Unsedated transnasal versus transoral sedated upper gastrointestinal endoscopy: A one-series prospective study on safety and patient acceptability

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Digestive and Liver Disease 40 (2008) 767–775

Digestive Endoscopy

Unsedated transnasal versus transoral sedated upper gastrointestinal endoscopy: A one-series prospective study on safety and patient acceptability I. Stroppa a,∗ , E. Grasso a , O.A. Paoluzi a , C. Razzini b , C. Tosti a , F. Andrei a , L. Biancone a , G. Palmieri c , F. Romeo b , F. Pallone a a

Gastrointestinal Unit, Department of Internal Medicine, Tor Vergata University, Rome, Italy b Cardiology Unit, Department of Internal Medicine, Tor Vergata University, Rome, Italy c Pathology Unit, Department of Biopathology, Tor Vergata University, Rome, Italy Received 25 October 2007; accepted 18 February 2008 Available online 18 April 2008

Abstract Background. While conventional oesophagogastroduodenoscopy is frequently performed under sedation to improve acceptability, transnasal oesophagogastroduodenoscopy would appear to be less invasive. Study aims. To compare diagnostic accuracy, feasibility, acceptability and safety of transnasal oesophagogastroduodenoscopy without sedation versus conventional oesophagogastroduodenoscopy under sedation. Patients. Following anxiety assessment, 30 dyspeptic patients underwent transnasal oesophagogastroduodenoscopy under local anaesthesia (lidocaine) and conventional oesophagogastroduodenoscopy under conscious sedation (i.v. midazolam) on two consecutive days. Transnasal oesophagogastroduodenoscopy was performed with an ultrathin and conventional oesophagogastroduodenoscopy with a standard endoscope. Methods. Safety, evaluated by monitoring cardio-respiratory functions. Acceptability, rated according to discomfort and preference between the two examinations. Diagnostic accuracy evaluated taking into account endoscopic patterns and adequacy of biopsy specimens for histology. Feasibility, defined according to endoscopic performance, quality of images and overall opinion of the endoscopist. Only gastric biopsies were evaluated. Results. All patients but one who refused conventional oesophagogastroduodenoscopy underwent both transnasal oesophagogastroduodenoscopy and conventional oesophagogastroduodenoscopy. No cardiorespiratory complications occurred during either technique. Majority of patients (87%) preferred transnasal oesophagogastroduodenoscopy. Examinations were completed in all cases, with comparable endoscopic patterns. All biopsy specimens were suitable for histology. Conclusions. Transnasal oesophagogastroduodenoscopy without sedation provides good diagnostic accuracy, is safer and better accepted than conventional oesophagogastroduodenoscopy under sedation and, therefore, represents a valid alternative in routine diagnosis of upper digestive tract diseases. © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Conscious sedation; Conventional oesophagogastroduodenoscopy; EGDS; Transnasal oesophagogastroduodenoscopy; Upper gastrointestinal endoscopy

1. Introduction

∗ Corresponding author at: Gastrointestinal Unit, Department of Intestinal Medicine, Tor Vergata University, Viale Oxford 81, 00133 Rome, Italy. Tel.: +39 06 20903753; fax: +39 06 20903740. E-mail address: [email protected] (I. Stroppa).

Conventional oesophagogastroduodenoscopy (C-EGDS), the method of choice in the diagnosis of inflammatory and neoplastic diseases of the upper gastrointestinal (GI) tract, although demonstrated to be safe and feasible in the majority of patients [1–3], is usually performed under sedation

1590-8658/$30 © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2008.02.033

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in order to improve acceptability. The drugs employed to induce sedation, namely benzodiazepines, and/or hypnotic drugs, such as propofol, may be associated with adverse events, mainly cardio-respiratory, such as hypoxia, arrhythmias, and hypotension, accounting for ∼50–60% of the complications related to EGDS [4,5]. Furthermore, sedation increases the costs of EGDS, recovery time and, therefore, delays discharge of the patient [6]. In order to reduce patient discomfort and increase safety, a transnasal approach to EGDS (T-EGDS) has been proposed, not requiring sedation. An ultrathin (UT) fiberscope (outer diameter 5.3 mm), is passed through the nose allowing complete examination of the oesophagus, stomach and duodenum [7]. Other Authors [8–14] have since confirmed the feasibility of unsedated TEGDS in comparison with C-EGDS under conscious sedation with benzodiazepines, showing a similar rate of successful EGDS with greater or comparable acceptability (minimal gagging, absence of retching, vomiting, choking and, thereby, the risk of aspiration) [15]. This early positive experience was not confirmed in later studies [16–18], limitations of T-EGDS having been reported, mostly related to the route of insertion, but also to the prolonged duration of the examination [16,17], pain upon insertion of the endoscope [17], failure of nasal insertion [16,18,19], and onset of epistaxis [16]. Three recent studies [19–21], comparing T-EGDS with C-EGDS, reported conflicting results. Finally, the safety of T-EGDS, in comparison to C-EGDS, has been assessed in almost all the studies appearing in the literature, by means of pulse oximetry, which provides information concerning respiratory function and heart rate but does not reveal possible cardiological changes, which have been reported during EGDS both in healthy subjects and in patients with heart disease [22]. Aim of the present study was to assess whether TEGDS would improve safety and acceptability of upper GI endoscopy, compared to C-EGDS, without loss of diagnostic yield. Data provide evidence that T-EGDS without sedation may represent a valid alternative to C-EGDS under sedation.

