on the frequency of proximal colonic PS. This suggests removal of tonic nitrergic inhibition of the colon might be a physiological stimulus for propagating activity.

Influence of selected tensides on the hydrocortisone concentration equilibrium balance in micelles and the dispersing center.

The degree of hydrocortisone binding, was investigated by means of equilibrium dialysis in the presence of 1% or 3% micellar solutions of polysorbate 20 and 80. Stabilization of the concentration equilibrium was found in all the cases investigated. The degree of hydrocortisone binding in micelles depends on the concentration and type of tenside used.

Inter-rater reliability and validity of automated impedance manometry analysis and fluoroscopy in dysphagic patients after head and neck cancer radiotherapy.

BACKGROUND: Pharyngeal automated impedance manometry (AIM) analysis is a novel non-radiological method to analyze swallowing function based on impedance-pressure recordings. In dysphagic head and neck cancer patients, we evaluated the reliability and validity of the AIM-derived swallow risk index (SRI) and a novel measure of postswallow residue (iZn/Z) by comparing it against videofluoroscopy as the gold standard. METHODS: Three blinded experts classified 88 videofluoroscopic swallows from 16 patients for aspiration and degree of postswallow residue. Pressure-impedance recordings of the patient and age-matched control swallows were analyzed using AIM by three observers who derived the SRI and iZn/Z. Intra-class correlation coefficients (ICC) were calculated for videofluoroscopic and AIM measures. Patient pressure/impedance measurements were compared with videofluoroscopy scores and control subjects to determine validity for detecting clinically relevant swallowing dysfunction. KEY RESULTS: Agreement among observers assessing presence of penetration and aspiration was modest (ICC 0.57) for videofluoroscopy and good (ICC 0.71, 0.82) for AIM-derived SRI and iZn/Z. When compared with age-matched controls, the SRI was higher in patients with aspiration (mean diff. 28.6, 95% CI [55.85, 1.355], p < 0.05). The iZn/Z had moderate positive correlation with bolus residue on fluoroscopy (BRS score) (rs (86) = 0.4120, p < 0.0001) and was increased in both patients with aspiration (∆244 [419.7, 69.52; p < 0.05]) and penetration (∆240 [394.3, 85.77]; p < 0.05) compared to controls. CONCLUSIONS & INFERENCES: AIM-based measures of swallowing function have better inter-rater reliability than comparable fluoroscopically derived measures. These measures are easily determined and objective markers of clinically relevant features of disordered swallowing following radiotherapy.

On tautomerism of the cytosine molecule.

Tautomerism of the cytosine molecule is discussed in connection with recent experimental matrix-isolation infrared spectroscopic measurements and recent ab initio calculations of relative stabilities of tautomers and of IR spectra for different tautomeric forms of the compound. Experimental IR spectra in the N-H and O-H stretching regions and in the C = O stretching region are presented for cytosine and for its several derivatives considered as model compounds. This experimental evidence, as well as the quantum-mechanical calculations (including both electron correlation and zero-point vibrational contributions), clearly indicate that two tautomers of cytosine, i.e. the amino-hydroxy and amino-oxo forms with the hydrogen atom at the N(1) position, exist in equilibrium when the cytosine molecule is isolated in an inert environment. The effect of the environment on the relative stabilities of several tautomers is also discussed briefly.

Influence of tensides on the release of medical agents from hydrophilic gels, part 2: The influence of selected tensides on hydrocortisone release from xerogels.

With the increase of polysorbates 20 and 21 concentration in xerogels, in the presence of 1,2-propylene glycol and PEG 200, hydrocortisone half-release periods from these preparations become longer while the half-release periods for polysorbate 80 and propylene glycol, and polysorbate 21 and PEG 200 are proportionally shortened. The concentration of tensides has no significant impact on the half-release periods of hydrocortisone with polysorbate 81 added to xerogels in the presence of propylene glycol and polysorbate 20 and 80 with PEG 200.

Influence of some polysorbates on hydrocortisone release from hydrophilic gels considered as two-compartment models.

Hydrocortisone release from hydrogels containing of 1% and 3% polysorbate 20 or polysorbate 80, in the presence of 1,2-propylene glycol or PEG 200 has two stages. In the first one the release rates are higher than those of the second stage. Half-release times in the first stage are in the range 0.31 h to 0.48 h and in the second stage 16.65 h to 23.22 h. Hydrocortisone release from the gels containing of 1% to 3% of polysorbate 21 or 81, in the presence of 1,2-propylene glycol or PEG 200 conform to second order kinetics. Release rates in this stage are in the range from 3.80 x 10(-4)%.h-1 to 5.97 x 10(-4)%.h-1.

Persistent dysphagia after head and neck radiotherapy: a common and under-reported complication with significant effect on non-cancer-related mortality.

