Flemming Holbæk Gravesen

Transoral Endoscopic Fundoplication in the Treatment of Gastroesophageal Reflux Disease: The Anatomic and Physiologic Basis for Reconstruction of the Esophagogastric Junction Using a Novel Device

Objective:To determine the safety, mechanism of action, immediate postprocedural anatomic impact on the esophagogastric junction, and short-term efficacy of the first entirely endolumenal antireflux procedure. Background:A safe and effective endoscopic antireflux procedure remains elusive. Transoral endolumenal surgery has enormous potential for the treatment of gastroesophageal reflux disease (GERD) and other esophagogastric diseases. A canine model was used to study a novel endoscopic device, which allows for creation of an endoluminal fundoplication. Methods:The transoral incisionless fundoplication (TIF) was performed in 21 canines in a phase I feasibility and safety study, and in 21 canines in a phase II study that included a detailed objective assessment of the effects of 2 variants of the TIF procedure (TIF 1.0 and TIF 2.0) versus sham on esophageal physiology and esophagogastric junction (EGJ) anatomy. Results:In phase I, TIF provided a safe and feasible endolumenal therapy for GERD, with histologic data that demonstrated serosal fusion of approximated full-thickness tissue plications and durability of the fundoplication. TIF procedures effectively reduced cardia circumference and improved Hill classification grade. In phase II, the TIF 2.0 procedure achieved normalization of distal esophageal acid exposure and increased lower esophageal sphincter (LES) pressure and length based on objective testing over a 2-week period. TIF 2.0 demonstrated superior results to TIF 1.0, and valve appearance and location exhibited similarity to the Nissen fundoplication by vector volume analysis. Conclusions:The TIF procedure is safe and results in a durable and functional fundoplication as well as a platform for further development and modification of the procedure, which can be use to impact outcome. This work provides the foundation for human translation and assessment of long-term outcomes.

An endoscopic method for thermal and chemical stimulation of the human oesophagus

Abstract  Previous methods for visceral thermal stimulation have lacked control of the temperature rate and visual inspection of the organ. The aims of this study was to develop a method for linear control of heat stimulation in the human oesophagus combined with endoscopy, to assess the reproducibility of this method and to investigate sensitivity to thermal stimulation of the distal oesophagus before and after acid perfusion. A probe with a 2.8 mm endoscope inside was constructed permitting heat and chemical stimulation. Three different temperature ramps were applied in the distal oesophagus in 12 healthy subjects by recirculation of heated water in a bag. Endoscopy of the oesophageal mucosa was performed prior to experimental stimulation. The temperature, the time of stimulation and the area under the temperature curve (AUC) were measured at the pain detection threshold. Thermal stimulation was repeated after perfusion of the oesophagus with acid. The method was tested on two subsequent days to assess reproducibility. All subjects had a normal endoscopic examination. Day‐to‐day reproducibility was good for the three temperature ramps (intra‐class correlations >0.6). The subjects tolerated less heat stimulation, a decrease in AUC (P = 0.0003), a decrease in time to pain detection threshold (P = 0.005) and decreased temperature at pain detection threshold (P = 0.0001) after acid perfusion. The slow ramp was the most sensitive, showing a decrease in AUC of 29%. The present method was easily implemented and showed good reproducibility. It can potentially be used in basic experiments, drug and clinical studies as it provides a controllable thermal stimulus.

Reproducibility of axial force and manometric recordings in the oesophagus during wet and dry swallows.

Background  Manometry is the golden standard to diagnose oesophageal motility disorders but it gives an indirect picture of the peristalsis by measuring radial force only. A novel probe design using electrical impedance recordings enabled axial force and manometry to be recorded simultaneously. Using this method the aims were to study the amplitude and duration of peristaltic contractions, to test the correlation between axial force and manometry, and the reproducibility of the method.

A new distensibility technique to measure sphincter of Oddi function

Background  Evaluation of the biliary tract is important in physiological, pathophysiological, and clinical studies. Although the sphincter of Oddi (SO) can be evaluated with manometry, this technique has several limitations. This may explain the difficulties in identifying pathophysiological mechanisms for dysfunction of the SO and in identifying patients who may benefit from certain therapies. To encompass problems with manometry, methods such as the functional lumen imaging probe (FLIP) technique have been developed to study GI sphincters. This study set about miniaturising the FLIP probe and validating it for measurements in the SO. In order to get a better physiological understanding of the SO the aims were to show the sphincter profile in vivo and motility patterns of SO in pilot studies using volunteers that were experiencing biliary type pain but had normal SO manometry.

Viscosity of food boluses affects the axial force in the esophagus

AIM To study the effect of viscosity on axial force in the esophagus during primary peristalsis using a newly validated impedance-based axial force recording technique. METHODS A probe able to simultaneously measure both axial force and manometry was positioned above the lower esophageal sphincter. Potable tap water and three thickened fluids were used to create boluses of different viscosities. Water has a viscosity of 1 mPa·s. The three thickened fluids were made with different concentrations of Clinutren Instant thickener. The viscous fluids were in appearance comparable to pudding (2 kPa·s), yogurt (6 kPa·s) and slush ice (10 kPa·s). Six healthy volunteers swallowed 5 and 10 mL of boluses multiple times. RESULTS The pressure amplitude did not increase with the bolus viscosity nor with the bolus volume whereas the axial force increased marginally with bolus volume (0.1 > P > 0.05). Both techniques showed that contraction duration increased with bolus viscosity (P < 0.01). Association was found between axial force and pressure but the association became weaker with increasing viscosity. The pressure amplitude did not increase with the viscosity or bolus volume whereas the axial force increased marginally with the bolus size. CONCLUSION This indicates a discrepancy between the physiological functions that can be recorded with axial force measurements and pressure measurements.

Measurement of the axial force during primary peristalsis in the oesophagus using a novel electrical impedance technology

The oesophagus serves to transport food and fluid from the pharynx to the stomach. Oesophageal function is usually evaluated by means of manometry which is a proxy of the force in the radial direction. However, force measurements in the axial direction will provide a better measure of oesophageal transport function. The aim of this study was to develop a probe based on electrical impedance measurements to quantify the axial force generated by oesophageal contractions, i.e. probe elongation was associated with the axial force. Calibration with weights up to 200 g was done. The dispersion, creep, temperature and bending dependence were studied at the bench. Subsequently, the probe was tested in vivo in a healthy human volunteer. The probe showed good reproducibility and the dispersion was <0.04. Some dependence on temperature, creep and bending was found. Interpolation of the calibration curves made it possible to compensate for temperature fluctuations. The maximum deviation was 6.1 +/- 3.7% at loads of 50 g. The influence of creep showed a maximum net creep of 6.1 g after 8 s. The swallowed bolus size correlated with the axial force measurements (P = 0.038) but not with manometric measurements. In conclusion, the new technique measures axial force in the oesophagus and may in the future provide valuable information about oesophageal function.

292 A NOVEL METHOD FOR THERMAL AND CHEMICAL STIMULATION OF THE HUMAN OESOPHAGUS

292 A NOVEL METHOD FOR THERMAL AND CHEMICAL STIMULATION OF THE HUMAN OESOPHAGUS I. Larsen *, B. Koch-Henriksen, Sø. Schou Olesen, A. Estrup Olesen, F. Gravesen, Aø. Mohr Drewes. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark; Center for Sensory-Motor Interactions (SMI), Department of Health Science and Technology, Aalborg University, Denmark, Aalborg, Denmark