2. Materials and methods 2.1. Selection, recruitment and characteristics of patients From April 2005 to December 2006, our Unit performs about 1615 T-EGDS, of which 750 were outpatients. Thirty non-consecutive outpatients (4%) referred for EGDS were enrolled in the study. These patients volunteered to undergo both T-EGDS and C-EGDS within 48 h. Exclusion criteria: age <17 years, history of allergy or hypersensitivity to benzodiazepines and/or anaesthetics, ongoing anti-coagulant treatment, presence of a coagulation defect. Hospitalised patients were not considered eligible since submitting these subjects twice to EGDS was judged, by the investigators, as unethical. During the study period, a total of 750 outpatients

Table 1 Demographic data and indication for EGDS in the study population Parameters

No. of patients

Sex Male Female

16 14

Indication to EGDS Epigastric pain Pyrosis and acid regurgitation Anaemia Vomiting

19 9 1 1

Previous EGDS Yes No

14 16

EGDS: oesophagogastroduodenoscopy.

were asked for inclusion and 720 patients (96%) denied to participate in the study. Demographic data and indications to EGDS of the study population are outlined in Table 1. In these 30 patients (16 male, 14 female, age range: 28–55 years, mean 48.47 ± 13.37 S.D.) years, (range: 28–55), indication to EGDS was presence of epigastric pain in 19 patients, pyrosis and acid regurgitation in 9, anaemia in 1 and vomiting in 1. Overall, 14 patients had previously been submitted to C-EGDS, while the remaining 16 were undergoing EGDS for the first time. Patients entering the study were not required to pay any fee for EGDS and none received any grant for taking part in the investigation. Endoscopies were performed once written informed consent has been given and patients had had the opportunity to examine the study design, including detailed information regarding aims and procedures. The study had been approved by the hospital’s clinical research ethics committee on 19 November 2004. 2.2. Pre-endoscopy assessment, schedule, and medications The sequence of the endoscopic examinations was randomly assigned to each patient according to a computergenerated randomization list in blocks of five, 15 patients were submitted to T-EGDS and 15 to C-EGDS as first endoscopy. In order to avoid a possible bias due to both examinations being performed on a same day (so-called ‘memory effect’ of first EGDS, persistence of sedation when C-EGDS was performed first), or to being aware of the endoscopic diagnosis after the first EGDS, patients underwent the second EGDS after an interval of 24 h with no information being made available concerning the endoscopic findings at the first examination. All patients were interviewed before the first EGDS concerning indication to examination, recent and past clinical history, drug intake. A validated scale A of Hamilton [24] was used to score the level of anxiety before the investigation, which was graded as absent (score < 6), mild (score = 6–14), moderate (score = 15–20), or severe (score > 21). Patients evaluation was blinded regarding the scope used. All

