Distension contraction plots of pharyngeal/esophageal peristalsis: next frontier in the assessment of esophageal motor function.

Esophageal peristalsis consists of initial inhibition (relaxation) followed by excitation (contraction), both of which move sequentially in the aboral direction. Initial inhibition results in receptive relaxation and bolus-induced luminal distension, which allows propulsion by the contraction with minimal resistance to flow. Similar to the contraction wave, luminal distension has unique waveform characteristics in normal subjects; both are modulated by bolus volume, bolus viscosity, and posture, suggesting a possible cause-and-effect relationship between the two. Distension contraction plots in patients with dysphagia with normal bolus clearance [high-amplitude esophageal contractions (HAECs), esophagogastric junction outflow obstruction (EGJOO), and functional dysphagia (FD)] reveal two major findings: 1) unlike normal subjects, there is luminal occlusion distal to bolus during peristalsis in certain patients, i.e., with type 3 achalasia and nonobstructive dysphagia; and 2) bolus travels through a narrow lumen esophagus during peristalsis in patients with HAECs, EGJOO, and FD. Aforementioned findings indicate a relative dynamic obstruction to the bolus flow during peristalsis and reduced distensibility of esophageal wall in the bolus segment of the esophagus. We speculate that a normal or supernormal contraction wave pushing bolus against resistance is the mechanism of dysphagia sensation in significant number of patients. Representations of distension and contraction, combined with objective measures of flow timing and distensibility are complementary to the current scheme of classifying esophageal motility disorders based solely on the characteristics of contraction phase of peristalsis. Better understanding of the distensibility of the bolus-containing segment of the esophagus during peristalsis will lead to the development of novel medical and surgical therapies in the treatment of dysphagia in significant number of patients.

Assessment of esophageal body peristaltic work using functional lumen imaging probe panometry.

The goal of this study was to conceptualize and compute measures of "mechanical work" done by the esophagus using data generated during functional lumen imaging probe (FLIP) panometry and compare work done during secondary peristalsis among patients and controls. Eighty-five individuals were evaluated with a 16-cm FLIP during sedated endoscopy, including asymptomatic controls (n = 14) and those with achalasia subtypes I, II, and III (n = 15, each); gastroesophageal reflux disease (GERD; n = 13); eosinophilic esophagitis (EoE; n = 9); and systemic sclerosis (SSc; n = 5). The FLIP catheter was positioned to have its distal segment straddling the esophagogastric junction (EGJ) during stepwise distension. Two metrics of work were assessed: "active work" (during bag volumes ≤ 40 mL where contractility generates substantial changes in lumen area) and "work capacity" (for bag volumes ≥ 60 mL when contractility cannot substantially alter the lumen area). Controls showed median [interquartile range (IQR)] of 7.3 (3.6-9.2) mJ of active work and 268.6 (225.2-332.3) mJ of work capacity. Patients with all achalasia subtypes, GERD, and SSc showed lower active work done than controls (P ≤ 0.003). Patients with achalasia subtypes I and II, GERD, and SSc had lower work capacity compared with controls (P < 0.001, 0.004, 0.04, and 0.001, respectively). Work capacity was similar between controls and patients with achalasia type III and EoE. Mechanical work of the esophagus differs between healthy controls and patient groups with achalasia, EoE, SSc, and GERD. Further studies are needed to fully explore the utility of this approach, but these work metrics would be valuable for device design (artificial esophagus), to measure the efficacy of peristalsis, to gauge the physiological state of the esophagus, and to comment on its pumping effectiveness.NEW & NOTEWORTHY Functional lumen imaging probe (FLIP) panometry assesses esophageal response to distension and provides a simultaneous assessment of pressure and dimension during contractility. This enables an objective assessment of "mechanical work" done by the esophagus. Eighty-five individuals were evaluated, and two work metrics were computed for each subject. Controls showed greater values of work compared with individuals with achalasia, gastroesophageal reflux disease (GERD), and systemic sclerosis (SSc). These values can quantify the mechanical behavior of the distal esophagus and assist in the estimation of muscular integrity.

