Observer variability of visible light spectroscopy during upper endoscopy

The abdominal aorta delivers three branches to the gastrointestinal tract: the
celiac arty (CA), the superior mesenteric artery (SMA) and the inferior
mesenteric artery (IMA). Between these vessels exists an extensive collateral
circulation. When one or more of these mesenteric arteries becomes significant
stenotic and the collateral circulation is insufficient, the oxygenated blood
supply to the gastrointestinal tract can decrease resulting in chronic
mesenteric ischemia (CMI)(1, 5-7). CMI is mostly caused due to atherosclerotic
stenosis of the supplying arteries, but other underlying mechanisms are
arterial stenosis based on vasculitis, median arcuate ligament syndrome (MALS)
or non-occlusive mesenteric ischemia due to a decreased cardiac output(8).

Patients with CMI suffer often from postprandial pain and unexplained weight
loss due to fear of eating. During physical examination a bruit in the abdomen
can be heard(4). The diagnosis of CMI is a clinical challenge because CMI is
difficult to distinguish by the frequent incidence of chronic abdominal pain
and the high prevalence of stenosis of one or more mesenteric arteries in the
general population(9-12). The current diagnostic work-up to diagnose CMI
comprises clinical symptoms, radiological imaging and a functional test to
detect mucosal ischemia (tonometry or visible light spectroscopy (VLS))(1, 5,
13, 14). Subsequently, all patients will be discussed in a
multidisciplinary team consisting a gastroenterologist, a vascular surgeon and
an interventional radiologist, all specialized in CMI leading to an
expert-based consensus
diagnosis(1).

Tonometry combined with radiological imaging has shown to be accurate in the
detection of CMI(5, 6, 13, 15). Previously, 24-hours tonometry was used in the
diagnostic work-up of CMI in our centre. However, tonometry has an invasive
character. Therefore, we currently use endoscopic VLS as mucosal ischemia test
in our centre. VLS is a minimally invasive test, performed during upper
endoscopy with no requirement of hospital admission.

VLS measures the mucosal capillary haemoglobin oxygen saturation(16). VLS
measurement is performed using a fiberoptic probe that uses white light to
detect differences in the absorption spectra of the oxygenated and deoxygenated
haemoglobin molecules(16). This saturation reflects the adequacy of the mucosal
blood flow. In patients diagnosed with CMI the mucosal saturation was
significant lower compared to healthy individuals(1, 3). VLS measurements are
performed at three different locations during upper endoscopy: the antrum of
the stomach, duodenal bulb and the descending duodenum. Based on cut-off values
determined by van Noord et al. in CMI suspected patients, the outcomes are
positive for ischemia if the measured saturation value is lower than 63% in the
antrum, 62% in the duodenal bulb and 58% in the descending duodenum in fasting
state.

The diagnostic accuracy of VLS measurements appears to be similar with prior
used tonometry. The sensitivity and specificity rates are 90% and 60%,
respectively(1). Whether VLS measurements are also reproducible is not clear
yet. The rationale of this study is to determine the inter-observer and
intra-observer variability of the VLS measurements in order to establish the
reliability and reproducibility of this method.

References:
1. Van Noord D, Sana A, Benaron DA, Pattynama PM, Verhagen HJ, Hansen BE, et
al. Endoscopic visible light spectroscopy: a new, minimally invasive technique
to diagnose chronic GI ischemia. Gastrointest Endosc. 2011;73(2):291-8.
2. van Noord D, Sana A, Moons LM, Pattynama PM, Verhagen HJ, Kuipers EJ, et al.
Combining radiological imaging and gastrointestinal tonometry: a minimal
invasive and useful approach for the workup of chronic gastrointestinal
ischemia. Eur J Gastroenterol Hepatol. 2013;25(6):719-25.
3. Friedland S, Benaron D, Coogan S, Sze DY, Soetikno R. Diagnosis of chronic
mesenteric ischemia by visible light spectroscopy during endoscopy.
Gastrointest Endosc. 2007;65(2):294-300.
4. Mensink PB, Moons LM, Kuipers EJ. Chronic gastrointestinal ischaemia:
shifting paradigms. Gut. 2011;60(5):722-37.
5. Mensink PB, van Petersen AS, Kolkman JJ, Otte JA, Huisman AB, Geelkerken RH.
Gastric exercise tonometry: the key investigation in patients with suspected
celiac artery compression syndrome. J Vasc Surg. 2006;44(2):277-81.
6. Mensink PB, van Petersen AS, Geelkerken RH, Otte JA, Huisman AB, Kolkman JJ.
Clinical significance of splanchnic artery stenosis. Br J Surg.
2006;93(11):1377-82.
7. van Noord D, Kuipers EJ, Mensink PB. Single vessel abdominal arterial
disease. Best Pract Res Clin Gastroenterol. 2009;23(1):49-60.
8. Clair DG, Beach JM. Mesenteric Ischemia. N Engl J Med. 2016;374(10):959-68.
9. Roobottom CA, Dubbins PA. Significant disease of the celiac and superior
mesenteric arteries in asymptomatic patients: predictive value of Doppler
sonography. AJR Am J Roentgenol. 1993;161(5):985-8.
10. Park CM, Chung JW, Kim HB, Shin SJ, Park JH. Celiac axis stenosis:
incidence and etiologies in asymptomatic individuals. Korean J Radiol.
2001;2(1):8-13.
11. Hansen KJ, Wilson DB, Craven TE, Pearce JD, English WP, Edwards MS, et al.
Mesenteric artery disease in the elderly. J Vasc Surg. 2004;40(1):45-52.
12. Wilson DB, Mostafavi K, Craven TE, Ayerdi J, Edwards MS, Hansen KJ.
Clinical course of mesenteric artery stenosis in elderly americans. Arch Intern
Med. 2006;166(19):2095-100.
13. Sana A, Vergouwe Y, van Noord D, Moons LM, Pattynama PM, Verhagen HJ, et
al. Radiological imaging and gastrointestinal tonometry add value in diagnosis
of chronic gastrointestinal ischemia. Clin Gastroenterol Hepatol.
2011;9(3):234-41.
14. Otte JA, Geelkerken RH, Oostveen E, Mensink PB, Huisman AB, Kolkman JJ.
Clinical impact of gastric exercise tonometry on diagnosis and management of
chronic gastrointestinal ischemia. Clin Gastroenterol Hepatol. 2005;3(7):660-6.
15. Mensink PB, Geelkerken RH, Huisman AB, Kuipers EJ, Kolkman JJ. Twenty-four
hour tonometry in patients suspected of chronic gastrointestinal ischemia. Dig
Dis Sci. 2008;53(1):133-9.
16. Benaron DA, Parachikov IH, Cheong WF, Friedland S, Rubinsky BE, Otten DM,
et al. Design of a visible-light spectroscopy clinical tissue oximeter. J
Biomed Opt. 2005;10(4):44005.
17. Walter SD, Eliasziw M, Donner A. Sample size and optimal designs for
reliability studies. Stat Med. 1998;17(1):101-10.