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pre-endoscopy data, including personal demographic information, were recorded on an individual patient chart. Each patient received local anaesthesia with two puffs of lidocaine (Ecocain, MolteniDental, Florence, Italy) by means of a cannula in the oropharynx before C-EGDS and in each nostril before T-EGDS. Patients undergoing T-EGDS also received two puffs of naphazoline (Rinazina, SmithKline Beecham, Milan, Italy) in both nostrils, while those undergoing C-EGDS received a bolus of midazolam i.v., at a dose of 0.035 mg/kg body weight. The administration of this amount of midazolam was defined according to Italian National Health System rules, the mean dose of the drug being 2.81 (±0.73 S.D.) mg (range, 2–4). The antidote Flumazenil i.v., at a dose of 0.2 mg (Anexate, Roche, Milan, Italy), was given when indicated. No oxygen supplementation was routinely administered during endoscopy but was readily available, in the case of need. 2.3. Endoscopy C-EGDS was performed in all patients with a standard (9.8 mm) endoscope (Olympus GIF- 145, Olympus Italia, Milan, Italy) equipped with a CV-160 videoprocessor. TEGDS was performed using either a 5.9 mm UT instrument (Olympus GIF-XP160 Olympus Italia, Milan, Italy) or a 4.9 mm UT instrument (Olympus GIF-N180 Olympus Italia, Milan, Italy). Features of GIF-N180 are up/down angulation of 210◦ /180◦ with no right/left deflection and compatibility with the Olympus CV-160 videoprocessor used for standard endoscopes. Lack of the right/left deflection may be overcome by handling a little torque if necessary. These two UT endoscopes are similar in terms of optical features (120◦ field of view and 3–100 mm depth of field), inner operative channel (2.0 mm in size; use of the same type of biopsy forceps) and air/water nozzle for insufflation and cleaning the lens. For T-EGDS, patients were assigned, according to a computer generated randomization list in blocks of three, to the 5.9 mm UT endoscope (15 patients) and the 4.9 mm UT instrument (15 patients). In order to standardize endoscopic findings, all endoscopies were performed by the same two endoscopists (I.S., E.G.), both of whom had >20 years experience of digestive endoscopy. These two endoscopists were unaware of each other’s findings. Both types of EGDS were carried out with the patient in a left lateral recumbent position and the endoscope was introduced, after prior lubrication, under direct vision. In T-EGDS, the endoscope was passed through the nose after testing both nostrils approaching the middle meatus to evaluate the turbinates, the status of which was defined as normal or hypertrophic by direct visualization. Following this procedure, the endoscope was introduced through the larger meatus, and gently pushed into the nose under aspiration and, when necessary, with a slight rotation of the endoscope. Upon reaching the pyriform sinus, the patient was asked to swallow to facilitate progression of the endoscope into the oesophagus

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both in T-EGDS and C-EGDS. Endoscopy was carried out performing standard manoeuvres, i.e. visualizing the entire oesophagus, stomach and duodenum up to the second portion, and including the intra-gastric retroversion to assess the fornix. Quality of images, during both EGDS procedures, was evaluated according to luminosity and resolution, in panoramic view of the pylorus, in panoramic retroflexed view of the cardia, and in close (2–3 cm) observation of the mucosal surface, all parameters being scored using a numerical scale (1 = poor; 2 = inadequate; 3 = average; 4 = good; 5 = very good), as described elsewhere [12]. During EGDS, at least three biopsy specimens were collected from the stomach (antrum, body and fundus) of each patient, also in the absence of macroscopic lesions of the mucosa, to evaluate the presence of gastritis and Helicobacter pylori infection which were graded according to the updated Sydney system [25]. In the patient with anaemia, duodenal biopsies were not taken as antiendomisium and anti-transglutaminases seronegativity had already been shown and duodenal biopsy samples were already taken in a previous C-EGDS. Moreover, at time of the study, the patient had epigastric pain. Each EGDS was recorded on a VHS tape and the entire duration of the investigation was recorded on the patient chart. 2.4. Acceptability evaluation To evaluate the acceptability of EGDS, following each examination, all patients were questioned about discomfort or pain experienced during endoscopy, which was graded according to a 5-point Likert scale [28] (absent to very severe) and which of the two procedures would he/she be willing to undergo again should further EGDS be necessary. Patients evaluation was blinded in order that the patients could be assured that their doctor would not know the score given. 2.5. Safety evaluation During EGDS, vital functions were evaluated in all patients: cardiological activity and respiratory function were continuously monitored by electrocardiogram (ECG) and pulse oxymetry (Zoll M-series, Biotronix Seda, Milan, Italy), while blood pressure levels were measured and recorded in the patients’ records before (baseline), during (in oesophagus, stomach and duodenum) and 5 min after EGDS. Myocardial consumption was also evaluated by calculating heart systolic blood pressure rate (pulse rate × systolic pressure/100) [26,27]. 2.6. Post-endoscopy feasibility and diagnostic accuracy Endoscopists were asked to express their opinion regarding the endoscopes used to perform T-EGDS and C-EGDS by means of a questionnaire assessing the ability to perform standard endoscopic manoeuvres (insertion, frontal and intra-gastric retroflexed view, complete examination up to

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the second part of the duodenum, collection of biopsy specimens) and quality of images. Overall feasibility was also expressed using a 5-point Likert scale (poor to very good). In order to evaluate agreement of the endoscopic findings observed during T-EGDS and C-EGDS, a third endoscopist (L.B.) was asked to take part to the study in order to review the VHS recordings of all examinations. The level of agreement between endoscopic findings emerging from the two examinations was estimated on the basis of the diagnosis reached by the third endoscopist. In the event of disagreement between the two endoscopists, the diagnosis of the third endoscopist was considered as conclusive having been based on viewing of the two endoscopy tapes. The size of the biopsy specimens was measured by the pathologist (G.P.) before processing for histological assessment in order to compare the size of mucosal samples, collected during the two endoscopic investigations, according to the ability to reach an appropriate diagnosis at histology.