Living System Adapts Harmonics of Peristaltic Wave for Cost-Efficient Optimization of Pumping Performance.

Wavelike patterns driving transport are ubiquitous in life. Peristaltic pumps are a paradigm of efficient mass transport by contraction driven flows-often limited by energetic constraints. We show that a cost-efficient increase in pumping performance can be achieved by modulating the phase difference between harmonics to increase occlusion. In experiments we find a phase difference shift in the living peristalsis model P. polycephalum as dynamic response to forced mass transport. Our findings provide a novel metric for wavelike patterns and demonstrate the crucial role of nonlinearities in life.

Clinical importance of cine-MRI assessment of small bowel motility in patients with chronic intestinal pseudo-obstruction: a retrospective study of 33 patients.

BACKGROUND: Although chronic intestinal pseudo-obstruction (CIPO) is a rare and extremely severe functional digestive disorder, its clinical course and severity show various patterns. We assessed small bowel peristalsis in CIPO patients using cine-MRI (video-motion MRI) and their clinical characteristics to evaluate the clinical importance of performing cine-MRI in patients with this intractable disease. METHODS: The medical records of 131 patients referred to our institution with a suspected diagnosis of CIPO between 2010 and 2015 were retrospectively evaluated. Thirty-three patients (22 female/11 male; age range 16-79 years) who met the criteria for CIPO and underwent cine-MRI were enrolled. Mean luminal diameter (MLD), contraction ratio (CR), and contraction cycle (CC) were determined and compared with these parameters in healthy volunteers. Clinical outcomes in patients with CIPO were also evaluated. RESULTS: The median follow-up time was 25.2 months (range, 1-65 months). Of the 33 patients with CIPO, 23 (70 %) showed apparently disturbed small intestinal peristalsis, whereas 10 (30 %) did not. The percentage of patients requiring intravenous alimentation was significantly higher (p = 0.03), and the mean serum albumin level was significantly lower (p = 0.04), in patients with than without impaired small intestinal peristalsis. Although both cine-MRI and CT findings in the latter ten cases were within the normal range, MLD and CR differed significantly from healthy volunteers. CONCLUSIONS: Cine-MRI is useful in predicting severe clinical features in patients with CIPO, and in detecting slightly impaired small contractility that cannot be detected on CT.

Esophageal chemical clearance is impaired in gastro-esophageal reflux disease--a 24-h impedance-pH monitoring assessment.

BACKGROUND: Impedance-pH monitoring allows assessment of retrograde and antegrade intra-esophageal movement of fluids and gas. Reflux is followed by volume clearance and chemical clearance, elicited by secondary and swallow-induced peristalsis, respectively. We aimed to assess whether chemical clearance is impaired in gastro-esophageal reflux disease (GERD). METHODS: Blinded retrospective review of impedance-pH tracings from patients with erosive reflux disease (ERD) and non-erosive reflux disease (NERD), and from proton pump inhibitor (PPI)-refractory patients before and after laparoscopic fundoplication. The number of refluxes followed within 30 s by swallow-induced peristaltic waves was divided by the number of total refluxes to obtain a parameter representing chemical clearance namely the postreflux swallow-induced peristaltic wave (PSPW) index. KEY RESULTS: The PSPW index was significantly lower in 31 ERD (15%) and in 44 NERD (33%) off-PPI patients than in 30 controls (75%), as well as in 18 ERD (16%) and in 48 NERD (31%) on-PPI patients than in 26 on-PPI functional heartburn (FH) cases (67%) (P < 0.05 for all comparisons). In 29 PPI-refractory patients, the median PSPW index was unaltered by otherwise effective antireflux surgery (20% postoperatively, 21% preoperatively). The overall sensitivity, specificity, positive, and negative predictive values of the PSPW index in identifying GERD patients were 97%, 89%, 96%, and 93%. CONCLUSIONS & INFERENCES: Impairment of chemical clearance is a primary pathophysiological mechanism specific to GERD: it is unaffected by medical/surgical therapy, is not found in FH, and is more pronounced in ERD than in NERD. Using the PSPW index could improve the diagnostic efficacy of impedance-pH monitoring.

