What standardization should be adopted in scintigraphy to evaluate lower esophageal sphincter dysfunction?
D. d'Ugo, V. Valenza, G. Castrucci, V. Porziella, O. Giacinto,
G. d'Andrea, G. Galli (Rome)
The development of computer based data processing has significantly highlighted the role of nuclear medicine in the quantitation of physiologic events in the digestive tract. Gastric emptying scintigraphy, introduced in 1966 by Griffith  whilst the evaluation of esophageal emptying function using a radionuclide esophageal transit study (RETS), was initially proposed by Kazem, in 1972 ; in 1979, Tolin  described the first quantitative esophageal scintigraphic measurement. Today RETS represents an easily performed physiologic test that is certainly well tolerated by patients who generally prefer this technique over esophageal manometry or 24-hour pH study. Moreover, it is relatively inexpensive and available to an average nuclear medicine lab. Even if esophageal scintigraphy cannot be considered as a first-line test for all kinds of dysphagia, the evaluation of "lower esophageal sphincter dysfunctions" is a common indication for a radionuclide esophageal transit study: as far as primary esophageal motor disorders are concerned, according to the data that have been published up to date, this unique quantitative functional test has shown a diagnostic sensitivity ranging from 100%  to 97%  compared with the gold standard represented by esophago-manometry. Such sensitivity is decreased to 92% , whenever the motor dysfunction is associated or is secondary to a gastroesophageal reflux disease, and to 75% if the esophageal transit is evaluated only by a solid bolus scintigram [6). As regards gastroesophageal reflux (GER) alone, it has been demonstrated that the radionuclide test is much less sensitive and cannot be compared to the accuracy of 24-hour pH study; it nevertheless assumes a relevant clinical role when pediatric reflux is concerned. On the other hand, it has been stated that scintigraphy may be considered as the diagnostic gold standard in the evaluation of gastric emptying [7, 8].
In our series of 118 consecutive patients, a total of 76 functional esophageal diseases (achalasia = 26, hypertensive LES = 3, diverticula = 15, diffuse esophageal spasms
(DES) = 3, non-cardiac chest pain with a diagnosis of nutcracker esophagus or non-specific motor disorder = 16, scleroderma or peptic strictures = 13) underwent a complete esophageal motility study plus a radionuclide transit study ("a" technique). In a selected subset of
32 patients with "LES dysfunction" (achalasia + hypertensive LES + hypertensive LES in DES) the sensitivity of our radionuclide test compared with the manometric gold standard has been 96.8% (31/32 total cases); this percentage rises up to 100%, if only achalasia and hypertensive LES patients are considered. Similarly to what has been reported by others, in a further subset of 42 patients with GER who underwent 24-hour pHmetry plus radionuclide gastroesophageal study ("b" technique), our personal observation has confirmed the limited diagnostic value of this type of scintigraphy in the detection and evaluation of gastroesophageal reflux: in this context we have found a sensitivity of 26.6% (4/15 cases with positive pHmetric findings) and a false positive rate of 11.1% (3/27 cases with normal pHmetric findings). In our view, these negative figures are balanced by the excellent results of radionuclide gastric emptying studies: such information is in any case beyond the subject of our paper and therefore it will not be discussed herein.
It has been commonly stressed that the reproducibility of scintigraphic results is impaired by a number of different technical factors that may potentially affect the radionuclide esophageal transit study, such as the bolus of choice (liquid, solid or semi-solid), the patients' position (clinostatic or orthostatic), the preferred radio-isotope, the conduction of the test and the acquisition of quantitative data.
Provided that the test is accomplished with the same technical modalities, the reproducibility of the resulting esophageal transit times has shown intraday variations
< 10% and interday variations < 12% ; these data are clearly affected by the patients' position, whereas the transit times are invariably decreased if the patient is sitting or standing compared to the supine position [9-11]. The evaluation of residual radioactivity after the completion of the test appears to be much less reproducible, with a reported intraday variation up to 38% and an interday variation of 35% .
In order to overcome such problems, we had previously proposed [12, 13] a standardized technique for the study of esophageal transit ("a" technique) and the detection of GER ("b" technique), either by liquid or solid bolus; nevertheless the low sensitivity of the solid phase test that has been evidenced through the years has prompted us to discard this part of the evaluation. Today, solid radionuclide bolus continues to represent our contrast medium of choice just for the scintigraphic evaluation of gastric emptying; this technique will not be discussed in the present paper.
Radionuclide esophageal transit study
Patients preparation requires a minimum 3-hour fasting and a total avoidance from smoking in the day of the examination. In our protocol, patients are evaluated in the upright position for two main reasons:
- physiologic transit is more commonly associated with this position;
- eventual aspiration has less serious consequences when patients are standing or sitting.