Table 2 Comparison of anxiety scores evaluated using Hamilton A scale in 30 patients before T-EGDS and C-EGDS Criteria

No. of patients

T-EGDS

C-EGDS

p-Value

Entire population

30

5.23 ± 6.76

4.90 ± 6.62

0.45

Age (years) ≤40 >40

11 19

6.76 ± 4.34 4.91 ± 2.07

5.35 ± 1.85 3.99 ± 2.02

<0.01 0.45

Sex Male Female

16 14

3.87 ± 5.57 6.78 ± 7.83

3.50 ± 5.33 6.50 ± 7.73

0.43 0.48

Previous EGDS Yes No

14 16

4.28 ± 6.32 6.06 ± 8.42

3.42 ± 6.19 6.18 ± 8.30

0.47 0.48

First examination T-EGDS C-EGDS

15 15

3.40 ± 4.65 7.06 ± 8.11

3.20 ± 4.54 6.53 ± 8.02

0.46 0.46

All anxiety scores are mean values ± S.D. p-values calculated by Student’s t-test. T-EGDS: transnasal oesophagogastroduodenoscopy; C-EGDS: conventional oesophagogastroduodenoscopy.

2.7. Evaluation and statistical analysis of results Inter- and intra-group comparisons of anxiety levels scored before T-EGDS and C-EGDS were made using Student t test for paired data. Differences between heart rate, oxygen saturation and blood pressure recorded during each EGDS with respect to baseline values were compared by oneway analysis of variance (ANOVA), whilst comparison of values of parameters recorded during the two types of EGDS was made using Student’s t-test for unpaired data. A value of p < 0.05 was considered statistically significant.

3. Results 3.1. T-EGDS versus C-EGDS 3.1.1. Pre-endoscopy assessment of anxiety About 4% of patients accepted to be enrolled in the study. All patients appropriately fulfilled the Hamilton A scale. Anxiety before C-EGDS was scored as absent in 21 patients, mild in 6, moderate in 2 and severe in 1, while before TEGDS as absent in 18 patients, mild in 9, moderate in 2 and severe in 1 (Table 2). Comparing the overall (all patients) mean score for anxiety before T-EGDS with that before C-EGDS, no statistically significant difference was found (5.23 ± 6.76 vs. 4.90 ± 6.62; p = 0.45). When patients were classified according to age, patients = 40 years were found to be more anxious before T-EGDS than before C-EGDS (6.76 ± 4.34 vs. 5.35 ± 1.85; p < 0.01), while no difference was observed in patients >40 years of age. No difference was found between anxiety scores evaluated before T-EGDS and C-EGDS comparing patients according to sex, previous experience of EGDS and sequence of examinations. At intra-group analysis, no statistically significant difference was found when patients were compared according to the dif-

ferent parameters, although anxiety scores before T-EGDS were approximately half those before C-EGDS regardless of whether T-EGDS was the first or second examination. 3.2. Patient acceptability Both types of EGDS were well tolerated by all patients except one, who, never undergone EGDS prior to the study, showed a moderate grade of anxiety (Hamilton A score: 15). Although midazolam was administered at a dosage of 3 mg, this patient, following insertion of the endoscope, refused to continue the C-EGDS and withdrawal of the endoscope was necessary. This patient had already been submitted to T-EGDS in this study. Upon insertion of the endoscope for T-EGDS, discomfort was scored as absent in 16 out of the 30 patients (53%), mild in 8 (27%), moderate in 5 (17%), severe in 1 (3%) and very severe in none, while during C-EGDS, discomfort was scored as absent in 16 out of the 30 patients (53%), mild in 6 (20%), moderate in 5 (17%), severe in 2 (7%) and very severe in one (3%) (Table 3). Comparison of mean scores showed no difference between the level of discomfort felt upon insertion of the endoscope in T-EGDS and C-EGDS (0.93 ± 1.14 vs. 1.03 ± 1.27; p = 0.28). Discomfort during T-EGDS, was scored as absent in 18 out of 30 patients (60%), mild in one (3%) and moderate in 11 (37%), while during C-EGDS discomfort was scored as absent in 15 out of the 30 patients (50%), moderate in 10 (33%), severe in 2 (7%) and very severe in 3 (10%). Comparing mean scores of discomfort during endoscopy, the level of discomfort felt during T-EGDS was significantly less than that during C-EGDS (0.87 ± 1.14 vs. 1.31 ± 1.61; p = 0.034).

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Table 3 Comparison of discomfort scores estimated by 5-point Likert scale at onset and during T-EGDS and C-EGDS Scores

T-EGDS (n = 30)

C-EGDS (n = 30)

At insertion of endoscope Absent 16 Mild 8 Moderate 5 Severe 1 Very severe –

16 6 5 2 1

During EGDS Absent Mild Moderate Severe Very severe

15 – 10 2 3

18 1 11 – –

Fig. 1. Heart frequency during different phases of T-EGDS () and CEGDS (). Comparing mean heart rates (beats per minute, bpm) during both examinations, increases in heart rates during C-EGDS were more frequent and higher than during T-EGDS (p < 0.05), the difference being statistically significant in each tract examined.