Upper esophageal sphincter and esophageal motility in patients with chronic cough and reflux: assessment by high-resolution manometry.

The pathophysiology of chronic cough and its association with dsymotility and laryngopharyngeal reflux remains unclear. This study applied high-resolution manometry (HRM) to obtain a detailed evaluation of pharyngeal and esophageal motility in chronic cough patients with and without a positive reflux-cough symptom association probability (SAP). Retrospective analysis of 66 consecutive patients referred for investigation of chronic cough was performed. Thirty-four (52%) were eligible for inclusion (age 55 [19-77], 62% female). HRM (ManoScan 360, Given/Sierra Scientific Instruments, Mountain View, CA) with 10 water swallows was performed followed by a 24-hour ambulatory pH monitoring. Of this group, 21 (62%) patients had negative reflux-cough SAP (group A) and 13 (38%) had positive SAP (group B). Results from 23 healthy controls were available for comparison (group C). Detailed analysis revealed considerable heterogeneity. A small number of patients had pathological upper esophageal sphincter (UES) function (n=9) or esophageal dysmotility (n=1). The overall baseline UES pressure was similar, but average UES residual pressure was higher in groups A and B than in control group C (-0.2 and -0.8mmHg vs. -5.4mmHg; P<0.018 and P<0.005). The percentage of primary peristaltic contractions was lower in group B than in groups A and C (56% vs. 79% and 87%; P=0.03 and P<0.002). Additionally, intrabolus pressure at the lower esophageal sphincter was higher in group B than in group C (15.5 vs. 8.9; P=0.024). HRM revealed changes to UES and esophageal motility in patients with chronic cough that are associated with impaired bolus clearance. These changes were most marked in group B patients with a positive reflux-cough symptom association.

Assessment of intestinal peristalsis in vitro.

The protocol detailed in this unit is designed to assess intestinal peristaltic motility in the isolated small intestine in vitro and to measure the effects of drugs able to interfere with gut propulsive activity. The procedure is based on Trendelenburg's classic technique, described at the beginning of the 20th century in the isolated guinea pig ileum and, later on, extended to other intestinal preparations from the same animal and other animal species. This unit illustrates the basic procedures for setting up the intestinal preparation, recording peristalsis under near-physiologic conditions, and testing the pharmaco-toxicological effects of drugs and pollutants on the contractile behavior of the gut wall. The protocol allows evaluating the action of drugs affecting sensory and/or motor neurons of the enteric nervous system and how these neurons control the development of the motor program of the gut wall. This model can be exploited to investigate novel compounds undergoing preclinical development and both inhibitors and stimulants of gastrointestinal peristaltic activity, as well as environmental or alimentary pollutants, like xenobiotics and naturally-occurring toxins, endowed with noxious activity with regard to digestive functions.

Assessment of gastrointestinal propulsive activity using three different models of peristalsis in vivo in the mouse.

The protocols described in this unit are designed to assess the acute effects of drugs on the propulsive activity of the gastrointestinal muscles in the conscious mouse. These protocols are currently applied to investigate the pharmacological activity of novel compounds undergoing preclinical development and to obtain predictive data needed to advance drugs into clinical trials. Moreover, these methods could be useful in evaluating the functional toxicity by environmental or alimentary pollutants, like xenobiotics and naturally occurring toxins endowed with noxious activity in the control of physiologic peristalsis. The three models detailed-the measurement of gastric emptying, ileal transit, and colonic propulsion-are substantially non-invasive and do not require analgesic pretreatments or the induction of general anesthesia. In contrast to an in vitro approach, these in vivo studies provide a unified understanding of drug effects on gut functionality, in particular when the central nervous system, the extrinsic nerves, or the (neuro)endocrine system is targeted by the test drugs.

The assessment of rat ureteral pressure generation in vitro: regional heterogeneity and influence of distending pressure.

