Bile Reflux and Bilitec System

What is DG- or DGE- Reflux? Retrograde movement of duodenal content such as bile, pancreatic and enteric juices to the stomach and esophagus: Duodeno-Gastric Reflux (DGR) Duodeno-Gastro-Esophageal Reflux (DGER) Acid reflux Bile reflux Esophagus LES Gallblader Duodenum Stomach Sphincter of Oddi Pancreas

Indications Patients with symptoms of gastroesophageal reflux (GER) Evaluation in patients with complications of GER such as: Barrett’s esophagus Strictures Ulceration of the esophagus Patients that have failed medical therapy for acid reflux Patients with poor response to medical treatment of reflux esophagitis Postgastrectomized patients with reflux symptoms Pre- and postoperative evaluation of anti-reflux surgery

How to Measure DG- and DGE- Reflux The Bilitec System has been recognized as being the best method for detecting duodenogastric/bile reflux 4 studies has validated that: Bilirubin is a suitable marker to measure the presence of bile acids – i.e. demonstrate that there is a correlation between Bilitec readout (presence of bilirubin) and presence of biliary salts In-vivo spectrophotometric reading of Bilitec is reliable - i.e. compare Bilitec reading with spectrophotometric measurements carried out on samples drawn from the stomach and/or esophagus; this could be defined as optical validation

Why is Bile Reflux Important? The main reason to measure bile-reflux is based on the indications that in GERD, duodenal juice is an important component in the refluxed gastric juice that causes damage to the esophageal mucosa.

Composition of Refluxed Juice in GERD* *From DeMeester et al: Biology of Gastroesophageal Reflux Disease, 1999

Is measurement of DGR/DGER relevant? Bile Reflux Increased Risk for Mucosal Damage The clinical benefit of the Bilitec system is to identify patients at risk for: Mucosal injury Barret’s esophagus High grade dysplasia. Select patients for further examination of esophageal damage (e.g. biopsy) and for whom anti-reflux surgery should be considered

Examples of Bile reflux studies “Patients with erosive esophagitis and Barrett’s metaplasia have increased esophageal exposure to duodenal juice compared to normal subjects”, Kauer et al, 1995 “The combined reflux of gastric and duodenal juices causes severe esophageal mucosal damage. The vast majority of duodenal reflux occurs at a pH range of 4 to 7, at which bile acids, the major component of duodenal juice, are capable of damaging the esophageal mucos”, Kauer et al, 1995 “Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa” Fein et al, 1997 “The prolonged simultaneous attack of bile and acid may play a key role in the development of Barrett's metaplasia”, Menges et al, 2001 ...

Detection of Bile/Bilirubin Bilitec uses two wavelengths for detection of bilirubin: 470 nm and 565 nm The absorbance is calculated from Beer’s law based on light intensities transmitted in absence and presence of absorbing substance (bilirubin) The absorbance is proportional to the concentration of bilirubin however, Bilirubin is only a marker and the knowledge of its concentration is not important from a clinical point of view Bilitec measures the exposure time of bile-containing reflux to the gastric-/esophageal mucosa Absorption spectrum of a gastric sample containing bile

Normal values

Selection of Absorbance Threshold A default threshold of 0.14 in absorbance values is considered in all the validations. This is the threshold introduced by P. Bechi: “it is the lowest value where the absorbance can be considered as an actual measurement of bilirubin and not as noise due to mucus in the stomach” There are different opinions on the threshold level, and in other studies higher absorbance values are used as threshold (e.g. 0.2 and 2.5). From presentation by T.DeMeester, DDW, 2001

Correction of absorbance values rel. pH Is Bile reflux underestimated in an acidic environment? This is a controversial subject discussed in a few papers: J.Richter: 30% underestimation of Bilitec reading for pH<3.5 P.Bechi: 18% underestimation of Bilitec reading for pH<3.5 J.Janssens: such underestimation has only minor effect on the results of Bile reflux testing and thereby, have no clinical impact. Only few centers consider this in their analysis of Bile reflux

Bilitec System Components Carrying case Cable for serial interface Optical calibration chambers Manuals Fiber Optic Bile Catheter Single-use catheter, length 175 cm, diam. 3.0 mm Bile Upload and analysis option for P98 pH Note: Available in US when 510(k) cleared Fiber Optic Catheter

The Bilitec Procedure Set-up Bilitec 2000 device Set average time and 1 or 2 channels Calibrate Bilitec system in water Intubate patient with single-use fiber optic probe w/wo pH recording Start the measurement Standard Diet: abs. < 0.05 at 470 nm Patient Keeps Diary: symptoms & events Extubate patient, upload and analyze data

Features and Benefits

Polygram Bile Analysis Software Technical Review of the Software

Protocol Settings 0-4 channels pH and 1-2 channels Bile Adjustment of Bile values

Protocol Settings Analysis of Bile Reflux:

Bile Analysis

Upload Procedure for Combined Studies Upload pH data first …awaiting data from the Bilitec2000 device connect Bilitec to the serial port go to data transfer mode and press “Enter” NB: Uses Digitrapper time for Combined Studies - the Bilitec 2000 has no Clock

Capture View

Review view

Combined pH and Bile Report

Pitfalls Variety of substances in food may result in false-positive readings. - Therefore, it is important to use a modified diet. If long periods of bile reflux are recorded, this may be simply a “contaminated” detector or other artifact. Presence of blood may distort the readings obtained from the device Underestimation of bile reflux in an acid environment (pH < 3.5)