T-EGDS: transnasal oesophagogastroduodenoscopy; C-EGDS: conventional oesophagogastroduodenoscopy. Table 4 Preference between T-EGDS and C-EGDS expressed by 30 patients Reasons

Better tolerability Comfort of sedation Fear of sedation Better tolerability + fear of sedation

Preference T-EGDS

C-EGDS

12 – 2 12

2 2 – –

T-EGDS: transnasal oesophagogastroduodenoscopy; C-EGDS: conventional oesophagogastroduodenoscopy.

When patients were asked to express their preference between the two procedures, 26/30 patients (87%) chose TEGDS and 4 (14%) C-EGDS. Although three out of the four patients who preferred C-EGDS were females, no statistically significant difference was observed among patients who chose T-EGDS and those who chose C-EGDS when compared according to sex, age and anxiety score before each examination. Reasons given for preference are outlined in Table 4. Discomfort, associated or not with fear of adverse events following sedation, was the reason given for their choice, most frequently (92%) reported by those patients who chose T-EGDS. Stratifying patients who would prefer to repeat T-EGDS following a previous experience of EGDS, the proportion of patients already having undergone EGDS was similar to that of patients who had never been submitted to this investigation (12 vs. 14 out of 26 patients). 3.3. Patient safety: cardiac and respiratory evaluations No cardio-respiratory complications occurred during either T-EGDS or C-EGDS. ECG did not reveal any ST-T changes or severe arrhythmias but only minor changes in heart rhythm, such as sinus tachycardia, ectopic supraventricular beats, and ectopic ventricular beats during both procedures. The incidence of sinus tachycardia (7 during T-EGDS vs. 18 during C-EGDS) and ectopic supraventricular beats (0 during T-EGDS vs. 4 during C-EGDS) was

not significantly different, while the incidence of ectopic ventricular beats during T-EGDS was significantly lower than that during C-EGDS (0 vs. 6, respectively; p = 0.05). Heart rate and the rate-pressure (myocardial consumption) increased significantly in comparison to baseline values during both T-EGDS (p < 0.05) and C-EGDS (p < 0.01), the maximal peak being observed in the stomach, and returning to baseline values at the end of EGDS. Comparing heart rates during both examinations, increases in heart rates during C-EGDS were more frequent than during T-EGDS (p < 0.05), and mean heart rates during C-EGDS were higher than those during T-EGDS, the difference being statistically significant in each tract examined (p < 0.01, Student’s t-test) (Fig. 1). Oxygen before/during the procedure was given in none of the patients in each EGDS-group. Oxygen saturation was good during both EGDS, in all patients except two, in whom values <90 mmHg were detected during the final phase of CEGDS. When compared with baseline values, no significant changes in oxygen saturation were observed during T-EGDS (p = 0.257), whilst oxygen saturation was significantly modified during C-EGDS (p < 0.05). A comparison of mean values of oxygen saturation recorded during the two examinations revealed that patients showed better concentrations of oxygen during T-EGDS than during C-EGDS, the difference being statistically significant in each upper digestive tract examined (p < 0.01). The monitored changes in oxygen saturation observed during C-EGDS had no biological effect in the sense of an adverse event. Nevertheless, the slightly better oxygen saturation by using T-EGDS versus C-EGDS may assume clinical relevance in the subgroup of patients with co-morbidity, particularly including the cardiopulmonary system. Blood pressure did not vary significantly, in systolic and diastolic values, during T-EGDS in comparison to those at baseline (p = 0.651 and 0.558, respectively), while systolic blood pressure decreased significantly during C-EGDS (p < 0.005). In our series, in the T-EGDS group no patients developed epistaxis.

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Table 5 Endoscopic findings using C-EGDS and T-EGDS Diagnosis

No. of patients

Oesophagitis Hiatal hernia Erosive gastritis Erosive duodenitis Duodenal ulcer Gastric polyps Gastric xantoma Oesophageal varices