Contraction of ureteral smooth muscle drives the urine bolus to the urinary bladder for storage prior to micturition. This study describes a novel approach to the measurement of ureteral pressure generation in vitro and the influence of distending pressure on acetylcholine-stimulated ureteral lumenal pressure generation. Isolated segments of ureters obtained from Wistar rats were pressurised in a blind-ended sac arrangement and contractile responses were recorded as phasic oscillations in ureteral luminal pressure. Distal segments generated greater luminal pressures than proximal segments (p<0.001) in response to acetylcholine. Increasing baseline distending pressures in the range 2-10 mmHg in proximal segments was associated with greater frequency of contraction (p<0.001) and decreased magnitude of contraction (p<0.001) when expressed as % maximum response. Nifedipine (10(-5) M) or removal of extracellular Ca(2+) abolished the contractions. Isometric contractile responses of ureteral ring preparations were not significantly influenced by pretensions equivalent to distending pressures in the range 2-10 mmHg. This is the first study to fully establish the influence of baseline ureteral distending pressure upon ureteral luminal pressure generation in vitro and demonstrates regional heterogeneity of ureteral contractile responses. It is suggested that this experimental approach may be a useful methodology for the investigation of ureteral function during urinary outflow obstruction.

[Choice of the method of isoperistaltic tubular esophagogastroplasty completion based on intraoperative assessment of vascularization of gastric transplant].

Intraoperative assessment of vascularization of isoperistaltic tubular gastric transplant using angiotensiometry and Doppler flowmetry was performed at 136 patients undergone extirpation of esophagus with esophagogastroplasty. The main criteria of gastric transplant convenience for anastomosis with esophagus were: clear intramural pulse on all circle of gastric transplant by flowmetry data; intramural arterial pressure according to angiotensiometry data have to be not less 80 mm Hg, and the ratio of venous to arterial pressure has not to be more 50%. At inadequate criteria the surgery must be finished with cervical esophago- and gastrostoma.

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.

[Peranal passage of a surgical sponge: fortunate outcome of an intraoperative oversight]. / Glücklicher Ausgang einer intraoperativen Unterlassung.

Four years after cholecystectomy and recurrent epigastric pain, a surgical sponge passed per anum in a 39-year-old man. Diagnostic procedures including clinical and laboratory examinations, ultrasound, coloscopy, and abdominal CT did not reveal any noteworthy residual changes by the foreign body. After 4 years in situ, the surgical sponge showed no alterations in structure. The representatives of the hospital concerned had to satisfy the patient's claims for damages. Pathology, technical diagnostic methods, and prognosis in cases of retained gauzes are presented. It is essential to count instruments and towels and advisable to use only single sponges in forceps in order to prevent intraoperative loss.

Long-term outcomes of endoluminal gastroplication: a U.S. multicenter trial.

BACKGROUND: Endoluminal gastroplication has shown promise for the treatment of GERD in short-term studies. Until now, long-term outcome data have been lacking. METHODS: A prospective, multicenter trial enrolled 85 patients with GERD to be treated with endoluminal gastroplication. Inclusion criteria were 3 or more heartburn or regurgitation episodes per week, >4.2% time in 24 hours with esophageal pH < 4, and dependency on antisecretory medications. Exclusion criteria were the presence of varices, achalasia, aperistalsis, or previous gastric resection. Patients underwent manometry, 24-hour pH monitoring, and symptom severity scoring before and after the procedure. Patient diaries were used to assess medication use and to estimate annual medication cost. RESULTS: At 1- and 2-year follow-up, patients had significant reductions in median heartburn symptom scores (72 at baseline [interquartile range (IQR) 90-48] vs. 4 at 12 months [IQR 43-0] and 16 at 24 months [IQR 53-3.5]; p < 0.0001 vs. baseline) and median regurgitation symptoms (2 at baseline [IQR 3-1] vs. 0 at 12 months (IQR 1-0) and 1 at 24 months [IQR 1-0]; p < 0.0001 vs. baseline). Of all patients, 59% and 52% showed heartburn symptom resolution at 12 and 24 months, respectively ( p < 0.0001 vs. baseline). Also, 83% and 77% had regurgitation symptom resolution at 12 and 24 months, respectively (p < 0.0001 vs. baseline). Proton pump inhibitor use also was significantly reduced at 12 and 24 months after the procedure. At 2-year follow-up, median annualized medication costs were reduced by 88% (1381 US dollars) (p < 0.0001). Endoluminal gastroplication significantly reduced the duration and the number of episodes of esophageal acid exposure (p < 0.0001 vs. baseline). Only 7 patients experienced adverse events. CONCLUSIONS: Endoscopic gastroplication is safe and effective, and is associated with symptom reductions in patients with GERD for at least 24 months.