AIMS: Dysphagia is a well-recognised acute complication after radiotherapy. However, knowledge about the long-term prevalence and effect remains limited. The aims of this study were to determine the prevalence, severity, morbidity, time course and reporting patterns of dysphagia symptoms after head and neck radiotherapy. MATERIALS AND METHODS: An observational cross-sectional study was conducted in a large consecutive series of head and neck cancer patients. All patients in the St George Hospital Cancer Care database who had received head and neck radiotherapy with curative intent 0.5-8 years previously and recorded as being alive were surveyed using the Sydney Swallow Questionnaire (SSQ). Case notes were reviewed to determine the level of awareness of swallowing dysfunction in all patients, as well as the causes of mortality in the 83 deceased patients. RESULTS: The mean follow-up at the time of survey was 3 years after radiotherapy (range 0.5-8 years). Of the 116 patients surveyed by questionnaire, the response rate was 72% (83). Impaired swallowing (SSQ score > 234) was reported by 59% of patients. Dysphagia severity was not predicted by tumour site or stage, nor by the time since therapy, age, gender or adjuvant chemotherapy. Review of the hospital medical records and cancer database revealed that cancer accounted for 55% of deaths and aspiration pneumonia was responsible for 19% of non-cancer-related deaths. Of those with abnormal SSQ scores, only 47% reported dysphagia during follow-up clinic visits. CONCLUSIONS: Persistent dysphagia is a prevalent, under-recognised and under-reported long-term complication of head and neck radiotherapy which currently cannot be predicted on the basis of patient, tumour or treatment characteristics. Aspiration pneumonia is an important contributor to non-cancer-related mortality in these patients. These data highlight the need for closer monitoring of swallow dysfunction and its sequelae in this population.

Modulation of esophageal afferent pathways by 5-HT3 receptor inhibition.

BACKGROUND: The study aims were to investigate whether neural pathways involving 5-HT3 receptors mediate: (i) distension-induced upper esophageal sphincter (UES) relaxation reflex, (ii) esophageal sensitivity to acid and electrical stimuli, and (iii) viserosomatic sensitization following acid exposure. METHODS: In Study I, in a double-blind crossover trial (n = 9) esophageal sensory and pain thresholds to electrical stimulation were measured in the esophagus, midsternum, and the foot, before subjects were randomized to receive either Ondansetron (8 mg i.v.) or NaCl (0.9% w/v). HCl (0.15 mol L(-1)) was then infused into distal esophagus and electrical thresholds were reassessed. Following electrical sensory threshold testing, subjects received a second esophageal infusion of HCl to evaluate esophageal sensitivity to acid. In Study II (N = 10), frequencies of distension-induced UES relaxation responses were scored before and after treatment with Ondansetron and NaCl in a double-blind crossover trial. KEY RESULTS: In Study I, ondansetron had no effect on esophageal sensitivity to HCl or acid-induced sensitization. However, blockade of 5-HT3 receptors did reduce midsternum somatic pain thresholds. Sixty minutes after esophageal acid exposure, pain thresholds were significantly lower in the ondansetron arm (mean Δ-1.36 ± 0.4 mA) when compared with NaCl (mean Δ-0.14 ± 0.58 mA) (P < 0.05). In Study II, 5-HT3 receptor blockade had no significant effect on UES relaxation reflex. CONCLUSIONS & INFERENCES: This study does not support the hypothesis that in health, 5-HT3 receptors play a significant role in esophago-UES distention-induced relaxation reflex and esophageal sensitivity to acid or electrical stimulation. It does provide new evidence for involvement of 5-HT3 receptors in viscerosomatic sensitization.

Long-term outcome following pneumatic dilatation as initial therapy for idiopathic achalasia: an 18-year single-centre experience.

BACKGROUND: Relapse after treatment for idiopathic achalasia is common and long-term outcome data are limited. AIM: To determine the cumulative relapse rate and long-term outcome after pneumatic dilatation (PD) for achalasia in a tertiary referral centre. METHODS: A retrospective study of 301 patients with achalasia treated with PD as first-line therapy. Short-term outcome was measured at 12 months. Long-term outcome was assessed in those who were in remission at 12 months by cumulative relapse rate and cross-sectional analysis of long-term remission rate regardless of any interval therapy, using a validated achalasia-specific questionnaire. RESULTS: Eighty-two percent of patients were in remission 12 months following initial PD. Relapse rates thereafter were 18% by 2 years; 41% by 5 years and 60% by 10 years. Whilst 43% patients underwent additional treatments [PD (29%), myotomy (11%) or botulinum toxin (3%)] beyond 12 months, 32% of those who had not received interval therapy had relapsed at cross-sectional analysis. After a mean follow-up of 9.3 years, regardless of nature, timing or frequency of any interval therapy, 71% (79/111) patients were in remission. The perforation rate from PD was 2%. Chest pain had a poor predictive value (24%) for perforation. CONCLUSIONS: Long-term relapse is common following pneumatic dilatation. While on-demand pneumatic dilatation for relapse yields a good response, one-third of relapsers neither seek medical attention nor receive interval therapy. Close follow-up with timely repeat dilatation is necessary for a good long-term outcome. Given the poor predictive value of chest pain for perforation, routine gastrografin swallow is recommended postdilatation.