7 11 3 3 2 2 1 1

3.4. Endoscopist satisfaction Endoscopists reported being able to perform all standard endoscopic manoeuvres both during T-EGDS and C-EGDS, in all the patients examined and judged the quality of images to be high (good to very good in all patients) with the two procedures. Overall feasibility was scored as very good in 26 patients and good in the remaining 4 submitted to T-EGDS, and very good in all 29 patients who underwent C-EGDS, the difference being not statistically significant. 3.5. Feasibility, endoscopic patterns and diagnostic accuracy Both T-EGDS and C-EGDS allowed complete examination of the oesophagus, stomach and duodenum as planned, the percentage of completion being 100% for both types of endoscopy. No difference was found between the two procedures with the exception of duration of the examination, which was longer with T-EGDS than with C-EGDS (7.00 ± 3.00 min vs. 5.5 ± 2.01 min; p < 0.02). During both EGDS, pathological findings were revealed by endoscopy: oesophagitis in 7 patients, hiatal hernia in 11, erosive gastritis in 3, erosive duodenitis in 3, duodenal ulcer in 2, gastric polyps in 2, gastric xanthoma in one, and oesophageal varices in one. The endoscopic findings using C-EGDS and T-EGDS are summarized in Table 5. Individual endoscopic diagnoses as well as review by a third endoscopist showed complete agreement between endoscopists. 3.6. Histology A total of 192 biopsies were collected during the examinations, 96 during T-EGDS and 96 during C-EGDS. In our series, only gastric biopsy was taken and the accuracy was

only evaluated for the diagnosis of gastritis and presence of H. pylori. No duodenal and oesophageal biopsies were taken using any of the two kind of biopsy forceps, as no patients showed indication to perform oesophageal or duodenal biopsies during EGDS. Although one patient had celiac disease, indication for EGDS was epigastric pain and duodenal biopsy samples were already recently taken. Specimens collected during T-EGDS measured 1–3 mm in maximum diameter and all but two (one of three specimens in two patients) were adequate for reliable histological assessment allowing gastritis to be scored in all cases. Biopsy specimens taken during C-EGDS measured 2–5 mm in maximum diameter and all were adequate for histology. When comparing histological findings of the two techniques, no significant difference was found as far as concerns reaching a conclusive diagnosis. The pathologist was blind to the endoscopy technique and the forceps used. Nevertheless, at time of histological analysis, the lower size of the biopsy samples taken using forceps for T-EGDS (1–3 mm) when compared to the size of the biopsy samples taken using forceps for C-EGDS (2–5 mm) revealed anyway to the pathologist the endoscopy technique used.

4. T-EGDS with 4.9 mm versus 5.9 mm Complete EGDS was possible with both standard 5.9 and the 4.9 mm UT endoscopes, in all 30 patients. Diagnostic accuracy was comparable, although images using the 4.9 mm UT instrument were larger and better defined than those with the 5.9 mm endoscope. Data regarding pre-endoscopy anxiety, pain upon insertion, pain during investigation as well as duration of the examination are outlined in Table 6. Patients examined with the 4.9 mm UT endoscope showed a lower mean score of anxiety than that of patients examined with the 5.9 mm UT endoscope (2.73 ± 4.33 and 6.40 ± 7.36, respectively; p < 0.05), while no difference was found in terms of discomfort. Duration of the examination performed using the 4.9 mm UT endoscope was slightly, but not significantly, longer than that of examinations in which the 5.9 mm instrument was used (7.64 ± 2.24 min vs. 6.20 ± 2.32 min, respectively). No difference was found in terms of cardio-respiratory variations occurring during EGDS performed with the 5.9 mm instrument versus those with the 4.9 mm model. Handling of the

Table 6 Data regarding pre-endoscopy anxiety, tolerability and feasibility during T-EGDS performed with GIF-N180 and GIF XP-160 endoscopes in 30 patients Parameters

GIF-N180a (N = 15)

Anxiety Pain at insertion Pain during investigation Duration of examination

2.73 0.86 0.80 7.64

Values are means ± S.D. a GIF-N180: 4.9 mm; GIF-XP160: 5.9 mm.

± ± ± ±

4.33 1.02 1.02 2.24

GIF-XP160 (N = 15) 6.40 1.14 0.93 6.20

± ± ± ±

7.36 1.29 1.30 2.32

p-Value <0.05 0.19 0.18 0.44

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5.9 and 4.9 mm UT endoscopes was judged to be comparable, although reaching the second part of the duodenum with the 5.9 mm instrument was reported, by endoscopists, to be easier than with the 4.9 mm endoscope.