Data acquisition begins with a liquid swallow; patients stand in an upright anterior oblique position close to a gamma-camera with a low energy all-purpose collimator that is interfaced to a computer. The field of view encompasses the mouth, pharynx, thorax and - in shorter subjects - a portion of the abdomen. The oro-pharyngeal area is highlighted by cobalt markers placed on the skin at the cricoid region and the mandibular angle. A "blank test" with 10 ml unmarked water is preliminarily done, instructing the patient to perform one single swallow with no other swallows in the next 30 seconds; the aim of this step is to lubricate the mucosae and to reduce the anxiety of the patient which may affect the final results. A bolus of 10 ml of water additioned with 37 MBq (1 mCi) of 99m-Tc-colloid are then administered and the patient is told to keep the radioactive liquid in the mouth until asked to swallow, according to the previous instructions. Computer data acquisition is started immediately before the swallow and it is conducted in a dynamic mode for 60 seconds at a frame rate of 8/sec (0.125 msec per frame) with an image matrix of 64x64 pixels. If after 60 seconds the entire bolus or part of it fails to reach down to the gastric cavity, the patient is asked to drink 100 ml of plain water in order to ascertain if the bolus can be washed into the stomach.
Qualitative analysis, based upon the observation of single frames and sequential imaging, provides useful information on the morphology of the pharynx and esophagus (diverticula, dilatations, strictures, spasms), the progression of the bolus (fragmented or compact, retrograde contractions, pharyngo-oral or pharyngo-nasal regurgitation), the eventual bolus retention (partial or total stasis) or aspiration into the airway.
Quantitative analysis is conversely based upon computing the time/activity curves obtained by the oral region, the pharynx, the esophagus and the stomach; when the transit is altered, the esophagus is divided into three regions of interest (ROI) for a separate evaluation. Four objective parameters are derived by the time/activity curves :
1) Oro-pharyngeal transit time (OTT): time needed for the bolus to leave the mouth. This curve is characterized by a rapid decrease of the activity in the mouth, from 100% to less than 5%; such an event generally takes less than 1 second.
2) Pharyngo-esophageal transit time (PTT): time interval between the entrance and the exit of the bolus from the pharynx. In normal subjects the curve shows a rapid increase from
0% to 100% of the activity, followed by an equally rapid decrease to 0%; such an event takes 1.2 seconds or less, with a residual activity of less than 5%.
3) Esophageal transit time (ETT): time interval between the entrance and the exit of the bolus from the esophagus. In normal subjects the curve shows a rapid increase of the activity followed by a slower decrease; normally, with orthostatic swallows the residual activity is less than 10% after less than 10 seconds ( average = 5.5 sec. + 2 sec. SD ).
4) Retention index (RI): amount of activity retained in the esophagus after 10 and 60 seconds. In normal subjects the RI is < 10% after 10 seconds; according to O'Connor  altered RIs may be used for grading the underlying motor disorder.
A further parameter not directly derived from the time/activity curves is represented by the wash-out test: after the completion of the dynamic study, normally is administered a total of 100 ml of plain water to all patients showing a residual activity of more than 10%. This test evaluates the late emptying of eventual diverticula and is a useful aid in the detection of the primary cause for the bolus retention: in case of LES dysfunctions (achalasia or hypertensive LES) there is an evident stasis with a residual activity reaching up to 70-100% and the wash-out causes just a partial emptying; in other kinds of primary esophageal motor disorder the residual activity is also high (30-70%), but it can be almost completely washed-out; in cases of mucosal damage (esophagitis) there is a limited stasis (residual activity = 20-35%) that does not decrease after wash-out or even increases with spontaneous refluxes.
Gastroesophageal reflux detection
The radionuclide evaluation of reflux is commonly peformed in association with RETS. After the completion of the esophageal study, 300 ml of plain water and lemon juice mixed in equal doses are administered. The patient is firstly instructed to perform repeated Valsalva maneuvers and then placed in a supine position beneath the gamma camera; the field of view must encompass both the esophagus and the stomach. Starting from the beginning of a series of Valsalva maneuvers, dynamic images are acquired for 5 minutes at a frame rate of 1/5 sec. An image matrix of 64x64 pixels is used.
Also under such circumstances our study implies a qualitative and a quantitative analysis; the first is based upon the visual evidence of a reflux, documented by sequential imaging. The quantitative analysis consists in the computing of the esophageal time/activity curves; during the test the number of reflux episodes may be registered and their entity is quantified. Refluxes of more than 4% of the total administered dose are conventionally considered as pathologic .
In conclusion, radionuclide esophageal transit study has shown to be an useful and cost-effective research tool in the evalutation of most kinds of functional dysphagia, dependent or independent of the presence of a "LES dysfunction". Scintigraphy is unique in providing quantitative information, but up to date the relevance of its clinical role is still to be defined and one of the main reasons for that consists in the lack of reproducibility of this test. Different laboratories are still using different techniques and an effort towards standardization of the method is certainly needed.
Figure 1. Preoperative RETS in a patient with achalasia. Cine-images: esophageal dilation with retention of bolus.
Figure 2. Postoperative RETS in the same patient that in Figure 1. Cine-images: the esophagus has regular form and normal transit.
Figure 3. Preoperative RETS in the same patient that in Figure 1. ROIs and curves: total esophageal retention. TT = 52"; RI = 100% at 10" and 60".
Figure 4. Postoperative RETS in the same patient that in Figure 1. ROIs and curves: normal esophageal transit. TT = 9.6"; RI = 12% at 10".
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