Small bowel motility assessment with magnetic resonance imaging.

PURPOSE: To assess primarily the feasibility of magnetic resonance imaging (MRI) as a tool to monitor small bowel peristaltic motion and secondarily to validate this technique by demonstrating drug-induced motility changes. MATERIALS AND METHODS: After a standardized oral preparation of Ispaghula husk (Metamucil) and meglumine gadoterate (Gd-DOTA; Dotarem), 10 volunteers underwent dynamic MRI using a two-dimensional turbofast field echo (TFE) sequence with a slice repetition time of 500 msec. Intraluminal cross-sectional caliber changes over time were assessed allowing quantification of the peristaltic frequencies and amplitudes of the small gut on various regions of interest. Pharmacologically induced alterations of the peristaltic motion after spasmolytics and gastrokinetic motion enhancers were investigated. RESULTS: Small bowel diameter measurement resulted in a peristalsis of 10.96 (SD = +/-2.51) waves per minute, oscillating regularly with mean amplitudes of 6.65 mm (SD = +/-1.15 mm). Peristaltic frequency in normal individuals is consistent with that observed with other techniques. Intravenous administration of scopolamine butylbromide (= hyoscine butylbromide/Buscopan) resulted in small bowel paralysis within 21.3 seconds (SD = +/-2.8 seconds). Prokinetic effect of intravenous metoclopramide (Paspertin) after Buscopan paralysis was tested in one volunteer, characterized by a slow recovery of peristalsis, which propagated from the proximal to the distal segments and enhanced contraction amplitudes. CONCLUSION: Dynamic MRI allows observing and quantifying small bowel peristalsis, characterizing motion patterns, and monitoring the effects of interfering factors such as drugs.

Functional evaluation of the postoperative gastrointestinal tract using kinematic MR imaging: Quantitative assessment of peristaltic activity.

The purpose of this study is to demonstrate the feasibility of kinematic MR imaging in visualizing peristaltic activity in the reconstructed gastrointestinal tract with quantitative measurements. Sixteen patients with gastrointestinal reconstruction were studied with kinematic MR imaging using HASTE and/or true FISP. Peristaltic waves were noted in the retrosternal gastric segment after gastric pull through (frequency = 3.0 +/- 0.5 times/min, velocity = 2.6 +/- 0.6 mm/s) and in the residual antrum after cardiectomy (frequency = 3 times/min, velocity = 4.0 mm/s). Peristaltic waves were not apparent in the residual fundus after distal gastrectomy and in the reconstructed jejunum after pancreatoduodenectomy and gastrojejunostomy.

Neural regulation of tone in the oesophageal body: in vivo barostat assessment of volume-pressure relationships in the feline oesophagus.

Recent combined manometric-barostat studies demonstrated that the oesophageal body exhibits both peristaltic contractions and tone. This study further characterized the neural modulation of tone in the feline oesophageal body. Simultaneous oesophageal barostat and manometry were performed in 20 adult cats under ketamine sedation. Oesophageal tone and peristalsis were assessed in the distal smooth muscle oesophagus. Cholinergic modulation was studied using neostigmine, erythromycin, atropine and vagotomy. Nitrergic regulation was assessed using sildenafil to increase cellular cyclic guanosine monophosphate and the nitric oxide synthase blocker Nomega-nitro-l-arginine (l-NNA). The presence of a tonic contractile activity in the distal oesophageal body was confirmed. Peristaltic contractions proceeded along the oesophageal body over the background tonic contraction. Neostigmine and erythromycin enhanced (20-30%) whereas bilateral vagotomy and atropine strongly decreased oesophageal tone (50-60%). However, l-NNA increased (40%) and sildenafil decreased oesophageal tone (30%). Therefore, tonic contractile activity in the oesophageal body is mainly caused by a continuous cholinergic excitatory input. A nitric oxide inhibitory mechanism may have a complementary role in the regulation of oesophageal tone.