Primary objectives:
- to determine the inter-observer variability of VLS
- to determine the intra-observer variability of VLS
Secondary objectives:
- to determine the inter-observer variability of VLS per specific measurement
location: antrum of the stomach, duodenal bulb and descending duodenum
- to determine the intra-observer variability of VLS per specific measurement
location: antrum of the stomach, duodenal bulb and descending duodenum

Inclusion
Patients planned for upper endoscopy at the department of Gastroenterology and
Hepatology, are asked to participate in our study. The patients will receive a
Patient Information Folder (PIF) about this study. Furthermore, the patient
will be asked permission to be called by one of the investigators minimally 24
hours later. Questions of the patient can be answered during the call and
participating in the study by the patient can be confirmed.
If the patient gives informed consent for this study, the upper endoscopy will
take place with the additional VLS measurements. If the patient declines
informed consent, the upper endoscopy will take place without the additional
VLS measurements.

Upper endoscopy
Upper endoscopy can be performed with or without sedation of the patient,
depending on the preferences of the patient and the endoscopist. Sedation will
be administered as midazolam 2.5-5 mg intravenously and combined with fentanyl
0.05 mg prior to the upper endoscopy. To prevent luminal spasms butylscopalamin
20mg is admitted intravenously before the start of VLS measurements. As to
minimize the effect of confounding by cardiopulmonary diseases we aim to keep
peripheral oxygen saturation above 94% by administering oxygen intra-nasally.
The systemic oxygen saturation is continuously monitored by pulse oximetry.

VLS measurements will be performed during upper endoscopy using a fiberoptic
catheter-based oximeter (T-Stat 303 Microvascular Oximeter, Spectros, Portola
Valley, California, USA), that can be passed through the accessory channel of
the endoscope. Measurements of the oxygen saturation will be performed at three
locations in the stomach and duodenum: antrum of the stomach, duodenal bulb and
descending duodenum. After irrigation of the target area and positioning the
probe approximately 1-5 mm above the mucosa, three repeated readings will be
taken of different areas of each location once a stable reading is obtained
with less than 5% variation in panel read-out. The average of the three
readings per location will be regarded as the actual measurement of that
specific location.

For the patients included for the intra-observer variability analysis, the
endoscopist will repeat the three measurements as described previously. The
endoscopist is blinded for the VLS outcomes. For the intra-observer variability
the same endoscopist will perform the measurements in all patients.
For the patients included for the inter-observer variability analysis, a second
endoscopist will continue the upper endoscopy and repeat the VLS measurements
as described previously. Both endoscopists are blinded for the VLS outcomes.
For the inter-observer variability the same two endoscopists will perform the
measurements in all patients.
All VLS measurements will be written down by one of the investigators of this
study. This investigator will also export the digital output of the device to
confirm the noted values.

After the upper endoscopy, the patient will be brought to the endoscopy
recovery room if the patient received sedation. The time to sleep off the
sedative is the usual amount of time after an upper endoscopy procedure. When
no sedation is used, the patient is allowed to go immediately after the upper
endoscopy.

Participation in our study includes once repeated mucosal saturation
measurements with VLS during one planned upper endoscopy. To participate in
this study no additional hospital visits are needed. The research investigator
can be contacted any time prior to procedure, should the patient have any
further questions or decide to withdraw from the study which is possible at any
time for any reason if a patient wish to do so. After withdrawal of the patient
new patients will be included until the required number of patients is reached
for the study.

Follow-up
Participants will not be followed-up after the upper endoscopy for this study.

Participation in this study will bring no additional benefit for the individual
patient.
The whole procedure will take 5 to 10 minutes longer compared to patients that
do not participate in this study.