5. Discussion In the late 1990s, several studies [8–14] introduced EGDS with trans-nasal access in order to improve acceptability of this investigation and as a possible alternative to C-EGDS, which is usually performed under sedation to overcome discomfort due to its invasiveness. In comparison to the trans-oral route, the alternative access through the nose offers several advantages, such as the absence of stimulation of the pharynx and no reactive reflexes of gagging and vomiting, no risk of aspiration, better control of respiratory function, possibility for patients to speak during the examination, and no risk of a patient biting the endoscope. Furthermore, lack of sedation reduces the risk of adverse cardio-respiratory events, which account for >50% of the complications related to gastrointestinal endoscopy [4,5,23], allows earlier discharge of outpatients, and, furthermore, reduces costs. Later reports [16–18,20] did not confirm the earlier encouraging experience with T-EGDS and stressed the failure of the trans-nasal access in some patients (12%), the occurrence of complications, such as epistaxis (22%) and microperforation of the oesophagus, as well as the endoscopist’s preference for transoral insertion due to lack of familiarity with nasal access. In the present study, patient acceptability of unsedated TEGDS was found to be better than that of sedated C-EGDS. All patients underwent T-EGDS while one patient, already submitted to T-EGDS, refused to undergo C-EGDS. Discomfort during T-EGDS was also judged as significantly less than that during C-EGDS, both upon insertion and throughout the remainder of the procedure. Finally, 26 out of 30 patients (87%) declared that they preferred unsedated T-EGDS versus only 4 patients (13%) who preferred sedated C-EGDS. These findings are in contrast to results of other studies [14,17,18] which failed to demonstrate better acceptability of T-EGDS. A high level of anxiety has been reported to negatively affect acceptability of EGDS, accounting for up to 40% of refusals to undergo T-EGDS [17,18]. This relationship would not appear to be supported by the finding, in the present investigation, that most of our patients (27 out of 30 patients, 90%) showed either no, or only mild, levels of anxiety. Furthermore, the level of anxiety, in the present series, was not significantly different before T-EGDS and C-EGDS, as would reasonably be expected given that both examinations were being performed in a same group of patients. Finally, when anxiety scores were correlated with various parameters, such as age, sex, previous EGDS and type of EGDS first experienced in the study, patients <40 years scored a higher level of anxiety before T-EGDS but, in contrast to what might be expected, they tolerated and accepted EGDS through the nose better

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than that performed through the mouth. Thus, it is tempting to suggest that anxiety is not the main factor related to tolerability of EGDS. Some authors [12,14,17] hypothesised the possible relationship of age and sex with acceptability of TEGDS having demonstrated less tolerance towards T-EGDS in patients aged <40 years and females. Although three out of four patients who preferred C-EGDS were females and aged <40 years, we are unable to confirm this hypothesis on the basis of the data emerging from the present study, since the difference was not statistically significant between the patients who chose T-EGDS and those who chose C-EGDS, according to age and sex, probably due to the characteristics of the study population. As far as safety is concerned, no cardio-respiratory complications occurred during C-EGDS and T-EGDS, in the present study population. However, tachycardia and ectopic supra-ventricular and/or ventricular beats, were more frequently observed during C-EGDS than during T-EGDS. Furthermore, during C-EGDS, systolic blood pressure was significantly lower compared to baseline values, while during T-EGDS, no significant variation was observed. Finally, no variations in oxygen saturation occurred during T-EGDS, while arterial desaturation was observed during C-EGDS. The finding could be due to the effect of benzodiazepines, administered during C-EGDS [4,5]. These changes, although not clinically relevant in healthy subjects, could be of great importance, especially in patients with undisclosed heart disease. Albeit, further studies are needed, in larger study populations, since in most of the studies [8,9,12,17,18] comparing T-EGDS with C-EGDS, possible differences between the procedures, in terms of changes of cardiac and respiratory functions, were not evaluated. On the basis of current data, unsedated T-EGDS seems to be better tolerated and safer than C-EGDS under sedation and should, therefore, be considered the method of choice in upper digestive endoscopy for diagnostic purposes, especially in patients with respiratory or heart diseases. In the present study, the relatively low inclusion rate observed may well be explained by the observation that the 30 enrolled voluntary patients performed two EGDS (C-EGDS and T-EGDS) within 48 h. Supporting this, no other studies compared these two EGDS in the same patients within this short time interval. Besides this may be because no fees were given to the patients. In our experience, T-EGDS allowed complete examination of the upper digestive tract to be performed in all patients, both with the 5.9 and with the 4.9 mm UT endoscope. Several authors [16,17,19,20] have reported a certain degree of difficulty in performing T-EGDS, particularly lack of familiarity with the nasal access, with a failure rate of intubation ranging from 8 to 22% of cases. In contrast to these reports, nasal intubation did not fail in any of the patients in the present series. The small number of patients might appear to suggest that the failure rate, in nasal insertion, is underestimated in the present study. However, it is worthwhile pointing out, that in our personal experience (>5000 T-EGDS), from September 2001 to