Dysphagia in Parkinson's disease. Assessment by solid phase radionuclide scintigraphy.

Patients with Parkinson's disease often experience dysphagia, in which case food seems to be blocked in the throat. The patient must swallow over and over to get it down. A radionuclide solid phase esophageal motility study was conducted to evaluate esophageal function of patients with Parkinson's disease. Twenty-seven patients and 27 age-matched normal volunteers were studied. Each subject was placed in the supine position above a gamma camera linked to a computer and was given a 4 mL bolus of solid gelatin containing 75 MBq Tc-99m pertechnetate. Data were acquired in the list mode. A computer routine was used to calculate the total mean transit time, the residual fraction after the first swallow, and the retrograde index. The preliminary results suggest: 1) patients with Parkinson's disease display significantly slowed transit time when compared with normal age-matched controls, and 2) dysphagia of Parkinson's disease may improve with medication. A solid phase esophageal motility study may be used as a monitor of dysphagia in patients with Parkinson's disease in our future studies.

Meal area index: a new technique for quantitative assessment in achalasia by ambulatory manometry during eating.

Ambulatory non-perfused oesophageal manometry was used to study oesophageal body function during consumption of a full meal in patients with achalasia. A measure of oesophageal body activity (the meal area index) was developed by calculating the total area under the pressure curve during eating, above the preprandial baseline oesophageal pressure, per meal minute. Untreated patients with achalasia (n = 13) were compared with normal subjects (n = 42), patients with benign stricture (n = 9) and patients with achalasia who had undergone Heller's myotomy (n = 17). The results showed a high meal area index in achalasia, due to a rise in baseline oesophageal pressure and frequent high-amplitude contractions during eating. This was not seen in normal subjects or patients with stricture. The high meal area index was abolished by successful Heller's myotomy but remained in two patients with persisting dysphagia. Sustained high intraoesophageal pressure is generated during consumption of a solid meal in untreated achalasia, resulting in a unique manometric profile. Manometry during eating using the meal area index permits quantitative assessment of oesophageal body function in achalasia and may aid in the assessment of response to treatment.

Manometry and radiology. Complementary studies in the assessment of esophageal motility disorders.

The relationship between radiological and manometric findings in esophageal motility disorders is poorly understood. Therefore, 20 subjects (4 normal; 13 diffuse spasm; 3 other motility disorders) were studied using synchronous manometry and videofluoroscopy with alternate 5-ml and 10-ml barium swallows. A total of 181 swallows were analyzed. Concordance between manometry and fluoroscopy was excellent for individual swallows (98%), groups of 5 swallows (97%), and final diagnoses (90%). Contraction onset intervals less than 0.8 s apart over 5 cm (velocity greater than 6.25 cm/s) were critical in determining abnormal bolus transit (98% sensitivity and positive predictive value). Radiologically, segmental tertiary activity (complete luminal obliteration) was always associated with disrupted primary peristalsis, but nonsegmental tertiary activity was often seen with normal bolus transit and did not have a specific manometric correlate. Four patterns of interrupted peristalsis radiologically were found--segmental tertiary contractions, a generalized esophageal contraction, absence of motor activity, or discoordinated "to-and-fro" movement. Surprisingly, nearly complete barium clearance occurred by the first two mechanisms in two thirds of swallows. Thus, the authors believe radiology and manometry are both excellent studies for identifying abnormal esophageal peristalsis. In difficult cases, these tests give complementary information because radiology assesses bolus movement while manometry provides quantitative pressure data.