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date, failure of transnasal intubation occurred very rarely (4% of cases, unpublished personal data) and, moreover, a skilled endoscopist will very soon become familiar with the approach through the nose. The use of naphazoline, a vasoconstrictor, in the present study, could also make transnasal introduction easier through the turbinates. However, Birkner et al. [20], using a vasoconstrictor before T-EGDS, reported a failure rate of 22% making nasal insertion. Thus, the usefulness of a vasoconstrictor in T-EGDS to facilitate access through the nose needs to be further investigated. Last, but not least, 50% of the patients underwent T-EGDS with a 4.9 mm endoscope, which is 1 mm less in diameter than the endoscopes used in previous studies [9,16,18] in which high failure rates, in nasal access, were reported. To our knowledge, the current study is the first to report the successful use of a 4.9 mm UT endoscope in performing a complete EGDS. These preliminary data with the use of this new 4.9 mm endoscope are in keeping with those in a recent paper [29] reporting a positive experience in performing transnasal oesophagoscopy with a 4 mm UT endoscope. The use of the 4.9 mm UT endoscope, without left-right movement presented here, led to some difficulty in intubating the second duodenal portion, a manoeuvre usually requiring a right or left rotation. Lack of the right left dial may be compensated by twisting the endoscope. The possibility, in the present study, to perform a complete EGDS, with scrupulous evaluation of the oesophagus, stomach and duodenum, in all the patients examined, with the new 4.9 mm UT endoscope, confirms the easy handling of this two-movement device. Furthermore, the GIF-N180 UT endoscope is equipped with a new charge coupled device (CCD) chip, which, with a higher density of pixels, offers the possibility to obtain larger images with a higher resolution than those obtained using the 5.9 mm UT endoscope, even if the same video-processor is used. Albeit, despite these technical differences between 5.9 and 4.9 mm UT endoscopes, images obtained with the UT endoscopes were adequate in all cases, and clearly defined the endoscopic patterns which were in agreement with those observed during C-EGDS. This finding is in keeping with that of other authors [8–10] in which a comparable imaging with T-EGDS and C-EGDS was reported. The diagnostic accuracy of T-EGDS is further supported by the evidence that biopsy specimens collected by 1.8 mm forceps were smaller and more superficial but were adequate, in all patients, to reach a final diagnosis, in agreement with those collected using standard forceps (2.2 mm in size) during C-EGDS. Indeed, it was possible, in all cases, to score the presence of gastritis and H. pylori infection, as well as gastric atrophy, by evaluating fibrosis and/or intestinal metaplasia. These findings are in agreement with those of others [12,19,20] and confirm the possibility of obtaining a reliable histological assessment of biopsy specimens collected by means of UT endoscopes [15]. In our opinion, the present study has several strong points. First of all, both types of EGDS were performed in all patients but one who

refused to undergo C-EGDS, a condition supporting the likelihood that all differences between T-EGDS and C-EGDS are probably related to the technical aspects. In this respect, the better tolerance and acceptability of T-EGDS seems, in fact, to be due to the smaller calibre of the endoscope and, more important, the transnasal route of intubation. Once introduced through the nose, endoscopy becomes easy to tolerate by the patient due to the lack of stimulation at the tongue base and the posterior wall of the pharynx. Second, continuous and scrupulous monitoring of cardiac and respiratory functions, together with the levels of oxygen saturation, confirms the importance of current data on the safety of EGDS. Finally, the new 4.9 mm UT double movement endoscope for a complete EGDS, described here for the first time, shows interesting technical features worthy of further investigation to confirm these promising findings. A possible drawback of the present study could be the relatively small number of patients investigated. Albeit, our study population is comparable to those of the only two previous investigations [8,9], on 24 and 10 patients respectively, in which T-EGDS and C-EGDS were compared in a same study group. On the other hand, it has to be borne in mind that it may be difficult to select a large number of subjects who are willing to undergo two EGDS in 2 days, especially in the event of a monocentric study. In conclusion, the findings emerging from the present study indicate that unsedated T-EGDS is a safe and wellaccepted investigation. The availability of the recently developed 4.9 UT double movement endoscope may further contribute to making T-EGDS easier to perform, technical features which, in our opinion, should be taken into account as a valid alternative to sedated C-EGDS in routine diagnostic assessments of the upper digestive tract. Cost analysis studies will no doubt confirm the advantages of T-EGDS from an economic viewpoint. Practice points • The transnasal oesophagogastroduodenoscopy (T-EGDS) is a less invasive procedure than the conventional oesophagogastroduodenoscopy (C-EGDS). • Tolerability of this method avoids sedation, decreases risks for the patient and costs of endoscopy. • In our experience failed intubation in the transnasal group rarely occurred even though this finding is not in accordance with that of other authors. • Biopsy specimens obtained both by 1.8 mm diameter ultrathin and 2.2 mm diameter standard forceps showed a similar diagnosis. • In both procedures the examination length was comparable.

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Research agenda • Application of the Health Technology Assessment to the EGDS-TN to better assess feasibility, tolerability, safety and cost-effectiveness is needed. • Use of the TN-route in patients selected for cardiorespiratory pathology should be planned.

Conflict of interest statement None declared.

Acknowledgements Authors thank MEPERTE, general practitioners association, for selection of patients and Mrs. Marian Shields for help with the English manuscript. The kind availability and careful assistance of the entire nursing staff of the gastrointestinal centre during all study procedures are gratefully acknowledged.

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